The decrease in healthcare-associated methicillin-resistant Staphylococcus aureus infections and savings from glycopeptide use.
We evaluated changes in the rate of healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) infections and healthcare-associated S. aureus infections after implementation of infection control precautions and the effect of this on glycopeptide use and expenditures for glycopeptides in a private medical center in Turkey in the years 2000-2005. A striking decrease was obtained in the number of MRSA infections, and the expenditure for glycopeptide use also decreased.


Protonation and Anion Binding Properties of Aromatic Bis-Urea Derivatives-Comprehending the Proton Transfer.
A series of aromatic bis-urea derivatives was prepared and their proton dissociation, as well as anion binding properties in DMSO were investigated. To this end, UV/Vis and 1 H NMR spectroscopies and computational methods were employed. The synthesized molecules differed in the relative position of the urea moieties (ortho- and meta-derivatives) and in the functional groups (-H, -CH3 , -OCH3 , -NO2 ) in the para-position of the pendant phenyl groups. Remarkably high acidities of the compounds (logK1 H ≈14), were ascribed primarily to the stabilizing effect of the aromatic subunits. Quantum chemical calculations corroborated the conclusions drawn from experimental data and provided information from the structural point of view. Knowledge regarding protonation properties proved to be essential for reliable quantitative determination of anion binding affinities. Studied receptors were selective for acetate and dihydrogen phosphate among several anions. Formation of their complexes of 1:1 and 1:2 (ligand/anion) stoichiometries was quantitatively characterized. Proton transfer was taken into account in the course of data analysis, which was especially important in the case of AcO- . ortho-Receptors were proven to be more efficient acetate binders, achieving coordination with all four NH groups. The meta-analogues preferred dihydrogen phosphate, which acted as both hydrogen bond donor and acceptor. Cooperative binding was detected in the case of 1:2 H2 PO4 - complexes, which was assigned to formation of interanionic hydrogen bonds.


Saturation kinetics and choleretic effects of iodoxamate and iodipamide.
The biliary excretion and choleretic effects of iodoxamate (Cholevue) and iodipamide (Cholografin) were compared in unanesthetized dogs with biliary fistulas in order to assess the potential of the two contrast agents for use in intravenous cholangiography. For any equimolar infusion rate, more iodoxamate was secreted in the bile than iodipamide was the same. At the constant basal bile flow maintained in these studies, there was no difference in the maximum biliary concentration of the two compounds. With the presently recommended doses, it is unlikely that iodoxamate will offer a striking improvement over iodipamide for intravenous cholangiography in patients with normal liver function.


[Effects of AdipoRon orally on the functions of spleen and pancreas in type 2 diabetic mice].
To observe the effects of AdipoRon orally on the functions of spleen and pancreas in type 2 diabetic mice, in order to present data for clinical application. Forty C57/BL6 male mice were randomly divided into 2 groups: normal control group (n=10) and model group (n=30), the former group was fed normally, while the later group was fed with high fat and sugar for 4 weeks.After that, type 2 diabetes model was established in DM group induced by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg).As type 2 diabetes model established successfully, the model mice were randomly divided into three groups (n=10): diabetes mellitus (DM) group, high dose of AdipoRon group (DM + H) and low dose of adiponRon group (DM + L).All the four groups were treated with saline, saline, AdipoRon at the doses of 20 mg/kg and 50 mg/kg by gavages respectively, once a day for 10 days.And then put them to death for collecting blood, pancreas and spleen.Pathological changes of pancreas were observed with a light microscope after HE staining.Protein contents of insulin receptor (INSR), insulin receptor substrate 1( IRS-1) and tumor necrosis factor-α(TNF-α) in pancreatic and spleen tissues were detected by ELISA.The protein level of phosphorylation insulin receptor substrate 1(p-IRS-1) in pancreas was determined by Western blot, and the expression of insulin mRNA in pancreas was tested by RT-PCR. Under the light microscope, it was visible that the pancreatic tissue in NC group was full and closely packed, and the islet was big.Pancreatic tissue of DM mice was incompact and the islet of DM mice was smaller than that of normal mice.As for the mice treated with AdipoRon orally, the pancreatic tissue was full and closely arranged, and the islet was slightly smaller.Compared with NC group, the levels of TNF-α in pancreas and spleen of DM group were increased markedly, the levels of INSR and IRS-1 were decreased, the spleen coefficient, p-IR-1 protein level and insulin mRNA expression in pancreas were decreased, all were significant statistically (P<0.05).Compared with DM group, the levels of TNF-α in pancreas and spleen of AdipoRon groups were decreased, the levels of INSR and IRS-1 in pancreas and spleen of AdipoRon groups were increased, while the spleen coefficient was increased (P<0.05).The p-IRS-1 protein level and insulin mRNA expression in pancreas in DM+H group were increased (P<0.05).Compared with DM + L group, the level of TNF-α was decreased, and the levels of INSR and IRS-1 were significantly increased (P<0.05) in DM + H group (P<0.05). Oral administration of AdipoRon can protect the spleen and pancreas of diabetic mice by decreasing the inflammatory response, up-regulating the expression of INSR, and increasing p-IRS-1 level in diabetic mice.


Transient orthostatic hypotension is common in adolescents.
We hypothesized that transient hypotension associated with the symptom of lightheadedness with standing is a common phenomenon in healthy adolescents but may be mistaken for orthostatic intolerance. We studied 23 healthy adolescents, combining upright tilt to 70 degrees and to 35 degrees (in 12 patients) with continuous heart rate and blood pressure (BP) measurements. We measured peripheral blood flow and venous pressure in the arms and legs by using venous plethysmography. Healthy subjects with normal vasoconstrictive responses to sustained upright tilt uniformly have a transient fall in BP during 70 degrees upright tilt that varies from almost undetectable to large decreases in BP easily exceeding the 20-mm Hg threshold for orthostatic hypotension. Large decreases are associated with short-lived symptoms of lightheadedness and are most marked in those with the largest calf blood flow. The higher the flow, the lower the BP falls. There is appropriate reflex tachycardia. We conclude that transient orthostatic hypotension is common in many healthy adolescents, especially after prolonged recumbency, and is related to dependent vascular tone.


Evaluation of Personalized Skincare Through in-silico Gene Interactive Networks and Cellular Responses to UVR and Oxidative Stress.
Personalized approaches in dermatology are designed to match the specific requirements based on the individual genetic makeup. One major factor accounting for the differences in skin phenotypes is single nucleotide polymorphism (SNP) within several genes with diverse roles that extend beyond skin tone and pigmentation. Therefore, the cellular sensitivities to the environmental stress and damage linked to extrinsic aging could also underlie the individual characteristics of the skin and dictate the unique skin care requirements. This study aimed to identify the likely biomarkers and molecular signatures expressed in skin cells of different ethnic backgrounds, which could aid further the design of personalized skin products based on specific demands. Using data mining and in-silico modeling, the association of SNP-affected genes with three major skin types of European, Asian and African origin was analyzed and compared within the structure-function gene interaction networks. Cultured dermal fibroblasts were subsequently subjected to ultraviolet radiation and oxidative stress and analyzed for DNA damage and senescent markers. The protective applications of two cosmetic ingredients, Resveratrol and Quercetin, were validated in both cellular and in-silico models. Each skin type was characterized by the presence of SNPs in the genes controlling facultative and constitutive pigmentation, which could also underlie the major differences in responses to photodamage, such as oxidative stress, inflammation, and barrier homeostasis. Skin-type-specific dermal fibroblasts cultured in-vitro demonstrated distinctive sensitivities to ultraviolet radiation and oxidative stress, which could be modulated further by the bioactive compounds with the predicted capacities to interact with some of the genes in the in-silico models. Evaluation of the SNP-affected gene networks and likely sensitivities of skin cells, defined as low threshold levels to extrinsic stress factors, can provide a valuable tool for the design and formulation of personalized skin products that match more accurately diverse ethnic backgrounds.


Sudden Onset Fluent Aphasia: Stroke or Seizure?
Conventional understanding of acute onset language deficits indicates that fluent aphasias are due to perisylvian lesions in the dominant hemisphere, most often in the setting of acute stroke. Case studies and retrospective analyses, however, suggest the need to keep ictal phenomena as an alternative diagnostic possibility. The following case illustrates an epileptic mechanism of sudden onset fluent aphasia mimicking an acute stroke presentation. We utilize the case to illustrate means by which to differentiate stroke versus ictal etiology by way of electroencephalography/response to antiseizure drugs as well as perfusion/diffusion imaging. We review the literature case reports to demonstrate that isolated fluent aphasia typically localizes to left-hemispheric, temporal foci. Finally, we provide a brief synthesis of potential neurologic mechanisms by which left temporal lesions may cause fluent aphasia.


Non-linear relationship between maternal work hours and child body weight: Evidence from the Western Australian Pregnancy Cohort (Raine) Study.
Using longitudinal data from the Western Australia Pregnancy Cohort (Raine) Study and both random-effects and fixed-effects models, this study examined the connection between maternal work hours and child overweight or obesity. Following children in two-parent families from early childhood to early adolescence, multivariate analyses revealed a non-linear and developmentally dynamic relationship. Among preschool children (ages 2 to 5), we found lower likelihood of child overweight and obesity when mothers worked 24 h or less per week, compared to when mothers worked 35 or more hours. This effect was stronger in low-to-medium income families. For older children (ages 8 to 14), compared to working 35-40 h a week, working shorter hours (1-24, 25-34) or longer hours (41 or more) was both associated with increases in child overweight and obesity. These non-linear effects were more pronounced in low-to-medium income families, particularly when fathers also worked long hours.


