Evaluation In Clinical Trials Research Articles

Clinicopathological Factors as Predictors for Establishment of Patient Derived Head and Neck Squamous Cell Carcinoma Organoids

IntroductionPatient derived organoids (PDOs) are 3D in vitro models and have shown to better reflect patient and tumor heterogeneity than conventional 2D cell lines. To utilize PDOs in clinical settings and trials for biomarker discovery or drug response evaluation, it is valuable to determine the best way to optimize sample selection for maximum PDO establishment. In this study, we assess patient, tumor and tissue sampling factors and correlate them with successful PDO establishment in a well-documented cohort of patients with head and neck squamous cell carcinoma (HNSCC).MethodsTumor and non-tumorous adjacent tissue samples were obtained from HNSCC patients during routine biopsy or resection procedures at the University Medical Center Utrecht. The tissue was subsequently processed to establish PDOs. The sample purity was determined as the presence of epithelial cells in the culture on the day of organoid isolation as visualized microscopically by the researcher. PDO establishment was recorded for all samples. Clinical data was obtained from the medical records and was correlated to PDO establishment and presence of epithelial cells.ResultsOrganoids could be established in 133/250 (53.2%) primary tumor site tissues. HNSCC organoid establishment tended to be more successful if patients were younger than the median age of 68 years (74/123 (60.2%) vs. 59/127 (46.5%), p = 0.03). For a subset of samples, the presence of epithelial cells in the organoid culture on the day of organoid isolation was recorded in 112/149 (75.2%) of these samples. When cultures were selected for presence of epithelial cells, organoid establishment increased to 76.8% (86/112 samples).ConclusionThis study found a trend between age and successful organoid outgrowth in patients with HNSCC younger than 68 years and emphasizes the value of efficient sampling regarding PDO establishment.

Natural product cell division cycle 25 (CDC25) inhibitors: A promising source for cancer drug discovery

Cell division cycle 25 (CDC25) is a family of proteins that play a vital role in regulating cell cycle progression. They activate cyclin-dependent kinases (CDKs), which are key enzymes controlling pivotal stages throughout the cell cycle to ensure proper transition between phases. Due to their overexpression or dysregulation in many human cancers, CDC25 phosphatases have become a prime target for cancer therapy. A vast number of structurally diverse molecules have been identified as potent and selective CDC25 phosphatase inhibitors, exhibiting promising therapeutic potential against various cancer types. However, only a small subset of CDC25 inhibitors such as pexiganan, PM-20, BN82002, and JUN1111 have progressed to clinical trials for evaluation. Natural products are being explored as potential sources of novel anticancer compounds due to their functional diversity. Plant-based and marine-based natural products are being investigated for CDC25 inhibition and for the development of phosphatase inhibitors. This review article comprehensively covers the role of CDC25 in the cell cycle, plant-based and marine-based natural products for CDC25 inhibition, and recent advances in the development of CDC25 phosphatase inhibitors as novel anticancer agents.

In situ tumor model for longitudinal in silico imaging trials

Objective. In this article, we introduce a computational model for simulating the growth of breast cancer lesions accounting for the stiffness of surrounding anatomical structures. Approach. In our model, ligaments are classified as the most rigid structures while the softer parts of the breast are occupied by fat and glandular tissues As a result of these variations in tissue elasticity, the rapidly proliferating tumor cells are met with differential resistance. It is found that these cells are likely to circumvent stiffer terrains such as ligaments, instead electing to proliferate preferentially within the more yielding confines of the breast’s soft topography. By manipulating the interstitial tumor pressure in direct proportion to the elastic constants of the tissues surrounding the tumor, this model thus creates the potential for realizing a database of unique lesion morphology sculpted by the distinctive topography of each local anatomical infrastructure. We modeled the growth of simulated lesions within volumes extracted from fatty breast models, developed by Graff et al with a resolution of 50 μm generated with the open-source and readily available Virtual Imaging Clinical Trials for Regulatory Evaluation (VICTRE) imaging pipeline. To visualize and validate the realism of the lesion models, we leveraged the imaging component of the VICTRE pipeline, which replicates the siemens mammomat inspiration mammography system in a digital format. This system was instrumental in generating digital mammogram (DM) images for each breast model containing the simulated lesions. Results. By utilizing the DM images, we were able to effectively illustrate the imaging characteristics of the lesions as they integrated with the anatomical backgrounds. Our research also involved a reader study that compared 25 simulated DM regions of interest (ROIs) with inserted lesions from our models with DM ROIs from the DDSM dataset containing real manifestations of breast cancer. In general the simulation time for the lesions was approximately 2.5 hours, but it varied depending on the lesion’s local environment. Significance. The lesion growth model will facilitate and enhance longitudinal in silico trials investigating the progression of breast cancer.

