Novel natural peptides from Hyla arborea schelkownikowi skin secretion.
Hyla arborea schelkownikowi is one of the leaf frog species inhabiting the southern territories of Russia and the former USSR. This frog species is a member of the Hylidae Rafinesque, 1815 batrachians family. The present study deals with the previously uninvestigated peptidome of the Hyla arborea schelkownikowi skin secretion. Nano-electrospray ionization Fourier transform mass spectrometry (nanoESI-FTMS) of the skin secretion, in the intact form and after acetylation, was selected as the general method of analysis. Electron-capture dissociation (ECD) and collision-induced dissociation (CID) fragmentation were both employed, while de novo sequencing was performed by manual interpretation of the MS data. The suppression of the cyclization of b-ions in the mass spectrometer by the acetylation reaction proved to be very efficient for the de novo sequencing of short peptides. Ten skin peptides were found and all of them, except for bradykinin, had not previously been reported. Six of the peptides belong to the tryptophyllins and related peptides, while three peptides are similar to the aureins.


Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects.
Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals' welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal's motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats' motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes.


Systematic review and meta-analysis of the effect of increased vegetable and fruit consumption on body weight and energy intake.
Increased vegetable and fruit consumption is encouraged to promote health, including the maintenance of a healthy body weight. Population health strategies (e.g. 5-A-Day or similar campaigns and subsidies on vegetables or fruit) that emphasize increased consumption may theoretically lead to increased energy intake and weight gain. We undertook a systematic review of trials that sought to increase vegetable and fruit consumption, in the absence of advice or specific encouragement to remove other foods from the diet, to understand the effect on body weight and energy intake. We included only randomised controlled trials. We pooled data using a random effects model for two outcomes: change in body weight and change in energy intake. Sensitivity and secondary analyses were also undertaken, including a one-study removed analysis and analysis by study sub-type to explore sources of heterogeneity. A total of eight studies, including 1026 participants, were identified for inclusion in the review. The mean study duration was 14.7 weeks (range four to 52 weeks). The mean difference in vegetable and fruit consumption between arms was 133 g (range 50 g to 456 g). The mean change in body weight was -0.54kg (95% CI: -1.05 to -0.04; n=8; I2 for heterogeneity = 73%, p<0.01) less in the 'high vegetable and fruit' intake arms than in the 'low vegetable and fruit intake' arms. There was no significant difference in measured change daily energy intake between the two arms (368 kJ; 95% CI: -27 to 762, comparing high vs low; n = 6; I2 = 42%, p = 0.07). Promoting increased fruit and vegetable consumption, in the absence of specific advice to decrease consumption of other foods, appears unlikely to lead to weight gain in the short-term and may have a role in weight maintenance or loss. Longer studies or other methods are needed to understand the long-term effects on weight maintenance and loss.


Direct quantification of intraparticle protein diffusion in chromatographic media.
Diffusion coefficients of proteins in chromatographic media are important parameters for the rational design of stationary phases and purification schemes. In contrast to free diffusion, intraparticle diffusion is hindered by the porous structure of the media. Direct intraparticle diffusion analysis (IDA) is a novel approach for the determination of intraparticle protein diffusion coefficients. IDA is based on the evaluation of spatially and temporally resolved intraparticle concentration profiles. To prevent adsorption and to study diffusion only, the chromatographic media are investigated in underivatized form. With IDA, intraparticle concentration profiles are measured in a microcolumn by confocal laser scanning microscopy (CLSM). From this dynamic data, the diffusion coefficients are determined by parameter estimation, using a spheric diffusion model. The boundary condition is given by the measured protein concentration in the bulk phase. IDA is applied to determine intraparticle diffusion coefficients of seven different proteins in Sepharose 6 FF. The results show excellent congruence of experimental data and simulation results. Moreover, the determined diffusion coefficients lie well within the range of data published in the literature. Given that the material in question allows optical analysis, IDA is a general approach for studying protein diffusion in porous particles and is easily adapted to different proteins, solution conditions and stationary phases.


Presidential address: Experimenting with the scientific past.
When it comes to knowledge about the scientific pasts that might have been - the so-called 'counterfactual' history of science - historians can either debate its possibility or get on with the job. Taking the latter course means re-engaging with some of the most general questions about science. It can also lead to fresh insights into why particular episodes unfolded as they did and not otherwise. Drawing on recent research into the controversy over Mendelism in the early twentieth century, this address reports and reflects on a novel teaching experiment conducted in order to find out what biology and its students might be like now had the controversy gone differently. The results suggest a number of new options: for the collection of evidence about the counterfactual scientific past, for the development of collaborations between historians of science and science educators, for the cultivation of more productive relationships between scientists and their forebears, and for heightened self-awareness about the curiously counterfactual business of being historical.


Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model.
Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13 C dehydroascorbate (DHA) and 13 C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham-operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13 C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13 C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13 C lactate/pyruvate ratio at day 7 compared with baseline, although the 13 C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham-operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13 C MRS for the non-invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI.


Opinion and evidence for treatments in endocrine disorders.
New treatments and treatment protocols for endocrine disorders are evolving rapidly, and research and development activity in the endocrinology field is high. Optimal therapy remains contentious in some areas. To help you keep up to date with the latest advances worldwide on all aspects of drug therapy and management of endocrine disorders, this section of the journal brings you information selected from the rapid drug news alerting service Inpharma WeeklyInpharma Weekly provides rapid alerts to news on drugs and drug therapy. Summarizing information selected from over 1600 biomedical journals, this newsletter is produced by Adis International Limited and is available in a variety of formats. Please contact your nearest Adis office for subscription details. The use of trade names, identified by ['~'] or the use of a registered (((R))) or trademark (trade mark) symbol, is for product identification purposes only and does not imply endorsement.. Each issue contains easy-to-read summaries of the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse drug reaction news, and expert opinion pieces published in the world's top endocrinology journals.


Kinetics and Muscle Activity Patterns during Unweighting and Reloading Transition Phases in Running.
Amongst reduced gravity simulators, the lower body positive pressure (LBPP) treadmill is emerging as an innovative tool for both rehabilitation and fundamental research purposes as it allows running while experiencing reduced vertical ground reaction forces. The appropriate use of such a treadmill requires an improved understanding of the associated neuromechanical changes. This study concentrates on the runner's adjustments to LBPP-induced unweighting and reloading during running. Nine healthy males performed two running series of nine minutes at natural speed. Each series comprised three sequences of three minutes at: 100% bodyweight (BW), 60 or 80% BW, and 100% BW. The progressive unweighting and reloading transitions lasted 10 to 15 s. The LBPP-induced unweighting level, vertical ground reaction force and center of mass accelerations were analyzed together with surface electromyographic activity from 6 major lower limb muscles. The analyses of stride-to-stride adjustments during each transition established highly linear relationships between the LBPP-induced progressive changes of BW and most mechanical parameters. However, the impact peak force and the loading rate systematically presented an initial 10% increase with unweighting which could result from a passive mechanism of leg retraction. Another major insight lies in the distinct neural adjustments found amongst the recorded lower-limb muscles during the pre- and post-contact phases. The preactivation phase was characterized by an overall EMG stability, the braking phase by decreased quadriceps and soleus muscle activities, and the push-off phase by decreased activities of the shank muscles. These neural changes were mirrored during reloading. These neural adjustments can be attributed in part to the lack of visual cues on the foot touchdown. These findings highlight both the rapidity and the complexity of the neuromechanical changes associated with LBPP-induced unweighting and reloading during running. This in turn emphasizes the need for further investigation of the evolution over time of these neuromechanical changes.


The Fragment Molecular Orbital Method Reveals New Insight into the Chemical Nature of GPCR-Ligand Interactions.
Our interpretation of ligand-protein interactions is often informed by high-resolution structures, which represent the cornerstone of structure-based drug design. However, visual inspection and molecular mechanics approaches cannot explain the full complexity of molecular interactions. Quantum Mechanics approaches are often too computationally expensive, but one method, Fragment Molecular Orbital (FMO), offers an excellent compromise and has the potential to reveal key interactions that would otherwise be hard to detect. To illustrate this, we have applied the FMO method to 18 Class A GPCR-ligand crystal structures, representing different branches of the GPCR genome. Our work reveals key interactions that are often omitted from structure-based descriptions, including hydrophobic interactions, nonclassical hydrogen bonds, and the involvement of backbone atoms. This approach provides a more comprehensive picture of receptor-ligand interactions than is currently used and should prove useful for evaluation of the chemical nature of ligand binding and to support structure-based drug design.