Human liver myeloid dendritic cells maturate in vivo into effector DC with a poor allogeneic T-cell stimulatory capacity.
We hypothesized that the relatively low immunogenicity of liver grafts might be related to a special maturation program of hepatic myeloid dendritic cells (MDC), yielding relatively immature effector MDC with weak allogeneic T-cell stimulatory capacity. To investigate whether maturation of human liver-derived MDC in vivo differs from maturation of MDC at another anatomical location, we compared the immunophenotypes and allogeneic T-cell stimulatory capacity of MDC from hepatic with those from inguinal lymph nodes (LN). MDC were purified by immunomagnetic selection from hepatic LN obtained from multi-organ donors (n = 8) and from inguinal LN of kidney transplant recipients (n = 7). MDC from hepatic LN had a significantly reduced capacity to stimulate allogeneic T-cell proliferation compared to MDC from inguinal LN. However, this was not due to an immaturity, since MDC from hepatic LN had significantly higher expressions of HLA-DR, CD80, and CD86 compared to MDC from inguinal LN. Hepatic MDC maturate in vivo to a mature type of effector MDC with relatively poor allogeneic T-cell stimulatory capacity.


No clear genetic influences on the association between dyslexia and anxiety in a population-based sample of female twins.
Individuals with dyslexia are at an increased risk for anxiety disorders (e.g. generalized anxiety disorder, stress disorders, panic disorder). The extent to which this association is mediated by genetic and/or environmental influences is unclear. The current study explored the relationship between these two phenotypes using a large population-based twin sample. In total, 940 monozygotic and 903 dizygotic female twin pairs were included in the analyses. The presence of dyslexia and anxiety was determined by self-report of diagnosis by a health professional. Tetrachoric correlations confirmed an association between the two phenotypes, but suggested that there was no evidence for shared genetic risks. Bivariate twin modelling corroborated this finding and indicated the relationship between dyslexia and anxiety is mediated by shared environmental factors. Future research should seek to identifying the environmental factors that increase the vulnerability of individuals with dyslexia to emotional problems should be a priority for future research.


Synthesis of Aspidodispermine via Pericyclic Framework Reconstruction.
A divergent approach to the pyrroloquinoline scaffold as present in the class of Aspidosperma alkaloids was developed. As a case study, abundant and renewable nicotinic acid was transformed via pericyclic framework reconstruction into aspidodispermine, a unique member of pyrroloquinoline alkaloids. The sequence comprises a [2 + 2]-photocycloaddition, a Ramberg-Bäcklund contraction, and a strain-promoted formal electrocyclic rearrangement of a bicyclo[2.2.0]hexene and is potentially extendable to pyrroloindole scaffolds as present in the ibophyllidine alkaloids.


[Alcoholic ketoacidosis: not rare cause of metabolic acidosis].
Alcoholic ketoacidosis is an often overlooked disorder, which affects chronic ethanol abusers who have usually had a binge culminating in severe vomiting with resulting hypovolemia, acute starvation and then a beta-hydroxybutyrate dominated ketoacidosis (due to the conjonction of enhanced Glucagon/Insuline and NADH/NAD ratios). Although the pathophysiology is complex, the syndrome is quickly reversible with the administration of saline and glucose solutions along with the correction of electrolyte disturbances, often unmasked during the treatment. Insuline and bicarbonates are not indicated. The prognosis, which is excellent, depends mainly on the coexisting acute disorders, which should be purchased and treated appropriately.


Electrophysiologic characteristics of atrial tachycardia originating from the right pulmonary veins or posterior right atrium: double potentials obtained from the posterior wall of the right atrium can be useful to predict foci of atrial tachycardia in right pulmonary veins or posterior right atrium.
The right pulmonary veins (RPVs) and posterior wall of the right atrium (PRA) are anatomically located adjacent to each other. The aim of this study was to demonstrate the electrophysiologic characteristics of atrial tachycardia (AT) originating from the PRA or RPVs. A total of 26 consecutive patients with AT originating from the RPVs or PRA underwent detailed atrial endocardial mapping and successful radiofrequency catheter ablation. Eight foci were found in the PRA and 18 foci in the RPVs. Analysis of P wave configuration showed that lead V1 was the most helpful in distinguishing the AT foci between these two sites. In all cases, double potential (DP) configurations were recorded from several electrodes of a multielectrode catheter placed in the PRA, and the first DP component (FP) was the earliest potential recorded from the right atrium during the tachycardia. The amplitude of the FP was higher than that of the second DP component (SP) for AT foci originating in the PRA, whereas the reverse occurred for those in the RPV. The activation sequence of the FP was from superior to inferior for the AT foci in the superior RPV, whereas the reverse occurred for the AT foci in the inferior RPV. P wave configuration in lead V1 is helpful in distinguishing AT foci between those originating in the PRA and RPVs. The DPs obtained from the PRA can be useful in predicting whether AT foci originate from the PRA or RPVs.


Association of Postmenopausal Osteoporosis and Periodontal Disease: A Double-Blind Case-Control Study.
Both osteoporosis (OP) and periodontitis are chronic inflammatory diseases associated with bone loss mediated by local and systemic factors. The two diseases share common risk factors. Previous studies have suggested that OP in itself is a predisposing factor for periodontal tissue destruction in postmenopausal women. However, only a moderate correlation has been shown between the two conditions. In this study, we compared the severity of periodontal disease in postmenopausal osteoporotic women and postmenopausal women without OP. The study group consisted of 100 postmenopausal women in the age group of 50-65 years: Group 1 (50 osteoporotic) and Group 2 (50 non-osteoporotic women). Periodontal parameters included sulcus bleeding index, oral hygiene index simplified, probing pocket depth (PPD), and clinical attachment loss (CAL), interproximal alveolar bone loss (ABL), and number of missing teeth. The correlation of periodontal disease status with systemic bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry. The results indicated that osteoporotic (Group 1) women had a significantly greater PPD, CAL, and ABL when compared with the non-osteoporotic Group 2 (P < 0.0001). There was no significant correlation between BMD and various parameters between the groups. Within the limitations of the present study it was noted that postmenopausal OP is associated with an increased incidence and severity of periodontal disease. Educating postmenopausal osteoporotic women regarding the importance of good oral care should be part of their management regime. Hence, it could be inferred a possibility of a probable relationship between OP and periodontal disease, but long-term prospective studies are warranted in the future in order to provide definitive evidence.


Botanical trash present in cotton before and after saw-type lint cleaning.
The % by weight content of leaf-like, stem, boll, seed, and weed materials sifted (3360 mum greater than particle size greater than or equal to 595 mum) from visible wastes of the Shirley Analyzer was determined for a lint sample taken after ginning but before cleaning and for a second lint sample taken after one stage of saw-type cleaning. The % by weight content for bract and leaf increased with decreasing trash particle size. The content of cotton seed coat fragments decreased with reduction in trash particle size. Approximately 1/4 of the botanical wastes consisted of weed materials, including grass particles. Lint cleaning was ineffective in reducing the % by weight content of leaf-like trash. Some selective removal of stem trash occurred as a function of lint cleaning.


Reovirus-specific polypeptides: analysis using discontinuous gel electrophoresis.
The electrophoretic analysis of reovirus-specific polypeptides in infected cells using a discontinuous gel system has allowed the resolution of additional viral-specific polypeptides, including one large-sized gamma3 and two (or possibly three) medium-sized (mu3, mu4, mu5(?)) species. The proteins designated mu0, sigma1, and sigma2 based on electrophoretic mobility in gel systems containing phosphate-urea correspond to mu4, sigma2, and sigma1, respectively, when analyzed in systems containing Tris-glycine. It is likely that protein modifications (phosphorylation and glycosylation) are responsible for at least some of these differences.


Sequence differences at orthologous microsatellites inflate estimates of human-chimpanzee differentiation.
Microsatellites--contiguous arrays of 2-6 base-pair motifs--have formed the cornerstone of population-genetic studies for over two decades. Their genotype data typically takes the form of PCR fragment lengths obtained using locus-specific primer pairs to amplify the genomic region encompassing the microsatellite. Recently, we reported a dataset of 5,795 human and 84 chimpanzee individuals with genotypes at 246 human-derived autosomal microsatellites as a resource to facilitate interspecies comparisons. A major assumption underlying this dataset is that PCR amplicons at orthologous microsatellites are commensurable between species. We find this assumption to be frequently incorrect owing to discordance in microsatellite organization and variability, as well as nontrivial length imbalances caused by small species-specific indels in microsatellite flanking sequences. Converting PCR fragment lengths into the repeat numbers they represent at 138 microsatellites whose organization and variability was found to be highly similar in both species, we show that interspecies incommensurability among PCR amplicons can inflate FST and DPS estimates by up to 10.6%. Separate investigations of determinants of microsatellite variability in humans and chimpanzees uncover similar patterns with mean and maximum numbers of repeats, as well as numbers and ranges of distinct alleles, all important factors in predicting heterozygosity. In contrast, across microsatellites, numbers of repeats were significantly smaller in chimpanzees than in humans, while numbers and ranges of distinct alleles were instead larger. Our findings have fundamental implications for interspecies comparisons using microsatellites and offer new opportunities for more accurate comparisons of patterns of human and chimpanzee genetic variation in numerous areas of application.


Proton field-cycling nuclear magnetic resonance relaxometry in the smectic A mesophase of thermotropic cyanobiphenyls: Effects of sonication.
Proton field-cycling nuclear magnetic resonance relaxometry is used to study the spin-lattice relaxation dispersion of selected standard smectic A liquid crystals at different temperatures. Relaxation features at both, in the presence and absence of a monochromatic ultrasonic field are considered. We show that the laboratory-frame spin-lattice relaxation time is mainly governed by translational diffusion. Order director fluctuations (ODF) are less important while rotational diffusion seems to be only relevant near the clearing point. Our study suggests that sonication enhances the ODF contribution in the SmA mesophase. Within the framework of the approach we have outlined, different features associated with the ODF mechanism can be investigated.


