The effect of formulation composition and adjuvant type on difenoconazole dislodgeable foliar residue.

Rigorous risk assessments for those exposed to pesticides are carried out to satisfy crop protection regulatory requirements. Non-dietary risk assessments involve estimating the amount of residue which can be transferred from plant foliage to the skin or clothes, known as dislodgeable foliar residues (DFRs). DFR data are less available than crop residue data as studies are costly and limited by seasonality. European regulatory authorities are reticent to allow extrapolation of study data to different scenarios as the contributory factors have hitherto been poorly identified. This study is the first to use a new laboratory DFR method to investigate how one such factor, pesticide formulation, may affect DFR on a variety of crops. The study used the active substance difenoconazole as both an emulsifiable concentrate (EC 10%) and a wettable powder (WP 10%) with and without adjuvants (Tween 20 and organophosphate tris(2-ethylhexyl)phosphate TEHP) on tomato, French bean and oilseed rape. A comparable DFR% was retained from the WP and EC formulation on most crops except for tomato, where lower DFR% was retained in the case of WP (39 ± 4.7%) compared to EC (60 ± 1.2%). No significant effect of adjuvant addition was observed for either formulation except when mixing TEHP (0.1% w/v) to the EC 10% on French bean, resulting in 8% DFR reduction compared to the EC formulation alone. This research demonstrates the value of a unique DFR laboratory technique in investigating the importance of the formulation and in-tank adjuvants as factors that affect DFR.

A new laboratory method to study the impact of leaf texture on pesticide dislodgeable foliar residues (DFR).

Pesticides are vital in meeting the challenge of feeding the rapidly increasing world population. However, it is crucial that they are used in a way that does not compromise the safety of humans or the environment. Non-dietary worker risk assessments consider the amount of residue which can be transferred from plant foliage to the skin or clothes, known as dislodgeable foliar residues (DFRs). DFR data scarcity due to the costly and seasonal characteristics of DFR studies is an obstacle to the extrapolation of DFR data to different crops/leaves. This paper validates a new proof-of-concept technique to investigate factors that may affect DFR (leaf texture) using the fungicide difenoconazole EC 10% as an example on various leaves (i.e., French bean, soybean, tomato, oilseed rape, and wheat). DFR was the lowest in the case of oilseed rape (31.0 ± 3.4%) and the highest in French beans (82.0 ± 2.9%). This significant difference in DFR in the findings of this study sheds light on the importance of the leaf surface as a major factor affecting DFR and supports the application of the laboratory method for more extensive data generation. More data generation would enable the extrapolation saving money and resources.

Probenecid induces the recovery of renal ischemia/reperfusion injury via the blockade of Pannexin 1/P2X7 receptor axis.

Renal ischemia/reperfusion injury (RI/RI) is one of the main driving causes of acute kidney injury. However, effective treatment to limit injury and promote recovery and/or survival is still unavailable. Probenecid (PBN), a drug indicated for refractory gout, exhibits protective activities against several preclinical diseases including cerebral and myocardial I/RI via Pannexin 1 (Panx1) and P2X7 receptors' (P2X7R) inhibition. However, its protective role against RI/RI has not been previously addressed. Accordingly, we subjected rats to bilateral RI/RI with/or without PBN treatment. Twenty-four hours post-reperfusion, PBN showed mild tubular injury and reduced serum nephrotoxicity indices, gene and protein expression levels of Panx 1 and P2X7R, and ATP and pro-inflammatory cytokines' levels. The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome signaling was also downregulated, as demonstrated by reduced gene and protein expression of NLRP3 and caspase-1, along with suppressed IL-1ß maturation. Furthermore, PBN enhanced Tregs activity as indicated by elevated FoxP3 gene expression, IL-10, and TGF-ß renal levels. On day 5 post-reperfusion, PBN noticeably enhanced renal recovery, as demonstrated by intact tubular epithelium and restored nephrotoxicity indices, Panx 1 and P2X7R gene and protein expression levels, ATP and pro-inflammatory cytokine levels, and NLRP3 inflammasome signaling. Besides, renal Tregs activity was also significantly increased. Our study elaborates for the first time the effectiveness of PBN in recovering post-ischemic renal injury through synergistic inhibition in Panx1/P2X7R axis leading to inactivation of NLRP3 inflammasome signaling and activation of Tregs in ischemic renal tissues. Therefore, PBN can be considered a promising drug for RI/RI treatment.

