Trajectory Analysis of the Campus Serial Rapist Assumption.
Rape on college campuses has been addressed recently by a presidential proclamation, federal legislation, advocacy groups, and popular media. Many initiatives assume that most college men who perpetrate rape are serial rapists. The scientific foundation for this perspective is surprisingly limited. To determine whether a group of serial rapists exists by identifying cohesive groups of young men, indicated by their trajectories of rape likelihood across high school and college. Latent class growth analysis of the 2 largest longitudinal data sets of adolescent sexual violence on college campuses using 2 distinct groups of male college students. The first group was used for derivation modeling (n = 847; data collected from August 1990 through April 1995) and the second for validation modeling (n = 795; data collected from March 2008 through May 2011). Final data analyses were conducted from February 16, 2015, through February 20, 2015. Rape perpetration assessed using the Sexual Experiences Survey. Across samples, 178 of 1642 participants (10.8%) reported having perpetrated at least 1 rape from 14 years of age through the end of college. A 3-trajectory model best fit both the derivation and validation data sets. Trajectories reflected low or time-limited (92.6% of participants), decreasing (5.3%), and increasing (2.1%) rape patterns. No consistently high trajectory was found. Most men who perpetrated a rape before college were classified in the decreasing trajectory. During college, the increasing trajectory included 14 men (15.2%) who reported having perpetrated a rape, the decreasing trajectory included 30 men (32.6%), and the low or time-limited included 48 men (52.2%). No participant in the low or time-limited trajectory reported perpetrating a rape during more than 1 period. Most men (67 [72.8%]) who committed college rape only perpetrated rape during 1 academic year. Although a small group of men perpetrated rape across multiple college years, they constituted a significant minority of those who committed college rape and did not compose the group at highest risk of perpetrating rape when entering college. Exclusive emphasis on serial predation to guide risk identification, judicial response, and rape-prevention programs is misguided. To deter college rape, prevention should be initiated before, and continue during, college. Child and adolescent health care professionals are well positioned to intervene during the early teenage years by informing parents about the early onset of nonconsensual sexual behavior.


Case of the month
Each month, we will present a challenging Case of the Month for Green Journal readers, who must use their clinical acumen to arrive at the correct answer. We will also post the case each month on the Journal's web site (http://www.ajmselect.com). Several possible answers may be consistent with the case presentation; use your best judgment. Please send your answer (one per respondent) to The Green Journal at firstname.lastname@example.com or via FAX to (415) 447-2799. Indicate the case to which you are responding and include your complete address. The correct answer will appear in the next issue of the Journal. The first five persons who submit correct answers will receive a free one-year subscription to the Journal. Because of the volume of answers we receive, neither correct nor incorrect answers can be individually acknowledged. Colleagues of Drs. Ismail H and Bhat at Kasturba Medical College in Mangalore are not eligible for this month's case. If you would like to contribute a case, please submit a brief synopsis (<250 words) to the editorial office.


Sustained delivery of insulin-like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart.
Activation of endogenous cardiac stem/progenitor cells (eCSCs) can improve cardiac repair after acute myocardial infarction. We studied whether the in situ activation of eCSCs by insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) could be increased using a newly developed hydrogel in chronic myocardial infarction (MI). One-month post-MI pigs underwent NOGA-guided intramyocardial injections of IGF-1/HGF (GF: both 0.5 μg/mL, n = 5) or IGF-1/HGF incorporated in UPy hydrogel (UPy-GF; both 0.5 μg/mL, n = 5). UPy hydrogel without added growth factors was administered to four control (CTRL) pigs. Left ventricular ejection fraction was increased in the UPy-GF and GF animals compared to CTRLs. UPy-GF delivery reduced pathological hypertrophy, led to the formation of new, small cardiomyocytes, and increased capillarization. The eCSC population was increased almost fourfold in the border zone of the UPy-GF-treated hearts compared to CTRL hearts. These results show that IGF-1/HGF therapy led to an improved cardiac function in chronic MI and that effect size could be further increased by using UPy hydrogel.


Nicaraven, a Potential Radioprotective Agent, has Very Limited Effects on the Survival of Cancer Cells and the Growth of Established Tumors.
Radiotherapy is one of the major treatment modalities for the management of various cancers, however, it is limited by the severe side effects and complications experienced by some patients. Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been shown to protect normal tissues from radiation-induced injury. We investigated the role of nicaraven in cancer cells and tumor growth. While nicaraven did not significantly change the colony-forming abilities and DNA damage levels in several cancer cell lines after irradiation, it significantly protected mouse bone marrow-derived hematopoietic stem cells from radiation injury. In established mouse tumor models in which radiation exposure significantly inhibited the growth of tumors, nicaraven did not significantly mitigate the radiation-induced inhibition of tumor growth. The results of this study showed that while nicaraven attenuated the toxicity of radiotherapy in hematopoietic stem cells, it had very limited effects on the survival of cancer cells and tumor growth. Nicaraven may be an ideal drug for mitigating the side effects of radiotherapy in patients with cancer.


The rapid effects of estrogen: a mini-review.
Estrogen is regulated through two intracellular receptors, estrogen receptor alpha and estrogen receptor beta, through a classic nuclear-initiated response. Recently, estrogen has also been shown to act more rapidly and it is proposed that these fast effects may be the consequence of membrane localized estrogen receptors that act through the second messengers. Although the identification of these receptors remains to be elucidated, the possible role that they play in female-specific mood disorders is of particular interest, especially in times of major hormonal fluctuation. The purpose of this mini-review is to outline the recent literature regarding the rapid effects of estrogen, to explore the intracellular signaling pathways that may be involved in this regulation as well as the connection between estrogen and serotonin neurotransmission and finally, to look into the antidepressant role that estrogen may have, with particular emphasis on female-specific mood disorders.


Giammusso corporoplasty for the treatment of isolated congenital ventral penile curvature: Results and long-term follow-up.
The aim was to retrospectively evaluate our experience in a large series of patients affected by isolated congenital ventral penile curvature, surgically treated using a previously described modified incisional corporoplasty. Two hundred and six patients with isolated congenital ventral penile curvature underwent a modified incisional corporoplasty. Mean age at surgery was 20.7 ± 5.5 years, and degree of ventral curvature was 60 ± 23°. After the point of maximum convexity identification, Buck's fascia was vertically opened along the deep dorsal vein, which was partially ligated, resected and removed. Tunica albuginea was then longitudinally incised and transversally closed. Post-operative follow-up examination was performed at 2 weeks, 6, 12 and 24 months and then annually. Surgical time was 79 ± 12 min. At follow-up, 189 out of 198 patients (95%) were completely satisfied, four patients (2%) complained a recurrence of penile curvature, and 6 (3%) complained about shortening of the penis. None of the patients had any interference with sexual activity. One patient (0.5%) showed erectile dysfunction 5 years after surgery, but there was no organic dysfunction during examination. The proposed technique allows correction of ventral congenital penile curvature without dorsal neurovascular bundle manipulation, resulting in minimum trauma of the erectile tissue, without injury to nerve fibres.


Prolonged outbreak of giardiasis with two modes of transmission.
Large outbreaks of giardiasis caused by person-to-person transmission, or a combination of transmission routes, have not previously been reported. A large, prolonged giardiasis outbreak affected families belonging to a country club in a suburb of Boston, Massachusetts, during June-December 2003. We conducted a retrospective cohort study to determine the source of this outbreak. Giardiasis-compatible illness was experienced by 149 (25%) respondents to a questionnaire, and was laboratory confirmed in 97 (65%) of these cases. Of the 30 primary cases, exposure to the children's pool at the country club was significantly associated with illness (risk ratio 3.3, 95% confidence interval 1.7-6.5). In addition, 105 secondary cases probably resulted from person-to-person spread; 14 cases did not report an onset date. This outbreak illustrates the potential for Giardia to spread through multiple modes of transmission, with a common-source outbreak caused by exposure to a contaminated water source resulting in subsequent prolonged propagation through person-to-person transmission in the community. This capacity for a common-source outbreak to continue propagation through secondary person-to-person spread has been reported with Shigella and Cryptosporidium and may also be a feature of other enteric pathogens having low infectious doses.


Evaluation of qPCR reference genes in two genotypes of Populus for use in photoperiod and low-temperature studies.
Quantitative PCR (qPCR) is a widely used technique for gene expression analysis. A common normalization method for accurate qPCR data analysis involves stable reference genes to determine relative gene expression. Despite extensive research in the forest tree species Populus, there is not a resource for reference genes that meet the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) standards for qPCR techniques and analysis. Since Populus is a woody perennial species, studies of seasonal changes in gene expression are important towards advancing knowledge of this important developmental and physiological trait. The objective of this study was to evaluate reference gene expression stability in various tissues and growth conditions in two important Populus genotypes (P. trichocarpa "Nisqually 1" and P. tremula x P. alba 717 1-B4) following MIQE guidelines. We evaluated gene expression stability in shoot tips, young leaves, mature leaves and bark tissues from P. trichocarpa and P. tremula. x P. alba grown under long-day (LD), short-day (SD) or SD plus low-temperatures conditions. Gene expression data were analyzed for stable reference genes among 18S rRNA, ACT2, CDC2, CYC063, TIP4-like, UBQ7, PT1 and ANT using two software packages, geNorm(PLUS) and BestKeeper. GeNorm(PLUS) ranked TIP4-like and PT1 among the most stable genes in most genotype/tissue combinations while BestKeeper ranked CDC2 and ACT2 among the most stable genes. This is the first comprehensive evaluation of reference genes in two important Populus genotypes and the only study in Populus that meets MIQE standards. Both analysis programs identified stable reference genes in both genotypes and all tissues grown under different photoperiods. This set of reference genes was found to be suitable for either genotype considered here and may potentially be suitable for other Populus species and genotypes. These results provide a valuable resource for the Populus research community.