[ANESTHESIOLOGY AND CRITICAL CARE, PERIOPERATIVE MEDICINE, PAIN MANAGEMENT, EMERGENCY MEDICINE AND RESUSCITATION].
Anesthesia and intensive care, perioperative medicine and pain management, emergency medicine and resuscitation, all together constitute the field of action of the anesthesiologist. The definition of "anesthesiologist" underestimates the profession, and the lack of anesthesiologists seems understandable when we examine the scope of their activities throughout the hospital. There is little awareness among the public of the extent of the anesthesiologist's activity. The anesthesia segment itself, with all its importance, occupies a unique, yet modest part. The main activity of the anesthesiologist during surgery is reanimation, maintaining the patient in good shape while under anesthesia, and coping with hemodynamic changes that occur at every moment. The advantage of the anesthesiologist is that he is a "hospitalist," both the internal medical and surgical doctor. He must be profoundly skilled in all areas of medicine, CPR, pediatrics, women's medicine, general surgery, heart surgery, brain and orthopedic surgery, blood vessels, and many other fields. An important goal is to maintain our patients almost painless. Thus, early at the patient interview, the anesthesiologist will determine the course of the multi-modal analgesic management during hospitalization. Preemptive analgesic medication prior to surgical incision will reduce the pain that the patient will suffer after surgery. Whenever possible, the patient will receive a nerve blockage, or minute doses of opioids added to regional anesthetics. Pain management in the recovery room will be intensified by patient-controlled analgesia via infusion pumps, or by a wide variety of therapies, minimizing the use of oral opioid medications, thus avoiding addictive-prone behavior. This special issue of "Harefuah" is dedicated to anesthesia, pain management, and intensive care. The articles published in the current issue deal with key topics, such as fundamental changes occurring in resident education, emphasizing competent judgement and technical skills, and personal and caring approaches to the patient. The possibility that anesthesia may be associated with cognitive changes in infancy and in older age became a major concern and an active research field. Anesthetic complications can rapidly deteriorate and endanger the life of the patient, may leave him confused, and incapacitated. Larger and complicated modern surgeries are now possible thanks to the special skills and capabilities of the modern anesthesiologist to keep the patient alive and well, even in the presence of major surgery.


The gender paradox in suicide.
In most Western countries females have higher rates of suicidal ideation and behavior than males, yet mortality from suicide is typically lower for females than for males. This article explores the gender paradox of suicidal behavior, examines its validity, and critically examines some of the explanations, concluding that the gender paradox of suicidal behavior is a real phenomenon and not a mere artifact of data collection. At the same time, the gender paradox in suicide is a more culture-bound phenomenon than has been traditionally assumed; cultural expectations about gender and suicidal behavior strongly determine its existence. Evidence from the United States and Canada suggests that the gender gap may be more prominent in communities where different suicidal behaviors are expected of females and males. These divergent expectations may affect the scenarios chosen by females and males, once suicide becomes a possibility, as well as the interpretations of those who are charged with determining whether a particular behavior is suicidal (e.g., coroners). The realization that cultural influences play an important role in the gender paradox of suicidal behaviors holds important implications for research and for public policy.


Endoscopic resolution and recurrence of gastric antral vascular ectasia after serial treatment with argon plasma coagulation.
To evaluate long-term endoscopic resolution and recurrence rate of gastric antral vascular ectasia (GAVE) after argon plasma coagulation (APC) treatment. This was an IRB-approved retrospective single center study that included patients endoscopically treated for GAVE between 1/1/2008 to 12/31/2014. The primary and secondary end points of the study were rate of endoscopic resolution of GAVE after APC treatment and recurrence rate of GAVE after endoscopic resolution, respectively. Endoscopic resolution of GAVE was defined as no endoscopic evidence of GAVE after treatment with APC. Recurrence of GAVE was defined as endoscopic reappearance of GAVE after prior resolution. Twenty patients met the study criteria. Median age (range) of the patients was 59.5 years (42-74 years). GAVE was associated with underlying cirrhosis in 16 (80%) patients. Indications for initial esophagogastroduodenoscopy (EGD) included hematemesis and/or melena (9/20, 45%), iron deficiency anemia (6/20, 30%), screening or surveillance of varices (4/20, 20%), and occult gastrointestinal bleeding (1/20, 5%). The patients were treated with a total of 55 APC sessions (range 1-7 sessions). Successful endoscopic resolution of GAVE was achieved in 8 out of 20 patients (40%). There was no correlation between number of treatment sessions and GAVE treatment success (P = NS). Recurrence of GAVE was noted on a subsequent EGD in 2 out of 8 patients (25%) with prior endoscopic resolution of GAVE. Median follow-up period for the study population was 627 d (range 63-1953 d). Endoscopic resolution rate of GAVE was low (40%) with a 25% recurrence rate after treatment with APC. These rates suggest that APC treatment of GAVE may not be optimal in many circumstances.


Prevalence and correlates of self-reported disordered eating: A cross-sectional study among 90 592 middle-aged Norwegian women.
Disordered eating (DE) is extensively studied among adolescents and young women. However, there is growing evidence that DE as well as the clinical eating disorders may occur at any age from childhood to advanced years. This study aimed to determine the prevalence and correlates of DE in a representative sample of middle-aged women from Norway. The study included 90 592 women (median age: 55 years) from the Norwegian Women and Cancer study who responded to a questionnaire between the years 2002-2005. Correlates of self-reported DE were assessed by logistic regression analyses. The overall period prevalence of DE between 2002-2005 was 0.28 (95% confidence interval 0.25-0.31) %, and was highest among women ≥ 66 years: 0.65 (0.60-0.70) %. DE was strongly associated with depression (Odds ratio [OR] 3.34 [95% confidence interval 2.53-4.41]), being unemployed (OR 1.78 [1.32-2.40]) and single (OR 1.66 [1.25-2.20]). Women with DE were more likely to report low energy intake (OR 1.41 [1.08-1.86]) and were less likely to be moderately physically active (OR 0.67 [0.47-0.95]). Using the largest study sample in the literature, the present findings confirm smaller studies showing that DE do occur in women in mid-life and older age as well. Our results contribute to address a somewhat under-communicated community health problem that needs attention in terms of age-specific treatment and prevention.


Unspoken meanings: qualitative research and multi-media analysis.
The use of interviews as qualitative data collection methods is common in nursing, nurse education and social science research ( 1 , 2 ). Once interviews have been carried out, they are usually transcribed by the researcher, who then attempts an analysis of them. Without the analysis, we would not, presumably, have research. Most people, I imagine, would claim that it was part of the researcher's role to attempt some sort of analysis.


Genetic targeting and anatomical registration of neuronal populations in the zebrafish brain with a new set of BAC transgenic tools.
Genetic access to small, reproducible sets of neurons is key to an understanding of the functional wiring of the brain. Here we report the generation of a new Gal4- and Cre-driver resource for zebrafish neurobiology. Candidate genes, including cell type-specific transcription factors, neurotransmitter-synthesizing enzymes and neuropeptides, were selected according to their expression patterns in small and unique subsets of neurons from diverse brain regions. BAC recombineering, followed by Tol2 transgenesis, was used to generate driver lines that label neuronal populations in patterns that, to a large but variable extent, recapitulate the endogenous gene expression. We used image registration to characterize, compare, and digitally superimpose the labeling patterns from our newly generated transgenic lines. This analysis revealed highly restricted and mutually exclusive tissue distributions, with striking resolution of layered brain regions such as the tectum or the rhombencephalon. We further show that a combination of Gal4 and Cre transgenes allows intersectional expression of a fluorescent reporter in regions where the expression of the two drivers overlaps. Taken together, our study offers new tools for functional studies of specific neural circuits in zebrafish.


Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly.
Antimicrobial peptides (AMPs) are generally cationic and amphipathic peptides that show potential applications to combat the growing threat of antibiotic resistant infections. AMPs are known to interact with bacterial membranes, but their mechanisms of toxicity and selectivity are poorly understood, in part because it is challenging to characterize AMP oligomeric complexes within lipid bilayers. Here, we used native mass spectrometry to measure the stoichiometry of AMPs inserted into lipoprotein nanodiscs with different lipid components. Titrations of increasing peptide concentration and collisional activation experiments reveal that AMPs can exhibit a range of behaviors from nonspecific incorporation into the nanodisc to formation of specific complexes. This new approach to characterizing formation of AMP complexes within lipid membranes will provide unique insights into AMP mechanisms.


A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients.
The use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus. To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis. A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%). Patients switched to sirolimus had improved survival (P < 0.001) and slower progression to cirrhosis (P = 0.001). In patients with HCC (n = 91), sirolimus duration rather than strategy was an independent predictor of survival (P = 0.001) and extended time to HCC recurrence (33 vs. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 μmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P = 0.03). These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome.


Synthesis of Core@Shell Nanostructures in a Continuous Flow Droplet Reactor: Controlling Structure through Relative Flow Rates.
Bimetallic nanostructures are primarily synthesized in small volume batches. However, droplet-based reactors are receiving attention due to their ability to maintain thermal and compositional equilibrium within and between droplets, enabling flow operations for inline analyses and the scale-up of nanomaterial syntheses. Here, the syntheses of shape-controlled core@shell Au@Pd nanostructures with variable shell thicknesses are reported through control of the relative flow rates of reagents within the microreactor. Specifically, Pd shells were grown on cubic or octahedral Au seeds, selected as a model system. In batch reactions, shell thickness is determined by precursor concentration; however, as shown here, precursor feedstock concentration can be held constant, with the precursor concentration within the droplets being controlled through relative flow rates. This approach allows process conditions to be modified inline rather than from batch to batch to achieve particles with different shell thicknesses, and this procedure should be applicable to other multicomponent systems.


Heisenberg-Fisher thermal uncertainty measure.
We establish a connection among (i) the so-called Wehrl entropy, (ii) Fisher's information measure I(beta), and (iii) the canonical ensemble entropy for the one-dimensional quantum harmonic oscillator (HO). We show that the contribution of the excited HO spectrum to the mean thermal energy is given by I(beta), while the pertinent canonical partition function is essentially given by another Fisher measure: the so-called shift invariant one. Our findings should be of interest in view of the fact that it has been shown that the Legendre transform structure of thermodynamics can be replicated without any change if one replaces the Boltzmann-Gibbs-Shannon entropy by Fisher's information measure [Phys. Rev. E 60, 48 (1999)]]. Fisher-related uncertainty relations are also advanced, together with a Fisher version of thermodynamics' third law.


