Ionic reverberation modulates the cellular fate of CD8+tissue resident memory T cells (TRMs) in patients with renal cell carcinoma: A novel mechanism.

In metastatic renal cell carcinoma (mRCC), existing treatments including checkpoint inhibitors are failed to cure and/or prevent recurrence of the disease. Therefore, in-depth understanding of tumor tissue resident memory T cells (TRMs) dysfunction are necessitated to enrich efficacy of immunotherapies and increasing disease free survival in treated patients. In patients, we observed dysregulation of K+, Ca2+, Na2+ and Zn2+ ion channels leads to excess infiltration of their respective ions in tumor TRMs, thus ionic gradients are disturbed and cells became hyperpolarized. Moreover, overloaded intramitochondrial calcium caused mitochondrial depolarization and trigger apoptosis of tumor TRMs. Decreased prevalence of activated tumor TRMs reflected our observations. Furthermore, disruptions in ionic concentrations impaired the functional activities and/or suppressed anti-tumor action of circulating and tumor TRMs in RCC. Collectively, these findings revealed novel mechanism behind dysfunctionality of tumor TRMs. Implicating enrichment of activated TRMs within tumor would be beneficial for better management of RCC patients.

Agronomic biofortification of forage crops with zinc and copper for enhancing nutritive potential: a systematic review.

Many developing countries are facing a silent increase in deficiency of micronutrients in forage crops that results in decreased levels of essential nutrients in animals. Micronutrients are essential not only for basic metabolic processes of forage crops but also for sustaining animal health. Forage productivity and quality are severely affected by soil micronutrients deficiencies, especially zinc and copper. This review summarizes the literature highlighting the significance of different methodologies used to increase the biomass and quality of forage so as to enhance the micronutrient content of the forage crops through biofortification. Biofortification is a promising and sustainable agriculture-based strategy to reduce micronutrient deficiency in crops. The experiments and trials conducted at different locations of the world showed that copper and zinc concentrations in animal fodders can be enhanced through the process of foliar application. Additionally, agronomic biofortification showed more promising results, and thus is an outstanding, fast, and cost-effective technique for the immediate enrichment of forage in order to overcome malnutrition in animals. © 2022 Society of Chemical Industry.

Serum prostate-specific antigen trends and prostate cancer detection on follow-up in men with a prior negative biopsy: A cohort study.

Introduction: Elevated serum prostate-specific antigen (PSA) is the most common trigger for a prostate biopsy. However, the range of normal PSA is poorly defined in many populations. Men with "elevated" PSA may not harbor cancer, and it is unclear if such men with a prior negative prostate biopsy should be biopsied again. We conducted a cohort study to assess the PSA trends and cancer detection rates in such men. Methods: In an Institutional Review Board-approved ambispective study, men who underwent prostate biopsy between January 2016 and December 2021 for PSA > 4 ng/mL were identified. Among them, those whose biopsy was negative for malignancy were contacted either telephonically or reviewed in person, and the most recent PSA and histopathology of any repeat prostate biopsy were determined. These were evaluated to assess the PSA trend, re-biopsy rate, and cancer detection rate. Results: During the study period, prostate biopsies were performed in a total of 1260 men; out of which 444 were negative for malignancy and 241 patients fulfilled the inclusion criteria. Their median prebiopsy PSA was 9.81 ng/mL (interquartile range [IQR]: 7.14-15.6), and the median follow-up PSA was 5.08 (IQR: 3.18-8.4). At a median follow-up of 53 months (range: 6-77 months), PSA had decreased in 177 (73.4%) patients, was static in 48 (19.9%) patients, and increased in only 16 (6.6%) patients. Repeat biopsy was performed on 20 patients; of whom seven had cancer (35%) with an overall positivity rate of 2.9% among the 241 patients. Although the positivity rate was higher in men with increased PSA, it was not statistically different from those with lower or similar PSA. No factors could be identified to predict a positive repeat biopsy. Conclusions: PSA, the sole trigger for a prostate biopsy, declined in nearly three-quarters of men with a negative first biopsy, and <3% of men were detected to have cancer on a repeat biopsy. This information could help appropriately counsel patients and allay anxiety after a negative biopsy.

Prepubic inflammatory liposarcoma presenting as urosepsis.

