C. elegans SUP-46, an HNRNPM family RNA-binding protein that prevents paternally-mediated epigenetic sterility.
In addition to DNA, gametes contribute epigenetic information in the form of histones and non-coding RNA. Epigenetic programs often respond to stressful environmental conditions and provide a heritable history of ancestral stress that allows for adaptation and propagation of the species. In the nematode C. elegans, defective epigenetic transmission often manifests as progressive germline mortality. We previously isolated sup-46 in a screen for suppressors of the hexosamine pathway gene mutant, gna-2(qa705). In this study, we examine the role of SUP-46 in stress resistance and progressive germline mortality. We identified SUP-46 as an HNRNPM family RNA-binding protein, and uncovered a highly novel role for SUP-46 in preventing paternally-mediated progressive germline mortality following mating. Proximity biotinylation profiling of human homologs (HNRNPM, MYEF2) identified proteins of ribonucleoprotein complexes previously shown to contain non-coding RNA. Like HNRNPM and MYEF2, SUP-46 was associated with multiple RNA granules, including stress granules, and also formed granules on active chromatin. SUP-46 depletion disrupted germ RNA granules and caused ectopic sperm, increased sperm transcripts, and chronic heat stress sensitivity. SUP-46 was also required for resistance to acute heat stress, and a conserved "MYEF2" motif was identified that was needed for stress resistance. In mammals, non-coding RNA from the sperm of stressed males has been shown to recapitulate paternal stress phenotypes in the offspring. Our results suggest that HNRNPM family proteins enable stress resistance and paternally-mediated epigenetic transmission that may be conserved across species.


Organic vapor sorption method of isostructural solvates and polymorph of tenofovir disoproxil fumarate.
Tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir that belongs to a class of antiretroviral drugs, a nucleotide reverse transcriptase inhibitor. An acetonitrile solvate of TDF I, another new solvated form of TDF, was prepared and solid state characterization of its form was conducted using powder X-ray diffraction, FT-IR spectroscopy, and organic vapor sorption isotherm. During the characterization work, it was discovered that (1) TDF I can form solvates and polymorph with a wide variety of organic solvents as well as water and (2) to different extents, these solvates undergoes anisotropic lattice contraction/expansion during desolvation/solvation process suggesting the formation of isostructural solvates of TDF. Solvents used in this study include ethanol, isopropyl alcohol, acetonitrile, cyclohexane, toluene, and water. Four new solvates using ethanol, isopropyl alcohol, acetonitrile, and toluene vapor and one polymorph using water vapor were discovered. Their solid state characterizations were conducted using powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. A variety of isostructural solvates and a polymorph of TDF was produced by an organic vapor sorption method, showing varying physicochemical properties. This study demonstrates an alternative crystallization method to obtain isostructural solvates.


Evaluation of the patient generated index as a measure of quality-of-life in people with severe traumatic brain injury.
Quality-of-life (QoL) measures may be useful in quantifying the personal impact of an acquired brain injury and as an indicator of the effectiveness of service provision. This study investigated the validity of the patient generated index (PGI) as a measure of QoL with a sample of adults who had sustained a severe traumatic brain injury. Fifty-five participants with an acquired brain injury were selected from four regional rehabilitation centres. Each participant completed validated questionnaires measuring subjective satisfaction with life, community integration, emotional distress, socially desirable responding and the patient generated index. The criterion-related validity of the PGI was demonstrated through a statistically significant positive correlation with life satisfaction. Evidence of construct validity was observed through significant correlations with measures of emotional distress and community integration. Depression had a strong negative association with QoL. Social desirability correlated significantly with both indices of QoL, suggesting that this variable may be treated as a covariate. The results offer some preliminary evidence for the validity of the PGI as a measure of QoL in people with severe brain injury.


Generation of a total of 6483 expressed sequence tags from 60 day-old bovine whole fetus and fetal placenta.
Expressed sequence tags (ESTs) generated based on characterization of clones isolated randomly from cDNA libraries are used to study gene expression profiles in specific tissues and to provide useful information for characterizing tissue physiology. In this study, two directionally cloned cDNA libraries were constructed from 60 day-old bovine whole fetus and fetal placenta. We have characterized 5357 and 1126 clones, and then identified 3464 and 795 unique sequences for the fetus and placenta cDNA libraries: 1851 and 504 showed homology to already identified genes, and 1613 and 291 showed no significant matches to any of the sequences in DNA databases, respectively. Further, we found 94 unique sequences overlapping in both the fetus and the placenta, leading to a catalog of 4165 genes expressed in 60 day-old fetus and placenta. The catalog is used to examine expression profile of genes in 60 day-old bovine fetus and placenta.


Leading malignant cells initiate collective epithelial cell invasion in a three-dimensional heterotypic tumor spheroid model.
Solid tumors consist of genetically and phenotypically diverse subpopulations of cancer cells with unique capacities for growth, differentiation, and invasion. While the molecular and microenvironmental bases for heterogeneity are increasingly appreciated, the outcomes of such intratumor heterogeneity, particularly in the context of tumor invasion and metastasis, remain poorly understood. To study heterotypic cell-cell interactions and elucidate the biological consequences of intratumor heterogeneity, we developed a tissue-engineered multicellular spheroid (MCS) co-culture model that recapitulates the cellular diversity and fully three-dimensional cell-cell and cell-matrix interactions that characterize human carcinomas. We found that "invasion-competent" malignant cells induced the collective invasion of otherwise "invasion-incompetent" epithelial cells, and that these two cell types consistently exhibited distinct leader and follower roles during invasion. Analysis of extracellular matrix (ECM) microarchitecture revealed that malignant cell invasion was accompanied by extensive ECM remodeling including matrix alignment and proteolytic track-making. Inhibition of cell contractility- and proteolysis-mediated matrix reorganization prevented leader-follower behavior and malignant cell-induced epithelial cell invasion. These results indicate that heterogeneous subpopulations within a tumor may possess specialized roles during tumor progression and suggest that complex interactions among the various subpopulations of cancer cells within a tumor may regulate critical aspects of tumor biology and affect clinical outcome.


Topiramate induced sudden loss of vision.
The case of a 20 year old female presenting with overnight acute loss of vision is reported. The patient was recently started on topiramate (Hitop) for her recurrent migraine and developed sudden loss of vision due to acute myopia. Topiramate was discontinued and the patient's vision returned to normal. Delayed and incorrect treatment may result in permanent vision loss, secondary to angle closure glaucoma; therefore it is imperative that prescribing physicians are aware of this rare but serious ocular emergency.


The effect of diets containing fish and fish oils on disease risk factors in humans.
Fish and fish oils are rich in omega 3 polyunsaturated fatty acids which are capable of acting as both a source of active eicosanoids and as inhibitors of synthesis of eicosanoids from arachidonic acid by a variety of human cells. There is an extensive literature on the role of omega 3 polyunsaturates in ameliorating the risk factors associated with coronary heart disease, including both atherosclerotic and thrombotic factors. In addition, there is a limited number of studies which report the results of trials testing the effects of fish oils on other clinical conditions including diabetes, arthritis, migraine and psoriasis. There appears to be sufficient evidence to suggest that patients at risk from heart disease could benefit from low dose (1-6 g/day) of fish oil in conjunction with a prudent diet.


Nano-selenium enhances melon resistance to Podosphaera xanthii by enhancing the antioxidant capacity and promoting alterations in the polyamine, phenylpropanoid and hormone signaling pathways.
Powdery mildew is one of the main problematic diseases in melon production, requiring the use of chemical pesticides with disease-resistant cultivars for control. However, the often rapid acquisition of fungicidal resistance by mildew pathogens makes this practice unsustainable. The identification of crop treatments that can enhance resistance to powdery mildew resistance is therefore important to reduce melon crop attrition. This study indicates that the application of Nano-Se can reduce the powdery mildew disease index by 21-45%. The Nano-Se treatment reduced reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation, with increases in glutathione (GSH), proline and 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH). Increases were also observed in the activities and transcriptional levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD). Assays with four different cultivars of melon with differing levels of mildew resistance demonstrated that relative to the control, the Nano-Se treatment resulted in larger responses to mildew infection, including increases in the levels of putrescine (PUT; 43-112%) and spermine (SPM; 36-118%), indoleacetic acid (IAA; 43-172%) and salicylic acid (SA; 24-73%), the activities of phenylalanine ammonium lyase (PAL), trans-cinnamate 4-hydroxylase (C4H) and 4-coumarate: Co A ligase (4CL) of the phenylpropanoid pathway (22-38%, 24-126% and 19-64%, respectively). Key genes in the polyamine and phenylpropanoid pathway were also upregulated. These results indicate that the foliar application of Nano-Se improved melon defenses against powdery mildew infection, with a significant reduction in mildew disease development.


Analysis of signaling pathways in recurrent breast cancer.
Breast cancer remains the second largest cause of death in women from cancer. By analyzing gene expression profiles in samples from breast cancer patients, 844 differentially expressed genes (DEGs) were identified in breast cancer metastasis. The 10 most significant signaling pathways identified through enrichment analysis contained DEGs were involved in oxidative phosphorylation, DNA replication, extracellular matrix-receptor interactions and others. Furthermore, survival analysis demonstrated that 5 of these signaling pathways were closely related to the survival time of breast cancer patients including basal transcription factors, cell cycle, ECM-receptor interaction, spliceosome, and DNA replication. Our findings increase the understanding of the network of signaling pathways involved in breast cancer metastasis and may provide theoretical support for further therapeutic study.


