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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.

Collective intelligence underpins the success of groups, organizations, markets and societies. Through distributed cognition and coordination, collectives can achieve outcomes that exceed the capabilities of individuals-even experts-resulting in improved accuracy and novel capabilities. Often, collective intelligence is supported by information technology, such as online prediction markets that elicit the 'wisdom of crowds', online forums that structure collective deliberation or digital platforms that crowdsource knowledge from the public. Large language models, however, are transforming how information is aggregated, accessed and transmitted online. Here we focus on the unique opportunities and challenges this transformation poses for collective intelligence. We bring together interdisciplinary perspectives from industry and academia to identify potential benefits, risks, policy-relevant considerations and open research questions, culminating in a call for a closer examination of how large language models affect humans' ability to collectively tackle complex problems., (© 2024. Springer Nature Limited.)

Background and Aims: Micro-elimination projects targeted to specific hepatitis C virus (HCV) risk populations have been successful. Systematic identification of persons with HCV viremia, regardless of risk group, based on already available laboratory records may represent an effective macroelimination approach to achieve global HCV elimination., Methods: Persons with a last positive HCV-RNA PCR result between 2008-2020 in the reference virology laboratories in eastern Austria were identified. First, (i) we described their demographic characteristics, (ii) we systematically recalled persons to the respective centers and (iii) started antiviral treatment if HCV-RNA viremia was confirmed, and (iv) recorded sustained virologic response (SVR). This interim report includes the preliminary results from 8 participating centers., Results: During the study period 22,682 persons underwent HCV-RNA PCR testing, 11,216 (49.4%) were positive at any point in time, and 6006 (26.5%) showed detectable HCV-RNA at the last PCR test, suggesting ongoing HCV viremia. At the time of this interim report, 2546/6006 HCV-RNA PCR(+) persons were evaluated: 443/2546 (17.4%) had died, 852/2546 (33.5%) had invalid contact data, and 547/2546 (21.5%) had achieved SVR between data retrieval and recall. Contact could be established in 236/704 (33.5%) of the remaining target population with 97/236 (41.1%) presenting at the clinic for treatment evaluation. Ultimately, 71/236 (30.1%) started antiviral treatment and SVR was documented in 47/71 (66.2%)., Conclusion: This ELIMINATE project based on systematic assessment of HCV-RNA PCR-records, identified 6006 persons with potential persisting HCV viremia. Invalid contact data and missed visits for treatment evaluation were the main barriers towards HCV elimination within this project. Importantly, many subjects with HCV viremia lost to follow-up were successfully linked to care and started antiviral treatment., (© 2023. The Author(s).)

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.

The ability of humans to create and disseminate culture is often credited as the single most important factor of our success as a species. In this Perspective, we explore the notion of 'machine culture', culture mediated or generated by machines. We argue that intelligent machines simultaneously transform the cultural evolutionary processes of variation, transmission and selection. Recommender algorithms are altering social learning dynamics. Chatbots are forming a new mode of cultural transmission, serving as cultural models. Furthermore, intelligent machines are evolving as contributors in generating cultural traits-from game strategies and visual art to scientific results. We provide a conceptual framework for studying the present and anticipated future impact of machines on cultural evolution, and present a research agenda for the study of machine culture., (© 2023. Springer Nature Limited.)

Artificial intelligence (AI) is often used to predict human behavior, thus potentially posing limitations to individuals' and collectives' freedom to act. AI's most controversial and contested applications range from targeted advertisements to crime prevention, including the suppression of civil disorder. Scholars and civil society watchdogs are discussing the oppressive dangers of AI being used by centralized institutions, like governments or private corporations. Some suggest that AI gives asymmetrical power to governments, compared to their citizens. On the other hand, civil protests often rely on distributed networks of activists without centralized leadership or planning. Civil protests create an adversarial tension between centralized and decentralized intelligence, opening the question of how distributed human networks can collectively adapt and outperform a hostile centralized AI trying to anticipate and control their activities. This paper leverages multi-agent reinforcement learning to simulate dynamics within a human-machine hybrid society. We ask how decentralized intelligent agents can collectively adapt when competing with a centralized predictive algorithm, wherein prediction involves suppressing coordination. In particular, we investigate an adversarial game between a collective of individual learners and a central predictive algorithm, each trained through deep Q-learning. We compare different predictive architectures and showcase conditions in which the adversarial nature of this dynamic pushes each intelligence to increase its behavioral complexity to outperform its counterpart. We further show that a shared predictive algorithm drives decentralized agents to align their behavior. This work sheds light on the totalitarian danger posed by AI and provides evidence that decentrally organized humans can overcome its risks by developing increasingly complex coordination strategies., (© 2023 The Authors. Topics in Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society.)

