Canadian guidelines for rhinosinusitis: practical tools for the busy clinician

Acute bacterial rhinosinusitis (ABRS) and chronic rhinosinusitis (CRS) frequently present in clinical practice. Guidelines for management of these conditions have been published extensively in the past. However, a set of guidelines that addressed issues specific to the Canadian environment while offering clear guidance for first-line clinicians was needed, and resulted in the recent publication of Canadian clinical practice guidelines for ABRS and CRS. In addition to addressing issues specific to Canadian physicians, the presented guidelines are applicable internationally, and offer single algorithms for the diagnosis and management of ABRS and CRS, as well as expert opinion in areas that do not have an extensive evidence base. This commentary presents major points from the guidelines, as well as the intended impact of the guidelines on clinical practice

Quantum critical lines in holographic phases with (un)broken symmetry

All possible scaling IR asymptotics in homogeneous, translation invariant holographic phases preserving or breaking a U(1) symmetry in the IR are classified. Scale invariant geometries where the scalar extremizes its effective potential are distinguished from hyperscaling violating geometries where the scalar runs logarithmically. It is shown that the general critical saddle-point solutions are characterized by three critical exponents ($\theta, z, \zeta$). Both exact solutions as well as leading behaviors are exhibited. Using them, neutral or charged geometries realizing both fractionalized or cohesive phases are found. The generic global IR picture emerging is that of quantum critical lines, separated by quantum critical points which correspond to the scale invariant solutions with a constant scalar.Comment: v3: 32+29 pages, 2 figures. Matches version published in JHEP. Important addition of an exponent characterizing the IR scaling of the electric potentia

Usefulness of event-related potentials in the assessment of mild cognitive impairment

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine if changes in latencies and amplitudes of the major waves of Auditory Event-Related Potentials (AERP), correlate with memory status of patients with mild cognitive impairment (MCI) and conversion to Alzheimer's disease (AD).</p> <p>91 patients with MCI (mean ± SD age = 66.6 ± 5.4, MMSE score = 27.7) and 30 age-matched healthy control (AMHC) subjects (mean ± SD age = 68.9 ± 9.9) were studied. 54 patients were re-examined after an average period of 14(± 5.2) months. During this time period 5 patients converted to AD. Between-group differences in latency and amplitude of the major AERP waves (N200, P300 and Slow Wave) were determined. Within each group, correlation coefficients (CC) between these characteristics of the different AERP waves were calculated. Finally, for patients, CCs were determined among each AERP wave and their age and MMSE scores. Confirmatory factor analysis (CFA) was used to examine the underlying structure of waveforms both in the control and the patient groups.</p> <p>Results</p> <p>Latencies of all major AERP components were prolonged in patients compared to controls. Patients presented with significantly higher N200 amplitudes, but no significant differences were observed in P300 amplitudes. Significant differences between follow-up and baseline measurements were found for P300 latency (p = 0.009), N200 amplitude (p < 0.001) and P300 amplitude (p = 0.05). MMSE scores of patients did not correlate with latency or amplitude of the AERP components. Moreover, the establishment of a N200 latency cut-off value of 287 ms resulted in a sensitivity of 100% and a specificity of 91% in the prediction of MCI patients that converted to AD.</p> <p>Conclusion</p> <p>Although we were not able to establish significant correlations between latencies and amplitudes of N200, P300 and SW and the patients' performance in MMSE, which is a psychometric test for classifying patients suffering from MCI, our results point out that the disorganization of the AERP waveform in MCI patients is a potential basis upon which a neurophysiologic methodology for identifying and "staging" MCI can be sought. We also found that delayed N200 latency not only identifies memory changes better than the MMSE, but also may be a potential predictor of the MCI patients who convert to AD.</p

High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy

BACKGROUND: The risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications. METHODS: We retrospectively reviewed the clinical outcome of 233 patients with a primary extremity soft tissue sarcoma treated between 1990 – 2000 with a mean follow-up of 35.8 (4–120) months in our institute. 41 patients had high grade, deep and large tumours (>8 cm), an AJCC stage III (no evidence of metastasis prior to treatment) and were treated with limb salvage surgery and irradiation but stayed without additional chemotherapy. Two groups of patients were compared: the first group received postoperative RTX after tumour resection (n = 33); the second group was treated with preoperative RTX (n = 8). Both groups did not differ concerning clinical parameters. We analysed primary and secondary outcomes. RESULTS: 56% (23/41) of the population developed metastatic disease, 24% (10/41) local recurrence. The risk of metastasis was higher in the group with preoperative irradiation (p = 0.046). The overall (p = 0.0248) and relapse free survival (p = 0.104) were worse in this group. The delay to tumour resection amounted 8 weeks on average in the preoperative group. Local control was not different (p = 0.38) in both study groups. Wound infections and other combined therapy related complications were equally distributed (p = 0.22). CONCLUSION: Without chemotherapy there remains a high risk of metastasis in AJCC grade 3 patients. In high risk patients treated without chemotherapy the elapsed time to tumour resection after preoperative radiation might contribute to the development of metastasis. This outcome may support the thesis that a combination of RTX and offensive multimodal treatment protocols is advantageous in such a subset of patient

Regional variations in and correlates of disability-free life expectancy among older adults in China