Prostate-Specimen Antigen (PSA) Screening and Shared Decision Making Among Deaf and Hearing Male Patients.
Some deaf men who use American Sign Language (ASL) experience barriers in patient-physician communication which may leave them at disparity for shared decision making compared to hearing men. Transparent communication accessibility is needed between deaf male ASL users and their physicians to maximize the benefit to risk ratio of using the prostate-specific antigen (PSA) as a screening tool for early detection. The objective is to compare shared decision-making outcomes between deaf and hearing males who are (1) age-eligible for PSA screening and (2) younger than 45 years old with a family history of cancer. An accessible health survey including questions about PSA test, PCC, modes of communication, and cancer history was administered in ASL to a nationwide sample of deaf adults from February 2017 to April 2018. Two subsamples were created: (1) 45- to 69-year-old men who were age-eligible for PSA testing and (2) 18- to 44-year-old men with a family history of cancer. Age-eligible and younger deaf men with a family history of cancer are at disparity for shared decision making compared to their hearing peers. Regardless of age and PSA testing status, deaf men felt significantly less engaged in shared decision making with their health care providers compared to hearing men. Participation in shared decision making requires not only accessible communication but also cultural competency in working with deaf patients. This is critical in the shared decision-making era in maximizing the benefit of prostate cancer screening in deaf male patient population.


cDNA cloning and characterization of the transcriptional activities of the hamster peroxisome proliferator-activated receptor haPPAR gamma.
We have isolated a cDNA corresponding to the hamster peroxisome proliferator-activated receptor haPPAR gamma, a member of the steroid nuclear hormone receptor superfamily of transcription factors. haPPAR gamma mRNA is highly expressed in adipose tissue, and is expressed in lung, heart, kidney, liver and spleen to a lower extent. Thus, haPPAR gamma may function in activating the transcription of target genes in a variety of tissues, including those not particularly subjected to peroxisomal beta-oxidation. haPPAR gamma binds efficiently in the presence of retinoid X receptor alpha (RXR alpha) to a peroxisome proliferator response element (PPRE) first identified in the acyl-CoA oxidase (ACO) promoter, the rate-limiting enzyme of peroxisomal beta-oxidation. The gene (ACO) encoding this enzyme has been previously shown to be under the transcriptional control of mouse PPAR (mPPAR). Although binding of haPPAR gamma/RXR alpha on the PPRE of the ACO promoter in vitro is similar to that observed for mPPAR/RXR alpha, we show that the transcriptional activities of mPPAR and haPPAR gamma are regulated differently in vivo in response to peroxisome proliferators and heterodimerization with RXR.


The barley (Hordeum vulgare) cellulose synthase-like D2 gene (HvCslD2) mediates penetration resistance to host-adapted and nonhost isolates of the powdery mildew fungus.
Cell walls and cellular turgor pressure shape and suspend the bodies of all vascular plants. In response to attack by fungal and oomycete pathogens, which usually breach their host's cell walls by mechanical force or by secreting lytic enzymes, plants often form local cell wall appositions (papillae) as an important first line of defence. The involvement of cell wall biosynthetic enzymes in the formation of these papillae is still poorly understood, especially in cereal crops. To investigate the role in plant defence of a candidate gene from barley (Hordeum vulgare) encoding cellulose synthase-like D2 (HvCslD2), we generated transgenic barley plants in which HvCslD2 was silenced through RNA interference (RNAi). The transgenic plants showed no growth defects but their papillae were more successfully penetrated by host-adapted, virulent as well as avirulent nonhost isolates of the powdery mildew fungus Blumeria graminis. Papilla penetration was associated with lower contents of cellulose in epidermal cell walls and increased digestion by fungal cell wall degrading enzymes. The results suggest that HvCslD2-mediated cell wall changes in the epidermal layer represent an important defence reaction both for nonhost and for quantitative host resistance against nonadapted wheat and host-adapted barley powdery mildew pathogens, respectively.


Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.
Germ-line mutations in the base-excision-repair gene MYH have been associated with recessive inheritance of multiple colorectal adenomas. Tumors from affected persons displayed excess somatic transversions of a guanine-cytosine pair to a thymine-adenine pair (G:C-->T:A) in the APC gene. We screened for germ-line MYH mutations in 152 patients with multiple (3 to 100) colorectal adenomas and 107 APC-mutation-negative probands with classic familial adenomatous polyposis (>100 adenomas). Subgroups were analyzed for changes in the related genes MTH1 and OGG1. Adenomas were tested for somatic APC mutations. Six patients with multiple adenomas and eight patients with polyposis had biallelic germline MYH variants. Missense and protein-truncating mutations were found, and the spectrums of mutations were very similar in the two groups of patients. In the tumors of carriers of biallelic mutations, all somatic APC mutations were G:C-->T:A transversions. In the group with multiple adenomas, about one third of patients with more than 15 adenomas had biallelic MYH mutations. In the polyposis group, no patient with biallelic MYH mutations had severe disease (>1000 adenomas), but three had extracolonic disease. No clearly pathogenic MTH1 or OGG1 mutations were identified. Germ-line MYH mutations predispose persons to a recessive phenotype, multiple adenomas, or polyposis coli. For patients with about 15 or more colorectal adenomas--especially if no germ-line APC mutation has been identified and the family history is compatible with recessive inheritance--genetic testing of MYH is indicated for diagnosis and calculation of the level of risk in relatives. Clinical care of patients with biallelic MYH mutations should be similar to that of patients with classic or attenuated familial adenomatous polyposis.


Validation of administrative hospital data for identifying incident pancreatic and periampullary cancer cases: a population-based study using linked cancer registry and administrative hospital data in New South Wales, Australia.
Informing cancer service delivery with timely and accurate data is essential to cancer control activities and health system monitoring. This study aimed to assess the validity of ascertaining incident cases and resection use for pancreatic and periampullary cancers from linked administrative hospital data, compared with data from a cancer registry (the 'gold standard'). Analysis of linked statutory population-based cancer registry data and administrative hospital data for adults (aged ≥18 years) with a pancreatic or periampullary cancer case diagnosed during 2005-2009 or a hospital admission for these cancers between 2005 and 2013 in New South Wales, Australia. The sensitivity and positive predictive value (PPV) of pancreatic and periampullary cancer case ascertainment from hospital admission data were calculated for the 2005-2009 period through comparison with registry data. We examined the effect of the look-back period to distinguish incident cancer cases from prevalent cancer cases from hospital admission data using 2009 and 2013 as index years. Sensitivity of case ascertainment from the hospital data was 87.5% (4322/4939), with higher sensitivity when the cancer was resected (97.9%, 715/730) and for pancreatic cancers (88.6%, 3733/4211). Sensitivity was lower in regional (83.3%) and remote (85.7%) areas, particularly in areas with interstate outflow of patients for treatment, and for cases notified to the registry by death certificate only (9.6%). The PPV for the identification of incident cases was 82.0% (4322/5272). A 2-year look-back period distinguished the majority (98%) of incident cases from prevalent cases in linked hospital data. Pancreatic and periampullary cancer cases and resection use can be ascertained from linked hospital admission data with sufficient validity for informing aspects of health service delivery and system-level monitoring. Limited tumour clinical information and variation in case ascertainment across population subgroups are limitations of hospital-derived cancer incidence data when compared with population cancer registries.


Ear anomalies in an infant with Potter's syndrome.
Microdissection and scanning electron microscopy were used to study temporal bone specimens from a newborn infant with Potter's syndrome. The 34-year-old mother of the infant had juvenile-onset rheumatoid arthritis and she took prostaglandin inhibitors (aspirin, indomethacin, and Clinoril) during pregnancy. Autopsy findings included bilateral renal dysgenesis, pulmonary hypoplasia, abnormal facies with low-set ears, and bilateral cataracts. The infant's left external ear canal was stenotic and the left tympanic anulus was narrowed. Otherwise, both middle ears, as well as the sensory structures of the cochleae and semicircular canals, were normal. The saccular and utricular muculae on the right were entirely devoid of otoconia, although they were covered by gelatinous otoconial membranes which appeared normal. On the left, the maculae were covered by thin layers of flat, lenticular crystals 2 to 10 mu in diameter. X-ray powder diffraction analysis showed these aberrant otoconia to be composed of calcium carbonate in the form of vaterite. No abnormalities of the neuroepithelia or macular nerve supply were found in either ear.


Single trial recognition of error-related potentials during observation of robot operation.
Recent works suggest that several human cognitive processes elicited during the observation and monitoring of tasks developed by others can be detected in real time. These works have also demonstrated that human brain activity can be used to recover from machine errors, and as reward signals to teach a simulated robot how to perform given tasks. This paper studies the elicitation of this activity during the operation of a real robot. Experimental results have been obtained with 4 participants observing the operation of a 5 d.o.f. robotic arm performing correct/incorrect reaching tasks, while an EEG system recorded their brain activity. The results give evidence that the brain areas that play a role in detection and monitoring of errors also play a role when observing the operation of a real robot, that a brain discriminative response is elicited during the observation of a correct/incorrect operation of a real robot, and that it is possible to learn a classifier that provides online categorization with high accuracy (80%).


