Sequence-to-sequence translation from mass spectra to peptides with a transformer model.

A fundamental challenge in mass spectrometry-based proteomics is the identification of the peptide that generated each acquired tandem mass spectrum. Approaches that leverage known peptide sequence databases cannot detect unexpected peptides and can be impractical or impossible to apply in some settings. Thus, the ability to assign peptide sequences to tandem mass spectra without prior information-de novo peptide sequencing-is valuable for tasks including antibody sequencing, immunopeptidomics, and metaproteomics. Although many methods have been developed to address this problem, it remains an outstanding challenge in part due to the difficulty of modeling the irregular data structure of tandem mass spectra. Here, we describe Casanovo, a machine learning model that uses a transformer neural network architecture to translate the sequence of peaks in a tandem mass spectrum into the sequence of amino acids that comprise the generating peptide. We train a Casanovo model from 30 million labeled spectra and demonstrate that the model outperforms several state-of-the-art methods on a cross-species benchmark dataset. We also develop a version of Casanovo that is fine-tuned for non-enzymatic peptides. Finally, we demonstrate that Casanovo's superior performance improves the analysis of immunopeptidomics and metaproteomics experiments and allows us to delve deeper into the dark proteome.

Pancreatic Stone Protein in the Diagnosis of Sepsis in Children Admitted to High-Dependency Care: A Single-Center Prospective Cohort Study.

OBJECTIVES: Blood level of pancreatic stone protein (PSP) is a promising biomarker of sepsis both in adults and children. The aim of our study was to investigate the diagnostic accuracy of PSP in children with suspected sepsis and to compare diagnostic performance with other sepsis biomarkers approved for clinical use, that is, procalcitonin (PCT) and C-reactive protein (CRP). DESIGN: Prospective study. SETTING: PICU and pediatric emergency department. INTERVENTION: Blood levels of PSP were measured using a nanofluidic point-of-care immunoassay (abioSCOPE, Abionic SA, Switzerland) within 24 hours of admission. MEASUREMENTS AND MAIN RESULTS: We studied 99 children aged between older than 1 month and younger than 18 years with signs and symptoms of systemic inflammatory response syndrome (irrespective of associated organ dysfunction). The prevalence of sepsis was 35 of 99 (35.4%). Patients with sepsis had higher PSP levels (p < 0.001) than patients with systemic inflammation of noninfectious cause. In this analysis, the optimal cutoff for the diagnosis of sepsis using PSP was 123 ng/mL, which resulted in a sensitivity of 0.63 (95% CI, 0.43-0.80), specificity of 0.89 (95% CI, 0.77-0.95). The PSP test area under the receiver operating characteristic curve (AUROC) was 0.82 (95% CI, 0.73-0.91) and, by comparison, procalcitonin and CRP AUROC were 0.70 (95% CI, 0.58-0.82) and 0.72 (95% CI, 0.60-0.84), respectively. Overall, the pretest to posttest probability of sepsis with a positive test changed from 0.35 to 0.73. CONCLUSIONS: In this single-center prospective pediatric cohort, admitted to the high intensive care and to the PICU, our findings suggested the potential use of PSP as a sepsis biomarker. However, because of the clinical diagnostic uncertainty with a positive result, further investigation is needed particularly in combination with other biomarkers.

Development of an Azobenzene-Based Cell Culture Photoresponsive Platform for In Situ Modulation of Surface Topography in Wet Environments.

Azopolymers are light-responsive materials that hold promise to transform in vitro cell culture systems. Through precise light illumination, they facilitate substrate pattern formation and erasure, allowing for the dynamic control and creation of active interfaces between cells and materials. However, these materials exhibit a tendency to locally detach from the supporting glass in the presence of aqueous solutions, such as cell culture media, due to the formation of blisters, which are liquid-filled cavities generated at the azopolymer film-glass interface. These blisters impede precise structurization of the surface of the azomaterial, limiting their usage for surface photoactivation in the presence of cells. In this study, we present a cost-effective and easily implementable method to improve the azopolymer-glass interface stability through silane functionalization of the glass substrate. This method proved to be efficient in preventing blister formation, thereby enabling the dynamic modulation of the azopolymer surface in situ for live-cell experiments. Furthermore, we proved that the light-illumination conditions used to induce azopolymer surface variations do not induce phototoxic effects. Consequently, this approach facilitates the development of a photoswitchable azopolymer cell culture platform for studying the impact of multiple in situ inscription and erasure cycles on cell functions while maintaining a physiological wet microenvironment.

