Evgeniy Kreydin

Yeast Adapt to Near-Freezing Temperatures by STRE/Msn2,4-Dependent Induction of Trehalose Synthesis and Certain Molecular Chaperones

Virtually nothing is known about the biochemical adaptations in eukaryotic cells that may enhance survival at low temperatures or upon freezing. Here we demonstrate an adaptive response in yeast that is activated below 10 degrees C and increases tolerance to low temperatures and freezing. This response involves a dramatic accumulation of the chemical chaperone trehalose and induction of trehalose-synthesizing enzymes (Tps1, Tps2) and certain heat shock proteins (Hsp104, Hsp42, Hsp12, Ssa4). mRNAs for these proteins increase dramatically below 10 degrees C and even at 0 degrees C. Their expression requires Msn2,4 transcription factors but also involves marked mRNA stabilization. Upon return to 30 degrees C, TPS1, TPS2, and HSP104 mRNAs, trehalose levels and tolerance to freezing fall dramatically within minutes. Mutants lacking trehalose or Msn2,4 die more rapidly at 0 degrees C and upon freezing. Thus, below 10 degrees C, yeast show an adaptive response that sustains viability at low or freezing temperatures, which are commonly encountered in natural environments and laboratory refrigerators.

Risk factors for sepsis after percutaneous renal stone surgery.

Since its introduction into the endourologists armamentarium almost 40 years ago, percutaneous nephrolithotomy (PCNL) has become the standard of care for patients with large-volume nephrolithiasis. Postoperative infection is one of the most common complications of the procedure, and postoperative sepsis is one of the most detrimental. A number of factors have been found to increase the risk of postoperative sepsis. These include patient characteristics that are known preoperatively, such as urine culture obtained from the bladder or from the renal pelvis if percutaneous access to the renal pelvis is obtained in advance to the procedure. Neurogenic bladder dysfunction secondary to spinal cord injury and anatomical renal abnormalities, such as pelvicalyceal dilatation, have also been associated with increased incidence of fever and sepsis after the procedure. Several intraoperative factors, such as the average renal pressure sustained during PCNL and the operative time, also seem to increase the risk of sepsis. Finally, the contribution of postoperative factors, such as presence of a nephrostomy tube or a urethral catheter, has also been investigated. A short preoperative course of antibiotics has been found to significantly decrease the rate of postoperative fever and sepsis. Novel agents targeted at sepsis prevention and treatment, such as anti-endotoxin antibodies and cholesterol-lowering drugs statins, are currently under investigation.

Primary spermatic cord tumors: Disease characteristics, prognostic factors, and treatment outcomes

INTRODUCTION Experience with management of spermatic cord tumors (SCTs) is uncommon. We utilized a large population-based cancer registry to characterize the demographic, pathological, treatment characteristics, and outcomes of SCTs. MATERIAL AND METHODS The Surveillance, Epidemiology, and End Results database (1973-2007) was queried. RESULTS From the database, 362 patients were identified with SCT. The annual incidence of SCT was 0.3 cases per million and did not change over time. The most common histologic types were liposarcoma (46%), leiomyosarcoma (20%), histiocytoma (13%), and rhabdomyosarcoma (9%). The median age of diagnosis for rhabdomyosarcomas was (26.3 y), whereas for other SCTs, it was (64.7 y) (P<0.001). On multivariate analysis, a worse outcome was observed with undifferentiated tumor grade, distant disease, positive lymph nodes, and leiomyosarcoma or histiocytoma cell histology. CONCLUSION We describe the largest cohort of SCT studied to date. Liposarcoma was most common, while leiomyosarcoma and histiocytoma histologic subtypes were observed to be the most aggressive. Multivariate analysis revealed that tumor grade, stage, histologic type, and lymph node involvement were independently predictive of prognosis.

Testicular Cancer: What the Radiologist Needs to Know

OBJECTIVE The purpose of this article is to review current imaging techniques and evolving technologies that are being used for detection and management of testicular cancer. CONCLUSION The primary goal of cancer imaging is accurate disease characterization at diagnosis and through all stages of management. Knowledge of the disease and diagnostic performance characteristics of each technique is critical to identify the appropriate modality for staging disease and to monitor for treatment response and recurrence that may dictate further intervention.

Immediate renal transplantation after radical prostatectomy for low-risk prostate cancer.

For most cancers, a two‐ to five‐yr period with no evidence of disease must be demonstrated before organ transplantation. The natural history of prostate cancer is unique both because of extensive pre‐treatment screening and the ease of post‐treatment monitoring for recurrence. Using available predictive models for prostate cancer recurrence, we examine whether current evidence supports a prolonged waiting period after radical prostatectomy and before renal transplantation.