The crystal structures of T. thermophilus lysyl-tRNA synthetase complexed with E. coli tRNA(Lys) and a T. thermophilus tRNA(Lys) transcript: anticodon recognition and conformational changes upon binding of a lysyl-adenylate analogue.
The crystal structures of Thermus thermophilus lysyl-tRNA synthetase, a class IIb aminoacyl-tRNA synthetase, complexed with Escherchia coli tRNA(Lys)(mnm5 s2UUU) at 2.75 A resolution and with a T. thermophilus tRNA(Lys)(CUU) transcript at 2.9 A resolution are described. In both complexes only the tRNA anticodon stem-loop is well ordered. The mode of binding of the anticodon stem-loop to the N-terminal beta-barrel domain is similar to that previously found for the homologous class IIb aspartyl-tRNA synthetase-tRNA(Asp) complex except in the region of the wobble base 34 where either mnm5 s2U or C can be accommodated. The specific recognition of the other anticodon bases, U-35 and U-36, which are both major identity elements in the lysine system, is also described. Additional crystallographic data on a ternary complex with a lysyl-adenylate analogue show that binding of the intermediate induces significant conformational changes in the vicinity of the active site of the enzyme.


Lay-delivered talk therapies for adults affected by humanitarian crises in low- and middle-income countries.
Published by the World Health Organization (WHO) and United Nations High Commissioner for Refugees (UNHCR) in 2015, the mental health Gap Action Programme Humanitarian Intervention Guide (mhGAP-HIG) recommends brief versions of structured psychological interventions for people experiencing symptoms of common mental disorders (CMDs). mhGAP-HIG acknowledges a growing body of evidence suggesting these interventions can be delivered by lay workers to people affected by humanitarian crises in low- and middle-income countries (LMICs). However, there has not yet been a systematic review and synthesis of this evidence. This paper reports the results of a systematic review of qualitative, quantitative, and mixed-methods studies assessing the implementation and/or effectiveness of talk therapies for CMDs when provided by lay workers in LMICs to adults who have survived or are currently living in humanitarian situations. Seven electronic databases were searched: MEDLINE, Embase, PsycINFO, PsycEXTRA, Global Health, Cochrane Library, and ClinicalTrials.gov . We also hand-searched the contents pages of three academic journals, reference lists of 30 systematic reviews, and online resource directories of two mental health networks. A preliminary list of included studies was circulated to topical experts for review, and all included studies were backward and forward searched. All titles, abstracts, and full-texts were independently double-screened. Quality appraisal and data extraction were carried out by a single reviewer and checked by a second reviewer, using standardised tools. Any disagreements were discussed and referred to a third reviewer as needed. We identified 23 unique studies and carried out a narrative synthesis of patient and implementation outcome data. Every evaluation of the effectiveness of lay-delivered talk therapies for adults affected by humanitarian crises in LMICs showed some treatment effect for at least one CMD, and often multiple CMDs. Implementation research generally found these interventions to be acceptable, appropriate and feasible to implement, with good fidelity to manualised therapies. Although results are promising, particularly for individually-delivered talk therapies based on cognitive behavioural therapy techniques, there is a high degree of heterogeneity in this literature. We make several recommendations on how to improve the quality and generalisability of research on this topic, to facilitate further evidence synthesis. PROSPERO registration number: CRD42017058287 .


The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke.
Evidence indicates that angiotensin II type 2 receptors (AT2R) exert cerebroprotective actions during stroke. A selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exert beneficial effects in models of cardiac and renal disease, as well as hemorrhagic stroke. Here, we hypothesize that C21 may exert beneficial effects against cerebral damage and neurological deficits produced by ischemic stroke. We determined the effects of central and peripheral administration of C21 on the cerebral damage and neurological deficits in rats elicited by endothelin-1 induced middle cerebral artery occlusion (MCAO), a model of cerebral ischemia. Rats infused centrally (intracerebroventricular) with C21 before endothelin-1 induced MCAO exhibited significant reductions in cerebral infarct size and the neurological deficits produced by cerebral ischemia. Similar cerebroprotection was obtained in rats injected systemically (intraperitoneal) with C21 either before or after endothelin-1 induced MCAO. The protective effects of C21 were reversed by central administration of an AT2R inhibitor, PD123319. While C21 did not alter cerebral blood flow at the doses used here, peripheral post-stroke administration of this agent significantly attenuated the MCAO-induced increases in inducible nitric oxide synthase, chemokine (C-C) motif ligand 2 and C-C chemokine receptor type 2 mRNAs in the cerebral cortex, indicating that the cerebroprotective action is associated with an anti-inflammatory effect. These results strengthen the view that AT2R agonists may have potential therapeutic value in ischemic stroke, and provide the first evidence of cerebroprotection induced by systemic post stroke administration of a selective AT2R agonist.


Development of a monoclonal antibody-based immunoassay for the detection and quantification of Anguillospora longissima colonizing leaf material.
Monoclonal antibodies (MAbs) to the aquatic hyphomycete Anguillospora longissima were raised in mice by using a coimmunization program. A cell line was raised that produced a MAb of the immunoglobulin M class that was specific for A. longissima both in an enzyme-linked immunosorbent assay (ELISA) and by immunofluorescence but that did not recognize other members of the aquatic hyphomycetes. This MAb (AL-HH8c) was used to develop a quantitative ELISA in vitro. The antigen recognized by AL-HH8c is produced throughout the mycelium, irrespective of mycelial age and culture conditions. By using this MAb, mycelium of A. longissima colonizing leaf material can be detected by ELISA, immunofluorescence, and immunoenzymatic staining methods.


On the search for an appropriate metric for reaction time to suprathreshold increments and decrements.
Weber contrast, DeltaL/L, is a widely used contrast metric for aperiodic stimuli. Zele, Cao & Pokorny [Zele, A. J., Cao, D., & Pokorny, J. (2007). Threshold units: A correct metric for reaction time? Vision Research, 47, 608-611] found that neither Weber contrast nor its transform to detection-threshold units equates human reaction times in response to luminance increments and decrements under selective rod stimulation. Here we show that their rod reaction times are equated when plotted against the spatial luminance ratio between the stimulus and its background (L(max)/L(min), the larger and smaller of background and stimulus luminances). Similarly, reaction times to parafoveal S-cone selective increments and decrements from our previous studies [Murzac, A. (2004). A comparative study of the temporal characteristics of processing of S-cone incremental and decremental signals. PhD thesis, New Bulgarian University, Sofia, Murzac, A., & Vassilev, A. (2004). Reaction time to S-cone increments and decrements. In: 7th European conference on visual perception, Budapest, August 22-26. Perception, 33, 180 (Abstract).], are better described by the spatial luminance ratio than by Weber contrast. We assume that the type of stimulus detection by temporal (successive) luminance discrimination, by spatial (simultaneous) luminance discrimination or by both [Sperling, G., & Sondhi, M. M. (1968). Model for visual luminance discrimination and flicker detection. Journal of the Optical Society of America, 58, 1133-1145.] determines the appropriateness of one or other contrast metric for reaction time.


Allometric scaling and proportion regulation in the freshwater planarian Schmidtea mediterranea.
The regulation of scale and proportion in living organisms is an intriguing and enduring problem of biology. Regulatory mechanisms for controlling body size and proportion are clearly illustrated by the regeneration of missing body parts after amputation, in which the newly regenerated tissues ultimately attain a size that is anatomically congruent with the size of the rest of the organism. Understanding the molecular processes underpinning scaling would have deep consequences for our comprehension of tissue regeneration, developmental ontogeny, growth, and evolution. Although many theories have been put forward to explain this process, it is interesting that no satisfactory mechanistic explanation is currently available to explain scalar relationships. We chose to investigate the freshwater planarian, a commonly used model system for the study of metazoan regeneration, to delineate a strategy for the molecular dissection of scale and proportion mechanisms in metazoans. Here, we report on the cloning and discrete expression pattern of a novel planarian gene, which shares homology with the DEG/ENaC super-family of sodium channels. We have named H.112.3c cintillo ("head ribbon" in Spanish) and present a strategy for using the expression of this gene to monitor scale and proportion regulation during regeneration, growth and degrowth in the freshwater planarian Schmidtea mediterranea.


Ecological feedbacks. Termite mounds can increase the robustness of dryland ecosystems to climatic change.
Self-organized spatial vegetation patterning is widespread and has been described using models of scale-dependent feedback between plants and water on homogeneous substrates. As rainfall decreases, these models yield a characteristic sequence of patterns with increasingly sparse vegetation, followed by sudden collapse to desert. Thus, the final, spot-like pattern may provide early warning for such catastrophic shifts. In many arid ecosystems, however, termite nests impart substrate heterogeneity by altering soil properties, thereby enhancing plant growth. We show that termite-induced heterogeneity interacts with scale-dependent feedbacks to produce vegetation patterns at different spatial grains. Although the coarse-grained patterning resembles that created by scale-dependent feedback alone, it does not indicate imminent desertification. Rather, mound-field landscapes are more robust to aridity, suggesting that termites may help stabilize ecosystems under global change.