Hydroxyapatite: An Eco-Friendly Material for Enzyme Immobilization.

Biocatalysis has emerged in the last decade as a valuable and eco-friendly tool in chemical synthesis, allowing in several instances to reduce or eliminate the use of hazardous reagents, environmentally dangerous solvents and harsh reaction conditions. Enzymes are indeed able to catalyse chemical transformations on non-natural substrates under mild reaction conditions, still maintaining their high chemo-, regio-, and stereoselectivity. Enzyme immobilization, i. e. the grafting of enzymes on solid supports, can be viewed as an enabling technology, as it allows a better control of the reaction and the recycling of the biocatalyst, thus rendering economically viable the use of expensive enzymes also on a large scale. To pursue a sustainable approach, the supports for enzyme immobilization should be eco-friendly and possibly renewable. This review highlights the use of hydroxyapatite (HAP), an inorganic biomaterial able to confer strength and stiffness to the bone tissue in animals, as carrier for enzyme immobilization. HAP is a cheap, non-toxic and biocompatible material, with high surface area and protein affinity. Different enzyme classes, immobilization strategies, and the use of diverse HAP-based supports will be discussed, underlining the immobilization conditions and the properties of the obtained biocatalysts.

Rotating curved spacetime signatures from a giant quantum vortex.

Gravity simulators1 are laboratory systems in which small excitations such as sound2 or surface waves3,4 behave as fields propagating on a curved spacetime geometry. The analogy between gravity and fluids requires vanishing viscosity2-4, a feature naturally realized in superfluids such as liquid helium or cold atomic clouds5-8. Such systems have been successful in verifying key predictions of quantum field theory in curved spacetime7-11. In particular, quantum simulations of rotating curved spacetimes indicative of astrophysical black holes require the realization of an extensive vortex flow12 in superfluid systems. Here we demonstrate that, despite the inherent instability of multiply quantized vortices13,14, a stationary giant quantum vortex can be stabilized in superfluid 4He. Its compact core carries thousands of circulation quanta, prevailing over current limitations in other physical systems such as magnons5, atomic clouds6,7 and polaritons15,16. We introduce a minimally invasive way to characterize the vortex flow17,18 by exploiting the interaction of micrometre-scale waves on the superfluid interface with the background velocity field. Intricate wave-vortex interactions, including the detection of bound states and distinctive analogue black hole ringdown signatures, have been observed. These results open new avenues to explore quantum-to-classical vortex transitions and use superfluid helium as a finite-temperature quantum field theory simulator for rotating curved spacetimes19.

Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure.

BACKGROUND: Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilpivirine long-acting (CAB + RPV LA) were expanded to include data beyond week 48, additional covariates, and additional participants. METHODS: Pooled data from 1651 participants were used to explore dosing regimen (every 4 or every 8 weeks), demographic, viral, and pharmacokinetic covariates as potential predictors of CVF. Prior dosing regimen experience was accounted for using 2 populations. Two models were conducted in each population-baseline factor analyses exploring factors known at baseline and multivariable analyses exploring baseline factors plus postbaseline model-predicted CAB/RPV trough concentrations (4 and 44 weeks postinjection). Retained factors were evaluated to understand their contribution to CVF (alone or in combination). RESULTS: Overall, 1.4% (n = 23/1651) of participants had CVF through 152 weeks. The presence of RPV resistance-associated mutations, human immunodeficiency virus-1 subtype A6/A1, and body mass index ≥30 kg/m2 were associated with an increased risk of CVF (P < .05 adjusted incidence rate ratio), with participants with ≥2 of these baseline factors having a higher risk of CVF. Lower model-predicted CAB/RPV troughs were additional factors retained for multivariable analyses. CONCLUSIONS: The presence of ≥2 baseline factors (RPV resistance-associated mutations, A6/A1 subtype, and/or body mass index ≥30 kg/m2) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (≤first quartile) did not improve the prediction of CVF beyond the presence of a combination of ≥2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA.

l-Theanine Goes Greener: A Highly Efficient Bioprocess Catalyzed by the Immobilized γ-Glutamyl Transferase from Bacillus subtilis.

l-Theanine (l-Th) was synthesized by simply mixing the reactants (l-glutamine and ethylamine in water) at 25 °C and Bacillus subtilis γ-glutamyl transferase (BsGGT) covalently immobilized on glyoxyl-agarose according to a methodology previously reported by our research group; neither buffers, nor other additives were needed. Ratio of l-glutamine (donor) to ethylamine (acceptor), pH, enzymatic units (IU), and reaction time were optimized (molar ratio of donor/acceptor=1 : 8, pH 11.6, 1 IU mL-1 , 6 h), furnishing l-Th in 93 % isolated yield (485 mg, 32.3 g L-1 ) and high purity (99 %), after a simple filtration of the immobilized biocatalyst, distillation of the volatiles (unreacted ethylamine) and direct lyophilization. Immobilized BsGGT was re-used (four reaction cycles) with 100 % activity retention. This enzymatic synthesis represents a straightforward, fast, high-yielding, and easily scalable approach to l-Th preparation, besides having a favorable green chemistry metrics.

