Growth of prostate cancer cells is dependent upon androgen stimulation of the androgen receptor (AR). Dihydrotestosterone (DHT), the most potent androgen, is usually synthesized in the prostate from ...testosterone secreted by the testis. Following chemical or surgical castration, prostate cancers usually shrink owing to testosterone deprivation. However, tumors often recur, forming castration-resistant prostate cancer (CRPC). Here, we show that CRPC sometimes expresses a gain-of-stability mutation that leads to a gain-of-function in 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1), which catalyzes the initial rate-limiting step in conversion of the adrenal-derived steroid dehydroepiandrosterone to DHT. The mutation (N367T) does not affect catalytic function, but it renders the enzyme resistant to ubiquitination and degradation, leading to profound accumulation. Whereas dehydroepiandrosterone conversion to DHT is usually very limited, expression of 367T accelerates this conversion and provides the DHT necessary to activate the AR. We suggest that 3βHSD1 is a valid target for the treatment of CRPC.
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•3βHSD1 catalyzes a rate-limiting step for DHT synthesis in CRPC•Selection for N367T mutant 3βHSD1 occurs in human CRPC tumors•The N367T 3βHSD1 mutation confers resistance to ubiquitination and degradation•Mutant 3βHSD1 protein accumulates, increasing DHT synthesis and causing CRPC
Dihydrotestosterone (DHT), a potent androgen secreted by the testis, promotes the development of prostate cancer. Castration limits tumor growth, but castration-resistant tumors often recur. A gain-of-stability mutation in the enzyme 3βHSD1, an upstream regulator of DHT biosynthesis, drives this resistance and may be a valid therapeutic target.
Male lower urinary tract symptoms, benign prostatic hyperplasia, enlargement of the prostate, and bladder outlet obstruction are common among aging men and will increase in socioeconomic and medical ...importance at a time of increased life expectancy and aging of the baby boomer generation. This article reviews the epidemiology, management, and therapeutic options for these conditions. In patients bothered by moderate to severe symptoms, providers can make educated and differential choices between several classes of drugs, alone or in combination, to treat effectively and improve the symptoms in most men. Despite the efficacy of medical therapy, there will be patients who require referral to a urologist either early, to rule out prostate cancer and other conditions, or later, after initial medical therapy and lifestyle management has failed. Perhaps as many as 30% of patients fail to achieve sufficient symptom improvement with medication, lifestyle adjustment, and fluid management, and may require more invasive or surgical treatment options.
To report 4-year outcomes of the randomized controlled trial of water vapor thermal therapy for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia.
Total ...188 subjects; 135 men ≥50years old, International Prostate Symptom Score ≥ 13, maximum flow rate (Qmax) ≤15 mL/s and prostate volume 30 to 80 cc treated with Rezūm System thermal therapy were followed 4 years; subset of 53 men who requalified for crossover from control to active treatment were followed 3years.
Lower urinary tract symptoms were significantly improved within ≤3 months after thermal therapy and remained consistently durable (International Prostate Symptom Score 47%, quality of life 43%, Qmax 50%, Benign Prostatic Hyperplasia Impact Index 52%) throughout 4years (P <.0001); outcomes were similarly sustained in crossover subjects at 3years. Surgical retreatment rate was 4.4% over 4years. No disturbances in sexual function were reported.
The minimally invasive thermal therapy provides effective symptom relief and improved quality of life that remains durable for over 4years. It is applicable to all prostate zones with procedures performed under local anesthesia in an office setting.
Over the last century, agriculture transformed from a labour-intensive industry towards mechanisation and power-intensive production systems, while over the last 15 years agricultural industry has ...started to digitise. Through this transformation there was a continuous labour outflow from agriculture, mainly from standardized tasks within production process. Robots and artificial intelligence can now be used to conduct non-standardised tasks (e.g. fruit picking, selective weeding, crop sensing) previously reserved for human workers and at economically feasible costs. As a consequence, automation is no longer restricted to standardized tasks within agricultural production (e.g. ploughing, combine harvesting). In addition, many job roles in agriculture may be augmented but not replaced by robots. Robots in many instances will work collaboratively with humans. This new robotic ecosystem creates complex ethical, legislative and social impacts. A key question, we consider here, is what are the short and mid-term effects of robotised agriculture on sector jobs and employment? The presented work outlines the conditions, constraints, and inherent relationships between labour input and technology input in bio-production, as well as, provides the procedural framework and research design to be followed in order to evaluate the effect of adoption automation and robotics in agriculture.
