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Objective: To present a list of key points for good Temporomandibular Disorders (TMDs) clinical practice on behalf of the International Network for Orofacial Pain and Related Disorders Methodology (INfORM) group of the International Association for Dental, Oral and Craniofacial Research (IADR)., Methods: An open working group discussion was held at the IADR General Session in New Orleans (March 2024), where members of the INfORM group finalized the proposal of a list of 10 key points., Results: The key points covered knowledge on the etiology, diagnosis, and treatment. They represent a summary of the current standard of care for management of TMD patients. They are in line with the current need to assist general dental practitioners advance their understanding and prevent inappropriate treatment., Conclusions: The key points can be viewed as a guiding template for other national and international associations to prepare guidelines and recommendations on management of TMDs adapted to the different cultural, social, educational, and healthcare requirements.

The finite number of pixels in a silicon photomultiplier (SiPM) limits its dynamic range to light pulses up to typically 80% of the total number of pixels in a device. Correcting the non-linear response is essential to extend the SiPM's dynamic range. One challenge in determining the non-linear response correction is providing a reference linear light source. Instead, the single-step method used to calibrate PMTs is applied, based on the difference in responses to two light sources. With this method, the response of an HPK SiPM (S14160-1315PS) is corrected to linearity within 5% while extending the linear dynamic range by a factor larger than ten. The study shows that the response function does not vary by more than 5% for a variation in the operating voltage between 2 and 5 V overvoltage in the gate length between 20 and 100 ns and for a time delay between the primary and secondary light of up to 40 ns.

This retrospective study shows that treatment with anti-eosinophilic antibodies in patients with severe eosinophilic asthma is associated with an increase in work productivity and a decrease in missed days at work https://bit.ly/3IIPppR., Competing Interests: Conflicts of interest: N. Drick reports speaker fees for AstraZeneca. H. Suhling reports speaker fees for AstraZeneca, GlaxoSmithKline (GSK) and Novartis. J. Fuge reports speaker fees for AstraZeneca. T. Welte reports personal fees from AstraZeneca, GSK and Sanofi Aventis, and his institution has received research grants from the German Ministry of Research and Education. L. Brinkmann has no relevant conflicts of interest., (Copyright ©The authors 2023.)

Interactions between humans and bots are increasingly common online, prompting some legislators to pass laws that require bots to disclose their identity. The Turing test is a classic thought experiment testing humans' ability to distinguish a bot impostor from a real human from exchanging text messages. In the current study, we propose a minimal Turing test that avoids natural language, thus allowing us to study the foundations of human communication. In particular, we investigate the relative roles of conventions and reciprocal interaction in determining successful communication. Participants in our task could communicate only by moving an abstract shape in a 2D space. We asked participants to categorize their online social interaction as being with a human partner or a bot impostor. The main hypotheses were that access to the interaction history of a pair would make a bot impostor more deceptive and interrupt the formation of novel conventions between the human participants. Copying their previous interactions prevents humans from successfully communicating through repeating what already worked before. By comparing bots that imitate behavior from the same or a different dyad, we find that impostors are harder to detect when they copy the participants' own partners, leading to less conventional interactions. We also show that reciprocity is beneficial for communicative success when the bot impostor prevents conventionality. We conclude that machine impostors can avoid detection and interrupt the formation of stable conventions by imitating past interactions, and that both reciprocity and conventionality are adaptive strategies under the right circumstances. Our results provide new insights into the emergence of communication and suggest that online bots mining personal information, for example, on social media, might become indistinguishable from humans more easily., (© 2023 The Authors. Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).)

