Nanoparticle-based chewable gels of praziquantel.

Chewable gels present significant advantages over conventional dosage forms, despite their development is not comprehensively assessed. In this sense, six formulations, varying gelatine concentration, dose, and form of incorporation of praziquantel, were developed and characterized. The novelty of this approach focused not only on the development of the formulation itself but also on the incorporation of the drug in a nanoparticulated form. The obtained results for moisture content, water activity, pH, and drug content were within the expected values for this type of formulation. On the other hand, texture and disintegration parameters were influenced by the form of incorporation of praziquantel and the amount of gelatine added. Finally, in vitro dissolution of chewable gels showed significant differences with intermediate products, though the improved dissolution of the nanoparticulated drug was maintained. In conclusion, nanoparticulate drugs can be incorporated into these semisolid formulations and could be successfully applied to other low-aqueous solubility drugs.

A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique

Purpose Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. Methods patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. Results 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2–22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2–7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. Conclusion Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed (AU)

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique.

PURPOSE: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. METHODS: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. RESULTS: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. CONCLUSION: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.

Diabetic retinopathy in well-controlled type 2 diabetes: Role of glycaemic memory.

AIMS: As diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to 'glucose memory' by evaluating patients' HbA1c over previous years and their skin autofluorescence (SAF). METHODS: In 334 patients with T2D and HbA1c levels≤8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment]. RESULTS: Our patients were mostly men (58.4%) aged 63±10years, with a duration of diabetes of 13±10years and HbA1c=7.1±0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods -4±3 months (n=255), -16±4months (n=152), -30±4months (n=93) and -62±26 months (n=105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR=6.75, 95% CI: 1.90-23.90. Moreover, SAF values were higher in those with DR [2.95±0.67 arbitrary units (AU)] vs 2.65±0.65 AU with no DR (P<0.01) and were also associated with the oldest previous HbA1c values (P<0.01). CONCLUSION: Our study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5years prior to study admission and their SAF values, a marker of glucose memory.

Work stress on rise? Comparative analysis of trends in work stressors using the European working conditions survey.

OBJECTIVE: The rapid transformation of labor markets has been accompanied by the belief of rising stress at work. However, empirical evidence on such trends based on reliable survey data is scarce. This study analyzes long-term trends in well-established measures of work stressors across Europe, as well as potential occupational differences. METHODS: We use repeated cross-sectional data of 15 European countries from waves 1995, 2000, 2005, 2010, and 2015 of the European Working Conditions Surveys. We apply three-way multilevel regressions (with employees nested in country-years, which are in turn nested in countries) to analyze trends in work stressors measured according to the demand-control and effort-reward imbalance models. Trends by occupational groups are also assessed. RESULTS: Our findings suggest that work stress generally increased from 1995 to 2015, and that the increase was mostly driven by psychological demands. People working in lower-skilled occupations had generally higher levels of job strain and effort-reward imbalance, as well as they tend to have a steeper increase in job strain than people working in higher-skilled occupations. Most of the change occurred from 1995 to 2005. CONCLUSION: Our results indicate that work stress has been on rise since 1995, specifically for people working in disadvantageous occupations. This directs the attention to the vulnerable position of the least skilled and also to the use of preventive measures to counteract some of the disadvantages experienced by this occupational group.

Correction to: Associations between change in labour market policies and work stressors: a comparative longitudinal survey data analysis from 27 European countries.

An amendment to this paper has been published and can be accessed via the original article.

Associations between change in labour market policies and work stressors: a comparative longitudinal survey data analysis from 27 European countries.

