Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Bilateral synchronous breast cancer: mode of detection and comparison of histologic features between the 2 breasts

BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%-2.6% of all patients with breast cancer), and most physicians do not accumulate a large personal experience of patients with this disease. We reviewed our experience with patients with bilateral synchronous breast cancer, focusing on the mode of detection and histologic features in the 2 breasts. METHODS: The charts of patients who were treated at this institution for bilateral synchronous breast cancer during the 15-year period of 1984 through 1999 were reviewed. Information regarding age, mode of detection, histopathologic features, treatment, and overall survival were analyzed. RESULTS: During the study period, 51 patients (all women) were treated at our institution for bilateral synchronous breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated for breast cancer during the same period of time. The first cancer was detected by palpation in 81% and by mammography in 14%. The corresponding figures for the contralateral cancer were 24% and 54%, respectively. The histologic type of cancer was identical in the 2 breasts in 29 patients (57%) and was different between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was 63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by mammography and is frequently of the same histologic type as the index cancer. A better awareness of the risk for this disease may help detect bilateral breast cancer earlier.     

Influence of mitoxantrone on nucleolar function in MDA-MB-231 human breast tumor cell line

The effect of mitoxantrone (DHAQ) on [3H]thymidine and [3H]uridine incorporation by exponentially growing MDA-MB-231, a human breast tumor cell line has been studied. The results have indicated that DHAQ was more effective in inhibiting [3H]thymidine than [3H]uridine incorporation in a concentration dependent manner. Following drug treatment at 20 ng/ml concentration, 50% inhibition of growth and [3H]thymidine incorporation were noted, whereas [3H]uridine incorporation was only inhibited by about 12%. At 2000 ng/ml of DHAQ the inhibition of cell growth, [3H]thymidine and [3H]uridine incorporations were 78%, 95% and 62%, respectively. Nuclear-associated radioactivity detected at light and electron microscope autoradiographic levels after [3H]thymidine and [3H]uridine incorporations, into DHAQ treated cells indicated that DHAQ prevented the accumulation of radioactivity into the nuclei in a concentration dependent manner. These results gave further indication that mitoxantrone induced a definitive alteration of nuclear template activities, correlated with nuclear functional-structural relation and suggested that the nucleoli were the primary site of DHAQ action.     

A tool for the management of personal protective equipment during COVID-19 pandemic: Abderrahmen Mami Hospital case study

Introduction: The COVID-19 pandemic is causing management difficulties in the Tunisian healthcare system inventory management and the supply of Personal Protective Equipment (PPE). Aim : Calculate the number of PPE needed for MAMI Hospital Ariana (dedicated hospital to COVID patients) to avoid stock-outs. Methods: This study proposed a calculation method of the PPE needs for the intensive care and pneumology departments. We developed a mathematical formulation of the number of PPE needed according to the number of visits per medical and other teams, their types, the number of patients, and the validity of each type of PPE. Results: Considering as input data: the number of visits for the different intervening teams (medical, paramedical, worker or other), the capacity of the different services (number of beds), the average length of stay of patients, the validity duration of an equipment and urgent visits, the developed model generates the required number of PPE (especially surgical masks, FFP2 masks, disposables gowns and coveralls). This allows to calculate the number of personal protective equipment (PPE) needed by the Mami hospital’s pharmacy in this period of COVID-19 crisis. Conclusion: Our configurable application allowed us to calculate PPE requirements for the intensive care and pneumology departments and estimate their use duration.     

The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

Ductal prostate cancer: Clinical features and outcomes from a multicenter retrospective analysis and overview of the current literature

ObjectiveThe aim of the study is to evaluate clinical features and outcomes after different therapeutic strategies for ductal prostate adenocarcinoma (DPC), a rare but aggressive subtype of invasive prostate cancer (PCa) accounting for, in the pure and mixed form, 1% or less and 5% or less, respectively, of all the newly diagnosed PCa.Materials and methodsPatients with a proven diagnosis of DPC undergoing surgery, radiotherapy, and androgen deprivation therapy, alone or in combination, were considered for this multicenter, retrospective study. The study assessed overall survival (OS), disease-free survival (DFS), and age-related disease-specific survival.ResultsEighty-one patients met the study inclusion criteria. Pure DPC was found in 29 patients (36%) and mixed ductal-acinar-PCa in 52 patients (64%). After a median follow-up of 63 months (range, 3–206 months), 3- and 5-year OS rates were 84% and 67%, respectively, and 3- and 5-year DFS rates were 54% and 34%, respectively. There were no significant differences in OS or DFS between the pure and mixed DPC groups. Pure DPC was associated with a higher rate of metastatic disease at onset. Patients 74 years or younger had better disease-specific survival (p=0.0019). A subgroup analysis favored radiotherapy as the primary treatment for nonmetastatic, organ-confined DPC (3- and 5-year DFS of 80% and 50%, respectively, compared with 5-year DFS of 35% for surgical patients; p = 0.023).ConclusionsOur study found DPC to be rarer, more aggressive, more likely to metastasize, and have a worse prognosis than the common acinar variant, especially in its pure form. Multicenter series are encouraged to obtain large data sets, or propensity score matching analyses with patients with conventional PCa are desirable to understand the best therapeutic approach and improve outcomes.     

