Can physiological engineering/programming increase multi-generational thermal tolerance to extreme temperature events?
Organisms increasingly encounter higher frequencies of extreme weather events as a consequence of global climate change. Currently, few strategies are available to mitigate climate change effects on animals arising from acute extreme high-temperature events. We tested the capacity of physiological engineering to influence the intra- and multi-generational upper thermal tolerance capacity of a model organism, Artemia, subjected to extreme high temperatures. Enhancement of specific physiological regulators during development could affect thermal tolerance or life-history attributes affecting subsequent fitness. Using experimental Artemia populations, we exposed F0 individuals to one of four treatments: heat hardening (28°C to 36°C, 1°C per 10 min), heat hardening plus serotonin (0.056 μg ml-1), heat hardening plus methionine (0.79 mg ml-1) and a control treatment. Regulator concentrations were based on previous literature. Serotonin may promote thermal tolerance, acting upon metabolism and life history. Methionine acts as a methylation agent across generations. For all groups, measurements were collected for three performance traits of individual thermal tolerance (upper sublethal thermal limit, lethal limit and dysregulation range) over two generations. The results showed that no treatment increased the upper thermal limit during acute thermal stress, although serotonin-treated and methionine-treated individuals outperformed controls across multiple thermal performance traits. Additionally, some effects were evident across generations. Together, these results suggest that phenotypic engineering provides complex outcomes, and if implemented with heat hardening can further influence performance in multiple thermal tolerance traits, within and across generations. Potentially, such techniques could be up-scaled to provide resilience and stability in populations susceptible to extreme temperature events.


All Health Is Global Health, All Medicine Is Social Medicine: Integrating the Social Sciences Into the Preclinical Curriculum.
As physicians work to achieve optimal health outcomes for their patients, they often struggle to address the issues that arise outside the clinic. Social, economic, and political factors influence patients' burden of disease, access to treatment, and health outcomes. This challenge has motivated recent calls for increased attention to the social determinants of health. At the same time, advocates have called for increased attention to global health. Each year, more U.S. medical students participate in global health experiences. Yet, the global health training that is available varies widely. The discipline of social medicine, which attends to the social determinants of disease, social meanings of disease, and social responses to disease, offers a solution to both challenges. The analyses and techniques of social medicine provide an invaluable toolkit for providing health care in the United States and abroad.In 2007, Harvard Medical School implemented a new course, required for all first-year students, that teaches social medicine in a way that integrates global health. In this article, the authors argue for the importance of including social medicine and global health in the preclinical curriculum; describe Harvard Medical School's innovative, integrated approach to teaching these disciplines, which can be used at other medical schools; and explore the barriers that educators may face in implementing such a curriculum, including resistance from students. Such a course can equip medical students with the knowledge and tools that they will need to address complex health problems in the United States and abroad.


On the evolution of structure in aminoacyl-tRNA synthetases.
The aminoacyl-tRNA synthetases are one of the major protein components in the translation machinery. These essential proteins are found in all forms of life and are responsible for charging their cognate tRNAs with the correct amino acid. The evolution of the tRNA synthetases is of fundamental importance with respect to the nature of the biological cell and the transition from an RNA world to the modern world dominated by protein-enzymes. We present a structure-based phylogeny of the aminoacyl-tRNA synthetases. By using structural alignments of all of the aminoacyl-tRNA synthetases of known structure in combination with a new measure of structural homology, we have reconstructed the evolutionary history of these proteins. In order to derive unbiased statistics from the structural alignments, we introduce a multidimensional QR factorization which produces a nonredundant set of structures. Since protein structure is more highly conserved than protein sequence, this study has allowed us to glimpse the evolution of protein structure that predates the root of the universal phylogenetic tree. The extensive sequence-based phylogenetic analysis of the tRNA synthetases (Woese et al., Microbiol. Mol. Biol. Rev. 64:202-236, 2000) has further enabled us to reconstruct the complete evolutionary profile of these proteins and to make connections between major evolutionary events and the resulting changes in protein shape. We also discuss the effect of functional specificity on protein shape over the complex evolutionary course of the tRNA synthetases.


ID-Migraine™ questionnaire and accurate diagnosis of migraine.
To analyze the applicability of the Portuguese version of ID-MigraineTM in a sample of Brazilian patients. Patients with headache were recruited from the neurology outpatient clinic of a tertiary hospital and submitted to the ID-MigraineTM questionnaire. The diagnosis of headache was made according to the ICHD-2 criteria. Of the 232 patients, 86% had migraine. The questionnaire showed a sensitivity of 92% (95%CI, 88% to 95%), specificity of 60% (95%CI, 43% to 77%) and a positive predictive value of 93% (95%CI, 89% to 96%). Our results were similar to other international studies of the ID-MigraineTM application. The Portuguese version is considered easy to use, and an appropriate screening tool for migraine diagnosis in our sample. Considering the characteristics of our health system, we can infer that this questionnaire would be beneficial in a Brazilian primary care setting; however, more studies are necessary.


Near Real-Time Implementation of An Adaptive Seismocardiography - ECG Multimodal Framework for Cardiac Gating.
Objective: Accurate gating for data acquisition of computed tomography (CT) is crucial to obtaining high quality images for diagnosing cardiovascular diseases. To illustrate the feasibility of an optimized cardiac gating strategy, we present a near real-time implementation based on fusing seismocardiography (SCG) and ECG. Methods: The implementation was achieved via integrating commercial hardware and software platforms. Testing was performed on five healthy subjects (age: 24-27; m/f: 4/1) and three cardiac patients (age: 41-71; m/f: 2/1), and compared with baseline quiescence derived from echocardiography. Results: The average latency introduced by computerized processing was 5.1 ms, well within a 100 ms tolerance bounded by data accumulation time for quiescence prediction. The average prediction error associated with conventional ECG-only versus SCG-ECG-based method over all subjects were 59.58 ms and 27.24 ms, respectively. Discussion: The results demonstrate that the multimodal framework can achieve improved quiescence prediction accuracy over the ECG-only-based method in near real-time.


Negative-Pressure Wound Therapy for Ludwig's Angina: A Case Series.
Negative-pressure wound therapy (NPWT) is a well-established therapeutic approach for various complex wound classes. There is currently limited information on the use of NPWT for the scope of head and neck wounds. However, NPWT has been used successfully in some cases, including malignancy, infection, and trauma. In West Virginia, the incidence of dental-related infections leading to Ludwig's Angina is high due to lack of access to dental care. Our case series describes the application of vacuum-based therapy in conjunction with antibiotic therapy for quick, effective closure of deep tissue infections before definitive complex wound repair via graft and flap reconstructions. Over a period of 3 months, 2 patients with submental infections extending to the lateral neck demonstrated clean, efficient wound closure with NPWT for less than 14 days while hospitalized at West Virginia University Medicine. Outpatient follow-up with these patients demonstrated excellent cosmetic outcomes with minimal contracture or hypertrophy of healing tissue. NPWT promotes wound healing through decreased edema, improved perfusion, and increased granulation of tissue based on our findings. Our series encourages the use of NPWT for initial closure of complex wounds secondary to deep neck infections.


Nitrate and nitrogen balances in men.
Nitrate is a nitrogen-containing compound that is not detected by the traditional Kjeldahl method of nitrogen analysis. Nitrate balance studies were done in order to determine if nitrate production in the human body contributes to the irrationally positive nitrogen balances that have been reported in healthy adults. Seven healthy young men, confined to a metabolic unit, received five diets for 9 days each: a mixed foods diet, a fiber-free egg formula diet, and egg formula with California small white beans, lima beans, and wheat bran added. Nitrate-nitrogen intake with the mixed foods diet was 75 mg/day and nonnitrate nitrogen intake was 19 g/day; crude Kjeldahl nitrogen balance (intake--(urinary + fecal)) was 0.64 +/- 1.23 g/day. Nitrate-nitrogen excretion exceeded intake by 0.10 +/- 0.05 g/day. With the four other diets, nitrate-nitrogen intake was almost nil (about 2 mg/day) and nonnitrate nitrogen intake was 95 mg/kg body weight; crude Kjeldahl nitrogen balances ranged from -0.63 +/- 0.73 to 0.02 +/- 0.45 g N/day. With these four diets, feces contained about 80 mg nitrate-nitrogen/day and urine contained about 8 mg. Saliva obtained before lunch had about 1 ppm nitrate-nitrogen with the formula diets and 5 ppm with the mixed foods diet. Net synthesis of nitrate is quite variable but appears to be of the order of 100 mg nitrate-nitrogen/day. Although the excess nitrate excretion increased total nitrogen excretion by less than 5%, it could account for as much as 10 to 20% of unexplained positive nitrogen balances previously reported in well-controlled studies.


Role of C'3 and Fc receptors in B-lymphocyte activation.
Attempts were made to identify the non-Ig lymphocyte receptor responsible for B-cell induction by antigen and polyclonal B-cell activators (PBA). As a first step, the role of C'3 and Fc receptors was analyzed. It was shown that complement could be fixed onto B cells to such an extent that the lymphocytes could not bind complement-coated red cells, but this did not result in induction of polyclonal antibody synthesis, nor did it inhibit the lymphocytes response to PBA. However, the C'3 receptros possessed a passive focussing role in the induction of polyclonal antibody responses. Thus, PBA that had fixed complement activated polyclonal responses at lower concentrations than the same substances that had not fixed complement. Most likely the dual binding of PBA molecules to B cells by the PBA and the C'3 receptors caused more PBA molecules to be bound to each cell. However, the focussing function of the C'3 receptors was several orders of magnitude smaller than that of the Ig receptors. Analogous studies were carried out with Fc receptors. Binding of different types of antigen-antibody complexes did not cause activation of polyclonal or specific antibody synthesis, nor did it significantly interfere with induction of antibody synthesis by PBA substances.