Variance component estimation for mixed model analysis of cDNA microarray data.
Microarrays provide a valuable tool for the quantification of gene expression. Usually, however, there is a limited number of replicates leading to unsatisfying variance estimates in a gene-wise mixed model analysis. As thousands of genes are available, it is desirable to combine information across genes. When more than two tissue types or treatments are to be compared it might be advisable to consider the array effect as random. Then information between arrays may be recovered, which can increase accuracy in estimation. We propose a method of variance component estimation across genes for a linear mixed model with two random effects. The method may be extended to models with more than two random effects. We assume that the variance components follow a log-normal distribution. Assuming that the sums of squares from the gene-wise analysis, given the true variance components, follow a scaled chi(2)-distribution, we adopt an empirical Bayes approach. The variance components are estimated by the expectation of their posterior distribution. The new method is evaluated in a simulation study. Differentially expressed genes are more likely to be detected by tests based on these variance estimates than by tests based on gene-wise variance estimates. This effect is most visible in studies with small array numbers. Analyzing a real data set on maize endosperm the method is shown to work well.


Acute respiratory infections: the forgotten pandemic. Communiqué from the International Conference on Acute Respiratory Infections, held in Canberra, Australia, 7-10 July 1997.
Acute respiratory infections kill 4 million children every year in developing countries, and most of these deaths are caused by pneumonia. This huge loss of life goes virtually unnoticed, despite the fact that we have two very effective ways of preventing many of the deaths from pneumonia: Haemophilus influenzae type b vaccine, and standardised antibiotic treatment regimens. Although H. influenzae type b vaccine has virtually eliminated diseases caused by this organism in children in developed countries, failure to appreciate the importance of this organism and the high cost of the vaccine has meant that it has not been used in developing countries; urgent steps need to be taken to ensure that children in developing countries receive H. influenzae vaccine. Streptococcus pneumoniae is a major cause of fatal pneumonia in developing countries. Controlled trials are needed to define the role of unconjugated 23-valent S. pneumoniae vaccine, and the new conjugate vaccine must be made available to children in developing countries soon after it is licensed. The World Health Organization has developed simple and effective guidelines for the treatment of pneumonia which have been incorporated into its Integrated Management of Childhood Illness strategy, and this programme should be strongly supported. In developed countries, acute respiratory infections are the leading cause of morbidity. The cost of these infections is enormous, because of lost earnings and the cost of treatment. There is an urgent need for systematic evaluation of existing knowledge about acute respiratory infections in developed countries, so that this knowledge can be applied to prevention and treatment. Approximately 75% of antibiotics are prescribed for acute respiratory infections, and many of these prescriptions are unnecessary. Unnecessary use of antibiotics is very expensive, and it has contributed to the rapid increase in resistance which has already made some bacteria resistant to all antibiotics. Rational guidelines for antibiotic prescribing need to be developed, and steps taken to see that they are followed. There should be greatly increased use of the existing influenza and pneumococcal vaccines in high risk groups in developed countries. New vaccines against pertussis, S. pneumoniae, non-serotypable H. influenzae, and respiratory syncytial virus have been developed and need to be carefully evaluated. Acute respiratory infections are responsible for 8.2% of the world's total burden of disability and premature death, but they receive only 0.15% of the research and development budget for health. More resources should be allocated to research on acute respiratory infections. Drug therapy has little effect on the course of viral upper respiratory tract infections. Worldwide, US$8 billion is wasted every year on drugs used to treat the symptoms of acute respiratory infections.


A single-molecule ELISA device utilizing nanofluidics.
Single molecule analysis is desired in many areas that require the analysis of ultra-small volume and/or extremely low concentration samples (e.g., single-cell biology, medicine diagnosis, virus detection, etc.). Due to the ultra-small volume or concentration, the sample contains only single or countable analyte molecules. Thus, specific single molecules should be precisely processed and detected for analysis. However, except nucleic acids, most molecules are difficult to amplify, and a new analytical methodology for specific single molecules is thus essential. For this, efficient chemical processing and detection, which are important analytical elements, should be developed. Here, we report a single-molecule ELISA (enzyme-linked immunosorbent assay) device utilizing micro/nanofluidic technology. Both chemical processing and detection were integrated into an ultra-small space (102 nm in size), and the integration allowed precise processing (∼100% capture) and detection of a specific single molecule (protein) for the first time. This new concept and enabling technology represent a significant innovation in analytical chemistry and will have a large impact on general biology and medicine.


An estimate of minimum number of brain stem neurons required for inhibition of a flexion reflex.
The tail-flick reflex elicited by noxious heat in lightly anesthetized rats is known to be prevented by trains of low-amplitude current pulses passed through a monopolar microelectrode in the rostromedial medulla ( RMM ). The effect of the distance from such an electrode on the threshold of cell bodies was described in the preceding paper (11). This paper estimates the density of cell bodies in the RMM and, subsequently, estimates the number of cell bodies excited by the aforementioned pulses, a figure whose upper bound is between 30 and 75. The mean chronaxy for suppression of tail flick was found to be 162 microS. Correspondingly, for activation of spikes in somata of the RMM , it was found to be 170 microS. The axons belonging to these somata, located in the spinal lateral columns, had mean chronaxies of 360 microS. These comparisons favor the idea that cell bodies in the RMM , not axons, mediate the suppression of tail flick. Other evidence for this conclusion is given in the text. Resting activity in the RMM was found to average 6.33 Hz. Thus if the inhibitory process depends only on the instantaneous sum of activity in the many thousands of RMM neurons, all nocifensive reflexes should be continuously suppressed. But since this is not so, the relative timing of spikes in the population may also be critical. The synchronizing effect of electrical stimulation then explains the low number of cells needed to prevent the reflex.


Pulmonary Vascular Response Patterns to Exercise: Is there a Role for Pulmonary Arterial Pressure Assessment during Exercise in the Post-Dana Point Era?
Pulmonary hypertension (PH) is often diagnosed late in its course when it purports a particularly poor prognosis. Exercise effectively unmasks early forms of several cardiopulmonary diseases but the role of performing pulmonary arterial pressure measurements during exercise in the evaluation of PH remains unclear. Whether pulmonary arterial pressure-flow relationships during exercise may provide a window into earlier diagnosis of functionally significant pulmonary arterial hypertension and left ventricular dysfunction,1 or add incrementally to our armentarium of diagnostic tests and prognostic indicators in PH, is the topic of active ongoing investigation. Evidence is emerging that abnormal pulmonary arterial pressure response patterns to exercise, when properly indexed to increased blood flow, may help to identify early forms of heart failure and pulmonary arterial hypertension. This article will discuss approaches to performing hemodynamic measurements during exercise as well as the potential clinical utility of identifying normal and abnormal pulmonary vascular response patterns to exercise.


Evaluation of new Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides for melanoma imaging.
The purpose of this study was to examine the melanoma targeting and imaging properties of two new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg(11))CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg(11))CCMSH peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg(11))CCMSH and RVD-Lys-(Arg(11))CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH displayed high melanoma uptake. (99m)Tc-RTD-Lys-(Arg(11))CCMSH exhibited the highest tumor uptake of 18.77 ± 5.13% ID/g at 2 h postinjection, whereas (99m)Tc-RVD-Lys-(Arg(11))CCMSH reached the highest tumor uptake of 19.63 ± 4.68% ID/g at 4 h postinjection. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h postinjection. The renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h postinjection, respectively. The melanoma lesions were clearly visualized by single-photon emission computed tomography (SPECT)/CT using either (99m)Tc-RTD-Lys-(Arg(11))CCMSH or (99m)Tc-RVD-Lys-(Arg(11))CCMSH as an imaging probe at 2 h postinjection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH. However, high renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH need to be reduced to facilitate their future applications.


Phylogenomic Analysis of Velvet Worms (Onychophora) Uncovers an Evolutionary Radiation in the Neotropics.
Onychophora ("velvet worms") are charismatic soil invertebrates known for their status as a "living fossil," their phylogenetic affiliation to arthropods, and their distinctive biogeographic patterns. However, several aspects of their internal phylogenetic relationships remain unresolved, limiting our understanding of the group's evolutionary history, particularly with regard to changes in reproductive mode and dispersal ability. To address these gaps, we used RNA sequencing and phylogenomic analysis of transcriptomes to reconstruct the evolutionary relationships and infer divergence times within the phylum. We recovered a fully resolved and well-supported phylogeny for the circum-Antarctic family Peripatopsidae, which retains signals of Gondwanan vicariance and showcases the evolutionary lability of reproductive mode in the family. Within the Neotropical clade of Peripatidae, though, we found that amino acid-translated sequence data masked nearly all phylogenetic signal, resulting in highly unstable and poorly supported relationships. Analyses using nucleotide sequence data were able to resolve many more relationships, though we still saw discordant phylogenetic signal between genes, probably indicative of a rapid, mid-Cretaceous radiation in the group. Finally, we hypothesize that the unique reproductive mode of placentotrophic viviparity found in all Neotropical peripatids may have facilitated the multiple inferred instances of over-water dispersal and establishment on oceanic islands.


Generation of rotationally symmetric power-exponent-phase vortex beams based on digital micromirror devices.
In this paper, what we believe to be a new method for the generation of rotationally symmetric power-exponent-phase vortex beams (RSPEPVBs) based on digital micromirror devices (DMD) was proposed and demonstrated. Based on the theory of binary amplitude holography and Lee method, the two-dimensional amplitude holograms for the generation of RSPEPVBs were obtained. Then, the experimental setup was established for the generation of RSPEPVBs based on DMD and to verify the phase structure of RSPEPVBs by the Mach-Zehnder interferometer. The experimental results showed that the RSPEPVBs can be generated based on DMD with high beam quality and stability, and the ±1st-order diffracted beams were respectively corresponding to the RSPEPVBs with contrary TCs, which was the first time to report the RSPEPVBs with negative TC. Besides, the overall and ±1st-order diffraction efficiencies of RSPEPVBs generated by DMD were 7.18% and 1.73%, respectively. The method can be applied for the generation of RSPEPVBs with different parameters and quickly achieve mode switching by loading different binary amplitude holograms, which provides a new choice for the generation of new structure beams based on DMD.


