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Alzheimer's disease, the most common form of dementia, was first formally described in 1907 yet its etiology has remained elusive. Recent proposals that Aβ peptide may be part of the brain immune response have revived longstanding contention about the possibility of causal relationships between brain pathogens and Alzheimer's disease. Research has focused on infectious pathogens that may colonize the brain such as herpes simplex type I. Some researchers have proposed the respiratory bacteria Chlamydia pneumoniae may also be implicated in Alzheimer's disease, however this remains controversial. This review aims to provide a balanced overview of the current evidence and its limitations and future approaches that may resolve controversies. We discuss the evidence from in vitro, animal and human studies proposed to implicate Chlamydia pneumoniae in Alzheimer's disease and other neurological conditions, the potential mechanisms by which the bacterium may contribute to pathogenesis and limitations of previous studies that may explain the inconsistencies in the literature., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to model Parkinson's disease (PD) as it specifically damages the nigrostriatal dopaminergic pathway. Recent studies in mice have, however, provided evidence that MPTP also compromises the integrity of the brain's vasculature. Photobiomodulation (PBM), the irradiation of tissue with low-intensity red light, mitigates MPTP-induced loss of dopaminergic neurons in the midbrain, but whether PBM also mitigates MPTP-induced damage to the cerebrovasculature has not been investigated. This study aimed to characterize the time course of cerebrovascular disruption following MPTP exposure and to determine whether PBM can mitigate this disruption. Young adult male C57BL/6 mice were injected with 80 mg/kg MPTP or isotonic saline and perfused with fluorescein isothiocyanate FITC-labelled albumin at various time points post-injection. By 7 days post-injection, there was substantial and significant leakage of FITC-labelled albumin into both the substantia nigra pars compacta (SNc; p < 0.0001) and the caudate-putamen complex (CPu; p ≤ 0.0003); this leakage partly subsided by 14 days post-injection. Mice that were injected with MPTP and treated with daily transcranial PBM (670 nm, 50 mW/cm 2 , 3 min/day), commencing 24 hours after MPTP injection, showed significantly less leakage of FITC-labelled albumin in both the SNc ( p < 0.0001) and CPu ( p = 0.0003) than sham-treated MPTP mice, with levels of leakage that were not significantly different from saline-injected controls. In summary, this study confirms that MPTP damages the brain's vasculature, delineates the time course of leakage induced by MPTP out to 14 days post-injection, and provides the first direct evidence that PBM can mitigate this leakage. These findings provide new understanding of the use of the MPTP mouse model as an experimental tool and highlight the potential of PBM as a therapeutic tool for reducing vascular dysfunction in neurological conditions., Competing Interests: The authors declare no conflict of interest.

Tetrahydrotetrazoles are five-membered-ring heterocycles containing four contiguous saturated nitrogen atoms. Very few examples of such compounds have been reported in the literature. Our previous attempt at the synthesis of a member of this class of compound suggested that the N-N bonds may be more labile than expected. This finding raised the question as to whether the structures of any of the previously reported tetrahydrotetrazoles had been properly assigned. We have reproduced the synthesis of a reported tetrahydrotetrazole, namely 1,2-di-tert-butyl 3-phenyl-1H,2H,3H,10bH-[1,2,3,4]tetrazolo[5,1-a]isoquinoline-1,2-dicarboxylate, C 25 H 30 N 4 O 4 , and have now confidently confirmed its structure via X-ray crystallography. However, while sufficiently stable in the crystal phase, we discovered that it remains very labile in solution (having a half-life of only 15 min at 20 °C in CDCl 3 ). A tentative reaction pathway for its dissociation based on 1 H NMR spectral evidence is provided.

Carborane-containing poly(dihexylfluorene)s experience drastic solvatochromism in both the solution and solid states, a characteristic that is advantageous for use in environmental and biological sensing applications. Understanding the intrinsic decay mechanisms that give rise to such sensitive emission properties is important for designing responsive sensors. The solution-state photophysical properties of homopolymer, poly(9,9-dihexyl(bisfluorenyl)carborane) (PFCY), and alternating copolymer, poly(9,9-dihexyl-2,7-fluorene- alt-9,9-dihexyl(bisfluorenyl)carborane) (PFCS), were deciphered using steady-state, electrochemical, spectroelectrochemical, and time-resolved spectroscopic methods. From these techniques, it was discovered that following excitation the conjugated fluorene local excited state (LES) donates an electron to the carborane molecule, forming an intramolecular charge transfer (ICT) state between a radical cation on the fluorene moiety and a radical anion on the carborane moiety. From the global analysis of transient absorption data, it was discovered that the rate of electron transfer from the fluorene to the carborane is heavily influenced by solvent polarity and is significantly faster in more polar solvents. Once formed, the ICT state can decay through radiative or nonradiative mechanisms and is more likely to undergo radiative decay in nonpolar solvents, due to an intramolecular restriction of the polar ICT state. This study elucidates the effects that polarity has on the excited-state formation and subsequent decay mechanisms of fluorene-carborane systems, conclusively explaining the solvatochromism and steady-state emission properties exhibited by this system.

