Numerical analysis of dynamic temperature in response to different levels of reactive hyperaemia in a three-dimensional image-based hand model.
Vascular reactivity (VR) is considered as an effective index to predict the risk of cardiovascular events. A cost-effective alternative technique used to evaluate VR called digital thermal monitoring (DTM) is based on the response of finger temperature to vessel occlusion and reperfusion. In this work, a simulation has been developed to investigate hand temperature in response to vessel occlusion and perfusion. The simulation consists of image-based mesh generation and finite element analysis of blood flow and heat transfer in tissues. In order to reconstruct a real geometric model of human hand, a computer programme including automatic image processing for sequential MR data and mesh generation based on the transfinite interpolation method is developed. In the finite element analysis part, blood flow perfused in solid tissues is considered as fluid phase through porous media. Heat transfer in tissues is described by Pennes bioheat equation and blood perfusion rate is obtained from Darcy velocities. Capillary pressure, blood perfusion and temperature distribution of hand are obtained. The results reveal that fingertip temperature is strongly dependent on larger arterial pressure. This simulation is of potential to quantify the indices used for evaluating the VR in DTM test if it is integrated with the haemodynamic model of blood circulation in upper limb.


Usability, Perceived Usefulness, and Shared Decision-Making Features of the AFib 2gether Mobile App: Protocol for a Single-Arm Intervention Study.
The Centers for Disease Control and Prevention has estimated that atrial fibrillation (AF) affects between 2.7 million and 6.1 million people in the United States. Those who have AF tend to have a much higher stroke risk than others. Although most individuals with AF benefit from anticoagulation (AC) therapy, a significant majority are hesitant to start it. To add, providers often struggle in helping patients negotiate the decision to start AC therapy. To assist in the communication between patients and providers regarding preferences and knowledge about AC therapy, different strategies are being used to try and solve this problem. In this research study, we will have patients and providers utilize the AFib 2gether app with hopes that it will create a platform for shared decision making regarding the prevention of stroke in patients with AF receiving AC therapy. The aim of our study is to measure several outcomes related to encounters between patients and their cardiology providers where AFib 2gether is used. These outcomes include usability and perceived usefulness of the app from the perspective of patients and providers. In addition, we will assess the extent and nature of shared decision making. Eligible patients and providers will evaluate the AFib 2gether mobile app for usability and perceived usefulness in facilitating shared decision making regarding understanding the patient's risk of stroke and whether or not to start AC therapy. Both patients and providers will review the app and complete multiple questionnaires about the usability and perceived usefulness of the mobile app in a clinical setting. We will also audio-record a subset of encounters to assess for evidence of shared decision making. Enrollment in the AFib 2gether shared decision-making study is still ongoing for both patients and providers. The first participant enrolled on November 22, 2019. Analysis and publishing of results are expected to be completed in spring 2021. The AFib 2gether app emerged from a desire to increase the ability of patients and providers to engage in shared decision making around understanding the risk of stroke and AC therapy. We anticipate that the AFib 2gether mobile app will facilitate patient discussion with their cardiologist and other providers. Additionally, we hope the study will help us identify barriers that providers face when placing patients on AC therapy. We aim to demonstrate the usability and perceived usefulness of the app with a future goal of testing the value of our approach in a larger sample of patients and providers at multiple medical centers across the country. ClinicalTrials.gov NCT04118270; https://clinicaltrials.gov/ct2/show/NCT04118270. DERR1-10.2196/21986.


[Acute postoperative pancreatitis].
The authors analysed 373 patients with acute pancreatitis which developed after operations on the organs of the pancreatoduodenal zone. Acute postoperative pancreatitis developed in 17.15% of cases after operations on the biliary tract, in 26.8% after resection of the stomach for ulcer, and in 51.47% of cases after resection of the stomach for carcinoma. A comparative evaluation of various methods for the prevention and treatment of acute postoperative pancreatitis (APP) is given, with appraisal of the traditional therapy (154 patients) without the use of protease inhibitors, and various methods of administration of protease inhibitors (135 patients) and cytostatics (84 patients). The mortality rate in progressive forms of APP was 25.2%, mortality being highest (30.4%) in treatment by the traditional methods including protease inhibitors and lowest in inclusion of cytostatics in the complex of therapeutic measures (7.1%).


A Call for Systems Epidemiology to Tackle the Complexity of Schistosomiasis, Its Control, and Its Elimination.
Ever since the first known written report of schistosomiasis in the mid-19th century, researchers have aimed to increase knowledge of the parasites, their hosts, and the mechanisms contributing to infection and disease. This knowledge generation has been paramount for the development of improved intervention strategies. Yet, despite a broad knowledge base of direct risk factors for schistosomiasis, there remains a paucity of information related to more complex, interconnected, and often hidden drivers of transmission that hamper intervention successes and sustainability. Such complex, multidirectional, non-linear, and synergistic interdependencies are best understood by looking at the integrated system as a whole. A research approach able to address this complexity and find previously neglected causal mechanisms for transmission, which include a wide variety of influencing factors, is needed. Systems epidemiology, as a holistic research approach, can integrate knowledge from classical epidemiology, with that of biology, ecology, social sciences, and other disciplines, and link this with informal, tacit knowledge from experts and affected populations. It can help to uncover wider-reaching but difficult-to-identify processes that directly or indirectly influence exposure, infection, transmission, and disease development, as well as how these interrelate and impact one another. Drawing on systems epidemiology to address persisting disease hotspots, failed intervention programmes, and systematically neglected population groups in mass drug administration programmes and research studies, can help overcome barriers in the progress towards schistosomiasis elimination. Generating a comprehensive view of the schistosomiasis system as a whole should thus be a priority research agenda towards the strategic goal of morbidity control and transmission elimination.


Retinotopic organization in human visual cortex and the spatial precision of functional MRI.
A method of using functional magnetic resonance imaging (fMRI) to measure retinotopic organization within human cortex is described. The method is based on a visual stimulus that creates a traveling wave of neural activity within retinotopically organized visual areas. We measured the fMRI signal caused by this stimulus in visual cortex and represented the results on images of the flattened cortical sheet. We used the method to locate visual areas and to evaluate the spatial precision of fMRI. Specifically, we: (i) identified the borders between several retinotopically organized visual areas in the posterior occipital lobe; (ii) measured the function relating cortical position to visual field eccentricity within area V1; (iii) localized activity to within 1.1 mm of visual cortex; and (iv) estimated the spatial resolution of the fMRI signal and found that signal amplitude falls to 60% at a spatial frequency of 1 cycle per 9 mm of visual cortex. This spatial resolution is consistent with a linespread whose full width at half maximum spreads across 3.5 mm of visual cortex.


Lactoferrin and transferrin damage of the gram-negative outer membrane is modulated by Ca2+ and Mg2+.
Lactoferrin and transferrin have antimicrobial activity against selected Gram-negative bacteria, but the mechanism of action has not been defined. We studied the ability of lactoferrin and transferrin to damage the Gram-negative outer membrane. Lipopolysaccharide release by the proteins could be blocked by concurrent addition of Ca2+ and Mg2+. Addition of Ca2+ also blocked the ability of lactoferrin to increase the susceptibility of Escherichia coli to rifampicin. Transferrin, but not lactoferrin, increased susceptibility of Gram-negative bacteria to deoxycholate, with reversal of sensitivity occurring with exposure to Ca2+ or Mg2+. In transmission electron microscopy studies polymyxin B caused finger-like membrane projections, but no morphological alterations were seen in cells exposed to EDTA, lactoferrin or transferrin. These data provide further evidence that lactoferrin and transferrin act as membrane-active agents with the effects modulated by Ca2+ and Mg2+.


Structural models of class a G protein-coupled receptors as a tool for drug design: insights on transmembrane bundle plasticity.
G protein-coupled receptors (GPCRs) interact with an extraordinary diversity of ligands by means of their extracellular domains and/or the extracellular part of the transmembrane (TM) segments. Each receptor subfamily has developed specific sequence motifs to adjust the structural characteristics of its cognate ligands to a common set of conformational rearrangements of the TM segments near the G protein binding domains during the activation process. Thus, GPCRs have fulfilled this adaptation during their evolution by customizing a preserved 7TM scaffold through conformational plasticity. We use this term to describe the structural differences near the binding site crevices among different receptor subfamilies, responsible for the selective recognition of diverse ligands among different receptor subfamilies. By comparing the sequence of rhodopsin at specific key regions of the TM bundle with the sequences of other GPCRs we have found that the extracellular region of TMs 2 and 3 provides a remarkable example of conformational plasticity within Class A GPCRs. Thus, rhodopsin-based molecular models need to include the plasticity of the binding sites among GPCR families, since the "quality" of these homology models is intimately linked with the success in the processes of rational drug-design or virtual screening of chemical databases.


Anatomy of female puberty: The clinical relevance of developmental changes in the reproductive system.
Puberty is the period of biologic transition from childhood to adulthood. The changes that occur at this time are related to the increasing concentrations of sex steroid hormones. In females, most pubertal changes are caused by estrogen stimulation that results from the onset of central puberty. Significant development occurs in the organs of the female reproductive system and results in anatomic changes that characterize reproductive maturity. Adrenal and ovarian androgens also increase during puberty, affecting change that includes the promotion of certain secondary sex characteristics. The ability to recognize normal pubertal anatomy and distinguish between estrogen and androgen effects is important in the ability to diagnose and treat disorders of sex development, precocious puberty, pubertal delay, and menstrual irregularities in children and adolescents. An understanding of this developmental process can also help clinicians identify and treat reproductive pathology in adults and across all female life stages.


Remodeling of the Golgi structure by ERK signaling.
Emerging evidence suggests that the Golgi functions as a regulatory node for various signaling cascades. Modules of the MAPK pathway are targeted to the Golgi upon stimulation of cells with mitogens. The target for activated ERK on the Golgi membranes is GRASP65, a peripheral membrane protein required for Golgi cisternal stacking. Phosphorylation of GRASP65 at Serine 277 results in a loss of its oligomerization and causes unstacking of Golgi cisternae. This reorganization of the Golgi structure is required for the polarization of the Golgi and the centrosomes towards the leading edge in migrating cells. Preventing GRASP65 phosphorylation with mutants lacking the phosphorylation site blocks Golgi and centrosome orientation. This demonstrates a mechanism for cell polarization involving dynamic remodeling of the Golgi mediated by local phosphorylation of a Golgi protein induced by mitogen signaling.


