Πέμπτη 19 Νοεμβρίου 2020

Urea entrapment in cellulose acetate microparticles obtained by electrospraying

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Abstract

Urea is a widely used source of nitrogen, but its rapid solubilization in water leads to significant wastage on application. Thus, the quest for an efficient and economical polymeric matrix able to encapsulated urea is a long-standing challenge. In this paper, we present a simple and economical method for urea entrapment in cellulose acetate (CA) microparticles produced by the electrospraying process. The morphology and diameter of the microparticles were optimized experimentally by evaluating the solvent composition (binary mixture) and polymer concentration. The electrospraying process parameters, such as particle collection distance, applied voltage and flow rate, were also evaluated. The particle diameter was determined by scanning electron microscopy (SEM) and the CA microparticle characteristics, urea incorporation and in vitro release profile were determined by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetr y (DSC). The morphological characteristics (shape and porosity) of the CA microparticles were affected by the diffusion rate and CA solubility due to solvent evaporation in the electrospraying process. The SEM images showed monodispersed and spherical CA microparticles with a diameter size of 2.2 ± 0.3 µm. The FTIR spectra and SEM images verified the urea entrapment in the CA microparticles (100 mg/g), and the particle morphology did not appear to be affected. The release of urea from the CA microparticles showed a maximum of 79% after 7 h, which is a significant difference in relation to in vitro urea release. The results obtained using the electrospray technology represent a step forward in the search to improve the incorporation of urea into CA microparticles.

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Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments

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Abstract

Autism spectrum disorders (ASD) are subdivided into idiopathic (unknown) etiology and secondary, based on known etiology. There are hundreds of causes of ASD and most of them are genetic in origin or related to the interplay of genetic etiology and environmental toxicology. Approximately 30 to 50% of the etiologies can be identified when using a combination of available genetic testing. Many of these gene mutations are either core components of the Wnt signaling pathway or their modulators. The full mutation of the fragile X mental retardation 1 (FMR1) gene leads to fragile X syndrome (FXS), the most common cause of monogenic origin of ASD, accounting for ~ 2% of the cases. There is an overlap of molecular mechanisms in those with idiopathic ASD and those with FXS, an interaction between various signaling pathways is suggested during the development of the autistic brain. This review summarizes the cross talk between neurobiological pathways found in ASD and FXS. These signaling pathways are currently under evaluation to target specific treatments in search of the reversal of the molecular abnormalities found in both idiopathic ASD and FXS.

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BDNF rs6265 Variant Alters Outcomes with Levodopa in Early-Stage Parkinson’s Disease

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Abstract

Disease outcomes are heterogeneous in Parkinson's disease and may be predicted by gene variants. This study investigated if the BDNF rs6265 single nucleotide polymorphism (SNP) is associated with differential outcomes with specific pharmacotherapy treatment strategies in the "NIH Exploratory Trials in PD Long-term Study 1" (NET-PD LS-1, n = 540). DNA samples were genotyped for the rs6265 SNP and others (rs11030094, rs10501087, rs1491850, rs908867, and rs1157659). The primary measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and its motor component (UPDRS-III). Groups were divided by genotype and treatment regimen (levodopa monotherapy vs levodopa with other medications vs no levodopa). T allele carriers were associated with worse UPDRS outcomes compared to C/C subjects when treated with levodopa monotherapy (+ 6 points, p = 0.02) and to T allele carriers treated with no levodopa treat ment strategies (UPDRS: + 8 points, p = 0.01; UPDRS-III: + 6 points, p = 0.01). Similar effects of worse outcomes associated with levodopa monotherapy were observed in the BDNF rs11030094, rs10501087, and rs1491850 SNPs. This study suggests the levodopa monotherapy strategy is associated with worse disease outcomes in BDNF rs6265 T carriers. Pending prospective validation, BDNF variants may be precision medicine factors to consider for symptomatic treatment decisions for early-stage PD patients.