Correlates of mucosal immunity and upper respiratory tract infections in girls.
In this study we examined whether salivary hormones, physical activity and adiposity were correlated with secretory immunoglobulin A (sIgA) and frequency of upper respiratory tract infections (URTI) in 43 early-pubertal and 59 late-pubertal girls. Physical activity was measured using accelerometers and relative body fat was assessed using bioelectrical impendence. Resting saliva samples were obtained between 1500 and 1800 hr and assayed for sIgA, cortisol and testosterone. Participants completed a one-month health log to record URTI frequency. Early-pubertal girls were more physically active, had less adiposity, but lower concentrations of sIgA than late-pubertal adolescents (122.7 +/- 91.6 vs 201.9 +/- 102.9 pg/ml, respectively). The frequency of URTI was similar in the two groups. Neither sIgA nor URTI were correlated with salivary hormones, physical activity or adiposity within the early-pubertal girls. In the late-pubertal group, sIgA was negatively associated (r = -0.44; p < 0.05) with cortisol, and positively associated (r = 0.41; p < 0.05) with the testosterone to cortisol ratio. These results suggest that mucosal immunity increases with pubertal maturation, while higher cortisol is associated with lower mucosal immunity in adolescents.


Inogatran, a novel direct low molecular weight thrombin inhibitor, given with, but not after, tissue-plasminogen activator, improves thrombolysis.
Coronary artery often reoccludes after therapy of acute myocardial infarction with recombinant tissue plasminogen activator rt-PA, most likely due to in situ thrombin generation during thrombolysis. Previous studies with high molecular weight thrombin inhibitors, such as hirudin, have shown variable improvement in the frequency of sustained thrombolysis. This study was conducted to examine the modulation of thrombolysis, indices of thrombin generation and activated partial thromboplastin time (APTT) by a novel low molecular weight direct thrombin inhibitor, inogatran. A stable occlusive intracoronary thrombus was created in 19 dogs. Nine dogs were given an intravenous bolus of saline (group A), and 5 dogs were given inogatran (group B) followed by rapid infusion of rt-PA (1 mg/kg over 20 min), whereas saline or inogatran was continuously infused for 2 hr. Five other dogs were given inogatran (bolus and continuous infusion) only after thrombolysis by rt-PA was obtained (group C). Time to reflow was similar in all dogs. None of the reperfused coronary arteries reoccluded in group B dogs (vs. 75% and 40% reocclusion rates in groups A and C, respectively, P < .02). Accordingly, the mean duration of reflow was > 120 min in group B dogs (vs. 39 +/- 7 and 44 +/- 14 min in group A and C dogs, respectively, P < .05). After infusion of inogatran, APTT was increased to 1.6 to 1.9 times the base-line value, and the changes in APTT were similar in group B and C dogs. Thrombin generation and activity, assessed by thrombin-antithrombin complex and fibrinopeptide A levels, increased in all dogs during thrombus formation. The increase in thrombin-antithrombin complex and fibrinopeptide A levels during thrombolysis was not evident in group B dogs. These data show that direct thrombin inhibition with inogatran, when initiated before rt-PA, results in sustained thrombolysis and only a modest increase in APTT. However, inogatran given after thrombolysis only partially prevents reocclusion because large amounts of thrombin generation occur during the early stages of thrombolysis.


The yeast N(alpha)-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides.
The majority of cytosolic proteins in eukaryotes contain a covalently linked acetyl moiety at their very N terminus. The mechanism by which the acetyl moiety is efficiently transferred to a large variety of nascent polypeptides is currently only poorly understood. Yeast N(alpha)-acetyltransferase NatA, consisting of the known subunits Nat1p and the catalytically active Ard1p, recognizes a wide range of sequences and is thought to act cotranslationally. We found that NatA was quantitatively bound to ribosomes via Nat1p and contained a previously unrecognized third subunit, the N(alpha)-acetyltransferase homologue Nat5p. Nat1p not only anchored Ard1p and Nat5p to the ribosome but also was in close proximity to nascent polypeptides, independent of whether they were substrates for N(alpha)-acetylation or not. Besides Nat1p, NAC (nascent polypeptide-associated complex) and the Hsp70 homologue Ssb1/2p interact with a variety of nascent polypeptides on the yeast ribosome. A direct comparison revealed that Nat1p required longer nascent polypeptides for interaction than NAC and Ssb1/2p. Delta nat1 or Delta ard1 deletion strains were temperature sensitive and showed derepression of silent mating type loci while Delta nat5 did not display any obvious phenotype. Temperature sensitivity and derepression of silent mating type loci caused by Delta nat1 or Delta ard1 were partially suppressed by overexpression of SSB1. The combination of data suggests that Nat1p presents the N termini of nascent polypeptides for acetylation and might serve additional roles during protein synthesis.


Characterization of intein homing endonuclease encoded in the DNA polymerase gene of Thermococcus marinus.
The DNA polymerase gene of Thermococcus marinus (Tma) contains an intein inserted at the pol-b site that possesses a 1611-bp ORF encoding a 537-amino acid residue. The LAGLIDADG motif, often found in site-specific DNA endonucleases, was detected within the amino acid sequence of the intein. The intein endonuclease, denoted as PI-Tma, was purified as a naturally spliced product from the expression of the complete DNA polymerase gene in Escherichia coli. PI-Tma cleaved intein-less DNA sequences, leaving four-base-long, 3'-hydroxyl overhangs with 5'-phosphate. Nonpalindromic recognition sequences 19 bp long were also identified using partially complementary oligonucleotide pair sequences inserted into the plasmid pET-22b(+). Cleavage by PI-Tma was optimal when present in 50mM glycine-NaOH (pH 10.5), 150mM KCl and 12mM MgCl(2) at 70 degrees C.


Incidence of Medication Error in Critical Care Unit of a Tertiary Care Hospital: Where Do We Stand?
Medication error in developed countries is of primary concern when there is a question of adversity to a patient's health, but in developing countries like India, it is just a term and its significance is undervalued. The incidence of medication error is essential to estimate the proper medical care provided in the healthcare system. The main objective of the study is to determine the incidences of medication error in critical care unit and to evaluate its risk outcomes. This is a prospective observational study conducted over a period of 6 months in a critical care unit of a tertiary care hospital. Medication chart review method was opted for data collection. The medication errors were mainly classified as prescription, transcription, indenting, dispensing, and administration error. A total of 6,705 charts were reviewed. The NCCMERP risk index was used to evaluate the outcome of errors. Of the total 6,705 charts, 410 medication errors were found, i.e., 6.11%. The most common error is transcription error that constitutes 44.1% of the total errors, followed by prescription error 40%, and administration error 14%. The frequency of indenting and dispensing errors is negligible with 1.5% and 0.5%, respectively. The main causes of medication errors are due to incomplete prescription 50.2% and wrong doses 22.9%. In drug class, antibiotics and antihypertensive agents are most prone to medication error. About 87.1% errors belonged to the Category B of National Coordinating Council for Medication Error Reporting and Prevention risk index. Majority of the errors are transcription errors followed by prescription and administration errors. Consultant doctors have to be more vigilant during prescribing and verifying the medication charts. Clinical pharmacists should act as a checkpoint at each step of medication process to identify and prevent medication errors. Zirpe KG, Seta B, Gholap S, Aurangabadi K, Gurav SK, Deshmukh AM, et al. Incidence of Medication Error in Critical Care Unit of a Tertiary Care Hospital: Where Do We Stand? Indian J Crit Care Med 2020;24(9):799-803.


Coexistence of diploid and triploid hybrid water frogs: population differences persist in the apparent absence of differential survival.
The role of differential selection in determining the geographic distribution of genotypes in hybrid systems has long been discussed, but not settled. The present study aims to asses the importance of selection in structuring all-hybrid Pelophylax esculentus populations. These populations, in which the parental species (P. lessonae with genotype LL and P. ridibundus with genotype RR) are absent, have pond-specific proportions of diploid (LR) and triploid (LLR and LRR) genotypes. With data from 12 Swedish ponds, we first show that in spite of significant changes in genotype proportions over time, the most extreme ponds retained their differences over a six year study period. The uneven distribution of genotypes among ponds could be a consequence of differential selection varying among ponds (selection hypothesis), or, alternatively, of different gamete production patterns among ponds (gamete pattern hypothesis). The selection hypothesis was tested in adults by a six year mark-recapture study in all 12 ponds. As the relative survival and proportion of LLR, LR and LRR did not correlate within ponds, this study provided no evidence for the selection hypothesis in adults. Then, both hypotheses were tested simultaneously in juvenile stages (eggs, tadpoles, metamorphs and one year old froglets) in three of the ponds. A gradual approach to adult genotype proportions through successive stages would support the selection hypotheses, whereas the presence of adult genotype proportions already at the egg stage would support the gamete pattern hypothesis. The result was a weak preference for the gamete pattern hypothesis. These results thus suggest that selection is of little importance for shaping genotype distributions of all-hybrid populations of P. esculentus, but further studies are needed for confirmation. Moreover, the study provided valuable data on genotype-specific body lengths, adult survival and sex ratios.