Quantitative trait loci controlling cyanogenic glucoside and dry matter content in cassava (Manihot esculenta Crantz) roots.
Cassava (Manihot esculenta Crantz) is a starchy root crop grown in the tropics mainly by small-scale farmers even though agro-industrial processing is rapidly increasing. For this processing market improved varieties with high dry matter root content (DMC) is required. Potentially toxic cyanogenic glucosides are synthesized in the leaves and translocated to the roots. Selection for varieties with low cyanogenic glucoside potential (CNP) and high DMC is among the principal objectives in cassava breeding programs. However, these traits are highly influenced by the environmental conditions and the genetic control of these traits is not well understood. An S(1) population derived from a cross between two bred cassava varieties (MCOL 1684 and Rayong 1) that differ in CNP and DMC was used to study the heritability and genetic basis of these traits. A broad-sense heritability of 0.43 and 0.42 was found for CNP and DMC, respectively. The moderate heritabilities for DMC and CNP indicate that the phenotypic variation of these traits is explained by a genetic component. We found two quantitative trait loci (QTL) on two different linkage groups controlling CNP and six QTL on four different linkage groups controlling DMC. One QTL for CNP and one QTL for DMC mapped near each other, suggesting pleiotrophy and/or linkage of QTL. The two QTL for CNP showed additive effects while the six QTL for DMC showed additive effect, dominance or overdominance. This study is a first step towards developing molecular marker tools for efficient breeding of CNP and DMC in cassava.


Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience.
Influenza is a common and potentially serious infection in children. Although there is interest in broadening the use of influenza vaccine in healthy children, there are few large, randomized, controlled trials that evaluate the safety and efficacy of inactivated vaccine in the pediatric population. From 1985 through 1990 a randomized, controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease was conducted at Vanderbilt University, and the cumulative results from this trial in patients of all ages have been previously published. We reanalyzed the data from this trial in the subset of patients who were younger than 16 years at the time of their participation. We determined vaccine safety, immunogenicity and efficacy, based on culture-positive illness and seroconversion, in this subset of patients. During the 5 years of the study, 791 children younger than 16 years received 1809 doses of either inactivated or cold-adapted vaccine or placebo. The vaccines were well-tolerated, and there were no serious reactions. Inactivated trivalent influenza vaccines were 91.4 and 77.3% efficacious in preventing symptomatic, culture-positive influenza A H1N1 and H3N2 illness, respectively. The efficacy of the inactivated vaccine based on hemagglutination inhibition assay seroconversion was 67.1 and 65.5%, respectively, for H1N1 and H3N2 serotypes. Inactivated trivalent influenza A vaccines are well-tolerated and efficacious in the prevention of influenza A disease in children 1 to 16 years old.


An Antimicrobial Stewardship Program Based on Systematic Infectious Disease Consultation in a Rehabilitation Facility.
OBJECTIVE To assess the impact of an antimicrobial stewardship program (ASP) on antibiotic consumption, Clostridium difficile infections (CDI), and antimicrobial resistance patterns in a rehabilitation hospital. DESIGN Quasi-experimental study of the periods before (from January 2011 to June 2012) and after (from July 2012 to December 2014) ASP implementation. SETTING 150-bed rehabilitation hospital dedicated to patients with spinal-cord injuries. INTERVENTION Beginning in July 2012, an ASP was implemented based on systematic bedside infectious disease (ID) consultation and structural interventions (ie, revision of protocols for antibiotic prophylaxis and education focused on the appropriateness of antibiotic prescriptions). Antibiotic consumption, occurrence of CDI, and antimicrobial resistance patterns of selected microorganisms were compared between periods before and after the ASP implementation. RESULTS Antibiotic consumption decreased from 42 to 22 defined daily dose (DDD) per 100 patient days (P<.001). The main reductions involved carbapenems (from 13 to 0.4 DDD per 100 patient days; P=.01) and fluoroquinolones (from 11.8 to 0.99 DDD per 100 patient days; P=.006), with no increases in mortality or length of stay. The incidence of CDI decreased from 3.6 to 1.2 cases per 10,000 patient days (P=.001). Between 2011 and 2014, the prevalence of extensively drug-resistant (XDR) strains decreased from 55% to 12% in P. aeruginosa (P<.001) and from 96% to 73% in A. baumannii (P=.03). The prevalence of ESBL-producing strains decreased from 42% to 17% in E. coli (P=.0007) and from 62% to 15% in P. mirabilis (P=.0001). In K. pneumoniae, the prevalence of carbapenem-resistant strains decreased from 42% to 17% (P=.005), and the prevalence of in methicillin-resistant S. aureus strains decreased from 77% to 40% (P<.0008). CONCLUSIONS An ASP based on ID consultation was effective in reducing antibiotic consumption without affecting patient outcomes and in improving antimicrobial resistance patterns in a rehabilitation hospital. Infect Control Hosp Epidemiol. 2016;1-7.


Does mitochondrial DNA length influence the frequency of spontaneous petite mutants in yeasts?
Results from the theory of random walks applied to the random excision hypothesis for production of petite mutants in yeast suggest that frequency of excision should increase as a linear function of mitochondrial DNA length (see appendix). For a series of petite positive yeasts we have determined the spontaneous petite frequency (ranging from about 0.003% to 9%) and length of mtDNA (ranging from about 19 Kbp to c. 108 Kbp) and found that, while the frequency of petite mutants does generally increase with mtDNA length, the relationship is far from linear. Although these results are inconclusive concerning the random excision hypothesis they do indicate that amongst related yeasts other factors have a greater influence than mtDNA length in determining the frequency of petite mutants.


HAM Gene Family and Shoot Meristem Development.
Land plants develop highly diversified shoot architectures, all of which are derived from the pluripotent stem cells in shoot apical meristems (SAMs). As sustainable resources for continuous organ formation in the aboveground tissues, SAMs play an important role in determining plant yield and biomass production. In this review, we summarize recent advances in understanding one group of key regulators - the HAIRY MERISTEM (HAM) family GRAS domain proteins - in shoot meristems. We highlight the functions of HAM family members in dictating shoot stem cell initiation and proliferation, the signaling cascade that shapes HAM expression domains in shoot meristems, and the conservation and diversification of HAM family members in land plants. We also discuss future directions that potentially lead to a more comprehensive view of the HAM gene family and stem cell homeostasis in land plants.


Thermoregulatory responses to hyperinsulinemic hypoglycemia and euglycemia in humans.
Hypoglycemia induces physiological changes that influence thermoregulatory mechanisms. We studied such responses in a group of healthy males (mean age 23.5 yr, body mass index 23.7 kg/m2) during hyperinsulinemic euglycemia (E; 4.5 mmol/l) and hypoglycemia (H; 2.5 mmol/l) and under placebo control conditions (P; saline). Plasma epinephrine (P < 0.0001) and norepinephrine (P < 0.01) levels increased during H and were unchanged during P and E. During H, early increases in metabolic rate (P < 0.05), forearm blood flow (P < 0.01), and sweating (P < 0.01) were followed by a fall in skin temperature (from -1.2 to -2.6 degrees C) and blood flow (P < 0.01). Core temperature fell after 40 min of H and continued to fall thereafter (-0.34 +/- 0.08 degrees C). E and P had minimal effect on skin temperature and blood flow. In summary, in healthy human subjects, H causes a fall in core temperature by heat dissipation at the skin surface through evaporative heat loss and conduction of heat to the periphery, despite an increase in metabolic heat production.


Congenital macroglossia treated by 2-stage partial glossectomy.
Persistent macroglossia affects speech, swallowing, and the dentofacial skeleton. A range of tongue reduction methods have been proposed to preserve the mobility and sensation of the tongue. However, recent reports have shown that speech or esthetic problems still exists, even after a comprehensive glossectomy in early childhood. Because a large volume reduction of the anterior tongue in young growing children might result in a short tongue tip with functional difficulties, it is important to select the appropriate tongue reduction method considering the growth of the tongue.In the current report, a staged tongue reduction was planned to minimize the functional and esthetic problems after surgery. A 3-year-old girl visited our clinic because of congenital macroglossia, phonation problems, and prognathic appearance of the mandible. The tongue was first reduced by a central glossectomy. The speech intelligibility, tongue movement, and skeletal growth pattern were improved after the first surgery. The secondary peripheral tongue reduction was performed 6 years later to achieve an esthetically pleasing tongue appearance.This 2-stage partial glossectomy, central tongue reduction first followed later by a peripheral tongue reduction, ensures functional integrity of the tongue and can provide an esthetically pleasing result in growing children. The results demonstrated that this strategic combination of a staged tongue reduction can be a successful treatment option for macroglossia.


Tanshinone‑IIA attenuates the deleterious effects of oxidative stress in osteoporosis through the NF‑κB signaling pathway.
Osteoclasts are responsible for bone resorption caused by bone microstructural damage and bone-related disorders. Evidence shows that tanshinone IIA (Tan‑IIA), a traditional Chinese medicine, is used clinically as a drug for the treatment of cardiovascular and cerebrovascular diseases. However, the efficacy and mechanism underlying the effect of Tan‑IIA on the viability of osteoclasts remain to be fully elucidated. The present study investigated the therapeutic effects of Tan‑IIA on osteoblast differentiation and oxidative stress in vitro and in vivo. Cell viability was analyzed and oxidative stress was examined in the osteoblasts. Wnt1sw/sw mice were used to investigate the therapeutic effects of Tan‑IIA on spontaneous tibia fractures and severe osteopenia. The bone strength, collagen and mineral were examined in the tibia. Osteoblast activity was also analyzed in the experimental mice. The Tan‑IIA‑induced differentiation of osteoclasts and the mechanism of action were investigated in osteocytes. The data showed that Tan‑IIA treatment improved cell viability. The data also demonstrated that Tan‑IIA decreased the levels of H2O2, accumulation of reactive oxygen species and apoptosis of osteoblasts. Tan‑IIA inhibited the deleterious outcomes triggered by oxidative stress. In addition, Tan‑IIA inhibited the activation of nuclear factor (NF)‑κB and its target genes, tumor necrosis factor (TNF)‑α, inducible nitric oxide synthase and cyclooxygenase 2, and increased the levels of TNF receptor‑associated factor 1 and inhibitor of apoptosis protein‑1/2 in the osteocytes. Furthermore, it was shown that Tan‑IIA reduced the propensity to fractures and severe osteopenia in mice with osteoporosis. Tan‑IIA also exhibited improved bone strength, mineral and collagen in the bone matrix of the experimental mice. It was found that the Tan‑IIA‑mediated benefits on osteoblast activity and function were through the NF‑κB signaling pathway. Taken together, the data obtained in the present study suggested that Tan‑IIA had protective effects against oxidative stress in osteoblastic differentiation in mice with osteoporosis by regulating the NF‑κB signaling pathway.