•Complementarity and substitution between labor and automation in agriculture.•Routine vs. non-routine and cognitive vs. manual tasks in agriculture.•Differences between agricultural robotics and industrial robotics.•Level of automation in agricultural production.
Small polymer particles with a diameter of less than 5 mm called microplastics find their way into the environment from polymer debris and industrial production. Therefore a method is needed to ...identify and quantify microplastics in various environmental samples to generate reliable concentration values. Such concentration values, i.e. quantitative results, are necessary for an assessment of microplastic in environmental media. This was achieved by thermal extraction in thermogravimetric analysis (TGA), connected to a solid-phase adsorber. These adsorbers were subsequently analysed by thermal desorption gas chromatography mass spectrometry (TDS-GC-MS). In comparison to other chromatographic methods, like pyrolyse gas chromatography mass spectrometry (Py-GC-MS), the relatively high sample masses in TGA (about 200 times higher than used in Py-GC-MS) analysed here enable the measurement of complex matrices that are not homogenous on a small scale. Through the characteristic decomposition products known for every kind of polymer it is possible to identify and even to quantify polymer particles in various matrices. Polyethylene (PE), one of the most important representatives for microplastics, was chosen as an example for identification and quantification.
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•Using a thermal decomposition method for analysing PE microplastics in environmental matrices in one step.•Direct measuring without a pre selection.•Identification and quantification of polymers in environmental samples.
This paper presents a methodological framework for the systematic literature review of agricultural sustainability studies. The framework synthesizes all the available literature review criteria and ...introduces a two-level analysis facilitating systematization, data mining, and methodology analysis. The framework was implemented for the systematic literature review of 38 crop agricultural sustainability assessment studies at farm-level for the last decade. The investigation of the methodologies used is of particular importance since there are no standards or norms for the sustainability assessment of farming practices. The chronological analysis revealed that the scientific community’s interest in agricultural sustainability is increasing in the last three years. The most used methods include indicator-based tools, frameworks, and indexes, followed by multicriteria methods. In the reviewed studies, stakeholder participation is proved crucial in the determination of the level of sustainability. It should also be mentioned that combinational use of methodologies is often observed, thus a clear distinction of methodologies is not always possible.
Objectives
To provide an update on novel minimally invasive lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) treatments in a non‐systematic review. To define ...potential target populations for the various new minimally invasive treatments.
Methods
Recent literature, meta‐analyses and guideline recommendations for aquablation (AquaBeam®; PROCEPT BioRobotics, Redwood City, CA, USA), water vapour thermal therapy (Rezūm®; Boston Scientific, Natick, MA, USA), prostate artery embolisation (PAE), prostatic urethral lift (UroLift®; NeoTract‐Teleflex, Pleasanton, CA, USA) and the temporary implantable nitinol device i‐TIND® (nitinol butterfly‐like stent ); Medi‐Tate Ltd., Or‐Akiva, Israel were reviewed.
Results
Procedures that can be performed on an outpatient basis (Rezūm, PAE, UroLift and i‐TIND) are not an alternative for the standard patient requiring BPH surgery. Their effect on urinary flow, post‐void residual urine volume or bladder outlet obstruction is less pronounced than that of transurethral resection of the prostate (TURP). Yet, these options appear to be valuable for those patients unfit for surgery, men who want to avoid medical therapy in general, or those who want to avoid sexual side‐effects associated with medical therapy or standard BPH surgery (e.g. TURP). Aquablation is the first successfully operationalised robotic resection system, especially for patients with prostates >50 g. Nevertheless, long‐term data are necessary for all novel, minimally invasive treatments.
Conclusions
Better designed clinical trials, a clearer definition of target populations and a more realistic marketing allow a better characterisation of novel minimally invasive therapies for LUTS/BPH. It is hoped that some of these novel devices will stand the test of time, in contrast to the vast majority of their predecessors.