Electrical and mechanical properties of poly(L-lactide)/carbon nanotubes/clay nanocomposites.
An organoclay containing epoxy groups, twice-functionalized organoclay (TFC), was synthesized by reacting (glycidoxypropyl)trimethoxy silane with Cloisite25A (C25A), which had already been modified with an amine compound. The introduction of epoxy groups to the clay surface and carboxylic group-functionalized multiwalled carbon nanotubes (MWCNTs) improved the interfacial adhesion between the poly(L-lactide) (PLLA) and nano-sized fillers when melt-compounded. The PLLA/MWCNTs/TFC nanocomposites showed superior tensile properties to those of PLLA and PLLA/CNTs. The dispersion of MWCNTs in the PLLA matrix decreased the electrical resistivity of the composite substantially due to the higher MWCNT loading. However, the introduction of TFC to the PLLA/MWCNTs nanocomposites resulted in a slight increase in volume resistivity. This increase was attributed to the individual MWCNTs being blocked by the TFC. The clays in the PLLA/MWCNTs/TFC nanocomposites prevented direct contact between the neighboring MWCNTs, which increased the electrical resistivity of the nanocomposites.


cAMP receptor protein from escherichia coli as a model of signal transduction in proteins--a review.
In Escherichia coli, cyclic AMP receptor protein (CRP) is known to regulate the transcription of about 100 genes. The signal to activate CRP is the binding of cyclic AMP. It has been suggested that binding of cAMP to CRP leads to a long-distance signal transduction from the N-terminal cAMP-binding domain to the C-terminal domain of the protein, which is responsible for interaction with specific sequences of DNA. The signal transduction plays a crucial role in the activation of the protein. The most sophisticated spectroscopic techniques, other techniques frequently used in structural biochemistry, and site-directed mutagenesis have been used to investigate the details of cAMP-mediated allosteric control over CRP conformation and activity as a transcription factor. The aim of this review is to summarize recent works and developments pertaining to cAMP-dependent CRP signal transduction in E. coli.


Voluntary activation of the trapezius muscle in cases with neck/shoulder pain compared to healthy controls.
Subjects reporting neck/shoulder pain have been shown to generate less force during maximal voluntary isometric contractions (MVC) of the shoulder muscles compared to healthy controls. This has been suggested to be caused by a pain-related decrease in voluntary activation (VA) rather than lack of muscle mass. The aim of the present study was to investigate VA of the trapezius muscle during MVCs in subjects with and without neck/shoulder pain by use of the twitch interpolation technique. Ten cases suffering from pain and ten age and gender matched, healthy controls were included in the study. Upper trapezius muscle thickness was measured using ultrasonography and pain intensity was measured on a 100mm visual analog scale (VAS). VA was calculated from five maximal muscle activation attempts. Superimposed stimuli were delivered to the accessory nerve at peak force and during a 2% MVC following the maximal contraction. Presented as mean±SD for cases and controls, respectively: VAS; 16.0±14.4mm and 2.1±4.1mm (P=0.004), MVC; 545±161N and 664±195N (P=0.016), upper trapezius muscle thickness; 10.9±1.9mm and 10.4±1.5mm (P=0.20), VA; 93.6±14.2% and 96.3±6.0% (P=0.29). In spite of significantly eight-fold higher pain intensity and ∼20% lower MVC for cases compared to controls, no difference was found in VA. Possible explanations for the reduction in MVC could be differences in co-activation of antagonists and synergists as well as muscle quality.


Calprotectin as new potential clinical marker for multiple myeloma.
Increased levels of inflammatory cytokines in multiple myeloma (MM) patients and the role of inflammation in disease pathogenesis, have recently been considered. The aim of this study was to quantitatively evaluation of fecal calprotectin (CP) as a non-invasive biomarker for the evaluation of inflammation in patients with multiple myeloma. This study is a hospital-based case control study. MM patients referred to patients referred to medical centers of Tehran province, Iran, were identified and classified into two groups of new MM patients (n = 40) and patients undergoing treatment (n = 28). Healthy individuals were included in the study as healthy control (n = 25). Morning stool samples were collected and CP was extracted immediately. After collecting the samples, CP was measured according to ELISA method and was determined in μg/g of feces. Values above 50 μg/g of feces are positive and indicate inflammation. The results revealed that there is a significant difference between groups in terms if CP mean (p = 0.001). The mean of CP among new cases, under treatment and control groups were 301.3 (SD: 141.0), 165.1 (SD: 153.9) and 36.9 (SD: 13.5), respectively. Then the groups were compared in pairs, the results showed that the new case group was significantly different from the under-treatment group (p = 0.001), and also the control group showed a significant difference with the new case group (p = 0.001) and the under-treatment group (p = 0.001) that the amount of CP in the control group was significantly lower than the other two groups. In addition, the results of the study showed a significant correlation between age and plasma cells with CP value, so that with increasing age and plasma cells, CP value also showed a significant increase. The results indicate that quantitative evaluation of CP as a non-invasive laboratory biomarker has a high potential as a clinical marker in patients with multiple myeloma and inflammation should considered as a hallmark of cancer. Further diagnostic studies are recommended.


Characterization of the intrarenal renin-angiotensin system in cats with naturally occurring chronic kidney disease.
The role of the renin-angiotensin-aldosterone system in cats with chronic kidney disease (CKD) is incompletely understood. To characterize components of the intrarenal renin-angiotensin system (RAS) in cats with CKD. Eleven cats with naturally occurring CKD (CKD group) and 8 healthy control cats. Renal tissue samples were evaluated by reverse-transcription polymerase chain reaction for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor transcript levels, and by liquid chromatography-mass spectrometry for quantification of angiotensin I, II, III, and IV concentrations. Linear mixed models were used to compare gene transcript levels and concentrations of angiotensin peptides between groups. Cats of the CKD group were significantly older (P < .001) and more likely to be neutered (P = .007) than healthy control cats. Kidneys from cats with CKD had significantly higher transcript levels of angiotensinogen (P < .001) and lower transcript levels of ACE (P < .001) than those from control cats. Renal angiotensin I concentrations were increased in CKD compared with control kidneys (P = .001). No other significant differences in renal transcript levels or angiotensin peptide concentrations were noted between groups. The intrarenal RAS might be activated in cats with CKD. Small sample size and differences in age, neuter status, and dietary sodium intake between groups might have limited the ability to identify a significant difference in concentration of renal angiotensin II.


Better living through ontologies at the Immune Epitope Database.
The Immune Epitope Database (IEDB) project incorporates independently developed ontologies and controlled vocabularies into its curation and search interface. This simplifies curation practices, improves the user query experience and facilitates interoperability between the IEDB and other resources. While the use of independently developed ontologies has long been recommended as a best practice, there continues to be a significant number of projects that develop their own vocabularies instead, or that do not fully utilize the power of ontologies that they are using. We describe how we use ontologies in the IEDB, providing a concrete example of the benefits of ontologies in practice. www.iedb.org.


Tissue-specific expression of tomato Ribonuclease LX during phosphate starvation-induced root growth.
Ribonuclease LX (RNaseLX) from tomato (Solanum lycopersicum L.) belongs to the RNase T2/S-RNase superfamily of plant endoribonucleases and this is a report on the characterization of the RNaseLX gene and its encoded protein as a member of the phosphate starvation response in tomato. RNaseLX gene sequences were cloned by a PCR-assisted approach. RNaseLX promoter sequences contained the conserved binding motif of the transcription factor PHR1 known to mediate phosphate starvation-dependent gene expression. The increase of RNaseLX transcript levels in roots during phosphate starvation correlated with high promoter activity in transgenic plants carrying a PromLX::uidA gene construct and pointed to transcriptional control of RNaseLX expression. Histochemical staining for beta-glucuronidase activity and immunodetection of RNaseLX protein revealed striking RNaseLX expression in main and lateral root tips of phosphate-starved transgenic plants, specifically in epidermal cells, as well as in lateral and adventitious root primordia. Induced RNaseLX expression in roots correlated with stimulated growth and elongation of primary and lateral roots during phosphate deprivation. Phosphate-starvation-induced RNaseLX transcript levels in roots were not modulated by auxin or ethylene. These data indicate that the role of intracellular RNaseLX in the phosphate starvation response is connected with specific RNA turnover processes at the root tip.


Microwave-assisted annulation for the construction of pyrido-fused heterocycles and their application as photoluminescent chemosensors.
A catalyst-free microwave-assisted annulation protocol for the preparation of biologically interesting pyrido-fused quinazolinones and pyrido[1,2-a]benzimidazoles is developed. This reaction involves the [3 + 3] annulation of various quinazolinones or benzimidazoles with 3-formylchromones to yield functionalized 11H-pyrido[2,1-b]quinazolin-11-one and pyrido[1,2-a] benzimidazole derivatives. This approach is successfully extended to the construction of various pyrazolo[4,3-d]pyrido[1,2-a]pyrimidin-10(1H)-ones. The present approach is complementary to the existing synthetic methodologies and offers a rapid and facile approach with a broad substrate scope, good yields, catalyst-free conditions, and a high functional group tolerance. The optimal synthesized compound is also employed as an "on-off" photoluminescent probe for the selective detection of Fe3+ and Ag+ metal ions.


New imaging technology system reduces patient radiation dose during peripheral arterial endovascular interventions.
Radiation exposure and imaging quality are among the main concerns in endovascular procedures. The Clear VD11 PURE platform technology system (Siemens Healthineers, Erlangen, Germany) has been reported to lower the radiation dose and improve image quality. In the present study, we evaluated whether the radiation dose during peripheral arterial endovascular procedures had decreased after implementation of this new imaging system. The patient characteristics (age, gender, body mass index [BMI]), procedure type (diagnostic, balloon angioplasty, atherectomy, stenting), body location (aortoiliac, superficial femoral artery, tibial artery), reference air kerma (RAK), kerma area product (KAP), and fluoroscopy time (FT) were recorded during peripheral artery interventions performed 1 year before (group A) and 1 year after (group B) the CLEAR system upgrade. The procedures were performed in an Artis zeego hybrid room (Siemens Healthineers) with the same providers. A general linear model was used to estimate the average difference between groups adjusted by procedure type and patient age, gender, and BMI. Additionally, to control for variations in case complexity, groups A and B were matched by age, gender, BMI, lesion location, and intervention type. Propensity score matching and a paired t test were used to compare the KAP, RAK, and FT stratified by single intervention procedures. A total of 487 endovascular procedures were performed: 209 in group A and 278 in group B. A total of 111 single intervention procedures from each group were matched (1:1), with a mean age of 61 ± 8 years and a BMI of 26.5 ± 4 kg/m2. The median KAP, RAK, and FT for group A were 28.8 Gy · cm2 (interquartile range [IQR], 24-34 Gy · cm2), 146 mGy (IQR, 123-173 mGy), and 12 minutes (IQR, 10-14 minutes), respectively. The median KAP, RAK, and FT for group B were 18.3 Gy · cm2 (IQR, 16-22 Gy · cm2), 71.2 mGy (IQR, 60-85 mGy), and 10.4 minutes (IQR, 9-12 minutes), respectively. The KAP, RAK, and FT were significantly decreased in group B by 24% (P = .005), 41% (P < .001), and 22% (P = .002), respectively, compared with the values for group A. Stratified by single intervention procedures, the KAP and RAK had decreased significantly in group B (36% [P = .002] and 51% [P < .001], respectively) compared with group A. The FT decrease of 13% in group B was not statistically significant (P = .20). Use of the Clear VD11 PURE platform system (Siemens Healthineers) reduced the patient radiation dose by 51% during endovascular peripheral interventions. The similar FTs for the matched single intervention procedures before and after the upgrade indicated consistent case complexity and surgeon practice. This platform appears to be an effective system for lowering the radiation dose.


