Effects on Bone and Muscle upon Treadmill Interval Training in Hypogonadal Male Rats

Testosterone deficiency in males is linked to various pathological conditions, including muscle and bone loss. This study evaluated the potential of different training modalities to counteract these losses in hypogonadal male rats. A total of 54 male Wistar rats underwent either castration (ORX, n = 18) or sham castration (n = 18), with 18 castrated rats engaging in uphill, level, or downhill interval treadmill training. Analyses were conducted at 4, 8, and 12 weeks postsurgery. Muscle force of the soleus muscle, muscle tissue samples, and bone characteristics were analyzed. No significant differences were observed in cortical bone characteristics. Castrated rats experienced decreased trabecular bone mineral density compared to sham-operated rats. However, 12 weeks of training increased trabecular bone mineral density, with no significant differences among groups. Muscle force measurements revealed decreased tetanic force in castrated rats at week 12, while uphill and downhill interval training restored force to sham group levels and led to muscle hypertrophy compared to ORX animals. Linear regression analyses showed a positive correlation between bone biomechanical characteristics and muscle force. The findings suggest that running exercise can prevent bone loss in osteoporosis, with similar bone restoration effects observed across different training modalities

Prolonged treadmill training is not able to prevent ovariectomy-induced bone loss

Introduction: Exercise is widely recognized as prophylaxis for osteoporosis. However, exactly which type of exercise is best to prevent loss of bone mass remains undefined. To find an appropriate form of treadmill exercise that would ameliorate postmenopausal loss of cortical and trabecular structures, we compared various training regimen in ovariectomized (OVX) C57BL/6J mice.Methods: Common to all regimen were training durations of 14 weeks including five 30 min-sessions per week. Two groups—one sham operated, one OVX—served as controls that did not perform any training. Three OVX groups ran at constant speed, either without any incline or at 20° in- and 20° decline, respectively. An additional OVX group ran an interval training, an alternation between intensive tempo sections and so-called slower regeneration phases. Femoral and humeral bone structures were assessed via micro-computed tomography (μCT), biomechanical stability of the femora via 3-point bending test, muscle volumes of the posterior extremities via magnetic resonance imaging (MRI), and bone metabolic parameters via ELISA on peripheral blood.Result: OVX resulted in loss of bone mass and stability and a transient rise in the N-terminal collagen type I pro-peptide (PINP). Training resulted in increased muscle volumes of the heart and the lower extremities as well as increased running velocities. However, none of the exercise programs was able to prevent ovariectomyinduced loss of bone mass.Discussion: These data therefore suggest that axial loading and tensile strain do not suffice as prophylaxis for postmenopausal osteoporosis yet may need to be complemented by low dose pharmaceutics or dietary supplements

Cold Atmospheric Pressure Plasma in Wound Healing and Cancer Treatment

Plasma medicine is gaining increasing attention and is moving from basic research into clinical practice. While areas of application are diverse, much research has been conducted assessing the use of cold atmospheric pressure plasma (CAP) in wound healing and cancer treatment—two applications with entirely different goals. In wound healing, a tissue-stimulating effect is intended, whereas cancer therapy aims at killing malignant cells. In this review, we provide an overview of the latest clinical and some preclinical research on the efficacy of CAP in wound healing and cancer therapy. Furthermore, we discuss the current understanding of molecular signaling mechanisms triggered by CAP that grant CAP its antiseptic and tissue regenerating or anti-proliferative and cell death-inducing properties. For the efficacy of CAP in wound healing, already substantial evidence from clinical studies is available, while evidence for therapeutic effects of CAP in oncology is mainly from in vitro and in vivo animal studies. Efforts to elucidate the mode of action of CAP suggest that different components, such as ultraviolet (UV) radiation, electromagnetic fields, and reactive species, may act synergistically, with reactive species being regarded as the major effector by modulating complex and concentration-dependent redox signaling pathways

Higher SARS-CoV-2 Spike Binding Antibody Levels and Neutralization Capacity 6 Months after Heterologous Vaccination with AZD1222 and BNT162b2