Background: Nephrolithiasis (NL) is a complex multifactorial disease affecting up to 10%-20% of the human population and causing a significant burden on public health systems worldwide. It results from a combination of environmental and genetic factors. Hyperoxaluria is a major risk factor for NL., Methods: We used a whole exome-based approach in a patient with calcium oxalate NL. The effects of the mutation were characterised using cell culture and in silico analyses., Results: We identified a rare heterozygous missense mutation (c.1519C>T/p.R507W) in the SLC26A6 gene that encodes a secretory oxalate transporter. This mutation cosegregated with hyperoxaluria in the family. In vitro characterisation of mutant SLC26A6 demonstrated that Cl - -dependent oxalate transport was dramatically reduced because the mutation affects both SLC26A6 transport activity and membrane surface expression. Cotransfection studies demonstrated strong dominant-negative effects of the mutant on the wild-type protein indicating that the phenotype of patients heterozygous for this mutation may be more severe than predicted by haploinsufficiency alone., Conclusion: Our study is in line with previous observations made in the mouse showing that SLC26A6 inactivation can cause inherited enteric hyperoxaluria with calcium oxalate NL. Consistent with an enteric form of hyperoxaluria, we observed a beneficial effect of increasing calcium in the patient's diet to reduce urinary oxalate excretion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Long-term care facilities (LTCF) residents are at high risk for severe coronavirus disease 2019 (COVID-19), and therefore, COVID-19 vaccinations were prioritized for residents and personnel in Finland at the beginning of 2021., Methods: We investigated COVID-19 outbreaks in two LTCFs, where residents were once or twice vaccinated. After the outbreaks we measured immunoglobulin G (IgG) antibodies to severe acute respiratory syndrome coronavirus 2 spike glycoprotein, neutralizing antibody (NAb) titers, and cell-mediated immunity markers from residents and healthcare workers (HCWs)., Results: In LTFC-1, the outbreak was caused by an Alpha variant (B.1.1.7) and the attack rate (AR) among once vaccinated residents was 23%. In LTCF-2 the outbreak was caused by a Beta variant (B.1.351). Its AR was 47% although all residents had received their second dose 1 month before the outbreak. We observed that vaccination had induced lower IgG concentrations, NAb titers and cell-mediated immune responses in residents compared to HCWs. Only 1/8 residents had NAb to the Beta variant after two vaccine doses., Conclusions: The vaccinated elderly remain susceptible to breakthrough infections caused by Alpha and Beta variants. The weaker vaccine response in the elderly needs to be addressed in vaccination protocols, while new variants capable of evading vaccine-induced immunity continue to emerge., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Distinguishing between natural and anthropogenic controls on the proportions of naturally occurring radioactive materials (NORMs) in the environment is important for water resource management. In this study, the dynamics of uranium (U) and thorium (Th), two of the most prominent NORM elements, were investigated in the Red Deer River basin using monitoring data collected from 2015 to 2018. More than twofold increases in median proportions of total U (from 0.73 to 1.53 µg/L) and Th (from 0.008 to 0.104 µg/L) were observed for sites located downstream of the Steveville badlands, an area of highly erodible bedrock that a ~ 300 km section of the river flows through. Input is highly variable, coinciding mainly with increases in total suspended solids during intense rainstorms in the late summer. In-depth examination of monitoring data through factor analysis, multiple linear regression, mass balance calculations, and land use analysis highlights the importance of erosion and subsequent particle transport along river banks in the badlands area on the distribution of total U and Th, while also revealing that groundwater-surface water interaction affects proportions of dissolved U throughout the river. No significant influence from industry or land use on U and Th export was found, and proportions of U and Th in water and suspended sediment are within the natural ranges expected for surface waters and sediments/soils. Methodology employed in this study provides a basic framework for analysis of environmental monitoring datasets, which can be employed in the absence of radiochemical data to study the fate, transport, and sources of NORMs., (© 2022. Crown.)

Horses lose high amounts of Na through excessive sweating. These fluid losses can often not be replaced completely by voluntary water intake, requiring saline solutions as rehydration therapy to regain electrolyte balance. The experiment aimed to evaluate the sensitivity and tolerance of Shetland ponies towards different Na concentrations in their drinking water and contained three phases: (1) control: only fresh water provided; (2) pairwise-preference test: choice between fresh water and saline solution with stepwise increasing sodium chloride (NaCl) concentration (0.25%, 0.5%, 0.75%, 1.0%, 1.25%, or 1.5%); and (3) free-choice test: six simultaneously provided buckets containing NaCl concentrations of 0%, 0.25%, 0.5%, 0.75%, 1.0%, or 1.25%. During the pairwise test, the ponies did not distinguish between fresh and 0.25% NaCl-water but demonstrated clear preference for 0.5%, whereas >0.75% NaCl was avoided/rejected. During the free-choice test, a pronounced preference of fresh over saline water was exhibited. The Na intake via salt lick was not reduced as response to higher Na intakes via water. The ponies exhibited a remarkable sensory discrimination capacity to detect different NaCl concentrations in their drinking water. The acceptance of solutions with low NaCl levels (0.25/0.5%) without adverse effects demonstrates potential as rehydration solution for voluntary intake., (© 2022 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