Home-Based Electrical Stimulation to Accelerate Wound Healing—A Double-Blinded Randomized Control Trial

Background:Electrical stimulation (E-Stim) may offer a unique adjunctive treatment to heal complicated diabetic foot ulcers (DFU). Our primary goal is to examine the effectiveness of daily home-based E-Stim therapy to speed-up wound healing.Methods:Patients with chronic DFUs and mild to severe peripheral arterial disease (PAD) were recruited and randomized to either control (CG) or intervention (IG) groups. The IG received 1-hour home-based E-Stim therapy on daily basis for 4 weeks (4W). E-Stim was delivered through electrical pads placed above the ankle joint using a bio-electric stimulation technology (BEST^®) platform (Tennant Biomodulator^® PRO). The CG was provided with an identical but non-functional device for the same period. The primary outcome included wound area reduction at 4W from baseline (BL).Results:Thirty-eight patients were recruited and 5 were removed due to non-compliance or infection, leaving 33 participants (IG, n = 16; CG, n =17). At 4W, the IG showed a significant wound area reduction of 22% (BL: 7.4 ± 8.5 cm² vs 4W: 5.8 ± 8.0 cm², P = 0.002). Average of wound area was unchanged in the CG (P = 0.982). The self-report adherence to daily home-therapy was 93.9%.Conclusions:Daily home-based E-Stim provides early results on the feasibility, acceptability, and effectiveness of E-Stim as an adjunctive therapy to speed up wound healings in patients with chronic DFU and mild to severe PAD.     

Smart Offloading Boot System for Remote Patient Monitoring: Toward Adherence Reinforcement and Proper Physical Activity Prescription for Diabetic Foot Ulcer Patients

Background:A critical factor in healing diabetic foot ulcers is patient adherence to offloading devices. We tested a smart offloading boot (SmartBoot) combined with a smartwatch app and cloud dashboard to remotely monitor patient adherence and activity. In addition, the impact of SmartBoot on balance, gait, and user experience was investigated.Methods:Fourteen volunteers (31.6±8.7 years; 64% female) performed natural activities (eg, sitting, standing, walking) with and without the SmartBoot for approximately 30 minutes. All participants completed balance tests, 10-meter walking tests at slow, normal, and fast pace while wearing the SmartBoot, and a user experience questionnaire. The accuracy of real-time adherence reporting was assessed by comparing the SmartBoot and staff observation. Center of mass (COM) sway and step counts were measured using a validated wearable system.Results:Average sensitivity, specificity, and accuracy for adherence and non-adherence were 90.6%, 88.0%, and 89.3%, respectively. The COM sway area was significantly smaller with the SmartBoot than without the SmartBoot regardless of test condition. Step count error was 4.4% for slow waking, 36.2% for normal walking, 16.0% for fast walking. Most participants agreed that the SmartBoot is easy to use, relatively comfortable, nonintrusive, and innovative.Conclusions:To our knowledge, this is the first smart offloading system that enables remote patient monitoring and real-time adherence and activity reporting. The SmartBoot enhanced balance performance, likely due to somatosensory feedback. Questionnaire results highlight SmartBoot’s technical and clinical potential. Future studies warrant clinical validation of real-time non-adherence alerting to improve wound healing outcomes in people with diabetic foot ulcers.     

Introduction of cadmium chloride additive to improve the performance and stability of perovskite solar cells

With the increase in the importance of using green energy sources to meet the world''s energy demands, attempts have been made to push perovskite solar cell technology toward industrialization all around the world. Improving the properties of perovskite materials as the heart of PSCs is one of the methods to fabricate favorable photovoltaic (PV) solar cells based on perovskites. Here, cadmium chloride (CdCl₂) was used as an additive source for the perovskite precursor to improve its PV properties. Results indicated CdCl₂ improves the perovskite growth and tailors its crystalline properties, suggesting boosted charge transport processes in the bulk and interfaces of the perovskite layer with electron–hole transport layers. Overall, by incorporation of 1.0% into the MAPbI₃ layer, a maximum power conversion efficiency of 15.28% was recorded for perovskite-based solar cells, higher than the 12.17% for the control devices. The developed method not only improved the PV performance of devices but also boosted the stability behavior of solar cells due to the passivated domain boundaries and enhanced hydrophobicity in the CdCl₂-based devices.

With the increase in the importance of using green energy sources to meet the world''s energy demands, attempts have been made to push perovskite solar cell technology toward industrialization all around the world.