Autonomous abortions: the inhibiting of women's autonomy through legal ultrasound requirements.
Recently, we have seen various proposed laws that would require that women considering abortions be given ultrasounds along with explanations of these ultrasounds. Proponents of these laws could argue that they are assisting with autonomous abortion choices by providing needed information, especially about the ontological status of the fetus. Arguing against these proposed laws, I first claim that their supporters fail to appreciate how personalized an abortion choice must be. Second, I argue that these laws would provide the pregnant woman no control over when and to what extent emotion is inserted into her deliberation. This unjustly inhibits her autonomy, making these ultrasound laws unjustified.


[Tentoriotomy in severe craniocerebral injuries].
The results of surgical treatment of 110 patients with severe craniocerebral trauma and acute midbrain dislocation syndrome are discussed. The principal operation for removal of the injured site (hematoma or focus of brain crushing) was supplemented in all cases by mildly injurious tentoriotomy. As a result, lethality in the group of patients subjected to tentoriotomy decreased. Criteria (clinical, electrophysiological, and angiographic) are characterized on the basis of which the indications for tentoriotomy in craniocerebral trauma are determined.


Validation of Hill-type muscle models in relation to neuromuscular recruitment and force-velocity properties: predicting patterns of in vivo muscle force.
We review here the use and reliability of Hill-type muscle models to predict muscle performance under varying conditions, ranging from in situ production of isometric force to in vivo dynamics of muscle length change and force in response to activation. Muscle models are frequently used in musculoskeletal simulations of movement, particularly when applied to studies of human motor performance in which surgically implanted transducers have limited use. Musculoskeletal simulations of different animal species also are being developed to evaluate comparative and evolutionary aspects of locomotor performance. However, such models are rarely validated against direct measures of fascicle strain or recordings of muscle-tendon force. Historically, Hill-type models simplify properties of whole muscle by scaling salient properties of single fibers to whole muscles, typically accounting for a muscle's architecture and series elasticity. Activation of the model's single contractile element (assigned the properties of homogenous fibers) is also simplified and is often based on temporal features of myoelectric (EMG) activation recorded from the muscle. Comparison of standard one-element models with a novel two-element model and with in situ and in vivo measures of EMG, fascicle strain, and force recorded from the gastrocnemius muscles of goats shows that a two-element Hill-type model, which allows independent recruitment of slow and fast units, better predicts temporal patterns of in situ and in vivo force. Recruitment patterns of slow/fast units based on wavelet decomposition of EMG activity in frequency-time space are generally correlated with the intensity spectra of the EMG signals, the strain rates of the fascicles, and the muscle-tendon forces measured in vivo, with faster units linked to greater strain rates and to more rapid forces. Using direct measures of muscle performance to further test Hill-type models, whether traditional or more complex, remains critical for establishing their accuracy and essential for verifying their applicability to scientific and clinical studies of musculoskeletal function.


Antimicrobial susceptibility profiles of Salmonella enterica serotypes recovered from pens of commercial feedlot cattle using different types of composite samples.
Salmonella enterica in cattle production systems may be associated with important human and animal disease issues. However, tremendous diversity exists among Salmonella recovered, and more information is needed about strains of greatest potential health concern, particularly those that are multidrug resistant (MDR). By characterizing Salmonella isolates from commercial feedlot pens, this study aimed to evaluate the strain diversity and prevalence of MDR Salmonella from different types of composite pen samples. Antimicrobial susceptibility profiles, serotype, and presence or absence of the integron-encoded intI1 gene were determined for 530 Salmonella isolates recovered using composite rope (n = 335), feces (n = 59), and water (n = 136) samples from 21 pens in 3 feedlots. The study investigated only pens with available isolates from multiple sample types. Most isolates (83.0%) of the 19 Salmonella serotypes identified were susceptible or intermediately susceptible to all the antimicrobials evaluated. Resistance to sulfisoxazole (14.9%), streptomycin (3.8%), and tetracycline (3.6%) were the most common. None of the isolates tested positive for a class 1 integron, and only 2.5% were resistant to multiple antimicrobials. All the MDR isolates, namely, serotypes Uganda (n = 9), Typhimurium (n = 2), and Give (n = 2), were resistant to at least five antimicrobials. Most MDR isolates (n = 11) were from two pens during 1 week within one feedlot. Overall, many Salmonella isolates collected within a pen were similar in terms of serotype and antimicrobial susceptibility regardless of sample type. However, MDR Salmonella and rare serotypes were not recovered frequently enough to suggest a general strategy for appropriate composite sampling of feedlot cattle populations for Salmonella detection and monitoring.


Inner nuclear membrane protein LEM-2 is required for correct nuclear separation and morphology in C. elegans.
The inner nuclear membrane proteins emerin and LEMD2 have both overlapping and separate functions in regulation of nuclear organization, gene expression and cell differentiation. We report here that emerin (EMR-1) and LEM domain protein 2 (LEM-2) are expressed in all tissues throughout Caenorhaditis elegans development but their relative distribution differs between cell types. The ratio of EMR-1 to LEM-2 is particularly high in contractile tissues, intermediate in neurons and hypodermis and lowest in intestine and germ line. We find that LEM-2 is recruited earlier than EMR-1 to reforming nuclear envelopes, suggesting the presence of separate mitotic membrane compartments and specific functions of each protein. Concordantly, we observe that nuclei of lem-2 mutant embryos, but not of emr-1 mutants, have reduced nuclear circularity. Finally, we uncover a so-far-unknown role of LEM-2 in nuclear separation and anchoring of microtubule organizing centers.


Impact of maternal substance use during pregnancy on childhood outcome.
The impact of maternal substance abuse is reflected in the 2002-2003 National Survey on Drug Use and Health. Among pregnant women in the 15-44 age group, 4.3%, 18% and 9.8% used illicit drugs, tobacco and alcohol, respectively. Maternal pregnancy complications following substance use include increases in sexually transmitted disorders, placental abruption and HIV-positive status. Effects on the neonate include a decrease in growth parameters and increases in central nervous system and autonomic nervous system signs and in referrals to child protective agencies. In childhood, behavioral and cognitive effects are seen after prenatal cocaine exposure; tobacco and alcohol have separate and specific effects. The ongoing use of alcohol and tobacco by the caretaker affects childhood behavior. Therefore, efforts should be made to prevent and treat behavioral problems as well as to limit the onset of drug use by adolescent children born to women who use drugs during pregnancy.


Unraveling the Driving Forces in the Self-Assembly of Monodisperse Naphthalenediimide-Oligodimethylsiloxane Block Molecules.
Block molecules belong to a rapidly growing research field in materials chemistry in which discrete macromolecular architectures bridge the gap between block copolymers (BCP) and liquid crystals (LCs). The merging of characteristics from both BCP and LCs is expected to result in exciting breakthroughs, such as the discovery of unexpected morphologies or significant shrinking of domain spacings in materials that possess the high definition of organic molecules and the processability of polymers. Here we report the bulk self-assembly of two families of monodisperse block molecules comprised of naphthalenediimides (NDIs) and oligodimethylsiloxanes (ODMS). These materials are characterized by waxy texture, strong long-range order, and very low mobility, typical properties of conformationally disordered crystals. Our investigation unambiguously reveals that thermodynamic immiscibility and crystallization direct the self-assembly of ODMS-based block molecules. We show that a synergy of high incompatibility between the blocks and crystallization of the NDIs causes nanophase separation, giving access to hexagonally packed columnar (Colh) and lamellar (LAM) morphologies with sub-10 nm periodicities. The domain spacings can be tuned by mixing molecules with different ODMS lengths and the same number of NDIs, introducing an additional layer of control. X-ray scattering experiments reveal macrophase separation whenever this constitutional bias is not observed. Finally, we highlight our "ingredient approach" to obtain perfect order in sub-10 nm structured materials with a simple strategy built on a crystalline "hard" moiety and an incompatible "soft" ODMS partner. Following this simple rule, our recipe can be extended to a number of systems.


Nasal carriage of highly resistant methicillin resistant Staphylococcus aureus (MRSA) strains by hospital staff in Hazara region of Pakistan.
To isolate and characterise multidrug resistant strains of Staphylococcus aureus from healthcare workers who are at potential risk of nosocomial infections. The observational, cross-sectional study was conducted from November 2014 to April 2015 at different hospitals of Haripur and Abbottabad, Pakistan, and comprised ward and operation theatre staff. The isolates were identified on the basis of microbiological and biochemical tests and further confirmed by polymerase chain reaction. Disc diffusion method was used for antibiotic sensitivity testing, and panton valentine leukocidin and methicillin resistance mecA genes were detected using polymerase chain reaction. Of 208 isolates, 108(52%) were from the ward staff and 100(48%) were from the operation theatre staff. Overall, 167(80.3%) isolates were positive for Staphylococcus aureus, and 75(36%) were methicillin-resistant Staphylococcus aureus. The number of antibiotic-resistant isolates was 75(45%) cefoxitin, 60(36%) ofloxacin, 152(91%) erythromycin, 52(31%) doxycycline, 127(76%) lincomycin, 53(32%) amoxicillin-clavulanate, 67(40%) ciprofloxacin, and 89(53%) ceftriaxone. A high number of hospital staff, including those working in operation theatres, were found to be carrying methicillin-resistant Staphylococcus aureus and multidrug resistant strains in their nasal passage that may be a source of infection to patients.


Giant Basal Cell Carcinoma Causing Axillary Contracture: A Case Report of an Unusual Localization of an Advanced Case.
Basal cell carcinoma (BCC) is the most common type of non-melanoma skin cancer. Although BCC arises most commonly in sun-exposed areas of the body, such as the head and neck, it infrequently can be seen in sun-protected parts as well. Axilla is one of the least encountered areas of BCC. Delay in the diagnosis or management alongside negligence of the patient can lead to a tumor reaching a giant size. We report a case of giant axillary BCC in a 59-years old female patient with no known risk factors for skin cancers. The tumor was excised with wide margins, and the tissue defect was reconstructed with latissimus dorsi musculocutaneous flap. A 3-year follow-up did not show any sign of recurrence or metastasis.