Comparison of automated medication-management systems.
Automated devices for managing medication distribution are described. Shrinking operating budgets are causing many departments of pharmacy to consider automation to maximize the cost-effective use of professional personnel. Many devices and systems that are currently available or under development can help with (1) distribution of medication to and from the patient care area, (2) distribution of medication directly to the patient, (3) inventory control, (4) management of controlled substances, or (5) documentation of medication administration. Medication-management devices based in the patient care unit (Lionville CDModule, Access, Meditrol, Argus, MedStation, Sure-Med, and SelecTrac-Rx) are designed to replace manual filling of unit dose carts or to increase control over floor-stock medications and controlled substances. They provide immediate access to medications but can take extra time to fill. Centrally located medication-management systems (Automated Pharmacy Station, ATC-212, and Medispense) are designed to replace or improve a manual system for filling unit dose carts. They may have financial and practical advantages over systems based in the patient care unit because they avoid redundant inventories. However, a manual system is still needed for some medications, particularly those that need refrigeration. Several point-of-care information systems also have medication-management components (MedTake, CliniCare, Automated Medication Administration Tracking, and MedLynk). They provide rapid access to patient information and facilitate documentation. Many incorporate bar-code technology and radio-frequency transmission of data. An automated management system can combine increased efficiency with decreased risk of error. Descriptions of available systems may help pharmacists choose a system that meets their needs.


The prevention of preterm delivery through prenatal care: an intervention study in Martinique.
During 1976-1978, improvements were made in the free prenatal care provided by the maternal and child health authority (PMI) of Martinique. Central to these changes was implementation of a program of preventive prenatal care developed in France by one of the authors (EP). Data on all births during 1980-1982 show no significant difference in pregnancy outcomes between women receiving free prenatal care from the government and women receiving private care from obstetricians.


Structure of the baboon endogenous virus genome: nucleotide sequences of the long terminal repeat.
The entire nucleotide sequence of the long terminal repeat (LTR) of baboon endogenous virus (BaEV) M7 was determined, which consisted of 554 base pairs (bp). At both ends of the LTR, 13 bp sequences, AAATGAAAAGTAA and TGATTCTAACATC, were detected to be inverted repeats. The structure with these inverted repeats resembles those of other retroviruses and transposable elements. a Hogness box, TATAAAA, and a putative poly(A)-addition signal, AGTAAA, were present within the right-hand half of the LTR, where the initiation and termination of the viral RNA synthesis seems to occur in the integrated BaEV genome. The primer-binding site of at least 14 bp long was found just outside of the LTR where the strong stop DNA started, and the primer for reverse transcription in BaEV seemed to be tRNAPro. Several structural features are commonly detected in the LTRs of BaEV and other retroviruses. Our studies suggest that BaEV has evolved from a common ancestor with other mammalian type C viruses. Close relationships between BaEV and a feline endogenous virus, RD114, are demonstrated.


Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis.
Long term survival rates for childhood cancers is steadily increasing, however cancer survivors can experience fertility problems as a consequence of chemotherapy treatment. This is particularly problematic for young boys, for whom no fertility preservation treatment is yet established. Here, we have determined the effects on prepubertal mouse testis of three commonly used chemotherapy drugs; cyclophosphamide (using its active metabolite phosphoramide mustard), cisplatin and doxorubicin, exposing testicular fragments to a clinically relevant range of concentrations in vitro. All three drugs induced a specific and highly significant loss of germ cells, including spermatogonial stem cells. In contrast, there was no significant effect on somatic cells, for either Sertoli or interstitial cells. Time course analysis of cleaved Caspase-3 expression showed a significant increase in apoptosis eight hours prior to a detectable decrease in germ cell numbers following exposure to phosphoramide mustard or cisplatin, although this pattern was not seen following doxorubicin-exposure. Moreover, analysis of DNA damage at 16 h showed increased γH2AX expression in response to all three drugs. Overall, results show that cisplatin, doxorubicin and cyclophosphamide all specifically induce loss of germ cells, including of spermatogonial stem cells, in the prepubertal mouse testis at concentrations relevant to human therapeutic exposures.


Pro-Con Debate: Electroencephalography-Guided Anesthesia for Reducing Postoperative Delirium.
Postoperative delirium (POD) has significant implications on morbidity, mortality, and health care expenditures. Monitoring electroencephalography (EEG) to adjust anesthetic management has gained interest as a strategy to mitigate POD. In this Pro-Con commentary article, the pro side supports the use of EEG to reduce POD, citing an empiric reduction in POD with processed EEG (pEEG)-guided general anesthesia found in several studies and recent meta-analysis. The Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) trial is the exception to this, and issues with methods and achieved depths are discussed. Meanwhile, the Con side advocates that the use of EEG to reduce POD is not yet certain, citing that there is a lack of evidence that associations between anesthetic depth and POD represent causal relationships. The Con side also contends that the ideal EEG signatures to guide anesthetic titration are currently unknown, and the potential benefits of reduced anesthesia levels may be outweighed by the risks of potentially insufficient anesthetic administration. As the public health burden of POD increases, anesthesia clinicians will be tasked to consider interventions to mitigate risk such as EEG. This Pro-Con debate will provide 2 perspectives on the evidence and rationales for using EEG to mitigate POD.


DHU1 negatively regulates UV-B signaling via its direct interaction with COP1 and RUP1.
Although DWD HYPERSENSITIVE TO UV-B 1 (DHU1) is reported to be a negative regulator in UV-B mediated cellular responses, its detailed role in UV-B signaling is still elusive. To further understand the action mechanism of DHU1 in UV-B response, physical and genetic interactions of DHU1 with various UV-B signaling components were investigated. Yeast two hybrid assay results suggested that DHU1 directly interacts with COP1 and RUP1, implying a functional connection with both COP1 and RUP1. In spite of the physical association between DHU1 and COP1, loss of DHU1 did not affect protein stability of COP1. Epistatic analysis showed that the functional loss of both DHU1 and UVR8 leads to alleviation of UV-B hypersensitivity displayed in dhu1-1. Moreover, phenotypic studies with dhu1-1 cop1-6 and dhu1-1 hy5-215 revealed that COP1 and HY5 are epistatic to DHU1, indicating that UV-B hypersensitivity of dhu1-1 requires both COP1 and HY5. In the case of dhu1-1 rup1-1, UV-B responsiveness was similar to that of both dhu1-1 and rup1-1, implying that DHU1 and RUP1 are required for each other's function. Collectively, these results show that the role of DHU1 as a negative regulator in UV-B response may be derived from its direct interaction with COP1 by sequestering COP1 from the active UVR8-COP1 complex, resulting in a decrease in the COP1 population that positively participates in UV-B signaling together with UVR8. Furthermore, this inhibitory role of DHU1 in UV-B signaling is likely to be functionally connected to RUP1. This study will serve as a platform to further understand more detailed action mechanism of DHU1 in UV-B response and DHU1-mediated core UV-B signaling in Arabidopsis.


[Gene therapy for esophageal cancer].
Esophageal cancer is a highly malignant disease in which progression is observed in most patients even at the first medical examination. Neoadjuvant cytoreduction treatments are frequently used for the purpose of tumor down-staging, increasing the resection rate, and possibly improving survival. Although combination therapy with radiation and anticancer agents is available, no satisfactory treatment regimen has yet been established due to the development of resistance. Based on the concepts of genetic alteration in carcinogenesis, cancer gene therapy has been developing rapidly. We previously reported the growth inhibitory effect of adenovirus-mediated wild-type p53 gene transfer into esophageal squamous carcinoma cell lines. After extensive preclinical study of p53 gene therapy in vitro and in vivo, we are conducting a phase I/II clinical trial. The target of this trial is patients with unresectable esophageal cancer resistant to chemoradiotherapy. As of December 1, 2001, 8 candidates had been admitted to our hospital. After extensive examination, 4 patients were enrolled in this trial. After giving informed consent, the first patient received injections of Ad5 CMV-p53 on December 19, 2000. No serious adverse events have occurred so far in these patients, and the trial has been conducted safely.


Subtrochanteric fractures of the femur in children.
Subtrochanteric fractures are relatively rare in children and usually result from severe trauma. The unique biomechnical forces about the hip following fracture tend to complicate treatment. Remodeling and growth stimulation generally ensure good results by nonoperative means in children under 10 years of age. Open reduction should be considered in older children when good alignment cannot be achieved by closed methods.


Conjunctival necrosis and scleritis following subtenon triamcinolone acetonide injection.
The present study aims to report a case of conjunctival necrosis and scleritis due to a subtenon injection of triamcinolone acetonate. A 15-year-old boy received a subtenon injection of triamcinolone acetonate after a pars plana vitrectomy due to an intraocular foreign body. Seven days later, conjunctival necrosis and scleritis appeared at the site of injection. No improvement was seen after seven days of conservative treatment, and necrotic tissue debridement was performed. Within one week the conjunctiva cleared. Conjunctival necrosis and scleritis are rare complications of periocular corticosteroid injections, but an early diagnosis can be very valuable. Improper dosage and injection site of corticosteroids with insufficient prophylactic antibiotics are predisposing factors. If conservative treatment is not sufficient, debridement should be considered as a potential critical treatment option.


