Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan.
Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities.


The cytostatic and cytotoxic effects of oridonin (Rubescenin), a diterpenoid from Rabdosia rubescens, on tumor cells of different lineage.
Rabdosia rubescens is a herbal medicine used to treat esophageal cancer in China. In this study, the sesquiterpene oridonin, an isoprenoid, was isolated from Rabdosia rubescens. Mass spectroscopy and carbon 13 NMR spectroscopy were used to identify the structure of the purified compound. It was then evaluated for biological activity against human cell lines derived from prostate (DU-145, LNCaP), breast (MCF-7), and ovarian (A2780 and PTX10) cancers. Oridonin exhibited anti-proliferative activity toward all cancer cell lines tested, with an IC50 estimated by the MTT cell viability assay ranging from 5.8+/-2.3 to 11.72+/-4.8 microM. Flow cytometric analysis demonstrated that oridonin induced a G1 phase arrest in androgen receptor-positive LNCaP cells containing wt p53, while it blocked the cell cycle at G2 and M phases in androgen receptor-negative DU-145 cells with mutated p53; the arrest in M was verified by examination of cell morphology and by the increased frequency of cells with Ser-10 phosphorylated histone H3. The increased incidence of apoptosis, identified by characteristic changes in cell morphology, was seen in tumor lines treated with oridonin. Notably, at concentrations that induced apoptosis among tumor cells, oridonin failed to induce apoptosis in cultures of normal human fibroblasts. Western blot analysis was used to determine the protein expression of cancer suppressor genes, p53 (wt) and Bax, and the proto-oncogene, Bcl-2 in LNCaP cells following treatment with oridonin. Oridonin up-regulated p53 and Bax and down-regulated Bcl-2 expression in a dose-dependent manner. To further explore the possible interaction between oridonin and DNA, its absorption spectrum was measured in the presence and absence of double stranded (ds) DNA. Spectral shifts and an increase in absorption band intensity were observed indicating interaction of oridonin with DNA bases. The nature of the binding is not clear at present though no evidence of histone H2AX phosphorylation on Ser-139 was apparent in DU-145 cells treated with oridonin that would indicate the induction of ds DNA breaks. In conclusion, oridonin inhibits cancer cell growth in a cell cycle specific manner and shifts the balance between pro- and anti-apoptotic proteins in favor of apoptosis. The present data suggest that further studies are warranted to assess the potential of oridonin in cancer prevention and/or treatment.


Unconventional, chemically stable, and soluble two-dimensional angular polycyclic aromatic hydrocarbons: from molecular design to device applications.
Polycyclic aromatic hydrocarbons (PAHs), consisting of laterally fused benzene rings, are among the most widely studied small-molecule organic semiconductors, with potential applications in organic field-effect transistors (OFETs) and organic photovoltaics (OPVs). Linear acenes, including tetracene, pentacene, and their derivatives, have received particular attention due to the synthetic flexibility in tuning their chemical structure and properties and to their high device performance. Unfortunately, longer acenes, which could exhibit even better performance, are susceptible to oxidation, photodegradation, and, in solar cells which contain fullerenes, Diels-Alder reactions. This Account highlights recent advances in the molecular design of two-dimensional (2-D) PAHs that combine device performance with environmental stability. New synthetic techniques have been developed to create stable PAHs that extend conjugation in two dimensions. The stability of these novel compounds is consistent with Clar's sextet rule as the 2-D PAHs have greater numbers of sextets in their ground-state configuration than their linear analogues. The ionization potentials (IPs) of nonlinear acenes decrease more slowly with annellation in comparison to their linear counterparts. As a result, 2-D bistetracene derivatives that are composed of eight fused benzene rings are measured to be about 200 times more stable in chlorinated organic solvents than pentacene derivatives with only five fused rings. Single crystals of the bistetracene derivatives have hole mobilities, measured in OFET configuration, up to 6.1 cm(2) V(-1) s(-1), with remarkable Ion/Ioff ratios of 10(7). The density functional theory (DFT) calculations can provide insight into the electronic structures at both molecular and material levels and to evaluate the main charge-transport parameters. The 2-D acenes with large aspect ratios and appropriate substituents have the potential to provide favorable interstack electronic interactions, and correspondingly high carrier mobilities. In stark contrast to the 1-D acenes that form mono- and bis-adducts with fullerenes, 2-D PAHs show less reactivity with fullerenes. The geometry of 2-D PAHs plays a crucial role in determining both the barrier and the adduct stability. The reactivity and stability of the 2-D PAHs with regard to Diels-Alder reactions at different reactive sites were explained via DFT calculations of the reaction kinetics and of thermodynamics of reactions and simple Hückel molecular orbital considerations. Also, because of their increased stability in the presence of fullerenes, these compounds have been successfully used in OPVs. The small-molecule semiconductors highlighted in this Account exhibit good charge-transport properties, comparable to those of traditional linear acenes, while being much more environmentally stable. These features have made these 2-D PAHs excellent molecules for fundamental research and device applications.


Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas.
The insulin-like growth factors I and II (IGF-I and -II) are proteins which stimulate cell proliferation and are important in normal human growth and development. They are coded for by separate genes and bind to specific cell surface receptors, eliciting a mitogenic response. IGFs are secreted by several cell lines derived from adult tumors. We have examined a number of human adult tumors for IGF messenger RNA (mRNA) expression and found IGF-II mRNA levels were consistently elevated in two types, colon carcinoma and liposarcoma. Adult colonic mucosa contains low levels of IGF-I and -II mRNA while several colon tumors, particularly of rectal and rectosigmoid origin, contained significantly elevated levels of IGF-II message. Over 90% of liposarcomas examined contained greatly elevated levels of IGF-II mRNA while control tissue (adipose) contained very low or undetectable IGF mRNA levels. Many of these tumors also contained elevated IGF-I mRNA levels. Northern analysis of these RNAs revealed differences in the abundance and sizes of IGF transcripts compared to other normal and malignant tissues known to express IGF.


Application of a 3D custom printed patient specific spinal implant for C1/2 arthrodesis.
The study aims to describe a three-dimensional printed (3DP) posterior fixation implant used for C1/C2 fusion in a 65-year-old female. Spinal fusion remains a common intervention for a range of spinal pathologies including degenerative disc and facet disease when conservative methods are unsuccessful. However, fusion devices are not always entirely efficacious in providing the desired fixation, and surgeons rely on 'off the shelf' implants which may not provide an anatomical fit to address the particular pathology. 3DP refers to a process where three-dimensional objects are created through successive layering of material, so called 'additive manufacturing'. Although this technology enables accurate fabrication of patient-specific orthopaedic and spinal implants, literature on its utilization in this regard is rare. A 65-year-old female, with severe facet arthropathy at the C1/C2 level, osteophyte formation and impingement of the exiting C2 nerve root underwent a C1/C2 posterior fusion and rhizolysis of the C2 nerve roots. A custom posterior fixation implant was designed and on-laid over the C2 spinous process and lamina, with screw holes made to a depth and angulation that was pre-calculated based on the preoperative CT based 3D modelling. The patient had an uneventful recovery and reported a significant reduction in occipital neuralgia and sub-occipital pain and 2-month follow-up. We report the first case of a customized 3DP spinal prosthesis for posterior C1/C2 fusion. The implant added significant value reducing the overall time of the procedure, and safety with a reduced risk of neurovascular compromise.


Antioxidant therapies for traumatic brain injury.
Free radical-induced oxidative damage reactions, and membrane lipid peroxidation (LP), in particular, are among the best validated secondary injury mechanisms in preclinical traumatic brain injury (TBI) models. In addition to the disruption of the membrane phospholipid architecture, LP results in the formation of cytotoxic aldehyde-containing products that bind to cellular proteins and impair their normal functions. This article reviews the progress of the past three decades in regard to the preclinical discovery and attempted clinical development of antioxidant drugs designed to inhibit free radical-induced LP and its neurotoxic consequences via different mechanisms including the O(2)(*-) scavenger superoxide dismutase and the lipid peroxidation inhibitor tirilazad. In addition, various other antioxidant agents that have been shown to have efficacy in preclinical TBI models are briefly presented, such as the LP inhibitors U83836E, resveratrol, curcumin, OPC-14177, and lipoic acid; the iron chelator deferoxamine and the nitroxide-containing antioxidants, such as alpha-phenyl-tert-butyl nitrone and tempol. A relatively new antioxidant mechanistic strategy for acute TBI is aimed at the scavenging of aldehydic LP byproducts that are highly neurotoxic with "carbonyl scavenging" compounds. Finally, it is proposed that the most effective approach to interrupt posttraumatic oxidative brain damage after TBI might involve the combined treatment with mechanistically complementary antioxidants that simultaneously scavenge LP-initiating free radicals, inhibit LP propagation, and lastly remove neurotoxic LP byproducts.


Mouse microsatellites from a flow-sorted 4:6 Robertsonian chromosome.
Twenty microsatellites were generated from a previously characterized lambda gt10 library containing C57BL/6J mouse DNA from a flow-sorted 4:6 Robertsonian chromosome. These sequences were analyzed for size variation between different strains of mice with the polymerase chain reaction (PCR) and mapped by use of either strain distribution patterns (SDPs) in recombinant inbred (RI) strains, or intra- and interspecific backcrosses. Eighty-five percent of the sequences showed allelic variations between different inbred strains of mice and the wild mouse, Mus spretus, and 70% were variant between inbred strains. Eight (62%) of the 13 repeats that have been mapped lie on Chromosomes (Chr) 4 and 6. This approach is an effective way of generating informative markers on specific chromosomes.