Development of a New Dislodgeable Foliar Residue Analytical Laboratory Method for Pesticides.

The dislodgeable foliar residue (DFR) is the amount of pesticide that exists on foliage after the pesticide has dried and which could dislodge to the skin or clothes of workers and is a key parameter for non-dietary risk assessments required to demonstrate safe use for pesticide registration. DFR data in the literature are described as insufficiently reliable, limited, and encompasses considerable statistical uncertainties. The purpose of this article is to describe a newly developed laboratory method for the quantification of DFR with an illustrative example. The laboratory method reflected available field DFR methodology but involved controlled application of droplets to leaves and validation of the wash-off process used to remove the residue from the leaf surface before the analytical quantification. A very high level of accuracy (99.7-102.1%) and precision (±1.5%) was achieved. Residue data generated from the illustrated application of the method showed a robust normal distribution, unlike field studies. The method is deemed to be controllable, cost-efficient, and time-saving, taking hours rather than days. This enables the generation of more data to allow extrapolation between the generated data by investigating multiple factors that may influence DFR. An improved understanding of DFR could save time, money, and resources.

Co-treatment with Esculin and erythropoietin protects against renal ischemia-reperfusion injury via P2X7 receptor inhibition and PI3K/Akt activation.

Renal ischemia/reperfusion (RI/R) is a critical clinical outcome with slightly reported improvement in mortality and morbidity. Effective therapies are still crucially required. Accordingly, the therapeutic effects of esculin (ESC, LCESI-MS/MS-isolated compound from Vachellia farnesiana flowers extract, with reported P2X7 receptor inhibitor activity) alone and in combination with erythropoietin (EPO) were investigated against RI/R injury and the possible underlying mechanisms were delineated. ESC and EPO were administered for 7 days and 30 min prior to RI, respectively. Twenty-four hour following reperfusion, blood and kidney samples were collected. Results revealed that pretreatment with either ESC or EPO reduced serum nephrotoxicity indices, renal oxidative stress, inflammatory, and apoptosis markers. They also ameliorated the renal histopathological injury on both endothelial and tubular epithelial levels. Notably, ESC markedly inhibited P2X7 receptors and NLRP3 inflammasome signaling (downregulated NLRP3 and Caspase-1 gene expressions), whereas EPO significantly upregulated PI3K and Akt gene expressions, also p-PI3K and p-Akt levels in renal tissues. ESC, for the first time, demonstrated effective protection against RI/R-injury and its combination with EPO exerted maximal renoprotection when compared to each monotherapy, thereby representing an effective therapeutic approach via inhibiting oxidative stress, inflammation, renal tubular and endothelial injury, apoptosis, and P2X7 receptors expression, and activating PI3K/Akt pathway.

Correlation between dietary and dislodgeable foliar (DFR) crop residues decline data; A proposed approach to refine non-dietary risk assessment.

Pesticide residues in crop plants are routinely measured in an edible commodity or in feed items to determine safe use. Pesticides present as dislodgeable foliar residues (DFR) are measured for use in non-dietary risk assessments where worker, resident and bystander re-entry may lead to contact with the treated foliage. Possible correlations between dietary and DFR residue decline have been investigated considering data from 177 dietary residue trials along with 56 DFR trials from outdoor studies on the same crops besides residue decline data available in the Plant Properties Database (PPDB).The residue studies proved to follow the non-normal distribution and the comparison between DT50 of both types of residues for all the active substances revealed higher numerical DT50 mean values of the dietary residue compared to the DFRs. The dissipation from dietary residue studies is slower with a higher population mean compared to the mean for DFR studies for most active substances studied. A DT50 value from dietary residue studies could potentially act as a conservative surrogate DT50 for DFR which could be useful in determining the length of DFR studies and benefit both the agrochemical industry and the regulatory bodies in supporting non-dietary pesticide risk assessment.

Repair of distal hypospadias by construction of neourethra from augmented urethral plate with two lateral strips of glans skin and coverage with dartos flap followed by skin closure with preputial flap: single center series.

