A novel G protein-coupled receptor for gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica): identification, expression and binding activity.
We recently identified a novel hypothalamic dodecapeptide inhibiting gonadotropin release in the Japanese quail (Coturnix japonica). This novel peptide was therefore named gonadotropin-inhibitory hormone (GnIH). The GnIH precursor encoded one GnIH and two GnIH-related peptides (GnIH-RP-1 and GnIH-RP-2) that shared the same C-terminal motif, Leu-Pro-Xaa-Arg-Phe-NH(2) (Xaa=Leu or Gln; LPXRF-amide peptides). Identification of the receptor for GnIH is crucial to elucidate the mode of action of GnIH. We therefore identified the receptor for GnIH in the quail diencephalon and characterized its expression and binding activity. We first cloned a cDNA encoding a putative GnIH receptor by a combination of 3' and 5' rapid amplification of cDNA ends (RACE) using PCR primers designed from the sequence for the receptor for rat RF-amide-related peptide (RFRP), an orthologous peptide of GnIH. Hydrophobic analysis revealed that the putative GnIH receptor possessed seven transmembrane domains, indicating a new member of the G protein-coupled receptor superfamily. The crude membrane fraction of COS-7 cells transfected with the putative GnIH receptor cDNA specifically bound to GnIH and GnIH-RPs in a concentration-dependent manner. Scatchard plot analysis of the binding showed that the identified GnIH receptor possessed a single class of high-affinity binding sites (K(d)=0.752 nM, B(max)=24.8 fmol/mg protein). Southern blotting analysis of reverse transcriptase-mediated PCR products revealed the expression of GnIH receptor mRNA in the pituitary gland and several brain regions including diencephalon in the quail. These results suggest that GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release. GnIH may also act on the hypothalamus to inhibit gonadotropin-releasing hormone release.


Towards a Mechanistic Understanding of the Effects of Body Posture on Facial Emotion Categorization.
This study investigated the causes of the face-body congruence effect (FBCE), which refers to the advantage in performance when participants are asked to categorize emotional faces compounded with emotional matching body postures (congruent) compared with incongruent face-body compound stimuli (body postures mismatching the facial emotions). Experiment 1 showed that manipulations aiming to alter holistic processing significantly reduced the FBCE. In particular, the disruption of holistic processing affected significantly the performance for congruent composites. However, no effect was obtained on the incongruent stimuli. In Experiment 2, the inversion manipulation showed a clear disadvantage for incongruent stimuli brought by the disruption of the single feature orientation information. Thus, we found confirmation of the different processing involved in perceiving congruent and incongruent stimuli. Finally, Experiment 3 confirmed that we are able to reduce entirely the FBCE when the orientation of the units (the face and the body) constituting the incongruent composites is matched.


Amorphization of Serpentine at High Pressure and High Temperature
Pressure-induced amorphization of serpentine was observed at temperatures of 200° to 300°C and pressures of 14 to 27 gigapascals with a combination of a multianvil apparatus and synchrotron radiation. High-pressure phases then crystallized rapidly when the temperature was increased to 400°C. These results suggest that amorphization of serpentine is an unlikely mechanism for generating deep-focus earthquakes, as the temperatures of subducting slabs are significantly higher than those of the rapid crystallization regime.


Delusion of pregnancy: a systematic review of 84 cases in the literature.
Case reports of delusion of pregnancy have emanated from all over the world, yet the rarity of this phenomenology has precluded systematic large scale descriptive or cohort studies. This systematic review was conducted to assess the demographic characteristics, clinical profile, treatment outcome and aetiological factors from the published case reports of delusion of pregnancy. Electronic databases including PubMed, PsychInfo and Google Scholar were used to identify case reports relating to delusion of pregnancy published in peer-reviewed English language journals. All such cases were systematically evaluated by investigators, and information was extracted using a structured proforma. A total 40 articles were reviewed which included 84 cases. Demographic characteristics revealed that about half of the patients were aged 20-40 years. The most common diagnoses were schizophrenia (35.7%), bipolar disorders (16.7%) and depression (9.5%). Single foetus was reported by 79.8% of the patients, and 45.2% perceived foetal movements. Good treatment response was noted in 64.3 % of the cases. The prominent aetiological factors that were implicated included psychosocial factors, coenaesthopathological processes, socio-cultural factors and hyperprolactinaemia. Delusion of pregnancy is a heterogeneous symptom which emerges during the course of various neuropsychiatric disorders. A range of aetiopathological mechanisms have been implicated in the causation of this disorder.


Gastrointestinal symptoms are associated with trajectories of chemotherapy-induced nausea.
Between 19 and 58% of oncology patients experience chemotherapy-induced nausea (CIN). In a sample of outpatients with breast, gastrointestinal (GI), gynecological, and lung cancer, the study purposes were to evaluate for inter-individual differences in the severity of CIN over two cycles of chemotherapy (CTX) and to determine which demographic and clinical characteristics and GI symptoms were associated with higher initial levels as well as with the trajectories of CIN severity. Patients completed study questionnaires at six time points over two cycles of CTX. These questionnaires provided information on demographic and clinical characteristics, as well as the occurrence of twelve GI symptoms. Hierarchical linear modeling based on full maximum likelihood estimation was performed. Of the 1251 patients, 47.2% reported CIN. Across two cycles of CTX, lower functional status scores and higher levels of comorbidity were associated with higher initial levels of CIN. Younger age and emetogenicity of the CTX regimen were associated with higher initial levels as well as worse trajectories of CIN. The occurrence of five GI symptoms (i.e., vomiting, lack of appetite, constipation, feeling bloated, and difficulty swallowing) was associated with higher initial levels of CIN. The occurrence of mouth sores was associated with higher initial levels as well as with worst trajectories of CIN. This study is the first to identify distinct demographic, clinical, and GI symptom characteristics associated with CIN severity. These findings suggest that the etiology of CIN is complex and may warrant interventions beyond standard antiemetics.


Predator diet breadth influences the relative importance of bottom-up and top-down control of prey biomass and diversity.
We investigated the effects of predator diet breadth on the relative importance of bottom-up and top-down control of prey assemblages, using microbial food webs containing bacteria, bacterivorous protists and rotifers, and two different top predators. The experiment used a factorial design that independently manipulated productivity and the presence or absence of two top predators with different diet breadths. Predators included a "specialist" predatory ciliate Euplotes aediculatus, which was restricted to feeding on small prey, and a "generalist" predatory ciliate Stentor coeruleus, which could feed on the entire range of prey sizes. Both total prey biomass and prey diversity increased with productivity in the predator-free control and specialist predator treatments, a pattern consistent with bottom-up control, but both remained unchanged by productivity in the generalist predator treatment, a pattern consistent with top-down control. Linear food chain models adequately described responses in the generalist predator treatment, whereas food web models incorporating edible and inedible prey (which can coexist in the absence of predators) adequately described responses in the specialist predator treatment. These results suggest that predator diet breadth can play an important role in modulating the relative strength of bottom-up and top-down forces in ecological communities.


Assessment of patient capacity to consent to treatment.
To compare results of a specific capacity assessment administered by the treating clinician, and a Standardized Mini-Mental Status Examination (SMMSE), with the results of expert assessments of patient capacity to consent to treatment. Cross-sectional study with independent comparison to expert capacity assessments. Inpatient medical wards at an academic secondary and tertiary referral hospital. One hundred consecutive inpatients facing a decision about a major medical treatment or an invasive medical procedure. Participants either were refusing treatment, or were accepting treatment but were not clearly capable according to the treating clinician. The treating clinician (medical resident or student) conducted a specific capacity assessment on each participant, using a decisional aid called the Aid to Capacity Evaluation. A specific capacity assessment is a semistructured evaluation of the participant's ability to understand relevant information and appreciate reasonably foreseeable consequences with regard to the specific treatment decision. Participants also received a SMMSE administered by a research nurse. Participants then had two independent expert assessments of capacity. If the two expert assessments disagreed, then an independent adjudication panel resolved the disagreement after reviewing videotapes of both expert assessments. Using the two expert assessments and the adjudication panel as the reference standard, we calculated areas under the receiver-operating characteristic curves and likelihood ratios. The areas under the receiver-operating characteristic curves were 0.90 for specific capacity assessment by treating clinician and 0.93 for SMMSE score (2p =.48). For the treating clinician's specific capacity assessment, likelihood ratios for detecting incapacity were as follows: definitely incapable, 20 (95% confidence interval [CI] 3. 6, 120); probably incapable, 6.1 (95% CI 2.6, 15); probably capable, 0.39 (95% CI 0.18, 0.81); and definitely capable, 0.05 (95% CI 0.01, 0.29). For the SMMSE, a score of 0 to 16 had a likelihood ratio of 15 (95% CI 5.3, 44), a score of 17 to 23 had a likelihood ratio of 0. 68 (95% CI 0.35, 1.2), and a score of 24 to 30 had a likelihood ratio of 0.05 (95% CI 0.01, 0.26). Specific capacity assessments by the treating clinician and SMMSE scores agree closely with results of expert assessments of capacity. Clinicians can use these practical, flexible, and evaluated measures as the initial step in the assessment of patient capacity to consent to treatment.