Within a year after the emergence of SARS-CoV-2, several vaccines had been developed, clinically evaluated, proven to be efficacious in preventing symptomatic disease, and licensed for global use. The remaining questions about the vaccines concern the duration of protection offered by vaccination and its efficacy against variants of concern. Therefore, we set out to analyze the humoral and cellular immune responses 6 months into homologous and heterologous prime-boost vaccinations. We recruited 190 health care workers and measured their anti-spike IgG levels, their neutralizing capacities against the Wuhan-Hu-1 strain and the Delta variant using a surrogate viral neutralization test, and their IFNγ-responses towards SARS-CoV-2-derived spike peptides. We here show that IFNγ secretion in response to peptide stimulation was significantly enhanced in all three vaccination groups and comparable in magnitude. In contrast, the heterologous prime-boost regimen using AZD1222 and BNT162b2 yielded the highest anti-spike IgG levels, which were 3–4.5 times more than the levels resulting from homologous AZD1222 and BNT162b2 vaccination, respectively. Likewise, the neutralizing capacity against both the wild type as well as the Delta receptor binding domains was significantly higher following the heterologous prime-boost regimen. In conclusion, our results suggest that mixing different SARS-CoV-2 vaccines might lead to more efficacious and longer-lasting humoral protection against breakthrough infections

Die differentielle Expression von MHC II-Genen als Mechanismus bei der Entstehung von Autoimmunerkrankungen

Protektive MHC II Allele sind sowohl für den Menschen als auch für die Maus beschrieben worden und verhindern die Entstehung von Autoimmunerkrankungen. Hier untersuche ich die differentielle Expression von MHC II Allelen auf den unterschiedlichen Antigen-praesentierenden Zellen als Wirkmechanismus, der das Typ 1-Typ 2 Gleichgewicht der T-Helferzellen beeinflusst. Ich konnte zeigen, dass die als protektiv geltenden murinen I-Ab und I-Ek Molekuele auf fast allen Knochenmark-Makrophagen fuer 5 - 8 Tage stark exprimiert werden und dass die Expression dann langsam abnimmt. Im Gegensatz dazu fanden wir eine etwa 100-fach schwaechere Expression des mit der Kollagen-induzierten Arthritis (CIA) assoziierten I-Aq. Diese Expression war von nur kurzer Dauer und nahm rasch ab. Eine aehnlich differentielle Expression konnten wir weder auf B- noch auf dendritischen Zellen (DZ) nachweisen. Zusätzlich konnte in in vitro Restimulationsexperimenten gezeigt werden, dass Makrophagen durch diese differentielle Expression die T-Zell-Zytokinantwort massgeblich beeinflussen. Unsere Ergebnisse deuten an, dass Makrophagen eines protektiven Haplotyps MHC II Molekuele in hoher Zahl exprimieren und damit bevorzugt Typ 1 Antworten hervorrufen, wohingegen eine niedrige MHC II Expression Typ 2 Antworten beguenstigt. Wir schliessen daraus, dass das Ausmass der MHC II Expression das Signal, welches von den T-Zellen zu den Makrophagen zurückgesendet wird, steuert und damit die Aktivitaet der Makrophagen reguliert. Dieser durch polymorphe, jedoch nicht-kodierende MHC II-Gensegmente hervorgerufene Effekt koennte bei der Empfaenglichkeit fuer Autoimmunerkrankungen sowohl beim Menschen als auch bei der Maus eine Rolle spielen. Tatsaechlich konnten wir auch auf menschlichen Monozyten und B-Zellen eine differentielle Expression von HLA II Genen nachweisen und sie scheint sich hier auf die nur gering-polymorphen DRB4 Gene, die sowohl mit dem Rheumatoide Arthritis (RA) assoziierten DR4 als auch mit dem neutralen DR7 koexprimiert werden, zu beschraenken. In meinem letzten Teil ziele ich darauf ab, das den Verlauf der RA und der CIA begleitende Typ 1 Übergewicht in ein Gleichgewicht mit Typ 2 zu revertieren. Dazu wurde ein Mausmodell etabliert, bei dem bereits polarisierte Typ 2 Th-Effektorzellen als Manipulatoren der für die Entstehung der CIA verantwortlichen, Kollagen-spezifischen Typ 1 Zellen eingesetzt wurden. Tatsaechlich konnte die CIA dann am effektivsten verhindert werden, wenn beide T-Zellpopulationen, die Manipulierer und die Kollagen-spezifischen, im selben Zellcluster aktiviert wurden. Diese Aktivierung im selben Zellcluster konnte dadurch erreicht werden, dass DZ gleichzeitig Kollagen und das fuer die Manipulierer spezifische Epitop praesentieren.Protective/suppressive MHC class II alleles have been identified in man and mouse where they exert a disease-protective and immunosuppressive effect. As a mode of action we here investigate differential expression of MHC class II genes in different types of antigen-presenting cells impacting on the Type 1-Type 2 balance. We found that the murine I-Ab and I-Ek molecules, both well characterized as protective/suppressive, are expressed at a high level on almost all bone marrow derived macrophages for five to eight days after which expression slowly declines. In contrast, the collagen-induced arthritis (CIA) associated I-Aq-expression is lower, peaks over a shorter period and declines more rapidly. No differential expression could be detected on B cells or dendritic cells (DC). In addition, the differential MHC class II expression found on macrophages skews the cytokine response of T cells as shown by an in vitro restimulation assay. The results indicate that macrophages of the protective/ suppressive haplotypes express MHC class II molecules at a high level and exert Type 1 bias whereas low level expression favors a Type 2 response. We suggest that the extent of expression of the class II gene gates the back-signal from T cells and in this way controls the activity of macrophages. This effect mediated by polymorphic non-exon segments of MHC class II genes may play a role in determining disease susceptibility in mouse and man. Indeed, we also found differential expression of HLA II genes on human antigen presenting cells. However, in humans, differential expression affects both, B cells and monocytes and seems to be restricted to the non-polymorphic DRB4 gene coexpressed with the rheumatoid arthritis (RA) associated DR4 and the neutral DR7. We finally aimed at reverting the Type 1 bias characteristic of RA and CIA. A murine system was developed where polarized Type 2 cells were used to manipulate collagen II-specific type 1 T cells responsible for the development of collagen induced arthritis. The polarized inducer cells indeed exerted their maximum effect when the two T-cell populations were activated within the same cluster, implemented by allowing a single DC to present both their epitopes