Epiregulin-dependent amphiregulin expression and ERBB2 signaling are involved in luteinizing hormone-induced paracrine signaling pathways in mouse ovary.
Sustained EGF receptor (EGFR) phosphorylation by de novo synthesis of EGFR ligands plays an essential role in mediating luteinizing hormone (LH)-induced ovulation process in the preovulatory follicles (POFs). In the present study, the effect of epiregulin (EREG) on oocyte maturation and ovulation was investigated using Ereg knockout (Ereg-/-) mice congenic on a C57BL/6 background. Rate of spontaneous oocyte meiotic resumption of denuded oocytes (DOs) or cumulus cell-oocyte complexes (COCs) in vitro is similar between wild-type and Ereg-/- mice. However, gonadotropin-induced meiotic resumption in vivo is attenuated, and the number of COCs with expanded cumulus matrix and superovulated eggs dramatically decrease in Ereg-/- mice. Nonetheless, the number of eggs ovulated during normal estrus cycles and litter sizes in Ereg-/- mice are comparable to those of wild-type littermates. In contrast to other EGFR ligands, induction of amphiregulin (Areg) mRNA is severely reduced in ovaries collected from Ereg-/- mice either after human chorionic gonadotropin (hCG) treatment in immature mice or LH surge in adults. Gonadotropin-induced EGFR and ERBB2 phosphorylation in ovaries is attenuated in immature Ereg-/- mice, and MAPK3/1 phosphorylation and prostaglandin synthase 2 (PTGS2) protein levels are reduced. This attenuation, however, is no longer detectable in adult Ereg-/- mice after LH surge. This study implicates that EREG mediates signals downstream of Areg mRNA expression and that EGFR-ERBB2 signals contributes to regulation of ovulation process.


Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial.
Postoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life. This is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veteran's RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p<0.05. Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) is approved by the ethics board at Washington University. Recruitment began in January 2015. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. NCT02241655; Pre-results.


Cometary science. On the nucleus structure and activity of comet 67P/Churyumov-Gerasimenko.
Images from the OSIRIS scientific imaging system onboard Rosetta show that the nucleus of 67P/Churyumov-Gerasimenko consists of two lobes connected by a short neck. The nucleus has a bulk density less than half that of water. Activity at a distance from the Sun of >3 astronomical units is predominantly from the neck, where jets have been seen consistently. The nucleus rotates about the principal axis of momentum. The surface morphology suggests that the removal of larger volumes of material, possibly via explosive release of subsurface pressure or via creation of overhangs by sublimation, may be a major mass loss process. The shape raises the question of whether the two lobes represent a contact binary formed 4.5 billion years ago, or a single body where a gap has evolved via mass loss.


First Report of Anthracnose of Crupina vulgaris Caused by a Colletotrichum sp. in Greece.
Crupina vulgaris Cass. (common crupina, family Asteraceae), an introduced invasive weed in the northwestern United States, is a target of biological control efforts. During the spring of 2002, ≈30 wilting C. vulgaris plants were found along a road from Volos to Portaria, Greece (39°22'58″N, 22°59'27″E, elevation 446 m). Wilting plants had irregular, purple, necrotic lesions extending along the main stems and petioles. In the laboratory, diseased leaves were surface disinfested and placed on moist filter paper in petri dishes. Acervuli with setae typical of a Colletotrichum sp. were observed after 2 to 5 days. A fungal isolate, DB 02-030, was isolated from these diseased leaves. Stems and leaves of 12- and 16-week-old plants (12 plants of each age) were spray inoculated with an aqueous suspension of 2 × 106 conidia per ml from 14-day-old cultures of DB 02-030 grown on acidified potato dextrose agar (APDA). Inoculated plants were placed in a dew chamber at 18 to 21°C with continuous dew and 8 h of light per day for 48 h. Plants were moved to a greenhouse bench with 8 h of light per day and watered twice daily. Symptoms developed after 7 days on 16-week-old plants (33% symptomatic) and 14 days on 12-week-old plants (17% symptomatic). No symptoms developed on control plants. By 61 days after inoculation, 67% of plants inoculated at 16 weeks of age were dead and 50% of plants inoculated at 12 weeks of age were wilted. Koch's postulates were repeated with isolates from two other plants. Isolate DB 02-030 was reisolated three times from 10 of 10 symptomatic leaves, 4 of 4 stems with necrotic lesions, and 4 of 4 stems with leaves from wilted inoculated plants. Conidia germination on water agar was 95% at 18 to 21°C with light compared with 19% in darkness or at 23 to 26°C. C. vulgaris is an annual plant that emerges during early spring and reproduces only by seeds. As a cool-temperature aggressive pathogen, isolate DB 02-030 has the potential as a biological control agent to reduce seed production and stands of C. vulgaris. This isolate fits the morphology of Colletotrichum gloeosporioides according to Sutton (2). On APDA, conidia were formed after 4 days. Conidia were hyaline, straight, cylindrical, nonseptate, and 18 to 27 × 3 to 6 μm. Setae produced in acervuli were abundant, straight, narrow, and 75 to 210 μm long × 3 μm at the base. Appressoria in vitro were subglobose to clavate and 8 to 12 μm in diameter. Nucleotide sequences were obtained for the internal transcribed spacer (GenBank Accession No. AY539806) and 28S (GenBank Accession No. AY539807) rDNA genes of this isolate. Parsimony analyses (unpublished), with sequences from GenBank and 25 isolates from established culture collections, indicate the isolate on C. vulgaris belongs to a clade of taxonomically problematic Colletotrichum spp. that are only distantly related to other isolates of C. gloeosporioides. A culture of DB 02-030 has been deposited at the Centraalbureau voor Schimmelcultures as CBS 114801. A dried culture voucher specimen has been deposited with the U.S. National Fungus Collections (BPI 843682). To our knowledge, no species of Colletotrichum has been reported previously on any Crupina spp. (1). References: (1) D. F. Farr et al. Fungal Databases. Systematic Botany and Mycology Laboratory, On-line publication. ARS, USDA, 2004. (2) B. C. Sutton. The Coelomycetes. CMI, Kew, Surrey, England, 1980.


Assessment of stress in laboratory beagle dogs constrained by a Pavlov sling.
The 3Rs - Replacement, Reduction and Refinement - have become increasingly important in designing animal experiments. The Pavlov sling is thought to be a non-invasive method to restrain dogs for examinations. The aim of our study was to investigate whether laboratory Beagle dogs that had been trained to tolerate restraint by a Pavlov sling are stressed by this procedure and, furthermore, to analyze their behavior during this period. Five male and five female Beagle dogs were used, each three years of age. Animals were restrained in the Pavlov sling for 30 min on six days with an interval of at least two days. The following behaviors were recorded every minute for each session: postures of body, head, and ears, as well as state of eyes, tail, legs, and mouth. Additionally, the animals were observed for the occurrence of particular stress signs, including body shaking, sweating of the paws, increased saliva production, piloerection, blinking of eyes, snout licking, yawning, and panting. As an indicator for stress, salivary cortisol levels were measured before, during, and after each session. Our results show that for most behavioral parameters, e.g., body, leg, head, tail, and ear posture, the frequency of changes between different behavior patterns, as well as cortisol concentration, were not influenced by restraint in the Pavlov sling. Therefore, the Pavlov sling does not seem to be perceived as a stressful situation by the Beagle dogs. Our study demonstrates that under certain conditions the use of the Pavlov sling in trained dogs can substitute for more ordinary methods of immobilization, e.g., the use of narcotics.


Species and dose differences in the accumulation of imipramine by mammalian lungs.
Adult male mice, guinea pigs, rabbits, and rats were injected ip with 14C-imipramine (IP) at doses of either 10 or 50 mg/kg and killed 15 min or 12 hr later. Plasma, lung, liver, and kidney were analyzed for total radioactivity and for IP and desmethylimipramine (DMI). Neither mouse nor guinea pig lungs accumulated IP-derived 14C relative to the other tissues at either dose or time. Indeed, tissue/plasma (T/P) ratios for liver in these species exceeded those for lung. Rabbit and rat lung did not selectively accumulate radioactivity at either time point after 10 mg/kg or at 15 min after 50 mg/kg. However, 12 hr after 50 mg/kg, rabbit and rat lungs contained significantly more radioactivity than other tissues, lung T/P ratios being 3-4 times those of liver and kidney. Most of the radioactivity retained in rat lung was present as DMI (approximately 70%), whereas the three other species retained predominantly unchanged IP (60-80%). In rats, increasing the IP dose from 10 to 100 mg/kg resulted in a 10-fold increase in radioactivity in plasma, 3-fold increases in liver and kidney, and a 20-fold increase in lung. Studies with lung slices revealed that although all species avidly accumulated IP from the medium, all species but rabbit rapidly released the drug by efflux into drugfree medium. The data suggest that only rat and rabbit lung retain significant amounts of IP after administration of large doses to intact animals, and probably by different mechanisms. Rabbit lung retains mainly unchanged IP due to slow efflux of the drug from the lung whereas the rat rapidly demethylates IP to DMI and this metabolite is then retained by the lung.


Self-Assembly of α-Tocopherol Transfer Protein Nanoparticles: A Patchy Protein Model.
We describe the mechanism of self-aggregation of α-tocopherol transfer protein into a spherical nanocage employing Monte Carlo simulations. The protein is modeled by a patchy coarse-grained representation, where the protein-protein interfaces, determined in the past by X-ray diffraction, are represented by simplified two-body interaction potentials. Our results show that the oligomerization kinetics proceeds in two steps, with the formation of metastable trimeric units and the subsequent assembly into the spherical aggregates. Data are in agreement with experimental observations regarding the prevalence of different aggregation states at specific ambient conditions. Finally, our results indicate a route for the experimental stabilization of the trimer, crucial for the understanding of the physiological role of such aggregates in vitamin E body trafficking.


