Exploring the detailed role of interleukins in cancer: A comprehensive review of literature.

The cancer cells that are not normal can grow into tumors, invade surrounding tissues, and travel to other parts of the body via the lymphatic or circulatory systems. Interleukins, a vital class of signaling proteins, facilitate cell-to-cell contact within the immune system. A type of non-coding RNA known as lncRNAs mediates its actions by regulating miRNA-mRNA roles (Interleukins). Because of their dual function in controlling the growth of tumors and altering the immune system's response to cancer cells, interleukins have been extensively studied concerning cancer. Understanding the complex relationships between interleukins, the immune system, the tumor microenvironment, and the components of interleukin signaling pathways that impact the miRNA-mRNA axis, including lncRNAs, has advanced significantly in cancer research. Due to the significant and all-encompassing influence of interleukins on the immune system and the development and advancement of cancers, lncRNAs play a crucial role in cancer research by modulating interleukins. Their diverse effects on immune system regulation, tumor growth encouragement, and tumor inhibition make them appealing candidates for potential cancer treatments and diagnostics. A deeper understanding of the relationship between the biology of interleukin and lncRNAs will likely result in more effective immunotherapy strategies and individualized cancer treatments.

Curcumin attenuates doxorubicin-induced cardiotoxicity via suppressing oxidative Stress, preventing inflammation and apoptosis: Ultrastructural and computational approaches.

Currently, doxorubicin (DOX) is one of the medications commonly used in chemotherapy to treat different types of tumors.Nonetheless, despite being effective in multiple tumors, yet its use is limited owing to its cytotoxic effects, the therapeutic use of DOX has been limited. This work aimed to explore whether curcumin (CMN) can prevents DOX-induced cardiotoxicity in rats. Four groups of rats were created, with the first functioning as a control, while the second group received CMN. DOX alone was administered to the third group, whereas CMN and DOX were administered to the fourth group. Lipid peroxidation assessed as Malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidative stress markers as catalase (CAT), superoxide dismutase (SOD), and inflammatory markers as tumor necrosis factor-alpha (TNF-α) in heart homogenates, each one was assessed. Heart specimens was investigated histologically and ultrastructurally. Increased, AST, and ALT serum levels, increased MDA levels, decreased SOD and CAT levels, and increased TNF-α concentrations in heart homogenates were all signs of DOX-induced myocardial injury. Histological and ultrastructural examinations revealed vacuoles and larger, swollen mitochondria in the cytoplasm. Furthermore, DOX caused significant changes in the myocardium, most notably nuclei disintegration, myofibrillar loss, and myocyte vacuolization. Using CMN with DOX reduced the harmful consequences of DOX on the myocardium by returning the increased AST and ALT levels to their original levels as compared to the control and reducing them. In cardiac tissue, CMN significantly increased the concentrations of SOD and CAT and significantly decreased the concentrations of MDA and TNF-α. Biochemical and histological studies have demonstrated that CMN has a heart-protective effect that might be related to its antioxidant and anti-inflammatory capabilities.

Therapeutic properties, biological effects, antiliver cancer, and anticolon cancer effects of some natural compounds: A biochemical approach.

Natural compounds, such as carotenoids, flavonoids, anthocyanins, or terpenoids, are physiologically active components found in plants (pigments), often known as phytochemicals or phytonutrients. The in vitro cytotoxic and anticolon cancer effects of biologically bavachin, bavachinin, artepillin C, and aromadendrin compounds against SW48, SNU-C1, COLO 205, RKO, LS411N, and SW1417 cancer cell lines were assessed. Results of enzymes and antibacterial, antifungal were in level of micromolar that is good impacts. These natural compounds may be antidiabetic, anticancer, and antibacterial candidates for drug design. IC50 results were obtained between 14-19 and 5-119 µM for α-amylase and α-glucosidase, respectively. Good inhibitor Bavachinin was detected for both enzymes (IC50 for α-amylase: 14.37 µM and IC50 for α-glucosidase: 5.27 µM). The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against pancreatic α-amylase and α-glucosidase were assessed by conducting the molecular docking study. The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against some of the expressed surface receptor proteins (CD44, CD47, CXCR4, EGFR, folate receptor, HER2, and endothelin receptor) in the mentioned cell lines were investigated using the molecular docking calculations. The results illustrated the atomic-level properties and potential interactions. These chemicals have high binding affinities to the enzymes and proteins, according to the docking scores. In addition, the compounds formed strong contacts with the enzymes and receptors. Thus, these compounds could be potential inhibitors for enzymes and cancer cells.

