Multilevel atlas comparisons reveal divergent evolution of the primate brain.

Whether the size of the prefrontal cortex (PFC) in humans is disproportionate when compared to other species is a persistent debate in evolutionary neuroscience. This question has left the study of over/under-expansion in other structures relatively unexplored. We therefore sought to address this gap by adapting anatomical areas from the digital atlases of 18 mammalian species, to create a common interspecies classification. Our approach used data-driven analysis based on phylogenetic generalized least squares to evaluate anatomical expansion covering the whole brain. Our main finding suggests a divergence in primate evolution, orienting the stereotypical mammalian cerebral proportion toward a frontal and parietal lobe expansion in catarrhini (primate parvorder comprising old world monkeys, apes, and humans). Cerebral lobe volumes slopes plotted for catarrhini species were ranked as parietal∼frontal > temporal > occipital, contrasting with the ranking of other mammalian species (occipital > temporal > frontal∼parietal). Frontal and parietal slopes were statistically different in catarrhini when compared to other species through bootstrap analysis. Within the catarrhini's frontal lobe, the prefrontal cortex was the principal driver of frontal expansion. Across all species, expansion of the frontal lobe appeared to be systematically linked to the parietal lobe. Our findings suggest that the human frontal and parietal lobes are not disproportionately enlarged when compared to other catarrhini. Nevertheless, humans remain unique in carrying the most relatively enlarged frontal and parietal lobes in an infraorder exhibiting a disproportionate expansion of these areas.

Systematic discovery of biomolecular condensate-specific protein phosphorylation.

Reversible protein phosphorylation is an important mechanism for regulating (dis)assembly of biomolecular condensates. However, condensate-specific phosphosites remain largely unknown, thereby limiting our understanding of the underlying mechanisms. Here, we combine solubility proteome profiling with phosphoproteomics to quantitatively map several hundred phosphosites enriched in either soluble or condensate-bound protein subpopulations, including a subset of phosphosites modulating protein-RNA interactions. We show that multi-phosphorylation of the C-terminal disordered segment of heteronuclear ribonucleoprotein A1 (HNRNPA1), a key RNA-splicing factor, reduces its ability to locate to nuclear clusters. For nucleophosmin 1 (NPM1), an essential nucleolar protein, we show that phosphorylation of S254 and S260 is crucial for lowering its partitioning to the nucleolus and additional phosphorylation of distal sites enhances its retention in the nucleoplasm. These phosphorylation events decrease RNA and protein interactions of NPM1 to regulate its condensation. Our dataset is a rich resource for systematically uncovering the phosphoregulation of biomolecular condensates.

Adaptation of a psycho-educational group programme to improve coping in dementia caregiving: a feasibility study with mixed-methods.

BACKGROUND: As the number of people living with dementia rapidly increases worldwide, the support provided by their informal caregivers remains key to the sustainability of most healthcare systems, this voluntary contribution representing 40% of the costs of dementia worldwide. Informal caregiving in dementia, however, is linked to long periods of chronic stress with frequent and serious negative consequences on the health and quality of life of the caregiver. A psycho-educational group intervention focusing on coping with the daily stress of dementia caregiving ("Learning to feel better… to help better"), developed in French-speaking Canada and showing broad effects on quality of life, was selected with the aim of 1) adapting it to a new cultural context (French-speaking Switzerland) based on identified facilitators and barriers, using a participative approach; and 2) conducting a feasibility study to evaluate whether the adapted programme showed similar or improved feasibility and effects compared to the original Canadian programme. METHODS: A mixed-methods concurrent nested design was used to evaluate the feasibility and the effects on five quantitative core outcomes. Additional qualitative data helped document in depth the acceptability and impact of the intervention. RESULTS: We shortened the programme from 30 to 21 h in total, which resulted in increased accessibility, in terms of facilitated recruitment of participants and inclusion of a broader range of informal caregivers. There were significant reductions in subjective burden (effect size: d = -0.32) and psychological distress (d = -0.48), as well as decreases in the stress reactions of informal caregivers related to the behaviour problems of the persons with dementia (d = -0.57). The qualitative results emphasized the usefulness of providing informal caregivers with structured procedures for efficiently tackling everyday challenges, and of enabling learning through a variety of channels and activities. CONCLUSIONS: Substantial improvements are associated with this 21-h group intervention, organised in 7 sessions of 3 h each, focused on learning more efficient strategies to cope with the daily stress of dementia caregiving. This intervention empowered informal caregivers to master their daily challenges with more confidence, satisfaction and calm. TRIAL REGISTRATION: ISRCTN13512408 (registration date 17.05.2021, retrospectively registered).