We tagged 12 Carcharhinus limbatus with acoustic transmitters and monitored their presence at five piers along the north-east coast of South Carolina, USA in 2016 and four piers in 2017 using acoustic receivers. Data were analysed with pier association indices (PAI), mixed models and fast Fourier transformation analyses to identify potential factors related to residence time and presence at piers and any cyclical patterns in visits to piers. While the majority of monitored C. limbatus were infrequently detected at piers, three (25.0%) were highly associated with piers (PAI ≥ 0.50). Of the C. limbatus that were detected after initial capture, three (25.0%) recorded detection events only at the pier where they were tagged and two individuals (16.7%) recorded at least one detection event at all monitored piers. The best-fit model explaining C. limbatus residence time at piers included terms for pier location and diel cycle (w i = 0.88), whereas the best fit model explaining presence-absence of C. limbatus at piers included terms for tidal height, diel cycle, barometric pressure and angler count (w i = 0.98). Carcharhinus limbatus did not appear to display cyclical patterns in their visits to piers. Along the north-east coast of South Carolina, association of C. limbatus with piers is a phenomenon for a proportion of mature individuals, but continued research is necessary to understand if this behaviour is driven by attraction to and feeding on angler discards or increased foraging opportunities resulting from the attraction of potential prey to the physical structure provided by piers., (© 2019 The Fisheries Society of the British Isles.)

This study assessed the combined effects of increased urbanization and climate change on streamflow in the Yadkin-Pee Dee watershed (North Carolina, USA) and focused on the conversion from forest to urban land use, the primary land use transition occurring in the watershed. We used the Soil and Water Assessment Tool to simulate future (2050-2070) streamflow and baseflow for four combined climate and land use scenarios across the Yadkin-Pee Dee River watershed and three subwatersheds. The combined scenarios pair land use change and climate change scenarios together. Compared to the baseline, projected streamflow increased in three out of four combined scenarios and decreased in one combined scenario. Baseflow decreased in all combined scenarios, but decreases were largest in subwatersheds that lost the most forest. The effects of land use change and climate change were additive, amplifying the increases in runoff and decreases in baseflow. Streamflow was influenced more strongly by climate change than land use change. However, for baseflow the reverse was true; land use change tended to drive baseflow more than climate change. Land use change was also a stronger driver than climate in the most urban subwatershed. In the most extreme land use and climate projection the volume of the 1-day, 100 year flood nearly doubled at the watershed outlet. Our results underscore the importance of forests as hydrologic regulators buffering streamflow and baseflow from hydrologic extremes. Additionally, our results suggest that land managers and policy makers need to consider the implications of forest loss on streamflow and baseflow when planning for future urbanization and climate change adaptation options., (Published by Elsevier B.V.)

Concentrated animal feeding operations (CAFOs) pose wide ranging environmental risks to many parts of the US and across the globe, but datasets for CAFO risk assessments are not readily available. Within the United States, some of the greatest concentrations of CAFOs occur in North Carolina. It is also one of the only states with publicly accessible location data for classes of CAFOs that are required to obtain water quality permits from the U.S. Environmental Protection Agency (EPA); however, there are no public data sources for the large number of CAFOs that do not require EPA water quality permits. We combined public records of CAFO locations with data collected in North Carolina by the Waterkeeper and Riverkeeper Alliances to examine the distribution of both permitted and non-permitted CAFOs across the state. Over half (55%) of the state's 6646 CAFOs are located in the Coastal Plain, a low-lying region vulnerable to flooding associated with regular cyclonic and convective storms. We identified 19% of CAFOs ≤ 100 m of the nearest stream, and some as close as 15 m to the nearest stream, a common riparian buffer width for water quality management. Future climate scenarios suggest large storm events are expected to become increasingly extreme, and dry interstorm periods could lengthen. Such extremes could exacerbate the environmental impacts of CAFOs. Understanding the potential impacts of CAFO agroecosystems will require remote sensing to identify CAFOs, fieldwork to determine the extent of environmental footprints, and modeling to identify thresholds that determine environmental risk under changing conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Readmission is increasingly being utilized as an important clinical outcome and measure of hospital quality. Our aim was to delineate rates, risk factors, and reasons for unplanned readmission in pediatric surgery., Materials and Methods: Retrospective review of pediatric patients (n=130,274) undergoing surgery (2013-2014) at hospitals enrolled in the Pediatric National Surgical Quality Improvement Program (NSQIP-P) was performed. Logistic regression was used to model factors associated with unplanned 30-day readmission. Reasons for readmission were reviewed to determine the most common causes of readmission., Results: There were 6059 (n=4.7%) readmitted children within 30days of the index operation. Of these, 5041 (n=3.9%) were unplanned, with readmission rates ranging from 1.3% in plastic surgery to 5.2% in general pediatric surgery, and 10.8% in neurosurgery. Unplanned readmissions were associated with emergent status, comorbidities, and the occurrence of pre- or postdischarge postoperative complications. Overall, the most common causes for readmission were surgical site infections (23.9%), ileus/obstruction/gastrointestinal (16.8%), respiratory (8.6%), graft/implant/device-related (8.1%), neurologic (7.0%), or pain (5.8%). Median time from discharge to readmission was 8days (IQR: 3-14days). Reasons for readmission, time until readmission, and need for reoperative procedure (overall 28%, n=1414) varied between surgical specialties., Conclusion: The reasons for readmission in children undergoing surgery are complex, varied, and influenced by patient characteristics and postoperative complications. These data inform risk-stratification for readmission in pediatric surgical populations, and help to identify potential areas for targeted interventions to improve quality. They also highlight the importance of accounting for case-mix in the interpretation of hospital readmission rates., Level of Evidence: 3., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Allergic contact dermatitis is a challenging diagnostic problem in children. Although epicutaneous patch testing is the diagnostic standard for confirmation of contact sensitization, it is less used in children by dermatologists treating children, pediatric dermatologists, and pediatricians, when compared with adult practitioners., Objective: The aim of the study was to create and evaluate standardization of a pediatric patch test series for children older than 6 years., Methods: We surveyed dermatologists and allergists conducting epicutaneous patch testing in children attending the 2017 American Contact Dermatitis Society meeting held in Washington, DC. This was followed by discussion of collected data and consensus review by a pediatric contact dermatitis working group at the conference., Conclusions: A baseline pediatric patch test panel was established through working group consensus.