INTRODUCTION: Hypospadias is one of the most common anomalies in boys. Many surgical techniques for reconstruction of distal hypospadias have been described, each method having a different success rate. Our objective in this study is the assessment of the surgical technique for repair of distal hypospadias by construction of a neourethra from the augmented urethral plate with two lateral strips of glanular skin, coverage with a dartos flap, and followed by skin closure with preputial skin flap. MATERIAL AND METHODS: From March 2016 to November 2018, repair of distal hypospadias was performed in 56 children with a mean age of 3.2 years (range 2 to 8 years old). Minimum follow-up was 12 months, maximum up to 24 months. Success was defined by cosmetic appearance of the penis, parent perception of penile appearance, and urinary function. Uroflowmetry was done in 22 children at the 12 months follow-up. Parents evaluation of procedure was done by questionnaire using the pediatric penile perception score (PPPS). RESULTS: The results were successful with straight penile shaft, conical glans, slit-like meatus located at the tip of the glans, with no rotation, and normal micturition. Five children had urethrocutaneous fistula (8.9%) that were treated with simple closure. Parents reported 'very satisfactory' (98.2%) and 'satisfactory' (1.8%). CONCLUSIONS: The described technique of repair of distal hypospadias in children with different variants of urethral plate width and glans size showed good results, both operator's and parent's perception of the results being very satisfactory. This technique is categorised stage 2a in the IDEAL (Idea, Development, Evaluation, Assessment, and Long-term study) staging system for surgical innovations.

Holmium Laser Enucleation vs Bipolar Plasmakinetic Enucleation of a Large Volume Benign Prostatic Hyperplasia: A Randomized Controlled Trial.

Objectives: To compare safety and efficacy of bipolar plasmakinetic enucleation of prostate (BPEP) vs holmium laser enucleation of prostate (HoLEP) for management of large benign prostatic hyperplasia (BPH) (>80 g). Patients and Methods: Patients with failed medical treatment, International Prostate Symptom Score (IPSS) >13, peak urinary flow rate (Qmax)<15 mL/s and prostate size ≥80 g were enrolled in this randomized controlled trial from November 2016 to February 2018 and managed by HoLEP (Group A; 33 patients) or BPEP (Group B; 31 patients). Patients on anticoagulants (AC) were not excluded. Patients were followed up for 12 months. Perioperative data were compared between both groups using Student's-t, Mann-Whitney, Paired-t, Wilcoxon signed rank, chi-square, or Fisher-exact tests as appropriate. Results: There was no significant difference between both groups in age, rate of presentation with urinary retention, recurrent hematuria, frequency of patients on ACs/antiplatelets, prostate size, prostate specific antigen (PSA), Qmax, IPSS, quality of life (QoL), and post-void residual urine (PVRU). Operative time was significantly longer in BPEP (p = 0.003) and catheterization duration (p = 0.019). Other perioperative parameters including level of Na+ and hemoglobin, resected tissue weight, hospital stay, and complications were not significantly different between both groups. There was no need for blood transfusion in all patients. There was significant postoperative improvement in IPSS, PVRU, QoL, PSA, and Qmax in each group. However, there was no significant difference between both groups in these parameters. Conclusion: HoLEP and BPEP are comparable regarding safety and efficacy for treatment of BPH (>80 g) including patients on ACs. However, BPEP required a longer catheterization duration and operative time. ClinicalTrials.gov Identifier: NCT03998150.

Upregulation of Twist2 in Non-Muscle Invasive Urothelial Carcinoma of the Bladder Correlate with Response to Treatment and Progression.

BACKGROUND: Twist2 is a transcription factor and an epithelial-to-mesenchymal transition that plays an important role in cell polarity, cell adhesion, and has a role in tumour invasion and metastases. AIM: In this study, we examined the expression of Twist2 in non-muscle invasive bladder carcinoma (NMIBC) and correlated the expression with response to treatment and tumour progression. METHODS: Data of 305 patients with NMIBC of Ta, T1 were retrieved from hospitals archives. Twist2 expression was examined in tissue samples by immunohistochemistry at initial diagnosis and final follow-up, normal control was 10 normal urothelium, 10 patients with muscle-invasive bladder cancer (MIBC) were a positive control. Treatment of NMIBC was implemented according to the European Association of Urology guidelines on NMIBC. The descriptive statistical analysis included means, standard deviation, p-value; Univariate and multivariate Cox regression analyses. RESULTS: Twist2 expression score was identified as negative, low (1-15%); medium (15-40%); and high (40-100%). Patients who had low or low medium scores at the initial diagnosis had a good response and a favourable prognosis. Expression of a high score of Twist2 in patients having high-grade T1 tumours showed non-responsiveness to repeated courses of intravesical bacillus Calmette Guerin (BCG) therapy and was upstaged to MIBC. CONCLUSION: Twist2 expression in tissue samples of NMIBC would indicate the tumour response to therapy, upgrading and upstaging in the follow up after intravesical BCG therapy.