<p>Abstract</p> <p>Background</p> <p>Considerable socioeconomic and health inequalities have been reported in China. However, because of a lack of appropriate data, limited research has been conducted on variations in disability-free life expectancy (DFLE) among older adults. This study aimed to use the most up-to-date disability survey data to explore geographical variations in DFLE at age 60 in China and to identify the socioeconomic and health care factors that partially account for these variations.</p> <p>Methods</p> <p>This study used 2006 mortality data extrapolated from the 1990 and 2000 Census and disability data from a national disability survey conducted in 2006. Disability was performance based and was diagnosed by trained physicians. DFLE was calculated by region using the Sullivan method. Multiple linear regression models by gender were conducted to explore correlates of DFLE.</p> <p>Results</p> <p>DFLE at age 60 varied widely by region, from 11.2 to 20.8 years in 2006. Per capita gross domestic product, proportion of urban residents, and access to health care were the primary factors associated with geographical variations in DFLE.</p> <p>Conclusion</p> <p>The pattern of differences in DFLE by region mirrors the pattern of regional economic development in China. Countermeasures to decrease regional differences in DFLE include accelerating regional economic development and improving health care distribution.</p

Hydroxybenzothiazoles as New Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1)

17β-estradiol (E2), the most potent estrogen in humans, known to be involved in the development and progession of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-HSD1, which catalyses the reduction of the weak estrogen estrone (E1) to E2, is often overexpressed in breast cancer and endometriotic tissues. An inhibition of 17β-HSD1 could selectively reduce the local E2-level thus allowing for a novel, targeted approach in the treatment of EDD. Continuing our search for new nonsteroidal 17β-HSD1 inhibitors, a novel pharmacophore model was derived from crystallographic data and used for the virtual screening of a small library of compounds. Subsequent experimental verification of the virtual hits led to the identification of the moderately active compound 5. Rigidification and further structure modifications resulted in the discovery of a novel class of 17β-HSD1 inhibitors bearing a benzothiazole-scaffold linked to a phenyl ring via keto- or amide-bridge. Their putative binding modes were investigated by correlating their biological data with features of the pharmacophore model. The most active keto-derivative 6 shows IC50-values in the nanomolar range for the transformation of E1 to E2 by 17β-HSD1, reasonable selectivity against 17β-HSD2 but pronounced affinity to the estrogen receptors (ERs). On the other hand, the best amide-derivative 21 shows only medium 17β-HSD1 inhibitory activity at the target enzyme as well as fair selectivity against 17β-HSD2 and ERs. The compounds 6 and 21 can be regarded as first benzothiazole-type 17β-HSD1 inhibitors for the development of potential therapeutics

Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor

BACKGROUND: Zellweger syndrome (ZS) is a fatal inherited disease caused by peroxisome biogenesis deficiency. Patients are characterized by multiple disturbances of lipid metabolism, profound hypotonia and neonatal seizures, and distinct craniofacial malformations. Median live expectancy of ZS patients is less than one year. While the molecular basis of peroxisome biogenesis and metabolism is known in considerable detail, it is unclear how peroxisome deficiency leads to the most severe neurological symptoms. Recent analysis of ZS mouse models has all but invalidated previous hypotheses. HYPOTHESIS: We suggest that a regulatory rather than a metabolic defect is responsible for the drastic impairment of brain function in ZS patients. TESTING THE HYPOTHESIS: Using microarray analysis we identify diazepam binding inhibitor/acyl-CoA binding protein (DBI) as a candidate protein that might be involved in the pathogenic mechanism of ZS. DBI has a dual role as a neuropeptide antagonist of GABA(A) receptor signaling in the brain and as a regulator of lipid metabolism. Repression of DBI in ZS patients could result in an overactivation of GABAergic signaling, thus eventually leading to the characteristic hypotonia and seizures. The most important argument for a misregulation of GABA(A) in ZS is, however, provided by the striking similarity between ZS and "benzodiazepine embryofetopathy", a malformation syndrome observed after the abuse of GABA(A) agonists during pregnancy. IMPLICATIONS OF THE HYPOTHESIS: We present a tentative mechanistic model of the effect of DBI misregulation on neuronal function that could explain some of the aspects of the pathology of Zellweger syndrome

Population variation in brain size of nine-spined sticklebacks (Pungitius pungitius) - local adaptation or environmentally induced variation?

Abstract Background Most evolutionary studies on the size of brains and different parts of the brain have relied on interspecific comparisons, and have uncovered correlations between brain architecture and various ecological, behavioural and life-history traits. Yet, similar intraspecific studies are rare, despite the fact that they could better determine how selection and phenotypic plasticity influence brain architecture. We investigated the variation in brain size and structure in wild-caught nine-spined sticklebacks (Pungitius pungitius) from eight populations, representing marine, lake, and pond habitats, and compared them to data from a previous common garden study from a smaller number of populations. Results Brain size scaled hypo-allometrically with body size, irrespective of population origin, with a common slope of 0.5. Both absolute and relative brain size, as well as relative telencephalon, optic tectum and cerebellum size, differed significantly among the populations. Further, absolute and relative brain sizes were larger in pond than in marine populations, while the telencephalon tended to be larger in marine than in pond populations. These findings are partly incongruent with previous common garden results. A direct comparison between wild and common garden fish from the same populations revealed a habitat-specific effect: pond fish had relatively smaller brains in a controlled environment than in the wild, while marine fish were similar. All brain parts were smaller in the laboratory than in the wild, irrespective of population origin. Conclusion Our results indicate that variation among populations is large, both in terms of brain size and in the size of separate brain parts in wild nine-spined sticklebacks. However, the incongruence between the wild and common garden patterns suggests that much of the population variation found in the wild may be attributable to environmentally induced phenotypic plasticity. Given that the brain is among the most plastic organs in general, the results emphasize the view that common garden data are required to draw firm evolutionary conclusions from patterns of brain size variability in the wild.</p

Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows

Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed