Human disease-associated genetic variation impacts large intergenic non-coding RNA expression.
Recently it has become clear that only a small percentage (7%) of disease-associated single nucleotide polymorphisms (SNPs) are located in protein-coding regions, while the remaining 93% are located in gene regulatory regions or in intergenic regions. Thus, the understanding of how genetic variations control the expression of non-coding RNAs (in a tissue-dependent manner) has far-reaching implications. We tested the association of SNPs with expression levels (eQTLs) of large intergenic non-coding RNAs (lincRNAs), using genome-wide gene expression and genotype data from five different tissues. We identified 112 cis-regulated lincRNAs, of which 45% could be replicated in an independent dataset. We observed that 75% of the SNPs affecting lincRNA expression (lincRNA cis-eQTLs) were specific to lincRNA alone and did not affect the expression of neighboring protein-coding genes. We show that this specific genotype-lincRNA expression correlation is tissue-dependent and that many of these lincRNA cis-eQTL SNPs are also associated with complex traits and diseases.


Erthropoietic protoporphyria: first report of cases in the American Nergo.
The first two cases of erthropoietic protoporphyria in the American Nergo are reported. The eruption was limited to the lips, subungual and periungual areas, which are relatively nonpigmented. Onset was at a later age and length of sun exposure required to produce symptoms was longer than that in most whites with the disease. The different presentation in Negroes is believed to be related to their increased pigmentation. Melanin appears to provide protection because of its free radical formation and absorption of 400 nm electromagnetic radiation.


[Doege-Potter syndrome is a solitary fibrotic tumour often leading to hypoglycaemia].
Doege-Potter syndrome is a rare paraneoplastic syndrome, in which a solitary fibrotic tumour secretes insulin-like growth factor II leading to hypoglycaemia. In this case report, a 70-year-old woman known with a big intra-abdominal tumour was admitted to hospital, unconscious with a blood sugar of 1.8 mmol/l. She was treated with intravenous glucose until surgery, which cured her temporarily. After four months she had relapse and no effect of chemotherapy. Surgery is the only curative treatment for Doege-Potter syndrome, which is important to remember, if a patient has unexplained hypoglycaemia and a tumour.


The Still-Face: A Greater Challenge for Infants of Mothers With Borderline Personality Disorder.
The main aim of this study was to ascertain whether infants as young as 3 months of age, whose mothers suffer from borderline personality disorder (BPD), are already at risk of greater dysregulation than infants of mothers without BPD when faced with a minor stressful experience. Nineteen mothers diagnosed with BPD and 41 controls with no history of psychopathology and their 3-month-old infants were observed using Tronick's Face-to-Face Still-Face paradigm. The authors found that infants whose mothers have BPD express less positive vocalizations and less nonautonomic self-regulation than infants of mothers with no psychopathology. The stress of the Still-Face episode affects their gaze and self-regulation behaviors more strongly than those of infants of controls. The Reunion episode seems particularly challenging for mothers with BPD, who show fewer smiles and an increase in intrusive behavior. Because infants and their mothers with BPD are already dysregulated at 3 months postpartum, envisaging very early intervention seems warranted.


Sexual rehabilitation after localized prostate cancer: current interventions and future directions.
Many published articles have documented the impact of prostate-cancer treatment on sexual functioning in men treated for localized disease. Surprisingly, the literature on interventions to rehabilitate men's sexual functioning is much more limited. In this article, we review the sexual-rehabilitation interventions for prostate-cancer patients and identify a number of common themes across interventions. We also identify areas where further research is needed and propose a conceptual model based on psychologic and nursing theories and informed by the published research.


Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells In Vivo.
Streptolysin S (SLS)-like virulence factors from clinically relevant Gram-positive pathogens have been proposed to behave as potent cytotoxins, playing key roles in tissue infection. Listeriolysin S (LLS) is an SLS-like hemolysin/bacteriocin present among Listeria monocytogenes strains responsible for human listeriosis outbreaks. As LLS cytotoxic activity has been associated with virulence, we investigated the LLS-specific contribution to host tissue infection. Surprisingly, we first show that LLS causes only weak red blood cell (RBC) hemolysis in vitro and neither confers resistance to phagocytic killing nor favors survival of L. monocytogenes within the blood cells or in the extracellular space (in the plasma). We reveal that LLS does not elicit specific immune responses, is not cytotoxic for eukaryotic cells, and does not impact cell infection by L. monocytogenes Using in vitro cell infection systems and a murine intravenous infection model, we actually demonstrate that LLS expression is undetectable during infection of cells and murine inner organs. Importantly, upon intravenous animal inoculation, L. monocytogenes is found in the gastrointestinal system, and only in this environment LLS expression is detected in vivo Finally, we confirm that LLS production is associated with destruction of target bacteria. Our results demonstrate therefore that LLS does not contribute to L. monocytogenes tissue injury and virulence in inner host organs as previously reported. Moreover, we describe that LlsB, a putative posttranslational modification enzyme encoded in the LLS operon, is necessary for murine inner organ colonization. Overall, we demonstrate that LLS is the first SLS-like virulence factor targeting exclusively prokaryotic cells during in vivo infections.IMPORTANCE The most severe human listeriosis outbreaks are caused by L. monocytogenes strains harboring listeriolysin S (LLS), previously described as a cytotoxin that plays a critical role in host inner tissue infection. Cytotoxic activities have been proposed as a general mode of action for streptolysin S (SLS)-like toxins, including clostridiolysin S and LLS. We now challenge this dogma by demonstrating that LLS does not contribute to virulence in vivo once the intestinal barrier has been crossed. Importantly, we show that intravenous L. monocytogenes inoculation leads to bacterial translocation to the gastrointestinal system, where LLS is specifically expressed, targeting the host gut microbiota. Our study highlights the heterogeneous modes of action of SLS-like toxins, and we demonstrate for the first time a further level of complexity for SLS-like biosynthetic clusters as we reveal that the putative posttranslational modification enzyme LlsB is actually required for inner organ colonization, independently of the LLS activity.


The influence of comorbidity on the risk of access-related bacteremia in chronic hemodialysis patients.
Access-related bacteremia is an important cause of morbidity in chronic hemodialysis patients. The incidence of bacteremia is higher in patients dialyzing through a tunneled central venous catheter (TCVC) compared with an arteriovenous fistula (AVF). Our aim was to explore if this is explained by patient comorbidity. Two groups of chronic hemodialysis outpatients were compared: all patients who dialyzed through a TCVC at any time during 2003 and were fit enough to subsequently have a functioning AVF or renal transplant even if it was after 2003 (Group 1; n=93); and all patients who dialyzed through a TCVC in 2003 and were not fit enough to have a functioning AVF or renal transplant (Group 2; n=119). Episodes of bacteremia (n=71) were identified and those not related to access were excluded. Patients in Group 1 were younger than Group 2 (57.5 years vs. 64.8 years; P=0.001). The incidences of bacteremia in Groups 1 and 2 were, respectively, 0.31 and 0.44 episodes per 1000 patient days while dialyzing through an AVF (P=0.77), and 2.21 and 2.27 per 1000 days while dialyzing through a TCVC (P=0.91). The 3-year actual survival from January 1, 2003 to January 1, 2006 was significantly higher in Group 1 than in Group 2 (80.6% vs. 26.1%; P<0.0001) confirming the higher comorbidity of the patients in Group 2. Patients dialyzing through a TCVC (compared with an AVF) have a significantly higher risk of access-related bacteremia, irrespective of comorbidity.


Intrauterine fetal bradycardia after accidental administration of the anesthetic agent in the subdural space during epidural labor analgesia -A case report-.
Subdural injection of epidural anesthesia is rare and is usually undiagnosed during epidural anesthesia causing severely delayed maternal hypotension, hypoxia, and fetal distress. A 38-year-old primiparous woman was administered epidural labor analgesia at 40(+6) weeks' gestation, and developed progressive maternal respiratory depression, bradycardia, and hypotension after accidental subdural administration of the anesthetic agent. Furthermore, fetal distress occurred soon after administration. The patient was managed with oxygen, position changes, fluid resuscitation, and ephedrine. Intrauterine fetal resuscitation was successfully performed with atropine before cesarean section, and a healthy baby was delivered. Although subdural injection is uncommon, this case emphasizes the importance of anesthesiologists monitoring patients for a sufficient period after epidural labor analgesia, and being prepared to perform maternal or fetal resuscitation.


Utilizing the dynamic stark shift as a probe for dielectric relaxation in photosynthetic reaction centers during charge separation.
In photosynthetic reaction centers, the electric field generated by light-induced charge separation produces electrochromic shifts in the transitions of reaction center pigments. The extent of this Stark shift indirectly reflects the effective field strength at a particular cofactor in the complex. The dynamics of the effective field strength near the two monomeric bacteriochlorophylls (BA and BB) in purple photosynthetic bacterial reaction centers has been explored near physiological temperature by monitoring the time-dependent Stark shift during charge separation (dynamic Stark shift). This dynamic Stark shift was determined through analysis of femtosecond time-resolved absorbance change spectra recorded in wild type reaction centers and in four mutants at position M210. In both wild type and the mutants, the kinetics of the dynamic Stark shift differ from those of electron transfer, though not in the same way. In wild type, the initial electron transfer and the increase in the effective field strength near the active-side monomer bacteriochlorophyll (BA) occur in synchrony, but the two signals diverge on the time scale of electron transfer to the quinone. In contrast, when tyrosine is replaced by aspartic acid at M210, the kinetics of the BA Stark shift and the initial electron transfer differ, but transfer to the quinone coincides with the decay of the Stark shift. This is interpreted in terms of differences in the dynamics of the local dielectric environment between the mutants and the wild type. In wild type, comparison of the Stark shifts associated with BA and BB on the two quasi-symmetric halves of the reaction center structure confirm that the effective dielectric constants near these cofactors are quite different when the reaction center is in the state P(+)QA(-), as previously determined by Steffen et al. at 1.5 K (Steffen, M. A.; et al. Science 1994, 264, 810-816). However, it is not possible to determine from static, low-temperature measurments if the difference in the effective dielectric constant between the two sides of the reaction center is manifest on the time scale of initial electron transfer. By comparing directly the Stark shift dynamics of the ground-state spectra of the two monomer bacteriochlorophylls, it is evident that there is, in fact, a large dielectric difference between protein environments of the two quasi-symmetric electron-transfer branches on the time scale of initial electron transfer and that the effective dielectric constant in the region continues to evolve on a time scale of hundreds of picoseconds.