Effect of thromboxane antagonists on ozone-induced airway responses in dogs.
Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness.


Secondary structure and domain architecture of the 23S and 5S rRNAs.
We present a de novo re-determination of the secondary (2°) structure and domain architecture of the 23S and 5S rRNAs, using 3D structures, determined by X-ray diffraction, as input. In the traditional 2° structure, the center of the 23S rRNA is an extended single strand, which in 3D is seen to be compact and double helical. Accurately assigning nucleotides to helices compels a revision of the 23S rRNA 2° structure. Unlike the traditional 2° structure, the revised 2° structure of the 23S rRNA shows architectural similarity with the 16S rRNA. The revised 2° structure also reveals a clear relationship with the 3D structure and is generalizable to rRNAs of other species from all three domains of life. The 2° structure revision required us to reconsider the domain architecture. We partitioned the 23S rRNA into domains through analysis of molecular interactions, calculations of 2D folding propensities and compactness. The best domain model for the 23S rRNA contains seven domains, not six as previously ascribed. Domain 0 forms the core of the 23S rRNA, to which the other six domains are rooted. Editable 2° structures mapped with various data are provided (http://apollo.chemistry.gatech.edu/RibosomeGallery).


Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation.
Adverse outcomes following virus-associated disease in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT) have encouraged strategies to control viral reactivation in immunosuppressed patients. However, despite timely treatment with antiviral medication, some viral infections remain refractory to treatment, which hampers outcomes after HSCT, and are responsible for a high proportion of transplant-related morbidity and mortality. Adoptive transfer of donor-derived lymphocytes aims to improve cellular immunity and to prevent or treat viral diseases after HSCT. Early reports described the feasibility of transferring nonspecific lymphocytes from donors, which led to the development of cell therapy approaches based on virus-specific T cells, allowing a targeted treatment of infections, while limiting adverse events such as graft versus host disease (GvHD). Both expansion and direct selection techniques have yielded comparable results in terms of efficacy (around 70⁻80%), but efficacy is difficult to predict for individual cases. Generating bespoke products for each donor⁻recipient pair can be expensive, and there remains the major obstacle of generating products from seronegative or poorly responsive donors. More recent studies have focused on the feasibility of collecting and infusing partially matched third-party virus-specific T cells, reporting response rates of 60⁻70%. Future development of this approach will involve the broadening of applicability to multiple viruses, the optimization and cost-control of manufacturing, larger multicentred efficacy trials, and finally the creation of cell banks that can provide prompt access to virus-specific cellular product. The aim of this review is to summarise present knowledge on adoptive T cell manufacturing, efficacy and potential future developments.


Variation in the myosin light chain kinase gene is associated with development of acute lung injury after major trauma.
Single nucleotide polymorphisms in the myosin light chain kinase (MYLK) gene have been implicated in the risk of sepsis-related acute lung injury and asthma. MYLK encodes protein isoforms involved in multiple components of the inflammatory response, including apoptosis, vascular permeability, and leukocyte diapedesis. We tested the association of MYLK gene variation in the development of acute lung injury in major trauma patients. We conducted a prospective cohort study of 273 subjects with major trauma (injury severity score > or = 16). All x-rays and clinical data were reviewed by three clinicians for acute lung injury classification. A total of 17 tagging single nucleotide polymorphisms in MYLK were genotyped. Single nucleotide polymorphisms were individually assessed at the genotype level, and multiple logistic regression models were used to adjust for baseline variables. Haplotype analyses of sliding windows including 2-5 single nucleotide polymorphisms were conducted. Ninety-one of the 273 subjects (33%) met criteria for acute lung injury within 5 days of traumatic insult. Three informative MYLK coding single nucleotide polymorphisms were individually associated with acute lung injury, with two informative risk-conferring genotypes His21Pro (CC genotype, odds ratio = 1.87, 95% confidence interval 1.06-3.33; p = 0.022) and Pro147Ser (TT, odds ratio = 2.13, 95% confidence interval 1.14-4.10; p = 0.011) more frequent than the noninformative Thr335Thr CC genotype (odds ratio = 0.42, 95% confidence interval 0.20-0.85; p = 0.010). Each of these genotypic associations was more pronounced in African Americans with trauma. Multivariate analyses demonstrated the association of each MYLK single nucleotide polymorphism with acute lung injury to be independent of age, injury severity score, Acute Physiology and Chronic Health Evaluation III, and the mechanism of trauma. Finally, haplotype analyses revealed strong acute lung injury associations with 2-4 single nucleotide polymorphism haplotypes, all involving His21Pro (p < 0.008). Three MYLK coding single nucleotide polymorphisms previously associated with sepsis-induced acute lung injury and severe asthma in African Americans were associated with acute lung injury development after trauma in African Americans, although effect directions differed. These results confirm our prior studies implicating MYLK as a susceptibility gene in a distinct acute lung injury subset other than sepsis.


Inversion of the stereochemistry around the sulfur atom of the axial methionine side chain through alteration of amino acid side chain packing in Hydrogenobacter thermophilus cytochrome C552 and its functional consequences.
In cytochrome c, the coordination of the axial Met Sδ atom to the heme Fe atom occurs in one of two distinctly different stereochemical manners, i.e., R and S configurations, depending upon which of the two lone pairs of the Sδ atom is involved in the bond; hence, the Fe-coordinated Sδ atom becomes a chiral center. In this study, we demonstrated that an alteration of amino acid side chain packing induced by the mutation of a single amino acid residue, i.e., the A73V mutation, in Hydrogenobacter thermophilus cytochrome c552 (HT) forces the inversion of the stereochemistry around the Sδ atom from the R configuration [Travaglini-Allocatelli, C., et al. (2005) J. Biol. Chem. 280, 25729-25734] to the S configuration. Functional comparison between the wild-type HT and the A73V mutant possessing the R and S configurations as to the stereochemistry around the Sδ atom, respectively, demonstrated that the redox potential (Em) of the mutant at pH 6.00 and 25 °C exhibited a positive shift of ∼20 mV relative to that of the wild-type HT, i.e., 245 mV, in an entropic manner. Because these two proteins have similar enthalpically stabilizing interactions, the difference in the entropic contribution to the Em value between them is likely to be due to the effect of the conformational alteration of the axial Met side chain associated with the inversion of the stereochemistry around the Sδ atom due to the effect of mutation on the internal mobility of the loop bearing the axial Met. Thus, the present study demonstrated that the internal mobility of the loop bearing the axial Met, relevant to entropic control of the redox function of the protein, is affected quite sensitively by the contextual stereochemical packing of amino acid side chains in the proximity of the axial Met.


Zinc speciation in a smelter-contaminated soil profile using bulk and microspectroscopic techniques.
A soil profile contaminated as a result of Zn smelting operations from the historic Palmerton, PA smelting facility was characterized using X-ray absorption fine structure spectroscopy (XAFS) and X-ray diffraction (XRD) as bulk techniques, coupled with electron microprobe (EM), and microfocused XAFS as microscopic techniques to determine the chemical forms of Zn and elucidate its geochemical fate. The black, organic matter-rich topsoil contained 6200 mg/ kg Zn and was strongly acidic (pH 3.2). Bulk XAFS revealed that about 2/3 of Zn was bound in franklinite and 1/3 bound in sphalerite. Both minerals may have been aerially deposited from the smelter operation. Microspectroscopy detected also minor amounts of Zn adsorbed to Fe and Mn (hydr)oxides as inner-sphere sorption complexes, which may have formed after weathering of the Zn minerals. About 10% of the total Zn in this sample could be easily leached. In contrast, the yellowish, loamy subsoil contained less Zn (890 mg/kg) and had a higher pH of 3.9. XAFS revealed that Zn was mostly bound to Al-groups and to a lesser extent to Fe and Mn (hydr)oxides. Minor amounts of outer-sphere complexes or organic matter-bound Zn species could also be detected. About 70% of the total Zn content could be easily leached, indicating that outersphere sorption complexes have been underestimated and/ or inner-sphere sorption complexes are weak due to the low pH. The Zn forms in the subsoil most likely derive from weathering of the Zn minerals in the topsoil. Due to the lack of minerals incorporating Zn and due to the low pH, the availability of Zn in the subsoil is as high as in the topsoil, while the total concentration is almost 1 order of magnitude smaller.


Minireview: Meeting the demand for insulin: molecular mechanisms of adaptive postnatal beta-cell mass expansion.
Type 2 diabetes results from pancreatic ss-cell failure in the setting of insulin resistance. This model of disease progression has received recent support from the results of genome-wide association studies that identify genes potentially regulating ss-cell growth and function as type 2 diabetes susceptibility loci. Normal ss-cell compensation for an increased insulin demand includes both enhanced insulin-secretory capacity and an expansion of morphological ss-cell mass, due largely to changes in the balance between ss-cell proliferation and apoptosis. Recent years have brought significant progress in the understanding of both extrinsic signals stimulating ss-cell growth as well as mediators intrinsic to the ss-cell that regulate the compensatory response. Here, we review the current knowledge of mechanisms underlying adaptive expansion of ss-cell mass, focusing on lessons learned from experimental models of physiologically occurring insulin-resistant states including diet-induced obesity and pregnancy, and highlighting the potential importance of interorgan cross talk. The identification of critical mediators of islet compensation may direct the development of future therapeutic strategies to enhance the response of ss-cells to insulin resistance.


Techniques to achieve optimal seed placement in salvage and primary brachytherapy for prostate cancer.
To delineate flexible, interactive prostate brachytherapy techniques relying extensively on intraoperative biplane ultrasound and fluoroscopic visualization as developed over a period of 10 years in a brachytherapy program involving more than 2,500 patients treated to date. Specialized techniques were developed and refined in pretreatment transrectal ultrasound evaluation, interactive seed placement, and postoperative evaluation of implant quality. Special methods were also designed and implemented for treatment of salvage patients and otherwise difficult cases involving large prostates, interfering pubic bone structure, and prostatic defects due to prior transurethral resection of the prostate. Favorable clinical results, including 79% actuarial disease-free survival at 5 years with low morbidity, have been recently reported in 543 patients with localized primary prostate cancer treated by brachytherapy using the specialized techniques. Promising results have also been recently described in 49 patients who had failed prior radiotherapy and then underwent salvage brachytherapy. Among the techniques found useful were the judicious use of curved stylets and disposable and nondisposable needles, as well as monitoring and minimizing intraoperative prostate movement and compensating for unavoidable movement. Prostate brachytherapy has attracted renewed interest, largely due to advancements in technique. The presented techniques allow brachytherapy to be performed optimally in a broad range of patients.