Inflammatory well-differentiated liposarcoma is a rare soft-tissue tumor which is predominantly retroperitoneal in origin. We report a 72-year-old male without co-morbidities with suspected urosepsis and an obstructing ureteric calculus. Despite adequate diversion and broad-spectrum antimicrobials, the leukocytosis persisted. Further imaging revealed a locally infiltrating prepubic mass which was suspicious of a lymphoid malignancy and was found to be a high-grade liposarcoma on biopsy. He underwent open wide local resection of the tumor and the histopathology revealed an inflammatory well-differentiated liposarcoma with areas of neutrophilic abscess and necrosis. A dramatic response to the surgical resection was seen and the leukocytosis resolved within a few days.

Association of heavy metals and trace elements in carcinoma urinary bladder: A case-controlled study.

Introduction: Abnormal levels of heavy metals (HM) and trace elements (TE) affect body metabolism and can induce carcinogenesis. This study aims to evaluate the role of HM and TE in carcinoma urinary bladder (CAUB). Methods: Patients with biopsy-proven CAUB (n = 100) were taken as the study group, while age-and sex-matched healthy volunteers were taken as control (n = 100). Blood and urine samples were compared for Arsenic (As), Copper (Cu), Manganese (Mn), Selenium (Se), Cadmium (Cd), Lead (Pb), and Mercury (Hg) levels. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels were assessed to know the redox status between the two groups. Results: A significantly higher blood level of As, Mn, and Pb was observed in CAUB cases as compared to controls. Blood Se level was significantly lower in CAUB patients. On comparing urinary levels, CAUB patients had a higher As, Mn, and Pb levels compared to controls. Further, 68% and 59% of patients had their blood and urinary HM and TE levels above the permitted level, respectively. CAUB cases also had a lower GSH-Px (113.5 ± 44.7 vs. 163.9 ± 120.5, P = 0.0002), lower SOD levels (11.35 ± 5.6 vs. 13.75 ± 3.9, P = 0.008), and a higher LPO levels (15.5 ± 14.7 vs. 11.18 ± 11.2, P = 0.02) in the serum. Conclusions: A significantly higher concentration of As, Mn, and Pb was noted in the blood and urine of CAUB patients compared to controls. CAUB cases also had lower serum GSH-Px and SOD levels with a concomitant increased serum LPO assay suggesting underlying oxidative stress.

Non-invasive diagnostic potential of microRNA-203 in liquid biopsy of urothelial carcinoma of bladder.

Increased CD44 antigen activity has been reported in recurrent cases of UBC. To date, no reliable biomarker is available with high significance and specificity for non-invasive detection of UBC. This study aimed to identify a CD44-linked microRNAs (miRNAs) (miR-9, miR-34a, miR-203) for non-invasive diagnosis of bladder cancer from other urinary tract malignancies. The expression of CD44-linked miRNAs was examined in serum, urine, and tissue specimens of Indian UBC patients (N = 25). For this purpose, healthy subjects (N = 25) and benign prostatic hyperplasia (BPH) (N = 10) patients were taken as controls. The relative expression of miRNAs was analyzed in serum, urine, and tissue samples using real-time quantitative reverse transcription PCR (qRT-PCR). The diagnostic potential of these miRNAs was accessed by plotting ROC curve. Increased miR-9 expression was observed in serum of UBC patients than healthy and BPH controls. In UBC patients, miR-34a expression was lower than healthy controls but non-significant as compared to BPH. miR-203 expression was considerably higher in serum of UBC patients but non-significant as compared to BPH controls. miR-203 was found to be considerably higher in urine samples from UBC patients as compared to BPH and healthy controls. The diagnostic potential of these miRNAs was evaluated using the ROC curve. Higher miR-203 levels in the urine of Indian UBC patients demonstrate its non-invasive diagnostic ability out of the three miRNAs studied. Our results characterize the non-invasive diagnostic potential of CD44-linked miR-203 in the urine of Indian UBC patients, which could be utilized in clinical settings in future after validation in larger patient cohort.

Impact of bariatric surgery on urinary incontinence in morbidly obese individuals.