BACKGROUND: Many studies have shown that work stressors have a negative impact on health. It is therefore important to gain an understanding of how work stressors can be reduced. Recent studies have shown that employees in countries with high investments into labour market policies less often report exposure to work stressors. Although these studies are indicative of an influence of the political level on work stressors, they are based on cross-sectional cross-country analyses where causal assumptions are problematic. The aim of this study is to extend the existing evidence by longitudinally testing whether changes in labour market policies are related to changes in work stressors. METHODS: We used comparative longitudinal survey data from the European Working Conditions Survey (27 countries; for the years 2005, 2010, 2015). The measurement of work stressors is based on two established work stress models: effort-reward imbalance (ERI) and job demand-control (job strain). To measure labour market policies, we used information on active (ALMP) and passive labour market policies (PLMP). After excluding persons with missing data, 64,659 participants were eligible for the ERI and 67,114 for job strain analyses. Estimation results are provided by three-way multilevel models (individuals, country-years, country), which allow us to estimate longitudinal and cross-country macro-effects. RESULTS: An increase in ALMP leads to a decrease of ERI. The analyses for the subcomponents 'effort' and 'reward' showed that mainly the 'reward' component is positively associated with ALMP. The association between ALMP and 'reward' shows that an increase in ALMP investments is related to an increase in rewards. Yet, no significant longitudinal associations between ALMP and job strain, and between PLMP and the work stressors, were observed. CONCLUSIONS: The study extends the current knowledge with longitudinal information by showing that an increase in ALMP is associated with an increase in rewards and a decrease of ERI. These longitudinal analyses may support a causal interpretation. The findings of this study have important policy implications. Our main result suggests that investments into ALMP can lead to better working conditions.

ChaperISM: improved chaperone binding prediction using position-independent scoring matrices.

MOTIVATION: Understanding the mechanisms of client protein interaction with Hsp70 chaperones is essential to analyze the complex dynamics in the context of normal or dysregulated metabolism. Because Hsp70 can bind millions of proteins, including key molecules involved in processes of stemness, tumorigenesis and survival, in silico prediction of Hsp70 interactions has great value in validating possible new clients. Currently, two algorithms are available to predict binding to DnaK-the bacterial Hsp70-but both are based on amino acid sequence and energy calculations of qualitative information-binders and non-binders. RESULTS: We introduce a new algorithm to identify Hsp70 binding sequences in proteins-ChaperISM-a position-independent scoring matrix trained on either qualitative or quantitative chemiluminescence data previously published, which were obtained from the interaction between DnaK and different ligands. Both versions of ChaperISM, qualitative or quantitative, resulted in an improved performance in comparison to other state-of-the-art chaperone binding predictors. AVAILABILITY AND IMPLEMENTATION: ChaperISM is implemented in Python version 3. The source code of ChaperISM is freely available for download at https://github.com/BioinfLab/ChaperISM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Orphan Formulations in Pediatric Schistosomiasis Treatment: Development and Characterization of Praziquantel Nanoparticle-Loaded Powders for Reconstitution.

Praziquantel is a broad spectrum antihelmintic agent and represents the drug of choice for the treatment of schistosomiasis. However, its low aqueous solubility and strong bitter taste highly affect the bioavailability and compliance in pediatric patients. Thus, the purpose of this study was to develop a dry nanosuspension, by a combination of high-pressure homogenization and spray drying, intended for redispersion in a pleasant taste vehicle for extemporaneous use. Three formulations, varying stabilizers to drug ratio, were developed and characterized in terms of particle size distribution, crystallinity, morphology, in vitro dissolution, and sedimentation-redispersibility behavior. A significant reduction in particle size was achieved after the high-pressure homogenization process, and the nanoparticles were further microencapsulated by spray drying technique. The redispersed dried powders exhibited a conserved particle size distribution (in the nanometric range) and certain crystallinity extent, with satisfactory redispersion ability. Besides, the enhancement of the dissolution performance obtained after comminution was conserved, even after drying and redispersion of the extemporaneous powdered formulation. In conclusion, the developed nanoparticle-loaded powders comprise an interesting tool for the administration of praziquantel to preschool-age children.

Near-infrared spectroscopic applications in pharmaceutical particle technology.

Near-infrared spectroscopy (NIRS) is nowadays an established analytical technique in the pharmaceutical industry. The aim of this review is to present the progress of NIRS in providing useful information for pharmaceutical particle technology. NIR methods are now developed to characterize a wide variety of materials (active pharmaceutical ingredients, excipients, co-processed powders, and physical mixtures) and pharmaceutical dosage forms (conventional, modified drug release technologies, and phytomedicines). This review also provides a number of spectra to illustrate the fundamental understanding of NIRS which has been gained. The sampling that must occur prior to the acquisition of near-infrared spectra is also discussed, as well as developments in monitoring mixing, tableting, and coating. This review will be valuable for product formulation and process engineering specialists.