Dopamine-Modified Alginate Hydrogel with Effectiveness and Safety for Preoperative Localization of Lung Nodules.
It is important to mark an early lung tumor manifested with small nodules during computed tomography-guided and minimally invasive surgery. The aim of this study is to develop an injectable hydrogel for clinical lung nodule localization. Dopamine, a typical catechol-containing compound, was used to modify alginate for better gel formation and performance needed for localization application. Through the addition of an adequate oxidant and catalase, the catechol-conjugated alginate (C-ALG) hydrogel showed rapid gelation for less than 5 min, similar mechanical properties to lung tissue, slight swelling degree, good cell compatibility, and enough tissue adhesion for localization around the lung tissue. In addition, the C-ALG hydrogel increased the bursting pressure of lung tissue up to 266 ± 15-385 ± 13 mm-H2O that could prevent hydrogel rupture and migration during localizing surgery, suggesting the injectable hydrogel with effectiveness and safety for clinical applications.


PERspective on PER phosphorylation.
Period (PER) proteins are essential parts of the molecular clocks that control circadian rhythms in flies and mammals. Phosphorylation regulates PER's stability and subcellular localization; however, the physiologically relevant sites have been difficult to identify in spite of knowing the relevant kinase. In this issue of Genes & Development, Chiu and colleagues (1758-1772) identify a key phosphorylation site on PER that recruits the F-box protein Slimb to trigger PER degradation and set clock speed.


Analysis of the elastic bending characteristics of cementless short hip stems considering the valgus alignment of the prosthetic stem.
The resultant hip force causes a varus torque which must be compensated by a shear force couple depending on the stem alignment of the prosthesis. Since the prosthesis is substantially less flexible than the bone, the interior of the femur is stiffened over the entire prosthesis length. The present study thus aims at analyzing short-stem prostheses for its elastic bending characteristics, considering inappropriate valgus alignment of the prosthetic stem. Five short stem prostheses were implanted each in synthetic femora in a standardized manner - in neutral and valgus stem alignments. Bending movements were recorded applying a tilting torque MX of ±3.5 Nm in medio-lateral direction. Variance analyses and Friedman tests were used. A P-value <.05 was considered statistically significant. Bending movements b1-b6 showed significant differences (P < .05). It could be shown that different stem alignments (P < .05) and different measuring points had a highly significant influence (P < .001) on the relative movements. Compared to the AIDA®, the MiniHip™ as well as the Metha® stiffened the femur to a higher degree (P < .001). Regarding the elastic bending behavior we see a relevant influence of the stems´ design. We conclude that the short-stem principle does not necessarily require the shortest possible prosthesis but rather a long and thin extending stem tip to optimize the lever ratios, ensuring a more physiological bending behavior of the femur. In addition, without sufficient anchoring of the prosthesis, the valgus stem alignment could favor tilting of the implant and should therefore be avoided.


Rare Presentation of Congenital Diaphragmatic Hernia in a Sexagenarian.
Congenital diaphragmatic hernia (CDH) usually presents in the neonatal period, and about 10% of reported cases occur in adults. The most common type is Bochdalek's hernia, which occurs through a defect in the posterolateral portion of the diaphragm with an estimated prevalence of 1 in 2500 live births. CDH in adults presents with gastrointestinal or respiratory symptoms, which can be acute or intermittent. We report a case of CDH diagnosed in a 55-year-old man, who presented with acute onset of chest pain and dyspnea with insignificant past history. This patient was initially evaluated medically for myocardial infarction followed by intercostal chest drainage placement, before a definitive diagnosis of CDH was made. This case is reported for its rarity and to highlight the high index of suspicion needed to diagnose CDH in adulthood. This is specially important as CDH, masquerades as other acute conditions in older individuals thereby delaying the diagnosis.


Retro-orbital and disseminated B-cell lymphoma in a yellow-collared macaw (Primolius auricollis).
A yellow-collared macaw was presented with unilateral left exophthalmia. The complete blood cell count and biochemistry revealed a heterophilic leukocytosis and elevation in liver parameters, respectively. A computed tomography scan showed a contrast-enhancing retrobulbar mass and hepatomegaly. Cytology of the liver was consistent with a round cell tumor, most likely lymphoma. The bird died after 2 months of palliative care. Postmortem examination confirmed a retro-orbital and disseminated B-cell lymphoma.


In situ characterization of a NO-sensitive peroxidase in the lignifying xylem of Zinnia elegans.
The lignifying xylem from Zinnia elegans stems gives an intense reaction with 3,3',5,5'-tetramethylbenzidine (TMB), a reagent previously reported to be specific for peroxidase/H2O2. However, the staining of lignifying xylem cells with TMB is apparently the result of two independent mechanisms: one, the catalase-sensitive (H2O2-dependent) peroxidase-mediated oxidation of TMB, and the other, the catalase-insensitive oxidation of TMB, probably mediated by xylem oxidases which are specific from lignifying tissues. The catalase-insensitive oxidation of TMB by the Z. elegans xylem was sensitive to sodium nitroprusside (SNP), a nitric oxide (NO)-releasing compound that, when used at 5.0 mM, is capable of sustaining NO concentrations of 6.1 &mgr;M in the aqueous phase. This effect of SNP was totally reversed by 150 &mgr;M 2-phenyl-4,4,5,5-tetramethyl imidazoline-1-oxyl-3-oxide (PTIO), an efficient NO scavenger in biological systems, so the above-mentioned effect must be ascribed to NO, and not to other nitrogen oxides. This response of the catalase-insensitive TMB-oxidase activity of the lignifying Z. elegans xylem was similar to that shown by a basic peroxidase isolated from the intercellular washing fluid, which showed TMB-oxidase activity, and which was also inhibited by 5 mM SNP, the effect of SNP also being reversed by 150 &mgr;M PTIO. These results suggest that peroxidase was the enzyme responsible for the NO-sensitive catalase-insensitive TMB-oxidase activity of the lignifying Z. elegans xylem. Further support for this statement was obtained from competitive inhibitor-dissected histochemistry, which showed that this stain responded to peroxidase-selective competitive inhibitors, such as ferulic acid and ferrocyanide, in a similar way to the Z. elegans basic peroxidase. From these results, we conclude that this NO-sensitive catalase-insensitive oxidation of TMB is apparently performed by the Z. elegans basic peroxidase, and that the regulation of this enzyme by NO may constitute an intrinsically programmed event during the differentiation and death of the xylem.


Fear of cancer recurrence and coping attitudes of breast cancer survivors.
This study aimed to determine the fear of cancer recurrence levels and coping orientation of breast cancer survivors. This descriptive exploratory study was conducted using a web-based online survey. This article is written using the STROBE checklist. The study was completed with 204 women participants. Data were collected using the 'Demographic and Clinical Information Form', 'Fear of Cancer Recurrence Inventory (FCRI)' and 'Coping Orientation to Problems Experienced Inventory-Revised (COPE-R)'. FCRI total score average within the scope of the study was calculated as 42.00 ± 18.88. Women's COPE-R total score average is 80.62 ± 13.20. There was a positive correlation between FCRI total score and COPE-R (r = 0.183, p = 0.009). According to the results of multiple linear regression analysis, age, education level, CAM usage, getting psychological support and COPE-R subscales (accommodation, avoidance, self-punishment) were associated with FCRI total score. The fear of cancer recurrence experienced by breast cancer survivors was associated with their coping orientation. Determining the fear of cancer recurrence level and coping orientation of breast cancer survivors by healthcare professionals will guide the reduction of women's fear of cancer recurrence and further the development of adaptive coping orientation.


Haemodynamic effects of acute intravenous landiolol in Takotsubo cardiomyopathy with dynamic left ventricular outflow tract obstruction.
Takotsubo cardiomyopathy (TCM) leads to serious left ventricular outflow tract (LVOT) obstruction with cardiogenic shock in 6%-20% of cases. The onset of LVOT obstruction, coupled with mitral regurgitation resulting from systolic anterior motion of mitral valve leaflets, can lead to haemodynamic instability in addition to severely impaired systolic function. We describe three patients who experienced chest discomfort following emotional stress. These patients displayed pronounced abnormalities on ECGs, insignificant obstructive coronary disease and haemodynamic instability due to LVOT obstruction. The infusion of landiolol, a short-acting beta blocker, was effective in releasing the gradient. Dynamic outflow obstruction is the major predictor of haemodynamic collapse. We suggested that an early identification of this complication in hypotensive patients with suspected TCM could be of utmost importance to optimise the therapeutic approach in the acute setting.


SpeckleCam: high-resolution computational speckle contrast tomography for deep blood flow imaging.
Laser speckle contrast imaging is widely used in clinical studies to monitor blood flow distribution. Speckle contrast tomography, similar to diffuse optical tomography, extends speckle contrast imaging to provide deep tissue blood flow information. However, the current speckle contrast tomography techniques suffer from poor spatial resolution and involve both computation and memory intensive reconstruction algorithms. In this work, we present SpeckleCam, a camera-based system to reconstruct high resolution 3D blood flow distribution deep inside the skin. Our approach replaces the traditional forward model using diffuse approximations with Monte-Carlo simulations-based convolutional forward model, which enables us to develop an improved deep tissue blood flow reconstruction algorithm. We show that our proposed approach can recover complex structures up to 6 mm deep inside a tissue-like scattering medium in the reflection geometry. We also conduct human experiments to demonstrate that our approach can detect reduced flow in major blood vessels during vascular occlusion.


Studies on immune competence in the rat: changes with age, sex, and strain.
Reticuloendothelial capacity (determined by colloidal carbon clearance) and cell-mediated immunity (determined by xenograft skin grafts and macrophage migration inhibition in vitro) were studied as a function of age for the first time in male and female Sprague-Dawley rats. The results of all three tests in the female rat indicated that maximal immune competence was reached at the onset of puberty (4 weeks) and, depending on the immune response, immune competence declined significantly with age (4 to 96 weeks). In the male Sprague-Dawley, a similar pattern was found in two out of the three tests (colloidal carbon clearance, xenograft skin grafts). Macrophage migration inhibition in the male was unaffected by age (4 to 40 weeks). Cell-mediated immunity (xenograft skin grafts) was also studied in male and female rats of another strain (Long Evans) as a function of age. Maximal competence occurred at the onset of puberty and declined thereafter.