Test-retest reliability of hemifield, central-field, and full-field chromatic pupillometry for assessing the function of melanopsin-containing retinal ganglion cells.
We evaluated the test-retest reliability of current methods of inducing the melanopsin-driven postillumination pupil response (PIPR) under hemifield, central-field, and full-field stimulation conditions. Pupil response was recorded with an eye tracker in 10 visually normal participants. Light stimuli were presented using a Ganzfeld screen with a custom-built device that allows specific regions of the retina to be stimulated. Blue light stimulation at 400 cd/m(2) intensity was presented for 400 ms to the lower and upper halves of the central 30° fields (hemifields), central 30° field (central-field), and full-field to induce PIPR. Red light full-field stimulation also was presented with the same intensity and duration as a control condition. Test-retest reliability of the PIPR measures was assessed by calculating the intraclass correlation coefficient (ICC) of six repetitions for lower and upper hemifield stimulation, and three repetitions for central-field and full-field stimulation. Hemifield, central-field, and full-field blue light stimulation induced increasingly greater PIPR in ascending order, while full-field red light stimulation induced no PIPR. Mean lower and upper hemifield PIPR was highly symmetric. Mean ICC of blue light PIPR was 0.87 for lower hemifield, 0.88 for upper hemifield, 0.95 for central-field, and 0.94 for full-field stimulation. We validated a new and repeatable method to measure PIPR induced by hemifield, central-field, and full-field light stimulation. Good PIPR measurement reliability was obtained under all conditions. This practical and reliable protocol will facilitate the clinical application of PIPR testing in different disease populations.


Stimulus set meaningfulness and neurophysiological differentiation: a functional magnetic resonance imaging study.
A meaningful set of stimuli, such as a sequence of frames from a movie, triggers a set of different experiences. By contrast, a meaningless set of stimuli, such as a sequence of 'TV noise' frames, triggers always the same experience--of seeing 'TV noise'--even though the stimuli themselves are as different from each other as the movie frames. We reasoned that the differentiation of cortical responses underlying the subject's experiences, as measured by Lempel-Ziv complexity (incompressibility) of functional MRI images, should reflect the overall meaningfulness of a set of stimuli for the subject, rather than differences among the stimuli. We tested this hypothesis by quantifying the differentiation of brain activity patterns in response to a movie sequence, to the same movie scrambled in time, and to 'TV noise', where the pixels from each movie frame were scrambled in space. While overall cortical activation was strong and widespread in all conditions, the differentiation (Lempel-Ziv complexity) of brain activation patterns was correlated with the meaningfulness of the stimulus set, being highest in the movie condition, intermediate in the scrambled movie condition, and minimal for 'TV noise'. Stimulus set meaningfulness was also associated with higher information integration among cortical regions. These results suggest that the differentiation of neural responses can be used to assess the meaningfulness of a given set of stimuli for a given subject, without the need to identify the features and categories that are relevant to the subject, nor the precise location of selective neural responses.


Organophosphate and carbamate poisoning in infants and children.
The clinical and laboratory features of moderate to severe organophosphate and carbamate toxicity in 37 infants and children are presented. Ingestion of an improperly stored liquid pesticide was the most common route of intoxication (76% of patients); five (14%) children became intoxicated after playing on carpets and floors of homes that had been sprayed or fogged by unlicensed exterminators. The transfer diagnoses were incorrect for 16 or 20 patients who were transferred to our center from another institution. Miosis (73%), excessive salivation (70%), muscle weakness (68%), and lethargy (54%) were the most common abnormal signs; 49% and 22% of patients had tachycardia and seizures, respectively, and 38% of children had respiratory insufficiency that required endotracheal intubation and mechanical ventilation. The results of erythrocyte and serum cholinesterase activity assays were concordant in 83% of patients. Thirty-four (92%) patients were treated with atropine and/or pralidoxime; three patients required only supportive care. Most patients had a prompt response to therapy; however, two patients with organophosphate toxicity required multiple doses of atropine during a 24-hour period; in both instances, the doses of atropine were subtherapeutic. There were no deaths. Pneumonitis and/or atelectasis developed in ten patients, including six who had ingested a petroleum distillate-containing insecticide.


Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats.
Because inhaled carbon monoxide (CO) provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects. Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors.


SU-E-I-77: X-Ray Coherent Scatter Diffraction Pattern Modeling in GEANT4.
To model X-ray coherent scatter diffraction patterns in GEANT4 for simulating experiments involving material detection through diffraction pattern measurement. Although coherent scatter cross-sections are modeled accurately in GEANT4, diffraction patterns for crystalline materials are not yet included. Here we describe our modeling of crystalline diffraction patterns in GEANT4 for specific materials and the validation of the results against experimentally measured data. Coherent scatter in GEANT4 is currently based on Hubbell's non-relativistic form factor tabulations from EPDL97. We modified the form-factors by introducing an interference function that accounts for the angular dependence between the Rayleigh-scattered photons and the photon wavelength. The modified form factors were used to replace the inherent form-factors in GEANT4. The simulation was tested using monochromatic and polychromatic x-ray beams (separately) incident on objects containing one or more elements with modified form-factors. The simulation results were compared against the experimentally measured diffraction images of corresponding objects using an in-house x-ray diffraction imager for validation. The comparison was made using the following metrics: number of diffraction rings, radial distance, absolute intensity, and relative intensity. Sharp diffraction pattern rings were observed in the monochromatic simulations at locations consistent with the angular dependence of the photon wavelength. In the polychromatic simulations, the diffraction patterns exhibited a radial blur consistent with the energy spread of the polychromatic spectrum. The simulated and experimentally measured patterns showed identical numbers of rings with close agreement in radial distance, absolute and relative intensities (barring statistical fluctuations). No significant change was observed in the execution time of the simulations. This work demonstrates the ability to model coherent scatter diffraction in GEANT4 in an accurate and efficient manner without compromising the accuracy or runtime of the simulation. This work was supported by the Department of Homeland Security under grant DHS (BAA 10-01 F075), and by the Department of Defense under award W81XWH-09-1-0066.


A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome.
Irritable Bowel Syndrome (IBS) is a common chronic gastrointestinal disorder and the evidence for efficacy of most drug therapies in the treatment of IBS is weak. A popular alternative is probiotics, which have been used in several conditions. including IBS. Probiotics are live microbial food supplements.The aim of this systematic review and meta-analysis of randomized trials study was to evaluate the efficacy of probiotics in alleviating symptoms in patients with irritable bowel syndrome. We searched Ovid versions of MEDLINE (1950-2007), EMBASE (1980-2007), CINAHL (1982-2007), AMED (1985-2007), the Cochrane library and hand searched retrieved papers. We identified 14 randomized placebo controlled trials. Combined data suggested a modest improvement in overall symptoms after several weeks of treatment: for dichotomous data from seven trials the overall Odds Ratio (OR) was 1.6 (95% CI, 1.2 to 2.2); for continuous data from six trials the standardised mean difference (SMD) was 0.23 (95% CI, 0.07 to 0.38).For individual symptoms the results differed between the pooled dichotomous and pooled continuous data. Trials varied in relation to the length of treatment (4-26 weeks), dose, organisms and strengths of probiotics used. Probiotics may have a role in alleviating some of the symptoms of IBS, a condition for which currently evidence of efficacy of drug therapies is weak. However, as IBS is a condition that is chronic and usually intermittent longer term trials are recommended. Such research should focus on the type, optimal dose of probiotics and the subgroups of patients who are likely to benefit the most.


An outcomes-based grading scale for the evaluation of cerebral aneurysms treated with flow diversion.
Despite the popularity of flow-diverting stents for the treatment of cerebral aneurysms, there is no widely accepted scale for the characterization of results. We present an outcomes-based grading scale that considers factors related to failure of flow diversion. The grading scale was developed using the results from consecutive patients at two institutions who were treated with flow diversion for a cerebral aneurysm. The initial treatment results were graded on patient, aneurysm, and treatment characteristics. A 6-point grading scale was developed based on these data. One hundred and seventy-one patients were included in the patient cohort. When compared by multivariate analysis with patients without residuals, patients with aneurysm residuals were found to be older (age ≥60 years, p=0.01, OR 1.17, 95% CI 1.03 to 1.33), to have larger aneurysms (size ≥15 mm, p<0.01, OR 1.38, 95% CI 1.17 to 1.62), to have aneurysms with associated side branches (p=0.02, OR 1.17, 95% CI 1.03 to 1.33), and to have a post-treatment Raymond score of 2 or 3 (p=0.01, OR 1.28, 95% CI 1.06 to 1.56). Using the Raymond score (1-3) as the foundation for the grading scale, additional points (0 or 1) were given for the other three identified factors, creating a 6-point scale. We found that patients with residual aneurysms had statistically higher final tabulated scores (p<0.01). We propose a novel straightforward outcomes-based scale to characterize results after flow diversion treatment of cerebral aneurysms. This scale may provide the basis for the common reporting of results in future studies.


Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+ and phosphorylation.
Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin. We have investigated the possibility that calsequestrin is a luminal calcium concentration sensor for the ryanodine receptor. We measured the luminal calcium concentration at which calsequestrin dissociates from the ryanodine receptor and the effect of calsequestrin on the response of the ryanodine receptor to changes in luminal calcium. We provide electrophysiological and biochemical evidence that: 1), luminal calcium concentration of >/=4 mM dissociates calsequestrin from junctional face membrane, whereas in the range of 1-3 mM calsequestrin remains attached; 2), the association with calsequestrin inhibits ryanodine receptor activity, but amplifies its response to changes in luminal calcium concentration; and 3), under physiological calcium conditions (1 mM), phosphorylation of calsequestrin does not alter its ability to inhibit native ryanodine receptor activity when the anchoring proteins triadin and junctin are present. These data suggest that the quaternary complex is intact in vivo, and provides further evidence that calsequestrin is involved in the sarcoplasmic reticulum calcium signaling pathway and has a role as a luminal calcium sensor for the ryanodine receptor.


