PAX3 haploinsufficiency in Maine Coon cats with dominant blue eyes and hearing loss resembling the human Waardenburg syndrome.

This study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from two different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some individuals exhibiting signs of deafness, and 8 stillborn kittens. Samples from the Topaz lineage included ten blue-eyed animals. A brainstem auditory evoked potential test (BAER) revealed a reduced to absent response to auditory stimuli and absent physiological waveforms in all of the eight examined DBE animals. We sequenced the genome of two affected cats from the Dutch line and searched for variants in 19 candidate genes for the human Waardenburg syndrome and pigmentary disorders. This search yielded nine private protein-changing candidate variants in the genes PAX3, EDN3, KIT, OCA2, SLC24A5, HERC2 and TYRP1. The genotype-phenotype co-segregation was observed for the PAX3 variant within all animals from the Dutch lineage. The mutant allele was absent from 461 control genomes and 241 additionally genotyped green-eyed Maine Coons. We considered the PAX3 variant as the most plausible candidate -a heterozygous nonsense single basepair substitution in exon 6 of PAX3 (NC_051841.1: g.205,787,310G>A, XM_019838731.3:c.937C>T, XP_019694290.1:p.Gln313*), predicted to result in a premature stop codon. PAX3 variants cause auditory-pigmentary syndrome in humans, horses, and mice. Together with the comparative data from other species, our findings strongly suggest PAX3:c.937C>T (OMIA:001688-9685) as the most likely candidate variant for the DBE, deafness and minimal white spotting in the Maine Coon Dutch line. Finally, we propose the designation of DBERE (Rociri Elvis Dominant Blue Eyes) allele in the domestic cat.

xECGArch: a trustworthy deep learning architecture for interpretable ECG analysis considering short-term and long-term features.

Deep learning-based methods have demonstrated high classification performance in the detection of cardiovascular diseases from electrocardiograms (ECGs). However, their blackbox character and the associated lack of interpretability limit their clinical applicability. To overcome existing limitations, we present a novel deep learning architecture for interpretable ECG analysis (xECGArch). For the first time, short- and long-term features are analyzed by two independent convolutional neural networks (CNNs) and combined into an ensemble, which is extended by methods of explainable artificial intelligence (xAI) to whiten the blackbox. To demonstrate the trustworthiness of xECGArch, perturbation analysis was used to compare 13 different xAI methods. We parameterized xECGArch for atrial fibrillation (AF) detection using four public ECG databases ( n = 9854 ECGs) and achieved an F1 score of 95.43% in AF versus non-AF classification on an unseen ECG test dataset. A systematic comparison of xAI methods showed that deep Taylor decomposition provided the most trustworthy explanations ( + 24 % compared to the second-best approach). xECGArch can account for short- and long-term features corresponding to clinical features of morphology and rhythm, respectively. Further research will focus on the relationship between xECGArch features and clinical features, which may help in medical applications for diagnosis and therapy.

Novel Metric for Non-Invasive Beat-to-Beat Blood Pressure Measurements Demonstrates Physiological Blood Pressure Fluctuations during Pregnancy.

Beat-to-beat (B2B) variability in biomedical signals has been shown to have high diagnostic power in the treatment of various cardiovascular and autonomic disorders. In recent years, new techniques and devices have been developed to enable non-invasive blood pressure (BP) measurements. In this work, we aim to establish the concept of two-dimensional signal warping, an approved method from ECG signal processing, for non-invasive continuous BP signals. To this end, we introduce a novel BP-specific beat annotation algorithm and a B2B-BP fluctuation (B2B-BPF) metric novel for BP measurements that considers the entire BP waveform. In addition to careful validation with synthetic data, we applied the generated analysis pipeline to non-invasive continuous BP signals of 44 healthy pregnant women (30.9 ± 5.7 years) between the 21st and 30th week of gestation (WOG). In line with established variability metrics, a significant increase (p < 0.05) in B2B-BPF can be observed with advancing WOGs. Our processing pipeline enables robust extraction of B2B-BPF, demonstrates the influence of various factors such as increasing WOG or exercise on blood pressure during pregnancy, and indicates the potential of novel non-invasive biosignal sensing techniques in diagnostics. The results represent B2B-BP changes in healthy pregnant women and allow for future comparison with those signals acquired from women with hypertensive disorders.

