Risk factors for suicidal behavior in patients hospitalized for adjustment disorders.

INTRODUCTION: Adjustment disorder (AD) is a common psychiatric diagnosis, but it is often considered less severe than other diagnoses. However, it is strongly associated with suicidal behavior. AIM: To identify the factors linked to suicidal behavior in patients hospitalized for AD. METHODS: This is a retrospective, descriptive, and analytical study conducted in the psychiatric department of Mahdia's hospital over a period of nine years. The study included patients who were hospitalized for the first time due to adjustment disorder, according to DSM-5 diagnostic criteria. RESULTS: The study population included 129 patients. AD was prevalent among young (median age 29 years) and female patients (75.2%). Almost half of the cases were single (48.1%) and having a history of suicidal behavior (48.3%). Sixty patients (46.5%) were hospitalized following a suicidal attempt (SA) and drugs were used as a way in half of the cases (50%). Conflicts were the dominant factor precipitating the SA in 88.3% of cases. Factors linked to suicidal behavior in patients with AD were being in an intimate relationship and the presence of family conflicts. Indeed, the risk of suicidal behavior was found to be increased by 3.15 times in patients with AD who experienced family conflicts. Besides, being in an intimate relationship in patients with AD multiplies the risk of suicidal behavior by 5.863. CONCLUSIONS: Given the high risk of suicide associated with AD, it is essential to have a more in-depth understanding of the suicidal process and AD through new studies.

Epigenetic insights to pediatric uropathology: Celebrating the fundamental biology vision of Tony Khoury.

INTRODUCTION: Many pediatric urology conditions affect putatively normal tissues or appear too commonly to be based solely on specific DNA mutations. Understanding epigenetic mechanisms in pediatric urology, therefore, has many implications that can impact cell and tissue responses to settings, such as environmental and hormonal influences on urethral development, uropathogenic infections, obstructive stimuli, all of which originate externally or extracellularly. Indeed, the cell's response to external stimuli is often mediated epigenetically. In this commentary, we highlight work on the critical role that epigenetic machinery, such as DNA methyltransferases (DNMTs), Enhancer of Zeste Polycomb Repressive Complex 2 Subunit (EZH2), and others play in regulating gene expression and cellular functions in three urological contexts. DESIGN: Animal and cellular constructs were used to model clinical pediatric uropathology. The hypertrophy, trabeculation, and fibrosis of the chronically obstructed bladder was explored using smooth muscle cell models employing disorganised vs. normal extracellular matrix (ECM), as well as a new animal model of chronic obstructive bladder disease (COBD) which retains its pathologic features even after bladder de-obstruction. Cell models from human and murine hypospadias or genital tubercles (GT) were used to illustrate developmental responses and epigenetic dependency of key developmental genes. Finally, using bladder urothelial and organoid culture systems, we examined activity of epigenetic machinery in response to non uropathogenic vs. uropathogenic E.coli (UPEC). DNMT and EZH2 expression and function were interrogated in these model systems. RESULTS: Disordered ECM exerted a principal mitogenic and epigenetic role for on bladder smooth muscle both in vitro and in CODB in vivo. Key genes, e.g., BDNF and KCNB2 were under epigenetic regulation in actively evolving obstruction and COBD, though each condition showed distinct epigenetic responses. In models of hypospadias, estrogen strongly dysregulated WNT and Hox expression, which was normalized by epigenetic inhibition. Finally, DNA methylation machinery in the urothelium showed specific activation when challenged by uropathogenic E.coli. Similarly, UPEC induces hypermethylation and downregulation of the growth suppressor p16INK4A. Moreover, host cells exposed to UPEC produced secreted factors inducing epigenetic responses transmissible from one affected cell to another without ongoing bacterial presence. DISCUSSION: Microenvironmental influences altered epigenetic activity in the three described urologic contexts. Considering that many obstructed bladders continue to display abnormal architecture and dysfunction despite relief of obstruction similar to after resection of posterior valves or BPH, the epigenetic mechanisms described highlight novel approaches for understanding the underlying smooth muscle myopathy of this crucial clinical problem. Similarly, there is evidence for an epigenetic basis of xenoestrogen on development of hypospadias, and UTI-induced pan-urothelial alteration of epigenetic marks and propensity for subsequent (recurrent) UTI. The impact of mechanical, hormonal, infectious triggers on genitourinary epigenetic machinery activity invite novel avenues for targeting epigenetic modifications associated with these non-cancer diseases in urology. This includes the use of deactivated CRISPR-based technologies for precise epigenome targeting and editing. Overall, we underscore the importance of understanding epigenetic regulation in pediatric urology for the development of innovative therapeutic and management strategies.