Cellular Plasticity: A Route to Senescence Exit and Tumorigenesis.
Senescence is a dynamic, multistep program that results in permanent cell cycle arrest and is triggered by developmental or environmental, oncogenic or therapy-induced stress signals. Senescence is considered as a tumor suppressor mechanism that prevents the risk of neoplastic transformation by restricting the proliferation of damaged cells. Cells undergoing senescence sustain important morphological changes, chromatin remodeling and metabolic reprogramming, and secrete pro-inflammatory factors termed senescence-associated secretory phenotype (SASP). SASP activation is required for the clearance of senescent cells by innate immunity. Therefore, escape from senescence and the associated immune editing would be a prerequisite for tumor initiation and progression as well as therapeutic resistance. One of the possible mechanisms for overcoming senescence could be the acquisition of cellular plasticity resulting from the accumulation of genomic alterations and genetic and epigenetic reprogramming. The modified composition of the SASP produced by these reprogrammed cancer cells would create a permissive environment, allowing their immune evasion. Additionally, the SASP produced by cancer cells could enhance the cellular plasticity of neighboring cells, thus hindering their recognition by the immune system. Here, we propose a comprehensive review of the literature, highlighting the role of cellular plasticity in the pro-tumoral activity of senescence in normal cells and in the cancer context.


Intramyocardial blood volume change in first moments of cardiac arrest in anesthetized goats.
The effect of cardiac relaxation on the intramyocardial blood volume was studied by measuring the integrated difference between arterial inflow and great cardiac venous outflow. In nine anesthetized goats, the left main coronary artery was perfused under constant pressure. The great cardiac vein was drained under pressure control. The venous flow signal was amplified so that the integrated intramyocardial blood volume was constant in the beating heart. With normal vasomotor tone, the mean change in vascular volume was 3.01 +/- 0.18 (SE) ml/100 g left ventricle (LV); 67% of the volume change was achieved in 1.60 +/- 0.09 s. For the fully dilated bed (adenosine infusion), the values were 4.13 +/- 0.33 ml/100 g and 0.96 +/- 0.06 s, respectively. The volume change could be correlated with the venous pressure during cardiac arrest (Pvd) and the change in mean left ventricular pressure after cardiac arrest (r = 0.95). The correlation improved when data were selected for Pvd less than 6 mmHg to r = 0.98. We assumed that the change in vascular transmural pressure can be approximated as half the mean left ventricular pressure change. The intramyocardial vascular compliance was then estimated as 0.104 +/- 0.012 and 0.146 +/- 0.028 ml X mmHg-1 X 100 g-1 for control and adenosine conditions, respectively. The long time constants excluded the large epicardial veins as the site of volume change; they were much longer than the duration of diastole in the beating heart. We conclude that the intramyocardial vascular compartment is capable of volume expansion on the order of 20% of its normal volume when myocardial compression by ventricular systole is suspended.


Subgingival microbiota of chronic periodontitis subjects from different geographic locations.
Most clinical studies assume that the subgingival microbiota is similar from one geographic location to another. The purpose of the present investigation was to examine the composition of the subgingival microbiota in chronic periodontitis subjects from four countries. Subjects with chronic periodontitis (N, Sweden=101; USA=115; Brazil=58; Chile=26) were recruited. Subjects were measured at baseline for plaque, gingivitis, bleeding on probing (BOP), suppuration, pocket depth (PD) and attachment level (AL) at six sites per tooth. Subgingival plaque samples taken from the mesial aspect of each tooth at baseline were individually analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization (total samples=6036). % DNA probe counts comprised by each species was determined for each site and averaged across sites in each subject. Significance of differences in proportions of each species among countries was determined using ancova adjusting for age, mean pocket depth, gender and smoking status. p-Values were adjusted for multiple comparisons. On average, all species were detected in samples from subjects in the four countries. Thirteen species differed significantly in adjusted mean proportions among countries even after adjusting for multiple comparisons. Porphyromonas gingivalis, one species that differed in proportions among countries, comprised adjusted means of 7.5, 11.9, 1.6 and 6.6% of the microbiota in subjects from Brazil, Chile, Sweden and USA (p<0.001), while mean proportions of Treponema denticola were 6.7, 4.2, 0.8 and 2.3, respectively (p<0.001). In contrast, a key periodontal pathogen, Tannerella forsythensis, exhibited mean proportions ranging from 6.2-8.5% and did not differ significantly among countries. Besides these species, prominent species in Brazil were Actinomyces naeslundii genospecies 1 and 2 (8.4%, 7.2%) and Prevotella intermedia (6.5%); in Chile, Prevotella melaninogenica (6.4%) and Neisseria mucosa (5.3%); in Sweden A. naeslundii genospecies 2 (8.4%), Capnocytophaga gingivalis (7.1%) and Peptostreptococcus micros (5.0%); in USA A. naeslundii genospecies 2 (7.5%), P. intermedia (6.8%) and C. gingivalis (6.1%). The microbial profiles of subgingival plaque samples from chronic periodontitis subjects in four countries showed surprisingly marked differences. These differences persisted after adjusting for age, mean pocket depth, gender and smoking status.


Incidence of cataract extraction in Pima Indians. Diabetes as a risk factor.
The incidence of visually disabling cataract was estimated by the rate of first cataract extraction in a population of Pima Indians in Arizona. The annual age-specific rates of cataract surgery (first and second eyes) were 3.7 to 5.9 times as high as the estimated US rates. Diabetes was a strong risk factor for first cataract surgery in all age and sex groups except in men aged 75 to 84 years. Overall, with age and sex controlled, the rate of first cataract surgery was 2.2 times as high (95% confidence interval, 1.3 to 3.9) in diabetic as in nondiabetic subjects. Cataract surgery was related to the duration and type of treatment of diabetes. Insulin-treated diabetics had about five times the rate of those with normal glucose tolerance. The rate of cataract surgery was lowest in subjects with normal glucose tolerance, somewhat higher in those with impaired glucose tolerance, and even higher with increasing duration of diabetes.


Increased interleukin-10 in the the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission?
Although non-ulcerative sexually transmitted diseases (STD) and bacterial vaginosis are implicated as cofactors in heterosexual HIV-1 transmission, the mechanisms have not been defined. Recent in vitro data suggest that interleukin (IL)-10 may increase susceptibility of macrophages to HIV-1 infection. Therefore, we performed this study to assess whether non-ulcerative STD are associated with detection of IL-10 in the female genital tract. Women with clinical pelvic inflammatory disease with or without cervicovaginal discharge were recruited from an STD clinic in Nairobi, Kenya. Endocervical and endometrial specimens were obtained for Neisseria gonorrhoeae and Chlamydia trachomatis DNA detection, Trichonomas vaginalis culture, and CD4 and CD8 T-cell enumeration. Bacterial vaginosis was diagnosed by Gram stain. IL-10 was detected in endocervical specimens using enzyme-linked immunosorbent assay. Blood was obtained for HIV-1 serology. One hundred and seventy-two women were studied. N. gonorrhoeae, C. trachomatis, bacterial vaginosis, and T. vaginalis were detected in 38 (21%), 17 (9%), 71 (43%), and 22 (12%) women, respectively. Cervical IL-10 was detected more often in women with N. gonorrhoeae [adjusted odds ratio (AOR), 3.4; 95% confidence interval (CI), 1.4-8.4], C. trachomatis (AOR, 4.4; 95% CI, 1.2-15.6), and bacterial vaginosis (AOR, 3.1; 95% CI, 1.4-6.9) than in women without these infections. The association of non-ulcerative STD and bacterial vaginosis with increased frequency of IL-10 detection in endocervical secretions suggests a potential mechanism through which these infections may alter susceptibility to HIV-1 infection in women.


Cognitive function and fatigue after diagnosis of colorectal cancer.
Cognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC). We evaluated CRC patients with stage I-III disease before or after surgery, participants with limited metastatic disease and healthy controls (HC). Neuropsychological evaluation included clinical and computerised tests. Participants completed questionnaires for fatigue and quality of life (QOL)-(FACT-F), anxiety/depression, and cognitive symptoms (FACT-Cog). Ten cytokines, clotting factors, sex hormones, carcinoembryonic antigen (CEA), and apolipoprotein E genotype were evaluated. Primary end points were cognitive function on clinical tests evaluated by a Global Deficit score (GDS) and fatigue. Associations between test results, demographic, and disease related factors were explored. We assessed 291 participants with early-stage disease [median age 59 (23-75) years, 63% men], 72 with metastatic disease, and 72 HC. Using GDS, 45% (126/281) of participants with early-stage CRC had cognitive impairment versus 15% (11/72) of HC (odds ratio 4.51, 95% confidence interval 2.28-8.93; P < 0.001), with complex processing speed, attention/working memory, and verbal learning efficiency being most affected. Women with early-stage CRC had greater cognitive impairment than men [55/105 (52%) versus 71/176 (40%), P < 0.050]. Cognitive symptoms were self-reported by 21% (59/286) of early-stage patients versus 17% (12/72) of HC; fatigue by 52% (149/287) of early-stage patients and 26% (19/72) of HC (P < 0.0001). Women reported more fatigue than men (P = 0.003). Fatigue, QOL, anxiety/depression, and cognitive symptoms were associated with each other (r = 0.43-0.71), but not with neuropsychological performance. Most cytokines were elevated in cancer patients. Cognitive function was not associated with cytokines, sex hormones, clotting factors, CEA, or apolipoprotein E genotype. The incidence of cognitive impairment was three to five times higher in CRC patients than HC, with women having higher impairment rates than men. The cognitive impairment profile suggests dysfunction primarily in fronto-subcortical brain systems. NCT00188331.


Role of magnesium in health and disease.
Appropriate intracellular and extracellular magnesium levels are necessary for proper body functioning. Imbalances of magnesium are common and are associated with a great deal of morbidity and mortality. Routine determination of serum magnesium levels in patients at risk for magnesium disorders must become the norm. As technology improves, cellular magnesium levels will become widely available and may be indicated to guide therapy and prevention of a wide variety of diseases.


