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.

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.

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.

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.

[Risk factors linked to the transmission of papilloma virus in the school environment. Alicante, 1999]. / Factores de riesgo asociados a la transmisión de papilomavirus en un ámbito escolar. Alicante, 1999.

OBJECTIVE: The aim of this study is to describe an outbreak of plantar warts and to analyse the risk factors wich determining the transmission. DESIGN: Cross-sectional survey. SETTING: A school of Alicante. PARTICIPANTS: 1,620 students. MEASUREMENTS AND MAIN RESULTS: Description and analysis of the outbreak. We studied the magnitude and the association between risk factors (sports activities and hygiene habits) and disease by logistic regression model. We estimated the crudes and adjusted odds ratio (OR) and the confidence intervals (CI) of 95%. We carry out environmental study and active search of cases. The global rate of answer to the cross-secctional survey was 70.86%. Reported cases were 221, the global attack rate was 19.25%. The outbreak occurred over 16 months. We did not find statistical significal difference either by sex (P=.138) or age (P=.233). The hygiene conditions of the swimming pool and the changing room were adapted. The risk of disease increased with the number of activities taking place (P=.001). The OR adjusted for hygiene habits was: use of changing room 0.95 (95% CI, 0.38%-2.41%), use of shower rooms 1.06 (95% CI, 0.70%-1.62%), walking barefoot in the changing room 1.97 (95% CI, 1.39%-2.79%) and showering barefoot 0.97 (95% CI, 0.58%-1.64%). CONCLUSIONS: Outbreak of person to person transmission, the floor of the changing rooms was the prime cause of transmission. We did not find any association between the use of public swimming pool and the disease

Effect of conservative management on the prevalence of surgery in patients with adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective analysis of outcome in terms of prevalence of surgery for adolescent idiopathic scoliosis in patients receiving conservative management. OBJECTIVES: To determine whether a centre with an active policy of conservative management has fewer patients who eventually undergo surgery for adolescent idiopathic scoliosis than a centre where the practice is non-intervention. BACKGROUND DATA: The efficacy of orthoses for the treatment of idiopathic scoliosis was called into question in a recent publication. Because the prevalence of surgery in an untreated group of patients (28.1%) was not significantly different from that in a braced group (22.4%), the authors concluded that bracing appears to make no difference. Based on prior experience, this conclusion is questioned. METHODS: Since 1991, bracing and physical therapy have been recommended for children with adolescent idiopathic scoliosis at a centre in Barcelona, Spain. The scoliosis database was searched for patients with adolescent idiopathic scoliosis who were at least 15 years of age at last review and who had adequate documentation of the Cobb angle. The prevalence of surgery was compared with that of published data from a centre where the practice is non-intervention. RESULTS: From a total of 106 braced cases out of which 97 were followed up, six cases (5.6%) ultimately underwent spinal fusion. A worst case analysis, which assumes that all nine cases that were lost to follow-up had operations, brings the uppermost number of cases that could have undergone spinal fusion to 15 (14.1%). Either percentage is significant statistically when compared to the 28.1% reported surgeries from the centre with the policy of non-intervention. CONCLUSIONS: If conservative management does reduce the proportion of children with adolescent idiopathic scoliosis that require surgery, it can be said to provide a real and meaningful advantage to both the patients and the community. It is contended that conservative methods of treatment should never be ruled out from scoliosis management, because they can and do offer a viable alternative to those patients who cannot or will not opt for surgical treatment.

Repair of common bile duct defects using the gallbladder or cystic duct as a pedicled graft.

To repair defects in the common bile duct, part of the gallbladder and the cystic duct may be used as a pedicled graft. This has the advantage of an independent blood supply and a related mucosal lining. The method is illustrated by four patients who had excellent primary and short term results. In two patients, the defect was due to large cholecystocholedochal fistulas caused by migrating large gallstones. In one patient with marked stenosis of the duct, the defect occurred when the stenosis was opened through a longitudinal incision. The fourth patient had a large duodenal ulcer that penetrated into the common duct, causing a defect that could not be closed by suture. A definite evaluation of the procedure must await a longer period of follow-up study.