Whole brain mapping of glutamate distribution in adult and old primates at 11.7T.

Glutamate is the amino acid with the highest cerebral concentration. It plays a central role in brain metabolism. It is also the principal excitatory neurotransmitter in the brain and is involved in multiple cognitive functions. Alterations of the glutamatergic system may contribute to the pathophysiology of many neurological disorders. For example, changes of glutamate availability are reported in rodents and humans during Alzheimer's and Huntington's diseases, epilepsy as well as during aging. Most studies evaluating cerebral glutamate have used invasive or spectroscopy approaches focusing on specific brain areas. Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a recently developed imaging technique that can be used to study relative changes in glutamate distribution in the entire brain with higher sensitivity and at higher resolution than previous techniques. It thus has strong potential clinical applications to assess glutamate changes in the brain. High field is a key condition to perform gluCEST images with a meaningful signal to noise ratio. Thus, even if some studies started to evaluate gluCEST in humans, most studies focused on rodent models that can be imaged at high magnetic field. In particular, systematic characterization of gluCEST contrast distribution throughout the whole brain has never been performed in humans or non-human primates. Here, we characterized for the first time the distribution of the gluCEST contrast in the whole brain and in large-scale networks of mouse lemur primates at 11.7 Tesla. Because of its small size, this primate can be imaged in high magnetic field systems. It is widely studied as a model of cerebral aging or Alzheimer's disease. We observed high gluCEST contrast in cerebral regions such as the nucleus accumbens, septum, basal forebrain, cortical areas 24 and 25. Age-related alterations of this biomarker were detected in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, 6 and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks, such as fronto-temporal and evaluative limbic networks. These results outline regional differences of gluCEST contrast and strengthen its potential to provide new biomarkers of cerebral function in primates.

A genetic analysis reveals novel histone residues required for transcriptional reprogramming upon stress.

Cells have the ability to sense, respond and adapt to environmental fluctuations. Stress causes a massive reorganization of the transcriptional program. Many examples of histone post-translational modifications (PTMs) have been associated with transcriptional activation or repression under steady-state growth conditions. Comparatively less is known about the role of histone PTMs in the cellular adaptive response to stress. Here, we performed high-throughput genetic screenings that provide a novel global map of the histone residues required for transcriptional reprogramming in response to heat and osmotic stress. Of note, we observed that the histone residues needed depend on the type of gene and/or stress, thereby suggesting a 'personalized', rather than general, subset of histone requirements for each chromatin context. In addition, we identified a number of new residues that unexpectedly serve to regulate transcription. As a proof of concept, we characterized the function of the histone residues H4-S47 and H4-T30 in response to osmotic and heat stress, respectively. Our results uncover novel roles for the kinases Cla4 and Ste20, yeast homologs of the mammalian PAK2 family, and the Ste11 MAPK as regulators of H4-S47 and H4-T30, respectively. This study provides new insights into the role of histone residues in transcriptional regulation under stress conditions.

Platelet-rich plasma as a potential prophylactic measure against frozen shoulder in an in vivo shoulder contracture model.

