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Cross-education: motor unit adaptations mediate the strength increase in non-trained muscles following 8 weeks of unilateral resistance training
Get PDFIntroduction Early increases in muscle strength following unilateral resistance training are typically accompanied by strength gains in the contralateral untrained muscles, a phenomenon known as cross-education. However, the specific motor unit adaptations responsible for this gain transfer remain poorly understood. To address this gap, we recorded myoelectrical activity from the biceps brachii using high-density electromyography. Methods Nine participants performed 8-week unilateral resistance training and were compared to nine control individuals who did no intervention. Discharge characteristics of longitudinally tracked motor units were assessed during maximal voluntary contractions and isometric ramp contractions at 35% and 70% of the maximal voluntary force (MVF) at baseline (T0), 4 weeks (T1), and 8 weeks (T2) post-intervention. Results MVF increased by 7% in untrained muscles at T1 and 10% at T2 (p < 0.05). These gains were accompanied by significant decreases in motor unit recruitment thresholds (p < 0.01) and higher net discharge rate (i.e., gain in discharge rate from recruitment to peak) following intervention (p < 0.05). Trained muscles presented greater MVF (+11%, T1; +19%, T2) with similar motor unit adaptations, including a lower recruitment threshold (p < 0.01) and a higher net discharge rate (p < 0.01). Discussion Our findings indicate that higher strength in untrained muscles is associated with a higher net discharge rate, implying a greater spinal motoneuron output to muscles. The present results underscore the role of motor unit adaptations in the transfer of strength gains to non-trained muscles, offering novel insights into the neural mechanisms underlying cross-education
Development of a self-assessment tool to address the functioning of community-dwelling older adults in general practice: a validation study of the EFA23 questionnaire
Get PDFBackground Multimorbidity is increasingly prevalent among ageing patients, leading to reduced daily functioning. To address the challenges posed by multimorbidity in older adults, a person- and context-centred approach is needed. This study aimed to develop a questionnaire as a self-assessment tool for older adults focusing on functioning in general practice based on the International Classification of Functioning, Disability and Health (ICF). Methods A mixed-methods approach was employed in the development and validation of the German EFA23 ( Erfassung Funktionaler Gesundheit im Alter – 23 Fragen; Assessing Functional Health in Old Age – 23 questions) questionnaire. Based on an ICF subset developed in a preparatory phase and consensus study, questionnaire items were formulated and tested in a qualitative pretest, followed by a validation study. A workshop with general practitioners (GPs) was held to develop a supplementary manual for GPs on how to interpret the questionnaire results and discuss them with the patients. Results A total of 69 items were developed and tested in the qualitative pretest with 15 respondents, resulting in 37 items for the validation study. The validation study, involving 237 older adults, showed the presence of one significant principal component. It demonstrated good internal consistency (Cronbach’s alpha = 0.967) and construct validity, showing positive correlations with established assessment tools. Descriptive statistics showed differences between the means of self-assessment by patients and an external GP assessment. The final EFA23 questionnaire consists of 23 items assessing limitations in functioning. Conclusions The EFA23 questionnaire can be used as a valid self-assessment instrument to measure functioning in older adults, supporting a person- and context-centred approach in general practice.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Digital analysis of the human maxilla to enable semistandardized template tool reconstructions with free fibula transplants
Get PDFObjectives This study analyzed the human maxilla to support the development of mean-value-based cutting guide systems for maxillary reconstruction, bridging the gap between freehand techniques and virtual surgical planning (VSP). Materials and methods This retrospective cohort study used routine CT scans. DICOM data enabled 3D modelling and the maxilla was divided into four regions: paranasal (R1), facial maxillary sinus wall (R2), zygomatic bone (R3) and alveolar process (R4). Surface comparisons were made with a reference skull. Statistical analyses assessed anatomical variations, focusing on mean distance (Dmean), area of valid distance (AVD), integrated distance (ID) and integrated absolute distance (IAD). The study addressed hemimaxillectomy defects for two-segmental reconstructions using seven defined bilateral points to determine segmental distances and angles. Results Data from 50 patients showed R2 as the most homogeneous and R4 as the most heterogeneous region. Significant age and gender differences were found in R3 