Effects of life history strategies and habitats on limb regeneration in plethodontid salamanders.

BACKGROUND: Salamanders are the only tetrapods that exhibit the ability to fully regenerate limbs. The axolotl, a neotenic salamander, has become the model organism for regeneration research. Great advances have been made providing a detailed understanding of the morphological and molecular processes involved in limb regeneration. However, it remains largely unknown how limb regeneration varies across salamanders and how factors like variable life histories, ecologies, and limb functions have influenced and shaped regenerative capacities throughout evolution. RESULTS: This study focuses on six species of plethodontid salamanders representing distinct life histories and habitats. Specimens were examined for regeneration ability after bite injuries as well as after controlled amputations. Morphological investigations revealed great regenerative abilities in all investigated species and frequent anatomical limb anomalies. Correlations were observed with respect to speed of regeneration and habitat. CONCLUSIONS: Investigating regeneration in non-model salamander taxa is essential for disentangling shared features of the regeneration process versus those that may be more taxon-specific. Gaining insights into variable aspects of regeneration under natural conditions and after conspecific biting rather than controlled amputations adds important new datapoints for understanding the evolutionary framework of regeneration and provides a broader context for interpreting findings made in the model organism axolotl.

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.

Background and Hypothesis: Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. Study Design: In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. Study Results: While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ±â€…13.4%, PSM + NAC: 72.7 ±â€…13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ±â€…15.3%, PSM + PLC: 39.0 ±â€…17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups. Conclusions: The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

The Amphibian Genomics Consortium: advancing genomic and genetic resources for amphibian research and conservation.

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomics resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomics resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, antipredator strategies, and resilience and adaptive responses. They also serve as critical models for understanding widespread genomic characteristics, including evolutionary genome expansions and contractions given they have the largest range in genome sizes of any animal taxon and multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The advent of long-read sequencing technologies, along with computational techniques that enhance scaffolding capabilities and streamline computational workload is now enabling the ability to overcome some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC) in early 2023. This burgeoning community already has more than 282 members from 41 countries (6 in Africa, 131 in the Americas, 27 in Asia, 29 in Australasia, and 89 in Europe). The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and outline how the AGC can enable amphibian genomics research to "leap" to the next level.

AFM-IR investigation of thin PECVD SiO x films on a polypropylene substrate in the surface-sensitive mode.

Thin silicon oxide films deposited on a polypropylene substrate by plasma-enhanced chemical vapor deposition were investigated using atomic force microscopy-based infrared (AFM-IR) nanospectroscopy in contact and surface-sensitive mode. The focus of this work is the comparison of the different measurement methods (i.e., contact mode and surface-sensitive mode) with respect to the chemical surface sensitivity. The use of the surface-sensitive mode in AFM-IR shows an enormous improvement for the analysis of thin films on the IR-active substrate. As a result, in this mode, the signal of the substrate material could be significantly reduced. Even layers that are so thin that they could hardly be measured in the contact mode can be analyzed with the surface-sensitive mode.

[APPS-Study 2020 - On outpatient psychotherapeutic care for people with psychotic disorders]. / APPS-Studie 2020 ­ Zur ambulanten psychotherapeutischen Versorgung von Menschen mit psychotischen Störungen.

BACKGROUND: Although patients with psychotic disorders (PPS) are indicated for outpatient psychotherapy at any stage of their illness, they are rarely treated in this way. For this purpose, structural conditions, the experience of competence of therapists, as well as content-related aspects of training and further education of psychotherapists are analyzed. METHODS: Based on a qualitative preliminary study, an online survey was conducted among 487 psychological psychotherapists. RESULTS: Half of the respondents indicated a high willingness to treat PPS. In the acute phase of the disease only 20% are willing to do so. In the studies as well as in the theoretical part of the education and further education, there is hardly any preparation for a corresponding treatment. In contrast, practical experience in psychiatric clinics is considered very important. With regard to structural framework conditions, low hourly quotas and inflexible billing modalities are criticized. With regard to patients, in addition to sufficient motivation for treatment, low reliability, low cognitive ability, low insight into the illness, and frequent discontinuation of therapy are stated. Contrary to some prejudices, patients are characterized as "peaceful" in their interactions. The reduction of psychotic relapses, social integration and reduction of comorbid symptoms are mainly mentioned as achievable outcomes. The reduction of psychotic symptoms is rated less optimistically. Psychotherapists from psychiatric outpatient clinics (PIA) differ from other outpatient psychotherapists by better competence experience and correspondingly more frequent work with PPS, also in the acute stage. DISCUSSION: Although every second therapist does not feel well trained, the willingness to treat PPS seems to be higher than the pure supply figures suggest. There is potential for optimization in education and training as well as in networking with other professional groups/relatives. This could be responsible for the fact that in the acute psychotic stage there are fears of contact and competence concerns. Psychotherapists in PIAs, where there is closer networking with other professional groups for structural reasons, experience corresponding deficits to a lesser extent. With regard to other structural barriers, the question arises as to whether these represent disorder-specific or rather general problems in psychotherapy.

