A comprehensive monitoring approach for a naturally anoxic aquifer beneath a controlled landfill.

The processes leading to high levels of arsenic (As), iron (Fe), and manganese (Mn) in groundwater, in a naturally reducing aquifer at a controlled municipal landfill site, are investigated. The challenge is to distinguish the natural water-rock interaction processes, that allow these substances to dissolve in groundwater, from direct pollution or enhanced dissolution of hydroxides as undesired consequences of the anthropic activities above. Ordinary groundwater monitoring of physical-chemical parameters and inorganic compounds (major and trace elements) was complemented by environmental isotopes of groundwater (tritium, deuterium, oxygen-18 and carbon-13) and dissolved gases (carbon-13 of methane and carbon dioxide and carbon-14 of methane). Pearson/Spearman correlation indices, as well as Principal Component Analysis (PCA), were used to determine the main correlations among variables. The concurrent presence of As, Fe and CH4, as reported in similar anoxic environments, suggests that anaerobic oxidation of methane could drive the reductive dissolution of As-rich Fe(III)(hydro)oxides. Manganese is more sensitive to carbon dioxide, possibly due to a decrease in pH which accelerates the dissolution of Mn-oxides. Finally, we found that tritium and deuterium, which have been used for decades as leachate tracer in groundwater, may be subject to false positives due to the reuse of water recovered from leachate treatment (which has the same isotopic signature of leachate) within the plants, to comply with the requirements of the circular economy. The integration of the environmental isotope analysis into the traditional monitoring approach can effectively support the comprehension of processes. However, this strategy needs to be complemented by a good conceptual hydrogeological model and expert evaluation to avoid misinterpretations.

Antarctic permafrost degassing in Taylor Valley by extensive soil gas investigation.

Ongoing studies conducted in northern polar regions reveal that permafrost stability plays a key role in the modern carbon cycle as it potentially stores considerable quantities of greenhouse gases. Rapid and recent warming of the Arctic permafrost is resulting in significant greenhouse gas emissions, both from physical and microbial processes. The potential impact of greenhouse gas release from the Antarctic region has not, to date, been investigated. In Antarctica, the McMurdo Dry Valleys comprise 10 % of the ice-free soil surface areas in Antarctica and like the northern polar regions are also warming albeit at a slower rate. The work presented herein examines a comprehensive sample suite of soil gas (e.g., CO2, CH4 and He) concentrations and CO2 flux measurements conducted in Taylor Valley during austral summer 2019/2020. Analytical results reveal the presence of significant concentrations of CO2, CH4 and He (up to 3.44 vol%, 18,447 ppmv and 6.49 ppmv, respectively) at the base of the active layer. When compared with the few previously obtained measurements, we observe increased CO2 flux rates (estimated CO2 emissions in the study area of 21.6 km2 ≈ 15 tons day-1). We suggest that the gas source is connected with the deep brines migrating from inland (potentially from beneath the Antarctic Ice Sheet) towards the coast beneath the permafrost layer. These data provide a baseline for future investigations aimed at monitoring the changing rate of greenhouse gas emissions from Antarctic permafrost, and the potential origin of gases, as the southern polar region warms.

Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study.

BACKGROUND: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. PATIENTS AND METHODS: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. RESULTS: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. CONCLUSION: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences.

Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. Moreover, the analysis of human prostate cancer and prostate control specimens confirmed the aberrant expression of miR-124-3p, miR-129-5p and miR-378 in primary tumors. Forced expression of the miRNAs mentioned above affected tumorigenic properties, such as proliferation, migration and invasion, in PC3 and LNCaP cells regardless of their hormone sensitivity. CPT1A, CACT and CrAT overexpression allow PCCs to be more prone on FA utilization than normal prostate cells, also in the presence of high pyruvate concentration. Finally, the simultaneous increase of CPT1A, CACT and CrAT is fundamental for PCCs to sustain FA oxidation in the presence of heavy lipid load on prostate cancer mitochondria. Indeed, the downregulation of only one of these proteins reduces PCCs metabolic flexibility with the accumulation of FA-intermediate metabolites in the mitochondria. Together, our data implicate carnitine cycle as a primary regulator of adaptive metabolic reprogramming in PCCs and suggest new potential druggable pathways for prevention and treatment of prostate cancer.

Prevalence of antibodies against Bubaline herpesvirus (BuHV-1) among Mediterranean water buffalo (Bubalus bubalis) with implications in buffalo trade.