A Cross-Over Randomized Controlled Clinical Trial for Evaluation of Two Hygiene Protocols on Microbial Load, Tissue Health, and Opinion of Ocular Prosthesis Wearers

The recommendations for the wear and hygiene of ocular prostheses can vary among practitioners, and it is still a controversial theme in the literature. This clinical trial evaluated the microbial load, tissue health of the socket, and the participants’ opinions before and after the use of two hygiene protocols. Thirty ocular prosthesis wearers used either a Daily Protocol (DPt: hygiene once a day) or Weekly Protocol (WPt: hygiene once a week) for 5 weeks with a washout of 7 days. The microbial load was quantified by the colony-forming unit count of the aerobic bacteria, Candida spp., Staphylococcus spp., and Gram-negative bacteria. The tissue health of the socket was evaluated by scores, and patients’ opinion of the protocols was evaluated using the analogic visual scale (VAS). Data were analyzed by ANOVA Repeated Measures, Friedman, Cochran’s Q Test, Wilcoxon, Fisher, and Pearson’s chi-square tests considering p < 0.05. There was no difference in the microbial load of the microorganisms (p > 0.05). Both protocols improved socket inflammation (p = 0.005) and discharge (p < 0.001); DPt improved edema (p = 0.021) and crusting (p = 0.020). There was no difference in patients’ rating responses (VAS) for all the questions of patients’ opinion (Q1: p = 1.0; Q2: p = 1.0; Q3: p = 1.0; Q4: p = 1.0; Q5: p = 1.0; Q6: p = 0.317; Q7: p = 1.0; Q8: p = 0.159). There was a correlation between eye drops/edema (p = 0.030), eye drops/pain (p = 0.016), microbial load with discharge, inflammation, eyelid edema, and pain. Inflammation was correlated with edema at baseline (p < 0.001) and after DPt (p = 0.018), and with crusting at baseline (p = 0.003); edema was correlated with crusting at baseline (p < 0.001); crusting was correlated with discharge after WPt (p < 0.001). The protocols showed no effects on the microbial load of the anophthalmic socket and ocular prosthesis. However, better tissue health and patient acceptance were observed after both regimens.

Randomized Clinical Trial for Evaluation of Efficacy of a Tissue-displacing Impression System in Comparison with Conventionally Used Gingival Displacement Materials in Young Adult Population

Randomized Clinical Trial for Evaluation of Efficacy of a Tissue-displacing Impression System in Comparison with Conventionally Used Gingival Displacement Materials in Young Adult Population

Clinical safety and efficacy observation of ex vivo-expanded peripheral blood-derived allogeneic NK cells in the treatment of refractory or recurrent ovarian cancer.

