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Benign prostatic hyperplasia (BPH) is a highly prevalent condition among aging men with significant negative impacts on quality of life. Although multiple surgical treatment modalities exist, there is an ongoing search for minimally invasive techniques to reduce hospital stays and adverse effects without compromising good functional outcomes. Aquablation is a novel minimally invasive surgical technique that combines robotic precision with heat-sparing ablation of obstructing prostate tissue. We describe the setup and mechanism of action of aquablation. A comprehensive literature search for clinical trials and recent meta-analyses was conducted and functional outcomes and adverse effects across multiple studies are summarized here. Aquablation produces comparable (if not superior) outcomes in terms of reduced International Prostate Symptom Score, improved Qmax (comparison of maximum flow velocity), and lower postvoid residuals to transurethral resection of the prostate. These findings are consistently reproduced across multiple clinical trials, including those conducted in the private sector. One major benefit of aquablation is that the risk of injury to the ejaculatory ducts appears to be significantly lower, as evident from the low percentage of cases of postoperative anejaculation issues. Adverse effects are rare, and the most significant one to mention is blood loss requiring transfusion. At present, the overall cost of aquablation is still higher than other methods of treating BPH and this is due to intraoperative and equipment costs. Postoperative care is no more expensive than other methods of BPH treatment. In conclusion, aquablation is a safe and effective surgical modality for the treatment of BPH. It can be offered as an alternative to other surgical modalities for those who wish to spare ejaculatory function. The procedure itself can be easily taught. With further development of this novel technology and increased availability, there is the potential for it to become a much more cost-effective method for surgical treatment of BPH.

Aims The Independent Forensic Mental Health Review (Scottish Government, 2021) highlighted an issue with timely transitions through and out of Scottish forensic inpatient services. Concerns were raised regarding the impact of transfer and discharge delays upon patients. As part of a wider service evaluation examining the pathways forensic mental health patients navigated through secure inpatient care, this study aimed to identify the requirements, processes and time-frames involved in transfer from The State Hospital (TSH), which provides male only, high secure care to Scotland and Northern Ireland. Methods Data for 69 patients noted on TSH transfer list (2017–2019) were collected. In addition to patient demographic, clinical and forensic variables, data was gathered about use of appeals against excessive security under section 264 and 265 of the Mental Health (Care and Treatment) (Scotland) Act 2003. Results Forty-nine (71.0%) patients were referred to medium secure care, 6 (12.2%) to low secure care and 14 (20.3%) for return to prison. Schizophrenia was the most common primary diagnosis (43, 62.3%), with 75.5% (37) of those referred to medium secure care vs 21.4% (3) returning to prison having received this diagnosis. There were statistically significant associations in terms of time between referral and transfer between individuals who had a primary diagnosis of Schizophrenia/Schizoaffective disorder (no 114, yes 388.5 days; Median) and whether they had lodged a section 264 appeal (no 109.5, yes 469.0 days; Median) or section 265 appeal (no 134.5, yes 517.0 days; Median) against excessive security. There were no significant differences in days from referral to transfer/discharge based on behaviour leading to admission or the number of formal attempts to transfer during current admission. Twenty (40.8%) patients referred to medium secure services made a successful section 265 appeal which resulted in a ruling that they should be transferred within three months. Seven (35%) of these patients were transferred inside three months. Conclusion Patients are waiting significantly variable lengths of time from referral to transfer depending on the service they are being referred to. The use of section 264 and 265 appeals against excessive security was implicated in a greatly increased length of time to transfer. Patients considered to have the most serious chronic mental health conditions are waiting the longest time for transfer with potential implications for their mental health. Patients’ human rights are potentially affected due to continuing to be placed in conditions of excessive security for more than a year following decision to refer.