Design of Modified Polymer Membranes Using Machine Learning.

Surface modification is an attractive strategy to adjust the properties of polymer membranes. Unfortunately, predictive structure-processing-property relationships between the modification strategies and membrane performance are often unknown. One possibility to tackle this challenge is the application of data-driven methods such as machine learning. In this study, we applied machine learning methods to data sets containing the performance parameters of modified membranes. The resulting machine learning models were used to predict performance parameters, such as the pure water permeability and the zeta potential of membranes modified with new substances. The predictions had low prediction errors, which allowed us to generalize them to similar membrane modifications and processing conditions. Additionally, machine learning methods were able to identify the impact of substance properties and process parameters on the resulting membrane properties. Our results demonstrate that small data sets, as they are common in materials science, can be used as training data for predictive machine learning models. Therefore, machine learning shows great potential as a tool to expedite the development of high-performance membranes while reducing the time and costs associated with the development process at the same time.

The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer.

Abnormal expression of ACSL members 1, 3, 4, 5, and 6 is frequently seen in human cancer; however, their clinical relevance is unclear. In this study, we analyzed the expression of ACSLs and investigated the effects of the ACSL inhibitor Triacsin C (TC) in lung cancer. We found that, compared to normal human bronchial epithelial (NHBE) cells, ACSL1, ACSL4, and ACSL6 were highly expressed, while ACSL3 and ACSL5 were lost in the majority of lung cancer cell lines. ACSL activity was associated with the expression levels of the ACSLs. In primary lung tumors, a higher expression of ACSL1, ACSL4, and ACSL5 was significantly correlated with adenocarcinoma (ADC). Moreover, ACSL5 was significantly reversely related to the proliferation marker Ki67 in low-grade tumors, while ACSL3 was positively associated with Ki67 in high-grade tumors. Combination therapy with TC and Gemcitabine enhanced the growth-inhibitory effect in EGFR wild-type cells, while TC combined with EGFR-TKIs sensitized the EGFR-mutant cells to EGFR-TKI treatment. Taken together, the data suggest that ACSL1 may be a biomarker for lung ADC, and ACSL1, ACSL4, and ACSL5 may be involved in lung cancer differentiation, and TC, in combination with chemotherapy or EGFR-TKIs, may help patients overcome drug resistance.

High Temperature Electron Diffraction on Organic Crystals: In Situ Crystal Structure Determination of Pigment Orange 34.

Small molecule structures and their applications rely on good knowledge of their atomic arrangements. However, the crystal structures of these compounds and materials, which are often composed of fine crystalline domains, cannot be determined with single-crystal X-ray diffraction. Three-dimensional electron diffraction (3D ED) is already becoming a reliable method for the structure analysis of submicrometer-sized organic materials. The reduction of electron beam damage is essential for successful structure determination and often prevents the analysis of organic materials at room temperature, not to mention high temperature studies. In this work, we apply advanced 3D ED methods at different temperatures enabling the accurate structure determination of two phases of Pigment Orange 34 (C34H28N8O2Cl2), a biphenyl pyrazolone pigment that has been industrially produced for more than 80 years and used for plastics application. The crystal structure of the high-temperature phase, which can be formed during plastic coloration, was determined at 220 °C. For the first time, we were able to observe a reversible phase transition in an industrial organic pigment in the solid state, even with atomic resolution, despite crystallites being submicrometer in size. By localizing hydrogen atoms, we were even able to detect the tautomeric state of the molecules at different temperatures. This demonstrates that precise, fast, and low-dose 3D ED measurements enable high-temperature studies the door for general in situ studies of nanocrystalline materials at the atomic level.