e17553 Background: Ovarian cancer is the most lethal gynecologic malignancy. Nearly 75% of patients were diagnosed at advanced stages. Despite 60%-80% of patients achieve complete remission after treatment with surgery combined with chemotherapy, about 60% of patients relapse within two years, more than 50% of patients develop chemotherapy tolerance with only 30% five-year survival rate. Platinum resistance-induced recurrence and platinum intolerance result in poor prognosis. Thus, there is an unmet need for innovative therapy of advanced ovarian cancer. We have developed a novel non-genetically modified ex vivo-expanded allogeneic NK cells from peripheral blood (PB). The expanded PB-NK cells have highly cytolytic activity and have the capacity to preferentially reside in ovary. We conducted a phase I clinical trial for evaluation of safety and efficacy of allogeneic NK cells in treatment of patients with refractory or recurrent ovarian cancers. Methods: Patients with advanced ovarian cancer who failed after multiline treatment were enrolled and received the treatment with allogeneic NK cells. The treatment was divided into low, medium and high dose groups with a 28-day cycle. safety and efficacy were evaluated after receiving two cycles of allogeneic NK cell infusion. Results: A total of 4 patients with advanced ovarian cancer who failed multiline therapy completed two courses of cell infusion therapy and evaluation. The median age of patients was 58 years (range 50 to 71 years). The median number of lines of treatment was 6 (range 3-7). One recurrent patient with platinum intolerance received low dose of NK cells and three relapse or refractory patients with platinum resistance received medium dose of allogeneic NK cell therapy. The patient in low-dose group and one patient in medium-dose group were evaluated for stable disease (SD), the other two patients in medium-dose group were disease progression after two courses of treatment. Notable, the patient in low-dose group continued to receive treatment with the same dose and achieved partial response (PR) after three courses of treatment. Upon receiving continuous NK cell therapy, the tumor lesions continued to shrink, with the best result was 60% reduction. It was re-evaluated as progressive disease (PD) 6 months after treatment was discontinued. Adverse events during the follow-up period included grade I fever in 4 (100%), grade I drowsiness in 1 (25%), grade I chills in 1 (25%), and grade I malaise in 1 (25%). No CRS or GVHD occurred. Conclusions: We report the safety and efficacy of allogeneic PB-NK cells in treatment of relapse or refractory ovarian cancer. The results showed that the allogeneic PB-NK cells are safe and feasible for the treatment of ovarian cancer, indicating a promising curative effect. There is no host versus graft reaction upon receiving continuous allogeneic NK cell therapy. Clinical trial information: NCT03619954 .

Practical RECIP: Visual assessment of response evaluation criteria In PSMA-PET 1.0

To evaluate the accuracy of Response Evaluation Criteria In PSMA-Imaging (RECIP) 1.0 determined by visual reads of nuclear medicine physicians for response evaluation using PSMA-PET/CT in men with mCRPC treated with 177Lu-PSMA radioligand therapy. In total, 124 patients were included in this multicenter retrospective study. All patients received 177Lu-PSMA and underwent PSMA-PET/CT scans at baseline (bPET) and at 12 weeks (iPET). Five nuclear medicine specialists individually interpreted each pair of PSMA-PET/CT scans for responses in PSMA-positive total tumor volume (PSMA-VOL) assessed visually and for occurrence of new lesions. Responses in PSMA-VOL were also assessed quantitatively using semi-automatic segmentation software. Occurrence of new lesions was combined: 1) with visual responses in PSMA-VOL to determine visual RECIP; and 2) with quantitative responses in PSMA-VOL to determine quantitative RECIP. RECIP response classes were dichotomized for differentiation of clinically relevant progressive (PD) vs. non-progressive disease (nPD): RECIP-PD vs. RECIP-nPD. Primary outcome measure was the inter-reader reliability of visual RECIP and agreement between visual vs. quantitative RECIP (by Cohen's κ coefficient). Secondary outcome measure was the prognostic value of visual RECIP (by Cox regression) for overall survival (OS). Based on readers’ majority rule, 41/124 (33%) and 83/124 (67%) patients had visual RECIP-PD and RECIP-nPD, respectively. Agreement among readers in classifying visual RECIP-PD vs. RECIP-nPD was observed in 103 (83%) patients (excellent agreement: κ = 0.81). Agreement between visual vs. quantitative RECIP was observed in 118 (95%) patients (excellent agreement: κ = 0.89). OS was significantly shorter in men with visual RECIP-PD vs. RECIP-nPD (HR 2.55; 95%CI, 1.71–3.81; P < 0.001). The median OS was 8.4 months (95%CI, 7.0–9.8) for patients with RECIP-PD and 16.1 months (95%CI, 13.6–18.5) for patients with RECIP-nPD. Visual RECIP demonstrated excellent inter-reader reliability and excellent agreement with quantitative RECIP calculated using semi-automatic segmentation software. Visual RECIP was prognostic for overall survival of men undergoing 177Lu-PSMA radioligand therapy. RECIP 1.0 evaluated visually by nuclear medicine physicians can be used in practice and clinical trials for response evaluation using PSMA-PET/CT in men with mCRPC.