Tetrahydrotetrazoles are a little-explored class of five-membered heterocycles with four contiguous singly-bonded N atoms. Recent work in our labs has demonstrated that urazole radicals are amenable to N-N bond formation via radical combination to form such a chain of four N atoms. Previously described 1,1-bis-urazole compounds appeared to be convenient precursors to the target tetrazoles via their oxidation to intermediate urazole diradicals, which upon N-N bond formation would complete the tetrazole framework. While oxidation proceeded smoothly, the novel 10-membered octaaza heterocycle 7,7,18,18-tetraacetyl-4,10,15,21-tetraphenyl-1,2,4,6,8,10,12,13,15,17,19,21-dodecaazapentacyclo[17.3.0.0 2,6 .0 8,12 .0 13,17 ]docosan-3,5,9,11,14,16,20,22-octone, C 42 H 32 N 12 O 12 , was obtained (36% yield) instead of the expected tetrazole product, as confirmed by X-ray crystallography. Calculations at the (U)B3LYP/6-311G(d,p) level of theory suggest that the desired tetrazoles have weak N-N bonds connecting the two urazole units.

Theoretically, interventions initiated with at-risk infants prior to the point in time a definitive autism spectrum disorder (ASD) diagnosis can be made will improve outcomes. Pursuing this idea, we tested the efficacy of a parent-mediated early intervention called Adapted Responsive Teaching (ART) via a randomized controlled trial with 87 one-year-olds identified by community screening with the First Year Inventory as at-risk of later ASD diagnoses. We found minimal evidence for main effects of ART on child outcomes. However, ART group parents showed significantly greater increases in responsiveness to their infants than control group parents. Further, significant indirect (mediation) effects of assignment group on multiple child outcomes through changes in parent responsiveness supported our theory of change.

Background: Whether BRCA1 and BRCA2 mutation carriers have a clinically relevant elevated risk of uterine cancer has implications for risk-reducing surgery., Aim: This multicentre, prospective cohort study assessed uterine cancer risk for mutation carriers compared with the general population., Methods: Eligible mutation carriers were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) cohort study, had a uterus present and no history of uterine cancer at cohort entry. Epidemiological, lifestyle and clinical data were collected at cohort entry and updated three-yearly. Cancer events were verified using pathology reports. Follow-up was censored at death or last contact. Relative risk of uterine cancer was estimated using the standardised incidence ratio (SIR), with the expected number of cases determined using population-based data for Australia., Results: Of 1,111 mutation carriers in kConFab, 283 were excluded due to prior hysterectomy (N = 278), prior uterine cancer (N = 2) or being non-residents (N = 3). After a median follow-up of 9.0 years, five incident uterine cancers were reported in the 828 eligible women (419 had prior breast cancer and 160 had prior tamoxifen use), compared to 2.04 expected (SIR = 2.45; 95% confidence interval [CI]: 0.80-5.72; P = 0.11). In 438 BRCA1 mutation carriers and 390 BRCA2 mutation carriers, three and two incident cases of uterine cancer were reported, respectively, compared to 1.04 expected (SIR = 2.87; 95% CI: 0.59-8.43; P = 0.18) and 0.99 expected (SIR = 2.01; 95% CI: 0.24-7.30; P = 0.52), respectively. All cases were endometrioid subtype, International Federation of Gynaecology and Obstetrics stage I-II disease. No serous uterine cancers were reported., Conclusions: Our findings are consistent with those from most other reports and do not support routine risk-reducing hysterectomy for BRCA1 and BRCA2 mutation carriers., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Nitrogen-centered urazole radicals exist in equilibrium with tetrazane dimers in solution. The equilibrium established typically favors the free-radical form. However, 1-arylurazole radicals bearing substituents at the ortho position favor the dimeric form. We were able to determine the structure of one of the dimers (substituted at both ortho positions with methyl groups), namely 1,2-(2,4-dimethylphenyl)-2-[2-(2,4-dimethylphenyl)-4-methyl-3,5-dioxo-1,2,4-triazolidin-1-yl]-4-methyl-1,2,4-triazolidine-3,5-dione, C 24 H 28 N 6 O 4 , via X-ray crystallography. The experimentally determined structure agreed well with the computationally obtained geometry at the B3LYP/6-311G(d,p) level of theory. The preferred syn conformation of these 1-arylurazole dimers results in the two aromatic rings being proximate and nearly parallel, which leads to some interesting shielding effects of certain signals in the 1 H NMR spectrum. Armed with this information, we were able to decipher the more complicated 1 H NMR spectrum obtained from a dimer that was monosubstituted at the ortho position with a methyl group.

