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Malignant hyperthermia (MH), a rare autosomal dominant pharmacogenetic disorder of skeletal muscle calcium regulation, is triggered by sevoflurane in susceptible individuals. We report a Korean having MH with multi-minicore myopathy functionally supported by RYR1-mediated intracellular Ca2+ release testing in B lymphocytes. A 14-year-old boy was admitted for the evaluation of progressive torticollis accompanied by cervicothoracic scoliosis. During the preoperative drape of the patient for the release of the sternocleidomastoid muscle under general anesthesia, his wrist and ankle were observed to have severe flexion contracture. The body temperature was 37.1 °C. To treat MH, the patient was administered a bolus of dantrolene intravenously (1.5 mg/kg) and sodium bicarbonate. After a few minutes, muscle rigidity, tachycardia, and EtCO2 all resolved. Next-generation panel sequencing for hereditary myopathy identified a novel RYR1 heterozygous missense variant (NM_000540.2: c.6898T > C; p.Ser2300Pro), which mapped to the MH2 domain of the protein, a hot spot for MH mutations. Ex vivo RYR1-mediated intracellular Ca2+ release testing in B lymphocytes showed hypersensitive Ca2+ responses to isoflurane and caffeine, resulting in an abnormal Ca2+ release only in the proband, not in his family members. Our findings expand the clinical and pathological spectra of information associated with MH with multi-minicore myopathy.

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The high level of progesterone and 17ß-estradiol ratio (P4/E2) in follicular fluid has been considered as a biomarker of follicular atresia. CYP11A1, the crucial gene encoding the rate-limiting enzyme for steroid hormone synthesis, has been reported differently expressed in the ovary during follicular atresia. However, the regulation mechanism of CYP11A1 expression during follicular atresia still remains unclear. Here, we have demonstrated that lnc2300, a novel pig ovary-specific highly expressed cis-acting long noncoding RNA (lncRNA) transcribed from chromosome 7, has the ability to induce the expression of CYP11A1 and inhibit the apoptosis of porcine granulosa cells (GCs). Mechanistically, lnc2300, mainly located in the cytoplasm of porcine GCs, sponges and suppresses the expression of miR-365-3p through acting as a competing endogenous RNA (ceRNA), which further relieves the inhibitory effects of miR-365-3p on the expression of CYP11A1. Besides, CYP11A1 is validated as a direct functional target of miR-365-3p in porcine GCs. Functionally, lnc2300 is an antiapoptotic lncRNA that reduces porcine GC apoptosis by inhibiting the proapoptotic function of miR-365-3p. In summary, our findings reveal a cis-acting regulation mechanism of CYP11A1 through lncRNA, and define a novel signaling pathway, lnc2300/miR-365-3p/CYP11A1 axis, which is involved in the regulation of GC apoptosis and follicular atresia.

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This is a summary report of the most important aspects discussed during the YSI 2300 Analyzer Replacement Meeting. The aim is to provide the interested reader with an overview of the complex topic and propose solutions for the current issue. This solution should not only be adequate for the United States or Europe markets but also for all other countries. The meeting addendum presents three outcomes of the meeting.

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Production of the YSI 2300 STAT PLUS Glucose and l-Lactate Analyzer (YSI Incorporated, Yellow Springs, OH, United States) has been discontinued. This benchtop instrument is the most widely used device for determining the accuracy of products that measure blood glucose and interstitial fluid glucose. An alternate comparator instrument must now be identified by the diabetes diagnostics industry. The available products should be reviewed by parties interested in accurate, fast, low-cost comparator benchtop, or portable (nonstrip) methods using small sample volumes with good ease-of-use and human factors. Stakeholders include glucose monitor manufacturers, test labs, clinical chemists, diabetes clinicians, professional organizations, and regulators. This article presents features of eleven possible alternative instruments to be considered as comparator methods for measuring the accuracy of glucose monitors.