and R4, with younger patients and females having more outliers. Cluster analysis indicated that males had R1 and R3 positioned anterior to the reference skull. The mean angle for segmental reconstruction was 131.24° ± 1.29°, with anterior segment length of 30.71 ± 0.57 mm and posterior length of 28.15 ± 0.86 mm. Conclusions Anatomical analysis supported the development of semistandardized segmental resection approaches. Although gender and anatomical differences were noted, they did not significantly impact the feasibility of mean-value-based cutting-guide systems. Clinical relevance This study provides essential anatomical data for creating cost-effective and efficient reconstruction options for maxillary defects, potentially improving surgical outcomes and expanding reconstructive possibilities beyond current techniques.Open Access funding enabled and organized by Projekt DEAL.Deutsche Gesellschaft für Zahn-, Mund- und Kieferheilkunde (DGZMK)Universitätsklinikum Erlangen (8546
Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression
Get PDFBackground Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer’s disease (AD) pathology and cognitive decline. Methods One hundred and fifty-one participants with normal cognition ( n = 76) or mild cognitive impairment ( n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. Results None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p = .034 and β = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081). Conclusion Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschunghttp://dx.doi.org/10.13039/501100001711Synapsis Foundation - Dementia Research Switzerlan
A Novel Tax-Responsive Reporter T-Cell Line to Analyze Infection of HTLV-1
Get PDFHuman T-cell leukemia virus type 1 (HTLV-1) infects CD4 + T-cells through close cell–cell contacts. The viral Tax-1 (Tax) protein regulates transcription by transactivating the HTLV-1 U3R promoter in the 5′ long terminal repeat of the integrated provirus. Here, we generated a clonal Tax-responsive T-cell line to track HTLV-1 infection at the single-cell level using flow cytometry, bypassing intracellular viral protein staining. Jurkat T-cells stably transduced with the SMPU vector carrying green fluorescent protein (GFP) under control of 18 × 21 bp Tax-responsive element repeats of the U3R were evaluated. Among 40 clones analyzed for Tax responsiveness, the top two were characterized. Upon overexpression of Tax, over 40% of the cells showed GFP positivity, and approximately 90% of the Tax-positive cells were GFP-positive, indicating efficient reporter activity. However, with CREB-deficient Tax mutant M47, both total GFP-positive cell counts and those within the Tax-positive group significantly decreased. Co-culture with chronically HTLV-1-infected MT-2 or C91-PL cells led to an average of 0.9% or 2.4% GFP-positive cells, respectively, confirming the suitability to monitor HTLV-1 transmission and that HTLV-1 infection is very low. Thus, the novel Tax-responsive reporter T-cell line is a suitable tool to monitor infection of HTLV-1 on the single-cell level.This research was funded by the Federal Ministry of Education and Research (BMBF) of the Federal Republic of Germany, project “Milk-TV”, grant number 01KI2023. Moreover, AKTK was supported by the Deutsche Forschungsgemeinschaft (DFG), GRK2504, project A2, project number 401821119, and by the DFG grant TH2166/1-2. S.H. was supported by the “Bavarian Equal Opportunities Sponsorship—Realisierung von Chancengleichheit von Frauen in Forschung und Lehre (FFL)—Realization Equal Opportunities for Women in Research and Teaching”.Federal Ministry of Education and Research (BMBF) of the Federal Republic of GermanyDeutsche Forschungsgemeinschaft (DFG)“Bavarian Equal Opportunities Sponsorship—Realisierung von Chancengleichheit von Frauen in Forschung und Lehre (FFL)—Realization Equal Opportunities for Women in Research and Teaching
First epileptic seizure and epilepsies in adulthood
No full textZusammenfassung In der neuen S2k-Leitlinie „Erster epileptischer Anfall und Epilepsien im Erwachsenenalter“ werden Empfehlungen zu klinisch relevanten Fragestellungen in fünf großen Themenblöcken gegeben: Management erster epileptischer Anfall, Pharmakotherapie, Epilepsiechirurgie, komplementäre und supportive Therapieverfahren und psychosoziale Aspekte. Beim Thema Management erster epileptischer Anfall werden in der Leitlinie zunächst Empfehlungen zur Unterscheidung der beiden maßgeblichen Differenzialdiagnosen, Synkope und psychogener nicht-epileptischer Anfall, gegeben. Zudem wird der Stellenwert von Zusatzuntersuchungen wie EEG, MRT und Liquor inklusive Autoantikörpern zur syndromalen und ätiologischen Zuordnung diskutiert. Weiterhin werden Empfehlungen zu neuropsychologischen und psychiatrischen Screeningtests ausgesprochen. Bei der Pharmakotherapie liegt der Schwerpunkt der Empfehlungen auf der anfallssuppressiven Monotherapie bei fokalen, genetischen generalisierten und unklassifizierten Epilepsien; Patientengruppen mit besonderen Herausforderungen wie Ältere, Frauen im gebärfähigen Alter und Menschen mit Intelligenzminderung werden hervorgehoben. Weitere Themen sind