INTRODUCTION: Frozen shoulder (adhesive capsulitis) is a common painful and functionally-limiting disease affecting around 2% of the population. So far, therapeutic options are limited and often unsatisfactory. Platelet-rich plasma (PRP) has been used as a treatment option in other orthopedic diseases since it contains growth factors that stimulate tissue repair. So far, the effect of PRP on frozen shoulder lacks evidence. We hypothesized that PRP may be valuable in the prophylaxis and treatment of secondary frozen shoulder due to capsular remodeling. MATERIALS AND METHODS: An experimental study of an in vivo frozen shoulder model was conducted. Twenty Sprague-Dawley rats underwent surgery in which the body of the scapula was connected to the humerus with a high-strength suture. Two groups of 8 weeks survival time were allocated; a treatment group with one intraoperative injection of PRP into the glenohumeral joint (n = 10) and a control group without PRP (n = 10). The primary outcome was the structural change in the posterior synovial membrane of the posterior and inferior part of the glenohumeral joint using a semi-quantitative grading from 0 (lowest) to 3 (highest). RESULTS: The posterior synovial membrane structural changes were significantly lower in the PRP group (median = 1 [interquartile range (IQR) = 0-1]) compared to controls (median = 2 [IQR = 1-3]) (p = 0.028). There were no differences for the remaining synovial membrane changes and fibrous capsule responses between groups. CONCLUSIONS: In this in vivo shoulder contracture model, PRP injections seem to reduce the histological severity grade of some parts (i.e., posterior synovial membrane changes) of the secondary frozen shoulder without causing any side effects. It may be considered to investigate this effect further in future studies as a potential prophylaxis of secondary frozen shoulder (e.g., in operated or immobilized shoulders) or as a treatment option for patients with frozen shoulder in the early stage.

Resting state functional atlas and cerebral networks in mouse lemur primates at 11.7 Tesla.

Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Characterizing neuronal networks in animals is complementary to studies in humans to understand how evolution has modelled network architecture. The mouse lemur (Microcebus murinus) is one of the smallest and more phylogenetically distant primates as compared to humans. Characterizing the functional organization of its brain is critical for scientists studying this primate as well as to add a link for comparative animal studies. Here, we created the first functional atlas of mouse lemur brain and describe for the first time its cerebral networks. They were classified as two primary cortical networks (somato-motor and visual), two high-level cortical networks (fronto-parietal and fronto-temporal) and two limbic networks (sensory-limbic and evaluative-limbic). Comparison of mouse lemur and human networks revealed similarities between mouse lemur high-level cortical networks and human networks as the dorsal attentional (DAN), executive control (ECN), and default-mode networks (DMN). These networks were however not homologous, possibly reflecting differential organization of high-level networks. Finally, cerebral hubs were evaluated. They were grouped along an antero-posterior axis in lemurs while they were split into parietal and frontal clusters in humans.

Widespread bacterial protein histidine phosphorylation revealed by mass spectrometry-based proteomics.

For decades, major difficulties in analyzing histidine phosphorylation have limited the study of phosphohistidine signaling. Here we report a method revealing widespread and abundant protein histidine phosphorylation in Escherichia coli. We generated an extensive E. coli phosphoproteome data set, in which a remarkably high percentage (∼10%) of phosphorylation sites are phosphohistidine sites. This resource should help enable a better understanding of the biological function of histidine phosphorylation.

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis.

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

Interferon-Induced Transmembrane Protein 1 Restricts Replication of Viruses That Enter Cells via the Plasma Membrane.

The acute antiviral response is mediated by a family of interferon-stimulated genes (ISGs), providing cell-intrinsic immunity. Mutations in genes encoding these proteins are often associated with increased susceptibility to viral infections. One family of ISGs with antiviral function is the interferon-inducible transmembrane proteins (IFITMs), of which IFITM3 has been studied extensively. In contrast, IFITM1 has not been studied in detail. Since IFITM1 can localize to the plasma membrane, we investigated its function with a range of enveloped viruses thought to infect cells by fusion with the plasma membrane. Overexpression of IFITM1 prevented infection by a number of Paramyxoviridae and Pneumoviridae, including respiratory syncytial virus (RSV), mumps virus, and human metapneumovirus (HMPV). IFITM1 also restricted infection with an enveloped DNA virus that can enter via the plasma membrane, herpes simplex virus 1 (HSV-1). To test the importance of plasma membrane localization for IFITM1 function, we identified blocks of amino acids in the conserved intracellular loop (CIL) domain that altered the subcellular localization of the protein and reduced antiviral activity. By screening reported data sets, 12 rare nonsynonymous single nucleotide polymorphisms (SNPs) were identified in human IFITM1, some of which are in the CIL domain. Using an Ifitm1-/- mouse, we show that RSV infection was more severe, thereby extending the range of viruses restricted in vivo by IFITM proteins and suggesting overall that IFITM1 is broadly antiviral and that this antiviral function is associated with cell surface localization.IMPORTANCE Host susceptibility to viral infection is multifactorial, but early control of viruses not previously encountered is predominantly mediated by the interferon-stimulated gene (ISG) family. There are upwards of 300 of these genes, the majority of which do not have a clearly defined function or mechanism of action. The cellular location of these proteins may have an important effect on their function. One ISG located at the plasma membrane is interferon-inducible transmembrane protein 1 (IFITM1). Here we demonstrate that IFITM1 can inhibit infection with a range of viruses that enter via the plasma membrane. Mutant IFITM1 proteins that were unable to localize to the plasma membrane did not restrict viral infection. We also observed for the first time that IFITM1 plays a role in vivo, and Ifitm1-/- mice were more susceptible to viral lung infection. These data contribute to our understanding of how ISGs prevent viral infections.