High glucose represses β-klotho expression and impairs fibroblast growth factor 21 action in mouse pancreatic islets: involvement of peroxisome proliferator-activated receptor γ signaling.
Circulating fibroblast growth factor 21 (FGF21) levels are elevated in diabetic subjects and correlate directly with abnormal glucose metabolism, while pharmacologically administered FGF21 can ameliorate hyperglycemia. The pancreatic islet is an FGF21 target, yet the actions of FGF21 in the islet under normal and diabetic conditions are not fully understood. This study investigated the effects of high glucose on islet FGF21 actions in a diabetic mouse model by investigating db/db mouse islet responses to exogenous FGF21, the direct effects of glucose on FGF21 signaling, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) in FGF21 pathway activation. Results showed that both adult db/db mouse islets and normal islets treated with high glucose ex vivo displayed reduced β-klotho expression, resistance to FGF21, and decreased PPARγ expression. Rosiglitazone, an antidiabetic PPARγ ligand, ameliorated these effects. Our data indicate that hyperglycemia in type 2 diabetes mellitus may lead to FGF21 resistance in pancreatic islets, probably through reduction of PPARγ expression, which provides a novel mechanism for glucose-mediated islet dysfunction.


Column generation algorithms for exact modularity maximization in networks.
Finding modules, or clusters, in networks currently attracts much attention in several domains. The most studied criterion for doing so, due to Newman and Girvan [Phys. Rev. E 69, 026113 (2004)], is modularity maximization. Many heuristics have been proposed for maximizing modularity and yield rapidly near optimal solution or sometimes optimal ones but without a guarantee of optimality. There are few exact algorithms, prominent among which is a paper by Xu [Eur. Phys. J. B 60, 231 (2007)]. Modularity maximization can also be expressed as a clique partitioning problem and the row generation algorithm of Grötschel and Wakabayashi [Math. Program. 45, 59 (1989)] applied. We propose to extend both of these algorithms using the powerful column generation methods for linear and non linear integer programming. Performance of the four resulting algorithms is compared on problems from the literature. Instances with up to 512 entities are solved exactly. Moreover, the computing time of previously solved problems are reduced substantially.


SCF-engineered powders for delivery of budesonide from passive DPI devices.
The objective of this study was to develop SEDS-engineered budesonide particles suitable for dry powder inhalation delivery and to evaluate their aerosol performance across a range of passive dry powder inhalers (DPI). SEDS budesonide powders were manufactured in Nektar's SCF manufacturing plant and compared to the micronized drug and commercial powder (Pulmicort Turbuhaler, AstraZeneca). Aerosol performance was evaluated by determining emitted dose (ED) by a variation of the USP method and fine particle fraction (FPF) using Andersen cascade impaction. The SCF powder dispersed best in the Turbospin and Eclipse devices, exhibiting high EDs (70%-80%) and relatively low variability (RSD 8%-13%). Regardless of the device, the SEDS material outperformed both the micronized drug and the commercial powder, while exhibiting good batch-to-batch reproducibility (RSD <5%). All powders exhibited flow rate-dependent ED, albeit for the SEDS material it was minimized at reduced fill weights. This was attributed to inadequate and variable powder clearance from the capsules at low inspiratory flow rates, which was more pronounced in the Eclipse and Cyclohaler. The results demonstrate that SEDS is an attractive particle-engineering process that may enhance pulmonary performance of budesonide and possibly facilitate development of other small molecule pulmonary products in passive DPI.


The location and extent of exfoliation of clay on the fracture mechanisms in nylon 66-based ternary nanocomposites.
The primary focus of this work is to elucidate the location and extent of exfoliation of clay on fracture (under both static and dynamic loading conditions) of melt-compounded nylon 66/clay/SEBS-g-MA ternary nanocomposites fabricated by different blending sequences. Distinct microstructures are obtained depending on the blending protocol employed. The state of exfoliation and dispersion of clay in nylon 66 matrix and SEBS-g-MA phase are quantified and the presence of clay in rubber is shown to have a negative effect on the toughness of the nanocomposites. The level of toughness enhancement of ternary nanocomposites depends on the blending protocol and the capability of different fillers to activate the plastic deformation mechanisms in the matrix. These mechanisms include: cavitation of SEBS-g-MA phase, stretching of voided matrix material, interfacial debonding of SEBS-g-MA particles, debonding of intercalated clay embedded inside the SEBS-g-MA phase, and delamination of intercalated clay platelets. Based on these results, new insights and approaches for the processing of better toughened polymer ternary nanocomposites are discussed.


Prevalence of methicillin resistant Staphylococcus aureus in a tertiary referral hospital in eastern Uttar Pradesh.
We report the prevalence of methicillin resistant Staphylococcus aureus (MRSA) infections and their antibiotic susceptibility pattern in our hospital located in eastern Uttar Pradesh. Out of total 549 strains of Staphylococcus aureus isolated from different clinical specimens 301 (54.85%) were found to be methicillin resistant. More than 80% of MRSA were found to be resistant to penicillin, cotrimoxazole, ciprofloxacin, gentamicin, erythromycin, tetracycline, 60.5% to amikacin and 47.5% to netilmicin. However, no strains were resistant to vancomycin. Many MRSA strains (32.0%) were multi-drug resistant. To reduce the prevalence of MRSA, the regular surveillance of hospital associated infection, monitoring of antibiotic sensitivity pattern and formulation of definite antibiotic policy may be helpful.


Epibrassinolide activates AKT to trigger autophagy with polyamine metabolism in SW480 and DLD-1 colon cancer cell lines.
Epibrassinolide (EBR), a plant-derived polyhydroxylated derivative of 5α-cholestane, structurally shows similarities to animal steroid hormones. According to the present study, EBR treatment triggered a significant stress response via activating ER stress, autophagy, and apoptosis in cancer cells. EBR could also increase Akt phosphorylation in vitro. While the activation of Akt resulted in cellular metabolic activation in normal cells to proceed with cell survival, a rapid stress response was induced in cancer cells to reduce survival. Therefore, Akt as a mediator of cellular survival and death decision pathways is a crucial target in cancer cells. In this study, we determined that EBR induces stress responses through activating Akt, which reduced the mTOR complex I (mTORC1) activation in SW480 and DLD-1 colon cancer cells. As a consequence, EBR triggered macroautophagy and led to lipidation of LC3 most efficiently in SW480 cells. The cotreatment of spermidine (Spd) with EBR increased lipidation of LC3 synergistically in both cell lines. We also found that EBR promoted polyamine catabolism in SW480 cells. The retention of polyamine biosynthesis was remarkable following EBR treatment. We suggested that EBR-mediated Akt activation might determine the downstream cellular stress responses to induce autophagy related to polyamines.


Promoting Institutional Change Through Bias Literacy.
The National Science Foundation and others conclude that institutional transformation is required to ensure equal opportunities for the participation and advancement of men and women in academic science, technology, engineering, mathematics, and medicine (STEMM). Such transformation requires changing the habitual attitudes and behaviors of faculty. Approaching implicit bias as a remediable habit, we present the theoretical basis and conceptual model underpinning an educational intervention to promote bias literacy among university faculty as a step toward institutional transformation regarding gender equity. We describe the development and implementation of a Bias Literacy Workshop in detail so others can replicate or adapt it to their setting. Of the 220 (167 faculty and 53 nonfaculty) attendees from the initial 17 departments/divisions offered this workshop, all 180 who completed a written evaluation found the workshop at least "somewhat useful" and 74% found it "very useful." Over 68% indicated increased knowledge of the workshop material. Of the 186 participants who wrote a commitment to engage in new activities to promote gender equity, 87% incorporated specific workshop content. Twenty-four participants were interviewed 4-6 months after attending the workshop; 75% of these not only demonstrated increased bias awareness, but described plans to change-or had actually changed-behaviors because of the workshop. Based on our sample of faculty from a Midwestern university, we conclude that at least one third of STEMM faculty who are invited will attend a 2.5-hr Bias Literacy Workshop, that nearly all will find it useful, and that most will complete a written commitment to promoting gender equity. These findings suggest that this educational intervention may effectively promote institutional change regarding gender equity.


Temperature and time variations during apical resection.
The aim of this study was to investigate temperature and time variations during root-end resection. Sixty human premolars were selected. The root canals were enlarged up to ProTaper X3 rotary instrument. A thermocouple was placed into the root canal 1 mm behind the resection line. The teeth were randomly divided into six groups according to the apical resection method: steel bur, tungsten carbide bur, Lindeman bur, diamond bur, laser and ultrasonic surgical piezo with a diamond tip. The root ends were resected 3 mm away from the root apex. The temperature of the root dentine during resection was recorded as maximum temperature, mean temperature and temperature change. The time required for apicectomy was recorded for each group. The Kruskal-Wallis method was used to analyse the differences between temperature changes during apical resections. The significance level was set at 5%. There was no significant difference between bur groups in terms of temperature increase. The maximum temperature in piezo surgery was significantly higher than the Lindeman, tungsten and steel burs (p < .001). In addition, the maximum temperature in laser surgery was higher than the Lindeman bur (p < .05). An increase in the temperature was mostly seen in piezo surgery and the least temperature change occurred in the Lindeman bur. Mean time stayed under 1 min in each group. Although piezo caused the highest temperature increase, the measured temperature increase was within physiological limits in all tested techniques.