Iron is essential for many biological processes, however, too much or too little iron can result in a wide variety of pathological consequences, depending on the organ system, tissue or cell type affected. In order to reduce pathogenesis, iron levels are tightly controlled in throughout the body by regulatory systems that control iron absorption, systemic transport and cellular uptake and storage. Altered iron levels and/or dysregulated homeostasis have been associated with several lung diseases, including chronic obstructive pulmonary disease, lung cancer, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. However, the mechanisms that underpin these associations and whether iron plays a key role in the pathogenesis of lung disease are yet to be fully elucidated. Furthermore, in order to survive and replicate, pathogenic micro-organisms have evolved strategies to source host iron, including freeing iron from cells and proteins that store and transport iron. To counter these microbial strategies, mammals have evolved immune-mediated defence mechanisms that reduce iron availability to pathogens. This interplay between iron, infection and immunity has important ramifications for the pathogenesis and management of human respiratory infections and diseases. An increased understanding of the role that iron plays in the pathogenesis of lung disease and respiratory infections may help inform novel therapeutic strategies. Here we review the clinical and experimental evidence that highlights the potential importance of iron in respiratory diseases and infections., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Regioregular poly[(3-hexylthiophene)-ran-(3-undecenylthiophene)] (pP3HT) and vinyl terminated poly(3-hexylthiophene) (xP3HT) were synthesized by the McCullough method and surface grafted to thiol modified silicon dioxide wafers using thiol-ene click chemistry. Utilizing this method, semiconducting, solvent impervious films were easily generated. Thiol-ene click chemistry is convenient for film stabilization in electronics because it does not produce side products that could be inimical to charge transport in the active layer. It was found through grazing incidence wide-angle X-ray scattering (GIWAXS) that there is no change in microstructure between as-spun films and thiol-ene grafted films, while there was a change after the thiol-ene grafted film was exposed to solvent. Organic field-effect transistors (oFETs) were fabricated from grafted films that had been swelled with chloroform, and these devices had mobilities on the order of 10 -6 cm 2 V -1 s -1 , which are consistent with poly(thiophene) monolayer devices.

Rapidly cooling pigs after heat stress (HS) results in a pathophysiological condition, and because rapid temperature fluctuations may be associated with reduced reproductive success in sows, it lends itself to the hypothesis that these conditions may be linked. Objectives were to determine the effects of rapid cooling on thermal response and future reproductive success in pigs. Thirty-six replacement gilts (137.8±0.9kg BW) were estrus synchronized and then 14.1±0.4 d after estrus confirmation, pigs were exposed to thermoneutral conditions (TN; n=12; 19.7±0.9°C) for 6h, or HS (36.3±0.5°C) for 3h, followed by 3h of rapid cooling (HSRC; n=12; immediate TN exposure and water dousing) or gradual cooling (HSGC; n=12; gradual decrease to TN conditions) repeated over 2 d. Vaginal (T V ) and gastrointestinal tract temperatures (T GI ) were obtained every 15min, and blood was collected on d 1 and d 2 during the HS and recovery periods at 180 and 60min, respectively. Pigs were bred 8.3±0.8 d after thermal treatments over 2 d. Reproductive tracts were collected and total fetus number and viability were recorded 28.0±0.8 d after insemination. HS increased T V and T GI (P=0.01; 0.98°C) in HSRC and HSGC compared to TN pigs. During recovery, T V was reduced from 15 to 105min (P=0.01; 0.33°C) in HSRC compared to HSGC pigs, but no overall differences in T GI were detected (P<0.05; 39.67°C). Rapid cooling increased (P<0.05) TNFα compared to HSGC and TN pigs during recovery-d 1 (55.2%), HS-d 2 (35.1%), and recovery-d 2 (64.9%). Viable fetuses tended to be reduced (P=0.08; 10.5%) and moribund fetuses tended to be increased (P=0.09; 159.3%) in HSRC compared to HSGC and TN pigs. In summary, rapid cooling prior to breeding may contribute to reduced fetal viability and reproductive success in pigs., (Published by Elsevier Ltd.)

Brugada syndrome (BrS) is recognized as a hereditary ion channel disorder with electrocardiographic changes. First appearing in the literature about 20 years ago, contemporary thoughts are that BrS may be responsible for many sudden cardiac deaths and is associated with ventricular dysrhythmias that can lead to syncope or cardiac arrest. Many individuals with BrS may have no or limited structural heart disease, whereas others may have subtle morphological changes in histopathology. This case reviews a single patient with BrS Type 1 who was found to have a high-level of coronary artery disease. Changes noted in the original electrocardiogram were of significant importance in reaching the diagnosis.

Changing climate and a legacy of fire-exclusion have increased the probability of high-severity wildfire, leading to an increased risk of forest carbon loss in ponderosa pine forests in the southwestern USA. Efforts to reduce high-severity fire risk through forest thinning and prescribed burning require both the removal and emission of carbon from these forests, and any potential carbon benefits from treatment may depend on the occurrence of wildfire. We sought to determine how forest treatments alter the effects of stochastic wildfire events on the forest carbon balance. We modeled three treatments (control, thin-only, and thin and burn) with and without the occurrence of wildfire. We evaluated how two different probabilities of wildfire occurrence, 1% and 2% per year, might alter the carbon balance of treatments. In the absence of wildfire, we found that thinning and burning treatments initially reduced total ecosystem carbon (TEC) and increased net ecosystem carbon balance (NECB). In the presence of wildfire, the thin and burn treatment TEC surpassed that of the control in year 40 at 2%/yr wildfire probability, and in year 51 at 1%/yr wildfire probability. NECB in the presence of wildfire showed a similar response to the no-wildfire scenarios: both thin-only and thin and burn treatments increased the C sink. Treatments increased TEC by reducing both mean wildfire severity and its variability. While the carbon balance of treatments may differ in more productive forest types, the carbon balance benefits from restoring forest structure and fire in southwestern ponderosa pine forests are clear.