Streptococcus pneumoniae among the children of Aden, Yemen: a cross-sectional report of post-pneumococcal conjugate vaccine.

INTRODUCTION: Streptococcus pneumoniae cause a significant global health challenge. We aimed to determine nasopharyngeal carriage, serotypes distribution, and antimicrobial profile of pneumococci among the children of Aden. METHODOLOGY: A total of 385 children, aged 2-17 years, were included. Asymptomatic samples were randomly collected from children in selected schools and vaccination centers. Symptomatic samples were obtained from selected pediatric clinics. The nasopharyngeal swabs were tested for pneumococci using culture and real time polymerase chain reaction (RT-PCR). Serotyping was done with a pneumotest-latex kit and antimicrobial susceptibility was tested by disc diffusion and Epsilometer test. RESULTS: The total pneumococcal carriage was 44.4% and 57.1% by culture and RT-PCR, respectively. There was a statistically significant association between carriage rate and living in single room (OR = 7.9; p = 0.00001), sharing a sleeping space (OR = 15.1; p = 0.00001), and low monthly income (OR = 2.02; p = 0.007). The common serotypes were 19, 1, 4, 5, 2, and 23. The proportion of non-pneumococcal conjugate vaccine (non-PCV13) serotypes was 24%. Pneumococci were resistant to penicillin (96.5%), cefepime (15.8%), ceftriaxone (16.4%), and amoxicillin-clavulanate (0%). Erythromycin, azithromycin, and doxycycline had resistance rates of 48%, 31%, and 53.3%, respectively. CONCLUSIONS: A high pneumococcal carriage rate was observed in Yemeni children, particularly in low-income households and shared living conditions. There was significant penicillin resistance at meningitis breakpoint. Furthermore, non-PCV13 serotypes were gradually replacing PCV13 serotypes. The findings underscore the urgent need for enhanced surveillance and stewardship to improve vaccination and antibiotic policies in Yemen.

New strategies for Helicobacter pylori isolation and sequencing analysis for virulence genes contributing to its pathogenicity.

BACKGROUND: Helicobacter pylori is a fastidious pathogen that is required a complicated medium for growth. Invading epithelial cells of the stomach. H. pylori virulence factors are classified by function, acidic resistivity, adhesion, chemotaxis and motility, molecular mimicry, immunological invasion and modulation, and toxins formation such as cytotoxin-associated genes A (cagA) and vacuolating cytotoxin A (vacA). This study aims to determine a simple and innovative technique to isolate H. pylori from gastric biopsies and assess pathogenicity by virulence factor gene detection. METHODS: A total of 200 patients who were suspected of having H. pylori infection had two antral gastric biopsies undertaken. A rapid urease test (RUT) was used for one, and Brain Heart Infusion broth (BHI) was used to cultivate the other. The molecular study included diagnostics utilizing the 16sRNA housekeeping gene along with the identification of the virulence factors genes (cagA, cagT, and vacA) and sequencing, RESULT: Of the 200 antral gastric biopsies collected, 135 were positive rapid urease tests, and 17 H. pylori isolates were successfully obtained from 135 biopsies. The 16SrRNA as a housekeeping gene is confirmed, and about 53%, 70.5%, and 82.3% of the 17 isolates show carrying cagA, cagT, and vacA genes, respectively. All peptic ulcer isolates have the cagA gene, while Gastroesophageal Reflux Disease (GERD) and non-peptic ulcer disease (NPUD) isolates show the lack of the cagA gene. All bacteria, which were isolated from peptic ulcer, nodular gastritis, and gastritis patients, have a vacA gene. CONCLUSION: The effective method for isolating H. pylori is centrifuging the transport broth after 24 h of incubation. The cagA toxin causes peptic ulcer while vacA toxin induces several histopathological changes in the stomach. Three virulence genes were present in all peptic ulcer-causing bacteria, while only one or none were present in the GERD and NPUD biopsy isolates.