Proteome response of fish under multiple stress exposure: Effects of pesticide mixtures and temperature increase.
Aquatic systems can be subjected to multiple stressors, including pollutant cocktails and elevated temperature. Evaluating the combined effects of these stressors on organisms is a great challenge in environmental sciences. To the best of our knowledge, this is the first study to assess the molecular stress response of an aquatic fish species subjected to individual and combined pesticide mixtures and increased temperatures. For that, goldfish (Carassius auratus) were acclimated to two different temperatures (22 and 32°C) for 15 days. They were then exposed for 96h to a cocktail of herbicides and fungicides (S-metolachlor, isoproturon, linuron, atrazine-desethyl, aclonifen, pendimethalin and tebuconazole) at two environmentally relevant concentrations (total concentrations of 8.4μgL-1 and 42μgL-1) at these two temperatures (22 and 32°C). The molecular response in liver was assessed by 2D-proteomics. Identified proteins were integrated using pathway enrichment analysis software to determine the biological functions involved in the individual or combined stress responses and to predict the potential deleterious outcomes. The pesticide mixtures elicited pathways involved in cellular stress response, carbohydrate, protein and lipid metabolisms, methionine cycle, cellular functions, cell structure and death control, with concentration- and temperature-dependent profiles of response. We found that combined temperature increase and pesticide exposure affected the cellular stress response: the effects of oxidative stress were more marked and there was a deregulation of the cell cycle via apoptosis inhibition. Moreover a decrease in the formation of glucose by liver and in ketogenic activity was observed in this multi-stress condition. The decrease in both pathways could reflect a shift from a metabolic compensation strategy to a conservation state. Taken together, our results showed (1) that environmental cocktails of herbicides and fungicides induced important changes in pathways involved in metabolism, cell structure and cell cycle, with possible deleterious outcomes at higher biological scales and (2) that increasing temperature could affect the response of fish to pesticide exposure.


Dietary lipid source and vitamin E effect on lipid oxidation stability of refrigerated fresh and cooked chicken meat.
The fatty acid composition of chicken muscle may affect the lipid oxidation stability of the meat, particularly when subjecting the meat to thermal processing and storage. The objective of this study was to evaluate the diet effect on lipid oxidation stability of fresh and cooked chicken meat. Six hundred broilers were raised for a 6-wk feeding period and were assigned to 8 treatments with 3 repetitions. Broilers were fed a basal corn-soybean meal diet, including 5% of either animal-vegetable, lard, palm kernel, or soybean (SB) oil, each supplemented with a low (33 mg/kg) or high (200 to 400 mg/kg) level of vitamin E. Fresh breast and thigh meat and skin were packaged and refrigerated (4°C) for 15 d. Breast and thigh meat were frozen (-20°C) and stored for ~6 mo and then thawed, deboned, ground, and formed into patties of 150 g each. Patties were cooked (74°C), cooled, packaged, and stored in refrigeration for 6 d. The lipid oxidation development of the products was determined using the TBA reactive substances analysis. The results showed that the lipid oxidation development, in both fresh chicken parts and cooked meat patties, was influenced by the interaction of either dietary lipid source or vitamin E level with storage time. Fresh breast meat showed no susceptibility to lipid oxidation, but thigh meat and skin presented higher (P < 0.05) malonaldehyde values in the SB oil treatment, starting at d 10 of storage. In cooked patties, during the entire storage time, the SB oil showed the highest (P < 0.05) lipid oxidation development compared with the other treatments. Regarding vitamin E, in both fresh parts and cooked meat patties, in most sampling days the high supplemented level showed lower (P < 0.05) malonaldehyde values than the control treatment. In conclusion, the lipid oxidation stability of chicken meat is influenced by the lipid source and vitamin E level included in the diet upon storage time and processing of the meat.


Photosensitized [2 + 2] cycloaddition of N-acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer.
Photocycloaddition between two adjacent bases in DNA produces a cyclobutane pyrimidine dimer (CPD), which is one of the major UV-induced DNA lesions, with either the cis-syn or trans-syn structure. In this study, we investigated the photosensitized intramolecular cycloaddition of partially-protected thymidylyl-(3'→5')-N(4)-acetyl-2'-deoxy-5-methylcytidine, to clarify the effect of the base modification on the cycloaddition reaction. The reaction resulted in the stereoselective formation of the trans-syn CPD, followed by hydrolysis of the acetylamino group. The same result was obtained for the photocycloaddition of thymidylyl-(3'→5')-N(4)-acetyl-2'-deoxycytidine, whereas both the cis-syn and trans-syn CPDs were formed from thymidylyl-(3'→5')-thymidine. Kinetic analyses revealed that the activation energy of the acid-catalyzed hydrolysis is comparable to that reported for the thymine-cytosine CPD. These findings provided a new strategy for the synthesis of oligonucleotides containing the trans-syn CPD. Using the synthesized oligonucleotide, translesion synthesis by human DNA polymerase η was analyzed.


Study of cytokine induced neuropathology by high resolution proton NMR spectroscopy of rat urine.
Multiple sclerosis is a major cause of non-traumatic neurological disability. The identification of markers that differentiate disease progression is critical to effective therapy. A combination of NMR spectroscopic metabolic profiling of urine and statistical pattern recognition was used to detect focal inflammatory central nervous system (CNS) lesions induced by microinjection of a replication-deficient recombinant adenovirus expressing TNF-alpha or IL1-beta cDNA into the brains of Wistar rats. These animals were compared with a group of naïve rats and a group of animals injected with an equivalent null adenovirus. Urine samples were collected 7 days after adenovirus injection, when the inflammatory lesion is maximally active. Principal components analysis and Partial Least Squares-Discriminate analysis of the urine (1)H NMR spectra revealed significant differences between each of the cytokine adenovirus groups and the control groups; for the TNF-alpha group the main differences lay in citrate and succinate, while for the IL-1beta group the predominant changes occurred in leucine, isoleucine, valine and myo-inositol. Thus, we can identify urinary metabolic vectors that not only separate rats with inflammatory lesions in the brain from control animals, but also distinguish between different types of CNS inflammatory lesions.


An sRNA Screen for Reversal of Quinolone Resistance in Escherichia coli.
In light of the rising prevalence of antimicrobial resistance (AMR) and the slow pace of new antimicrobial development, there has been increasing interest in the development of adjuvants that improve or restore the effectiveness of existing drugs. Here, we use a novel small RNA (sRNA) screening approach to identify genes whose knockdown increases ciprofloxacin (CIP) sensitivity in a resistant strain of Escherichia coli 5000 sRNA constructs were initially screened on a gyrA S83L background, ultimately leading to 30 validated genes whose disruption reduces CIP resistance. This set includes genes involved in DNA replication, repair, recombination, efflux, and other regulatory systems. Our findings increase understanding of the functional interactions of DNA Gyrase, and may aid in the development of new therapeutic approaches for combating AMR.


Health services utilization by school going Omani adolescents and youths with DSM IV mental disorders and barriers to service use.
Recent corpus of research suggests that psychiatric disorders amongst adolescents and youths are an emerging global challenge, but there is paucity of studies exploring health services utilization by this age group in Arab region. This study focus on the health services utilization and the barriers among school going adolescents and youths with DSM IV disorders in the country Oman, whose population is predominantly youthful. Representative sample of secondary school Omani adolescents and youths were concurrently interviewed for the (i) presence of DSM IV mental disorders using the face-to-face interview, World Mental Health-Composite International Diagnostic Interview (WMH-CIDI), (ii) tendency for health care utilization and (iii) predictors of utilization with clinical and demographic background. The proportions of lifetime cases having ever made treatment contact are low, being 5.2% for any anxiety disorder and 13.2% for any mood disorder category. None of these anxiety cases made treatment contact in the year of onset of the disorder, and the median delay when they eventually made treatment contact is about 14 years. In any mood disorders category only 3.6% made contact within the 1st year of onset with the median delay in initial treatment contact is two years for the Bipolar disorder (broad), four years for Any Mood disorder and nine years for the Major Depressive Disorder group. Male gender is significantly associated with less likelihood of making treatment contact when suffering from Social phobia (p = 0.000), Major Depressive Disorder (p = 0.000) and Bipolar Disorder (p = 0.000). The younger cohorts of 14-16 years and 17-18 years of Social phobic made significantly less lifetime any treatment contact (p = 0.000). The 14-16 year olds were significantly less likely to make lifetime any treatment contact for Bipolar Mood disorder (p = 0.000), while the 17-18 group were 1.5 times more likely to do so. Over past 12 months only between 6 to 12% of those having some form of mental disorder avail of any treatment facility with utilization pattern nearly equal between the any healthcare and any non healthcare facilities. In the any healthcare services, more of those with anxiety disorders seek help from general medical doctors while those with Major Depressive Disorder and any Mood disorders are comparatively treated more by non allopathic services. Females were 13.5 times more likely to avail treatment(chi sq 7.1) as also those cases with increased severity of illness were 7 times more likely(chi sq 9.6). In the any treatment category for any 12 month disorder in general, the younger cohort of 14-16 years is 2.2 times more likely to receive any treatment over past 12 months (p = 0.042) while the situation shows marked reversal in the 17-18 age groups. Having any mood disorder is a significant predictor for the same (p = 0.040). Present findings confer with other studies from elsewhere suggesting under utilization of health care services for those with mental illness. Since cultural teaching and traditional coping with mental illness are contributing significantly in furnishing mental health need for many in Oman, the findings are discussed within social-cultural context that forms the basis of the complex health care utilization in Oman. This could foster policies that help bridge the gap between allopathic and non-allopathic care services.


Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A.
Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.


