Organic Photovoltaics: Understanding the Preaggregation of Polymer Donors in Solution and Its Morphological Impact.
In bulk-heterojunction organic solar cells, it is well established that the active-layer morphology significantly impacts device performance. However, morphology control remains very challenging. An interesting step in that direction was recently provided by the development of polymer donors that display a temperature-dependent aggregation behavior in solution; the aggregation characteristics were found indeed to play a determining role in the eventual active-layer morphology. Here, a combination of thermodynamic analyses, molecular dynamics simulations, and long-range corrected density functional theory calculations enables us (i) to establish the Flory-Huggins interaction parameter, χ, as a useful figure of merit that allows us to integrate the contributions from all inter-related molecular interactions and to describe the extent of polymer preaggregation in solution at room temperature; (ii) to correlate the χ values for various polymer solutions to the extent of polymer aggregation and the morphological characteristics of the active layers; and (iii) to assess how polymer-polymer and polymer-solvent intermolecular interactions contribute to the variations in χ values among different polymer solutions. We have chosen to examine four representative polymer donors (PBT4T-2OD, PBTff4T-2OD, PffBT4T-2OD, and PffBTff4T-2DT) in solution in chlorobenzene or dichlorobenzene. With χ as a robust bridge, our results provide an unprecedented, detailed description of the relationships among intermolecular interactions, extent of polymer solution aggregation, and morphological features of the active layers.


Acute increase of complexity in the neurocardiovascular dynamics following carotid stenting.
Percutaneous carotid angioplasty and stenting (CAS) has been used to improve cerebral circulation and autoregulation. However, whether CAS ameliorates the autonomic regulatory dynamics remains unclear. This prospective study examines the neurocardiovascular dynamics following carotid stenting. Thirty minutes electrocardiograms were recorded at three different time points (pre-operative, 1-h post-operative, 1-day post-operative) on twelve male patients (mean age 70.8 ± 9.6 years) receiving unilateral primary CAS. The HR data were analyzed by the conventional heart rate variability (HRV) and the multiscale entropy (MSE) methods; the former associates with autonomic activities and the latter quantifies the regulatory complexity of heart beat intervals. Loss of complexity at multiple scales has been associated with decoupled regulatory network in vivo. Conventional HRV indices showed no difference after CAS. Complexity indices increased significantly on scales 2-8 at 1-h and on scales 2-3 1-day post-treatment. The lower scale MSE (1-5) correlated with the frequency components of conventional HRV indices. The increased complexity could imply a restoration of the neurocardiovascular dynamics on the path to a healthier state. Primary CAS can induce a recovery in the neurocardiovascular regulatory dynamics in patients with high-grade carotid stenosis.


Lectin Microarray-Based Sero-Biomarker Verification Targeting Aberrant O-Linked Glycosylation on Mucin 1.
Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC.


Dysregulation of INF2-mediated mitochondrial fission in SPOP-mutated prostate cancer.
Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alternations. SPOP (Speckle-type POZ Protein) was one of the most frequently mutated genes in primary prostate cancer, suggesting SPOP is a potential driver of prostate cancer development and progression. However, how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. ER-localized isoform of the formin protein inverted formin 2 (INF2) mediates actin polymerization at ER-mitochondria intersections and facilitates DRP1 recruitment to mitochondria, which is a critical step in mitochondrial fission. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. INF2 mutant escaping from SPOP-mediated ubiquitination is more potent in prompting mitochondrial fission. Moreover, prostate cancer-associated SPOP mutants increase INF2 localization in ER and promote mitochondrial fission, probably through a dominant-negative effect to inhibit endogenous SPOP. Moreover, INF2 is important for SPOP inactivation-induced prostate cancer cell migration and invasion. These findings reveal novel molecular events underlying the regulation of INF2 function and localization, and provided insights in understanding the relationship between SPOP mutations and dysregulation of mitochondrial dynamics in prostate cancer.


Proteolysis of the collagen fibril in osteoarthritis.
The development of cartilage pathology in osteoarthritis involves excessive damage to the collagen fibrillar network, which appears to be mediated primarily by the chondrocyte-generated cytokines interleukin-1 and tumour necrosis factor alpha and the collagenases matrix metalloproteinase-1 (MMP-1) and MMP-13. The damage to matrix caused by these and other MMPs can result in the production of sufficient degradation products that can themselves elicit further degradation, leading to chondrocyte differentiation and eventually matrix mineralization and cell death. Knowledge of these MMPs, cellular receptors and cytokine pathways, and the ability to selectively antagonize them by selective blockade of function, may provide valuable therapeutic opportunities in the treatment of osteoarthritis and other joint diseases involving cartilage resorption, such as rheumatoid arthritis. The ability to detect the products of these degradative events released into body fluids of patients may enable us to monitor disease activity, predict disease progression and determine more rapidly the efficacy of new therapeutic agents.


(1-->3)-Beta-D-glucans and respiratory health: a review of the scientific evidence.
(1-->3)-Beta-D-glucan are non-allergenic structural cell wall components of most fungi that have been suggested to play a causal role in the development of respiratory symptoms associated with indoor fungal exposure. This review describes the currently available epidemiological literature on health effects of (1-->3)-beta-D-glucan, focusing on atopy, airway inflammation and symptoms, asthma, and lung function. In addition to population studies, studies in human volunteers experimentally exposed to (1-->3)-beta-D-glucan are described as well as relevant animal studies. Furthermore, the review discusses exposure assessment methods, the potential for exposure control and it concludes with identifying research needs. The observational and experimental studies reviewed suggested some association between (1-->3)-beta-D-glucan exposure, airway inflammation and symptoms, however, results were mixed and specific symptoms and potential underlying inflammatory mechanisms associated with exposure could not be identified. Large observational studies using well validated exposure assessment methods are needed to further our knowledge regarding the potential health effects of indoor (1-->3)-beta-D-glucan exposure. The currently available epidemiological data do not permit conclusions to be drawn regarding the presence (or absence) of an association between environmental (1-->3)-beta-D-glucan exposure and specific adverse health effects, nor is it clear from the currently available evidence which specific immunological mechanisms underlie the presumed health effects. More and larger observational studies are needed to asses whether (1-->3)-beta-D-glucan exposure plays a significant role in respiratory morbidity. In addition, existing methods to assess environmental (1-->3)-beta-D-glucan exposure require validation and further development before they can be used routinely in large scale epidemiological studies.


Diversification, biogeographic pattern, and demographic history of Taiwanese Scutellaria species inferred from nuclear and chloroplast DNA.
The ragged topography created by orogenesis generates diversified habitats for plants in Taiwan. In addition to colonization from nearby mainland China, high species diversity and endemism of plants is also present in Taiwan. Five of the seven Scutellaria species (Lamiaceae) in Taiwan, for example, are endemic to the island. Hypotheses of multiple sources or in situ radiation have arisen to explain the high endemism of Taiwanese species. In this study, phylogenetic analyses using both nuclear and chloroplast markers revealed the multiple sources of Taiwanese Scutellaria species and confirmed the rapid and recent speciation of endemic species, especially those of the "indica group" composed of S. indica, S. austrotaiwanensis, S. tashiroi, and S. playfairii. The common ancestors of the indica group colonized first in northern Taiwan and dispersed regionally southward and eastward. Climate changes during glacial/interglacial cycles led to gradual colonization and variance events in the ancestors of these species, resulting in the present distribution and genetic differentiation of extant populations. Population decline was also detected in S. indica, which might reflect a bottleneck effect from the glacials. In contrast, the recently speciated endemic members of the indica group have not had enough time to accumulate much genetic variation and are thus genetically insensitive to demographic fluctuations, but the extant lineages were spatially expanded in the coalescent process. This study integrated phylogenetic and population genetic analyses to illustrate the evolutionary history of Taiwanese Scutellaria of high endemism and may be indicative of the diversification mechanism of plants on continental islands.


A Retrospective Study of the Pattern of Sexually Transmitted Infections in Males: Viral Infections in Emerging Trend.
Sexually transmitted infections (STIs) continue to be a major public health problem with significant burden on the society even after so many health care programmes being organized by the governmental and non-governmental organizations and awareness created among general public about STIs. Male patients are common visitors to STI clinic than females who are generally traced as a contact in our society. The aim of this study was to give an overview of the pattern of STIs among males at a tertiary care teaching hospital over a period of 5 years. A retrospective chart review of the data collected from the clinical records of all male patients, who had attended the STI clinic of Chengalpattu Medical College Hospital, Chengalpattu, Tamil Nadu, for various complaints during the 5 year period from 2010 to 2014 was carried out. All male patients with confirmed STIs were included in the study and those patients without any evidence of STIs either clinically or serologically were excluded from the study. Out of the 4454 male cases who had attended the STI clinic, 175 (3.93%) patients had STIs. Genital wart accounted for the maximum number among the STIs with 61 cases (34.86%), followed by genital herpes 56 (32%), urethral discharge 19(10.86%), non-herpetic genital ulcerative diseases 17(9.71%) and serological test for syphilis (RPR) was reactive in 22 (12.57%) patients. HIV was positive in 68 (1.53%) among the total 4454 male patients attended the clinic. Viral STIs occur significantly more than the bacterial STIs because of its incurable and recurrent nature. Health programmes should be still more focused on creating awareness about the minor STIs and to remove the stigma so that the patients attend the proper health care facilities in the early stage itself for treatment thereby, complications and further transmission of the STIs can be avoided.