Dexmedetomidine and magnesium sulfate in preventing junctional ectopic tachycardia after pediatric cardiac surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) is a serious tachyarrhythmia following pediatric cardiac surgery. It isn't easy to treat and better to be prevented. This study aimed to examine the prophylactic effects of dexmedetomidine, MgSO4, or their combination in reducing JET following pediatric open cardiac surgery. METHODS: Hundred and twenty children under 5 years, weighing more than 5 kg, who were scheduled for corrective acyanotic cardiac surgeries were randomized into three groups. Group MD (Dexmedetomidine-MgSO4 group): received dexmedetomidine 0.5 µg/kg IV over 20 min after induction, then infusion 0.5 µg/kg/h for 72 h, and 50 mg/kg bolus of MgSO4 with aortic cross-clamp release, then continued administration for 72 h postoperatively at a dose of 30 mg/kg/day. Group D (the dexmedetomidine group) received the same dexmedetomidine as the MD group in addition to normal saline instead of MgSO4. Group C (control group): received normal saline instead of dexmedetomidine and MgSO4. The primary outcome was the detection of JET incidence; the secondary outcomes were hemodynamic parameters, ionized Mg, vasoactive-inotropic score, extubation time, PCCU and hospital stay, and perioperative complications. RESULTS: The incidence of JET was significantly reduced in Group MD and Group D (p = .007) compared to Group C. Ionized Mg was significantly higher in Group MD than in Groups D and C during rewarming and in the ICU (p < .001). Better hemodynamic profile in Group MD compared to Group D and Group C throughout surgery and in the ICU, the predictive indexes were significantly better in Group MD than in Groups D and C (p < .001). Including the extubation time, PCCU, and hospital stay. CONCLUSION: Dexmedetomidine alone or combined with MgSO4 had a therapeutic role in the prevention of JET in children after congenital heart surgery.

Successful Completion of Left Laparoendoscopic Single-Site Donor Nephrectomy in a Patient with Duplicated Inferior Vena Cava: Case Report and Review of Literature.

Duplication of the inferior vena cava is a rare vascular anomaly that increases the complexity of living donor nephrectomy and subsequent transplant. We present the case of a successful left-side laparoendoscopic single-site donor nephrectomy performed in a donor with a duplicated inferior vena cava. The length of the left renal vein was adequate for anastomosis in the recipient, with no late surgical complications at 9 months for both donor and recipient. Duplicated inferior vena cava is not a contraindication for left kidney transplant. Preoperative assessment and planning with computed tomography angiography are essential. Laparoendoscopic single-site donor nephrectomy can be performed safely in patients with duplicated inferior vena cava.

Successful Endovascular Repair of Infectious External Iliac Artery Anastomotic Pseudoaneurysm With Graft Preservation Post-Kidney Transplantation: Case Report and Review of Literature.

BACKGROUND: Allograft artery-infected pseudoaneurysm (PA) represents a rare but life-threatening complication of kidney transplantation (KT). A review of the literature, showed that nearly all these cases ended resulted in graft loss. We presented a case of post-KT-infected external iliac artery anastomotic PA successfully managed by endovascular stenting with graft preservation. Additionally, we reviewed the pertinent literature. METHOD: In this article, we described a hypertensive, 47-year-old man who presented 1 month post-cadaveric KT with acute kidney injury and gram-negative bacteremia secondary to a large infectious anastomotic PA of the external iliac artery. RESULTS: Because of favorable anatomy, successful arterial angio-stent fixation of the main renal artery PA, sparing the lower polar artery, was performed after 1 week of antibiotic and fungal coverage. CONCLUSION: Patient was discharged after 2 weeks with functioning graft. Graft function was stable after 3 months.

MicroRNA-940 as a Potential Serum Biomarker for Prostate Cancer.