Secundum Naturam Vivere: Stoic Thoughts of Greco-Roman Antiquity on Nature and Their Relation to the Concepts of Sustainability, Frugality, and Environmental Protection in the Anthropocene.

This paper wants to shed light on the way the philosophical school of Stoicsm in Greco-Roman antiquity has dealt with the relationship of men and nature by pointing out to some of the key texts in which these issues are mentioned. Although the modern concept of sustainability or environmental protection did not really exist in antiquity, the Stoa was convinced that individual decisions had a direct impact on this world. Following the concept of environmental humanities, the ancient texts and authors are collected as historical ideas of the multifaceted interactions between nature and men that can be fruitfully mirrored with the arguments of the current Anthropocene discourse and its focus on (post)industrialism. By doing so we might come across helpful approaches deeply rooted in our cultural heritage that we could possibly adopt and find practical answers for our age in terms of individual behaviour as well as management decisions to face the ecological and social challenges ahead.

Prevention of First-Episode Psychosis in People at Clinical High Risk: A Randomized Controlled, Multicentre Trial Comparing Cognitive-Behavioral Therapy and Clinical Management Plus Low-Dose Aripiprazole or Placebo (PREVENT).

BACKGROUND: There is limited knowledge of whether cognitive-behavioral therapy (CBT) or second-generation antipsychotics (SGAs) should be recommended as the first-line treatment in individuals at clinical high risk for psychosis (CHRp). HYPOTHESIS: To examine whether individual treatment arms are superior to placebo and whether CBT is non-inferior to SGAs in preventing psychosis over 12 months of treatment. STUDY DESIGN: PREVENT was a blinded, 3-armed, randomized controlled trial comparing CBT to clinical management plus aripiprazole (CM + ARI) or plus placebo (CM + PLC) at 11 CHRp services. The primary outcome was transition to psychosis at 12 months. Analyses were by intention-to-treat. STUDY RESULTS: Two hundred eighty CHRp individuals were randomized: 129 in CBT, 96 in CM + ARI, and 55 in CM + PLC. In week 52, 21 patients in CBT, 19 in CM + ARI, and 7 in CM + PLC had transitioned to psychosis, with no significant differences between treatment arms (P = .342). Psychopathology and psychosocial functioning levels improved in all treatment arms, with no significant differences. CONCLUSIONS: The analysis of the primary outcome transition to psychosis at 12 months and secondary outcomes symptoms and functioning did not demonstrate significant advantages of the active treatments over placebo. The conclusion is that within this trial, neither low-dose aripiprazole nor CBT offered additional benefits over clinical management and placebo.

The psychological consequences of living with coronary heart disease: Are patients' psychological needs served? A mixed-method study in Germany.