Alpha-tubulin from early-diverging eukaryotic lineages and the evolution of the tubulin family.
The tubulin gene family, which includes alpha-,beta-, and gamma-tubulin subfamilies, is composed of highly conserved proteins which are the principle structural and functional components of eukaryotic microtubules. We are interested in (1) establishing when in eukaryotic evolution the duplications leading to paralogous alpha, beta, and gamma subfamilies occurred and (2) the possible utility of tubulin sequences in reconstructing organismal phylogeny. To broaden the taxonomic representation of alpha-tubulins so that it roughly equals that of beta-tubulins, alpha-tubulin genes from three Microsporidia (Encephalitozoon hellem, Nosema locustae, and Spraguea lophii), two Parabasalia (Monocercomonas sp. and Trichomitus batrachorum), and one Heterolobosean (Acrasis rosea) were sequenced. With these new genes, phylogenetic trees of alpha- and beta-tubulins were constructed and compared. Trees were congruent with each other, but incongruent with other molecular phylogenies. The agreement between alpha- and beta-tubulin trees could arise by the co-adaptation of one molecule to variants of the other as a result of their intimate steric association in microtubules. Thus, these trees may not be providing independent support for the phylogenetic results. However, one of these unexpected results, that microsporidia cluster with fungi, is supported by other circumstantial evidence, and may therefore reflect a real relationship despite the basal position usually assigned to microsporidia. Relationships between the three tubulins were also examined by constructing trees of all three types. These trees were found to be of limited value for determining the position of the root within each subfamily because of the great interfamily distances, but they do confirm the classification of all known genes into three monophyletic subfamilies. Divergent genes from Caenorhabditis elegans and Saccharomyces cerevisiae that have been proposed to represent the novel classes delta- and epsilon-tubulin were found to be specifically related to gamma-tubulins from animals and fungi respectively, and therefore are best seen as rapidly evolving orthologues of gamma-tubulin.


Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature.
Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient's triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.


Mapping the dengue scientific landscape worldwide: a bibliometric and network analysis.
Despite the current global trend of reduction in the morbidity and mortality of neglected diseases, dengue's incidence has increased and occurrence areas have expanded. Dengue also persists as a scientific and technological challenge since there is no effective treatment, vaccine, vector control or public health intervention. Combining bibliometrics and social network analysis methods can support the mapping of dengue research and development (R&D) activities worldwide. The aim of this paper is to map the scientific scenario related to dengue research worldwide. We use scientific publication data from Web of Science Core Collection - articles indexed in Science Citation Index Expanded (SCI-EXPANDED) - and combine bibliometrics and social network analysis techniques to identify the most relevant journals, scientific references, research areas, countries and research organisations in the dengue scientific landscape. Our results show a significant increase of dengue publications over time; tropical medicine and virology as the most frequent research areas and biochemistry and molecular biology as the most central area in the network; USA and Brazil as the most productive countries; and Mahidol University and Fundação Oswaldo Cruz as the main research organisations and the Centres for Disease Control and Prevention as the most central organisation in the collaboration network. Our findings can be used to strengthen a global knowledge platform guiding policy, planning and funding decisions as well as to providing directions to researchers and institutions. So that, by offering to the scientific community, policy makers and public health practitioners a mapping of the dengue scientific landscape, this paper has aimed to contribute to upcoming debates, decision-making and planning on dengue R&D and public health strategies worldwide.


Do clinical features and survival of single hormone receptor positive breast cancers differ from double hormone receptor positive breast cancers?
The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.


Muskie Lunacy: does the lunar cycle influence angler catch of muskellunge (Esox masquinongy)?
We analyzed angling catch records for 341,959 muskellunge (Esox masquinongy) from North America to test for a cyclic lunar influence on the catch. Using periodic regression, we showed that the number caught was strongly related to the 29-day lunar cycle, and the effect was consistent across most fisheries. More muskellunge were caught around the full and new moon than at other times. At night, more muskellunge were caught around the full moon than the new moon. The predicted maximum relative effect was ≈5% overall. Anglers fishing exclusively on the peak lunar day would, on average, catch 5% more muskellunge than anglers fishing on random days. On some lakes and at night, the maximum relative effect was higher. We obtained angler effort data for Wisconsin, Mille Lacs (MN), and Lake Vermilion (MN). For Lake Vermilion there was a significant effect of the lunar cycle on angler effort. We could therefore not conclude that the lunar effect on catch was due to an effect on fish behavior alone. Several factors affected the amount of variation explained by the lunar cycle. The lunar effect was stronger for larger muskellunge (>102 cm) than for smaller fish, stronger in midsummer than in June or October, and stronger for fish caught at high latitudes (>48°N) than for fish caught further south. There was no difference in the lunar effect between expert and novice muskellunge anglers. We argue that this variation is evidence that the effect of the lunar cycle on catch is mediated by biological factors and is not due solely to angler effort and reflects lunar synchronization in feeding. This effect has been attributed to variation among moon phases in lunar illumination, but our results do not support that hypothesis for angler-caught muskellunge.


A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure.
Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy expenditure. Here we report that total energy expenditure (doubly labeled water) measured in 89 nondiabetic Pima Indians was 244 kcal/ day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.056). The 24-h resting energy expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.026). These findings are the first evidence that a genetic mutation is associated with reduced energy expenditure in humans. Because the impact of this mutation on human obesity is small, we suggest that either the energy deficit induced is not large enough to significantly influence body weight in this population and/or that the Cys311-encoding allele is also associated with reduced energy intake.


Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin.
Natural protection from cholera is associated with local intestinal antibacterial and antitoxic antibodies, which appear to act synergistically. Although current parenteral cholera vaccines offer insufficient protection, new vaccines administered orally have more promise. Killed Vibrio cholerae, alone or given with the B subunit of cholera toxin, was evaluated in adult volunteers. Vaccinees, who received three doses of either vaccine, and unvaccinated controls ingested 10(6) V. cholerae organisms to determine the protective efficacy of the vaccines. The combination vaccine provided 64% protection, and the whole vibrio vaccine given alone provided 56% protection. In addition, illnesses in vaccines were milder than those in controls, and both vaccines gave complete protection against more severe disease. This substantial level of protection against a dose of V. cholerae that caused cholera in nearly 90% of controls suggests that these vaccines might provide at least as high a level of protection if given to the population of an endemic area. Indeed, a field efficacy trial is underway in Bangladesh, and preliminary data indicate a protective efficacy of 85% for a killed whole vibrio plus B subunit vaccine similar to that tested in volunteers and an efficacy of 58% for the killed whole vibrio vaccine alone. Thus, the studies in human volunteers were successful in predicting the substantial protection afforded by the vaccines in a cholera endemic area.


Clinical, cytogenetic and CYP1A1 exon-1 gene mutation analysis of Beedi workers in Vellore region, Tamil Nadu.
Beedi rollers are exposed to unburnt tobacco dust through cutaneous and pharyngeal route and it is extremely harmful to the body since it is carcinogenic in nature and can cause cancer during long exposure. This indicates that occupational exposure to tobacco imposes considerable genotoxicity among beedi workers. In the present study, 27 beedi workers and age and sex matched controls were enrolled for clinical, cytogenetics and molecular analysis. Clinical features were recorded. The workers were in the age group of 28-67 years and were workers exposure from 8-60 years. Blood samples were collected from workers and control subjects and lymphocyte cultures were carried out by using standard technique, slides were prepared and 50 metaphases were scored for each sample to find the chromosomal abnormalities. For molecular analysis the genomic DNA was extracted from peripheral blood, to screen the variations in gene, the exon 1 of CYP1A1 gene was amplified by polymerase chain reaction (PCR) and then screened with Single Strand Conformation Polymorphism (SSCP) analysis. A statistically significant increase was observed in the frequencies of chromosomal aberrations in exposed groups when compared to the respective controls and variations observed in Exon 1 of CYP1A1(Cytochrome P450, family 1, subfamily A, polypeptide 1) gene. This study shows that, the toxicants present in the beedi that enter into human body causes disturbance to normal state and behavior of the chromosomes which results in reshuffling of hereditary material causing chromosomal aberrations and genomic variations.