Identification of potential inhibitors of SARS-CoV-2 main protease from Aloe vera compounds: A molecular docking study.

SARS-CoV-2 is the pathogen agent of the new corona virus disease that appeared at the end of 2019 in China. There is, currently, no effective treatment against COVID-19. We report in this study a molecular docking study of ten Aloe vera molecules with the main protease (3CLpro) responsible for the replication of coronaviruses. The outcome of their molecular simulation and ADMET properties reveal three potential inhibitors of the enzyme (ligands 6, 1 and 8) with a clear preference of ligand 6 that has the highest binding energy (-7.9 kcal/mol) and fully obeys the Lipinski's rule of five.

Defeating Major Contaminants in Fe3+- Immobilized Metal Ion Affinity Chromatography (IMAC) Phosphopeptide Enrichment.

Here we demonstrate that biomolecular contaminants, such as nucleic acid molecules, can seriously interfere with immobilized metal ion affinity chromatography (IMAC)-based phosphopeptide enrichments. We address and largely solve this issue, developing a robust protocol implementing methanol/chloroform protein precipitation and enzymatic digestion using benzonase, which degrades all forms of DNA and RNA, before IMAC-column loading. This simple procedure resulted in a drastic increase of enrichment sensitivity, enabling the identification of around 17,000 unique phosphopeptides and 12,500 unambiguously localized phosphosites in human cell-lines from a single LC-MS/MS run, constituting a 50% increase when compared with the standard protocol. The improved protocol was also applied to bacterial samples, increasing the number of identified bacterial phosphopeptides even more strikingly, by a factor 10, when compared with the standard protocol. For E. coli we detected around 1300 unambiguously localized phosphosites per LC-MS/MS run. The preparation of these ultra-pure phosphopeptide samples only requires marginal extra costs and sample preparation time and should thus be adoptable by every laboratory active in the field of phosphoproteomics.

A New Tool to Reveal Bacterial Signaling Mechanisms in Antibiotic Treatment and Resistance.

The rapid emergence of antimicrobial resistance is a major threat to human health. Antibiotics modulate a wide range of biological processes in bacteria and as such, the study of bacterial cellular signaling could aid the development of urgently needed new antibiotic agents. Due to the advances in bacterial phosphoproteomics, such a systemwide analysis of bacterial signaling in response to antibiotics has recently become feasible. Here we present a dynamic view of differential protein phosphorylation upon antibiotic treatment and antibiotic resistance. Most strikingly, differential phosphorylation was observed on highly conserved residues of resistance regulating transcription factors, implying a previously unanticipated role of phosphorylation mediated regulation. Using the comprehensive phosphoproteomics data presented here as a resource, future research can now focus on deciphering the precise signaling mechanisms contributing to resistance, eventually leading to alternative strategies to combat antimicrobial resistance.

Gaining Confidence in the Elusive Histidine Phosphoproteome.

Recent technological advances have made it possible to investigate the hitherto rather elusive protein histidine phosphorylation. However, confident site-specific localization of protein histidine phosphorylation remains challenging. Here, we address this problem, presenting a mass-spectrometry-based approach that outperforms classical HCD fragmentation without compromising sensitivity. We use the phosphohistidine immonium ion as a diagnostic tool as well as ETD-based fragmentation techniques to achieve unambiguous identification and localization of histidine-phosphorylation sites. The work presented here will allow more confident investigation of the phosphohistidine proteome to reveal the roles of histidine phosphorylation in cellular signaling events.