Retrieval of granular bait by the Argentine ant (Hymenoptera: Formicidae): effect of clumped versus scattered dispersion patterns.
Argentine ants, Linepithema humile (Mayr), use mass recruitment foraging, with clumped prey items being retrieved more efficiently than dispersed prey. However, in prior field experiments, granular baits, whether dispensed in containers or broadly scattered, had a similar impact on Argentine ant populations. In laboratory experiments, granular insecticide bait was encountered faster by Argentine ant workers and more granules were initially returned to the colony when the granules were scattered versus clumped. After 2 h, granules from both dispersion patterns were retrieved equally. Our results suggest that Argentine ant colonies adjust their foraging patterns to resources of different quality (prey versus bait). Also, foraging activity patterns for bait in the laboratory are consistent with prior field results demonstrating no efficacy advantages to discrete granular bait placements.


Detection of genital HPV types in fingertip samples from newly sexually active female university students.
Little is known about detection of genital human papilloma virus (HPV) types in women's fingertips. The study objectives were to determine the presence of genital HPV types in fingertip samples and the agreement between fingertip and genital samples for detecting HPV. At triannual visits, genital and fingertip samples were collected from female university students and tested for 37 HPV genotypes by PCR-based assay. Type-specific concordance between paired fingertip and genital samples was evaluated using kappa statistics for percent positive agreement (kappa+). Paired samples with type-specific concordant fingertip and genital results were selected for variant characterization. A total of 357 fingertip samples were collected from 128 women. HPV prevalence in fingertip samples was 14.3%. Although percent positive agreement between fingertips and genitals for detecting type-specific HPV was low (17.8%; kappa+ = 0.17; 95% confidence interval, 0.10-0.25), 60.4% of type-specific HPV detected in the fingertips was detected in a concurrent genital sample. All but one of 28 paired concordant samples were positive for the same type-specific variant in the fingertip and genital sample. Redetection of HPV types at the subsequent visit was more common in genital samples (73.3%) than in fingertip samples (14.5%; P < 0.001). Detection of genital HPV types in the fingertips was not uncommon. Although impossible to distinguish between deposition of DNA from the genitals to the fingertips and true fingertip infection, the rarity of repeat detection in the fingertips suggests that deposition is more common. Finger-genital transmission is plausible but unlikely to be a significant source of genital HPV infection.


A combined approach of bedside clinical examination and flexible endoscopic evaluation of swallowing in poststroke dysphagia: A pilot study.
As with most neurologic conditions, stroke involves impairment of the swallowing mechanism. This could be a spectrum of issues, the worst of which is aspiration. At the same time, the prolonged presence of a naso-gastric tube (NGT) has its own morbidity. Flexible endoscopic evaluation of swallowing (FEES) is one reliable method to assess the structural and functional status of the oropharynx and larynx, during the swallowing process. To study the utility of FEES in decision-making with respect to resumption of oral intake in stroke patients. To document the findings of FEES in stroke patients, and to look for correlations between these and the site of stroke. Protocol insertion of naso-gastric tube in all stroke patients, at presentation. Initial assessment by a neurologist and swallowing therapist, depending on cognitive status of the patient. All patients underwent MRI Brain with diffusion weighted sequences. After detailed clinical examination, they underwent swallow exercises under the supervision of a trained swallowing therapist. The decision to remove NGT was taken clinically by the combined decision of neurologist and swallowing therapist. Then all patients underwent FEES by the ENT surgeon. The final decision for NGT removal was taken as per the FEES findings. Sixteen stroke patients underwent the FEES procedure during a period of six months. The oropharyngeal and laryngeal findings varied depending on the area of stroke involvement. Of these, change in decision regarding swallowing rehabilitation or NGT removal was needed in four patients, following the FEES findings. FEES is an easy, efficient and reliable method to evaluate the swallowing status in stroke patients. In combination with good bedside clinical examination and swallow exercises, it can be a good tool in assessing patients with post- stroke dysphagia. Post-stroke rehabilitation and prevention of aspiration pneumonia can be effectively done with the help of FEES.


[Predicting the course of wound healing after appendectomy using the hydroxyproline test].
A test for free hydroxyproline in blood plasma, urine, and wound exudate was conducted in a group of children who were operated on for acute catarrhal and destructive forms of appendicitis in an uncomplicated or complicated post-operative wound process. The changes in the concentration of the biochemical index were most regular in the wound exudate. Free hydroxyproline increased after the operation, reached highest values in 48 hours, and then reduced coming close to the control values 5-6 days after. In wound complications it increased three- to four-fold as compared to the control values, which could serve as an informative test in predicting the course of the postoperative wound process in children.


Nucleus-encoded periplastid-targeted EFL in chlorarachniophytes.
Chlorarachniophytes are cercozoan amoeboflagellates that acquired photosynthesis by enslaving a green alga, which has retained a highly reduced nucleus called a nucleomorph. The nucleomorph lacks many genes necessary for its own maintenance and expression, suggesting that some genes have been moved to the host nucleus and their products are now targeted back to the periplastid compartment (PPC), the reduced eukaryotic cytoplasm of the endosymbiont. Protein trafficking in chlorarachniophytes is therefore complex, including nucleus-encoded plastid-targeted proteins, nucleomorph-encoded plastid-targeted proteins, and nucleus-encoded periplastid-targeted proteins. A major gap in our understanding of this system is the PPC-targeted proteins because none have been described in any chlorarachniophytes. Here we describe the first such protein, the GTPase EFL. EFL was characterized from 7 chlorarachniophytes, and 2 distinct types were found. One is related to foraminiferan EFL and lacks an amino-terminal extension. The second, distantly related, type encodes an amino-terminal extension consisting of a signal peptide followed by sequence sharing many characteristics with transit peptides from nucleus-encoded plastid-targeted proteins and which we conclude is most likely PPC targeted. Western blotting with antibodies specific to putative host and PPC-targeted EFL from the chlorarachniophytes Bigelowiella natans and Gymnochlora stellata is consistent with posttranslational cleavage of the leaders from PPC-targeted proteins. Immunolocalization of both proteins in B. natans confirmed the cytosolic location of the leaderless EFL and a distinct localization pattern for the PPC-targeted protein but could not rule out a plastid location (albeit very unlikely). We sought other proteins with a similar leader and identified a eukaryotic translation initiation factor 1 encoding a bipartite extension with the same properties. Transit peptide sequences were characterized from all 3 classes of targeted protein by comparing all examples of each class from expressed sequence tag surveys of B. natans and G. stellata. No recognizable difference between plastid- and PPC-targeted proteins was observed, but nucleomorph-encoded transit peptides differ, likely reflecting high AT content of nucleomorph genomes. Taken together, the data suggest that the system that directs proteins to the PPC in chlorarachniophytes uses a bipartite targeting sequence, as does the PPC-targeting system that evolved independently in cryptomonads.


Cross-validated factor structures and factor-based subscales for PASS and PASSING.
Program Analysis of Service Systems (PASS 3) and Program Analysis of Service Systems' Implementation of Normalization Goals (PASSING) are used internationally to assess service quality in mental retardation and other fields. In two studies, we derived and cross-validated the factor structures of these program evaluation instruments. In Study 1, based on 626 PASS 3 evaluations, four factors provided a good fit to the cross-validation data. In Study 2, based on 633 PASSING evaluations, three factors furnished a good fit to the cross-validation data. Similarities between the two factor structures, parallels with the structural and functional service dimensions emphasized in ecological approaches to evaluation, and practical uses in program evaluation of subscales based on the factors were discussed.


Energy landscape of a native protein: jumping-among-minima model.
We have investigated energy landscape of human lysozyme in its native state by using principal component analysis and a model, jumping-among-minima (JAM) model. These analyses are applied to 1 nsec molecular dynamics trajectory of the protein in water. An assumption embodied in the JAM model allows us to divide protein motions into intra-substate and inter-substate motions. By examining intra-substate motions, it is shown that energy surfaces of individual conformational substates are nearly harmonic and mutually similar. As a result of principal component analysis and JAM model analysis, protein motions are shown to consist of three types of collective modes, multiply hierarchical modes, singly hierarchical modes, and harmonic modes. Multiply hierarchical modes, the number of which accounts only for 0.5% of all modes, dominate contributions to total mean-square atomic fluctuation. Inter-substate motions are observed only in a small-dimensional subspace spanned by the axes of multiplyhierarchical and singly hierarchical modes. Inter-substate motions have two notable time components: faster component seen within 200 psec and slower component. The former involves transitions among the conformational substates of the low-level hierarchy, whereas the latter involves transitions of the higher level substates observed along the first four multiply hierarchical modes. We also discuss dependence of the subspace, which contains conformational substates, on time duration of simulation.