Transient paraplegia caused by acute aortic dissection--case report.
A case of acute aortic dissection (AAD) presenting as sudden, transient paraplegia and severe back pain is reported. The patient was a 66-year-old male with a 10-year-history of hypertension. The pain characteristically migrated from the back to the neck and then returned to the back. He showed complete transverse myelopathy at the level of the 9th thoracic cord. Computed tomography disclosed internal displacement of aortic intimal calcifications, without abnormalities in the spinal canal, and myelography showed no spinal canal block or stenosis. Electrocardiography and chest x-ray indicated nonspecific changes of high amplitudes and mild cardiomegaly, respectively. Together, these findings suggested acute aortic dissection with spinal cord ischemia. The initial systolic blood pressure of 220 mmHg was lowered with medication, and the pain was controlled with morphine. He recovered fully and was discharged 80 days after the onset of symptoms, with no neurological deficits. AAD carries a very poor prognosis unless treated immediately. Therefore, it is very important to promptly differentiate this disorder from spinal vascular conditions that also produce back pain and paraparesis.


Health care reform starts with primary care.
Under the Clinton health care reform plan, primary care physicians will be the gatekeepers of the health care system. Patrick E. Kapsner, FACMPE, writes about how the primary care physician will be a part of managed competition and how they will interrelate with specialty practices.


Flexible cystoscopy: a revolution in urological practice.
Flexible cystoscopy has revolutionized the field of diagnostic urology. It can be done under local anaesthesia in the outpatient setting and is thus a highly useful tool. Its role in therapeutic urology is more limited but it still has a place in the management of certain conditions.


Cycling Skill Inventory: Assessment of motor-tactical skills and safety motives.
Objective: It is well established within the traffic psychology literature that a distinction can be made between driving skill and driving style. The majority of self-report questionnaires have been developed for car drivers, whereas only limited knowledge exists on the riding skill and style of cyclists. Individual differences in cycling skills need to be understood in order to apply targeted interventions.Methods: This study reports on a psychometric analysis of the Cycling Skill Inventory (CSI), a self-report questionnaire that asks cyclists to rate themselves from definitely weak to definitely strong on 17 items. Herein, we administered the CSI using an online crowdsourcing method, complemented with respondents who answered the questionnaire using paper and pencil (n = 1,138 in total). Our analysis focuses on understanding the major sources of variance of the CSI and its correlates with gender, age, exposure, and self-reported accident involvement as a cyclist.Results: The results showed that 2 components underlie the item data: Motor-tactical skills and safety motives. Correlational analyses indicated that participants with a higher safety motives score were involved in fewer self-reported cycling accidents in the past 3 years. The analysis also confirmed well-established gender differences, with male cyclists having lower safety motives but higher motor-tactical skills than female cyclists.Conclusions: The nomological network of the CSI for cyclists is similar to that of the Driving Skill Inventory for car drivers. Safety motives are a predictor of self-reported accident involvement among cyclists.


Transanal proctocolectomy and ileal pouch-anal anastomosis (TaIPAA) for ulcerative colitis: medium term functional outcomes in a single centre.
Transanal dissection of the rectum has been recently introduced for ileal pouch-anal anastomosis (IPAA) in UC showing promising results. Thanks to the precise identification of the rectotomy site the risk of long rectal stump is avoided, and a single stapled anastomosis is performed easily. The aim of this study is to analyze our initial experience of transanal proctocolectomy and ileal pouch-anal anastomosis (TaIPAA), considering postoperative complications and medium-term functional outcomes. Our Center has experienced the transanal approach for proctectomy and IPAA since August 2018. All patients underwent Enhanced Recovery After Surgery (ERAS) protocol. Postoperative complications occurring within 30 days after surgery were taken into consideration. Fecal continence, genito-urinary activity and global quality of life at 1 and 6 months after ileostomy reversal have been assessed. Until March 2019, 8 patients underwent transanal proctocolectomy and ileal pouch-anal anastomosis (TaIPAA). In all cases the laparoscopic approach was performed during the transabdominal phase; abdominal drainage was never used. At the time of the pouch construction a defunctioning loop ileostomy was created in all patients. Stoma closure was performed in all cases at a median time of 6 months after surgery. Postoperative complications occurred in only one patient, who showed rectal bleeding, not required a re-invertation. There were no cases of anastomotic leakage. Medium-term functional outcomes were determined prospectively using previously validated quality of life questionnaires (Cleveland Global Quality of Life). Fecal incontinence for liquid or solid stool, genitourinary and sexual functions were also investigated, showing comparable results with the literature data. In our experience, transanal proctocolectomy and ileal pouch-anal anastomosis provided good short and medium-term functional results in UC.


Mountain colonisation, miniaturisation and ecological evolution in a radiation of direct-developing New Guinea Frogs (Choerophryne, Microhylidae).
Mountain ranges in the tropics are characterised by high levels of localised endemism, often-aberrant evolutionary trajectories, and some of the world's most diverse regional biotas. Here we investigate the evolution of montane endemism, ecology and body size in a clade of direct-developing frogs (Choerophryne, Microhylidae) from New Guinea. Phylogenetic relationships were estimated from a mitochondrial molecular dataset using Bayesian and maximum likelihood approaches. Ancestral state reconstruction was used to infer the evolution of elevational distribution, ecology (indexed by male calling height), and body size, and phylogenetically corrected regression was employed to examine the relationships between these three traits. We obtained strong support for a monophyletic lineage comprising the majority of taxa sampled. Within this clade we identified one subclade that appears to have diversified primarily in montane habitats of the Central Cordillera (>1,000 m a.s.l.), with subsequent dispersal to isolated North Papuan Mountains. A second subclade (characterised by moderately to very elongated snouts) appears to have diversified primarily in hill forests (<1,000 m a.s.l.), with inferred independent upwards colonisations of isolated montane habitats, especially in isolated North Papuan Mountains. We found no clear relationship between extremely small body size (adult SVL less than 15 mm) and elevation, but a stronger relationship with ecology-smaller species tend to be more terrestrial. Orogeny and climatic oscillations have interacted to generate high montane biodiversity in New Guinea via both localised diversification within montane habitats (centric endemism) and periodic dispersal across lowland regions (eccentric endemism). The correlation between extreme miniaturisation and terrestrial habits reflects a general trend in frogs, suggesting that ecological or physiological constraints limit niche usage by miniaturised frogs, even in extremely wet environments such as tropical mountains.


Hypertonic induction of COX-2 expression in renal medullary epithelial cells requires transactivation of the EGFR.
Hypertonic stress increases expression of cyclooxygenase-2 (COX-2) in renal medullary epithelial and interstitial cells. Because hypertonic COX-2 expression is, in part, sensitive to inhibition of the ERK MAPK, an effector of activated receptor tyrosine kinases such as the EGF receptor, we investigated a role for this receptor in signaling to COX-2 expression. Hypertonic stress increased COX-2 expression at the mRNA and protein levels at 6 and 24 h of hypertonic treatment. Two potent, specific inhibitors of the EGF receptor kinase, AG-1478 and PD-153035, abrogated this effect. These inhibitors also blocked the ability of hypertonic stress to increase PGE2 release; in addition, they partially blocked tonicity-dependent phosphorylation of ERK but not of the related MAPKs, JNK or p38. Pharmacological inhibition of ERK activation partially blocked tonicity-dependent COX-2 expression. Hypertonic induction of COX-2 was likely transcriptionally mediated, as NaCl stress increased luciferase reporter gene activity under control of the human COX-2 promoter, and this effect was also sensitive to inhibition of the EGF receptor kinase. Metalloproteinase action is required for transactivation of the EGF receptor. Pharmacological inhibition of metalloproteinase function blocked tonicity-inducible COX-2 expression. Furthermore, the effect of hypertonicity on COX-2 expression was also evident in the EGF-responsive Madin-Darby canine kidney and 3T3 cell lines but was virtually absent from the EGF-unresponsive (and EGF receptor null) Chinese hamster-derived CHO cell line. Taken together, these data indicate that hypertonicity-dependent COX-2 expression in medullary epithelial cells requires transactivation of the EGF receptor and, potentially, ectodomain cleavage of an EGF receptor ligand.


Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression.
The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.


[Late diagnosis of Morquio syndrome. Clinical histopathological findings in a rare mucopolysaccharidosis].
The Morquio syndrome is a rare autosomal-recessive mucopolysaccharidosis. The Morquio syndrome is characterized by a reduced activity of N-acetylgalactosamine-6-sulfate-sulfatase (type A), or beta-galactosidase (type B). This deficiency leads to a lysosomal storage disease with accumulation of keratan sulfate und chondroitin-6-sulfate in connective tissue, skeletal system und teeth. Consequently, abnormalities of the skeletal system, aortic valvular disease and dental abnormalities occur. Ophthalmologically, diffuse corneal opacification and alterations of the trabecular meshwork--occasionally leading to glaucoma--can be found. A 44-year-old woman asked for perforating corneal transplantation because of corneal clouding on both eyes. Besides, she suffered from dwarfism of unclear reason. The diffuse corneal clouding and the dwarfism suggested a systemic-metabolic disease. Thus, further radiologic and medical investigation was started. Radiologically, a kyphoscoliosis, a pectus carinatum, a luxation of both hips, and a gonarthrosis were recognized. Fibroblast culture of a skin biopsy showed reduced activity of N-acetyl-galactosamine-6-sulfate-sulfatase. This was the proof of Morquio syndrome type A. The explanted corneal button showed granules of acid mucopolysaccharides. Those were in the epithelial and endothelial cells and in the corneal stroma. To our knowledge, a Morquio syndrome has never been diagnosed with an adult and only after the ophthalmologist gave a hint. This can only be explained by the comparative mild expression of the disease in this patient. Diagnosis of Morquio syndrome is important because the frequent odontoid hypoplasia can lead to a deadly atlanto-axial instability, if not treated.