Proofreading of DNA polymerase eta-dependent replication errors.
Human DNA polymerase eta, the product of the skin cancer susceptibility gene XPV, bypasses UV photoproducts in template DNA that block synthesis by other DNA polymerases. Pol eta lacks an intrinsic proofreading exonuclease and copies DNA with low fidelity, such that pol eta errors could contribute to mutagenesis unless they are corrected. Here we provide evidence that pol eta can compete with other human polymerases during replication of duplex DNA, and in so doing it lowers replication fidelity. However, we show that pol eta has low processivity and extends mismatched primer termini less efficiently than matched termini. These properties could provide an opportunity for extrinsic exonuclease(s) to proofread pol eta-induced replication errors. When we tested this hypothesis during replication in human cell extracts, pol eta-induced replication infidelity was found to be modulated by changing the dNTP concentration and to be enhanced by adding dGMP to a replication reaction. Both effects are classical hallmarks of exonucleolytic proofreading. Thus, pol eta is ideally suited for its role in reducing UV-induced mutagenesis and skin cancer risk, in that its relaxed base selectivity may facilitate efficient bypass of UV photoproducts, while subsequent proofreading by extrinsic exonuclease(s) may reduce its mutagenic potential.


[Characteristics of intravenous drug users who share injection equipment in Catalonia (Spain)].
To estimate the prevalence of direct and indirect syringe sharing among intravenous drug users (IDUs) attending a harm reduction center in Catalonia (Spain) and to identify factors associated with risk behaviors. A cross-sectional study was conducted between 2008 and 2009 in harm reduction centers. Behavioral data were collected using anonymous questionnaires administered by trained interviewers. Of the 748 respondents, 31.5% had shared syringes at least once in the previous 6 months and 55.2% reported sharing injection paraphernalia (spoons, water, filters). A higher risk of syringe sharing was found among IDUs who injected daily (OR=1.5), injected cocaine (OR=1.6), had less than half their supply of syringes from a free source (OR=2.5), had an IDU sexual partner (OR=1.8) or who reported indirect sharing (OR=4.1). A higher risk of indirect sharing was found in respondents who had an illegal source of income (OR=1.5), injected daily (OR=1, 5), injected cocaine (OR=1.4), reported sharing syringes (OR=3.9), or who reported a previous overdose (OR=1.5). Despite the widespread use of harm reduction programs in Catalonia, a significant proportion of IDUs continue to practise injection-related risk behaviors. Further reductions in risk behaviors could be achieved by improving access to all sterile injecting equipment, especially among cocaine injectors and IDUs who inject frequently, and by including IDU sexual partners within the current network of harm reduction centers.


Comparison of Marlex and Gore-tex to repair abdominal wall defects in the rat.
Marlex and Gore-tex, two prosthetic materials used to close abdominal wounds, were compared with respect to strength and adhesion formation. A 2.5 X 3.5-cm full-thickness area of abdominal wall was excised in 32 CD rats. The defect was repaired using identically sized patches of Marlex or 1-mm Gore-tex, determined by alternate assignment, and sutured with continuous 4-0 Gore-tex. Adhesion formation was graded at necropsy and recorded photographically in each animal. The mean adhesion index (none = 0, maximal = 4) was 1.37 +/- 0.12 and 2.62 +/- 0.12 (mean +/- SEM) for Gore-tex and Marlex groups respectively (p less than 0.005, unpaired t-test). A template was used to fashion 2-cm coronal strips of abdominal wall for tensile-strength testing. The relative strengths were 2.67 +/- 0.14 and 3.02 +/- 0.16 kg/cm (mean +/- SEM) for the Gore-tex and Marlex groups respectively (NS). Histologically, there were more epithelioid giant cells and less collagen formation in the Gore-tex group. Abdominal wall reconstruction with Gore-tex resulted in wound strength equal to that of Marlex and fewer adhesions. Gore-tex is preferred when prosthetic material and viscera are in close proximity.


Interactions between glycolytic enzymes and components of the cytomatrix.
Evidence is provided that enzymes absorb to cellular structures in a wide range of tissues. In particular, the interactions between glycolytic enzymes and the microfilaments of the cytoplasm are described. The relevance of these interactions to the compartmentation of carbohydrate metabolism is discussed. Examples are given of the variations in degree of binding during alteration of tissue metabolism and, for individual glycolytic enzymes, during fetal development and differentiation. Overall, these data support the concept that metabolic activities in the cytoplasm have an organized structure. Just as the structural elements of the cytosolic compartment have evolved with the capacity to assemble and disassemble in response to the changing requirements of the organism, so the metabolic elements appear to have evolved a parallel system that provides for the appropriate positioning of an energy-producing sequence in relation to the specific, dynamic requirements of the cytoskeleton.


Skin manifestations of drug allergy.
Cutaneous adverse drug reactions range from mild to severe and from those localized only to skin to those associated with systemic disease. It is important to distinguish features of cutaneous drug reactions which help classify the underlying mechanism and likely prognosis as both of these influence management decisions, some of which necessarily have to be taken rapidly. Severe cutaneous reactions are generally T cell-mediated, yet this immunological process is frequently poorly understood and principles for identification of the culprit drug are different to those of IgE mediated allergic reactions. Furthermore, intervention in severe skin manifestations of drug allergy is frequently necessary. However, a substantial literature reports on success or otherwise of glucocorticoids, cyclophsphamide, ciclosporin, intravenous immunoglobulin and anti-tumour necrosis factor therapy for the treatment of toxic epidermal necrolysis without clear consensus. As well as reviewing the recommended supportive measures and evidence base for interventions, this review aims to provide a mechanistic overview relating to a proposed clinical classification to assist the assessment and management of these complex patients.


Facilitating classroom based interprofessional learning: a grounded theory study of university educators' perceptions of their role adequacy as facilitators.
The provision of inter professional learning (IPL) within undergraduate programmes is now well established within many Higher Education Institutions (HEIs). IPL aims to better equip nurses and other health professionals with effective collaborative working skills and knowledge to improve the quality of patient care. Although there is still ambiguity in relation to the optimum timing and method for delivering IPL, effective facilitation is seen as essential. This paper reports on a grounded theory study of university educators' perceptions of the knowledge and skills needed for their role adequacy as IPL facilitators. Data was collected using semi structured interviews with nine participants who were theoretically sampled from a range of professional backgrounds, with varied experiences of education and involvement in facilitating IPL. Constant comparative analysis was used to generate four data categories: creating and sustaining an IPL group culture through transformational IPL leadership (core category), readiness for IPL facilitation, drawing on past interprofessional learning and working experiences and role modelling an interprofessional approach. The grounded theory generated from this study, although propositional, suggests that role adequacy for IPL facilitation is dependent on facilitator engagement in a process of 'transformational interprofessional learning leadership' to create and sustain a group culture.


Complementary and alternative medicine use in dermatology in the United States.
Complementary and alternative medicine (CAM) has an increasing presence in dermatology. Complementary therapies have been studied in many skin diseases, including atopic dermatitis and psoriasis. This study sought to assess oral CAM use in dermatology relative to medicine as a whole in the United States, using the National Ambulatory Medical Care Survey. Variables studied include patient demographic characteristics, diagnoses, and CAM documented at the visits. A brief literature review of the top 5 CAM treatments unique to dermatology visits was performed. Most CAM users in both dermatology and medicine as a whole were female and white and were insured with private insurance or Medicare. Fish oil, glucosamine, glucosamine chondroitin, and omega-3 were the most common complementary supplements used in both samples. CAM use in dermatology appears to be part of a larger trend in medicine. Knowledge of common complementary therapies can help dermatologists navigate this expanding field.


Evaluation of the Amount of Root Canal Dentin Removed and Apical Transportation Occurrence after Instrumentation with ProTaper Next, OneShape, and EdgeFile Rotary Systems.
The aim of this study was to evaluate the amount of root canal dentin removed and apical transportation occurrence after instrumentation of mesiobuccal canals of maxillary molars with ProTaper Next (PTN [Dentsply Maillefer, Ballaigues, Switzerland]), OneShape (OS [MicroMega, Besançon, France]), and EdgeFile (EF [Edge Endo, Albuquerque, NM]) rotary systems. Twenty-seven mesiobuccal canals of maxillary molars were used. Canals were randomly divided into 3 groups for canal preparation: PTN, EF X3, or OS (n = 9 for each group). Micro-computed tomographic imaging was used to measure apical transportation (mm) and the volume of dentin removed (mm3). The amount of dentin removed was measured for the coronal portion and for the whole canal length. Superposition of pre- and postoperative cross-sectional apical slices were used to measure apical transportation at 1 mm from the apex; the differences were evaluated using the Kruskal-Wallis test and Wilcoxon analysis. The Spearman correlation coefficient was used to display the relationship between variables for each group. The significance level was set at P < .05. The percentages of the amount of dentin removed on the coronal portion and the amount removed for the whole canal length were statistically similar between groups (P > .05). The average amount of apical transportation for the PTN, OS, and EF X3 were 0.197, 0.263, and 0.218 mm, respectively. Statistically, there were no significant differences between the 3 rotary instruments for apical transportation. The amount of dentin removed for the coronal third portion and the whole canal length was similar for the PTN, OS, and EF X3 rotary instruments. Although there were differences in the sizes of apical enlargement, no apical transportation was observed in any of the instrumentation systems.