Validation of the Penn Acoustic Neuroma Quality-of-Life Scale (PANQOL) for Spanish-Speaking Patients.
Objective To perform translation, cross-cultural adaptation, and validation of the Penn Acoustic Neuroma Quality-of-Life Scale (PANQOL) to the Spanish language. Study Design Prospective study. Setting Tertiary neurotologic referral center. Subjects and Methods PANQOL was translated and translated back, and a pretest trial was performed. The study included 27 individuals diagnosed with vestibular schwannoma. Inclusion criteria were adults with untreated vestibular schwannoma, diagnosed in the past 12 months. Feasibility, internal consistency, test-retest reliability, construct validity, and ceiling and floor effects were assessed for the present study. Results The mean overall score of the PANQOL was 69.21 (0-100 scale, lowest to highest quality of life). Cronbach's α was 0.87. Intraclass correlation coefficient was performed for each item, with an overall score of 0.92. The κ coefficient scores were between moderate and almost perfect in more than 92% of patients. Anxiety and energy domains of the PANQOL were correlated with both physical and mental components of the SF-12. Hearing, balance, and pain domains were correlated with the SF-12 physical component. Facial and general domains were not significantly correlated with any component of the SF-12. Furthermore, the overall score of the PANQOL was correlated with the physical component of the SF-12. Conclusion Feasibility, internal consistency, reliability, and construct validity outcomes in the current study support the validity of the Spanish version of the PANQOL.


Membrane properties of aggregate of collagenase-dissociated rat heart cells.
Aggregates of collagenase-dissociated neonatal rat heart cells have been tested for several membrane properties and shown to be comparable with cells from the intact heart. Action potentials, recorded from driven aggregates, are fully suppressed by tetrodotoxin (TTX). Under Mn2+, the plateau phase of the action potential disappears and no more mechanical activity can be detected. In aggregates, therefore, apparently both the fast sodium inward current and a slow inward current, which is at least partly carried by Ca2+ ions, contribute to the action potential. Pacemaker activity in spontaneously active aggregates is enhanced by adrenaline and slowed down by acetylcholine. Adrenaline also increases the plateau phase amplitude of the action potential and thereby the rate of repolarization. Acetylcholine shortens the action potential duration and increases the resting membrane potential. The electrical coupling between the cells in the aggregates is so tight that the aggregate seems to behave passively, like a single cell. It is concluded that aggregates of collagenase-dissociated neonatal rat heart cells may be used to study active electrical properties using the voltage clamp technique.


Phosphorylation regulates TRPV1 association with β-arrestin-2.
Post-translational modifications in TRPV1 (transient receptor potential vanilloid 1) play a critical role in channel activity. Phosphorylation of serine/threonine residues within the N- and C-termini of TRPV1 are implicated in receptor sensitization and activation. Conversely, TRPV1 desensitization occurs via a calcium-dependent mechanism and leads to receptor de-phosphorylation. Importantly, we recently demonstrated that TRPV1 association with β-arrestin-2 is critical to receptor desensitization via its ability to scaffold the phosphodiesterase PDE4D5 to the receptor, regulating TRPV1 phosphorylation. In the present study, we demonstrate that phosphorylation of TRPV1 and β-arrestin-2 regulates this association at the membrane. Under serum-free media conditions, we observed a significant decrease in TRPV1 and β-arrestin-2 association in transfected CHO (Chinese-hamster ovary) cells. Pharmacological activation of the kinases PKA (protein kinase A) and PKC (protein kinase C) led to a robust increase in TRPV1 and β-arrestin-2 association, whereas inhibition of PKA and PKC decreased association. Previously, we identified potential PKA residues (Ser(116), Thr(370)) in the N-terminus of TRPV1 modulated by β-arrestin-2. In the present study we reveal that the phosphorylation status of Thr(370) dictates the β-arrestin-2 and TRPV1 association. Furthermore, we demonstrate that CK2 (casein kinase 2)-mediated phosphorylation of β-arrestin-2 at Thr(382) is critical for its association with TRPV1. Taken together, the findings of the present study suggest that phosphorylation controls the association of TRPV1 with β-arrestin-2.


The Arabidopsis organelle-localized glycyl-tRNA synthetase encoded by EMBRYO DEFECTIVE DEVELOPMENT1 is required for organ patterning.
Leaves develop as planar organs, with a morphology that is specialized for photosynthesis. Development of a planar leaf requires genetic networks that set up opposing adaxial and abaxial sides of the leaf, which leads to establishment of dorsoventral polarity. While many genes have been identified that regulate adaxial and abaxial fate there is little information on how this is integrated with cellular function. EMBRYO DEFECTIVE DEVELOPMENT1 (EDD1) is a nuclear gene that encodes a plastid and mitochondrial localized glycyl-tRNA synthetase. Plants with partial loss of EDD1 function have changes in patterning of margin and distal regions of the leaf. In combination with mutations in the MYB domain transcription factor gene ASYMMETRIC LEAVES1 (AS1), partial loss of EDD1 function results in leaves with reduced adaxial fate. EDD1 may influence leaf dorsoventral polarity through regulating the abaxial fate genes KANADI1 (KAN1) and ETTIN (ETT)/AUXIN RESPONSE FACTOR3 (ARF3) since these genes are upregulated in the edd1 as1 double mutant. SCABRA3 (SCA3), a nuclear gene that encodes the plastid RNA polymerase is also required for leaf adaxial fate in the absence of AS1. These results add a novel component to networks of genetic regulation of leaf development and suggest that organelles, particularly plastids, are required in leaf patterning. Potentially, signalling from organelles is essential for coordination of different cell fates within the developing leaf.


Effect of aerobic and anaerobic metabolism on free radical generation swimmers.
In this study, changes in antioxidant systems due to free radicals were investigated in short distance (100-m) and long-distance (800-m) swimmers, within whom the anaerobic and aerobic metabolisms dominate, respectively. For this study, swimmers aged between 15 and -21 yr swam 800 m (N = 10) and 100 m (N = 9). Venous blood samples were taken before swimming, and at 1-, 20-, and 40-min intervals after swimming. Lactate, catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) levels were determined in the blood samples. The increase of lactate levels was statistically significant in the swimmers, both after the 100- and 800-m distances as compared with the preswimming levels (P < 0.001, P < 0.001). Catalase activity was increased in the first minute postswimming as compared with preswimming levels. Catalase activity then decreased at the 20- and 40-min intervals as compared with the 1-min postswimming interval, at both 100- and 800-m distances (P < 0.01, P < 0.001). GPx activity was also increased in the first minute after swimming as compared with preswimming levels. GPx activity then decreased at the 20- and 40-min intervals when compared with the 1-min postswimming level. This occurred in both 100- and 800-m swimmers (P < 0.001, P < 0.001). GSH activity was decreased in the first minute after swimming, compared with the preswimming levels. GSH activity then increased at the 20- and 40-min postswimming intervals, as compared with the first-minute level. Again, this occurred in both the 100- and 800-m swimmers (P < 0.001, P < 0.01). We concluded that both long-distance and particularly short-distance (100-m) swimming increased the activities of antioxidant defense enzymes.


Phenolic acid-chitosan derivatives: An effective strategy to cope with food preservation problems.
Chitosan, a cost-effective and eco-friendly natural polymeric material, possesses excellent film-forming properties. However, it has low solubility and biological activity, which hinders its widespread applications. To overcome these limitations, researchers have developed phenolic acid-chitosan derivatives that greatly enhance the mechanical, antibacterial and antioxidant properties of chitosan, expanding its potential application, particularly in food preservation. This review aims to provide an in-depth understanding of the structure and biological activity of chitosan and phenolic acid, as well as various synthetic techniques employed in their modification. Phenolic acid-chitosan derivatives exhibit improved physicochemical properties, such as enhanced water solubility, thermal stability, rheological properties, and crystallinity, through grafting techniques. Moreover, these derivatives demonstrate significantly enhanced antibacterial and antioxidant activities. Through graft modification, phenolic acid-chitosan derivatives offer promising applications in food preservation for diverse food products, including fruits, vegetables, meat, and aquatic products. Their ability to improve the preservation and quality of these food items makes them an appealing option for the food industry. This review intends to provide a deeper understanding of phenolic acid-chitosan derivatives by delving into their synthetic technology, characterization, and application in the realm of food preservation.


Terbuthylazine exposure induces innate immune response and inflammation through activating cGAS-STING/NF-κB pathway in myocardium of broiler chicken (Gallus gallus).
Terbuthylazine (TBA), a triazine herbicide, is extensively employed in agriculture for its wide range of effectiveness. However, prolonged utilization of TBA can pose a potential hazard to animals and human health. Here, a total of 180 broiler chickens (Gallus gallus) were stochastically assigned to three groups (control group, 0.4 mg/kg TBA group, and 4 mg/kg TBA group) for investigating the impact of TBA on cardiotoxicity. The results revealed that TBA exposure resulted in pathological alterations in the myocardium. Moreover, TBA exposure activated cGAS-STING pathway and markedly elevated the mRNA and protein expression levels of innate immune response (cGAS, STING, TBK1, and IRF3) in myocardium. Additionally, NF-κB signal was also activated under TBA exposure, which was characterized by the increasing mRNA expression levels of NF-κB, IKKα and the protein expression levels of p-NF-κB/NF-κB, IKKα, p-IκBα/IκBα in the TBA treatment groups. Meanwhile, the expression of pro-inflammatory cytokines (TNF-α and IL-1β) were also significantly increased. In summary, our findings suggested that cGAS-STING/NF-κB pathway functionated in the innate immune response and inflammation in myocardium brought on by TBA exposure, which provided new insights into the TBA toxicology.