2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation.
The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in atrial fibrillation (AF) management. This 2018 Focused Update addresses: (1) anticoagulation in the context of cardioversion of AF; (2) the management of antithrombotic therapy for patients with AF in the context of coronary artery disease; (3) investigation and management of subclinical AF; (4) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (5) acute pharmacological cardioversion of AF; (6) catheter ablation for AF, including patients with concomitant AF and heart failure; and (7) an integrated approach to the patient with AF and modifiable cardiovascular risk factors. The recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. Individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included as Supplementary Material and are available on the CCS Web site. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF guidelines recommendations, from 2010 to the present 2018 Focused Update, which is provided in the Supplementary Material.


Gastric endoscopic submucosal dissection using novel 2.6-mm articulating devices: an ex vivo comparative and in vivo feasibility study.
The conventional procedure of endoscopic submucosal dissection (ESD) is technically demanding. This study investigated the efficiency of novel articulating devices (maximum diameter 2.6 mm), which can be used with commercially available, standard endoscopes. In an ex vivo comparative study, eight endoscopists were divided into novices and experienced operators, and performed ESD using new devices and the conventional setup. An in vivo animal experiment was performed by two experts. Procedure times for incision and dissection were recorded, and unit times for circumferential length and area of specimens were calculated. All procedures were successfully completed with en bloc resection. In the ex vivo study, the unit procedure times for incision and dissection by novices were significantly shorter using the new system (P < 0.01 and P < 0.05), whereas there was no significant difference for experienced endoscopists. Perforation occurred during one procedure in which the new system was used. The in vivo experiments were successfully completed without adverse events. ESD using novel articulating devices was feasible. These devices were able to reduce the procedure time for novices.


Multidisciplinary staged surgical management of bifrontal meningoencephalocele with long-term follow-up.
The authors report on an infant with a bifrontal encephalocele that was associated with multisuture craniosynostosis, spasticity, and a progressively severe epilepsy. They describe the initial presentation, genetic screening results, staged multidisciplinary operative plans, clinical course, complications, and long-term surgical and developmental follow-up. To their knowledge, the comprehensive surgical management of this type of complicated congenital cranial anomaly has not been previously described. Surgical management was staged and multidisciplinary and required careful attention to all 3 components of the condition: 1) hydrocephalus, 2) frontal meningoencephalocele, and 3) epilepsy.


Diets supplemented with raw and roasted pumpkin (Cucurbita pepo L) seeds improved some biochemical parameters associated with erectile function in rats.
This study investigated the effect of diet supplemented with raw and roasted pumpkin seeds on some key biochemical parameters relevant to erectile function in corpus cavernosal tissues of male rats. Rats were fed with basal diets (NC), diet supplemented with raw (5% and 10%) and roasted (5% and 10%) pumpkin seeds for the evaluation of adenosine deaminase (ADA), phosphodiesterase-5 (PDE-5), arginase, acetylcholinesterase (AChE) activities, including nitric oxide level and malondialdehyde (MDA) content. Diet supplemented with roasted pumpkin seeds showed better PDE-5, ADA, arginase activities, as well as NO and MDA levels. No significant difference was observed in AChE activities of rats treated with raw and roasted pumpkin seeds. The modulatory effects of raw and roasted pumpkin seeds on enzymes associated with erectile dysfunction suggest the biochemical rationale for its therapeutic role in enhancing erectile function. However, roasted pumpkin seeds (10%, w/w of diet) possess more beneficial effects than the raw seeds. PRACTICAL APPLICATIONS: Pumpkin is a nutritious vegetable used in folklore for the treatment of bladder, prostate, and kidney diseases. The seeds are known to contain phenolic compounds which exert different health benefits. Processing of foods has been shown to either improve the quality or reduce the bioactive components which affect its functionality. In this study, roasting improved the biochemical parameters associated with erectile function in male rats. Roasted pumpkin seeds also reduced the oxidative stress parameters in rats' penile tissues when compared to raw pumpkin seeds. This study revealed that thermal processing associated with roasting could improve the antioxidant activity of pumpkin seeds and crucial enzymes related to erectile function. Hence, consumption of roasted pumpkin seeds could be more beneficial compared to raw pumpkin seeds.


Identification of Tyr413 as an active site residue in the flavoprotein tryptophan 2-monooxygenase and analysis of its contribution to catalysis.
The flavoenzyme tryptophan 2-monooxygenase catalyzes the oxidation of tryptophan to indoleacetamide, carbon dioxide, and water. The enzyme is a homologue of l-amino acid oxidase. In the structure of l-amino acid oxidase complexed with aminobenzoate, Tyr372 hydrogen bonds with the carboxylate of the inhibitor in the active site. All 10 conserved tyrosine residues in tryptophan 2-monooxygenase were mutated to phenylalanine; steady state kinetic characterization of the purified proteins identified Tyr413 as the residue homologous to Tyr372 of l-amino acid oxidase. Y413F and Y413A tryptophan 2-monooxygenase were characterized more completely with tryptophan as the substrate to probe the contribution of this residue to catalysis. Mutation of Tyr413 to phenylalanine results in a decrease in the value of the first-order rate constant for reduction of 35-fold and a decrease in the rate constant for oxidation of 11-fold. Mutation to alanine decreases the rate constant for reduction by 200-fold and that for oxidation by 33-fold. Both mutations increase the K(d) value for tryptophan and the K(i) values for the competitive inhibitors indoleacetamide and indole pyruvate by 5-10-fold. Both mutations convert the enzyme to an oxidase, in that the products of the catalytic reactions of both are indolepyruvate and hydrogen peroxide. The V/K(trp)-pH profiles for the Tyr413 mutant enzymes no longer show the pK(a) value of 9.9 seen in that for the wild-type enzyme, allowing identification of Tyr413 as the active site residue in the wild-type enzyme which must be protonated for catalysis. Substitution of Tyr413 abolishes the formation of the long wavelength charge transfer species observed in the wild-type enzyme. The data are consistent with the main role of Tyr413 being to maintain the correct orientation of tryptophan for effective hydride transfer and imino acid decarboxylation.


Mediating between the muse and the masses: inspiration and the actualization of creative ideas.
Within the creativity domain, inspiration is a motivational state posited to energize the actualization of creative ideas. The authors examined the construct validity, predictive utility, and function of inspiration in the writing process. Study 1, a cross-lagged panel study, showed that getting creative ideas and being inspired are distinct and that the former precedes the latter. In Study 2, inspiration, at the between-person level, predicted the creativity of scientific writing, whereas effort predicted technical merit. Within persons, peaks in inspiration predicted peaks in creativity and troughs in technical merit. In Study 3, inspiration predicted the creativity of poetry. Consistent with its posited transmission function, inspiration mediated between creativity of the idea and creativity of the product, whereas effort, positive affect, and awe did not. Study 4 extended the Study 3 findings to fiction writing. Openness to aesthetics and positive affect predicted creativity of the idea, whereas approach temperament moderated the relation between creativity of the idea and inspiration. Inspiration predicted efficiency, productivity, and use of shorter words, indicating that inspiration not only transmits creativity but does so economically.


Social Inequalities of Oral Anticoagulation after the Introduction of Non-Vitamin K Antagonists in Patients with Atrial Fibrillation.
Nationwide social inequalities of oral anticoagulation (OAC) usage after the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) have not been well identified in patients with atrial fibrillation (AF). This study assessed overall rate and social inequalities of OAC usage after the introduction of NOAC in Korea. Between January 2002 and December 2016, we identified 888,540 patients with AF in the Korea National Health Insurance system database. The change of OAC rate in different medical systems after the introduction of NOAC were evaluated. In all population, overall OAC use increased from 13.2% to 23.4% (p for trend <0.001), and NOAC use increased from 0% to 14.6% (p for trend <0.001). Compared with pre-reimbursement (0.48%), the annual increase of OAC use was significantly higher after partial (1.16%, p<0.001), and full reimbursement of OAC (3.72%, p<0.001). Full reimbursement of NOAC (adjusted odds ratio, 2.10; 95% confidence interval, 2.04-2.15) was independently associated with higher OAC use. However, the difference of overall OAC usage between tertiary referral hospitals and nursing or public health centers increased from 17.9% in 2010 to 36.8% in 2016. Moreover, usage rate of NOAC was significantly different among different medical systems from 37.2% at the tertiary referral hospital and 5.5% at nursing or public health centers. Introduction of NOACs in routine practice for stroke prevention in AF was associated with improved rates of overall OAC use. However, significant practice-level variations in OAC and NOAC use remain producing social inequalities of OAC despite full reimbursement.


Does surgical closure technique affect early mammographic detection of tumor recurrence after breast-conserving therapy?
Scarring in the tumor bed may mask or mimic local recurrence of tumor on surveillance mammography. Type of surgical closure technique used during lumpectomy may impact the pattern or density of scar tissue apparent in the tumor bed on mammography. This study sought to determine whether surgical closure type affects tumor-bed scar formation and impacts interpretation of surveillance mammography in women treated with breast-conserving therapy for early-stage breast cancer. One hundred women who received breast-conserving therapy were selected; 99 of them had 2-year post-treatment mammograms for the treated breast. Craniocaudal and mediolateral oblique views were reviewed by 3 subspecialty radiologists who routinely read mammograms. The mammograms were scored on 5-point scales for overall breast density and scarring within the tumor bed. The analyses did not demonstrate greater scarring or density in breast status post superficial closure compared with breast status post full-thickness closure, or vice versa (P > 0.05 for scarring and density). There were no detectable differences between the 2 closure techniques either within the data from individual reviewers, within the composite data for the entire group of reviewers, or in instances where 2 of 3 reviewers agreed (P > 0.05). There was significant interobserver variability in scoring among the mammographers for both scarring (P = 0.001) and density (P < 0.0001). Based on our study of the 2-year post-treatment mammograms, there was no evidence that closure technique impacts degree of scarring in the tumor bed. However, striking interobserver variability in scoring density and scarring was noted.