We evaluated the effects of chronic exposure to environmental radiological contamination on the reproductive fitness of sensitive fern (Onoclea sensibilis) by quantifying viability in haploid gametophytes of spores collected from ferns from background and contaminated areas of the Chalk River site. Dose rates measured in situ at field sites ranged from 60 to 849 μGy h -1 , with effects possible at the more contaminated sites (greater than 400 μGy h -1 ). Fern spores were also irradiated from 1 to 1000 Gy to develop dose-response curves. We found no effects on gametophyte viability at the most contaminated areas of the Chalk River site, where we estimated growing season doses of 0.3-3.7 Gy. Dose-response curves show evidence of hormesis, with an increase in gametophyte viability up to 10 Gy, followed by a rapid decline to no viable gametophytes at doses of 1000 Gy. The sensitive fern is not a radiosensitive plant species, but effects do occur within the normal range (10-1000 Gy) of most plant species, making it useful as a sentinel species from a community perspective. Sensitive fern spore germination is high and stable over field dose ranges, with effects primarily on gametophyte viability. This method shows promise as an effects monitoring tool for sites with radiological contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Despite considerable effort, the neural correlates of altered threat-related processing in panic disorder (PD) remain inconclusive. Mental imagery of disorder-specific situations proved to be a powerful tool to investigate dysfunctional threat processing in anxiety disorders. The current functional magnetic resonance imaging (fMRI) study aimed at investigating brain activation in PD patients during disorder-related script-driven imagery. Seventeen PD patients and seventeen healthy controls (HC) were exposed to newly developed disorder-related and neutral narrative scripts while brain activation was measured with fMRI. Participants were encouraged to imagine the narrative scripts as vividly as possible and they rated their script-induced emotional states after the scanning session. PD patients rated disorder-related scripts as more arousing, unpleasant and anxiety-inducing as compared to HC. Patients relative to HC showed elevated activity in the right amygdala and the brainstem as well as decreased activity in the rostral anterior cingulate cortex, and the medial and lateral prefrontal cortex to disorder-related vs. neutral scripts. The results suggest altered amygdala/ brainstem and prefrontal cortex engagement and point towards the recruitment of brain networks with opposed activation patterns in PD patients during script-driven imagery.

Anticipation of potentially threatening social situations is a key process in social anxiety disorder (SAD). In other anxiety disorders, recent research of neural correlates of anticipation of temporally unpredictable threat suggests a temporally dissociable involvement of amygdala and bed nucleus of the stria terminalis (BNST) with phasic amygdala responses and sustained BNST activation. However, the temporal profile of amygdala and BNST responses during temporal unpredictability of threat has not been investigated in patients suffering from SAD. We used functional magnetic resonance imaging (fMRI) to investigate neural activation in the central nucleus of the amygdala (CeA) and the BNST during anticipation of temporally unpredictable aversive (video camera observation) relative to neutral (no camera observation) events in SAD patients compared to healthy controls (HC). For the analysis of fMRI data, we applied two regressors (phasic/sustained) within the same model to detect temporally dissociable brain responses. The aversive condition induced increased anxiety in patients compared to HC. SAD patients compared to HC showed increased phasic activation in the CeA and the BNST for anticipation of aversive relative to neutral events. SAD patients as well as HC showed sustained activity alterations in the BNST for aversive relative to neutral anticipation. No differential activity during sustained threat anticipation in SAD patients compared to HC was found. Taken together, our study reveals both CeA and BNST involvement during threat anticipation in SAD patients. The present results point towards potentially SAD-specific threat processing marked by elevated phasic but not sustained CeA and BNST responses when compared to HC., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Several cesium and strontium bioaccumulation models are used widely in national and international guidance for ecological and human health risk assessments for radiocesium ( 134 Cs and 137 Cs) and radiostrontium ( 90 Sr), but have not been used to make predictions of radiological risk from nuclear accidents under variable environmental conditions on broad geographical scales. In this paper, we first present models for predicting the bioaccumulation of cesium and strontium by aquatic biota based on ambient concentrations of dissolved potassium and calcium, respectively, and then test these models using independent data from aquatic ecosystems at Canadian nuclear sites. Secondly, models yielding the best predictions across a wide range of input parameters were selected to estimate bioaccumulation factors (BAFs) for cesium and strontium in aquatic ecosystems across Canada, using trophic level of organisms and dissolved potassium for cesium and calcium concentrations for strontium as predictor variables, and presented as contour maps of radiological risk. The models show that risk from bioaccumulation of cesium and strontium can vary by several orders of magnitude depending on site-specific environmental conditions and trophic ecology. Overall, our results suggest that single-parameter approaches taken by regulatory standards may either over- or under-predict radiological risk at many locations, and are thus not readily suitable to inform siting decisions for new nuclear developments.