Rhodococcus equi Infections in Goats: Characterization of Virulence Plasmids.
Rhodococcus equi is an uncommon cause of systemic pyogranulomatous infections in goats with macroscopic similarities to caseous lymphadenitis caused by Corynebacterium pseudotuberculosis. Caprine cases have previously been reported to be caused by avirulent R. equi strains. Six cases of R. equi infection in goats yielding 8 R. equi isolates were identified from 2000 to 2017. Lesions varied from bronchopneumonia, vertebral and humeral osteomyelitis, and subcutaneous abscesses, to disseminated infection involving the lungs, lymph nodes, and multiple visceral organs. Isolates of R. equi from infected goats were analyzed by polymerase chain reaction for R. equi virulence-associated plasmid ( vap) genes. Seven of 8 isolates carried the VapN plasmid, originally characterized in bovine isolates, while 1 isolate lacked virulence plasmids and was classified as avirulent. The VapN plasmid has not been described in isolates cultured from goats.


NFKB1 Signalling Activation Contributes to TRPV1 Over-expression via Repressing MiR-375 and MiR-455: a Study on Neuropathic Low Back Pain.
Transient receptor potential cation channel subfamily V member 1 (TRPV1) has been found over-expressed in low back pain (LBP) patients with neuropathic pain (NP), but the underlying mechanism is still unclear. In the present study, the up-regulation of the TRPV1 protein level in sinuvertebral nerve biopsies from patients with NP was verified by immunoblotting, but the TRPV1 mRNA level was not significantly changed. MiRNAs targeting TRPV1 mRNA were predicted by a bioinformatic tool, and the interactions between the miRNAs and TRPV1 were confirmed by dual luciferase assay. The correlation between NFKB1 signalling and TRPV1 expression was analysed and confirmed by using sNF96.2 cells after lipopolysaccharide stimulation. We found that five out of 18 miRNAs repressed TRPV1 expression, and the levels of miR-375 and miR-455 were negatively correlated with the protein level of TRPV1 in patients with NP. MiR-375 and miR-455 were identified to repress TRPV1 expression via targeting the 3'UTR of TRPV1 mRNA. NFKB1 signalling activation down-regulated the expression of miR-375 and miR-455, and thus up-regulated the TRPV1 protein level. In conclusion, we partially unveiled the mechanism of how TRPV1 is over-expressed in chronic LBP patients with NP and provided two potential candidate miRNAs for NP treatment.


Partial purification and functional identification of a calmodulin-activated, adenosine 5'-triphosphate-dependent calcium pump from synaptic plasma membranes.
Synaptic plasma membranes isolated from rat brain contain a calmodulin-activated Ca2+ pump. It has been purified 80- to 160-fold by solubilization with Triton X-100 and affinity chromatography on a calmodulin-Sepharose 4B column. After reconstitution into phospholipid vesicles, the affinity-purified pump efficiently catalyzed ATP dependent Ca2+ transport, which was activated 7- to 9-fold by calmodulin. The major protein component of the affinity-purified preparation had a Mr = 140,000; it was virtually the only band visualized on a Coomassie blue-stained SDS polyacrylamide gel. It has been identified as the Ca2+ pump by two functional criteria. First, it was phosphorylated by [gamma-32P]ATP in a Ca2+-dependent manner; the phosphorylated protein had the chemical reactivity of an acyl phosphate, characteristic of the phosphorylated intermediates of ion-transporting ATPases. Second, the protein was enriched by transport-specific fractionation, a density gradient procedure which uses the transport properties of the reconstituted Ca2+ pump as a physical tool for its purification. By analogy with calmodulin-activated (Ca2+ + Mg2+) ATPases of other cell types, and because of its presence in a synaptic plasma membrane fraction, we hypothesize that the calmodulin-activated Ca2+ pump functions in vivo to extrude Ca2+ from nerve terminals.


Timing of caffeine ingestion alters postprandial metabolism in rats.
The association between caffeine intake and the risk for chronic diseases, namely type 2 diabetes, has not been consistent, and may be influenced by the timing of caffeine ingestion. The aim of this study was to investigate the acute effect of caffeine administered in different scenarios of meal ingestion on postprandial glycemic and lipidemic status, concomitant with changes in body glycogen stores. Forty overnight-fasted rats were randomly divided into five groups (meal-ingested, caffeine-administered, post-caffeine meal-ingested, co-caffeine meal-ingested, post-meal caffeine-administered), and tube-fed the appropriate intervention, then sacrificed 2 h later. Livers and gastrocnemius muscles were analyzed for glycogen content; blood samples were analyzed for glucose, insulin, triglycerides, and non-esterified fatty acid concentrations. Postprandial plasma glucose concentrations were similar between groups, while significantly higher levels of insulin were witnessed following caffeine administration, irrespective of the timing of meal ingestion. Triglyceride concentrations were significantly lower in the caffeine-administered groups. Regarding glycogen status, although caffeine administration before meal ingestion reduced hepatic glycogen content, co- and post-meal caffeine administration failed to produce such an effect. Muscle glycogen content was not significantly affected by caffeine administration. Caffeine administration seems to decrease insulin sensitivity as indicated by the sustenance of glucose status despite the presence of high insulin levels. The lower triglyceride levels in the presence of caffeine support the theory of retarded postprandial triglyceride absorption. Caffeine seems to play a biphasic role in glucose metabolism, as indicated by its ability to variably influence hepatic glycogen status.


Concise Review: Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer: A Horse in the Race?
Embryonic stem cells (ESC) hold promise for the treatment of human medical conditions but are allogeneic. Here, we consider the differences between autologous pluripotent stem cells produced by nuclear transfer (NT-ESCs) and transcription factor-mediated, induced pluripotent stem cells (iPSCs) that impact the desirability of each of these cell types for clinical use. The derivation of NT-ESCs is more cumbersome and requires donor oocytes; however, the use of oocyte cytoplasm as the source of reprogramming factors is linked to a key advantage of NT-ESCs-the ability to replace mutant mitochondrial DNA in a patient cell (due to either age or inherited disease) with healthy donor mitochondria from an oocyte. Moreover, in epigenomic and transcriptomic comparisons between isogenic iPSCs and NT-ESCs, the latter produced cells that more closely resemble bona fide ESCs derived from fertilized embryos. Thus, although NT-ESCs are more difficult to generate than iPSCs, the ability of somatic cell nuclear transfer to replace aged or diseased mitochondria and the closer epigenomic and transcriptomic similarity between NT-ESCs and bona fide ESCs may make NT-ESCs superior for future applications in regenerative medicine. Stem Cells 2017;35:26-34.


Genotype-by-environment and epistatic interactions in Drosophila melanogaster: the effects of Gpdh allozymes, genetic background and rearing temperature on larval developmental time and viability.
The possible role of temperature as a component of natural selection generating the latitudinal clines in Gpdh allele frequencies in natural populations of Drosophila melanogaster was examined. Effects of rearing temperature (16 degrees, 22 degrees and 29 degrees) and of Gpdh allozymes (S and F) on larval developmental time and viability were measured. Eight genetic backgrounds from each of three populations (continents) were used to assess the generality of any effects. Analyses of variance indicated significant temperature effects and allozyme-by-genetic background interaction effects for both characters. Viability showed significant genetic background effects, as well as significant temperature-by-allozyme and temperature-by-allozyme-by-population interactions. In general, the S/S genotype was significantly lower in viability than the F/F and F/S genotypes at extreme temperatures (16 degrees and 29 degrees), with no significant differences at 22 degrees. However, each population had a slightly different pattern of viability associated with temperature, and only the Australian population showed a pattern that could contribute to the observed cline formation. Although the same two interactions were not significant for developmental time, examination of the means showed that the S/S genotype had a slightly faster rate of development at 16 degrees than the F/F genotype in all populations (by an average of 0.25 day or 1.1%). The low temperature effect on developmental time is consistent with the clines observed in nature, with the S allele increasing in frequency with higher latitudes. The results for both viability and developmental time are consistent with the interpretation of Gpdh as a minor polygene affecting physiological phenotypes, as indicated by previous work with adult flight metabolism. Finally, it is proposed that the temperature-dependent antagonistic effects of the allozymes on viability vs. developmental time and flight metabolism may be the underlying force giving rise to the worldwide polymorphism.


Phylogenetic relationships and the evolution of BMP4 in triggerfishes and filefishes (Balistoidea).
The triggerfishes (family Balistidae) and filefishes (family Monacanthidae) comprise a charismatic superfamily (Balistoidea) within the diverse order Tetraodontiformes. This group of largely marine fishes occupies an impressive ecological range across the world's oceans, and is well known for its locomotor and feeding diversity, unusual body shapes, small genome size, and ecological and economic importance. In order to investigate the evolutionary history of these important fish families, we used multiple phylogenetic methods to analyze molecular data from 86 species spanning the extant biodiversity of Balistidae and Monacanthidae. In addition to three gene regions that have been used extensively in phylogenetic analyses, we include sequence data for two mitochondrial regions, two nuclear markers, and the growth factor gene bmp4, which is involved with cranial development. Phylogenetic analyses strongly support the monophyly of the superfamily Balistoidea, the sister-family relationship of Balistidae and Monacanthidae, as well as three triggerfish and four filefish clades that are well resolved. A new classification for the Balistidae is proposed based on phylogenetic groups. Bayesian topology, as well as the timing of major cladogenesis events, is largely congruent with previous hypotheses of balistid phylogeny. However, we present a novel topology for major clades in the filefish family that illustrate the genera Aluterus and Stephanolepis are more closely related than previously posited. Molecular rates suggest a Miocene and Oligocene origin for the families Balistidae and Monacanthidae, respectively, and significant divergence of species in both families within the past 5 million years. A second key finding of this study is that, relative to the other protein-coding gene regions in our DNA supermatrix, bmp4 shows a rapid accumulation of both synonymous and non-synonymous substitutions, especially within the family Monacanthidae. Overall substitution patterns in bmp4 support the hypothesis of stabilizing selection during the evolutionary history of regulatory genes, with a small number of isolated examples of accelerated non-synonymous changes detected in our phylogeny.