Prostate cancer is one of the leading causes of death despite an astoundingly high survival rate for localized tumors. Though prostate specific antigen (PSA) test, performed in conjunction with digital rectal examinations, is reasonably accurate, there are major caveats requiring a thorough assessment of risks and benefits prior to conducting the test. MicroRNAs, a class of small non-coding RNAs, are stable molecules that can be detected in circulation by non-invasive methods and have gained importance in cancer prognosis and diagnosis in the recent years. Here, we investigate circulating miR-940, a miRNA known to play a role in prostate cancer progression, in both cell culture supernatants as well as patient serum and urine samples to determine the utility of miR-940 as a new molecular marker for prostate cancer detection. We found that miR-940 was significantly higher in serum from cancer patients, specifically those with clinically significant tumors (GS ≥ 7). Analysis of receiver operating characteristic curve demonstrated that miR-940 in combination with PSA had a higher area under curve value (AUC: 0.818) than the miR-940 alone (AUC: 0.75) for the diagnosis of prostate cancer. This study provides promising results suggesting the use of miR-940 for prostate cancer diagnosis.

Prevalence of burnout syndrome and its related risk factors among physicians working in primary health care centers of the Ministry of Health, Al Ahsa region, Saudi Arabia, 2018-2019.

Burnout syndrome (BS) is a relatively common occupational problem. It is a psychological and behavioral syndrome described by three dimensions: emotional exhaustion (EE); depersonalization (DP); and low personal accomplishment (PA). OBJECTIVES: This study aims to calculate the prevalence of BS and its related risk factors among physicians of primary health care centers (PHCCs) of the Ministry of Health (MOH, Al Ahsa, Saudi Arabia. MATERIALS AND METHOD: A cross-sectional study was conducted in which 280 physicians working in PHCCs were selected as a comprehensive sample, the response rate was 80.7%. We excluded the trainee of residency programs, interns, and hospital physicians providing partial service in PHCCs. The data was collected by using two-part self-administered questionnaire including sociodemographic data, working conditions, and Maslach Burnout Inventory™-Human Services Survey for Medical Personnel-MBI-HSS (MP). This data was analyzed using Statistical Package for Social Sciences (SPSS) program. RESULTS: The mean score for EE was 24.99 ± 11.54 SD. The mean score for DP was 9.19 ± 6.13 SD. For PA, it was 29.41 ± 9.9 SD. The percentage of participants who scored high in EE was 47.3%. About one-half of the participants scored high DP and 59.7% had diminished PA. About one-quarter of the participants (24.3%) scored high burnout in all three dimensions. High EE was present in ages from 35 to 45 years, Saudi participants, rotating or covering physicians, and participants who were satisfied with their job. High DP was seen in Saudi physicians, family physicians, rotating or covering physicians, those who were not satisfied with their job, and physicians who work in rural areas. Low PA was seen in physicians who were not satisfied with their job, rotating or covering physicians, participants who do not have tasks other than clinical work, and physicians who work in Omran sector. CONCLUSION: There is a significant level of burnout among physicians working in PHCCs in Al Ahsa. High burnout was associated with some risk factors. Further research is needed to study this problem in depth.

Chronic exposure to cadmium induces a malignant transformation of benign prostate epithelial cells.

Epidemiological evidence suggests that cadmium (Cd) is one of the causative factors of prostate cancer, but the effect of Cd on benign prostatic hyperplasia (BPH) remains unclear. This study aimed to determine whether Cd exposure could malignantly transform BPH1 cells and, if so, to dissect the mechanism of action. We deciphered the molecular signaling responsible for BPH1 transformation via RNA-sequencing and determined that Cd induced the expression of zinc finger of the cerebellum 2 (ZIC2) in BPH1 cells. We noted Cd exposure increased ZIC2 expression in the Cd-transformed BPH1 cells that in turn promoted anchorage-independent spheroids and increased expression of stem cell drivers, indicating their role in stem cell renewal. Subsequent silencing of ZIC2 expression in transformed cells inhibited spheroid formation, stem cell marker expression, and tumor growth in nude mice. At the molecular level, ZIC2 interacts with the glioma-associated oncogene family (GLI) zinc finger 1 (GLI1), which activates prosurvival factors (nuclear factor NFκB, B-cell lymphoma-2 (Bcl2), as well as an X-linked inhibitor of apoptosis protein (XIAP)) signaling in Cd-exposed BPH1 cells. Conversely, overexpression of ZIC2 in BPH1 cells caused spheroid formation confirming the oncogenic function of ZIC2. ZIC2 activation and GLI1 signaling induction by Cd exposure in primary BPH cells confirmed the clinical significance of this oncogenic function. Finally, human BPH specimens had increased ZIC2 versus adjacent healthy tissues. Thus, we report direct evidence that Cd exposure induces malignant transformation of BPH via activation of ZIC2 and GLI1 signaling.