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge.

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Physical Activity Among Medical Students at the University of Khartoum, Sudan, 2022: Knowledge, Practice, and Barriers.

Introduction Physical inactivity is a highly prevalent modifiable risk factor for many diseases, including cardiovascular and cerebrovascular diseases, the leading causes of death. Many health institutes have issued and adopted guidelines and recommendations on physical activity. This study aims to study the knowledge, practice, and barriers of medical students enrolled at the University of Khartoum, Sudan, regarding physical activity. It aimed to assess the students' knowledge about physical activity, to determine the levels of physical activity and compare it with the WHO recommended levels and data from other countries, to compare the activity and sedentary levels between males and females, and to take a look on the barriers to physical activity. Methods An observational, descriptive, cross-sectional study was conducted at the Faculty of Medicine, University of Khartoum in December 2022. A total of 336 students were included using systematic random sampling. Data were collected using an online questionnaire that included the Global Physical Activity Questionnaire (GPAQ). Levels of physical activity were described and compared between males and females. Results Around 40.5% of the students achieved the recommended level of physical activity. The mean level of vigorous-intensity physical activity was 50.9 minutes/week (SD= 125.7), the mean level of moderate-intensity physical activity was 156.5 minutes/week (SD= 316.1), the mean level of total physical activity was 207 minutes/week (SD= 356). Between males and females, there was a significant mean difference in the level of vigorous-intensity physical activity and total physical activity. The mean level of sedentary behavior was 7.61 hours/day (SD= 4.62) with no significant difference between males and females (p=0.127). Students showed good knowledge about the cardiovascular and mental benefits of physical activity but not about its protective benefits against cancer. Only 19.4% knew the WHO-recommended levels of physical activity. The most common major barriers toward physical activity reported by the students were lack of time (43.8%), and lack of suitable facilities (31.3%) among others. Conclusion More than half (59.5%) of the students were insufficiently active. Levels of physical activity were significantly associated with the participants' sex but not their knowledge of the recommended levels of physical activity. Males showed higher levels of physical activity. Lack of time was the most common barrier to exercise. More knowledge and education about physical activity should be provided as well as suitable facilities.

Oxidative Stress Biomarkers in Cystic Fibrosis and Cystic Fibrosis-Related Diabetes in Children: A Literature Review.

The most common inherited condition that results in death, particularly in those of Caucasian heritage, is cystic fibrosis (CF). Of all the young adults diagnosed with cystic fibrosis, 20% will develop hyperglycemia as a complication, later classified as a disease associated with cystic fibrosis. Impaired insulin secretion and glucose intolerance represent the primary mechanisms associated with diabetes (type 1 or type 2) and cystic fibrosis. Oxidative stress represents the imbalance between oxygen-reactive species and antioxidant defense mechanisms. This pathogenic mechanism is vital in triggering other chronic diseases, including cystic fibrosis-related diabetes. It is essential to understand oxidative stress and the significant impact it has on CFRD. This way, therapies can be individually adjusted and tailored to each patient's needs. This review aims to understand the connection between CFRD and oxidative stress. As a subsidiary element, we analyzed the effects of glycemic balance on complications and their evolution over time, providing insights into their potential benefits in mitigating oxidative stress-associated complications.

Pterostilbene ameliorates the disrupted Adars expression and improves liver fibrosis in DEN-induced liver injury in Wistar rats: A novel potential effect.