CMV seroprevalence and coronary CMV-DNA detection in immunocompetent patients with heart diseases.

BACKGROUND: Acute coronary syndromes (ACS) are a major cause of morbidity and mortality. As cytomegalovirus (CMV) may contribute to cardio-vascular (CV) manifestations, we sought to provide a proof-of-concept for the involvement of coronary and/or systemic CMV-reactivation as a possible ACS trigger. METHODS: We prospectively enrolled consecutive patients undergoing a coronary angiography for ACS (acute-cases, N.=136), or non-ACS reasons (chronic-cases, N.=57). Matched coronary and peripheral blood-samples were processed for quantification of CMV-DNAemia (RT-PCR), CMV-IgG/IgM, and CMV-IgG avidity (ELISA). Peripheral-blood samples from 17 healthy subjects were included as controls. RESULTS: Out of the 193 cases included, 18.1% were aged ≤55 years, 92.5% were Central-European, and 100% immunocompetent. CMV-IgG seroprevalence was 91.7% (95%CI: 87.8-95.6), significantly higher than in healthy-controls (52.9% [95%CI: 29.2-76.5]; P<0.001), yet consistent across age-groups (P=0.602), male/females (P=0.765), and acute/chronic-cases (P=0.157). Median (IQR) IgG titers were 110 (84-163) AU/mL, with 0.62 (0.52-0.72) avidity, supporting a long history of infection. No acute CMV infections were found. In 22.6% (n/N.=40/177) of the IgG-positive cases low-level coronary and/or systemic CMV-DNAemia (always <40 copies/mL) was detected. While no differences in peripheral CMV-DNAemia prevalence were observed nor among cases nor controls, coronary CMV-DNAemia was more frequent in acute-cases without modifiable CV risk-factors (n/N.=4/10; 40.0%), than in chronic-cases (n/N.=6/55, 10.9%; P=0.029), or acute-cases with risk-factors (n/N.=16/112, 14.3%; P=0.058). CONCLUSIONS: CMV-IgG seroprevalence was high in patients with heart diseases. CMV-DNAemia can be found, although uncommonly, in coronary circulation during an ACS, with increased prevalence in older subjects and in absence of CV risk-factors, identifying possible areas for novel interventions.

Effectiveness of platelet-rich plasma as an adjunct to core decompression to treatment outcomes and femoral head preservation in avascular necrosis of the hip: A meta-analysis of randomized controlled trials

Background@#Avascular necrosis (AVN) of the femoral head results from intraosseous pathology causing functional impairment. Early diagnosis allows conservative treatment like core decompression, delaying total hip arthroplasty.@*Objective@#This meta-analysis aims to summarize platelet-rich plasma's (PRP) impact as an adjunct to core decompression (CD) on treatment outcomes and femoral head preservation in hip AVN. @*Methods@#The study conducted a comprehensive literature search using PubMed, Cochrane Library, Science Direct, Google Scholar and Med Line, including randomized controlled trials (RCTs) and previous meta-analyses from various databases. Using a random effects model, it compared PRP+CD with bone grafting to CD with bone grafting alone in AVN patients, evaluating function, pain scores, disease progression and the need for hip surgery.@*Results@#The meta-analysis examined 1041 records and included three studies. The primary outcomes were function and pain scores using Harris Hip Scoring (HHS) and Visual Analog Scale (VAS). Postoperative HHS scores at final follow-up favored the PRP+CD group significantly over CD alone. Postoperative VAS scores showed a trend towards higher scores in the CD alone group. The PRP+CD group demonstrated higher survival from disease progression compared to CD alone. Overall, the study suggests that PRP+CD led to better functional outcomes and disease progression outcomes than CD alone in AVN of the hip.@*Conclusion@#The PRP+CD treatment group showed significant benefits in AVN patients compared to CD alone, including higher HHS scores, improved disease progression survival and reduced need for hip surgery. Although PRP+CD resulted in decreased VAS scores, the difference was not statistically significant.