BACKGROUND: Both Bovine herpesvirus (BoHV-1) and Bubaline herpesvirus (BuHV-1) have been reported to cross the species barrier. Antibody seroconversion in glycoprotein E (gE) blocking ELISA during BuHV-1 infection has been documented. Recent diagnostic efforts have focused on the development and application of discriminatory tests to distinguish between infections with BoHV-1 and BuHV-1. OBJECTIVE: To evaluate the impact and distribution of these two infections in water buffalo farms in two regions (Piedmont (n = 3) and Campania (n = 10), Italy) where infectious bovine rhinotracheitis control programs have been implemented. ANIMALS AND METHODS: Sampling was carried out on 13 buffalo farms comprising 1089 animals using specific gE-indirect ELISA's test able to discriminate among BoHV-1 and BuHV-1 infections. RESULTS: 59.0% of animals reacted positive to ELISA (irrespective of whether BoHV-1 or BuHV-1 antigen was used) and 86.4% of these were reactive to BuHV-1 only, whereas 11.8% showed absorbance values for both antigens and were classified as inconclusive. There was a statistically significant age-related difference in BuHV-1 infection rates but not in overall individual (47% vs. 58%) or herd prevalence (100% vs. 90%) of infection between the two regions. CONCLUSION: The low percentage of sera reactive to BoHV-1 (1.8%, 12/643) indicates that BuHV-1 may be the main circulating alphaherpesvirus infection in Mediterranean water buffalo in the two study areas. Since Bubalus bubalis is included in Directive 64/432/EEC on animal health problems affecting intra-community trade in bovine animals, diagnostic testing with nonspecific ELISA for BoHV-1 infection in buffalo may yield false-positive reactions. This scenario could lead to economic losses and hamper buffalo trade and movement, particularly for reproduction purposes.

Motion correction in MRI of the brain.

Subject motion in MRI is a relevant problem in the daily clinical routine as well as in scientific studies. Since the beginning of clinical use of MRI, many research groups have developed methods to suppress or correct motion artefacts. This review focuses on rigid body motion correction of head and brain MRI and its application in diagnosis and research. It explains the sources and types of motion and related artefacts, classifies and describes existing techniques for motion detection, compensation and correction and lists established and experimental approaches. Retrospective motion correction modifies the MR image data during the reconstruction, while prospective motion correction performs an adaptive update of the data acquisition. Differences, benefits and drawbacks of different motion correction methods are discussed.

Conventional imaging and multiparametric magnetic resonance (MRI, MRS, DWI, MRP) in the diagnosis of prostate cancer.

The evaluation and management of prostate cancer (PCa) are based mainly on parameters such as the serum prostate-specific antigen level, clinical stage, and pathologic findings at biopsy or after surgery. The aim of this paper was to review the current roles of conventional imaging and multiparametric magnetic resonance imaging (mpMRI) techniques in the diagnosis of PCa. A non systematic literature search using the Medline and Cochrane Library databases was performed up to January 2012. Bibliographies of retrieved articles and review articles were also examined. Only those articles reporting complete data with clinical relevance for the present review (i.e., diagnosis, staging) were selected. The advent of a high performance (1.5T) and higher fields strength (3T), and thus, higher spatial resolution, increased the potentiality and the diffusion of MR examinations. Intense research has focused on the use of complementary techniques to improve the detection, characterization, and staging of PCa by MRI. This review article is divided into two major parts: the first one considers the technical aspects of mpMRI; the second part is intended to provide the impact of this technique on patients with PCa. Published data indicate an emerging role for MRI (particularly mpMRI combining T2 weighted imaging, diffusion weighted imaging, contrast enhanced MR, and spectroscopy) as the most sensitive and specific tool available for imaging PCa. MpMRI can provide metabolic information, characterize tissue and tumor vascularity, as well as tissue cellularity and correlate with tumor aggressiveness.

Development of an educational software for the learningof obstetric anatomy addressed to nursing

Computational technology, such as software, computer program, has been a great tool for the Teaching-Learning process, mainly in Health Sciences. The aim of this study was to develop software (didactic CD‑ROM)on the Learning process of Obstetric Anatomy for Nursing by means of a judicious choice (Portuguese andEnglish languages) of 107 anatomical keywords related to the Obstetrics and sites related to the theme.This CD-ROM (Macromedia Dreamweaver® a computational tool), addressed to the Learning of ObstetricAnatomy for Nursing, could provide logical apprehension of obstetric anatomical terms from didactic texts,images and sites from Web. The educational software development favors an interaction between experts ofHuman Anatomy, Pedagogy and Computer Science. Computing tools applied to Health Sciences are useful topromote knowledge on virtual environments and to complement the Learning of Obstetric Anatomy.