Learning strategies and their correlation with academic success in biology and physiology examinations during the preclinical years of medical school.

BackgroundEfficient learning is essential for successful completion of the medical degree and students use a variety of strategies to cope with university requirements. However, strategies that lead to academic success have hardly been explored. We therefore evaluated the individual learning approaches used by a cohort of medical students in their first and second preclinical years and analyzed possible correlations with examination scores.Methods107 students participated in our longitudinal survey on cognitive, meta-cognitive and resource-oriented learning strategies using the LIST-questionnaire (Lernstrategien im Studium). The students were surveyed twice while in their first and second year of medical school, respectively and academic performances were assessed as scores obtained in two examinations written shortly after the LIST surveys. Statistical evaluations included comparisons and cluster analyses.ResultsWe here identified four different patterns of learning strategy combinations, describing the relaxed, diligent, hard-working, and sociable learners. About half of the students stayed true to their initially registered pattern of learning strategy combinations while 53 students underwent a change between the first and second surveys. Changes were predominantly made between the relaxed and the sociable and between the diligent and the hard-working learners, respectively. Examination results suggested that the diligent and hard-working learners were academically more successful than the relaxed and sociable ones.ConclusionEarly habits of sociable learning were quickly abandoned however, not in favor of more successful patterns. It is therefore essential to develop interventions on learning skills that have a lasting impact on the pattern of the students´ learning strategy combinations

Degenerative Joint Damage Is Not a Risk Factor for Streptococcal Sepsis and Septic Arthritis in Mice