From Batch to Continuous Flow Bioprocessing: Use of an Immobilized γ-Glutamyl Transferase from B. subtilis for the Synthesis of Biologically Active Peptide Derivatives.

γ-Glutamyl-peptides are frequently endowed with biological activities. In this work, "kokumi peptides" such as γ-glutamyl-methionine (1) and γ-glutamyl-(S)-allyl-cysteine (2), as well as the neuroprotective γ-glutamyl-taurine (3) and the antioxidant ophthalmic acid (4), were synthesized through an enzymatic transpeptidation reaction catalyzed by the γ-glutamyl transferase from Bacillus subtilis (BsGGT) using glutamine as the γ-glutamyl donor. BsGGT was covalently immobilized on glyoxyl-agarose resulting in high protein immobilization yield and activity recovery (>95%). Compounds 1-4 were obtained in moderate yields (19-40%, 5-10 g/L) with a variable purity depending on the presence of the main byproduct (γ-glutamyl-glutamine, 0-16%). To achieve process intensification and better control of side reactions, the synthesis of 2 was moved from batch to continuous flow. The specific productivity was 1.5 times higher than that in batch synthesis (13.7 µmol/min*g), but it was not accompanied by a paralleled improvement of the impurity profile.

Preparation, Characterization and In Vitro Stability of a Novel ACE-Inhibitory Peptide from Soybean Protein.

A soy protein isolate was hydrolyzed with Alcalase®, Flavourzyme® and their combination, and the resulting hydrolysates (A, F and A + F) were ultrafiltered and analyzed through SDS-PAGE. Fractions with MW < 1 kDa were investigated for their ACE-inhibitory activity, and the most active one (A < 1 kDa) was purified by semi-preparative RP-HPLC, affording three further subfractions. NMR analysis and Edman degradation of the most active subfraction (A1) enabled the identification of four putative sequences (ALKPDNR, VVPD, NDRP and NDTP), which were prepared by solid-phase synthesis. The comparison of their ACE-inhibitory activities suggested that the novel peptide NDRP might be the main agent responsible for A1 fraction ACE inhibition (ACE inhibition = 87.75 ± 0.61%; IC50 = 148.28 ± 9.83 µg mL−1). NDRP acts as a non-competitive inhibitor and is stable towards gastrointestinal simulated digestion. The Multiple Reaction Monitoring (MRM) analysis confirmed the presence of NDRP in A < 1 kDa.

A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach.

Mechanical forces, acting on eukaryotic cells, are responsible for cell shape, cell proliferation, cell polarity, and cell differentiation thanks to two cells abilities known as mechanosensing and mechanotransduction. Mechanosensing consists of the ability of a cell to sense mechanical cues, while mechanotransduction is the capacity of a cell to respond to these signals by translating mechanical stimuli into biochemical ones. These signals propagate from the extracellular matrix to the nucleus with different well known physical connections, but how the mechanical signals are transduced into biochemical ones remains an open challenge. Recent findings showed that the cell-generated forces affect the translocation of transcription factors (TFs) from the cytoplasm to the nucleus. This mechanism is affected by the features of nuclear pore complexes. Owing to the complex patterns of strains and stresses of the nuclear envelope caused by cytoskeletal forces, it is likely that the morphology of NPC changes as cytoskeleton assemblies' change. This may ultimately affect molecular transport through the nucleus, hence altering cell functions. Among the various TFs, Yes-associated protein (YAP), which is typically involved in cell proliferation, survival, and differentiation, is able to activate specific pathways when entrapped into the cell nucleus. Here, starting from experimental results, we develop a multiscale finite element (FE) model aimed to simulate the macroscopic cell spreading and consequent changes in the cell mechanical behaviour to be related to the NPCs changes and YAP nuclear transport.

Bictegravir/emtricitabine/tenofovir alafenamide ensures high rates of virological suppression maintenance despite previous resistance in PLWH who optimize treatment in clinical practice.