Objectives: To estimate the population attributable fraction (PAF) and numbers of cancers occurring in Australia in 2010 attributable to tobacco smoking, both personal and by a partner., Methods: We used a modified Peto-Lopez approach to calculate the difference between the number of lung cancer cases observed and the number expected assuming the entire population developed lung cancer at the same rate as never smokers. For cancers other than lung, we applied the standard PAF formula using relative risks from a large cohort and derived notional smoking prevalence. To estimate the PAF for partners' smoking, we used the standard formula incorporating the proportion of non-smoking Australians living with an ever-smoking partner and relative risks associated with partner smoking., Results: An estimated 15,525 (13%) cancers in Australia in 2010 were attributable to tobacco smoke, including 8,324 (81%) lung, 1,973 (59%) oral cavity and pharynx, 855 (60%) oesophagus and 951 (6%) colorectal cancers. Of these, 136 lung cancers in non-smokers were attributable to partner tobacco smoke., Conclusions: More than one in eight cancers in Australia is attributable to tobacco smoking and would be avoided if nobody smoked., Implications: Strategies to reduce the prevalence of smoking remain a high priority for cancer control., (© 2015 The Authors.)

Because childhood rashes may be difficult to differentiate by appearance alone, it is important to consider the entire clinical presentation to help make the appropriate diagnosis. Considerations include the appearance and location of the rash; the clinical course; and associated symptoms, such as pruritus or fever. A fever is likely to occur with roseola, erythema infectiosum (fifth disease), and scarlet fever. Pruritus sometimes occurs with atopic dermatitis, pityriasis rosea, erythema infectiosum, molluscum contagiosum, and tinea infection. The key feature of roseola is a rash presenting after resolution of a high fever, whereas the distinguishing features in pityriasis rosea are a herald patch and a bilateral and symmetric rash in a Christmas tree pattern. The rash associated with scarlet fever usually develops on the upper trunk, then spreads throughout the body, sparing the palms and soles. Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children. Erythema infectiosum is characterized by a viral prodrome followed by the "slapped cheek" facial rash. Flesh-colored or pearly white papules with central umbilication occur with molluscum contagiosum, a highly contagious viral infection that usually resolves without intervention. Tinea is a common fungal skin infection in children that affects the scalp, body, groin, feet, hands, or nails. Atopic dermatitis is a chronic, relapsing inflammatory skin condition that may present with a variety of skin changes.

Acute traumatic central cord syndrome (ATCCS) occurs in more than 11,000 individuals annually. A common cause in older adult is a low-velocity hypertension neck injury. This article reviews ATCCS from the perspective of an older adult who, after a fall at his primary residence, sustained a facial laceration. Just prior to discharge, neurological deficits were noted, which required further investigation with magnetic resonance imaging. Subsequently, the findings required emergent surgical intervention. Emergency nurses should be familiar with muscle assessment, deep tendon reflex assessment, and nervous system dermatomes. The value of repeating the physical examination prior to discharge is discussed.

Background: 3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed., Methods: Cytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L, and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats. Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a rodent allograft model of high-grade glioma, both as a monotherapy and in combination with temozolomide (TMZ) and radiation therapy (XRT)., Results: 3-BrPA and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5% 3-BrPA wafer-treated animals had significantly increased survival compared with controls (P = .0027). The median survival of rats with the 50% DCA wafer increased significantly compared with both the oral DCA group (P = .050) and the controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination with TMZ had significantly increased survival over either therapy alone. No statistical difference in survival was noted when the wafers were added to the combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in combination with TMZ and XRT resulted in long-term survivorship of 30%., Conclusion: Intracranial delivery of 3-BrPA and DCA polymer was safe and significantly increased survival in an animal model of glioma, a potential novel therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a synergistic effect., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

PHACE (posterior fossa, hemangioma, arterial lesions, cardiac, and eye) syndrome consists of infantile hemangiomas of the head and neck along with a spectrum of noncutaneous anomalies. Neurodevelopmental abnormalities have also been noted. Here we describe the association between PHACE syndrome and abnormalities in oropharyngeal development and coordination manifesting as dysphagia or speech and language delay. A retrospective chart review was conducted of 34 patients with PHACE syndrome. Data were collected from prior clinical notes and radiographic studies and the results of a comprehensive questionnaire that those who attended the July 2012 PHACE Syndrome Family Conference completed. Seventeen of 34 patients with PHACE syndrome and signs or symptoms of dysphagia or speech or language problems were included for analysis. Nine had dysphagia, seven had a history of cardiac surgery, four had a posterior fossa malformation, and seven had lip or oropharynx hemangiomas. Speech or language delay was noted in 16; posterior fossa abnormalities and lip or oropharynx hemangiomas were the most commonly seen associated finding in this group. There was considerable overlap between subset populations with dysphagia, speech delay, and language delay. A subset of individuals with PHACE syndrome experience dysphagia, speech delay, or language delay. This risk seems to be greater in certain subsets of patients, including those with posterior fossa malformations or lip or oropharynx hemangiomas and those with a history of cardiac surgery. Although this descriptive study was not comprehensive enough to examine prevalence, the high incidence of dysphagia and speech and language delay seen in our cohort warrants future prospective studies to further investigate the association., (© 2014 Wiley Periodicals, Inc.)

