Rapid identification of dysregulated genes in cutaneous malignant melanoma metastases using cDNA technology

One important application of DNA microarray technology is the simultaneous analysis of gene expression of different mRNAs. Comparison of mRNA patterns of diseased and healthy tissue may help to understand the pathogenesis of a given disorder. In cancer tissue, identified dysregulated genes may serve as new molecular markers for diagnosis or prognosis or may ideally serve as new targets for therapy. Using membrane cDNA array technology, we analyzed gene expression in human melanomas, one of the most aggressive types of cancer with a high metastatic potential and with markedly increased incidence worldwide. To account for the heterogeneity of tumors, we compared total RNA from cutaneous melanoma metastases of 10 different patients with primary human melanocytes. An abundance of genes was dysregulated (up-/downregulated), which involved for example the apoptosis gene growth factor receptor-bound protein 10, Bcl2-associated X membrane protein, Bcl2 antagonist of cell death, glutathione S-transferase theta(1) and glutathione reductase. Ultimately, the identification of melanoma-associated genes may provide a potential therapeutic strategy for identifying and targeting malignant melanoma.     

Bone mineral density is related to blood pressure in men

The aim of this study was to determine the relationships between bone mineral density (BMD) and blood pressure in 214 men, age 20–76. BMD measurements were done by dual X‐ray absorptiometry using a Lunar DPXMD densitometer at the lumbar spine (L2–L4) and different femoral regions. Systolic (SBP) and diastolic (DBP) blood pressure were measured using an MPC‐350 sphygmomanometer. Physicians gathered demographic data and participants' dietary intake of calcium were determined by using food frequency questionnaires. After adjusting for age, body mass index, dietary calcium, and exercise history, multiple linear regression models showed that DBP was negatively related to femoral neck BMD (β = ?0.145, P = 0.032) and just shy of significant association with femoral neck BMC (β = ?0.114, P = 0.079). SBP was correlated with femoral neck (r = ?0.171, P = 0.012) and Ward's (r = ?0.186, P = 0.006) BMD but not after adjusting for possible confounders. Further studies are needed to determine whether elevated blood pressure is causally related to the development of low bone mass. Am. J. Hum. Biol. 16:168–171, 2004. © 2004 Wiley‐Liss, Inc.     

Effects of Different Doses of Caffeinated Coffee on Muscular Endurance,Cognitive Performance,and Cardiac Autonomic Modulation in Caffeine Naive Female Athletes

Caffeine is widely consumed among elite athletes for its well-known ergogenic properties, and its ability to increase exercise performance. However, studies to date have predominantly focused on the anhydrous form of caffeine in male participants. The aim of the study was to investigate the effect of caffeinated coffee ingestion on lower-upper body muscular endurance, cognitive performance, and heart rate variability (HRV) in female athletes. A total of 17 participants (mean ± standard deviation (SD): age = 23 ± 2 years, body mass = 64 ± 4 kg, height = 168 ± 3 cm) in a randomized cross-over design completed three testing sessions, following the ingestion of 3 mg/kg/bm of caffeine (3COF), 6 mg/kg/bm of caffeine (6COF) provided from coffee or decaffeinated coffee (PLA) in 600 mL of hot water. The testing results included: (1) repetition number for muscular endurance performance; (2): reaction time and response accuracy for cognitive performance; (3): HRV parameters, such as standard deviation of normal-to-normal (NN) intervals (SDNN), standard deviation of successive differences (SDSD), root mean square of successive differences (RMSSD), total power (TP), the ratio of low- and high-frequency powers (LF/HF), high-frequency power (HF), normalized HF (HFnu), low-frequency power (LF), and normalized LF (LFnu). A one-way repeated measures ANOVA revealed that 3COF (p = 0.024) and 6COF (p = 0.036) improved lower body muscular endurance in the first set as well as cognitive performance (p = 0.025, p = 0.035 in the post-test, respectively) compared to PLA. However, no differences were detected between trials for upper body muscular endurance (p = 0.07). Lastly, all HRV parameters did not change between trials (p > 0.05). In conclusion, ingesting caffeinated coffee improved lower body muscular endurance and cognitive performance, while not adversely affecting cardiac autonomic function.     