Long-term impact of resilience and extraversion on psychological distress during the COVID-19 pandemic: a longitudinal investigation among individuals with and without mental health disorders.

Background: Over the past years, the COVID-19 pandemic has caused significant disruptions in daily routines. Although the pandemic has affected almost everyone, it has been particularly challenging for people with pre-existing mental health conditions. Therefore, this study investigated the long-term impact of resilience and extraversion on psychological distress in individuals diagnosed with mental health disorders (MHD) compared to the general population. In addition, possible gender-specific differences were investigated. Methods: 123 patients with pre-existing MHD and 343 control subjects from Austria and Italy participated in three online surveys that had been conducted after the initial wave of the COVID-19 pandemic (t0), during the second lockdown in both countries (t1), and one year thereafter (t2). Participants completed standardized questionnaires on psychological distress (Brief-Symptom-Checklist), resilience (Resilience Scale), and extraversion (Big Five Inventory). A mediation model was employed to test the primary hypothesis. Possible gender-specific differences were analyzed using a moderated mediation model. Results: The prevalence of psychological distress was consistently higher in patients compared to controls (t0: 37.3% vs. 13.2%, t1: 38.2% vs 11.7%, t2: 37.4% vs. 13.1%). This between-group difference in psychological distress at the first follow-up was fully mediated by baseline resilience scores (65.4% of the total effect). During the second-follow up, extraversion accounted for 18% of the total effect, whereas resilience slightly decreased to 56% of the total effect. Gender was not a significant moderator in the model. Conclusion: Next to showing that people with MHD were particularly affected by the pandemic, these findings indicate that higher degrees of resilience and extraversion are related to less long-term psychological distress. Our findings stress the relevance of strengthening resilience and extraversion and to provide mental health support in times of crises, both to patients with MHD and the general population.

RoboEM: automated 3D flight tracing for synaptic-resolution connectomics.

Mapping neuronal networks from three-dimensional electron microscopy (3D-EM) data still poses substantial reconstruction challenges, in particular for thin axons. Currently available automated image segmentation methods require manual proofreading for many types of connectomic analysis. Here we introduce RoboEM, an artificial intelligence-based self-steering 3D 'flight' system trained to navigate along neurites using only 3D-EM data as input. Applied to 3D-EM data from mouse and human cortex, RoboEM substantially improves automated state-of-the-art segmentations and can replace manual proofreading for more complex connectomic analysis problems, yielding computational annotation cost for cortical connectomes about 400-fold lower than the cost of manual error correction.

Effect of Low-Frequency Renal Nerve Stimulation on Renal Glucose Release during Normoglycemia and a Hypoglycemic Clamp in Pigs.

Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2-5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS.

Controlling the function of bioactive worm micelles by enzyme-cleavable non-covalent inter-assembly cross-linking.

Drugs that form self-assembled supramolecular structures to be most-active is a promising way of creating new highly specific and active pharmaceuticals. Controlling the activity of bioactive supramolecular structures such as drug-loaded micelles is possible by both core/shell and inter-assembly cross-linking. However, if the flexibility of the assembly is mandatory for the activity cross-linking is not feasible. Thus, such structures cannot be manipulated in their activity. The present study demonstrates a novel concept to control the activity of not drug-releasing, non-cross-linked bioactive superstructures. This is achieved by formation of nanostructured nanoparticles derived by non-covalent inter-assembly cross-linking of the superstructures. This is shown on the example of amphiphilic diblock-copolymers conjugated with the antibiotic ciprofloxacin (CIP). These polymer-antibiotic conjugates form worm micelles, which greatly activate the conjugated antibiotic without releasing it. Non-covalent inter-assembly cross-linking of these CIP-worm-micelles with amphiphilic triblock copolymers terminated with lipase-cleavable esters leads to nanostructured nanoparticles that resemble cross-linked worm micelles and show an up to 135-fold lower activity than the free worm micelles. The activity of the worm-micelles can be fully recovered by cleaving the end groups of the polymeric cross-linker with lipase.

