Publications by authors named "Michael Schneider"

591 Publications

NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain.

Mol Cell 2021 Oct 6. Epub 2021 Oct 6.

Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address:

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin.
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http://dx.doi.org/10.1016/j.molcel.2021.09.020DOI Listing
October 2021

Evaluation of United States chiropractic professional subgroups: a survey of randomly sampled chiropractors.

BMC Health Serv Res 2021 Oct 5;21(1):1049. Epub 2021 Oct 5.

Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Professional subgroups are common and may play a role in aiding professional maturity or impeding professional legitimization. The chiropractic profession in the United States has a long history of diverse intra-professional subgroups with varying ideologies and practice styles. To our knowledge, large-scale quantification of chiropractic professional subgroups in the United States has not been conducted. The purpose of this study was to quantify and describe the clinical practice beliefs and behaviors associated with United States chiropractic subgroups.

Methods: A 10% random sample of United States licensed chiropractors (n = 8975) was selected from all 50 state regulatory board lists and invited to participate in a survey. The survey consisted of a 7-item questionnaire; 6 items were associated with chiropractic ideological and practice characteristics and 1 item was related to the self-identified role of chiropractic in the healthcare system which was utilized as the dependent variable to identify chiropractic subgroups. Multinomial logistic regression with predictive margins was used to analyze which responses to the 6 ideology and practice characteristic items were predictive of chiropractic subgroups.

Results: A total of 3538 responses were collected (39.4% response rate). Respondents self-identified into three distinct subgroups based on the perceived role of the chiropractic profession in the greater healthcare system: 56.8% were spine/neuromusculoskeletal focused; 22.0% were primary care focused; and 21.2% were vertebral subluxation focused. Patterns of responses to the 6 ideologies and practice characteristic items were substantially different across the three professional subgroups.

Conclusions: Respondents self-identified into one of three distinct intra-professional subgroups. These subgroups can be differentiated along themes related to clinical practice beliefs and behaviors.
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http://dx.doi.org/10.1186/s12913-021-07081-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491397PMC
October 2021

Ventral Striatal-Hippocampus Coupling During Reward Processing as a Stratification Biomarker for Psychotic Disorders.

Biol Psychiatry 2021 Jul 24. Epub 2021 Jul 24.

Systems Neuroscience in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. Electronic address:

Background: Altered ventral striatal (vST) activation to reward expectancy is a well-established intermediate phenotype for psychiatric disorders, specifically schizophrenia (SZ). Preclinical research suggests that striatal alterations are related to a reduced inhibition by the hippocampal formation, but its role in human transdiagnostic reward-network dysfunctions is not well understood.

Methods: We performed functional magnetic resonance imaging during reward processing in 728 individuals including healthy control subjects (n = 396), patients (SZ: n = 46; bipolar disorder: n = 45; major depressive disorder: n = 60), and unaffected first-degree relatives (SZ: n = 46; bipolar disorder: n = 50; major depressive disorder: n = 85). We assessed disorder-specific differences in functional vST-hippocampus coupling and transdiagnostic associations with dimensional measures of positive, negative, and cognitive symptoms. We also probed the genetic underpinning using polygenic risk scores for SZ in a subset of healthy participants (n = 295).

Results: Functional vST-hippocampus coupling was 1) reduced in patients with SZ and bipolar disorder (p < .05, small-volume corrected [SVC]); 2) associated transdiagnostically to dimensional measures of positive (p = .01, SVC) and cognitive (p = .02, SVC), but not negative, (p > .05, SVC) symptoms; and 3) reduced in first-degree relatives of patients with SZ (p = .017, SVC) and linked to the genetic risk for SZ in healthy participants (p = .035).

Conclusions: We provide evidence that reduced vST-hippocampus coupling during reward processing is an endophenotype for SZ linked to positive and cognitive symptoms, supporting current preclinical models of the emergence of psychosis. Moreover, our data indicate that vST-hippocampus coupling is familial and linked to polygenic scores for SZ, supporting the use of this measure as an intermediate phenotype for psychotic disorders.
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http://dx.doi.org/10.1016/j.biopsych.2021.07.016DOI Listing
July 2021

Mental Health Literacy in Zurich: A First Measurement Attempt Using the General HLS-EU-Q47.

Front Public Health 2021 13;9:723900. Epub 2021 Sep 13.

Health Literacy Division, Careum Foundation, Zurich, Switzerland.

Mental health literacy (MHL) promises to be an important factor for public health by enabling people to take responsibility for their own mental health. To date, there is no measurement tool that allows the assessment of a comprehensive understanding of MHL as part of health literacy (HL). Nonetheless, the widely used Health Literacy Survey European Questionnaire 47 (HLS-EU-Q47) includes items assessing at least some MHL-aspects in the context of HL. The present study aimed at investigating how these MHL-aspects are related to HL, health behavior and health outcome and how they differ between sociodemographic groups. Data from the Health Literacy Survey Zurich 2018, collected by an adapted version of the HLS-EU-Q47, served to investigate these relationships. MHL-aspects were related to HL, health behavior and health outcome. Nearly half of all respondents (45%; = 904) showed low MHL levels, particularly those with higher age and higher financial deprivation. Relations of MHL-aspects with HL, health behavior, and health outcome indicate their potential importance for future interventions in public health, addressing mental health and MHL. A specific MHL tool is needed to comprehensively investigate these relations, which could be developed by extending the present measurement approach.
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http://dx.doi.org/10.3389/fpubh.2021.723900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473678PMC
September 2021

Robust Pressure Sensor in SOI Technology with Butterfly Wiring for Airfoil Integration.

Sensors (Basel) 2021 Sep 13;21(18). Epub 2021 Sep 13.

Institute of Microtechnology, TU Braunschweig, 38124 Brunswick, Germany.