Modulation of NKG2D, KIR2DL and Cytokine Production by Pleurotus ostreatus Glucan Enhances Natural Killer Cell Cytotoxicity Toward Cancer Cells.

Medicinal mushrooms have been used for centuries against cancer and infectious diseases. These positive biological effects of mushrooms are due in part to the indirect action of stimulating immune cells. The objective of the current study is to investigate the possible immunomodulatory effects of mushroom polysaccharides on NK cells against different cancer cells. In this current study, fruiting bodies isolated from cultured Pleurotus ostreatus were extracted and partially purified using DEAE ion-exchange chromatography. The activation action of the collected fractions on Natural Killer cells was quantified against three different cancer cell lines in the presence or absence of human recombinant IL2 using three different activation and co-culture conditions. The possible modes of action of mushroom polysaccharides against cancer cells were evaluated at the cellular and molecular levels. Our results indicate that P. ostreatus polysaccharides induced NK-cells cytotoxic effects against lung and breast cancer cells with the largest effect being against breast cancer cells (81.2%). NK cells activation for cytokine secretion was associated with upregulation of KIR2DL genes while the cytotoxic activation effect of NK cells against cancer cells correlated with NKG2D upregulation and induction of IFNγ and NO production. These cytotoxic effects were enhanced in the presence of IL2. Analysis of the most active partially purified fraction indicates that it is predominantly composed of glucans. These results indicate bioactive 6-linked glucans present in P. ostreatus extracts activate NK-cell cytotoxicity via regulation of activation and induction of IFNγ and NO. These studies establish a positive role for bioactive P. ostreatus polysaccharides in NK-cells activation and induction of an innate immune response against breast and lung cancer cells.

Combination of androgen receptor inhibitor and cisplatin, an effective treatment strategy for urothelial carcinoma of the bladder.

PURPOSE: The role of androgen receptor (AR) signaling in bladder cancer (BCa) is not fully characterized. This study aimed to delineate the role of AR signaling in BCa and to determine whether the combination of AR inhibitor, Enzalutamide (Enz), and Cisplatin (Cis) efficiently inhibit the growth of BCa cells. METHODS: AR expression was determined in 89 human urothelial BCa specimens by immunohistochemistry. A panel of BCa cell lines was treated with Cis, Enz, or a combination of both (Enz + Cis). We determined the expression of AR, changes in apoptotic signaling, DNA damage, and analyzed effect on epithelial mesenchymal transformation markers. RESULT: AR expression was detected in 61.4% of tumors from male BCa patients. Inhibition of AR signaling by Enz effectively inhibited the growth of AR+ BCa cells by inducing apoptosis (26%) in AR+ TCCSUP (P = 0.0201) and J82 (15%, P = 0.0386) cells. Interestingly, Enz + Cis synergistically inhibited the proliferation of BCa cells even at low concentrations by inducing proapoptotic signaling in AR+ BCa cells. Invasive and migratory potential of TCCSUP and J82 cells were reduced with Enz + Cis treatment, and associated with down-regulation of mesenchymal markers. CONCLUSIONS: A high percentage of the bladder tumors from male patients in our cohort expressed AR. The combination of Enz and Cis synergistically inhibited growth of BCa cells more efficiently than single agent alone. This supports the rationale for future investigation of AR antagonists in combination with standard chemotherapy in MIBC.

miR-301a expression: Diagnostic and prognostic marker for prostate cancer.