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 & Aims: Despite effective direct-acting antivirals (DAAs), hepatitis C virus (HCV) prevalence is high among people who inject drugs (PWIDs) and non-adherence to therapy remains a major obstacle towards HCV elimination in this subpopulation. To overcome this issue, we have combined ongoing opioid agonist therapy (OAT) with DAAs in a directly-observed therapy (DOT) setting., Method: From September 2014 until January 2021 PWIDs at high risk of non-adherence to DAA therapy, who were also on OAT, were included into this microelimination project. Individuals received their OAT and DAAs under supervision of healthcare workers as DOT in a pharmacy or low-threshold facility., Results: In total, 504 HCV RNA-positive PWIDs on OAT (387 men, 76.8%; median age: 38 years [IQR 33-45], HIV: 4.6%; hepatitis B: 1.4%) were included into this study. Two thirds reported ongoing intravenous drug use (IDU) and half of them had no permanent housing. Only 41 (8.1%) were lost to follow-up and two (0.4%) died of reasons unrelated to DAA toxicity. Overall, 90.7% of PWIDs achieved sustained virological response 12 weeks after treatment (SVR12) (95% CI: 88.1-93.2%). By excluding those lost to follow-up and hose who had died of causes unrelated to DAAs, the SVR12 rate was 99.1% (95% CI: 98.3-100.0%; modified intention-to-treat analysis). Four PWIDs (0.9%) experienced treatment failure. Over a median follow-up of 24 weeks (IQR 12-39), 27 reinfections (5.9%) were observed in individuals with the highest IDU rates (81.2%). Importantly, even though some were lost to follow-up, all completed their DAA treatment. By using DOT, adherence to DAAs was excellent with only a total of 86 missed doses (0.3% of 25,224 doses)., Conclusions: In this difficult-to-treat population of PWIDs with high rates of IDU , coupling DAA treatment to OAT in a DOT setting resulted in high SVR12 rates equivalent to conventional treatment settings in non-PWID populations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: -Michael Schwarz, Austria (schwarz.medizin@gmail.com): received speaking honoraria from BMS and travel support from BMS, AbbVie, Gilead, and MSD.-Caroline Schwarz, Austria (schwarz.caroline1990@gmail.com): received travel support from Gilead, Abbvie, and Gebro; speaking honoraria from Abbvie and Gilead; and served as a consultant for Gilead.-Angelika Schütz, Austria (angelika.schuetz@suchthilfe.at): no conflicts of interest.-Cornelia Schwanke, Austria (cornelia.schwanke@suchthilfe.at): no conflicts of interest.-Eva Krabb, Austria (eva.krabb@suchthilfe.at) no conflicts of interest.-Raphael Schubert, Austria (raphael.schubert@outlook.at): received travel support from Gilead.-Sophie-Therese Liebich, Austria (sophie-therese.liebich@suchthilfe.at): no conflicts of interest.-David Bauer (david.bauer@meduniwien.ac.at): received travel support from Gilead and Abbvie and speaker fees from Abbvie.-Lukas Burghart (lukas.burghart@gesundheitsverbund.at): no conflicts of interest.-Leonard Brinkmann (leonard-ruben.brinkmann@gesundheitsverbund.at): no conflicts of interest.-Enisa Gutic, Austria (enisa.gutic@extern.gesundheitsverbund.at): received travel support from Gilead and AbbVie.-Thomas Reiberger, Austria (thomas.reiberger@meduniwien.ac.at): received grant support from Abbvie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Boehringer-Ingelheim, Gilead and Roche.-Hans Haltmayer, Austria (hans.haltmayer@suchthilfe.at): no conflicts of interest.-Michael Gschwantler, Austria (michael.gschwantler@gesundheitsverbund.at): received grant support from Abbvie, Gilead and MSD; speaking honoraria from Abbvie, Gilead, Intercept, Janssen, BMS, Roche, Norgine, AstraZeneca, Falk, Shionogi, and MSD; consulting/advisory board fees from Abbvie, Gilead, Intercept, Janssen, BMS, Roche, Alnylam, Norgine, AstraZeneca, Falk, Shionogi and MSD; and travel support from Abbvie and Gilead., (© 2023 The Authors.)

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.)