Current research in the field of aviation considers actively controlled high-lift structures for future civil airplanes. Therefore, pressure data must be acquired from the airfoil surface without influencing the flow due to sensor application. For experiments in the wind and water tunnel, as well as for the actual application, the requirements for the quality of the airfoil surface are demanding. Consequently, a new class of sensors is required, which can be flush-integrated into the airfoil surface, may be used under wet conditions-even under water-and should withstand the harsh environment of a high-lift scenario. A new miniature silicon on insulator (SOI)-based MEMS pressure sensor, which allows integration into airfoils in a flip-chip configuration, is presented. An internal, highly doped silicon wiring with "butterfly" geometry combined with through glass via (TGV) technology enables a watertight and application-suitable chip-scale-package (CSP). The chips were produced by reliable batch microfabrication including femtosecond laser processes at the wafer-level. Sensor characterization demonstrates a high resolution of 38 mVV bar. The stepless ultra-smooth and electrically passivated sensor surface can be coated with thin surface protection layers to further enhance robustness against harsh environments. Accordingly, protective coatings of amorphous hydrogenated silicon nitride (a-SiN:H) and amorphous hydrogenated silicon carbide (a-SiC:H) were investigated in experiments simulating environments with high-velocity impacting particles. Topographic damage quantification demonstrates the superior robustness of a-SiC:H coatings and validates their applicability to future sensors.
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http://dx.doi.org/10.3390/s21186140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473241PMC
September 2021

Spinal manipulative therapy and cervical artery dissection: A retrospective comparison with spontaneous, traumatic, and iatrogenic etiologies at a single academic medical center.

Clin Neurol Neurosurg 2021 Oct 11;209:106941. Epub 2021 Sep 11.

Department of Neurosurgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. Electronic address:

Objective: Cervical artery dissection (CAD) has been associated with spinal manipulative therapy (SMT). Although uncommonly reported, SMT-associated CADs hold devastating neurological consequences, warranting further exploration. We endeavored to investigate this association through the comparison of all CAD etiologies at a single academic medical center.

Methods: A retrospective chart review was conducted of patients diagnosed with CAD or transferred to our institution for primary management of CAD during the 10-year period from 2010 to 2020 (n = 578). Patients were divided into SMT-associated (within 1 month of presentation), spontaneous, traumatic, and iatrogenic cohorts.

Results: SMT-associated dissections represented 23/578 (4%) of all dissections and 5.9% of vertebral artery dissections specifically. These patients were generally younger than those in the spontaneous (p = .004) and iatrogenic groups (p < .001), and more often non-smokers or former smokers compared to the spontaneous (p = .009), traumatic (p = .001), and iatrogenic (p = .008) groups. Additionally, the SMT group had a higher mean low-density lipoprotein (LDL) than the spontaneous (p = .009) and traumatic (p = .003) types. SMT-associated CADs were more often vertebral and bilateral, compared to the spontaneous (p = .003; p < .001), traumatic (p = .047; p = .004), and iatrogenic (p = .002; p = .002) groups. Outcomes including infarct (p = .112), medical treatment (p = .523), intervention (p = .47), and length of stay (p = .512) were similar between the SMT and spontaneous groups.

Conclusions: In this unique study comparing SMT-associated CADs with other dissection etiologies, SMT-associated CADs were uncommon and not associated with worse clinical outcomes. However, SMT-associated CADs were more likely to be bilateral and affected the vertebral arteries in young, non-smoking patients with high LDL.
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http://dx.doi.org/10.1016/j.clineuro.2021.106941DOI Listing
October 2021

Identification of Stability Constraints in the Particle Engineering of an Inhaled Monoclonal Antibody Dried Powder.

J Pharm Sci 2021 Aug 25. Epub 2021 Aug 25.

Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas at Austin, 2409 University Ave, Austin TX, 78712. Electronic address:

Monoclonal antibody (mAb) based therapies may provide a valuable new treatment modality for acute and chronic lung diseases, including asthma, respiratory infections, and lung cancer. Currently mAbs are delivered via systemic administration routes, but direct delivery to the lungs via the inhaled route could provide higher concentrations at the site of disease and reduced off-target effects. Though lyophilized mAbs may be reconstituted and delivered to the lungs using nebulizers, dry powder inhalers provide a more patient-friendly delivery method based upon their fast administration time and portability. However, particle engineering processes required to prepare respirable dried powders for DPI delivery involve multiple potential stressors for mAbs, which have not been fully explored. In this study, a systematic examination of various aspects of the particle engineering process (atomization, freezing, drying, and storage) was performed to further understand their impact on mAb structure and aggregation. Using anti-streptavidin IgG1 as a model mAb, atomization settings were optimized using a design of experiments approach to elucidate the relationship between feed flow rate, formulation solid content, and atomization airflow rate and protein structural changes and aggregation. The optimized atomization conditions were then applied to spray drying and spray freezing drying particle engineering processes to determine the effects of freezing and drying on IgG1 stability and aerosol performance of the powders. IgG1 was found to be particularly susceptible to degradation induced by the expansive air-ice interface generated by spray freeze drying and this process also produced powders that exhibited decreased storage stability. This study further delineates the design space for manufacturing of respirable biologic therapies and is intended to serve as a roadmap for future development work.
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http://dx.doi.org/10.1016/j.xphs.2021.08.022DOI Listing
August 2021

Sarcopenia and major complications in patients undergoing oncologic colon surgery.

J Cachexia Sarcopenia Muscle 2021 Aug 22. Epub 2021 Aug 22.

Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland.

Background: Sarcopenia is a surrogate marker for malnutrition and frailty, which has been linked to higher complication rates and prolonged length of stay (LOS) after surgery. The study aim was to assess the correlation between computed tomography (CT)-based sarcopenia and short-term clinical outcomes after oncologic colon surgery.