A review of nutrition in Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a recessive X linked genetic disorder characterised by progressive muscle weakness and reduced muscle tone. Affecting only boys, it limits life expectancy to approximately 20 years. A literature review was conducted using MEDLINE and the Cochrane Library, employing the term 'Duchenne muscular dystrophy'. A total of 1491 articles in English were recovered. These papers were searched thematically under the headings: body composition (n = 10), energy expenditure (n = 10), nutrition (n = 6), corticosteroid therapy (n = 55) and gene therapy (n = 199). Key dietetic practice points were identified relevant to nutritional management. Papers supporting these key themes were assigned a level of evidence and grade of recommendation. There is limited high-quality evidence to guide the nutritional management of boys with DMD. Currently, the majority of evidence is based on expert opinion and clinical expertise. Delayed growth, short stature, muscle wasting and increased fat mass are characteristics of DMD and impact on nutritional status and energy requirements. The early introduction of steroids has altered the natural history of the disease, but can exacerbate weight gain in a population already susceptible to obesity. Prior to commencing steroids, anticipatory guidance for weight management should be provided. Malnutrition is a feature of end stage disease requiring a multidisciplinary approach, such as texture modification and supplemental feeding. Micronutrient requirements are yet to be determined but, as a result of corticosteroid treatment, vitamin D and calcium should be supplemented. Some evidence exists supporting supplementation with creatine monohydrate to improve muscle strength. More research is needed to provide a higher quality of evidence for dietitians working within this area.


Absolute humidity and the human nose: A reanalysis of climate zones and their influence on nasal form and function.
Investigations into the selective role of climate on human nasal variation commonly divide climates into four broad adaptive zones (hot-dry, hot-wet, cold-dry, and cold-wet) based on temperature and relative humidity. Yet, absolute humidity-not relative humidity-is physiologically more important during respiration. Here, we investigate the global distribution of absolute humidity to better clarify ecogeographic demands on nasal physiology. We use monthly observations from the Climatic Research Unit Timeseries 3 (CRU TS3) database to construct global maps of average annual temperature, relative humidity and absolute humidity. Further, using data collected by Thomson and Buxton (1923) for over 15,000 globally-distributed individuals, we calculate the actual amount of heat and water that must be transferred to inspired air in different climatic regimes to maintain homeostasis, and investigate the influence of these factors on the nasal index. Our results show that absolute humidity, like temperature, generally decreases with latitude. Furthermore, our results demonstrate that environments typically characterized as "cold-wet" actually exhibit low absolute humidities, with values virtually identical to cold-dry environments and significantly lower than hot-wet and even hot-dry environments. Our results also indicate that strong associations between the nasal index and absolute humidity are, potentially erroneously, predicated on individuals from hot-dry environments possessing intermediate (mesorrhine) nasal indices. We suggest that differentially allocating populations to cold-dry or cold-wet climates is unlikely to reflect different selective pressures on respiratory physiology and nasal morphology-it is cold-dry, and to a lesser degree hot-dry environments, that stress respiratory function. Our study also supports assertions that demands for inspiratory modification are reduced in hot-wet environments, and that expiratory heat elimination for thermoregulation is a greater selective pressure in such environments.


Vividness of visual imagery questionnaire scores and their relationship to visual short-term memory performance.
Mechanisms underlying visual imagery, the ability to create vivid mental representations of a scene in the absence of sensory input, remain to be fully understood. Some previous studies have proposed that visual imagery might be related to visual short-term memory (STM), with a common mechanism involving retention of visual information over short periods of time. Other observations have shown a strong relationship between visual imagery and functional activity in the hippocampus and primary visual cortex, both regions also associated with visual STM. Here we examined the relationship of visual imagery to STM and hippocampal and primary visual cortex volumes, first in a large sample of healthy people across a large age range (N = 229 behavioural data; N = 56 MRI data in older participants) and then in patients with Alzheimer's disease and Parkinson's disease (N = 19 in each group compared to 19 age-matched healthy controls). We used a variant of the "What was where?" visual object-location binding task to assess the quality of remembered information over short delays. In healthy people, no evidence of a relationship between the vividness of visual imagery and any visual STM performance parameter was found. However, there was a significant positive correlation between visual imagery and the volumes of the hippocampus and primary visual cortex. Although visual STM performance was significantly impaired in patients with Alzheimer's disease, their vividness of visual imagery scores were comparable to those of age-matched elderly controls and patients with Parkinson's disease. Despite hippocampal volumes also being reduced in Alzheimer's patients, there appeared to be no impact on their self-reported visual imagery. In conclusion, visual imagery was not significantly related to visual STM performance, either in healthy controls or Alzheimer's or Parkinson's disease but it was related to hippocampal and visual cortex volume in healthy people.


Up-regulation of acid-gated Na(+) channels (ASICs) by cystic fibrosis transmembrane conductance regulator co-expression in Xenopus oocytes.
Cystic fibrosis transmembrane conductance regulator (CFTR) functions as both a chloride channel and an epithelial transport regulator, interacting with Na(+) (epithelial sodium channel), Cl(-), renal outer medullary potassium channel(+), and H(2)O channels and some exchangers (i.e. Na(+)/H(+)) and co-transporters (Na(+)-HCO(3)(minus sign), Na(+)-K(+)-2Cl(-)). Acid-sensitive ion channels (ASICs), members of the epithelial sodium channel/degenerin superfamily, were originally cloned from neuronal tissue, and recently localized in epithelia. Because CFTR has been immunocytochemically and functionally identified in rat, murine, and human brain, the regulation of ASICs by CFTR was tested in oocytes. Our observations show that the proton-gated Na(+) current formed by the heteromultimeric ASIC1a/2a channel was up-regulated by wild type but not by Delta F508-CFTR. In contrast, the acid-gated Na(+) current associated with either the homomultimeric ASIC1a or ASIC2a channel was not influenced by wild type CFTR. The apparent equilibrium dissociation constant for extracellular Na(+) for ASIC1a/2a was increased by CFTR, but CFTR had no effect on the gating behavior or acid sensitivity of ASIC1a/2a. CFTR had no effect on the pH activation of ASIC1a/2a. We conclude that wild type CFTR elevates the acid-gated Na(+) current of ASIC1a/2a in part by altering the kinetics of extracellular Na(+) interaction.


Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons.
The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral blood flow responses during intermittent light stimulation (ILS) between photosensitive (PS) and healthy control (CTL) baboons using H 2 (15) O-PET. We examined effective connectivity associated with visual stimulation in both groups using structural equation modeling (SEM). Eight PS and six CTL baboons, matched for age, gender and weight, were classified on the basis of scalp EEG findings performed during the neuroimaging studies. Five H 2 (15) O-PET studies were acquired alternating between resting and activation (ILS at 25 Hz) scans. PET images were acquired in 3D mode and co-registered with MRI. SEM demonstrated differences in neural connectivity between PS and CTL groups during ILS that were not previously identified using traditional activation analyses. First-level pathways consisted of similar posterior-to-anterior projections in both groups. While second-level pathways were mainly lateralized to the left hemisphere in the CTL group, they consisted of bilateral anterior-to-posterior projections in the PS baboons. Third- and fourth-level pathways were only evident in PS baboons. This is the first functional neuroimaging study used to model the photoparoxysmal response (PPR) using a primate model of photosensitive, generalized epilepsy. Evidence of increased interhemispheric connectivity and bidirectional feedback loops in the PS baboons represents electrophysiological synchronization associated with the generation of epileptic discharges. PS baboons demonstrated decreased model stability compared to controls, which may be attributed to greater variability in the driving response or PPRs, or to the influence of regions not included in the model.


Quantum chemical calculations on the interaction between flavonol and functional monomers (methacrylic acid and 4-vinylpyridine) in molecularly imprinted polymers.
Quantum chemical calculations were performed to characterize the interaction of the flavonol molecule (FL) with methacrylic acid (MAA) and 4-vinylpyridine (4VPy) in the formation of imprinted polymers. The polarizable continuum model (PCM) was used to gain insight on the type of interaction between the reactant molecules under vacuum conditions and in the presence of different solvents. The effect of solvent on the pre-polymerization complex formation was evaluated through the stability energy, in which chloroform behaves as the best solvent for the synthesis of the imprinted polymers since it facilitates the reaction by lowering its degree of stabilization. The reactivity was analyzed in terms of the electrostatic surface potential (ESP) and Mulliken charge. By means of these results, it has been possible to determine two potential recognition sites for the interaction of the MAA monomer and one for the 4VPy in relation to the strength of interaction with FL. In this concern, the interaction of the system FL-MAA is stronger than FL-4VPy.


Assessing the structure of the CAST (Cannabis Abuse Screening Test) in 13 European countries using multigroup analyses.
Our aims are to describe and explain the structure of the Cannabis Abuse Screening Test (CAST) across countries. Standard statistical analyses fail to describe and explain several variables simultaneously while taking account of the group structure of individuals. The 2011 European School Survey Project on Alcohol and other Drugs (ESPAD): 5204 last-year cannabis users aged 15-16 from 13 European countries. Multigroup principal component analysis (mgPCA) and multigroup partial least squares (mgPLS). MgPCA shows that the CAST has a two-dimensional structure (frequency of use/problems and non-recreational use/dependency symptoms). All the countries present a good concordance with the common structure, except Kosovo, Lichtenstein and Romania. MgPLS shows that three explanative variables (in a total of eight) are mainly related with the CAST (the frequencies of cannabis use in the last 12 months and in the last 30 days and the age at first cannabis use) while Kosovo, Lichtenstein and Romania also present specificities. The CAST structure appears stable in the 13 countries except for Kosovo, Lichtenstein and Romania that also show specific relationships between the CAST variables and their determinants.