Treatment of an adrenomyeloneuropathy patient with Lorenzo's oil and supplementation with docosahexaenoic acid--a case report.
This is a case report of adrenomyeloneuropathy (AMN), the adult variant of adrenoleukodystryphy (ALD). The diagnoses in the patient, aged 34, was confirmed via increased serum very long chain fatty acid concentration (VLCFA). Treatment started with the cholesterol lowering drug, atorvastatin, followed by add-on therapy with Lorenzo's oil (LO) and finally supplementation with docosahexaenoic acid (DHA). The magnetic resonance imaging (MRI) scan of the AMN patient before DHA treatment, already showed abnormal white matter in the brain. Although the MRI showed no neurological improvement after 6 months of DHA treatment, no selective progression of demyelination was detected in the AMN patient. Contrary to what was expected, LO failed to sustain or normalize the VLCFA levels or improve clinical symptoms. It was however, shown that DHA supplementation in addition to LO, increased DHA levels in both plasma and red blood cells (RBC). Additionally, the study showed evidence that the elongase activity in the elongation of eicosapentaenoic acid (EPA) to docosapentaenoic acid (DPA) might have been significantly compromised, due to the increased DHA levels.


Noninvasive methods in evaluation of inflammatory bowel disease: where do we stand now? An update.
The inflammatory bowel diseases, consisting of Crohn's disease, ulcerative colitis and indeterminate colitis, are distinguished by idiopathic and chronic inflammation of the digestive tract. The distinction between inflammatory bowel diseases and functional bowel disorders, such as irritable bowel syndrome, can be complex because they often present with similar symptoms. Rapid and inexpensive noninvasive tests that are sensitive, specific and simple are needed to prevent patient discomfort, delay in diagnosis, and unnecessary costs. None of the current commercially available serological biomarker tests can be used as a stand-alone diagnostic in clinics. Instead, these are used as an adjunct to endoscopy in diagnosis and prognosis of the disease. Along these lines,, fecal lactoferrin and calprotectin tests seem to be one step further from other tests with larger number of studies, higher sensitivity and specificity and wider availability.


Histone acetylation in chicken erythrocytes. Rates of acetylation and evidence that histones in both active and potentially active chromatin are rapidly modified.
Of the modifiable histone lysine sites, 2-4% participate in dynamic acetylation in chicken erythrocytes, suggesting the involvement of no more than 1-2% of the total genome. The rates and chromatin locality of this dynamic acetylation were studied in both chicken mature and immature red blood cells. In mature erythrocytes, two rates of acetylation of radiolabelled, monoacetylated H4 are observed, with half-lives of approximately 12 and approximately 300 min. In contrast, only one rate with a half-life (t1/2) of 12 min is observed in immature cells, and further experiments rule out the possibility of a slow rate of acetylation (with a t1/2 of approximately 300 min) for any form of H4 in this cell type. The simplest interpretation of these quantitative results, taken together with the behaviour of H3, H2B and H4 observed on the fluorograms used for rate analysis, is that a portion of the rapidly acetylated histone is converted to a more slowly acetylated form during erythrocyte maturation. The transcriptionally active adult beta-globin and H5 nucleohistone, which are presumably converted to potentially active chromatin during the maturation process, remain of the rapidly acetylated form in the mature cell.


Oxidative stress and aging: is methylglyoxal the hidden enemy?
Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.


The relationship of gingival crevicular fluid short chain carboxylic acid concentration to gingival inflammation.
Short-chain carboxylic acids (SCCA; C < or = 5; e.g., lactic acid, propionic acid, butyric acid) are metabolic by-products of bacterial metabolism which accumulate in the gingival crevice, and exhibit significant biological activity, including the ability to alter gene expression. It has been hypothesized that among the activities of SCCAs are their ability to contribute to gingival inflammation. This concept complements the notion that specific periodontal pathogens are the causative agents of gingival inflammation. To begin testing these 2 hypotheses, we examined the relationship between SCCA concentrations, specific putative periodontal pathogens, and gingival inflammation in medically healthy periodontally diseased subjects. We reasoned that if SCCAs and/or specific periodontal pathogens were causative gingival inflammatory agents, gingival inflammation should increase with increasing concentration of the inflammatory mediator. We also recognized that other clinical variables needed to be controlled for, and an objective quantitative assessment of gingival inflammation used. To accomplish these tasks, sites within subjects were stratified by location and pocket depth, and the following quantified: bacterial presence; SCCA concentration; and gingival inflammation. The results indicated that gingival inflammation directly and significantly correlated with SCCA concentrations in the maxillary and mandibular molars, incisors and canines (all r > or = 0.47; all p < or = 0.015; too few bicuspids were available for complete analysis). The relationship between gingival inflammation and SCCA concentration was best described by a natural log relationship. Gingival inflammation did not, however, correlate positively with either the total number of specific putative periodontal pathogens, or the sum of subsets of these pathogens (-0.31 < or = r < or = 0.39; 0.08 < or = p < or = 0.75) for any of the locations. Finally, the SCCA concentration did not correlate with the level of individual or groups of pathogens. These data, together with historical work and other preliminary data, support the hypothesis that SCCA, rather than specific putative periodontal pathogens, may be a causative agent in gingival inflammation. This work may, in part, begin to explain the apparent lack of a direct relationship between current gingival inflammation and the prediction of bacterially mediated periodontal attachment loss.


Stage-specific expression of mouse germ cell-less-1 (mGCL-1), and multiple deformations during mgcl-1 deficient spermatogenesis leading to reduced fertility.
A mouse homologue of Drosophila germ cell-less, mouse germ cell-less-1 (mgcl-1), is highly expressed in the testis. Previous report revealed that the fertility of the mgcl-1(-/-) male mice is reduced significantly as a result of various morphological abnormalities in the sperm (Kimura et al., 2003). To elucidate the function of mgcl-1 in spermatogenesis, the expression of mGCL-1 in the wild-type testis was examined. Immunohistochemical studies demonstrated that mGCL-1 first appeared in the nuclei of the pachytene spermatocytes at stage VI of the seminiferous epithelium, and existed in those of spermatids until step 8 during spermatogenesis. mGCL-1 was not detectable after step 9 spermatids. The testicular cells and epididymal sperm were further analyzed morphologically using mgcl-1(-/-) mice. In the testis, deformed nuclei first occurred in the pachytene spermatocytes at stage VI, which is consistent with the time of the first appearance of the mGCL-1 protein in the wild-type testis. Abnormal nuclei and acrosomes were found in spermatids after step 5, and nuclei of the spermatids and epididymal sperm were frequently invaginated. In addition, variously deformed sperm such as bent-neck, multi-headed or multi-nucleated sperm were observed in the mgcl-1(-/-) cauda epididymidis. However, several key structures such as the acroplaxome marginal ring (Kierszenbaum et al., 2003), postacrosomal sheath, and posterior ring apparently formed. In addition, MN7 and MN13, essential substances for fertilization that are located in sperm heads, were detectable in the mgcl-1 null sperm. These observations provide important insights into the mechanisms regulating the nuclear architecture and causes of human infertility.


Prokaryotic extracellular enzymatic activity in relation to biomass production and respiration in the meso- and bathypelagic waters of the (sub)tropical Atlantic.
Prokaryotic extracellular enzymatic activity, abundance, heterotrophic production and respiration were determined in the meso- and bathypelagic (sub)tropical North Atlantic. While prokaryotic heterotrophic production (PHP) decreased from the lower euphotic layer to the bathypelagic waters by two orders of magnitude, prokaryotic abundance and cell-specific PHP decreased only by one order of magnitude. In contrast to cell-specific PHP, cell-specific extracellular enzymatic activity (alpha- and beta-glucosidase, leucine aminopeptidase, alkaline phosphatase) increased with depth as did cell-specific respiration rates. Cell-specific alkaline phosphatase activity increased from the intermediate water masses to the deep waters up to fivefold. Phosphate concentrations, however, varied only by a factor of two between the different water masses, indicating that phosphatase activity is not related to phosphate availability in the deep waters. Generally, cell-specific extracellular enzymatic activities were inversely related to cell-specific prokaryotic leucine incorporation. Thus, it is apparent that the utilization of deep ocean organic matter is linked to higher cell-specific extracellular enzymatic activity and respiration and lower cell-specific PHP than in surface waters.


Socioeconomic factors and the incidence of hospitalized burn injuries in New England counties, USA.
This study demonstrates that readily available socioeconomic data routinely collected by the US Census can be used to estimate the incidence of burn injuries within the 66 counties of the populous six-state New England region of the USA. The burn data were collected during the National Burn Demonstration Project and included New England residents admitted for hospital care of burns sustained between 1 July 1978 and 30 June 1979. Linear regression analysis revealed strong associations between calculated burn rates and a number of socioeconomic variables. Associations with five such variables are described, including per capita income, percentage of persons below poverty level, percentage of residences built prior to 1940, percentage of adults with 16 years or more of education, and percentage of persons moving since 1975 with previous residence in the same county. Estimates of burn incidence for counties, together with a previously reported study at the level of census tracts for a major Standard Metropolitan Statistical Area, can be used to reduce the time and cost of burn injury case reporting by health care providers or case-finding efforts for large population groups, and can be used to predict the effectiveness of social and economic programmes and policies that improve the overall well-being of county populations.