Methods: This retrospective study included consecutive patients operated between May 2014 and December 2019. Three radiological indices of sarcopenia were measured at the level of the third lumbar vertebra on preoperative CT scans: skeletal muscle area (SMA), skeletal muscle index (SMI) (both markers of muscle quantity), and skeletal muscle radiation attenuation (SMRA) (marker of muscle quality). Patients with major complications (grade ≥ 3b according to the Clavien classification) were compared with those without. Statistical correlation between sarcopenia indices, LOS, and comprehensive complication index (CCI) was tested with the Pearson correlation coefficient.

Results: A total of 325 patients were included. Mean age was 67 years [standard deviation (SD) 14.3], mean body mass index was 26.0 kg/m (SD 5.3), and 193 (59%) were male. Fifty patients (15.4%) had major complications, while 275 (84.6%) did not. Patients with major complications had more open surgery (52 vs. 21%, P < 0.01), intraoperative blood loss (257 vs. 102 mL, P = 0.035), and intraoperative complications (22 vs. 9%, P = 0.012). Patients with major complications had significantly increased CCI scores (53 vs. 6, P < 0.01), reoperations (74 vs. 0%, P < 0.01), and LOS (33 vs. 7, P < 0.01). SMA and SMI were comparable between both groups (126.0 vs. 125.2 cm , P = 0.974, and 43.4 vs. 44.3 cm /m , P = 0.636, respectively), while SMRA was significantly lower in patients with major complications (33.6 vs. 37.3 HU, P = 0.018). A lower SMRA was correlated with prolonged LOS (r = -0.207, P < 0.01) and higher CCI (r = -0.144, P < 0.01), while the other sarcopenia indices had no influence on surgical outcomes.

Conclusions: Muscle quality (SMRA) as a specific sarcopenia marker was lower in patients with major complications and seems to prevail over muscle quantity (SMA and SMI) in the prediction of adverse outcomes after oncologic colon surgery.
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http://dx.doi.org/10.1002/jcsm.12771DOI Listing
August 2021

Labour Induction with Misoprostol in German Obstetric Clinics: What Are the Facts on Such Use?

Geburtshilfe Frauenheilkd 2021 Aug 9;81(8):955-965. Epub 2021 Aug 9.

Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Germany.

While the synthetic prostaglandin E1 analogue misoprostol is the most effect labour induction agent, its use is off-label for the most part. For this reason, and in view of its potential adverse effects and varying approaches to its administration, the drug has recently once again become a focus of critical attention. The objective of this survey was thus to establish a record of labour induction with misoprostol in German clinics and determine the impact of the negative reporting on everyday obstetric practice. In this cross-sectional study, 635 obstetrics and gynaecology departments in Germany were requested by email to participate in our survey in February/March 2020. Online responses to 19 questions were requested regarding the clinic, use of misoprostol before and after the critical reporting, use of misoprostol (sourcing, method of administration, dosage, monitoring) and other labour induction methods. A total of 262 (41.3%) of the clinics solicited for the survey completed the questionnaire. There were no differences regarding the care level (Perinatal Centre Level I, Perinatal Centre Level II, Clinic with Perinatal Focus or Obstetric/Private Clinic; p = 0.2104) or birth counts (p = 0.1845). In most cases, misoprostol was prepared in the clinic's own pharmacy (54%) or imported from another country (46%) and administered orally in tablet form (95%). Misoprostol dosage levels varied (25 µg [48%], 50 µg [83%], 75 µg [6%], 100 µg [47%] and > 100 µg [5%]). Most of the clinics used premanufactured tablets/capsules (59%), although Cytotec tablets were also divided (35%) or dissolved in water (5%). Misoprostol administration intervals were mainly every 4 hours (64%) or every 6 hours (30%). CTG checks were run in most cases before and after administration of a dose of misoprostol (78% and 76%) and before and after administration of a dose of prostaglandin E2 (both 88%). Presence of contractions led to no misoprostol (59%) or no prostaglandin E2 (64%) being administered in most cases. The critical reporting resulted in discontinuation of use of misoprostol in 17% of the clinics - mainly smaller obstetric/private clinics with fewer than 1000 births. Labour cocktails were used mainly in obstetric and private clinics (61%). Misoprostol is an established agent for labour induction in German clinics. The dosing schemes used vary. Improvements of currently common management practices are required, especially in the area of labour induction (CTG checks before and after administration of labour-inducing medication, no administration of prostaglandin if contractions are ongoing). The discussion of use of misoprostol in the media resulted in stoppage of its use mainly in smaller clinics.
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http://dx.doi.org/10.1055/a-1538-2200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354357PMC
August 2021

What sixty years of research says about the effectiveness of patient education on health: a second order meta-analysis.

Health Psychol Rev 2021 Aug 24:1-25. Epub 2021 Aug 24.

Department of Educational Psychology, University of Trier, Trier, Germany.

Although meta-analyses have examined the association between patient education and health, the validity and quality of this evidence have not been comprehensively assessed. This second order meta-analysis combined previous meta-analyses that examined the effectiveness of patient education on health outcomes as an overall weighted grand mean . Further, measures of methodological quality, meaningful variability across first order meta-analyses, and evidence for publication bias were examined. Forty meta-analyses were identified, investigating 156 associations between patient education and health summarizing data from over 776 studies including more than 74.947 patients. Quantitative analyses showed that patient education positively affects health outcomes with  = 0.316 (95% CI [0.304, 0.329]). Summarizing data exclusively from randomized controlled trials indicated a causal effect. Patient education was effective for patients with neoplasms, diabetes, mental and behavioral disorders, diseases of the circulatory system, the respiratory system, and the musculoskeletal system. Patient education was effective in the reduction of medication use, pain, and visits to medical facilities, and significantly improved physiological, physical, psychological outcomes, and patients' general function. Overall, the findings reveal firm evidence for the effectiveness of patient education on health outcomes. However, theory-based interventions are lacking and need to be implemented to enable a successful transfer from theory to practice.
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http://dx.doi.org/10.1080/17437199.2021.1967184DOI Listing
August 2021

Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant.