Background: Severe air pollution generated by forest fires is becoming an increasingly frequent public health management problem. We measured the association between forest fire smoke events and hospital emergency department (ED) attendances in Sydney from 1996-2007., Methods: A smoke event occurred when forest fires caused the daily citywide average concentration of particulate matter (PM10 or PM2.5) to exceed the 99th percentile of the entire study period. We used a time-stratified case-crossover design and conditional logistic regression models adjusted for meteorology, influenza epidemics, and holidays to estimate odds ratios (OR) and 95% confidence intervals (CI) for ED attendances on event days compared with non-event days for all non-trauma ED attendances and selected cardiorespiratory conditions., Results: The 46 validated fire smoke event days during the study period were associated with same day increases in ED attendances for all non-trauma conditions (1.03, 95% CI 1.02, 1.04), respiratory conditions (OR 1.07, 95% CI 1.04, 1.10), asthma (OR 1.23, 95% CI 1.15, 1.30), and chronic obstructive pulmonary disease (OR 1.12, 95% CI 1.02, 1.24). Positive associations persisted for one to three days after the event. Ischaemic heart disease ED attendances were increased at a lag of two days (OR 1.07, 95% CI 1.01, 1.15) while arrhythmias had an inverse association at a lag of two days (OR 0.91, 95% CI 0.83, 0.99). In age-specific analyses, no associations present in children less than 15 years of age for any outcome, although a non-significant trend towards a positive association was seen with childhood asthma. A further association between smoke event and heart failure attendances was present for the 15-65 year age group, but not older adults at a lag of two days (OR 1.37 95% CI 1.05, 1.78)., Conclusion: Smoke events were associated with an immediate increase in presentations for respiratory conditions and a lagged increase in attendances for ischaemic heart disease and heart failure. Respiratory impacts were either absent or considerably attenuated in those <15 years. Similar to previous studies we found inconsistent associations between fire smoke and cardiovascular diseases. Better characterisation of the spectrum of population health risks is needed to guide public heath responses to severe smoke events as this exposure becomes increasingly common with global climate change.

The reaction of N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with acenaphthylene and indene leads not only to the formation of the expected [2 + 2] diazetidine cycloadducts but also to unexpected 2:1 adducts of MeTAD with substrate. The structures of the products derived from acenaphthylene were confirmed by X-ray crystallography. A similar distribution of products was afforded from indene. The 2:1 adducts appear to derive from a diradical intermediate, the radical centers of which are strongly stabilized by the bridging urazoyl ring and benzylic delocalization. The triplet states of these diradical intermediates may be trapped via exposure to molecular oxygen to afford oxygen-containing adducts. Computational studies at the (U)B3LYP/6-31G* level provide additional support for the conclusions of our experimental work.

Over 70 species of intertidal fishes from 12 families breathe air while emerging from water. Amphibious intertidal fishes generally have no specialized air-breathing organ but rely on vascularized mucosae and cutaneous surfaces in air to exchange both oxygen and carbon dioxide. They differ from air-breathing freshwater fishes in morphology, physiology, ecology and behaviour. Air breathing and terrestrial activity are present to varying degrees in intertidal fish species, correlated with the tidal height of their habitat. The gradient of amphibious lifestyle includes passive remainers that stay in the intertidal zone as tides ebb, active emergers that deliberately leave water in response to poor aquatic conditions and highly mobile amphibious skipper fishes that may spend more time out of water than in it. Normal terrestrial activity is usually aerobic and metabolic rates in air and water are similar. Anaerobic metabolism may be employed during forced exercise or when exposed to aquatic hypoxia. Adaptations for amphibious life include reductions in gill surface area, increased reliance on the skin for respiration and ion exchange, high affinity of haemoglobin for oxygen and adjustments to ventilation and metabolism while in air. Intertidal fishes remain close to water and do not travel far terrestrially, and are unlikely to migrate or colonize new habitats at present, although in the past this may have happened. Many fish species spawn in the intertidal zone, including some that do not breathe air, as eggs and embryos that develop in the intertidal zone benefit from tidal air emergence. With air breathing, amphibious intertidal fishes survive in a variable habitat with minimal adjustments to existing structures. Closely related species in different microhabitats provide unique opportunities for comparative studies., (© 2013 The Fisheries Society of the British Isles.)

Circumscribed juvenile pityriasis rubra pilaris (PRP) is an uncommon dermatosis. We describe the unusual clustering of circumscribed juvenile PRP cases in our pediatric dermatology clinic in 2011. A retrospective chart review was done of patients presenting during the summer of 2011 with classic findings of circumscribed juvenile PRP. Clinical data including past medical and family history, presenting symptoms, infectious disease history and evaluation, biopsy results, and management were recorded. Seven patients, ages 5 to 19 years, all had strikingly similar skin findings of pink to hyperpigmented, well-defined, scaly papules and plaques on their elbows, knees, dorsal hands, ankles, and Achilles tendons. Four of the seven also had palmoplantar involvement. Four were sibling pairs and the other three were unrelated. Streptococcus pyogenes infection was suspected as a trigger in four of the patients. The unusual clustering of this uncommon disease, along with the occurrence in two sibling pairs, suggests that a genetic susceptibility unmasked by an infectious agent may play a role in its pathogenesis., (© 2014 Wiley Periodicals, Inc.)

Background: There is a poor understanding of the interplay between cognitive and physiological functions in leading to falls. We hypothesized that poorer physiological function would modify the effect of poorer cognitive function on increased risk of falling in older people., Methods: A range of cognitive (executive function/attention, memory, processing speed, and visuospatial ability) and physiological functions (vision, proprioception, sway, leg strength, reaction time) were measured using standardized tests in 386 randomly selected adults aged 60-86. Incident falls were recorded over 12 months. Log-multinomial regression was used to model the relationships and test for interactions between cognition and physiological function in explaining the risk of single or multiple falls., Results: Overall, 94 people (24.4%) had a single fall, and 78 (20.2%) had multiple falls. No significant associations were observed between cognitive function and the risk of single falls. The risk of multiple falls was increased with poorer function in Stroop dot time (RR = 1.03, 95% CI [1.01, 1.05], p = .002) and Stroop word time (RR = 1.02 [1.01, 1.03], p = .001) and reduced with better function in Category Fluency (RR = 0.94 [0.91, 0.98], p = .001) and visuospatial function (RR = 0.95 [0.92, 0.98], p < .001). These associations were amplified by the presence of greater body sway, less ambulatory physical activity, slower reaction time and gait speed, weaker muscle strength, and poorer visual contrast (p for interactions <.05)., Conclusions: Preventing falls due to physiological impairments in community-dwelling older people may need to be tailored based on cognitive impairment, a key factor in their inability to compensate for physical decline.