BACKGROUND: Prostate-specific antigen screening for prostate cancer (CaP) remains controversial. This study establishes the role of microRNA 301a (miR-301a) as a supplemental biomarker that can distinguish between patients with benign prostate hyperplasia and clinically significant CaP. We evaluate the ability of miR-301a to predict the adverse pathology of CaP. METHODS: In the first cohort, serum and prostate tumor samples were obtained from thirteen patients with Benign prostate hyperplasia (BPH), twelve patients with Gleason 6, and sixteen patients with Gleason 7 prostate adenocarcinoma. In the second cohort, 40 prostatectomy cases were selected (BPH:12, Gleason 6:12 and Gleason 7:16). MiRNA was extracted from serum and tumor samples. Quantitative reverse transcription-polymerase chain reaction was performed for detection of miR-301a. To understand the molecular role of miR-301a, we performed cell viability, Western blots, promoter analysis, overexpression, and silencing studies in BPH and DU-145 cell lines. RESULTS: MiR-301a demonstrated a significantly higher expression in both serum and tumor tissue in patients with CaP when compared to patients with BPH (P = 0.011 and 0.013 for serum and tissue expression, respectively). Expression of miR-301a in prostatectomy specimens correlated with increased Gleason score. We demonstrated that miR-301a inhibited the pro-apoptotic function of RUNX3, and activated ROCK1-mediated pro-survival signal in CaP. Silencing miR-301a initiated the pro-apoptotic function of RUNX3 by inhibiting ROCK1 expression in CaP cells. CONCLUSIONS: Expression of miR-301a could be a valuable adjunct tool for stratifying patients with elevated prostate-specific antigen, as well as those diagnosed with CaP. Including the miR-301a as an additional variable in MSKCC post-prostatectomy nomogram improved its ability in facilitating clinical decision-making.

High rate of uterine rupture in a conflict setting of Hajjah, Yemen.

A descriptive study was conducted to investigate the epidemiology and the outcome of uterine rupture at Hajjah Hospital, Yemen, during September 2014-August 2016. There were 110 cases of ruptured uterus and 3457 deliveries (31.8 per 1000 delivery). The majority (82, 74.5%) of these patients were illiterate. One hundred and four (96.3%) of them had no antenatal care. Seventy-eight of these women (70.9%) delivered at home and 32 (29.1%) delivered at hospital. Out of these 110 cases, 74 (67.3%) and 36 (32.7%) had unscarred uterus and scarred uterus, respectively. The causes of ruptured uterus were as follows: obstructed labour 59 (53.6%), previous caesarean delivery 36 (32.7%), use of oxytocin 10 (9.1%) and misoprostol 5 (4.6%). Hysterectomy was carried out in 50 (45.4%) %), repair in 39 (35.4%), repair with tubal ligation in 18 (16.4%) patients and 3 (2.7%) patients died before operation. There was 8 (7.2%) and 101 (91.8%) maternal and perinatal mortality, respectively. Nineteen (17.3%), 6 (5.4%) and 2 (1.8%) women developed sepsis, had urinary bladder injury and developed vesicovaginal fistulae, respectively.

Highly efficient biosensors by using well-ordered ZnO/ZnS core/shell nanotube arrays.

We have studied the fabrication of highly efficient glucose sensors using well-ordered heterogeneous ZnO/ZnS core/shell nanotube arrays (CSNAs). The modified electrodes exhibit a superior electrochemical response towards ferrocyanide/ferricyanide and in glucose sensing. Further, the fabricated glucose biosensor exhibited good performance over an acceptable linear range from 2.39 × 10-5 to 2.66 × 10-4 mM, with a sensitivity of 188.34 mA mM-1 cm-2, which is higher than that of the ZnO nanotube array counterpart. A low limit of detection was realized (24 µM), which is good compared with electrodes based on conventional structures. In addition, the enhanced direct electrochemistry of glucose oxidase indicates the fast electron transfer of ZnO/ZnS CSNA electrodes, with a heterogeneous electron transfer rate constant (K s) of 1.69 s-1. The fast electron transfer is attributed to the high conductivity of the modified electrodes. The presented ZnS shell can facilitate the construction of future sensors and enhance the ZnO surface in a biological environment.