Efficacy and Safety of Korean Herbal Medicine for Patients with Post-Accident Syndrome, Persistent after Acute Phase: A Pragmatic Randomized Controlled Trial

This is a pragmatic, two-armed, parallel, single-center, randomized controlled clinical trial for comparative evaluation between the effectiveness of integrated Korean medicine (IKM) and herbal medicine treatment with that of IKM monotherapy (control) for post-accident syndrome persistent after the acute phase. Participants were randomized into Herbal Medicine (HM, n = 20) and Control groups (n = 20) to receive the allocated treatment of 1-3 sessions/week for 4 weeks. Intention-to-treat analysis was conducted. The Difference of Numeric Rating Scale (NRS) change of overall post-accident syndromes from baseline to week 5 for the two groups was 1.78 (95% CI: 1.08-2.48; p < 0.001). Regarding secondary outcomes, a significant decrease compared to the baseline values was confirmed for NRS of musculoskeletal, neurological, psychiatric complaints and general symptoms of post-accident syndromes. In a survival analysis based on the recovery criteria of "patients with a reduction in the NRS of overall post-accident syndromes of ≥50%," the HM group showed a shorter time to recovery than the control group during the 17-week study period (p < 0.001 by the log-rank test). IKM combined with herbal medicine treatment significantly improved the quality of life by relieving somatic pain and alleviating the overall post-accident syndrome persistent after the acute phase; this effect was maintained for at least 17 weeks.

Immunotherapies for the Treatment of Drug Addiction.

Substance use disorders (SUD) are a serious public health concern globally. Existing treatment platforms suffer from a lack of effectiveness. The development of immunotherapies against these substances of abuse for both prophylactic and therapeutic use has gained tremendous importance as an alternative and/or supplementary to existing therapies. Significant development has been made in this area over the last few decades. Herein, we highlight the vaccine and other biologics development strategies, preclinical, clinical updates along with challenges and future directions. Articles were searched in PubMed, ClinicalTrial.gov, and google electronic databases relevant to development, preclinical, clinical trials of nicotine, cocaine, methamphetamine, and opioid vaccines. Various new emerging vaccine development strategies for SUD were also identified through this search and discussed. A good number of vaccine candidates demonstrated promising results in preclinical and clinical phases and support the concept of developing a vaccine for SUD. However, there have been no ultimate success as yet, and there remain some challenges with a massive push to take more candidates to clinical trials for further evaluation to break the bottleneck.

Efficacy of Motor Imagery on Lower Extremity Functioning and Gait in Chronic Stroke Patients: Systematic review

Background: Numerous stroke rehabilitation techniques have been developed in recent years. In orderto learn or improve a motor movement or ability, a subject will frequently enter a dynamic conditionknown as mental practise (MP). Although MP(mental practise) induces brain activation patterns thatare comparable to those of movement, functional imaging has yet to prove the clinical efficacy of suchtreatments in rehabilitation and functional recovery.Methodology: Systematic review of all clinical studies about motor imagery in stroke rehabilitation thatwere published between 2008 and 2022 in the major scientific databases. We chose three clinical trialsevaluating various motor imaging techniques in chronic hemiparesis patients.Conclusion: When combined with traditional physical therapy, mental practice is helpful for thefunctional rehabilitation of the lower limbs as well as for the restoration of everyday activities andskills. More research is required to identify the ideal treatment protocol and patient profile due tothe variety of the studies in terms of the intervention protocol, particular imagery technique, practiseduration, patient characteristics, etc.

OP11 Implementation of Economic Evaluation in Clinical Trials: The Study of Stakeholders Perspectives in Ukraine

Economic evaluation in clinical trials (CTs) is emerging actively as a valuable instrument of generating new knowledge and data-driven decisions within HTA process. Developing best practices for cost-effectiveness analysis (CEA) at the stage of clinical study is up-to-date which requires appropriate response and preparedness of the industry stakeholders. This study aims at defining the awareness about the key aspects of economic evaluation in CTs and perceptions of its barriers among specialists involved in clinical research.