Effect of slow- and fast-breathing exercises on autonomic functions in patients with essential hypertension.
Breathing exercises practiced in various forms of meditations such as yoga may influence autonomic functions. This may be the basis of therapeutic benefit to hypertensive patients. The study design was a randomized, prospective, controlled clinical study using three groups. The subjects comprised 60 male and female patients aged 20-60 years with stage 1 essential hypertension. Patients were randomly and equally divided into the control and other two intervention groups, who were advised to do 3 months of slow-breathing and fast-breathing exercises, respectively. Baseline and postintervention recording of blood pressure (BP), autonomic function tests such as standing-to-lying ratio (S/L ratio), immediate heart rate response to standing (30:15 ratio), Valsalva ratio, heart rate variation with respiration (E/I ratio), hand-grip test, and cold pressor response were done in all subjects. Slow breathing had a stronger effect than fast breathing. BP decreased longitudinally over a 3-month period with both interventions. S/L ratio, 30:15 ratio, E/I ratio, and BP response in the hand grip and cold pressor test showed significant change only in patients practicing the slow-breathing exercise. Both types of breathing exercises benefit patients with hypertension. However, improvement in both the sympathetic and parasympathetic reactivity may be the mechanism that is associated in those practicing the slow-breathing exercise.


Structural basis for drug resistance conferred by β-tubulin mutations: a molecular modeling study on native and mutated tubulin complexes with epothilone B.
Using molecular modeling, we have investigated the structure and dynamic properties of epothilone B-tubulin complexes with wild-type and mutated tubulin, aimed at identifying the molecular factors involved in the emergence of drug resistance induced by four protein mutations at Phe270Val, Thr274Ile, Arg282Gln, and Gln292Glu. Our results revealed that tubulin mutations render significant changes in the protein conformation in regions involved either in the binding of the ligand or in interdimer contacts that are relevant to the assembly of stable microtubules. In addition, point mutations induce drastic changes in the binding pose of the ligand and in the interaction networks responsible for the epothilone-tubulin association. Large ligand displacements inside the binding pocket and an overall decrease in the strength of drug-receptor polar contacts suggest a looser binding of the ligand in tubulin mutants. These results explain the loss of activity for epothilone B against cancer cells that contain tubulin mutants and provide valuable information to enhance the understanding of the atomic source of epothilones' activity, which can be helpful to conduct further research on the rational design of more potent therapeutic tubulin-binding agents.


Data preparation and interannotator agreement: BioCreAtIvE task 1B.
We prepared and evaluated training and test materials for an assessment of text mining methods in molecular biology. The goal of the assessment was to evaluate the ability of automated systems to generate a list of unique gene identifiers from PubMed abstracts for the three model organisms Fly, Mouse, and Yeast. This paper describes the preparation and evaluation of answer keys for training and testing. These consisted of lists of normalized gene names found in the abstracts, generated by adapting the gene list for the full journal articles found in the model organism databases. For the training dataset, the gene list was pruned automatically to remove gene names not found in the abstract; for the testing dataset, it was further refined by manual annotation by annotators provided with guidelines. A critical step in interpreting the results of an assessment is to evaluate the quality of the data preparation. We did this by careful assessment of interannotator agreement and the use of answer pooling of participant results to improve the quality of the final testing dataset. Interannotator analysis on a small dataset showed that our gene lists for Fly and Yeast were good (87% and 91% three-way agreement) but the Mouse gene list had many conflicts (mostly omissions), which resulted in errors (69% interannotator agreement). By comparing and pooling answers from the participant systems, we were able to add an additional check on the test data; this allowed us to find additional errors, especially in Mouse. This led to 1% change in the Yeast and Fly "gold standard" answer keys, but to an 8% change in the mouse answer key. We found that clear annotation guidelines are important, along with careful interannotator experiments, to validate the generated gene lists. Also, abstracts alone are a poor resource for identifying genes in paper, containing only a fraction of genes mentioned in the full text (25% for Fly, 36% for Mouse). We found that there are intrinsic differences between the model organism databases related to the number of synonymous terms and also to curation criteria. Finally, we found that answer pooling was much faster and allowed us to identify more conflicting genes than interannotator analysis.


Cationic liposome systems in gene therapy.
Cationic liposomes are well known to assist the delivery of genes and other nucleic acids to cells in vitro. This has held out the tantalizing possibility that cationic liposome systems could play a major role as vectors (ie, gene delivery vehicles) for the delivery of therapeutic genes and/or other nucleic acids into diseased cells and organs of patients, in order to treat disease by gene therapy. How realistic is this? Certainly, a number of cationic liposome systems have been used to mediate the delivery of nucleic acids in vivo with gene therapy applications in mind. However, this approach is still fraught with technical problems and further progress in basic research will be necessary if cationic liposomes are to be a gene therapy vector of the future.


Immobilization of laccase in kappa-carrageenan based semi-interpenetrating polymer networks.
Laccase enzyme (L) was immobilized by entrapment into semi-interpenetrating polymer networks (semi-IPNs) prepared from kappa-carrageenan with either poly(acrylamide-acrylic acid) [P(AAm-AA)/kappa-car] or poly(acrylamide-itaconic acid) [P(AAm-IA)/kappa-car]. For both systems, immobilized enzymes achieved the same optimum values observed for free enzyme (pH=5.0 and T=40 degrees C), except for P(AAm-IA)/kappa-car system there was a shift to 5.5 in optimum pH value. At the end of 42 days of storage immobilized enzymes retained more than 80% of their original activities while the retained activities of both systems after 10 uses in batch type application were found to be higher than 50%. K(m) values were calculated as 2.52x10(-2) mM and 1.08x10(-2) mM and V(max) values were found as 6.8x10(-3) mM min(-1) and 4.4x10(-3) mM min(-1), for P(AAm-AA)/kappa-car-L and P(AAm-IA)/kappa-car-L, respectively. When methyl orange containing solutions (10 mg/L) were treated with the immobilized laccases (68.2U), enzymatic decolorization of methyl orange in 6 h was achieved to the level of 35% for both systems. Supplementing the reaction medium with ABTS as the redox mediator increased this value to about 70%. These initial results show that, laccase containing semi-IPNs can find some applications in decolorization of the industrial wastes.


Uniform magnetic core/shell microspheres functionalized with Ni2+-iminodiacetic acid for one step purification and immobilization of his-tagged enzymes.
A facile approach has been developed to synthesize Fe3O4/PMG (poly (N,N'-methylenebisacrylamide-co-glycidyl methacrylate)) core/shell microspheres using distillation-precipitation polymerization. Treating PMG shell with iminodiacetic acid (IDA) and Ni2+ yields composite microspheres of Fe3O4/PMG/IDA-Ni2+. The Ni2+ ions loaded on the surface of microspheres provide abundant docking sites for immobilization of histidine-tagged proteins. The high saturation magnetization of Fe3O4/PMG (23 emu/g), determined by vibrating sample magnetometer (VSM), allows an easy separation of the microspheres from solution under an external magnetic field. The composite microspheres were used to purify two His-tagged cellulolytic enzymes (Cel48F and Cel9G) directly from crude cell lysates with high binding affinity, capacity, and specificity. The microspheres can be recycled for many times without significant loss of binding capacity to enzymes. The immobilized enzymes on the surface of microspheres well retain their biological activities in degradation of cellulose. These materials show great potential in the biomedical and biotechnological applications that require low-cost purification of recombinant proteins and instant enzyme immobilization at an industrial scale.


Influence of SHH/GLI1 axis on EMT mediated migration and invasion of breast cancer cells.
Sonic Hedgehog signaling is critical for breast morphogenesis and cancer. The present study was conducted to explore the influence of SHH/GLI1 axis on epithelial mesenchymal transition and invasion in breast cancer cells. SHH/GLI1 positive samples demonstrated high expression of Snail and Vimentin with relatively low expression of E-cadherin. Overexpression of Vimentin and Snail in SHH/GLI1 positive patients was also associated with poor overall survival. Interestingly, GANT61 (GLI1 inhibitor) exposure significantly reduced cell viability and induced apoptosis at 10 µM. Suppression of Hedgehog pathway either by CRISPR mediated SHH knock out or GANT61 altered regulation of EMT markers in breast cancer cells. Moreover, in-activation of SHH/GLI1 axis also significantly restricted cell migration and invasiveness. These findings suggest that targeting SHH/GLI1 axis alters expression of EMT markers and abrogates neoplastic invasion in breast cancer cells.


N-Heterocyclic carbene metal complexes in medicinal chemistry.
Metal complexes with N-heterocyclic carbene (NHC) ligands are widely used in chemistry due to their catalytic properties and applied for olefin metathesis among other reactions. The enhanced application of this type of organometallics has over the last few years also triggered a steadily increasing number of studies in the fields of medicinal chemistry, which take advantage of the fascinating chemical properties of these complexes. In fact it has been demonstrated that metal NHC complexes can be used to develop highly efficient metal based drugs with possible applications in the treatment of cancer or infectious diseases. Complexes of silver and gold have been biologically evaluated most frequently but also platinum or other transition metals have demonstrated promising biological properties.


CD14-159 C allele is associated with increased risk of mortality after burn injury.
Although comprehension of postburn pathophysiology has grown in recent years, we are still unable to accurately identify burn patients who are at an increased risk of infectious complications and death. This unexplained variation is likely influenced by heritable factors; the genetic predisposition for death from infection has been estimated as greater than that for cardiovascular disease or cancer. Identify genetic variants associated with increased mortality after burn injury. A total of 233 patients with burns of 15% of total body surface area or greater or smoke inhalation injury who survived more than 48 h after admission and were without significant nonburn-related trauma (injury severity score > or = 16), traumatic or anoxic brain injury, or spinal cord injury. We examined the influence of genotype at five candidate loci (interleukin [IL]-1beta, IL-6, tumor necrosis factor-alpha, toll-like receptor 4, CD14) on mortality risk after burn injury. DNA was isolated from residual blood from laboratory draws and candidate genotypes were determined by real-time polymerase chain reaction using TaqMan probes. Clinical data were prospectively collected into a local, curated database. Allelic associations were analyzed by multivariate logistic regression. After adjustment for age, full-thickness burn size, inhalation injury, ethnicity, and sex, carriage of the CD14-159 C allele imparted at least a 1.3-fold increased risk for death after burn injury, relative to TT homozygotes (adjusted odds ratio, 2.9; 95% confidence interval, 1.3-6.8; P = 0.01). This association was stronger (adjusted odds ratio, 3.3; 95% confidence interval, 1.3-8.4; P = 0.01) when the analysis was conducted only on deaths accompanied by severe sepsis. In addition, a gene dosage effect for increased mortality was apparent for carriage of the CD14-159 C allele (P = 0.006). The gene dosage effect remained when white, Hispanic, or African American patients were analyzed independently, although statistical significance was not achieved in the subgroup analysis. None of the other single nucleotide polymorphisms examined were significantly associated with mortality. These data provide strong evidence that a CD14 promoter allele that is known to impart lower baseline and induced CD14 transcription also affects mortality risk after burn injury. A potential (although untested) mechanism for our observation is that reduced signaling through CD14/toll-like receptor 4 in response to challenge by gram-negative bacteria after burns results in a blunted innate immune response and subsequent increased likelihood for systemic infection and death.