INTRODUCTION: This mixed-method study explores psychological needs, access and barriers in coronary heart disease (CHD) patients with and without mental health issues (MHI) within the German healthcare system. METHODS: This study was conducted in three different healthcare settings: two hospitals, two rehabilitation clinics and three cardiology practices in Cologne, Germany. Patients were screened for angiographically documented CHD and other inclusion criteria. In total, 364 CHD patients took part in this study. It consisted of two parts: In the first part, participants filled in a newly developed questionnaire about their psychological needs, access and barriers within the healthcare system and their contact with their doctor in these matters. Then, patients were screened for MHIs with the help of the Hospital Anxiety and Depression Scale (HADS). When a score above seven was scored on the HADS, patients were additionally screened for specific MHIs using the Structured Clinical Interview for DSM-IV Axis I Disorders. In the second part, 20 participants were subsequently interviewed in a semi-structured interview to generate more in-depth findings. RESULTS: The interviews show that CHD patients with and without MHI experienced a cardiac event as life-changing and had an urgent need to talk about CHD with their doctor, mostly the general practitioner (GP). When the GP spoke to the patient shortly after the cardiac event, patients experienced relief and were better able to cope with their illness. Only 9.1% reported being aided in their search for psychotherapeutic treatment or drug treatment (4.1%). CONCLUSION: The needs of CHD patients with and without MHI were not adequately satisfied within our sample. Psychological measures are necessary for sufficient improvement, such as training of doctors in doctor-patient communication (e.g., better support in coping with MHI/CHD), improvements in the procedure (more time for conversations during doctor contacts), and improvement of structural requirements (referring patients faster to psychotherapists). PATIENT OR PUBLIC CONTRIBUTION: We received input from patients during pretests and used the feedback to tailor our questionnaire and the interview guidelines. Afterwards, we disseminated the main results for the patient and public involvement (e.g., public lectures, leaflets for self-help groups, etc.).

Bridging the phenomenological gap between predictive basic-symptoms and attenuated positive symptoms: a cross-sectional network analysis.

Attenuated positive symptoms (APS), transient psychotic-like symptoms (brief, limited intermittent psychotic symptoms, BLIPS), and predictive cognitive-perceptive basic-symptoms (BS) criteria can help identify a help-seeking population of young people at clinical high-risk of a first episode psychosis (CHRp). Phenomenological, there are substantial differences between BS and APS or BLIPS. BS do not feature psychotic content as delusion or hallucinations, and reality testing is preserved. One fundamental problem in the psychopathology of CHRp is to understand how the non-psychotic BS are related to APS. To explore the interrelationship of APS and predictive BS, we fitted a network analysis to a dataset of 231 patients at CHRp, aged 24.4 years (SD = 5.3) with 65% male. Particular emphasis was placed on points of interaction (bridge symptoms) between the two criteria sets. The BS 'unstable ideas of reference' and "inability to discriminate between imagination and reality" interacted with attenuated delusional ideation. Perceptual BS were linked to perceptual APS. Albeit central for the network, predictive cognitive basic BS were relatively isolated from APS. Our analysis provides empirical support for existing theoretical accounts that interaction between the distinct phenomenological domains of BS and APS is characterized by impairments in source monitoring and perspective-taking. Identifying bridge symptoms between the symptom domains holds the potential to empirically advance the etiological understanding of psychosis and pave the way for tailored clinical interventions.

What is the "normal" wound bed temperature? A scoping review and new hypothesis.

Wound bed temperature measurement holds the potential to be a safe, easy to use, and low-cost tool to aid objective wound bed assessment, clinical decision making and improved patient outcomes. However, there is no consensus on the normal range of wound bed temperature in chronic wounds. We conducted a scoping review including any study type, from 2010 to 2020 in which chronic wound bed temperature was reported. Thirteen studies including 477 patients met our criteria. Venous ulcers (VLU) accounted for 46.5% (n = 222) of wounds; diabetic foot ulcers (DFU) for 25.4% (n = 121) with pressure ulcers (PU), mixed arterial venous ulcers (MAVLU) and unknown aetiology accounting for the remainder. The weighted mean of means for wound bed temperature was 31.7°C (n = 395) for all wound types; 31.7°C for VLU; 31.6°C for DFU; 33.3°C for PU; 30.9°C for MAVLU; and 32.0°C for those with unknown aetiology. Based on our review, we hypothesise that normal wound bed temperature is within a range of 30.2-33.0°C.

A comprehensive meta-analysis of the self-serving bias in schizophrenia spectrum disorders compared to non-clinical subjects.

We conducted a comprehensive meta-analysis to investigate the self-serving bias SSB in schizophrenia spectrum disorders (SSD) to examine its specificity for persecutory delusions, paranoia, and to explore sources of heterogeneity in previous findings. We included 56 studies with n = 2501 patients with SSD and n = 2601 non-clinical controls in the main random-effects model using Hedges' g. Data quality and risk of bias were assessed. Results showed that SSB was a function of the method of measurement, and the cultural background of the participants, thereby identifying important sources of heterogeneity in measuring SSB in patients with SSD. The SSD group was somewhat more prone to SSB (g = 0.17), especially, when in a state of active persecutory delusion (g = 0.32/0.57), when they scored high in paranoid ideation (r = 0.25), or tended to jump to conclusions (r = 0.43). High self-esteem in the SSD group was associated with high SSB (r = 0.34); depression with low SSB (r=-0.39).