Praziquantel systems with improved dissolution rate obtained by high pressure homogenization.

Praziquantel (PZQ), an antihelmintic agent commonly administered to humans and cattle, has low aqueous solubility, which compromises its bioavailability and efficacy. The purpose of this study was to develop a new formulation, in order to improve PZQ dissolution rate. PZQ dispersions have been developed by high-pressure homogenization (HPH) using different stabilizers, selected upon PZQ saturation solubility. After the screening, two promising formulations were developed, combining poloxamer 188 with polyvinylpyrrolidone or maltodextrin. Characterization studies including particle size distribution, crystallinity, morphology, drug content, and in vitro dissolution profiles, were performed over selected formulations. The scanning electronic micrographs revealed that the morphology of suspended particles corresponded to elongated shapes, with an average particle size close to the micron range. X-ray powder diffractometry and differential scanning calorimetry results confirmed the drug crystallinity, before and after the HPH process. Besides, differential scanning calorimetry revealed the absence of interactions between PZQ and excipients. The dissolution rate of PZQ dispersions was significantly enhanced compared with raw PZQ, either in phosphate buffer or hydrochloric acid, mainly due to particle size reduction, thus improved saturation solubility.

2,4,6-Triphenylphosphinine and 2,4,6-triphenylposphabarrelene revisited: synthesis, reactivity and coordination chemistry.

The synthesis of 2,4,6-triphenylphosphinine has been revisited and a general protocol for the preparation of such low-coordinate phosphorus compounds in good to excellent yields could be established. This allows to investigate several aspects of the chemistry of 2,4,6-triarylphosphinine, such as the reaction with in situ generated benzyne to give 2,4,6-triphenylphosphabarrelene. The corresponding 2,4,6-triphenylphosphabarrelene-selenide could be characterized crystallographically for the first time and the structural and electronic properties of this cage-compound in comparison to classical triarylphosphines could be evaluated. Moreover, [(L)W(CO)5)] complexes of both 2,4,6-triphenylphosphinine and 2,4,6-triphenylphosphabarrelene were prepared and characterized by means of X-ray crystallography. This allowed for the first time a direct structural comparison of these related phosphorus compounds, coordinated to the same metal fragment.

Responsivity to PGE2 labor induction involves concomitant differential prostaglandin E receptor gene expression in cervix and myometrium.

Prostaglandin E2 (dinoprostone) is largely used for labor induction. However, one-third of patients do not respond to treatment. One cause of this poor response may be associated with changes in regulation of prostaglandin E receptors (EP1-4). In this study, we investigated EP mRNA expression in the uterine cervix and lower uterine segment myometrium for term births. Biopsies were obtained from women with successful (responders) and failed (non-responders) dinoprostone labor induction, while women that underwent spontaneous labor were included as controls. EP1 mRNA was upregulated in the cervical tissue of women who did not respond to dinoprostone induction. In addition, in the myometrium, significantly higher levels of EP3 mRNA were observed in women treated with dinoprostone, independent of their responsiveness. Dinoprostone-responders presented 3.6-fold higher levels of EP3 mRNA expression than the spontaneous labor group. Significantly higher levels of EP3 mRNA in the myometrium of the dinoprostone-treated group indicated that dinoprostone may regulate the EP3 gene on the transcriptional level. These results highlight the relationship between EP gene expression and delivery and indicate that understanding the regulation of prostaglandin E receptors may lead to improved labor induction.

Actual evidence in the medical approach to adolescents with idiopathic scoliosis.