Structural control of flank volcanism in continental rifts.
Many volcanoes emerge from the flank (footwall) of normal faults in continental rift zones. Because such locations are commonly topographically high and exhibit minor compressional structures, the association is enigmatic. A simple flexing plate model shows that deformation of a flexurally supported upper crust during normal faulting generates a dilational strain field in the footwall at the base of the crust. This strain field allows cracking and tapping of preexisting melt.


Thalamo-cortical network activity during spontaneous migraine attacks.
We used MRI to search for changes in thalamo-cortical networks and thalamic microstructure during spontaneous migraine attacks by studying at the same time structure with diffusion tensor imaging and resting state function in interconnected brain networks with independent component analysis. Thirteen patients with untreated migraine without aura (MI) underwent 3T MRI scans during an attack and were compared to a group of 19 healthy controls (HC). We collected resting state data in 2 selected networks identified using group independent component (IC) analysis. Fractional anisotropy (FA) values of bilateral thalami were calculated in the same participants and correlated with resting state IC z scores. Functional connectivity between the executive and the dorso-ventral attention networks was reduced in MI compared to HC. In HC, but not in MI, the higher the IC24 z score, encompassing interconnected areas of the dorso-ventral attention system, the lower the bilateral thalamic FA values. In patients, the higher the executive control network z scores, the lower the number of monthly migraine days. These results provide evidence for abnormal connectivity between the thalamus and attentional cerebral networks at rest during migraine attacks. This abnormality could subtend the known ictal impairment of cognitive performance and suggests that the latter might worsen with increasing attack frequency.


Expression pattern of nanos, piwil, dnd, vasa and pum genes during ontogenic development in Nile tilapia Oreochromis niloticus.
Primordial germ cells (PGCs) are specified by maternally provided determinants in fish. PGCs migrate then into prospective gonadal sites during early development and give rise to germ cell lineage. PGC disrupted animals do not sexually mature which has a range of commercial as well as environmental benefits. To find potential target genes for sterilisation of Nile tilapia, relative mRNA abundance patterns and tissue distribution of four nanos, two piwil, dnd1, vasa and three pum genes were investigated during ontogenic development from unfertilised eggs to newly hatched larvae and in adult tissues, respectively. The ontogenic pattern of RNA abundance revealed that all the investigated gene transcripts are maternally deposited to varying degrees, except for nanos2 which is not expressed in eggs. The ontogenic patterns of relative RNA abundance could be grouped into three categories. The first one, including nanos3, piwil1, piwil2, dnd1 and vasa, showed abundant transcript levels during early developmental stages which are then degraded during the period of maternal to zygotic transition between blastula and gastrula stages with a reduction in expression of four to five orders of magnitude by hatching stage. Another, including pum2 and pum3, showed similar patterns to the first group, but the transcript levels are reduced by only two orders of magnitude. The third group, including nanos1a, nanos1b and pum1, was characterised by a zygotic increase. nanos2 had no detectable transcripts until hatching stage. The tissue screening of nanos1a, nanos1b, pum1, pum2 and pum3 showed that they are expressed in various tissues, implying their potential pleiotropic effects in these tissues apart from gonads. In contrast, nanos3, piwil1, piwil2, dnd1 and vasa appeared to be exclusively expressed in gonads (both ovary and testis), and nanos2 showed testis-specific expression. Based on these results nanos3, piwil1, piwil2, dnd1 and vasa were prioritised among the 11 selected genes as potential target genes for sterilisation in Nile tilapia as they have no significant zygotic expression during embryogenesis, they are expressed exclusively in gonads and maternally deposited. These features suggest a potential role of these genes in the specification and maintenance of PGCs during the ontogenic development of Nile tilapia.


Creating a global rare disease patient registry linked to a rare diseases biorepository database: Rare Disease-HUB (RD-HUB).
A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT_REGISTRIES_WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before.


Joint Mobilization and Stretching Exercise vs Steroid Injection in the Treatment of Plantar Fasciitis: A Randomized Controlled Study.
This study compared the effectiveness of joint mobilization combined with stretching exercises (JM&Str) vs steroid injection (SI) in the treatment of plantar fasciitis (PF). A total of 43 patients (mean age, 45.5 ± 8.5 years; range, 30-60 years; 23 females) with PF were randomly assigned to receive either JM&Str (n = 22) or SIs (n = 21). JM&Str was applied 3 times per week for 3 weeks for a total of 9 visits. The SI group received 1 injection at baseline. The patients' functional scores were assessed using the Foot and Ankle Ability Measure (FAAM), and pain was evaluated using the Visual Analog Scale (VAS). Outcomes of interest were captured at baseline and at 3-week, 6-week, 12-week, and 1-year follow-ups. The primary aim was examined using a mixed-model analysis of variance (ANOVA). Pairwise comparisons were performed to examine differences between the baseline and follow-up periods using Bonferroni equality at an alpha level of 0.05. Age, sex, body mass index, and dorsiflexion range of motion did not significantly impact pain relief or functional outcome (P > .05) at the 3-, 6- or 12-week follow-ups compared to baseline. Planned pairwise comparisons demonstrated significant improvements in pain relief and functional outcomes in both groups (P < .05) at the 3-, 6-, and 12-week follow-ups compared to baseline. However, at the 12-week and 1-year follow-ups, pain and functional outcomes were significantly improved in only the JM&Str group (P = .002). The overall group-by-time interaction was statistically significant for both FAAM (P = .001; F = 7.0) and VAS (P = .001; F = 8.3) scores. Between-group differences favored the SI group at the 3-week (P = .001, P = .001), 6-week (P = .002, P = .001), and 12-week (P = .008, P = .001) follow-ups for pain relief and functional outcomes. However, no significant differences (P = .62, P = .57) were detected in the measured outcomes at the 1-year follow-up. Our study demonstrated that while both groups achieved significant improvements at the 3-, 6-, and 12-week follow-ups, the SI group exhibited better outcomes at all 3 time points. The noted improvements continued in only the JM&Str group for a period of time ranging from 12 weeks to 1 year. Level II, comparative study.


Verification of extreme event attribution: Using out-of-sample observations to assess changes in probabilities of unprecedented events.
Independent verification of anthropogenic influence on specific extreme climate events remains elusive. This study presents a framework for such verification. This framework reveals that previously published results based on a 1961-2005 attribution period frequently underestimate the influence of global warming on the probability of unprecedented extremes during the 2006-2017 period. This underestimation is particularly pronounced for hot and wet events, with greater uncertainty for dry events. The underestimation is reflected in discrepancies between probabilities predicted during the attribution period and frequencies observed during the out-of-sample verification period. These discrepancies are most explained by increases in climate forcing between the attribution and verification periods, suggesting that 21st-century global warming has substantially increased the probability of unprecedented hot and wet events. Hence, the use of temporally lagged periods for attribution-and, more broadly, for extreme event probability quantification-can cause underestimation of historical impacts, and current and future risks.


Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia.
The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA's relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.


Maternal and perinatal outcomes after caesarean delivery in early and late onset preeclampsia with HIV positive and HIV negative South African Women.
We analyzed the maternal and perinatal outcomes in early onset preeclampsia (EOPE) and late onset preeclampsia (LOPE) pregnant women who had scheduled caesarean deliveries. We sub-analyzed the two categories into HIV positive and HIV negative. This prospective study was conducted at a regional hospital in Durban, South Africa during 14 months. A total of 14304 deliveries were registered. Out of the 1759 preeclampsia, 351 (19.9%) were EOPE and 1408 (80.1%) were LOPE. Hundred and twenty preeclamptics (n = 120) scheduled for caesarean delivery were selected and divided into two categories namely EOPE (n = 60) and LOPE (n = 60). Each preeclampsia category was then further stratified into HIV positive (n = 30) and HIV negative (n = 30) groups. Maternal demographic, clinical details for preeclampsia, blood laboratory tests, maternal, and perinatal outcomes were recorded. Women with EOPE were older compared to those with LOPE (P = 0.0001). Also the HIV positive women were older compared to the HIV negative groups in both EOPE and LOPE categories (P = 0.03). However, multiparous and primiparous were predominant in EOPE and LOPE categories, respectively (P = 0.00 and P = 0.00). The severity of hypertension and the HIV status did not differentiate the 2 groups. Overall, maternal complications (eclampsia, persistent postpartum hypertension, HELLP syndrome, maternal death) and poor fetal outcomes occurred predominately in EOPE. This study confirms the heterogeneity of preeclampsia and shows that the timing of onset of this pregnancy disorder is important to disease severity. Further HIV status influences maternal and neonatal outcome.


The effects of interprofessional education - Self-reported professional competence among prehospital emergency care nursing students on the point of graduation - A cross-sectional study.
The aim of the study was to investigate whether interprofessional education (IPE) and interprofessional collaboration (IPC) during the educational program had an impact on prehospital emergency care nurses' (PECN) self-reported competence towards the end of the study program. A cross-sectional study using the Nurse Professional Competence (NPC) Scale was conducted. A comparison was made between PECN students from Finland who experienced IPE and IPC in the clinical setting, and PECN students from Sweden with no IPE and a low level of IPC. Forty-one students participated (Finnish n=19, Swedish n=22). The self-reported competence was higher among the Swedish students. A statistically significant difference was found in one competence area; legislation in nursing and safety planning (p<0.01). The Finnish students scored significantly higher on items related to interprofessional teamwork. Both the Swedish and Finnish students' self-reported professional competence was relatively low according to the NPC Scale. Increasing IPC and IPE in combination with offering a higher academic degree may be an option when developing the ambulance service and the study program for PECNs.