Mechanisms of glucocorticoid resistance in human leukemic cells: implication of abnormal 90 and 70 kDa heat shock proteins.
The unliganded glucocorticoid receptor is a multi-oligomer complex consisting of a ligand-binding protein with which two 90 kDa heat shock proteins (hsp90s) are associated. Upon binding of glucocorticoid to the receptor, the ligand-binding protein, which dissociated from hsp90s, enters the nucleus, binds to a specific site in DNA, and thus transmits signal(s). The 70 kDa heat shock protein (hsp70) also works as a molecular chaperone when the ligand-binding protein enters the nucleus. Regarding the mechanisms of glucocorticoid resistance, a decreased expression of glucocorticoid receptor and a mutant protein with low ligand binding affinity have been reported. In the present study, to address other mechanisms of glucocorticoid resistance, we examined the expression of hsp90 and hsp70 in addition to the number of glucocorticoid-binding sites and their affinity using glucocorticoid-sensitive and -resistant human leukemic cell lines. We showed that two of nine resistant cell lines with normal glucocorticoid-binding proteins express aberrant hsp90 and extremely low hsp70, while another seven resistant cell lines had decreased binding sites with normal hsps. These results suggest that there are at least two independent mechanisms of glucocorticoid resistance in human leukemic cell lines: the decreased ligand-binding sites and the abnormal hsps expression.


Urinary dopamine in man and rat: effects of inorganic salts on dopamine excretion.
1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion.


Transcriptional response of mucoid Pseudomonas aeruginosa to human respiratory mucus.
Adaptation of bacterial pathogens to a host can lead to the selection and accumulation of specific mutations in their genomes with profound effects on the overall physiology and virulence of the organisms. The opportunistic pathogen Pseudomonas aeruginosa is capable of colonizing the respiratory tract of individuals with cystic fibrosis (CF), where it undergoes evolution to optimize survival as a persistent chronic human colonizer. The transcriptome of a host-adapted, alginate-overproducing isolate from a CF patient was determined following growth of the bacteria in the presence of human respiratory mucus. This stable mucoid strain responded to a number of regulatory inputs from the mucus, resulting in an unexpected repression of alginate production. Mucus in the medium also induced the production of catalases and additional peroxide-detoxifying enzymes and caused reorganization of pathways of energy generation. A specific antibacterial type VI secretion system was also induced in mucus-grown cells. Finally, a group of small regulatory RNAs was identified and a fraction of these were mucus regulated. This report provides a snapshot of responses in a pathogen adapted to a human host through assimilation of regulatory signals from tissues, optimizing its long-term survival potential. The basis for chronic colonization of patients with cystic fibrosis (CF) by the opportunistic pathogen Pseudomonas aeruginosa continues to represent a challenging problem for basic scientists and clinicians. In this study, the host-adapted, alginate-overproducing Pseudomonas aeruginosa 2192 strain was used to assess the changes in its transcript levels following growth in respiratory CF mucus. Several significant and unexpected discoveries were made: (i) although the alginate overproduction in strain 2192 was caused by a stable mutation, a mucus-derived signal caused reduction in the transcript levels of alginate biosynthetic genes; (ii) mucus activated the expression of the type VI secretion system, a mechanism for killing of other bacteria in a mixed population; (iii) expression of a number of genes involved in respiration was altered; and (iv) several small regulatory RNAs were identified, some being mucus regulated. This work highlights the strong influence of the host environment in shaping bacterial survival strategies.


Whole-exome sequencing and digital PCR identified a novel compound heterozygous mutation in the NPHP1 gene in a case of Joubert syndrome and related disorders.
Joubert syndrome and related disorders (JSRD) is a clinically and genetically heterogeneous condition with autosomal recessive or X-linked inheritance, which share a distinctive neuroradiological hallmark, the so-called molar tooth sign. JSRD is classified into six clinical subtypes based on associated variable multiorgan involvement. To date, 21 causative genes have been identified in JSRD, which makes genetic diagnosis difficult. We report here a case of a 28-year-old Japanese woman diagnosed with JS with oculorenal defects with a novel compound heterozygous mutation (p.Ser219*/deletion) in the NPHP1 gene. Whole-exome sequencing (WES) of the patient identified the novel nonsense mutation in an apparently homozygous state. However, it was absent in her mother and heterozygous in her father. A read depth-based copy number variation (CNV) detection algorithm using WES data of the family predicted a large heterozygous deletion mutation in the patient and her mother, which was validated by digital polymerase chain reaction, indicating that the patient was compound heterozygous for the paternal nonsense mutation and the maternal deletion mutation spanning the site of the single nucleotide change. It should be noted that analytical pipelines that focus purely on sequence information cannot distinguish homozygosity from hemizygosity because of its inability to detect large deletions. The ability to detect CNVs in addition to single nucleotide variants and small insertion/deletions makes WES an attractive diagnostic tool for genetically heterogeneous disorders.


Comparison of treatment delay associated with tunneled hemodialysis catheter placement between interventionists.
Fragmented care in nephrology can cause treatment delays. Nephrologists are qualified to perform vascular access-related procedures because they understand the pathophysiology of renal disease and perform physical examination for vascular access. We compared treatment delays associated with tunneled hemodialysis catheter (TDC) placement between interventional radiologists and nephrologists. We collected data by radiologists from January 1, 2011 through December 31, 2011 and by nephrologists from since July 1, 2012 through June 30, 2013. We compared the duration from the hemodialysis decision to TDC placement (D-P duration) and hemodialysis initiation (D-H duration), catheter success and the complication rate, and the frequency and the usage time of non-tunneled hemodialysis catheters (NDCs) before TDC placement. The study analyzed 483 placed TDCs: 280 TDCs placed by radiologists and 203 by nephrologists. The D-P durations were 319 minutes (interquartile range [IQR], 180 to 1,057) in the radiologist group and 140 minutes (IQR, 0 to 792) in the nephrologist group. Additionally, the D-H durations were 415 minutes (IQR,260 to 1,091) and 275 minutes (IQR, 123 to 598), respectively. These differences were statistically significant (p = 0.00). The TDC success rate (95.3% vs. 94.5%, respectively; p = 0.32) and complication rate (16.2% vs. 11%, respectively; p = 0.11) did not differ between the groups. The frequency (24.5 vs. 26%, respectively; p = 0.72) and the usage time of NDC (8,451 vs. 8,416 minutes, respectively; p = 0.91) before TDC placement were not statistically significant. Trained interventional nephrologists could perform TDC placement safely, minimizing treatment delays.


The effect of simvastatin and fenofibrate on the expression of leukocyte adhesion molecules and lipopolysaccharide receptor CD14 in type 2 diabetes mellitus.
Mixed hyperlipidemia is often associated with type 2 diabetes mellitus and contributes to atherosclerosis progression in diabetes patients. Leukocyte activation plays an important role in atherogenesis. Both statins and fibrates are used in the treatment of mixed dyslipidemia, but their specific effect on leukocyte function remains to be elucidated. We have therefore compared the effect of simvastatin and fenofibrate on several leukocyte activation markers in diabetes patients. Twenty patients with type 2 diabetes and mixed hyperlipidemia were sequentially treated with simvastatin (20 mg/day) and fenofibrate (200 mg/day) in a randomized cross-over study (12 weeks each treatment). We measured adhesion molecules LFA-1, VLA-4 and CD18; in addition, lipopolysaccharide receptor CD14 on monocytes was analyzed as a marker of innate immunity. Leukocyte expression of these molecules was quantified using flow cytometry. Laboratory examinations were done at baseline and at the end of each treatment. Baseline values were compared to those of 29 healthy controls. Expression of integrin CD18 (in all leukocyte populations), lipopolysaccharide receptor and VLA-4 (on lymphocytes only) was significantly higher in patients than in controls. Both treatments resulted in significant decrease in CD18 and CD14 expression; LFA-1 and VLA-4 were not influenced. Both simvastatin and fenofibrate had similar favorable effect on leukocyte activation markers. This result supports the use of both statins and fibrates for the treatment of mixed hyperlipidemia in patients with type 2 diabetes mellitus.


Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa.
It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition of twitching by tear fluid was dose-dependent with dilutions to 6.25% retaining activity. Purified lactoferrin, lysozyme, and contrived tears containing these, and many other, tear components lacked the activity. Systematic protein fractionation, mass spectrometry, and immunoprecipitation identified the glycoprotein DMBT1 (Deleted in Malignant Brain Tumors 1) in tear fluid as required. DMBT1 purified from human saliva also inhibited twitching, as well as P. aeruginosa traversal of human corneal epithelial cells in vitro, and reduced disease pathology in a murine model of corneal infection. DMBT1 did not affect PilA expression, nor bacterial intracellular cyclicAMP levels, and suppressed twitching motility of P. aeruginosa chemotaxis mutants (chpB, pilK), and an adenylate cyclase mutant (cyaB). However, dot-immunoblot assays showed purified DMBT1 binding of pili extracted from PAO1 suggesting that twitching inhibition may involve a direct interaction with pili. The latter could affect extension or retraction of pili, their interactions with biotic or abiotic surfaces, or cause their aggregation. Together, the data suggest that DMBT1 inhibition of twitching motility contributes to the mechanisms by which mucosal fluids protect against P. aeruginosa infection. This study also advances our understanding of how mucosal fluids protect against infection, and suggests directions for novel biocompatible strategies to protect our surface epithelia against a major opportunistic pathogen.