Specific regulation of IRS-2 expression by glucose in rat primary pancreatic islet beta-cells.
Insulin receptor substrate 2 (IRS-2) plays a critical role in pancreatic beta-cells. Increased IRS-2 expression promotes beta-cell growth and survival, whereas decreased IRS-2 levels lead to apoptosis. It was found that IRS-2 turnover in rat islet beta-cells was rapid, with mRNA and protein half-lives of approximately 90 min and approximately 2 h, respectively. However, this was countered by specific glucose-regulated IRS-2 expression mediated at the transcriptional level. Glucose (> or = 6 mM) increased IRS-2 mRNA and protein levels in a dose-dependent manner, reaching a maximum 4-fold increase in IRS-2 mRNA and a 5-6-fold increase in IRS-2 protein levels at > or = 12 mM glucose (p < or = 0.01). Glucose (15 mM) regulation of islet beta-cell IRS-2 gene expression was rapid, with a significant increase in IRS-2 mRNA levels within 2 h that reached a maximum 4-fold increase by 4 h. IRS-2 protein expression in beta-cells followed that of IRS-2 mRNA. Glucose metabolism was necessary for increased IRS-2 expression in beta-cells. Moreover, inhibition of a glucose-induced rise in islet beta-cell cytosolic [Ca2+]i prevented an increase in IRS-2 expression, indicating this was Ca2+-dependent. The glucose-induced rise in IRS-2 levels correlated with increased IRS-2 tyrosine phosphorylation and downstream activation of protein kinase B. These data indicate that fluctuations of glucose in the normal physiological range (5-15 mM) promote beta-cell survival via regulation of IRS-2 expression and a subsequent parallel protein kinase B activation. Given that the onset of type-2 diabetes is marked by loss of beta-cells, these data further the idea that controlled IRS-2 expression in beta-cells could be a therapeutic means to promote beta-cell survival and delay the onset of the disease.


Triggered Transience of Plastic Materials by a Single Electron Transfer Mechanism.
Transient polymers rapidly and controllably depolymerize in response to a specific trigger, typically by a chain-end unzipping mechanism. Triggers, such as heat, light, and chemical stimuli, are generally dependent on the chemistry of the polymer backbone or end groups. Single electron transfer (SET), in contrast to other triggering mechanisms, is achievable by various means including chemical, electrochemical, and photochemical oxidation or reduction. Here, we identify SET and subsequent mesolytic cleavage as the major thermal triggering mechanism of cyclic poly(phthalaldehyde) (cPPA) depolymerization. Multimodal SET triggering is demonstrated by both chemical and photoredox-triggered depolymerization of cPPA. Redox-active small molecules (p-chloranil and 1,3,5-trimethoxybenzene) were used to tune the depolymerization onset temperature of cPPA over the range 105-135 °C. Extending this mechanism to photoredox catalysis, N-methylacridinium hexafluorophosphate (NMAPF6) was used to photochemically degrade cPPA in solution and thin films. Finally, we fabricated photodegradable cPPA monoliths with a storage modulus of 1.8 GPa and demonstrated complete depolymerization within 25 min of sunlight exposure. Sunlight-triggered depolymerization of cPPA is demonstrated and potentially useful for the manufacture of transient devices that vanish leaving little or no trace. Most importantly, this new mechanism is likely to inspire other SET-triggered transient polymers, whose development may address the ongoing crisis of plastic pollution.


Characterization of a novel epigenetically-silenced, growth-suppressive gene, ADAMTS9, and its association with lymph node metastases in nasopharyngeal carcinoma.
By using a functional complementation approach, suppression of tumorigenicity was observed after transfer of intact or truncated copies of chromosome 3 into a nasopharyngeal carcinoma (NPC) HONE1 cell line. The extra exogenous chromosome 3 in the microcell hybrids (MCHs) significantly extended the lag period of tumor formation, which may be associated with loss or inactivation of wild type alleles from the normal donor chromosome 3. Representative tumors, which grew in nude mice were reconstituted into culture and expanded as tumor segregants (TSs). In our study, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9), a gene mapping to 3p14.2, was identified to be critically associated with tumor suppression in NPC. Gene expression analysis showed that ADAMTS9 was either not expressed or was downregulated in HONE1 cells, TSs and NPC cell lines. The mechanism of ADAMTS9 gene inactivation in the NPC cell lines and tissues was attributed to promoter hypermethylation. Using a tissue microarray and immunohistochemical staining, 31 of 66 (47%) of the NPC cases showed downregulated or absence of ADAMTS9 expression. ADAMTS9 expression was downregulated or lost in 17 of 23 (73.9%) lymph node metastatic NPC specimens, which was significantly higher than in 14 of 43 (32.6%) primary tumors. After transfection of the ADAMTS9 gene into 7 NPC cell lines, a dramatic reduction of colony forming ability was observed. These findings support ADAMTS9 as a putative tumor suppressor gene in vivo in NPC that is significantly associated with lymph node metastases.


One dozen considerations when working with women in substance abuse groups.
Women and men have different histories, presentations, and behaviors in substance abuse groups. Twelve considerations are offered for the beginning group leader when encountering women with substance abuse issues. These include understanding sexism, what brings women to treatment, and how women behave in group treatment. Implications for clinical practice with women in single-gender and mixed-gender groups are included.


MET expression in sporadic renal cell carcinomas.
Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.


[Human clonorchiasis survey in Taiwan and its immunodiagnostic technics].
In a series of control study on human clonorchiasis, surveys had been carried out for four years. During the fourth year of study, immunodiagnosis was also tried. Skin test and stool examination were performed as a routine epidemiological survey in this study. The result of skin test revealed that 7 out of 738 primary school children and 2 out of 274 inhabitants in Tong-ho Township, Taitung County showed positive reaction. Four out of 500 children and none of 9 teachers tested from the primary school of Nan-hua Township, Hualien County were positive. For stool examinations, only one was found with Clonorchis eggs among 34 children from Nan-hua school, Hualien County, but none of 549 children from Tong-ho school, Taitung County was found with eggs. When stool examination was performed to those who had history of eating raw fresh water fish, positive cases increased in numbers, such as in Pingtung County, 19 out of 96 children and in Meinung Township of Kaohsiung County, 52 out of 86 children and 14 out of 19 teachers were shown positive for Clonorchis eggs. Immunodiagnosis by means of ELISA had been carried out in 72 sera of clonorchiasis patients and CFT, CIE in 30 sera. Results showed that ELISA detectable antibody titer was between 1,600 and 25,600, CFT, between 16 and 128 and CIE, under 4. In 8 sera of non-infected and 6 infected with various intestinal helminths, negative reactions were obtained from each technic.


Prominent differences in left ventricular performance and myocardial properties between right ventricular and left ventricular-based pacing modes in rats.
Biventricular pacing is an important modality to improve left ventricular (LV) synchronization and long-term function. However, the biological effects of this treatment are far from being elucidated and existing animal models are limited and demanding. Recently, we introduced an implanted device for double-site epicardial pacing in rats and echocardiographically demonstrated favorable effects of LV and biventricular (LV-based) pacing modes typically observed in humans. Here, this new animal model was further characterized. Electrodes were implanted either on the right atria (RA) and right ventricle (RV) or on the RV and LV. Following recovery, rats were either used for invasive hemodynamic measurements (pressure-volume analysis) or exposed to sustained RV vs. biventricular tachypacing for 3 days. RV pacing compromised, while LV-based pacing modes markedly enhanced cardiac performance. Changes in LV performance were associated with prominent compensatory changes in arterial resistance. Sustained RV tachypacing increased the electrocardiogram QTc interval by 7.9 ± 3.1 ms (n = 6, p < 0.05), dispersed refractoriness between the right and left pacing sites and induced important molecular changes mainly in the early-activated septal tissue. These effects were not observed during biventricular tachypacing (n = 6). Our results demonstrate that the rat is an attractive new model to study the biological consequences of LV dyssynchrony and resynchronization.


A comprehensive analysis of gene expression changes provoked by bacterial and fungal infection in C. elegans.
While Caenorhabditis elegans specifically responds to infection by the up-regulation of certain genes, distinct pathogens trigger the expression of a common set of genes. We applied new methods to conduct a comprehensive and comparative study of the transcriptional response of C. elegans to bacterial and fungal infection. Using tiling arrays and/or RNA-sequencing, we have characterized the genome-wide transcriptional changes that underlie the host's response to infection by three bacterial (Serratia marcescens, Enterococcus faecalis and otorhabdus luminescens) and two fungal pathogens (Drechmeria coniospora and Harposporium sp.). We developed a flexible tool, the WormBase Converter (available at http://wormbasemanager.sourceforge.net/), to allow cross-study comparisons. The new data sets provided more extensive lists of differentially regulated genes than previous studies. Annotation analysis confirmed that genes commonly up-regulated by bacterial infections are related to stress responses. We found substantial overlaps between the genes regulated upon intestinal infection by the bacterial pathogens and Harposporium, and between those regulated by Harposporium and D. coniospora, which infects the epidermis. Among the fungus-regulated genes, there was a significant bias towards genes that are evolving rapidly and potentially encode small proteins. The results obtained using new methods reveal that the response to infection in C. elegans is determined by the nature of the pathogen, the site of infection and the physiological imbalance provoked by infection. They form the basis for future functional dissection of innate immune signaling. Finally, we also propose alternative methods to identify differentially regulated genes that take into account the greater variability in lowly expressed genes.