A surprisingly large number of fish and amphibian species reproduce terrestrially despite the absence of the key evolutionary innovation of the amniotic egg. In contrast with shelled eggs of reptiles and birds, eggs of teleost fish and amphibians are typically much smaller and enclosed in relatively simple chorionic membranes. Incubation times may be brief or prolonged, and resultant hatchlings typically require the return to an aquatic habitat. Advantages of terrestrial incubation include the increased availability of warmer temperatures and avoidance of aquatic hypoxia, whereas disadvantages include desiccation, exposure to novel predators, and the risk of hatching into a hostile habitat. Hatching may be environmentally cued. Use of energy in the yolk may require trade-offs between growth of the embryo and extended incubation, as exemplified by a case study of the California Grunion. The physical challenges of terrestrial incubation, constraints for hatching, effects of egg size, and parental care are explored. Eight different types of early life history among anamniotic embryos incubating in a terrestrial environment are identified, with examples of these alternate routes to the invasion of land by vertebrates.

Dermatologists have been placed in a prime position to make new genetic discoveries. Tissue is easily obtained from the skin or mucosa for the study of germline and somatic mosaic disorders. This, along with the recent development of next-generation sequencing, makes dermatology an exciting field with essentially endless possibilities for discovering genes responsible for disease, better understanding complex molecular pathways, and eventually developing targeted therapies. To take advantage of this great opportunity, a basic understanding of the advances in genetic testing is vital. Herein we give an overview of next-generation sequencing, including some of the applications it may be used for. We also review various study designs for genetic discovery, each of their benefits and downfalls, and how they may be applied to the study of dermatologic disease., (© 2012 Wiley Periodicals, Inc.)

Background: Gait impairments are associated with falls and loss of independence. The study of factors associated with poorer gait may assist in developing methods to preserve mobility in older people. The aim of this study was to examine the associations between a range of cognitive functions and gait and gait variability in a population-based sample of older people., Methods: Gait and intra-individual gait variability measures were obtained using the GAITRite walkway in a sample of older people, aged 60-85 years (N = 422), randomly selected from the Tasmanian electoral roll. Raw scores from a cognitive battery were subjected to principal component analyses deriving four summary domains: executive function/attention, processing speed, memory, and visuospatial ability. Multivariable linear regression was used to examine associations between cognitive domains and gait measures adjusting for age, sex, ambulatory activity, medication use, and mood., Results: The mean age of the sample was 72.0 years (SD = 7.0), with 238 men (56%). Poorer executive function was independently associated with poorer performance in most absolute gait measures and with greater variability in double support phase and step time. Processing speed was associated with absolute gait measures and double support phase variability. Visuospatial ability was only associated with greater double support phase variability, independently of executive function and processing speed. Memory was not independently associated with any gait measure., Conclusions: In community-dwelling older people, executive function/attention and processing speed were associated with many aspects of gait, whereas visuospatial ability may only play a role in double support phase variability.

Objective: We examined the association between validated bushfire smoke pollution events and hospital admissions in three eastern Australian cities from 1994 to 2007., Methods: Smoke events were defined as days on which bushfire smoke caused the 24-hour citywide average concentration of airborne particles to exceed the 99(th) percentile of the daily distribution for the study period. We used a time-stratified case-crossover design to assess the association between smoke events and hospital admissions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for cardiovascular and respiratory conditions on event days compared with non-event days. Models were adjusted for daily meteorology, influenza epidemics and holidays., Results: Smoke events occurred on 58 days in Sydney (population: 3,862,000), 33 days in Wollongong (population: 406,000) and 50 days in Newcastle (population: 278,000). In Sydney, events were associated with a 6% (OR=1.06, 95%CI=1.02-1.09) same day increase in respiratory hospital admissions. Same day chronic obstructive pulmonary disease admissions increased 13% (OR=1.13, 95%CI=1.05-1.22) and asthma admissions by 12% (OR=1.12, 95%CI=1.05-1.19). Events were also associated with increased admissions for respiratory conditions in Newcastle and Wollongong., Conclusions: Smoke events were associated with increased hospital admissions for respiratory but not cardiovascular conditions. Large populations are needed to assess the impacts of brief exposures. Implications : Public health impacts from bushfire pollution events are likely to increase in association with a warming climate and more frequent severe fire weather., (© 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.)

Glucuronosyl diacylglycerides (GlcAGroAc2) are functionally important glycolipids and membrane anchors for cell wall lipoglycans in the Corynebacteria. Here we describe the complete synthesis of distinct acyl-isoforms of GlcAGroAc2 bearing both acylation patterns of (R)-tuberculostearic acid (C19:0) and palmitic acid (C16:0) and their mass spectral characterization. Collision-induced fragmentation mass spectrometry identified characteristic fragment ions that were used to develop "rules" allowing the assignment of the acylation pattern as C19:0 (sn-1), C16:0 (sn-2) in the natural product from Mycobacterium smegmatis, and the structural assignment of related C18:1 (sn-1), C16:0 (sn-2) GlcAGroAc2 glycolipids from M. smegmatis and Corynebacterium glutamicum. A synthetic hydrophobic octyl glucuronoside was used to characterize the GDP-mannose-dependent mannosyltransferase MgtA from C. glutamicum that extends GlcAGroAc2. This enzyme is an Mg(2+)/Mn(2+)-dependent metalloenzyme that undergoes dramatic activation upon reduction with dithiothreitol.