Renoprotective effects of estrogen on acute kidney injury: the role of SIRT1

Acute kidney injury (AKI) is a common syndrome associated with high morbidity and mortality, despite progress in medical care. Many studies have shown that there are sex differences and different role of sex hormones particularly estrogens in kidney injury. In this regard, the incidence and rate of progression of kidney diseases are higher in men compared with women. These observations suggest that female sex hormone may be renoprotective. Silent information regulator 2 homolog 1 (SIRT1) is a histone deacetylase, which is implicated in multiple biologic processes in several organisms. In the kidneys, SIRT1 inhibits renal cell apoptosis, inflammation, and fibrosis. Studies have reported a link between SIRT1 and estrogen. In addition, SIRT1 regulates ERα expression and inhibition of SIRT1 activity suppresses ERα expression. This effect leads to inhibition of estrogen-responsive gene expression. In this text, we review the role of SIRT1 in mediating the protective effects of estrogen in the onset and progression of AKI.

     

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol

International Urology and Nephrology - The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy...     

How Can We Differentiate Local Recurrence From Heterotopic Ossification After Resection and Implantation of an Oncologic Knee Prosthesis in Patients with a Bone Sarcoma?

BackgroundHeterotopic ossification (HO) is common after total joint arthroplasty and usually does not cause diagnostic problems. However, the occurrence of HO after oncologic prostheses implantation can be troublesome as it may mimic a locally recurrent tumor. Because this distinction could have a profound impact on the surgeon and patient, it is important to distinguish the two entities; to our knowledge, no study has evaluated this after oncologic endoprosthetic reconstruction around the knee after tumor resection.Questions/purposes(1) How common is the occurrence of HO compared with local recurrence (LR) after resection of bone sarcoma and the use of an oncologic knee prosthesis? (2) Are there any factors associated with the development of HO after limb salvage procedures with an endoprosthesis? (3) What features allow the surgeon to differentiate HO from a locally recurrent tumor in this setting?Methods‏Between 2002 and 2018, we performed 409 resections of primary bone tumors followed by reconstructions with oncologic endoprostheses. Of these, 17% (71 of 409) died before 2 years and did not have HO at that time, 2% (8 of 409) were lost to follow-up before 2 years, and another 2% (10 of 409) did not have radiographs available at a minimum of 2 years after surgery (and had not developed HO before then), and so could not be analyzed, leaving 320 patients for analysis in this retrospective study. Forty-two patients were excluded; 2% (5 of 320) for a history of failed allograft reconstruction, 3% (8 of 320) for pathologic fracture at presentation, 2% (6 of 320) for inadequate or complicated biopsy, 1% (2 of 320) for stem fractures, 2% (7 of 320) for stem loosening, and 4% (14 of 320) for extracortical bone bridging, leaving 278 patients for final evaluation. Two observers analyzed AP and lateral radiographs for signs of HO at a mean follow-up of 63 ± 33 months after surgery. We defined HO as extraskeletal bone formation in soft tissues. The primary study endpoint was survivorship free from HO, as ascertained by a competing-risks estimator. To identify factors associated with HO appearance, the demographic, radiographic, clinical, pathologic, and surgical characteristics were compared between patients with HO and those who had no lesion. Characteristic features were also compared between patients with HO and those with LR to help their differentiation. Univariate analysis was used for all statistical evaluations.ResultsHO developed in 8% (21 of 278) of patients in whom oncologic knee prosthesis was implanted. LR developed in 10% (28 of 278) of the patients. According to survivorship estimates, the HO-free survival rate was not different from the LR-free survival rate at 2 years after oncologic knee reconstruction (76 ± 5% [95% CI 63 to 87] versus 74 ± 5% [95% CI 62 to 88]; p = 0.19). History of infection was more common in patients with HO than in patients with no lesion (19% [4 of 21] versus 5% [12 of 229], Odds ratio [OR] 6 [95% CI 2 to 17]; p < 0.001). The male sex was more common in the HO group as well (76% [16 of 21] versus 55% [128 of 229], OR 2 [95% CI 1 to 5]; p = 0.03). The Modular Universal Tumor and Revision System prosthesis was more frequently used in patients with HO (67% [14 of 21]) compared to those with no lesions (40% [92 of 229]; OR 2 [95% CI 1 to 5]; p = 0.02).‏ The lesion border in radiographs was ill-defined in 19% (4 of 21) of patients with HO and 100% (28 of 28) of patients with LR (OR 8 [95% CI 3 to 20]; p < 0.001). The median time to the appearance of HO was shorter than the time to LR (8 months [3 to 13] versus 16 months [11 to 21], [95% CI 10 to 13]; p < 0.001). Pain at presentation was more frequent in patients with LR than in those with HO (86% [24 of 28] versus 14% [3 of 21], OR 36 [95% CI 7 to 181]; p < 0.001).ConclusionHO may occur after the use of oncologic knee prostheses for reconstruction after tumor resection. In most patients, HO could be differentiated from local recurrence through identifying a well-defined border on radiographs. Otherwise, factors such as an earlier time of presentation and absence of pain could suggest an HO, rather than an LR.Level of EvidenceLevel III, therapeutic study.     