Eur J Pediatr 2021 Aug 5. Epub 2021 Aug 5.

Department of Pediatrics, University of Erlangen-Nürnberg, Loschgestr. 15, 91054, Erlangen, Germany.

The risk and potential consequences of mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy are still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Two PCR-confirmed perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded. In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, drug use, or maternal disease during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants.Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as support COVID-19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412. Date of registration: November 18, 2020 What is Known: •Materno-fetal transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) during pregnancy has rarely been reported so far, but was demonstrated in isolated cases. What is New: •In a study of complete households with documented SARS-CoV-2 infection, including a cohort of pregnant women, we observed perinatal coronavirus transmission at a higher frequency than expected. •We also describe a newborn boy with an eye malformation reminiscent of rubella embryopathy but associated with early gestation SARS-CoV-2 infection of his mother. •A coronavirus-related embryopathy, reported here for the first time, is a finding that requires further investigation.
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http://dx.doi.org/10.1007/s00431-021-04221-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341836PMC
August 2021

High-order replica bands in monolayer FeSe/SrTiO revealed by polarization-dependent photoemission spectroscopy.

Nat Commun 2021 Jul 28;12(1):4573. Epub 2021 Jul 28.

Quantum Matter Institute, University of British Columbia, Vancouver, BC, Canada.

The mechanism of the enhanced superconductivity in monolayer FeSe/SrTiO has been enthusiastically studied and debated over the past decade. One specific observation has been taken to be of central importance: the replica bands in the photoemission spectrum. Although suggestive of electron-phonon interaction in the material, the essence of these spectroscopic features remains highly controversial. In this work, we conduct angle-resolved photoemission spectroscopy measurements on monolayer FeSe/SrTiO using linearly polarized photons. This configuration enables unambiguous characterization of the valence electronic structure with a suppression of the spectral background. We consistently observe high-order replica bands derived from various Fe 3d bands, similar to those observed on bare SrTiO. The intensity of the replica bands is unexpectedly high and different between d and d bands. Our results provide new insights on the electronic structure of this high-temperature superconductor and the physical origin of the photoemission replica bands.
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http://dx.doi.org/10.1038/s41467-021-24783-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319137PMC
July 2021

Feasibility of simple exercise interventions for men with osteoporosis - A prospective randomized controlled pilot study.

Bone Rep 2021 Dec 24;15:101099. Epub 2021 Jun 24.

Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Germany.

Background: Aging is associated with progressive loss of musculoskeletal performance. Exercise interventions can improve physical function in the elderly but there is a paucity of comparative assessments in order to understand what specific goals can be achieved particularly with less demanding exercise interventions readily accessible for untrained men.

Methods: Prospective randomized, controlled, single center exploratory trial to compare four distinct exercise interventions, i.e. Resistance Training (RT), Whole Body Vibration Exercise (WBV), Qi Gong (QG) and wearing a Spinal orthosis (SO) for 6 months in men at risk for osteoporosis aged 65-90 years. Primary endpoint was change in isometric one repetition maximum force trunk strength for extension (TSE) and flexion (TSF) compared to baseline, secondary endpoints covered key parameters of geriatric functional assessment, including Handgrip Strength (HS), Chair-Rise-Test (CRT), Usual Gait Speed (UGS) and Timed-Up-and-Go (TUG).

Results: Altogether 47 men (mean age 77 ±6.1 years) were randomized to RT, ( = 11) WBV ( = 13), QG ( = 10) and SO(n = 13). RT, defined as reference exercise intervention, lead to significant improvements for TSE ( = 0.009) and TSF ( = 0.013) and was significantly superior in the between-group analysis for TSE ( = 0.038). Vibration exercise caused sign. Improvements in TSE ( = 0.014) and CRT ( = 0.005), the Spinal orthosis improved CRT ( = 0.003) and Gait Speed ( = 0.027), while the QG intervention did not attain any sig. Developments.Subgroup analyses revealed most pronounced musculoskeletal progress in vulnerable patients (age ≥ 80 years, pre-sarcopenia, multimorbidity ≥3chronic diseases). Irrespective of the type of exercise, participants ≥80 years experienced significant gains in TSE ( = 0.029) and CRT ( = 0.017). Presarcopenic subjects (Skeletal muscle Index (SMI) ≤10.75 kg/m) improved in TSE ( = 0.003), CRT ( = 0.001) and UGS ( = 0.016). Multimorbid participants achieved sig. Gains in TSE ( < 0.001), TSF ( = 0.002), UGS ( = 0.036) and HS ( = 0.046).

Conclusions: In this exploratory trial we found that simple exercise interventions are feasible in elderly men eliciting specific benefits, i.e. improvements are attained in those tasks addressed with the respective exercise modality. While targeted resistance training is superior in increasing TSE, alternative simple exercise interventions also appear to elicit beneficial effects, even in vulnerable patients, i.e. those with low muscle mass, above 80 years of age or multimorbidity.
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http://dx.doi.org/10.1016/j.bonr.2021.101099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255176PMC
December 2021

Lr21 diversity unveils footprints of wheat evolution and its new role in broad-spectrum leaf rust resistance.

Plant Cell Environ 2021 Oct 28;44(10):3445-3458. Epub 2021 Jul 28.

Department of Plant Breeding, Institute of Crop Science and Resource Conservation, University of Bonn, Bonn, Germany.

