Biochemical recurrence after radical prostatectomy: Current status of its use as a treatment endpoint and early management strategies.

Prostate cancer is one of the most common urological malignancies managed by a practicing urologist. Treatment strategies are varied, but radical prostatectomy (RP) remains a viable and commonly used option for many patients. A continuing challenge in the management is how to approach a patient who has biochemical recurrence (BCR) after RP. There are no consensus guidelines on the appropriate strategy, and the current recommendations, although useful, are at times confusing. The natural history of BCR is heterogeneous. Published studies aid in the clinician's ability to predict patients most likely to recur; however, this remains inexact. In addition, recent changes in the recommendations for disease screening, as well as technological advances, have added to the already challenging task of the clinician. The objective of this review is to provide an up-to-date summary of the definitions, diagnosis, and management strategies of BCR after RP. This narrative review was conducted by searching Medline for all relevant articles in English with the key terms of biochemical recurrence, prostate cancer, management, and other relevant terms. Information was compiled and reviewed for relevance to the article. Consideration was given to all articles with sufficient evidence including systematic review, retrospective studies, and clinical trials.

Initial series of magnetic resonance imaging (MRI)-fusion targeted prostate biopsy using the first transperineal targeted platform available in the USA.

OBJECTIVES: To describe a step-by-step guide for using the first transperineal targeted prostate biopsy platform available in the USA. PATIENTS AND METHODS: A total of 32 men with elevated prostate-specific antigen (PSA) levels were diagnosed with a region of interest on multiparametric magnetic resonance imaging (mpMRI) between February 2017 and January 2018. The transperineal targeted prostate biopsy procedure was accomplished via a transperineal approach and used a stepper, combined with advanced mpMRI/transrectal ultrasound fusion software, to perform targeted prostate biopsy. The detection of overall and clinically significant prostate cancer (PCa) was assessed as well as the rate of complications. RESULTS: The median patient age was 68.0 years and the median PSA was 8.0 ng/mL. Two patients (6%) were active surveillance candidates and 16 (50%) had a prior negative prostate biopsy. The detection rates for overall and clinically significant PCa were 81% and 59%, respectively. The two candidates for active surveillance and eight of the patients with a prior negative prostate biopsy had clinically significant PCa confirmed on targeted biopsy. There were no peri-operative complications. CONCLUSION: These results demonstrate the promising potential of the first transperineal targeted prostate biopsy platform in the USA as an alternative diagnostic method for PCa.

Physiological and pathophysiological reactive oxygen species as probed by EPR spectroscopy: the underutilized research window on muscle ageing.

Reactive oxygen and nitrogen species (ROS and RNS) play crucial roles in triggering, mediating and regulating physiological and pathophysiological signal transduction pathways within the cell. Within the cell, ROS efflux is firmly controlled both spatially and temporally, making the study of ROS dynamics a challenging task. Different approaches have been developed for ROS assessment; however, many of these assays are not capable of direct identification or determination of subcellular localization of different ROS. Here we highlight electron paramagnetic resonance (EPR) spectroscopy as a powerful technique that is uniquely capable of addressing questions on ROS dynamics in different biological specimens and cellular compartments. Due to their critical importance in muscle functions and dysfunction, we discuss in some detail spin trapping of various ROS and focus on EPR detection of nitric oxide before highlighting how EPR can be utilized to probe biophysical characteristics of the environment surrounding a given stable radical. Despite the demonstrated ability of EPR spectroscopy to provide unique information on the identity, quantity, dynamics and environment of radical species, its applications in the field of muscle physiology, fatiguing and ageing are disproportionately infrequent. While reviewing the limited examples of successful EPR applications in muscle biology we conclude that the field would greatly benefit from more studies exploring ROS sources and kinetics by spin trapping, protein dynamics by site-directed spin labelling, and membrane dynamics and global redox changes by spin probing EPR approaches.

The efficacy of simultaneous successive classic and variant infectious bronchitis virus vaccines versus circulating variant II Egyptian field virus.