BACKGROUND: There is scanty evidence on the impact of bariatric surgery on urinary incontinence (UI) in the Asian population. METHODOLOGY: Patients who underwent bariatric surgery from June 2018 to June 2019 were screened using the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) questionnaire. Patients having UI were identified and followed until 1 year of surgery using the ICIQ-UI-SF. These were classified as having stress, urge, or mixed type of UI. The prevalence, change in scores, and the number of pads used were compared at baseline and at follow-up. RESULTS: A total of 148 patients underwent bariatric surgery of whom, 41 patients (M = 2, F = 39) had UI. Stress incontinence was seen in 70.7%, 19.5% had urge incontinence, and rest had the mixed type. Using logistic regression, it was found that female gender was the most important predictor of having UI (OR: 8.33). The prevalence of UI decreased from 27.7% at baseline to 8.1% at 6 months and 3.4% at 12 months. The mean ICIQ-UI-SF score improved from 8.76 (SD = 3.2) at baseline to 0.66 (SD = 2.1) at 12 months of follow-up. The proportion of patients with UI using any number of pads decreased from 92.7% at baseline to 9.8% at 12 months. There was a decrease in the number of patients having moderate to very severe UI from 35 (85.4%) at baseline to 2 (4.9%) at 12 months. Proportion of patients showing resolution was highest among the stress incontinence group at 96.5%. Presence or absence of comorbidities did not significantly influence the ICIQ-UI-SF scores. CONCLUSION: Bariatric surgery leads to profound improvement in UI in obese individuals which is well sustained until 1 year of follow-up. Resolution rates might be higher in Asian population.

Comparative evaluation of the analgesic efficacy of ultrasound-guided erector spinae plane block versus intrathecal morphine in patients undergoing percutaneous nephrolithotomy surgery: A prospective randomized pilot study.

OBJECTIVES: Existing research on erector spinae plane block and intrathecal morphine in patients undergoing percutaneous nephrolithotomy surgery is limited. METHODS: In this prospective, randomized study, 60 patients aged between 18 and 60 years were randomized into two groups (erector spinae plane block and intrathecal morphine). In the erector spinae plane block group, ultrasound-guided erector spinae plane block was performed, following which a mixture of 20 mL of 0.375% ropivacaine and 0.5 mcg/kg of clonidine was injected. In the intrathecal morphine group, 150 mcg preservative-free morphine with 2 mL of normal saline was administered intrathecally. The primary outcome was to evaluate the perioperative opioid consumption in the first 24 h. The secondary outcomes were to evaluate hemodynamic response to surgical stimulus, visual analogue scale score, time to first analgesic requirement, postoperative nausea and vomiting, postoperative opioid consumption, urethral irritation, and incidence of drug-related adverse effects. RESULTS: Total perioperative opioid consumption in the erector spinae plane block group was 355.0 (265.0, 485.0) µg and 240.0 (145.0, 370.0) µg in the intrathecal morphine group (P = 0.09). However, the patients in the erector spinae plane block group had significantly greater postoperative fentanyl consumption (235.0 [120.0, 345.0] µg) compared with those in the intrathecal morphine group (105.0 [30.0, 225.0] µg). There were no statistically significant differences noted for intraoperative opioid consumption, postoperative visual analogue scale score, time to first analgesic request, postoperative nausea and vomiting, and catheter irritation between the two groups. CONCLUSIONS: Although no statistically significant difference in intraoperative opioid consumption was seen between the erector spinae plane block and intrathecal morphine groups, postoperative opioid consumption was significantly higher in the erector spinae plane block group than in the intrathecal morphine group in patients undergoing percutaneous nephrolithotomy surgery.

Interactive Effects of Molybdenum, Zinc and Iron on the Grain Yield, Quality, and Nodulation of Cowpea (Vignaunguiculata (L.) Walp.) in North-Western India.