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Green synthesis of CuFeS 2 nanoparticles using mimosa leaves extract for photocatalysis and supercapacitor applications

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Abstract

We successfully synthesized CuFeS2 nanoparticles (NPs) using a simple synthesis method mediated by touch me not (Mimosa pudica) leaves extract. X-ray diffraction (XRD) was used to analyze the structural properties, and it shows that the CuFeS2 NPs have a tetragonal structure and quasi-pyramidal NPs of an average crystallite size of 31.0 nm with a secondary phase of few minor peaks of covellite (CuS). The optical characterization showed that CuFeS2 NPs have band gap energy ranges of 1.98–2.46 eV for different annealing temperatures. The electrochemical properties of the CuFeS2 NPs were investigated using cyclic voltammetry (CV), galvanostatic charge discharge (GCD), and electrochemical impedance spectroscopy (EIS). An appreciable value of specific capacitance of 501.4 F/g was obtained at a scan rate of 10 mV/s for the CuFeS2 NPs annealed at 250 °C which can be said to be within the optimum ideal annealing temperature for CuFeS2 NPs. The CuFeS2 NPs was used in the photodegradation of methylene blue (MB) under of solar irradiation. The highest rate constant of 3.1 × 10−2 min−1 and degradation efficiency of 98% were obtained for the unannealed CuFeS2 NPs with good stability after three cycles. Therefore, the synthesized CuFeS2 NPs were obtained using a Mimosa pudica leaves extract prospective application in both electrochemical energy storage devices and treatment of water contaminants. GO was added to increase the active sites for these ions, surface area, and conductivity of these electrodes for enhanced supercapacitive performance.

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Laparoscopic Greater Curvature Plication for the Treatment of Obesity: a Systematic Review

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Abstract

Background

During the last decade, laparoscopic greater curvature plication (LGCP) has been used as a bariatric procedure for the treatment of obesity, regarded as less invasive and less expensive than other surgical bariatric procedures. We aimed to systematically review the literature and highlight recent clinical data regarding outcomes of LGCP in the treatment of obesity.

Methods

A comprehensive research of Pubmed database on LGCP was performed. The search was conducted on the first of May 2020 and was not limited to any date range. Outcomes of interest were surgical technique, postoperative complications, weight loss outcomes, comorbidities improvement or resolution, and revisional surgeries after technical failure or weight regain.

Results

Fifty-three articles were eligible for inclusion, with 3103 patients undergoing LGCP (mean age: 13.8–55 years). Mean preoperative body mass index (BMI) ranged from 31.2 to 47.8 kg/m2. Mean operative time ranged from 48 to 193 min. Length of hospital stay ranged from 0.75 to 7.2 days. Most studies provided postoperative follow-up up to 12 months. Mean percentage of excess weight loss (%EWL) ranged from 30.2 to 71.1% and 35 to 77.1% at 6 and 12 months post-LGCP, respectively. Only one study followed patients for more than 10 years and mean %EWL at 1, 5, and 10 years was 67%, 55%, and 42%, respectively.

Conclusion

LGCP seems to be an acceptable surgical procedure for the treatment of obesity, especially in centers having a low medical budget. However, most existing comparative studies report superiority of LSG regarding weight loss.

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A Randomized, Controlled Trial Comparing the Impact of a Low-Calorie Ketogenic vs a Standard Low-Calorie Diet on Fat-Free Mass in Patients Receiving an Elipse™ Intragastric Balloon Treatment

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Abstract

Background

The Elipse™ intragastric balloon (EIGB) is a new swallowable balloon for weight loss (WL). Preserving metabolically active fat-free mass (FFM) and resting metabolic rate (RMR) during WL are crucial to maximize fat mass (FM) loss. After EIGB placement, a standard low-calorie diet (LCD) is generally prescribed. A low-calorie ketogenic diet (LCKD) has proven to be safe and effective in reducing FM while preserving FFM and RMR.

Objective

To prospectively compare the effects on WL, FM, FFM, and RMR in two groups of patients who were randomized to two different diets: LCKD and a standard LCD after EIGB placement.

Methods

WL, FM, FFM, and RMR were measured before EIGB and at 4 months in 48 patients who received either a LCKD (n = 24) or a standard LCD (n = 24). Compliance in following the prescribed diet was determined with food frequency questionnaires in all patients. The impact of LCKD and LCD on renal function was also evaluated.

Results

The LCKD group showed a significantly lower decrease in FFM and RMR when compared with the LCD group (3.55 vs 14.3%, p < 0.001; 9.79 vs 11.4%, p < 0.001, respectively). FM decreased more significantly with LCKD compared to LCD (41.6 vs 33.1%, p = 0.0606). Compliance in following the prescribed diets, without negative impact on renal function, was found.