Chronic Cyclosporine-A treatment is associated with serious side effects, including kidney toxicity and anemia. Although pathophysiology of Cyclosporine-A-induced kidney injury remains incompletely understood, hypoxia is likely involved. Here, we investigated the effect of the hypoxia inducible factor activator daprodustat on Cyclosporine-A -induced kidney toxicity. As Cyclosporine-A profoundly alters protein phosphorylation by inhibiting the phosphatase calcineurin, special attention was directed towards the kidney phospho-proteome. Mice received Cyclosporine-A with or without daprodustat for up to eight weeks. In kidney homogenates, 1360 selected proteins were analyzed at expression and phosphorylation levels. Of these, Cyclosporine-A changed the expression of 79 and the phosphorylation of 86 proteins. However, when Cyclosporine-A treatment was combined with daprodustat, the expression of 95 proteins and phosphorylation of only six proteins was altered suggesting that daprodustat prevented most protein phosphorylation brought about by Cyclosporine-A. Although daprodustat showed only marginal effect on its own, angiogenesis-related pathways were among the most profoundly impacted by daprodustat when given on top of Cyclosporine-A. Additionally, Cyclosporine-A lowered the blood hemoglobin concentration and caused kidney capillary rarefaction, which daprodustat prevented. Thus, combined daprodustat/Cyclosporine-A treatment prevented deleterious Cyclosporine-A effects on microcirculation and hemoglobin, and the protective action of daprodustat involves suppression of broad protein phosphorylation changes caused by Cyclosporine-A., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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.)

Humans are impressive social learners. Researchers of cultural evolution have studied the many biases shaping cultural transmission by selecting who we copy from and what we copy. One hypothesis is that with the advent of superhuman algorithms a hybrid type of cultural transmission, namely from algorithms to humans, may have long-lasting effects on human culture. We suggest that algorithms might show (either by learning or by design) different behaviours, biases and problem-solving abilities than their human counterparts. In turn, algorithmic-human hybrid problem solving could foster better decisions in environments where diversity in problem-solving strategies is beneficial. This study asks whether algorithms with complementary biases to humans can boost performance in a carefully controlled planning task, and whether humans further transmit algorithmic behaviours to other humans. We conducted a large behavioural study and an agent-based simulation to test the performance of transmission chains with human and algorithmic players. We show that the algorithm boosts the performance of immediately following participants but this gain is quickly lost for participants further down the chain. Our findings suggest that algorithms can improve performance, but human bias may hinder algorithmic solutions from being preserved. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'.

Objectives: Geriatric nursing staff are exposed to high workloads, which often lead to stress, incapacity to work and early retirement. Personal resources can help deal with work demands and can have a positive effect on health. To design tailored interventions, this study aims to identify personal resources of staff and its impact on stress levels., Measures: Data on 195 geriatric nurses (87.4% female, 40.1±12.2 years) were collected using a set of validated questionnaires consisting of Slesina questionnaire, Nordic Questionnaire, SF-12, personal resources (according to WHO criteria), AVEM questionnaire and the SSCS scale of the TICS questionnaire. According to the SSCS scale, nursing staff were divided into stressed and non-stressed. To further investigate potential factors influencing the development of stress, a four-step regression analysis was carried out., Results: Non-stressed geriatric nursing staff felt less burdened by work-related stress factors, had fewer physical complaints, had higher physical (p<0.001) and mental well-being (p <0.001), better personal resources and healthier work-related behavior and experience. The regression analysis showed that personal resources such as satisfaction with health status, nutritional behavior, frequency of being calm and relaxed, frequency of being full of energy as well as the stress level can improve physical and mental well-being, but cannot decrease the emergence of stress in case of unhealthy work coping behavior (R²=0.760)., Conclusion: When developing stress prevention interventions, the focus should be on strengthening personal resources. In addition, individual work-related behavior and experience patterns should be taken into account., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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.)