Interferometric array illuminator with analysis of nonobservable fringes.
Interferometric methods for array generation offer various advantages over diffractive methods. Use of polarizing elements in an interferometric array illuminator results in interesting properties in addition to improving the efficiency considerably from low levels. The array pattern appears as nonobservable fringes that can be observed only with a polarizer, and the interferometer is insensitive to one of the tilt components. A thorough analysis of such an interferometric array illuminator is presented in this paper. Several possible applications of such an interferometer in addition to use as an array illuminator are proposed.


Differential effects of fluticasone and montelukast on allergen-induced asthma.
Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.


Striatal dopamine ramping may indicate flexible reinforcement learning with forgetting in the cortico-basal ganglia circuits.
It has been suggested that the midbrain dopamine (DA) neurons, receiving inputs from the cortico-basal ganglia (CBG) circuits and the brainstem, compute reward prediction error (RPE), the difference between reward obtained or expected to be obtained and reward that had been expected to be obtained. These reward expectations are suggested to be stored in the CBG synapses and updated according to RPE through synaptic plasticity, which is induced by released DA. These together constitute the "DA=RPE" hypothesis, which describes the mutual interaction between DA and the CBG circuits and serves as the primary working hypothesis in studying reward learning and value-based decision-making. However, recent work has revealed a new type of DA signal that appears not to represent RPE. Specifically, it has been found in a reward-associated maze task that striatal DA concentration primarily shows a gradual increase toward the goal. We explored whether such ramping DA could be explained by extending the "DA=RPE" hypothesis by taking into account biological properties of the CBG circuits. In particular, we examined effects of possible time-dependent decay of DA-dependent plastic changes of synaptic strengths by incorporating decay of learned values into the RPE-based reinforcement learning model and simulating reward learning tasks. We then found that incorporation of such a decay dramatically changes the model's behavior, causing gradual ramping of RPE. Moreover, we further incorporated magnitude-dependence of the rate of decay, which could potentially be in accord with some past observations, and found that near-sigmoidal ramping of RPE, resembling the observed DA ramping, could then occur. Given that synaptic decay can be useful for flexibly reversing and updating the learned reward associations, especially in case the baseline DA is low and encoding of negative RPE by DA is limited, the observed DA ramping would be indicative of the operation of such flexible reward learning.


Changes in blood pressure and vascular reactivity in normotensives following regular alcohol consumption.
Blood pressure and vascular reactivity to infusions of noradrenaline and angiotensin II (ANG II) were measured in 10 normotensive volunteers who had consumed 80 g alcohol per day for 4 days after a similar period of abstaining from alcohol. Supine systolic and diastolic blood pressure and heart rate, and erect systolic blood pressures rose significantly following alcohol. Vascular reactivity to noradrenaline decreased following alcohol, while reactivity to ANG II did not change in a consistent manner. Although plasma noradrenaline levels did not alter following alcohol, the decrease in vascular reactivity to noradrenaline may indicate down-regulation of alpha-receptors and provide indirect evidence that increased sympathetic activity contributes to the rise in blood pressure that follows regular, moderate alcohol consumption.


Cardiac electrophysiological assessment in patients with sarcoidosis.
Sarcoidosis is a multisystem granulomatous disease of unknown origin that can cause sudden death. Electrophysiological evaluation of patients with suspected sarcoidosis with cardiac involvement. We studied 22 patients with mean age of 55.32 ± 13.13 years, diagnosed with sarcoidosis and suspected cardiac involvement. These patients underwent clinical evaluation, laboratory tests, electrocardiogram, echocardiogram, 24-hour Holter, technetium or gallium scintigraphy and electrophysiological study. In selected cases, we performed positron emission tomography or magnetic resonance imaging. Patients were followed up in the outpatient care service with quarterly visits. Cardiac involvement was confirmed in four (18.2%) patients. Ventricular extrasystoles with density > 100/24 h were documented in 24-Holter monitoring in 12 (54.5%) patients. Electrophysiological studies revealed an increased HV interval in seven patients (31.8%) and increased Wenckebach point in four (18.2%) patients. There was induction of atrial fibrillation in seven patients (31.8%) and sustained ventricular tachycardia in one patient (4.5%). Four patients with confirmed cardiac sarcoidosis had documented ventricular extrasystoles with density > 100/24 h. Out of these, two had prolonged HV interval and atrial fibrillation was induced in two of them. Sustained ventricular tachycardia was not induced in any of these patients. After mean follow-up period of 20.9 ± 15.7 months, one patient with cardiac sarcoidosis had sudden death. Patients with sarcoidosis and suspected cardiac involvement have a high prevalence of ventricular extrasystoles (VEs) and conduction system disorders.


Menopause with cardiovascular disease and its risk factors among rural Chinese women in Beijing: a population-based study.
This study was to explore the independent influence of menopause on cardiovascular disease (CVD) and its risk factors in rural Chinese females. This cross-sectional population-based study enrolled 2245 premenopausal and 2498 postmenopausal women aged 40-59 years in Fangshan district, Beijing, China. Data was collected by face-to-face interview, physical examination and biochemical examination during 2009 and 2010. General liner models were employed to calculate age-adjusted means of cardiovascular risk factors (CRFs). The comparisons of CVD and it risk factors according to menopausal status, and calculation of adjusted odds ratios/coefficients and their 95% confidence intervals for the associations of quartiles of elapsed time since menopause and age at menopause with CVD and its risk factors was performed by multivariate logistic/liner regression models separately. After adjustment for age and other confounders, no statistically significant association of menopause with CVD was observed in our participants; however, dyslipidemia prevalence and levels of waist-to-hip ratio, triglycerides, total cholesterol and low-density lipoprotein cholesterol were presented higher in postmenopausal group, compared to the premenopausal one (P<0.05). Compared to women who had been menopausal for less than1 year, those with the elapsed time since menopause of 2-3 years had higher CHD prevalence, higher triglycerides level and lower high-density lipoprotein cholesterol level (P<0.05). Postmenopausal women in rural China had worse CRFs profile than the premenopausal ones, which implied menopause might aggravate the CRFs epidemic beyond effects of aging, and would increase the CVD burden during and after their middle ages.


[Experience with the clinical study of cordaron].
Complex examination including continuous long-term observation by means of a computer showed that because of a wide spectrum of action cordaron is among the effective agents for the treatment of ischemic heart disease. The capacity of cordaron to reduce the zone of myocardial damage makes its use expedient in the acute period of myocardial infarction. Long-term treatment of patients suffering from chronic ischemic disease of the heart with cordaron raises the tolerance to physical exercise and improves myocardial nutrition. The coronarolytic effect of cordaron is evidently associated to a definite measure with the action of the agent on adenosine metabolism, which is manifested in an increase in its production and inhibition of its inactivation.


Does flower color variation matter in deception pollinated Psychilis monensis (Orchidaceae)?
Negative frequency dependent selection (FDS) had been proposed as a mechanism for the maintenance of the high levels of variability in floral traits of rewardless plants. Thus far the evidence has been equivocal for discontinuous traits. We experimentally tested the FDS hypothesis for continuous variation in flower color of Psychilis monensis, a rewardless, epiphytic orchid of Mona Island, Puerto Rico. P. monensis flowers all year long with a peak in June and July. Plants are self-incompatible. Individual flowers last 9-15 days if unpollinated. Over a 9-month observation of an unmanipulated population, a high percentage of plants showed pollinarium removals (79%) and fruit initiation (63%), but the actual percentage of flowers visited was very low (12%) and final fruit set was as low as the lowest recorded for orchids (2.4%). In a FDS experiment using a Latin Square design, we manipulated flower color in three populations. Over 50% of the variation in either male or female reproductive success was explained by time and site with no significant effect of treatment except as part of a three-way interaction of time x site x treatment. Paired comparisons with the controls gave equivocal results for both male and female measures of reproductive success. Major community changes had occurred during the FDS experiment with flower activity falling dramatically and by the third run of the experiment, only P. monensis was in flower. Coincidentally, the numbers of effective visits increased with time, presumably as pollinators became less discriminating in search of new food resources. Thus, negative frequency dependent selection is either sporadic or non-existent. Reproductive success was statistically related to locality and date, which was reflected in the flowering phenology of the local communities. High natural levels of color variation may be more influenced by drift than selection.


Chromosome differentiation and pairing behavior of polyploids: an assessment on preferential metaphase I associations in colchicine-induced autotetraploid hybrids within the genus Secale.
Preferential chromosome association at metaphase I has been analyzed and compared in autotetraploid cells obtained by colchicine treatment of hybrid diploid rye plants with different degrees of chromosomal divergence between homologs. The tendency to identical over homologous, but not identical, pairing preferences detected when homologous partners are contributed by less related parental lines indicates that chromosome differentiation may play an important role on preferential pairing behavior of polyploids. However, associations between more similar (identical) partners are not always favored, thus suggesting that additional factors must be considered. Other hypotheses for explaining pairing preferences in competitive situations are discussed. No clear relationship has been found between multivalent frequencies at metaphase I and chromosome differentiation between homologs or preferential pairing behavior. Therefore evolutionary divergences among related genomes should be carefully stated when evaluated from metaphase I configuration frequencies.