An early-curricular team learning activity to foster integration of biochemical concepts and clinical sciences in undergraduate medical education.

The ability to connect key concepts of biochemistry with clinical presentations is essential for the development of clinical reasoning skills and adaptive expertise in medical trainees. To support the integration of foundational and clinical sciences in our undergraduate health science curricula, we developed a small group active learning exercise during which interprofessional groups of students use clinical cases to explore the biochemistry, diagnostic strategy, and evidence-based treatment options of inborn errors of metabolism (IEM). We designed multistage learning modules consisting of (1.) low-fidelity case simulations of pediatric patients presenting with IEMs, (2.) guided group discussions on clinical biochemistry, differential diagnoses, and diagnostic strategies, (3.) oral presentations of clinical reasoning strategies, and (4.) discussion of relevant evidence-based medicine topics related to the cases. These modules Scientific Knowledge Integrated in Patient Presentations (SKIPPs) were added to a first-semester foundational sciences course serving five health professions programs. The assessment of learning outcomes by students and faculty shows that SKIPPs sessions are well-received activities that significantly improve trainees' ability to integrate foundational science concepts into clinical scenarios, to practice interprofessional teamwork and to develop clinical reasoning skills.

Brain stimulation with 40 Hz heterochromatic flicker extended beyond red, green, and blue.

Alzheimer's disease (AD) is associated with electrophysiological changes in the brain. Pre-clinical and early clinical trials have shown promising results for the possible therapy of AD with 40 Hz neurostimulation. The most notable findings used stroboscopic flicker, but this technique poses an inherent barrier for human applications due to its visible flickering and resulting high level of perceived discomfort. Therefore, alternative options should be investigated for entraining 40 Hz brain activity with light sources that appear less flickering. Previously, chromatic flicker based on red, green, and blue (RGB) have been studied in the context of brain-computer interfaces, but this is an incomplete representation of the colours in the visual spectrum. This study introduces a new kind of heterochromatic flicker based on spectral combinations of blue, cyan, green, lime, amber, and red (BCGLAR). These combinations are investigated by the steady-state visually evoked potential (SSVEP) response from the flicker with an aim of optimising the choice of 40 Hz light stimulation with spectrally similar colour combinations in BCGLAR space. Thirty healthy young volunteers were stimulated with heterochromatic flicker in an electroencephalography experiment with randomised complete block design. Responses were quantified as the 40 Hz signal-to-noise ratio and analysed using mixed linear models. The size of the SSVEP response to heterochromatic flicker is dependent on colour combinations and influenced by both visual and non-visual effects. The amber-red flicker combination evoked the highest SSVEP, and combinations that included blue and/or red consistently evoked higher SSVEP than combinations only with mid-spectrum colours. Including a colour from either extreme of the visual spectrum (blue and/or red) in at least one of the dyadic phases appears to be more important than choosing pairs of colours that are far from each other on the visual spectrum. Spectrally adjacent colour pairs appear less flickering to the perceiver, and thus the results motivate investigations into the limits for how alike the two phases can be and still evoke a 40 Hz response. Specifically, combining a colour on either extreme of the visual spectrum with another proximal colour might provide the best trade-off between flickering sensation and SSVEP magnitude.

Treatment of Hereditary Haemorrhagic Telangiectasia with Bevacizumab - What More Needs to be Known?

Introduction: Hereditary haemorrhagic telangiectasia (HHT) is a rare multi-organ vascular disease. It is characterised by mucocutaneous telangiectasia, epistaxis, and arteriovenous malformations. Some 70% of patients with HHT are thought to have issues with gastrointestinal (GI) bleeding. Traditional management of GI bleeding in HHT includes monitoring for iron deficiency anaemia, iron replacement, antifibrinolytic therapy and control of identifiable bleeding sites with argon photocoagulation during gastrointestinal endoscopy. Blood transfusion may also be required. Case description: Our case describes a man in his 40s with confirmed HHT, with transfusion-dependent anaemia secondary to GI bleeding. He was commenced on fortnightly bevacizumab (5 mg/kg) for 12 weeks in an attempt to reduce his blood transfusion requirement and manage his anaemia. In the months prior to starting bevacizumab, our patient's transfusion requirement ranged from 3-5 units of packed red cells per month to maintain an Hb >8 g/dl. He had a marked improvement in his symptoms within the first month of treatment and did not require any further blood transfusion during the three months of treatment. He was given one further IV iron infusion in the final month of his 3-month bevacizumab treatment and did not experience any adverse side effects from bevacizumab. Discussion: HHT results from alterations to genes which encode proteins involved in blood vessel formation. This provides the rationale for using anti VEGF drugs such as bevacizumab. Current evidence for this treatment approach is limited. Conclusion: Bevacizumab can be an effective treatment option in patients with HHT refractory to traditional management. LEARNING POINTS: Gastrointestinal bleeding in hereditary haemorrhagic telangiectasia can be difficult to treat.Bevacizumab, an anti-vascular endothelial growth factor, can be used to treat refractory anaemia secondary to gastrointestinal bleeding in hereditary haemorrhagic telangiectasia.

Evaluating a Situational Judgment Test for Use in Medical School Admissions: Two Years of AAMC PREview Exam Administration Data.

PURPOSE: To examine the relationship between the Association of American Medical Colleges (AAMC) Professional Readiness Exam (PREview) scores and other admissions data, group differences in mean PREview scores, and whether adding a new assessment tool affected the volume and composition of applicant pools. METHOD: Data from the 2020 and 2021 PREview exam administrations were analyzed. Two U.S. schools participated in the PREview pilot in 2020 and 6 U.S. schools participated in 2021. PREview scores were paired with data from the American Medical College Application Service (undergraduate grade point averages [GPAs], Medical College Admission Test [MCAT] scores, race, and ethnicity) and participating schools (interview ratings). RESULTS: Data included 19,525 PREview scores from 18,549 unique PREview examinees. Correlations between PREview scores and undergraduate GPAs ( r = .16) and MCAT scores ( r = .29) were small and positive. Correlations between PREview scores and interview ratings were also small and positive, ranging between .09 and .14 after correcting for range restriction. Small group differences in mean PREview scores were observed between White and Black or African American and White and Hispanic, Latino, or of Spanish origin examinees. The addition of the PREview exam did not substantially change the volume or composition of participating schools' applicant pools. CONCLUSIONS: Results suggest the PREview exam measures knowledge of competencies that are distinct from those measured by other measures used in medical school admissions. Observed group differences were smaller than group differences observed with traditional academic assessments and evaluations. The addition of the PREview exam did not substantially change the overall volume of applications or the proportions of out-of-state, underrepresented in medicine, or lower socioeconomic status applicants. While more research is needed, these results suggest the PREview exam may provide unique information to the admissions process without adversely affecting applicant pools.

MFSD2A frameshift variant in Kerry Hill sheep with microcephaly.

Microcephaly is a rare neurodevelopmental disorder characterized by reduced skull circumference and brain volume that occurs sporadically in farm animals. We investigated an early-onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly. The pedigree of the lambs suggested monogenic autosomal recessive inheritance. We sequenced the genome of one affected lamb, and comparison with 115 control genomes revealed a single private protein-changing variant. This frameshift variant, MFSD2A: c.285dupA, p.(Asp96fs*9), represents a 1-bp duplication predicted to truncate 80% of the open reading frame. MFSD2A is a transmembrane protein that is essential for maintaining blood-brain barrier homeostasis and plays a key role in regulating brain lipogenesis. Human MFSD2A pathogenic variants are associated with a neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA, OMIM 616486). Here we present evidence for the occurrence of a recessively inherited form of microcephaly in sheep due to a loss-of-function variant in MFSD2A (OMIA 002371-9940). To the best of our knowledge, this is the first report of a spontaneous MFSD2A variant in domestic animals.