Comparison of Times to Ureteral Efflux after Administration of Sodium Fluorescein and Phenazopyridine

Purpose: There is currently a national shortage of indigo carmine. In efforts to identify the most efficient aid for visualizing ureteral efflux intraoperatively we investigated the time to excretion of phenazopyridine vs a newly identified alternative, sodium fluorescein. Materials and Methods: We analyzed prospectively collected data on a cohort of women who underwent pelvic reconstructive surgery in 2015. Per provider preference patterns a number of patients were administered 200 mg phenazopyridine orally with a sip of water 1 hour prior to the start of operative time. Other patients were given 0.5 ml 10% sodium fluorescein intravenously in the operating room. In all cases time was measured between the administration of the agent and the visualization of color changes consistent with agent efflux in an indwelling catheter, which was placed at the start of the operation. Differences in excretion times between the groups were compared with the Wilcoxon rank sum test. Results: Seven women received phenazopyridine and 5 received sodium fluorescein. Mean excretion time was significantly longer in the phenazopyridine group compared to the sodium fluorescein group (81.9 vs 5.1 minutes, p = 0.0057). Median excretion time for phenazopyridine was 70 minutes (range 59 to 127) and for sodium fluorescein it was 5 minutes (range 3 to 9). Conclusions: Sodium fluorescein is excreted significantly faster in the operating room compared to phenazopyridine. Depending on the cost of these agents at an institution, in addition to the desire to decrease operative time, this may impact practice patterns and agent selection.

Role of imaging in testicular cancer: current and future practice.

The article provides a summary of the epidemiologic and clinical aspects of testicular malignancy. Current standard imaging and novel techniques are reviewed. Present data and clinical treatment trends have favored surveillance protocols over adjuvant radiation or chemotherapy for low-stage testicular malignancy. This has resulted in increasing numbers of imaging studies and the potential for increased long-term exposure risks. Understanding imaging associated risks as well as strategies to minimize these risks is of increasing importance. The development, validation and incorporation of alternative lower risk highly efficacious and cost-effective imaging techniques is essential.

Differential Response to Medical Therapy for Male Lower Urinary Tract Symptoms

Medical therapy has assumed a critical role in the treatment of male lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction. Targeting both bladder and prostate, these medications provide an effective means to manage LUTS for millions of men. However, significant proportion of men do not respond adequately to medical therapy and go on to surgical treatment of bladder outlet obstruction. In order to provide patients with appropriate therapy, prevent unnecessary exposure to drug side effects, and reduce medical costs, it is important to identify those men in whom medication will not be effective. In this review, we focus on the risk factors that predict failure of the common medical therapies for male LUTS. In addition, we describe recently discovered molecular targets that show promise for treatment of LUTS recalcitrant to conventional therapies.

Surveillance and management of urologic complications after spinal cord injury

PurposeNeurogenic bladder due to spinal cord injury has significant consequences for patients’ health and quality of life. Regular surveillance is required to assess the status of the upper and lower urinary lower urinary tracts and prevent their deterioration. In this review, we examine surveillance techniques in neurogenic bladder, describe common complications of this disease, and address strategies for their management.MethodsThis work represents the efforts of SIU-ICUD joint consultation on Urologic Management of the Spinal Cord injury. For this specific topic, a workgroup was formed and comprehensive literature search of English language manuscripts regarding neurogenic bladder management was performed using key words of neurogenic bladder. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for Levels of Evidence (LOEs) and Grades of Recommendation (GORs).ResultsAt a minimum, patients should undergo an annual history and physical examination, renal functional testing (e.g., serum creatinine), and upper tract imaging (e.g., renal ultrasonography). The existing evidence does not support the use of other modalities, such as cystoscopy or urodynamics, for routine surveillance. Urologic complications in neurogenic bladder patients are common and often more complex than in the general population.ConclusionsThere is a shortage of high-quality evidence to support any particular neurogenic bladder surveillance protocol. However, there is consensus regarding certain aspects of regular genitourinary system evaluation in these patients. Proper surveillance allows the clinician to avoid or address common urological complications, and to guide, alter, or maintain appropriate therapeutic regimens for individual patients.

The Association of Serum Testosterone Levels and Urinary Incontinence in Women

Purpose: Pelvic floor integrity is an important predictor of stress urinary incontinence. Androgen receptors have been found in the pelvic floor musculature and fascia, and testosterone administration has been shown to increase levator ani hypertrophy and improve stress incontinence in a rodent model. We examined the relationship between serum total testosterone levels and self‐reported urinary incontinence in women. Materials and Methods: We included women older than 20 years in the 2012 NHANES (National Health and Nutrition Examination Survey) cycle who underwent serum total testosterone measurement and answered self‐reported urinary incontinence questions. A weighted, multivariate logistic regression model was used to determine the association between incontinence and serum testosterone levels after adjusting for age, body mass index, diabetes, race, parity, menopause and time of venipuncture. Results: A total of 2,321 women were included in analysis, of whom 37.5% had stress incontinence, 29.8% had urge incontinence and 16.4% had mixed incontinence. Women in the lowest quartile of serum testosterone were more likely to complain of stress and mixed incontinence (OR 1.45, 95% CI 1.03–2.12 and OR 1.68, 95% CI 1.23–2.22, respectively). No association was noted between serum testosterone levels and urge incontinence. Conclusions: Low serum testosterone is associated with an increased likelihood of stress and mixed incontinence in women. Given the role of pelvic musculature in maintaining urethral support and the anabolic effect of androgens on skeletal muscle, a physiological mechanism for this relationship can be proposed and further evaluated in prospective and translational studies.