Modeling the initiation of others into injection drug use, using data from 2,500 injectors surveyed in Scotland during 2008-2009.
The prevalence of injection drug use has been of especial interest for assessment of the impact of blood-borne viruses. However, the incidence of injection drug use has been underresearched. Our 2-fold aim in this study was to estimate 1) how many other persons, per annum, an injection drug user (IDU) has the equivalent of full responsibility (EFR) for initiating into injection drug use and 2) the consequences for IDUs' replacement rate. EFR initiation rates are strongly associated with incarceration history, so that our analysis of IDUs' replacement rate must incorporate when, in their injecting career, IDUs were first incarcerated. To do so, we have first to estimate piecewise constant incarceration rates in conjunction with EFR initiation rates, which are then combined with rates of cessation from injecting to model IDUs' replacement rate over their injecting career, analogous to the reproduction number of an epidemic model. We apply our approach to Scotland's IDUs, using over 2,500 anonymous injector participants who were interviewed in Scotland's Needle Exchange Surveillance Initiative during 2008-2009. Our approach was made possible by the inclusion of key questions about initiations. Finally, we extend our model to include an immediate quit rate, as a reasoned compensation for higher-than-expected replacement rates, and we estimate how high initiates' quit rate should be for IDUs' replacement rate to be 1.


Inulin-type fructans and reduction in colon cancer risk: review of experimental and human data.
Inulin-type fructans (beta(2,1)fructans) extracted from chicory roots (Cichorium intybus) are prebiotic food ingredients, which in the gut lumen are fermented to lactic acid and SCFA. Research in experimental animal models revealed that inulin-type fructans have anticarcinogenic properties. A number of studies report the effects of inulin-type fructans on chemically induced pre-neoplastic lesions (ACF) or tumours in the colon of rats and mice. In twelve studies, there were twenty-nine individual treatment groups of which twenty-four measured aberrant crypt foci (ACF) and five measured tumours. There was a significant reduction of ACF in twenty-one of the twenty-four treatment groups and of tumour incidence in five of the five treatment groups. Higher beneficial effects were achieved by synbiotics (mixtures of probiotics and prebiotics), long-chain inulin-type fructans compared to short-chain derivatives, and feeding high-fat Western style diets. Inulin-type fructans reduced tumour incidence in APC(Min) mice in two of four studies and reduced growth and metastasising properties of implanted tumour cells in mice (four studies). The effects have been reported to be associated with gut flora-mediated fermentation and production of butyrate. In human cells, inulin-derived fermentation products inhibited cell growth, modulated differentiation and reduced metastasis activities. In conclusion, evidence has been accumulated that shows that inulin-type fructans and corresponding fermentation products reduced the risks for colon cancer. The involved mechanisms included the reduction of exposure to risk factors and suppression of tumour cell survival. Thus, this specific type of dietary fibre exerted both blocking agent and suppressing agent types of chemopreventive activities.


Frailty and Clinical Outcomes in Chronic Obstructive Pulmonary Disease.
Frailty represents an increased vulnerability to adverse health outcomes. The frailty phenotype conceptual model (three or more patient attributes of wasting, exhaustion, low activity, slowness, and weakness) is associated with increased morbidity and mortality in geriatric populations. Our objective was to describe the risks associated with frailty in patients with chronic obstructive pulmonary disease. Data from the National Emphysema Treatment Trial (NETT) were retrospectively analyzed. The frailty phenotype conceptual model was operationalized as three or more frailty parameters (a body mass index decrease of ≥5% over 12 months, self-reported exhaustion, low 6-minute walk distance, or physical activity or respiratory muscle strength in the lowest quartile). Frail participants were compared with participants with two or fewer frailty parameters. Participants were followed starting 12 months after NETT randomization (to minimize surgical effect) for 24 months. Univariate, multivariate, Kaplan-Meier, and Cox proportional hazard analyses were performed, adjusting for treatment arm, age, modified Medical Research Council dyspnea scale, sex, and baseline forced expiratory volume in 1 second (FEV1). Multiple imputation was used for missing values. The participants (N = 902) were predominantly white (94.5%) males (59.5%), with a median age of 67 years (interquartile range, 63-70 yr) and a median FEV1% predicted of 26 (interquartile range, 20-33). Six percent of the participants (95% confidence interval [CI], 4.5 to 7.6) were frail. The incidence rate of frailty was 6.4 per 100 person-years. Frail participants reported significantly worse disease-specific and overall quality of life by St. George's Respiratory Questionnaire total score (mean difference of 11.6; 95% CI, 7.6 to 15.6; P < 0.001), mental composite on Medical Outcomes Survey Short Form-36 (mean difference -6.8; 95% CI, -10.0 to -3.6; P < 0.001), and physical composite scores on Medical Outcomes Survey Short Form-36 (mean difference -16.7; 95% CI, -21.3 to -12.1; P = 0.001). Frail participants had an increased rate of hospitalization (adjusted hazard ratio, 1.6; 95% CI, 1.1 to 2.5; P = 0.02) and an adjusted increase in hospital use of 8.0 days (95% CI, 4.4 to 11.6; P < 0.001) compared with nonfrail participants. Frail participants had a higher mortality rate (adjusted hazard ratio, 1.4; 95% CI, 0.97 to 2.0; P = 0.07). Among adults with chronic obstructive pulmonary disease, our measure of frailty (modified from the Fried frailty phenotype) was associated with incident and longer-duration hospitalization, and with poor quality of life.


A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6-hydroxydopamine identifies dopamine transporter mutants impacting transporter biosynthesis and trafficking.
The presynaptic dopamine (DA) transporter (DAT) is a major determinant of synaptic DA inactivation, an important target for psychostimulants including cocaine and amphetamine, and a mediator of DA neuron vulnerability to the neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium ion. To exploit genetic approaches for the study of DATs and neural degeneration, we exploited the visibility of green fluorescent protein (GFP)-tagged DA neurons in transgenic nematodes to implement a forward genetic screen for suppressors of 6-OHDA sensitivity. In our initial effort, we identified three novel dat-1 alleles conferring 6-OHDA resistance. Two of the dat-1 alleles derive from point mutations in conserved glycine residues (G55, G90) in contiguous DAT-1 transmembrane domains (TM1 and TM2, respectively), whereas the third allele results in altered translation of the transporter's COOH terminus. Our studies reveal biosynthetic, trafficking and functional defects in the DAT-1 mutants, exhibited both in vitro and in vivo. These studies validate a forward genetic approach to the isolation of DA neuron-specific toxin suppressors and point to critical contributions of the mutated residues, as well as elements of the DAT-1 COOH terminus, to functional expression of catecholamine transporters in neurons.


A nanohybrid system for taste masking of sildenafil.
A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN-MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN-MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN-MMT and Viagra(®), an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN-MMT during the first 2 hours while almost 100% of drug was released from Viagra(®). However, an in vivo experiment showed that the AEA-coated SDN-MMT exhibited higher drug exposure than Viagra(®). For the AEA-coated SDN-MMT, the area under the plasma concentration- time curve from 0 hours to infinity (AUC(0-∞)) and maximum concentration (C(max)) were 78.8 ± 2.32 μg · hour/mL and 12.4 ± 0.673 μg/mL, respectively, both of which were larger than those obtained with Viagra(®) (AUC(0-∞) = 69.2 ± 3.19 μg · hour/mL; C(max) = 10.5 ± 0.641 μg/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure.


Phenolic composition and antimicrobial and antiquorum sensing activity of an ethanolic extract of peels from the apple cultivar Annurca.
This study investigated the phenolic composition and antioxidant capacity of an ethanolic extract from the peel of the Annurca (Malus domestica var. Annurca), which is widespread in the Campania region of southern Italy. The antimicrobial effect of the extract on different pathogens was also examined. The potential antiquorum sensing activity of the extract was tested by using the microorganism Chromobacterium violaceum. Ultra-performance liquid chromatography revealed that rutin, epicatechin, dicaffeoylquinic acid, and caffeic acid were the most abundant phenolic compounds in the extract; these compounds constituted 27.43%, 24.93%, 16.14%, and 15.3% of the total phenols, respectively. The test for 2,2-diphenyl-1-picryl-hydrazyl free radical-scavenging activity showed that the extract possessed an impressive antioxidant capacity (50% effective concentration of 2.50 μg/g of product). Furthermore, the extract clearly exhibited antimicrobial activity against Bacillus cereus (11- to 14-mm diameter of inhibition halo, depending on the strain) and Escherichia coli serotype O157:H7 (10-mm diameter of inhibition halo). No activity was observed against the probiotic lactobacilli tested or against Staphylococcus aureus. Antiquorum sensing activity was reported for the first time for apple extracts. In conclusion, these results indicate the potential of this extract for treating some microbial infections through cell growth inhibition or quorum sensing antagonism, thereby validating the health benefits of apples.


Turbulent heating in galaxy clusters brightest in X-rays.
The hot (10(7) to 10(8) kelvin), X-ray-emitting intracluster medium (ICM) is the dominant baryonic constituent of clusters of galaxies. In the cores of many clusters, radiative energy losses from the ICM occur on timescales much shorter than the age of the system. Unchecked, this cooling would lead to massive accumulations of cold gas and vigorous star formation, in contradiction to observations. Various sources of energy capable of compensating for these cooling losses have been proposed, the most promising being heating by the supermassive black holes in the central galaxies, through inflation of bubbles of relativistic plasma. Regardless of the original source of energy, the question of how this energy is transferred to the ICM remains open. Here we present a plausible solution to this question based on deep X-ray data and a new data analysis method that enable us to evaluate directly the ICM heating rate from the dissipation of turbulence. We find that turbulent heating is sufficient to offset radiative cooling and indeed appears to balance it locally at each radius-it may therefore be the key element in resolving the gas cooling problem in cluster cores and, more universally, in the atmospheres of X-ray-emitting, gas-rich systems on scales from galaxy clusters to groups and elliptical galaxies.