Septic arthritis (SA) is an aggressive joint disorder causing invalidity and mortality. Although epidemiological studies suggest osteoarthritis (OA) as a risk factor for SA, experimental insights into the relatedness of both diseases are lacking. We therefore sought to investigate whether pre-existing OA indeed promotes SA frequency or severity. We used STR/ort mice that spontaneously develop OA and, in addition, induced OA via anterior cruciate ligament transection (ACLT) in C57BL/6J mice. Mice were infected with Group A Streptococcus (GAS) and then were monitored for clinical signs of sepsis and SA. Sepsis was confirmed via elevated inflammatory cytokines in plasma, while bone morphology was assessed by micro-computed tomography. Cartilage integrity was evaluated histologically. Mice with spontaneous OA developed life-threatening SA, with GAS only moderately affecting the femoral bone structure. Surgically induced OA neither impacted on SA incidence nor on mortality when compared to infected mice without the preceding joint disease. Furthermore, only insignificant differences in bone morphology were detected between both groups. Our data indicate that degenerative joint damage due to ACLT, by itself, does not predispose mice to SA. Hence, we propose that other factors such as prosthetic joint replacement or high age, which frequently coincide with OA, pose a risk for SA development

Testing anxiety in undergraduate medical students and its correlation with different learning approaches.

ObjectivesUndergraduate medical students experience a considerable amount of stress and anxiety due to frequent exams. The goal of the present study was to examine the development of exam related anxiety and to test for a correlation between anxiety and learning approaches.MethodsA whole class of 212 medical students was invited to participate in the study. During their first term, trait anxiety and learning approaches were assessed by use of the state-trait-anxiety inventory (STAI-T) and the approaches-and-study-skills-inventory-for-students (ASSIST), respectively. Acute state anxiety was assessed twice in the course of the second term. To that extent, the STAI-S in combination with measuring salivary cortisol were employed immediately before two oral anatomy exams.ResultsOur most important results were that a surface learning approach correlated significantly with anxiety as a trait and that students with a predominantly strategic approach to learning were the least anxious yet academically most successful.ConclusionAs surface learners are at risk of being academically less successful and because anxiety is a prerequisite for burn-out, we suggest that medical faculties place particular emphasis on conveying strategies for both, coping with stress and successful learning

Semantic fluency including task switching predicts academic success in medical school.

ObjectivesThe future state treaty on the admission of students to German medical schools calls for a variety of selection criteria among which at least two are required to be independent of school leaving grades. Against this background, the present study investigated achievement motivation and executive functions as predictors of academic success in medical school.Material and methodsSecond year medical students were assessed for executive functioning by using the Tower of London Test (ToL), a German version of the Controlled Oral Word Association Test (COWAT), the Trail Making Test (TMT-A) and for motivation by using the Achievement Motivation Inventory (AMI). Academic success was evaluated twofold, i) whether the first state exam (M1) was passed at the earliest possible, after completion of the second year and ii) via the grades obtained.Results81 out of 226 students enrolled participated in our study. Passing the M1 was best explained by semantic fluency including task switching. Moreover, academically successful students achieved significantly higher levels in the AMI-facets "compensatory effort" and "engagement". All students scored above average in the TMT-A and average in the ToL.ConclusionAlternating semantic fluency-requiring simultaneously inhibition, updating and task shifting-turned out highly predictive of academic success in medical school. Moreover, higher levels in "compensatory effort" and "engagement" suggested that both, increased energy expenditure as response to fear of failure and elevated readiness to exert effort also impacted positively on success

Vaccine-Induced T-Cell and Antibody Responses at 12 Months after Full Vaccination Differ with Respect to Omicron Recognition

More than a year after the first vaccines against the novel SARS-CoV-2 were approved, many questions still remain about the long-term protection conferred by each vaccine. How long the effect lasts, how effective it is against variants of concern and whether further vaccinations will confer additional benefits remain part of current and future research. For this purpose, we examined 182 health care employees—some of them with previous SARS-CoV-2 infection—12 months after different primary immunizations. To assess antibody responses, we performed an electrochemiluminescence assay (ECLIA) to determine anti-spike IgGs, followed by a surrogate virus neutralization assay against Wuhan-Hu-1 and B.1.1.529/BA.1 (Omicron). T cell response against wild-type and the Omicron variants of concern were assessed via interferon-gamma ELISpot assays and T-cell surface and intracellular cytokine staining. In summary, our results show that after the third vaccination with an mRNA vaccine, differences in antibody quantity and functionality observed after different primary immunizations were equalized. As for the T cell response, we were able to demonstrate a memory function for CD4+ and CD8+ T cells alike. Importantly, both T and antibody responses against wild-type and omicron differed significantly; however, antibody and T cell responses did not correlate with each other and, thus, may contribute differentially to immunity