Replacing alfalfa silage with tannin-containing birdsfoot trefoil silage in total mixed rations for lactating dairy cows.
Two lactation trials were conducted comparing the feeding value of silages made from birdsfoot trefoil (BFT, Lotus corniculatus L.) that had been selected for low (BFTL), medium (BFTM), and high (BFTH) levels of condensed tannins (CT) to an alfalfa silage (AS) when fed as the principal forage in total mixed rations. Diets also included corn silage, high-moisture shelled corn, soybean meal, soy hulls, and supplemental fat. In trial 1, 32 lactating Holstein cows were blocked by days in milk, assigned to treatment sequences in 8 balanced 4 × 4 Latin squares, and fed 50% dietary dry matter from AS or 1 of 3 BFT silages containing 0.6, 1.2, or 1.7% CT. Diets averaged 17.5 to 19.5% crude protein and 26% neutral detergent fiber on a dry matter basis. Data were collected over the last 2 wk of each 4-wk period. Intakes were 1.3 to 2.8 kg of dry matter/d greater on BFT than on AS and cows gained 0.5 kg of body weight/d on BFT diets while losing 0.14 kg of body weight/d on the AS diet; this resulted in greater milk per dry matter intake (DMI) on AS. Linear effects indicated true protein yield and milk urea nitrogen declined with increasing CT concentration and quadratic effects indicated DMI, energy-corrected milk, and fat yield were increased at intermediate CT concentration. True protein yield and apparent N-efficiency were greater, and milk urea nitrogen lower, on all BFT diets than on AS. In trial 2, 50 lactating Holstein cows were fed a covariate AS diet for 2 wk and then blocked by parity and days in milk and randomly assigned to 1 of 5 diets that were fed continuously for 12 wk. Diets contained (dry matter basis) 48% AS, 16% AS plus 32% of 1 of 3 BFT silages with 0.5, 0.8, or 1.5% CT, or 48% of an equal mixture of each BFT silage. Diets averaged 16.5% crude protein and 30% neutral detergent fiber. Intake and milk yield tended to be lower on AS than BFT, but body weight gains averaged 0.6 kg/d on all diets. Cows fed any of the BFT silages had reduced milk urea nitrogen and ruminal ammonia and reduced urinary N excretion. Feeding the BFT mixture reduced concentrations of milk true protein and milk urea nitrogen and depressed apparent nutrient digestibility. Among diets containing the individual BFT silages, linear reductions in DMI and yield of milk, fat, true protein, lactose, and SNF were observed with increasing CT concentration. By contrast, a previous trial with the same BFT populations showed that substituting BFTH silage containing 1.6% CT for AS in rations containing 60% silage dry matter had no effect on intake, increased yield of milk, energy-corrected milk and milk components, elevated protein use-efficiency, but with a more modest reduction in milk urea nitrogen and urinary N excretion. Silage analyses suggested that the inconsistent responses among trials were related to growth environment or ensiling effects that altered tannin-protein interactions in BFT silage. Differences in diet formulation among trials may have also influenced responses. Results from the current and previous trials indicate further work is needed to identify optimum tannin levels in forages.


Recent Advances of Using Hybrid Nanocarriers in Remotely Controlled Therapeutic Delivery.
The development of hybrid biomaterials has been attracting great attention in the design of materials for biomedicine. The nanosized level of inorganic and organic or even bioactive components can be combined into a single material by this approach, which has created entirely new advanced compositions with truly unique properties for drug delivery. The recent advances in using hybrid nanovehicles as remotely controlled therapeutic delivery carriers are summarized with respect to different nanostructures, including hybrid host-guest nanoconjugates, micelles, nanogels, core-shell nanoparticles, liposomes, mesoporous silica, and hollow nanoconstructions. In addition, the controlled release of guest molecules from these hybrid nanovehicles in response to various remote stimuli such as alternating magnetic field, near infrared, or ultrasound triggers is further summarized to introduce the different mechanisms of remotely triggered release behavior. Through proper chemical functionalization, the hybrid nanovehicle system can be further endowed with many new properties toward specific biomedical applications.


Construction of ZnO/SnO2 Heterostructure on Reduced Graphene Oxide for Enhanced Nitrogen Dioxide Sensitive Performances at Room Temperature.
The employment of n-n homotypic heterogeneous junctions is an efficient method to improve sensitive performance of metal oxide-based gas sensors owing to the generation of charge accumulation regions. Herein, in order to further enhance nitrogen dioxide (NO2) sensing properties of the sensors based on reduced graphene oxide (RGO) at room temperature (RT), n-type ZnO nanoparticles (NPs) decorated n-type SnO2 NPs heterojunctions were successfully constructed on RGO nanosheets (NSs) by combination of the hydrothermal method and the wet-chemical deposition method. The formation of heterostructures between ZnO NPs and SnO2 NPs was confirmed by the nonlinear behavior of current versus voltage (I-V) curve of ZnO/SnO2-RGO. ZnO/SnO2-RGO based sensor displayed remarkably enhanced response (141.0%) for detecting 5 ppm of NO2 at RT, which is almost 4 and 3 times higher than that of SnO2-RGO (34.8%) and ZnO-RGO (43.3%), respectively. Moreover, as far as the ZnO/SnO2-RGO-based sensor is concerned, its response and recovery time (33 and 92 s) are also significantly decreased, compared to SnO2-RGO-based sensor (70 and 39 s) and ZnO-RGO-based sensor (272 and 1297 s). In this work, the improved NO2 sensing properties of the sensors based on RGO not only benefit from the effects of the heterostructures between SnO2 and ZnO, but also derive from the superior electrical characteristics of RGO. In particular, the n-n heterojunctions could offer facile access to effective electronic interaction and improve transfer efficiency of the charges at the interface to adsorbed oxygen. Meanwhile, the n-n heterojunctions can also provide additional reaction center for adsorbing gas.


Adenomyoepithelial tumors of the breast: molecular underpinnings of a rare entity.
Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs. The aim of this study was to provide insight into the molecular underpinnings of a spectrum of AMEs. Seven cases of AMEs of the breast (benign-1, atypical-2, in situ-1, invasive-3) were identified in our files. The seven samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Two atypical AMEs and the malignant in situ AME harbored the same gain-of-function PIK3CA mutation. The malignant in situ AME also showed EGFR amplification, not described previously. Both a benign AME and a malignant invasive AME shared the same gain-of-function AKT1 variant. The benign AME also showed a GNAS mutation. Moreover, the same gain-of-function HRAS mutation was present in an atypical AME and a malignant invasive AME. We also identified co-occurring HRAS and PIK3CA mutations in an ER-positive atypical AME, which has not been previously described. No fusion drivers were detected. We describe the molecular characteristics of the spectrum of AME tumors of the breast, which harbor alterations in the PI3K/AKT pathway. Our findings are clinically relevant with respect to the current options of targeted therapy in the rare instances where malignant AME tumors of the breast progress.


The cl2/dro1/ccdc80 null mice develop thyroid and ovarian neoplasias.
We have previously reported that the expression of the CL2/CCDC80 gene is downregulated in human papillary thyroid carcinomas, particularly in follicular variants. We have also reported that the restoration of CL2/CCDC80 expression reverted the malignant phenotype of thyroid carcinoma cell lines and that CL2/CCDC80 positively regulated E-cadherin expression, an ability that likely accounts for the role of the CL2/CCDC80 gene in thyroid cancer progression. In order to validate the tumour suppressor role of the CL2/CCDC80 gene in thyroid carcinogenesis we generated cl2/ccdc80 knock-out mice. We found that embryonic fibroblasts from cl2/ccdc80(-/-) mice showed higher proliferation rate and lower susceptibility to apoptosis. Furthermore, cl2/ccdc80(-/-) mice developed thyroid adenomas and ovarian carcinomas. Finally, ret/PTC1 transgenic mice crossed with the cl2/ccdc80 knock-out mice developed more aggressive thyroid carcinomas compared with those observed in the single ret/PTC1 transgenic mice. Together, these results indicate CL2/CCDC80 as a putative tumour suppressor gene in human thyroid carcinogenesis.


Mortality in red-sided garter snakes, Thamnophis sirtalis parietalis, due to larval nematode, Eustrongylides sp.
Garter snakes, Thamnophis sirtalis parietalis, that had been fed wild-caught banded killifish, Fundulus diaphanus, and laboratory-bred leopard frogs, Rana pipiens, were infected by larval nematode, Eustrongylides sp; 7 of the 25 snakes died. Signs of infection in 20 snakes included subcutaneous "lumps," violent contortions, and bloody exudate, apparently from the nares. Nemotodes were collected at necropsy from beneath the skin, in the lungs, in the body cavity, and along the spinal column. Nematodes were surgically removed from subcutaneous sites in 2 garter snakes, which recovered completely.


Effect of active-layer structures on temperature characteristics of InGaN blue laser diodes.
We investigate temperature characteristics of 445-nm-emitting InGaN blue laser diodes (LDs) with several types of active-layer structures. The double quantum-well (QW) LD structures having an n-type doped barrier show negative or very high characteristic temperature depending on the barrier In composition. On the contrary, the double QW structures having an undoped barrier and the single QW structure show normal temperature dependence of LD characteristics. From the simulation of carrier density and optical gain, it is found that the anomalous temperature characteristics of blue LDs are closed related to the inhomogeneous hole distribution between QWs due to the low hole mobility of InGaN materials.