Low-Income, African American, Adolescent Mothers' Depressive Symptoms, Perceived Stress, and Social Support.
The purpose of this descriptive repeated-measures study was to describe depressive symptom patterns and report changes over time in levels of perceived stress and social support depending on patterns of depressive symptoms in single, low-income, African American, adolescent mothers during the initial, 6-month postpartum period. Thirty-five adolescent subjects between the ages of 16 and 22 years old were recruited at health care clinics in two Midwestern cities. Data collections by advanced practice nurses were completed at 1 week, 6 weeks, 3 months, and 6 months postpartum at mothers' homes. Established instruments were used to measure depressive symptoms, perceived stress and social support. Results indicated 63% of adolescent mothers' experienced depressive symptoms sometime during this transition period and 11.4% of these subjects had depressive symptoms at all 4 time points. Depressive symptoms were associated with perceived stress at each time point. Emotional support was inversely associated with depressive symptoms at 2 of the 4 time points. Depressive symptoms and problematic support were significantly related at 3 months and 6 months. Although single, low-income, African American, adolescent mothers are considered a high risk group, some are at even greater risk. This extremely high risk group have depressive symptoms throughout the first 6 months postpartum with the highest level of perceived stress and the most variability in social support relative to groups that were never depressed or were in and out of depression. More studies are needed to understand how to best help these high risk adolescents successfully transition to motherhood.


Individual differences in executive functions are almost entirely genetic in origin.
Recent psychological and neuropsychological research suggests that executive functions--the cognitive control processes that regulate thought and action--are multifaceted and that different types of executive functions are correlated but separable. The present multivariate twin study of 3 executive functions (inhibiting dominant responses, updating working memory representations, and shifting between task sets), measured as latent variables, examined why people vary in these executive control abilities and why these abilities are correlated but separable from a behavioral genetic perspective. Results indicated that executive functions are correlated because they are influenced by a highly heritable (99%) common factor that goes beyond general intelligence or perceptual speed, and they are separable because of additional genetic influences unique to particular executive functions. This combination of general and specific genetic influences places executive functions among the most heritable psychological traits. These results highlight the potential of genetic approaches for uncovering the biological underpinnings of executive functions and suggest a need for examining multiple types of executive functions to distinguish different levels of genetic influences.


Gender differences in non-adherence among Brazilian patients initiating antiretroviral therapy.
We conducted a study to identify gender differences in factors associated with the first episode of non-adherence in the 12 months following the first antiretroviral prescription. A concurrent prospective study of patients initiating antiretroviral therapy in Brazil was conducted from 2001-2002. The self-reported measurement of adherence was defined as an intake of less than 95% of the prescribed number of doses. Only the first occurrence of non-adherence was considered in this analysis. All analyses were stratified by gender. A Cox proportional hazard model was used to estimate the risk of non-adherence, and the time to non-adherence was estimated using the Kaplan-Meier method. The cumulative incidence of non-adherence was 34.6% (29.7% and 43.9% among men and women, respectively; p=0.010). Marital status (being married or in stable union; p=0.022), alcohol use in the month prior to the baseline interview (p=0.046), and current tobacco use (p=0.005) increased the risk of non-adherence among female participants only, whereas a self-reported difficulty with the antiretroviral treatment was associated with non-adherence in men only. For both men and women, we found that a longer time between the HIV test and first antiretroviral therapy prescription (p=0.028) also presented an increased risk of non-adherence. In this cohort study, the incidence of non-adherence was 1.5 times greater among women compared to men. Our results reinforce the need to develop interventions that account for gender differences in public referral centers. Additionally, we emphasize that, to achieve and maintain appropriate adherence levels, it is important to understand the barriers to seeking and utilizing health care services.


Preventing bacterial contamination and proliferation during the harvest, storage, and feeding of fresh bovine colostrum.
The objectives of this study were to identify control points for bacterial contamination of bovine colostrum during the harvesting and feeding processes, and to describe the effects of refrigeration and use of potassium sorbate preservative on bacteria counts in stored fresh colostrum. For objective 1, first-milking colostrum samples were collected aseptically directly from the mammary glands of 39 cows, from the milking bucket, and from the esophageal feeder tube. For objective 2, 15-mL aliquots of colostrum were collected from the milking bucket and allocated to 1 of 4 treatment groups: 1) refrigeration, 2) ambient temperature, 3) refrigeration with potassium sorbate preservative, and 4) ambient temperature with potassium sorbate preservative. Subsamples from each treatment group were collected after 24, 48, and 96 h of storage. All samples underwent bacteriological culture for total plate count and coliform count. Bacteria counts were generally low or zero in colostrum collected directly from the gland [mean (SD) log10 cfu/mL(udder) = 1.44 (1.45)]. However, significant bacterial contamination occurred during the harvest process [mean (SD) log10 cfu/mL(bucket) = 4.99 (1.95)]. No additional bacterial contamination occurred between the bucket and the esophageal feeder tube. Storing colostrum at warm ambient temperatures resulted in the most rapid increase in bacteria counts, followed by intermediate rates of growth in nonpreserved refrigerated samples or preserved samples stored at ambient temperature. The most effective treatment studied was the use of potassium sorbate preservative in refrigerated samples, for which total plate count and total coliform counts dropped significantly and then remained constant during the 96-h storage period.


Synergy between cilofungin and amphotericin B in a murine model of candidiasis.
The efficacies of cilofungin and amphotericin B separately and together in mice with disseminated candidiasis were studied. Male CD-1 mice (age, 5 weeks) were infected intravenously with 3 X 10(5) CFU of Candida albicans. At 4 days postinfection, intraperitoneal therapy was initiated and was continued for 14 days. Therapy groups included those given cilofungin at 6.25 or 62.5 mg/kg/day (given twice daily), amphotericin B at 0.625 mg/kg/day (given once daily), cilofungin at 6.25 mg/kg/day plus amphotericin B, and cilofungin at 62.5 mg/kg/day plus amphotericin B. Mice were observed through 30 days postinfection. All infected untreated mice died of infection between days 6 and 18. Eighty-five percent of mice receiving cilofungin at 6.25 mg/kg/day died between days 13 and 30. All other mice survived. Quantitative determination of the number of CFU of C. albicans in the spleens and kidneys of all survivors revealed that mice that had received both drugs had lower residual burdens of C. albicans. All mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B had sterile spleens, whereas 42 to 58% of mice given cilofungin or amphotericin B monotherapy had sterile spleens. All kidneys were infected in mice which had received cilofungin at 62.5 mg/kg/day or amphotericin B. Neither organ was infected in 17% of each group receiving combination therapy with cilofungin and amphotericin B. The number of CFU in the kidneys of mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B was lower than those cultured from mice treated with cilofungin at 62.5 mg/kg/day (P less than 0.001, Mann-Whitney) or amhotericin B (P less than 0.05). Modest synergy was noted in inhibition of the C. albicans isolate in vitro. Pharmacokinetic studies showed elevated levels of cilofungin but not amphotericin B in sera of mice treated with combined therapy compared with those in mice given monotherapy. No overt toxicity was evident with any regimen. The mechanism of increased efficacy may be altered cilofungin distribution, excretion, or metabolism; antifungal synergy; or both. These results indicate that concurrent cilofungin-amphotericin B therapy has synergistic or additive efficacy in vivo.


Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse.
The mitochondrial network within cells is mediated by fission and fusion processes. We investigated the expression of the proteins responsible for these events during conditions of altered oxidative capacity. With chronic contractile activity, the mitochondrial reticulum increased in size, along with concomitant increases in the fusion proteins Opa1 and Mfn2 (by 36% and 53%; P < 0.05). When we induced muscle disuse through denervation for 7 days, fragmented mitochondria were observed, along with significant decreases in the expression of Mfn2 and Opa1 (by 84% and 70%). To assess the effects of aging on mitochondrial morphology, young (5 month) and aged (35 month) Fisher 344 Brown Norway rats were used. Aged animals also possessed smaller mitochondria and displayed increased levels of fission proteins. Chronic muscle use increases the ratio of fusion:fission proteins, leading to reticular mitochondria, whereas muscle disuse and aging result in a decrease in this ratio, culminating in fragmented organelles.


A sixteen year survey of Canadian contact lens prescribing.
To understand long-term contact lens prescribing habits of Canadian optometrists. One thousand optometrists were surveyed annually from 2000 to 2015. Information was requested on the first ten patients examined after receiving the survey. Over the 16-year survey period, 1987 optometrists provided information on 19,143 patients. Mean age of the patients was 32.7±14.4years. Ratio of females to males was 2:1, the ratio of new fits to refits was 2:3. Soft contact lenses represented 94.5% of all fits. Rigid lenses were more often used as a refit compared to a new fit. Over the 16 years, market share for silicone hydrogel materials grew from 0% to 69.6%, mid-water content materials declined from 75.7% to 14.1%. The multifocal market share grew at the expense of spherical designs, with no change in toric lens fitting. Monthly soft lens replacement remained the preferred option at 48.2%, followed by daily disposable at 40.8%; two-weekly replacement declined to less than10% of patients by 2015. Extended wear was likely used to refit and only to a small proportion of wearers, representing 2.6% of SCL by 2015. The lens care system of choice throughout the period was multipurpose solutions, although the proportion for peroxide systems more than doubled by 2015 from 9.6%, to 21.1%. Over the 16-year period, SCL material preference changed to silicone hydrogels with monthly replacement being preferred; daily disposables replacing 2-weekly as the alternate. Lens care preference continued to be multipurpose solutions. Rigid lenses appear to be sustained for specialist fitting.