Effect of school eye health promotion on children's eye health literacy in Vietnam.
Health promotion intervention in schools is a useful strategy to improve students' health awareness. The purpose of this study was to assess the effect of eye health promotion interventions on eye health literacy in school children in Vietnam. A piloted questionnaire was administered to 300 children from five secondary schools in Ba Ria-Vung Tau, Vietnam at baseline and re-administered after the eye health promotion interventions. McNemar chi-square and logistic regression were used for statistical analysis. A total of 300 children aged 12-15 years (mean, 13.3 ± 1.3 years; 60% female) participated in the baseline survey. The participation rate in the post-health promotion survey was 94.7%. After the health promotion interventions, number of children who had correct eye health knowledge increased by 10-20% (60-75% to 70-95%), more children reported having had an eye examination (63.3% to 84.7%; p < 0.001) and more reported wearing spectacles (36.1% to 43.4%; p = 0.04). Children in urban schools were twice as likely to have improved knowledge of vision loss compared with children in rural schools (odds ratio, 2.1-4.1; p = 0.01 to p < 0.001). Children from rural schools had significantly higher odds of visiting doctor after the eye problems worsened (odds ratio, 4.5; p < 0.001). These results imply that eye health promotion interventions significantly improve eye health knowledge, attitudes and practices of school children. Additionally, participation of parents and teachers as change agents may further improve children's health literacy.


Differential expression of interleukin-2 by anti-CD3-stimulated peripheral blood mononuclear cells in patients with psoriatic arthritis and patients with cutaneous psoriasis.
The differences in systemic T-cell responses between patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis (Ps) are still largely unknown. To determine differential features that could be used to distinguish PsA from Ps, we compared the cytokine secretion profile of circulating T cells in patients with PsA, patients with cutaneous Ps and control subjects. We determined Th1, Th2 and Th17 cytokine secretion of anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) using a cytokine bead array. Normality of data distribution was assessed by the Shapiro-Wilk test, and statistical significance was calculated by the Mann-Whitney test. Phenotypic characterization of circulating T cells was performed by fluorescence-activated cell sorting analysis. We found that the major systemic differences distinguishing PsA from cutaneous Ps were the increased secretion of interleukin (IL)-2 by α-CD3-stimulated PBMCs and a higher percentage of circulating CD3+ T cells expressing the proliferation marker CD71 in PsA. These results indicate IL-2 as a possible biomarker of PsA, and suggest a role of circulating T cells with high proliferative capacity in the pathogenesis of PsA.


Autonomous early detection of eye disease in childhood photographs.
The "red reflex test" is used to screen children for leukocoria ("white eye") in a standard pediatric examination, but is ineffective at detecting many eye disorders. Leukocoria also presents in casual photographs. The clinical utility of screening photographs for leukocoria is unreported. Here, a free smartphone application (CRADLE: ComputeR-Assisted Detector of LEukocoria) was engineered to detect photographic leukocoria and is available for download under the name "White Eye Detector." This study determined the sensitivity, specificity, and accuracy of CRADLE by retrospectively analyzing 52,982 longitudinal photographs of children, collected by parents before enrollment in this study. The cohort included 20 children with retinoblastoma, Coats' disease, cataract, amblyopia, or hyperopia and 20 control children. For 80% of children with eye disorders, the application detected leukocoria in photographs taken before diagnosis by 1.3 years (95% confidence interval, 0.4 to 2.3 years). The CRADLE application allows parents to augment clinical leukocoria screening with photography.


Catheter rupture and distal embolisation: a rare complication of central venous ports.
Central venous access devices placed through a percutaneous subclavian approach may be compressed by neighbouring bony structures, leading to biomaterial fatigue, catheter fracture at the compression site, and possible embolisation of distal fragment into the central veins. The aim of this paper is to review the experience of the authors, including more than 1300 subclavian port placements, carried out during a five-year period, discussing possible causes and therapeutic options of this rare complication. Nine patients out of 1320 (0.68%) experienced this complication during the five-year period of this study. Two patients only showed a retrospective radiologic evidence of the 'pinch-off sign' (e.g. initial compression of the catheter at the costo-clavicular junction). No patients had symptoms from the embolised catheter fragment; the most frequent symptom (8 out of 9 cases) was a painful swelling around the port area during infusion, related to the extravasation of medications or fluids into the subcutaneous tissue. The site of embolised segment varied from azygos vein to right pulmonary artery; however, these findings did not affect the outcome, and all the embolised fragments were successfully retrieved through a transfemoral approach using a radiologic interventional technique. No fatality occurred. The catheter fracture and embolisation of the distal fragment are a well-known complication of subclavian central venous long-term cannulation, whose estimated overall incidence is 0.5-1%. Diagnosis is usually based on the radiologic appearance of the catheter compression (so called 'pinch-off sign'), which is far from being constant; a clinical suspicion can derive from intermittent malfunction, which claims differential diagnosis with the pres-ence of a fibrin sleeve around the tip of the catheter. Once diagnosed, the treatment is always an interventional radiologic approach, which has a very high success rate. When it fails, the possibility to leave the fragment embolised in the central veins, heart or pulmonary arteries, should be considered, being the thoracotomy and open catheter retraction questionable, at present time, in patients who have no symptoms and limited life-expectancy.


Spindle Cell Variant of Embryonal Rhabdomyosarcoma: A Rare Entity with Diagnostic Challenges.
The spindle cell variant of embryonal rhabdomyosarcoma is a rare and a better differentiated variant of embryonal rhabdomyosarcoma, having a better prognosis compared to other types of rhabdomyosarcomas. So, it needs to be distinguished from classical forms of the neoplasm. Its morphological resemblance to spindle cell neoplasms like leiomyosarcomas and fibrosarcomas may pose diagnostic difficulties for the pathologist. This problem can be overcome by careful search for rhabdomyoblasts in sections, which are usually few, and Immunohistochemistry for myogenin. In the present case, a 15-year-old female presented with a progressively increasing swelling in the right upper eyelid, which was diagnosed as a rare variant of rhabdomyosarcoma. We have also attempted to discuss its differential diagnosis, and to emphasize the fact that this rare entity may be misdiagnosed.


Incontinence brief use in acute hospitalized patients with no prior incontinence.
The aim of the study was to evaluate the incidence of in-hospital incontinence brief use among older patients who did not use diapers prior to admission. A second aim was to identify factors affecting the use of incontinence briefs, commodes, urinals, and self-toileting. The study was conducted in 5 medical acute-care units of a 900-bed teaching hospital in Israel. The data presented here were collected from a total of 465 patients (age ≥ 70 years) who did not use incontinence briefs prior to admission. The current study is part of a larger prospective cohort study conducted from February to November 2009. Patients or proxies were interviewed on admission regarding their functional status, mobility, continence status, and type of voiding patterns prior to hospital stay. Interviews regarding in-hospital voiding and mobility patterns were conducted each day after the first 48 hours of hospitalization. Electronic medical records were extracted to calculate the severity of illness, comorbidity score, and length of hospital stay. The incidence of in-hospital adult incontinence brief use was 14% (65/465), whereas the rate of in-hospital commodes/urinals was 8.2% (38/465). The relative risk (RR) of incontinence brief use versus self-toileting was 18.76 (95% confidence intervals [CI]: 4.36-43.72) and 10.12 (95% CI: 2.23-13.48) higher for patients with low or moderate in-hospital mobility, respectively, versus those who were highly mobile. Patients who used incontinence briefs were more likely to be female (RR = 1.65; CI: 1.20-2.23) and were more likely to have low mobility (RR = 1.59; 95% CI: 1.10-2.35) than patients who used commodes/urinals. Adult incontinence briefs are frequently used in continent patients, especially women, with low mobility. However, the current literature identifies incontinence briefs use as leading to multiple adverse outcomes. Therefore, the use of adult incontinence briefs among hospitalized older adults requires more scrutiny.


Brief communication: coracoclavicular joint in Northwest Indians.
The incidence of an articular facet on the conoid tubercle of the clavicle indicating the presence of a coracoclavicular joint was studied in paired clavicles obtained from 1,000 adult subjects aged 18 to 95 years (748 males, 252 females), and 75 children (45 males, 30 females) of known age on whom a medicolegal postmortem had been performed by the second author during 1972-90. The subjects were inhabitants of northwest India. In addition, paired clavicles from 50 neonates and 35 fetuses were also examined. The facet was absent in the fetuses, neonates, and young children. The youngest clavicle showing the facet was from a girl of 13 years, in which it was present bilaterally. In adults the incidence of the facet was 10.1% (bilateral 5.7%, unilateral 4.4%) in males and 8.3% (bilateral 3.6%, unilateral 4.8%) in females. Absence of the facet in the fetuses, neonates, and young children shows that it is not a congenital anomaly.


Unraveling Spatiotemporal Transient Dynamics at the Nanoscale via Wavelet Transform-Based Kelvin Probe Force Microscopy.
Mechanistic probing of surface potential changes arising from dynamic charge transport is the key to understanding and engineering increasingly complex nanoscale materials and devices. Spatiotemporal averaging in conventional heterodyne detection-based Kelvin probe force microscopy (KPFM) inherently limits its time resolution, causing an irretrievable loss of transient response and higher-order harmonics. Addressing this, we report a wavelet transform (WT)-based methodology capable of quantifying the sub-ms charge dynamics and probing the elusive transient response. The feedback-free, open-loop wavelet transform KPFM (OL-WT-KPFM) technique harnesses the WT's ability to simultaneously extract spatial and temporal information from the photodetector signal to provide a dynamic mapping of surface potential, capacitance gradient, and dielectric constant at a temporal resolution 3 orders of magnitude higher than the lock-in time constant. We further demonstrate the method's applicability to explore the surface-photovoltage-induced sub-ms hole-diffusion transient in bismuth oxyiodide semiconductor. The OL-WT-KPFM concept is readily applicable to commercial systems and can provide the underlying basis for the real-time analysis of transient electronic and electrochemical properties.