Postterm pregnancy.
Postterm pregnancy is a pregnancy that extends to 42 weeks of gestation or beyond. Fetal, neonatal and maternal complications associated with this condition have always been underestimated. It is not well understood why some women become postterm although in obesity, hormonal and genetic factors have been implicated. The management of postterm pregnancy constitutes a challenge to clinicians; knowing who to induce, who will respond to induction and who will require a caesarean section (CS). The current definition and management of postterm pregnancy have been challenged in several studies as the emerging evidence demonstrates that the incidence of complications associated with postterm pregnancy also increase prior to 42 weeks of gestation. For example the incidence of stillbirth increases from 39 weeks onwards with a sharp rise after 40 weeks of gestation. Induction of labour before 42 weeks of gestation has the potential to prevent these complications; however, both patients and clinicians alike are concerned about risks associated with induction of labour such as failure of induction and increases in CS rates. There is a strong body of evidence however that demonstrates that induction of labour at term and prior to 42 weeks of gestation (particularly between 40 & 42 weeks) is associated with a reduction in perinatal complications without an associated increase in CS rates. It seems therefore that a policy of induction of labour at 41 weeks in postterm women could be beneficial with potential improvement in perinatal outcome and a reduction in maternal complications.


Mutations in radial spoke head genes and ultrastructural cilia defects in East-European cohort of primary ciliary dyskinesia patients.
Primary ciliary dyskinesia (PCD) is a rare (1/20,000), multisystem disease with a complex phenotype caused by the impaired motility of cilia/flagella, usually related to ultrastructural defects of these organelles. Mutations in genes encoding radial spoke head (RSPH) proteins, elements of the ciliary ultrastructure, have been recently described. However, the relative involvement of RSPH genes in PCD pathogenesis remained unknown, due to a small number of PCD families examined for mutations in these genes. The purpose of this study was to estimate the involvement of RSPH4A and RSPH9 in PCD pathogenesis among East Europeans (West Slavs), and to shed more light on ultrastructural ciliary defects caused by mutations in these genes. The coding sequences of RSPH4A and RSPH9 were screened in PCD patients from 184 families, using single strand conformational polymorphism analysis and sequencing. Two previously described (Q109X; R490X) and two new RSPH4A mutations (W356X; IVS3_2-5del), in/around exons 1 and 3, were identified; no mutations were found in RSPH9. We estimate that mutations in RSPH4A, but not in RSPH9, are responsible for 2-3% of cases in the East European PCD population (4% in PCD families without situs inversus; 11% in families preselected for microtubular defects). Analysis of the SNP-haplotype background provided insight into the ancestry of repetitively found mutations (Q109X; R490X; IVS3_2-5del), but further studies involving other PCD cohorts are required to elucidate whether these mutations are specific for Slavic people or spread among other European populations. Ultrastructural defects associated with the mutations were analyzed in the transmission electron microscope images; almost half of the ciliary cross-sections examined in patients with RSPH4A mutations had the microtubule transposition phenotype (9+0 and 8+1 pattern). While microtubule transposition was a prevalent ultrastructural defect in cilia from patients with RSPH4A mutations, similar defects were also observed in PCD patients with mutations in other genes.


Estrogen receptor beta in prostate cancer: friend or foe?
Prostate cancer is the commonest, non-cutaneous cancer in men. At present, there is no cure for the advanced, castration-resistant form of the disease. Estrogen has been shown to be important in prostate carcinogenesis, with evidence resulting from epidemiological, cancer cell line, human tissue and animal studies. The prostate expresses both estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive, but trials of ERB-selective agents have not translated into improved clinical outcomes. The role of ERB in the prostate remains unclear and there is increasing evidence that isoforms of ERB may be oncogenic. Detailed study of ERB and ERB isoforms in the prostate is required to establish their cell-specific roles, in order to determine if therapies can be directed towards ERB-dependent pathways. In this review, we summarise evidence on the role of ERB in prostate cancer and highlight areas for future research.


Effect of atrial natriuretic peptides on renal medullary solute gradients.
Studies were performed to examine the effect of the atrial natriuretic peptides on the solute gradient of the renal medulla. Experiments were performed in anesthetized male Sprague-Dawley rats given an infusion of either a purified atrial extract (n = 13), atrial natriuretic peptide 8-33 (1 microgram prime followed by 100 ng/min) (n = 8), furosemide (75 micrograms prime and 7.5 micrograms/min, n = 3), or vehicle alone (n = 17). Kidneys were removed 5 min after beginning the infusion, except in four animals, which were infused with atrial extract for 15 min before kidney removal. Both synthetic atrial peptides and an atrial extract result in rapid dissipation of the medullary gradient for urea, sodium, and total solute. No additional loss of solute was apparent at 15 min compared with 5 min. Furosemide caused equally rapid dissipation of the solute gradient at an approximately equidiuretic dose. The fall in tissue concentrations of urea and sodium was attributable to a loss of solute rather than addition of water. Administration of all three agents was associated with an increase in urinary urea excretion, which peaked earlier than the natriuresis. Urinary losses appear to account for a substantial portion of the loss of medullary solute.


Location bias in controlled clinical trials of complementary/alternative therapies.
To systematically investigate location bias of controlled clinical trials in complementary/alternative medicine (CAM). Literature searches were performed to identify systematic reviews and meta-analyses, which were used to retrieve controlled clinical trials. Trials were categorised by whether they appeared in CAM-journals or mainstream medical (MM)-journals, and by their direction of outcome, methodological quality, and sample size. 351 trials were analysed. A predominance of positive trials was seen in non-impact factor CAM- and MM-journals, (58) / (78) (74%) and (76) / (102) (75%) respectively, and also in low impact factor CAM- and MM-journals. In high impact factor MM-journals there were equal numbers of positive and negative trials, a distribution significantly (P < 0.05) different from all other journal categories. Quality scores were significantly lower for positive than negative trials in non-impact factor CAM-journals (P < 0.02). A similar trend was seen in low-impact factor CAM journals, but not to a level of significance (P = 0.06). There were no significant differences between quality scores of positive and negative trials published in MM-journals, except for high impact factor journals, in which positive trials had significantly lower scores than negative trials (P = 0.048). There was no difference between positive and negative trials in any category in terms of sample size. More positive than negative trials of complementary therapies are published, except in high-impact factor MM-journals. In non-impact factor CAM-journals positive studies were of poorer methodological quality than the corresponding negative studies. This was not the case in MM-journals which published on a wider range of therapies, except in those with high impact factors. Thus location of trials in terms of journal type and impact factor should be taken into account when the literature on complementary therapies is being examined.


Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh: a cluster randomised open-label trial.
Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting. We did this cluster-randomised open-label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845. Of 268,896 people present at baseline, we analysed 267,270: 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioural change, and 80,056 assigned to non-intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0·002) in the vaccination group and 45% (95% CI lower bound 24%; p=0·001) in the vaccination and behavioural change group. We recorded no vaccine-related serious adverse events. Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations. Bill & Melinda Gates Foundation.


A landscape analysis of leadership training in postgraduate medical education training programs at the University of Ottawa.
There is growing recognition of the importance of physician leadership in healthcare. At the same time, becoming an effective leader requires significant training. While educational opportunities for practicing physicians exist to develop their leadership skills, there is a paucity of leadership opportunities for post graduate trainees. In response to this gap, both the Royal College of Physicians and Surgeons of Canada and the Association of Faculties of Medicine of Canada have recommended that leadership training be considered a focus in Post Graduate Medical Education (PGME). However, post-graduate leadership curricula and opportunities in PGME training programs in Canada are not well described. The goal of this study was to determine the motivation for PGME leadership training, the opportunities available, and educational barriers experienced by PGME programs at the University of Ottawa. An electronic survey was distributed to all 70 PGME Program Directors (PDs) at the University of Ottawa. Two PDs were selected, based on strong leadership programs, for individual interviews. The survey response rate was 55.7%. Seventy-seven percent of responding PDs reported resident participation in leadership training as being "important," while only 37.8% of programs incorporated assessment of resident leadership knowledge and/or skills into their PGME program. Similarly, only 29.7% of responding residency programs offered chief resident leadership training. While there is strong recognition of the importance of training future physician leaders, the nature and design of PGME leadership training is highly variable. These data can be used to potentially inform future PGME leadership training curricula.


Liquid chromatographic determination of benzo[a]pyrene at part-per-billion concentrations in highly refined coal- and petroleum-derived fuels.
Benzo[a]pyrene (BaP), a well-known carcinogen, is frequently measured as an "indicator" of the potential dermal tumorigenicity of a sample. The present sequential high-performance liquid chromatography--high-performance liquid chromatography method overcomes problems in trace-level sample enrichment and recovery corrections encountered earlier. An amount of 5 g of naphtha or fuel oil is diluted to 10 ml with dichloromethane and spiked with a small quantity (ca. 0.25 micrograms) of 14C-labeled BaP tracer. A BaP-enriched fraction is obtained from a 1-ml aliquot of this sample by semipreparative chromatography on a Partisil PAC 10 column with dichloromethane-hexane (10:90) as the eluent, and concentrated to exactly 0.3, 0.5, or 1.0 ml in acetonitrile. Quantitation is performed using a reversed-phase Vydac 201 TP 5415 column with acetonitrile-water (75:25) as eluent and a Waters Model 420 E/420 AC fluorescence detector, employing an excitation/emission filter pair of 360/425 nm. The recovery of the radiolabeled tracer is evaluated by combustion of 50 microliter of the final isolate in pure oxygen, collection of the liberated 14CO2 in an alkaline desorber, and liquid scintillation counting. The recovery of BaP normally exceeded 90%, but values as low as ca. 50% were occasionally observed. Potential matrix interferences in the recovery determination were eliminated by sample combustion. The nominal precision of the overall method is approximately +/- 30% relative standard deviation at a BaP concentration of 30 ppb. The nominal analysis time for a single sample is approximately 4 h.