Opto-mechanical analysis of nonlinear elastomer membrane deformation under hydraulic pressure for variable-focus liquid-filled microlenses.
Nonlinear large deformation of a transparent elastomer membrane under hydraulic pressure was analyzed to investigate its optical performance for a variable-focus liquid-filled membrane microlens. In most membrane microlenses, actuators control the hydraulic pressure of optical fluid so that the elastomer membrane together with the internal optical fluid changes its shape, which alters the light path of the microlens to adapt its optical power. A fluid-structure interaction simulation was performed to estimate the transient behavior of the microlens under the operation of electroactive polymer actuators, demonstrating that the viscosity of the optical fluid successfully stabilizes the fluctuations within a fairly short period of time during dynamic operations. Axisymmetric nonlinear plate theory was used to calculate the deformation profile of the membrane under hydrostatic pressure, with which optical characteristics of the membrane microlens were estimated. The effects of gravitation and viscoelastic behavior of the elastomer membrane on the optical performance of the membrane microlens were also evaluated with finite element analysis.


Nonlinear optical spectroscopy of soft matter interfaces.
Soft matter consists of complex molecules that can undergo drastic structural transformations under mild changes of chemical and physical conditions. Since a wide variety of chemical, physical and biological processes occur at soft matter interfaces, they can exhibit complex behavior. This is even more so for interfaces of colloidal soft matter since the relative amount of interface material increases by orders of magnitude. Herein, we focus on new developments that enable us to obtain detailed molecular structural changes in the topmost molecular layers of soft matter interfaces composed of complex bio-molecules. In particular, the possibilities to probe interfaces of colloidal soft matter systems are discussed.


Effect of Different Positions During Surgical Preparation With Combined Spinal-Epidural Anesthesia for Elective Cesarean Delivery: A Randomized Controlled Trial.
The intraoperative 15° left-tilt position during cesarean delivery has more recently been questioned regarding its effect on fetal acid-base balance and is a frequent source of complaints by surgeons. We hypothesized that a 30° left-tilt position during surgical preparation could improve the acid-base balance of the fetus compared with the 15° left-tilt or supine position during surgical preparation. Women undergoing elective cesarean delivery under combined spinal epidural anesthesia were randomized to a supine position, 15° left-lateral tilt position or 30° left-lateral tilt position; the position was changed to supine before the incision. Anesthetic management was standardized and included fluid loading with 10 mL/kg of normal saline followed by colloid loading. Hypotension (systolic blood pressure [SBP] reduction >20% baseline value or SBP <90 mm Hg) was treated with boluses of phenylephrine or ephedrine according to maternal heart rate. The primary outcome was umbilical arterial blood pH and the secondary outcomes included maternal SBP within 15 minutes after induction of anesthesia, the amount of vasoactive drug administered before end of the surgery, and the incidence of hypotension during cesarean delivery. Seventy-five patients were included. After testing by analysis of variance, there was no significant difference in the umbilical arterial pH among the 3 groups (supine group: 7.31 ± 0.03 vs 15° group: 7.30 ± 0.04 vs 30° group: 7.31 ± 0.02, P = .28). The 30° group required significantly less phenylephrine (P = .007) and ephedrine (P = .005) before the end of surgery than the supine group; however, the only benefit observed in the 15° group was that the mean SBP at 3 minutes after spinal injection was significantly improved compared with the supine group. Compared with the supine position, the 30° left-tilt position during surgical preparation did not significantly improve the fetal acid-base status, but it significantly reduced the use of phenylephrine and ephedrine and reduced the incidence of hypotension; however, these benefits were not observed in the 15° left-tilt group.


Sub-surface channels in sapphire made by ultraviolet picosecond laser irradiation and selective etching.
We demonstrate the realization of sub-surface channels in sapphire prepared by ultraviolet picosecond laser irradiation and subsequent selective wet etching. By optimizing the pulse energy and the separation between individual laser pulses, an optimization of channel length can be achieved with an aspect ratio as high as 3200. Due to strong variation in channel length, further investigation was done to improve the reproducibility. By multiple irradiations the standard deviation of the channel length could be reduced to 2.2%. The achieved channel length together with the high reproducibility and the use of a commercial picosecond laser system makes the process attractive for industrial application.


Tyrosine phosphorylation of scavenger receptor cysteine-rich WC1 is required for the WC1-mediated potentiation of TCR-induced T-cell proliferation.
Workshop cluster 1 (WC1) molecules are transmembrane glycoproteins uniquely expressed by gammadelta T cells. They belong to the scavenger receptor cysteine-rich superfamily and are encoded by a multi-gene family, which is divided on the basis of antibody reactivity, into three groups, WC1.1, WC1.2, and WC1.3. The potential role of WC1 as a co-stimulatory molecule for the gammadelta TCR is suggested by the presence of several tyrosine-based motifs in their intracellular domains. In this study, we found that WC1 was constitutively phosphorylated in ex vivo bovine gammadelta T cells and associated with src family tyrosine kinases. Crosslinking of WC1 molecules resulted in an increase in WC1 phosphorylation and co-crosslinking of WC1 and gammadelta TCR together prolonged WC1 phosphorylation. We identified the second tyrosine residue as the primary phosphorylation target in WC1.1 and WC1.2 intracellular sequences in both in vitro and in vivo assays. The cytoplasmic tails of WC1.1 and WC1.2 were phosphorylated on serine and PKC activity was required for PMA-induced endocytosis of WC1.1 or WC1.2. We found that phosphorylation of the second tyrosine in the WC1 cytoplasmic domain was required for the WC1-mediated potentiation of TCR-induced T-cell proliferation, suggesting that WC1 acts as a co-stimulatory molecule for gammadelta TCR.


Alcohol and club drug use among same-sex attracted young people: associations with frequenting the lesbian and gay scene and other bars and nightclubs.
This study aimed to determine whether the lesbian and gay "scene" of bars and nightclubs is a more common site for club drug use than other bars and clubs. A cross-sectional, online survey was conducted with 254 same-sex attracted women and 318 men aged 18-25 in Sydney, Australia. Drug use was more likely in those who attended any venue type more frequently. Men, but not women, were more likely to report drug use in lesbian and gay venues than other venues. Club drug use may be more normalized within the lesbian and gay scene than elsewhere, particularly among young men. The study's limitations are noted.


Saccharides mediate the attachment of rat macrophages to bone in vitro.
Macrophages (M phi) are multipotential cells capable of giving rise to osteoclasts and of resorbing bone. Since both of these processes are ultimately dependent upon the attachment of cells to a mineralized bone surface, we have examined in this study the mechanism by which such attachment is achieved. The data show that elicited rat peritoneal M phi bind to bone in a temperature-dependent and -saturable manner with half-maximal attachment occurring within 10 min at 37 degrees C and reaching a plateau by approximately 60 min. The kinetics of binding are essentially the same whether devitalized bone particles or viable calvaria are used as a substrate. The attachment of M phi to bone is inhibited by some sugars (e.g., N-acetyl-galactosamine, thiogalactoside, beta-lactose), fetuin and asialofetuin, and by pretreating the bone with periodate. Binding is also significantly reduced when M phi are preincubated with tunicamycin and swainsonine at nontoxic concentrations sufficient to inhibit or alter glycosylation. On the other hand, exposing the cells to neuraminidase increases the capacity of M phi to bind to bone. Collectively, our observations indicate that the attachment of M phi to bone is a highly regulated process and is mediated, at least in part, by saccharides located on both the cell and the bone surface.


A power pack based on organometallic perovskite solar cell and supercapacitor.
We present an investigation on a power pack combining a CH3NH3PbI3-based solar cell with a polypyrrole-based supercapacitor and evaluate its performance as an energy pack. The package achieved an energy storage efficiency of 10%, which is much higher than that of other systems combining a PV cell with a supercapacitor. We find a high output voltage of 1.45 V for the device under AM 1.5G illumination when the CH3NH3PbI3-based solar cell is connected in series with a polypyrrole-based supercapacitor. This system affords continuous output of electric power by using CH3NH3PbI3-based solar cell as an energy source mitigating transients caused by light intensity fluctuations or the diurnal cycle.


Interphase chromosome positioning affects the spectrum of radiation-induced chromosomal aberrations.
In interphase, chromosomes occupy defined nuclear volumes known as chromosome territories. To probe the biological consequences of the described nonrandom spatial positioning of chromosome territories in human lymphocytes, we performed an extensive FISH-based analysis of ionizing radiation-induced interchanges involving chromosomes 1, 4, 18 and 19. Since the probability of exchange formation depends strongly on the spatial distance between the damage sites in the genome, a preferential formation of exchanges between proximally positioned chromosomes is expected. Here we show that the spectrum of interchanges deviates significantly from one expected based on random chromosome positioning. Moreover, the observed exchange interactions between specific chromosome pairs as well as the interactions between homologous chromosomes are consistent with the proposed gene density-related radial distribution of chromosome territories. The differences between expected and observed exchange frequencies are more pronounced after exposure to densely ionizing neutrons than after exposure to sparsely ionizing X rays. These experiments demonstrate that the spatial positioning of interphase chromosomes affects the spectrum of chromosome rearrangements.