Aegilops tauschii, the progenitor of the wheat D genome, contains extensive diversity for biotic and abiotic resistance. Lr21 is a leaf rust resistance gene, which did not enter the initial gene flow from Ae. tauschii into hexaploid wheat due to restrictive hybridization events. Here, we used population genetics and high-resolution comparative genomics to study evolutionary and functional divergence of Lr21 in diploid and hexaploid wheats. Population genetics identified the original Lr21, lr21-1 and lr21-2 alleles and their evolutionary history among Ae. tauschii accessions. Comparative genetics of Lr21 variants between Ae. tauschii and cultivated genotypes suggested at least two independent polyploidization events in bread wheat evolution. Further, a recent re-birth of a unique Lr21-tbk allele and its neofunctionalization was discovered in the hexaploid wheat cv. Tobak. Altogether, four independent alleles were investigated and validated for leaf rust resistance in diploid, synthetic hexaploid and cultivated wheat backgrounds. Besides seedling resistance, we uncover a new role of the Lr21 gene in conferring an adult plant field resistance. Seedling and adult plant resistance turned out to be correlated with developmentally dependent variation in Lr21 expression. Our results contribute to understand Lr21 evolution and its role in establishing a broad-spectrum leaf rust resistance in wheat.
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http://dx.doi.org/10.1111/pce.14144DOI Listing
October 2021

Psychotropic drug-induced hyponatremia: results from a drug surveillance program-an update.

J Neural Transm (Vienna) 2021 Aug 1;128(8):1249-1264. Epub 2021 Jul 1.

Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.

Hyponatremia (HN) is the most common electrolyte imbalance (defined as a serum sodium concentration Na(S) of  < 130 mmol/l) and often induced by drugs including psychotropic drugs. AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicenter drug surveillance program that assesses severe or unusual adverse drug reactions (ADRs) occurring during treatment with psychotropic drugs. This study presents data from 462,661 psychiatric inpatients treated in participating hospitals between 1993 and 2016 and serves as an update of a previous contribution by Letmaier et al. (JAMA 15(6):739-748, 2012). A total of 210 cases of HN were observed affecting 0.05% of patients. 57.1% of cases presented symptomatically; 19.0% presented with severe symptoms (e.g., seizures, vomiting). HN occurred after a median of 7 days following the first dose or dose increase. Incidence of HN was highest among the two antiepileptic drugs oxcarbazepine (1.661% of patients treated) and carbamazepine (0.169%), followed by selective serotonin-norepinephrine reuptake inhibitors (SSNRIs, 0.088%) and selective serotonin reuptake inhibitors (0.071%). Antipsychotic drugs, tricyclic antidepressants, and mirtazapine exhibited a significantly lower incidence of HN. The risk of HN was 16-42 times higher among patients concomitantly treated with other potentially HN-inducing drugs such as diuretic drugs, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and proton pump inhibitors. Female SSNRI-users aged  ≥ 65 years concomitantly using other HN-inducing drugs were the population subgroup with the highest risk of developing HN. The identification of high-risk drug combinations and vulnerable patient subgroups represents a significant step in the improvement of drug safety and facilitates the implementation of precautionary measures.
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http://dx.doi.org/10.1007/s00702-021-02369-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322004PMC
August 2021

Inter-examinerreliability study of physical examination procedures to assess the cervical spine.

Chiropr Man Therap 2021 06 14;29(1):20. Epub 2021 Jun 14.

Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA, USA.

Objective: The objective of this study was to establish the level of inter-examiner reliability for six common cervical manual and physical examination procedures used to assess the cervical spine.

Materials: Reliability study that used a convenience sample of 51 patients between the ages of 16-70 years presenting with a chief complaint of neck pain. Two physical therapists independently performed the same series of cervical physical examination procedures on each of the participant. The clinicians were blinded to each other's findings and the clinical status of the patient. Kappa coefficients (κ) were calculated for levels of agreement between the clinicians for each procedure.

Results: When assessing for asymmetrical motion, excellent levels of reliability (κ range: 0.88-0.96) were observed for the Bilateral Modified Lateral Shear (asymmetry criterion), Bilateral C2 Spinous Kick (asymmetry criterion) and Flexion-Rotation Tests. When pain provocation was used as the indicator of a positive test during palpation of the cervical facet joints, moderate to substantial levels of reliability (κ range: 0.53-0.76) were observed. When patients were instructed not to provide feedback to the clinicians about pain provocation during facet joint palpation and clinicians relied solely on their qualitative assessment of segmental mobility, the level of reliability was lower (κ range: 0.45-0.53). Due to 100 % prevalence of negative findings, Kappa values could not be calculated for the Sharp-Purser test or the Unilateral C2 Spinous Kick Test.

Conclusions: Most physical examination procedures examined in this study demonstrated moderate to excellent levels of inter-examiner reliability. Palpation for segmental mobility without pain provocation demonstrated a lower level of reliability compared to palpation for pain provocation. Correlation with clinical findings is necessary to establish validity and the applicability of these procedures in clinical practice.
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http://dx.doi.org/10.1186/s12998-021-00377-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201716PMC
June 2021

Probability of Postoperative Complication after Liver Resection: Stratification of Patient Factors,Operative Complexity, and Use of Enhanced Recovery after Surgery.

J Am Coll Surg 2021 Sep 7;233(3):357-368.e2. Epub 2021 Jun 7.

Department of Visceral Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: The current study aimed to assess the performance of the 3-level complexity classification that stratified liver resection procedures into 3 complexity grades (grade I, low; grade II, intermediate; and grade III, high complexity) and to evaluate whether the Enhanced Recovery after Surgery (ERAS) protocol improves postoperative outcomes for each complexity grade.

Study Design: Consecutive patients undergoing open liver resection and laparoscopic liver resection at Lausanne University Hospital during 2010 to 2020 were assessed.