The knowledge of RNA editing modifications and its subsequent proteomic diversity in is still limited and represents only the tip of the iceberg. Adenosine to inosine (A-to-I) RNA editing is the most prevalent in RNA editome with a rising role for ADARgene family as a major regulator of the dynamic landscape of RNA editing. This study aimed at evaluating the potential chemopreventive effects of the epigenetic regulator "pterostilbene" in diethylnitrosamine (DEN)-exposedrat model. Consequently, the hepatic Adars expression was investigated as a possible mechanism for mediation of the putative pterostilbene-induced chemopreventive effect. The effects of administration of pterostilbene were investigated on the structural changes, immunohistochemical staining, liver function test, serum alpha feto-protein (AFP), IL-6, and hepatic Adar1 and Adar2 relative gene expression at the beginning and at the 6th week of the study. Pterostilbene attenuated DEN-induced liver injury, improves hepatocyte parrafin-1 (Hep Par-1), decreases heat shock protein 70 (HSP70), improved AFP, serum albumin, transaminases, IL-6 with alleviation of disturbed hepatic Adar1 and Adar2 expression. This study spotlights the role of pterostilbene in attenuation of DEN-induced liver injury which could be mediated, at least partially, through the alleviation of the aberrant expression of Adar enzymes. Yet, more in-depth studies are needed to further elucidate the molecular mechanisms underlying the effects of pterostilbene on RNA editing enzymes.

Experience with modified two stage inner preputial flap for repair of proximal hypospadias with chordee: A single institution study with intermediate follow up.

PURPOSE: We present our modified technique of using the inner preputial flap to cover the penile shaft, while removing the subcutaneous tissue of the distal part of the flap to act similar to graft. Herein, we present our experience with modified two stage inner preputial flap for repair of proximal hypospadias with chordee. PATIENTS AND METHODS: The current study was a single-institution retrospective study between January 2016 and December 2020. Thirty-one patients with proximal hypospadias with chordee were included and underwent our modified technique. We excluded re-operative hypospadias and incomplete follow-up cases (<6 month of follow up). Patient demographics, outcomes and complications in the form of fistula formation, diverticulum, metal stenosis, stricture formation and glans dehiscence were reviewed. RESULTS: A total of 31 patients were included in the study and underwent our modified technique. The median age was 18 months (9-60) & IQR 15-25). The median follow up was 40 months. Overall, success was achieved in 24 cases (77.4%). Complications occurred in seven cases (22.6%) and included urethrocutanous fistula in three patients (9.7%), diverticulum in two patients (6.5.%), metal stenosis in one patient (3.2%) and glans dehiscence in one patient (3.2%). CONCLUSION: Our technique provides a favourable outcome with a low complication rate for repair of proximal severe hypospadias. LEVEL OF EVIDENCE: Case Series Study (Level IV).

"Real-world" radiomics from multi-vendor MRI: an original retrospective study on the prediction of nodal status and disease survival in breast cancer, as an exemplar to promote discussion of the wider issues.

BACKGROUND: Most MRI radiomics studies to date, even multi-centre ones, have used "pure" datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in "real-world" scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice. METHODS: One hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests. RESULTS: Prediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9-51.8% (radiomic features from different combinations of image contrasts), and 26.7-35.6% (clinical plus radiomics features). CONCLUSIONS: Radiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results.

Role of dietary selenium in alleviating bisphenol A toxicity of liver albino rats: Histological, ultrastructural, and biomarker assessments.