Background: Being a ubiquitous, highly contagious virus with a continuous mutation and a large number of evolutions worldwide, the infectious bronchitis virus (IBV) continues to wreak problems among Egyptian chickens and generate economic losses. The commonly applied IBV vaccination protocols in broilers include alternatives to classic and/or variant attenuated live virus vaccines. Aim: The current study targeted to assess the protective efficacy of concurrent and successive Ma5 and 4/91 vaccine strain regimens against the field variant II IBV strain (IBV-EGY-ZU/Ck-127/2021) in chickens. Methods: Commercial broiler chickens were vaccinated with Ma5 and 4/91 strains simultaneously at 1 and 14 days of age. The evaluation parameters included clinical protection and humoral and early innate immunity aspects in the renal tissues of vaccinated and infected birds. Results: The vaccine regimen ameliorated the clinical and histopathological lesions against variant II IBV and enhanced body gain as well as succeeded in preventing tracheal shedding and minimizing cloacal shedding of the field virus. The IL-1ß mRNA gene expression was evident as early as 24 hours, with highly significant upregulation at 48 hours post vaccination and 24 hours post challenge (PC) in vaccinated birds. Remarkable upregulation was observed in oligoadenylate synthetases (OAS) expression 48 hours PC in vaccinated and unvaccinated infected birds. The vaccinated birds developed a significant antibody titer of 704.0 ± 111.98 at 28 days of age, with a consistent antibody titer increase after the challenge. Conclusion: Overall, a combination of heterologous protectotype commercial vaccines achieved good protection against the Egyptian variant II IBV strain. This vaccine program could be an effective protocol against the threat posed by IBV viruses circulating in the Egyptian field.

Have Bilateral Free Trade Agreements (BFTAs) been beneficial? Lessons learned from 11 U.S. BFTAs between 1992 and 2017.

This study analyzes aggregate data on trade flows to examine the performance of bilateral free trade agreements (BFTAs) between the United States and 11 BFTA nations in a two-dimensional approach. In line with the literature, this study applies the gravity model and analyzes the effect of the treatment using Poisson pseudo-maximum likelihood (PPML) panel data from 1992 to 2017. We use the PPML as an alternative methodology to an ordinary least squares model, as it can treat zero trade values and lead to unbiased estimates and different consistencies. We consider the trade in goods but excluded services because of the different nature of trade for services. Moreover, this study highlights the quantitative performance of BFTAs without considering the industry level to compare the overall benefits for the trade flows from the U.S. as an exporter to BFTA countries and vice versa. It thus adds to the debate on the effect of FTAs on trade flows and conducts pre-FTA and post-FTA analyses to compare the volumes of exports and imports during both periods. Findings vary according to the direction of trade; notably, some trading partners increased their trading volume to 388%. In sum, this paper provides a collective current state assessment to demonstrate the most plausible reasons for the effects of the 11 BFTAs, in addition to informing policymakers on the lessons learned from each BFTA.

Autism spectrum disorder (ASD)-associated mitochondrial deficits are revealed in children's platelets but unimproved by hyperbaric oxygen therapy.

Mitochondrial and immune dysfunctions are often implicated in the aetiology of autism spectrum disorder (ASD). Here, we studied for the first time the relationship between ASD severity measures and mitochondrial respiratory rates in freshly isolated platelets as well as the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in isolated neutrophils. We also verified the impact of hyperbaric oxygen therapy (HBOT) on mitochondrial and immune functions as well as on ASD severity measures. Blood samples were collected from three age-matched male groups (Control (Norm-N), autistic (Aut-N), and autistic + HBOT (Aut-H); N = 10 per group). Using high resolution respirometry, we found that routine basal respiration, complex I- and complex I + II-dependent oxidative phosphorylation rate were significantly impaired in Aut-N platelets. Similarly, deficits in immune response of neutrophils were evidenced through lower rates of oxygen consumption and reactive oxygen species (ROS) production by phagocytic NOX. ASD-related behavioural outcomes were found to moderately correlate with platelets' mitochondrial bioenergetic parameters as well as with NOX-mediated activity in neutrophils. HBOT was not able to improve mitochondrial dysfunctions or to counteract ASD-related behavioral deficits. Although HBOT improved one measure of the immune response; namely, NOX-mediated superoxide burst, this was not associated with significant changes in trends of recurrent infections between groups. Taken together, our data suggest that ASD-associated mitochondria and immune deficits are detectable in platelets and neutrophils. We also found no evidence that HBOT confers any significant improvement of ASD-associated physiological or behavioural phenotypes.

Outcomes of Lisfranc Injuries Treated with Joint-Preserving Fixation.