Implementation of new standard operating procedures for geriatric trauma patients with multiple injuries: a single level I trauma centre study.

BACKGROUND: The demographic changes towards ageing of the populations in developed countries impose a challenge to trauma centres, as geriatric trauma patients require specific diagnostic and therapeutic procedures. This study investigated whether the integration of new standard operating procedures (SOPs) for the resuscitation room (ER) has an impact on the clinical course in geriatric patients. The new SOPs were designed for severely injured adult trauma patients, based on the Advanced Trauma Life Support (ATLS) and imply early whole-body computed tomography (CT), damage control surgery, and the use of goal-directed coagulation management. METHODS: Single-centre cohort study. We included all patients ≥65 years of age with an Injury Severity Score (ISS) ≥ 9 who were admitted to our hospital primarily via ER. A historic cohort was compared to a cohort after the implementation of the new SOPs. RESULTS: We enrolled 311 patients who met the inclusion criteria between 2000 and 2006 (group PreSOP) and 2010-2012 (group SOP). There was a significant reduction in the mortality rate after the implementation of the new SOPs (P = .001). This benefit was seen only for severely injured patients (ISS ≥ 16), but not for moderately injured patients (ISS 9-15). There were no differences with regard to infection rates or rate of palliative care. CONCLUSIONS: We found an association between implementation of new ER SOPs, and a lower mortality rate in severely injured geriatric trauma patients, whereas moderately injured patients did not obtain the same benefit. TRIAL REGISTRATION: Clinicaltrials.gov NCT03319381, retrospectively registered 24 October 2017.

Rate of intraoperative problems during sacroiliac screw removal: expect the unexpected.

BACKGROUND: The indications for sacroiliac screw (SI) removal have been under debate. Data on complication rates of SI screw removal is missing in the current literature. The objective of this study was to compare the rate of intra- and perioperative problems and complications during SI screw removal to those with SI screw fixation. METHODS: A retrospective observational study with two interventions in the same cohort was performed. Consecutive patients who underwent both sacroiliac screw fixation for an isolated fracture of the pelvic ring and removal of the same implants between November 2008 and September 2015 (n = 19; age 57.3, SD 16.1 years) were included. Intraoperative technical problems, postoperative complications, duration of surgery, and radiation dose were analysed. RESULTS: Intraoperative technical problems occurred in 1/19 patients (5%) during SI screw fixation and in 7/19 cases (37%) during SI screw removal (p = .021). Postoperative complications were seen in 3/19 patients after SI screw fixation and in 1/19 patients after SI screw removal (p = 0.128). The surgical time needed per screw was longer for screw removal than for implantation (p = .005). The amount of radiation used for the whole intervention (p = .845) and per screw (p = .845) did not differ among the two interventions. CONCLUSIONS: Intraoperative technical problems were more frequent with SI screw removal than with SI screw fixation. Most of the intraoperative technical problems in this study were implant-related. They resulted in more surgical time needed per screw removed but similar radiation time.

[Quality of the diagnoses' coding (main or associated diagnoses) in the medico-administrative database for psychiatric care (RIM-P) in 2015 and 2016, France]. / Qualité du codage des diagnostics et motifs de prise en charge (principal et associés) dans le recueil d'informations médicalisé en psychiatrie (RIM-P) en 2015 et 2016, France.