Role of magnetic resonance spectroscopic imaging ([¹H]MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) in identifying prostate cancer foci in patients with negative biopsy and high levels of prostate-specific antigen (PSA).

PURPOSE: The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging (MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting tumour foci in patients with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (TRUS)-guided biopsy. MATERIALS AND METHODS: This prospective randomised trial was conducted on 150 patients who underwent [¹H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with random biopsies. RESULTS: After the second biopsy, the diagnosis of prostate adenocarcinoma was made in 64/150 cases. On a per-patient basis, MRSI had 82.8% sensitivity, 91.8% specificity, 88.3% positive predictive value (PPV), 87.8% negative predictive value (NPV) and 85.7% diagnostic accuracy. The sensitivity, specificity, PPV, NPV and accuracy for DCE-MRI was 76.5%, 89.5%, 84.5%, 83.7% and 82%, respectively. The combination of MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV and 90.9% accuracy in detecting prostate carcinoma. CONCLUSIONS: The combined study with [¹H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy.

The IGF axis in prostate cancer.

Prostate cancer, the most frequent non-cutaneous malignancy in men from industrialized countries, is a growing medical problem, representing the second leading cause of male cancer deaths. In the last decade, converging evidence from epidemiological and biological studies suggests that the Insulin-like Growth Factor (IGF) axis is involved in the tumorigenesis and neoplastic growth of prostate cancer. Epidemiological observations indicated that circulating IGF-I levels are positively associated with the increased risk of prostate cancer. The activation of type I IGF receptor (IGF-IR) by IGF-I and/or IGF-II, has mitogenic and antiapoptotic effects on normal and malignant prostate cells. Altered expression of IGF axis components has also been reported in vitro and in animal models of prostate cancer, as well as in human prostate cancer tissue samples. In this review we address and analyze epidemiological studies, in vitro and in vivo cancer models, and human ex vivo prostate cancer researches performed to date supporting the role of IGF axis in prostate cancer.

New perspective in the management of neuroendocrine differentiation in prostate adenocarcinoma.

In this review, we will present some of the information that is known about neuroendocrine (NE) cells and differentiation in the prostate. We will then speculate on the potential role that NE differentiation in prostate carcinoma may play and how this differentiation may be clinically analysed and treated. The androgen-independent growth of prostate cancer can be caused by different mechanisms; one of these is receptor-specific paracrine or autocrine growth modulation of human prostatic cancer cells by neuropeptides secreted by NE cells. Our results affirm that different methods of androgen deprivation can influence the serum chromogranin A (CgA) levels to different extents in prostate cancer. In particular, bicalutamide produces a significantly lower increase in serum CgA compared with castration therapy. In the light of other evidence that supports a significant relationship between serum CgA levels, tissue CgA expression and NE activity, we hypothesise that bicalutamide may reduce the risk of NE cell hyperactivation in prostate cancer. It is important to determine whether increases in CgA levels and NE cell activation are associated with progression towards hormone-independent prostate cancer. We recently proposed as therapy of NE activation in hormone-independent prostate cancer, a combination of oestrogens and somatostatin analogues. The combination of ethinyl estradiol and lanreotide had a favourable toxicity profile, offered objective and symptomatic responses in patients with limited treatment options and refractoriness to conventional hormonal therapy strategies and, in particular, offered a median overall survival that was superior to the 10-month median survival in patients with hormone refractory disease. This combination therapy also sustains the novel concept in cancer treatment in which therapies may target not only cancer cells but also its microenvironment in combination, which can confer protection from apoptosis.

Benign prostatic hyperplasia: what about a campaign for prevention?

OBJECTIVES: In an era when prevention is considered better than cure, is there a rationale for benign prostatic hyperplasia (BPH) prevention? MATERIALS AND METHODS: Medline and Current Content databases were searched for studies conduced in the last 10 years on BPH and the feasibility of prevention program. RESULTS: Some important criteria for promoting prevention can be found in BPH disease. The significant impact of BPH on the male population and on its quality of life is well established. Knowledge of the etiopathogenesis of this disease is rapidly improving. However, the use of PSA or other markers to select a population at higher risk for developing BPH and its clinical manifestations needs to be better established. More data are available for secondary prevention against BPH progression. Although the action of some natural and nutritional agents on BPH tissue has been demonstrated experimentally, data from prospective clinical trials are not available. Synthetic agents such as 5alpha-reductase inhibitors or COX-2 inhibitors may be effective, but clinical results for primary prevention of BPH have not been reported. CONCLUSION: At present, we propose a BPH prevention program as a basis for discussion and future work.

Variation of chromogranin A serum levels after radical retropubic prostatectomy for prostate adenocarcinoma.