BACKGROUND: Open reduction and internal fixation (ORIF) with transarticular screws to stabilize Lisfranc injuries may increase the risk of arthritis or affect outcomes. Joint-preserving fixation using staples, bridge plating, or Lisfranc screws avoids iatrogenic articular damage. This study analyzes functional outcomes and complications in Lisfranc-injury patients who underwent joint-preserving fixation. MATERIALS AND METHODS: We conducted a retrospective review of patients treated for Lisfranc injury at a Level 1 trauma center from July 2008 to October 2015. Patients over 18 years of age, with no concomitant procedures in the lower extremities, were included. Functional outcomes were evaluated through American Orthopaedic Foot and Ankle Society (AOFAS) scores. RESULTS: Fourteen patients met the inclusion criteria. The average followup time was 57 months (range 22-102 months). AOFAS scores averaged 80.4 (standard deviation [SD] 16) at the time of the latest followup, with time to return to regular activities averaging 34 weeks (SD 25 weeks). Five patients had their hardware removed, and two required subsequent fusion during the followup period. The single complication involved a screw backing out, with subsequent removal. CONCLUSIONS: In this case series, joint-preserving fixation for Lisfranc injuries offered similar AOFAS scores as those reported for ORIF with transarticular screws but with a decreased rate of hardware removal and need for midfoot fusion.

Vasectomy reversal utilizing fibrin glue.

Over 500,000 men in America have a vasectomy annually; 2% to 6% of these individuals later elect to have a vasectomy reversal. Vasovasostomies are typically performed using a single- or double-layer closure, with no demonstrated difference between the two in terms of success rates. In 2005, Ho et al described a microscopic technique in which three full-thickness sutures are used and the anastomosis is reinforced with fibrin glue. At our institution, a similar technique has been used for >10 years. To describe our experience, a retrospective chart review was undertaken. Patient demographic information and operative characteristics were analyzed. In each case, fibrin glue was circumferentially applied to reinforce the anastomosis. The overall patency rate was 88.4%, and rates comparing individuals who had their vasectomy reversal within 10 years of vasectomy reached statistical significance with an odds ratio of 2.91 (P = 0.048). Median operative time was 94 minutes. Other demographic variables analyzed did not have a correlation with patency. In conclusion, our technique provides acceptable patency rates, especially with obstructive intervals of 10 years or less, while likely resulting in cost savings given the decreased operating room time and suture used.

Early Stone Manipulation in Urinary Tract Infection Associated with Obstructing Nephrolithiasis.

A urinary tract infection (UTI) and sepsis secondary to an obstructing stone are one of the few true urological emergencies. The accepted management of infected ureteral stones includes emergent decompression of the collecting system as well as antibiotic therapy. Despite this, no consensus guidelines clarify the optimal time to undergo definitive stone management following decompression. Historically, our institution has performed ureteroscopy with laser lithotripsy (URS-LL) treatment at least 1 to 2 weeks after decompression to allow for clinical improvement and completion of an antibiotic course. In this case series, we retrospectively review four cases in which patients had a documented UTI secondary to an obstructive ureteral stone. The patients underwent urgent decompression and, based on labs and clinical improvement, were subsequently treated with URS-LL. The presented patients received URS-LL within 5 days of decompression and antibiotics. The patients had no sepsis related postoperative complications from the accelerated course of treatment, resulting in discharge within 2 days following URS-LL. We provide a detailed examination of each patient presentation to describe our institution's experience with treating infected kidney stones within days of urgent decompression in order to question the previous standard of treating an infected kidney stone with a more delayed intervention.

Atypical small acinar proliferation at index prostate biopsy: rethinking the re-biopsy paradigm.

PURPOSE: Guidelines for atypical small acinar proliferation (ASAP) diagnosed on prostate biopsy recommend repeat biopsy within 3-6 months after diagnosis. We sought to discern the rate of detecting clinically significant prostate cancer on repeat biopsy and predictors associated with progression. MATERIALS AND METHODS: We performed a retrospective chart review of patients who underwent prostate biopsy at our institution from January 1, 2008, to December 31, 2015. Gleason grade group (GGG) system and D'Amico stratification were used to report pathology and risk stratification, respectively. Logistic and linear regression analyses were performed. RESULTS: A total of 593 patients underwent transrectal ultrasound-guided prostate biopsy, of which 27 (4.6%) had the diagnosis of ASAP. Of these, 11 (41%) had a repeat biopsy. Median time from diagnosis to repeat biopsy was 147 days (IQR 83.5-247.0). Distribution across the GGG system on repeat biopsy was as follows: 7 (63.6%) benign, 3 (27.3%) GG1, and 1 (9.1%) GG2. ASAP was not associated with subsequent diagnosis of clinically significant prostate cancer (OR 0.46, 95% CI 0.064-3.247, P = 0.432). There was no association between ASAP and high cancer risk (ASAP: ß = - 0.12; P = 0.204). CONCLUSIONS: Patients diagnosed with ASAP managed according to guideline recommendations are more likely diagnosed with benign pathology and indolent prostate cancer on repeat biopsy. These findings support prior studies suggesting refinement of guidelines in regard to the appropriateness and timeliness of repeat biopsy among patients diagnosed with ASAP.