Serum annexin A2 levels in patients with colon cancer in comparison to healthy controls and in relation to tumor pathology.
The deregulation and localization of the Annexins is consistently reported to have close relation to tumor cell malignancy, invasion, and metastasis as well as clinical progression of tumors. This study aimed to evaluate serum Annexin A2 (Anx A2) levels in patients with colon cancer in comparison to healthy controls and in relation to demographics and tumor pathology. A total of 100 patients (mean (SD) age: 58 (5.8) years, 55.0% females) with colon cancer and 70 controls (mean (SD) age: 59 (5.4) years, 50.0% females) were included. Serum levels for Anx A2 were evaluated in relation to study group, demographics, and tumor pathology. Serum levels for Anx A2 were significantly lower in patients with colon cancer than in controls (13.1 (4.5) vs. 22.8 (2.1) ng/mL, p<0.001) and significantly decreased with increase in tumor size (p=0.003), and at higher stages of TNM (p=0.004), tumor invasion (p=0.005), lymph node metastasis (p=0.003), and distant metastasis (p=0.005). Our findings indicate a significant decrease in Anx A2 expression in colon cancer patients compared to healthy controls and in parallel with tumor progression.


Characterization of surface and photooxidative properties of supported metal oxide photocatalysts using solid-state NMR.
In situ solid-state NMR (SSNMR) methodologies have been used to investigate the surface properties and photooxidative reactivities of a number of metal oxide photocatalysts. Adsorption of ethanol on single monolayers of TiO2, SnO2, V205, and WO3 supported on porous Vycor glass results in the formation of hydrogen-bonded ethanol species and metal-bound ethoxide species. The chemical shift of the metal-bound ethoxide species varies with the metal oxide catalyst while the chemical shift of the hydrogen-bonded species is independent of the metal oxide. X-ray powder diffraction, UV-VIS spectroscopy, and SSNMR investigations of ethanol adsorption show that increasing the number of monolayers of TiO2 on the Vycor surface changes the morphology of the catalyst from amorphous at a single monolayer coverage to anatase at a four monolayer coverage. The rate of photocatalytic oxidation of ethanol, acetone, and 2-propanol also increases with increasing TiO2 monolayer coverage.


Classic and Non-classic (Surrepticius) Scabies: Diagnostic and Treatment Considerations.
The morphology of scabies, a mite infestation of worldwide proportion, is characterized by a variety of cutaneous lesions. Patients with classic scabies present with characteristic burrows often located on the web spaces of the fingers and toes. Scabies surrepticius refers to the non-classic atypical presentation of scabies; establishing the diagnosis of scabies in these individuals can be difficult. To facilitate the diagnosis of scabies, criteria have been proposed by the International Alliance for the Control of Scabies (IACS). These criteria are intended for scabies research; however, they can be utilized by clinicians to establish either a confirmed diagnosis, a clinical diagnosis or a suspected diagnosis of scabies. Visualization of mites, eggs or feces is necessary for a confirmed diagnosis of scabies. A clinical diagnosis can be established by observation of either genital lesions in men or burrows or classically distributed classical lesions in individuals with two historic features: pruritus and close contact with an individual who itches and has classically distributed classical scabetic lesions. The clinical features and management of a woman residing in an assisted living environment with a confirmed diagnosis of scabies and a man with a clinical diagnosis of scabies are described. The criteria for the suspected diagnosis of scabies require either one historic feature and typical lesions in a typical distribution or both historic features and the presence of atypical lesions or an atypical distribution of the skin lesions. Once the diagnosis of scabies is established, not only the patient but also close contacts should receive treatment with either a topical medication (such as permethrin 5% cream) or a systemic drug (ivermectin) or both. The number and frequency of treatments are variable; classic scabies typically is managed with a total of two treatments performed weekly to biweekly. Patients with crusted scabies usually require multiple topical and oral antiscabetic treatments in addition to topical keratolytic therapy. Bacterial impetiginization or infection (most commonly by Staphylococcus aureus or Streptococcus pyogenes) can complicate scabies infestation and potentially result in cellulitis, abscess, sepsis, rheumatic fever, rheumatic heart disease and post-streptococcal glomerulonephritis; therefore, in some patients, systemic antimicrobial therapy may be necessary in addition to scabies-directed treatment. In addition to systemic antihistamines, oral and/or topical corticosteroids may be used to provide symptomatic pruritus relief once the diagnosis of scabies has been established and mite-directed treatment has been initiated. The clinician should consider several potential causes (such as inadequate treatment, reinfection, mite resistance, delusions of parasitosis and the development of a new non-scabetic dermatosis) in scabies patients who fail to respond to treatment with a topical or oral scabicide therapy.


Age-related changes in osteogenic stem cells in mice.
Osteoblasts arise from partially differentiated osteogenic progenitor cells (OPCs) which in turn arise from undifferentiated marrow stromal mesenchymal stem cells (MSCs). It has been postulated that age-related defects in osteoblast number and function may be due to quantitative and qualitative stem cell defects. To examine this possibility, we compared osteogenic stem cell number and in vitro function in marrow cells from 4-month-old and 24-month-old male BALB/c mice. Histologic studies demonstrated that these mice undergo age-related bone loss resembling that seen in humans. In primary MSC cultures grown in media supplemented with 10 nM dexamethasone, cultures from older animals yielded an average of 41% fewer OPC colonies per given number of marrow cells plated (p < 0.001). This implies that for a given number of marrow cells there are fewer stem cells with osteogenic potential in older animals than there are in younger animals. The basal proliferative rate in cultures from older animals, as measured by 3H-thymidine uptake, was more than three times that observed in cultures from young animals (p < 0.005). However, the increase in proliferative response to serum stimulation was 10-fold in the younger cultures (p <0.001) and insignificant (p <0.4) in the older cultures. Colonies in both age groups became alkaline phosphatase positive at the same rate, and virtually all colonies were positive after 12 days of culture. Cultures from both age groups produced abundant type I collagen. These studies suggest that defects in the number and proliferative potential of MSCs may underlie age-related defects in osteoblast number and function.


Systematic inference of highways of horizontal gene transfer in prokaryotes.
Horizontal gene transfer (HGT) plays a crucial role in the evolution of prokaryotic species. Typically, no more than a few genes are horizontally transferred between any two species. However, several studies identified pairs of species (or linages) between which many different genes were horizontally transferred. Such a pair is said to be linked by a highway of gene sharing. Inferring such highways is crucial to understanding the evolution of prokaryotes and for inferring past symbiotic and ecological associations among different species. We present a new improved method for systematically detecting highways of gene sharing. As we demonstrate using a variety of simulated datasets, our method is highly accurate and efficient, and robust to noise and high rates of HGT. We further validate our method by applying it to a published dataset of >22 000 gene trees from 144 prokaryotic species. Our method makes it practical, for the first time, to perform accurate highway analysis quickly and easily even on large datasets with high rates of HGT. An implementation of the method can be freely downloaded from: http://acgt.cs.tau.ac.il/hide.


A review of modern sample-preparation techniques for the extraction and analysis of medicinal plants.
Sample preparation is the crucial first step in the analysis of herbs. In recent years there has been increasing interest worldwide in the use of alternative/herbal medicine for the prevention and treatment of various illnesses. Currently, however, quality-related problems (lack of consistency, safety, and efficacy) seem to be overshadowing the potential genuine health benefits of various herbal products. Thus, the development of "modern" sample-preparation techniques with significant advantages over conventional methods for the extraction and analysis of medicinal plants is likely to play an important role in the overall effort of ensuring and providing high-quality herbal products to consumers worldwide. In this article, recent developments and applications of modern sample-preparation techniques for the extraction, clean-up, and concentration of analytes from medicinal plants or herbal materials are reviewed. These modern techniques include solid-phase microextraction, supercritical-fluid extraction, pressurized-liquid extraction, microwave-assisted extraction, solid-phase extraction, and surfactant-mediated extraction.


Community Participation, Supports and Barriers of Adolescents with and without Attention Deficit Hyperactivity Disorder.
Aim: To compare participation patterns, environmental supports, and barriers to community activities in adolescents with and without attention deficit hyperactivity disorder (ADHD) in Turkey.Methods: Participants were 94 adolescents with ADHD and 109 adolescents without ADHD ages 13-17 years (mean age 14.6, S.D 1.49 years) Participation frequency, involvement rate, mothers who desired change, and environmental supports and barriers in a community setting were assessed with the Participation and Environment Measure for Children and Youth (PEM-CY).Results: Adolescents with ADHD participated 20.3% less frequently in socializing with peers in the community than adolescents without ADHD. With moderate to large effect sizes, the mean involvement rate in four community activities, including neighborhood outings, community events, socializing with peers in the community, and religious activities, was significantly lower for adolescents with ADHD than for adolescents without ADHD.Conclusion: Adolescents with ADHD participate less frequently and are less involved in socializing with peers in the community. Almost half of all ADHD adolescents never participate in community events. It was seen that cognitive difficulties, sensory qualities, and safety may prevent adolescents with ADHD from socializing with peers in the community.


Radiofrequency ablation of liver and lung tumors.
Radiofrequency ablation (RFA) is a procedure in which radiofrequency energy is used to heat and destroy abnormal tissue. This article discusses the evolution of RFA and its use to treat liver and lung tumors.


Relationships Between Three Eating Behaviors and Nine Motives for Food Choices Among Brazilian Adults: A Structural Equation Model.
We examined the relationships between three eating behaviors and nine motives underlying food choices made by Brazilian adults. Using participant responses to the short version of the Three-Factor Eating Questionnaire and the Food Choice Questionnaire, we investigated eating behaviors (cognitive restriction, uncontrolled eating, and emotional eating) and motives for food choices (health, mood, convenience, sensory appeal, natural content, price, weight control, familiarity, and ethical concern). We used a structural equation model to test relationship pathways (β), with eating behaviors as independent variables and motives for food choices as dependent variables. Participants were 1297 individuals (69.5% female) with a mean age of 25.0 years (SD = 5.8). We confirmed the validity and reliability of the questionnaires in this sample. Restrictive eating behavior was significantly related to motives of health (β = .415), mood (β = .127), natural content (β = .364), weight control (β = .681), and ethical concern (β = .161). Emotional eating behavior was related to motives of mood (β = .277), health (β = -.137), and natural content (β = -.136). Uncontrolled eating behavior was related to motives of convenience (β = .226), sensory appeal (β = .121), price (β = .153), and familiarity (β = .090). We believe these findings can now help design future research and clinical interventions for managing people's risky eating behaviors and promoting beneficial food choices.