die Indikationen zur Bestimmung der Serumkonzentration von Anfallssuppressiva und die möglichen Risiken eines Herstellerwechsels. In dem Themenblock Epilepsiechirurgie werden die Indikationen zur prächirurgischen Diagnostik und zu den vielfältigen Therapieverfahren wie Resektion, Laserablation und Neurostimulation dargestellt. Einen großen Stellenwert nehmen die Empfehlungen zur postoperativen Versorgung der Patient:innen inklusive Rehabilitation und psychosozialer Beratung ein. Beim Thema komplementäre und supportive Therapieverfahren werden Empfehlungen zur Diagnostik und Therapie von die Epilepsien häufig begleitenden Angststörungen, Depressionen und Psychosen gegeben. Ein weiterer Schwerpunkt ist die Behandlung von psychogenen nicht-epileptischen Anfällen als neuropsychiatrische Differenzialdiagnose oder Begleiterkrankung von epileptischen Anfällen. Weiterhin werden Empfehlungen zum Stellenwert der ketogenen Diät sowie zu Akupunktur, Homöopathie und weiteren komplementären Behandlungsansätzen gegeben. Die Empfehlungen zu psychosozialen Aspekten umfassen alltagsrelevante Themen wie Kraftfahreignung, Ausbildung und Beruf, medizinische Rehabilitation, Sport, Transition, Selbsthilfe, Schulungen von Patient:innen und Angehörigen, Adhärenz, Aufklärung zu SUDEP (Sudden Unexpected Death in Epilepsy).The new S2k guideline “First epileptic seizure and epilepsies in adulthood” provides recommendations on clinically relevant issues in five major topics: management of first epileptic seizures, pharmacotherapy, epilepsy surgery, complementary and supportive treatment, and psychosocial aspects. For the topic management of first epileptic seizures , the guideline provides recommendations on identifying the two major differential diagnoses, syncope and psychogenic non-epileptic seizure. The importance of additional examinations such as EEG, MRI and cerebrospinal fluid for syndromic classification and etiological allocation is discussed. Recommendations on neuropsychological and psychiatric screening tests are also given. The topic pharmacotherapy issues recommendations on antiseizure medication in monotherapy for focal, generalized and unclassified epilepsies; patient groups with special challenges such as the aged, women of childbearing potential and people with mental retardation are emphasized. Further issues are indications for measuring serum concentrations of antiseizure medication and possible risks of switching manufacturers. In the topic epilepsy surgery , indications for presurgical assessment and the multiple therapeutic approaches, such as resection, laser ablation, and neurostimulation are presented. Recommendations on postoperative management of patients, including rehabilitation and psychosocial counselling, are given. The topic complementary and supportive therapeutic approaches comprises recommendations on the diagnostics and treatment of common psychiatric comorbidities of epilepsy, such as anxiety disorder, depression and psychosis. Another important issue is the management of psychogenic non-epileptic seizures as a neuropsychiatric differential diagnosis or comorbidity of epileptic seizures. Furthermore, recommendations on the potential role of ketogenic diet and on acupuncture, homeopathy and other complementary approaches are made. The recommendations on psychosocial aspects comprise practical issues, such as fitness to drive a car, training and occupation, medical rehabilitation, sport, transition, patients’ self-help, education programs for patients and next of kin, adherence, advise on SUDEP.Open Access funding enabled and organized by Projekt DEAL.Charité - Universitätsmedizin Berlin (3093
Investigation of the influence of the support structure on violin components in experimental modal analysis
Get PDFVarious support structures are utilized in the investigation of the vibration characteristics of violins. Common mountings include rigid ropes, rubber ropes, and foam blocks arranged in different configurations. The impact of the support structure on the outcomes of experimental modal analysis on musical instruments has yet to be explored. This study aims to determine the most suitable support structure for experimental modal analysis of violin components by comparing results from various experimental modal analyses conducted on a violin top and back using different mounting configurations. Results were evaluated using criteria such as vibration characteristics, rigid body frequencies, number of modes, modal damping, amplitude, and mode shapes. In summary, the support structures using rubber ropes and foam blocks yielded the best results. The recommended configurations for rubber ropes are X‐shaped or orthogonal to the longitudinal axis of the violin plates. When using foam blocks, it is essential to select foam with appropriate material parameters, as differences in density and stiffness resulted in significant variations of the measurement results
The impact of the tumor microenvironment on the survival of penile cancer patients