Results: A total of 437 patients were included. Operative time, estimated blood loss, and length of hospital stay increased significantly, with a stepwise increase of the grades from I to III in open liver resection and laparoscopic liver resection (all, p < 0.05). The same trend for Comprehensive Complication Index was found in open liver resection (p < 0.005). Age (p = 0.004), 3-level complexity classification (grade II vs I; p = 0.001; grade III vs I; p < 0.001), no use of the ERAS protocol (p = 0.016), and biliary reconstruction (p < 0.001) were significant predictors for postoperative complication, defined as Comprehensive Complication Index ≥ 26.2 in a multivariable logistic regression analysis. The prediction model incorporating the 4 factors had a calculated Concordance Index of 0.735 and 0.742 based on the bootstrapping method. The use of ERAS protocol was associated with lower probability of postoperative complication for each complexity grade and age.

Conclusions: The use of ERAS protocol can decrease the probability of postoperative complication for each surgical complexity of liver resection and patient age. This finding emphasized the importance of tailoring perioperative management according to surgical complexity and patient age to improve outcomes after liver resection.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.05.020DOI Listing
September 2021

A case series of serious and unexpected adverse drug reactions under treatment with cariprazine.

Clin Case Rep 2021 May 4;9(5):e04084. Epub 2021 May 4.

Department of Psychiatry Social Psychiatry and Psychotherapy Hannover Medical School Hannover Germany.

Reporting of new or unexpected adverse drug reactions of medicines that are subject to additional monitoring ("black triangle" label), such as the antipsychotic drug cariprazine, is of paramount importance to improve pharmacotherapy safety.
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http://dx.doi.org/10.1002/ccr3.4084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142394PMC
May 2021

Interference between naïve and scientific theories occurs in mathematics and is related to mathematical achievement.

Cognition 2021 09 29;214:104789. Epub 2021 May 29.

University of Graz, Graz, Austria.

When students learn a scientific theory that conflicts with their earlier naïve theories, the newer and more correct knowledge does not always replace the older and more incorrect knowledge. Both may coexist in a learner's long-term memory. Using a new speeded reasoning task, Shtulman and Valcarcel (2012) showed that naïve theories interfere with retrieving scientific theories. Although mathematics learning is a central aim of schooling and a vital prerequisite for success in life, no study has tested whether Shtulman and Valcarcel's (2012) findings generalize to mathematical subdomains such as algebra, geometry, and probability. Additionally, it is unclear how the interference strength relates to domain-specific and domain-general competencies. We investigated these questions using the speeded reasoning task with new mathematical items in a sample of 62 university students. Solution rates and reaction times indicated interference between naïve and scientific mathematical theories. Additionally, interference strength was inversely related to mathematical achievement and unrelated to general inhibitory control. After controlling for general inhibitory control, mathematical achievement was still substantially related to interference strength. These findings indicate that interference strength reflects domain-specific achievement rather than domain-general inhibitory control.
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http://dx.doi.org/10.1016/j.cognition.2021.104789DOI Listing
September 2021

Correcting QUEST Magnetic Resonance Imaging-Sensitive Free Radical Production in the Outer Retina In Vivo Does Not Correct Reduced Visual Performance in 24-Month-Old C57BL/6J Mice.

Invest Ophthalmol Vis Sci 2021 05;62(6):24

Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, United States.

Purpose: To test the hypothesis that acutely correcting a sustained presence of outer retina free radicals measured in vivo in 24-month-old mice corrects their reduced visual performance.

Methods: Male C57BL/6J mice two and 24 months old were noninvasively evaluated for unremitted production of paramagnetic free radicals based on whether 1/T1 in retinal laminae are reduced after acute antioxidant administration (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]). Superoxide production was measured in freshly excised retina (lucigenin assay). Combining acute antioxidant administration with optical coherence tomography (i.e., QUEST OCT) tested for excessive free radical-induced shrinkage of the subretinal space volume. Combining antioxidant administration with optokinetic tracking tested for a contribution of uncontrolled free radical production to cone-based visual performance declines.

Results: At two months, antioxidants had no effect on 1/T1 in vivo in any retinal layer. At 24 months, antioxidants reduced 1/T1 only in superior outer retina. No age-related change in retinal superoxide production was measured ex vivo, suggesting that free radical species other than superoxide contributed to the positive QUEST MRI signal at 24 months. Also, subretinal space volume did not show evidence for age-related shrinkage and was unresponsive to antioxidants. Finally, visual performance declined with age and was not restored by antioxidants that were effective per QUEST MRI.

Conclusions: An ongoing uncontrolled production of outer retina free radicals as measured in vivo in 24 mo C57BL/6J mice appears to be insufficient to explain reductions in visual performance.
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http://dx.doi.org/10.1167/iovs.62.6.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164372PMC
May 2021

Preclinical trial of a MAP4K4 inhibitor to reduce infarct size in the pig: does cardioprotection in human stem cell-derived myocytes predict success in large mammals?

Basic Res Cardiol 2021 05 20;116(1):34. Epub 2021 May 20.

National Heart and Lung Institute, Imperial College London, Du Cane Road, London, W12 0NN, UK.