"Tumour marker guided" salvage treatment prolongs survival of breast cancer patients: final report of a 7-year study.
Randomised trials on breast cancer showed no significant benefit from post-operative follow-up with clinical and/or conventional radiological means. We hypothesised that carcinoembryonic antigen (CEA), tissue polipeptyde antigen (TPA), breast cancer associated antigen 115 D8/DF3 (CA15.3) tumour marker panel is sensitive enough for significantly anticipating salvage treatment and prolonging survival of relapsing breast cancer patients. From October 1981 to May 1999, 68 (62%) of 109 patients with distant metastases were recruited. Thirty-six (53%) received salvage treatment at the time of significant increase in one or more components of CEA-TPA-CA15.3 tumour marker panel and negative instrumental examinations ("tumour marker guided" treatment) and 32 (47%) were treated only after radiological confirmation of metastases (conventional treatment). The prognostic factors of the two groups did not show any statistically significant difference. The time from one or more tumour marker increase to clear clinical and/or radiological signs of distant metastases (lead time) was significantly prolonged in the 36 patients with "tumour marker guided" treatment (17.3 +/- 13.1 vs. 2.9 +/- 2.9 months, P < 0.001, Wilcoxon test) as well as the survival curves from salvage therapy and from mastectomy (the proportion of survivors was: at 36 months from salvage therapy 28% vs. 9%, P = 0.0094; at 84 months from mastectomy 42% vs. 19%, P = 0.0017). The multivariate Cox analysis showed that time from mastectomy to tumour marker increase and "tumour marker guided" salvage treatment were the only significantly different variables (P = 0.00001 and 0.005, respectively). These data point out that "tumour marker guided" salvage treatment significantly prolongs disease-free and overall survivals of relapsing responsive patients.


Induced deletions within a cluster of resistance genes in the mec region of the chromosome of Staphylococcus aureus.
Variants of a methicillin-resistant Staphylococcus aureus showing loss of or reduced resistance to the antibiotic were isolated at frequencies of 0.1-100% from cultures which had been starved, grown at elevated temperature, or given small doses of UV radiation. Three types of variant were identified on the basis of population distribution of resistance to the antibiotic, and field-inversion gel electrophoresis of digests of the chromosome cut with the rare-cutting restriction endonuclease SmaI. Type I variants are methicillin-sensitive and have a deletion in the mec region of the chromosome. Type II variants have reduced methicillin resistance and rearranged DNA elsewhere in the chromosome. Type II variants show reduced methicillin resistance and no detectable change in the chromosome. Type I deletions were mapped using cloned fragments from the mec region. In 13 of the 16 independently isolated deletion mutants, one of the deletion endpoints appears to correlate with the positions of insertion sequences or transposons found in this region of the staphylococcal chromosome.


N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1).
Expression of the CDK inhibitor p21(Cip1) is tightly regulated by signals that control cell division. p21 is an unstable protein that is degraded by the proteasome; however, the pathway that leads to proteasomal degradation of p21 has proven to be enigmatic. An important issue is whether proteasomal degradation of p21 occurs independently of ubiquitylation or, alternatively, whether ubiquitylation on its N terminus is crucial. We resolve this uncertainty by showing that endogenous cellular p21 is completely acetylated at its amino terminus and is therefore not a substrate for N-ubiquitylation. We further show that inactivation of essential components of the ubiquitylation machinery does not directly impact endogenous p21 degradation. Our results underscore the importance of N-acetylation in restricting N-ubiquitylation and show, in particular, that ubiquitylation of endogenous p21 either at internal lysines or on the N terminus is unlikely to control its degradation by the proteasome.


A new lignan glycoside from Astragalus yunnanensis.
A new lignan glycoside, astrayunoside A (1), along with eight known compounds (2-9), were obtained from the methanol extract of roots of Astragalus yunnanensis. All the compounds were obtained from A. yunnanensis for the first time. Their structures were elucidated by extensive spectroscopic analysis (1D and 2D-NMR, MS, UV, CD, and IR). The weak antibacterial activities of the crude extracts of A. yunnanensis against Staphyloccocus aureus, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Shigella dysenteriae, Salmonella typhi H901, Candida albicans, Streptococcus mutans, and Actinomyces viscosus were observed.


Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model.
Consumers are increasingly turning to plant-based complementary and alternative medicines to treat hypercholesterolemia. Many of these treatments are untested and their efficacy is unknown. This multitude of potential remedies necessitates a model system amenable to testing large numbers of organisms that maintains similarity to humans in both mode of drug administration and overall physiology. Here we develop the larval zebrafish (4-30 days post fertilization) as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model. Larval zebrafish were fed high cholesterol diets infused with fluorescent sterols and phytomedicines. Plants were ground with mortar and pestle into a fine powder before addition to food. Fluorescent sterols were utilized to optically quantify relative difference in intravascular cholesterol levels between groups of fish. We utilized the Zeiss 7-Live Duo high-speed confocal platform in order to both quantify intravascular sterol fluorescence and to capture video of the heart beat for determination of cardiac output. In this investigation we developed and utilized a larval zebrafish model to investigate dietary plant-based intervention of the pathophysiology of hypercholesterolemia. We found BODIPY-cholesterol effectively labels diet-introduced intravascular cholesterol levels (P < 0.05, Student's t-test). We also established that zebrafish cardiac output declines as cholesterol dose increases (difference between 0.1% and 8% (w/w) high cholesterol diet-treated cardiac output significant at P < 0.05, 1-way ANOVA). Using this model, we found hawthorn leaves and flowers significantly reduce intravascular cholesterol levels (P < 0.05, 1-way ANOVA) and interact with cholesterol to impact cardiac output in hypercholesterolemic fish (2-way ANOVA, P < 0.05 for interaction effect). The results of this study demonstrate that the larval zebrafish has the potential to become a powerful model to test plant based dietary intervention of hypercholesterolemia. Using this model we have shown that hawthorn leaves and flowers have the potential to affect cardiac output as well as intravascular cholesterol levels. Further, our observation that hawthorn leaves and flowers interact with cholesterol to impact cardiac output indicates that the physiological effects of hawthorn may depend on diet.


Ectopic expression of wheat expansin gene TaEXPA2 improved the salt tolerance of transgenic tobacco by regulating Na+ /K+ and antioxidant competence.
High salinity is one of the most serious environmental stresses that limit crop growth. Expansins are cell wall proteins that regulate plant development and abiotic stress tolerance by mediating cell wall expansion. We studied the function of a wheat expansin gene, TaEXPA2, in salt stress tolerance by overexpressing it in tobacco. Overexpression of TaEXPA2 enhanced the salt stress tolerance of transgenic tobacco plants as indicated by the presence of higher germination rates, longer root length, more lateral roots, higher survival rates and more green leaves under salt stress than in the wild type (WT). Further, when leaf disks of WT plants were incubated in cell wall protein extracts from the transgenic tobacco plants, their chlorophyll content was higher under salt stress, and this improvement from TaEXPA2 overexpression in transgenic tobacco was inhibited by TaEXPA2 protein antibody. The water status of transgenic tobacco plants was improved, perhaps by the accumulation of osmolytes such as proline and soluble sugar. TaEXPA2-overexpressing tobacco lines exhibited lower Na+ but higher K+ accumulation than WT plants. Antioxidant competence increased in the transgenic plants because of the increased activity of antioxidant enzymes. TaEXPA2 protein abundance in wheat was induced by NaCl, and ABA signaling was involved. Gene expression regulation was involved in the enhanced salt stress tolerance of the TaEXPA2 transgenic plants. Our results suggest that TaEXPA2 overexpression confers salt stress tolerance on the transgenic plants, and this is associated with improved water status, Na+ /K+ homeostasis, and antioxidant competence. ABA signaling participates in TaEXPA2-regulated salt stress tolerance.


Inosine monophosphate dehydrogenase expression: transcriptional regulation of the type I and type II genes.
Inosine 5'-monophosphate dehydrogenase (IMPDH) is an essential rate-limiting enzyme in the de novo guanine nucleotide synthetic pathway that catalyzes the conversion of IMP to XMP. Enzyme activity is accounted for by the expression of two distinct but closely related genes termed IMPDH I and II. Increased IMPDH activity has been linked to both cellular proliferation and neoplastic transformation and generally ascribed to an increase in the expression of the type II gene. We have characterized the type I and type II genes and identified elements important in the transcriptional regulation of both genes. The type II IMPDH gene contains a 466 bp 5' flanking region spanning the translation start site that contains several transcription factor binding sites and mediates increased transcription of a CAT reporter gene in peripheral blood T lymphocytes when these cells are induced to proliferate. The single functional IMPDH type I gene contains exon-intron boundaries and exon structures that are nearly identical to those in the type II gene. In contrast to the type II gene, however, it contains two putative promoter sites, each with the potential for transcriptional regulation. We conclude that these two genes most probably arose from an early gene duplication event and that their highly conserved structures and differential regulation at the transcriptional level argue strongly for a significant role for each gene in cellular metabolism, growth, and differentiation.


Reproducibility of Resting State Connectivity in Patients with Stable Multiple Sclerosis.
Given increasing efforts to use resting-state fMRI (rfMRI) as a biomarker of disease progression in multiple sclerosis (MS) we here explored the reproducibility of longitudinal rfMRI over three months in patients with clinically and radiologically stable MS. To pursue this aim, two approaches were applied in nine rfMRI networks: First, the intraclass correlation coefficient (ICC 3,1) was assessed for the mean functional connectivity maps across the entire network and a region of interest (ROI). Second, the ratio of overlap between Z-thresholded connectivity maps for each network was assessed. We quantified between-session functional reproducibility of rfMRI for 20 patients with stable MS and 14 healthy controls (HC). Nine rfMRI networks (RSNs) were examined at baseline and after 3 months of follow-up: three visual RSNs, the default-mode network, sensorimotor-, auditory-, executive control, and the left and right fronto-parietal RSN. ROI analyses were constrained to thresholded overlap masks for each individual (Z>0) at baseline and follow-up.In both stable MS and HC mean functional connectivity across the entire network did not reach acceptable ICCs for several networks (ICC<0.40) but we found a high reproducibility of ROI ICCs and of the ratio of overlap. ROI ICCs of all nine networks were between 0.98 and 0.99 for HC and ranged from 0.88 to 0.99 in patients with MS, respectively. The ratio of overlap for all networks was similar for both groups, ranging from 0.60 to 0.75.Our findings attest to a high reproducibility of rfMRI networks not only in HC but also in patients with stable MS when applying ROI analysis. This supports the utility of rfMRI to monitor functional changes related to disease progression or therapeutic interventions in MS.