Conclusion

Based on our findings, despite the small sample size, we were able to support the hypothesis that LCKD is associated with an increased FM loss while reducing the FFM loss and the RMR, without interfering with renal function after EIGB.

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Antimicrobial Stewardship in the Intensive Care Unit: The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics

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Abstract

The high prevalence of infectious diseases in the intensive care unit (ICU) and consequently elevated pressure for immediate and effective treatment have led to increased antimicrobial therapy consumption and misuse. Moreover, the emerging global threat of antimicrobial resistance and lack of novel antimicrobials justify the implementation of judicious antimicrobial stewardship programs (ASP) in the ICU. However, even though the importance of ASP is generally accepted, its implementation in the ICU is far from optimal and current evidence regarding strategies such as de-escalation remains controversial. The limitations of clinical guidance for antimicrobial therapy initiation and discontinuation have led to multiple studies for the evaluation of more objective tools, such as biomarkers as adjuncts for ASP. C-reactive protein and procalcitonin can be adequate for clinical use in acute infectious diseases, the latter being the most studied for ASP purposes. Althoug h promising, current evidence highlights challenges in biomarker application and interpretation. Furthermore, the physiological alterations in the critically ill render pharmacokinetics and pharmacodynamics crucial parameters for adequate antimicrobial therapy use. Individual pharmacokinetic and pharmacodynamic targets can reduce antimicrobial therapy misuse and risk of antimicrobial resistance.

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Physical Activity, Medical Home, and Health Behavior Counseling Among Adolescents with Special Health Care Needs: NSCH 2016–2017

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Abstract

Objectives

Aim 1 was to establish updated prevalence estimates for meeting national physical activity (PA) guidelines among adolescents with and without special healthcare needs (SHCN), 12–17 years old. To identify at-risk subgroups, our sub-aim was to compare the distribution of prevalence estimates across PA levels by SHCN subtypes, and in reference to peers without SHCN. Aim 2 was to examine the association between meeting PA guidelines, having a medical home, and receiving positive health behavior counseling in this population.

Methods

Weighted prevalence estimates for meeting the 2018 National PA Guidelines (inactive, insufficiently active, sufficiently active: guidelines met) were calculated from a secondary analysis of the National Survey of Children's Health 2016–2017 ( n = 16,171, 27% SHCN). Adjusted odds ratios and 95% CIs were estimated from logistic regression models to measure the association between PA, medical home, and postive health behavior counseling.

Results

Of adolescents with SHCN, 15% were reported to be meeting PA guidelines compared to 19% of peers without SHCN peers. Among adolescents with a medical home, regardless of SHCN status, those receiving positive health behavior counseling had 1.70 times the adjusted odds of meeting PA guidelines compared to peers without counseling.

Conclusions for Practice

Adolescents with and without SHCN were more likely to meet PA guidelines if they had a medical home and received positive health behavior counseling, highlighting the value of comprehensive healthcare practices for PA promotion.

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Seeking international consensus on approaches to primary tumour treatment in Ewing sarcoma

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Abstract

Background

The local treatment of Ewing sarcoma of bone involves surgery, radiotherapy or both. The selection of treatment depends on the anatomical extent of the tumour, the effectiveness of the proposed treatment, its morbidity, and the expectation of cure. However, not only are there variations in the approach to local treatment between individual patients, but also between treatment centres and countries. Our aim was to explore variation in practice and develop consensus statements about local treatment.

Methods

A three stage modified Delphi technique was used with international collaborators. This involved an expert panel to identify areas of controversy, an online survey of international collaborators and a consensus meeting in London, UK in June 2017. In the consensus meeting, teams of clinicians discussed the local management of selected cases and their responses were collected with electronic voting.

Results

Areas of greater or less consensus were identified. The lack of evidence underpinning different approaches was noted and areas for collaborative research became apparent.

Conclusion

This has demonstrated that there is an international consensus around many aspects of the local treatment of Ewing sarcoma of bone, including the use of specialist MultiDisciplinary Team (MDT) meetings with access to all appropriate treatments. However, considerable variation remains including the use of different staging investigations, decision making, definitions of response, and radiotherapy doses and timing. Further collaborative work should be undertaken to determine the impact of these variations in order to define best practice.