Micronutrient deficiency is a major constraint for the growth, yield and nutritional quality of cowpea which results in nutritional disorders in humans. Micronutrients including molybdenum (Mo), iron (Fe) and zinc (Zn) play a pivotal role in crop nutrition, and their role in different metabolic processes in crops has been highlighted. In order to increase the nutritional quality of cowpea, a field experiment was conducted for two years in which the effect of Mo along with iron (Fe) and zinc (Zn) on productivity, nitrogen and micronutrient uptake, root length and the number of nodules in cowpea cultivation was investigated. It was found that the foliar application of Fe and Zn and their interaction with Mo application through seed priming as well as soil application displayed increased yield, nutrient concentration, uptake and growth parameters which helped to enhance the nutritional quality of cowpea for consumption by the human population. The results of the above experiments revealed that among all the treatments, the soil application of Mo combined with the foliar application of 0.5% each of FeSO4·7H2O and ZnSO4·7H2O (M2F3 treatment) enhanced the grain and stover yield of cowpea, exhibiting maximum values of 1402 and 6104.7 kg ha-1, respectively. Again, the M2F3 treatment resulted in higher Zn, Fe and Mo concentrations in the grain (17.07, 109.3 and 30.26 mg kg-1, respectively) and stover (17.99, 132.7 and 31.22 mg kg-1, respectively) of cowpea. Uptake of Zn, Fe and Mo by the grain (25.23, 153.3 and 42.46 g ha-1, respectively) as well as the stover (104.2, 809.9 and 190.6 g ha-1, respectively) was found to be maximum for the M2F3 treatment. The root length (30.5 cm), number of nodules per plant (73.0) and N uptake in grain and stover (55.39 and 46.15 kg ha-1) were also higher for this treatment. Overall, soil application of Mo along with the foliar application of FeSO4·7H2O (0.5%) and ZnSO4·7H2O (0.5%) significantly improved yield outcomes, concentration, uptake, root length, nodules plant-1 and N uptake of cowpea to alleviate the micronutrient deficiency.

Retrospective analysis of IgG4-related disease cases at a tertiary care centre in India.

Objectives: IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder with prominent fibrosis. This retrospective analysis was undertaken to study the clinical, laboratory, and radiological characteristics of patients with extra-pancreatic IgG4-RD and their response to treatment at a tertiary care centre located in northern India. Material and methods: Patient data from our centre between January 2017 and January 2021 were reviewed. Probable/definite IgG4-RD cases were included in the analysis. Results: A total of 14 cases were identified with a median age of 39 years (range 19-56 years). There were 10 males and 4 females. All patients presented with slowly progressive soft tissue swellings with pain/discomfort related to local mass effect. The median delay in diagnosis was 9.5 months (range 2-72 months). Cross-sectional imaging showed soft tissue masses in all cases. All contrast-enhanced studies (n = 7) showed enhancement on computed tomography and magnetic resonance imaging scan. F-18 fluorodeoxyglucose-avidity was observed in 8 of 9 (88.9%) cases. Biopsies performed in 12 of these were classified as definite in 8 and possible IgG4-RD in 4 cases. Patients were treated with a median dose of 1 mg/kg/day (range 0.5-1 mg/kg/day) prednisolone. Steroids were successfully tapered in all 12 cases with 41.6% (5 of 12) being off corticosteroids at a median follow-up of 10 months (range 0-18 months). Two patients were lost to follow-up. Conclusions: IgG4-related disease is a chronic illness with a wide spectrum of manifestations, in which the diagnosis is often delayed, but it shows an excellent response to treatment. Efforts must be made to increase awareness among physicians about this disease to institute appropriate treatment as early as possible.

Association of human papillomavirus in penile cancer: A single-center analysis.

Introduction: Human papillomavirus (HPV) is a known risk factor of penile cancer (PeCa). However, studies evaluating its true association are limited. In this study, we aimed to estimate HPV prevalence and its true association with PeCa in terms of molecular biological activities. Materials and Methods: This single-institutional prospective observational study was conducted between June 2016 and August 2019. We included 40 men with PeCa as a study group and 20 age-matched uncircumcised men who underwent circumcision for phimosis as a control group. Both the groups underwent deoxyribonucleic acid isolation for HPV subtyping followed by evaluation of relative E6/E7 messenger ribonucleic acid (mRNA) expression profile and relative telomerase activity in tissue samples. HPV-16 and -18 were categorized as high-risk, whereas HPV-6 and -11 were categorized as low-risk subtypes. Results: The mean (±standard deviation) age of PeCa was 51 ± 15.9 years. The majority of patients had stage II disease, and the most common procedure done was partial penectomy. The overall prevalence of HPV in PeCa was 42.5% (n = 17) as compared to 20% (n = 4) in controls. Among the subtypes, the most common subtype was HPV-16 noted in 33.3% (8/24) of cases, followed by HPV-18 in 29.2% (7/24) of cases. PeCa tissues had a significantly higher relative E7 mRNA expression for HPV-18 than the control group (P = 0.016). The mean relative telomerase activity was significantly higher in the PeCa tissues than the control group (138.66 vs. 14.46, P < 0.001). A significantly higher relative telomerase activity was noted in the PeCa tissues positive for high-risk HPV subtypes than controls (141.90 vs. 14.46, P = 0.0008), but not between high-risk HPV-positive and HPV-negative PeCa cases (141.90 vs. 137.03, P = 0.79). High-risk subtypes were not associated with tumor stage (P = 0.76) or lymph node metastasis (P = 0.816). Conclusions: HPV was associated in 42.5% of PeCa cases based on our experience from a single institution. PeCa tissues had a higher relative E7 mRNA expression for HPV-18 and relative telomerase activity as compared to controls suggesting their potential role as surrogate markers of virus-induced tumorigenesis.

Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries.

BACKGROUND: The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. OBJECTIVES: This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations. METHODS: Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated. RESULTS: No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%-0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%-52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil. CONCLUSIONS: There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.

Effects of horizontal versus vertical bolster alignment on anatomical orientation of kidney as applied to prone percutaneous nephrolithotomy.

PURPOSE: To evaluate the anatomical changes in kidney orientation in prone position with use of horizontal or vertical bolster alignment. METHODS: Patients having renal stone(s) on ultrasonogram or X-ray underwent split bolus computed-tomo-urography (CTU) in prone position with horizontal and vertical bolster positions. CTUs were read by a single radiologist to quantify the cranio-caudal, antero-posterior, side to side and rotational movements of kidneys as relevant to prone percutaneous nephrolithotomy. RESULTS: 19 adult patients with 38 renal units and mean basal metabolic index of 25.6 kg/m2 underwent CTU. Greater inferior displacement of both kidneys was seen with horizontal bolsters as compared to vertical bolsters. The right upper calyceal-diaphragm distance was 2.1 ± 1.5 cm and the lower calyceal-diaphragm distance was 2.0 ± 1.6 cm greater with the horizontal bolsters (p < 0.01). Similarly, the displacement on the left side was 1.5 ± 0.8 cm and 1.4 ± 0.8 cm, respectively (p < 0.01). Horizontal bolsters also result in significantly longer calyceal-skin distance at both poles of both kidneys [right upper: 0.4 ± 0.5 cm (p < 0.01), right lower: 0.8 ± 0.7 cm (p < 0.01), left upper: 0.4 ± 0.6 cm (p = 0.02), left lower: 0.8 ± 1.1 cm (p < 0.01)] and wider erector spinae-mid posterior calyceal-colon angle (124.8 v/s 110.0 on the right and 96.2 v/s 85.7 on the left) (p < 0.01). CONCLUSION: Horizontal bolsters provide significantly more caudal displacement of the kidneys; the right kidney being displaced more as compared to the left. However, there is also an increase in the skin-calyceal distance with horizontal as compared to the vertical bolsters. These assessments may help the surgeons decide optimal bolster position individualized to the patient.

Impact of vesicovaginal fistula repair on urinary and sexual function: patient-reported outcomes over long-term follow-up.

INTRODUCTION AND HYPOTHESIS: While the anatomical closure rates of vesicovaginal fistula (VVF) following transabdominal (TA) and transvaginal (TV) repairs seem comparable, studies comparing urinary and sexual outcomes following successful repair are lacking. We aimed to report patient-reported outcomes on sexual and urinary functions after long-term follow-up with successful repair. METHODS: We retrospectively reviewed 81 women who had successful VVF repair at our institute. Pre-, intra- and post-operative details were retrieved from electronic data software. Patient-reported sexual and urinary function outcomes were assessed using the Female Sexual Function Index (FSFI) questionnaire and International Consultation of Incontinence Questionnaire-Short Form (ICIQ-SF), respectively, at last follow-up. We also compared such outcomes among TA and TV repairs. RESULTS: Of 81 women, 28 (34.6%) had TA and 53 (65.4%) had TV repairs. Mean age was 37.5 years and mean fistula diameter was 12.9 mm. The most common aetiology was hysterectomy. Thirty-three patients (40.7%) had previous failed repairs. At a mean follow-up of 29.8 months, 24 (34.3%) women had sexual dysfunction and 15 (18.5%) women experienced urinary dysfunction. The TA and TV groups had comparable mean FSFI scores (28.7 ± 6.1 vs. 30.9 ± 5.2, p = 0.13) and ICIQ-SF scores (0.7 ± 1.7 vs. 0.5 ± 1.4, p = 0.59). In multivariate analysis, fistula size and site were significant predictors of urinary dysfunction whereas multiparity was the most significant predictor of sexual dysfunction. CONCLUSIONS: Sexual and urinary dysfunction is found in a considerable number of women after VVF repair. However, our data suggest comparable long-term sexual and continence outcomes between TA and TV repairs.