Morphometric analysis of cardiac hypertrophy during development, maturation, and senescence in spontaneously hypertensive rats.
Hypertrophy of the mammalian heart, regardless of the initiating event, results in architectural remodeling of ventricular components that maintain structural and functional characteristics of this organ. Ventricular components that vary their morphology and morphometry in a hypertrophic state are the muscle cells, connective tissue elements, vasculature, or a combination of some or all of the above. Morphologic quantification of the progressive tissue changes occurring throughout the natural life span of the spontaneously hypertensive and normotensive Wistar-Kyoto rats has not been thoroughly documented. Using perfused-fixed tissue from both strains at 1, 6, 12, 18, and 24 months of age, we have determined the morphometric changes that occurred in the subepicardial and midwall regions of the left ventricle. Myocyte cell size, wall thickness, and arterial blood pressure were elevated in 1-month-old spontaneously hypertensive rats, reached significance by 6 months, and remained significantly greater throughout the 24 months examined. Tissue morphometry demonstrated significant tissue component volumetric differences at 6 months in the spontaneously hypertensive rat. Age-related morphometric tissue changes occurred in both strains yet were exacerbated (percent volume of myocytes) or diminished (percent volume interstitial space) in the mature and aging spontaneously hypertensive rat. Capillary density of SHR left ventricle showed a drastic decline so that 6-month-old SHR had the same density as a senescent Wistar-Kyoto. Tissue morphometry and capillary density data strongly support the hypothesis that tissue oxygenation is diminished in the spontaneously hypertensive rat, and as a result, tissue necrosis and myocyte cell death occur.


Assisting carers using the ACTION model for working with family carers.
This article is the first in a series of four that describes recent developments in Sweden aimed at promoting partnerships between older people, their families and formal service providers. The focus in this article is on the use of information and communication technology (ICT) to help family carers to be more prepared for their caregiving role. It is based upon the PREP (preparedness, enrichment and predictability) model of nursing intervention (Archbold et al, 1995) which is applied in the context of a major ICT project called ACTION (Assisting Carers using Telematics Interventions to meet Older persons' Needs). The way in which ACTION has developed is briefly considered and the range of interventions used is described. Subsequent articles in the series reflect upon users' perceptions of the acceptability of the ACTION approach and a case study of the benefits of ACTION is also presented. Finally, the series concludes with an article which outlines the development of a call centre which is used to complement and augment the ACTION service.


Minimizing memory as an objective for coarse-graining.
Coarse-graining a molecular model is the process of integrating over degrees of freedom to obtain a reduced representation. This process typically involves two separate but related steps, selection of the coordinates comprising the reduced system and modeling their interactions. Both the coordinate selection and the modeling procedure present challenges. Here, we focus on the former. Typically, one seeks to integrate over the fast degrees of freedom and retain the slow degrees of freedom. Failure to separate timescales results in memory. With this motivation, we introduce a heuristic measure of memory and show that it can be used to compare competing coordinate selections for a given modeling procedure. We numerically explore the utility of this heuristic for three systems of increasing complexity. The first example is a four-particle linear model, which is exactly solvable. The second example is a sixteen-particle nonlinear model; this system has interactions that are characteristic of molecular force fields but is still sufficiently simple to permit exhaustive numerical treatment. The third example is an atomic-resolution representation of a protein, the class of models most often treated by relevant coarse-graining approaches; we specifically study an actin monomer. In all three cases, we find that the heuristic suggests coordinate selections that are physically intuitive and reflect molecular structure. The memory heuristic can thus serve as an objective codification of expert knowledge and a guide to sites within a model that requires further attention.


Dynamics of lactate concentration and blood oxygen level-dependent effect in the human visual cortex during repeated identical stimuli.
In vivo (1)H NMR spectroscopy at 7 T was utilized to measure the changes in lactate concentration upon repeated identical visual stimuli, each lasting for 2 min. The average amplitude of these increases was found to be reduced over time (P < 0.01), from 0.13 +/- 0.02 micromol/g during the first half of the stimulation paradigm, to 0.06 +/- 0.02 micromol/g during the second half of the stimulation paradigm. In contrast, the blood oxygen level-dependent (BOLD) effect on the fMRI water signal and on the height of the total creatine signal at 3.03 ppm was persistent during the whole observation period. This finding may suggest a differential adaptation of cortical output that is not reflected at the level of the global excitation-inhibition activity of the cortical canonical circuits. Alternative possibilities that could account for an adaptation of [Lac] changes are also discussed.


SU-E-I-85: Evaluation of a Solid-State Dosimeter Module for Measuring Nuclear Medicine Radionuclides.
A recently introduced solid-state dosimeter module (UDOS001, Teledyne Microelectronic Technologies, Los Angeles, CA) requires only external power (e.g., from two nine-volt batteries in series) and a battery- powered data recorder to assemble a compact, portable dosimeter. This device was developed for radiation detection and monitoring of a wide range of radiation types. It has a nominal minimum energy of 100 keV. The present study sought to determine its suitability for measuring the dose from radionuclides used in nuclear medicine. Three radionuclides (initially 4.77 mCi of F-18, 3.86 mCi of I-131, and 12.4 mCi of Tc-99m) were measured at a distance of one meter and at several different angles of incidence. The most sensitive analog output of the dosimeter was digitized by a battery-powered data logging device (Track-It 5VDC, Monarch Instrument, Amherst NH). These data were transferred from the data logger into a Windows 7 personal computer, formatted as an Excel 2010 spreadsheet and converted from voltage to dose using the manufacturer's nominal calibration factor of 14 urad/19.5 mV step. The dose rate was determined from the slope of a linear fit to the cumulated dose as a function of time. The nominal calibration of the dosimeter gives dose rate measurements that are close to published gamma ray dose rate constants for these radionuclides (0.65 vs. 0.70, 0.25 vs. 0.28, and 0.071 vs. 0.078 mrad/mCi-hr respectively). The angular dependence of the response is greater at 140 keV than at 511 keV, but an acceptance angle of at least 90 degrees has uniform response with all three radionuclides. A better calibration factor would be 0.154 urad/19.5 mV step at these gamma ray energies. This dosimeter can be used to measure the dose from common radionuclides used in nuclear medicine.


MRI to Assess Neurological Function.
This article describes a detailed set of protocols for mouse brain imaging using MRI. We focus primarily on measuring changes in neuroanatomy, and provide both instructions for mouse preparation and details on image acquisition, image processing, and statistics. Practical details as well as theoretical considerations are provided. © 2018 by John Wiley & Sons, Inc.


Low viscous separation media for genomics and proteomics analysis on microchip electrophoresis system.
Microchip electrophoresis has widely grown during the past few years, and it has showed a significant result as a strong separation tool for genomic as well as proteomic researches. To enhance and expand the role of microchip electrophoresis, several studies have been proposed especially for the low viscous separation media, which is an important factor for the success of microchip with its narrow separation channels. In this paper we show an overview for the done researches in the field of low viscous media developed for the use in microchip electrophoresis. For genomic separation studies polyhydroxy additives have been used enhance the separation of DNA at low polymer concentration of HPMC (Hydroxypropylmethyl cellulose) which could keep the viscosity low. Mixtures of poly(ethylene oxide) as well as Hydroxyporpyl cellulose have been successfully introduced for chip separation. Furthermore high molecular mass polyacrylamides at low concentrations have been studied for DNA separation. A mixture of polymer nanoparticle with conventional polymers could show a better resolution for DNA at low concentration of the polymer. For the proteomic field isoelectric focusing on chip has been well overviewed since it is the most viscous separation media which is well used for the protein separation. The different types of isoelectric focusing such as the ampholyte-free type, the thermal type as well as the ampholyte-depended type have been introduced in this paper. Isoelectric focusing on chip with its combination with sodium dodecyl sulfate (SDS) page or free solution could give a better separation. Several application for this low viscous separation medias for either genomic or proteomic could clearly show the importance of this field.


Recognition of complications after pancreaticoduodenectomy for cancer determines inpatient mortality.
While perioperative mortality after pancreaticoduodenectomy is decreasing, key factors remain to be elucidated. The purpose of this study was to investigate inpatient mortality after pancreaticoduodenectomy in the Nationwide Inpatient Sample (NIS), a representative inpatient database in the USA. Patient discharge data (diagnostic and procedure codes) and hospital characteristics were investigated for years 2009 and 2010. The inclusion criteria were a procedure code for pancreaticoduodenectomy, elective procedure, and a pancreatic or peripancreatic cancer diagnosis. Chi-square test determined statistical significance. A logistic regression model for mortality was created from significant variables. Two-thousand and 958 patients were identified with an average age of 65±12 years; 53% were male. The mean length of stay was 15±12 days with a mortality of 4% and a complication rate of 57%. Eighty-six percent of pancreaticoduodenectomy occurred in teaching hospitals. Pancreaticoduodenectomy performed in teaching hospitals in the first half of the academic year were associated with higher mortality than in the latter half (5.5% vs. 3.4%, P=0.005). On logistic regression analysis, non-surgical complications are the largest predictor of death (P<0.001) while operations in the latter half of the academic year are associated with decreased mortality (P<0.01). The timing of pancreaticoduodenectomy for cancer remained more predictive of mortality than age or length of stay; only complications were more predictive of death than time of year. This suggests that there remains a clinically and statistically significant learning curve for trainees in identifying complications; further study is needed to prove that identification of complications leads to a decrease in mortality rate by taking corrective actions.


Inhibitory effect of the methanolic extract of Verbascum latisepalum Hub.-Mor. on endothelium-dependent relaxation in rat thoracic aorta.
The leaves and flowers of Verbascum species are used to treat respiratory disorders, haemorrhoids, rheumatic pain, and wounds as well as for the treatment of eczema and other types of inflammatory skin conditions in traditional Turkish medicine. We examined the effect of the methanolic extract of the aerial parts of Verbascum latisepalum Hub.-Mor. on the endothelium-dependent relaxation response in rat aortic rings which is mediated by nitric oxide (NO). Six fractions, A-F, were obtained from the methanolic extract through bioassay-guided fractionation procedures. The phenylethanoid glycoside verbascoside was isolated from fraction D and its structure elucidated by spectral techniques. The inhibitory effects of the extract, its fractions, and verbascoside on the acetylcholine-induced relaxation response in phenylephrine-precontracted aorta was examined in the absence and presence of L-arginine, a precursor in the synthesis of NO. The observation that the effects of the methanolic extract, of fraction D, and of verbascoside were reversed by L-arginine, indicates that verbascoside has an inhibitory effect on the synthesis of NO. This effect should be taken into consideration in view of the wide range of uses of Verbascum species in Turkish folk medicine.