Phylogenetic analysis of LSU and SSU rDNA group I introns of lichen photobionts associated with the genera Xanthoria and Xanthomendoza (Teloschistaceae, lichenized Ascomycetes).
We studied group I introns in sterile cultures of selected groups of lichen photobionts, focusing on Trebouxia species associated with Xanthoria s. lat. (including Xanthomendoza spp.; lichen-forming ascomycetes). Group I introns were found inserted after position 798 (Escherichia coli numbering) in the large subunit (LSU) rRNA in representatives of the green algal genera Trebouxia and Asterochloris. The 798 intron was found in about 25% of Xanthoria photobionts including several reference strains obtained from algal culture collections. An alignment of LSU-encoded rDNA intron sequences revealed high similarity of these sequences allowing their phylogenetic analysis. The 798 group I intron phylogeny was largely congruent with a phylogeny of the Internal Transcribed Spacer Region (ITS), indicating that the insertion of the intron most likely occurred in the common ancestor of the genera Trebouxia and Asterochloris. The intron was vertically inherited in some taxa, but lost in others. The high sequence similarity of this intron to one found in Chlorella angustoellipsoidea suggests that the 798 intron was either present in the common ancestor of Trebouxiophyceae, or that its present distribution results from more recent horizontal transfers, followed by vertical inheritance and loss. Analysis of another group I intron shared by these photobionts at small subunit (SSU) position 1512 supports the hypothesis of repeated lateral transfers of this intron among some taxa, but loss among others. Our data confirm that the history of group I introns is characterized by repeated horizontal transfers, and suggests that some of these introns have ancient origins within Chlorophyta.


Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study.
The purpose of this study is to assess if diagnosis of type 2 diabetes affected health-related quality of life (HRQoL) among participants in the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study and changes with treatment or diabetes duration. 3,210 participants with pre-diabetes were randomized to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB). HRQoL was assessed using the SF-36 including: (1) 8 SF-36 subscales; (2) the physical component (PCS) and mental component summary (MCS) scores; and (3) the SF-6D. The sample was categorized by diabetes free versus diagnosed. For diagnosed subgroup, mean scores in the diabetes-free period, at 6 months, 2, 4 and 6 years post-diagnosis, were compared. PCS and SF-6D scores declined in all participants in all treatment arms (P < .001). MCS scores did not change significantly in any treatment arm regardless of diagnosis. ILS participants reported a greater decrease in PCS scores at 6 months post-diagnosis (P < .001) and a more rapid decline immediately post-diagnosis in SF-6D scores (P = .003) than the MET or PLB arms. ILS participants reported a significant decrease in the social functioning subscale at 6 months (P < .001) and two years (P < .001) post-diagnosis. Participants reported a decline in measures of overall health state (SF-6D) and overall physical HRQoL, whether or not they were diagnosed with diabetes during the study. There was no change in overall mental HRQoL. Participants in the ILS arm with diabetes reported a more significant decline in some HRQoL measures than those in the MET and PLB arms that developed diabetes.


Radish (Raphanus sativus) and Diabetes.
For more than three decades, various in vitro and in vivo studies have linked radishes with diabetes, though this link has not been discussed. This review systematically addresses and summarizes the effect of radishes on diabetes. We searched the Web of Science, PubMed, and EMBASE databases for English language articles from June 1987 through May 2017 using the key words "radish" and "diabetes," and the references from particular reports were also considered if relevant. In summary, radish has been identified as having antidiabetic effects, making it favorable for those with diabetic conditions. This may be due to its ability to enhance the antioxidant defense mechanism and reduce the accumulation of free radicals, affect hormonal-induced glucose hemostasis, promote glucose uptake and energy metabolism, and reduce glucose absorption in the intestine. However, this summary requires further confirmation in research in vivo studies and clinical trials.


Novel exploitation of a nuclear function by influenza virus: the cellular SF2/ASF splicing factor controls the amount of the essential viral M2 ion channel protein in infected cells.
We show that a cellular nuclear protein, the SR splicing factor SF2/ASF, controls the level of production of an essential influenza virus protein, the M2 ion channel protein. The M2 mRNA that encodes the ion channel protein is produced by alternative splicing of another viral mRNA, M1 mRNA. The production of M2 mRNA is controlled in two ways. First, a distal (stronger) 5' splice site in M1 mRNA is blocked by the complex of viral polymerase proteins synthesized during infection, allowing the cellular splicing machinery to switch to the proximal (weaker) M2 5' splice site. Second, utilization of the weak M2 5' splice site requires its activation by the cellular SF2/ASF protein. This activation is mediated by the binding of the SF2/ASF protein to a purine-rich splicing enhancer sequence that is located in the 3' exon of M1 mRNA. We demonstrate that activation of the M2 5' splice site is controlled by the SF2/ASF protein in vivo during influenza virus infection. Utilizing four cell lines that differ in their levels of production of the SF2/ASF protein, we show that during virus infection of these cell lines both M2 mRNA and the M2 ion channel protein are produced in amounts that are proportional to the different expression levels of the SF2/ASF protein.


Tobacco industry strategies undermine government tax policy: evidence from commercial data.
Taxation equitably reduces smoking, the leading cause of health inequalities. The tobacco industry (TI) can, however, undermine the public health gains realised from tobacco taxation through its pricing strategies. This study aims to examine contemporary TI pricing strategies in the UK and implications for tobacco tax policy. Review of commercial literature and longitudinal analysis of tobacco sales and price data. A high-income country with comprehensive tobacco control policies and high tobacco taxes (UK). 2009 to 2015 Nielsen Scantrak electronic point of sale systems data. Tobacco segmentation; monthly prices, sales volumes of and net revenue from roll-your-own (RYO) and factory-made (FM) cigarettes by segment; use of price-marking and pack sizes. The literature review and sales data concurred that both RYO and FM cigarettes were segmented by price. Despite regular tax increases, average real prices for the cheapest FM and RYO segments remained steady from 2013 while volumes grew. Low prices were maintained through reductions in the size of packs and price-marking. Each year, at the point the budget is implemented, the TI drops its revenue by up to 18 pence per pack, absorbing the tax increases (undershifting). Undershifting is most marked for the cheapest segments. The TI currently uses a variety of strategies to keep tobacco cheap. The implementation of standardised packaging will prevent small pack sizes and price-marking but further changes in tax policy are needed to minimise the TI's attempts to prevent sudden price increases.


14-3-3 is not essential for Raf-1 function: identification of Raf-1 proteins that are biologically activated in a 14-3-3- and Ras-independent manner.
Recent reports have demonstrated the in vivo association of Raf-1 with members of the 14-3-3 protein family. To address the significance of the Raf-1-14-3-3 interaction, we investigated the enzymatic activity and biological function of Raf-1 in the presence and absence of associated 14-3-3. The interaction between these two molecules was disrupted in vivo and in vitro with a combination of molecular and biochemical techniques. Biochemical studies demonstrated that the enzymatic activities of Raf-1 were equivalent in the presence and absence of 14-3-3. Furthermore, mixing of purified Raf-1 and 14-3-3 in vitro was not sufficient to activate Raf-1. With a molecular approach, Cys-165 and Cys-168 as well as Ser-259 were identified as residues of Raf-1 required for the interaction with 14-3-3. Cys-165 and Cys-168 are located within the conserved cysteine-rich region of the CR1 domain, and Ser-259 is a conserved site of serine phosphorylation found within the CR2 domain. Mutation of either Cys-165 and Cys-168 or Ser-259 prevented the stable interaction of Raf-1 with 14-3-3 in vivo. Consistent with the model in which a site of serine phosphorylation is involved in the Raf-1-14-3-3 interaction, dephosphorylated Raf-1 was unable to associate with 14-3-3 in vitro. Phosphorylation may represent a general mechanism mediating 14-3-3 binding, because dephosphorylation of the Bcr kinase (known to interact with 14-3-3) also eliminated its association with 14-3-3. Finally, mutant Raf-1 proteins unable to stably interact with 14-3-3 exhibited enhanced enzymatic activity in human 293 cells and Xenopus oocytes and were biologically activated, as demonstrated by their ability to induced meiotic maturation of Xenopus oocytes. However, in contrast to wild-type Raf-1, activation of these mutants was independent of Ras. Our results therefore indicate that interaction with 14-3-3 is not essential for Raf-1 function.


No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.
Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years. In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50-2.31; P < .001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83-1.58; P = .41). There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens.


Prevalence and dynamics of clinically significant bacterial contaminants in herbal medicines sold in East Africa from 2000 to 2020: a systematic review and meta-analysis.
Infectious diseases remain a leading cause of mortality and morbidity around the world, and those caused by bacteria are common in the East African region. In this region, trade and consumption of herbal medicine has been expanding in the recent decades. Herbal medicines may be contaminated with pathogenic bacteria; however, there is limited information due to fragmented studies in East Africa. In this meta-analysis, we critically analyzed original research related to the incidence of pathogenic bacterial contaminants of HM in the East African region since 2000. The aim was to create a comprehensive understanding of the extent and dynamics of bacterial contamination in HM, to guide future research and concerted public health protection in the region. The study was conducted according to the standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. We searched and evaluated published articles from eleven electronic databases (Google Scholar, PubMed, HerbMed, MEDLINE, Science Direct, Scifinder Scholar, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, Biological Abstracts and Commonwealth Agricultural Bureau Abstracts). Prevalences of different bacterial species, Cochran's Q test, and the I2 statistic for heterogeneity were evaluated using a software called MedCalcs. Random and fixed effects models were used to determine the pooled prevalence of clinically significant bacteria from studies which were included in this meta-analysis. The potential sources of heterogeneity were examined through sensitivity analysis, sub-group analysis, and meta-regression at 95% level of significance. Fourteen studies met our inclusion criteria. Overall, the studies were highly heterogeneous (I2 = 98.48%) and there was no evidence of publication bias. Escherichia coli was the most prevalent contaminant. Salmonella spp. and Shigella spp. were the most frequently reported primary pathogens with pooled prevalence of 10.4% and 6.3%, respectively. Our findings are in tandem with recent systematic reviews conducted in Europe and Asia, but are in discrepancy with the reviews recently conducted in southern Africa. The East African herbal medicine industry poses considerable health risks to communities through dissemination of clinically significant bacteria. Presence of enteric bacterial contaminants indicates possible fecal pollution of herbal medicine region-wide. Adequate research pertaining to microbial safety of herbal medicine in the East African countries remains highly desired. The latter will enable establishment of strong, region-wide herbal safety mechanisms in order to support comprehensive public health protection in East Africa.