COVID-19 and the restrictive measures towards containing the spread of its infections have seriously affected the agricultural workforce and jeopardized food security. The present study aims at ...assessing the COVID-19 pandemic impacts on agricultural labor and suggesting strategies to mitigate them. To this end, after an introduction to the pandemic background, the negative consequences on agriculture and the existing mitigation policies, risks to the agricultural workers were benchmarked across the United States’ Standard Occupational Classification system. The individual tasks associated with each occupation in agricultural production were evaluated on the basis of potential COVID-19 infection risk. As criteria, the most prevalent virus transmission mechanisms were considered, namely the possibility of touching contaminated surfaces and the close proximity of workers. The higher risk occupations within the sector were identified, which facilitates the allocation of worker protection resources to the occupations where they are most needed. In particular, the results demonstrated that 50% of the agricultural workforce and 54% of the workers’ annual income are at moderate to high risk. As a consequence, a series of control measures need to be adopted so as to enhance the resilience and sustainability of the sector as well as protect farmers including physical distancing, hygiene practices, and personal protection equipment.
Benign prostatic hyperplasia (BPH) represents a significant burden in ageing men due to frequently associated lower urinary tract symptoms (LUTS), which may impair quality of life. BPH is also a ...progressive disease, mainly characterized by a deterioration of LUTS over time, and in some patients by the occurrence of serious outcomes such as acute urinary retention (AUR) and need for BPH‐related surgery. The goals of therapy for BPH are not only to improve bothersome LUTS but also to identify those patients at risk of unfavourable outcomes, to optimize their management.
In selected patients, combination of an α1‐blocker and a 5α‐reductase inhibitor is the most effective form of BPH medical therapy to reduce the risk of clinical progression and relieve LUTS. Monotherapy also significantly reduces the risk of BPH clinical progression, mainly through a reduction of LUTS deterioration for α1‐blockers while 5α‐reductase inhibitors also reduce the risk of AUR and need for BPH‐related surgery.
Enlarged prostate and high serum prostate‐specific antigen levels have been consistently found to be good clinical predictors of AUR and BPH‐related surgery in longitudinal population‐based studies and placebo arms of controlled studies. High post‐void residual urine (PVR) is also associated with an increased risk of LUTS deterioration and should thus be reconsidered in practice as a predictor of BPH progression. Conversely, baseline LUTS severity and low peak flow rate, initially identified as predictors of unfavourable outcomes in community setting, behave paradoxically in controlled trials, probably as a consequence of strict inclusion criteria and subsequent regression to the mean and glass ceiling effects. Lastly, there is increasing evidence that dynamic variables, such as LUTS and PVR worsening, and lack of symptomatic improvement with α1‐blockers are important predictors of future LUTS/BPH‐related events, allowing better identification and management of patients at risk of BPH progression.
To report 3-year outcomes of a prospective, multicenter, randomized, blinded control trial after treatment with convective radiofrequency (RF) water vapor thermal therapy for moderate to severe lower ...urinary tract symptoms due to benign prostatic hyperplasia (BPH).
Fifteen centers enrolled and randomized 197 men ≥50 years old with International Prostate Symptom Score (IPSS) ≥13, maximum flow rate (Qmax) ≤15 mL/s, and prostate volume 30 to 80 cc to thermal therapy with Rezūm System or control (2:1). Rigid cystoscopy with simulated active treatment sound effects served as the control procedure. Convective RF thermal energy was delivered into obstructive prostate tissue including the median lobe as needed. After randomized comparison at 3 months, thermal therapy subjects were followed annually for 3 years.
Convective RF thermal therapy yielded IPSS improvement of 160% compared with control subjects at 3 months (P <.0001). Maximal symptom relief of at least 50% improvement in IPSS, quality of life, Qmax, and BPH Impact Index remained durable throughout 3 years (P <.0001). Subjects with a treated median lobe had similar responses. No late-related adverse events occurred, and no de novo erectile dysfunction was reported. The surgical retreatment rate was 4.4% over 3 years.
The minimally invasive convective RF thermal therapy is an office or ambulatory outpatient procedure with minimal transient perioperative side effects. It provides early effective and durable relief of BPH symptoms with preservation of sexual function in subjects followed up for 3 years and is applicable to treatment of the median lobe and hyperplastic central zone tissue.
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