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Background: To avoid inconvenience to patients due to linear accelerator down time in busy radio-therapy departments, treatment plans can be switched between linear accelerators provided that all exhibit the same same dosimetric characteristics. In other words linear accelerators should be beam-matched. Aim: The aim of this study was to evaluate the clinical significance of beam-matching using VMAT plans. Materials and Methods: Dosimetric data with a 6MV beam from am Clinac 2100CD were taken as baseline values and other two units, a 2300CD and a Unique Performance, were factory tuned in accordance. An analysis of PDD data was performed for different field sizes to evaluate energy matching. Beam profiles for field sizes of 10×10 cm2 and 40 × 40 cm2 at depths of 1.5 cm and 10 cm were analyzed. The relative output factor and MLC dosimetric properties were compared with each machine to determine variability among the different models. Thirty patients from our database were selected, ten each for head and neck, thorax and pelvis sites. VMAT plans were created in the Eclipse treatment planning system for a Clinac 2100 CD for reference. and verification plans were created for each to compare point dose measurements. Results: The TPR 20/10 for 10 × 10 cm2 was well matched, showing no energy differences. Deviation of all point dose measurements fell within ±3%. Planar dose maps all showed greater than 95% of points with a passed area γ-value less than 1. Conclusion: Our study evaluation of beam matching with treatment planning modeling showed good agreement fior 6 MV beams across all three linear accelerators used in our clinical environment.

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Detecting small quantities of specific target molecules is of major importance within bioanalytics for efficient disease diagnostics. One promising sensing approach relies on combining plasmonically-active waveguides with microfluidics yielding an easy-to-use sensing platform. Here we introduce suspended-core fibres containing immobilised plasmonic nanoparticles surrounding the guiding core as a concept for an entirely integrated optofluidic platform for efficient refractive index sensing. Due to the extremely small optical core and the large adjacent microfluidic channels, over two orders of magnitude of nanoparticle coverage densities have been accessed with millimetre-long sample lengths showing refractive index sensitivities of 170 nm/RIU for aqueous analytes where the fibre interior is functionalised by gold nanospheres. Our concept represents a fully integrated optofluidic sensing system demanding small sample volumes and allowing for real-time analyte monitoring, both of which are highly relevant within invasive bioanalytics, particularly within molecular disease diagnostics and environmental science.

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The Larval Amphibian Growth and Development Assay (LAGDA) is a globally harmonized chemical testing guideline developed by the U.S. Environmental Protection Agency in collaboration with Japan's Ministry of Environment to support risk assessment. The assay is employed as a higher tiered approach to evaluate effects of chronic chemical exposure throughout multiple life stages in a model amphibian species, Xenopus laevis. To evaluate the utility of the initial LAGDA design, the assay was performed using a mixed mode of action endocrine disrupting chemical, benzophenone-2 (BP-2). X. laevis embryos were exposed in flow-through conditions to 0, 1.5, 3.0 or 6.0 mg l-1 BP-2 until 2 months post-metamorphosis. Overt toxicity was evident throughout the exposure period in the 6.0 mg l-1 treatment due to elevated mortality rates and observed liver and kidney pathologies. Concentration-dependent increases in severity of thyroid follicular cell hypertrophy and hyperplasia occurred in larval tadpoles indicating BP-2-induced impacts on the thyroid axis. Additionally, gonads were impacted in all treatments with some genetic males showing both testis and ovary tissues (1.5 mg l-1 ) and 100% of the genetic males in the 3.0 and 6.0 mg l-1 treatments experiencing complete male-to-female sex reversal. Concentration-dependent vitellogenin induction occurred in both genders with associated accumulations of protein in the livers, kidneys and gonads, which was likely vitellogenin and other estrogen-responsive yolk proteins. This is the first study that demonstrates the endocrine effects of this mixed mode of action chemical in an amphibian species and demonstrates the utility of the LAGDA design for supporting chemical risk assessment. Copyright © 2016 John Wiley & Sons, Ltd.

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The Larval Amphibian Growth and Development Assay (LAGDA) is a globally harmonized test guideline developed by the U.S. Environmental Protection Agency in collaboration with Japan's Ministry of the Environment. The LAGDA was designed to evaluate apical effects of chronic chemical exposure on growth, thyroid-mediated amphibian metamorphosis and reproductive development. During the validation phase, two well-characterized endocrine-disrupting chemicals were tested to evaluate the performance of the initial assay design: xenoestrogen 4-tert-octylphenol (tOP) and xenoandrogen 17ß-trenbolone (TB). Xenopus laevis embryos were exposed, in flow-through conditions, to tOP (nominal concentrations: 0.0, 6.25, 12.5, 25 and 50 µg l-1 ) or TB (nominal concentrations: 0.0, 12.5, 25, 50 and 100 ng l-1 ) until 8 weeks post-metamorphosis, at which time growth measurements were taken, and histopathology assessments were made of the gonads, reproductive ducts, liver and kidneys. There were no effects on growth in either study and no signs of overt toxicity, sex reversal or gonad dysgenesis. Exposure to tOP caused a treatment-related decrease in circulating thyroxine and an increase in thyroid follicular cell hypertrophy and hyperplasia (25 and 50 µg l-1 ) during metamorphosis. Müllerian duct development was affected after exposure to both chemicals; tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs, whereas TB exposure caused accelerated Müllerian duct regression in males and complete regression in >50% of the females in the 100 ng l-1 treatment. Based on these results, the LAGDA performed adequately to evaluate apical effects of chronic exposure to two endocrine-active compounds and is the first standardized amphibian multiple life stage toxicity test to date. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