Utilization and implications of the Static-99 in practice.
The Static-99 is the most commonly used risk assessment instrument for sexual violence in North America and its results can affect highly consequential decisions made in the criminal and civil justice systems. Despite its influence, few studies have systematically examined how the Static-99 is used by clinicians in practice. The current study compares the Static-99 ratings of clinicians to those of researchers for 100 adult males who completed an outpatient sex offender treatment program and were followed up over an average of about 4 years. Results showed good agreement between the ratings of clinicians and researchers for total scores on the Static-99, as well as for most individual items. Ratings by clinicians tended to be slightly lower than those made by researchers. The predictive validity of ratings made by clinicians and researchers was very similar and moderate in terms of effect size. In 30 cases, clinicians used discretion to "override" or adjust the Static-99 ratings when making final risk judgments, but the predictive validity of the clinical adjusted ratings was worse than that of the original Static-99 ratings made by clinicians. The need for quality assurance and training are discussed along with the need for clear empirically supported guidelines regarding overrides.


Contribution of nasal pathways to low frequency respiratory impedance in infants.
In infants the impedance of the nasal pathways (Zn) is a significant proportion of the total respiratory impedance (Zrs). In 11 infants Zrs was partitioned into Zn and lower respiratory system impedance (Zlrs) using a nasal catheter. A low frequency oscillatory signal (0.5-20 Hz) was applied during a pause in breathing to obtain the impedance spectra. A model of the respiratory system containing an airway and tissue compartment was then fitted to Zrs and Zlrs. The airway compartment consisted of a frequency independent resistance (R) and inertance (I), while the tissue compartment was described by coefficients of tissue damping (G) and elastance (H). Zrs could be reliably partitioned into Zn and Zlrs. The nasal pathway acted as a purely resistive-inertive impedance and contributed approximately half of the airway resistance (mean (SE) 44.6 (4.9)%) and most of the respiratory system inertance (71.7 (3.5)%). In studies investigating changes in airway resistance in nasally breathing infants, the separation of nasal and lower respiratory system mechanics will increase the sensitivity of the tests.


Primary malignant tumours associated with renal cell carcinoma.
Of 360 patients with primary renal cell carcinoma seen at the Vancouver General Hospital between 1957 and 1976, 33 had associated primary malignant lesions. A review of the 166 patients who had ablative surgery revealed that they were four times more likely to have a synchronous primary malignant tumour than the other patients. The incidence of asynchronous primary malignant tumours was not increased. This may be related to the fact that the patients' full life charts were not available. In 18 patients dying of other causes in whom an incidental renal cell carcinoma was found, 5 (28%) died of other malignant tumours. In a comparable age group from the general population, 19% are at risk of death from malignant disease. The frequency of synchronous contralateral renal cell carcinoma in our series was 50 times greater than the frequency of primary renal cell carcinoma in a corresponding sector of the general population.


Differential regulation of rat testicular 5alpha-reductase type 1 and 2 isoforms by testosterone and FSH.
Testosterone is metabolised to the more potent androgen, dihydrotestosterone, by the 5alpha-reductase (5alphaR) enzyme. We previously showed that 5alpha-reduced androgens are important for maintaining androgen action on rat spermatogenesis when testicular testosterone concentrations are reduced. This study investigated expression and activity of the 5alphaR isoforms, type 1 (5alphaR-1) and type 2 (5alphaR-2), in the rat during hormone manipulation in order to understand the factors that regulate the testicular concentration of 5alphaR and testicular 5alpha-reduced androgen biosynthesis. Testicular 5alphaR-1 and 5alphaR-2 mRNA and enzyme activity were measured by real-time PCR and specific enzyme assays respectively. Hormone levels were first suppressed using two models of gonadotrophin suppression: testosterone and oestradiol treatment (LH/testosterone deficiency) or GnRH immunisation (LH/testosterone and FSH deficiency). Hormones were then either restored or suppressed for 6 days by a variety of hormonal treatments. 5alphaR-1 mRNA and enzyme activity increased when testosterone was suppressed, yet restoration of testosterone decreased 5alphaR-1 mRNA and enzyme activity, suggesting that testosterone negatively regulates 5alphaR-1. suppression of FSH decreased 5alphaR-1 mRNA yet FSH administration increased 5alphaR-1 mRNA, but no changes in 5alphaR-1 activity were observed within the 6 day period. In contrast to 5alphaR-1, testosterone did not affect the testicular concentration of 5alphaR-2 mRNA or activity, but there was evidence for modulation of 5alphaR-2 activity by FSH. Measurement of testicular androgens revealed that 5alphaR-1 was primarily responsible for the production of 5alpha-reduced metabolites. It is concluded that the 5alphaR isoforms in rat testis are differentially regulated by testosterone and FSH: testosterone negatively regulated 5alphaR-1 mRNA and enzyme activity but had no affect on 5alphaR-2, whereas FSH positively regulated 5alphaR-1 mRNA and appeared to regulate 5alphaR-2.


Effectiveness of decision aids on cancer-screening decision-making: an umbrella review protocol.
Although systematic reviews have shown how decision aids about cancer-related clinical decisions improve selection of key options and shared decision-making, whether or not particular decision aids, defined by their specific presentation formats, delivery methods and other attributes, can perform better than others in the context of cancer-screening decisions is uncertain. Therefore, we planned an overview to address this issue by using standard umbrella review methods to repurpose existing systematic reviews and their component comparative studies. We will search PubMed, Embase, the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects from inception through 31 December 2021 with no language restriction and perform full-text evaluation of potentially relevant articles. We will include systematic reviews of randomised controlled trials or non-randomised studies of interventions that assessed a decision aid about cancer-screening decisions and compared it with an alternative tool or conventional management in healthy average-risk adults. Two reviewers will extract data and rate the study validity according to standard quality assessment measures. Our primary outcome will be intended and actual choice and adherence to selected options. The secondary outcomes will include attributes of the option-selection process, achieving shared decision-making and preference-linked psychosocial outcomes. We will qualitatively assess study, patient and intervention characteristics and outcomes. We will also take special care to investigate the presentation format, delivery methods and quality of the included decision aids and assess the degree to which the decision aid was delivered and used as intended. If appropriate, we will perform random-effects model meta-analyses to quantitatively synthesise the results. Ethics approval is not applicable as this is a secondary analysis of publicly available data. The review results will be submitted for publication in a peer-reviewed journal. CRD42021235957.


Male circumcision and risk of HIV infection among heterosexual African American men attending Baltimore sexually transmitted disease clinics.
Male circumcision has received international attention as an intervention for reducing HIV infection among high-risk heterosexual men; however, few US studies have evaluated its association with the risk of HIV infection. We analyzed visit records for heterosexual African American men who underwent HIV testing while attending sexually transmitted disease (STD) clinics in Baltimore, Maryland, from 1993 to 2000. We used multivariable binomial regression to evaluate associations between circumcision and the risk of HIV infection among visits by patients with known and unknown HIV exposure. Overall, 1096 (2.7%) of 40,571 clinic visits yielded positive HIV test results. Among 394 visits by patients with known HIV exposure, circumcision was significantly associated with lower HIV prevalence (10.2% vs. 22.0%; adjusted prevalence rate ratio [PRR], 0.49 [95% confidence interval [CI], 0.26-0.93]). Conversely, among 40,177 visits by patients with unknown HIV exposure, circumcision was not associated with reduced HIV prevalence (2.5% vs. 3.3%; adjusted PRR, 1.00 [95% CI, 0.86-1.15]), and age >or=25 years old and diagnosis of ulcerative STD were associated with increased prevalence. Circumcision was associated with substantially reduced HIV risk in patients with known HIV exposure, suggesting that results of other studies demonstrating reduced HIV risk for circumcision among heterosexual men likely can be generalized to the US context.


Atypical Colony Morphology of Staphylococcus lugdunensis Isolated from a Wound Specimen.
The incidence of infections due to coagulase-negative staphylococci (CoNS) has been steadily increasing in recent years. In this report, we describe an isolate of the CoNS Staphylococcus lugdunensis from a wound specimen with a colony morphology distinct from that of a classical S. lugdunensis colony. Specifically, wrinkled, medium-sized, beta hemolytic, opaque, rough white colonies were detected on blood agar. Catalase-positive, coagulase-negative, gram-positive cocci-yielding such colonies should be suspected of being S. lugdunensis.


Ghrelin enhances appetite and increases food intake in humans.
Ghrelin is a recently identified endogenous ligand for the growth hormone secretagogue receptor. It is synthesized predominantly in the stomach and found in the circulation of healthy humans. Ghrelin has been shown to promote increased food intake, weight gain and adiposity in rodents. The effect of ghrelin on appetite and food intake in man has not been determined. We investigated the effects of intravenous ghrelin (5.0 pmol/kg/min) or saline infusion on appetite and food intake in a randomised double-blind cross-over study in nine healthy volunteers. There was a clear-cut increase in energy consumed by every individual from a free-choice buffet (mean increase 28 +/- 3.9%, p<0.001) during ghrelin compared with saline infusion. Visual analogue scores for appetite were greater during ghrelin compared to saline infusion. Ghrelin had no effect on gastric emptying as assessed by the paracetamol absorption test. Ghrelin is the first circulating hormone demonstrated to stimulate food intake in man. Endogenous ghrelin is a potentially important new regulator of the complex systems controlling food intake and body weight.


Exoproduct secretions of Pseudomonas aeruginosa strains influence severity of alveolar epithelial injury.
To determine whether exoenzyme S plays a role in alveolar epithelial injury, two parental strains of Pseudomonas aeruginosa, PAK and PA103, were tested that produced large quantities of exoenzyme S. Strains PAK and PA103 differ in the form of exoenzyme S they produce. Strain PAK produces a 53-kDa protein that does not possess ADP-ribosyltransferase activity and large quantities of a 49-kDa protein that expresses ADP-ribosyltransferase activity. Strain PA103 produces the 53-kDa protein and low amounts of exoenzyme S activity. A quantitative experimental protocol was used to measure the protein permeability of the alveolar epithelium and the dissemination of the bacteria to the pleural space and circulation. The results indicate that instillation of PAK and PA103 resulted in significant lung injury. Control experiments utilizing isogenic, exoenzyme S-deficient, regulatory mutants in the infection model reduced the lung injury and the dissemination of instilled bacteria. Taken together these results suggest that alveolar epithelial injury correlated with the production of the 53-kDa form of exoenzyme S or other coordinately regulated factors.