An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes.
A possible mechanism of antipsychotic-induced weight gain is activation of hypothalamic monophosphate-dependent kinase (AMPK) mediated by histamine 1 receptors. Alpha-lipoic acid (ALA), a potent antioxidant, counteracts this effect and may be helpful in reducing weight for patients taking antipsychotics. The objective of this open-label study was to assess the efficacy of ALA (1,200 mg) on twelve non-diabetic schizophrenia patients over ten weeks. Participants lost significant weight during the intervention (-2.2 kg±2.5 kg). ALA was well tolerated and was particularly effective for individuals taking strongly antihistaminic antipsychotics (-2.9 kg±2.6 kg vs. -0.5 kg±1.0 kg). NCT01355952.


Effect of a jig on EMG activity in different orofacial pain conditions.
The bite stop (jig) is commonly used in clinical practice. It has been recommended as a simple means to routinely record or provide centric relation closure and, more recently, to reduce migraines and tension-type headaches. However, the reason for the jig effect has yet to be explained. This study tested the hypothesis that it works through a decrease in masticatory muscle activity. The effect of a jig placed on the maxillary anterior teeth was investigated by recording the electromyographic (EMG) activity of the superficial masseter and anterior temporal muscles at postural position and when swallowing on the jig. EMG recordings were obtained from 2 groups of pain patients (myofascial and neuropathic) and from 2 groups of pain-free patients (disc derangement and controls) unaware of the role of dental occlusion treatments. EMG activity in postural position was higher in pain groups than in pain-free groups. The jig strongly but temporarily decreased the postural EMG activity for masseter muscles in all groups except for the neuropathic group and for temporal muscles in the myofascial group. The EMG activity when swallowing with the jig was reduced in control, disc derangement, and myofascial groups; however, EMG "hyperactivity" in the neuropathic pain group seemed to be locked. The decrease of postural EMG activity, especially in the myofascial group, was short lasting and cannot be considered as evidence to support the hypothesis of a long-term muscle relaxation jig effect. However, the results may uphold certain short-term clinical approaches.


Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, nutrient levels control multiple cellular processes. Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not accumulate the storage polysaccharide glycogen. The impaired glycogen synthesis is due to maintenance of glycogen synthase in a hyperphosphorylated, inactive state. In a screen for second site suppressors of the glycogen storage defect of snf1 cells, we identified a mutant gene that restored glycogen accumulation and which was allelic with PHO85, which encodes a member of the cyclin-dependent kinase family. In cells with disrupted PHO85 genes, we observed hyperaccumulation of glycogen, activation of glycogen synthase, and impaired glycogen synthase kinase activity. In snf1 cells, glycogen synthase kinase activity was elevated. Partial purification of glycogen synthase kinase activity from yeast extracts resulted in the separation of two fractions by phenyl-Sepharose chromatography, both of which phosphorylated and inactivated glycogen synthase. The activity of one of these, GPK2, was inhibited by olomoucine, which potently inhibits cyclin-dependent protein kinases, and contained an approximately 36-kDa species that reacted with antibodies to Pho85p. Analysis of Ser-to-Ala mutations at the three potential Gsy2p phosphorylation sites in pho85 cells implicated Ser-654 and/or Thr-667 in PHO85 control of glycogen synthase. We propose that Pho85p is a physiological glycogen synthase kinase, possibly acting downstream of Snf1p.


ReFacto and Advate: a single-dose, randomized, two-period crossover pharmacokinetics study in subjects with haemophilia A.
ReFacto is a recombinant B-domain-deleted, monoclonal antibody-purified, solvent-detergent-treated factor VIII (BDDrFVIII) with no albumin added to the final formulation. Although ReFacto has been shown to be bioequivalent to a plasma-derived FVIII product (Hemophil-M) in a randomized, crossover pharmacokinetic (PK) study, the comparability of ReFacto with the full-length (complete sequence) recombinant FVIII (FLrFVIII, Advate) product has not been previously examined in this manner. The primary objective of this study was to compare the PKs of ReFacto with those of Advate in patients with severe haemophilia A. This was a third-party unblinded, randomized, multicentre, two-period crossover PKs study of ReFacto and Advate in subjects with severe haemophilia A (FVIII:C < or =1%). Blood samples were collected over a 48-h period after i.v. administration of each of the FVIII products. FVIII:C was determined using the chromogenic substrate assay (CSA) in a central laboratory. The plasma FVIII:C PK parameters of ReFacto and Advate were determined using non-compartmental analysis. Bioequivalence was assessed on maximum plasma concentration (C(max)) and the area under the plasma concentration vs. time curves (AUCs) using an anova. The two products were judged to be equivalent if the 90% confidence limits of the ratio of the geometric mean values of C(max) and AUCs fell within the interval of 80-125%. Results from this PKs comparison of two different rFVIII products, using chromogenic substrate assay to measure FVIII:C, showed that ReFacto and Advate are bioequivalent to each other.


From "a Fair Game" to "a Form of Covert Research": Research Ethics Committee Members' Differing Notions of Consent and Potential Risk to Participants Within Social Media Research.
Social media (SM) research presents new challenges for research ethics committees (RECs) who must balance familiar ethical principles with new notions of public availability. This article qualitatively examines how U.K. REC members view this balance in terms of risk and consent. While it found significant variance overall, there were discernible experience-based trends. REC members with less experience of reviewing SM held inflexible notions of consent and risk that could be categorized as either relying on traditional notions of requiring direct consent, or viewing publicly available data as "fair game." More experienced REC members took a more nuanced approach to data use and consent. We conclude that the more nuanced approach should be best practice during ethical review of SM research.


The potential impact of physical activity during pregnancy on maternal and neonatal outcomes.
Pregnancy is a critical period of body weight regulation. Maternal obesity and excessive gestational weight gain have become increasingly common and contribute to poor obstetrical outcomes for mother and baby. Regular participation in physical activity may improve risk profiles in pregnant women. Our objectives were to provide an overview of maternal-fetal exercise physiology, summarize current evidence on the effects of physical activity during pregnancy on maternal-fetal outcomes, and review the most recent clinical practice guidelines. In addition, we summarize the findings in the context of the current obesity epidemic and discuss implications for clinical practice. A literature review was completed in which we queried OVID (Medline), EMBASE, and PSYCHINFO databases with title words "exercise or physical activity" and "pregnancy or gestation" from 1950 to March 1, 2010. A total of 212 articles were selected for review. Care providers should recommend physical activity to most pregnant women (i.e., those without contraindications) and view participation as a safe and beneficial component of a healthy pregnancy. Obstetricians & Gynecologists and Family Physicians. After participating in this CME activity, physicians should be better able to classify the potential impact of physical activity on maternal glycemic control and fetal growth outcomes. Assess maternal lifestyle and provide recommendations on appropriate gestational weight gain, evaluate pregnant women for contraindications to physical activity participation, make individualized recommendations for exercise participation, and educate patients on the merits of physical activity for health benefit.


Age and diet affect gene expression profile in canine skeletal muscle.
We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridize extracted RNA. Age had the greatest effect on gene transcription (262 differentially expressed genes), whereas the effect of diet was relatively small (22 differentially expressed genes). Effects of age (regardless of diet) were most notable on genes related to metabolism, cell cycle and cell development, and transcription function. All these genes were predominantly down-regulated in geriatric dogs. Age-affected genes that were differentially expressed on only one of two diets were primarily noted in the PPB diet group (144/165 genes). Again, genes related to cell cycle (22/35) and metabolism (15/19) had predominantly decreased transcription in geriatric dogs, but 6/8 genes related to muscle development had increased expression. Effects of diet on muscle gene expression were mostly noted in geriatric dogs, but no consistent patterns in transcription were observed. The insight these data provide into gene expression profiles of canine skeletal muscle as affected by age, could serve as a foundation for future research pertaining to age-related muscle diseases.


Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis.
People with epilepsy who became seizure-free while taking antiepileptic drugs might consider discontinuing their medication, with the possibility of increased quality of life because of the elimination of adverse events. The risk with this action, however, is seizure recurrence. The objectives of our study were to identify predictors of seizure recurrence and long-term seizure outcomes and to produce nomograms for estimation of individualised outcomes. We did a systematic review and meta-analysis, and identified eligible articles and candidate predictors, using PubMed and Embase databases with a last update on Nov 6, 2014. Eligible articles had to report on cohorts of patients with epilepsy who were seizure-free and had started withdrawal of antiepileptic drugs; articles also had to contain information regarding seizure recurrences during and after withdrawal. We excluded surgical cohorts, reports with fewer than 30 patients, and reports on acute symptomatic seizures because these topics were beyond the scope of our objective. Risk of bias was assessed using the Quality in Prognosis Studies system. Data analysis was based on individual participant data. Survival curves and proportional hazards were computed. The strongest predictors were selected with backward selection. Models were converted to nomograms and a web-based tool to determine individual risks. We identified 45 studies with 7082 patients; ten studies (22%) with 1769 patients (25%) were included in the meta-analysis. Median follow-up was 5·3 years (IQR 3·0-10·0, maximum 23 years). Prospective and retrospective studies and randomised controlled trials were included, covering non-selected and selected populations of both children and adults. Relapse occurred in 812 (46%) of 1769 patients; 136 (9%) of 1455 for whom data were available had seizures in their last year of follow-up, suggesting enduring seizure control was not regained by this timepoint. Independent predictors of seizure recurrence were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, age at onset of epilepsy, history of febrile seizures, number of seizures before remission, absence of a self-limiting epilepsy syndrome, developmental delay, and epileptiform abnormality on electroencephalogram (EEG) before withdrawal. Independent predictors of seizures in the last year of follow-up were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, number of antiepileptic drugs before withdrawal, female sex, family history of epilepsy, number of seizures before remission, focal seizures, and epileptiform abnormality on EEG before withdrawal. Adjusted concordance statistics were 0·65 (95% CI 0·65-0·66) for predicting seizure recurrence and 0·71 (0·70-0·71) for predicting long-term seizure freedom. Validation was stable across the individual study populations. We present evidence-based nomograms with robust performance across populations of children and adults. The nomograms facilitate prediction of outcomes following drug withdrawal for the individual patient, including both the risk of relapse and the chance of long-term freedom from seizures. The main limitations were the absence of a control group continuing antiepileptic drug treatment and a consistent definition of long-term seizure freedom. Epilepsiefonds.