Revisiting the role of antiandrogen strategies in ovarian cancer.
Androgen receptors are frequently expressed in epithelial ovarian cancer (EOC). Their role in the development of EOC is not fully understood. In the present review we first discuss the epidemiological data linking a hyperandrogen state to a higher risk for ovarian cancer, second describe in vitro studies of the role of androgens in influencing the growth of EOC, and finally review the completed clinical trials with compounds that exploit the androgen axis in patients with ovarian cancer. The therapeutic approaches that inhibit androgen signaling have so far produced only modest response rates. In the light of new data regarding the role of androgen stimulation in the evolution of EOC and the emergence of new compounds used for the treatment of other hormone-driven malignancies, such as prostate and breast cancer, we provide suggestions for new studies of antiandrogen therapeutics in the treatment of EOC. A specific example is the new agent abiraterone. In addition, we propose a panel of molecules that could be assessed as potential biomarkers that may aid patient selection for this approach in the future.


Microstructured optical fibers as high-pressure microfluidic reactors.
Deposition of semiconductors and metals from chemical precursors onto planar substrates is a well-developed science and technology for microelectronics. Optical fibers are an established platform for both communications technology and fundamental research in photonics. Here, we describe a hybrid technology that integrates key aspects of both engineering disciplines, demonstrating the fabrication of tubes, solid nanowires, coaxial heterojunctions, and longitudinally patterned structures composed of metals, single-crystal semiconductors, and polycrystalline elemental or compound semiconductors within microstructured silica optical fibers. Because the optical fibers are constructed and the functional materials are chemically deposited in distinct and independent steps, the full design flexibilities of both platforms can now be exploited simultaneously for fiber-integrated optoelectronic materials and devices.


Timosaponin B-II ameliorates diabetic nephropathy via TXNIP, mTOR, and NF-κB signaling pathways in alloxan-induced mice.
Many synthesized drugs with clinical severe side effects have been used for diabetic nephropathy (DN) treatment. Therefore, it is urgent and necessary to identify natural and safe agents to remedy DN. Timosaponin B-II (TB-II), a major steroidal saponin constituent in Anemarrhena asphodeloides Bunge, exhibits various activities, including anti-inflammatory and hypoglycemic functions. However, the anti-DN effects and potential mechanism(s) of TB-II have not been previously reported. To investigate the effect of TB-II on DN in alloxan-induced diabetic mice. TB-II was isolated and purified from A. asphodeloides Bunge using macroporous adsorption resin and preparative high-performance liquid chromatography. The effect of TB-II on DN was evaluated in alloxan-induced diabetic mice using an assay kit and immunohistochemical determination in vivo. The expression of mammalian target of rapamycin (mTOR), thioredoxin-interacting protein (TXNIP), and nuclear transcription factor-κB (NF-κB) signaling pathways was also measured using Western blot analysis. TB-II significantly decreased the blood glucose levels and ameliorated renal histopathological injury in alloxan-induced diabetic mice. In addition, TB-II remarkably decreased the levels of renal function biochemical factors, such as kidney index, blood urea nitrogen, serum creatinine, urinary uric acid, urine creatinine, and urine protein, and it reduced lipid metabolism levels of total cholesterol and triglycerides and the levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-α in alloxan-induced mice. Furthermore, TB-II inhibited the expression of mTOR, TXNIP, and NF-κB. The results revealed that TB-II plays an important role in DN via TXNIP, mTOR, and NF-κB signaling pathways. Overall, TB-II exhibited a prominently ameliorative effect on alloxan-induced DN.


Coordination of health behavior counseling in primary care.
We wanted to examine how coordinated care is implemented in primary care practices to address patients' health behavior change needs. Site visit notes, documents, interviews, and online implementation diaries were collected from July 2005 to September 2007 from practice-based research networks (PBRNs) participating in Prescription for Health: Promoting Healthy Behaviors in Primary Care Research Networks (P4H). An iterative group process was used to conduct a cross-case comparative analysis of 9 interventions. Published patient outcomes reports from P4H interventions were referenced to provide information on intervention effectiveness. In-practice health risk assessment (HRA) and brief counseling, coupled with referral and outreach to a valued and known counseling resource, emerged as the best way to consistently coordinate and encourage follow-through for health behavior counseling. Findings from published P4H outcomes suggest that this approach led to improvement in health behaviors. Automated prompts and decision support tools for HRA, brief counseling and referral, training in brief counseling strategies, and co-location of referral with outreach facilitated implementation. Interventions that attempted to minimize practice or clinician burden through telephone and Web-based counseling systems or by expanding the medical assistant role in coordination of health behavior counseling experienced difficulties in implementation and require more study to determine how to optimize integration in practices. Easy-to-use system-level solutions that have point-of-delivery reminders and decision support facilitate coordination of health behavior counseling for primary care patients. Infrastructure is needed if broader integration of health behavior counseling is to be achieved in primary care.


Integrating Community Health Workers (CHWs) into Health Care Organizations.
Health care organizations increasingly employ community health workers (CHWs) to help address growing provider shortages, improve patient outcomes, and increase access to culturally sensitive care among traditionally inaccessible or disenfranchised patient populations. Scholarly interest in CHWs has grown in recent decades, but researchers tend to focus on how CHWs affect patient outcomes rather than whether and how CHWs fit into the existing health care workforce. This paper focuses on the factors that facilitate and impede the integration of the CHWs into health care organizations, and strategies that organizations and their staff develop to overcome barriers to CHW integration. We use qualitative evaluation data from 13 awardees that received Health Care Innovation Awards from the Centers of Medicare and Medicaid Innovation to enhance the quality of health care, improve health outcomes, and reduce the cost of care using programs involving CHWs. We find that organizational capacity, support for CHWs, clarity about health care roles, and clinical workflow drive CHW integration. We conclude with practical recommendations for health care organizations interested in employing CHWs.


Early transient depletion of extracellular Ca during individual cardiac muscle contractions.
Extracellular free [Ca] in rabbit papillary muscles was monitored using double-barreled Ca microelectrodes. These electrodes had tip diameters of 4-12 microns, electrical time constants of 2-5 ms, and electrochemical time constants of less than 30 ms. During individual beats a transient depletion of extracellular Ca (CaO) was recorded. This decrease of [Ca]O begins very early during the action potential, before significant tension development, and reaches a maximum much before the peak of developed tension (T). The depletion of CaO is blocked by CoCl2 or verapamil and enhanced by 10(-8) M isoproterenol or reduction of extracellular Na concentration to 35 mM. The magnitude of this early depletion of CaO increases in parallel with tension as a function of [Ca]O (8.46 +/- 0.98 microM at 0.2 mM CaO, 16.9 +/- 1.6 microM at 0.5 mM CaO, and 44.7 +/- 3.7 microM at 2.0 mM CaO). However the magnitude (in mV) of the recorded signal decreases with increasing [Ca]O and T, suggestive of saturation. The magnitude of this early transient CaO depletion also increases in parallel with the increase of T produced by initiating stimulation from rest (except for the first beat, which may be more dependent on stored Ca). It is probable that the depletions recorded represent Ca influx into cardiac cells from the extracellular space. The magnitude of Ca influx represented by the CaO depletions is difficult to quantitate but may be roughly in the range of Ca entry that would be required for direct activation of the myofilaments.


Nightmares and psychiatric symptoms: A systematic review of longitudinal, experimental, and clinical trial studies.
Nightmares occur across a wide range of psychiatric disorders, but outside of PTSD presentations are infrequently considered a treatment priority. We aimed to assess evidence for a contributory causal role of nightmares to the occurrence of psychiatric disorders, and vice versa. A systematic review was conducted of longitudinal, experimental, and clinical trial studies. Twenty-four longitudinal, sixteen trials, and no experimental studies were identified. Methodological shortcomings were common, especially the use of single-item nightmare assessment. Thirty-five studies assessed the path from nightmares to psychiatric symptoms. Depression (n = 10 studies), PTSD (n = 10) and anxiety (n = 5) were the most commonly assessed outcomes in trials. Most were not designed to assess the effect of nightmare treatment on psychiatric symptoms. Treating nightmares led to moderate reductions in PTSD and depression, small to moderate reductions in anxiety, and potentially moderate reductions in paranoia. Nightmares increased the risk of later suicide outcomes (n = 10), but two small pilot trials indicated that treating nightmares might potentially prevent recovery of suicidal ideation. PTSD treatment led to large reductions in trauma-related nightmares (n = 3). The limited literature suggests that treating nightmares may be one route to lessening threat-based disorders in particular, suggestive of a causal relationship. Overall, however, nightmares in most disorders are greatly understudied.


Dissociation between recognition and recall in developmental amnesia.
Developmental amnesia (DA) is a memory disorder due to hypoxia/ischaemia-induced damage to the hippocampus early in life. To test the hypothesis that this disorder is associated with a disproportionate impairment in recall vis-à-vis recognition, we examined a group of 10 patients with DA on the Doors and People test, which affords a quantitative comparison between measures of the two memory processes. The results supported the hypothesis in that the patients showed a sharp, though not complete, recall-recognition dissociation, exhibiting impairment on both measures relative to their matched controls, but with a far greater loss in recall than in recognition. Whether their relatively spared recognition ability is due to restriction of their medial temporal lobe damage to the hippocampus or whether it is due instead to their early age at injury is still uncertain.


Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI).
Evidence is accumulating that the rho family, a member of the ras p21-related small GTP-binding protein superfamily, regulates cell morphology, cell motility, and smooth muscle contraction through the actomyosin system. The actomyosin system is also known to be essential for cytoplasmic division of cells (cytokinesis). In this study, we examined the action of rho p21, its inhibitory GDP/GTP exchange protein, named rho GDI, its stimulatory GDP/GTP exchange protein, named smg GDS, and botulinum ADP-ribosyltransferase C3, known to selectively ADP-ribosylate rho p21 and to impair its function, in the cytoplasmic division using Xenopus embryos. The sperm-induced cytoplasmic division of Xenopus embryos was not affected by microinjection into the embryos of either smg GDS or the guanosine-5'-(3-O-thio)triphosphate (GTP gamma S)-bound form of rhoA p21, one member of the rho family, but completely inhibited by microinjection of rho GDI or C3. Under these conditions, nuclear division occurred normally but the furrow formation, which was induced by the contractile ring consisting of actomyosin just beneath the plasma membrane, was impaired. Comicroinjection of rho GDI with the GTP gamma S-bound form of rhoA p21 prevented the rho GDI action. Moreover, the sperm-induced cytoplasmic division of Xenopus embryos was inhibited by microinjection into the embryos of the rhoA p21 pre-ADP-ribosylated by C3 which might serve as a dominant negative inhibitor of endogenous rho p21. These results indicate that rho p21 together with its regulatory proteins regulates the cytoplasmic division through the actomyosin system.


Pancreatic islet beta-cells transiently metabolize pyruvate.
Pancreatic beta-cell metabolism was followed during glucose and pyruvate stimulation of pancreatic islets using quantitative two-photon NAD(P)H imaging. The observed redox changes, spatially separated between the cytoplasm and mitochondria, were compared with whole islet insulin secretion. As expected, both NAD(P)H and insulin secretion showed sustained increases in response to glucose stimulation. In contrast, pyruvate caused a much lower NAD(P)H response and did not generate insulin secretion. Low pyruvate concentrations decreased cytoplasmic NAD(P)H without affecting mitochondrial NAD(P)H, whereas higher concentrations increased cytoplasmic and mitochondrial levels. However, the pyruvate-stimulated mitochondrial increase was transient and equilibrated to near-base-line levels. Inhibitors of the mitochondrial pyruvate-transporter and malate-aspartate shuttle were utilized to resolve the glucose- and pyruvate-stimulated NAD(P)H response mechanisms. These data showed that glucose-stimulated mitochondrial NAD(P)H and insulin secretion are independent of pyruvate transport but dependent on NAD(P)H shuttling. In contrast, the pyruvate-stimulated cytoplasmic NAD(P)H response was enhanced by both inhibitors. Surprisingly the malate-aspartate shuttle inhibitor enabled pyruvate-stimulated insulin secretion. These data support a model in which glycolysis plays a dominant role in glucose-stimulated insulin secretion. Based on these data, we propose a mechanism for glucose-stimulated insulin secretion that includes allosteric inhibition of tricarboxylic acid cycle enzymes and pH dependence of mitochondrial pyruvate transport.


[Effects of two Sicilian red wines on some cardiovascular risk factors].
The aim of this study was to evaluate whether Sicilian red wine consumption is associated with a lower cardiovascular risk. Forty-eight subjects of both sexes (age range 35-65 years) nondrinkers or rarely drinkers of moderate red wine intake were selected. Subjects were divided into two groups (group A and group B), assigned to receive with a crossover design 250 ml/die (during the meals) of one of two types of Sicilian red wines (Nero d'Avola and Etna Torrepalino respectively). At all visits (-15 days, basal, +4 and +8 weeks) the following parameters were measured: blood glucose, total cholesterol and triglycerides (by enzyme kit methods, Boehringer Mannheim, Milan, Italy), HDL cholesterol (by selective precipitation with dextran-magnesium chloride), LDL cholesterol (by calculation with the Friedewald formula), LDL/HDL ratio, apolipoproteins A1 and B (by radial immunodiffusion, Behring Institute, Scoppito, Italy), lipoprotein(a) (ELISA, Technoclone, Vienna, Austria), plasma C-reactive protein (high-sensitivity, Dade Behring, Marburg, Germany), D-dimer (Turbiquant, Dade Behring), factor VII (coagulant activity, Dade Behring), plasminogen activator inhibitor antigen (ELISA), tissue-type plasminogen activator antigen (ELISA), fibrinogen (coagulant), oxidized LDL antibody (ELISA), total plasma antioxidant capacity (FRAP method). At the end of the red wine intake period, HDL cholesterol was significantly increased (p < 0.01) and the LDL/HDL ratio was significantly decreased (p < 0.05) in both study groups, while apolipoprotein A1 was significantly increased (p < 0.05) only in group A. In both group A and group B fibrinogen (p < 0.01 and p < 0.005, respectively), factor VII (p < 0.01 and p < 0.05, respectively), plasma C-reactive protein (p < 0.005 and p < 0.05, respectively) and oxidized LDL antibody (p < 0.05) were significantly decreased, while tissue-type plasminogen activator (p < 0.005), plasminogen activator inhibitor (p < 0.005) and total plasma antioxidant capacity (p < 0.005) were significantly increased. Our results show a positive effect of these Sicilian red wines on many risk factors, suggesting a moderate consumption of red wine in the adult population as a component of the Mediterranean diet.


The interaction of lexical semantics and cohort competition in spoken word recognition: an fMRI study.
Spoken word recognition involves the activation of multiple word candidates on the basis of the initial speech input--the "cohort"--and selection among these competitors. Selection may be driven primarily by bottom-up acoustic-phonetic inputs or it may be modulated by other aspects of lexical representation, such as a word's meaning [Marslen-Wilson, W. D. Functional parallelism in spoken word-recognition. Cognition, 25, 71-102, 1987]. We examined these potential interactions in an fMRI study by presenting participants with words and pseudowords for lexical decision. In a factorial design, we manipulated (a) cohort competition (high/low competitive cohorts which vary the number of competing word candidates) and (b) the word's semantic properties (high/low imageability). A previous behavioral study [Tyler, L. K., Voice, J. K., & Moss, H. E. The interaction of meaning and sound in spoken word recognition. Psychonomic Bulletin & Review, 7, 320-326, 2000] showed that imageability facilitated word recognition but only for words in high competition cohorts. Here we found greater activity in the left inferior frontal gyrus (BA 45, 47) and the right inferior frontal gyrus (BA 47) with increased cohort competition, an imageability effect in the left posterior middle temporal gyrus/angular gyrus (BA 39), and a significant interaction between imageability and cohort competition in the left posterior superior temporal gyrus/middle temporal gyrus (BA 21, 22). In words with high competition cohorts, high imageability words generated stronger activity than low imageability words, indicating a facilitatory role of imageability in a highly competitive cohort context. For words in low competition cohorts, there was no effect of imageability. These results support the behavioral data in showing that selection processes do not rely solely on bottom-up acoustic-phonetic cues but rather that the semantic properties of candidate words facilitate discrimination between competitors.


Comparative proteomics analysis of cardiac muscle samples from pufferfish Takifugu rubripes exposed to excessive fluoride: initial molecular response to fluorosis.
Comparative proteomics was performed to identify proteins in the cardiac muscle of Takifugu rubripes in initial response to excessive fluoride. Sixteen fish were randomly divided into a control group and an experimental group. The control group was raised in softwater alone (F(-) = 0.4 mg/L), and the experimental group was raised in the same water with sodium fluoride at a high concentration of 35 mg/L. After 3 days, proteins were extracted from the fish cardiac muscle and then were subjected to 2D PAGE analysis. The matrix assisted laser desorption ionization time of flight mass spectrometry (Maldi TOF MS) was applied to identify the proteins that were differentially expressed from the two groups of fish. Average of 318 and 275 proteins detected in the control and the experimental group, respectively, 167 spots were matched and 21 highly differentially expressed proteins were further analyzed by Maldi TOF-TOF MS, and 15 were identified by MASCOT. These 15 proteins include Telomerase reverse transcriptase, 4SNc-Tudor domain protein, protein disulfide isomerase ER-60, Tuba1 protein, mitogen-activated protein kinase 10, and SMC4 protein. Consistent with their previously known functions, these identified proteins seem to be involved in apoptosis and other functions associated with fluorosis. These results will contribute to our understanding for the effects of fluoride exposure on the physiological and biochemical functions of takifugu, and the toxicological mechanism of fluoride causing fluorosis in both fish and human.


Influencing the attitudes of medical students toward diabetes. Results of a controlled study.
To determine the effect of two educational interventions on the diabetes-related attitudes of medical students. We studied 67 junior and senior medical students who were participating in the University of Michigan Medical School's Family Practice elective clerkship. Students were assigned to one of two interventions. The first was a 1-wk living-with-diabetes behavioral simulation that involved injections, blood glucose monitoring, diet, exercise, and record keeping. The second intervention involved reading an autobiography about living with diabetes and viewing a videotape about the psychosocial impact of diabetes. No differential impact was found between the two interventions. However, both interventions were followed by a modest positive change in the attitudes of the medical students (which were very positive to begin with) toward the importance of patient autonomy and the value of the team approach to diabetes care. The attitude gains persisted at follow-up for patient autonomy but returned to baseline for team care. This study suggests that these two educational interventions resulted in modest increases in the already positive attitudes of medical students toward the importance of patient autonomy and team care in diabetes. However, because the study did not include a group that received no treatment, we cannot be certain on this point. The attitude gain related to team care did not persist at follow-up. These findings are consistent with classical attitude research, which suggests that attitudes are sensitive to influences such as these interventions, but that attitude changes may not persist when those influences are changed or withdrawn. We were not able to find a differential impact between the two interventions and suspect that the general nature of the DAS used as the dependent measure may not have been sensitive enough to capture such a differential impact.