Analysis of the anti-fatigue activity of polysaccharides from Spirulina platensis: role of central 5-hydroxytryptamine mechanisms.
This study evaluated the effects of polysaccharides from Spirulina platensis (PSP) on endurance during treadmill exercise; levels of some biochemical indicators including hemoglobin (Hb), lactic acid (LA), creatine kinase (CK), and blood urea nitrogen (BUN); concentrations of 5-hydroxytryptamine (5-HT); and expressions of second isoforms of tryptophan hydroxylase (TPH2) and serotonergic type 1B inhibitory autoreceptor (5-HT1B) in the caudate putamen of exercising rats. Sixty Sprague-Dawley male rats were randomly divided into six groups: control group, exercise group, exercise and PSP (50, 100, or 200 mg kg-1)-treated groups, and exercise and caffeine (10 mg kg-1)-treated group (positive control). In the exercise groups, rats were put on a treadmill and forced to run for 30 min once a day for 6 consecutive days. On the 7th day of the experiment, time to exhaustion during the treadmill exercise was determined for the trained groups. Immediately after determination of the exhaustion time, all rats were sacrificed. Levels of Hb and LA were tested by the HiCN (Hemoglobin ferricyanide) colorimetry method and a colorimetric assay, respectively. Levels of CK and BUN were determined by automatic biochemical analyzer. 5-HT concentrations were detected by HPLC analysis. TPH2 and 5-HT1B expressions were measured by western blotting and real-time PCR. The results demonstrated that PSP prolonged the time to exhaustion during the treadmill exercise; increased Hb levels; decreased LA, BUN, and CK levels in the blood; suppressed the exercise-induced increase of 5-HT concentrations and TPH2 expression; and prevented the exercise-induced decrease of 5-HT1B expression in the caudate putamen. The most potent effects were observed at the PSP dose of 200 mg kg-1. These results suggest that the mechanism of promotion of physical performance by PSP might be related to increase in Hb levels; decrease in LA, BUN, and CK levels in the blood; inhibition of the exercise-induced 5-HT and TPH2 expressions; and the increase in the 5-HT1B expression in the caudate putamen of exercised rats.


Effects of specific inspiratory muscle training combined with whole-body endurance training program on balance in COPD patients: Randomized controlled trial.
This study aims to assess the effect of inspiratory muscle training (IMT) combined with endurance training (ET) on balance in patients with chronic obstructive pulmonary disease (COPD). We studied 32 male patients (62 ± 6 years) with moderate to very severe COPD. They were randomly assigned to an experimental group (IMT+ET) n = 16 or a control group (ET) n = 16 with similar characteristics. The evaluations were carried out at inclusion and after eight weeks of the training period. Functional balance was assessed by the Berg Balance Scale (BBS), the Timed-up and Go (TUG), the Single Leg Stance test (SLS), and the Activities-specific Balance Confidence (ABC) scale. The strength of the inspiratory muscles (PImax) was assessed by maximal inspiratory mouth pressure. Functional exercise performance was assessed by the 6 minutes walking test (6MWT). IMT program consists in performing two daily sets of 30 inspirations with 50% of PImax increased by 10% every two weeks. ET program consists in performing 30 min treadmill exercise at 60% to 80% of the average speed achieved during the 6MWT three days per week. After the training period, the experimental group demonstrated greater improvements in BBS (IMT+ET vs. ET; p = 0.019), and in ABC (IMT+ET vs. ET; p = 0.014). However, no significant differences between groups were observed for TUG, SLS, and 6MWT. There was a significant difference between groups in PImax (IMT+ET vs. ET; p = 0.030). Significant moderate correlations were obtained between ΔPImax and ΔBBS for both groups (IMT+ET: r = 0.624, p = 0.010; ET r = 0.550, p = 0.027) as well as for ΔABC but only in the experimental group (IMT+ET: r = 0.550, p = 0.027). Compared to ET alone, the results suggest that IMT combined with ET enhances inspiratory muscle function and functional balance according to BBS and ABC in patients with COPD. We suggest that inspiratory muscle training might be introduced as additional training to pulmonary rehabilitation programs aimed at improving balance in COPD patients. The trial registry name: Clinical Trials; Registration number: NCT04084405; URL: https://clinicaltrials.gov/ct2/show/NCT04084405.


A genome-wide comparative evolutionary analysis of zinc finger-BED transcription factor genes in land plants.
Zinc finger (Zf)-BED proteins are a novel superfamily of transcription factors that controls numerous activities in plants including growth, development, and cellular responses to biotic and abiotic stresses. Despite their important roles in gene regulation, little is known about the specific functions of Zf-BEDs in land plants. The current study identified a total of 750 Zf-BED-encoding genes in 35 land plant species including mosses, bryophytes, lycophytes, gymnosperms, and angiosperms. The gene family size was somewhat proportional to genome size. All identified genes were categorized into 22 classes based on their specific domain architectures. Of these, class I (Zf-BED_DUF-domain_Dimer_Tnp_hAT) was the most common in the majority of the land plants. However, some classes were family-specific, while the others were species-specific, demonstrating diversity at different classification levels. In addition, several novel functional domains were also predicated including WRKY and nucleotide-binding site (NBS). Comparative genomics, transcriptomics, and proteomics provided insights into the evolutionary history, duplication, divergence, gene gain and loss, species relationship, expression profiling, and structural diversity of Zf-BEDs in land plants. The comprehensive study of Zf-BEDs in Gossypium sp., (cotton) also demonstrated a clear footprint of polyploidization. Overall, this comprehensive evolutionary study of Zf-BEDs in land plants highlighted significant diversity among plant species.


Ranibizumab: in diabetic macular oedema.
Ranibizumab, an intravitreally administered inhibitor of vascular endothelial growth factor (VEGF), is approved for the treatment of visual impairment associated with diabetic macular oedema (DME) in the EU. In four well designed, phase II or III trials (RESOLVE, RESTORE, RIDE and RISE), 1-2 years' treatment with ranibizumab was more effective than sham or focal/grid laser therapy in improving best corrected visual acuity (BCVA) and reducing central retinal thickness (CRT) in patients with visual impairment associated with DME. Additionally, in two well designed phase III trials (RESTORE and DRCR.net-1), 1 year of treatment with ranibizumab as an adjunct to laser therapy was more effective than laser monotherapy in improving BCVA and CRT in patients with visual impairment associated with DME. Improvements in BCVA with ranibizumab alone or as an adjunct to laser therapy were observed at the first follow-up visits in these studies (i.e. 1-4 weeks after the start of treatment), and were associated with gains in vision-related quality of life, as assessed using the National Eye Institute Visual Functioning Questionnaire-25. The ocular and non-ocular adverse event profile of ranibizumab in patients with DME is similar to that observed in patients with neovascular (wet) age-related macular degeneration or retinal vein occlusion. Based on tolerability data from clinical trials, there is no indication that ranibizumab alone or combined with laser is associated with an increased risk of cardiovascular or cerebrovascular events potentially related to systemic VEGF inhibition.


Physiology of chemokines in the cancer microenvironment.
Chemokines are chemotactic cytokines whose canonical functions govern movement of receptor-expressing cells along chemical gradients. Chemokines are a physiological system that is finely tuned by ligand and receptor expression, ligand or receptor oligomerization, redundancy, expression of atypical receptors, and non-GPCR binding partners that cumulatively influence discrete pharmacological signaling responses and cellular functions. In cancer, chemokines play paradoxical roles in both the directed emigration of metastatic, receptor-expressing cancer cells out of the tumor as well as immigration of tumor-infiltrating immune cells that culminate in a tumor-unique immune microenvironment. In the age of precision oncology, strategies to effectively harness the power of immunotherapy requires consideration of chemokine gradients within the unique spatial topography and temporal influences with heterogeneous tumors. In this article, we review current literature on the diversity of chemokine ligands and their cellular receptors that detect and process chemotactic gradients and illustrate how differences between ligand recognition and receptor activation influence the signaling machinery that drives cellular movement into and out of the tumor microenvironment. Facets of chemokine physiology across discrete cancer immune phenotypes are contrasted to existing chemokine-centered therapies in cancer.


The random number generation task: psychometric properties and normative data of an executive function task in a mixed sample.
We investigated the psychometric properties of the random number generation (RNG) task in four studies using a mixed sample of young adults (n = 306), middle-aged adults (n = 40), and patients diagnosed with schizophrenia (n = 26). Data in study 1 were best accounted for by a three-factor solution representing inhibition of stereotypical schemas (seriation), output inhibition (repetition), and monitoring of previous output (cycling). Modest test-retest correlations were found, with the seriation factor showing acceptable stability across time (study 2). In study 3, RNG task performance was related to scores on concurrent neurocognitive tasks to establish construct validity. RNG scores correlated with healthy controls' performance on the Stroop color-word test and patients diagnosed with schizophrenia with executive dysfunctions. Patients diagnosed with schizophrenia performed poorer on the seriation factor of the RNG than healthy control participants (study 4). Our results indicate that the RNG task has modest to acceptable psychometric properties. It primarily taps executive subfunctions (i.e., inhibition, updating, and monitoring), which are affected by psychopathological or neurological deficits.


Time-resolved optical spectroscopy of wood.
We have proposed and experimentally demonstrated that picosecond time-resolved optical spectroscopy in the visible/near-infrared (NIR) region (700-1040 nm) is a useful technique for noninvasive characterization of wood. This technique has been demonstrated on both softwood and hardwood samples treated in different ways simulating the aging process suffered by waterlogged woods. In all the cases, alterations of absorption and scattering spectra were observed, revealing changes of chemical and structural composition.


Violence-related morbidity among people released from prison in Australia: A data linkage study.
People released from prison have an increased risk of morbidity, including from nonfatal violence. We examined the incidence and predictors of violence-related morbidity after release from prison and investigated whether there are differences according to sex and Indigenous status. Baseline data were collected from 1325 people within 6 weeks of release from prisons in Queensland, Australia, between 1 August 2008 and 31 July 2010. Data were linked to state-wide health (ambulance, emergency department and hospital) and prison records, and national death records until 31 July 2012. Predictors were identified using a multivariable Andersen-Gill model. Differences according to sex and Indigenous status were investigated using effect modification. A total of 225 (18.2%) people experienced 410 violence-related events that were recorded in health records. The incidence was 12.8 per 100 person-years [95% confidence interval (CI) 11.7, 14.1]. Risk factors for violence-related morbidity included diagnosed mental illness [hazard ratio (HR) = 2.0, 95% CI 1.1, 3.8], substance use disorder (HR = 1.6, 95% CI 1.1, 2.3) or dual diagnosis (HR = 3.2, 95% CI 2.2, 4.8); high-risk alcohol use (HR = 2.1, 95% CI 1.5, 2.8); being Indigenous (HR = 1.7, 95% CI 1.2, 2.5); and two or more prison releases (HR = 1.7, 95% CI 1.2, 2.6). Indigenous status modified the risk of violence-related morbidity, with Indigenous men having twice the risk of non-Indigenous men (HR = 1.9, 95% CI 1.3, 2.8). Approximately one in five people released from prisons in Queensland experienced violence-related morbidity. Coordinated and continuous mental health and substance use treatment from prison to the community may reduce the risk of violence-related morbidity in this population.