Clinical versus Pathologic staging of Renal Tumors: Role of Multi-Detector CT Urography.

INTRODUCTION: Our ability to diagnose renal cell carcinoma (RCC) has increased in the past 30 years as a result of the extensive application of imaging techniques, such as ultrasonography, computed tomography, and magnetic resonance imaging. Multi-detector computed tomography (MDCT) remains the most appropriate imaging modality for the diagnosis and staging of RCC. The aim of this work was to compare the findings of MDCT with surgical pathology to determine the accuracy of delineating tumor size, localization, organ confinement, lymph node metastases, and the extent of tumor thrombus in the renal vein and inferior vena cava. METHODS: The clinical, surgical, and anatomo-pathologic records of 99 patients treated by nephrectomy (radical or partial) for solid renal tumors at Theodor Bilharz Research Institute and Nasser Institute from 2005 to 2011 were reviewed retrospectively. All cases were staged pre-operatively with abdominal MDCT (pre- and post-contrast enhancement) in addition to the routine biochemical, hematological, and radiological work-up. The tumors' histologic types were determined according to the WHO classification of renal tumors in adults in 2004, and staging was updated to the TNM 2010 system. Data were analyzed using the t-test. RESULTS: The mean age was 52 (range 21-73). Seventy-eight patients were males, and 21 patients were females (Male/Female ratio: 3.7:1). There were no significant differences in the mean tumor size between radiographic and pathologic assessments in different tumor stages. The overall incidence of lymph node invasion in surgical specimens was 76%, whereas MDCT showed a positive incidence in 68.4% of cases (false negative result in 7 cases, 7.6%). CONCLUSION: Our findings indicated that MDCT urography is an accurate method to estimate renal tumor size, lymph node, vascular and visceral metastases preoperatively. Also, preoperative staging of renal tumors with MDCT represents a valuable and accurate tool.

Value of Computed Tomography for Predicting the Outcome After Percutaneous Nephrolithotomy.

INTRODUCTION: Computerized tomography of the urinary tract (CT-UT) has been established as the diagnostic procedure of choice for urinary stones. This study aimed to evaluate its role in predicting the outcome of percutaneous nephrolithotomy (PCNL) in terms of stone free rate and residual fragments. METHOD: This prospective cohort study was conducted on 34 patients in the Urology Department of Theodor Bilharz Research Institute from January 2013 to March 2014. The patients who had large and/or multiple renal stones, including staghorn stones, in 19 renal units scheduled for PCNL were included in this study. All had a pre-operative CT-UT to determine the stones' characteristics and renal anatomy. CT-UT, together with a kidney-Ureter-Bladder (KUB) film, was taken on the first post-operative day. The data were analyzed by SPSS version 17 using independent-samples t-test and the chi-squared test. RESULTS: CT-UT showed a statistical significant sensitivity in detecting residual fragments over standard KUB, yet this significance was lost when corrected to significant residual. Stone size and density were independent factors for the presence of residual stones. CONCLUSION: CT-UT post PCNL was sensitive to detect residual fragments, yet it showed no superiority over standard KUB in detecting significant residual.

Single-step renal dilatation in percutaneous nephrolithotomy: A prospective randomised study.

OBJECTIVE: To perform an economical single-step renal dilatation (RD) during percutaneous nephrolithotomy (PCNL), using directly a 30-F Amplatz dilator over the central Alken dilator, in a trial to reduce the operative duration and radiation exposure during RD while avoiding an exchange of dilators that might increase the risk of blood loss. PATIENTS AND METHODS: In a prospective randomised study including 49 patients divided into two groups, the first had RD before PCNL using the standard metallic telescopic dilators (Alken), and the second had RD using the 30-F Amplatz dilator over the central Alken dilator. The operative duration, with X-ray exposure, was calculated. The procedure outcome in terms of complications, stone-free rates and hospital stay was evaluated statistically. RESULTS: The tract was dilated correctly in all cases. The operative duration and X-ray exposure was shorter in patients undergoing single-step RD (P < 0.05). There were perioperative complications, according to the Clavien grading system, in 17 (34%) patients but there was no statistically significant difference between the groups. The stone-free rates were comparable in both groups. CONCLUSION: A single-step RD during PCNL is feasible, with a shorter operative duration and X-ray exposure. The outcomes were comparable with those of a standard metallic telescopic RD.