Inefficient internalization of receptor-bound low density lipoprotein in human carcinoma A-431 cells.
Human epithelioid carcinoma A-431 cells are known to express unusually large numbers of receptors for the polypeptide hormone epidermal growth factor. The current studies demonstrate that this cell line also expresses 5- to 10-fold more low density lipoprotein (LDL) receptors per cell than either human fibroblasts or Chinese hamster ovary (CHO) cells. As visualized with an LDL-ferritin conjugate, the LDL receptors in A-431 cells appeared in clusters that were distributed uniformly over the cell surface, occurring over flat regions of the membrane as well as over the abundant surface extensions. Only 4% of the LDL receptors were located in coated pits. The LDL receptors in A-431 cells showed the same affinity and specificity as the LDL receptors in human fibroblasts and other cell types. In addition, they were subject to feedback regulation by sterols in the same manner as the LDL receptors in other cells. However, in contrast to other cell types in which the receptor-bound LDL is internalized with high efficiency, in the A-431 cells only a small fraction of the receptor-bound LDL entered the cell. In CHO cells approximately 66% of the LDL receptors were located over coated regions of membrane, and the efficiency of LDL internalization was correspondingly 10-fold higher than in A-431 cells. These findings support the concept that the rate of LDL internalization is proportional to the number of LDL receptors in coated pits and that the inefficiency of internalization in the A-431 cells is caused by a limitation in the ability of these cells to incorporate their LDL receptors into coated pits.


Effects of different forages on the chemical compositions and antiosteoporotic activities of velvet antlers.
For this study, we aimed to assess the dose-response antiosteoporotic effects of the middle section of velvet antlers (VAs) from sika deers (Cervus nippon) fed with different types of fodders. VAs prepared from farmed sika deers fed with feed mixtures containing sorghum distillery residue (VA-SDR) or without SDR (SDR replaced with hay, VA-Hay) were divided into upper (VAU), middle (VAM) and basal (VAB) sections. The chemical constituents of the middle sections obtained from each VA type were compared, and their antiosteoporotic activities were evaluated using rats with ovaries removed surgically (ovariectomy, OVX). The VA-Hay exhibited markedly increased iron and cysteine levels, whereas the VA-SDR exhibited markedly increased level of alcoholic extract and testosterone. Both VA-Hay- and VA-SDR-treated rats exhibited increased femur strength compared with the control group. However, VA-SDR exhibited greater bone-strengthening effects than did VA-Hay. The serum osteocalcin and estradiol levels were significantly moderated in the VA-Hay group alone. These results suggest that VA-SDR and VA-Hay prevent the loss of bone strength, and preserve trabecular architecture connectivity in an estrogen-deficient state. However, differences in the chemical compositions of different forages may be responsible for the varying antiosteoporotic mechanisms observed. Thus, the addition of SDR in deer forage may enhance antiosteoporosis activity in VAs, and confer considerable economic and ecological benefits.


Hydrogen Sulfide: A Novel Player in Airway Development, Pathophysiology of Respiratory Diseases, and Antiviral Defenses.
Hydrogen sulfide (H2S) is a biologically relevant signaling molecule in mammals. Along with the volatile substances nitric oxide (NO) and carbon monoxide (CO), H2S is defined as a gasotransmitter. It plays a physiological role in a variety of functions, including synaptic transmission, vascular tone, angiogenesis, inflammation, and cellular signaling. The generation of H2S is catalyzed by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST). The expression of CBS and CSE is tissue specific, with CBS being expressed predominantly in the brain, and CSE in peripheral tissues, including lungs. CSE expression and activity are developmentally regulated, and recent studies suggest that CSE plays an important role in lung alveolarization during fetal development. In the respiratory tract, endogenous H2S has been shown to participate in the regulation of important functions such as airway tone, pulmonary circulation, cell proliferation or apoptosis, fibrosis, oxidative stress, and inflammation. In the past few years, changes in the generation of H2S have been linked to the pathogenesis of a variety of acute and chronic inflammatory lung diseases, including asthma and chronic obstructive pulmonary disease. Recently, our laboratory made the critical discovery that cellular H2S exerts broad-spectrum antiviral activity both in vitro and in vivo, in addition to independent antiinflammatory activity. These findings have important implications for the development of novel therapeutic strategies for viral respiratory infections, as well as other inflammatory lung diseases, especially in light of recent significant efforts to generate controlled-release H2S donors for clinical therapeutic applications.


Apoptotic megakaryocyte dysplasia in the myelodysplastic syndromes.
The terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis to form compact, denuded megakaryocyte nuclei (DMK) surrounded by a thin rim of cytoplasm. Increased numbers of DMK have been reported in patients with acquired immune deficiency syndrome (AIDS) and chronic myeloproliferative disorders. In this study the bone marrow biopsies of 20 patients with various FAB subtypes of myelodysplastic syndrome (MDS) were examined for the presence of DMK cells and semiquantified for marrow reticulin level. For all MDS subtypes, a 9% or greater incidence of DMK in the total megakaryocyte population of the bone marrow was associated with a significant deposit of reticulin in the marrow. Immunocytochemical staining for Factor VIII (Von Willebrand factor), showed the abnormal deposition of this megakaryocyte protein in the extravascular stroma around many of the DMK cells. These findings are consistent with a hypothesis for excess stromal reticulin based on the defective maturation and intramedullary death of large numbers of megakaryocytes. The number of DMK in the marrow biopsies of MDS patients may have prognostic significance.


Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid.
The formation of 5-lipoxygenase (EC 188.8.131.52) products from endogenous substrate by intact rat neutrophilic granulocytes and from exogenous arachidonic acid by rat granulocyte 105,000 x g supernatants and affinity chromatography-purified human leukocyte 5-lipoxygenase was inhibited by acetyl-11-keto-beta-boswellic acid (IC50 values of 1.5 microM, 8 microM, and 16 microM, respectively). With other pentacyclic triterpenes lacking the 11-keto function and/or the carboxyl function on ring A (e.g., amyrin and ursolic acid), no 5-lipoxygenase inhibition was observed. The presence of the noninhibitory pentacyclic triterpenes both in intact cells and in the cell-free system caused a concentration-dependent reversal of the 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid, whereas the inhibitory actions of 5-lipoxygenase inhibitors from different chemical classes (MK-886, L-739,010, ZM-230,487, and nordihydroguaiaretic acid) were not modified. The inhibition by acetyl-11-keto-beta-boswellic acid and the antagonism by noninhibitory pentacyclic triterpenes were not due to nonspecific lipophilic interactions, because lipophilic four-ring compounds (cholesterol, cortisone, and testosterone) neither inhibited the activity of the 5-lipoxygenase nor antagonized the inhibitory action of acetyl-11-keto-beta-boswellic acid. Therefore, we conclude that acetyl-11-keto-beta-boswellic acid acts directly on the 5-lipoxygenase enzyme at a selective site for pentacyclic triterpenes that is different from the arachidonate substrate binding site.


Human leukocyte antigen class 1 genotype distribution and analysis in persons with active tuberculosis and household contacts from Central Uganda.
To determine the distribution of Human leukocyte antigen (HLA) class I genotypes in a Ugandan population of persons with tuberculosis (TB) and establish the relationship between class I HLA types and Mycobacterium tuberculosis (MTB) disease. Blood samples were drawn from HIV negative individuals with active TB and HIV negative household controls. DNA was extracted from blood samples and HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. HLA-A*02, B*15, C*07, C*03, B*58, C*04, A*01, A*74, C*02 and A*30 were the dominant genotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the household controls with only HLA-A*03 allele showing a statistically significant difference (p = 0.017 crude; OR = 6.29 and p = 0.016; OR = 11.67 after adjustment for age). However, after applying the Benjamini and Hochberg adjustment for multiple comparisons the difference was no longer statistically significant (p = 0.374 and p = 0.176 respectively). We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results do not show a positive association between the HLA class I alleles and TB in this Ugandan population however the study sample was too small to draw any firm conclusions about the role of HLA class I alleles and TB development in Uganda.


Baseline predictors of visual acuity and retinal thickness outcomes in patients with retinal vein occlusion: Standard Care Versus COrticosteroid for REtinal Vein Occlusion Study report 10.
To investigate baseline factors associated with visual acuity and central retinal thickness outcomes in patients with macular edema secondary to retinal vein occlusion in the Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study. Two multicenter, randomized clinical trials: one evaluating participants with central retinal vein occlusion (CRVO) and one evaluating participants with branch retinal vein occlusion (BRVO). Participants with follow-up data of 1 year or more, including 238 with CRVO and 367 with BRVO. Visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) method, and central retinal thickness was measured by optical coherence tomography (OCT). Regression analysis related these outcomes to 20 baseline measures. Multiple P values were adjusted to control the false discovery rate. Outcome measures of visual acuity letter score included absolute change from baseline, a gain of ≥ 15 from baseline, and a loss of ≥ 15 from baseline. Outcome measures of center point thickness included absolute change from baseline, a measurement of ≤ 250 μm, and a measurement of ≥ 500 μm. Outcomes were assessed at 1 and 2 years. For CRVO and BRVO, younger age was associated with improved visual acuity and central retinal thickness outcomes. For CRVO, triamcinolone treatment and less severe anatomic abnormalities of the retina (center point thickness and areas of retinal hemorrhage, thickening, and fluorescein leakage) were predictive of better visual acuity outcomes. For BRVO, no history of coronary artery disease was predictive of improved visual acuity outcomes. For center point thickness outcomes, shorter duration of macular edema was associated with improvement in both disease entities. For CRVO, higher baseline visual acuity letter score was predictive of favorable OCT outcomes. For BRVO, lower baseline visual acuity letter score, presence of dense macular hemorrhage, and no prior grid photocoagulation were predictive of favorable OCT outcomes. Several factors were predictive of better visual acuity outcomes and more favorable OCT outcomes, including younger age and shorter duration of macular edema, respectively. These factors may assist clinicians in predicting disease course for patients with CRVO and BRVO.