Transient Nanoscopic Phase Separation in Biological Lipid Membranes Resolved by Planar Plasmonic Antennas.
Nanoscale membrane assemblies of sphingolipids, cholesterol, and certain proteins, also known as lipid rafts, play a crucial role in facilitating a broad range of important cell functions. Whereas on living cell membranes lipid rafts have been postulated to have nanoscopic dimensions and to be highly transient, the existence of a similar type of dynamic nanodomains in multicomponent lipid bilayers has been questioned. Here, we perform fluorescence correlation spectroscopy on planar plasmonic antenna arrays with different nanogap sizes to assess the dynamic nanoscale organization of mimetic biological membranes. Our approach takes advantage of the highly enhanced and confined excitation light provided by the nanoantennas together with their outstanding planarity to investigate membrane regions as small as 10 nm in size with microsecond time resolution. Our diffusion data are consistent with the coexistence of transient nanoscopic domains in both the liquid-ordered and the liquid-disordered microscopic phases of multicomponent lipid bilayers. These nanodomains have characteristic residence times between 30 and 150 μs and sizes around 10 nm, as inferred from the diffusion data. Thus, although microscale phase separation occurs on mimetic membranes, nanoscopic domains also coexist, suggesting that these transient assemblies might be similar to those occurring in living cells, which in the absence of raft-stabilizing proteins are poised to be short-lived. Importantly, our work underscores the high potential of photonic nanoantennas to interrogate the nanoscale heterogeneity of native biological membranes with ultrahigh spatiotemporal resolution.


A neurobiological basis for ELF guidelines.
It is well understood that electric currents applied directly to the body can stimulate peripheral nerve and muscle tissue; such effects can be fatal if breathing is inhibited or ventricular fibrillation is induced. Exposure to extremely low frequency electric and magnetic fields will also induce electric fields and currents within the body, but these are almost always much lower than those that can stimulate peripheral nerve tissue. Guidance on exposure to such fields is based on the avoidance of acute effects in the central nervous system. This paper reviews the physiological processes involved in nerve cell excitability in the peripheral and central nervous system, and the experimental evidence for physiologically weak electric field effects. It is concluded that the integrative properties of the synapses and neural networks of the central nervous system render cognitive function sensitive to the effects of physiologically weak electric fields, below the threshold for peripheral nerve stimulation. However, the only direct evidence of these weak field interactions within the central nervous system is the induction of phosphenes in humans--the perception of faint flickering light in the periphery of the visual field, by magnetic field exposure. Other tissues are potentially sensitive to induced electric fields through effects on voltage-gated ion channels, but the sensitivity of these ion channels is likely to be lower than those of nerve and muscle cells specialized for rapid electrical signaling. In addition, such tissues lack the integrative properties of synapses and neuronal networks that render the central nervous system potentially more vulnerable.


Staphylococcus epidermidis Phages Transduce Antimicrobial Resistance Plasmids and Mobilize Chromosomal Islands.
Staphylococcus epidermidis is a leading opportunistic pathogen causing nosocomial infections that is notable for its ability to form a biofilm and for its high rates of antibiotic resistance. It serves as a reservoir of multiple antimicrobial resistance genes that spread among the staphylococcal population by horizontal gene transfer such as transduction. While phage-mediated transduction is well studied in Staphylococcus aureus, S. epidermidis transducing phages have not been described in detail yet. Here, we report the characteristics of four phages, 27, 48, 456, and 459, previously used for S. epidermidis phage typing, and the newly isolated phage E72, from a clinical S. epidermidis strain. The phages, classified in the family Siphoviridae and genus Phietavirus, exhibited an S. epidermidis-specific host range, and together they infected 49% of the 35 strains tested. A whole-genome comparison revealed evolutionary relatedness to transducing S. aureus phietaviruses. In accordance with this, all the tested phages were capable of transduction with high frequencies up to 10-4 among S. epidermidis strains from different clonal complexes. Plasmids with sizes from 4 to 19 kb encoding resistance to streptomycin, tetracycline, and chloramphenicol were transferred. We provide here the first evidence of a phage-inducible chromosomal island transfer in S. epidermidis Similarly to S. aureus pathogenicity islands, the transfer was accompanied by phage capsid remodeling; however, the interfering protein encoded by the island was distinct. Our findings underline the role of S. epidermidis temperate phages in the evolution of S. epidermidis strains by horizontal gene transfer, which can also be utilized for S. epidermidis genetic studies.IMPORTANCE Multidrug-resistant strains of S. epidermidis emerge in both nosocomial and livestock environments as the most important pathogens among coagulase-negative staphylococcal species. The study of transduction by phages is essential to understanding how virulence and antimicrobial resistance genes spread in originally commensal bacterial populations. In this work, we provide a detailed description of transducing S. epidermidis phages. The high transduction frequencies of antimicrobial resistance plasmids and the first evidence of chromosomal island transfer emphasize the decisive role of S. epidermidis phages in attaining a higher pathogenic potential of host strains. To date, such importance has been attributed only to S. aureus phages, not to those of coagulase-negative staphylococci. This study also proved that the described transducing bacteriophages represent valuable genetic modification tools in S. epidermidis strains where other methods for gene transfer fail.


Correlation between DNA synthesis in the second, third and fourth generations of spermatogonia and the occurrence of apoptosis in both spermatogonia and spermatocytes.
In the seminiferous epithelium, both DNA synthesis and apoptosis occur at equivalent stages in various species, with apoptosis taking place mainly at the same stages as DNA replication in the second, third and fourth spermatogonial generations. As preservation of the cellular associations found at these stages may have some functional significance, it is important to determine whether there is a correlation between these cellular events. In this study, pairs of immunoperoxidase-stained adjacent testis sections from rats, mice, rabbits and cats in which either bromodeoxyuridine incorporated into the newly synthesized DNA strand (BrdU labelling) or DNA 3' end labelling of the apoptotic DNA fragments (TUNEL assay) were detected were compared. In addition, both events were analysed in double-labelled sections. These two methods revealed a clear correlation between the occurrence of DNA replication in the second to fourth generations of spermatogonia and most physiological apoptosis taking place in both spermatogonia and spermatocytes in the three different mammalian orders (Rodentia, Lagomorpha and Carnivora). This correlation may result from the synchronization of mitotic spermatogonial and meiotic spermatocyte cell cycle checkpoints operating at these stages.


Social capital and vulnerable urban youth in five global cities.
Social capital is essential for the successful development of young people. The current study examines direct measures of social capital in young people in five urban global contexts. The Well-Being of Adolescents in Vulnerable Environments is a global study of young people aged 15-19 years living in disadvantaged, urban settings. Respondent-driven sampling was used to recruit approximately 500 participants from each site. The sample included 2,339 young people (mean age 16.7 years; 47.5% female). We examined the associations between social capital in four domains-family, school, peers, and neighborhood and demographic characteristics-using gender-stratified ordinary least-squares regression. We also examined associations between self-reported health and the four social capital domains, which was minimal. School enrollment was positively associated with social capital for young women in Baltimore, Delhi, and Shanghai; the association was less consistent for young men. The same pattern is true for perceived wealth. Unstable housing was associated with low familial social capital in all groups except young women in Shanghai and young men in Ibadan and Johannesburg. Being raised outside a two-parent family has a widespread, negative association with social capital. Self-reported health had a mainly positive association with social capital with the most consistent association being neighborhood social capital. Different types of social capital interact with social contexts and gender differently. Strategies that aim to build social capital as part of risk reduction and positive youth development programming need to recognize that social capital enhancement may work differently for different groups and in different settings.


Allee effects, invasion pinning, and species' borders.
All species' ranges are the result of successful past invasions. Thus, models of species' invasions and their failure can provide insight into the formation of a species' geographic range. Here, we study the properties of invasion models when a species cannot persist below a critical population density known as an "Allee threshold." In both spatially continuous reaction-diffusion models and spatially discrete coupled ordinary-differential-equation models, the Allee effect can cause an invasion to fail. In patchy landscapes (with dynamics described by the spatially discrete model), range limits caused by propagation failure (pinning) are stable over a wide range of parameters, whereas, in an uninterrupted habitat (with dynamics described by a spatially continuous model), the zero velocity solution is structurally unstable and thus unlikely to persist in nature. We derive conditions under which invasion waves are pinned in the discrete space model and discuss their implications for spatially complex dynamics, including critical phenomena, in ecological landscapes. Our results suggest caution when interpreting abrupt range limits as stemming either from competition between species or a hard environmental limit that cannot be crossed: under a wide range of plausible ecological conditions, species' ranges may be limited by an Allee effect. Several example systems appear to fit our general model.