QoI Resistance in Fusicladium carpophilum Populations from Almond in California and Evaluation of Molecular Resistance Mechanisms.
Disease management failures have been reported in California for almond scab caused by Fusicladium carpophilum following quinone outside inhibitor (QoI) applications. Resistance in the pathogen populations was found to be common and at high incidence in the major almond-growing regions beginning in 2003, 4 years after registration of azoxystrobin on this crop. Two levels of azoxystrobin resistance, moderate and high, were identified with 50% effective concentration (EC50) values between 0.15 and 10 μg/ml or >40 μg/ml, respectively. Reference isolates collected before resistance was detected had EC50 values <0.05 μg/ml. High-resistance was associated with a G143A mutation in the mitochondrial cytochrome b gene. For the less commonly found moderately resistant isolates, no mutations in the gene were detected between codons 122 and 212. Using primers targeting the G143A mutation or the cytochrome b gene of all F. carpophilum isolates in quantitative polymerase chain reaction (qPCR) analyses, the frequency of highly resistant isolates was accurately determined in mixtures of conidia with selected ratios of sensitive and resistant isolates. The frequency of high resistance in bulked samples of scab lesions, however, was generally underestimated compared with in vitro testing of fungicide sensitivity of fungal isolates from the same lesions. Competition experiments using conidial suspensions demonstrated stability of the highly resistant genotype in the presence of different amounts of sensitive and moderately resistant genotypes. Analysis of covariance of linear regressions of cycle threshold values on DNA concentrations derived from qPCR amplifications using two primer pairs for cytochrome b alleles with and without the G143 mutation showed that several isolates differed in their slopes and midpoints. Thus, heteroplasmy of mitochondrial-inherited QoI resistance is suggested as a likely cause for incongruence in estimating resistance frequencies using the two methods.


Uterine Adenosarcoma: A Retrospective 12-Year Single-Center Study.
Synopsis: Lymphovascular space invasion is an independent risk factor for disease progression and presence of tumor stalk an independent protective factor. Fertility sparing surgery may be acceptable in cases whose tumors present with stalks and without high risk factors. Objectives: The aim of the present study was to investigate the potential prognostic factors of uterine adenosarcoma. Methods: A total of 49 cases of uterine adenosarcoma were retrospectively reviewed at our institution between April 2006 and October 2018. Results: Median follow-up time was 34 months (range: 1-148). Median age was 47.50 years (19-75). Nineteen (38.9%) patients were uterine cervical adenosarcoma and 30 (61.22%) patients were uterine corpus adenosarcoma. Twenty-nine (59.2%) patients were polypoid with a stalk to the uterine cervix or corpus. Twenty-six (38.8%) patients were stage IA. Fifteen (30.6%) patients showed sarcomatous overgrowth. Six (12.2%) patients displayed lymphovascular space invasion (LVSI). Four (8.16%) patients had heterologous elements. In univariate analysis, Disease-free-survival (DFS) was associated with tumor location, presence of tumor stalk, heterologous elements, LVSI. In multivariate analysis, presence of tumor stalk remained an independently protective factor for recurrence (HR = 0.088, P = 0.005), and LVSI a risk factor for recurrence (HR = 11.953, P = 0.002). Fertility-sparing surgery (FSS) was performed in seven stage IA patients. When patients of stage IA analyzed separately, FSS was not significant with the DFS or OS. Conclusions: Presence of tumor stalk remained an independently protective factor for recurrence. Along with adequate counseling, FSS may be acceptable in cases whose tumors present with stalks and without high risk factors.


PCPPI: a comprehensive database for the prediction of Penicillium-crop protein-protein interactions.
Penicillium expansum , the causal agent of blue mold, is one of the most prevalent post-harvest pathogens, infecting a wide range of crops after harvest. In response, crops have evolved various defense systems to protect themselves against this and other pathogens. Penicillium -crop interaction is a multifaceted process and mediated by pathogen- and host-derived proteins. Identification and characterization of the inter-species protein-protein interactions (PPIs) are fundamental to elucidating the molecular mechanisms underlying infection processes between P. expansum and plant crops. Here, we have developed PCPPI, the Penicillium -Crop Protein-Protein Interactions database, which is constructed based on the experimentally determined orthologous interactions in pathogen-plant systems and available domain-domain interactions (DDIs) in each PPI. Thus far, it stores information on 9911 proteins, 439 904 interactions and seven host species, including apple, kiwifruit, maize, pear, rice, strawberry and tomato. Further analysis through the gene ontology (GO) annotation indicated that proteins with more interacting partners tend to execute the essential function. Significantly, semantic statistics of the GO terms also provided strong support for the accuracy of our predicted interactions in PCPPI. We believe that all the PCPPI datasets are helpful to facilitate the study of pathogen-crop interactions and freely available to the research community. : http://bdg.hfut.edu.cn/pcppi/index.html.


Predicting health: the interplay between interpersonal communication and health campaigns.
The present study experimentally investigated the interplay between interpersonal communication and health message exposure in relation to alcohol consumption intentions. Participants were 174 students who took part in a study on the effects of an antialcohol message. At baseline, the authors assessed intention to refrain from binge drinking. At the second wave (2 weeks later), participants were assigned to the conditions of a 2 (antialcohol message or no-alcohol message) × 2 (alcohol conversation or control conversation) between-subjects design, after which intention was again assessed. Results showed that when participants talked about alcohol (instead of the control topic) and were not exposed to an antialcohol message, they were less inclined to refrain from binge drinking, an effect that was not visible when participants talked about alcohol after viewing an antialcohol message. These findings suggest that health campaign exposure moderates the influence of interpersonal communication on health variables.


Promoting healthy eating in pregnancy: what kind of support services do women say they want?
To identify characteristics of the services and support women want to enable them to eat healthily during pregnancy to make a potential future service acceptable to this population. An unhealthy diet during pregnancy may have a significant influence on pregnancy outcome, either directly through nutrient deficiencies or indirectly through maternal weight gain. Many pregnant women in the United Kingdom gain too much weight in pregnancy, and this weight gain may lead to an increased risk of preeclampsia, gestational diabetes and having an obese child. Thus, there is a need for interventions aimed at improving healthy eating in pregnancy. It is crucial in developing successful interventions to understand how participation can be maximised by optimising intervention acceptability. Four focus groups were conducted; two with prenatal women (n = 9) and two with postnatal women (n = 14). Discussion focused on identifying relevant characteristics of a service targeting prenatal and postnatal women's eating to ensure that a future service was acceptable to the women. The participants' responses were clustered into three broad themes: (1) early information leading to routine formation of healthier eating habits, (2) the delivery of practical sessions to increase information and (3) health professionals providing support and signposting to services. The participants reported wanting a practical service held in a convenient location, preferably led by women who have been pregnant themselves. The participants also reported wanting to be offered this service in pregnancy to help them get into a routine before they gave birth. Several suggestions for how this service should be marketed were mentioned, including through midwives and the internet. This research provides practical information for how to design support for prenatal women to increase their knowledge and practical skills regarding eating healthily during their pregnancy.


Antidepressant- and anxiolytic-like activities of an oil extract of propolis in rats.
Propolis biological effects are mainly attributed to its polyphenolic constituents such as flavonoids and phenolic acids that were recently described in the chemical composition of an extract of propolis obtained with edible vegetal oil (OEP) by our group. The aim of this study was to evaluate the effect of OEP on the behavior of rats. An in vivo open field (OF), elevated Plus-maze (EPM), and forced swimming (FS) tests were performed to evaluate locomotor activity, anxiolytic- and antidepressant effects of the extract. Besides, oxidative stress levels were measured in rat blood samples after the behavioral assays by evaluation of the Trolox equivalent antioxidant capacity (TEAC) and nitric oxide levels. OEP increased locomotion in the OF test (50mg/kg) and central locomotion and open arm entries in the OF and EPM tests (10-50mg/kg) and decreased the immobility time in the FS test (10-50mg/kg). Moreover, OEP reduced nitric oxide levels in response to swim stress induced in rats. OEP exerted stimulant, anxiolytic and antidepressant effects on the Central Nervous System and antioxidant activity in rats, highlighting propolis as a potential therapeutic compound for behavior impairment of anxiety and depression.


Asymptomatic bacteriuria rates in schoolchildren: results from a rural city in Turkey.
Although the treatment of asymptomatic bacteriuria (ABU) is recommended in certain conditions, and screening for ABU is generally not recommended in healthy children, high prevalence of ABU in infants in a former study from eastern Turkey, led us to conduct a study to discover ABU rates in schoolchildren in the province of Isparta, Turkey. Children (n = 10289) from 14 schools and aged 6-14 years participated voluntarily. Two clean-catch midstream urine samples were collected, and screened by microscope and culture for infection. Bacterial agents were identified by Gram's stain. Urological and radiological examinations were suggested to the parents of the children identified with ABU. Five thousand and seventy three participants (49.3 per cent) were girls and 5216 (50.7 per cent) were boys. The median age was 10 (6-14) years. The prevalence of ABU in the total population was 0.37 per cent. The prevalence for ABU was higher in female students 134 (0.67 per cent) vs. 4 (0.08 per cent)], [x 2 (df = 1) = 24.44, p < 0.01]. A decline of ABU from the first to the second screening was observed. In 30 (79 per cent) children with ABU, Escherichia coli was isolated. One year later 27 (71.1 per cent) of the 38 children with ABU were found to be culture negative. The prevalence of ABU in our sample population was consistent with the literature. Lower prevalence of ABU in boys may be linked to the high circumcision frequency in Turkey.