Neuroimaging observations in a cohort of elderly manifesting with new onset seizures: Experience from a university hospital.
The occurrence of epilepsy is higher among elderly patients. The clinical manifestations of seizures, causes of epilepsy, and choice of anti-epileptic drugs (AEDs) are different in elderly people with epilepsy compared to the young. To evaluate the imaging (CT/MRI) observations in elderly patients manifesting with new-onset seizures. Two hundred and one elderly patients with new onset seizures, >60 years (age: 68.0 ± 7.5 years; M:F = 1.8:1) from Jan' 07 to Jan' 09, were prospectively recruited. Observations of cranial CT scan (n = 201) and MR imaging (n = 43) were analyzed. THE TYPE OF SEIZURES INCLUDED: Simple partial (42%), generalized tonic-clonic (30.3%), and complex partial (27.4%). The pattern of epilepsy syndromes were acute symptomatic (42.3%), remote symptomatic (18.4%), cryptogenic (37.8%), and idiopathic (1.5%). Seizures were controlled with monotherapy in 85%. The CT scan (n = 201) revealed cerebral atrophy (139), mild (79), moderate (43), and severe (18); focal lesions (98), infarcts (45), hemorrhages (18), granuloma (16), tumor (15) and gliosis (4), and hemispheric atrophy (1), white matter changes (75) and diffuse edema (21). An MRI (n = 43) showed variable degree of cerebral atrophy (31); white matter changes (20); focal cerebral lesions (24); - infarct (7); intracranial hemorrhage (6); granuloma (5); tumor (6); gliosis (1); hemispheric atrophy (1); and prominent Virchow-Robin spaces (7); and UBOs (12). Patients with focal lesions in neuroimaging more often had partial seizures, symptomatic epilepsy, past stroke, focal deficit, absence of diffuse atrophy, focal EEG slowing, abnormal CSF, seizure recurrence at follow-up (P < 0.05). Brain imaging observations in elderly patients with new-onset seizures revealed underlying symptomatic nature, hence the etiology and thereby assisted in deciding the specific therapy.


Three-dimensional versus four-dimensional dose calculation for volumetric modulated arc therapy of hypofractionated treatments.
Respiratory motion is a non-negligible source of uncertainty in radiotherapy. A common approach is to delineate the target volume in all respiratory phases (ITV) and to calculate a treatment plan using the average reconstruction of the four-dimensional computed tomography (4DCT) scans. In this study the extent of the interplay effect caused by interaction between dynamic dose delivery and respiratory tumor motion, as well as other motion effects were investigated. These effects are often ignored when the ITV concept is used. Nine previously treated patients with in ten abdominal or thoracic cancer lesions (3 liver, 3 adrenal glands and 4 lung lesions) were selected for this planning study. For all patients, phase-sorted respiration-correlated 4DCT scans were taken, and volumetric modulated arc therapy (VMAT) treatments were planned using the ITV concept. Margins from ITV to planning target volume (PTV) of 3-10mm were used. Plans were optimized and dose distributions were calculated on the average reconstruction of the 4DCT. 4D dose distributions were calculated to evaluate motion effects, caused by the interference of dynamic treatment delivery with respiratory tumor motion and inhomogeneously planned target dose. These calculations were performed on the phase-sorted CT series with a respiration-correlated assignment of the treatment plan's monitor units (MU) to the respiration phases of the 4DCT. The 4D dose was accumulated with rigid as well as deformable registrations of the CT series and compared to the original 3D dose distribution. Maximum, minimum and mean doses to ITV and PTV, and maximum or mean doses to organs at risk (OAR), were compared after rigid accumulation. The dose variation in the gross tumor volume (GTV) was compared after deformable registration. Using rigid registrations, variations in the investigated dose parameters between 3D and 4D dose calculations were found to be within -2.1% to 1.4% for all target volumes and within -0.8% to 1.7% in OAR. Using deformable registrations, dose differences in the GTV were below 3.8% for dose accumulation of lung and adrenal gland patients. For liver patients the used deformable registrations were not considered to be robust enough. It was also shown that a major part of the dose differences originates from the Hounsfield unit differences between 3D and 4D calculations, regardless of the interplay effect. The evaluated motion effects during VMAT treatments resulted in negligible dose variability. Therefore, the approximation of calculating the dose on the average reconstruction of the 4DCT (3D dose calculation), instead of calculating on the respiration-correlated phase CTs (4D dose calculation) with assignment of the corresponding MUs, gives acceptable results.


Effects of limb posture on reactive hyperemia.
To examine the role of limb posture on vascular conductance during rapid changes in vascular transmural pressure, we determined brachial (n = 10) and femoral (n = 10) artery post-occlusive reactive hyperemic blood flow (RHBF, ultrasound/Doppler) and vascular conductance in healthy humans with each limb at three different positions-horizontal, up and down. Limb posture was varied by raising or lowering the arm or leg from the horizontal position by 45°. In both limbs, peak RHBF and vascular conductance were highest in the down or horizontal position and lowest in the up position (arm up 338 ± 38, supine 430 ± 52, down 415 ± 52 ml/min, P < 0.05; leg up 1,208 ± 88, supine 1,579 ± 130, down 1,767 ± 149 ml/min, P < 0.05). In contrast, the maximal dynamic fall in blood flow following peak RHBF (in ml/s/s) in both limbs was highest in the limb-down position and lowest with the limb elevated (P < 0.05). These data suggest that the magnitude and temporal pattern of limb reactive hyperemia is in part related to changes in vascular transmural pressure and independent of systemic blood pressure and sympathetic control.


Kidneys in chronic liver diseases.
Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support.


The value of ethanol as a fixative in urinary cytology.
Although 50% ethanol is widely used as a fixative in urinary cytology, the value of this procedure has received little systematic analysis. The purpose of this study was to examine the preservative qualities of 50% ethanol when added to freshly collected urine for both immediate and delayed processing. The results indicate that: (1) degenerative changes occurring in vivo are common among urothelial cells and probably represent the single most important factor in cell preservation in voided urine; (2) with few exceptions, fresh, unfixed urine yields the greatest number of well-preserved cells; and (3) reconstitution in either saline or 25% ethanol-saline and 24-hour storage result in increased cellular degeneration. For Millipore filter preparations, the addition of 50% ethanol has no apparent advantage, even when processing must be delayed for several hours.


The H-loop in the second nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator is required for efficient chloride channel closing.
The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that functions as a cAMP-activated chloride channel. The recent model of CFTR gating predicts that the ATP binding to both nucleotide-binding domains (NBD1 and NBD2) of CFTR is required for the opening of the channel, while the ATP hydrolysis at NBD2 induces subsequent channel closing. In most ABC proteins, efficient hydrolysis of ATP requires the presence of the invariant histidine residue within the H-loop located in the C-terminal part of the NBD. However, the contribution of the corresponding region (H-loop) of NBD2 to the CFTR channel gating has not been examined so far. Here we report that the alanine substitution of the conserved dipeptide HR motif (HR-->AA) in the H-loop of NBD2 leads to prolonged open states of CFTR channel, indicating that the H-loop is required for efficient channel closing. On the other hand, the HR-->AA substitution lead to the substantial decrease of CFTR-mediated current density (pA/pF) in transfected HEK 293 cells, as recorded in the whole-cell patch-clamp analysis. These results suggest that the H-loop of NBD2, apart from being required for CFTR channel closing, may be involved in regulating CFTR trafficking to the cell surface.


Microsatellite instability typing in serum and tissue of patients with colorectal cancer: comparing real time PCR with hybridization probe and high-performance liquid chromatography.
Allelic variation of BAT-25 (a 25-repeat quasimonomorphic poly T) and BAT-26 (a 26-repeat quasimonomorphic polyA) loci as two mononucleotide microsatellite markers, were analyzed with high-performance liquid chromatography (HPLC) compared with Real-Time PCR using hybridization probes. BAT-26 and BAT-25 markers were used to determine an appropriate screening technique with high sensitivity and specificity to diagnose microsatellite instability (MSI) status in patients with colorectal cancer (CRC). One of the pathways in colorectal tumor genesis is microsatellite instability (MSI+). MSI is detected in about 15% of all CRCs; 3% are of these are associated with Lynch syndrome and the other 12% are caused by sporadic. Colorectal tumors with MSI have distinctive features compared with microsatellite stable tumors. Due to the high percentage of MSI+ CRC in Iran, screening of this type of CRC is imperative. Two markers were analyzed in tissues and sera of 44 normal volunteers and tumor and matched normal mucosal tissues as well as sera of 44 patients with sporadic CRC. The sensitivity and specificity of BAT-26 with real time PCR method (Hybridization probe) were 100% in comparison with sequencing method as the gold standard, while HPLC had a lower sensitivity and specificity. According to HPLC data, BAT-26 was more sensitive than BAT-25 in identifying MSI tumors. Therefore, MSI typing using the BAT-26 hybridization probe method compared to HPLC could be considered as an accurate method for diagnosing MSI in CRC tumors but not in serum circulating DNAs.