Symptomatic intraspinal air entrapment.
A 59-year-old man who had undergone the removal of a lipoma of the thoracic spine presented with progressive weakness of the lower limbs when lumbar puncture followed drainage of a subcutaneous collection of cerebrospinal fluid. Computed tomography showed entrapped intraspinal air which compressed the spinal cord. This rare, but serious complication can occur in a patient with altered intrathecal pressure following spinal surgery.


Antagonistic coevolution between quantitative and Mendelian traits.
Coevolution is relentlessly creating and maintaining biodiversity and therefore has been a central topic in evolutionary biology. Previous theoretical studies have mostly considered coevolution between genetically symmetric traits (i.e. coevolution between two continuous quantitative traits or two discrete Mendelian traits). However, recent empirical evidence indicates that coevolution can occur between genetically asymmetric traits (e.g. between quantitative and Mendelian traits). We examine consequences of antagonistic coevolution mediated by a quantitative predator trait and a Mendelian prey trait, such that predation is more intense with decreased phenotypic distance between their traits (phenotype matching). This antagonistic coevolution produces a complex pattern of bifurcations with bistability (initial state dependence) in a two-dimensional model for trait coevolution. Furthermore, with eco-evolutionary dynamics (so that the trait evolution affects predator-prey population dynamics), we find that coevolution can cause rich dynamics including anti-phase cycles, in-phase cycles, chaotic dynamics and deterministic predator extinction. Predator extinction is more likely to occur when the prey trait exhibits complete dominance rather than semidominance and when the predator trait evolves very rapidly. Our study illustrates how recognizing the genetic architectures of interacting ecological traits can be essential for understanding the population and evolutionary dynamics of coevolving species.


Sequence-dependent interactions of cationic naphthalimides and polynucleotides.
The binding interactions of three naphthalimide derivatives with heteropoly nucleic acids have been evaluated using fluorescence, absorption and circular dichroism spectroscopies. Mono- and bifunctionalized naphthalimides exhibit sequence-dependent variations in their affinity toward DNA. The heteropoly nucleic acids, [Poly(dA-dT)]2 and [Poly(dG-dC)]2, as well as calf thymus (CT) DNA, were used to understand the factors that govern binding strength and selectivity. Sequence selectivity was addressed by determining the binding constants as a function of polynucleotide composition according to the noncooperative McGhee-von Hippel binding model. Binding affinities toward [poly(dA-dT)](2) were the largest for spermine-substituted naphthalimides (Kb = 2-6 x 10(6) M(-1)). The association constants for complex formation between the cationic naphthalimides and [poly(dG-dC)]2 or CT DNA (58% A-T content) were 2-500 times smaller, depending on the naphthalimide-polynucleotide pair. The binding modes were also assessed using a combination of induced circular dichroism and salt effects to determine whether the naphthalimides associate with DNA through intercalative, electrostatic or groove-binding. The results show that the monofunctionalized spermine and pyridinium-substituted naphthalimides associate with DNA through electrostatic interactions. In contrast, intercalative interactions are predominant in the complex formed between the bifunctionalized spermine compound and all of the polynucleotides.


[Chemical elements in the blood, bronchial lavage fluid and lung tissue of patients with pulmonary tuberculosis and lung cancer].
The examined groups included 58 patients with cancer, 61 subjects with pulmonary tuberculosis and 50 healthy persons as controls. The content of trace elements in blood, bronchial lavage fluid from the most affected portions of the lungs, and in pathologic and healthy lung tissues was determined by a C-115 atomic absorption spectrophotometer. The examination findings demonstrated that the content of blood serum ferric zinc and magnesium, and erythrocyte zinc, manganese, potassium and calcium was higher in patients with pulmonary tuberculosis than in those with lung cancer. At the same time the content of magnesium and calcium in bronchial lavage fluid was higher in persons with a malignant process than in those with pulmonary tuberculosis. As far as differential diagnosis of pulmonary tuberculosis and lung cancer is concerned, it is advisable to measure the levels of erythrocyte trace elements since the latter most precisely reflects their content in the lung pathologic tissue.


The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review.
Since the 2008 introduction of the human papillomavirus (HPV) vaccination programme for adolescent girls in the UK, parents and other groups have expressed fears that immunisation condones sexual activity, promotes promiscuity and encourages risky sexual behaviour. This study aimed to explore whether HPV vaccination programmes have increased knowledge surrounding HPV and associated disease and whether uptake has influenced sexual behaviour. MEDLINE, Embase, Cochrane Library and PsycINFO electronic databases were interrogated. Studies of behaviour, attitudes and knowledge associated with HPV vaccination (or vaccination intent) in subjects of any age and gender in programmes reflective of UK practice were included in the review (n = 58). The evidence regarding the association of HPV vaccination with high-risk sexual behaviour was varied, primarily due to the heterogeneous nature of the included studies. Young females typically exhibited better knowledge than males, and vaccinated respondents (or those with vaccination intent) had higher levels of knowledge than the unvaccinated. However, knowledge surrounding HPV and genital warts was generally poor. This review highlights the need to provide effective education regarding the HPV vaccine and HPV-associated disease to adolescents of vaccination age, nurses, teachers, parents and guardians to ultimately allow informed decisions to be made regarding receipt of the HPV vaccine.


Acute Dystonic Reaction After Propofol Administration: A Pediatric Case Report.
We present a case of a 12-year-old female with a history of infantile spasms who developed a propofol-associated acute dystonic reaction after emergence from general anesthesia for foot surgery. Uniquely, the patient's postoperative symptoms of an acute dystonic reaction were refractory to standard treatment with anticholinergics but were successfully treated with corticosteroids. The absence of any dystonic symptoms following subsequent foot surgery under general anesthesia without propofol supported a propofol-associated etiology. This case may contribute to a better understanding of the underlying mechanisms of propofol-associated acute dystonic reactions and adds a possible new treatment option.


Competitive regulation of phospholipase C responses by cAMP and calcium.
DDT1-MF2 smooth muscle cells demonstrated a robust phospholipase C response to norepinephrine, as detected by inositol phosphate accumulation. A selective A1-adenosine receptor agonist, cyclopentyladenosine, caused only a minor stimulation of phospholipase C, which was eliminated in the absence of added extracellular calcium. The simultaneous addition of norepinephrine and cyclopentyladenosine resulted in a synergistic increase in phosphoinositide hydrolysis either in the absence or in the presence of external calcium. In the presence of external calcium and a calcium ionophore, and adenosine agonist caused a significant stimulation of phosphoinositide hydrolysis without the addition of norepinephrine. Influx of extracellular calcium through voltage-sensitive calcium channels did not appear to be required to observe an effect of cyclopentyladenosine, because neither calcium channel antagonists (nifedipine, verapamil, and LaCl3) nor a chelator of extracellular calcium (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid) were able to alter the degree of potentiation of norepinephrine-stimulated phosphoinositide hydrolysis due to the adenosine agonist. On the other hand, buffering of intracellular calcium concentration with the membrane-permeant calcium chelator quin2 blocked the potentiation. This blockade of potentiation by quin2 was reversed by the addition of extracellular calcium. Agents that stimulated cAMP production or membrane-permeable analogues of cAMP also blocked the action of the adenosine agonist to potentiate norepinephrine-stimulated phosphoinositide hydrolysis. This effect of cAMP was less pronounced in the presence of elevated extracellular calcium and was abolished in the presence of a calcium ionophore. When norepinephrine-stimulated calcium transients were quantitated using fura-2 fluorescence, a reduction in the amplitude of the calcium response was observed in the presence of forskolin. Conversely, both the amplitude and the duration of the calcium response were enhanced by the addition of the adenosine agonist. The results of these studies suggest that the mechanism by which adenosine receptors enhance the stimulation of phosphoinositide hydrolysis is dependent upon a rise in intracellular Ca2+ concentration resulting from the simultaneous activation of alpha 1-adrenergic receptors. The results further suggest that cAMP inhibits this mechanism by decreasing the norepinephrine-stimulated rise in intracellular Ca2+ concentration.


Paired synovium and lymph nodes from rheumatoid arthritis patients differ in dendritic cell and chemokine expression.
The aim of this study was to compare the cellular composition and organization of rheumatoid (RA) synovium, which has several of the characteristics of lymphoid organs, with lymph nodes. To clarify further whether RA synovium can be classified as an ectopic lymphoid organ, paired RA synovium and lymph node (LN) tissues from 11 patients were compared in terms of T-cell-B-cell and germinal centre (GC) organization, dendritic cell (DC) subsets, and chemokine expression. Tonsil, a normal secondary lymphoid organ, was used as a tissue control. In paired RA LN and synovium, more follicular DC-positive GCs were observed in LN, but when observed in synovium, they shared the same T-cell-B-cell organization and mean GC size. In LN, a predominance of mature DC-LAMP-positive DCs of myeloid (CD11c-positive) or lymphoid (CD123-positive) origin was observed, whereas paired RA synovium was characterized by the relative accumulation of immature CD1a-positive DCs. In the same way, CCL19-CCL21/CCR7, a chemokine/chemokine receptor complex involved in mature DC migration, was more frequently seen in LN than in paired RA synovium. In synovium, such expression was associated with lymphoid follicle formation, with or without a GC. Conversely, CCL20, a chemokine involved in immature DC migration, was expressed in RA synovium and tonsils but not in paired LNs. In conclusion, although similarities were observed, this study, using paired samples, indicates that the RA synovium lacks some of the features that are characteristic of a lymphoid organ.


Synthetic pre-microRNAs reveal dual-strand activity of miR-34a on TNF-α.
Functional microRNAs (miRNAs) are produced from both arms of their precursors (pre-miRNAs). Their abundances vary in context-dependent fashion spatiotemporarily and there is mounting evidence of regulatory interplay between them. Here, we introduce chemically synthesized pre-miRNAs (syn-pre-miRNAs) as a general class of accessible, easily transfectable mimics of pre-miRNAs. These are RNA hairpins, identical in sequence to natural pre-miRNAs. They differ from commercially available miRNA mimics through their complete hairpin structure, including any regulatory elements in their terminal-loop regions and their potential to introduce both strands into RISC. They are distinguished from transcribed pre-miRNAs by their terminal 5' hydroxyl groups and their precisely defined terminal nucleotides. We demonstrate with several examples how they fully recapitulate the properties of pre-miRNAs, including their processing by Dicer into functionally active 5p; and 3p-derived mature miRNAs. We use syn-pre-miRNAs to show that miR-34a uses its 5p and 3p miRNAs in two pathways: apoptosis during TGF-β signaling, where SIRT1 and SP4 are suppressed by miR-34a-5p and miR-34a-3p, respectively; and the lipopolysaccharide (LPS)-activation of primary human monocyte-derived macrophages, where TNF (TNFα) is suppressed by miR-34a-5p indirectly and miR-34a-3p directly. Our results add to growing evidence that the use of both arms of a miRNA may be a widely used mechanism. We further suggest that syn-pre-miRNAs are ideal and affordable tools to investigate these mechanisms.


Identification and expression analysis of connexin-45 and connexin-60 as major connexins in porcine oocytes.
During mammalian oogenesis, intercellular communication between oocytes and the surrounding follicle cells through gap junction channels is crucial for oocyte development and maturation. The channel properties of gap junctions may be affected by the composition or combination of connexins, the expression of which is regulated by gonadotropins and other factors. Thus, identification and expression analysis of connexin genes in oocytes and follicle cells will help us to better understand how oogenesis and folliculogenesis are regulated in a species-specific manner in mammals. We previously reported the spatiotemporal expression of multiple connexin genes in porcine follicle cells. Here, we searched for connexin genes specifically expressed in porcine oocytes that may be involved in the formation of gap junctions between oocytes and follicle cells. To achieve this, we constructed an oocyte-specific cDNA library to identify which connexin genes are expressed in these cells and found that gap junction protein, alpha 10, which encodes connexin-60, and a porcine ortholog of mouse gap junction protein, gamma 1 encoding connexin-45, are the major connexins expressed in porcine oocytes during folliculogenesis. Immunostaining and in situ hybridization of sectioned porcine ovaries confirmed oocyte expression of these genes at 3 different stages of ovary development. Furthermore, their gap junction channel activity was assessed using a heterologous cell system. However, gap junction protein, alpha 4, which encodes connexin-37 and is expressed in the oocytes of several other mammals, was undetectable. We demonstrate that there is diversity in the connexin genes expressed in mammalian oocytes, and hence in the gap junctions connecting oocytes and cumulus cells.


Clinical pharmacokinetic and pharmacodynamic considerations in patients with liver disease. An update.
The effects of liver disease on pharmacokinetics and pharmacodynamics are highly variable, and difficult to predict as the mechanisms of these effects are not well understood. Since the majority of the published literature is concerned with cirrhotic liver disease, this review also focuses mainly on this area. Four different theories have been proposed to account for the effects of chronic liver disease with cirrhosis on hepatic drug elimination: the sick cell theory; the intact hepatocyte theory; the impaired drug uptake theory; and the oxygen limitation theory. While some data in support of each of the first 2 theories have been published recently, a large amount of clinical data would appear to refute both of these theories. These clinical data are substantially consistent with the latter 2 theories, which regard the decreased permeability of the capillarised sinusoid as the critical feature in cirrhosis. Further work is required to determine the applicability of each of these theories. In cirrhosis, drug glucuronidation is spared relative to oxidative drug metabolism; however, in advanced cirrhosis this pathway may also be impaired substantially. There is evidence that in cirrhosis other conjugation pathways may also be impaired to variable degrees. Growing evidence suggests that biliary drug excretion is impaired in cirrhosis. Recent studies with several racemic drugs indicate that the disease can have different effects on the hepatic elimination of individual enantiomers, which may lead to a change in the concentration-response relationships of racemic drugs in cirrhosis. A major finding which has emerged in recent years is that, even with moderate degrees of hepatic impairment, there is a decrease in clearance of drugs or active metabolites normally cleared by the kidney. The effect on renal clearance of unbound drug may be masked if there is a concomitant decrease in plasma protein binding of the drug. Neither serum creatinine levels nor creatinine clearance are useful markers of the renal dysfunction associated with cirrhosis. Both may greatly overestimate renal function in patients with cirrhosis due to increased fractional renal tubular secretion of creatinine. Altered receptor sensitivity has been observed with some drugs in cirrhosis, while for other drugs there is no change in pharmacodynamics. Precise determination of drug dosage in cirrhosis requires information on changes in pharmacodynamics and plasma protein binding in addition to changes in drug elimination. Pharmacokinetic investigations in a variety of chronic liver diseases without cirrhosis (e.g. carcinoma, schistosomiasis and viral hepatitis) suggest that in the absence of cirrhosis, impairment of drug elimination is not sufficient to warrant reduction of drug dosage. However, if cirrhosis is present, 'safe' drug use requires an awareness of the possibility of multiple interactions between changes in hepatic and renal disposition and pharmacodynamics. In chronic liver disease with cirrhosis, dosage reduction is the general rule regardless of the route of elimination of drug or metabolite.


Characterization of natural illuminants in forests and the use of digital video data to reconstruct illuminant spectra.
We describe illumination spectra in forests and show that they can be accurately recovered from recorded digital video images. Natural illuminant spectra of 238 samples measured in temperate forests were characterized by principal-component analysis. The spectra can be accurately approximated by the mean and the first two principal components. Compared with illumination under open skies, the loci of forest illuminants are displaced toward the green region in the chromaticity plots, and unlike open sky illumination they cannot be characterized by correlated color temperature. We show that it is possible to recover illuminant spectra accurately from digital video images by a linear least-squares-fit estimation technique. The use of digital video data in spectral analysis provides a promising new approach to the studies of the spatial and temporal variation of illumination in natural scenes and the understanding of color vision in natural environments.


Change and stability in childhood clique membership, isolation from cliques, and associated child characteristics.
This study explored the role of clique membership and clique isolation in children's psychosocial adjustment. We identified change and stability in early elementary school clique membership and investigated behavioral characteristics related to this change and stability. Participants were first-grade pupils (N = 300), followed over a 1-year period. Clique membership was identified through social network analysis. Differences between children with a stable versus changing clique membership status were tested using peer nominations and teacher ratings. Clique members were better adjusted than nonclique members. Externalizing behavior, less prosocial behavior, and low social preference preceded clique estrangement. Stable-isolates increased in externalizing behavior, whereas children who became part of a dyad or included in a clique showed a decrease in externalizing behavior.


Psychological Safety for Mental Health in Elite Sport: A Theoretically Informed Model.
Elite sports contexts are highly pressurised and frequently enforce a win-at-all-costs approach. This narrow focus on performance outcomes can potentially contribute in negative ways to the mental health of those within these environments. In this Current Opinion paper, we propose a model that outlines how key elements contributing to psychologically safe or unsafe environments may contribute to better or worse mental health outcomes, respectively. In an environment in which individuals feel safe to show their authentic selves rather than 'wear a mask', different experiences of mental health are likely to be normalised, help-seeking behaviour increased, and thus, mental health outcomes enhanced. We outline how sports teams and organisations can contribute to this through the creation of appropriate policies and procedures, in addition to leaders modelling and reinforcing positive cultural norms. It is intended that the theoretical model can inform stakeholders in elite sport as well as future research directions.


Effect of co-activation of tongue protrudor and retractor muscles on tongue movements and pharyngeal airflow mechanics in the rat.
1. The purpose of these experiments was to examine the mechanisms by which either co-activation or independent activation of tongue protrudor and retractor muscles influence upper airway flow mechanics. We studied the influence of selective hypoglossal (XIIth) nerve stimulation on tongue movements and flow mechanics in anaesthetized rats that were prepared with an isolated upper airway. In this preparation, both nasal and oral flow pathways are available. 2. Inspiratory flow limitation was achieved by rapidly lowering hypopharyngeal pressure (Php) with a vacuum pump, and the maximal rate of flow (VI,max) and the nasopharyngeal pressure associated with flow limitation (Pcrit) were measured. These experimental trials were repeated while nerve branches innervating tongue protrudor (genioglossus; medial XIIth nerve branch) and retractor (hyoglossus and styloglossus; lateral XIIth nerve branch) muscles were stimulated either simultaneously or independently at frequencies ranging from 20-100 Hz. Co-activating the protrudor and retractor muscles produced tongue retraction, whereas independently activating the genioglossus resulted in tongue protrusion. 3. Co-activation of tongue protrudor and retractor muscles increased VI, max (peak increase 44 %, P < 0.05), made Pcrit more negative (peak decrease of 44 %, P < 0.05), and did not change upstream nasopharyngeal resistance (Rn). Independent protrudor muscle stimulation increased VI,max (peak increase 61 %, P < 0.05), did not change Pcrit, and decreased Rn (peak decrease of 41 %, P < 0.05). Independent retractor muscle stimulation did not significantly alter flow mechanics. Changes in Pcrit and VI,max at all stimulation frequencies were significantly correlated during co-activation of protrudor and retractor muscles (r2 = 0.63, P < 0.05), but not during independent protrudor muscle stimulation (r2 = 0.09). 4. These findings indicate that either co-activation of protrudor and retractor muscles or independent activation of protrudor muscles can improve upper airway flow mechanics, although the underlying mechanisms are different. We suggest that co-activation decreases pharyngeal collapsibility but does not dilate the pharyngeal airway. In contrast, unopposed tongue protrusion dilates the oropharynx, but has a minimal effect on pharyngeal airway collapsibility.