Background: Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder., Methods: The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI)., Results: We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder., Limitations: The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure., Conclusion: Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD., (© The Author (2017). Published by Oxford University Press.)

Mammals typically keep their body temperature (T b ) within a narrow limit with changing environmental conditions. There are indications that some wild ungulates can exhibit certain forms of energy saving mechanisms when ambient temperatures are low and/or food is scarce. Therefore, the aim of the study was to determine if the llama, one of the most extensively kept domestic livestock species, exhibits seasonal adjustment mechanisms in terms of energy expenditure, T b and locomotion. For that purpose llamas (N = 7) were kept in a temperate habitat on pasture. Locomotor activity, T b (measured in the rumen) and the location of each animal were recorded continuously for one year using a telemetry system. Daily energy expenditure was measured as field metabolic rate (FMR). FMR fluctuated considerably between seasons with the lowest values found in winter (17.48 ± 3.98 MJ d -1 , 402 kJ kg -0.75  d -1 ) and the highest in summer (25.87 ± 3.88 MJ d -1 , 586 kJ kg -0.75  d -1 ). Llamas adjusted their energy expenditure, T b and locomotor activity according to season and also time of day. Thus, llamas seem to have maintained the ability to reduce their energy expenditure and adjust their T b under adverse environmental conditions as has been reported for some wild ungulates.

Feelings of uncontrollability and anxiety regarding possibly harmful events are key features of post-traumatic stress disorder (PTSD) symptomatology. Due to a lack of studies, the neural correlates of anticipatory anxiety in PTSD are still poorly understood. During functional magnetic resonance imaging, female PTSD patients with interpersonal violence trauma and healthy controls (HC) anticipated the temporally unpredictable presentation of aversive (human scream) or neutral sounds. Based on separate analysis models, we investigated phasic and sustained brain activations. PTSD patients reported increased anxiety during anticipation of aversive versus neutral sounds. Furthermore, we found both increased initial, phasic amygdala activation and increased sustained activation of the bed nucleus of the stria terminalis (BNST) during anticipation of aversive versus neutral sounds in PTSD patients in comparison to HC. PTSD patients as compared with HC also showed increased phasic responses in mid-cingulate cortex (MCC), posterior cingulate cortex (PCC), mid-insula and lateral prefrontal cortex (PFC) as well as increased sustained responses in MCC, PCC, anterior insula and lateral and medial PFC. Our results demonstrate a relationship between anticipatory anxiety in PTSD patients and hyperresponsiveness of brain regions that have previously been associated with PTSD symptomatology. Additionally, the dissociation between amygdala and BNST indicates distinct temporal and functional characteristics and suggests that phasic fear and sustained anxiety responses are enhanced during unpredictable anticipation of aversive stimuli in PTSD. Hum Brain Mapp 38:2190-2205, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Unintentional and uncontrollable processing of threat has been suggested to contribute to the pathology of social anxiety disorder (SAD). The present study investigated the neural correlates of processing task-irrelevant, highly ecologically valid, disorder-related stimuli as a function of symptom severity in SAD. Twenty-four SAD patients and 24 healthy controls (HC) performed a feature-based comparison task during functional magnetic resonance imaging, while task-irrelevant, disorder-related or neutral scenes were presented simultaneously at a different spatial position. SAD patients showed greater activity than HC in response to disorder-related versus neutral scenes in brain regions associated with self-referential processing (e.g. insula, precuneus, dorsomedial prefrontal cortex) and emotion regulation (e.g. dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus). Symptom severity was positively associated with amygdala activity, and negatively with activation in dorsal anterior cingulate cortex and dlPFC in SAD patients. Additional correlation analysis revealed that amygdala-prefrontal coupling was positively associated with symptom severity. A network of brain regions is thus involved in SAD patients' processing of task-irrelevant, complex, ecologically valid, disorder-related scenes. Furthermore, increasing symptom severity in SAD patients seems to reflect a growing imbalance between neural mechanisms related to stimulus-driven bottom-up and regulatory top-down processes resulting in dysfunctional regulation strategies.