To examine the adaptive physiological responses to increasing salinity of drinking water in a choice situation, twelve female non-lactating Boer goats were used. After a control period with fresh water, in phase 2 the choice between different salt concentrations (0.25, 0.5, 0.75, 1.0, 1.25 and 1.5% NaCl) and tap water was offered for two weeks. Subsequently, goats were stepwise habituated to saline water by only offering the choice between salted water with different increasing concentrations (up to 1.5% NaCl) for four weeks. In phase 4 the procedure of phase 2 was repeated. BW was not affected by saline water intake, whereas BCS decreased. Total water intakes differed between ages (P < .001), and increased (P < .001) from 91.6 to 118.0 g/kg BW 0.82 /day and from 105.5 to 142.9 g/kg BW 0.82 /day in young and old goats in phase 3, respectively. In adult goats, rumen temperature decreased (P < .05) with prolonged saline water intake, while it remained unaffected in young goats. Increasing consumption of saline water decreased plasma concentrations of magnesium (from 0.95 to a minimum of 0.80 mmol/L in phase 3, P < .001). Creatinine increased from 82.92 to 93.39 μmol/L in the post-trial period 4 (P < .02) and potassium concentration increased from phase 2 (P < .001). ALT, AST, glucose, urea, calcium, sodium, osmolality were unaffected. All measured blood parameters remained within reference ranges, indicating that the stepwise adaptation to saline drinking water applying concentrations up to 1.5% across 4 weeks caused no harmful effects. Young animals were less resistant to salt toxicity compared to older ones., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Due to global climatic changes, water and soil salinization is an increasing worldwide phenomenon, thus creating new threats for farm animal production. The present study was designed to investigate the adaptation capacity of goats towards sodium chloride (NaCl) in drinking water. Twelve non-pregnant Boer goats with an average body weight of 50.5 ± 9.0 kg were kept in individual pens. The study was conducted in four phases applying a two-choice preference test. In the control phase (phase 1) only fresh water was supplied in two containers. In phase 2, water with different salt concentrations (0.25%, 0.5%, 0.75%, 1.0%, 1.25% and 1.5%) was offered in one container and tap water in the other (sensitivity test). During the third phase (adaptation), goats were stepwise habituated to saline water by offering only saline water with different increasing concentrations (between 0% and 1.5% NaCl) in both containers. Subsequently, in phase 4 (sensitivity re-test) the same treatment as in phase 2 was repeated. Goats had ad libitum access to hay, water and a mineral licking block. Individual water and feed intake were recorded daily, while body weight and body condition score were measured every 2nd week. Body weight was not affected by saline water intake, whereas dry matter intake and body condition scores decreased significantly during the experiment. Water intake was significantly (P<0.001) higher in phase 2 (sensitivity test) and phase 3 (adaptation), compared to phase 1 (control) and phase 4 (sensitivity re-test). Total sodium intake followed the same pattern. In phase 2, when goats had the choice between fresh and saline water for the first time they preferred higher salt concentrations and consumed significantly (P<0.001) higher amounts of saline water (75.4 ± 53.2 g/kg BW0.82 per day) than in the re-test (40.4 ± 34.0 g/kg BW0.82 per day) after the habituation period. Thus, salt discrimination rejection thresholds were lowered to 1.25% in phase 4 compared to 1.5% in phase 2. The results suggest that a stepwise adaptation to saline drinking water in goats is an effective method to habituate the animals to saline water intake when concentrations were below 1.5%. Goats reacted more sensitively to the salinity of drinking water after prolonged exposure to saline water indicating flexible regulation mechanisms depending on the total sodium balance of the animal.

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.

Salinization of groundwater and soil is a prevalent global issue with serious consequences on animal health and production. The present study was conducted to investigate the capacity of Boer goats to adjust their salt intake from saline drinking water in a free-choice system. In total, 12 non-pregnant Boer goats aged between 1 and 8 years with an average BW of 46.4±8.3 kg were kept in individual pens for 4 weeks. In the control phase (1 week), only fresh water was supplied in five identical buckets for each pen. During the subsequent treatment phase (3 weeks), fresh water and four different concentrations (0.75, 1.0, 1.25 and 1.5% NaCl) of saline water were offered simultaneously in a free-choice system. The positions of the concentrations were changed daily at random. Cut hay and water were provided ad libitum, and a mineral supplement was allocated. Feed and water intake, mineral supplement intake, ambient temperature and relative humidity were recorded daily, whereas BW and body condition score were measured weekly. Dry matter intake, total water intake and total sodium intake were significantly (P&lt;0.001) higher during the treatment phase. Body weight and body condition were not affected by saline water intake. Across the treatment phase, saline water consumption was significantly (P&lt;0.001) lower in young (19.6±27.1 g/kg BW0.82 per day) than in adult goats (27.9±31.5 g/kg BW0.82 per day), indicating that young goats were more sensitive towards the saline water. All goats had a significant preference for fresh water (0% salt) over saline water. At the first offering of the simultaneous choice situation (week 2), animals did not differentiate between the salt concentration of 0.75% and 1.0%. However, with successive treatment (weeks 3 and 4), animals distinguished between saline water concentrations and preferred the 0.75% salt concentration. Salt concentrations of 1% to 1.5% were avoided. The total sodium intake of the goats ranged between 0.37 and 0.55 g /kg BW0.75 per day during the treatment phase, being 8- to 11-fold higher than the daily requirements of sodium for body maintenance. The results suggest that goats are able to differentiate between saline water concentrations and to adjust their sodium intake by quick adjustments in self-selection in a free-choice system. Compared with two-choice preference tests, the present free-choice situation allows evaluating changes in saline water acceptance with prolonged exposure.