Selective inhibition of chymotrypsin-like activity of the immunoproteasome and constitutive proteasome in Waldenstrom macroglobulinemia.
Proteasome inhibition represents a valid antitumor approach and its use has been validated in Waldenström macroglobulinemia (WM), where bortezomib has been successfully tested in clinical trials. Nevertheless, a significant fraction of patients relapses, and many present toxicity due to its off-target effects. Selective inhibition of the chymotrypsin-like (CT-L) activity of constitutive proteasome 20S (c20S) and immunoproteasome 20S (i20S) represents a sufficient and successful strategy to induce antineoplastic effect in hematologic tumors. We therefore studied ONX0912, a novel selective, irreversible inhibitor of the CT-L activity of i20S and c20S. Primary WM cells express higher level of i20S compared with c20S, and that ONX0912 inhibited the CT-L activity of both i20S and c20S, leading to induction of toxicity in primary WM cells, as well as of apoptosis through c-Jun N-terminal kinase activation, nuclear factor kappaB (NF-kappaB) inhibition, caspase cleavage, and initiation of the unfolded protein response. Importantly, ONX0912 exerted toxicity in WM cells, by reducing bone marrow (BM)-derived interleukin-6 (IL-6) and insulin-like growth factor 1 (IGF-1) secretion, thus inhibiting BM-induced p-Akt and phosphorylated extracellular signal-related kinase (p-ERK) activation in WM cells. These findings suggest that targeting i20S and c20S CT-L activity by ONX0912 represents a valid antitumor therapy in WM.


The effects of relative gain and age on peripheral blood mononuclear cell mitochondrial enzyme activity in preweaned Holstein and Jersey calves.
Mitochondria are central to metabolism, nutrition, and health, but many factors can influence their efficiency. The objectives of this study were to determine if the mitochondrial enzyme activities of citrate synthase, complex I, complex IV, and complex V from peripheral blood mononuclear cells in Holstein and Jersey dairy calves were affected by age or relative gain as a percent of initial weight. Twenty-three Holstein and 23 Jersey heifer calves were enrolled between 3 and 6 d of age and whole blood samples were collected via jugular venipuncture at 1, 2, and 8 wk of age. Crude mitochondrial extracts were obtained from the peripheral blood mononuclear cell fraction at each time point and subsequently assayed for enzymatic activity. Age-dependent changes in activity were observed in complex V for both breeds. In Jersey calves complex IV and citrate synthase activity differed with age. Complex I activity was greater for high relative gain Jerseys and tended to be greater for high relative gain Holstein calves. Holstein calves had greater incidence of scours compared with Jersey calves, and in both breeds scouring calves exhibited greater complex V activity compared with those without scours. These data suggest that age and immune challenge in the form of scours affect mitochondrial complex V activity. Additionally, complex I activity may serve as a marker for calf growth potential because it was influenced by relative gain and not age.


'Everyday memory' impairments in autism spectrum disorders.
'Everyday memory' is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Children's Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed.


Immunotherapy and radiation therapy for gastrointestinal malignancies: hope or hype?
Immunotherapy represents the newest pillar in cancer care. Although there are increasing data showing the efficacy of immunotherapy there is a spectrum of response across unselected populations of cancer patients. In fact, response rates can be poor even among patients with immunogenic tumors for reasons that remain poorly understood. A promising clinical strategy to improve outcomes, which is supported by an abundance of preclinical data, is combining immunotherapy with radiation therapy. Here we review the existing evidence and future directions for combining immunotherapy and radiation therapy for patients with gastrointestinal cancers.


Disability meanings according to patients and clinicians: imagined recovery choice pathways.
The purpose of this study was to explore how the meaning of disability varies between patients with acute-onset activity limitations and clinicians, and between males and females. Seventy-nine patients undergoing inpatient rehabilitation and 93 practicing rehabilitation clinicians in the USA developed personal recovery choice pathways through recovery preference exploration (RPE). Imagining complete dependence in 18 activities as diverse as eating and expression, each individual determined an optimal sequence of recovery. This sequence was used to determine the relative value of each activity compared with the other 17. Three comparisons were made by calculating the mean absolute difference (MAD) in median utilities, including patients versus clinicians, male versus female patients, and male versus female clinicians. The MAD shows the relative magnitude of disparity between each pair. The MAD value between patients and clinicians was 3.4 times larger and 4.8 times larger than the MAD values between male and female patients and male and female clinicians, respectively. The much larger difference in recovery preferences between patients and clinicians compared with differences between genders suggests that life contexts of being a patient with disabilities versus a clinician are more potent determinants of activity limitation perspectives than being a man or woman.


Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies.
The restricted neutralization breadth of vaccine-elicited antibodies is a major limitation of current human immunodeficiency virus-1 (HIV-1) candidate vaccines. In order to permit the efficient identification of vaccines with enhanced capacity for eliciting cross-reactive neutralizing antibodies (NAbs) and to assess the overall breadth and potency of vaccine-elicited NAb reactivity, we assembled a panel of 109 molecularly cloned HIV-1 Env pseudoviruses representing a broad range of genetic and geographic diversity. Viral isolates from all major circulating genetic subtypes were included, as were viruses derived shortly after transmission and during the early and chronic stages of infection. We assembled a panel of genetically diverse HIV-1-positive (HIV-1(+)) plasma pools to assess the neutralization sensitivities of the entire virus panel. When the viruses were rank ordered according to the average sensitivity to neutralization by the HIV-1(+) plasmas, a continuum of average sensitivity was observed. Clustering analysis of the patterns of sensitivity defined four subgroups of viruses: those having very high (tier 1A), above-average (tier 1B), moderate (tier 2), or low (tier 3) sensitivity to antibody-mediated neutralization. We also investigated potential associations between characteristics of the viral isolates (clade, stage of infection, and source of virus) and sensitivity to NAb. In particular, higher levels of NAb activity were observed when the virus and plasma pool were matched in clade. These data provide the first systematic assessment of the overall neutralization sensitivities of a genetically and geographically diverse panel of circulating HIV-1 strains. These reference viruses can facilitate the systematic characterization of NAb responses elicited by candidate vaccine immunogens.


Antibiotic resistance in childhood urinary tract infections: A single-center experience.
Urinary tract infections are the most common genitourinary tract disease in children, and inappropriate antibiotic and/or dose selection increase the likelihood of resistance. The aim of this study was to determine the prevalence of urinary tract infection pathogens, patterns of resistance to antibiotics, and empirical treatment options. Between January 2013 and December 2017, urine culture and antibiogram results of pediatric patients aged 0 days to 16 years were analyzed retrospectively. Antibiotic susceptibilities were determined using disc diffusion according to methods of the Clinical and Laboratory Standards Institute. Of the 1326 children with culture growth, 1070 (80.6%) were female and 256 (19.3%) were male. The most common microorganism found was (1138, 85.8%) E. Coli, followed by Klebsiella spp. (71, 5.3%), Enterobacter spp. (44, 3.3%), and Proteus spp. (28, 2.1%). High frequency of resistance to ampicillin, ampicillin-sulbactam, amoxicillin-clavulanate, cefuroxime axetil, as TMP-SMX was detected in all microorganisms, whereas resistance to amikacin, meropenem, imipenem, ertapenem, fosfomycin, and nitrofurantoin was low. E. coli was the most common causative agent of urinary tract infections in childhood. High resistance to ampicillin, ampicillin-sulbactam, amoxicillin-clavulanate, cefuroxime axetil, and TMP-SMX was detected in all agents in our center.


Drosophila duplication hotspots are associated with late-replicating regions of the genome.
Duplications play a significant role in both extremes of the phenotypic spectrum of newly arising mutations: they can have severe deleterious effects (e.g. duplications underlie a variety of diseases) but can also be highly advantageous. The phenotypic potential of newly arisen duplications has stimulated wide interest in both the mutational and selective processes shaping these variants in the genome. Here we take advantage of the Drosophila simulans-Drosophila melanogaster genetic system to further our understanding of both processes. Regarding mutational processes, the study of two closely related species allows investigation of the potential existence of shared duplication hotspots, and the similarities and differences between the two genomes can be used to dissect its underlying causes. Regarding selection, the difference in the effective population size between the two species can be leveraged to ask questions about the strength of selection acting on different classes of duplications. In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than in D. melanogaster. This is also true for duplications segregating at high frequency, where we find evidence in D. simulans that a sizeable fraction of these mutations is being driven to fixation by positive selection.