Parallel evolution of direct development in frogs - Skin and thyroid gland development in African Squeaker Frogs (Anura: Arthroleptidae: Arthroleptis).

BACKGROUND: Cases of parallel evolution offer the possibility to identify adaptive traits and to uncover developmental constraints on the evolutionary trajectories of these traits. The independent evolution of direct development from the ancestral biphasic life history in frogs is such a case of parallel evolution. In frogs, aquatic larvae (tadpoles) differ profoundly from their adult forms and exhibit a stunning diversity regarding their habitats, morphology and feeding behaviors. The transition from the tadpole to the adult is a climactic, thyroid hormone (TH)-dependent process of profound and fast morphological rearrangement called metamorphosis. One of the organ systems that experiences the most comprehensive metamorphic rearrangements is the skin. Direct-developing frogs lack a free-swimming tadpole and hatch from terrestrial eggs as fully formed froglets. In the few species examined, development is characterized by the condensed and transient formation of some tadpole-specific features and the early formation of adult-specific features during a "cryptic" metamorphosis. RESULTS: We show that skin in direct-developing African squeaker frogs (Arthroleptis) is also repatterned from a tadpole-like to an adult-like histology during a cryptic metamorphosis. This repatterning correlates with histological thyroid gland maturation. A comparison with data from the Puerto Rican coqui (Eleutherodactylus coqui) reveals that the evolution of direct development in these frogs is associated with a comparable heterochronic shift of thyroid gland maturation. CONCLUSION: This suggests that the development of many adult features is still dependent on, and possibly constrained by, the ancestral dependency on thyroid hormone signaling.

Detection and treatment of mental disorders in patients with coronary heart disease (MenDis-CHD): A cross-sectional study.

Mental disorders (MD) are associated with an increased risk of developing coronary heart disease (CHD) and with higher CHD-related morbidity and mortality. There is a strong recommendation to routinely screen CHD patients for MDs, diagnosis, and treatment by recent guidelines. The current study aimed at mapping CHD patients' (1) state of diagnostics and, if necessary, treatment of MDs, (2) trajectories and detection rate in healthcare, and (3) the influence of MDs and its management on quality of life and patient satisfaction. The design was a cross-sectional study in three settings (two hospitals, two rehabilitation clinics, three cardiology practices). CHD patients were screened for MDs with the Hospital Anxiety and Depression Scale (HADS), and, if screened-positive, examined for MDs with the Structured Clinical Interview for DSM-IV (SCID-I). Quality of Life (EQ-5D), Patient Assessment of Care for Chronic Conditions (PACIC), and previous routine diagnostics and treatment for MDs were examined. Descriptive statistics, Chi-squared tests, and ANOVA were used for analyses. Analyses of the data of 364 patients resulted in 33.8% positive HADS-screenings and 28.0% SCID-I diagnoses. The detection rate of correctly pre-diagnosed MDs was 49.0%. Physicians actively approached approximately thirty percent of patients on MDs; however, only 6.6% of patients underwent psychotherapy and 4.1% medication therapy through psychotherapists/psychiatrists. MD patients scored significantly lower on EQ-5D and the PACIC. The state of diagnostic and treatment of comorbid MDs in patients with CHD is insufficient. Patients showed a positive attitude towards addressing MDs and were satisfied with medical treatment, but less with MD-related advice. Physicians in secondary care need more training inadequately addressing mental comorbidity.

Comparison of Patient and Proxy Assessment of Patient-Centeredness in the Care of Coronary Heart Disease: A Cross Sectional Survey Using the PACIC-S11.1.