Idiopathic scoliosis (IS) is a three-dimensional deformity of the spine and trunk. The most common form involve adolescents. The prevalence is 2-3% of the population, with 1 out of 6 patients requiring treatment of which 25% progress to surgery. Physical and rehabilitation medicine (PRM) plays a primary role in the so-called conservative treatment of adolescents with IS, since all the therapeutic tools used (exercises and braces) fall into the PRM domain. According to a Cochrane systematic review there is evidence in favor of bracing, even if it is of low quality. Recently, a controlled prospective trial including a randomised arm gave more strength to this conclusion. Another Cochrane review shows that there is evidence in favor of exercises as an adjunctive treatment, but of low quality. Three meta-analysis have been published on bracing: one shows that bracing does not reduce surgery rates, but studies with bracing plus exercises were not included and had the highest effectiveness; another shows that full time is better than part-time bracing; the last focuses on observational studies following the Scoliosis Research Society (SRS) criteria and shows that not all full time rigid bracing are the same: some have the highest effectiveness, others have less than elastic and nighttime bracing. Two very important RCTs failed in recruitment, showing that in the field of bracing for scoliosis RCTs are not accepted by the patients. Consensuses by the international Society on Scoliosis Orthopedic and Rehabilitation Treatment (SOSORT) show that there is no agreement among experts either on the best braces or on their biomechanical action, and that compliance is a matter of clinical more than patients' behavior (there is strong agreement on the management criteria to achieve best results with bracing). A systematic review of all the existing studies shows effectiveness of exercises, and that auto-correction is their main goal. A systematic review shows that there are no studies on manual treatment. The SOSORT Guidelines offer the actual standard of conservative care.

Bracing for scoliosis in 2014: state of the art.

Bracing is currently the primary method for treating moderate idiopathic scoliosis (IS) during the developmental phase of growth. Following a lengthy debate, during which researchers and authors questioned the role of bracing in the treatment of IS due to inconsistent evidence, the Bracing in Adolescent Idiopathic Scoliosis Trial study have provided a high level of evidence to the value of bracing and may have convinced most of those who were skeptic. However, although some guidelines have been published, there remains no standard for constructing scoliosis orthoses and no standard treatment protocol. The Scoliosis Research Society criteria were established to provide a framework by which to research bracing and adolescent idiopathic scoliosis, and the Society on Scoliosis Orthopedic and Rehabilitation Treatment criteria were published to guarantee a minimum level of expertise for MDs and CPOs involved in the brace treatment. However, very few contemporary papers follow both sets of criteria, and the extensive variety of braces makes it difficult to determine if one is superior to another. The aim of this paper is to provide an overview of state-of-the-art brace treatment, highlighting commonly used braces and their history, biomechanical concept, and results, as reported in published literature. Specific focus is placed on European (i.e., Chêneau and derivatives, Dynamic Derotating, Lyon, PASB, Sforzesco, TLI, TriaC) and North American (i.e. Boston, Charleston, Milwaukee, Providence, Rosenberger, SpineCor, Wilmington) designs. Details about different building techniques are also reported, along with recently developed tools that are designed to monitor compliance.

Challenges and opportunities in polymer technology applied to veterinary medicine.

An important frontier in the administration of therapeutic drugs to veterinary species is the use of different polymers as drug delivery platforms. The usefulness of polymers as platforms for the administration of pharmaceutical and agricultural agents has been clearly recognized in the recent decades. The chemical versatility of polymers and the wide range of developed controlled-release strategies enhance the possibilities for the formulation of active molecules. In particular, the veterinary area offers opportunities for the development of novel controlled-release drug delivery technologies adapted to livestock or companion animal health needs. In some cases, it also allows to improve profitability in meat production or to meet the safety criteria related to drug residues. A number of factors affect the selection of polymers and subsequent properties of the controlled-release drug delivery system. However, their selection also dictates the release kinetics of the drug from the delivery system. Such choices are therefore crucial as they affect the success and potential of the delivery system for achieving the therapeutic goals of the veterinarian. It is the intention of this review to give an overview of the most relevant polymers, which are used or have been tested as drug delivery release rate modifiers in the veterinary field. The article highlights some recent developments focusing on their advantages and applications and analyzes the future direction of the scientific and technological advancements in this area.

The functional role of oxytocin in the induction of oocyte meiotic resumption in cattle.