Bacteria forming drag-increasing streamers on a drop implicates complementary fates of rising deep-sea oil droplets.
Competing time scales involved in rapid rising micro-droplets in comparison to substantially slower biodegradation processes at oil-water interfaces highlights a perplexing question: how do biotic processes occur and alter the fates of oil micro-droplets (<500 μm) in the 400 m thick Deepwater Horizon deep-sea plume? For instance, a 200 μm droplet traverses the plume in ~48 h, while known biodegradation processes require weeks to complete. Using a microfluidic platform allowing microcosm observations of a droplet passing through a bacterial suspension at ecologically relevant length and time scales, we discover that within minutes bacteria attach onto an oil droplet and extrude polymeric streamers that rapidly bundle into an elongated aggregate, drastically increasing drag that consequently slows droplet rising velocity. Results provide a key mechanism bridging competing scales and establish a potential pathway to biodegradation and sedimentations as well as substantially alter physical transport of droplets during a deep-sea oil spill with dispersant.


[Middle ear physiology].
The middle ear forms part of the sound transformer mechanism, together with the outer ear and the conducting system of the inner ear. An intermediate sensory organ, sensitive to acoustic vibration, and linked to the inner ear, the middle ear made its appearance during the period of adaptation of marine creatures to a terrestrial habitat; its presence is therefore a phylogenetic requirement. It is classical to ascribe three functions to the middle ear: the transmission of acoustic vibrations from the tympanic membrane to the cochlea, impedance matching between the air in the external auditary meatus and the labyrinthine fluids, and protection of the inner ear by means of the acoustic reflex. If the classical mechanical explanation has been able to explain its function, the conceptualization of its physiology in terms of energy allows an even better understanding, as well as providing and explanation for the paradoxes which arise in clinical practice when the classical model is used.


Serum concentrations of pepsinogen A in healthy dogs after food deprivation and after feeding.
To develop and validate an ELISA for measurement of serum canine pepsinogen A (cPG A) as a diagnostic marker of gastric disorders in dogs and to measure serum cPG A in healthy dogs after food deprivation and after feeding. Sera from 72 healthy dogs. A sandwich ELISA was developed and validated. The reference range for serum concentrations of cPG A was determined in 64 healthy dogs. Postprandial changes in serum concentrations of cPG A were evaluated in 8 healthy dogs. Assay sensitivity was 18 microg/L, and the maximum detectable concentration was 1,080 microg/L. The observed-to-expected ratio (O:E) for 3 serial dilutions of 3 serum samples ranged from 69.3 to 104.1%. The O:E for 3 serum samples spiked with 8 concentrations of cPG A ranged from 58.8 to 120.4%. Coefficients of variation for intra- and interassay variability of 3 serum samples ranged from 7.6 to 11.9% and from 10.1 to 13.1%, respectively. Mean +/- SD serum concentration of cPG A in healthy dogs was 63.8 +/- 31.0 microg/L and the reference range was 18 to 129 microg/L. Significant increases in serum concentrations of cPG A were observed between 1 and 7 hours after feeding. The ELISA for measuring cPG A was sufficiently sensitive, linear, accurate, precise, and reproducible for clinical use. Serum concentrations of cPG A increase substantially after feeding, which should be taken into account when conducting clinical studies.


Epidemiology and natural history of non-alcoholic fatty liver disease.
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD) that leads to progressive liver disease and presents a growing challenge to public health. Because of the increased prevalence of metabolic syndrome and obesity, NAFLD and NASH have expanded to a substantial extent. In NASH patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH is mandatory. Although there is currently no validated test of serum biomarkers available to diagnose NASH, and histologic evaluation with a liver biopsy remains the gold standard, screening for fibrosis is recommended in patients with suspicion of NASH. Clinical prediction models and serum biomarkers for advanced fibrosis have relatively good negative predictive value and can be useful for screening. Also, transient elastography is increasingly available to estimate fibrosis in NASH. Therefore, due to the lack of a reliable and accepted non-invasive diagnostic modality, screening for NASH in the general population is not currently recommended. Better understanding of the natural history of NASH is needed to evaluate the utility and cost-effectiveness of screening.


Enhancer of zeste homologue 2 plays an important role in neuroblastoma cell survival independent of its histone methyltransferase activity.
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer. High EZH2 expression correlated with poor prognosis and overall survival independent of MYCN amplification status. Unexpectedly, treatment of 3 EZH2-high expressing neuroblastoma cell lines (IMR32, CHP134 and NMB), with EZH2-specific inhibitors (GSK126 and EPZ6438) resulted in only a slight G1 arrest, despite maximum histone methyltransferase activity inhibition. Furthermore, colony formation in cell lines treated with the inhibitors was reduced only at concentrations much higher than necessary for complete inhibition of EZH2 histone methyltransferase activity. Knockdown of the complete protein with three independent shRNAs resulted in a strong apoptotic response and decreased cyclin D1 levels. This apoptotic response could be rescued by overexpressing EZH2ΔSET, a truncated form of wild-type EZH2 lacking the SET transactivation domain necessary for histone methyltransferase activity. Our findings suggest that high EZH2 expression, at least in neuroblastoma, has a survival function independent of its methyltransferase activity. This important finding highlights the need for studies on EZH2 beyond its methyltransferase function and the requirement for compounds that will target EZH2 as a complete protein.


Jasmonic acid signalling mediates resistance of the wild tobacco Nicotiana attenuata to its native Fusarium, but not Alternaria, fungal pathogens.
We recently characterized a highly dynamic fungal disease outbreak in native populations of Nicotiana attenuata in the southwestern United States. Here, we explore how phytohormone signalling contributes to the observed disease dynamics. Single inoculation with three native Fusarium and Alternaria fungal pathogens, isolated from diseased plants growing in native populations, resulted in disease symptoms characteristic for each pathogen species. While Alternaria sp.-infected plants displayed fewer symptoms and recovered, Fusarium spp.-infected plants became chlorotic and frequently spontaneously wilted. Jasmonic acid (JA) and salicylic acid (SA) levels were differentially induced after Fusarium or Alternaria infection. Transgenic N. attenuata lines silenced in JA production or JA conjugation to isoleucine (JA-Ile), but not in JA perception, were highly susceptible to infection by F. brachygibbosum Utah 4, indicating that products derived from the JA-Ile biosynthetic pathway, but not their perception, is associated with increased Fusarium resistance. Infection assays using ov-nahG plants which were silenced in pathogen-induced SA accumulations revealed that SA may increase N. attenuata's resistance to Fusarium infection but not to Alternaria. Taken together, we propose that the dynamics of fungal disease symptoms among plants in native populations may be explained by a complex interplay of phytohormone responses to attack by multiple pathogens.


Mature form of ameloblastic fibrodentinoma: a case report.
Ameloblastic fibrodentinoma (AFD) is classified as a rarely seen benign mixed odontogenic tumor. Ameloblastic fibrodentinoma is common in children and young adults with painless swelling and mostly seen at the mandibular posterior region and usually associated with unerupted tooth. In this clinical report, an 11-year-old-boy referred to Ankara University, Faculty of Dentistry, with the complaint of pain and swelling at the mandibular posterior region, diagnosed as AFD, is presented. Extraoral examination showed swelling at the affected side. In intraoral examination, a rough painful swelling was invincible with a delayed eruption of deciduous second molar tooth. Panoramic radiography revealed well-defined radiolucency with large radiopacity above the crown of unerupted permanent second molar in the left mandible. The provisional diagnosis was complex odontoma. Biopsy resulted as AFD. The treatment achieved with total excision of the tumor and the second premolar tooth. Resorbable fixation plates were used for strengthening the excised region of the mandible. No recurrence or clinical complaints were noted during 1-year follow-up.


Host-pathogen interactions in scrapie.
There are many strains of the agent which causes scrapie and these can be used singly or given as mixed infections to investigate the ways in which agent and host control mechanisms interact during the pathogenesis of the disease. Two genes in mice are described; one only affects the kinetics of the disease when extraneural injections are used, the other acts irrespective of the route of injection and it is suggested that it determines the structure of a multimeric agent-replication site, the number of such subcellular sites in the body being strictly limited.--Different agent strain/host genotype combinations give such a wide range of results that conventional quantitative analysis can yield little of predictive genetical value unless the major biological variables in host and agent can be specified.


Hand Grip Strength and Gender: Allometric Normalization in Older Adults and Implications for the NIOSH Lifting Equation.
Many countries are experiencing an aging workforce with women workers making up a growing proportion. Workplaces often require employees to complete lifting tasks that require the ability of the hand to grasp an implement (coupling). The National Institute for Occupational Safety and Health (NIOSH) has developed an equation for manual lifting tasks hoping to minimize the potential for a workplace back-injury related to a lifting task. The NIOSH lifting equation relies upon stress variables including a coupling factor. However, little is known regarding grip strength as related to the NIOSH lifting equation coupling factor. The purpose of this study was to investigate differences in grip strength due to gender in older adults. The participant's (68-88 years) maximal grip (MG) strength measures were collected for each hand with a hand grip dynamometer (kg). MG scores were converted to Newtons (N), normalized to body mass, and allometrically scaled. Measures of MG were than compared between genders with an independent t-test. The hand grip measures of MG (kg) [male: 30.3 ± 5.6, female: 10.6 ± 3.3], MG (kg) / body mass (kg) [male: 0.35 ± 0.06, female: 0.16 ± 0.04], MG (N) / (body mass (kg))0.67 [male: 15.1 ± 2.5, female: 6.2 ± 1.7], and MG (N) / (body height (m))1.84 [male: 103.6 ± 18.6, female: 42.6 ± 10.6] were all significantly lower (p < 0.0001) for women than men. Regardless of how grip strength was reported, there is a strong difference in grip strength between genders in this sample. The NIOSH lifting equation does not account for varying grip strength due to aging and gender differences. It is recommended that grip strength variability be accounted for in the coupling factor of the NIOSH lifting equation.