Reliability and interobserver variability of a grading system of ventricular distension in dogs.

Introduction: Internal hydrocephalus is the most common malformation of the central nervous system in dogs. Although the grades of ventricular distension have importance for long-term prognosis, there is no standard classification scheme describing the grade of the ventricular distension in dogs. Materials and methods: Magnetic resonance imaging (MRI) scans from 147 dogs of various breed, sex, skull conformation, and weight were reviewed retrospectively and blinded between three observers. Based on objectively assessable morphologic characteristics, the lateral cerebral ventricles were graded as normal, minimally, mildly, moderately, severely enlarged or end stage (grade 0 to grade 5), respectively. Evans' index or the ventricle brain index was also measured in all animals. Interobserver agreement between a very experienced, experienced, and unexperienced person was evaluated by the Spearman coefficient and kappa tests. Additionally, correlation to the ventricle brain index was determined using the Spearman coefficient and F-tests. Results: The Spearman correlation coefficient reached a very strong correlation (r = 0.97) between the experienced and very experienced observer and a strong correlation (r = 0.91) between the very experienced and unexperienced observer. The kappa value revealed excellent interobserver agreement between the very experienced and experienced observers (weighted kappa 0.91) and moderate between the very experienced and unexperienced observers (weighted kappa 0.75). The ventricular-brain index correlated (r = 0.94, Spearman coefficient test) with the grading system, indicating that a more elevated ratio was related to a more advanced degree of ventricular enlargement. The interobserver agreement with regard to the grade between the neurologist in training and a board-certified neurologist was excellent and between the board-certified neurologist and general practitioner achieved lower values. Conclusion: The presented MRI-based grading of ventricular enlargement is a reliable and functional method for an objective grading of the ventricular system in dogs. Some experience in MRI and brain anatomy is needed for interpretation and grading.

Contributors to beat-to-beat stroke volume variability during acute mental stress in healthy volunteers.

Acute mental stress elicits sympathetic activation, increasing heart rate and shortening the QT interval, but it is unknown whether this activation translates to stroke volume (SV) changes. Multivariate power spectral decomposition was used to assess the influence of heart rate and QT variabilities on SV variability at rest and during acute mental stress. Acute mental stress elicits mild but statistically significant increase in SV variability. Heart rate variability contributes almost one third of SV variability, while the contribution of QT variability is below 3%. In conclusion, although heart rate variability appears to contribute directly to increase in SV variability during acute mental stress, most of SV variability is attributed to sources independent of heart rate and QT variabilities.Clinical Relevance-Acute mental stress elicits small fluctuations in stroke volume in healthy volunteers. Its significance for clinical populations remains to be established.

Relevance of spirituality and perceived social support to mental health of people with pre-existing mental health disorders during the COVID-19 pandemic: a longitudinal investigation.