Objective: Hepatic glucose metabolism is profoundly perturbed by excessive alcohol intake. miR-141/200c expression is significantly induced by chronic ethanol feeding. This study aimed at identifying the role of miR-141/200c in glucose homeostasis during chronic ethanol exposure. Methods: WT and miR-141/200c KO mice were fed a control or an ethanol diet for 30 days, followed by a single binge of maltose dextrin or ethanol, respectively. Untargeted metabolomics analysis of hepatic primary metabolites was performed along with analyses for liver histology, gene expression, intracellular signaling pathways, and physiological relevance. Primary hepatocytes were used for mechanistic studies. Results: miR-141/200c deficiency rewires hepatic glucose metabolism during chronic ethanol feeding, increasing the abundance of glucose intermediates including G6P, an allosteric activator for GS. miR-141/200c deficiency replenished glycogen depletion during chronic ethanol feeding accompanied by reduced GS phosphorylation in parallel with increased expression of PP1 glycogen targeting subunits. Moreover, miR-141/200c deficiency prevented ethanol-mediated increases in AMPK and CaMKK2 activity. Ethanol treatment reduced glycogen content in WT-hepatocytes, which was reversed by dorsomorphin, a selective AMPK inhibitor, while KO-hepatocytes displayed higher glycogen content than WT-hepatocytes in response to ethanol treatment. Furthermore, treatment of hepatocytes with A23187, a calcium ionophore activating CaMKK2, lowered glycogen content in WT-hepatocytes. Notably, the suppressive effect of A23187 on glycogen deposition was reversed by dorsomorphin, demonstrating that the glycogen depletion by A23187 is mediated by AMPK. KO-hepatocytes exhibited higher glycogen content than WT-hepatocytes in response to A23187. Finally, miR-141/200c deficiency led to improved glucose tolerance and insulin sensitivity during chronic ethanol feeding. Conclusions: miR-141/200c deficiency replenishes ethanol-mediated hepatic glycogen depletion through the regulation of GS activity and calcium signaling coupled with the AMPK pathway, improving glucose homeostasis and insulin sensitivity. These results underscore miR-141/200c as a potential therapeutic target for the management of alcohol intoxication.

IntroductionThis study reports on an assessment of mental health needs among Scotland's prison population which aimed to describe the scale and nature of need as well as identify opportunities to improve upon the services available. The project was commissioned by the Scottish Government to ensure that future changes to the services available to support the mental health and wellbeing of people in prison would be evidence-based and person-centered.MethodsA standardized approach to health needs assessments was employed. The study was comprised of four phases. In phase I a rapid literature review was undertaken to gather evidence on the prevalence of mental health needs experienced by people in prison in the UK. In Phase II a multi-method and multi-informant national mapping exercise involving providers to all Scottish prisons was undertaken to describe the mental health services available, and any gaps in these services, for people in and leaving prison. In Phase III prevalence estimates of several mental health needs were derived for Scotland's current prison population, modeled from a national survey dataset of Scotland's community population using logistic regression. Finally in Phase IV, professional stakeholders and individuals with lived experience were interviewed to understand their experiences and insights on challenges to supporting the mental health and wellbeing of people in prison, and ideas on how these challenges could be overcome.ResultsEvidence across the four phases of this needs assessment converged indicating that existing provision to support the mental health of people in prison in Scotland was considered inadequate to meet these needs. Barriers to effective partnership working for justice, health, social work and third sector providers appear to have led to inadequate and fragmented care, leaving prisoners without the support they need during and immediately following imprisonment.ConclusionsJoint and coordinated action from justice, health and social care, and third sector providers is needed to overcome enduring and structural challenges to supporting the mental health of people in prison. Eighteen evidence-based recommendations were proposed to the Scottish Government relating to the high-level and operational-level changes required to adequately meet the prison population's mental health needs.

Background: Surgical options are limited when treating large (>80 cm3) prostates for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Open simple prostatectomy remains the most common procedure performed for large prostates. There is a need for novel surgical approaches with shorter learning curves and effective treatment. Aquablation could be this novel tool. Objective: To compare the outcome of Aquablation for 30–80-cm3 prostates with the outcome for 80–150-cm3 prostates at 2-yr follow-up. Design, setting, and participants: We used data from two trials. WATER is a prospective, double-blind, multicenter, international clinical trial comparing the safety and efficacy of Aquablation and transurethral resection of the prostate in the treatment of LUTS/BPH in men aged 45–80 yr with a prostate of 30–80 cm3. WATER II is a prospective, multicenter, single-arm international clinical trial of Aquablation in men with a prostate of 80–150 cm3. Intervention: Aquablation, an ultrasound-guided, robotically executed waterjet ablative procedure. Outcome measurements and statistical analysis: We compared 24-mo outcomes between 116 WATER and 101 WATER II study subjects. Student’s t test or a Wilcoxon test was used to compare continuous variables and Fisher’s test for categorical variables. Results and limitations: The International Prostate Symptom Score (IPSS) reductions at 24 mo was 14.5 points for WATER and 17.4 points for WATER II (p = 0.31). At baseline, the maximum urinary flow rate (Qmax) was 9.4 and 8.7 cm3/s in WATER and WATER II, improving to 20.5 and 18.2 cm3/s, respectively (p = 0.60) at 24 mo. Improvements in both IPSS and Qmax were immediate and sustained throughout follow-up. At 2 yr, the surgical retreatment rate was 4% in WATER and 2% in WATER II. Conclusions: Aquablation is effective in patients with a prostate of 30–80 cm3 and patients with a prostate of 80–150 cm3 treated for LUTS/BPH, with comparable outcomes in both groups. It has low complication and retreatment rates at 2 yr of follow-up, with durable improvements in functional outcome. Patient summary: Outcomes of Aquablation for both small-to-moderately-sized and large prostates are similar and sustainable at 2 yr of follow-up.