For several stimulus categories (e.g., pictures, odors, and words), the arousal of both negative and positive stimuli has been shown to modulate amygdalar activation. In contrast, previous studies did not observe similar amygdalar effects in response to negative and positive facial expressions with varying intensity of facial expressions. Reasons for this discrepancy may be related to analytical strategies, experimental design and stimuli. Therefore, the present study aimed at re-investigating whether the intensity of facial expressions modulates amygdalar activation by circumventing limitations of previous research. Event-related functional magnetic resonance imaging was used to assess brain activation while participants observed a static neutral expression and positive (happy) and negative (angry) expressions of either high or low intensity from an ecologically valid, novel stimulus set. The ratings of arousal and intensity were highly correlated. We found that amygdalar activation followed a u-shaped activation pattern with highest activation to high intense facial expressions as compared to low intensity facial expressions and to the neutral expression irrespective of valence, suggesting a critical role of the amygdala in valence-independent arousal processing of facial expressions. Additionally, consistent with previous studies, intensity effects were also found in visual areas and generally increased activation to angry versus happy faces were found in visual cortex and insula, indicating enhanced visual representations of high arousing facial expressions and increased visual and somatosensory representations of threat.

Blood-injection-injury (BII) phobia differs from other subtypes of specific phobia in that it is associated with elevated disgust-sensitivity as well as specific autonomic and brain responses during processing of phobia-relevant stimuli. To what extent these features play a role already during threat anticipation is unclear. In the current fMRI experiment, 16 female BII phobics and 16 female healthy controls anticipated the presentation of phobia-specific and neutral pictures. On the behavioral level, anxiety dominated the anticipatory period in BII phobics relative to controls, while both anxiety and disgust were elevated during picture presentation. By applying two different models for the analysis of brain responses to anticipation of phobia-specific versus neutral stimuli, we found initial and sustained increases of activation in anterior cingulate cortex (ACC), insula, lateral and medial prefrontal cortex (PFC), thalamus and visual areas, as well as initial activation in the amygdala for BII phobics as compared to healthy controls. These results suggest that BII phobia is characterized by activation of a typical neural defense network during threat anticipation, with anxiety as the predominant emotion.

Background: Despite considerable effort, the neurobiological underpinnings of hyper-responsive threat processing specific to patients suffering from generalized anxiety disorder (GAD) remain poorly understood. The current functional magnetic resonance imaging (fMRI) study aims to delineate GAD-specific brain activity during immediate threat processing by comparing GAD patients to healthy controls (HC), to social anxiety disorder (SAD) and to panic disorder (PD) patients., Method: Brain activation and functional connectivity patterns to threat vs. neutral pictures were investigated using event-related fMRI. The sample consisted of 21 GAD, 21 PD, 21 SAD and 21 HC., Results: GAD-specific elevated activity to threat vs. neutral pictures was found in cingulate cortex, dorsal anterior insula/frontal operculum (daI/FO) and posterior dorsolateral prefrontal cortex (dlPFC). Defining these effects as seed regions, we detected GAD-specific increased functional connectivity to threat vs. neutral pictures between posterior dlPFC and ventrolateral prefrontal cortex, between cingulate cortex and amygdala, between cingulate cortex and anterior insula, as well as decreased functional connectivity between daI/FO and mid-dlPFC., Conclusion: The findings present the first evidence for GAD-specific neural correlates of hyper-responsive threat processing, possibly reflecting exaggerated threat sensitivity, maladaptive appraisal and attention-allocation processes.