The influence of protein adsorption on interactions of cultured human endothelial cells with polymers.
A systematic study of the effects of polymer surface properties on the interaction with human endothelial cells (HEC) may lead to the development of small-diameter vascular grafts. HEC, suspended in culture medium containing 20% serum adhered and spread onto moderately wettable polymers such as TCPS (tissue culture polystyrene). Reduced or no adhesion of HEC was observed upon the hydrophobic polymers PETP (polyethyleneterephthalate, Dacron) and FEP (fluoroethylenepropylene copolymer, Teflon). Polymers precoated with the proteins albumin (Alb), high density lipoprotein (HDL), and immunoglobulin G (IgG) inhibited the adhesion of HEC, whereas fibronectin (Fn) coatings promoted cell adhesion. Endothelialization of PETP and FEP only occurred after precoating of these materials with Fn. The adsorption of Fn, Alb, HDL, and IgG from solutions of different serum concentrations onto TCPS, PETP, and FEP was related to the adhesion of HEC. Serum Fn only adsorbed onto TCPS, with the maximum at 0.1% serum concentration. Maximal cell adhesion onto TCPS was also observed after pretreatment with a solution containing 0.1% serum. The cell adhesion inhibiting proteins Alb and HDL preferentially adsorbed at higher serum concentrations. Desorption of these proteins and exchange for, e.g., cellular Fn may result in cell spreading and proliferation of HEC upon TCPS.


[Polypharmacy - Solutions for Enhanced Drug Safety].
Polypharmacy (≥ 5 drugs) is common among older people and may lead to falls, ADEs and delirium. Adherence is an important part in the medication management. Simple questions (i. e. for OTC, handling and omission of drugs) are effective. As most old people are treated by general practitioners (GP), they play a key role for drug safety and reducing polypharmacy. The involvement of pharmacists in analyzing one patient's drugs can enhance solutions for drug problems ("two-man rule"). An IT-based medication plan acts as an important communication tool for an enhanced team work between doctors, pharmacists and nursing care.


[Comparative characteristics of molecular forms of human thyroxine-binding globulin].
Two molecular variants, of thyroxin-binding globulin (TBG), TBG-1 and TBG-2, were obtained from human retroplacental blood by fractionation of pure TBG on concanavalin A-Sepharose. It was found that both variants are immunologically identical, have similar molecular weights, amino acid composition and spectral properties, and possess the same affinity for thyroid hormones. However, TBG-1 and TBG-2 differed in charge upon isoelectrofocusing and had different monosaccharide composition. The existence of two molecular variants of TBG in pregnancy is probably due to the peculiarities of the polypeptide chain glycosylation during TBG biosynthesis.


A twin study of human obesity.
Height, weight, and body mass index (BMI) were assessed in a sample of 1974 monozygotic and 2097 dizygotic male twin pairs. Concordance rates for different degrees of overweight were twice as high for monozygotic twins as for dizygotic twins. Classic twin methods estimated a high heritability for height, weight, and BMI, both at age 20 years (.80, .78, and .77, respectively) and at a 25-year follow-up (.80, .81, and .84, respectively). Height, weight, and BMI were highly correlated across time, and a path analysis suggested that the major part of that covariation was genetic. These results are similar to those of other twin studies of these measures and suggest that human fatness is under substantial genetic control.


Effects of Dexmedetomidine on Postoperative Delirium and Expression of IL-1β, IL-6, and TNF-α in Elderly Patients After Hip Fracture Operation.
Postoperative delirium (POD) is a common surgical complication in elderly patients. This study investigated the effects of dexmedetomidine on POD and pro-inflammatory markers in elderly patients with hip fracture. This randomized, double-blind, controlled trial enrolled patients ≥65 years of age who underwent an operation for hip fracture at Beijing JiShuiTan Hospital from October 2016 to January 2017. The patients were divided into the DEX group (injected with dexmedetomidine 0.5 µg/kg/h) and the NS group (injected with normal saline). After surgery, the incidence of delirium at postoperative day 1 (T1), 2 (T2), and 3 (T3) was assessed using the Confusion Assessment Method delirium scale. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α blood levels were detected at T0 (before surgery), T1, and T3. Data from 240 patients were analyzed, with 120/group (intent-to-treat analysis). Dexmedetomidine decreased POD incidence (18.2 vs. 30.6%, P = 0.033). Compared to T0, all three pro-inflammatory markers were higher at T1 and then decreased at T3 (time interaction, all P < 0.001). IL-6 (P < 0.001) levels were lower in the DEX group at T1, and TNF-α (P = 0.003) levels were lower in the DEX group at T1 and T3, but IL-1β levels were similar between the two groups. The rate of adverse events was similar in the two groups. Dexmedetomidine reduced the incidence of POD in elderly patients on the first day after hip fracture surgery, and reduced IL-6 and TNF-α levels over the first 3 days after surgery.


Left atrial systolic force in hypertensive patients with left ventricular hypertrophy: the LIFE study.
In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial systolic force and left ventricular geometry and function have not been investigated in high-risk hypertrophic hypertensive patients. Participants in the Losartan Intervention For Endpoint reduction in hypertension echocardiography substudy without prevalent cardiovascular disease or atrial fibrillation (n = 567) underwent standard Doppler echocardiography. Left atrial systolic force was obtained from the mitral orifice area and Doppler mitral peak A velocity. Patients were divided into groups with normal or increased left atrial systolic force (>14.33 kdyn). Left atrial systolic force was high in 297 patients (52.3%), who were older and had higher body mass index and heart rate (all P < 0.01) but similar systolic and diastolic blood pressure, in comparison with patients with normal left atrial systolic force. After controlling for confounders, increased left atrial systolic force was associated with larger left ventricular diameter and higher left ventricular mass index (both P < 0.01). Prevalence of left ventricular hypertrophy was greater (84 vs. 64%; P < 0.001). Participants with increased left atrial systolic force exhibited normal ejection fraction; higher stroke volume, cardiac output, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P < 0.01). Enhanced left atrial systolic force identifies hypertensive patients with greater left ventricular mass and prevalence of left ventricular hypertrophy, but normal left ventricular chamber systolic function with increased transmitral flow gradient occurring during early filling, consistent with increased preload.


Rat tissue collagen modified by advanced glycation: correlation with duration of diabetes and glycemic control.
Collagenous proteins are especially prone to nonenzymatic glycation, because they contain several dibasic amino acid residues with free amino groups, have a very slow turnover rate, and are exposed to ambient levels of glucose. The aim of this study was to determine the time-dependent course of advanced glycation process in diabetic rats in relation to glycemic control and duration of diabetes, compared to age-matched controls. Immunochemical assay with antibodies to advanced glycation end products (AGE) was first developed to qualitatively detect and quantify the AGE formed in rat tendon and aortic collagen. Individual collagen samples were extracted by extensive pepsin and collagenase digestion. The amount of AGE was measured by competitive ELISA and results were expressed as AGE U/mg collagen. Diabetic rats showed a significant increase in AGE content in aortic collagen at 20 weeks (n = 6, 206.6 +/- 16.7 U/mg collagen) compared with that measured at 4 and 12 weeks (n = 6, 110 +/- 12.8 U/mg collagen, and n = 13, 184.9 +/- 12.3 U/mg collagen at 4 and 12 weeks, respectively; p < 0.001 between 20 weeks and 4 weeks; p < 0.01 between 20 weeks and 12 weeks). The amount of AGE in tendon collagen of diabetic rats increased from 1.9 +/- 0.38 U/mg at 4 weeks to 11.2 +/- 6.1 U/mg collagen at 20 weeks, p < 0.001. Considerable disparity was observed in the intensity of glycation between aortic and tendon collagen. AGE-content per mg of aortic collagen was several-fold to that found in tendon collagen (p < 0.001). To investigate the effect of glycemic control on the advanced glycation process, total aortic AGE-collagen content was compared between untreated diabetic rats (D; n = 13, 184.9 +/- 12.3 U/mg) and diabetic rats treated for 12 weeks with insulin (DI; n = 6, 133.9 +/- 10.7 U/mg), or phlorizin (DP; n = 6, 132.4 +/- 8.9 U/mg), or by a combination of insulin/phlorizin (DIP; n = 6, 124.3 +/- 6.5 U/mg). In spite of therapy used, all groups of diabetic animals had a significantly higher aortic AGE-collagen content than those in the nondiabetic control group (C: n = 8, 104.6 +/- 14.9 U/mg) of the same age (D, DI, DP, DIP vs. C, p < 0.001). Comparison between the mean levels of glycated hemoglobin (D: 5.62 +/- 0.38 % vs. C: 1.7 +/- 0.05%) and mean AGE levels in the studied group of animals yielded a very good exponential correlation (r = 0.89, p < 0.001). Glycation-derived late-stage collagen modification was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and by immunoblotting confirmed to contain (an) AGE-structure(s). Our study provides strong immunochemical evidence of AGE formation in vivo during hyperglycemia, and of their temporal association with structural alterations of extracellular matrix proteins. The advanced glycation process is retarded and reduced in intensity, but not completely abolished, by glycemia regulation with, or independently of, insulin.


Special care nurseries: admitting to a policy.
Few criteria exist for identifying which babies merit special nursing care, and many asymptomatic babies are offered such care unnecessarily. Birth weight is usually used to identify babies in need of special care at birth, but gestational age is a better discriminator. Babies of more than 35 weeks' gestation do not normally require admission to a special care nursery. Those preterm babies who are admitted can usually be discharged at 37 weeks' gestation even if they still weigh less than 2000 g.