Disordered meiotic regulation of oocytes by duration of diabetes mellitus in BBdp rat.
Diabetes mellitus (DM) disturbs normal functions from the level of cells to the level of organs. In this study, the authors explore the detrimental effects of type 1 diabetes on meiotic regulation depending on the duration of DM. In non-diabetes-prone BioBreeding (BBdr) control rats, most of the large follicles had germinal vesicle (GV)-intact oocytes. Conversely, a decrease of intact GV that was dependent on the duration of diabetic symptoms was observed; only 54% of the large follicles of diabetes-prone BB (BBdp) rats had GV-intact oocytes at 6 weeks after diabetes induction. Furthermore, some of the secondary follicles in BBdp rats also had germinal vesicle breakdown (GVB) oocytes. The nuclear status of the euglycemia BBdp rat was similar to those of the BBdr rat. In BBdp rats, the rate of meiotic progression to the metaphase II stage was significantly lower; however, the rate of segregated oocytes was significantly increased compared with controls during induction of in vitro maturation. The rate of segregated oocytes was not affected by the presence of the cumulus after chronic symptoms. These results indicate that chronic DM has a detrimental effect on meiotic regulation during folliculogenesis and results in a reduced number of competent oocytes. In addition, these data suggest that the follicle cells can resume supporting the meiotic regulation under euglycemia through insulin administration, independent of the duration of DM.


Aging: Drawing a Map for the Future.
I live on a short street in a small town, Hastings-on-Hudson, some fifteen miles up the Hudson River from New York City. Over the past decade a number of families have moved in, with about sixteen children among them. More than a bit housebound now because of old age and watching them romping about, I try to imagine what their world will be like when they have reached my present age, some eighty years from now. But I have a problem. I just can't imagine it. The demographic changes now appearing on the horizon will force unforeseeable changes. What would it have been like in 1930, when I was born, if someone then had to project the future of aging? They could not have guessed. Some momentous changes are now emerging, and they are bound to change the aging picture. What's being done to respond to those growing pressures?


Prevention of pancreatic cancer in a hamster model by cAMP decrease.
Smoking and alcoholism are risk factors for the development of pancreatitis-associated pancreatic ductal adenocarcinoma (PDAC). We have previously shown that these cancers overexpressed stress neurotransmitters and cyclic adenosine monophosphate (cAMP) while the inhibitory neurotransmitter γ-aminobutyric acid (GABA) was suppressed. Using a hamster model, the current study has tested the hypothesis that cAMP decrease by GABA supplementation in the drinking water prevents the development of pancreatitis-associated PDAC. Our data reveal strong preventive effects of GABA supplementation on the development of PDAC and pancreatic intraductal neoplasia (PanIN). ELISA assays and immunohistochemistry revealed significant decreases in the levels of cAMP and interleukin 6 accompanied by reductions in the expression of several cancer stem cell markers and phosphorylated signaling proteins, which stimulate cell proliferation, and migration in pancreatic exocrine cells of GABA treated animals. We conclude that cAMP decrease by GABA supplementation inhibits multiple cancer stimulating pathways in cancer stem cells, differentiated cancer cells and the immune system, identifying this approach as promising novel tool for the prevention of PDAC in individuals with a history of smoking and alcoholism.


Avian influenza H9N2 seroprevalence among swine farm residents in China.
In parts of southern China, some large-scale swine farms are adjacent to lakes and ponds that are home to many types of birds. Some swine farms will also raise poultry for consumption and sale. Swine farms in rural China may be the source of the AIV outbreak. A seroepidemiological study was conducted among swine farm residents to understand the prevalence of antibodies against avian influenza virus (AIV) H9N2 in southern China. A total of 2,006 swine farm residents were sampled. Serum samples were tested for the presence of antibodies against H9N2 AIV by hemagglutination inhibition (HI) and microneutralization assays. A total of 37 serum samples from swine farm residents were HI positive for A/chicken/Guangdong/V/2008(H9N2), and 24 serum samples (all of which were also HI positive) were microneutralization assays positive for A/chicken/Guangdong/V/2008(H9N2). Due to the special pig farming model in southern China, the residents are in close contact with different kinds of birds. Thus, controlling bird-to-human transmission of AIV in swine farms with poultry may be an important means of preventing widespread AIV infection in humans.


Bed rest does not induce hypercoagulability.
Although there is no direct evidence, it is generally believed that bed rest shifts the haemostatic system towards hypercoagulability; thus, immobilized patients are commonly treated with anticoagulants. We therefore aimed to investigate whether long-term bed rest actually leads to an elevated risk for thromboembolic events. Eleven healthy men were enrolled in our study (bed rest campaign in MEDES Clinique d'Investigation, Toulouse, France). Besides various standard laboratory methods, we used calibrated automated thrombography (CAT) and thrombelastometry (TEM). Activation of samples with minute amounts of relipidated tissue factor allowed sensitive detection of hyper- or hypocoagulable states. CAT and TEM values were not indicative of bed rest-induced hypercoagulability. On the contrary, several parameters were indicative of a tendency towards a hypocoagulable state. Peak and thrombin formation velocity (VELINDEX) were significantly decreased during bed rest compared to baseline. Coagulation times were significantly increased and alpha angles were significantly decreased, indicating attenuated clot formation. Moreover, F1 + 2 and thrombin/antithrombin complex (TAT) values were significantly decreased during bed rest, indicating suppressed coagulation activation. FVII plasma levels were also significantly decreased during the first week of bed rest. Our data indicate that the re-ambulation period is associated with a tendency towards hypercoagulability: ttPeak and StartTail were significantly shorter, Peak and VELINDEX were significantly higher compared to baseline. Moreover, plasma levels of F1 + 2, TAT, FVII and FVIII were significantly higher compared to baseline. The results from our study suggest that bed rest by itself is not associated with hypercoagulable states in healthy subjects.


[Eulogy for Pierre Chirac by Fontenelle].
Bernard Le Bovier de Fontenelle (1657-1757) in the "Eloges des Academiciens des Sciences" who died between 1699 and 1740, allowed to Pierre Chirac - Louis XV Chief Doctor - a worthy scientific place. Born at Conques, in the Rouergue country (Aveyron), in 1650, Chirac purposed to enter the priesthood when, settling in Montpellier, he was spotted by the Chancellor and Judge of Montpellier University, Michel Chicoyneau, in 1678, who encouraged him to take up medicine studies. Became a Montpellier Faculty member in 1682, Chirac will teach, here, medicine, five years after; he got great success. Then he started practising, and in 1692, the Marechal de Noailles appointed him in the Roussillon Army Heath Service as a Doctor. In 1693, he had to fight against a dysentery epidemic and later, at Rochefort, against the "Mal de Siam" (Yellow fever) which infected him but, nevertheless, he was cured. In 1706, the Duc d'Orleans promoted him his private doctor and attached him to go to Italy and Spain. Coming back to France, Chirac went to Paris and remained here till his death. In 1715, the Duc d'Orleans became Regent and selected him for Principal Doctor, In 1718, he succeeded to Guy Crescent Fagon as "Jardin du Roy" Superintendant. In 1720, he was called in Marseille where a plague epidemic was raging. In the funeral oration, Fontenelle was very insistent about the fact that Pierre Chirac endeavoured to set up a Medicine Academy. Unfortunately, his death (March the 1st 1732) kept him from succeeding in such a way.


Modeling Electrokinetic Flows by the Smoothed Profile Method.
We propose an efficient modeling method for electrokinetic flows based on the Smoothed Profile Method (SPM) [1-4] and spectral element discretizations. The new method allows for arbitrary differences in the electrical conductivities between the charged surfaces and the the surrounding electrolyte solution. The electrokinetic forces are included into the flow equations so that the Poisson-Boltzmann and electric charge continuity equations are cast into forms suitable for SPM. The method is validated by benchmark problems of electroosmotic flow in straight channels and electrophoresis of charged cylinders. We also present simulation results of electrophoresis of charged microtubules, and show that the simulated electrophoretic mobility and anisotropy agree with the experimental values.


Clinical approach to Parkinson's disease: features, diagnosis, and principles of management.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The condition causes a heavy burden both on those affected, as well as their families. Accurate diagnosis is critical and remains founded on clinical grounds as no specific diagnostic test is available so far. The clinical picture of PD is typical in many instances; however, features distinguishing it from other disorders should be thoroughly sought. Monogenic forms of PD also have some distinctive characteristics in many cases. This text is a roadmap to accurate diagnosis in PD, as it approaches clinical features, diagnostic methodology, and leading differential diagnoses. Therapeutic issues are also briefly discussed.


Identical cis-acting elements and related trans-acting factors control activity of nonviral promoter in Schizosaccharomyces pombe and mammalian cells.
We have analyzed the transcriptional activity of the human plasminogen activator inhibitor-1 promoter in the fission yeast Schizosaccharomyces pombe. This promoter is active in S. pombe, and the initiation site of transcription corresponds to the site identified previously in mammalian cells. Mutations in the AP-1-binding site (PAI-1 A box) or the HLTF-binding site (the B box), which reduced the basal and phorbol ester-induced levels of PAI-1 expression in human cells, also decreased the transcriptional activity in S. pombe. Gel retardation assays showed that an S. pombe protein binds specifically to this B box element and displays the same B box sequence requirement as HLTF. Furthermore, this yeast protein binds specifically to other HLTF-binding sites in the human immunodeficiency virus-1 long terminal repeat (LTR) and the simian virus 40 (SV40) enhancer. The B box (but not a mutated B box) strongly stimulated transcription when combined with adh downstream promoter elements, indicating that the S. pombe B box-binding protein, like HLTF, is a transcriptional activator. We conclude that the transcriptional activity of the nonviral PAI-1 promoter is controlled by the same promoter elements in S. pombe as in mammalian cells. In addition, mammalian trans-acting factors that bind to these promoter elements were shown to have counterparts with conserved DNA-binding activity in S. pombe. These results further illustrate the conservation of the mechanism of transcription between mammalian cells and fission yeast.