Comparisons of disease cluster patterns, prevalence and health factors in the USA, Canada, England and Ireland.
Identification of those who are most at risk of developing specific patterns of disease across different populations is required for directing public health policy. Here, we contrast prevalence and patterns of cross-national disease incidence, co-occurrence and related risk factors across population samples from the U.S., Canada, England and Ireland. Participants (n = 62,111) were drawn from the US Health and Retirement Study (n = 10,858); the Canadian Longitudinal Study on Ageing (n = 36,647); the English Longitudinal Study of Ageing (n = 7938) and The Irish Longitudinal Study on Ageing (n = 6668). Self-reported lifetime prevalence of 10 medical conditions, predominant clusters of multimorbidity and their specific risk factors were compared across countries using latent class analysis. The U.S. had significantly higher prevalence of multimorbid disease patterns and nearly all diseases when compared to the three other countries, even after adjusting for age, sex, BMI, income, employment status, education, alcohol consumption and smoking history. For the U.S. the most at-risk group were younger on average compared to Canada, England and Ireland. Socioeconomic gradients for specific disease combinations were more pronounced for the U.S., Canada and England than they were for Ireland. The rates of obesity trends over the last 50 years align with the prevalence of eight of the 10 diseases examined. While patterns of disease clusters and the risk factors related to each of the disease clusters were similar, the probabilities of the diseases within each cluster differed across countries. This information can be used to better understand the complex nature of multimorbidity and identify appropriate prevention and management strategies for treating multimorbidity across countries.


Update on medical overuse.
Overuse of medical care, consisting primarily of overdiagnosis and overtreatment, is a common clinical problem. To identify and highlight the most significant clinical articles published in 2013 related to medical overuse. A systematic review of English-language articles published in 2013 that related to medical overuse in adults. We reviewed 478 published articles that met our inclusion criteria. Of these, 126 were ranked most relevant based on quality of methodology, strength of results, potential effects on patient care, and the number of patients potentially affected. The 10 most relevant articles were selected using the same criteria. These 10 articles (organized into the categories overdiagnosis, overtreatment, and methods to avoid overuse) were reviewed and interpreted for their effect on clinical medicine. The literature on overuse of medical care is rapidly expanding. In 2013, both clinical trials and observational studies highlighted frequently overused or unnecessary care. Overuse of testing causes false-positive results and overdiagnosis. Negative test results do not appear to genuinely reassure patients. Overtreatment, with both medical therapies and procedural interventions, places patients at risk of unnecessary adverse events.


Investigation of interfacial adhesion between the top ends of carbon nanotubes.
Understanding the interfacial forces of carbon nanotubes (CNTs) is fundamental to the development of electromechanical systems based on the contact of CNTs. However, experimental studies on the adhesion properties between CNTs are scarce despite the remarkable contact quality of CNTs. Here, we present an experimental investigation of the adhesion between the top ends of aligned, self-adjusted CNTs using a CNT-integrated microelectromechanical actuator. The pull-out and pull-in behaviors of the contact as a function of the applied force by the actuator are precisely identified by measuring the contact resistance between the CNTs. The adhesion between the top ends of individual CNTs is extracted from the measured adhesive strength between the CNT arrays, and it agrees with the theoretical values of the van der Waals interactions. By exploiting the adhesion of the CNT-to-CNT contact, a programmable and reliable microelectromechanical switching device is demonstrated. Our results offer design strategies for diverse CNT-based nano- and microelectromechanical devices that need repeatable contacting interfaces.


Mapping of alkaline proteins in bovine skeletal muscle.
In agricultural sciences, proteomics has become the new hope for analyzing the meat quality traits that are closely related to the skeletal muscle traits. 2-DE muscle maps of many species have been recently reported and used to find molecular markers of meat quality traits. However, one limitation of 2-DE based analyses is due to the limited alkaline protein separation. Considering this problem, there is a need to use recent advances that have markedly improved the 2-DE based analysis of alkaline proteins. Hence, the present study provides additional information concerning the alkaline proteome of bovine skeletal muscle by using an appropriate protocol to characterize proteins over the entire range of pH 7-11. A total of 32 distinct gene products corresponding to 60 protein spots were identified by PMF and grouped in seven categories according to their main function. This 2-D map will contribute to muscle proteome studies since a significant portion of proteins is in the alkaline pH range.


O-GlcNAcylation Negatively Regulates Cardiomyogenic Fate in Adult Mouse Cardiac Mesenchymal Stromal Cells.
In both preclinical and clinical studies, cell transplantation of several cell types is used to promote repair of damaged organs and tissues. Nevertheless, despite the widespread use of such strategies, there remains little understanding of how the efficacy of cell therapy is regulated. We showed previously that augmentation of a unique, metabolically derived stress signal (i.e., O-GlcNAc) improves survival of cardiac mesenchymal stromal cells; however, it is not known whether enhancing O-GlcNAcylation affects lineage commitment or other aspects of cell competency. In this study, we assessed the role of O-GlcNAc in differentiation of cardiac mesenchymal stromal cells. Exposure of these cells to routine differentiation protocols in culture increased markers of the cardiomyogenic lineage such as Nkx2.5 and connexin 40, and augmented the abundance of transcripts associated with endothelial and fibroblast cell fates. Differentiation significantly decreased the abundance of O-GlcNAcylated proteins. To determine if O-GlcNAc is involved in stromal cell differentiation, O-GlcNAcylation was increased pharmacologically during the differentiation protocol. Although elevated O-GlcNAc levels did not significantly affect fibroblast and endothelial marker expression, acquisition of cardiomyocyte markers was limited. In addition, increasing O-GlcNAcylation further elevated smooth muscle actin expression. In addition to lineage commitment, we also evaluated proliferation and migration, and found that increasing O-GlcNAcylation did not significantly affect either; however, we found that O-GlcNAc transferase--the protein responsible for adding O-GlcNAc to proteins--is at least partially required for maintaining cellular proliferative and migratory capacities. We conclude that O-GlcNAcylation contributes significantly to cardiac mesenchymal stromal cell lineage and function. O-GlcNAcylation and pathological conditions that may affect O-GlcNAc levels (such as diabetes) should be considered carefully in the context of cardiac cell therapy.


Carbon-based drug delivery carriers for cancer therapy.
In the search to improve anticancer therapies, several drug carriers, including carbon-based nanomaterials have been studied. Both liposomes and polymeric microspheres have been used in anticancer drugs. However, there remains an on-going need for better therapeutic materials that have good drug solubility, an ability to reduce systemic toxicity through specific-tumor targeting, and rapid clearance. In this regard, carbon allotropes such as graphene oxide (GOs), carbon nanotubes (CNTs), and nanodiamonds (NDs), have been investigated, as they possess sufficient surface-to-volume ratio, thermal conductivity, rigid structural properties capable of post-chemical modification, and excellent biocompatibility. This review is aimed at exploring these carbon-based nanomaterials for use as multifaceted cancer drug carriers and is intended to demonstrate that GOs, CNTs, and NDs are likely to improve chemotherapeutical strategy for cancers in either a sole or combinational manner.


Intersex gonad differentiation in cultured Russian (Acipenser gueldenstaedtii) and Siberian (Acipenser baerii) sturgeon.
Among sturgeons, the occurrence of individuals with gonads containing both testis and ovary components is considered pathological, and such fish are described as intersex individuals or intersexes. Intersexes are observed in both wild and cultured populations of sturgeon, usually at low frequencies. In the present study, intersex Russian (Acipenser gueldenstaedtii) and Siberian (Acipenser baerii) sturgeons constituted 30% of the studied populations. Macroscopically, intersex gonads were recognizable from 500 days posthatching (dph). Initially, gonads with predominantly male characteristics (testis-ova) were observed, but in older fish gonads with predominantly female traits (ova-testis) were more frequent. Using microscopic analysis, intersex gonads were discernible by 130-200 dph. Observations of intersex germinal epithelium development and analysis of sex distribution in the study populations indicated that feminization was occurring. Histological analysis revealed that differentiation of the germinal epithelium in such gonads was accompanied by various morphological alterations (transformations) that were described using quantitative and localization criteria. The most common type of transformations, massive subepithelial transformations, was manifested by the presence of abundant female germinal tissue located under the gonad surface epithelium in the developing testis. These transformations were identified in the early development stage (100-200 dph). In this type of transformation, differentiation of female germinal tissue at the gonad surface and male tissue at the mesorchium/mesovarium resulted in complete formation of both male and female germinal epithelia within the same gonad.