Reducing infarct size (IS) by interfering with mechanisms for cardiomyocyte death remains an elusive goal. DMX-5804, a selective inhibitor of the stress-activated kinase MAP4K4, suppresses cell death in mouse myocardial infarction (MI), human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), and 3D human engineered heart tissue, whose fidelity to human biology is hoped to strengthen the route to clinical success. Here, DMX-10001, a soluble, rapidly cleaved pro-drug of DMX-5804, was developed for i.v. testing in large-mammal MI. Following pharmacodynamic studies, a randomized, blinded efficacy study was performed in swine subjected to LAD balloon occlusion (60 min) and reperfusion (24 h). Thirty-six animals were enrolled; 12 were excluded by pre-defined criteria, death before infusion, or technical issues. DMX-10001 was begun 20 min before reperfusion (30 min, 60 mg/kg/h; 23.5 h, 17 mg/kg/h). At all times tested, beginning 30 min after the start of infusion, DMX-5804 concentrations exceeded > fivefold the levels that rescued hPSC-CMs and reduced IS in mice after oral dosing with DMX-5804 itself. No significant reduction occurred in IS or no-reflow corrected for the area at ischemic risk, even though DMX-10001 reduced IS, expressed in grams or % of LV mass, by 27%. In summary, a rapidly cleaved pro-drug of DMX-5804 failed to reduce IS in large-mammal MI, despite exceeding the concentrations for proven success in both mice and hPSC-CMs.
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http://dx.doi.org/10.1007/s00395-021-00875-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137473PMC
May 2021

The patterning toolbox FIB-o-mat: Exploiting the full potential of focused helium ions for nanofabrication.

Beilstein J Nanotechnol 2021 6;12:304-318. Epub 2021 Apr 6.

Corelab Correlative Microscopy and Spectroscopy, Helmholtz-Zentrum Berlin für Materialien und Energie, Hahn-Meitner-Platz 1, 14109 Berlin, Germany.

Focused beams of helium ions are a powerful tool for high-fidelity machining with spatial precision below 5 nm. Achieving such a high patterning precision over large areas and for different materials in a reproducible manner, however, is not trivial. Here, we introduce the Python toolbox FIB-o-mat for automated pattern creation and optimization, providing full flexibility to accomplish demanding patterning tasks. FIB-o-mat offers high-level pattern creation, enabling high-fidelity large-area patterning and systematic variations in geometry and raster settings. It also offers low-level beam path creation, providing full control over the beam movement and including sophisticated optimization tools. Three applications showcasing the potential of He ion beam nanofabrication for two-dimensional material systems and devices using FIB-o-mat are presented.
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http://dx.doi.org/10.3762/bjnano.12.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042487PMC
April 2021

Stratified care to prevent chronic low back pain in high-risk patients: The TARGET trial. A multi-site pragmatic cluster randomized trial.

EClinicalMedicine 2021 Apr 30;34:100795. Epub 2021 Mar 30.

Department of Family Medicine, Boston Medical Center, 1 Boston Medical Center Place, Dowling 5 South, Boston, MA 02118 USA.

Background: Many patients with acute low back pain (LBP) first seek care from primary care physicians. Evidence is lacking for interventions to prevent transition to chronic LBP in this setting. We aimed to test if implementation of a risk-stratified approach to care would result in lower rates of chronic LBP and improved self-reported disability.

Methods: We conducted a pragmatic, cluster randomized trial using 77 primary care clinics in four health care systems across the United States. Practices were randomly assigned to a stratified approach to care (intervention) or usual care (control). Using the STarTBack screening tool, adults with acute LBP were screened low, medium, and high-risk. Patients screened as high-risk were eligible. The intervention included electronic best practice alerts triggering referrals for psychologically informed physical therapy (PIPT). PIPT education was targeted to community clinics geographically close to intervention primary care clinics. Primary outcomes were transition to chronic LBP and self-reported disability at six months. Trial Registry: ClinicalTrials.gov NCT02647658.

Findings: Between May 2016 and June 2018, 1207 patients from 38 intervention and 1093 from 37 control practices were followed. In the intervention arm, around 50% of patients were referred for physical therapy (36% for PIPT) compared to 30% in the control. At 6 months, 47% of patients reported transition to chronic LBP in the intervention arm (38 practices,  = 658) versus 51% of patients in the control arm (35 practices,  = 635; OR=0.83 95% CI 0.64, 1.09;  = 0.18). No differences in disability were detected (difference -2·1, 95% CI -4.9-0.6;  = 0.12). Opioids and imaging were prescribed in 22%-25% and 23%-26% of initial visits, for intervention and control, respectively. Twelve-month LBP utilization was similar in the two groups.

Interpretation: There were no differences detected in transition to chronic LBP among patients presenting with acute LBP using a stratified approach to care. Opioid and imaging prescribing rates were non-concordant with clinical guidelines.

Funding: Patient-Centered Outcomes Research Institute (PCORI) contract # PCS-1402-10867.
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http://dx.doi.org/10.1016/j.eclinm.2021.100795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040279PMC
April 2021

A custom virtual reality training solution for ophthalmologic surgical clinical trials.

Adv Simul (Lond) 2021 Apr 16;6(1):12. Epub 2021 Apr 16.

Genentech, Inc., South San Francisco, CA, USA.

We present a summary of the development and clinical use of two custom designed high-fidelity virtual-reality simulator training platforms. This simulator development program began in 2016 to support the phase III clinical trial Archway (ClinicalTrials.gov identifier, NCT03677934) intended to evaluate the Port Delivery System (PDS) developed by Genentech Inc. and has also been used to support additional clinical trials. The two simulators address two specific ophthalmic surgical procedures required for the successful use of PDS and provide state-of-the-art physical simulation models and graphics. The simulators incorporate customized active haptic feedback input devices that approximate different hand pieces including a custom hand piece specifically designed for PDS implantation. We further describe the specific challenges of the procedure and the development of corresponding training strategies realized within the simulation platform.
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http://dx.doi.org/10.1186/s41077-021-00167-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052818PMC
April 2021

Non-Surgical Interventions for Lumbar Spinal Stenosis Leading To Neurogenic Claudication: A Clinical Practice Guideline.

J Pain 2021 Sep 12;22(9):1015-1039. Epub 2021 Apr 12.

American Hip Institute, Des Plaines, Illinois; Clinical and Translational Science Institute, University of Pittsburgh, Pennsylvania.