Effects of phosphine ligands in nickel-catalyzed decarbonylation reactions of lactone.
Due to the ubiquity of carbonyl compounds and the abundance of nickel on the earth, nickel-catalyzed decarbonylation has garnered increasing attention in recent years. This type of reaction has seen significant developments in various aspects; however, certain challenges concerning reactivity, selectivity, and transformation efficiency remain pressing and demand urgent resolution. In this study, we employed DFT calculations to investigate the mechanism of nickel-catalyzed decarbonylation reactions involving lactones, as well as the effects of phosphine ligands. Mechanically, Ni(0) first activates the C(acyl)-O bond of the lactone, followed by a decarbonylation step, and ultimately results in reductive elimination under carbonyl coordination to yield the product. Through a comprehensive examination of the electronic and steric effects of the phosphine ligands, we deduced that the electronic effect of the ligand plays a dominant role in the decarbonylation reaction. By enhancing the electron-withdrawing ability of the ligand, the energy barrier of the entire reaction can be significantly reduced. The obtained insights should be valuable for understanding the detailed mechanism and the role of phosphine ligands in nickel catalysis. Moreover, they offer crucial clues for the rational design of more efficient catalytic reactions.


Current concepts and issues in Diamond-Blackfan anemia.
Diamond-Blackfan anemia, although rare, has been the focus of much attention with respect to both its clinical features and the characterization of the in vitro erythroid defect. Despite this, its pathophysiology is still unclear, and the treatment of steroid-refractory patients is still unsatisfactory. The recent chromosomal localization of a gene for familial Diamond-Blackfan anemia represents an important step forward toward the elucidation of this disorder. Therapeutic advances will depend on the development of collaborative studies, employing consensus criteria for diagnosis and response to therapy.


The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex.
The biogenesis of the mitochondrial inner membrane is dependent on two distinct 70 kDa protein complexes. TIMM8a partners with TIMM13 in the mitochondrial intermembrane space to form a 70 kDa complex and facilitates the import of the inner membrane substrate TIMM23. We have identified a new class of substrates, citrin and aralar1, which are Ca2+-binding aspartate/glutamate carriers (AGCs) of the mitochondrial inner membrane, using cross-linking and immunoprecipitation assays in isolated mitochondria. The AGCs function in the aspartate-malate NADH shuttle that moves reducing equivalents from the cytosol to the mitochondrial matrix. Mohr-Tranebjaerg syndrome (MTS/DFN-1, deafness/dystonia syndrome) results from a mutation in deafness/dystonia protein 1/translocase of mitochondrial inner membrane 8a (DDP1/TIMM8a) and loss of the 70 kDa complex. A lymphoblast cell line derived from an MTS patient had decreased NADH levels and defects in mitochondrial protein import. Protein expression studies indicate that DDP1 and TIMM13 show non-uniform expression in mammals, and expression is prominent in the large neurons in the brain, which is in agreement with the expression pattern of aralar1. Thus, insufficient NADH shuttling, linked with changes in Ca2+ concentration, in sensitive cells of the central nervous system might contribute to the pathologic process associated with MTS.


TDAE strategy for the synthesis of 2,3-diaryl N-tosylaziridines.
We report herein an original and rapid synthesis of 2,3-diaryl N-tosylaziridines by TDAE strategy starting from ortho- or para-nitro(dichloromethyl)benzene derivatives and N-tosylimines. A mixture of cis/trans isomers was isolated from 1-(dichloromethyl)-4-nitrobenzene, whereas only trans-aziridines were obtained from ortho-nitro derivatives.


Care Bundle to Improve Oxygen Maintenance and Events.
Prolonged periods spent outside the target range of oxygen saturation (SpO2) in preterm infants, along with frequent desaturation events, predispose them to retinopathy of prematurity (ROP) and long-term neurodevelopmental impairment. The primary aim of this study was to increase the mean time spent within the target SpO2 range (WTR) by 10% and to reduce the frequency of desaturation events by 5 events per patient day, respectively, within 18 months of implementing a care bundle. This study was completed in a 46-bed neonatal intensive care unit (NICU), involving 246 staff members and led by a quality improvement team. The change interventions included implementing new practice guidelines, reviewing daily summaries of SpO2 maintenance, daily infant wellness assessment, standardizing workflow, and responding to SpO2 alarms. In addition, we collected staff satisfaction and compliance with change interventions, resource use, and morbidity and mortality data at discharge. The mean time spent WTR increased from 65.3% to 75.3%, and the frequency of desaturation events decreased from 25.1 to 16.5 events per patient day, respectively, with a higher magnitude of benefit in infants on days with supplemental oxygen. Postimplementation, the duration of high-frequency ventilation and supplemental oxygen were lower, but morbidity and mortality rates were similar. Staff satisfaction with training workshops, coaching, use of the infant wellness assessment tool, and SpO2 alarm management algorithms were 74%, 82%, 80%, and 74%, respectively. Implementing a care bundle to improve oxygen maintenance and reduce desaturation events increased the time spent WTR and reduced the frequency of desaturation events.


Pregnancy after oocyte donation in a patient with NLRP7 gene mutations and recurrent molar hydatidiform pregnancies.
Molar pregnancies are benign trophoblastic diseases associated with a risk of malignant transformation. If aetiology remains mostly unknown, the risk of recurrent molar pregnancy is around 1.5% after one molar pregnancy and around 25% after 2 molar pregnancies. In the later situation, genetic mutations have been described, increasing hugely this risk. In case of mutations, probability to obtain a normal pregnancy is estimated around 1.8%. We report the case of a Caucasian 30-year-old woman whose previous five spontaneous pregnancies had a negative outcome: a spontaneous miscarriage and then 4 complete hydatidiform moles. Genetic testing revealed that the patient carried two heterozygous mutations in the NLRP7 gene (c.2982-2A > G and Y318CfsX7). According to this, counselling was conducted to advocate for oocyte donation in order to obtain a normal pregnancy. This technique enabled a complication-free, singleton pregnancy that resulted in a healthy term live birth of a 2900 g female. Few months after delivery, the patient presented a new complete hydatidiform mole. Women presented with mutations in the NLRP7, KHDC3L or PADI6 genes are unlikely to obtain normal pregnancies, with a major risk of reproductive failure. In such a context, oocyte donation may be the best option. Only 4 normal pregnancies and deliveries have been published in this situation through this technique to our knowledge.


(Acetato-κO)bis-(1,10-phenanthroline-κN,N')copper(II) acetate hepta-hydrate.
In the title complex, [Cu(CH(3)CO(2))(C(12)H(8)N(2))(2)](CH(3)CO(2))·7H(2)O, the central Cu(II) ion is five coordinate, being bound to four N atoms from two 1,10-phenanthroline ligands and one O atom from an acetate anion in a strongly distorted square-pyramidal configuration. Hydrogen-bonded water mol-ecules and an uncoordinated acetate anion form a two-dimensional polymeric structure parallel to (010). The cations are linked to this layer via O-H⋯O hydrogen bonds between one of the water mol-ecules and the coordinated acetate anion.


When avoidance leads to approach: how ear preference interacts with neuroticism to predict disinhibited approach.
A series of eight studies focuses on how the avoidance system represented by neuroticism can lead to disinhibited approach tendencies. Based on research which argues that hemispheric preferences predispose the left hemisphere to fast action goal formation, and contralateral pathways between ear and brain, it is proposed that (a) people with a right ear preference will engage in fast action goal formation and (b) disinhibited approach results from neurotic people who reduce anxiety by means of fast action goal formation. Study 1 provides evidence from telesales operators of a link between self-rated ear preference and objective ear preference and provides evidence that disinhibited approach is predicted by a neuroticismxear preference interaction. Studies 2, 3, and 4 provide evidence that ear preference is related to other measures of objective aural preference and action goal formation. Studies 5, 6, 7, and 8 provide evidence that the neuroticismxear preference interaction predicts a variety of different disinhibited approach tendencies.


Direct treatment versus indirect: Thermo-ablative and mild hyperthermia effects.
Hyperthermia is a rapidly growing field in cancer therapy and many advances have been made in understanding and applying the mechanisms of hyperthermia. Secondary effects of hyperthermia have been increasingly recognized as important in therapeutic effects and multiple studies have started to elucidate their implications for treatment. Immune effects have especially been recognized as important in the efficacy of hyperthermia treatment of cancer. Both thermo-ablative and mild hyperthermia activate the immune system, but mild hyperthermia seems to be more effective at doing so. This may suggest that mild hyperthermia has some advantages over thermo-ablative hyperthermia and research into immune effects of mild hyperthermia should continue. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery.


Assembly of RNA nanostructures on supported lipid bilayers.
The assembly of nucleic acid nanostructures with controlled size and shape has large impact in the fields of nanotechnology, nanomedicine and synthetic biology. The directed arrangement of nano-structures at interfaces is important for many applications. In spite of this, the use of laterally mobile lipid bilayers to control RNA three-dimensional nanostructure formation on surfaces remains largely unexplored. Here, we direct the self-assembly of RNA building blocks into three-dimensional structures of RNA on fluid lipid bilayers composed of cationic 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or mixtures of zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) and cationic sphingosine. We demonstrate the stepwise supramolecular assembly of discrete building blocks through specific and selective RNA-RNA interactions, based on results from quartz crystal microbalance with dissipation (QCM-D), ellipsometry, fluorescence recovery after photobleaching (FRAP) and total internal reflection fluorescence microscopy (TIRF) experiments. The assembly can be controlled to give a densely packed single layer of RNA polyhedrons at the fluid lipid bilayer surface. We show that assembly of the 3D structure can be modulated by sequence specific interactions, surface charge and changes in the salt composition and concentration. In addition, the tertiary structure of the RNA polyhedron can be controllably switched from an extended structure to one that is dense and compact. The versatile approach to building up three-dimensional structures of RNA does not require modification of the surface or the RNA molecules, and can be used as a bottom-up means of nanofabrication of functionalized bio-mimicking surfaces.


