Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice.

Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key elements from the ECG waveform (RR-, PR-, ST-, QT-interval, QT corrected, and QRS complex) demonstrate minimal sexual dimorphism. As expected, anesthesia induces a decrease in heart rate and was shown for both inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. In the absence of pharmacological, environmental, or genetic challenges, we did not observe major age-related ECG changes in C57BL/6N-inbred mice as the differences in the reference ranges of 12-week-old compared to 62-week-old mice were negligible. The generalizability of the C57BL/6N substrain reference ranges was demonstrated by comparison with ECG data from a wide range of non-IMPC studies. The close overlap in data from a wide range of mouse strains suggests that the C57BL/6N-based reference ranges can be used as a robust and comprehensive indicator of normality. We report a unique ECG reference resource of fundamental importance for any experimental study of cardiac function in mice.

Does combined individualized orofacial manual therapy, pain neuroscience education, and brain training change orofacial pain, chronic face dysfunction, (facial) body perception and pain? An observational mixed methods case series study.

BACKGROUND: Orofacial pain is a complex disabling condition. Multimodal physical therapy intervention may be helpful, yet studies of such approaches are not available and are the basis of this study. OBJECTIVE: To identify whether combined orofacial manual therapy, pain neuroscience education, graded motor imagery, and face emotional expression training has an impact on orofacial pain and associated features. DESIGN: Mixed-methods case series report. METHODS: Eight subjects (five females) with predominant chronic unilateral face pain (mean duration 7.3 years) were given six individualized treatment sessions and a home program. The primary outcome was orofacial pain, while secondary outcomes were depression, quality of life, alexithymia, 2-point discrimination (TPD), laterality and emotional recognition, as well as qualitative analysis were evaluated post intervention. RESULTS: Following the intervention orofacial pain intensity significantly reduced (p = 0.03) from 3.0 (0.53) to 2.2 (1.75) on the Graded Chronic Pain Status questionnaire. As well, secondary outcome measures depression, alexithymia, TPD, and quality of life also significantly improved. Changes were not significant in aspects of facial perception. Qualitative analysis of perception of therapy is discussed. CONCLUSION: Multimodal therapy had a positive outcome in terms of improvement in unilateral persistent facial pain, depression score, facial body perception and quality of life, and pain in people with chronic unilateral facial pain. Based on the qualitative analysis of their perception of the therapy, multimodal therapy had beneficial effects through increased motivation and joy to exercise.

Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.

[Profile of an alternative general practice]. / Profil einer alternativen Allgemeinpraxis.

Comparing cases' profiles of a five years frequency recorded by the same doctor in a "normal" small rural general practice near Vienna with the profiles of frequency in his following Tyrolean small rural private practice during 4 years, where he preferably had applied alternative methods, showed very similar rankings of his results of consultations. Never before case-statistics of such material had been published.