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.)

Interpersonal violence (IPV) is one of the most frequent causes for the development of posttraumatic stress disorder (PTSD) in women. One key component in PTSD is altered processing of trauma-related cues, leading to emotional symptoms. In the everyday environment, words with trauma-associated semantic content represent typical, albeit abstract, trauma-related stimuli for patients suffering from PTSD. However, the functional neuroanatomy associated with processing single trauma-related words in IPV-PTSD is not understood. The present event-related functional magnetic resonance imaging study investigated the neural basis of trauma-related word processing in women with IPV-PTSD relative to healthy controls (HC) during a non-emotional vigilance task in which the emotional content of the words was task-irrelevant. On the behavioral level, trauma-related relative to neutral word stimuli evoked more unpleasant feelings, higher arousal as well as anxiety in IPV-PTSD patients as compared to HC. Functional imaging data showed hyperactivation to trauma-related versus neutral words in the basolateral amygdala (BLA) and cortical language-processing regions (inferior frontal gyrus, posterior cingulate cortex, angular/supramarginal gyrus) in IPV-PTSD compared to HC. These results propose a role of the BLA in hypervigilant responding to verbal trauma associated cues in IPV-PTSD. Furthermore, the particular involvement of cortical language-processing regions indicates enhanced processing of trauma-related words in brain regions associated with analysis and memory of verbal material. Taken together, our findings suggest that both subcortical and cortical mechanisms contribute to automatic responsivity to verbal trauma cues in PTSD., (Copyright © 2018 Elsevier B.V. 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: Altered amygdala activation to fear-related stimuli has been proposed to be a potential neural correlate of heightened threat sensitivity in anxiety- and stress-related disorders. However, the role of stimulus awareness and disorder specificity remains widely unclear. Here we investigated amygdala responses to conscious and unconscious fearful faces in patients suffering from panic disorder (PD), generalized anxiety disorder (GAD), or post-traumatic stress disorder (PTSD) and in a large sample of healthy controls (HC)., Methods: During event-related functional magnetic resonance imaging participants (n = 120; 20 PD, 20 GAD, 20 PTSD, 60 HC) were confronted with briefly presented fearful faces, neutral faces, and non-faces in a backward masking paradigm. The design allowed for the analysis of trial-by-trial face detection performance and amygdala responses to fearful v. neutral faces., Results: All participants exhibited increased amygdala activation to fearful v. neutral faces during conscious trials. Specifically during unconscious face processing, the PTSD, compared with all other groups, showed higher right basolateral (BLA) amygdala activity to fearful v. neutral faces., Conclusions: The present study shows that BLA amygdala hyperactivity during unconscious, but not conscious, processing of fearful faces differentiates PTSD from the investigated disorders. This finding suggests an automatic and specific neural hyper-responsivity to general fear cues in PTSD and supports the idea of categorical differences between PTSD and other anxiety-related disorders.

Background: Worrying has been suggested to prevent emotional and elaborative processing of fears. In cognitive-behavioral therapy (CBT), generalized anxiety disorder (GAD) patients are exposed to their fears during the method of directed threat imagery by inducing emotional reactivity. However, studies investigating neural correlates of directed threat imagery and emotional reactivity in GAD patients are lacking. The present functional magnetic resonance imaging (fMRI) study aimed at delineating neural correlates of directed threat imagery in GAD patients., Method: Nineteen GAD patients and 19 healthy controls (HC) were exposed to narrative scripts of either disorder-related or neutral content and were encouraged to imagine it as vividly as possible., Results: Rating results showed that GAD patients experienced disorder-related scripts as more anxiety inducing and arousing than HC. These results were also reflected in fMRI data: Disorder-related v. neutral scripts elicited elevated activity in the amygdala, dorsomedial prefrontal cortex, ventrolateral prefrontal cortex and the thalamus as well as reduced activity in the ventromedial prefrontal cortex/subgenual anterior cingulate cortex in GAD patients relative to HC., Conclusion: The present study presents the first behavioral and neural evidence for emotional reactivity during directed threat imagery in GAD. The brain activity pattern suggests an involvement of a fear processing network as a neural correlate of initial exposure during directed imagery in CBT in GAD.