Activators of SIRT1 in the kidney and protective effects of SIRT1 during acute kidney injury (AKI) (effect of SIRT1 activators on acute kidney injury)

Clinical and Experimental Nephrology - Acute kidney injury (AKI) is a complex disorder and a clinical condition characterized by acute reduction in renal function. If AKI is not treated, it can...     

Does the type of cryoprobe affect oncological and functional outcomes in men with clinically localized prostate cancer treated with primary whole gland prostate cryoablation?

Background:This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe^®) and the conventional fixed-size ice probe.Materials and methods:We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe^® and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage.Results:A total of 1124 men were included. Median age, Gleason score, and pretreatment PSA were 70 years (interquartile range [IQR]: 65–74 years), 7 (IQR: 6–7) and 5.9 ng/mL (IQR: 4.6–8.1 ng/mL), respectively. The median follow-up time was 25.0 months (IQR: 11.2–48.6 months). V-Probes^® were used in 269 (23.9%) cases and fixed-size ice probes in 858 (76.1%) cases. After adjusting for clinical T stage, PSA, neoadjuvant androgen deprivation therapy and preoperative Gleason score, on the multivariate Cox regression model, we found that there was no significant difference between the type of probe and timing to biochemical recurrence (p = 0.35). On multivariate logistic regression, using the V-Probe^® was associated with a 91% increase in postoperative urinary retention compared to the fixed-size ice probe (p = 0.003).Conclusions:The use of the V-Probe^® versus conventional fixed-size ice probe was not associated with a difference in biochemical recurrence in patients undergoing primary cryoablation of the prostate.     

Attitudes and experience of urology trainees in interpreting prostate magnetic resonance imaging

IntroductionMultiparametric magnetic resonance imaging (mpMRI) has resulted in accurate prostate cancer localization and image-guided targeted sampling for biopsy. Despite its more recent uptake, knowledge gaps in interpretation and reporting exist. Our objective was to determine the need for an educational intervention among urology residents working with mpMRIs.MethodsWe administered an anonymous, cross-sectional, self-report questionnaire to a convenience sample of urology residents in U.S. and Canadian training programs. The survey included both open- and closed-ended questions employing a five-point Likert scale. It was designed to assess familiarity, exposure, experience, and comfort with interpretation of mpMRI.ResultsFifty-three surveys were completed by residents in postgraduate years (PGY) 1–5 and of these, only 12 (23%) reported any formal training in mpMRI interpretation. Most residents’ responses demonstrated significant experience with prostate biopsies, as well as familiarity with reviewing mpMRI for these patients. However, mean (± standard deviation [SD]) Likert responses suggested a relatively poor understanding of the components of Prostate Imaging-Reporting and Data System (PI-RADS) v2 scoring for T2-weighted films (2.45±1.01), diffusion-weighted imaging (DWI) films (2.26±0.90), and dynamic contrast-enhanced (DCE) films (2.21±0.99). Similar disagreement scores were observed for questions around interpretation of the different functional techniques of MRI images. Residents reported strong interest (4.21±0.91) in learning opportunities to enhance their ability to interpret mpMRI.ConclusionsWhile mpMRI of the prostate is a tool frequently used by care teams in teaching centers to identify suspicious prostate cancer lesions, there remain knowledge gaps in the ability of trainees to interpret images and understand PI-RADS v2 scoring. Online modules were suggested to balance the needs of trainee education with the residency workflow.