BACKGROUND: The COVID-19 pandemic and related measures have negatively impacted mental health worldwide. The main objective of the present longitudinal study was to investigate mental health in people living in Tyrol (Austria) and South Tyrol (Italy) during the COVID-19 pandemic and to report the prevalence of psychological distress among individuals with versus those without pre-existing mental health disorders (MHD) in the long-term (summer 2020-winter 2022). Here, we specifically focus on the relevance of spirituality and perceived social support in this regard. METHODS: 161 individuals who had been diagnosed with MHD and 446 reference subjects participated in this online survey. Electronic data capture was conducted using the Computer-based Health Evaluation System and included both sociodemographic and clinical aspects as well as standardized questionnaires on psychological distress, spirituality, and the perception of social support. RESULTS: The prevalence of psychological distress was significantly higher in individuals with MHD (36.6% vs. 12.3%) and remained unchanged among both groups over time. At baseline, the perception of social support was significantly higher in healthy control subjects, whereas the two groups were comparable in regards of the subjective relevance of faith. Reference subjects indicated significantly higher spiritual well-being in terms of the sense of meaning in life and peacefulness, which mediated in large part the between-group difference of psychological distress at follow-up. Notably, both faith and the perception of social support did not prove to be relevant in this context. CONCLUSIONS: These findings point to a consistently high prevalence of psychological distress among people suffering from MHD and underscore the prominent role of meaning in life and peacefulness as a protective factor in times of crisis. Therapeutic strategies that specifically target spirituality may have a beneficial impact on mental health.

Case report: A severe case of generalized tetanus in a young cat.

A 10-month-old, 3 kg, female spayed Domestic Shorthair cat was presented with a chronic, infected wound at the level of the proximo-lateral left pelvic limb. General physical examination revealed a weight-bearing lameness of the left pelvic limb, which was moderately and circumferentially swollen and edematous proximal to the tarsal joint. On the lateral aspect of the proximal thigh, there was a chronic wound of 1 cm in diameter and an additional exudative skin lesion was present throughout the whole length of the caudo-lateral thigh. Complete blood count and serum biochemistry profile revealed mild anemia, increased serum amyloid A, hyponatraemia, hypochloraemia, hypocalcaemia, hyperkalaemia, hypermagnesaemia, hyperglycaemia, increased creatine kinase, and increased liver parameters. Surgical exploration of the wound was performed, and necrotizing fasciitis was suspected. The affected limb was amputated and swabs for bacterial culture were taken from both the skin lesions and surgical site before wound closure. One day after surgery, mild muscular contractions on the forehead and an increased muscle tone of the right pelvic limb were evident. One day later, the cat developed a generalized increase in extensor tone, with intermittent opisthotonos, resulting in lateral recumbency. Based on these clinical signs, a diagnosis of generalized tetanus was made and treatment with midazolam, methocarbamol, and metronidazole was started. Despite an improvement of all blood parameters, the cat progressively deteriorated and 4 days after surgery, it developed episodes of tetanic convulsions, associated with hyperthermia and ventricular arrhythmias. Despite intensive care and medical management, the cat died following a cardio-respiratory arrest 3 days later. This case report describes a rare case of severe generalized tetanus in a young cat.

Assessment of the human response to acute mental stress-An overview and a multimodal study.

Numerous vital signs are reported in association with stress response assessment, but their application varies widely. This work provides an overview over methods for stress induction and strain assessment, and presents a multimodal experimental study to identify the most important vital signs for effective assessment of the response to acute mental stress. We induced acute mental stress in 65 healthy participants with the Mannheim Multicomponent Stress Test and acquired self-assessment measures (Likert scale, Self-Assessment Manikin), salivary α-amylase and cortisol concentrations as well as 60 vital signs from biosignals, such as heart rate variability parameters, QT variability parameters, skin conductance level, and breath rate. By means of statistical testing and a self-optimizing logistic regression, we identified the most important biosignal vital signs. Fifteen biosignal vital signs related to ventricular repolarization variability, blood pressure, skin conductance, and respiration showed significant results. The logistic regression converged with QT variability index, left ventricular work index, earlobe pulse arrival time, skin conductance level, rise time and number of skin conductance responses, breath rate, and breath rate variability (F1 = 0.82). Self-assessment measures indicated successful stress induction. α-amylase and cortisol showed effect sizes of -0.78 and 0.55, respectively. In summary, the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system were successfully activated. Our findings facilitate a coherent and integrative understanding of the assessment of the stress response and help to align applications and future research concerning acute mental stress.