Bisphenol A (BPA) is used as a plasticizer in polycarbonate plastics. It has been used in consumer products and epoxy resins for decades as protective coatings and linings for food and beverage bottles. This can trigger human reactions to BPA which interferes with estrogen receptors. Our study explored the ameliorative effects of selenium (Se) in male rats on liver damage caused by BPA. Rats were divided into four groups at random: The first one obtained olive oil and acted as a control. Se (0.5 mg/kg diet) was given for the second group. The third one was treated with BPA (10 mg/kg body weight/day) orally. Concomitantly Se (0.5 mg/kg diet) and BPA (10 mg/kg body weight/day) were given orally in the fourth one. Liver specimens were prepared for light, electron microscopes and the serum samples were screened for biochemical markers. In the BPA received group, histological findings indicated apoptotic hepatic histological changes such as sinusoidal congestion, cytoplasmic vacuolation and leukocyte infiltration. Ultrastructurally, the same group had mitochondrial degeneration, rough endoplasmic reticulum swelling, and nuclear pyknosis, as well as fat droplet deposition and lysosome enhancement. Liver enzymes: In the BPA group, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been substantially increased. Moreover, histological and ultrastructural improvements were seen in the rat population treated with BPA and Se, whereas ALT and AST levels were lowered and malondialdehyde (MDA), glutathione peroxidase (GPx), human C reactive protein (hCRP), and the serum levels of interleukin-6 (IL-6) were significantly modulated. PRACTICAL APPLICATIONS: Bisphenol A (BPA) is used in the manufacturing of polycarbonate plastic (e.g., water bottles, baby bottles) and epoxy resins (e.g., inner coating in metallic food cans). It is a non-polymer preservative for other plastics, one of the contaminants of the atmosphere and a common endocrine estrogenic disruptor. Our study explored the ameliorative effects of selenium (Se) in male rats on liver damage caused by BPA. Rats were divided into four groups at random: The first one obtained olive oil and acted as a control. Se (0.5 mg/kg diet) was given for the second group. The third one was treated with BPA (10 mg/kg body weight/day) orally. Concomitant Se (0.5 mg/kg diet) and BPA (10 mg/kg body weight/day) were given in the fourth one. Liver specimens were prepared for light, electron microscopes and the serum samples were screened for biochemical markers.

A three-step repair of post circumcision coronal fistula: A glans flap, urethral closure, and dartos flap interposition.

PURPOSE: To evaluate the outcomes of patients who underwent a post-circumcision coronal fistula repair by means of a three-step repair technique: glans flap, urethral closure, and dartos flap interposition. MATERIALS AND METHODS: We retrospectively reviewed the outcomes of 23 patients with postcircumcision urethrocutaneous fistulas who were treated at our institution between January of 2014 and December of 2018. The patients included in this review had exclusively a coronal fistula with an adequate glans bridge between the fistula and the urethral meatus and underwent surgical repair at least 6 months after the initial injury. We excluded from the study patients who had multiple level fistulas, glans dehiscence and patients that were lost to follow-up less than 6 months post fistula repair. RESULTS: The median age at the time of the repair was 9.2 (range: 6.3 to 31) months. The fistulas were classified according to their size as small (ranging from pinpoint to ≤4 mm; n = 19) or large (>4 mm; n = 4). The overall success rate was 87% (20 of 23 patients). The success rates for the small and the large fistulas were 94.7% (18 of 19) and 50% (2 of 4), respectively. An indwelling urethral stent was used in all patients, except in those with pinpoint fistulas. The mean follow-up was 19.9 (6-60) months. CONCLUSIONS: Post-circumcision coronal urethrocutaneous fistulas less or equal to 4 mm in diameter without glans dehiscence can be successfully repaired using a three-step repair technique, with a recurrence rate of less than 6%. For larger fistulas, a formal urethroplasty is recommended due to high recurrence rate of the three-step repair technique. LEVEL OF EVIDENCE: Case Series (Level IV).

Pharmacokinetic modeling of dynamic contrast-enhanced MRI using a reference region and input function tail.

PURPOSE: Quantitative analysis of dynamic contrast-enhanced MRI (DCE-MRI) requires an arterial input function (AIF) which is difficult to measure. We propose the reference region and input function tail (RRIFT) approach which uses a reference tissue and the washout portion of the AIF. METHODS: RRIFT was evaluated in simulations with 100 parameter combinations at various temporal resolutions (5-30 s) and noise levels (σ = 0.01-0.05 mM). RRIFT was compared against the extended Tofts model (ETM) in 8 studies from patients with glioblastoma multiforme. Two versions of RRIFT were evaluated: one using measured patient-specific AIF tails, and another assuming a literature-based AIF tail. RESULTS: RRIFT estimated the transfer constant Ktrans and interstitial volume ve with median errors within 20% across all simulations. RRIFT was more accurate and precise than the ETM at temporal resolutions slower than 10 s. The percentage error of Ktrans had a median and interquartile range of -9 ± 45% with the ETM and -2 ± 17% with RRIFT at a temporal resolution of 30 s under noiseless conditions. RRIFT was in excellent agreement with the ETM in vivo, with concordance correlation coefficients (CCC) of 0.95 for Ktrans , 0.96 for ve , and 0.73 for the plasma volume vp using a measured AIF tail. With the literature-based AIF tail, the CCC was 0.89 for Ktrans , 0.93 for ve and 0.78 for vp . CONCLUSIONS: Quantitative DCE-MRI analysis using the input function tail and a reference tissue yields absolute kinetic parameters with the RRIFT method. This approach was viable in simulation and in vivo for temporal resolutions as low as 30 s.