Muscle recovery from a short fatigue test and consequence on the reliability of EMG indices of fatigue.
The purpose of the present study was to evaluate if rest intervals of 10 or 15 min allow the back muscles to recover completely, from an electromyographic (EMG) point of view, after performing a fatiguing contraction. Twelve healthy males stood in a dynamometer with the trunk in a vertical position and performed three trunk extension fatiguing trials (30 s contractions sustained at 75% of the maximal voluntary contraction) separated successively by a 15 min (between trial 1 and 2) and a 10 min (between trial 2 and 3) rest period. The EMG signals from four pairs of back muscles were collected at 2,048 Hz with active surface electrodes. Different EMG indices computed from the temporal and frequency domains of the EMG signal were considered to evaluate muscular fatigue and recovery from trial 1 to trial 2 and from trial 2 to trial 3. No significant differences (one-way ANOVAs between the three trials, alpha=0.05) were obtained for the different EMG indices computed. The percentage of variance explained by the inter-trial effect was none in most cases, corroborating that no systematic error was present between the trials and suggesting that complete muscle recovery was allowed with 10 or 15 min rest periods. These results support the use of rest periods of 10 to 15 min between multiple fatigue tests, at least for back muscles and for high intensity short duration fatigue tasks as the one used in the present study.


Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics.
Most upper respiratory tract infections are caused by viruses and require no antibiotics. This clinical report focuses on antibiotic prescribing strategies for bacterial upper respiratory tract infections, including acute otitis media, acute bacterial sinusitis, and streptococcal pharyngitis. The principles for judicious antibiotic prescribing that are outlined focus on applying stringent diagnostic criteria, weighing the benefits and harms of antibiotic therapy, and understanding situations when antibiotics may not be indicated. The principles can be used to amplify messages from recent clinical guidelines for local guideline development and for patient communication; they are broadly applicable to antibiotic prescribing in general.


Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers.
In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.


The effect of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinoma: the Radiation Therapy Oncology Group 75-06 and 77-06 experience.
From 1976 to 1983, 1091 patients were entered into RTOG protocols 75-06 and 77-06. Of these, 780 patients complied with protocol requirements, received a minimum tumor dose of greater than or equal to 6500 cGy, and received no endocrine therapy. There were 78, 342, and 360 patients with localized prostate carcinoma, Stages T1b(A2), T2(B), and T3,4(C), respectively. The potential follow-up period ranges from 6 years 5 months to 13 years 3 months, with a median follow-up of 9 years. This study examines the influence of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinoma in this patient population. Within each stage, patients were divided into three groups according to the total number of elapsed days while on treatment: within 49 days (less than or equal to 7 weeks); 50 to 63 days (8 to 9 weeks); and greater than or equal to 64 days (greater than 9 weeks). Based on actuarial analysis, within each stage, the overall treatment time did not have any impact on the following: overall survival, NED survival, or local/regional control. When grouped under different histologic grades, that is, Gleason scores 2-5, 6-7, and 8-10, the actuarial local/regional control showed no statistical difference among the three groups. The actual local/regional failures were analyzed and stratified by stage and Gleason scores, and no statistical difference was noted among the three groups for each stratification. The range of local/regional failure rates among the three groups for T1b(A2), T2(B), and T3,4(C) disease were 0%-8%, 16%-23%, and 24%-27%, respectively. The corresponding range of local/regional failure rates for patients with Gleason scores of 2-5, 6-7, and 8-10 were 13%-14%, 18%-22%, and 22%-33%, respectively. The incidence of late complications was not related to the number of elapsed treatment days. Therefore, the overall treatment time does not have an impact on the outcome of definitive radiotherapy for localized prostate carcinoma. It is hypothesized that prostate carcinoma behaves as late-reacting tissue in which there is little, if any, accelerated repopulation of clonogenic tumor cells during the later half of a protracted course of radiotherapy. This observation is in direct contrast to that suggested for head and neck carcinoma and bears important implications in daily radiotherapeutic management of patients with prostate carcinoma.


Influenza epidemiology and influenza vaccine effectiveness during the 2016-2017 season in the Global Influenza Hospital Surveillance Network (GIHSN).
The Global Influenza Hospital Surveillance Network (GIHSN) aims to determine the burden of severe influenza disease and Influenza Vaccine Effectiveness (IVE). This is a prospective, active surveillance and hospital-based epidemiological study to collect epidemiological data in the GIHSN. In the 2016-2017 influenza season, 15 sites in 14 countries participated in the GIHSN, although the analyses could not be performed in 2 sites. A common core protocol was used in order to make results comparable. Here we present the results of the GIHSN 2016-2017 influenza season. A RT-PCR test was performed to all patients that accomplished the requirements detailed on a common core protocol. Patients admitted were included in the study after signing the informed consent, if they were residents, not institutionalised, not discharged in the previous 30 days from other hospitalisation with symptoms onset within the 7 days prior to admission. Patients 5 years old or more must also complied the Influenza-Like Illness definition. A test negative-design was implemented to perform IVE analysis. IVE was estimated using a logistic regression model, with the formula IVE = (1-aOR) × 100, where aOR is the adjusted Odds Ratio comparing cases and controls. Among 21,967 screened patients, 10,140 (46.16%) were included, as they accomplished the inclusion criteria, and tested, and therefore 11,827 (53.84%) patients were excluded. Around 60% of all patients included with laboratory results were recruited at 3 sites. The predominant strain was A(H3N2), detected in 63.6% of the cases (1840 patients), followed by B/Victoria, in 21.3% of the cases (618 patients). There were 2895 influenza positive patients (28.6% of the included patients). A(H1N1)pdm09 strain was mainly found in Mexico. IVE could only be performed in 6 sites separately. Overall IVE was 27.24 (95% CI 15.62-37.27. Vaccination seemed to confer better protection against influenza B and in people 2-4 years, or 85 years old or older. The aOR for hospitalized and testing positive for influenza was 3.02 (95% CI 1.59-5.76) comparing pregnant with non-pregnant women. Vaccination prevented around 1 in 4 hospitalisations with influenza. Sparse numbers didn't allow estimating IVE in all sites separately. Pregnancy was found a risk factor for influenza, having 3 times more risk of being admitted with influenza for pregnant women.


Ultrasonographic findings in Fitz-Hugh-Curtis syndrome: a thickened or three-layer hepatic capsule.
Fitz-Hugh-Curtis syndrome (FHCS) is characterized by inflammation of the perihepatic capsules associated with the pelvic inflammatory disease (PID). FHCS is not a serious disease, but if not treated properly, it can result in increased medical costs, prolonged treatment, and dissatisfaction with treatment. However, early recognition of FHCS in the emergency department can be difficult because its symptoms or physical findings may mimic many other diseases. Although contrast-enhanced computed tomography (CECT) is the useful imaging modality for recognition of FHCS, it is available only when a high suspicion is established. We performed point-of-care ultrasonography in an 18-year-old woman who had a sharp right upper quadrant (RUQ) abdominal pain without PID symptoms and found a thickened or three-layer hepatic capsule. These findings coincided with areas showing increased hepatic capsular enhancement in the arterial phase of CECT. These results show that if the thickened or three-layer hepatic capsule without evidence of a common cause of RUQ pain is observed on ultrasonography in women of childbearing age with RUQ abdominal pain, the physician can consider the possibility of FHCS.


Randomised controlled trial of ultrasonography in diagnosis of acute appendicitis, incorporating the Alvarado score.
To determine whether diagnosis by graded compression ultrasonography improves clinical outcomes for patients with suspected appendicitis. A randomised controlled trial comparing clinical diagnosis (control) with a diagnostic protocol incorporating ultrasonography and the Alvarado score (intervention group). Single tertiary referral centre. 302 patients (age 5-82 years) referred to the surgical service with suspected appendicitis. 160 patients were randomised to the intervention group, of whom 129 underwent ultrasonography. Ultrasonography was omitted for patients with extreme Alvarado scores (1-3, 9, or 10) unless requested by the admitting surgical team. Time to operation, duration of hospital stay, and adverse outcomes, including non-therapeutic operations and delayed treatment in association with perforation. Sensitivity and specificity of ultrasonography were measured at 94. 7% and 88.9%, respectively. Patients in the intervention group who underwent therapeutic operation had a significantly shorter mean time to operation than patients in the control group (7.0 v 10.2 hours, P=0.016). There were no differences between groups in mean duration of hospital stay (53.4 v 54.5 hours, P=0.84), proportion of patients undergoing a non-therapeutic operation (9% v 11%, P=0.59) or delayed treatment in association with perforation (3% v 1%, P=0.45). Graded compression ultrasonography is an accurate procedure that leads to the prompt diagnosis and early treatment of many cases of appendicitis, although it does not prevent adverse outcomes or reduce length of hospital stay.