Beer volatile analysis: optimization of HS/SPME coupled to GC/MS/FID.
A powerful technique was developed for the identification and quantification of 9 volatile compounds of beer, using headspace solid phase micro-extraction (HS/SPME) and gas chromatograph coupled to a mass spectrometer and a flame ionization detector (GC/MS/FID). Optimized parameters included type of fiber, desorption time, and exposure time. Optimization was achieved with standard solutions of the target compounds. All samples were analyzed in triplicate. An exposure time of 45 min with PDMS fiber in the sample headspace was enough to reach equilibrium of the phases. A desorption time of 15 min in the gas chromatograph injector was enough for the fiber to desorb the target compounds. It was found that less polar compounds were more readily absorbed by the fiber (for example, isoamyl acetate) than more polar compounds (for example, acetaldehyde), under the extraction conditions, due to the nature of the fiber. Extraction conditions are important criteria to perform a good quantification of volatile compounds. Concentrations found in sampled beer, for the compounds of interest, ranged between 0.32 and 41.7 ppm. Results show that the reproducibility of the technique depends on the compounds. Esters have higher values (RSD mean value 5.05%) than higher alcohols (RSD mean value 2.5%) and aldehydes (RSD 3.7%). The simplicity of the validated methodology enables its use as a regular quality control procedure for beer flavor analysis. This study describes a technique successfully used to identify and quantify volatiles of interest in beer that can be used for quality control purposes under normal brewery production conditions. The technique uses a gas chromatograph coupled to a mass spectrometer with a flame ionization detector.


Adrenocorticotropic Hormone-Secreting Neuroendocrine Tumor of the Rectum Demonstrated on 68Ga-DOTATATE and 18F-FDG PET Imaging.
An 81-year-old man with Cushing syndrome was referred for a Ga-DOTATATE PET/CT study to investigate for an ectopic source of adrenocorticotropic hormone. The scan demonstrated mildly increased octreopeptide uptake at a rectal mass and focal uptake at multiple regions throughout the bone marrow of the axial skeleton, consistent with metastases. A subsequent F-FDG PET/CT study was performed for further evaluation and demonstrated markedly increased metabolism at the previously identified rectal mass, in addition to the liver and multiple regions throughout the skeleton. Histopathology from biopsy of the rectal mass confirmed a small cell neuroendocrine carcinoma.


A comparison of two automated monitors in the measurement of blood pressure reactivity. Trials of Hypertension Prevention Collaborative Research Group.
Cardiovascular reactivity is the change in blood pressure, pulse, and other parameters of cardiovascular function in response to a challenging task. During the conduct of cardiovascular reactivity protocols, researchers frequently use automated blood pressure devices to measure blood pressure reactivity. However, the accuracy of automated devices in measuring blood pressure reactivity is unknown. To investigate the accuracy and precision of the Dinamap 1846 SXP and the VitaStat 2600B in the measurement of blood pressure reactivity, we compared blood pressure reactivity recorded by the VitaStat and Dinamap with that obtained by observers using a conventional mercury sphygmomanometer. At three sites, 159 normotensive subjects performed the same task twice, once with blood pressure reactivity measured by the manual observers and once by the VitaStat (n = 79) or Dinamap (n = 80), with the order determined at random. Ratios (VitaStat/Dinamap) of aggregate within-person variance for baseline and task, systolic and diastolic blood pressures ranged from 1.53 to 4.93 (all P < 0.01), suggesting that the Dinamap has better precision than the VitaStat. For both diastolic and systolic blood pressure reactivity and for both types of automated devices, the mean differences in blood pressure reactivity between manual and automated measurements were small (range, -1.8 to 0.8 mm Hg). However, the VitaStat versus manual scatter plot of diastolic blood pressure reactivity showed greater dispersion (correlation coefficient r = 0.16, P = 0.15) than the Dinamap versus manual scatter plot (r = 0.36, P = 0.001). For systolic blood pressure reactivity, the VitaStat versus manual and Dinamap versus manual scatter plots were similar. Our data indicate that the Dinamap is superior to the VitaStat in the measurement of blood pressure reactivity. The substantial performance differences between the VitaStat and Dinamap suggest that other automated blood pressure monitors must be evaluated prior to use in cardiovascular reactivity studies.


Relationship between Side-Chain Polarity and the Self-Assembly Characteristics of Perylene Diimide Derivatives in Aqueous Solution.
Perylene-3,4,9,10-tetracarboxylic acid diimides (PDIs) have recently gained considerable interest for water-based biosensing applications. PDIs have been studied intensively in the bulk state, but their physical properties in aqueous solution in interplay with side-chain polarity are, however, poorly understood. Therefore, three perylene diimide based derivatives were synthesized to study the relationship between side-chain polarity and their self-assembly characteristics in water. The polarity of the side chains was found to dictate the size and morphology of the formed aggregates. Side-chain polarity rendered the self-assembly and photophysical properties of the PDIs-both important for imminent water-based applications-and these were revealed to be especially responsive to changes in solvent composition.


Synovial Sarcoma of the Nerve-Clinical and Pathological Features: Case Series and Systematic Review.
Synovial sarcoma of the nerve is a rare entity with several cases and case series reported in the literature. Despite an improved understanding of the biology, the clinical course is difficult to predict. To compile a series of patients with synovial sarcoma of the peripheral nerve (SSPN) and assess clinical and pathological factors and their contribution to survival and recurrence. Cases from 2 institutions collected in patients undergoing surgical intervention for SSPN. Systematic review including PubMed and Scopus databases were searched for related articles published from 1970 to December 2018. Eligibility criteria: (1) case reports or case series reporting on SSPN, (2) clinical course and/or pathological features of the tumor reported, and (3) articles published in English. From patients treated at our institutions (13) the average follow-up period was 3.2 yr. Tumor recurrence was seen in 4 cases and death in 3. Systematic review of the literature yielded 44 additional cases with an average follow-up period of 3.6 yr. From pooled data, there were 10 recurrences and 7 deaths (20% and 14%, respectively). Adjuvant treatment used in 62.5% of cases. Immunohistochemical markers used in diagnosis varied widely; the most common are the following: Epithelial membrane antigen (EMA), cytokeratin, vimentin, cluster of differentiation (CD34), and transducin-like enhancer of split 1 (TLE1). Statistical analysis illustrated tumor size and use of chemotherapy to be negative predictors of survival. No other factors, clinically or from pathologist review, were correlated with recurrence or survival. By combining cases from our institution with historical data and performing statistical analysis we show correlation between tumor size and death.


Environmental injury of the lung: role of humoral mediators.
Environmental lung injury may take the form of acute tracheobronchitis, asthma, pulmonary edema, chronic bronchitis, emphysema, allergic pneumonitis, fibrosing alveolitis, pleurisy, and neoplastic disease. Environmental factors eliciting these responses include irritant gases and fumes, oxidants, organic allergens, inorganic dust, bacterial enzymes, and high partial pressures of oxygen. The basic pulmonary reactions to these toxic agents--bronchoconstriction, vasoconstriction, increased vascular permeability, inflammation, carcinogenesis--may be mediated, aggravated, or modulated by biologically active substances. These humoral agents include biogenic amines (e.g. histamine): peptides (e.g., bradykinin, vasoactive intestinal peptide, and spasmogenic lung peptide); enzymes (e.g., proteases, superoxide dismutase, and mixed function oxidases); and acidic lipids (e.g., prostaglandins, prostaglandin endoperoxides, and thromboxanes).


Distractability under the influence of an ACTH 4-9 derivative.
Event-related brain potentials, autonomic responses, and response latency under distraction conditions served to investigate the effects of an ACTH 4-9 derivative (ORG 2766) on attention. Male volunteers (45) received either 40 mg ORG 2766 or placebo in a double-blind setting. Two-stimulus trials with acoustic warning signal (S1) and acoustic S2 which had to be interrupted by immediate button press, preceded trials with distraction during the warning interval in 50% of the trials. A final period without distraction served to test for rebound effects. A reduction in early CNV was found in placebo subjects under distraction, while subjects under ORG 2766 showed no reduced early negativity, but increased late negativity under this condition. Peptide subjects differed from controls in evoked potential components, showing enhanced N1 and P3 amplitudes. Activity in the alpha band was elevated. Postexperimental systolic blood pressure was raised by 15 mm Hg under ORG 2766. Results are in agreement with previous findings and suggest ORG 2766 effects on distraction resistance and attention fixation.


A computer-based systematic survey reveals the predominance of small inverted-repeat elements in wild-type rice genes.
Several recent reports indicate that mobile elements are frequently found in and flanking many wild-type plant genes. To determine the extent of this association, we performed computer-based systematic searches to identify mobile elements in the genes of two "model" plants, Oryza sativa (domesticated rice) and Arabidopsis thaliana. Whereas 32 common sequences belonging to nine putative mobile element families were found in the noncoding regions of rice genes, none were found in Arabidopsis genes. Five of the nine families (Gaijin, Castaway, Ditto, Wanderer, and Explorer) are first described in this report, while the other four were described previously (Tourist, Stowaway, p-SINE1, and Amy/LTP). Sequence similarity, structural similarity, and documentation of past mobility strongly suggests that many of the rice common sequences are bona fide mobile elements. Members of four of the new rice mobile element families are similar in some respects to members of the previously identified inverted-repeat element families, Tourist and Stowaway. Together these elements are the most prevalent type of transposons found in the rice genes surveyed and form a unique collection of inverted-repeat transposons we refer to as miniature inverted-repeat transposable elements or MITEs. The sequence and structure of MITEs are clearly distinct from short or long interspersed nuclear elements (SINEs or LINEs), the most common transposable elements associated with mammalian nuclear genes. Mobile elements, therefore, are associated with both animal and plant genes, but the identity of these elements is strikingly different.