LUNCH—Lung Ultrasound for early detection of silent and apparent aspiratioN in infants and young CHildren with cerebral palsy and other developmental disabilities: study protocol of a randomized controlled trial

BackgroundChildren with neurological impairment may have dysphagia and/or gastro-esophageal reflux disease (GERD), which predispose to complications affecting the airways, increasing risk for aspiration-induced acute and chronic lung disease, or secondarily malnutrition, further neurodevelopmental disturbances, stressful interactions with their caregivers and chronic pain. Only multidisciplinary clinical feeding evaluation and empirical trials are applied to provide support to the management of feeding difficulties related to dysphagia or GERD, but no standardized feeding or behavioral measure exists at any age to assess aspiration risk and support the indication to perform a videofluoroscopic swallowing study (VFSS) or a fibre-optic endoscopic examination of swallowing (FEES), in particular in newborns and infants with neurological impairments. Lung ultrasound (LUS) has been proposed as a non-invasive, radiation-free tool for the diagnosis of pulmonary conditions in infants, with high sensitivity and specificity.MethodsA RCT will be conducted in infants aged between 0 and 6 years having, or being at risk for, cerebral palsy, or other neurodevelopmental disease that determines abnormal muscular tone or motor developmental delay assessed by a quantitative scale for infants or if there is the suspicion of GERD or dysphagia based on clinical symptoms. Infants will be allocated in one of 2 groups: 1) LUS-monitored management (LUS-m); 2) Standard care management (SC-m) and after baseline assessment (T0), both groups will undergo an experimental 6-months follow-up. In the first 3 months, infants will be evaluated a minimum of 1 time per month, in-hospital, for a total of 3 LUS-monitored meal evaluations. Primary and secondary endpoint measures will be collected at 3 and 6 months.DiscussionThis paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the benefits of the use of LUS for monitoring silent and apparent aspiration in the management of dysphagia and its impact on pulmonary illness and growth and (2) to investigate the impact of the LUS management on blood sample and bone metabolism, pain and interaction with caregivers.Trial registrationTrial registration date 02/05/2020; ClinicalTrials.gov Identifier: NCT04253951.

Phase I clinical safety and efficacy observation of αPD-1-mesoCAR-T cells in the treatment of advanced gynecologic cancer.

e17535 Background: Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death among women. Most of patients often have refractory or relapse. We have developed a CAR T cell secreting PD-1 nanoantibodies and targeting mesothelin (αPD-1-mesoCAR-T) and conducted a phase I clinical trial for evaluation of safety and efficacy of the αPD-1-mesoCAR-T cells in gynecologic tumors. Methods: This study is a single-arm, open, dose-increasing clinical study and two infusions (interval 14-35 days). Patients with advanced gynecological cancer were enrolled when immunohistochemical analysis for positive mesothelin over 70% and failed second-line treatment in Mengchao Cancer Hospital affiliated to Shanghai University and Shanghai Tenth People's Hospital affiliated to Tongji University. All patients underwent lymphodepletion before infusion at a dose of 1 to 15x106/kg. CAR copies, nanobody levels, cytokines, T lymphocyte subtypes were determined before and after infusion. Results: a total of 7 patients were enrolled so far and completed the first evaluation. After treatment, most symptoms of the patients were alleviated, two patients (#2, #3) had their lesions decreased. By RECIST 1.1, all 7 patients’ diseases became stable, and the disease control rate was 100%. The PFS of #3 patient with stable disease (SD) was 5.3 months, the patient #2 was 4.1 months. The frequent adverse events were fever, fatigue, nausea and pruritus. No sever adverse events above grade 3 occurred. The number of CAR-T cells in the peripheral blood increased significantly during day 4-14 after the infusion, and the PD-1 nanoantibody levels and the contents of INF-γ、IL-6、IL-2 and MCP-1 also increased at day 1-4. Conclusions: The preliminary clinical study showed that the aPD-1-mesoCAR-T cells are safe for the treatment of gynecologic cancer and stabilized the diseases. More data of the treatment is warrantied to continually follow up these patients.

Effective sealing of biliary and pancreatic fistulas with a novel biodegradable polyurethane-based tissue sealant patch.