MMPI vulnerability indicators for schizophrenia and attention deficit disorder: UCLA family study of biological parents of offspring with childhood-onset schizophrenia or ADHD.
Minnesota Multiphasic Personality Inventory (MMPI) scores were examined for 50 parents of children with an onset of schizophrenia prior to 14 years of age, 153 parents of children with attention deficit hyperactivity disorder (ADHD), and 168 parents of community comparison children. The parents were participants in the UCLA Family Study. The mean scores on all standard MMPI scales were within normal limits for all three groups of participants. Parents of schizophrenia probands were significantly higher on scale Sc than parents of community comparison children. Previous research has shown that scale Sc may be associated with a genetic liability to developing schizophrenia. Thus, scale Sc shows promise as an indicator of a heightened risk for the development of schizophrenia. The parents of the ADHD probands were significantly higher on standard clinical scale Pd than community comparison parents. Mothers of both schizophrenia and ADHD probands shared some personality indicators of stress reactivity. Although this study, like all non-adoptee family studies, cannot disentangle genetic effects on the development of these personality characteristics from environmental effects, we speculate that the emotional distress resulting in higher levels of the MMPI characteristics seen in the patients' mothers reflects the impact of raising a psychiatrically ill offspring.


Menopause status is associated with circadian- and sleep-related alterations.
The aim of the study was to investigate whether postmenopausal women show differences in circadian-related variables and sleep characteristics compared with premenopausal women, and to analyze potential associations between these circadian-related variables and abdominal fat distribution or metabolic syndrome (MetS) components. A total of 177 women were studied (127 premenopausal, 50 postmenopausal). Sixty percent of the total population was overweight/obese, with no significant differences between premenopausal (60%) and postmenopausal women (62%) (P = 0.865). Wrist temperature (WT) and rest-activity cycles were measured during 8 consecutive days, and sleep and food diaries collected. MetS characteristics and daily patterns of saliva cortisol were analyzed. Sleep characteristics were assessed with domiciliary polysomnography. Postmenopausal women showed a less robust rhythm in WT with lower amplitude (°C) (0.8 ± 0.4 vs 0.9 ± 0.5) (P < 0.05) and lower mean temperature values at the midpoint of sleep than premenopausal women. Postmenopausal women were also more morning-type than premenopausal women, showing a phase advance of approximately 1 hour in WT and rest-activity rhythms, and more morning-type habits (earlier sleep onset/offset and breakfast intake) (P < 0.05). Postmenopausal women showed higher levels of activity in the morning and lower in the evening compared with premenopausal women (P < 0.05). Daily variability in cortisol was significantly reduced in postmenopausal women compared with premenopausal women (P < 0.05). Postmenopausal women had increased frequency of sleep-related breathing abnormalities (P < 0.0001). In the women studied, abdominal fat and MetS were associated with an increase in circadian alterations (high fragmentation and low amplitude of the rhythm) (P < 0.05). Postmenopausal women exhibit loss of circadian robustness and an increase in sleep abnormalities compared with premenopausal women.


Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes (NRG Oncology RTOG 9501 and RTOG 0234).
Prospective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study was to investigate the association between lymph node counts from neck dissection, local-regional recurrence, and overall survival. The number of lymph nodes counted from neck dissection in patients treated in 2 NRG Oncology trials (Radiation Therapy Oncology Group [RTOG] 9501 and RTOG 0234) was evaluated for its prognostic impact on overall survival with a multivariate Cox model adjusted for demographic, tumor, and lymph node data and stratified by the postoperative treatment group. Five hundred seventy-two patients were analyzed at a median follow-up of 8 years. Ninety-eight percent of the patients were pathologically N+. The median numbers of lymph nodes recorded on the left and right sides were 24 and 25, respectively. The identification of fewer than 18 nodes was associated with worse overall survival in comparison with 18 or more nodes (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09-1.74; P = .007). The difference appeared to be driven by local-regional failure (HR, 1.46; 95% CI, 1.02-2.08; P = .04) but not by distant metastases (HR, 1.08; 95% CI, 0.77-1.53; P = .65). When the analysis was limited to NRG Oncology RTOG 0234 patients, adding the p16 status to the model did not affect the HR for dissected nodes, and the effect of nodes did not differ with the p16 status. The removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local-regional failure, and this should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma. Cancer 2016;122:3464-71. © 2016 American Cancer Society.


Architecture and gene repertoire of the flexible genome of the extreme acidophile Acidithiobacillus caldus.
Acidithiobacillus caldus is a sulfur oxidizing extreme acidophile and the only known mesothermophile within the Acidithiobacillales. As such, it is one of the preferred microbes for mineral bioprocessing at moderately high temperatures. In this study, we explore the genomic diversity of A. caldus strains using a combination of bioinformatic and experimental techniques, thus contributing first insights into the elucidation of the species pangenome. Comparative sequence analysis of A. caldus ATCC 51756 and SM-1 indicate that, despite sharing a conserved and highly syntenic genomic core, both strains have unique gene complements encompassing nearly 20% of their respective genomes. The differential gene complement of each strain is distributed between the chromosomal compartment, one megaplasmid and a variable number of smaller plasmids, and is directly associated to a diverse pool of mobile genetic elements (MGE). These include integrative conjugative and mobilizable elements, genomic islands and insertion sequences. Some of the accessory functions associated to these MGEs have been linked previously to the flexible gene pool in microorganisms inhabiting completely different econiches. Yet, others had not been unambiguously mapped to the flexible gene pool prior to this report and clearly reflect strain-specific adaption to local environmental conditions. For many years, and because of DNA instability at low pH and recurrent failure to genetically transform acidophilic bacteria, gene transfer in acidic environments was considered negligible. Findings presented herein imply that a more or less conserved pool of actively excising MGEs occurs in the A. caldus population and point to a greater frequency of gene exchange in this econiche than previously recognized. Also, the data suggest that these elements endow the species with capacities to withstand the diverse abiotic and biotic stresses of natural environments, in particular those associated with its extreme econiche.


The association between ambient exposure to organophosphates and Parkinson's disease risk.
There is a general consensus that pesticides are involved in the aetiology of Parkinson's disease (PD), although associations between specific pesticides and the risk of developing PD have not been well studied. This study examines the risk of developing PD associated with specific organophosphate (OP) pesticides and their mechanisms of toxicity. This case-control study uses a geographic information system-based exposure assessment tool to estimate ambient exposure to 36 commonly used OPs from 1974 to 1999. All selected OPs were analysed individually and also in groups formed according to their presumed mechanisms of toxicity. The study included 357 incident PD cases and 752 population controls living in the Central Valley of California. Ambient exposure to each OP evaluated separately increased the risk of developing PD. However, most participants were exposed to combinations of OPs rather than a single pesticide. Risk estimates for OPs grouped according to different presumed functionalities and toxicities were similar and did not allow us to distinguish between them. However, we observed exposure-response patterns with exposure to an increasing number of OPs. This study adds strong evidence that OPs are implicated in the aetiology of idiopathic PD. However, studies of OPs at low doses reflective of real-world ambient exposure are needed to determine the mechanisms of neurotoxicity.


[Thiamine in patients with alcohol use disorder and Wernicke's encephalopathy].
- Patients with alcohol use disorder frequently have a thiamine deficiency.- A potential life-threatening complication of thiamine deficiency is Wernicke's encephalopathy.- Since it is clinically difficult to recognize Wernicke's encephalopathy, this condition is often treated inadequately. - Early supplementation of thiamine is important to avoid irreversible neurological damage. - There are differences between the Dutch guidelines regarding the supplementation of thiamine for the treatment of alcoholic use disorder, and those for Wernicke's encephalopathy. - There are no solid evidence-based recommendations about the best dosage, route of administration and duration of thiamine supplementation for the treatment of alcohol use disorder and Wernicke's encephalopathy. - Based on the pharmacokinetic properties of thiamine, it is more appropriate to give patients with alcohol use disorder 25 mg four times a day rather than 50 mg twice a day. - Patients at high risk of Wernicke's encephalopathy should immediately receive an intravenous or intramuscular dose of thiamine; patients with suspected Wernicke's encephalopathy should preferably receive an intravenous dose.- Reports of anaphylactic reaction to parenteral administration of thiamine are rare and are not a reason to refrain from parenteral treatment.


Optimizing Savitzky-Golay parameters for improving spectral resolution and quantification in infrared spectroscopy.
Calculating derivatives of spectral data by the Savitzky-Golay (SG) numerical algorithm is often used as a preliminary preprocessing step to resolve overlapping signals, enhance signal properties, and suppress unwanted spectral features that arise due to nonideal instrument and sample properties. Addressing these issues, a study of the simulated and measured infrared data by partial least-squares regression has been conducted. The simulated data sets were modeled by considering a range of undesired chemical and physical spectral anomalies and variations that can occur in a measured spectrum, such as baseline variations, noise, and scattering effects. The study has demonstrated the importance of the optimization of the SG parameters during the conversion of spectra into derivative form, specifically window size and polynomial order of the fitting curve. A specific optimal window size is associated with an exact component of the system being estimated, and this window size does not necessarily apply for some other component present in the system. Since the optimization procedure can be time-consuming, as a rough guideline spectral noise level can be used for assessment of window size. Moreover, it has been demonstrated that, when the extended multiplicative signal correction (EMSC) is used alongside the SG procedure, the derivative treatment of data by the SG algorithm must precede the EMSC normalization.