Virtual delivery: a panacea for the financial and ethical challenges associated with physiology laboratory classes?
There has been a gradual shift in the delivery of physiology laboratory classes over the last 30 years. For many, wet-lab demonstrations using animal tissues have been reduced or replaced with student-led investigations where students are both subjects and researchers. Despite these changes, expectations remain that physiology courses should include a practical component to encourage deeper and higher-order learning. Wet-lab tissue experiments and student-based group research formats can be expensive to run, associated with various ethical constraints, and, as discovered in these times of COVID-19, difficult to operate while adhering to physical distancing. We address the proposition that online and/or remote delivery of laboratory classes using digital technologies may provide a solution to both financial and ethical constraints of on-campus laboratory classes. Our discussions, as an international group of 10 physiologists from the United States, the United Kingdom, Canada, and Australia, revealed that although some of the financial and ethical constraints of using animal tissues and student-led investigations were addressed by the introduction of online alternatives, the construction and maintenance of online delivery modes could also be expensive and ethical issues, not previously considered, included digital equity and student data security. There was also a collective perception that if face-to-face laboratory classes were changed to an entirely virtual mode there was a risk that some intended learning outcomes would not be met. It was concluded that the "ideal" approach is likely a hybrid model whereby student attendance in face-to-face, on-campus classes is supported with interactive digital content either developed in house or obtained through third-party providers.


Occupational therapy in hospice care.
As hospice care becomes more integrated in the overall health care delivery system, the profession of occupational therapy needs to analyze further its potential within this unique system. This article briefly discusses the goals and philosophy of the hospice concept from the perspective of the National Hospice Organization. Occupational therapy intervention in terminal care is examined, with emphasis on locus of control and occupation as determinants in enhancing quality of life for the terminally ill in a nontraditional rehabilitative environment. A brief case study illustrates some of the general principles discussed throughout the article.


Lateral elongation of flat irregular pigment epithelial detachment: A novel optical coherence tomography biomarker in polypoidal choroidal vasculopathy.
To explore novel Optical Coherence Tomography (OCT) biomarkers and precursor lesions in Polypoidal Choroidal Vasculopathy (PCV). This retrospective cohort study included 76 treatment naïve fellow eyes of PCV. Focus was given to analyse the various morphological changes in the clinically unaffected fellow retina during the follow-up period. 11 fellow eyes (14.47%) developed disease activity in the form of Sub Retinal Fluid (SRF) or Intra Retinal Fluid (IRF) within a mean follow-up of 17 months. All 11 eyes (100%) showed the presence of flat irregular pigment epithelial detachment (FIPED) and a peculiar property of lateral elongation of FIPED during disease activity. A positive correlation with the disease progression was found for the same (P < 0.0001). The mean horizontal dimension of the flat irregular PED at the enrolment was 1984 ± 376u and the mean expansion of FIPED at SRF formation was 461 ± 152u. ICG taken at the time of disease activity in the fellow eye revealed branching vascular network (BVN) in 9 (81.8%) eyes, polyps in 7 (63.6%) eyes, a combination of both in 5 (45.4%) eyes. Type one BVN with interconnecting channels showed faster disease progression than type two BVN. Eye tracking ICG illustrated that BVN corresponded to the FIPED in OCT and polypoidal lesions developed at the end of expanding FIPED. Flat irregular pigment epithelial detachment with its characteristic property of lateral elongation may be considered as a precursor lesion for PCV and as a novel OCT biomarker for the disease activity. Fellow eyes with FIPED need close monitoring to identify development of disease activity at the earliest.


Pain Reduction After Laser Acupuncture Treatment in Geriatric Patients with Knee Osteoarthritis: a Randomized Controlled Trial.
to compare the effectiveness of active laser acupuncture with placebo on reducing pain intensity and improving functional outcome in geriatric patients with knee osteoarthritis (OA). a double-blind randomized controlled trial was conducted in geriatrics with knee OA at Medical Acupuncture Outpatient Clinic, Integrated Geriatric Outpatient Clinic, Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital, Jakarta, during May to October 2015. Sixty two patients with knee OA were randomly assigned into two groups: active laser acupuncture group or placebo laser acupuncture group. Interventions were carried out using a gallium aluminum arsenide laser device at the ST35 Dubi, ST36 Zusanli, SP9 Yinlingquan, GB34 Yanglingquan and EX - LE - 4 Neixiyan acupuncture points on the affected knee for ten sessions of treatment, i.e. twice a week. Patients were assessed using a visual analogue scale (VAS) and Lequesne index at baseline, after four sessions, after nine sessions and at 2 weeks after the treatment had been stopped. the VAS scores were significantly improved in the active laser acupuncture group compared to the placebo group. The evaluation of VAS scores was carried out after four treatment sessions (mean difference: 0.39; p<0.001), after nine treatment sessions (mean difference: 37.48; p<0.001) and at 2 weeks post intervention (mean difference: 39.15; p<0.001). The evaluation also showed significant improvement of Lequesne index after four treatment sessions (mean difference: 4.68; p<0.001), after nine treatment sessions (mean difference: 5.90; p<0.001) and at 2 weeks post intervention (mean difference: 6.48; p<0.001). active laser acupuncture is effective in reducing pain.


Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study.
Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.


Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine: implications for animal models of the motivational symptoms of depression.
Motivated behaviors are often characterized by a high degree of behavioral activation, and work output and organisms frequently make effort-related decisions based upon cost/benefit analyses. Moreover, people with major depression and other disorders often show effort-related motivational symptoms such as anergia, psychomotor retardation, and fatigue. It has been suggested that tasks measuring effort-related choice behavior could be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, because of its selective inhibition of VMAT-2, it preferentially depletes dopamine (DA). Rats were assessed using a concurrent fixed-ratio 5/chow feeding choice task that is known to be sensitive to dopaminergic manipulations. Tetrabenazine shifted response choice in rats, producing a dose-related decrease in lever pressing and a concomitant increase in chow intake. However, it did not alter food intake or preference in parallel free-feeding choice studies. The effects of tetrabenazine on effort-related choice were reversed by the adenosine A2A antagonist MSX-3 and the antidepressant bupropion. A behaviorally active dose of tetrabenazine decreased extracellular DA in nucleus accumbens and increased expression of DARPP-32 in accumbens medium spiny neurons in a pattern indicative of reduced transmission at both D1 and D2 DA receptors. These experiments demonstrate that tetrabenazine, which is used in animal models to produce depression-like effects, can alter effort-related choice behavior. These studies have implications for the development of animal models of the motivational symptoms of depression and related disorders.


Seascape genetics along a steep cline: using genetic patterns to test predictions of marine larval dispersal.
Coupled biological and physical oceanographic models are powerful tools for studying connectivity among marine populations because they simulate the movement of larvae based on ocean currents and larval characteristics. However, while the models themselves have been parameterized and verified with physical empirical data, the simulated patterns of connectivity have rarely been compared to field observations. We demonstrate a framework for testing biological-physical oceanographic models by using them to generate simulated spatial genetic patterns through a simple population genetic model, and then testing these predictions with empirical genetic data. Both agreement and mismatches between predicted and observed genetic patterns can provide insights into mechanisms influencing larval connectivity in the coastal ocean. We use a high-resolution ROMS-CoSINE biological-physical model for Monterey Bay, California specifically modified to simulate dispersal of the acorn barnacle, Balanus glandula. Predicted spatial genetic patterns generated from both seasonal and annual connectivity matrices did not match an observed genetic cline in this species at either a mitochondrial or nuclear gene. However, information from this mismatch generated hypotheses testable with our modelling framework that including natural selection, larval input from a southern direction and/or increased nearshore larval retention might provide a better fit between predicted and observed patterns. Indeed, moderate selection and a range of combined larval retention and southern input values dramatically improve the fit between simulated and observed spatial genetic patterns. Our results suggest that integrating population genetic models with coupled biological-physical oceanographic models can provide new insights and a new means of verifying model predictions.


Biophysics of radiofrequency ablation using an irrigated electrode.
Previous reports have proposed that prevention of electrode-endocardial interfacial boiling is the key mechanism by which radiofrequency application using an irrigated electrode yields a larger ablation lesion than a non-irrigated electrode. It has been suggested that maximal myocardial temperature is shifted deep into myocardium during irrigated ablation. To examine the biophysics of irrigated ablation by correlating electrode and myocardial temperatures with ablation circuit impedance and lesion morphology, and to perform a comparison with non-irrigated ablation modes. To assess the influence of irrigant rate, composition, temperature and blood flow velocity. I. Ablation with and without electrode irrigation was performed in vitro utilizing a whole blood-superfused system. Electrode, electrode-endocardial interface, and intramyocardial temperatures were assessed, as were ablation circuit impedance, total delivered energy, and lesion and electrode morphology. Irrigants assessed were room temperature normal saline, iced normal saline, and dextrose. Irrigant flow rates assessed were 20 and 100 cc/min. Blood flow velocities assessed were 0 and 0.26 m/s. II. Finite element simulations of myocardial temperature during irrigated ablation were performed to further elucidate irrigation biophysics and provide a more detailed myocardial temperature profile. Two models were constructed, each utilizing a different core assumption regarding the electrode-tissue boundary: 1. electrode temperature measured in vitro; 2. interfacial temperature measured in vitro. Intramyocardial temperatures predicted by each model were correlated with corresponding temperatures measured in vitro. I. Ablation during electrode irrigation with normal saline was associated with greater ablation energy deposition and larger lesion dimensions than non-irrigated ablation. The mechanism underlying the larger lesion was delay or inhibition of impedance rise; this was associated with attenuation or prevention of electrode coagulum. Irrigation did not prevent interfacial boiling, which occurred during uninterrupted radiofrequency energy deposition and lesion growth. Irrigation using saline at 100 cc/min was associated with no impedance rise regardless of blood flow velocity, whereas during irrigation at 20 cc/min impedance rise was blood flow rate-dependent. Iced saline produced results equivalent to room temperature saline. Irrigation with dextrose was associated with curtailed energy application and relatively small lesions. II. The finite element simulation that used electrode-endocardial interfacial temperature as the core assumption predicted a myocardial temperature profile which correlated significantly better with in vitro than did the simulation which used electrode temperature as the core assumption. Regardless of irrigant and blood flow rates, maximal myocardial temperature was always within 1 mm of the endocardial surface. Radiofrequency energy application via a saline irrigated electrode resulted in a larger lesion due to attenuation or eradication of electrode coagulum, thus preventing an impedance rise. Irrigation did not prevent interfacial boiling, but boiling did not prevent lesion growth. The site of maximal myocardial temperature during irrigated ablation was relatively superficial, always within 1 mm of the endocardial surface. Irrigation with iced saline was no more effective than with room temperature saline; both were far more effective than dextrose. Higher irrigation rates immunized the electrode from the influence of blood flow. The biophysical effects of blood flow and irrigation were similar.