This study evaluated perioperative and postoperative variations in serum CgA levels induced by radical retropubic prostatectomy (RRP) and their relationship with serum PSA levels in prostate cancer patients. Thirty consecutive patients with clinically localized adenocarcinoma of the prostate undergoing RRP were prospectively analyzed. Serum levels of CgA and total PSA were analyzed in each case preoperatively (time 0), at removal of the prostate (time 1), 1 h after the end of RRP (time 2) and then at regular postoperative intervals till 12 weeks (time 14). During the postoperative period no adjuvant therapies were performed and none of the 30 cases showed biochemical (PSA > 0.2 ng/mL) and/or clinical progression. Mean preoperative serum levels of CgA were 57 +/- 14 ng/mL. Immediately after the surgical removal of the prostate gland (time 1), in all 30 cases there was a significant (time 0-time 1: p = .001) increase in serum PSA, but a nonsignificant modification in serum CgA levels (60 +/- 15 ng/mL). After time 1, serum PSA levels progressively decreased to below the detection limit of 0.2 ng/mL. On the contrary, at time 2, serum CgA levels were postoperatively increased (time 2 = 145 +/- 47) and they remained significantly higher than preoperative values (time 0) till the 21-day postoperative interval (time 11). Moreover, at the last control (time 14) mean and median CgA levels were very similar to those shown preoperatively (time 14: 58 +/- 18 ng/mL). In patients with untreated clinically localized adenocarcinoma of the prostate submitted to RRP, surgical and postoperative stress, more than surgical manipulation of the prostate gland, could produce a significant increase in serum CgA levels maintained for a longer period when compared to the increase in serum PSA levels.

[Heredity and urologic tumors]. / Ereditarietà e tumori di interesse urologica.

Most human malignant tumours derive from a series of several mutations in cell growth regulatory genes. Neoplastic transformation is a multistep, or at times multigenic event where several mutations must intervene. Hereditary forms have been identified for a number of human neoplasias. In hereditary forms, the individual already inherits one or more of these mutations and assumes an increased risk of developing a specific carcinoma and at an earlier age. On the other hand, in sporadic forms, the risk is lower because the environmental factors must provoke in sequence all the mutations necessary for neoplastic transformation. These genic mutations are often associated with the deletion of oncosuppressor genes which negatively regulate cell proliferation and/or with the hyper-expression and activation of protoncogenes which favour cell proliferation. The products of these genes are often growth factors or receptors of growth factors. The present review analyses the definition and more or less proven identification of familial and hereditary forms in neoplasias of urological interest.

Importance and evaluation of comorbidity in rehabilitation.

PURPOSE: The aim of this study is to evaluate the relationship between comorbidity and the disability in patients referred to a rehabilitation centre. Patients often suffer from associated diseases which may negatively influence the outcome. METHOD: After evaluation of several scales, the Cumulative Illness Rating Scale (CIRS) was selected. For the study 413 consecutive patients were enrolled. RESULTS: In this series, neurological patients presented with higher severity and higher comorbidity than orthopaedic patients. Orthopaedic cases were older but neurological cases had higher severity and higher comorbidity. Indeed, a significant negative correlation between severity and dependence scores was found. Comorbidity, also, showed a significant negative correlation with FIM both in the orthopaedic and in the neurological patients. These data show that severe comorbid conditions influence functional autonomy. Severity and Comorbidity were correlated both in orthopaedic cases and in neurological cases as well. CONCLUSIONS: A review of geriatric literature demonstrates lower values in the patients in rehabilitation. The difference is due to our accurate selection of patients at admission, where general health conditions are considered. In conclusion the CIRS scale should be used as a method for selecting patients at admission or as a prognostic index for improvement at discharge. CIRS, however, has some inconveniences and amelioration is necessary, such as the inclusion of a double testing (admission-discharge), psychiatric disturbances and a new item for skin alone. CIRS should not be applied if a patient referred for rehabilitation has the worst score in even a single item.

Very old people can have favorable outcome after hip fracture: 58 patients referred to rehabilitation.

We examined both impairment and disability of 58 patients who were referred to our rehabilitation center after surgery of hip fracture. The mean age was 86.7 years. The impairment was measured by the Motricity Index (MI) scale and disability by means of the Functional Independence Measure (FIM) scale. At admission, the MI median value was 64 and at discharge the value was 84 (range of scale, 0-100). The FIM median value was 57.5 at admission and 82 at discharge (range of scale, 18-126). Our data indicate that, on average, patients recover, even at very advanced age, but still require supervision at discharge. Twelve patients died after complications of previous risk factors. When general conditions were satisfactory, no complications arose.