An influential framework suggests that the central nucleus of the amygdala (CeA) is involved in phasic responses to threat, while the bed nucleus of the stria terminalis (BNST) mediates sustained anxiety. However, this model has been questioned, proposing that the role of the BNST is not limited to sustained threat contexts. Rather, amygdala and BNST also seem to work in concert in the processing of discrete and briefly presented threat-related stimuli, likely dependent on inter-individual differences in anxiety. A direct test of this assumption with sufficient experimental power is missing in human research and the degree to which individual differences in trait anxiety moderate phasic responses and functional connectivity of amygdala and BNST during threat processing remains unclear. The current event-related functional magnetic resonance imaging (fMRI) study investigated activation and connectivity of amygdala and BNST, as well as modulating effects of trait anxiety, during processing of briefly presented threat-related relative to neutral standardized pictures in 93 psychiatrically healthy individuals. Both amygdala and BNST activation was increased during presentation of threat-related relative to neutral pictures. Furthermore, functional connectivity between BNST and amygdala in response to threat was positively associated with trait anxiety. These findings suggest that amygdala and BNST form a functional unit during phasic threat processing whereby their connectivity is shaped by inter-individual differences in trait anxiety., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Domesticated horses are increasingly kept under semi-natural housing conditions, whereas their adaptation capacity is not fully investigated. In all, 10 Shetland pony mares were held under semi-extensive conditions for 1 year. In winter animals were allocated into two feeding groups (60% and 100% of maintenance energy requirement, respectively). Triiodothyronine, thyroxine, non-esterified fatty acids (NEFA), total bilirubin, total protein, triglyceride, glucose, insulin and hair length were measured at monthly intervals, whereas BW, body condition score, cresty neck score and resting heart rate were recorded every 2 weeks. From summer to winter all Ponies showed a reduction in resting heart rate (P0.05). Refeeding of restrictively fed ponies resulted in a rapid increase in resting heart rate and BW and a return of blood parameters to reference values. Adequately supplied animals adapted without difficulty to varying environmental conditions, whereas feed restriction in ponies during winter resulted in reduced resting heart rates suggesting a reduced basal metabolic rate. The energy restriction was compensated by mobilizing body fat reserves which led to changes in blood parameters. Refeeding in feed restricted animals revealed a remarkably quick recovery of physiological and blood parameters to reference values. We therefore suggest that year round-outdoor housing can be a suitable housing system for robust horse breeds provided that an adequate food supply is available.

Health-promoting efforts strongly depend on individual cognitions such as attitudes as well as social cognitive aspects of the work environment such as leadership and support. Using the theory of planned behavior (TPB) as a theoretical frame, participation behavior of employees in courses offered by the workplace health promotion (WHP) program of the German Armed Forces was investigated. Social cognitive aspects of the work environment, such as leadership behaviors by setting an example or optimizing organization of work, were included in the TPB components of subjective norm and perceived behavioral control, which allowed for an investigation of the specific effects of leadership on WHP participation. A survey study with N=1385 members of the German Armed Forces was conducted in 2015 in Germany. Results showed that perceived behavioral control and attitudes towards WHP were the strongest predictors for WHP participation. While subjective norm was positively related to attitudes, it had a slightly negative effect on intention to participate in WHP activities. These findings suggest that the most effective way for leadership to increase WHP participation is to enhance perceived behavioral control. Quite contrary, creating a positive subjective norm regarding WHP participation may even result in psychological reactance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Panic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD., Methods: Using functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations., Results: PD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks., Conclusions: We demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

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.)

Staphylococcus aureus is an opportunistic human pathogen, which can cause life-threatening disease. Proteome analyses of the bacterium can provide new insights into its pathophysiology and important facets of metabolic adaptation and, thus, aid the recognition of targets for intervention. However, the value of such proteome studies increases with their comprehensiveness. We present an MS-driven, proteome-wide characterization of the strain S. aureus HG001. Combining 144 high precision proteomic data sets, we identified 19 109 peptides from 2088 distinct S. aureus HG001 proteins, which account for 72% of the predicted ORFs. Peptides were further characterized concerning pI, GRAVY, and detectability scores in order to understand the low peptide coverage of 8.7% (19 109 out of 220 245 theoretical peptides). The high quality peptide-centric spectra have been organized into a comprehensive peptide fragmentation library (SpectraST) and used for identification of S. aureus-typic peptides in highly complex host-pathogen interaction experiments, which significantly improved the number of identified S. aureus proteins compared to a MASCOT search. This effort now allows the elucidation of crucial pathophysiological questions in S. aureus-specific host-pathogen interaction studies through comprehensive proteome analysis. The S. aureus-specific spectra resource developed here also represents an important spectral repository for SRM or for data-independent acquisition MS approaches. All MS data have been deposited in the ProteomeXchange with identifier PXD000702 (http://proteomecentral.proteomexchange.org/dataset/PXD000702)., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.)