Objectives To evaluate functional outcomes following Aquablation in various prostate volume and anatomical subgroups.Design A meta-analysis with individual patient data undergoing Aquablation therapy from four prospective, global, clinical studies that have been conducted with Aquablation; WATER, WATER II, FRANCAIS WATER and OPEN WATER.Setting Australia, Canada, Lebanon, Germany, New Zealand, UK and the USA.Participants 425 men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) with 1-year follow-up.Interventions Aquablation therapy is an ultrasound guided, robotically executed waterjet ablative procedure for the prostate.Main outcome measures The analyses focus International Prostate Symptom Score (IPSS), uroflowmetry, postoperative Incontinence Severity Index (ISI) and surgical retreatment.Results 425 men with prostates ranging in size from 20 to 150 mL underwent Aquablation therapy. The outcomes from the seven questions in the IPSS questionnaire were grouped by the following; prostates 4, and regardless of prostate size, showed a reduction in incontinence during patient follow-up. Surgical retreatment due to BPH symptoms occurred in 0.7% (95% CI 0.1%–2.0%).Conclusions Across a variety of prostate anatomies, Aquablation therapy showed remarkable functional improvements following the index procedure. Additionally, men with moderate to severe LUTS/BPH and overactive bladder resulting in urge incontinence showed a reduction in incontinence symptoms postprocedure.

Benign prostatic hyperplasia (BPH) is a highly prevalent condition among aging men with significant negative impacts on quality of life. Although multiple surgical treatment modalities exist, there is an ongoing search for minimally invasive techniques to reduce hospital stays and adverse effects without compromising good functional outcomes. Aquablation is a novel minimally invasive surgical technique that combines robotic precision with heat-sparing ablation of obstructing prostate tissue. We describe the setup and mechanism of action of aquablation. A comprehensive literature search for clinical trials and recent meta-analyses was conducted and functional outcomes and adverse effects across multiple studies are summarized here. Aquablation produces comparable (if not superior) outcomes in terms of reduced International Prostate Symptom Score, improved Qmax (comparison of maximum flow velocity), and lower postvoid residuals to transurethral resection of the prostate. These findings are consistently reproduced across multiple clinical trials, including those conducted in the private sector. One major benefit of aquablation is that the risk of injury to the ejaculatory ducts appears to be significantly lower, as evident from the low percentage of cases of postoperative anejaculation issues. Adverse effects are rare, and the most significant one to mention is blood loss requiring transfusion. At present, the overall cost of aquablation is still higher than other methods of treating BPH and this is due to intraoperative and equipment costs. Postoperative care is no more expensive than other methods of BPH treatment. In conclusion, aquablation is a safe and effective surgical modality for the treatment of BPH. It can be offered as an alternative to other surgical modalities for those who wish to spare ejaculatory function. The procedure itself can be easily taught. With further development of this novel technology and increased availability, there is the potential for it to become a much more cost-effective method for surgical treatment of BPH. [ABSTRACT FROM AUTHOR]

Patients suffering from temporal lobe epilepsy (TLE) show severe problems in hippocampus dependent memory consolidation. Memory consolidation strongly depends on an intact dialog between the hippocampus and neocortical structures. Deficits in hippocampal signal transmission are known to provoke disturbances in memory formation. In the present study, we investigate changes of synaptic plasticity at hippocampal output structures in an experimental animal model of TLE. In pilocarpine-treated rats, we found suppressed long-term potentiation (LTP) in hippocampal and parahippocampal regions such as the subiculum and the entorhinal cortex (EC). Subsequently we focused on the subiculum, serving as the major relay station between the hippocampus proper and downstream structures. In control animals, subicular pyramidal cells express different forms of LTP depending on their intrinsic firing pattern. In line with our extracellular recordings, we could show that LTP could only be induced in a minority of subicular pyramidal neurons. We demonstrate that a well-characterized cAMP-dependent signaling pathway involved in presynaptic forms of LTP is perturbed in pilocarpine-treated animals. Our findings suggest that in TLE, disturbances of synaptic plasticity may influence the information flow between the hippocampus and the neocortex.