Making the diagnosis of labour: midwives' diagnostic judgement and management decisions.
This paper reports a study examining midwives' perceptions of the way in which they diagnose labour. Diagnosis of active labour is often problematic. A midwifery workforce planning tool identified that up to 30% of women admitted to United Kingdom labour wards subsequently turned out not to have been in labour. There is evidence that if a woman is admitted to a labour ward in early labour, she is more likely to have some form of medical intervention. However, despite the impact of misdiagnosis, there is little research on the process of decision-making by midwives in relation to diagnosis of labour. This was a qualitative study, employing focus group methods. Participants were a convenience sample of midwives working in a maternity unit in the North of England during 2002. They were asked to discuss their experience of admission of women in labour. Data were analysed using latent content analysis. Thirteen midwives participated in one of two groups. They described using information cues, which could be separated into two categories: those arising from the woman (Physical signs, Distress and coping, Woman's expectations and Social factors) and those from the institution (Midwifery care, Organizational factors and Justifying actions). Midwives' decision-making process could be divided into two stages. The diagnostic judgement was based on the physical signs of labour: the management decision would then be made by considering the diagnostic judgement as well as cues such as how the woman was coping, her expectations and those of her family and the requirements of the institution. Midwives may experience more difficulty with the management decision than with the initial diagnosis. It may be that the number of inappropriate admissions to labour wards could be reduced by supporting midwives to negotiate the complex management hurdles, which accompany diagnosis of labour.


CD44s and CD44v8-10 isoforms confer acquired resistance to osimertinib by activating the ErbB3/STAT3 signaling pathway.
Although epidermal growth factor receptor (EGFR)-mutant lung cancers respond well to osimertinib, acquired resistance to osimertinib eventually develops through EGFR-dependent and EGFR-independent resistance mechanisms. CD44 splicing variants are widely expressed in lung cancer tissues. However, it remains unclear whether specific splicing variants are involved in acquired resistance to osimertinib. The real-time PCR was performed to measure the expression levels of total CD44 and specific CD44 splicing variants (CD44s or CD44v). Gene knockdown and restoration were performed to investigate the effects of CD44 splicing variants on osimertinib sensitivity. Activation of the signaling pathway was evaluated using receptor-tyrosine-kinase phosphorylation membrane arrays, co-immunoprecipitation, and western blotting. Clinical analysis demonstrated that the expression level of total CD44 increased in primary cancer cells from lung adenocarcinomas patients after the development of acquired resistance to osimertinib. Furthermore, osimertinib-resistant cells showed elevated levels of either the CD44s variant or CD44v variants. Manipulations of CD44s or CD44v8-10 were performed to investigate their effects on treatment sensitivity to osimertinib. Knockdown of CD44 increased osimertinib-induced cell death in osimertinib-resistant cells. However, restoration of CD44s or CD44v8-10 in CD44-knockdown H1975/AZD-sgCD44 cells induced osimertinib resistance. Mechanically, we showed that ErbB3 interacted with CD44 and was transactivated by CD44, that consequently triggered activation of the ErbB3/STAT3 signaling pathway and led to CD44s- or CD44v8-10-mediated osimertinib resistance. CD44 is a co-receptor for ErbB3 and triggers activation of the ErbB3 signaling axis, leading to acquired resistance to osimertinib. CD44/ErbB3 signaling may represent a therapeutic target for overcoming osimertinib resistance.


Predictors of treatment response in patients with non-erosive reflux disease.
Up to 40% of patients with non-erosive reflux disease (NERD) fail to respond to proton pump inhibitor therapy. To determine useful prognostic factors for response to and suppression in NERD. A pooled analysis from three multicentre, double-blind trials of patients with a normal endoscopy and heartburn for 4 days or more during the 7 days prior to the start of each treatment. Patients received omeprazole 20 mg, esomeprazole 20 mg or esomeprazole 40 mg/day for 4 weeks. Complete resolution of heartburn was defined as no heartburn during the last week. Of 2458 patients included, complete heartburn resolution was achieved in 63% at the end of 4 weeks treatment. Response on days 5-7 provided an 85% probability of complete resolution of heartburn at 4 weeks; the probability of complete heartburn resolution at 4 weeks in those with moderate to severe symptoms on days 5-7 was 22%. Sensitivity and specificity of no heartburn on days 5-7 was 55% and 83% respectively. Patient demographics, duration of symptoms, medications used, other symptoms and body mass index were not predictors. Assessment of heartburn resolution during the first week of therapy was the best predictor of treatment success at 4 weeks in non-erosive reflux disease, but was suboptimal as a test.


Peroxisome proliferator-activated receptor subtype- and cell-type-specific activation of genomic target genes upon adenoviral transgene delivery.
Investigations of the molecular events involved in activation of genomic target genes by peroxisome proliferator-activated receptors (PPARs) have been hampered by the inability to establish a clean on/off state of the receptor in living cells. Here we show that the combination of adenoviral delivery and chromatin immunoprecipitation (ChIP) is ideal for dissecting these mechanisms. Adenoviral delivery of PPARs leads to a rapid and synchronous expression of the PPAR subtypes, establishment of transcriptional active complexes at genomic loci, and immediate activation of even silent target genes. We demonstrate that PPARgamma2 possesses considerable ligand-dependent as well as independent transactivation potential and that agonists increase the occupancy of PPARgamma2/retinoid X receptor at PPAR response elements. Intriguingly, by direct comparison of the PPARs (alpha, gamma, and beta/delta), we show that the subtypes have very different abilities to gain access to target sites and that in general the genomic occupancy correlates with the ability to activate the corresponding target gene. In addition, the specificity and potency of activation by PPAR subtypes are highly dependent on the cell type. Thus, PPAR subtype-specific activation of genomic target genes involves an intricate interplay between the properties of the subtype- and cell-type-specific settings at the individual target loci.


Separable Effects of Childhood Maltreatment and Adult Adaptive Functioning on Amygdala Connectivity During Emotion Processing.
Individuals with a history of maltreatment show altered amygdala reactivity to emotional stimuli, atypical frontal regulatory control, and differences in frontolimbic connectivity compared with nonmaltreated controls. However, despite early trauma, many individuals who experience maltreatment show resilience or adaptive functioning in adulthood including positive social, educational, and occupational outcomes. The present study used a psychophysiological interaction model to examine the effect of adult adaptive functioning on group differences between maltreated and nonmaltreated adults in task-based amygdala functional connectivity. The task used was a facial emotion-matching paradigm. Functional magnetic resonance imaging scans were collected from 41 adults with a history of substantiated childhood maltreatment and 39 nonmaltreated adults who were well matched on demographic variables, all of whom had been studied since childhood. Adaptive functioning was measured with a composite score of success on stage-salient developmental tasks. Consistent with previous research, we found differences in task-related amygdala functional connectivity between the maltreated and nonmaltreated groups. Effects were seen in the left hippocampus, right dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and right thalamus. However, when adult functioning was included in the model, maltreatment-related differences in amygdala connectivity were observed only in the hippocampus. Adult adaptive functioning independently predicted task-related amygdala connectivity in frontal and parietal regions across the entire sample. These results suggest that frontolimbic functional connectivity is predicted by positive developmental adaptation in this high-risk population, regardless of maltreatment history, whereas intralimbic connectivity (amygdala and hippocampus) is more specifically associated with maltreatment history.


GRP78 positively regulates estrogen‑stimulated cell growth mediated by ER‑α36 in gastric cancer cells.
Estrogen receptor (ER)‑α36, a novel isoform of ER, primarily mediates non‑classical estrogen signaling. It has been reported that ER‑α36‑mediated growth stimulating signals are involved in the malignancy of gastric tumor cells. However, the mechanism underlying the regulation of ER‑α36 function in development of gastric cancer remains to be elucidated. The present study investigated the role of 78 kDa glucose‑regulated protein (GRP78) in the regulation of ER‑α36 expression and signaling during the growth of gastric tumor cells. It was demonstrated that GRP78 expression was detectable in gastric cancer tumor tissues, and was positively‑correlated with tumor stage, lymphatic metastasis and ER‑α36 expression (P<0.05). An increased growth rate, and increased expression of ER‑α36 and the cell cycle regulator cyclin D1 was detected in cells with GRP78 overexpression (SGC‑High78 cells). SGC‑High78 cells are more sensitive to estrogen compared with SGC‑Control cells. Therefore, the results of the present study demonstrated that GRP78 positively regulated ER‑α36 expression and signaling with cell growth in gastric cancer, which is involved in gastric carcinogenesis.


Deletion in the peripherin/RDS gene in two unrelated Sardinian families with autosomal dominant butterfly-shaped macular dystrophy.
Autosomal dominant butterfly-shaped macular dystrophy is associated with different mutations of the peripherin/RDS gene. We studied the phenotype of two families with a novel large deletion in the peripherin/RDS gene. Clinical study, fluorescein angiography, color vision testing, automatic perimetry, electrophysiologic studies, and DNA analysis were performed on all the members of the two families. Fundus examination in patients aged 30 to 60 years showed yellow deposits in the macula with a butterfly-shaped pattern. Central choroidal atrophy was present in the older patients only. Macular visual function tests (color vision and central visual field) were abnormal, and electro-oculograms were slightly subnormal in five individuals tested. Electroretinograms and results of dark adaptometry were normal. Linkage analysis with intragenic polymorphic markers and quantitative polymerase chain reaction showed heterozygosity for a large deletion that removed exons 2 and 3 of the peripherin/RDS gene in all affected members of two families. This deletion escaped detection by direct analysis of amplified exons and was identified by intragenic polymorphic markers analysis, resulting in loss of heterozygosity from affected parents to affected children, and by quantitative polymerase chain reaction. The delineation of the molecular defect associated with the disease in these two families allows us to verify the presence or absence of the disease in clinically unaffected members.