During winter, free-living herbivores are often exposed to reduced energy supply at the same time that energy needs for thermoregulation increase. Several wild herbivores as well as robust horse breeds reduce their metabolism during times of low ambient temperature and food shortage. Thyroid hormones (THs) affect metabolic intensity and a positive effect of THs on basal metabolic rate (BMR) has been demonstrated in mammals and birds. As BMR and field metabolic rate (FMR) are often assumed to be intrinsically linked, THs may represent a reliable indicator for FMR. To test this hypothesis, 10 Shetland pony mares were kept under semi-extensive central European conditions. During the winter season, one group was fed 60% and one group 100% of their maintenance energy requirements. We measured FMR, locomotor activity, resting heart rate and TH levels in summer and winter. FMR, locomotor activity, resting heart rate and total T3 concentrations decreased substantially in winter compared with summer, whereas total T4 increased. Food restriction led to a reduced FMR and resting heart rate, while THs and locomotor activity were not affected. Across both seasons, FMR, resting heart rate and locomotor activity were positively correlated with total T3 but negatively and more weakly correlated with total T4., (© 2016. Published by The Company of Biologists Ltd.)

Several lines of evidence suggest that the amygdala and the bed nucleus of the stria terminalis (BNST) are differentially involved in phasic and sustained fear. Even though, results from neuroimaging studies support this distinction, a specific effect of a temporal dissociation with phasic responses to onset versus sustained responses during prolonged states of threat anticipation has not been shown yet. To explore this issue, we investigated brain activation during anticipation of threat in 38 healthy participants by means of functional magnetic resonance imaging. Participants were presented different visual cues indicated the temporally unpredictable occurrence of a subsequent aversive or neutral stimulus. During the onset of aversive versus neutral anticipatory cues, results showed a differential phasic activation of amygdala, anterior cingulate cortex (ACC), and ventrolateral prefrontal cortex (PFC). In contrast, activation in the BNST and other brain regions, including insula, dorsolateral PFC, ACC, cuneus, posterior cingulate cortex, and periaqueductal grey was characterized by a sustained response during the threat versus neutral anticipation period. Analyses of functional connectivity showed phasic amygdala response as positively associated with activation, mainly in sensory cortex areas whereas sustained BNST activation was negatively associated with activation in visual cortex and positively correlated with activation in the insula and thalamus. These findings suggest that the amygdala is responsive to the onset of cues signaling the unpredictable occurrence of a potential threat while the BNST in concert with other areas is involved in sustained anxiety. Furthermore, the amygdala and BNST are characterized by distinctive connectivity patterns during threat anticipation., (© 2015 Wiley Periodicals, Inc.)

Recent results suggest that wild Northern herbivores reduce their metabolism during times of low ambient temperature and food shortage in order to reduce their energetic needs. It is, however, not known whether domesticated animals are also able to reduce their energy expenditure. We exposed 10 Shetland pony mares to different environmental conditions (summer and winter) and to two food quantities (60% and 100% of maintenance energy requirement) during low winter temperatures to examine energetic and behavioural responses. In summer, ponies showed a considerably higher field metabolic rate (FMR; 63.4±15.0 MJ day(-1)) compared with food-restricted and control animals in winter (24.6±7.8 and 15.0±1.1 MJ day(-1), respectively). During summer, locomotor activity, resting heart rate and total water turnover were considerably elevated (P<0.001) compared with winter. Animals on a restricted diet (N=5) compensated for the decreased energy supply by reducing their FMR by 26% compared with control animals (N=5). Furthermore, resting heart rate, body mass and body condition score were lower (29.2±2.7 beats min(-1), 140±22 kg and 3.0±1.0 points, respectively) than in control animals (36.8±41 beats min(-1), 165±31 kg, 4.4±0.7 points; P<0.05). While the observed behaviour did not change, nocturnal hypothermia was elevated. We conclude that ponies acclimatize to different climatic conditions by changing their metabolic rate, behaviour and some physiological parameters. When exposed to energy challenges, ponies, like wild herbivores, exhibited hypometabolism and nocturnal hypothermia., (© 2014. Published by The Company of Biologists Ltd.)