Human immunology studies using organ donors: Impact of clinical variations on immune parameters in tissues and circulation.
Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here a coordinate analysis of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (2 months-93 years; n = 291) across eight clinical parameters. Overall, the blood of donors exhibited similar monocyte and lymphocyte content and low serum levels of pro-inflammatory cytokines as healthy controls; however, donor blood had increased neutrophils and serum levels of IL-8, IL-6, and MCP-1 which varied with cause of death. In tissues, the frequency and composition of monocytes, neutrophils, B lymphocytes and T cell subsets in lymphoid or mucosal sites did not vary with clinical state, and was similar in donors independent of the extent of clinical complications. Our results reveal that organ donors maintain tissue homeostasis, and are a valuable resource for fundamental studies in human immunology.


Occurrence and persistence of "Australia" antigen determinants.
"Australia" (Au) antigens from various groups of individuals were examined for the presence of d and y determinants. Antigens from all of the 214 individuals examined were found to possess either the d or y determinant, in addition to the a determinant. With the ay antiserum employed, antibody absorption was found to be a more effective means than demonstration of spur formation for detection of the y determinant. Antigens with ad specificity predominated in a collection of sera from non-ill Tongan children and adults, but no significant differences were noted in the specificities of antigens from individuals from four different regions. Almost all of the antigens from various groups of individuals in California, including inmates of a state hospital, a group of heroin users, and hepatitis patients from San Francisco General Hospital, were of the ay specificity. With one exception, antigenic specificities were found to persist for 3 years in a group of Tongan school children. Specificities also persisted in chronic carriers from California and in hepatitis patients over the course of antigenemia. Of 15 human and 4 animal antisera examined, antibodies to the y determinant were demonstrable only in a single (human) antiserum, and antibodies to the d determinant were demonstrable in one guinea pig antiserum and one horse antiserum.


Ambient air pollution and the risk of stillbirth.
The purpose of the present study was to examine the risk of stillbirth associated with ambient air pollution during pregnancy. Using live birth and fetal death data from New Jersey from 1998 to 2004, the authors assigned daily concentrations of air pollution to each birth or fetal death. Generalized estimating equation models were used to estimate the relative odds of stillbirth associated with interquartile range increases in mean air pollutant concentrations in the first, second, and third trimesters and throughout the entire pregnancy. The relative odds of stillbirth were significantly increased with each 10-ppb increase in mean nitrogen dioxide concentration in the first trimester (odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.03, 1.31), each 3-ppb increase in mean sulfur dioxide concentration in the first (OR = 1.13, 95% CI: 1.01, 1.28) and third (OR = 1.26, 95% CI: 1.03, 1.37) trimesters, and each 0.4-ppm increase in mean carbon monoxide concentration in the second (OR = 1.14, 95% CI: 1.01, 1.28) and third (OR = 1.14, 95% CI: 1.06, 1.24) trimesters. Although ambient air pollution during pregnancy appeared to increase the relative odds of stillbirth, further studies are needed to confirm these findings and examine mechanistic explanations.


Novel and highly diverse fungal endophytes in soybean revealed by the consortium of two different techniques.
Fungal endophytes were isolated from the leaves of soybean cultivars in Brazil using two different isolation techniques - fragment plating and the innovative dilution-to-extinction culturing - to increase the species richness, frequency of isolates and diversity. A total of 241 morphospecies were obtained corresponding to 62 taxa that were identified by analysis of the internal transcribed spacer (ITS) of the ribosomal DNA (rDNA). The Phylum Ascomycota predominated, representing 99% and 95.2% of isolates in the Monsoy and Conquista cultivars, respectively, whereas the Phylum Basidiomycota represented 1% and 4.8% of isolates, respectively. The genera Ampelomyces, Annulohypoxylon, Guignardia, Leptospora, Magnaporthe, Ophiognomonia, Paraconiothyrium, Phaeosphaeriopsis, Rhodotorula, Sporobolomyces, and Xylaria for the first time were isolated from soybean; this suggests that soybean harbours novel and highly diverse fungi. The yeasts genera Rhodotorula and Sporobolomyces (subphylum Pucciniomycotina) represent the Phylum Basidiomycota. The species richness was greater when both isolation techniques were used. The diversity of fungal endophytes was similar in both cultivars when the same isolation technique was used except for Hill's index, N1. The use of ITS region sequences allowed the isolates to be grouped according to Order, Class and Phylum. Ampelomyces, Chaetomium, and Phoma glomerata are endophytic species that may play potential roles in the biological control of soybean pathogens. This study is one of the first to apply extinction-culturing to isolate fungal endophytes in plant leaves, thus contributing to the development and improvement of this technique for future studies.


Priming in plant-pathogen interactions.
Plants can acquire enhanced resistance to pathogens after treatment with necrotizing attackers, nonpathogenic root-colonizing pseudomonads, salicylic acid, beta-aminobutyric acid and many other natural or synthetic compounds. The induced resistance is often associated with an enhanced capacity to mobilize infection-induced cellular defence responses - a process called 'priming'. Although the phenomenon has been known for years, most progress in our understanding of priming has been made only recently. These studies show that priming often depends on the induced disease resistance key regulator NPR1 (also known as NIM1 or SAI1) and that priming has a major effect on the regulation of cellular plant defence responses.


Oxyresveratrol (trans-2,3',4,5'-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia.
Oxidative stress is one of the major pathological factors in the cascade that leads to cell death in cerebral ischemia. Here, we investigated the neuroprotective effect of a naturally occurring antioxidant, oxyresveratrol, to reduce brain injury after cerebral stroke. We used the transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia to induce a defined brain infarction. Oxyresveratrol was given twice intraperitoneally: immediately after occlusion and at the time of reperfusion. Oxyresveratrol (10 or 20 mg/kg) significantly reduced the brain infarct volume by approximately 54% and 63%, respectively, when compared to vehicle-treated MCAO rats. Also, the neurological deficits as assessed by different scoring methods improved in oxyresveratrol-treated MCAO rats. Histological analysis of apoptotic markers in the ischemic brain area revealed that oxyresveratrol treatment diminished cytochrome c release and decreased caspase-3 activation in MCAO rats. Also, staining for apoptotic DNA showed that the number of apoptotic nuclei in ischemic brain was reduced after oxyresveratrol treatment as compared to the vehicle-treated MCAO rats. This dose-dependent neuroprotective effect of oxyresveratrol in an in vivo stroke model demonstrates that this drug may prove to be beneficial for a therapeutic strategy to limit brain injury in acute brain ischemia.


Serum amyloid A induces WISH cell apoptosis.
Serum amyloid A (SAA) is an important mammalian acute reactant. Here, we aim to investigate the effect of SAA on apoptosis and its mechanism of action in human amniotic WISH cells. The expression of formyl peptide receptor (FPRL1), which is reported as a SAA receptor, was tested using RT-PCR and ligand binding assay with radio-labeled FPRL1 ligand. The effect of SAA on proliferating cell population was evaluated by thymidine incorporation assay. The protein phosphorylation levels and caspase-3 activity were detected by Western blot assay. SAA inhibits thymidine incorporation in human amniotic WISH cells. A SAA-induced decrease of proliferating cell population was accompanied with nuclear condensation and caspase-3 activation in WISH cells, suggesting that SAA induces WISH cell apoptosis. Since FPRL1 has been reported as a SAA receptor, we investigated the effects of several FRPL1 agonists on a proliferating cell population in WISH cells. Among the tested FPRL1 agonists, only SAA induced a decrease of proliferating cell population in WISH cells. On the downstream signaling of SAA, we found that SAA stimulated extracellular signal-regulated kinase and p38 kinase, which were not inhibited by pertussis toxin (PTX), ruling out the role of PTX-sensitive G-proteins. Furthermore a SAAinduced decrease of proliferating cell population was not affected by PTX, suggesting that SAA inhibits WISH cell apoptosis in a PTX-sensitive G-proteinindependent manner. A SAA-induced decrease of a proliferating cell population was completely blocked by PD98059 and SB203580, suggesting that mitogenactivated protein kinase activities are essentially required for the process. SAA is a novel inducer for WISH cell apoptosis, and the PTX-insensitive pathway is involved in the process.


The FAD cofactor of RebC shifts to an IN conformation upon flavin reduction.
RebC is a putative flavin hydroxylase functioning together with RebP to carry out a key step in the biosynthesis of rebeccamycin. To probe the mechanism of flavin-based chemistry in RebC, we solved the structure of RebC with reduced flavin. Upon flavin reduction, the RebC crystal undergoes a change in its unit cell dimension concurrent with a 5 A movement of the isoalloxazine ring, positioning the flavin ring adjacent to the substrate-binding pocket. Additionally, a disordered helix becomes ordered upon flavin reduction, closing off one side of the substrate-binding pocket. This structure, along with previously reported structures, increases our understanding of the RebC enzyme mechanism, indicating that either the reduction of the flavin itself or binding of substrate is sufficient to drive major conformational changes in RebC to generate a closed active site. Our finding that flavin reduction seals the active site such that substrate cannot enter suggests that our reduced flavin RebC structure is off-pathway and that substrate binding is likely to precede flavin reduction during catalysis. Along with kinetic data presented here, these structures suggest that the first cycle of catalysis in RebC may resemble that of p-hydroxybenzoate hydroxylase, with substrate binding promoting flavin reduction.


Implementation of the hierarchical reference theory for simple one-component fluids.
Combining renormalization group theoretical ideas with the integral equation approach to fluid structure and thermodynamics, the hierarchical reference theory is known to be successful even in the vicinity of the critical point and for subcritical temperatures. We present here a software package independent of earlier programs for the application of this theory to simple fluids composed of particles interacting via spherically symmetrical pair potentials, restricting ourselves to hard-sphere reference systems. Using the hard-core Yukawa potential with z=1.8/sigma for illustration, we discuss our implementation and the results it yields, paying special attention to the core condition and emphasizing the decoupling assumption's role.