Enrichment of Zinc and Iron Micronutrients in Lentil (Lens culinaris Medik.) through Biofortification.

Biofortification of pulse crops with Zn and Fe is a viable approach to combat their widespread deficiencies in humans. Lentil (Lens culinaris Medik.) is a widely consumed edible crop possessing a high level of Zn and Fe micronutrients. Thus, the present study was conducted to examine the influence of foliar application of Zn and Fe on productivity, concentration, uptake and the economics of lentil cultivation (LL 931). For this, different treatment combinations of ZnSO4·7H2O (0.5%) and FeSO4·7H2O (0.5%), along with the recommended dose of fertilizer (RDF), were applied to the lentil. The results of study reported that the combined foliar application of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at pre-flowering (S1) and pod formation (S2) stages was most effective in enhancing grain and straw yield, Zn and Fe concentration, and uptake. However, the outcome of this treatment was statistically on par with the results obtained under the treatment ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage. A single spray of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage enhanced the grain and straw yield up to 39.6% and 51.8%, respectively. Similarly, Zn and Fe concentrations showed enhancement in grain (10.9% and 20.4%, respectively) and straw (27.5% and 27.6% respectively) of the lentil. The increase in Zn and Fe uptake by grain was 54.8% and 68.0%, respectively, whereas uptake by straw was 93.6% and 93.7%, respectively. Also the benefit:cost was the highest (1.96) with application of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage. Conclusively, the combined use of ZnSO4·7H2O (0.5%) + FeSO4·7H2O (0.5%) at S1 stage can contribute significantly towards yield, Zn and Fe concentration, as well as uptake and the economic returns of lentil to remediate the Zn and Fe deficiency.

RASSF1A-Hippo pathway link in patients with urothelial carcinoma of bladder: plausible therapeutic target.

RASSF1A is a tumor suppressor gene, and its hypermethylation has been observed in cancers. RASSF1A acts as an upstream regulator of Hippo pathway and modulates its function. The aim of this study was to analyze expression of RASSF1A, Hippo pathway molecules (YAP, MST) and downstream targets (CTGF, Cyr61 and AREG) in bladder cancer patients. Later, the link between RASSF1A and Hippo pathway and a potential therapeutic scope of this link in UBC were also studied. MSPCR was performed to study methylation of RASSF1A promoter. Expression of molecules was studied using qPCR, Western blot and IHC. The link between RASSF1A and Hippo pathway was studied using Spearman's correlation in patients and validated by overexpressing RASSF1A in HT1376 cells and its effect on Hippo pathway was observed using qPCR and Western blot. Further therapeutic potential of this link was studied using MTT and PI assays. The expression of RASSF1A was lower, whereas the expression of YAP, CTGF and CYR61 was higher. The expression of RASSF1A protein gradually decreased, while the expression of YAP, CTGF and CYR61 increased with severity of disease. Based on Spearman's correlation, RASSF1A showed a negative correlation with YAP, CTGF and CYR61. YAP showed a positive correlation with CTGF and CYR61. To validate this link, RASSF1A was overexpressed in HT1376 cells. Overexpressed RASSF1A activated Hippo pathway, followed by a decrease in CTGF and CYR61 at mRNA, and enhanced cytotoxicity to chemotherapeutic drugs. This study finds a previously unrecognized role of RASSF1A in the regulation of CTGF and CYR61 through mediation of Hippo pathway in UBC and supports the significance of this link as a potential therapeutic target for UBC.

Urological infections in the developing world: an increasing problem in developed countries.