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To monitor biofilm growth on polydimethylsiloxane in a photobioreactor effectively, the biofilm cells and liquids were separated and measured using a sensor with two U-shaped, double-tapered, fiber-optic probes (Sen. and Ref. probes). The probes' Au-coated hemispherical tips enabled double-pass evanescent field absorption. The Sen. probe sensed the cells and liquids inside the biofilm. The polyimide-silica hybrid-film-coated Ref. probe separated the liquids from the biofilm cells and analyzed the liquid concentration. The biofilm structure and active biomass were also examined to confirm the effectiveness of the measurement using a simulation model. The sensor was found to effectively respond to the biofilm growth in the adsorption through exponential phases at thicknesses of 0-536 µm.

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In line with the embodied cognition view, some researchers have suggested that our capacity to retain information relies on the perceptual and motor systems used to interact with our environment (Barsalou, 1999; Glenberg, 1997). For instance, the language production architecture would be responsible for the retention of verbal materials such as a list of words (Acheson & MacDonald, 2009). However, evidence for the role of the motor system in object memory is still limited. In the present experiments, participants were asked to retain lists of objects in memory. During encoding, participants had to pantomime an action to grasp (Experiments 1A & 1B) or to use the objects (Experiment 2) that was either congruent or incongruent with the objects to be retained. The results showed that performing an incongruent action impaired memory performance compared to a congruent action. This suggests that motor affordances play a role during object retention. The results are discussed in light of the embodied cognition view.

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Measurement of bioluminescent or fluorescent optical reporters with an implanted fiber-optic probe is a promising approach to allow real-time monitoring of molecular and cellular processes in conscious behaving animals. Technically, this approach relies on sensitive light detection due to the relatively limited light signal and inherent light attenuation in scattering tissue. In this paper, we show that specific geometries of lensed fiber probes improve photon collection in turbid tissue such as brain. By employing Monte Carlo simulation and experimental measurement, we demonstrate that hemispherical- and axicon-shaped lensed fibers increase collection efficiency by up to 2-fold when compared with conventional bare fiber. Additionally we provide theoretical evidence that axicon lenses with specific angles improve photon collection over a wider axial range while conserving lateral collection when compared to hemispherical lensed fiber. These findings could guide the development of a minimally-invasive highly sensitive fiber optic-based light signal monitoring technique and may have broad implications such as fiber-based detection used in diffuse optical spectroscopy.

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This study investigated whether participants prefer contexts with relatively little cognitive conflict and whether this preference is related to context-specific control. A conflict selection task was administered in which participants had to choose between two categories that contained different levels of conflict. One category was associated with 80% congruent Stroop trials and 20% incongruent Stroop trials, while the other category was associated with only 20% congruent Stroop trials and 80% incongruent Stroop trials. As predicted, participants selected the low-conflict category more frequently, indicating that participants avoid contexts with high-conflict likelihood. Furthermore, we predicted a correlation between this preference for the low-conflict category and the control implementation associated with the categories (i.e., context-specific proportion congruency effect, CSPC effect). Results however did not show such a correlation, thereby failing to support a relationship between context control and context selection.

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Children with developmental disorders such as cerebral palsy have limited opportunities for effortful interactions with objects and tools. The goal of the study was to investigate whether children with cerebral palsy have deficits in their ability to perceive object length by dynamic touch when compared to typically developing children. Fourteen children with typical development and 12 children with cerebral palsy were asked to report the length of hand-held rods after wielding them out of sight. Multilevel regression models indicated that I1 (maximum principal moment of inertia) was a significant predictor of perceived length - LP (p<.0001). The effect of I1 on LP was significantly different among children (p=.001) and the presence of cerebral palsy (group factor) partially explained such variance (p=.002). In addition, accuracy and reliability of the length judgments made by children with cerebral palsy were significantly lower than the typically developing children (p<.05). Theoretical and clinical implications of these results were identified and discussed.