Influence of Dynesys system screw profile on adjacent segment and screw.
Displacement-controlled finite element analysis was used to evaluate the mechanical behavior of the lumbar spine after insertion of the Dynesys dynamic stabilization system. This study aimed to investigate whether different depths of screw placement of Dynesys would affect load sharing of screw, range of motion (ROM), annulus stress, and facet contact force. In clinical follow-up, a high rate of screw complications and adjacent segment disease were found after using Dynesys. The pedicle screw in the Dynesys system is not so easy to implant into the standard position and causes the screw to protrude more prominently from the pedicle. Little is known about how the biomechanical effects are influenced by the Dynesys screw profile. The Dynesys was implanted in a 3-dimensional, nonlinear, finite element model of the L1 to L5 lumbar spine. Different depths of screw position were modified in this model by 5 and 10 mm out of the pedicle. The model was loaded to 150 N preload and controlled the same ROMs by 20, 15, 8, and 20 degrees in flexion, extension, torsion, and lateral bending, respectively. Resultant ROM, annulus stress, and facet contact force were analyzed at the surgical and adjacent level. Under flexion, extension, and lateral bending, the Dynesys provided sufficient stability at the surgical level, but increased the ROM at the adjacent level. Under flexion and lateral bending, the Dynesys alleviated annulus stress at the surgical level, but increased annulus stress at the adjacent level. Under extension, the Dynesys decreased facet loading at the surgical level but increased facet loading at the adjacent level. This study found that the Dynesys system was able to restore spinal stability and alleviate loading on disc and facet at the surgical level, but greater ROM, annulus stress, and facet loading were found at the adjacent level. In addition, profile of the screw placement caused only a minor influence on the ROM, annulus stress, and facet loading, but the screw stress was noticeably increased.


Climate change and larval transport in the ocean: fractional effects from physical and physiological factors.
Changes in larval import, export, and self-seeding will affect the resilience of coral reef ecosystems. Climate change will alter the ocean currents that transport larvae and also increase sea surface temperatures (SST), hastening development, and shortening larval durations. Here, we use transport simulations to estimate future larval connectivity due to: (1) physical transport of larvae from altered circulation alone, and (2) the combined effects of altered currents plus physiological response to warming. Virtual larvae from islands throughout Micronesia were moved according to present-day and future ocean circulation models. The Hybrid Coordinate Ocean Model (HYCOM) spanning 2004-2012 represented present-day currents. For future currents, we altered HYCOM using analysis from the National Center for Atmospheric Research Community Earth System Model, version 1-Biogeochemistry, Representative Concentration Pathway 8.5 experiment. Based on the NCAR model, regional SST is estimated to rise 2.74 °C which corresponds to a ~17% decline in larval duration for some taxa. This reduction was the basis for a separate set of simulations. Results predict an increase in self-seeding in 100 years such that 62-76% of islands experienced increased self-seeding, there was an average domainwide increase of ~1-3% points in self-seeding, and increases of up to 25% points for several individual islands. When changed currents alone were considered, approximately half (i.e., random) of all island pairs experienced decreased connectivity but when reduced PLD was added as an effect, ~65% of connections were weakened. Orientation of archipelagos relative to currents determined the directional bias in connectivity changes. There was no universal relationship between climate change and connectivity applicable to all taxa and settings. Islands that presently export large numbers of larvae but that also maintain or enhance this role into the future should be the focus of conservation measures that promote long-term resilience of larval supply.


Sentinel node localization in oral cavity and oropharynx squamous cell cancer.
To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. Tertiary referral center. Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.


The Effect of Socioeconomic Status on the Choice of Treatment for Patients With Cruciate Ligament Injuries in the Knee: A Population-Based Cohort Study.
The socioeconomic status (SES) of patients has been widely recognized as playing an important role in many health-related conditions, including orthopaedic conditions, in which a higher SES has been associated with a higher utilization of more advanced medical treatments such as drugs, diagnostics, and surgery. However, the association between SES and cruciate ligament surgery has not been thoroughly investigated. To evaluate the association between SES and choice of treatment in patients with a cruciate ligament injury. Cohort study; Level of evidence, 3. All Swedish patients with a diagnosed cruciate ligament injury between 1987 and 2010 were identified from the Swedish National Patient Register (N = 98,349). The Longitudinal Integration Database for Health Insurance and Labor Market Studies (LISA) provided information on household income and highest achieved educational level, which were used as socioeconomic indices. The exposure was the SES of patients as determined by the household income and educational level, and the main outcome measure was treatment choice (surgical reconstruction vs nonoperative treatment). Poisson regression models estimated the association. A total of 52,566 patients were included in the study; of these, 20,660 (39%) were treated operatively. Patients in the highest quartile of household income had a significantly higher likelihood of undergoing surgery than those in the lowest quartile (relative risk [RR], 1.16; 95% CI, 1.11-1.20). Patients classified as highly educated had a significantly increased likelihood of being treated operatively compared with those with a low education (RR, 1.29; 95% CI, 1.19-1.39). This study provides a population-based validation that having a higher SES as determined by the household income and/or level of education increases the likelihood of undergoing operative treatment after a cruciate ligament injury. All Swedish citizens are entitled by law to the same quality of health care; therefore, unmotivated differences in treatment between different socioeconomic groups are to be seen as a challenge. It is important to evaluate the specific mechanisms by which the patient's SES influences the decision of whether to treat a cruciate ligament injury operatively.


Oxytocin makes a face in memory familiar.
Social recognition is the basis of all social interactions. Here, we show that, in humans, the evolutionarily highly conserved neuropeptide oxytocin, after intranasal administration, specifically improves recognition memory for faces, but not for nonsocial stimuli. With increased oxytocin levels, previously presented faces were more correctly assessed as "known," whereas the ability of recollecting faces was unchanged. This pattern speaks for an immediate and selective effect of the peptide strengthening neuronal systems of social memory.


Faint Ring around the Spiral Galaxy M82.
Photography of fainter surface brightnesses than heretofore detected shows a very unusual feature in the vicinity of the spiral galaxy M81. If this faint feature is synchrotron radiation from electrons exploded by the neighboring galaxy, M82, then the existence of an overall magnetic field in M81 can be established and calculated at a few microgauss. Other properties of M81 and its companion are implied and can be derived from further observation.


5-methylcytosine in RNA: detection, enzymatic formation and biological functions.
The nucleobase modification 5-methylcytosine (m(5)C) is widespread both in DNA and different cellular RNAs. The functions and enzymatic mechanisms of DNA m(5)C-methylation were extensively studied during the last decades. However, the location, the mechanism of formation and the cellular function(s) of the same modified nucleobase in RNA still remain to be elucidated. The recent development of a bisulfite sequencing approach for efficient m(5)C localization in various RNA molecules puts ribo-m(5)C in a highly privileged position as one of the few RNA modifications whose detection is amenable to PCR-based amplification and sequencing methods. Additional progress in the field also includes the characterization of several specific RNA methyltransferase enzymes in various organisms, and the discovery of a new and unexpected link between DNA and RNA m(5)C-methylation. Numerous putative RNA:m(5)C-MTases have now been identified and are awaiting characterization, including the identification of their RNA substrates and their related cellular functions. In order to bring these recent exciting developments into perspective, this review provides an ordered overview of the detection methods for RNA methylation, of the biochemistry, enzymology and molecular biology of the corresponding modification enzymes, and discusses perspectives for the emerging biological functions of these enzymes.


Outcomes of genetic evaluation for hereditary cancer syndromes in unaffected individuals.
Genetic testing (GT) for inherited cancer predisposition is most informative when initiated in individuals with cancer, thus standard practice recommends GT start in an affected individual. This strategy can be frustrating for unaffected consultands and providers. Retrospective review of cases was performed to compare outcomes of testing the unaffected consultand and recommending that testing start in an affected relative. Records from cancer-free consultands (N = 101), presenting to the University of Michigan Cancer Genetics Clinic between 6/1/2011 and 12/30/2011 were reviewed. All genetics records for these consultands were reviewed through 3/31/2013 for GT recommendations (117 total). The unaffected consultand was offered testing in 14.5 % of cases, testing was completed in 64.7 % of these with one mutation identified. Of consultands tested initially, 70.5 % received cancer-screening recommendations based on family history and test results. Testing was recommended to start in an affected family member in 30.7 % of cases. Fifty percent returned to clinic with information on an affected family member; 83.3 % documented that their family member underwent GT with one mutation identified. Consultands reported the affected family member refused testing in 22.2 % and two of these consultands subsequently pursued GT, identifying one mutation. Fifty percent of cases where testing the family member first was recommended were lost to follow-up with 66.6 % of these never given cancer-screening recommendations. Cancer genetic risk evaluation of healthy consultands should consider the option of pursuing GT in the unaffected consultand and should implement a plan for tailored risk management in the absence of informative genetic evaluation within the family.