Induction of ocular herpes simplex virus shedding by iontophoresis of epinephrine into rabbit cornea.
Ocular herpes simplex virus type 1 (HSV-1) shedding from the latently infected rabbit was induced by iontophoresis of 0.01% epinephrine into the eye. The iontophoresis of epinephrine was at 0.8 mAmp for 8 min once a day for 3 consecutive days. Shedding was determined by the presence of HSV-1 in the tear film obtained with eye swabs. Unilateral epinephrine iontophoresis performed 60 days after inoculation of the virus resulted in ipsilateral HSV-1 shedding in all cases (7/7). Bilateral epinephrine iontophoresis performed on selected days during 170 to 365 days after inoculation resulted in HSV-1 shedding in 75% of the eyes (21/28) and 100% of the rabbits (14/14). All shedding was initiated within 3 days after the third treatment with epinephrine iontophoresis. The shedding frequency induced by epinephrine iontophoresis was significantly higher (pb less than 0.05) than that induced by the other methods employed. HSV-1 was detected in one or both cocultivated explants of trigeminal and superior cervical ganglia for every eye in all experimental groups, indicating that all eyes had the potential to shed. In conclusion, epinephrine iontophoresis induced ocular HSV-1 shedding reliably and with a high frequency in the latently infected rabbits. Furthermore, we suggest that this easily reproducible model of viral shedding offers a system for studying the factors involved in recurrent HSV-1 ocular infections.


Associations between family structure and young people's physical activity and screen time behaviors.
Identifying factors that can influence young peoples' physical activity and sedentary behaviors is important for the development of effective interventions. The family structure in which children grow up may be one such factor. As the prevalence of single parent and reconstituted families have increased substantially over the last decades, the objective of this study was to examine whether these family structures are differentially associated with young people's MVPA, participation in organized sports and screen-time activities (screen-based passive entertainment, gaming, other screen-based activities) as compared to traditional nuclear families. The data stem from the 2013/2014 "Health Behaviour in School- aged Children (HBSC) study". A large Norwegian sample of 11-16 years old students (n = 4509) participated. Cluster-adjusted regression models were estimated using full information maximum likelihood with robust standard errors (MLR). After adjusting for covariates, living with a single parent was negatively associated with days/week with 60 min MVPA (b = -.39, 95%CI: -.58, -.20), and positively associated with hours/weekday of total screen time (b = .50, 95%CI: .08, .93). Young people living with a single parent were also more likely to report no participation in organized sports (OR = 1.40, 95%CI: 1.09, 1.79). Living in a reconstituted family was negatively associated with days/week with 60 min MVPA (b = -.31, 95%CI: -.53, -.08), and positively associated with hours/weekday of total screen time (b = .85, 95%CI: .37, 1.33). For all outcomes, the interaction effects of family structure with sex, and with having siblings were not statistically significant. For material affluence, a significant interaction effect was found for participation in organized sports (χ2 [4] =13.9, p = .008). Those living in a reconstituted family with low or high material affluence had an increased risk for not participating in organized sports whereas those with medium material affluence did not. This study suggests that living with a single parent or in reconstituted families was unfavorably associated with physical activity, sport participation and screen-based behaviors among Norwegian youth. The findings indicate that family structure could be an important factor to take into account in the development and testing of interventions. More in-depth research is needed to identify the mechanisms involved.


A simple assay to identify peroxisomal proteins involved in 12-oxo-phytodienoic acid metabolism.
Peroxisomes are vital eukaryotic organelles that house a variety of metabolic functions. To fully define the proteome of plant peroxisomes, we recently performed a proteomic analysis of peroxisomes from etiolated Arabidopsis seedlings, verified the peroxisomal localization of candidate proteins by in vivo targeting analysis of fluorescent proteins, and subjected the T-DNA mutants of the newly confirmed proteins to a series of phenotypic analysis. Our reverse genetics approach revealed the role of a cysteine protease - Response to Drought 21A-like Cysteine Protease1 (RDL1) - in seed germination, indole-3-butyric acid (IBA) β-oxidation and stress response. Here, we developed a quick assay aimed at identifying peroxisomal proteins involved in the metabolism of 12-oxo-phytodienoic acid (OPDA), which is converted to jasmonic acid in the peroxisome through β-oxidation. We performed a survey of the same mutants analyzed in our previous reverse genetics study with this new assay by measuring the response of mutants to OPDA's inhibitory effect on root elongation. Mutants of RDL1 and SERINE CARBOXYPEPTIDASE-LIKE20 (SCPL20) exhibited statistically significant hypersensitivity to OPDA, indicating the potential involvement of these proteins in OPDA metabolism. This convenient assay may be used in the future to rapidly screen for mutants defective in OPDA metabolism or signaling.


Differential maternal feeding practices, eating self-regulation, and adiposity in young twins.
Restrictive feeding is associated with childhood obesity; however, this could be due to other factors that drive children to overeat and parents to restrict (eg, child genetics). Using a twin design to better control for confounders, we tested differences in restrictive feeding within families in relation to differences in twins' self-regulatory eating and weight status. Sixty-four same-gender twin pairs (4-7 years old) were studied with their mothers. Child caloric compensation ability (COMPX% index) was assessed by using a laboratory-based protocol. The Child Feeding Questionnaire assessed mothers' self-reported feeding styles toward each twin. Child BMI (kg/m(2)) and BMI z score were calculated by using measured weight and height; percent body fat and waist circumference were also assessed. Partial correlations examined within-twin pair differences in Child Feeding Questionnaire subscales in relation to within-twin pair differences in anthropometry and caloric compensation (COMPX%). Differences in maternal restriction were significantly associated with within-pair differences in child COMPX% and BMI z score. Mothers reported more restriction toward the heavier and more poorly compensating twin. Additionally, within-pair differences in parental pressure to eat were associated with significant differences in BMI z score, percent body fat, and waist circumference. Mothers were more pressuring toward the lighter twin. Mothers vary in their feeding practices, even among same-gender twin pairs, which might influence differences in adiposity. Future research needs to elucidate cause-and-effect and intervention implications regarding parental restriction and pressure-to-eat prompts.


Diagnostic neuroimaging across diseases.
Fully automated classification algorithms have been successfully applied to diagnose a wide range of neurological and psychiatric diseases. They are sufficiently robust to handle data from different scanners for many applications and in specific cases outperform radiologists. This article provides an overview of current applications taking structural imaging in Alzheimer's disease and schizophrenia as well as functional imaging to diagnose depression as examples. In this context, we also report studies aiming to predict the future course of the disease and the response to treatment for the individual. This has obvious clinical relevance but is also important for the design of treatment studies that may aim to include a cohort with a predicted fast disease progression to be more sensitive to detect treatment effects. In the second part, we present our own opinions on i) the role these classification methods can play in the clinical setting; ii) where their limitations are at the moment and iii) how those can be overcome. Specifically, we discuss strategies to deal with disease heterogeneity, diagnostic uncertainties, a probabilistic framework for classification and multi-class classification approaches.


Comparative evaluation of cephalometric occlusal characteristics between the long face pattern and pattern I.
To compare the cephalometric and intraoral characteristics between Long Face pattern and Pattern I patients, besides evaluating associations between subjective facial patterns, cephalometric facial patterns and the intraoral characteristics. Through evaluation of frontal and right side extraoral photographs, three previously calibrated and experienced examiners selected 30 Long Face patients (Group 1) and 30 Pattern I patients (Group 2), aged between 9 and 19 years, of both genders. The cephalometric characteristics were assessed by the following variables: SN.GoGn, NS.Gn, AIFH, SNA, SNB, ANB, 1.1, 1.NA,1-NA, 1.NB, 1-NB, NA.Po, nasolabial angle and H-Nose. Clinical evaluations were also performed to determine the presence of posterior crossbite, anterior open bite and type of Angle's malocclusion. The cephalometric data were compared by independent t test. The chi-square test was used to evaluate the association between qualitative variables. Significant differences were observed between groups regarding the variables SN.GoGn, NS.Gn, AIFH, ANB, NA.Pog, 1-NA, 1.NB and 1-NB, with an increase of these measures in Group 1. There were also significant differences between groups on variable 1.1, being lower in Group 1 than in Group 2. The Long Face was associated to Angle Class II malocclusion, to the presence of posterior crossbite and to anterior open bite. The Long Face subjective facial pattern was associated to dolichofacial cephalometric pattern.


Regional variations in the incidence of upper urinary tract stones in England and Wales.
Data from the Hospital In-patient Enquiry were used to define the regional patterns of hospital discharge rates for upper urinary tract stones and renal colic in England and Wales. By combining the rates for stones and colic, and by distinguishing emergency from planned admissions, the biases produced by repeated admissions of the same patient and by regional variations in diagnosis and coding may be reduced. There are regional variations in incidence of upper urinary tract stones: Wales and the southern regions of England have a generally higher incidence than northern regions. These variations may be related to regional differences in diet or occupation; or they may partly depend on associations between stone incidence and atmospheric temperature, exposure to ultraviolet irradiation, and hardness of drinking water.