The aim of the present study was to examine the role of oxytocin (OT) in the progesterone (P4) and prostaglandins (PGs) pathway to induce oocyte meiotic resumption. Cumulus-oocyte complexes were co-cultured with follicular hemisections for 15 h to determine the effects of different doses of OT or atosiban (ATO; oxytocin receptor antagonist) on oocyte meiotic resumption. In another experiment, we examined the effect of the interaction between P4, OT and PGs on the regulatory cascade of the oocyte meiotic resumption. Oxytocin at 1 µm was effective in inducing meiotic resumption in oocytes co-cultured with follicular cells (84.0%), not differing from the positive control group (74.4%). Atosiban inhibited in a dose-dependent manner the positive effect of OT on the meiotic resumption (27.6% metaphase I with 10 µm of ATO, which did not differ from the 25.5% of the negative control group). Furthermore, a third experiment showed that P4 was able to induce oocyte meiotic resumption, which was inhibited by ATO. However, the OT positive effect was not blocked by mifepristone (P4 antagonist), but was inhibited by indomethacin (a non-selective PTGS2 inhibitor). Collectively, these data suggest a sequential role of P4, OT and PGs in the induction of oocyte meiotic resumption.

Fabrication of a porous fiber cladding material using microsphere templating for improved response time with fiber optic sensor arrays.

A highly porous optical-fiber cladding was developed for evanescent-wave fiber sensors, which contains sensor molecules, maintains guiding conditions in the optical fiber, and is suitable for sensing in aqueous environments. To make the cladding material (a poly(ethylene) glycol diacrylate (PEGDA) polymer) highly porous, a microsphere templating strategy was employed. The resulting pore network increases transport of the target analyte to the sensor molecules located in the cladding, which improves the sensor response time. This was demonstrated using fluorescein-based pH sensor molecules, which were covalently attached to the cladding material. Scanning electron microscopy was used to examine the structure of the templated polymer and the large network of interconnected pores. Fluorescence measurements showed a tenfold improvement in the response time for the templated polymer and a reliable pH response over a pH range of five to nine with an estimated accuracy of 0.08 pH units.

'SOSORT consensus paper on brace action: TLSO biomechanics of correction (investigating the rationale for force vector selection)'.

BACKGROUND: The effectiveness of orthotic treatment continues to be controversial in international medical literature due to differences in the reported results and conclusions of various studies. Heterogeneity of the samples has been suggested as a reason for conflicting results. Besides the obvious theoretical differences between the brace concepts, the variability in the technical factors can also explain the contradictory results between same brace types. This paper will investigate the degree of variability among responses of scoliosis specialists from the Brace Study Ground of the International Society on Scoliosis Orthopedic and Rehabilitation Treatment SOSORT. Ultimately, this information could be a foundation for establishing a consensus and framework for future prospective controlled studies. METHODS: A preliminary questionnaire on the topic of 'brace action' relative to the theory of three-dimensional scoliosis correction and brace treatment was developed and circulated to specialists interested in the conservative treatment of adolescent idiopathic scoliosis. A particular case was presented (main thoracic curve with minor lumbar). Several key points emerged and were used to develop a second questionnaire which was discussed and full filed after the SOSORT consensus meeting (Milano, Italy, January 2005). RESULTS: Twenty-one questionnaires were completed. The Chêneau brace was the most frequently recommended. The importance of the three point system mechanism was stressed. Options about proper pad placement on the thoracic convexity were divided 50% for the pad reaching or involving the apical vertebra and 50% for the pad acting caudal to the apical vertebra. There was agreement about the direction of the vector force, 85% selecting a 'dorso lateral to ventro medial' direction but about the shape of the pad to produce such a force. Principles related to three-dimensional correction achieved high consensus (80%-85%), but suggested methods of correction were quite diverse. CONCLUSION: This study reveals that among participating SOSORT specialists there continues to be a strongly held and conflicting if not a contentious opinion regarding brace design and treatment. If the goal of a 'treatment consensus' is realistic and achievable, significantly more effort will be required to reconcile these differences.