To date, no approved sealants for the prevention of postoperative pancreatic fistulas (POPFs) or bile leakage are available. The aim of the study is to assess the feasibility of a new synthetic and biodegradable polyurethane-based sealant patch (PBSP) for hepato-pancreato-biliary (HPB) surgery. Benchmarking of the PBSP with commercially available products with a historical use in HPB surgery (Tachosil®, Hemopatch®, Surgicel® and Veriset®) was followed by performance testing in randomized controlled porcine animal studies. These studies focused on haemostasis as well as the prevention of POPFs and bile leakage. The newly designed PBSP demonstrated the strongest adherence to liver tissue compared to Tachosil®, Hemopatch® and Veriset®. The new patch was the only patch with complete intra- and postoperative hemostasis (72h after application) compared to Tachosil and Veriset in a porcine liver abrasion study on 12 animals. In addition, the new patch demonstrably prevents the development of POPFs. The rate of postoperative pancreatitis and clinically relevant POPFs was significantly lower compared to the control groups in a porcine pancreatic fistula model based on 14 animals (14-day follow-up). Furthermore, the incidence of biloma after 7 days, considered as significant bile leakage, was significantly lower in the new PBSP compared to the Veriset® group. The PBSP was as effective as suturing in a porcine bile leakage model (7-day follow-up). The PBSP induces constant hemostasis in the context of liver resection and prevents pancreatic fistulas and bile leakage. The promising preclinical data implicate clinical trials for further evaluation of this newly developed patch.

POS-359 Developing targeted therapies for kidney disease in public private partnerships

Integrating public and private research efforts is key to expediting precision medicine for glomerular diseases. The Nephrotic Syndrome Study Network (NEPTUNE) has developed an innovative research and business model: “MATCH”, to enable targeted patient enrollment in clinical trials via the NEPTUNE public private partnership (NP5). The NEPTUNE community knowledge base is leveraged to identify a molecular signal matching therapeutic targets under development by NP5 industry partners. The three steps of MATCH are: (1) predictive biomarker development; (2)patient communication about precision medicine; and (3) return of results from NP5 partner clinical trials for evaluation of patient stratification effects on trial outcomes. MATCH begins with NEPTUNE patient education on risks and benefits of the study. Once enrolled in MATCH, a patient’s biosamples undergo biomarker profiling. MATCH provides individual pathway activation information to patients for consideration in their independent decision to enroll in a trial that may be more tailored to their specific disease and stage. Finally, clinical trial outcomes will be reported by NP5 partners to NEPTUNE to evaluate the MATCH impact on treatment responses. MATCH aims to assess the ability to communicate molecular information to patients, and to test precision medicine across multiple trials and partners to move science closer to the overall goal: reaching the right patient with the right medicine at the right time. MATCH is an open framework available to additional partners interested in joining NP5.

Matrixmetalloproteinase Inhibitors: Promising Therapeutic Targets Against Cancer.

Cancer is a wide range cellular level disease that occurs when cells go through uncontrolled division and growth. The mechanisms by which the cells undergo metastasis are complex and involve many interactions between the tumor cells and their cellular environment. Matrix metalloproteinases (MMPs) have been found to over-express at various stages of tumor progression and their inhibition using MMP inhibitors has been a subject of potential therapy against cancer. This review discusses recent research in MMP inhibitors (MMPI) used for preventing tumor progression. In this review, we explored the role of MMPs in cancer progression and summarized the current developments in MMPIs, their role in cancer suppression in in vitro and in vivo studies and their evaluation in clinical trials from the current research data. MMPIs have shown to be very successful in in vitro models, cell lines and in some in vivo studies. Unfortunately, their efficacy in clinical trials has been found to be hit and miss. Recent studies have shown that the novel delivery approaches of MMP inhibitors may enhance their therapeutic effects towards the prevention of cancer. In this review, we presented different MMP inhibitors, their performance at different stages of models - in vitro, in vivo, small animal models and eventually clinical trials. We provide newer methods of MMPI delivery that may be better targeted to suppress only specific MMPs and avoid toxic side effects in healthy cells.

Green Line Hospital-Territory Study: A Single-Blind Randomized Clinical Trial for Evaluation of Technological Challenges of Continuous Wireless Monitoring in Internal Medicine, Preliminary Results.