A fragmentation scheme based upon the molecular fractionation with conjugated caps (MFCC) method and derived previously [J. Chem. Phys., 2009, 130, 144104] within the remit of density functional theory (DFT) based on local and semi-local functionals, enables one to perform order-N high-quality DFT calculations on extended systems (e.g. collections of organic molecules) via considering its smaller fragments. Here we discuss in detail a considerably improved method which broadens its applicability to a wider class of extended systems: (i) when each individual fragment is considered, the surrounding part of the entire system is not ignored anymore; instead, it is represented by point charges; (ii) the method is generalised to a system of any complexity enabling studying periodic and porous systems in real space; (iii) an appropriate Coulomb correction term is derived where clear distinction is made between charge densities of the same cap regions appearing in different fragments. Consequently, our correction term turns out to differ substantially from that derived e.g. by Li et al. [J. Chem. Phys. A, 2007, 111(11), 2193]. We also discuss a possibility for the point charges surrounding each fragment to update self-consistently following the calculations of every individual fragment. We examine here a new implementation of our method and its application to a metal-organic framework system. Specifically, we consider the structure of MOF-16 and adsorption of Hydrogen molecules in its pores. Possible ways of improving precision and to further widen up applicability of the method are also discussed.

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.

Macrophages are essential components of the innate immune system and crucial for pathogen elimination in early stages of infection. We previously observed that bone marrow-derived macrophages (BMMs) from C57BL/6 mice exhibited increased killing activity against Burkholderia pseudomallei compared to BMMs from BALB/c mice. This effect was particularly pronounced when cells were treated with IFN-γ. To unravel mechanisms that could explain these distinct bactericidal effects, a comparative combined proteome and transcriptome analysis of untreated and IFN-γ treated BALB/c and C57BL/6 BMMs under standardized serum-free conditions was carried out. We found differences in gene expression/protein abundance belonging to cellular oxidative and antioxidative stress systems. Genes/proteins involved in the generation of oxidant molecules and the function of phagosomes (respiratory chain ATPase, lysosomal enzymes, cathepsins) were predominantly higher expressed/more abundant in C57BL/6 BMMs. Components involved in alleviation of oxidative stress (peroxiredoxin, mitochondrial superoxide dismutase) were more abundant in C57BL/6 BMMs as well. Thus, C57BL/6 BMMs seemed to be better equipped with cellular systems that may be advantageous in combating engulfed pathogens. Simultaneously, C57BL/6 BMMs were well protected from oxidative burst. We assume that these variations co-determine differences in resistance between BALB/c and C57BL/6 mice observed in many infection models., Biological Significance: In this study we performed combined transcriptome and proteome analyses on BMMs derived from two inbred mouse strains that are frequently used for studies in the field of host-pathogen interaction research. Strain differences between BALB/c and C57BL/6 BMMs were found to originate mainly from different protein abundance levels rather than from different gene expression. Differences in abundance of respiratory chain complexes and lysosomal proteins as well as differential regulation of components belonging to various antioxidant stress systems help to explain long-known differences between the mouse strains concerning their different susceptibility in several infection models., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Water is an essential nutrient necessary to support life, and adequate water supply is crucial for animal survival and productivity. The present study was designed to determine seasonal changes in the water metabolism of horses under outdoor conditions. Total body water (TBW) and total water intake (TWI) of 10 adult Shetland pony mares were estimated at monthly intervals for 14 mo by using the deuterium dilution technique. During the last 4 mo, 5 ponies were fed restrictively to simulate natural feed shortage in winter, and 5 ponies served as controls. The TBW (kg) was closely related to body mass [TBW (kg) = -2.86 + 0.67 × body mass (kg); P < 0.001; n = 105] explaining 86% of the variation. In contrast to TBW (kg), TBW (%) remained relatively stable across all measurements (57.8 to 71.2%). The TWI showed an increase in summer and a decrease in winter [TWI (mL·kg(-1)·d(-1)) = 15.07 + 23.69 × month - 1.45 × month(2) (R(2) = 0.64, P < 0.01)]. However, TWI measured at ambient temperatures (Ta) < 0°C did not follow the same trend as TWI at Ta > 0°C. Therefore, removing TWI values measured at Ta < 0°C from the analysis resulted in high correlations with locomotor activity (r = 0.87), Ta (r = 0.86), and resting heart rate (r = 0.88). The multiple regression among TWI, Ta, and heart rate explained 84% of the variation in TWI [TWI (mL·kg(-1)·d(-1)) = -13.38 + 1.77 × heart rate (beats/min) + 2.11 × Ta (°C); P < 0.001]. Feed restriction had no effect on TWI and TBW. The TBW content was unaffected by season and physical activity. The established regression equation for TBW and body mass can be used to predict TBW from body mass in ponies under field conditions. The comparison of TWI with published data on drinking water intake revealed that ponies had 1.7 to 5.1 times greater total water intakes when other sources of water such as feed and metabolic water were included. The TWI was highly influenced by environmental conditions and metabolic rate. Contrary to expectation, water supply during the cold seasons might be more critical than under summer conditions when water content of grass is high to allow for the compensation of limited availability of drinking water.