Balance training for neuromuscular control and performance enhancement: a systematic review.
As a result of inconsistencies in reported findings, controversy exists regarding the effectiveness of balance training for improving functional performance and neuromuscular control. Thus, its practical benefit in athletic training remains inconclusive. Our objective was to evaluate the effectiveness of training interventions in enhancing neuromuscular control and functional performance. Two independent reviewers performed a literature search in Cochrane Bone, Joint and Muscle Trauma Group Register and Cochrane Controlled Trials Register, MEDLINE, EMBASE, PEDro (Physiotherapy Evidence Database), and SCOPUS. Randomized controlled trials and controlled trials without randomization with healthy and physically active participants aged up to 40 years old were considered for inclusion. Outcomes of interest were postural control, muscle strength, agility, jump performance, sprint performance, muscle reflex activity, rate of force development, reaction time, and electromyography. Data of interest were methodologic assessment, training intervention, outcome, timing of the outcome assessment, and results. Standardized mean differences and 95% confidence intervals were calculated when data were sufficient. In total, 20 randomized clinical trials met the inclusion criteria. Balance training was effective in improving postural sway and functional balance when compared with untrained control participants. Larger effect sizes were shown for training programs of longer duration. Although controversial findings were reported for jumping performance, agility, and neuromuscular control, there are indications for the effectiveness of balance training in these outcomes. When compared with plyometric or strength training, conflicting results or no effects of balance training were reported for strength improvements and changes in sprint performance. We conclude that balance training can be effective for postural and neuromuscular control improvements. However, as a result of the low methodologic quality and training differences, further research is strongly recommended.


Physical Activity for Improving the Immune System of Older Adults During the COVID-19 Pandemic.
COVID-19 has spread rapidly around the world and reached pandemic proportions. With no definitive treatment to date, prevention is critical, and strengthening the immune system is a valuable tool in reducing the risk of infection. While the aging process can weaken the immune system, physical activity may boost it. The review intended to examine the interaction between the changes in the immune system during aging and the development of a COVID-19 infection, focusing on pathophysiological factors, and to evaluate whether regular physical activity can strengthen the immune system in older adults. The research team performed a narrative review by searching databases. During the COVID-19 pandemic, older people can stay active and healthy through playing sports such as yoga, walking, jogging, and cycling. Also, they can use online or virtual yoga and Pilates classes and videos, perform resistance exercises with minimal facilities at home, and do daily housework, such as gardening. In general, due to the positive role of regular exercise training on the immune system of the older adults as well as the involvement of the immune system in COVID-19, it's necessary to guide and implement home-based exercises for older adults.


Intratesticular varicocele: Report of two cases.
Intratesticular varicocele is a rare entity and describes dilated intratesticular veins radiating from the mediastinum testis into the testicular parenchyma. Scrotal ultrasonography of two patients who presented to our urology clinic due to left scrotal pain revealed multiple tubular structures in the testes with diameters of more than 2 mm. Duplex spectral analysis showed a reversed flow response to Valsalva's maneuver. Apropos of two cases, intratesticular varicocele is reviewed.


Syphilitic Pulmonary Inflammatory Pseudotumor: A Diagnostic Challenge.
A 46-year-old man presented with nonproductive cough and lower limb swelling. Chest radiograph showed a left lower lobe lung mass and multiple subpleural nodules. Other investigations revealed that he had nephrotic syndrome. Core biopsies of the left lower lobe lung mass showed features of inflammatory pseudotumor with endarteritis obliterans and a lymphoplasmacytic infiltrate. Immunohistochemical stain for Treponema pallidum was positive. Resolution of the lung mass and nephrotic syndrome was achieved after treatment with intramuscular benzathine benzylpenicillin. The differential diagnosis of pulmonary inflammatory pseudotumor, manifestations of pulmonary syphilis, and a literature review of secondary syphilis of the lung are discussed.


Resonance imaging of the eustachian tube cartilage in microtia.
The purpose of this study was to determine whether external and internal defects in microtia are related. Magnetic resonance images of the eustachian tube cartilage were evaluated for 20 patients who had unilateral microtia. Nineteen patients were classified as Grade 2, and one was classified as Grade 3. The Grade 3 patient also had unilateral facial palsy. On T1-, T2-, and proton-density-weighted images, the eustachian tube cartilage was clearly identified as a pair of straight lines with low signal intensity. There was no evidence of hypoplasia of the eustachian tube cartilage on the microtic side in any Grade 2 patient, but hypoplasia was evident on the microtic side of the patient classified as Grade 3. These findings are consistent with the view that impairment of embryonic development before 6 weeks results in injury to the immature primordium and malformation of both the external and middle ear. In contrast, injuries that occur at a later fetal age (i.e., after 3 months) do not appear to cause middle ear malformations.


Phenotypic plasticity is maintained despite geographical isolation in an African cichlid fish, Pseudocrenilabrus multicolor.
Gene flow among populations in different selective environments should favor the evolution of phenotypic plasticity over local adaptation. Plasticity in development is a common response to long-term hypoxia in some widespread African fishes, including Pseudocrenilabrus multicolor, a cichlid that exploits both normoxic (high oxygen) rivers/lakes and hypoxic (low oxygen) swamps. Previous studies have shown that fish from normoxic and hypoxic sites differ in many traits, including gill size, brain size and body shape, and that much of this variation reflects developmental plasticity. However, these earlier studies focused on areas in Uganda where gene flow between swamp and river or lake populations is high. In this study we tested the hypothesis that P. multicolor from a relatively isolated lake population (Lake Saka, Uganda) exhibit low levels of plasticity in traits related to oxygen uptake. Multiple broods of P. multicolor from Lake Saka were reared under low and high dissolved oxygen, and traits related to gill size, brain mass and body shape were quantified. Surprisingly, both gill size and brain mass showed high levels of developmental plasticity. We suggest that high levels of plasticity, particularly in the gill size of P. multicolor, reflects low costs of maintaining the plastic response, even in relatively isolated populations.


Functional proteomics identifies miRNAs to target a p27/Myc/phospho-Rb signature in breast and ovarian cancer.
The myc oncogene is overexpressed in almost half of all breast and ovarian cancers, but attempts at therapeutic interventions against myc have proven to be challenging. Myc regulates multiple biological processes, including the cell cycle, and as such is associated with cell proliferation and tumor progression. We identified a protein signature of high myc, low p27 and high phospho-Rb significantly correlated with poor patient survival in breast and ovarian cancers. Screening of a miRNA library by functional proteomics in multiple cell lines and integration of data from patient tumors revealed a panel of five microRNAs (miRNAs) (miR-124, miR-365, miR-34b*, miR-18a and miR-506) as potential tumor suppressors capable of reversing the p27/myc/phospho-Rb protein signature. Mechanistic studies revealed an RNA-activation function of miR-124 resulting in direct induction of p27 protein levels by binding to and inducing transcription on the p27 promoter region leading to a subsequent G1 arrest. Additionally, in vivo studies utilizing a xenograft model demonstrated that nanoparticle-mediated delivery of miR-124 could reduce tumor growth and sensitize cells to etoposide, suggesting a clinical application of miRNAs as therapeutics to target the functional effect of myc on tumor growth.


Cervical wear and occlusal wear from a periodontal perspective.
The aim of this study was to investigate whether cervical wear was associated with occlusal wear and clinical periodontal parameters in relatively older adults. A total of 30 patients, with multiple non-carious cervical lesions (NCCLs) and without a disease or condition that could cause heavy tooth wear, were included in the study. The periodontal parameters including plaque index, probing pocket depth, gingival recession (GR) and tooth mobility were obtained from 641 teeth of which 475 (74·1%) displayed NCCLs. The levels of cervical wear and occlusal wear were determined according to a tooth wear index. Premolars were more likely to develop cervical wear than canines, molars and incisors. Cervical wear was significantly associated with less plaque accumulation and the presence of shallow pockets. The teeth with advanced GR and without increased mobility were 2·583 and 1·715 times more likely to develop deeper cervical lesions, respectively. Age and the level of occlusal wear were not linked to the bucco-lingual depth of cervical wear. In conclusion, the significant association of advanced cervical wear with the relatively healthy periodontal status suggested the role of abrasion and its possible combined action with erosion in the aetiology of NCCLs. The rate of GR and the lack of tooth mobility could constitute predisposing factors for the progression of cervical wear because the exposed root surfaces could be more susceptible to abrasion and/or erosion, and the non-mobile teeth resisting strongly against frictional forces, thus abrasive effects, could possibly develop cervical wear.


Effect of smoking on the lipid composition of lung lining fluid and relationship between immunostimulatory lipids, inflammatory cells and foamy macrophages in extrinsic allergic alveolitis.
Normal lung lining fluid suppresses lymphoproliferative responses. This effect is mediated by the major phospholipid components, but minor lipid components can stimulate lymphocyte proliferation. The aim of this study was to discover whether the changes in lung lipid composition reported in patients with extrinsic allergic alveolitis (EAA) might influence the levels of lymphocytes which occur in the lungs of these patients. Since cigarette smokers are less susceptible to EAA, we also investigated the effect of smoking on the lipid composition of lung lining fluid. Lung lining fluid was sampled by bronchoalveolar lavage (BAL) from 15 patients with EAA, and 9 non-smokers and 13 smokers without lung disease. The smoking controls had increases in phosphatidylethanolamine, sphingomyelin and phosphatidylglycerol, but lower levels of cholesterol and cholesterol:total phospholipid ratios compared with the nonsmoking controls. By contrast, the patients with EAA had increases in total phospholipid and sphingomyelin; there were no smoking related decreases in cholesterol; and several patients had levels of cholesterol and cholesterol:total phospholipid ratios above the upper limit for the controls. In the BAL fluids of the EAA patients, the levels.ml-1 of the immunostimulatory lipids sphingomyelin, phosphatidylethanolamine, cholesterol and cholesterol esters correlated with the number.ml-1 of lymphocytes, mast cells, neutrophils and "foamy" macrophages. Cholesterol levels (rs = 0.82) and lymphocyte counts (rs = 0.90) correlated most closely with "foamy" macrophages (p less than 0.001), suggesting that uptake of cholesterol by macrophages may enhance antigen-presenting function. These observations provide some support for the hypothesis that inflammatory reactions in the lungs might be influenced by the local lipid environment.