Initial laparoscopy and optimized approach for unilateral nonpalpable testis: review of 8-year single-center experience.

PURPOSE: We evaluated the role of initial laparoscopy and optimized approach in cases of unilateral nonpalpable testis. METHODS: Seventy-four patients with nonpalpable testes were presented. We excluded 9 patients, with palpable testes under anesthesia. Laparoscopy was offered to 65 patients. Contralateral testis hypertrophy with length ≥ 1.8 cm was confirmed in 47 patients. Ultrasound results were available for 35 patients. RESULTS: Age ranged from 1 to 10 years. Of 65 nonpalpable testes, right side comprised 23 (35.4%) and the left 42 (64.6%). Laparoscopy revealed intra-abdominal testis in 18 patients (27.7%), blind-ending vessels and vas in 8 (12.3%), and vas and vessels traversing the internal ring in 39 (60%). Treatment of intra-abdominal testes included Fowler-Stephens orchiopexy in 7 patients, laparoscopic orchiopexy in 9, and laparoscopic orchiectomy in 2. In 8 patients with blind-ending vas and vessels, laparoscopy was terminated. In 39 patients with vas and vessels traversing the internal ring, scrotal exploration was performed in 36 patients with closed internal ring and inguinal exploration in 3 with open internal ring. Vanished testes were present in 43/47(91.5%) of patients with contralateral testis hypertrophy ≥ 1.8 cm. Ultrasound detected the presence of a testis in only 4/11 (36.3%) of patients, although it could not identify vanished testis. CONCLUSIONS: Initial laparoscopy should be retained as one of the standard treatment for nonpalpable testis. It was the only required modality in 26 patients (40%) and optimized further treatment in 39 patients (60%) by evaluation of the condition of the internal ring.

An extended reference region model for DCE-MRI that accounts for plasma volume.

The reference region model (RRM) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides pharmacokinetic parameters without requiring the arterial input function. A limitation of the RRM is that it assumes that the blood plasma volume in the tissue of interest is zero, but this is often not true in highly vascularized tissues, such as some tumours. This study proposes an extended reference region model (ERRM) to account for tissue plasma volume. Furthermore, ERRM was combined with a two-fit approach to reduce the number of fitting parameters, and this was named the constrained ERRM (CERRM). The accuracy and precision of RRM, ERRM and CERRM were evaluated in simulations covering a range of parameters, noise and temporal resolutions. These models were also compared with the extended Tofts model (ETM) on in vivo glioblastoma multiforme data. In simulations, RRM overestimated Ktrans by over 10% at vp  = 0.01 under noiseless conditions. In comparison, ERRM and CERRM were both accurate, with CERRM showing better precision when noise was included. On in vivo data, CERRM provided maps that had the highest agreement with ETM, whilst also being robust at temporal resolutions as poor as 30 s. ERRM can provide pharmacokinetic parameters without an arterial input function in tissues with non-negligible vp where RRM provides inaccurate estimates. The two-fit approach, named CERRM, further improves on the accuracy and precision of ERRM.

Investigating the role of functional imaging in the management of soft-tissue sarcomas of the extremities.