Outdoor group housing is increasingly recognized as an appropriate housing system for domesticated horses. The objective of this study was therefore to investigate the effect of potential feed shortage in semi-natural horse keeping systems in winter on animal health and welfare. In 10 female Shetland ponies blood concentrations (NEFA, total protein (TP), total bilirubin (TB), beta-hydroxybutyrate (BHB) and thyroxine (T4)), body mass and the body condition score (BCS) were monitored for 7 months including a 4 months period of feed restriction in five of the 10 ponies. Restrictively fed animals lost 18.4±2.99% of their body mass and the BCS decreased by 2.2±0.8 points (BCS scale: 0=emaciated, 5=obese). Feed restriction led to a continuous increase in TB (P<0.001) and NEFA (P<0.01) concentrations compared to control ponies. The TP and BHB values only differed at the end of the trial with lower concentrations in restricted fed mares (P<0.05). Feed restriction had no effect on thyroxine concentrations. TB concentrations in the feed restricted group were out of the reference range during the entire feeding trial. The increased NEFA concentrations in feed restricted compared to control ponies suggest that fat was mobilized. The BCS, as well as plasma NEFA and TB concentrations were good indicators for a rapid detection of possible health problems caused by undernourishment in horses when kept under semi-natural conditions. In contrast, blood parameters of the control animals were within the reference ranges, suggesting that a year round outdoor housing with additional feed supply is an adequate housing system for a robust horse breed like the Shetland pony., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

In recent years scarless surgery (axillo-bilateral-breast aproach [ABBA], natural orifice transluminal endoscopic surgery [NOTES], single-port surgery) has gained importance in order to improve postoperative outcome in laparoscopic surgery. As part of this effort minilaparoscopic surgery might be a suitable alternative concerning cosmetic outcome without implementing a completely new technique. Due to the definition minilaparoscopic surgery is based on instruments which reduce the total length of trocar incisions to less than 2.5 cm. Nevertheless the total number of incisions is similar to conventional laparoscopic techniques. Most recent indications for minilaparoscopic surgery are cholecystectomy, appendectomy, hernia and colorectal surgery. This article describes the technical aspects and feasibility of minilaparoscopic cholecystectomy and transabdominal preperitoneal hernia repair (TAPP).While the trocar positions remain in the original setting the laparoscopic surgeon benefits from experience gained in conventional laparoscopic surgery. Although the cosmetic outcome is not comparable to single-port surgery, in the author's opinion minilaparoscopic surgery is a useful alternative in scarless surgery due to the fact that it is easy to adapt without establishing a completely new technique.

Evaluation of psychological distress has received relatively little attention in research on persons with disorders of sex development (DSD). Results of previous studies varied considerably, but most studies did not find increased levels of psychological distress. We conducted a pilot study based on a sample of 37 persons with diverse forms of DSD recruited via various strategies. The Brief Symptom Inventory (BSI) was used to assess self-reported psychological distress. Psychological distress varied broadly across all diagnostic subgroups. Overall, the BSI Global Severity Index indicated higher distress in the sample of persons with DSD compared to a non-clinical norm population of women, with an effect size of d = 0.67. According to predefined BSI criteria, 59% of participants were classified as a clinical case. Self-harming behavior and suicidal tendencies were also assessed and compared to a community based sample of women, including subgroups of traumatized women with a history of physical or sexual abuse. The prevalence rates of self-harming behavior and suicidal tendencies in the DSD sample exceeded the rates of the non-traumatized comparison subgroup, with rates comparable to the traumatized comparison groups of women with physical or sexual abuse. As possible explanations for the higher distress found here compared to most previous studies, differences in measures and sample recruitment are discussed. Our results suggest that adults with DSD are markedly psychologically distressed with rates of suicidal tendencies and self-harming behavior on a level comparable to non-DSD women with a history of physical or sexual abuse, but sample recruitment procedures do not permit a firm generalization.