Dynamic Ocean-Atmosphere Coupling: A Thermostat for the Tropics
The ocean currents connecting the western tropical Pacific Ocean with the eastern tropical Pacific Ocean are driven by surface winds. The surface winds are in turn driven by the sea-surface temperature (SST) differences between these two regions. This dynamic coupling between the atmosphere and ocean may limit the SST in the tropical Pacific Ocean to below 305 kelvin even in the absence of cloud feedbacks.


Risk of persistent palatal fistula in patients with cleft palate.
Many individuals with a cleft palate also have an associated craniofacial syndrome or anomaly. To investigate the predictive associations of persistent palatal fistulas in patients with previously repaired cleft palate. We performed a case-control study of patients with cleft palate repairs from January 1, 1986, through December 31, 2000, at a major tertiary care hospital center in the Bronx, New York. The study population consisted of patients who had their primary surgery before the age of 3 years and had all their cleft-related treatment completed at the same hospital center. Palatal fistula was defined as a breakdown of the primary surgical repair of the palate, resulting in persistent patency between the oral and nasal cavities. Data collection was conducted by using the hospital centers' electronic medical records and patient tracking systems and confirmed by review of hard copies of patient records. The Veau classification system was used to classify the preoperative cleft severity. A total of 130 patients were identified-23 patients with palatal fistula and 107 controls. A total of 12 girls and 11 boys were identified in the palatal fistula group and 56 girls and 51 boys in the control group. The mean patient age at the time of palatoplasty was 12.6 and 14.5 months in the palatal fistula and control groups, respectively. A statistically significant association was found between the outcome of fistula and severity of cleft, as defined by the Veau classification system (P = .01). Furthermore, for each Veau class increase, the odds of a palatal fistula increased by 2.64 (95% CI, 1.35-5.13; P = .004). No statistically significant associations were found between the outcome of fistula and the following independent variables: patient sex (P = .98), patient age at palatoplasty (P = .82), type of palatoplasty (P = .57), surgeon (P = .15), orthodontic treatment (P = .59), ear infection (P = .30), or clefts associated with syndromes (P = .96). Palatal fistulas are reliably associated with severity of cleft, as defined by the Veau classification system. This knowledge gives the health care professional a more reliable method of preoperatively assessing the risk of postoperative palatal fistula in the cleft palate population. 3.


Heterodimeric neurotoxic phospholipases A2--the first proteins from venom of recently established species Vipera nikolskii: implication of venom composition in viper systematics.
For the first time the venom of recently established viper species Vipera nikolskii was fractionated and two heterodimeric phospholipases A(2) (HDP-1 and HDP-2) were isolated. Isolation of HDP-1 and HDP-2 is the first indication of the presence of two heterodimeric phospholipases A(2) in the venom of one viper species. When tested on the frog neuromuscular junction, isolated proteins affected neuromuscular transmission acting presynaptically. Using RP-HPLC, each heterodimer was separated into two monomeric subunits: basic phospholipase A(2) (HDP-1P and HDP-2P) and acidic component without enzymatic activity (HDP-In). The complete primary structures of subunits were deduced from corresponding sequences of cDNAs. The determined amino acid sequences were homologous to those of vipoxin from Vipera ammodytes and vaspin from Vipera aspis. Similar proteins were not found earlier in the well-studied venom of Vipera berus, the species from which V. nikolskii was recently separated. Our finding supports at the biochemical level the correctness of the establishment of V. nikolskii as an independent species. The finding of similar proteins (HDPs and vipoxin) in geographically remote species (V. nikolskii and V. ammodytes) corroborates the hypothesis about the pre-existence of genes encoding these proteins in all true viper species and their expression under certain conditions.


Reduced soluble transferrin receptor concentrations in acute malaria in Vanuatu.
Soluble transferrin receptor (sTfR) concentration is a sensitive index of iron deficiency when used in conjunction with ferritin measurements in adults. One advantage of this assay is that unlike ferritin it does not appear to be affected by a range of infectious and inflammatory conditions or by pregnancy, rendering it a promising adjunct to the diagnosis of iron deficiency in tropical populations. We have measured plasma sTfR concentrations in a group of malaria patients (n = 21) and asymptomatic (18) and aparasitemic (76) controls in Vanuatu. Plasma sTfR concentration was significantly reduced in individuals with acute malaria (P = 0.003). While this observation provides evidence that erythropoeitic suppression may be an important etiologic component in malarial anemia, it also suggests that malaria may be a confounding factor when interpreting sTfR concentrations in such populations. The role of sTfR in the diagnosis of iron deficiency in tropical populations remains to be established.


A pilot study on the lung morphology of shelter dogs in relation to air pollution in Trinidad.
To identify and characterize the gross and histological lesions associated with air pollution in the lungs of dogs from various locations in Trinidad. 56 fresh lungs were obtained from already euthanized adult dogs collected from different locations in Trinidad at the Trinidad and Tobago Society for the Prevention of Cruelty to Animals. Lung specimens were examined grossly and tissue samples were taken for routine histologic examination. Histological examination showed that 51.8% of the dogs had evidence of anthracosis. Dogs with anthracosis had greater median lesion scores compared to dogs without anthracosis (P = .022). There was no association between the presence of anthracosis and any other lesion in this study (P > .05). There was evidence that dogs with anthracosis had a greater degree of nonspecific lung histologic lesions. Using the dog as a sentinel model for human exposure in Trinidad, our findings indicate that environmental air pollution may also have an effect on the respiratory health of the human population. It is important for the public to be aware of air pollution, and the government of Trinidad and Tobago should develop an intervention protocol along with veterinary and human medical epidemiologists to reduce air pollution in the country.


"We are not being heard": Aboriginal perspectives on traditional foods access and food security.
Aboriginal peoples are among the most food insecure groups in Canada, yet their perspectives and knowledge are often sidelined in mainstream food security debates. In order to create food security for all, Aboriginal perspectives must be included in food security research and discourse. This project demonstrates a process in which Aboriginal and non-Aboriginal partners engaged in a culturally appropriate and respectful collaboration, assessing the challenges and barriers to traditional foods access in the urban environment of Vancouver, BC, Canada. The findings highlight local, national, and international actions required to increase access to traditional foods as a means of achieving food security for all people. The paper underscores the interconnectedness of local and global food security issues and highlights challenges as well as solutions with potential to improve food security of both Aboriginal and non-Aboriginal peoples alike.


[Treatment of recurrent furunculosis].
The management of recurrent furunculosis is difficult, and often disappointing. We present the case of a 23-year-old female patient suffering from recurrent furunculosis. The furunculosis persisted after treatment with mupirocin nasal ointment, chlorhexidine soap and instructions for washing clothes, towels and bed sheets for a period of 7 days. Treatment with low-dose clindamycin for three months ultimately proved successful. We propose a structural approach for recurrent furunculosis in which extensive history-taking is followed by appropriate tests. Before prescribing an oral antibiotic (preferably low-dose clindamycin or a macrolide for 3 months), the patient should use an antimicrobial nasal ointment and soap and follow hygienic instructions as mentioned above. Members of the household who also have signs of the infection should be treated. Hygienic education is an essential component of treatment. We believe that this approach will lead to a treatment that is more effective and efficient.


Models of experimental competitive intensities predict home and away differences in invasive impact and the effects of an endophytic mutualist.
Understanding the role of competition in the organization of communities is limited in part by the difficulty of extrapolating the outcomes of small-scale experiments to how such outcomes might affect the distribution and abundance of species. We modeled the community-level outcomes of competition, using experimentally derived competitive effects and responses between an exotic invasive plant, Centaurea stoebe, and species from both its native and nonnative ranges and using changes in these effects and responses elicited by experimentally establishing symbioses between C. stoebe and fungal endophytes. Using relative interaction intensities (RIIs) and holding other life-history factors constant, individual-based and spatially explicit models predicted competitive exclusion of all but one North American species but none of the European species, regardless of the endophyte status of C. stoebe. Concomitantly, C. stoebe was eliminated from the models with European natives but was codominant in models with North American natives. Endophyte symbiosis predicted increased dominance of C. stoebe in North American communities but not in European communities. However, when experimental variation was included, some of the model outcomes changed slightly. Our results are consistent with the idea that the effects of competitive intensity and mutualisms measured at small scales have the potential to play important roles in determining the larger-scale outcomes of invasion and that the stabilizing indirect effects of competition may promote species coexistence.