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Two studies explored the effects of forget instructions on autobiographical memory at immediate test and following delays of either 12-13 months, or 3-4 months. Using the Autobiographical Think/No-Think procedure (cf., Noreen & MacLeod, 2013), 24 never-depressed participants (Study 1) first generated 12 positive and 12 negative autobiographical memories and associated cues. Participants were then asked to recall the memory associated with some of the cues (i.e., 'think' condition), or to avoid saying or thinking about the memory associated with other cues (i.e., 'no-think' condition). Participants were then asked to recall the memories associated with all the cues at immediate test and following a delay of 12-13 months. Participants were found to be successful at forgetting both positive and negative autobiographical memories following 'no-think' instructions at immediate test but this forgetting effect did not persist following a 12-13 month delay. This pattern of remembering and forgetting was replicated in a second study (using 27 never-depressed participants) following a 3-4 month delay. Participants who had been less successful at forgetting 'no-think' memories at immediate test, were more likely to show rebound effects for those memories following a delay compared to memories which received neither 'think' nor 'no-think' instructions. Individual differences in inhibitory control and the efficacy of potential therapeutic interventions of 'no-think' instructions are considered.

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The verbalization of one's thoughts has been shown to impair judgment and decision making in some cases, particularly when targets are perceptual. This finding has been attributed to the fact that non-verbal processes are sometimes difficult to verbalize, which may cause a shift in processing that is maladaptive to the task. The study shows that concurrent written explanations can also enhance judgment and decision making in certain visual choice tasks. This finding suggests that the effect of verbalization on perceptual tasks is not dependent on whether the targets of the judgment are verbal or perceptual but rather on whether there is adequate vocabulary to execute the task and whether the task benefits from a more analytic approach.

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Goal-directed behavior is characterized by the anticipation of the resulting effect during response selection. Such anticipations can be contextualized in the sense that response-effect relationships in one stimulus context are inverted in another stimulus context. The primary study aim was to test the hypothesis that contextualized effect anticipation might depend on whether subjects adopt either an effect-based action control style or a stimulus-based control style. Importantly, we hypothesized that the choice of control styles depends on explicit instruction. Effect anticipation during response selection was determined by assessing the behavioral impact of spatial compatibility between the required response and an additional task-irrelevant spatial feature attached to the anticipated effect that would be produced by that response in a given context. In two experiments we found a compatibility effect exclusively in blocks with effect-based instruction but not in stimulus-based blocks. Furthermore, subjects could quickly switch between styles without one strategy dominating the others. Together, this shows that contextualized anticipation of distal visual effects is not an automatic process but depends on the intention to produce an effect.

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Research has identified multiple category-learning systems with each being "tuned" for learning categories with different task demands and each governed by different neurobiological systems. Rule-based (RB) classification involves testing verbalizable rules for category membership while information-integration (II) classification requires the implicit learning of stimulus-response mappings. In the first study to directly test rule priming with RB and II category learning, we investigated the influence of the availability of information presented at the beginning of the task. Participants viewed lines that varied in length, orientation, and position on the screen, and were primed to focus on stimulus dimensions that were relevant or irrelevant to the correct classification rule. In Experiment 1, we used an RB category structure, and in Experiment 2, we used an II category structure. Accuracy and model-based analyses suggested that a focus on relevant dimensions improves RB task performance later in learning while a focus on an irrelevant dimension improves II task performance early in learning.

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In a recent paper, we provided independent evidence on the accuracy of 'haptically' measured geographical slant perception (Taylor-Covill & Eves, 2013). Durgin (2013) argues that the devices used in our work, namely the palm-board, and palm-controlled inclinometer (PCI), are not measures of perception. In response, we outline four failures of replication in the laboratory work of Durgin and colleagues on which they base their model of slant perception. We also highlight fundamental differences between the perceptual tasks Durgin and colleagues ask of participants relative to those of Proffitt and colleagues' traditional measures. These subtle differences might help explain how the two groups have arrived at discrepant conclusions.

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There has been little research on the fluency of language production and individual difference variables, such as intelligence and executive function. In this study, we report data from 106 participants who completed a battery of standardized cognitive tasks and a sentence production task. For the sentence production task, participants were presented with two objects and a verb and their task was to formulate a sentence. Four types of disfluency were examined: filled pauses (e.g. uh, um), unfilled pauses, repetitions, and repairs. Repetitions occur when the speaker suspends articulation and then repeats the previous word/phrase, and repairs occur when the speaker suspends articulation and then starts over with a different word/phrase. Hierarchical structural equation modeling revealed a significant relationship between repair disfluencies and inhibition. Conclusions focus on the role of individual differences in cognitive ability and their role in models and theories of language production.

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