Chronic allograft dysfunction: diagnosis and management. Is it always progressive?
1. There are many causes of graft dysfunction post-liver transplant, but recurrent disease remains the most common cause. 2. Viral hepatitis, nonalcoholic and alcoholic steatohepatitis, and autoimmune diseases are the most common causes of recurrent disease. 3. Graft hepatitis occurs frequently and in many cases will not progress. 4. Cirrhosis in the absence of any identifiable cause develops in a minority. 5. Treatment is of the underlying cause but some, such as recurrent and de novo autoimmune hepatitis and recurrent primary sclerosing cholangitis may not respond well, and regraft may be required.


Increased Severity of Neonatal Abstinence Syndrome Associated With Concomitant Antenatal Opioid and Benzodiazepine Exposure.
Polysubstance use is common among opioid-using women, yet its association with pharmacotherapy for neonatal abstinence syndrome (NAS) remains unclear. We hypothesized that benzodiazepine exposure would increase risk of an infant developing pharmacologically treated NAS. We conducted a retrospective cohort study of maternal-infant dyads enrolled in Tennessee Medicaid, using individual-level data linkage of vital records and administrative (ie, outpatient, inpatient, and prescription) data from 2009 to 2011. These data underwent chart review from 2013 to 2016 to obtain clinically relevant exposure data (eg, toxicology testing). The association of antenatal exposures with pharmacologically treated NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant factors and clustered by hospital. Among 112 029 maternal-infant dyads, we confirmed 822 cases of NAS, of which 598 (72.7%) were cases of pharmacologically treated NAS. Infants who developed pharmacologically treated NAS were more likely to have been exposed to antenatal benzodiazepines compared with infants with confirmed NAS not treated pharmacologically (40.9% vs 30.8%; P = .008). In adjusted analyses, benzodiazepine exposure was associated with greater risk of developing pharmacologically treated NAS (odds ratio: 1.51; 95% confidence interval: 1.04-2.21). Alternatively, exposure to tobacco, marijuana, cocaine, gabapentin, and selective serotonin reuptake inhibitors were not associated with increased risk of developing pharmacologically treated NAS. Among a population of infants with intrauterine polysubstance exposure, benzodiazepine exposure was an independent predictor of an infant developing pharmacologically treated NAS. Obtaining history of antenatal benzodiazepine exposure among opioid-exposed infants may allow for risk stratification and development of personalized care plans.


[Subacute sclerosing panencephalitis. Report of 31 cases (author's transl)].
We present 31 cases of subacute sclerosing panecephalitis from the epidemiologic, clinical, electroencephalographic, laboratory and anatomopatological point of view. Psychical disorders (51,59%) and generalized convulsive fits (19,45%) stand out as a first cause of consultation. A high visual hallucinatory incidence (35,48%) was observed. Repeated complexes were of great value for the early diagnosis as well as the high titers of measles-virus antibody in the serum and cerebrospinal fluid for the diagnosis corroboration.


Intravitreal bevacizumab combined with photodynamic therapy for the treatment of occult choroidal neovascularization associated with serous pigment epithelium detachment in age-related macular degeneration.
To evaluate the efficacy of intravitreal injection of bevacizumab combined with photodynamic therapy (PDT) for the treatment of occult choroidal neovascularization (CNV) associated with serous pigment epithelium detachment (s-PED) due to age-related macular degeneration (AMD). In this retrospective study, six patients (six eyes) with subfoveal occult CNV associated with s-PED due to AMD were treated with intravitreal bevacizumab combined with PDT. All patients were treated at baseline with PDT followed by intravitreal bevacizumab 1.25 mg 1 hour later. Afterwards, according to the findings of optical coherence tomography and fluorescein angiography, repeat bevacizumab injections were given, if necessary, monthly for three doses followed by further doses every 3 months. PDT was repeated every 3 months according to the same criteria. Follow-up time was 9 months. All patients completed their treatment during the first 3 months from baseline. Best-corrected visual acuity (BCVA) improved or remained stable related to the baseline values in all patients at the end of the follow-up time. Mean BCVA improved from 20/67 to 20/42. S-PED and subretinal fluid decreased or disappeared. The mean central 1-mm retinal thickness was reduced from baseline value for the 9-month follow-up period by 128 microm. Intravitreal bevacizumab combined with PDT seems to be a promising treatment with good functional and anatomical results for occult CNV associated with s-PED due to AMD.


High-level visual object representations are constrained by position.
It is widely assumed that high-level visual object representations are position-independent (or invariant). While there is sensitivity to position in high-level object-selective cortex, position and object identity are thought to be encoded independently in the population response such that position information is available across objects and object information is available across positions. Contrary to this view, we show, with both behavior and neuroimaging, that visual object representations are position-dependent (tied to limited portions of the visual field). Behaviorally, we show that the effect of priming an object was greatly reduced with any change in position (within- or between-hemifields), indicating nonoverlapping representations of the same object across different positions. Furthermore, using neuroimaging, we show that object-selective cortex is not only highly sensitive to object position but also the ability to differentiate objects based on its response is greatly reduced across different positions, consistent with the observed behavior and the receptive field properties observed in macaque object-selective neurons. Thus, even at the population level, the object information available in response of object-selective cortex is constrained by position. We conclude that even high-level visual object representations are position-dependent.


Fatality Due to Button Battery Lodgment in the Upper Digestive Tract of a Neonate: An Unusual Presentation.
Foreign body ingestion is not uncommonly seen in children, with most such ingestions occurring between 6 months to 3 years of age. Button battery ingestion constitutes approximately 2% of all ingested foreign bodies in children. Button batteries are disc-shaped power units used for various electronic appliance, gadgets, and toys and often contain various toxic chemical substances such as heavy metal salts and alkali. Button batteries may become lodged in the upper digestive tract, producing severe damage to the adjacent tissues by various mechanisms. A death of a neonate due to a button battery lodging in the upper digestive tract leading to tracheoesophageal fistula and esophageal perforation is presented. To the best of authors' knowledge, the present case is the youngest death reported due to button battery lodgment, and the challenges of investigation in such a case are discussed.


Commercial Sample Identification and Characterization Challenges in Medicinal Mushroom Research.
A recent study published in this journal demonstrates the pitfalls faced by researchers who utilize commercial products as their test samples without proper characterization. Labeling of commercial mushroom products is often incorrect, which can lead to erroneous interpretations and conclusions. Nine of the 10 samples of commercially branded products used in the study and identified as ground mushrooms were actually grain spawn: mycelium propagated on grain.


Phytoestrogenic compounds in alfalfa sprout (Medicago sativa) beyond coumestrol.
Coumestrol has long been known as the phytoestrogenic compound in alfalfa. However, it has been demonstrated that the ethyl acetate extract of alfalfa sprout (AEA) attenuated the disease severity and increased survival and life span of autoimmune-prone MRL-lpr/lpr mice. Coumestrol, on the contrary, decreased the survival. This study thus aimed to isolate and identify phytoestrogenic compounds other than coumestrol in AEA. AEA was fractionated and separated by successive silica gel chromatography and preparative HPLC. The activity of collected fractions was tracked by a transactivation assay for ERα and ERβ, respectively. In addition to coumestrol, liquiritigenin, isoliquiritigenin, loliolide, and (4S,6S)- and (4R,6S)-4-hydroxy-6-pentadecyltetrahydropyr-2-one were isolated and chemically identified. Except for loliolide, these compounds showed higher transactivation via ERβ than via ERα. The maximal activation via ERα of coumestrol reached 80% that of 1 nM 17β-estradiol (E(2)), whereas the activations of the remaining five compounds as well as AEA ranged from 8 to 49%. In addition, isoliquiritigenin, loliolide, and (4S,6S)- and (4R,6S)-4-hydroxy-6-pentadecyltetrahydropyr-2-one, but not coumestrol, preferentially inhibited 1 nM E(2) induced ERα activation, compared to that ERβ activation. The selectivity of these phytoestrogens might account for the difference between the effects of AEA and coumestrol in autoimmune-prone MRL-lpr/lpr mice observed previously.


Cancer incidence in the Tobruk area, eastern Libya: first results from Tobruk Medical Centre.
Cancer is a major cause of morbidity and mortality worldwide, and it is an increasing problem in developing countries. Estimation of the incidence of cancer is important, especially in regions with limited epidemiological data on cancer. Therefore, the aim of this study was to provide an updated report on the incidence of cancers in the Tobruk region in eastern Libya. Data on cancer patients from the records of the Department of Histopathology of Tobruk Medical Centre from January 2013 to June 2020 were included. In total, 402 cases were recorded. Men patients accounted for 30.3% (n=122) of cases, and women patients represented 69.6% (n=280). The overall mean age at the time of the first diagnosis was 49.0±17.1 years. The most common malignancies were breast and uterine cancer in women (18.4%, n=74; 15.9%, n=64, respectively), colorectal cancer (11.6%, n=47; 26 in women and 21 in men), bladder cancer (8.2%, n=33; 8 in women and 25 in men), and thyroid cancer (8.0%, n=32; 23 in women and 9 in men). Breast and uterine cancers were the most common cancers in women, and bladder and colorectal cancer were the most common cancers in men, followed by colorectal cancer in both genders. These data will help health authorities launch preventive plans for cancer in the region. Further studies to identify aetiological factors and cancer-related risk factors need to be conducted in the region.


Synthesis of new chiral monodentate phosphite ligands and their use in catalytic asymmetric hydrogenation.
[reaction: see text] New monodentate phosphite ligands have been developed from axially chiral biphenols, which show excellent enantioselectivity in the Rh(I)-catalyzed hydrogenation of dimethyl itaconate. The new chiral ligand system is suitable to create libraries and possesses fine-tuning capability.