Staphylococcus aureus is a human pathogen that can cause a wide range of diseases. Although formerly regarded as extracellular pathogen, it has been shown that S. aureus can also be internalized by host cells and persist within these cells. In the present study, we comparatively analyzed survival and physiological adaptation of S. aureus HG001 after internalization by two human lung epithelial cell lines (S9 and A549), and human embryonic kidney cells (HEK 293). Combining enrichment of bacteria from host-pathogen assays by cell sorting and quantitation of the pathogen's proteome by mass spectrometry we characterized S. aureus adaptation during the initial phase between 2.5 h and 6.5 h post-infection. Starting with about 2 × 10(6) bacteria, roughly 1450 S. aureus proteins, including virulence factors and metabolic enzymes were identified by spectral comparison and classical database searches. Most of the bacterial adaptation reactions, such as decreased levels of ribosomal proteins and metabolic enzymes or increased amounts of proteins involved in arginine and lysine biosynthesis, enzymes coding for terminal oxidases and stress responsive proteins or activation of the sigma factor SigB were observed after internalization into any of the three cell lines studied. However, differences were noted in central carbon metabolism including regulation of fermentation and threonine degradation. Since these differences coincided with different intracellular growth behavior, complementary profiling of the metabolome of the different non-infected host cell types was performed. This revealed similar levels of intracellular glucose but host cell specific differences in the amounts of amino acids such as glycine, threonine or glutamate. With this comparative study we provide an impression of the common and specific features of the adaptation of S. aureus HG001 to specific host cell environments as a starting point for follow-up studies with different strain isolates and regulatory mutants.

Recent results suggest that the wild ancestor of the horse, the Przewalski horse, exhibits signs of a hypometabolism. However, there are speculations that domestic animals lost the ability to reduce energy expenditure during food shortage and adverse environmental conditions. Therefore, we investigated physiological and behavioural strategies employed by a robust domesticated horse breed, the Shetland pony, over the course of a year under temperate conditions by measuring ambient temperature (T(a)), subcutaneous temperature (T(s)), locomotor activity (LA), lying time, resting heart rate, body mass and body condition score. Ten animals were kept on pasture in summer and in open stables in winter; further, in winter the animals were allocated into one control and one feed-restricted group of five animals each to simulate natural seasonal food shortage. The annual course of the mean daily T(s) of all horses showed distinct fluctuations from a mean of 35.6±0.5°C, with higher variations in summer than in winter. Diurnal amplitudes in T(s) were highest (P<0.001) in April (12.6°C) and lowest in January (4.0°C), with a nadir around dawn and a peak around mid-day. The feed-restricted group had a significantly lower daily T(s) compared with the control group on cold winter days, with T(a) values below 0°C. Mean annual heart rate and LA followed T(a) closely. Heart rate of the feed-restricted animals significantly decreased from a mean of 52.8±8.1 beats min(-1) in summer to 29±3.9 beats min(-1) in winter and differed from the control group (P<0.001). Mean daily LA was lowest at the end of winter (7000 activity impulses day(-1)) and highest in summer (25,000 activity impulses day(-1)). Our results show that Shetland ponies exhibit signs of a winter hypometabolism indicated by reduced heart rate and T(s). Thus, domesticated horses seem to have maintained the capacity for seasonal adaptation to environmental conditions by seasonal fluctuations in their metabolic rate.

A remote data entry (RDE) module was successfully integrated within a Web-based telemedicine system in a German multi-centric research network for a rare disease called Epidermolysis Bullosa. The use of standards like XML and HL7 CDA (Clinical Document Architecture) for structured data storage, guarantees long-term accessibility and high level interoperability.