INTRODUCTION: When making medical care more patient-centered, surveys on patients' and their relatives' experiences can be helpful in identifying opportunities for improvement. In cases where the targeted patients are unable to express their own perspective, for example, due to them being too young or suffering from severe impairments, proxies can serve as substitutes. Proxies are frequently used in care planning and consent. Nevertheless, it is unclear whether patients' assessments of how patient-centered their medical care is are similar to those of their proxies. This study aims to assess the level of consistency between patients' and their proxies' assessments using an adapted version of the Patient Assessment of Chronic Illness Care (PACIC) short form questionnaire. METHODS: In a cross-sectional study, patients with coronary heart disease were recruited at cardiologists' offices, rehabilitation clinics and hospitals. Participants were surveyed with regard to the perceived level of patient-centeredness during their care using an adapted version of the German PACIC short form (PACIC-S11.1). Correlations in the assessments made by each patient and their respective proxy were analyzed. On the level of the patients group and the relatives group differences between mean ratings for each item were compared using paired t-tests. RESULTS: In total, 74 pairs of patients and proxies submitted the completed questionnaire. On the level of the individual patient/proxy pairs, no correlation, or significant but low correlation, was found between the ratings. On the group level, patients' and their proxies' item ratings were similar in the interpretation of averages, but still demonstrated statistically significant differences. Overall, patients rated their care as more patient-centered than their proxies did. CONCLUSION: The study shows that, on the individual level, proxies' ratings do not necessarily reflect the patients' assessment of PCC. On the group level, the assessments of relatives regarding PCC are similar to those of the patients. TRIAL REGISTRATION: German clinical trials register (Deutsches Register Klinischer Studien, DRKS) Registration Number: DRKS00012434 (URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012434).

[Cortisol concentration before, during and after sham foot trimming in German Holstein cows - the suitability of different matrices]. / Kortisolkonzentration bei Deutsch-Holstein-Kühen vor, während und nach der Klauenbehandlung im Durchtreibestand ­ Eignung verschiedener Matrizes.

OBJECTIVE: The objective of this study was to determine whether changes in cortisol concentration measured in blood serum (KoB) of cows exposed to an acute stressor shows a correlation to cortisol concentrations in saliva (KoS), tears (KoT) and milk (KoM) as well as the concentration of cortisol metabolites in feces (KoK). MATERIALS AND METHODS: In 10 healthy German Holstein cows, sham foot trimming (sKB) including the movement/fixation of the cows through/in a foot trimming chute was used as a model for acute stress. KoB, KoS, KoT, KoM and KoK were measured once a day for 10 days. During sKB, performed on day 4, KoB and KoT were measured at the initiation of foot trimming (minute 0) as well as 15, 25, 30, 40, 50, 60 and 80 minutes later. Additionally, KoK was measured 480, 540, 600 and 660 minutes after the start of sKB. RESULTS: KoB and KoT increased during sKB and reached a maximum at 60 minutes followed by a decrease. KoK increased after sKB and reached a maximum at 660 minutes. There was a significant correlation between KoB and KoT, KoK and KoB and a trend towards a significant correlation between KoK and KoT during sKB. KoB and KoT were significantly correlated (area under the curve, minute 0-10, p = 0.04). KoB decreased significantly from day 1 to day 4 (p < 0.01). On day, 5 KoB (p = 0.03) and KoK (p < 0.01) were significantly higher. KoS and KoT served as good proxies for KoB throughout the study, and KoK and KoB exhibited similar profiles. There were several differences between the profiles of KoM and KoB. During the 10-day measurement period, a significant positive correlation was detected between KoB and KoS (p = 0.002) as well as between KoB and KoT (p = 0.002). CONCLUSIONS AND CLINICAL RELEVANCE: The collection of tear fluid and saliva for determination of cortisol concentrations are non-invasive alternatives to blood sampling. Calm handling of cows may reduce their stress reaction and thus improve animal welfare.

[Effect of different pain management protocols on the health status of German Holstein heifer calves undergoing hot iron disbudding]. / Einfluss der thermischen Enthornung mit unterschiedlichem Schmerzmanagement auf die Gesundheit von Kälbern.