BACKGROUND AND PURPOSE: In this work, we validate a texture-based model computed from positron emission tomography (PET) and magnetic resonance imaging (MRI) for the prediction of lung metastases in soft-tissue sarcomas (STS). We explore functional imaging at different treatment time points and evaluate the feasibility of radiotherapy dose painting as a potential treatment strategy for patients with higher metastatic risk. MATERIALS AND METHODS: We acquired fluorodeoxyglucose (FDG)-PET, fluoromisonidazole (FMISO)-PET, diffusion weighting (DW)-MRI and dynamic contrast enhanced (DCE)-MRI data for 18 patients with extremity STS before, during, and after pre-operative radiotherapy. We tested the lung metastases prediction model using pre-treatment images. We evaluated the feasibility of dose painting using volumetric arc therapy (VMAT) via treatment re-planning with a prescription of 50 Gy to the planning target volume (PTV50Gy) and boost doses of 60 Gy to the FDG hypermetabolic gross tumour volume (GTV60Gy) and 65 Gy to the low-perfusion DCE-MRI hypoxic GTV contained within the GTV60Gy (GTV65Gy). RESULTS: The texture-based model for lung metastases prediction reached an area under the curve (AUC), sensitivity, specificity and accuracy of 0.71, 0.75, 0.85 and 0.82, respectively. Dose painting resulted in adequate coverage and homogeneity in the re-planned treatments: D95% to the PTV50Gy, GTV60Gy and GTV65Gy were 50.0 Gy, 60.3 Gy and 65.4 Gy, respectively. CONCLUSIONS: Textural biomarkers extracted from FDG-PET and MRI could be useful to identify STS patients that might benefit from dose escalation. The feasibility of treatment planning with double boost levels to intratumoural GTV functional sub-volumes was established.

Increased robustness in reference region model analysis of DCE MRI using two-step constrained approaches.

PURPOSE: Reference region models (RRMs) can quantify tumor perfusion in dynamic contrast-enhanced MRI without an arterial input function. Inspection of the RRM reveals that one of the free parameters in the fit is uniquely linked to the reference region and is common to all voxels. A two-step approach is proposed that takes this constraint into account. METHODS: Three constrained RRM (CRRM) approaches were devised and evaluated. Simulations were performed to compare their accuracy and precision over a range of noise and temporal resolutions. The CRRM was also applied on a virtual phantom that simulates different perfusion values. In vivo evaluation was performed on data from breast cancer and soft tissue sarcoma. RESULTS: In simulations, the CRRM consistently improved precision and had better accuracy at low signal-to-noise ratio (SNR). In virtual phantom, the CRRMs were able to fit voxels that had similar kinetics to the reference tissue, whereas the unconstrained models failed to accurately fit these voxels. In the in vivo data, the constrained approaches produced parameter maps that had less variability and were in better agreement with the Tofts model. CONCLUSION: These findings indicate that the two-step fitting approach of the CRRM can reduce the variability of perfusion estimates for quantifying perfusion with dynamic contrast-enhanced (DCE) MRI. Magn Reson Med 78:1547-1557, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Transurethral Pneumatic Cystolithotripsy: A Novel Approach.

OBJECTIVE: Various endoscopic instruments used in treating renal stones have been used in managing bladder calculi. Our aim is to evaluate the use of transurethral ureteroscopic pneumatic cystolithotripsy for the management of large bladder calculi. PATIENTS AND METHODS: In a retrospective study conducted between May 2005 and July 2011, 53 patients with solitary bladder stones were subjected to our technique, transurethral ureteroscopic pneumatic cystolithotripsy. The mean patient age was 54.3 years. The mean stone size was 4.8 cm. Diagnostic cystoscopy was performed first. A semirigid ureteroscope with a pneumatic probe was introduced through the cystoscope sheath, and pneumatic lithotripsy was performed. The cystoscope sheath works as a draining channel, allowing bladder evacuation. The bladder collapses over the stone and, subsequently, prevents stone migration, which shortens the lithotripsy's duration. Stone immobilization allows the transmission of full pneumatic power to the stone. The stone fragments were removed through periodic bladder irrigation using an Ellick evacuation-irrigation system, and a 16F Foley catheter was placed at the end of the procedure. RESULTS: Our technique was effective in all cases, including stone-free bladders. No surgical complications were detected. The mean operative time was 83 ± 21.0 minutes, which is comparable to that of standard management. The mean duration of lithotripsy and evacuation was 29.7 ± 18.4 minutes. In the postoperative period, patients were followed up for 18 months, with no urethral stricture being reported in any case. CONCLUSION: The transurethral ureteroscopic pneumatic cystolithotripsy procedure is a safe technique for the management of large bladder calculi. It allows the bladder to collapse over the stone, leading to stone immobilization and, subsequently, decreasing lithotripsy duration. Our procedure is associated with a minimal chance of postoperative urethral injury because all stone fragments are evacuated through the cystoscope sheath, without contact with the urethral urothelium.