Association of Distance to Treatment Facility With Survival and Quality Outcomes After Radical Cystectomy: A Multi-Institutional Study.

BACKGROUND: We sought to determine the effect of the travel distance on mortality and quality outcomes after radical cystectomy in a large multi-institutional cohort. PATIENTS AND METHODS: A total of 3957 patients who had undergone radical cystectomy for urothelial carcinoma at 6 North American tertiary care institutions were included. The association of travel distance with quality-of-care endpoints, 90-day mortality, and long-term survival were evaluated. RESULTS: The median patient age was 69 years (interquartile range, 61-76 years), and most patients were men (80%). Most patients had clinical stage T2 (45.2%) and T1 (24.7%) tumors. The median distance to the treatment facility was 102.9 miles (interquartile range, 24-271 miles). Patients residing in the first quartile of travel distance to treatment facility (< 24 miles) had lower usage of neoadjuvant chemotherapy compared with patients in the fourth distance quartile (adjusted odds ratio, 1.58; 95% confidence interval, 1.22-2.05; P = .001). Patients in the first distance quartile were also less likely to experience a delay in time to cystectomy (> 3 months) compared with patients with a greater travel distance (adjusted odds ratio, 0.673; 95% confidence interval, 0.532-0.851). Distance to the treatment facility was not associated with 90-day mortality or cancer-specific or all-cause mortality on multivariate analysis. CONCLUSION: Despite the potential health care disparities for bladder cancer patients residing distant to a regional surgical oncology facility, the study results suggest that the travel distance is not a barrier to appropriate oncologic care at regional tertiary care centers.

Prognostic value of tissue-based biomarker signature in clear cell renal cell carcinoma.

OBJECTIVE: To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence. RESULTS: The median (interquartile range) follow-up was 63.5 (24.0-85.3) months. Five out of 24 markers were selected by LASSO Cox regression for the risk classifier: N-cadherin, E-cadherin, Ki67, cyclin D1 and phosphorylated eukaryotic initiation factor 4E binding protein-1 (p-4EBP1). Patients were classified as either low, intermediate or high risk of disease recurrence by tertiles of risk score. The 5-year recurrence-free survival (RFS) was 93.8%, 87.7% and 70% for patients with low-, intermediate- and high-risk scores, respectively (P < 0.001). Patients with a high marker score had worse RFS on multivariate analysis adjusted for age, gender, race and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score (hazard ratio 3.66, 95% confidence interval 1.58-8.49, P = 0.003 for high vs low marker score in the overall cohort). The five-marker classifier increased the concordance index of the clinical model in both the training and validation sets. CONCLUSION: We developed a five-marker-based prognostic tool that can effectively classify patients with ccRCC according to risk of disease recurrence after surgery. This tool, if prospectively validated, could provide individualised risk estimation for patients with ccRCC.

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

PURPOSE: To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). METHODS: We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. CONCLUSION: Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer.

Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03-2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02-1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators.

Characterization of Crude Oil Degrading Bacteria Isolated from Contaminated Soils Surrounding Gas Stations.

A total of twenty bacterial cultures were isolated from hydrocarbon contaminated soil. Of the 20 isolates, RAM03, RAM06, RAM13, and RAM17 were specifically chosen based on their relatively higher growth on salt medium amended with 4 % crude oil, emulsion index, surface tension, and degradation percentage. These bacterial cultures had 16S rRNA gene sequences that were most similar to Ochrobactrum cytisi (RAM03), Ochrobactrum anthropi (RAM06 and RAM17), and Sinorhizobium meliloti (RAM13) with 96 %, 100 % and 99 %, and 99 % similarity. The tested strains revealed a promising potential for bioremediation of petroleum oil contamination as they could degrade >93 % and 54 % of total petroleum hydrocarbons (TPHs) in a liquid medium and soil amended with 4 % crude oil, respectively, after 30 day incubation. These bacteria could effectively remove both aliphatic and aromatic petroleum hydrocarbons. In conclusion, these strains could be considered as good prospects for their application in bioremediation of hydrocarbon contaminated environment.