Reconstructing a hydrogen-driven microbial metabolic network in Opalinus Clay rock.
The Opalinus Clay formation will host geological nuclear waste repositories in Switzerland. It is expected that gas pressure will build-up due to hydrogen production from steel corrosion, jeopardizing the integrity of the engineered barriers. In an in situ experiment located in the Mont Terri Underground Rock Laboratory, we demonstrate that hydrogen is consumed by microorganisms, fuelling a microbial community. Metagenomic binning and metaproteomic analysis of this deep subsurface community reveals a carbon cycle driven by autotrophic hydrogen oxidizers belonging to novel genera. Necromass is then processed by fermenters, followed by complete oxidation to carbon dioxide by heterotrophic sulfate-reducing bacteria, which closes the cycle. This microbial metabolic web can be integrated in the design of geological repositories to reduce pressure build-up. This study shows that Opalinus Clay harbours the potential for chemolithoautotrophic-based system, and provides a model of microbial carbon cycle in deep subsurface environments where hydrogen and sulfate are present.


Hearing status, need for recovery after work, and psychosocial work characteristics: results from an internet-based national survey on hearing.
The main aim of the study is to address the relationship between hearing status and need for recovery. In addition, the role of hearing status in the relationship between psychosocial work characteristics (i.e. job demands and job control) and need for recovery was assessed. The sample comprised 925 normally-hearing and hearing-impaired working adults (aged 18-65 years) participating in the National Longitudinal Study on Hearing. Hearing status was determined using the national hearing (speech-in-noise) test over the internet. Psychosocial work characteristics and need for recovery were assessed using the job content questionnaire and the Dutch questionnaire on the experience and assessment of work. Regression models revealed a significant association between hearing status and need for recovery after work, poorer hearing leading to an increasing need for recovery. Additionally, poorer hearing led to a higher odds for risky levels of need for recovery. Hearing status did not influence the significant relationship between psychosocial work characteristics (i.e. job demand and job control) and need for recovery after work. Implications for clinical practice, such as the necessity of having adequate enablement programs for this specific group of patients, are discussed.


Monetary, Food, and Social Rewards Induce Similar Pavlovian-to-Instrumental Transfer Effects.
Multiple types of reward, such as money, food or social approval, are capable of driving behavior. However, most previous investigations have only focused on one of these reward classes in isolation, as such it is not clear whether different reward classes have a unique influence on instrumental responding or whether the subjective value of the reward, rather than the reward type per se, is most important in driving behavior. Here, we investigate behavior using a well-established reward paradigm, Pavlovian-to-instrumental transfer (PIT), and three different reward types: monetary, food and social rewards. The subjective value of each reward type was matched using a modified Becker-DeGroot-Marschak (BDM) auction where subjective reward value was expressed through physical effort using a bimanual grip force task. We measured the influence of reward-associated stimuli on how participants distributed forces between hands when reaching a target effort range on the screen bimanually and on how much time participants spent in this target range. Participants spent significantly more time in the target range (15% ± 2% maximal voluntary contraction) when a stimulus was presented that was associated with a reward used during instrumental conditioning or Pavlovian conditioning compared to a stimulus associated with a neutral outcome (i.e., general PIT). The strength of the PIT effect was modulated by subjective value (i.e., individuals who showed a stronger PIT effect rated the value of rewards more highly), but not by reward type, demonstrating that stimuli of all reward types were able to act as appetitive reinforcers and influenced instrumental responding, when matched to the same subjective reward value. This is the first demonstration that individually matched monetary, food and social rewards are equally effective as appetitive reinforcers in PIT. These findings strengthen the hypotheses that the subjective value is crucial for how much reward-associated stimuli influence behavior.


Developmental evaluation in children experiencing febrile convulsions.
The objective of this study was to determine the effect of febrile convulsion (FC) on neuromotor development. Data of 325 patients, who were followed up at our outpatient clinic and diagnosed with FC between January 2012 and December 2018, were retrospectively evaluated. Of these patients, 203 underwent the Denver Developmental Screening Test II (DDST II) and were included in the study as the patient group and 100 healthy children as the control group. Of the study group, 84 (41.4%) were girls and 119 (58.6%) were boys (B/G: 1.4). Of all patients, 163 (80.3%) were diagnosed with simple FC, 22 (10.8%) with complicated FC, and 18 (8.9%) with FC+. There was no significant relationship found between FC subtypes and gender, family history of FC, family history of epilepsy, iron (Fe) deficiency, and Fe deficiency anemia. DDST II subtest points were significantly lower in all developmental areas in the patient group when compared to the controls (p < 0.001), while suspected and abnormal test results were higher in all developmental areas in the patient group compared to the controls (p=0.01). It was also determined that the language points were lower as the age of first seizure increased (r=- 0.319, p < 0.01). Although FC is known to usually having a good prognosis, the low DDST II test results measured in this study indicated that the FC may pose a developmental risk and patients with FC should be followed up in terms of developmental features. Because of the retrospective nature of the study, there was no `preconvulsion` developmental evaluation. This is a major limitation of our study.


Pathologic review of atypical hyperplasia identified by image-guided breast needle core biopsy. Correlation with excision specimen.
Management of breast needle core biopsies diagnosed as atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ is controversial. Current recommendations involve excisional biopsy to rule out ductal carcinoma in situ and/or invasive carcinoma, which have been reported in more than 50% of cases in some series. To determine how frequently these diagnoses made on needle core biopsy are ultimately found to represent in situ or invasive carcinoma based on excisional biopsy specimens, in order to identify predictive factors. One thousand eight hundred thirty-six image-guided needle core biopsies were performed between January 1, 1995 and May 1, 2001. Fifty-four (2.9%) patients diagnosed with atypical ductal hyperplasia (n = 36), atypical lobular hyperplasia (n = 12), atypical ductal hyperplasia + atypical lobular hyperplasia (n = 3), or lobular carcinoma in situ (n = 3) subsequently underwent breast excisions. Pathologic features were reviewed in each of the needle core biopsies using Page's criteria and were then correlated with excision specimens. University medical center. Review of the needle core biopsy cases with either ductal carcinoma in situ or invasive carcinoma + ductal carcinoma in situ on final excision showed that nucleoli were evident in most of the needle core cases, with foci of nuclear pleomorphism and individual cell necrosis or apoptosis. A more precise diagnosis can be made by using strict criteria for atypical ductal hyperplasia versus ductal carcinoma in situ on needle core biopsy. Cytologic atypia, even if in a small area, particularly when there is apoptosis/individual cell necrosis, correlates with the finding of a more serious lesion on excision.


Enhanced activated carbon cathode performance for microbial fuel cell by blending carbon black.
Activated carbon (AC) is a useful and environmentally sustainable catalyst for oxygen reduction in air-cathode microbial fuel cells (MFCs), but there is great interest in improving its performance and longevity. To enhance the performance of AC cathodes, carbon black (CB) was added into AC at CB:AC ratios of 0, 2, 5, 10, and 15 wt % to increase electrical conductivity and facilitate electron transfer. AC cathodes were then evaluated in both MFCs and electrochemical cells and compared to reactors with cathodes made with Pt. Maximum power densities of MFCs were increased by 9-16% with CB compared to the plain AC in the first week. The optimal CB:AC ratio was 10% based on both MFC polarization tests and three electrode electrochemical tests. The maximum power density of the 10% CB cathode was initially 1560 ± 40 mW/m(2) and decreased by only 7% after 5 months of operation compared to a 61% decrease for the control (Pt catalyst, 570 ± 30 mW/m(2) after 5 months). The catalytic activities of Pt and AC (plain or with 10% CB) were further examined in rotating disk electrode (RDE) tests that minimized mass transfer limitations. The RDE tests showed that the limiting current of the AC with 10% CB was improved by up to 21% primarily due to a decrease in charge transfer resistance (25%). These results show that blending CB in AC is a simple and effective strategy to enhance AC cathode performance in MFCs and that further improvement in performance could be obtained by reducing mass transfer limitations.


Outcomes after esophagectomy: a ten-year prospective cohort.
The Department of Veterans Affairs National Surgical Quality Improvement Program is a unique resource to prospectively analyze surgical outcomes from a cross-section of surgical services nationally. We used this database to assess risk factors for morbidity and mortality after esophagectomy in Veterans Affairs Medical Centers from 1991 to 2001. A total of 1,777 patients underwent an esophagectomy at 109 Veterans Affairs hospitals with complete in-hospital and 30-day outcomes recorded. Bivariate and multivariable analyses were completed. Thirty-day mortality was 9.8% (174/1,777) and the incidence of one or more of 20 predefined complications was 49.5% (880/1,777). The most frequent postoperative complications were pneumonia in 21% (380/1,777), respiratory failure in 16% (288/1,777), and ventilator support more than 48 hours in 22% (387/1,777). Preoperative predictors of mortality based on multivariable analysis included neoadjuvant therapy, blood urea nitrogen level of more than 40 mg/dL, alkaline phosphatase level of more than 125 U/L, diabetes mellitus, alcohol abuse, decreased functional status, ascites, and increasing age. Preoperative factors impacting morbidity were increasing age, dyspnea, diabetes mellitus, chronic obstructive pulmonary disease, alkaline phosphatase level of more than 125 U/L, lower serum albumin concentration, increased complexity score, and decreased functional status. Intraoperative risk factors for mortality included the need for transfusion; intraoperative risk factors for morbidity included the need for transfusion and longer operative time. These data constitute the largest prospective outcomes cohort in the literature and document a near 50% morbidity rate and 10% mortality rate after esophagectomy. Data from this study can be used to better stratify patients before esophagectomy.