LLC-PK1 mutant with increased Na+-H+ exchange and decreased sensitivity to amiloride.
LLC-PK1 cells contain a well-characterized Na+-H+ antiporter that is sensitive to ethylisopropylamiloride (EIPA) in the submicromolar range. Using a modification of the method of Franchi et al. (J. Biol. Chem. 261: 14614-14620, 1986), we have selected mutants that can recover from an acid load in the presence of 100 microM EIPA. One such mutant, designated PKE20, has been studied in detail. The maximal velocity (Vmax) for the Na+-H+ antiporter, assayed as EIPA-sensitive 22Na+ uptake, has increased from 44 nmol.min-1.10(6) cells-1 in the parent cells to 106 nmol.min-1.10(6) cells-1 in PKE20. No detectable change has occurred in the Km for Na+ (118 mM in the parent, 111 mM in the mutant) or in the dependence of Na+ uptake on intracellular pH. However, the PKE20 antiporter exhibits a greatly decreased sensitivity to amiloride and its derivatives, with drops in inhibitory potency ranging from 25-fold (amiloride) to 100-fold (EIPA). The mutation is specific for the antiporter; measurements of Na+-K+ pump and Na+-dependent amino acid uptake show only small changes, which appear to result from minor antiporter-induced alterations in internal Na+ concentration. PKE20 cells should prove useful in experiments to identify and isolate the antiporter protein.


Frequency of transient hypothyroxinaemia in low birthweight infants. Potential pitfall for neonatal screening programmes.
Thyroid function was studied in 54 low birthweight infants during a 3-week period. Each infant was placed in one of three groups. Group 1 (n = 21), infants who were well and appropriately grown fro gestational age; group 2 (n = 23), infants who were appropriately grown but who had hyaline membrane disease; group 3 (n = 10), infants who were small-for-gestational-age. In group 1, 5 (24%) infants had at least one serum thyroxine value less than 3.0 micrograms/100 ml (39 nmol/l). There were 8 (35%) infants in group 2 who had similarly low serum thyroxine values as did 5 (50%) of the 10 infants in group 3. Serum thyrotropin levels and serum binding of the thyroid hormones, as measured by a T3-charcoal uptake test, were normal in all infants. In all instances but 2, serum thyroxine values were at least 4.0 micrograms/100 ml (51 nmol/l) by the end of the 3-week period. There is thus a high incidence of transient 'hypothyroxinaemia' in low birthweight infants, particularly if such infants have hyaline membrane disease or are small-for-gestational-age. These findings must be considered when interpreting results of screening programmes for congenital hypothyroidism and they lend further support to the use of a combination of serum thyroxine and thyrotropin determinations for optimum screening of such infants.


Impaired fibrinolysis in premenopausal women and age-matched men with Type 2 diabetes mellitus: a pilot study.
The presence of Type 2 diabetes mellitus (DM) is one of the strongest predictors of cardiovascular disease (CVD) in women. Although the specific mechanisms underlying this increased risk are unknown, one factor that may contribute to CVD in women with Type 2 DM is impaired fibrinolysis. Healthy premenopausal women have a low rate of CVD and excellent fibrinolytic potential. Impairment in fibrinolysis in people with DM has been demonstrated mainly in men, whereas the fibrinolytic potential of women with Type 2 DM has not been characterized well. This pilot study compared fibrinolytic measures in premenopausal women and men with DM with those of healthy age-matched control women and men to help determine whether fibrinolysis is abnormal in women with DM. Fibrinolytic measurements included euglobulin clot lysis time (ELT), fibrinogen, plasminogen activator inhibitor 1, and tissue-type plasminogen activator. Poststasis ELT was significantly impaired in the women with DM as compared with the control women. The men with DM had a tendency toward slower poststasis ELT than did the control men, but the differences between the men's groups were not significant. In the women's groups only, we observed a trend toward increased plasminogen activator inhibitor 1 among the women with DM. Women with DM have a more significant abnormality in poststasis ELT than do men with DM as compared with sex-specific counterparts without DM.


The Oglala Sioux Tribe CHOICES Program: Modifying an Existing Alcohol-Exposed Pregnancy Intervention for Use in an American Indian Community.
Alcohol-exposed pregnancies are a health issue for many American Indian communities. The goal of this manuscript is to outline how an existing alcohol-exposed pregnancy prevention program with non-pregnant women (Project CHOICES) was modified to fit the needs and norms of an American Indian community. The Oglala Sioux Tribe CHOICES Program was developed and implemented using community feedback through initial meetings, reviewing materials, gathering input into recruitment and intervention logistics, and conducting interviews to evaluate the program. The intervention was implemented and has been enrolling non-pregnant American Indian women for the past several years. While data collection is ongoing, it has shown preliminary success in changing behaviors and in impacting how the community views the prevention of alcohol-exposed pregnancies. Overall, this study highlights the potential to expand this prevention program to other sites and with other populations, such as adolescents. By the end of this article, readers will comprehend the steps necessary to replicate such a program at other tribal and rural sites.


James F. T. Bugental (1915-2008).
James F. T. Bugental died peacefully at age 92 at his Petaluma, California, home on September 18, 2008. Jim was a leading psychotherapist and a founding father, with Abraham Maslow and others, of humanistic psychology, or the "third force" (in contrast to psychoanalysis and behaviorism). Jim was also the creator, along with Rollo May, of existential-humanistic psychotherapy. Jim was born in Fort Wayne, Indiana, on Christmas Day in 1915. Jim earned his doctorate in 1948 from Ohio State University, where he was influenced by Victor Raimy and George Kelly. After a brief time on the University of California, Los Angeles (UCLA) faculty in psychology, Jim resigned in 1953 to found the first group practice of psychotherapy, Psychological Service Associates, with Alvin Lasko. With Abraham Maslow and others, Jim was a cofounder of the Journal of Humanistic Psychology (JHP) and the Association for Humanistic Psychology in 1961. Jim also wrote many books on the topic of psychotherapy during his lifetime. Jim was a great and bold spirit--his many writings and teachings are cherished today widely, and the field of psychology is much richer for his efforts.


Using latent class and quantum models to value equity in health care: a tale of 2 stories.
Cost-effectiveness analysis (CEA) with quality-adjusted life-year (QALY) was introduced to address health equity concerns in value assessment. However, QALY fails to capture patient preference. Stated preference methods (eg, discrete choice experiment [DCE]) have been increasingly used to incorporate patient preference into the value assessment framework in health care. Still, ones with a moral dimension such as health equity do not exist. The objective of this paper was to describe 2 stated preference approaches that can empirically value health equity. First, the decision-maker perceptions of the prevalence of equity dimensions in DCE choice tasks are identified. A latent class model based on random utility theory is proposed to derive the value of equity from the decision makers with different perceptions of the prevalence of equity dimensions. Second, equity attributes are incorporated in DCE choice tasks, and a quantum choice model, which can capture stochasticity during the decision process in the mind of the decision makers, is used to value the equity. These approaches will improve existing value assessment methods to address health equity adequately. DISCLOSURES: This study received no outside funding. Ngorsuraches has received research grants from Bristol Myers Squibb and through the University of Utah and PhRMA Foundation.


Scoping Review of PTSD Treatments for Natural Disaster Survivors.
This scoping review explores the current research on PTSD interventions for Natural Disaster survivors. It includes fourteen randomized control trials (RCTs). The included interventions were, pharmaceuticals, nutraceuticals, herbal supplements, CBT, yoga, narrative exposure therapy, acupuncture stimulation, web-based interventions, and a multimodal art and meditation program. CBT is considered the standard of care for general PTSD treatment and was also found to be effective for the treatment of natural disaster-related PTSD symptoms. However, higher-level clinical evidence is needed. There are inconsistencies with the use of pharmaceuticals, nutraceuticals, and herbal supplements, while there is insufficient clinical evidence to effectively determine the efficacy of yoga, acupuncture, art, and narrative exposure therapies. Factors like the availability of resources, cultural sensitivity, and values and preferences impact the effectiveness of interventions used to treat PTSD in natural disaster survivors. Clinical studies in this field need to be further expanded regardless of the study type.


[Ultrastructure of bacteroid-containing tissue of Pisum sativum L. peas having various regulatory mechanisms of nodulation].
The infected root nodule cells of Pisum sativum cvs. Torsdag, Rondo and its supernodulating mutant nod3 have been investigated by transmission electron microscopy and morphometrically. Torsdag and nod3 developed effective nodules, when grown with or without nitrates in the growth medium. The nodules developed by Rondo were ineffective in the presence of nitrates, and otherwise effective. An obvious similarity in the fine structure of bacteroid tissue of root nodules has been observed in Torgsdag (Nod5) and the supernodulating mutant nod3, both forms being nitrate-tolerant, but nodulation being controlled by different genetic systems. The statistical processing results showed significant differences in the respective morphometric parameters of nodule cells between the plants grown according to either scheme: with and without nitrates. Combined nitrogen is likely to affect the ratio of symbionts in the infected nodule cells of cultivars with nitrate-tolerant nodulation.


Moderate alcohol use is associated with decreased brain volume in early middle age in both sexes.
The aim was to examine cross-sectional association between moderate alcohol consumption and total brain volume in a cohort of participants in early middle-age, unconfounded by age-related neuronal change. 353 participants aged 39 to 45 years reported on their alcohol consumption using the AUDIT-C measure. Participants with alcohol abuse were excluded. Brain MRI was analyzed using a fully automated method. Brain volumes were adjusted by intracranial volume expressed as adjusted total brain volume (aTBV). AUDIT-C mean of 3.92 (SD 2.04) indicated moderate consumption. In a linear regression model, alcohol consumption was associated with smaller aTBV (B = - 0.258, p < .001). When sex and current smoking status were added to the model, the association remained significant. Stratified by sex, the association was seen in both males (B = - 0.258, p = 0.003) and females (B = - 0.214, p = 0.011). Adjusted for current smoking, the association remained in males (B = - 0.268, p = 0.003), but not in females. When alcohol consumption increased, total brain volume decreased by 0.2% per one AUDIT-C unit already at 39-45 years of age. Moderate alcohol use is associated with neuronal changes in both males and females suggesting health risks that should not be overlooked.