Acute kidney injury after cardiac surgery is associated with mid-term but not long-term mortality: A cohort-based study.
Acute kidney injury (AKI) in cardiac surgery is associated with complications, early and late mortality and increased health care expenditures. The overall dynamic comorbidity-adjusted contributions of an episode of AKI on mortality during long-term follow-up have not been fully explored. A longitudinal cohort of 7075 adult patients admitted for cardiac surgery were enrolled in the study. Follow-up data were obtained through telephonic survey after 1, 5, 10, and 15 years or from the National Mortality Registry. All-cause mortality was assessed at five time intervals: I) 30 days after surgery to 1 year; II) 1 to 3 years; III) 3 to 5 years; IV) 5 to 10 years; and V) 10 to 15 years. For the adjustment of mortality for comorbidity and pre-, intra- and postoperative variables, Cox proportional hazard regression models were conducted within each period. The overall incidence of AKI was 36.1%. AKI was an independent predictor of death only during the first five years after surgery (30 days to 1 year: HR 1.834, 95% CI 1.459 to 2.306; 1 to 3 years: HR 1.285, 95% CI 1.023 to 1.610; and 3 to five years: HR 1.330, 95% CI 1.123 to 1.750). Only age, diabetes mellitus and CHF were associated with increased risk of death over the entire follow-up period. Our study demonstrates a transient association of AKI with long-term mortality that progressively decreases and vanishes five years after surgery. The knowledge of this dynamic is crucial to understanding this complex association, planning health care and allocating resources.


Identification of a lifespan extending mutation in the Schizosaccharomyces pombe cyclin gene clg1+ by direct selection of long-lived mutants.
Model organisms such as budding yeast, worms and flies have proven instrumental in the discovery of genetic determinants of aging, and the fission yeast Schizosaccharomyces pombe is a promising new system for these studies. We devised an approach to directly select for long-lived S. pombe mutants from a random DNA insertion library. Each insertion mutation bears a unique sequence tag called a bar code that allows one to determine the proportion of an individual mutant in a culture containing thousands of different mutants. Aging these mutants in culture allowed identification of a long-lived mutant bearing an insertion mutation in the cyclin gene clg1(+). Clg1p, like Pas1p, physically associates with the cyclin-dependent kinase Pef1p. We identified a third Pef1p cyclin, Psl1p, and found that only loss of Clg1p or Pef1p extended lifespan. Genetic and co-immunoprecipitation results indicate that Pef1p controls lifespan through the downstream protein kinase Cek1p. While Pef1p is conserved as Pho85p in Saccharomyces cerevisiae, and as cdk5 in humans, genome-wide searches for lifespan regulators in S. cerevisiae have never identified Pho85p. Thus, the S. pombe system can be used to identify novel, evolutionarily conserved lifespan extending mutations, and our results suggest a potential role for mammalian cdk5 as a lifespan regulator.


The economics of physical activity in low-income and middle-income countries: protocol for a systematic review.
Evidence on the economic costs of physical inactivity and the cost-effectiveness of physical activity interventions in low-income and middle-income countries (LMICs) is sparse, and fragmented where they are available. This is the first review aimed to summarise available evidence on economics of physical activity in LMICs, identify potential target variables for policy, and identify and report gaps in the current knowledge on economics of physical activity in LMICs. Peer-reviewed journal articles of observational, experimental, quasi-experimental and mixed-method studies on economics of physical activity in LMICs will be identified by a search of electronic databases; Scopus, Web of Science and SPORTDiscus. Websites of WHO, the National Institute for Health and Care Excellence international, World Bank and reference lists of included studies will be searched for relevant studies. The study selection process will be a two-stage approach; title and abstract screen for inclusion, followed by a review of selected full-text articles by two independent reviewers. Disagreements will be resolved by consensus and discussion with a third reviewer. Data will be extracted using standardised piloted data extraction forms. Risk of bias will be critically appraised using standard checklists based on study designs. Descriptive synthesis of data is planned. Where relevant, summaries of studies will be classified according to type of economic analysis, country or country category, population, intervention, comparator, outcome and study design. Meta-analysis will be performed where appropriate. This protocol for systematic review is prepared according to the Preferred Reporting Items for Systematic review and Meta-analysis for Protocols -2015 statement. Ethical approval is not obtained as original data will not be collected as part of this review. The completed review will be submitted for publication in a peer-reviewed journal and presented at conferences. CRD42018099856.


Evolutionary selection of pestivirus variants with altered or no microRNA dependency.
Host microRNA (miRNA) dependency is a hallmark of the human pathogen hepatitis C virus (HCV) and was also described for the related pestiviruses, which are important livestock pathogens. The liver-specific miR-122 binds within the HCV 5' untranslated region (UTR), whereas the broadly expressed let-7 and miR-17 families bind two sites (S1 and S2, respectively) in the pestiviral 3' UTR. Here, we dissected the mechanism of miRNA dependency of the pestivirus bovine viral diarrhea virus (BVDV). Argonaute 2 (AGO2) and miR-17 binding were essential for viral replication, whereas let-7 binding was mainly required for full translational efficiency. Furthermore, using seed site randomized genomes and evolutionary selection experiments, we found that tropism could be redirected to different miRNAs. AGO cross-linking and immunoprecipitation (CLIP) experiments and miRNA antagonism demonstrated that these alternative variants bound and depended on the corresponding miRNAs. Interestingly, we also identified miRNA-independent variants that were obtained through acquisition of compensatory mutations near the genomic 3' terminus. Rescue experiments demonstrated that miRNA binding and 3' mutagenesis contribute to replication through mutually exclusive mechanisms. Altogether, our findings suggest that pestiviruses, although capable of miRNA-independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation.


Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking.
The current research article reports the synthesis of coumarinyl pyrazolinyl thioamide derivatives and their biological activity as inhibitors of jack bean urease. The coumarinyl pyrazolinyl thioamides were synthesized by reacting thiosemicarbazide with newly synthesized chalcones to afford the products in good yields and the synthesized compounds were purified by recrystallization. Coumarinyl pyrazolinyl thioamide derivatives 5a - 5q showed significant activity against Urease enzyme and also exhibited good antioxidant potential. The compound 3-(2-oxo-2H-chromen-3-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (5n) was found to be superior agent in the series with an IC50 = 0.358 ± 0.017 μm compared to standard thiourea with an IC50 = 4720 ± 174 μm. To undermine the binding mode of inhibition kinetic studies were performed for most potent derivative and it was found that compound 5n inhibits urease enzyme by non-competitive mode of inhibition. Molecular docking studies were carried out to delineate the binding affinity of the synthesized derivatives.


Challenges and success of recruiting and retention for a culturally tailored diabetes prevention program for adults of Mexican descent.
The purpose of this article is to describe methods used to recruit and retain high-risk, Spanish-speaking adults of Mexican origin in a randomized clinical trial that adapts Diabetes Prevention Program (DPP) content into a community-based, culturally tailored intervention. Multiple passive and active recruitment strategies were analyzed for effectiveness in reaching the recruitment goal. Of 91 potential participants assessed for eligibility, 58 participated in the study, with 38 in the intervention and 20 in the attention control group. The American diabetes association risk assessment questionnaire, body mass index, and casual capillary blood glucose measures were used to determine eligibility. The recruitment goal of 50 individuals was met. Healthy living diabetes prevention presentations conducted at churches were the most successful recruiting strategy. The retention goal of 20 individuals was met for the intervention group. Weekly reminder calls were made by the promotora to each intervention participant, and homework assignments were successful in facilitating participant engagement. A community advisory board made significant and crucial contributions to the recruitment strategies and refinement of the intervention. support the feasibility of adapting the DPP into a community-based intervention for reaching adults of Mexican origin at high risk for developing diabetes.


Hepatitis C Virus Mediated Metastasis in Hepatocellular Carcinoma as a Therapeutic Target for Cancer Management.
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer associated deaths. Prognosis is relatively poor in cases where Hepatitis C Virus (HCV) is associated as causative agent, mainly due to increased risk of metastasis. Metastasis is the major cause of all cancer related deaths. We reviewed reports linking expression of HCV encoded proteins with changes in cellular functions. We also compared reports on HCV-induced HCC with those on non-viral and Hepatitis B Virus (HBV) induced HCC. Novel therapeutic approaches for handling metastatic HCC were also reviewed. HCV infection is associated with expression of multiple pro-metastatic factors in HCC patients. HCV encoded proteins can directly induce pro-metastasis cellular functions. HCV-induced HCC has a greater chance of recurrence than any non-viral and Hepatitis B Virus (HBV) induced HCC. Recent advances in understanding of evolutionary dynamics of tumor argue that trying to prevent spreading of cancer may ultimately prove to be a better approach than striving to cure it. Inhibiting the metastasis can thereby substantially increase the survival period in patients. Host cell protein Nm23-H1 is a known suppressor of tumor metastasis and has been shown to be modulated by proteins encoded by different viruses associated with cancers. Nm23-H1 is an important therapeutic target for virus mediated malignancies. This review is an attempt to summarize the current state of understanding of cancer cell metastasis in HCV induced tumors, and argues for approaches based on targeting host and viral factors critical for cancer metastasis as therapeutic targets.


Sugarcane Water Stress Tolerance Mechanisms and Its Implications on Developing Biotechnology Solutions.
Sugarcane is a unique crop with the ability to accumulate high levels of sugar and is a commercially viable source of biomass for bioelectricity and second-generation bioethanol. Water deficit is the single largest abiotic stress affecting sugarcane productivity and the development of water use efficient and drought tolerant cultivars is an imperative for all major sugarcane producing countries. This review summarizes the physiological and molecular studies on water deficit stress in sugarcane, with the aim to help formulate more effective research strategies for advancing our knowledge on genes and mechanisms underpinning plant response to water stress. We also overview transgenic studies in sugarcane, with an emphasis on the potential strategies to develop superior sugarcane varieties that improve crop productivity in drought-prone environments.


Optical computation of the Laplace operator using phase-shifted Bragg grating.
Diffraction of a 3D optical beam on a multilayer phase-shifted Bragg grating (PSBG) is considered. It is shown that the PSBG enables optical computation of the spatial Laplace operator of the electromagnetic field components of the incident beam. The computation of the Laplacian is performed in reflection at normal incidence. As a special case, the parameters of the PSBG transforming the incident Gaussian beam into a Laguerre-Gaussian mode of order (1,0) are obtained. Presented numerical results demonstrate high quality of the Laplace operator computation and confirm the possibility of the formation of Laguerre-Gaussian mode. We expect the proposed applications to be useful for all-optical data processing.