Fever management: Evidence vs current practice.
Fever is a very common complaint in children and is the single most common non-trauma-related reason for a visit to the emergency department. Parents are concerned about fever and it's potential complications. The biological value of fever (i.e., whether it is beneficial or harmful) is disputed and it is being vigorously treated with the belief of preventing complications such as brain injury and febrile seizures. The practice of alternating antipyretics has become widespread at home and on paediatric wards without supporting scientific evidence. There is still a significant contrast between the current concept and practice, and the scientific evidence. Why is that the case in such a common complaint like fever The article will discuss the significant contrast between the current concepts and practice of fever management on one hand, and the scientific evidence against such concepts and practice.


Virus-specific spatial differences in the interference with silencing of the chs-A gene in non-transgenic petunia.
Potyviruses, such as potato virus Y and tobacco etch virus, as well as cucumber mosaic cucumovirus, interfere with post-transcriptional gene silencing (PTGS). When RedStar-type Petunia hybrida cultivars, whose flowers have alternating white and pigmented sectors, were infected with these viruses, each virus induced a different pattern of restoration of floral anthocyanin pigmentation. Local reversion to coloured phenotypes in the white sectors, which occurred through interference with PTGS of the chalcone synthase A (chs-A) gene, was correlated with locally increased levels of chs-A mRNA and virus concentration. Our results show that virus infection can interfere with PTGS of a native plant gene, and that this can have profound effects on symptom expression.


A 10-year experience with laparoscopic gastric banding for morbid obesity: high long-term complication and failure rates.
Since its introduction about 10 years ago, and because of its encouraging early results regarding weight loss and morbidity, laparoscopic gastric banding (LGB) has been considered by many as the treatment of choice for morbid obesity. Few long-term studies have been published. We present our results after up to 8 years (mean 74 months) of follow-up. Prospective data of patients who had LGB have been collected since 1995, with exclusion of the first 30 patients (learning curve). Major late complications are defined as those requiring band removal (major reoperation), with or without conversion to another procedure. Failure is defined as an excess weight loss (EWL) of <25%, or major reoperation. Between June 1997 and June 2003, LGB was performed in 317 patients, 43 men and 274 women. Mean age was 38 years (19-69), mean weight was 119 kg (79-179), and mean BMI was 43.5 kg/m(2) (34-78). 97.8% of the patients were available for follow-up after 3 years, 88.2% after 5 years, and 81.5% after 7 years. Overall, 105 (33.1%) of the patients developed late complications, including band erosion in 9.5%, pouch dilatation/slippage in 6.3%, and catheter- or port-related problems in 7.6%. Major reoperation was required in 21.7% of the patients. The mean EWL at 5 years was 58.5% in patients with the band still in place. The failure rate increased from 13.2% after 18 months to 23.8% at 3, 31.5% at 5, and 36.9% at 7 years. LGB appeared promising during the first few years after its introduction, but results worsen over time, despite improvements in the operative technique and material. Only about 60% of the patients without major complication maintain an acceptable EWL in the long term. Each year adds 3-4% to the major complication rate, which contributes to the total failure rate. With a nearly 40% 5-year failure rate, and a 43% 7-year success rate (EWL >50%), LGB should no longer be considered as the procedure of choice for obesity. Until reliable selection criteria for patients at low risk for long-term complications are developed, other longer lasting procedures should be used.


Lipid transfer protein cross-reactivity assessed in vivo and in vitro in the office: pros and cons.
Few studies analyze cross-reactivity between lipid transfer proteins (LTP) from a large spectrum of botanically unrelated plant-derived foods using routine diagnostic tests. To assess the clinical usefulness of currently available in vivo and in vitro tests in LTP-hypersensitive patients. An in vitro and in vivo study was performed of 15 peach-allergic adults monosensitized to LTP in order to analyze their allergy and hypersensitivity to apple, hazelnut, walnut, peanut, soybean, lentil, maize, celery, carrot, banana, melon, tomato, kiwi, buckwheat, and sunflower, poppy, mustard, and sesame seeds. The study revealed that 8, 7, 10, 5, 3, 2, 1, 1, and 1 patients were allergic to apple, hazelnut, walnut, peanut, tomato, kiwi, melon, lentil, and maize, respectively. Immunoglobulin (Ig) E levels for peach were strongly associated with the total number of offending foods other than peach and with levels of IgE specific for all the study foods except carrot. Both in vivo and in vitro tests showed excellent sensitivity and negative predictive value, but poor specificity and positive predictive value. Sensitized but tolerant patients showed lower IgE levels than those with a history of local or systemic symptoms, although the difference between the 3 subsets was not statistically significant. This study confirms that peach is the primary sensitizer to LTP and that the level of IgE to peach LTP is the main factor associated with cross-reactivity (and clinical allergy) to non-Rosaceae foods. Clinically irrelevant sensitization is common in LTP-hypersensitive patients, and positive in vivo and/or in vitro test results are of little help in detecting potential clinical reactors.


Sex-Dependent Differences in Physical Exercise-Mediated Cognitive Recovery Following Middle Cerebral Artery Occlusion in Aged Rats.
Stroke remains a leading cause of death and disability in the United States. No current treatments exist to promote cognitive recovery in survivors of stroke. A previous study from our laboratory determined that an acute bout of forced treadmill exercise was able to promote cognitive recovery in 3 month old male rats after middle cerebral artery occlusion (MCAo). In this study, we tested the hypothesis that 6 days of intense acute bout of forced treadmill exercise (physical exercise - PE) promotes cognitive recovery in 11-14 month old male rats. We determined that PE was able to ameliorate cognitive deficits as determined by contextual fear conditioning. Additionally, we also tested the hypothesis that PE promotes cognitive recovery in 11-13 month old reproductive senescent female rats. In contrast to males, the same intensity of exercise that decrease cognitive deficits in males was not able to promote cognitive recovery in female rats. Additionally, we determined that exercise did not lessen infarct volume in both male and female rats. There are many factors that contribute to higher stroke mortality and morbidities in women and thus, future studies will investigate the effects of PE in aged female rats to identify sex differences.


Knowledge and attitudes regarding pain management among nurses in Hong Kong medical units.
To investigate knowledge levels and attitudes regarding pain management among nurses working in medical units in Hong Kong and factors that might influence their knowledge and attitudes. Pain, a common symptom for patients in medical units, can be relieved by effective pain management. Nurses have a vital role in implementing pain management effectively and must, therefore, have a solid foundation of knowledge and a positive attitude towards pain management. Cross-sectional study. A self-administered survey including demographics and the nurses' knowledge and attitudes survey regarding pain-Chinese version (NKASRP-C) was completed by 143 nurses working at medical units in a public hospital. Descriptive statistics and stepwise regression were used in the data analysis. A deficit in knowledge and attitudes related to pain management was prominent (percentage of total score = 47.72, range = 20-76%). Although nurses had developed appropriate attitudes towards pain management, discrepancies between practice and attitudes existed. Those with a higher percentage of correct scores in NKASRP-C had longer clinical working experience and applied knowledge of pain to their daily work. The findings of this study, identifying problems of inadequate knowledge and inappropriate attitudes regarding pain management, are of concern. A better understanding of the factors that affect such knowledge and attitudes and of the discrepancy between attitudes and practice, can provide useful information to be included in education programmes for nurses and to inform policy on the provision of pain management.


Application Research of Artificial Intelligence Screening System for Diabetic Retinopathy.
According to the latest data from the Bureau of Disease Control and Prevention of the National Health and Family Planning Commission, China currently has 199.6 million diabetic patients and has become the world's largest country with diabetes. The prevalence rate is as high as 14.3%, which is much higher than the world average of 5.8%. The primary-level ophthalmic screening service is one of the important tasks to improve primary-level medical services, and the corresponding ophthalmic imaging diagnosis technology is an important support for primary-level medical and health services. Therefore, it is very necessary for us to study the application of artificial intelligence image recognition technology for diabetic retinopathy under the medical consortium mode and to study the precise initial diagnosis, precise referral, and precise follow-up of diabetic retina under the medical conjoined mode, so as to better promote the transformation of the ophthalmology primary service model. Based on this background, in this article, we have proposed and carried out the following solution: (1) diabetes data collation. Based on medical artificial intelligence technology, this paper collected 2,265 electronic medical records from an eye hospital in Ningbo and selected 2,000 qualified medical records for data integration and preprocessing. The contents of electronic medical records mainly include age, gender, and examination records. (2) Establish diabetic retinopathy diagnosis model based on neural network algorithm. This article first uses the classic algorithm of BP neural network for modeling, chooses the Levenberg-Marquardt method as the training function, and selects 10 hidden layer units through comparison experiments. After that, ophthalmologists assessed 80 sets of test results and determined the right diagnosis rate. Finally, this article compares and analyzes the accuracy of the two routes in 80 tests.


Cationic transfection lipids in gene therapy: successes, set-backs, challenges and promises.
The clinical success of gene therapy is critically dependent on the development of efficient and safe gene delivery reagents, popularly known as "Transfection Vectors". The transfection vectors commonly used in gene therapy are mainly of two types: viral and non-viral. The efficiencies of viral transfection vectors are, in general, superior to their non-viral counterparts. However, the myriads of potentially adverse immunogenic aftermaths associated with the use of viral vectors are increasingly making the non-viral gene delivery reagents as the vectors of choice. Among the existing arsenal of non-viral gene delivery reagents, the distinct advantages associated with the use of cationic transfection lipids include their: (a) robust manufacture; (b) ease in handling & preparation techniques; (c) ability to inject large lipid:DNA complexes and (d) low immunogenic response. The present review will highlight the successes, set-backs, challenges and future promises of cationic transfection lipids in non-viral gene therapy.