To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectively for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit., (Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Incidence rates of melanoma continue to rise, especially in young women, despite the enormous body of evidence that identifies ultraviolet radiation as a skin carcinogen. It is time for a change in societal norms, an increase in counseling of young adults about the risks of indoor tanning facilities, and to prevent young adults from tanning by introducing new legislation.

Background: Treatment of head and neck cancer with radiation often results in damage to surrounding normal tissues such as salivary glands. Permanent loss of function in the salivary glands often leads patients to discontinue treatment due to incapacitating side effects. It has previously been shown that IGF-1 suppresses radiation-induced apoptosis and enhances G2/M arrest leading to preservation of salivary gland function. In an effort to recapitulate the effects of IGF-1, as well as increase the likelihood of translating these findings to the clinic, the small molecule therapeutic Roscovitine, is being tested. Roscovitine is a cyclin-dependent kinase inhibitor that acts to transiently inhibit cell cycle progression and allow for DNA repair in damaged tissues., Methodology/principal Findings: Treatment with Roscovitine prior to irradiation induced a significant increase in the percentage of cells in the G(2)/M phase, as demonstrated by flow cytometry. In contrast, mice treated with radiation exhibit no differences in the percentage of cells in G(2)/M when compared to unirradiated controls. Similar to previous studies utilizing IGF-1, pretreatment with Roscovitine leads to a significant up-regulation of p21 expression and a significant decrease in the number of PCNA positive cells. Radiation treatment leads to a significant increase in activated caspase-3 positive salivary acinar cells, which is suppressed by pretreatment with Roscovitine. Administration of Roscovitine prior to targeted head and neck irradiation preserves normal tissue function in mouse parotid salivary glands, both acutely and chronically, as measured by salivary output., Conclusions/significance: These studies suggest that induction of transient G(2)/M cell cycle arrest by Roscovitine allows for suppression of apoptosis, thus preserving normal salivary function following targeted head and neck irradiation. This could have an important clinical impact by preventing the negative side effects of radiation therapy in surrounding normal tissues.

APOBEC3G (A3G) is packaged into human immunodeficiency virus type 1 (HIV-1) virions unless HIV-1 virion infectivity factor (Vif) counteracts it. Virion A3G restricts HIV-1 reverse transcription and integration in target cells. Some A3G in producer cells colocalizes with specific cytoplasmic structures, in what are called "A3G complexes" here. Functional effects of producer cell A3G complexes on HIV-1 replication were studied. HeLa cells were cotransfected with HIV-1 constructs producing pseudoviruses, as well as either wild-type (WT) A3G or a mutant A3G (C97A, Y124A, W127A, or D128K A3G). Pseudovirus particle production was decreased from cells expressing any of the A3Gs that formed complexes by 24 h after transfection, relative to cells with C97A A3G that did not form detectable A3G complexes by 24 h or A3G-negative cells. The intracellular HIV-1 Gag half-life was shorter in cells containing A3G complexes than in those lacking complexes. HIV-1 virion output was decreased in a single round of replication from a T cell line containing A3G complexes (CEM cells) after infection with Vif-negative HIV-1, compared to Vif-positive HIV-1 that depleted A3G. Levels of production of Vif-negative and Vif-positive virus were similar from cells not containing A3G (CEM-SS cells). Knockdown of the mRNA processing body (P-body) component RCK/p54, eliminated A3G complex formation, and increased HIV-1 production. We conclude that endogenous A3G complexes in producer cells decrease HIV-1 production if not degraded by Vif.

Background: There is a paucity of research on substance use in the pediatric trauma population. This study aims to describe trends in substance use and screening in the Canadian pediatric trauma population., Materials and Methods: A retrospective review of the London Health Sciences Centre trauma database from April 1999 to January 2009 identified patients less than 18 years old admitted after major trauma [injury severity score (ISS) > 12]. Data extracted included age, gender, ISS, blood alcohol concentration (BAC), and results of toxicology screens., Results: BAC data were available for 799 patients and toxicology screens for 761 patients. BAC testing was completed in 30% (21% positive). Toxicology screens were completed in 7% (44% positive). Increasing age was associated with screening for alcohol (odds ratio = 1.4; 95% confidence interval 1.3-1.5). Screening for drug use had a bimodal distribution, with no children aged 4-10 years screened. Those screened for drugs and alcohol had a significantly higher ISS than those not tested (BAC 28 versus 23, P < 0.001, toxin screening 29 versus 24, P = 0.003). The most common ingestions were alcohol, benzodiazepines, cannabinoids, and opiates., Conclusions: Screening for drugs and alcohol is sporadic in the pediatric trauma population. Further study utilizing a universal approach to drug and alcohol screening is needed to further delineate the true prevalence of substance use in this population.

Background: it is uncertain as to which measures of gait best predict those who are likely to fall. Our aim was to investigate the associations of gait and gait variability measures with incident falls risk., Methods: individuals aged 60-86 years (n = 412) were randomly selected from the Tasmanian electoral roll. Average gait and gait variability measures were collected on a computerised walkway. Falls were recorded prospectively over 12 months. Log multinomial regression was used to estimate the relative risk of single and multiple falls associated with gait measures. Covariates included age, sex, sensorimotor and cognitive measures, mood and medications., Results: in this population-based study greater intra-individual variability in step length and double-support phase were linearly associated with increased risk of multiple falls (P = 0.04). Non-linear associations with multiple falls were found for gait speed P = 0.002, cadence P = 0.004 and step time variability P = 0.03. None of the gait measures predicted risk of single falls., Conclusion: there is an increased risk of multiple falls, but not single falls, in older people with poorer gait. Specific measures of gait and gait variability seem to confer this risk and may be amenable to interventions designed to reduce the risk of multiple falls in older people.