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Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study

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Abstract

Background

We recently reported outcomes from a Scandinavian Sarcoma Group adjuvant study (SSG XX group A) conducted on localized and operable high risk soft tissue sarcoma (STS) of the extremities and trunk wall. SSG XX, group B, comprised of patients in a defined cohort with locally advanced STS considered at high risk for intralesional surgery. These patients received preoperative accelerated radiotherapy, together with neoadjuvant and adjuvant chemotherapy. Herein we report the results of this group B.

Methods

Twenty patients with high-grade, locally advanced and deep STS located in lower extremities (n = 12), upper extremities (5) or trunk wall (3) were included. The median age was 59 years and 14 patients were males. The treatment regimen consisted of 6 cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2), with three cycles given neoadjuvantly, and preoperative radiotherapy (1, 8 Gyx2/daily to 36 Gy) between cycles 2 and 3. After a repeated MRI surgery was then conducted, and the remaining 3 chemotherapy cycles were given postoperatively at 3 weeks intervals. Survival data, local control, toxicity of chemotherapy and postoperative complications are presented.

Results

Median follow-up time for metastasis-free survival (MFS) was 2.8 years (range 0.3–10.4). The 5-year MFS was 49.5% (95% confidence interval [CI] 31.7–77.4). The median follow-up time was 5.4 years (range 0.3–10.4) for overall survival (OS). The 5-year OS was 64.0% (95% CI 45.8–89.4). The median tumour size was 13 cm, with undifferentiated pleomorphic sarcoma (n = 10) and synovial sarcoma (n = 6) diagnosed most frequently. All patients completed surgery. Resection margins were R0 in 19 patients and R1 in 1 patient. No patients had evidence of disease progression preoperatively. Three patients experienced a local recurrence, in 2 after lung metastases had already been diagnosed. Eleven patients (55%) had postoperative wound problems (temporary in 8 and persistent in 3).

Conclusions

Preoperative chemotherapy and radiotherapy were associated with temporary wound-healing problems. Survival outcomes, local control and toxicities were deemed satisfactory when considering the locally advanced sarcoma disease status at primary diagnosis.

Trial registration This study was registered at ClinicalTrials.gov Identifier NCT00790244 and with European Union Drug Regulating Authorities Clinical Trials No. EUDRACT 2007-001152-39

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Solitary extrapleural fibrous tumor with hepatic bilobar metastases: multimodal approach treatment

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Abstract

Background

Solitary fibrous tumor is an unusual fibroblastic mesenchymal neoplasm typically described in the pleura. It may appear anywhere with a varied anatomic distribution and essentially it can develop from any soft tissue or visceral location. Its course is usually indolent and it rarely causes distant metastases, so it has a prolonged survival rate. It sometimes presents itself as a disseminate disease being the liver the most frequently involved location. In these occasions, the management should be discussed in a multidisciplinary tumor committee formed by surgeons, oncologists and radiologists. Surgery remains the gold standard for treatment.

Case representation

We present the case of a woman with a tumor in the left abdominal wall and bilobar massive liver metastases, both locations histologically diagnosed as solitary fibrous tumor. She receives biological treatment for a severe case of Crohn´s disease. Evaluated in a multidisciplinary committee, surgery was recommended for both the primary lesion and the liver metastases. The hepatobiliary surgeons considered a two-stage hepatectomy with portal vein embolization (PVE) as the best strategy. After the first procedure consisting in cleaning the left hepatic lobe followed by PVE the future liver remnant volume (FLRV) was considered inadequate, so the patient was also treated with right transarterial radioembolizacion with yttrium 90 (TARE-Y90) intending a double goal: to treat the tumor and to increased the FLRV. Furthermore, a severe flare of Crohn´s disease forced us to intensify the patient's treatment with the addition of biological agents (infliximab and adal imumab) until complete remission of the symptoms. The second stage of the liver surgery had to be postponed for more than 6 months and could finally be carried out without complications, achieving an R0 resection. The postoperative course was uneventful and the follow up has showed no recurrence to date.

Conclusion

Solitary fibrous tumours with extensive liver metastases are infrequent but when they appear modern surgical strategies like two stage hepatectomy are the treatment of choice and must be carried out by specialised units. The therapeutic decisions should be guided by a multidisciplinary committee.

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