Distribution of human granulocyte colony-stimulating factor receptors on hematopoietic and nonhematopoietic tumor cell lines.
Introduction of two tyrosine residues into human granulocyte colony-stimulating factor (G-CSF) allowed us to obtain radioiodinated material efficiently. By using this material, specific receptors for human G-CSF were analyzed. It was found that human G-CSF receptors were expressed on several myelocytic and monocytic leukemia cell lines. Furthermore, they were also expressed on two choriocarcinoma cell lines. However, the human G-CSF receptors were not detected on other nonhematopoietic tumor cell lines examined, indicating that expression of G-CSF receptors is strictly limited as compared with receptors for granulocyte/macrophage colony-stimulating factor (GM-CSF), which are widely distributed on nonhematopoietic tumors.


Absence of minimal residual disease detectable by FACS, Southern blot or PCR in patients with chronic lymphocytic leukaemia treated with fludarabine.
We report the results of assessment of minimal residual disease in four patients with chronic lymphocytic leukaemia, who achieved clinical and haematological complete response following treatment with fludarabine. Patients were assessed both before and after treatment by immunophenotyping, DNA electrophoresis, Southern blotting and PCR amplification to detect immunoglobulin gene rearrangements. Immediately after treatment, no patient had disease detectable by any method and there was evidence of recovery of normal B-cells. No patient has yet shown evidence of clinical or haematological relapse (follow-up 59-142 weeks). Two patients remain in immunophenotypic and molecular remission at 141 and 59 weeks. These methods have allowed more sensitive definition of elimination of residual disease, with PCR demonstrating the capacity to detect disease recurrence before any other evidence is available.


Duplication and concerted evolution of MiSp-encoding genes underlie the material properties of minor ampullate silks of cobweb weaving spiders.
Orb-web weaving spiders and their relatives use multiple types of task-specific silks. The majority of spider silk studies have focused on the ultra-tough dragline silk synthesized in major ampullate glands, but other silk types have impressive material properties. For instance, minor ampullate silks of orb-web weaving spiders are as tough as draglines, due to their higher extensibility despite lower strength. Differences in material properties between silk types result from differences in their component proteins, particularly members of the spidroin (spider fibroin) gene family. However, the extent to which variation in material properties within a single silk type can be explained by variation in spidroin sequences is unknown. Here, we compare the minor ampullate spidroins (MiSp) of orb-weavers and cobweb weavers. Orb-web weavers use minor ampullate silk to form the auxiliary spiral of the orb-web while cobweb weavers use it to wrap prey, suggesting that selection pressures on minor ampullate spidroins (MiSp) may differ between the two groups. We report complete or nearly complete MiSp sequences from five cobweb weaving spider species and measure material properties of minor ampullate silks in a subset of these species. We also compare MiSp sequences and silk properties of our cobweb weavers to published data for orb-web weavers. We demonstrate that all our cobweb weavers possess multiple MiSp loci and that one locus is more highly expressed in at least two species. We also find that the proportion of β-spiral-forming amino acid motifs in MiSp positively correlates with minor ampullate silk extensibility across orb-web and cobweb weavers. MiSp sequences vary dramatically within and among spider species, and have likely been subject to multiple rounds of gene duplication and concerted evolution, which have contributed to the diverse material properties of minor ampullate silks. Our sequences also provide templates for recombinant silk proteins with tailored properties.


T1, diffusion tensor, and quantitative magnetization transfer imaging of the hippocampus in an Alzheimer's disease mouse model.
Alzheimer's disease (AD) pathology causes microstructural changes in the brain. These changes, if quantified with magnetic resonance imaging (MRI), could be studied for use as an early biomarker for AD. The aim of our study was to determine if T1 relaxation, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) metrics could reveal changes within the hippocampus and surrounding white matter structures in ex vivo transgenic mouse brains overexpressing human amyloid precursor protein with the Swedish mutation. Delineation of hippocampal cell layers using DTI color maps allows more detailed analysis of T1-weighted imaging, DTI, and qMTI metrics, compared with segmentation of gross anatomy based on relaxation images, and with analysis of DTI or qMTI metrics alone. These alterations are observed in the absence of robust intracellular Aβ accumulation or plaque deposition as revealed by histology. This work demonstrates that multiparametric quantitative MRI methods are useful for characterizing changes within the hippocampal substructures and surrounding white matter tracts of mouse models of AD.


How do we manage blood donors and recipients after a positive Zika screening result?
Zika virus (ZIKV) is a mosquito-borne flavivirus that is the focus of an ongoing pandemic. ZIKV is notable for its severe neurologic sequelae in babies born to infected mothers. High rates of subclinical infection, as evidenced by the finding of ZIKV RNA in asymptomatic donors, raise concerns of risk to the blood supply. To date, a total of four suspected cases of transfusion-transmitted ZIKV have been reported (all in Brazil), none of which were associated with clinical infection in the transfusion recipients. In 2016, the US Food and Drug Administration issued a guidance mandating national blood donor screening for ZIKV in the United States. Five days after implementation of donor screening at our facility, we encountered a ZIKV-positive donor. We provide a practical approach to donor, recipient, and blood product management in the setting of a positive donor ZIKV result. Such has been informed by the challenges we faced in the workup of a ZIKV-reactive donation and recipient lookback.


Genomic evidence for convergent evolution of a key trait underlying divergence in island birds.
Reproductive isolation can be initiated by changes in one or a few key traits that prevent random mating among individuals in a population. During the early stages of speciation, when isolation is often incomplete, there will be a heterogeneous pattern of differentiation across regions of the genome between diverging populations, with loci controlling these key traits appearing the most distinct as a result of strong diversifying selection. In this study, we used Illumina-sequenced ddRAD tags to identify genomewide patterns of differentiation in three recently diverged island populations of the Monarcha castaneiventris flycatcher of the Solomon Islands. Populations of this species have diverged in plumage colour, and these differences in plumage colour, in turn, are used in conspecific recognition and likely important in reproductive isolation. Previous candidate gene sequencing identified point mutations in MC1R and ASIP, both known pigmentation genes, to be associated with the difference in plumage colour between islands. Here, we show that background levels of genomic differentiation based on over 70,000 SNPs are extremely low between populations of distinct plumage colour, with no loci reaching the level of differentiation found in either candidate gene. Further, we found that a phylogenetic analysis based on these SNPs produced a taxonomy wherein the two melanic populations appear to have evolved convergently, rather than from a single common ancestor, in contrast to their original classification as a single subspecies. Finally, we found evidence that the pattern of low genomic differentiation is the result of both incomplete lineage sorting and gene flow between populations.


Motivation, self-efficacy, perception, curiosity, and barriers toward medical research among undergraduates in China.
Medical research is important to scientific progress and medical education. Institutions worldwide have sought to increase student involvement in research such as clinician-scientists training programs, while little is known about how medical undergraduates perceive research. A cross-sectional study was conducted in Chongqing Medical University, Chongqing, China, with first-fourth year undergraduates. An online, anonymous, and self-rating 5-point Likert questionnaire was conducted to investigate medical undergraduates' demographic characteristics and assess motivation, self-efficacy, perception, curiosity, and barriers regarding medical research. Content validity was checked with experts and face validity was checked for clarity and understanding of the questionnaire. The Cronbach's alpha coefficient of the questions ranged from 0.813 to 0.879. A total of 3273 medical undergraduates were surveyed, and 86.62% (2835) participants (male 962, female 1873) were identified as effective. Males scored higher than females on self-efficacy (p < 0.001), perception (p = 0.017), and curiosity (p < 0.001), and lower on barriers (p < 0.001). The second year students are at the peak of their perception (p = 0.006) and lowest barrier scores (p = 0.003). Students with scientific research experience scored higher in motivation (p = 0.002), self-efficacy (p < 0.001), perception (p < 0.001), and curiosity (p < 0.001). Lack of proper mentoring opportunity (86.2%) and knowledge (84.5%) were the main barriers in conducting research. Even though they have a positive perspective, only a few undergraduates enrolled in research. Medical universities should encourage faculties to supervise and guide undergraduates' projects, and provide feasible solutions for students to learn scientific knowledge and skills. It is vital to build a research-oriented environment and academic atmosphere.


Quantitative analysis of NOR expression in a B chromosome of the grasshopper Eyprepocnemis plorans.
The B24 chromosome in the Torrox population of the grasshopper Eyprepocnemis plorans is recurrently attached to a nucleolus in diplotene cells, indicating the activity of its distally located ribosomal DNA (rDNA). The frequency of males expressing the B chromosome nucleolus organizer region (B-NOR) almost doubled in 4 years. The likelihood of expressing the B-NOR increased with the B number and, in males expressing it, about 20% of their cells showed a nucleolus attached to the B. When active, the B-NOR contributed more than 25% of total cell nucleolar area (NA). Within males expressing the B-NOR, total cell NA did not differ between cells showing the active or inactive B-NOR, suggesting that total cell NA is tightly regulated in this species. However, this parameter tended to increase in this population from 1999 to 2004, in parallel to the neutralization process which is taking place in this population. Finally, an analysis of A chromosome NOR interdependence for activity revealed a positive correlation among autosomes but a negative correlation between autosomes and the X chromosome, the manifestation of which depends on B-NOR activity. These results are discussed in the context of the nucleolus as a sensor of the stress caused by parasitic B chromosomes.


Adaptively controlled fast production of defect-free beryllium ion crystals using pulsed laser ablation.
Trapped atomic ions find wide applications ranging from precision measurement to quantum information science and quantum computing. Beryllium ions are widely used due to the light mass and convenient atomic structure of beryllium; however, conventional ion loading from thermal ovens exerts undesirable gas loads for a prolonged duration. Here, we demonstrate a method to rapidly produce pure linear chains of beryllium ions with pulsed laser ablation, serving as a starting point for large-scale quantum information processing. Our method is fast compared to thermal ovens, reduces the gas load to only 10-12 Torr (10-10 Pa) level, yields a short recovery time of a few seconds, and also eliminates the need for a deep ultraviolet laser for photoionization. We also study the loading dynamics, which show non-Poissonian statistics in the presence of sympathetic cooling. In addition, we apply feedback control to obtain defect-free ion chains with desirable lengths.