Get PDFPeCa is a rare entity with rising incidence rates due to increased infections with human papillomaviruses (HPV). The distinct subtypes of PeCa with an individual pathogenesis demand biomarkers for a precise patient risk assessment regarding disease progression and therapeutic susceptibility. We recently identified promising candidates associated with an HPV-instructed tumor microenvironment (TME) using HPV-positive PeCa cell lines and tissue microarrays (TMA). The capacity of HPV + p63 + PeCa cells to release neutrophil-attracting CXCL-8 provided a molecular link explaining the infiltration of CD15 + myeloid cells in PeCa specimens. The candidate biomarkers HPV, p63, CD15, DKK1, and CD147 linked a tumor-promoting TME with a higher TNM classification reflecting more aggressive and metastasizing cancers. Based on immune-reactive scores (IRS) from TMA staining for these biomarkers, we calculated correlations and conducted association analyses to assess the degree of relationship between all biomarkers. We then conducted Kaplan–Meier survival estimates and Cox regression analyses to delineate the impact on PeCa patient survival. There is a notable predictive potential regarding the survival of patients with biomarker profiles beyond the potency of the individual biomarker. From all candidate biomarkers and biomarker profiles, the combination of CD147 and infiltrating CD15 + cells linked to an active HPV-driven transformation displayed cancer-immune dynamics with dismal prognosis for patients. After deciphering relevant interdependencies, the HPV + CD147 + CD15 + status was the most potent profile predicting metastasis-free survival of PeCa patients. The results of this report underscore the need for analysis of the TME and the development of multi-parameter composite scores that reflect fundamental cancer-immune relationships to tailor therapeutic interventions based on actual cancer immune dynamics.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Universität des Saarlandeshttp://dx.doi.org/10.13039/501100005690Leibniz-Institut für Neue Materialien gGmbH (INM) (3452
Video double-lumen tube for one lung ventilation: implementation and experience in 343 cases of routine clinical use during the first 20 months of the SARS-CoV-2 pandemic
Get PDFBackground Double-lumen tubes (DLTs) are the preferred device for lung isolation. Conventional DLTs (cDLT) need a bronchoscopic position control. Visualisation of correct DLT positioning could be facilitated by the use of a video double-lumen tube (vDLT). During the SARS-CoV-2-pandemic, avoiding aerosol-generation was suggesting using this device. In a large retrospective series, we report both general and pandemic related experiences with the device. Methods All anesthesia records from patients aged 18 years or older undergoing surgery from April 1st, 2020 to December 31st, 2021 in the department of thoracic surgery requiring intraoperative lung isolation were analyzed retrospectively. Results During the investigation period 343 left-sided vDLTs (77.4%) and 100 left-sided cDLTs (22.6%) were used for one lung ventilation. In the vDLT group bronchoscopy could be reduced by 85.4% related to the cDLT group. Additional bronchoscopy to reach or maintain correct position was needed in 11% of the cases. Other bronchoscopy indications occured in 3.6% of the cases. With cDLT, in 1% bronchoscopy for other indications than conforming position was observed. Conclusions The Ambu® VivaSight™ vDLT is an efficient, easy-to-use and safe airway device for the generation of one lung ventilation in patients undergoing thoracic surgery. The vDLT implementation was achieved easily with full interchangeability to the left-sided cDLT. Using the vDLT can reduce the need for aerosol-generating bronchoscopic interventions by 85.4%. Continuous video view to the carina enabling position monitoring of the DLT without need for bronchoscopy might be beneficial for both employee’s and patient’s safety.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Combination of Fentanyl with an Antidote in Transdermal Delivery Systems as an Anti-Abuse-Strategy
Get PDFTransdermal delivery systems (TDS) containing fentanyl are widely used for the treatment of strong pain due to many advantages like low fluctuations in plasma concentration of the API for a longer period of time and the avoidance of plasma spikes. However, opioid analgesics like fentanyl have a certain potential for abuse with possibly fatal consequences. Opioid drug products are well known for their abuse potential. Therefore, their prescription is closely monitored and there is a special interest in the development of abuse-deterrent formulations that lower the ability of abusive application of an opioid drug product. The current ADF on the market are solid or liquid formulations, but no abuse-deterrent TDS is available. Therefore, the focus of this work was to develop an abuse-deterrent fentanyl transdermal patch combining the opioid fentanyl with the antidote naloxone HCl. The goal was that, comparably to the marketed liquid formulation Valoron N® or the solid ADF Embeda®, the antidote should not have any clinical effect when the formulation is used at the intended therapeutical application but it should be released in case of misuse and antagonise the effects of the opioid