PURPOSE: Infectious diseases that often follow geographical distribution patterns are increasingly crossing such boundaries, aided by human travel and commerce. These pose a new challenge to physicians who are required to diagnose previously unseen conditions and address drug-resistant organisms. We review some such common infections. METHODS: A literature review was performed for six common urological infections and a narrative review based on recent publications on these infections was compiled. RESULTS: In Urology, some infections that are now crossing geographical boundaries include Brucellosis, Schistosomiasis, Tuberculosis, Filariasis, Hydatidosis and emphysematous pyelonephritis. Brucellosis, a zoonotic infection, is common in the Mediterranean areas, Asia, South America and Africa. Infection can involve all parts of the genitourinary tract. Schistosomiasis, a parasitic disease, is particularly common in Sub-Saharan Africa and may have bacterial superinfection. Voiding symptoms are common and bladder carcinoma may develop. Tuberculosis affects almost every organ in the body and in the male genital system, often presents with abscesses, nodules, ulcers and infertility that is difficult to manage. Filariasis is caused by two species of worms and is transmitted through a bite from a mosquito carrying larvae of the worm. It causes lymphatic obstruction leading to scrotal edema, hydrocoele to elephantiasis of scrotum. Emphysematous pyelonephritis is a life-threatening suppurative necrotizing infection of the renal parenchyma. While not being geographically limited, it is more common in developing areas with poor health care access. Genitourinary hydatidosis is a rare disease that is associated mainly with renal involvement in the genitourinary tract. Large cysts with destruction of renal parenchyma may be found. CONCLUSIONS: Although uncommon, these urological infections are associated with significant morbidity and mortality and awareness in all healthcare settings is now an essential requirement.

Phenylalanine dimer assembly structure as the basic building block of an amyloid like photoluminescent nanofibril network.

A phenylalanine dimer assembly (Phe-DA) is reported as a basic constituent of a light emitting ß-amyloid type nanofibril network. The size and composition of the Phe-DA structure were characterized using various theoretical and experimental techniques. Further, the mechanism involved in the phenylalanine self-assembly process from Phe-DA to the nanofibril network was studied using optical spectroscopy and small angle X-ray scattering (SAXS). The discovery of Phe-DA and its unique optical properties may pave the way for design and development of novel theranostics against metabolite based pathalogical disorders. Further, the role of the Phe-DA structure as the elementary unit in the formation of a long range assembly structure may provide vital understanding for the development of functional materials using simple organic molecules.

Role of miRNA-182 and miRNA-187 as potential biomarkers in prostate cancer and its correlation with the staging of prostate cancer.

PURPOSE: The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer. MATERIALS AND METHODS: This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied. RESULTS: Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p<0.001) in prostate cancer tissue specimens. However, the expression of these miRNAs did not significantly differ in the urine of prostate cancer patients as compared to controls. Serum Prostatic Specific Antigen (PSA) inversely correlated with the median expression of miR-187 in prostatic tissue (p=0.002). Further, the expression of miRNA-187 in prostate cancer tissue was significantly decreased in metastatic prostate cancer (p=0.037). Using ROC analysis, miRNA-187 expression was able to distinguish the presence or absence of bone metastasis [area under ROC (AUROC) (±SD) was 0.873±0.061, p<0.001]. CONCLUSION: The miRNA-182 and miRNA-187 appear to be promising biomarkers in prostate cancer and miRNA-187 can serve as an important diagnostic marker of metastatic prostate cancer.

Laparoscopic and robotic transperitoneal repair of retrocaval ureter: A comparison of the surgical outcomes from two centres with a comprehensive literature review.

Background: The use of minimally invasive surgical approaches for the repair of retrocaval ureter (RCU) has been increased in time. However, the results of the robotic approach have not yet been compared with those of open or laparoscopic approaches. We aimed to compare the results of laparoscopic and robotic transperitoneal repair of RCU from two centres. Patients and Methods: Initially, we performed a systemic literature search using MEDLINE/PubMed and Google Scholar about the RCU. Finally, a comparison of the efficacy and outcomes of the laparoscopic and robotic transperitoneal approaches for RCU repair was performed with the results of two centers. Results: The mean age was 27.5 ± 3.6 years. The mean operative time was 147 ± 63.6 min. The median estimated blood loss was 100 (20-423.9) ml. The median drain removing time and hospital stay were 2 (2-3) and 3 (2-4) days, respectively. The mean follow-up period was 17.85 ± 14.6 months. All of the parameters were similar between the laparoscopic and robotic repair groups except for the mean operative time. It was significantly shorter in robotic repair group than those of laparoscopic repair group (P = 0.02). Furthermore, a ureteral stricture of the anastomotic segment was detected in a patient treated with laparoscopy during the follow-up. Conclusions: Robotic transperitoneal approach may shorten the operative time enabling a greater comfort in repair of RCU.