OBJECTIVES: We evaluated virological response and resistance profiles in individuals who were virologically suppressed who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in real life. METHODS: Survival analysis was used to assess probability of virological rebound (VR). Cumulative major resistance mutations (MRM) and cumulative genotypic susceptibility score (cGSS) were evaluated before the switch. RESULTS: Overall, 283 individuals virologically suppressed for a median (interquartile [IQR]) time of 7 (3-9) y were analyzed. Of these, 20.8% were in first-line treatment, 13.1% were highly treatment-experienced (HTE), and 8.5% had experienced previous integrase inhibitor (INI)-failures. Before the switch, nucleotide reverse transcriptase inhibitor NRTI MRM prevalence was 29% (M184V:13.8%; any thymidine analogue mutation: 14.1%; K65R: 0.7%; K70E 0.4%); only three (2.1%) individuals showed INI major resistance mutations (Y143C/H/R [n = 1]; Y143C [n = 1]; N155H [n = 1]), and 82.0% of individuals received fully active B/F/TAF. Ninety-six wk after switch, the probability of VR was 5%, with only 12 events of VR at a median (IQR) viremia level of 284 (187-980) copies/mL, mainly transient. No significant associations between virological outcomes and genotypic susceptibility to B/F/TAF were observed. People who experienced previous INI failures showed a significantly higher adjusted hazard ratio (AHR [95% CI]) to experience VR under B/F/TAF (3.9 [1.1-13.4], P = 0.031). This AHR increased in people who experienced INI failures and received partially active B/F/TAF (5.5 [1.4-21.1], P = 0.013). CONCLUSION: Within 96 wk, a switch to B/F/TAF in individuals who were virologically suppressed ensured a very high rate of virological control in a clinical setting. Previous resistance alone did not affect B/F/TAF response. However, people who had previous INI failures were more prone to losing virological control under B/F/TAF.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Cannabis use disorder and dissociation: A report from a prospective first-episode psychosis study.

BACKGROUND: Cannabis is the most used recreational drug worldwide. Its use can increase the risk of developing psychotic disorders and exacerbate their course. However, the relationship between cannabis use and dissociative symptoms has been scarcely investigated. AIMS: To examine differences in psychotic and dissociative symptoms, and in functioning in first-episode psychotic patients (FEPp) using cannabis compared with those not using cannabis. METHODS: Between January 2014 and December 2019, seventy FEPp with cannabis use disorder (N = 35) and without it (N = 35) were recruited in psychiatric inpatient facilities in the Italian regions of Lazio and Piemonte. All subjects were assessed at FEP, after 4 and 8 months, using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Dissociative Experiences Scale - II (DES-II). Detailed information on the pattern of cannabis and other substance use were collected. RESULTS: FEP using cannabis showed higher levels of positive symptomatology, dissociative experiences and worse functioning than their non-user counterpart, despite a comparable antipsychotic treatment. At an eight-month prospective evaluation, FEP using cannabis still showed higher levels of positive symptomatology and dissociation. Moreover, global functioning worsened over time in FEPp using cannabis, whereas it improved those not using it. DISCUSSION: Our findings suggest that a greater degree of dissociation and positive symptoms at FEPp and their persistence over time may characterise cannabis-associated psychosis. Both these factors might explain the overall functioning worsening over time that we observed in the cannabis-user group compared to the functioning improvement in the non-user group.

An overall framework for the E. coli γ-glutamyltransferase-catalyzed transpeptidation reactions.

γ-Glutamyl derivatives of proteinogenic or modified amino acids raise considerable interest as flavor enhancers or biologically active compounds. However, their supply, on a large scale and at reasonable costs, remains challenging. Enzymatic synthesis has been recognized as a possible affordable alternative with respect to both isolation procedures from natural sources, burdened by low-yield and by the requirement of massive amount of starting material, and chemical synthesis, inconvenient because of the need of protection/deprotection steps. The E. coli γ-glutamyltransferase (Ec-GGT) has already been proposed as a biocatalyst for the synthesis of various γ-glutamyl derivatives. However, enzymatic syntheses using this enzyme usually provide the desired products in limited yield. Hydrolysis and autotranspeptidation of the donor substrate have been identified as the side reactions affecting the final yield of the catalytic process. In addition, experimental conditions need to be specifically adjusted for each acceptor substrate. Substrate specificity and the fine characterization of the activities exerted by the enzyme over time has so far escaped rationalization. In this work, reactions catalyzed by Ec-GGT between the γ-glutamyl donor glutamine and several representative acceptor amino acids have been finely analyzed with the identification of single reaction products over time. This approach allowed to rationalize the effect of donor/acceptor molar ratio on the outcome of the transpeptidation reaction and on the distribution of the different byproducts, inferring a general scheme for Ec-GGT-catalyzed reactions. The propensity to react of the different acceptor substrates is in agreement with recent findings obtained using model substrates and further supported by x-ray crystallography and will contribute to characterize the still elusive acceptor binding site of the enzyme.

Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.