Modified penile disassembly technique for boys with epispadias and those undergoing complete primary repair of exstrophy: long-term outcomes.

OBJECTIVES: To describe our experience performing the modified penile disassembly technique for boys with epispadias and for those undergoing complete primary repair of exstrophy. METHODS: Between January 2004 and July 2009, 34 boys underwent the modified penile disassembly technique at our institution. The first group included 15 boys with bladder exstrophy who underwent complete primary repair of exstrophy. The second group comprised 11 boys with penopupic epispadias after previous closure of bladder exstrophy. The third group included 8 boys with isolated complete epispadias. RESULTS: The age range was 3 months to 8 years (median, 9 months). The follow-up time ranged from 36 months to 8 years (mean, 63 months). A conical-shaped glans with the absence of any ischemic changes occurred in 94% of patients. A mild degree of penile dorsal tilt occurred in 11.7% of patients, urethrocutanous fistula in 17.6% and meatal stenosis 5.8%. In cases of complete primary repair of exstrophy, hydronephrosis occurred in 66.6% of patients. Vesicoureteral reflux appeared in 60% of patients; despite suppressive antibiotic therapy, 33.3% are awaiting reimplantation. Continence with volitional voiding with dry intervals of ≥3 h was achieved in 40% of patients. CONCLUSIONS: The modified penile disassembly technique can be used in epispadias and complete primary repair of exstrophy with excellent cosmetic results. Preservation of the distal urethral plate along with both hemiglans avoids shortening and prevents occurrence of hypospadias. Complete primary repair of exstrophy is a feasible technique with positive effects on continence with preservation of kidney function.

Identification of key mechanisms controlling gene expression in Leishmania infected macrophages using genome-wide promoter analysis.

The present study describes the in silico prediction of the regulatory network of Leishmania infected human macrophages. The construction of the gene regulatory network requires the identification of Transcription Factor Binding Sites (TFBSs) in the regulatory regions (promoters, enhancers) of genes that are regulated upon Leishmania infection. The promoters of human, mouse, rat, dog and chimpanzee genes were first identified in the whole genomes using available experimental data on full length cDNA sequences or deep CAGE tag data (DBTSS, FANTOM3, FANTOM4), mRNA models (ENSEMBL), or using hand annotated data (EPD, TRANSFAC). A phylogenetic footprinting analysis and a MATCH analysis of the promoter sequences were then performed to predict TFBS. Then, an SQL database that integrates all results of promoter analysis as well as other genome annotation information obtained from ENSEMBL, TRANSFAC, TRED (Transcription Regulatory Element Database), ORegAnno and the ENCODE project, was established. Finally publicly available expression data from human Leishmania infected macrophages were analyzed using the genome-wide information on predicted TFBS with the computer system ExPlain™. The gene regulatory network was constructed and activated signal transduction pathways were revealed. The Irak1 pathway was identified as a key pathway regulating gene expression changes in Leishmania infected macrophages.

Identifying neuropathic pain among patients with chronic low-back pain: use of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale.

BACKGROUND AND OBJECTIVES: Although the literature contains information about prevalence and incidence of low-back pain (LBP), little information is available about the contribution of the neuropathic element to LBP. Our study was designed to investigate the prevalence of neuropathic pain among a sample of chronic LBP patients in Saudi Arabia by use of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale. METHODS: A total of 1,169 patients from 117 centers agreed to participate in the study over a period of 6.5 months. The LANSS pain scale was applied to each patient in an interview format. The characteristics of pain and sensory dysfunction were tested and recorded. RESULTS: According to the LANSS pain scale, 639 patients (54.7%) had scores of 12 points or more, which suggested a neuropathic type of pain, and 530 patients (45.3%) had scores of less than 12, which suggested a nociceptive type of pain. Factors that are associated with neuropathic pain are advanced age, female gender, increased height, white race, hypertension and diabetes, a history of smoking, previous back surgery, and previous medications. CONCLUSION: Neuropathic pain is a major contributor to chronic LBP, and the LANSS pain scale is a useful tool to distinguish patients with neuropathic pain from those with nociceptive pain.