Background: Wireless vital parameter continuous monitoring (WVPCM) after discharge is compared to regular monitoring to provide data on the clinical-economic impact of complex patients (CPs) discharged from Internal Medicine Units of Ospedale dei Castelli, Lazio. Primary outcome: Major complications (MC) reduction. Secondary outcomes: Patients who reached discharge criteria within the 7th day from admission; difference in MC incidence at the conclusion of the standard telemonitoring/clinical monitoring phase, 5 and 30 days after discharge; and conditions predisposing to MC occurrence. Methods: Open label randomized controlled trial with wearable wireless system that creates alerts on portable devices. Continuous glycemic monitoring is performed for patients with diabetes mellitus. Results: There were 110 patients enrolled (mean age: 76.2 years). Comorbidity: Cumulative Illness Rating Scale CIRS-CI (comorbidities index): 3.93, CIRS SI (severity index): 1.93. About 19% scored a BRASS (Blaylock Risk Assessment Screening Score) ≥20 indicating need for discharge planning requiring step-down care. Globally, 48% of patients in the control group had major complications (27 out of 56 patients), in contrast to 22% in the intervention group (12 out of 54 patients). Conclusions: Since WVPCM detects early complications during the post-discharge CPs monitoring, it increases safety and reduces inappropriate access to the Emergency Room, preventing avoidable re-hospitalizations.

Hematopoietic Stem Cell Therapy for Wiskott-Aldrich Syndrome: Improved Outcome and Quality of Life.

The Wiskott–Aldrich syndrome (WAS) is an X-linked disorder caused by mutations in the WAS gene resulting in congenital thrombocytopenia, eczema, recurrent infections and an increased incidence of autoimmune diseases and malignancies. Without curative therapies, affected patients have diminished life expectancy and reduced quality of life. Since WAS protein (WASP) is constitutively expressed only in hematopoietic stem cell-derived lineages, hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are well suited to correct the hematologic and immunologic defects. Advances in high-resolution HLA typing, new techniques to prevent GvHD allowing the use of haploidentical donors, and the introduction of reduced intensity conditioning regimens with myeloablative features have increased overall survival (OS) to over 90%. The development of GT for WAS has provided basic knowledge into vector selection and random integration of various viral vectors into the genome, with the possibility of inducing leukemogenesis. After trials and errors, inactivating lentiviral vectors carrying the WAS gene were successfully evaluated in clinical trials, demonstrating cure of the disease except for insufficient resolution of the platelet defect. Thus, 50 years of clinical evaluation, genetic exploration and extensive clinical trials, a lethal syndrome has turned into a curable disorder.

Electrophoresis SDS-PAGE and Tricine-SDS-PAGE to differentiate black and yellow soybean: a molecular approach

Soybean is well recognized for having several bioactive compounds. Black soybeans have been used in Eastern countries as a healthy food and as an medicinal alternative. The identification of natural substances, such as peptides, present in black and yellow soybeans is necessary. An evaluation of the contribution of these molecules to positive effects to human health molecular studies should be done. The search for molecular aspects that may explain this difference between black soybean and yellow soybean is extremely important. In order to have a peptide-protein extract with semi-purified aspects for further molecular characterization, soybeans grains were grounded in a home-use coffee grinder and fat was removed by using acetone. The protein extracts obtained were characterized by two eletrophorectic techniques (SDS-PAGE and Tricine-SDS-PAGE). Polyacrylamide gels with clear and well-defined polypeptide chains showed that both black and yellow soybean genotypes presented the peptide 5 kDa, while, the 4 kDa peptide was only found in black soybeans. This study, on molecular bases, showed that this method to obtain peptide-protein extracts was effective, to separate peptides in that region and could contribute to choose black or yellow soybean genotypes for clinical trials in evaluation of different health effects.

Electrophoresis SDS-PAGE and Tricine-SDS-PAGE to differentiate black and yellow soybean: a molecular approach

Soybean is well recognized for having several bioactive compounds. Black soybeans have been used in Eastern countries as a healthy food and as an medicinal alternative. The identification of natural substances, such as peptides, present in black and yellow soybeans is necessary. An evaluation of the contribution of these molecules to positive effects to human health molecular studies should be done. The search for molecular aspects that may explain this difference between black soybean and yellow soybean is extremely important. In order to have a peptide-protein extract with semi-purified aspects for further molecular characterization, soybeans grains were grounded in a home-use coffee grinder and fat was removed by using acetone. The protein extracts obtained were characterized by two eletrophorectic techniques (SDS-PAGE and Tricine-SDS-PAGE). Polyacrylamide gels with clear and well-defined polypeptide chains showed that both black and yellow soybean genotypes presented the peptide 5 kDa, while, the 4 kDa peptide was only found in black soybeans. This study, on molecular bases, showed that this method to obtain peptide-protein extracts was effective, to separate peptides in that region and could contribute to choose black or yellow soybean genotypes for clinical trials in evaluation of different health effects.