BACKGROUND: Based on the observation of the misuse of ICD-10 to code the diagnoses in the RIM-P (lack of completeness, conformity and diversity), the Technical Agency for information on Hospital Care (ATIH), which provides tools for collecting medical information, conducted two actions in 2016. First, a chapter devoted to the instructions of coding has been written in the methodological guide of production of the RIM-P, second, a variable "type psy" was added to the ICD-10 nomenclature's file framing ICD-10 coding in the RIM-P. The purpose of this study is to describe the quality of diagnosis coding using ICD-10 in the RIM-P in 2015 and 2016. METHODS: The quality of diagnosis coding using ICD-10 in the summaries of activity of the RIM-P national databases was described in 2015 and 2016. The study focused on the completeness, the conformity and the diversity of coding. RESULTS: Between 2015 and 2016, the percentage of summaries without primary diagnosis ("DP") decreased slightly for full-time (5.2% vs. 3.8%), part-time (6.3% vs. 4.9%) inpatient stays and outpatient care (9.9% vs. 8.9%). ICD-10 codes used to code DP or associated diagnosis ("DA"), while prohibited, mainly belong to Chapter V Mental and behavioral disorders. Per year, only one-third of the summaries and one-half of patients had two or more ICD-10 codes reported for inpatient stays (one-fifth of the summaries and one-fourth of the patients for outpatient care). In addition, per year and per facility, the average number of distinct ICD-10 codes used to fill "DP" or "DA" was approximately half as important in part-time hospitalization, as in full-time hospitalization or for outpatient care. Moreover, 90% of the health facilities used<550 distinct ICD-10 codes in full-time inpatient stays,<270 in part-time inpatient stays and<950 for outpatient care to code the "DP" or the "DA". The diversity of ICD-10 codes used was low and similar between 2015 and 2016, especially to describe the socio-economic environment, resistance to treatment or non-compliance. CONCLUSION: This study emphasizes the need for a collective effort to improve the diversity of the diagnoses' coding in the RIM-P.

Standards for external fixation application: national survey under the auspices of the German Trauma Society.

INTRODUCTION: External fixation is widely accepted as a provisional or sometimes definitive treatment for long-bone fractures. Indications include but are not limited to damage control surgery in poly-traumatized patients as well as provisional bridging to definite treatment with soft tissue at risk. As little is known about surgeon's habits in applying this treatment strategy, we performed a national survey. METHODS: We utilized the member database of the German Trauma Society (DGU). The questionnaire encompassed 15 questions that addresses topics including participants' position, experience, workplace, and questions regarding specifics of external fixation application in different anatomical regions. Furthermore, we compared differences between trauma centre levels and surgeon-related factors. RESULTS: The participants predominantly worked in level 1 trauma centres (42.7%) and were employed as attendings (54.7%). There was widespread consensus for planning and intra-operative radiographical control of external fixation. Surgeons appointed at a level I trauma centre preferred significantly more often supra-acetabular pin placement in external fixation of the pelvis rather than the utilization of iliac pins (75.8%, p = 0.0001). Moreover, they were more likely to favor a mini-open approach to insert humeral pins (42.4%, p = 0.003). Overall, blunt dissection and mini-open approaches seemed equally popular (38.2 and 34.1%). Department chairmen indicated more often than their colleagues to follow written pin-care protocols for minimization of infection (16.7%, p = 0.003). CONCLUSION: Despite the fact that external fixation usage is widespread and well established among trauma surgeons in Germany, there are substantial differences in the method of application.

[What influence do increased physical performance, age, sex and training frequency have on the effectiveness of back training?] / Welche Bedeutung haben physische Leistungssteigerungen, Alter, Geschlecht und Trainingsumfang für die Wirksamkeit eines Rückentrainings?

BACKGROUND: Active exercising can effectively reduce low back pain but the mechanisms of action are still unclear. OBJECTIVE: What are the influences of training frequency, increased physical performance, age and gender on the effectiveness of a multimodal back training? MATERIAL AND METHODS: A total of 1395 persons with back pain (mean age 46.9 ± 12.3 years, 65% female) took part in a multimodal back training over 24 months in the context of a multicenter study (39 locations). Back pain, physical capacity of strength, mobility and bilateral strength ratio of the spine stabilizing muscles were measured at the beginning of the training and after 6, 12 and 18 months. RESULTS AND DISCUSSION: The participants trained on average for 41.0 (SD ± 17.8) 60-min training units. This resulted in an increase of strength (28.1%), mobility (14.7%) and strength ratio (6.5%) compared to an age and gender-matched cohort without back pain. Back pain was reduced by 37.5%. The reduction in back pain can be ascribed to the training frequency by 70% and to increased physical performance by 30%. Age only marginally influenced the effect of training, while gender had no significant effect. CONCLUSION: Increases in physical performance have positive effects on the reduction of back pain but the number of training sessions was shown to be more relevant in the reduction of low back pain.