Sex-specific differences in mitochondria biogenesis, morphology, respiratory function, and ROS homeostasis in young mouse heart and brain.

Sex-specific differences in mitochondrial function and free radical homeostasis are reported in the context of aging but not well-established in pathogeneses occurring early in life. Here, we examine if sex disparity in mitochondria function, morphology, and redox status starts early and hence can be implicated in sexual dimorphism in cardiac as well as neurological disorders prevalent at young age. Although mitochondrial activity in the heart did not significantly vary between sexes, female brain exhibited enhanced respiration and higher reserve capacity. This was associated with lower H2O2 production in female cardiac and brain tissues. Using transmission electron microscopy, we found that the number of female cardiac mitochondria is moderately greater (117 ± 3%, P = 0.049, N = 4) than male's, which increased significantly for cortical mitochondria (134 ± 4%, P = 0.001, N = 4). However, male's cardiac mitochondria exhibited fragmented, circular, and smaller mitochondria relative to female's mitochondria, while no morphologic sex-dependent differences were observed in cortical mitochondria. No sex differences were detected in Nox2 and Nox4 proteins or O2-consuming/H2O2-producing activities in brain homogenate or synaptosomes. However, a strong trend of increased EPR-detected NOX superoxide in male synaptosomes hinted at higher superoxide dismutase activity in female brains, which was confirmed by two independent protocols. We also provide direct evidence that respiring mitochondria generally produce an order-of-magnitude lower reactive oxygen species (ROS) proportions than currently estimated. Our results indicate that sex differences in mitochondrial biogenesis, bioenergetics, and morphology may start at young age and that sex-dependent SOD capacity may be responsible for differences in ROS homeostasis in heart and brain.

Corrigendum to "Resolving Contributions of Oxygen-Consuming and ROS-Generating Enzymes at the Synapse".

[This corrects the article DOI: 10.1155/2016/1089364.].

Transcriptional profiling of breast cancer cells in response to mevinolin: Evidence of cell cycle arrest, DNA degradation and apoptosis.

The merging of high-throughput gene expression techniques, such as microarray, in the screening of natural products as anticancer agents, is considered the optimal solution for gaining a better understanding of the intervention mechanism. Red yeast rice (RYR), a Chinese dietary product, contains a mixture of hypocholesterolemia agents such as statins. Typically, statins have this effect via the inhibition of HMG­CoA reductase, the key enzyme in the biosynthesis of cholesterol. Recently, statins have been shown to exhibit various beneficial antineoplastic properties through the disruption of tumor angiogenesis and metastatic processes. Mevinolin (MVN) is a member of statins and is abundantly present in RYR. Early experimental trials suggested that the mixed apoptotic/necrotic cell death pathway is activated in response to MVN exposure. In the current study, the cytotoxic profile of MVN was evaluated against MCF­7, a breast cancer­derived cell line. The obtained results indicated that MVN­induced cytotoxicity is multi­factorial involving several regulatory pathways in the cytotoxic effects of MVN on breast cancer cell lines. In addition, MVN­induced transcript abundance profiles inferred from microarrays showed significant changes in some key cell processes. The changes were predicted to induce cell cycle arrest and reactive oxygen species generation but inhibit DNA repair and cell proliferation. This MVN­mediated multi­factorial stress triggered specific programmed cell death (apoptosis) and DNA degradation responses in breast cancer cells. Taken together, the observed MVN­induced effects underscore the potential of this ubiquitous natural compound as a selective anticancer activity, with broad safety margins and low cost compared to benchmarked traditional synthetic chemotherapeutic agents. Additionally, the data support further pre­clinical and clinical evaluations of MVN as a novel strategy to combat breast cancer and overcome drug resistance.

Resolving Contributions of Oxygen-Consuming and ROS-Generating Enzymes at the Synapse.

Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H2O2 generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory. Our results indicate that although synaptic mitochondria exhibit substantially higher respiratory activities (8-82-fold greater than NOX oxygen consumption depending on mitochondrial respiratory state), NADPH-dependent oxygen consumption is associated with greater H2O2 production (6-7-fold higher NOX-H2O2). We also show that, in terms of the consumed oxygen, while synaptic mitochondria "leaked" 0.71% ± 0.12 H2O2 during NAD+-linked resting, 0.21% ± 0.04 during NAD+-linked active respiration, and 0.07% ± 0.02 during FAD+-linked active respiration, NOX converted 38% ± 13 of O2 into H2O2. Our results indicate that NOX rather than mitochondria is the major source of synaptic H2O2. The present approach may assist in the identification of redox-modulating synaptic factors that underlie a variety of physiological and pathological processes in neurons.

Effects of plant-derived anti-leukemic drugs on individualized leukemic cell population profiles in Egyptian patients.

Leukemias are a group of cancer types that originate from blood-forming tissues. In this disease, an abnormally large number of immature white blood cells is produced by the bone marrow. The relationship between treatments with plant-derived drugs and leukemia-associated immunophenotypes (LAIPs) of clinically isolated leukemia cells has yet to be established. The aim of the present study was to develop a preliminary clinical prognostic map for commonly expressed LAIPs in patients clinically diagnosed with leukemia, as well as to assess the potential involvement of LAIPs in the response rate to 10 natural products of plant origin. An increased expression of LAIPs, including CD4, CD14, CD33 and CD34, was considered a surrogate marker of the desired response of leukemia cells to treatment with plant-derived drugs. By contrast, the increased expression of the LAIPs, MPO and DR, was associated with poor prognostic outcomes following treatment with the plant-derived drugs. The results showed that 5 of the 10 plant-derived drugs tested induced the expression of several desirable LAIPs biomarkers. These findings clearly highlight the potential treatment efficacy of certain plant-derived drugs against leukemic cell types.

The spectrum of cutaneous infection in diabetic patients with hepatitis C virus infection: a single-center study from egypt.

CONTEXT: Hepatitis-C virus (HCV) infection and diabetes mellitus (DM) have a significant association with skin disorders. AIMS: The aim of this study was to assess the impact of HCV infection on the pattern of cutaneous infections among diabetic patients. METHODS AND MATERIAL: A prospective study included diabetic patients who attended Al-Hussein University hospital, Cairo during the period from 2008 to 2010. Patients were examined for skin infections, and investigated for HCV infection. STATISTICAL ANALYSIS USED: SPSS (version 11.5). RESULTS: The study included 163 patients (102 males and 61 females) with a mean age of 46.2 ± 4.83 years. Ninety five patients (58.3%) were HCV+ve (group A) while 68 patients (41.8%) were HCV-ve (group B). Skin infections in group A included fungal (48.4%), viral (26.3%), bacterial (22.1%) and parasitic (3.2%) while in group B, the spectrum included bacterial (41.2%), fungal (39.7%), viral (11.7%) and parasitic (7.4%). Onychomycosis was the commonest infection in group A (25.2%) compared with folliculitis in group B (19.1%). Cutaneous infections in HCV+ patients were more characterized by increased severity, aggressive course, resistance to treatment and rapid relapse. CONCLUSIONS: HCV infection has a significant impact in increasing and changing the spectrum of skin infections in diabetic patients. Severe and resistant infections in diabetics could be an important sign of HCV infection.

Eichhornia crassipes (Mart) solms: from water parasite to potential medicinal remedy.

Water hyacinth, Eichhornia crassipes (Mart) Solms, originating in the amazonian basin, is a warm water aquatic plant. Water hyacinth is considered one of the most productive plants on earth and, accordingly, is considered one of the top 10 world's worst weeds. Water hyacinth spread to other tropical and subtropical regions by humans. It invaded about 62 countries in Africa, Asia and North America, and propagated extremely serious ecological, economical and social problems in the region between 40 degrees north and 45 degrees south. The dense weed of water hyacinth forms dense monocultures that can threaten local native species diversity and change the physical and chemical aquatic environment, thus altering ecosystem structure and function by disrupting food chains and nutrient cycling. We have separated and identified nine active fractions from water hyacinth and showed their promising therapeutic activities. Several compounds (alkaloid, phthalate derivatives, propanoid and phenyl derivatives) were identified in the extract of water hyacinth.