The incidence of non-melanoma skin cancer and malignant melanoma is increasing. Diagnosing these skin lesions is primarily done visually, making it suitable to use new technology, such as teledermoscopy. Before the implementation of teledermoscopy, patient satisfaction, clinician satisfaction and diagnostic accuracy, need to be evaluated. A cross-sectional quantitative survey was conducted to evaluate patient satisfaction and expectations regarding a mobile teledermoscopy service, and to identify factors influencing patient satisfaction and choice of diagnostic method. A total of 287 out of 476 participants responded to the questionnaire. Almost 90% of respondents were satisfied with, or neutral towards, teledermoscopy. No associations between patient satisfaction and age, smartphone/tablet usage, travel time, prior history of non-melanoma skin cancer and malignant melanoma, or worries about malignancy, were found. There was equal distribution between patients who preferred teledermoscopy and those who preferred face-to-face consultation. Respondents with a high level of smartphone usage significantly preferred teledermoscopy.

Abstract Background Radical prostatectomy is the most common treatment for localised prostate cancer in New Zealand. Active surveillance was introduced to prevent overtreatment and reduce costs while preserving the option of radical prostatectomy. This study aims to evaluate the cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy. Methods Markov models were constructed to estimate the life-time cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer patients aged 45–70 years, using national datasets in New Zealand and published studies including the SPCG-4 study. This study was from the perspective of the Ministry of Health in New Zealand. Results Radical prostatectomy is less costly than active surveillance in men aged 45–55 years with low risk localised prostate cancer, but more costly for men aged 60–70 years. Scenario analyses demonstrated significant uncertainty as to the most cost-effective option in all age groups because of the unavailability of good quality of life data for men under active surveillance. Uncertainties around the likelihood of having radical prostatectomy when managed with active surveillance also affect the cost-effectiveness of active surveillance against radical prostatectomy. Conclusions Active surveillance is less likely to be cost-effective compared to radical prostatectomy for younger men diagnosed with low risk localised prostate cancer. The cost-effectiveness of active surveillance compared to radical prostatectomy is critically dependent on the ‘trigger’ for radical prostatectomy and the quality of life in men on active surveillance. Research on the latter would be beneficial.

Background: In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin) is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB). However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin resistance and diabetes are few and contradictory. Methods: We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6) as well as other inflammatory and diabetes-related markers were measured pre- and post-surgically. Results: Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative changes in S100A8/A9 and IL-6 correlated significantly (r = 0.905, p = 0.005) only in the group with persistent diabetes. In contrast, leukocyte count and C-reactive protein correlated significantly to S100A8/A9 only in the control group. Conclusion: Our study is suggestive of S100A8/A9 and IL-6 being related to a persistent diabetes status post-surgically and of different pathophysiological mechanisms being involved in the post-surgical changes in the three groups, despite similar decreases in BMI.

Abstract The immunoproteasome (iP) represents a specialized type of proteasomes, which plays an important role in the clearance of oxidant-damaged proteins under inflammatory and pathological conditions determining the outcome of various diseases. In Alzheimer’s disease (AD)-like APPPS1 mice Aβ-deposition is paralleled by iP upregulation, most likely mediated through type I interferon induction. To define the impact of increased iP expression we crossed APPPS1 mice with mice deficient in the iP subunit LMP7 resulting in impaired iP function. While LMP7 deficient APPPS1 mice showed no major change in cerebral Aβ-pathology, we observed an altered cytokine response in microglia isolated from LMP7 deficient APPPS1 mice compared to LMP7 expressing APPPS1 control mice. The altered microglial cytokine profile upon iP deficiency in the presence of extracellular Aβ-pathology was associated with an improvement of Aβ-associated cognitive deficits typically present in APPPS1 mice. Our findings suggest a role for iP in the regulation of the innate immune response towards extracellular Aβ-pathology and indicate that inhibition of iP function can modulate the cognitive phenotype upon overexpression of Aβ.