OBJECTIVE: Hot iron disbudding of calves is a stressful and painful procedure. Previous parts of an ongoing comprehensive study on disbudding in dairy calves dealt with various types of pain management and the direct effects of the procedure on physiological, biochemical and behavioral processes. The goal of this study part was to investigate the effects of the disbudding procedure per se, pain management and the age of the calf at the time of disbudding on the health status of the calf. MATERIALS AND METHODS: A total of 337 German Holstein heifer calves were used for this prospective, randomized and triple-blinded study. The calves were disbudded at 4-10 days or at 15-28 days of age. Each calf was randomly assigned to one of 9 treatment groups, which differed with respect to pain management (sedation, local anesthesia, nonsteroidal antiinflammatory drugs, placebo). All but the sham-disbudded calves underwent hot iron disbudding and all calves were monitored clinically before and until 4 weeks after the procedure. The findings were analyzed using valuation scores and a threshold model of the SAS software. RESULTS: Disbudding exhibited adverse effects on respiratory health. Calves undergoing sham disbudding experienced the lowest incidence of respiratory disease and calves that did not receive any anesthesia or pain medication displayed the highest frequency. All treatments showed mitigating effects on the incidence of respiratory tract diseases, however the effects varied with the type of pain management. Fever was less common in calves that were disbudded early in life than calves that underwent disbudding at an older age. CONCLUSION: Disbudding of young calves poses a risk to respiratory health. If breeding of polled offspring is not possible or when farming of horned cattle is not feasible, the risk of respiratory disease induced by disbudding can be minimized by adequate pain management. Disbudding of very young calves is feasible and recommended. CLINICAL RELEVANCE: The present study underlines the importance of optimal pain management during disbudding of dairy calves.

Cognitive behavioral therapy in adolescents with early-onset psychosis: a randomized controlled pilot study.

Cognitive behavioral therapy for psychosis (CBT) is an effective treatment in adult patients with schizophrenia. However, no randomized controlled and blinded trial in adolescents with early-onset psychosis (EOP) has been conducted. Therefore, the present pilot study explores the acceptance, tolerability, feasibility, and safety of a modified CBT in adolescents with EOP. Twenty-five adolescents with EOP were randomized to either 9 months (20 sessions) of CBT + treatment as usual (TAU) or TAU alone. The primary endpoint was the PANSS-positive subscale (P1-7). Secondary endpoints included psychopathology, global functioning, and quality of life (QoL). Acceptance, tolerability, feasibility, and safety were assessed. Blinded assessments took place by the end of the treatment (9 months) and at 24-month follow-up. Despite improvements in both groups and lack of statistical significance between CBT + TAU and TAU regarding the primary endpoint, we observed between-group effect sizes of at least d = 0.39 in favor of CBT + TAU at post-treatment for delusions, negative symptoms, functioning and QoL after the intervention and effect sizes of at least d = 0.35 after 24 months. CBT in EOP was highly acceptable (73.5% agreed to randomization), well-tolerated (83.1% attendance rate, no drop-outs), and safe (one serious adverse event (SAE) in CBT + TAU in comparison with six SAEs in TAU). These findings suggest that CBT adapted to the needs of adolescents with EOP is a promising approach regarding negative symptoms, functioning, and QoL. CBT is a safe and tolerable treatment. However, due to the small sample size and the pilot character of the study, these conclusions are limited, and should be tested in a larger, adequately powered randomized controlled trial.

Astrocytic GABA Accumulation in Experimental Temporal Lobe Epilepsy.

An imbalance of excitation and inhibition has been associated with the pathophysiology of epilepsy. Loss of GABAergic interneurons and/or synaptic inhibition has been shown in various epilepsy models and in human epilepsy. Despite this loss, several studies reported preserved or increased tonic GABAA receptor-mediated currents in epilepsy, raising the question of the source of the inhibitory transmitter. We used the unilateral intracortical kainate mouse model of temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) to answer this question. In our model we observed profound loss of interneurons in the sclerotic hippocampal CA1 region and dentate gyrus already 5 days after epilepsy induction. Consistent with the literature, the absence of interneurons caused no reduction of tonic inhibition of CA1 pyramidal neurons. In dentate granule cells the inhibitory currents were even increased in epileptic tissue. Intriguingly, immunostaining of brain sections from epileptic mice with antibodies against GABA revealed strong and progressive accumulation of the neurotransmitter in reactive astrocytes. Pharmacological inhibition of the astrocytic GABA transporter GAT3 did not affect tonic inhibition in the sclerotic hippocampus, suggesting that this transporter is not responsible for astrocytic GABA accumulation or release. Immunostaining further indicated that both decarboxylation of glutamate and putrescine degradation accounted for the increased GABA levels in reactive astrocytes. Together, our data provide evidence that the preserved tonic inhibitory currents in the epileptic brain are mediated by GABA overproduction and release from astrocytes. A deeper understanding of the underlying mechanisms may lead to new strategies for antiepileptic drug therapy.