DU145 human prostate cancer cells express functional receptor activator of NFkappaB: new insights in the prostate cancer bone metastasis process.
Prostate cancer metastases to bone are observed in around 80% of prostate cancer patients and represent the most critical complication of advanced prostate cancer, frequently resulting in significant morbidity and mortality. As the underlying mechanisms are not fully characterized, understanding the biological mechanisms that govern prostate cancer metastases to bone at the molecular level should lead to the determination of new potential therapeutic targets. Receptor activator of NFkappaB ligand (RANKL)/RANK/Osteoprotegerin (OPG) are the key regulators of bone metabolism both in normal and pathological condition, including prostate cancer bone metastases. In the present study, we demonstrated that human prostate cancer cell lines, DU145 and PC3 express biologically functional RANK. Indeed, soluble human RANKL (shRANKL, 100 ng/ml) treatment induced ERK 1/2, p38 and IkappaB phosphorylations in these cells. shRANKL administration also promoted DU145 and PC3 prostate cancer cell invasion in vitro. Whereas human OPG (hOPG) administration alone (100 ng/ml) had no marked effect, combined association of both agents abolished the RANKL-induced DU145 cell invasion. As RANKL had no direct effect on DU145 cell proliferation, the observed effects were indeed related to RANKL-induced cell migration. DU145 human prostate cancer cells promoted osteoclastogenesis of osteoclast precursors generated from mouse bone marrow. Moreover, DU145 cells produced soluble factor(s) that up-regulate the proliferation of MC3T3-E1 pre-osteoblasts through the activation of the ERK 1/2 and STAT3 signal transduction pathways. This stimulation of pre-osteoblast proliferation resulted in an increased local RANKL expression that can activate both osteoclasts/osteoclast precursors and prostate cancer cells, thus facilitating prostate cancer metastasis development in bone. We confirm that RANKL is a factor that facilitates metastasis to bone by acting as an activator of both osteoclasts and RANK-positive prostate cancer cells in our model. Furthermore, the present study provides the evidence that blocking RANKL-RANK interaction offer new therapeutic approach not only at the level of bone resorbing cells, but also by interfering with RANK-positive prostate cancer cells in the prostate cancer bone metastasis development.


Cholangiopathy and Biliary Fibrosis in Cyp2c70-Deficient Mice Are Fully Reversed by Ursodeoxycholic Acid.
Bile acids (BAs) aid intestinal fat absorption and exert systemic actions by receptor-mediated signaling. BA receptors have been identified as drug targets for liver diseases. Yet, differences in BA metabolism between humans and mice hamper translation of pre-clinical outcomes. Cyp2c70-ablation in mice prevents synthesis of mouse/rat-specific muricholic acids (MCAs), but potential (patho)physiological consequences of their absence are unknown. We therefore assessed age- and gender-dependent effects of Cyp2c70-deficiency in mice. The consequences of Cyp2c70-deficiency were assessed in male and female mice at different ages. Cyp2c70-/- mice were devoid of MCAs and showed high abundances of chenodeoxycholic and lithocholic acids. Cyp2c70-deficiency profoundly impacted microbiome composition. Bile flow and biliary BA secretion were normal in Cyp2c70-/- mice of both sexes. Yet, the pathophysiological consequences of Cyp2c70-deficiency differed considerably between sexes. Three-week old male Cyp2c70-/- mice showed high plasma BAs and transaminases, which spontaneously decreased thereafter to near-normal levels. Only mild ductular reactions were observed in male Cyp2c70-/- mice up to 8 months of age. In female Cyp2c70-/- mice, plasma BAs and transaminases remained substantially elevated with age, gut barrier function was impaired and bridging fibrosis was observed at advanced age. Addition of 0.1% ursodeoxycholic acid to the diet fully normalized hepatic and intestinal functions in female Cyp2c70-/- mice. Cyp2c70-/- mice show transient neonatal cholestasis and develop cholangiopathic features that progress to bridging fibrosis in females only. These consequences of Cyp2c70-deficiency are restored by treatment with UDCA, indicating a role of BA hydrophobicity in disease development.


Clinical experience with cyanoacrylate tissue adhesive.
In this paper 385 cases treated with cyanoacrylate tissue adhesive during the years 1980-1995 are studied. The indications, outcomes and complications of cyanoacrylate adhesive are investigated and the results are analysed. It is encouraging that except for three cases of ocular hypotony and two cases of microbial infection no other complications occurred. Even in desperate cases with corneal perforation greater than 3 mm and ocular infection, enucleation was avoided. The early use of a bandage contact lens, inserted just after the glue application and the coverage with topical antibiotics switched every 15 days until the removal of the glue, may explain the small incidence of infection. Our experience from the use of cyanoacrylate tissue adhesive in cases with corneal perforation greater than 3 mm is very encouraging. In these cases a running 10.0 nylon suture was used to create a reticulum over the space of the corneal perforation upon which the glue was applied. The use of cyanoacrylate tissue adhesive offers to the clinician a safe technique for healing corneal wounds that avoids tectonic penetrating keratoplasty with its associated complications.


Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies.
Type 1 diabetes (T1D) is a disease in which autoimmune attacks are directed at the insulin-producing β-cell in the pancreatic islet. Autoantigens on the β-cell surface membrane are specific markers for molecular recognition and targets for engagement by autoreactive B lymphocytes, which produce islet cell surface autoantibody (ICSA) upon activation. We report the cloning of an ICSA (mAb43) that recognizes a major T1D autoantigen, ZnT8, with a subnanomolar binding affinity and conformation specificity. We demonstrate that cell-surface binding of mAb43 protects the extracellular epitope of ZnT8 against immunolabeling by serum ICSA from a patient with T1D. Furthermore, mAb43 exhibits in vitro and ex vivo specificity for islet cells, mirroring the exquisite specificity of islet autoimmunity in T1D. Systemic administration of mAb43 yields a pancreas-specific biodistribution in mice and islet homing of an mAb43-linked imaging payload through the pancreatic vasculature, thereby validating the in vivo specificity of mAb43. Identifying ZnT8 as a major antigenic target of ICSA allows for research into the molecular recognition and engagement of autoreactive B cells in the chronic phase of T1D progression. The in vivo islet specificity of mAb43 could be further exploited to develop in vivo imaging and islet-specific immunotherapies.


Detection of Borrelia burgdorferi DNA in museum specimens of Ixodes dammini ticks.
In order to investigate the potential for Borrelia burgdorferi infection before the recognition of Lyme disease as a clinical entity, the polymerase chain reaction (PCR) was used to examine museum specimens of Ixodes dammini (deer ticks) for the presence of spirochete-specific DNA sequences. One hundred and thirty-six archival tick specimens were obtained representing various continental U.S. locations; DNA sequences characteristic of modern day isolates of B. burgdorferi were detected in 13 1940s specimens from Montauk Point and Hither Hills, Long Island, New York. Five archival specimens of Dermacentor variabilis (dog tick) from the same collection and 118 Ixodes specimens from other endemic and nonendemic sites were negative. These data suggest that the appearance of the Lyme disease spirochete in suitable arthropod vectors preceded, by at least a generation, the formal recognition of this disease as a clinical entity in the United States.


A new hybrid algorithm for finding the lowest minima of potential surfaces: approach and application to peptides.
A new algorithm is presented for finding the global minimum, and other low-lying minima, of a potential energy surface (PES) of biological molecules. The algorithm synergetically combines three well-known global optimization methods: the diffusion equation method (DEM), which involves smoothing the PES; a simulated annealing (SA) algorithm; and evolutionary programming (EP), whose population-oriented approach allows for a parallel search over different regions of the PES. Tests on five peptides having between 6 and 9 residues show that the code implementing the new combined algorithm is efficient and is found to outperform the constituent methods, DEM and SA. Results of the algorithm, in the gas phase and with the GBSA implicit solvent model, are compared with crystallographic data for the test peptides; good accord is found in all cases. Also, for all but one of the examples, our hybrid algorithm finds a minimum deeper than those obtained by a very extensive scan. TINKERs implementation of the OPLS-AA force field is employed for the structure prediction. The results show that the new algorithm is a powerful structure predictor, when a reliable potential function is available. Our implementation of the algorithm is time-efficient, and requires only modest computational resources. Work is underway on applications of the new algorithm to structural prediction of proteins and other biological macro-molecules.


Verrucous carcinoma of the larynx: a review of 53 patients.
Verrucous carcinoma of the larynx is a rare laryngeal neoplasm that can be confused with a benign process. Although usually curable at an early stage, it can be locally aggressive if left untreated. We describe our experience with this tumor and make recommendations for diagnosis and treatment. From 1960 through 1990, 53 patients received initial treatment for verrucous carcinoma of the larynx at the Mayo Clinic. We retrospectively reviewed the presentation, diagnosis, treatment, and outcomes in these patients. All cases were confirmed by histologic examination. All but two patients were men, and most were smokers. Most tumors were found in the glottis, and 72% were T1 lesions at presentation. Six patients had hybrid tumors consisting of conventional squamous cell carcinoma along with the verrucous component. Sixteen patients had lesions that had been diagnosed as benign before they were seen at our institution. Treatment ranged from transoral excision to laryngopharyngectomy. Ten patients experienced recurrence, but only two patients died of the tumor. No pure verrucous lesion metastasized, and overall survival was similar to that of an age- and sex-matched cohort from the Western North Central U.S. white population. When discovered early, verrucous carcinoma of the larynx can be treated by local excision with good results; extensive lesions, however, may require more-aggressive procedures. Close communication between the pathologist and the clinician as well as adequate biopsy is essential for diagnosis. Patients with a conventional squamous cell carcinoma coexistent with a verrucous lesion must be treated as if they had invasive squamous cell carcinoma.


Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or discrete genotypes?
Schizophrenia and affective disorder have been considered to be nosologically and etiologically distinct disorders. This postulate is challenged by progress in new biological research. Both disorders are strongly influenced by genetic factors; thus genetic research is a main contributor to this discussion. We review current evidence of the genetic relationship between schizophrenia and affective disorders, mainly bipolar disorder (the various genetic research methods have been particularly applied to bipolar disorder). Recent family and twin studies reveal a growing consistency in demonstrating cosegregation between both disorders which is difficult to detect with certainty given the low base rates. Systematic molecular genetic search for specific genes impacting on either disorder has now identified one gene which is apparently involved in both disorders (G72/G30); other candidate genes reveal some evidence to present as susceptibility genes with very modest effects for each of both disorders, although not consistently so (e. g., COMT, BDNF). There is room for speculation about other common susceptibility genes, given the overlap between candidate regions for schizophrenia and those for bipolar disorder emerging from linkage studies.


The streptococcal collagen-binding protein CNE specifically interferes with alphaVbeta3-mediated cellular interactions with triple helical collagen.
Collagen fibers expose distinct domains allowing for specific interactions with other extracellular matrix proteins and cells. To investigate putative collagen domains that govern integrin α(V)β(3)-mediated cellular interactions with native collagen fibers we took advantage of the streptococcal protein CNE that bound native fibrillar collagens. CNE specifically inhibited α(V)β(3)-dependent cell-mediated collagen gel contraction, PDGF BB-induced and α(V)β(3)-mediated adhesion of cells, and binding of fibronectin to native collagen. Using a Toolkit composed of overlapping, 27-residue triple helical segments of collagen type II, two CNE-binding sites present in peptides II-1 and II-44 were identified. These peptides lack the major binding site for collagen-binding β(1) integrins, defined by the peptide GFOGER. Peptide II-44 corresponds to a region of collagen known to bind collagenases, discoidin domain receptor 2, SPARC (osteonectin), and fibronectin. In addition to binding fibronectin, peptide II-44 but not II-1 inhibited α(V)β(3)-mediated collagen gel contraction and, when immobilized on plastic, supported adhesion of cells. Reduction of fibronectin expression by siRNA reduced PDGF BB-induced α(V)β(3)-mediated contraction. Reconstitution of collagen types I and II gels in the presence of CNE reduced collagen fibril diameters and fibril melting temperatures. Our data indicate that contraction proceeded through an indirect mechanism involving binding of cell-produced fibronectin to the collagen fibers. Furthermore, our data show that cell-mediated collagen gel contraction does not directly depend on the process of fibril formation.


Memory impairment in schizophrenia--a comparison with that observed in the Alcoholic Korsakoff syndrome.
Until very recently, memory impairment was not considered to be a central feature of schizophrenia, except in chronic, deteriorated patients. In this study of a heterogeneous sample of 40 patients with DSM-III-R schizophrenia, episodic memory impairment was found to be prevalent, and in some cases, severe. The degree of memory impairment was not attributable to neuroleptic or anticholinergic medication, or to poor motivation or cooperation. These results, therefore, replicate those reported by McKenna et al. (1990) and Tamlyn et al. (1992), who suggested that the pattern of memory impairment in schizophrenia may conform in important respects to that of the classic amnesic syndrome. However, in a direct comparison of the schizophrenic sample with 18 patients suffering from the Alcoholic Korsakoff Syndrome (AKS), both quantitative and qualitative differences were found to exist between the two groups of patients. In particular, the level of long-term episodic memory impairment was found in the AKS sample to be far greater than that in the schizophrenic group. An interesting possible double-dissociation emerged between the two groups; although demonstrating superior episodic memory functioning, the schizophrenic sample were found to perform significantly more poorly than the AKS sample on a test of semantic memory.


Use of complementary therapies among breast and prostate cancer patients during treatment: a multisite study.
The purpose of this study was to compare the use of complementary therapies (CT) among breast and prostate cancer patients during active cancer treatment. The authors compared use and beliefs about the role of CT in cancer recovery. A self-report survey was completed by 126 breast cancer patients and 82 prostate cancer patients as part of a multisite research project. The self-report questionnaire inquired about the use of various CTs, sources of information about CT, reasons for using CT, beliefs about the benefits and risks of CT, demographic characteristics, and cancer treatment history. Most of the respondents were older than 50 years, Caucasian, married, had attended or completed college, and were less than 1 year post-diagnosis. Prostate cancer patients were significantly older than the breast cancer patients (P < .001). Several differences emerged between the groups. Compared to the prostate cancer patients, significantly more of the breast cancer patients reported using CT because they wanted to reduce the risk of recurrence (P < .01), play a more active role in recovery (P < .01), help manage stress (P < .01), take a more holistic approach (P < .01), or boost the immune system (P < .01). More of the prostate cancer patients reported using CT to have more control of their recovery (P < .05). The 2 groups also differed significantly (P < .01) on several beliefs about the potential benefits and risks of using CT. Most of the patients in this study had used some form of CT since the time of their diagnosis. Differences among breast and prostate cancer patients with regard to their use of CT during cancer treatment should be considered by oncology professionals who are discussing this topic with their patients.


The molecular diversity of the 5S rRNA gene in Kengyilia alatavica (Drobov) J.L. Yang, Yen & Baum (Poaceae:Triticeae): potential genomic assignment of different rDNA units.
5S rRNA sequences from several accessions of Kengyilia alatavica, a member of a tribe that includes wheat and wheat relatives, have been amplified by the polymerase chain reaction, cloned, and sequenced. From an evaluation of the aligned sequences, five 5S unit classes have been discerned. One class consists of short units, while the other four contain longer units. BLAST searches of the GenBank database have allowed us to tentatively assign these to classes found in genomes of other species. For example, the short 5S unit class and one long 5S unit class were designated, respectively, "short P1" and "long P1" because of their match with the comparable sequenced 5S rDNA accessions of Agropyron cristatum, a carrier of the P genome. Another unit class, is coined as "long R1", because of its similarity to the units sequenced from Secale cereale and Secale vavilovii, carriers of the R genome. The third unit class was designated "long S1" and is found also in Elytrigia spicata, a carrier of the S genome. Implications of these findings on the possible association of some unit classes with cytological haplome and on concerted evolution are discussed.


First Report of Leek yellow stripe virus in Allium sativum in Western India.
Garlic (Allium sativum L.) is an important bulbous spice crop in India as well as other parts of world. Garlic is well known for its medicinal properties. Degeneration due to viral infections is one of the important constraints in exploiting its yield potential. Leek yellow stripe virus (LYSV), genus Potyvirus, family Potyviridae, is a prominent virus known to infect garlic worldwide (4). During July 2013, potyvirus-like symptoms such as mosaic, streaking, stunting, mottling of leaves were observed on garlic cv. G-41 and landrace Ranibennur local, collected from Karnataka, India, and maintained at the Directorate of Onion and Garlic Research, Rajgurunagar, Pune, India. The incidence of symptomatic plants was estimated at 70% for Ranibennur local and 68% for cv. G-41. The symptomatic leaves were sampled diagonally from the field. Twenty symptomatic plants per cultivar with each sample was composited from young, middle, and lower (basal) leaves of the plant. These samples were tested by double-antibody sandwich (DAS)-ELISA for LYSV using commercially available kit (Agdia Inc., Elkhart, IN). ELISA-positive plants were further subjected to molecular studies. Total RNA from the infected leaf samples were extracted by RNeasy Plant Mini kit (Qiagen GmbH, Hilden, Germany) and assayed by reverse transcription (RT)-PCR using primer pair LYSV-F 2 (5'-GCACCATACAGTGAATTGAG-3') (1), LYSV-R (5'-GCCTCGCGCGCTCTAA-3') (3) to amplify 874 bases of partial Nib and partial coat protein gene. The amplified product of 874 bp derived from A. sativum isolate was purified (QIAquick PCR Purification Kit, Qiagen) and cloned using vector pDrive (Qiagen). The recombinant clones were sequenced and submitted in NCBI database (GenBank Accession No. KF850539). The sequence analysis performed on CLC Main Workbench Version 6.8.4 gave confirmation of LYSV. Further, phylogenetic analysis of the 874-nt sequence revealed the highest nucleotide identity (80 to 82%) with LYSV isolates (DQ925453, JN127339, AB005611, and JX429965). To the best of our knowledge, this is the first report of natural infection of garlic by LYSV in western India. LYSV is known to cause direct losses in garlic and other related Allium spp. Up to 54% reduction in bulb weight was observed due to single infection of this virus (2). Hence, our first report about this virus has significant impact on garlic production scenario, if this virus found to be widespread in the country. For this, additional surveys and genotype screenings are needed to obtain a better understanding of the potential impact of LYSV on garlic production in India. References: (1) H. Fidan and S. Baloglu. Plant Dis. 93:672, 2009. (2) H. Lot et al. Plant Dis. 82:1381, 1998. (3) P. Lunello et al. J. Virol. Methods. 118:15, 2004. (4) H. R. Pappu et al. Plant Dis. 89:205, 2005.


Mindfulness-based interventions for preadolescent children: A comprehensive meta-analysis.
Among the many social and emotional learning (SEL) interventions available, mindfulness-based interventions (MBIs) have become increasingly popular, particularly for preadolescent children who were once thought to not possess the metacognitive abilities or cognitive resources to benefit from such training. Although previous research syntheses indicate that MBIs show promise in promoting positive outcomes across a range of domains, the effectiveness of MBIs for preadolescent children may be masked by the effects of older children who have comprised the majority of samples in past meta-analyses. Hence, to better understand the impact of mindfulness-based training on preadolescent children (ages 6-12 years), the present study reviewed treatment effect estimates across a range of outcomes, including mindfulness, attention, metacognition and cognitive flexibility, emotional and behavioral regulation, academic achievement and school functioning, positive emotion and self-appraisal, negative emotion and subjective distress, externalizing problems, internalizing problems, social competence and prosocial behavior, and physical health. Thirty-two studies (nparticipants = 3640) were identified and included in a random-effects meta-analyses. The results from multiple meta-analytical analyses conducted in the present study suggest that preadolescents have experienced significant benefits across attention, emotional and behavioral regulation, positive emotion and self-appraisal, and social competence and prosocial behavior (g = 0.19 to 0.39). However, the overall effect was deemed small (g = 0.34). Due to the lack of comparison studies with SEL interventions, it remains unclear whether MBIs are as effective as traditional approaches in promoting healthy development and academic achievement for preadolescent children. Additionally, results from the present meta-analysis suggest various recommendations for future studies to ensure a continued growth in understanding how MBIs can be used with children.