Purpose: 5-HT2AR exists in high and low affinity states. Agonist PET tracers measure binding to the active high affinity site and thus provide a functionally relevant measure of the receptor. Limited in vivo data have been reported so far for a comparison of agonist versus antagonist tracers for 5-HT2AR used as a proof of principle for measurement of high and low affinity states of this receptor. We compared the in vivo binding of [11C]CIMBI-5, a 5-HT2AR agonist, and of the antagonist [11C]M100907, in monkeys and baboons. Methods: [11C]CIMBI-5 and [11C]M100907 baseline PET scans were performed in anesthetized male baboons (n=2) and male vervet monkeys (n=2) with an ECAT EXACT HR+ and GE 64-slice PET/CT Discovery VCT scanners. Blocking studies were performed in vervet monkeys by pretreatment with MDL100907 (0.5 mg/kg, i.v.) 60 minutes prior to the scan. Regional distribution volumes and binding potentials were calculated for each ROI using the likelihood estimation in graphical analysis and Logan plot, with either plasma input function or reference region as input, and simplified reference tissue model approaches. Results: PET imaging of [11C]CIMBI-5 in baboons and monkeys showed the highest binding in 5-HT2AR-rich cortical regions, while the lowest binding was observed in cerebellum, consistent with the expected distribution of 5-HT2AR. Very low free fractions and rapid metabolism were observed for [11C]CIMBI-5 in baboon plasma. Binding potential values for [11C]CIMBI-5 were 25-33% lower than those for [11C]MDL100907 in the considered brain regions. Conclusion: The lower binding potential of [11C]CIMBI-5 in comparison to [11C]MDL100907 is likely due to the preferential binding of the former to the high affinity site in vivo in contrast to the antagonist, [11C]MDL100907, which binds to both high and low affinity sites.

Metabolic surgery is superior to lifestyle intervention in reducing weight and lowering glycemia and recently suggested as treatment for type 2 diabetes mellitus. Especially Roux-en-Y gastric bypass (RYGB) has been focus for much research, but still the mechanisms of action are only partly elucidated. We suggest that several mechanisms might be mediated by sphingolipids like sphingomyelin. We measured serum sphingomyelin before and up to 2 years after RYGB surgery in 220 patients, divided before surgery in one non-diabetic subgroup and two diabetic subgroups, one of which contained patients obtaining remission of type 2 diabetes after RYGB, while patients in the other still had diabetes after RYGB. Pre- and postoperative sphingomyelin levels were compared within and between groups. Sphingomyelin levels were lower in diabetic patients than in non-diabetic patients before surgery. Following RYGB, mean sphingomyelin concentration fell significantly in the non-diabetic subgroup and the preoperative difference between patients with and without diabetes disappeared. Changes in diabetic subgroups were not significant. Relative to bodyweight, an increase in sphingomyelin was seen in all subgroups, irrespective of diabetes status. We conclude that RYGB has a strong influence on sphingomyelin metabolism, as seen reflected in changed serum levels. Most significantly, no differences between the two diabetic subgroups were detected after surgery, which might suggest that patients in both groups still are in a “diabetic state” using the non-diabetic subgroup as a reference.

Temporal lobe epilepsy is believed to develop after an initial precipitating injury, usually suffered in childhood or adolescence, and aspects include impaired maturation of the hippocampus, and specifically the dentate gyrus. The dentate gyrus receives a major serotonergic input from the brainstem raphe nuclei, and the serotonergic system may regulate neurogenesis in the developing and mature hippocampus. The aim of this work was to investigate changes which may be associated with abnormal functioning of the serotonergic system in the pilocarpine model of epilepsy, where spontaneous seizures are induced by administration of pilocarpine at 6 weeks of age. Application of serotonin (100 μM) led to a transient hyperpolarization of the resting membrane potential and decrease of the input resistance mediated by the 5-HT1A receptor that was similar between control and pilocarpine-treated animals and unaffected by the age of the animal. In the younger, but not in older control animals, serotonin led to a 5-HT2 receptor-mediated long-term depression of evoked postsynaptic currents, a normal functional shift in the early adulthood of the Wistar rat. In pilocarpine-treated animals, this long-term depression persisted in older animals, indicating impaired maturation of the dentate gyrus. These data may indicate 5-HT2 receptor function to be affected by the pathology of temporal lobe epilepsy.

In this review, we have looked at three important areas in understanding male lower urinary tract symptoms. These are improvement in terminology, detrusor underactivity, and nocturia. Benign prostatic hyperplasia leading to bladder outlet obstruction has been covered in a previous review.

Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial.

Addresses issues of power in relationship to adult education, language, and women; how accountability and autonomy relate to women in adult education; and the discourse that continues to define women as "other." Finds a lack of response to these issues in adult education literature. (SK)