Ciguatera fish poisoning following travel to the tropics.
A 40-year-old man-as well as 15 more participants of the same meal-suddenly experienced vomiting and watery diarrhea four hours after having eaten a meal of grouper in the Dominican Republic. Symptoms persisted for four hours and were followed by a generalized pruritus and paresthesias of the lips, tongue, palms, and soles of the feet. Physical examination was normal with the exception of a pulse of 45 beats per minute, a blood pressure of 80/50 mmHg, and paradoxical temperature perception. Laboratory values were regular except for the erythrocyte sedimentation rate of 40 mm per hour. 24-hour Holter electrocardiogram showed a normal sinus rhythm with impaired heart rate variability (37-100 beats per minute). Due to the typical history and the clinical findings, ciguatera toxin ingestion was diagnosed. Pruritus decreased slightly with symptomatic therapy, but it took 16 weeks for all symptoms to resolve. Ciguatera fish poisoning is rare in temperate countries. Symptoms of this neurotoxic disease are gastrointestinal, neurologic, and cardiovascular manifestations with paresthesias, paradoxical sensor disturbances, and muscular weakness as well as bradycardia and hypotension. With travel to and from the tropics and increasing imports of tropical fish ciguatera will be of growing importance even in nontropical areas.


Mortality and cancer risk among the offspring (F1) of atomic bomb survivors.
The Atomic Bomb Casualty Commission (ABCC) and its successor Radiation Effect Research Foundation (RERF) has over the years conducted many studies to determine possible genetic effects of atomic bomb radiation among the offspring of atomic bomb survivors. Findings concerning mortality and cancer incidence of the offspring are summarized in this chapter.


Lymphatic drainage patterns of the human eyelid: assessed by lymphoscintigraphy.
To describe the lymphatic drainage patterns of the human eyelids. Twenty-eight consenting patients who underwent unilateral eyelid surgery at McMaster University between March 2001 and July 2003 had their contralateral eyelids injected with 0.2 ml (0.250 mCi) of Tc 99 m sulphur colloid. The patients were divided into 1 of 5 injection sites of the eyelid, namely upper lateral, upper medial, medial canthus, lower medial, and lower lateral. Lymphoscintigraphy was performed between 2 and 6 hours later with a conventional planar gamma camera. Nodes in the head and neck were identified. In 15 patients, the right eye was injected, and in 13 patients, the left eye was injected. Three patients had no nodes that were identifiable. The remaining 25 patients had at least one node identified. In 11 patients, more than one node was identified. In 18 patients, the preauricular node was most intense and recognized first. Regardless of location on the eyelid, the sentinel node was most commonly the preauricular node. These results conflict with previously described classic drainage patterns of the eyelid lymphatics. In 72% (18/25) of cases, the first-order sentinel node was the preauricular node, regardless of location of the injection site on the eyelid. Many individuals did not fit the classic drainage patterns.


Using a cutoff of <10 ppm for breath hydrogen testing: a review of five years' experience.
To assess the clinical use of the breath hydrogen test in a large community hospital using a <10 ppm cutoff, we reviewed 222 tests performed over a 5-year period to evaluate patients for disaccharidase deficiency or bacterial overgrowth of the small intestine. Of these, the vast majority (195) were for lactose malabsorption, although fructose (17), sucrose (8) and lactulose (2) were also occasionally administered. One hundred eleven tests (50 percent) were positive, with an increase of at least 10 ppm hydrogen above the fasting level and a maximum value most commonly observed (42.3 percent of the time) at 3 hours post-administration. Only 34 patients (15.3 percent) had symptoms noted during the test, as compared with 185 (83.3 percent) who had experienced persistent intestinal problems prior to the test. Recent conditions which may have caused intestinal distress, such as transient disaccharidase deficiency, infections, surgery or other disorders like Crohn's disease, ulcerative colitis or food poisoning, were recorded in only 14 cases. Patterns consistent with bacterial overgrowth of the small intestine were observed in only 3 cases. Of 111 positives, 9 cases had increases between 10 and 20 ppm hydrogen and 7 showed the increase in the 3-hour sample, possibly reflecting a delayed transit through the intestine. Final diagnoses in 6 of these where information was available were for conditions other than malabsorption. We conclude that using a rise of 10 ppm to interpret a positive test does not contribute significantly to an increased frequency of false positives, but that patients with increases between 10 and 20 ppm probably are not lactase deficient.


PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury.
The significant consequences of spinal cord injury (SCI) include sensory and motor disability resulting from the death of neuronal cells and axon degeneration. In this respect, overcoming the consequences of SCI including the recovery of sensory and motor functions is considered to be a difficult tasks that requires attention to multiple aspects of treatment. The breakthrough in tissue engineering through the integration of biomaterial scaffolds and stem cells has brought a new hope for the treatment of SCI. In the present study, human endometrial stem cells (hEnSCs) were cultured with human Schwann cells (hSC) in transwells, their differentiation into nerve-like cells was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry techniques. The differentiated cells (co-hEnSC) were then seeded on the poly ε-caprolactone (PCL)/gelatin scaffolds. The SEM images displayed the favorable seeding and survival of the cells on the scaffolds. The seeded scaffolds were then transplanted into hemisected SCI rats. The growth of neuronal cells was confirmed with immunohistochemical study using NF-H as a neuronal marker. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions. The results suggested that combination therapy using the differentiated hEnSC seeded on PCL/gelatin scaffolds has the potential to heal the injured spinal cord and to limit the secondary damage.


DAPK1 variants are associated with Alzheimer's disease and allele-specific expression.
Genetic factors play an important role in the etiology of late-onset Alzheimer's disease (LOAD). We tested gene-centric single nucleotide polymorphisms (SNPs) on chromosome 9 and identified two SNPs in the death-associated protein kinase, DAPK1, that show significant association with LOAD. SNP rs4878104 was significantly associated with LOAD in our discovery case-control sample set (WU) and replicated in each of two initial validation case-control sample sets (P<0.05, UK1, SD). The risk-allele frequency of this SNP showed a similar direction in three other case-control sample sets. A meta-analysis of the six sample sets combined, totaling 2012 cases and 2336 controls, showed an allelic P-value of 0.0016 and an odds ratio (OR) of 0.87 (95%CI: 0.79-0.95). Minor allele homozygotes had a consistently lower risk than major allele homozygotes in the discovery and initial two replication sample sets, which remained significant in the meta-analysis of all six sample sets (OR=0.7, 95%CI: 0.58-0.85), whereas the risk for heterozygous subjects was not significantly different from that of major allele homozygotes. A second SNP, rs4877365, which is in high linkage disequilibrium with rs4878104 (r2=0.64), was also significantly associated with LOAD (meta P=0.0017 in the initial three sample sets). Furthermore, DAPK1 transcripts show differential allelic gene expression, and both rs4878104 and rs4877365 were significantly associated with DAPK1 allele-specific expression (P=0.015 to <0.0001). These data suggest that genetic variation in DAPK1 modulates susceptibility to LOAD.


Thrombin-induced NF-κB activation and IL-8/CXCL8 release is mediated by c-Src-dependent Shc, Raf-1, and ERK pathways in lung epithelial cells.
In addition to its functions in thrombosis and hemostasis, thrombin also plays an important role in lung inflammation. Our previous report showed that thrombin activates the protein kinase C (PKC)α/c-Src and Gβγ/Rac1/PI3K/Akt signaling pathways to induce IκB kinase α/β (IKKα/β) activation, NF-κB transactivation, and IL-8/CXCL8 expressions in human lung epithelial cells (ECs). In this study, we further investigated the mechanism of c-Src-dependent Shc, Raf-1, and extracellular signal-regulated kinase (ERK) signaling pathways involved in thrombin-induced NF-κB activation and IL-8/CXCL8 release. Thrombin-induced increases in IL-8/CXCL8 release and κB-luciferase activity were inhibited by the Shc small interfering RNA (siRNA), p66Shc siRNA, GW 5074 (a Raf-1 inhibitor), and PD98059 (a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor). Treatment of A549 cells with thrombin increased p66Shc and p46/p52Shc phosphorylation at Tyr239/240 and Tyr317, which was inhibited by cell transfection with the dominant negative mutant of c-Src (c-Src DN). Thrombin caused time-dependent phosphorylation of Raf-1 and ERK, which was attenuated by the c-Src DN. Thrombin-induced IKKα/β phosphorylation was inhibited by GW 5074 and PD98059. Treatment of cells with thrombin induced Gβγ, c-Src, and p66Shc complex formation in a time-dependent manner. Taken together, these results show for the first time that thrombin activates Shc, Raf-1, and ERK through Gβγ, c-Src, and Shc complex formation to induce IKKα/β phosphorylation, NF-κB activation, and IL-8/CXCL8 release in human lung ECs.


Large-scale characterization of natural ligands explains the unique gluten-binding properties of HLA-DQ2.
Celiac disease is an enteropathy caused by intolerance to dietary gluten. The disorder is strongly associated with DQA1*0501/DQB1*0201 (HLA-DQ2) as approximately 95% of celiac patients express this molecule. HLA-DQ2 has unique Ag-binding properties that allow it to present a diverse set of gluten peptides to gluten-reactive CD4+ T cells so instigating an inflammatory reaction. Previous work has indicated that the presence of negatively charged amino acids within gluten peptides is required for specific binding. This, however, only partly explains the scale of the interaction. We have now characterized 432 natural ligands of HLA-DQ2 representing length variants of 155 distinct sequences. The sequences were aligned and the binding cores were inferred. Analysis of the amino acid distribution of these cores demonstrated that negatively charged residues in HLA-DQ2-bound peptides are favored at virtually all positions. This contrasts with a more restricted presence of such amino acids in T cell epitopes from gluten. Yet, HLA-DQ2 was also found to display a strong preference for proline at several anchor and nonanchor positions that largely match the position of proline in gluten T cell epitopes. Consequently, the bias for proline at p6 and p8 facilitates the enzymatic conversion of glutamine into glutamic acid in gluten peptides at p4 and p6, two important anchor sites. These observations provide new insights in the unique ability of HLA-DQ2 to bind a large repertoire of glutamine- and proline-rich gluten peptides. This knowledge may be an important asset in the development of future treatment strategies.