Sealing properties of a self-etching primer system to normal caries-affected and caries-infected dentin.
To compare the ability of an experimental antibacterial self-etching primer adhesive system to seal exposure sites in normal, caries-affected and caries-infected human dentin. 30 extracted human third molars were used within 1 month of extraction. 10 intact normal teeth comprised the normal group. 20 teeth with occlusal caries that radiographically extended halfway to the pulp were excavated using caries-detector solution (CDS) and a #4 round carbide bur in a slowspeed handpiece. Half of those teeth were fully excavated free of CDS-stained material without exposing the pulp, and were designated as the caries-affected dentin group. The remaining 10 teeth were excavated as close to the pulp as possible without obtaining an exposure, but whose dentin continued to stain red with CDS; this group was designated as the caries-infected dentin group. The remaining dentin thickness in all of the specimens in the other two groups was then reduced to the same extent as the caries-infected group. Direct exposures of the pulp chamber were made with a 1/4 round bur in the normal dentin or a 25 gauge needle in the other two groups. After measuring the fluid flow through the exposure, the sites were then sealed with an experimental antibacterial fluoride-containing self-etching primer adhesive systems (ABF). Fluid conductance was remeasured every week for 16 weeks. The fluid conductance through the exposure fell 99% in all groups following resin sealing. The seals of normal and caries-affected dentin remained relatively stable over the 16 weeks, while the seals of caries-infected dentin gradually deteriorated, reaching significance at 8 weeks. TEM examination revealed very thin (ca. 0.5 mm) hybrid layers in normal dentin, 3-4 microm thick hybrid layers in caries-affected dentin and 40 microm thick hybrid layers in caries-infected dentin. The tubules of caries-infected dentin were enlarged and filled with bacteria. Resin tags passed around these bacteria in the top 20-40 microm thereby encapsulating them in resin.


Leukemia propagating cells rebuild an evolving niche in response to therapy.
Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent microenvironment in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a protective niche. We investigated patients' BM biopsies and found evidence of a similar process in patients receiving induction therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or function. We therefore identified a therapy-induced niche that protects CPCs.


Analysis of the globose basal cell compartment in rat olfactory epithelium using GBC-1, a new monoclonal antibody against globose basal cells.
The olfactory epithelium (OE) supports ongoing neurogenesis throughout life and regenerates after experimental injury. Although evidence indicates that proliferative cells within the population of globose (light) basal cells (GBCs) give rise to new neurons, little is known about the biology of GBCs. Because GBCs have been identifiable only by an absence of staining with reagents that mark other cell types in the epithelium, we undertook to isolate antibodies that specifically react against GBCs and to characterize the GBC compartment in normal and regenerating OE. Monoclonal antibodies were produced using mice immunized with regenerating rat OE, and a monoclonal antibody designated GBC-1, which reacts against GBCs of the rat OE, was isolated. In immunohistochemical analyses, antibody GBC-1 was found to label GBCs in both normal and regenerating OE as we are currently able to define them: basal cells that incorporate the mitotic tracer bromodeoxyuridine and fail to express cytokeratins or neural cell adhesion molecule. During epithelial reconstitution after direct experimental injury with methyl bromide, expression of the GBC-1 antigen overlaps to a limited extent with expression of cell-specific markers for horizontal basal cells, Bowman's gland and sustentacular cells, and neurons. These data suggest that GBC-1 may mark multipotent cells residing in the GBC compartment, which are prominent during regeneration. However, a limited number of cells in the regenerating OE with other phenotypic characteristics of GBCs lack expression of the GBC-1 antigen. GBC-1 has revealed novel aspects of GBC biology and will be useful for studying the process of olfactory neurogenesis.


The effect of strength training and short-term detraining on maximum force and the rate of force development of older men.
This study examined the effect of strength training (ST) and short-term detraining on maximum force and rate of force development (RFD) in previously sedentary, healthy older men. Twenty-four older men (70-80 years) were randomly assigned to a ST group (n = 12) and C group (control, n = 12). Training consisted of three sets of six to ten repetitions on an incline squat at 70-90% of one repetition maximum three times per week for 16 weeks followed by 4 weeks of detraining. Regional muscle mass was assessed before and after training by dual-energy X-ray absorptiometry. Training increased RFD, maximum bilateral isometric force, and force in 500 ms, upper leg muscle mass and strength above pre-training values (14, 25, 22, 7, 90%, respectively; P < 0.05). After 4 weeks detraining all neuromuscular variables were significantly (P < 0.05) lower than after 16 weeks training but remained significantly (P < 0.05) higher than pre-training levels except for RFD which had returned to pre-training levels. These findings demonstrate that high-intensity ST can improve maximum force and RFD of older men. However, older individuals may lose some neuromuscular performance after a period of short-term detraining and that resistance exercise should be performed on a regular basis to maintain training adaptations.


Two-dimensional periodic texture of actin filaments formed upon drying.
We found that a solution of actin filaments can form a periodic texture in the process of drying on a flat glass surface in the air; the periodic texture was composed of smooth meandering bundles of actin filaments. We also found that a branched salt crystal grows in the space between the meandering bundles of actin filaments. The distance between the adjacent striae (striation period) in the resulting dried two-dimensional pattern of striation decreased from about 50 to 2 μm, as the ambient temperature was increased from 4 to 40°C at 1 mg/ml actin, and showed an increasing tendency from a few to several tens μm with the increase in the initial concentration of actin filaments from 0.6 to 2.0mg/ml at room temperature. As the speed of drying is increased at a certain temperature, the striation period was also found to decrease. We propose that the formation of the two-dimensional striation pattern of bundles of actin filaments is the result of condensation of proteins due to dehydration, and suggest that the solvent flow from the center to the periphery of the sample causes the meandering of actin filaments.


Manage migraine with acupuncture: a review of acupuncture protocols in randomized controlled trials.
The aim of this article is to present a standardized protocol of acupuncture for the management of migraine. A systematic review of available randomized controlled trials of acupuncture for migraineurs was conducted in the five following electronic databases: Cochrane Central Register of Controlled trials, MEDLINE, EMBASE, PsycINFO and CINAHL. Information of selected acupoints and treatment course was extracted from the included trials. Then we analyzed the treatment methods used in these trials, to identify any similarities of therapeutic approaches. Additionally, quality of all the included trials was assessed. At last, the extracted information of acupuncture protocols was analyzed, and the similarities of therapeutic approaches were summed up. Bilateral use of the following points is recommended: Fengchi (GB20), Taiyang (EX-HN5), etc. De-qi sensation is requested in acupuncture manipulating procedure, and manual stimulation is suggested. The optimal treatment frequency is twice a week with one week rest between the first 10 and the last 10 sessions. Additionally, the duration of one treatment session ought to be 30 minutes, while it is recommended to use about 20 needles in one session. The total duration of an acupuncture treatment should be at least 10 weeks. The protocol analyzed from trials with positive results is different from trials with negative in number of treatment sessions. Therefore in future trials, enough acupuncture treatment sessions should be fully considered.


Ctk1 function is necessary for full translation initiation activity in Saccharomyces cerevisiae.
Translation is a fundamental and highly regulated cellular process. Previously, we reported that the kinase and transcription elongation factor Ctk1 increases fidelity during translation elongation in Saccharomyces cerevisiae. Here, we show that loss of Ctk1 function also affects the initiation step of translation. Translation active extracts from Ctk1-depleted cells show impaired translation activity of capped mRNA, but not mRNA reporters containing the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Furthermore, the formation of 80S initiation complexes is decreased, which is probably due to reduced subunit joining. In addition, we determined the changes in the phosphorylation pattern of a ribosome enriched fraction after depletion of Ctk1. Thus, we provide a catalogue of phosphoproteomic changes dependent on Ctk1. Taken together, our data suggest a stimulatory function of Ctk1 in 80S formation during translation initiation.


Understanding an emerging treatment population: Protocol for and baseline characteristics of a prospective cohort of people receiving treatment for pharmaceutical opioid dependence.
Despite large increases in pharmaceutical opioid dependence and related mortality, few studies have focused on the characteristics and treatment experiences of those with pharmaceutical opioid dependence. We describe the formation of a prospective cohort of people receiving treatment for pharmaceutical opioid dependence and describe their baseline characteristics. People who had entered treatment for pharmaceutical opioid dependence (n = 108) were recruited through drug treatment services in New South Wales, Australia. We describe baseline characteristics of those that commenced pharmaceutical opioids for pain or other reasons and conducted a thematic analysis of responses regarding their treatment experience. Mean age was 41 years (SD 11), half were male (48%). Just over half reported lifetime heroin use (57%). Oxycodone (49%) and codeine (29%) were the most common opioids reported. Most (85%) reported past-year problematic pain, 38% reported chronic pain. Half (52%) reported moderate to severe depression symptoms. Most (66%) commenced opioids for pain, and this group were older, less likely to report a previous overdose and less likely to report use of illicit drugs compared to those commencing for other reasons. Five themes related to treatment expectations: (i) stigma; (ii) the restrictive nature of treatment; (iii) knowledge; (iv) pain; and (v) positive experience with buprenorphine. This study describes the complexities in an important emerging treatment population of pharmaceutical opioid-dependent people. Findings highlights that addressing knowledge and perceptions around treatment may be critical to address the rising mortality associated with pharmaceutical opioid dependence.


Sensitivity Analysis in Observational Research: Introducing the E-Value.
Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.