Lumbar spinal stenosis (LSS) causing neurogenic claudication (NC) is increasingly common with an aging population and can be associated with significant symptoms and functional limitations. We developed this guideline to present the evidence and provide clinical recommendations on nonsurgical management of patients with LSS causing NC. Using the GRADE approach, a multidisciplinary guidelines panel based recommendations on evidence from a systematic review of randomized controlled trials and systematic reviews published through June 2019, or expert consensus. The literature monitored up to October 2020. Clinical outcomes evaluated included pain, disability, quality of life, and walking capacity. The target audience for this guideline includes all clinicians, and the target patient population includes adults with LSS (congenital and/or acquired, lateral recess or central canal, with or without low back pain, with or without spondylolisthesis) causing NC. The guidelines panel developed 6 recommendations based on randomized controlled trials and 5 others based on professional consensus, summarized in 3 overarching recommendations: (Grade: statements are all conditional/weak recommendations) Recommendation 1. For patients with LSS causing NC, clinicians and patients may initially select multimodal care nonpharmacological therapies with education, advice and lifestyle changes, behavioral change techniques in conjunction with home exercise, manual therapy, and/or rehabilitation (moderate-quality evidence), traditional acupuncture on a trial basis (very low-quality evidence), and postoperative rehabilitation (supervised program of exercises and/or educational materials encouraging activity) with cognitive-behavioral therapy 12 weeks postsurgery (low-quality evidence). Recommendation 2. In patients LSS causing NC, clinicians and patients may consider a trial of serotonin-norepinephrine reuptake inhibitors or tricyclic antidepressants. (very low-quality evidence). Recommendation 3. For patients LSS causing NC, we recommend against the use of the following pharmacological therapies: nonsteroidal anti-inflammatory drugs, methylcobalamin, calcitonin, paracetamol, opioids, muscle relaxants, pregabalin (consensus-based), gabapentin (very low-quality), and epidural steroidal injections (high-quality evidence). PERSPECTIVE: This guideline, on the basis of a systematic review of the evidence on the nonsurgical management of lumbar spine stenosis, provides recommendations developed by a multidisciplinary expert panel. Safe and effective non-surgical management of lumbar spine stenosis should be on the basis of a plan of care tailored to the individual and the type of treatment involved, and multimodal care is recommended in most situations.
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http://dx.doi.org/10.1016/j.jpain.2021.03.147DOI Listing
September 2021

Pilot study of an occupational healthcare program to assess the SARS-CoV-2 infection and immune status of employees in a large pharmaceutical company.

Curr Med Res Opin 2021 06 29;37(6):939-947. Epub 2021 Apr 29.

New Biological Entities, Boehringer Ingelheim Animal Health France SCS, Saint-Priest, France.

Objective: To safeguard key workers involved in development and production of medicines and ensure business continuity, we developed an occupational healthcare program, performed by our company's occupational healthcare services, to assess the infection and immune status for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pilot program, conducted at our company facilities, evaluated the suitability of diagnostic tools in our setting for program upscaling.

Methods: We used different marketed diagnostics (including tests for antibodies against spike protein subunits S1 and S2 and nucleocapsid [N] protein) combined with medical history, symptoms and likelihood of infection. We evaluated the testing strategy over four visits in 141 employees (known positive COVID-19 history,  = 20; unknown status,  = 121) between April and June 2020 at four company locations in Germany. Digital self-monitoring over the pilot program duration was also included.

Results: No incident infections were detected. Based on immune status, medical history and likelihood of infection, 10 participants (8.3%) with previously unknown history of COVID-19 were identified to have been infected before entering the program. These participants, who recalled no or mild symptoms in the preceding months, were primarily identified using an assay that detected both S1 and S2 immunoglobulin (Ig) G. The frequency of positive lateral flow assay (LFA) results (IgM or IgG directed against the N-protein) in this cohort was lower compared with participants with a known history of COVID-19 (0‒10.8% vs. 33.8‒75.7%, respectively).

Conclusions: Data from this pilot program suggest that LFA for antibodies may not always reliably detect current, recent or past infections; consequently, these have not been included in our upscaled occupational healthcare program. Regular testing strategies for viral RNA and antibodies directed against different SARS-CoV-2 proteins, combined with hygiene rules and a comprehensive baseline assessment, are recommended to ensure avoidance of infections at workplace as reliably as possible.
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http://dx.doi.org/10.1080/03007995.2021.1914943DOI Listing
June 2021

Balls to the Wall: Human Pluripotent Cell-Derived Cardiac Muscle Spheres Enhance Preclinical Heart Repair.

JACC Basic Transl Sci 2021 Mar 22;6(3):255-256. Epub 2021 Mar 22.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

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http://dx.doi.org/10.1016/j.jacbts.2020.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987535PMC
March 2021

Secondary Osseous Integration of Cementless Unicompartmental Knee Arthroplasty After Internal Fixation of a Felix Type IIIB Fracture: A Case Report.

JBJS Case Connect 2021 03 11;11(1). Epub 2021 Mar 11.

Department of Orthopaedics and Traumatology, St. Josefs Hospital Wiesbaden, Wiesbaden, Germany.

Case: A 76-year-old man presented with periprosthetic tibial plateau fracture (TPF), with a completely loosened tibial component 3 weeks after cementless unicompartmental knee arthroplasty (UKA). Internal fixation by buttress plating was performed, and the tibial component was retained and left in situ primarily as a spacer. Revision was planned after fracture consolidation, but at 3 months, the patient was able to walk without support, without pain, and with full range of motion. At 1 year, he is free of complaints. The initial loosened tibial component reintegrated.

Conclusion: Internal fixation combined with preserving the loosened tibial component may be a treatment option for TPF involving a cementless UKA.
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http://dx.doi.org/10.2106/JBJS.CC.20.00885DOI Listing
March 2021
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