[Assessment of different pain management methods for the treatment of claw lesions in Meat Merino ewes]. / Bewertung verschiedener Methoden des Schmerzmanagements während der Behandlung von Klauenlederhaut-Läsionen bei weiblichen Merinofleischschafen.

OBJECTIVE: Pain management during veterinary procedures is a significant component of animal welfare and has legal as well as ethical implications. Even though regional intravenous anaesthesia (RIVA) is an accepted method for painful procedures involving the distal digits of sheep, this anaesthetic technique is rarely applied in the field. The primary goal was to investigate the feasibility, safety and efficacy of RIVA in sheep. A secondary goal was to examine whether the anaesthetic procedure can be improved by combining RIVA with sedation and whether these methods have a positive effect on the postoperative wellbeing of the animals. METHODS: A total of 36 Meat Merino sheep with contagious interdigital dermatitis and 12 healthy control sheep were used. Behaviour was observed during treatment of the lame sheep using various pain management protocols and during routine claw trimming of the healthy sheep, and all the sheep were observed after the procedures. The observed behaviours were assessed using scores and the scores compared among the animals of the 4 study groups (RIVA, sedation with xylazine hydrochloride + RIVA, placebo, control). RESULTS: RIVA was successfully conducted in sheep. Local reactions at the application sight and in the tourniquet area in 2 animals resolved completely. A significant reduction in defensive movements during the painful procedure confirmed the efficacy of RIVA. Stress-associated behaviours, including head shaking and idle chewing, occurred with a similar frequency in RIVA and placebo animals, leading to the conclusion that stress levels due to the handling in dorsal recumbency were comparable between these 2 groups. Sedation reduced the frequency of pain- and stress-associated behaviours, including guarding, favouring limbs, vocalisation, idle chewing and bruxism. Xylazine hydrochloride-RIVA animals displayed better weight-bearing in the affected limb, better food uptake and ruminated more postoperatively than sheep from the other study groups. CONCLUSION: RIVA in sheep is straightforward, safe and effective. Additional sedation reduces the stress and pain response. This pain and stress management has a positive effect on the postoperative wellbeing of sheep.

Quality of health care with regard to detection and treatment of mental disorders in patients with coronary heart disease (MenDis-CHD): study protocol.

BACKGROUND: Mental disorders (MD), such as depression, anxiety, and cognitive impairment, are highly prevalent in patients with coronary heart disease (CHD). Current guidelines on cardiovascular diseases recommend screening and appropriate treatment of MD; however, the degree of implementation of such recommendations in clinical practice is unknown. This study aims to analyze the quality of health care of patients with CHD and MD. Specifically, we aim to analyze (1) the quality of care, (2) trajectories of care, and (3) barriers regarding the detection and treatment of MD. Moreover, we want to identify potentials of changes in health care delivery towards more patient-centered care. The results of this study shall be the first step towards value-based care of people with CHD and comorbid mental disorders. METHODS: We aim to include the following participants: adult patients with CHD (n = 400), their relatives (n = 350) and physicians (n = 80). A particular focus will be on the vulnerable subgroups of patients with CHD and congestive heart failure (left ventricular ejection fraction < 40%) and on the underrepresented group of women with CHD. We will apply a mixed-method approach with a quantitative and a qualitative part. Patient-related outcomes (e.g., health-related quality of life, needs, and preferences regarding health care, reasons for non-detection, and lack of treatment of MD) will be explored in a multi-perspective approach including patients, relatives, and physicians' perspectives. Furthermore, routine data from four statutory health insurance funds (SHI) will be analyzed regarding the frequency and treatment of MD in CHD patients. DISCUSSION: MenDis-CHD will provide important insights into the trajectories of health care, quality of health care, barriers, patient needs and preferences as well as expectations and satisfaction with health care in patients with CHD and MD. Potential implications of MenDis-CHD are to enable health care providers to redesign care pathways concerning the treatment of mental comorbidity in patients with CHD by proposing value-based changes in health care and by understanding the barriers to and facilitators of change towards patient-centered care. TRIALS REGISTRATION: German clinical trials register (Deutsches Register Klinischer Studien, DRKS) ieRegistration Number: DRKS00012434, date of registration: May 11th, 2017.