PCN74 Cost-Effectiveness of Radium-223 Dichloride (Radium-223) In Alsympca: A Cost-Effectiveness Analysis of Radium-223+Best Standard of Care (Bsoc) Compared With Placebo+Bsoc In Treatment of Castration-Resistant Prostate Cancer (Crpc) And Symptomatic Bone Metastases In Canada

Current models of sexual functioning imply an important role for both automatic and controlled appraisals. Accordingly, it can be hypothesized that erectile dysfunction may be due to the automatic activation of negative appraisals at the prospect of sexual intercourse. However, previous research showed that men with sexual dysfunction exhibited relatively strong automatic sex-positive instead of sex-negative associations. This study tested the robustness of this unexpected finding and, additionally, examined the hypothesis that perhaps more specific sex-failure versus sex-success associations are relevant in explaining sexual dysfunction and distress. Male urological patients (N = 70), varying in level of sexual functioning and distress, performed two Single-Target Implicit Association Tests (ST-IATs) to assess automatic associations of visual erotic stimuli with attributes representing affective valence (“liking”; positive versus negative) and sexual success versus sexual failure. Consistent with the earlier findings, the lower the scores on sexual functioning, the stronger the automatic sex-positive associations. This association was independent of explicit associations and most prominent in the younger age group. Automatic sex-positive and sex-failure associations showed independent relationships with sexual distress. The relationship between sexual distress and sex-failure associations is consistent with the view that automatic associations with failure may contribute to sexual distress

PERMISSIVE INFLUENCE OF STRESS IN THE EXPRESSION OF A U-SHAPED RELATIONSHIP BETWEEN SERUM CORTICOSTERONE LEVELS AND SPATIAL MEMORY ERRORS IN RATS

The relationship between glucocorticoids (GCs) and memory is complex, in that memory impairments can occur in response to manipulations that either increase or decrease GC levels. We investigated this issue by assessing the relationship between serum corticosterone (the primary rodent GC) and memory in rats trained in the radial arm water maze, a hippocampus-dependent spatial memory task. Each day, rats learned a new location of the hidden escape platform and then 30 min later their memory of the location of the platform was tested. Under control conditions, well-trained rats had excellent spatial memory and moderately elevated corticosterone levels (~26 μg/dl versus a baseline of ~2 μg/dl). Their memory was impaired when corticosterone levels were either reduced by metyrapone (a corticosterone synthesis inhibitor) or increased by acute stress (predator exposure), forming an overall U-shaped relationship between corticosterone levels and memory. We then addressed whether there was a causal relationship between elevated corticosterone levels and impaired memory. If elevated corticosterone levels were a sufficient condition to impair memory, then exogenously administered corticosterone, alone, should have impaired performance. However, we found that spatial memory was not impaired in corticosterone-injected rats that were not exposed to the cat. This work demonstrates that an intermediate level of corticosterone correlated with optimal memory, and either a decrease or an increase in corticosterone levels, in conjunction with strong emotionality, impaired spatial memory. These findings indicate that fear-provoking conditions, which are known to engage the amygdala, interact with stress levels of corticosterone to influence hippocampal functioning

Stakeholder Perceptions of Point-of-Care Ultrasound Implementation in Resource-Limited Settings

Nearly half of the world lacks access to diagnostic imaging. Point of care ultrasound (POCUS) is a versatile and relatively affordable imaging modality that offers promise as a means of bridging the radiology gap and improving care in low resource settings. Methods: We performed semi-structured interviews of key stakeholders at two diverse hospitals where POCUS implementation programs had recently been conducted: one in a rural private hospital in Haiti and the other in a public referral hospital in Malawi. Questions regarding the clinical utility of POCUS, as well as barriers and facilitators of its implementation, were asked of study participants. Using the Framework Method, analysis of interview transcripts was guided by the WHO ASSURED criteria for point of care diagnostics. Results: Fifteen stakeholders with diverse roles in POCUS implementation were interviewed. Interviewees from both sites considered POCUS a valuable diagnostic tool that improved clinical decisions. They perceived barriers to adequate training as one of the most important remaining barriers to POCUS implementation. Conclusions: In spite of the increasing affordability and portability of ultrasounds devices, there are still important barriers to the implementation of POCUS in resource-limited settings

Stakeholder Perceptions of Point-of-Care Ultrasound Implementation in Resource-Limited Settings

Nearly half of the world lacks access to diagnostic imaging. Point of care ultrasound (POCUS) is a versatile and relatively affordable imaging modality that offers promise as a means of bridging the radiology gap and improving care in low resource settings. Methods: We performed semi-structured interviews of key stakeholders at two diverse hospitals where POCUS implementation programs had recently been conducted: one in a rural private hospital in Haiti and the other in a public referral hospital in Malawi. Questions regarding the clinical utility of POCUS, as well as barriers and facilitators of its implementation, were asked of study participants. Using the Framework Method, analysis of interview transcripts was guided by the WHO ASSURED criteria for point of care diagnostics. Results: Fifteen stakeholders with diverse roles in POCUS implementation were interviewed. Interviewees from both sites considered POCUS a valuable diagnostic tool that improved clinical decisions. They perceived barriers to adequate training as one of the most important remaining barriers to POCUS implementation. Conclusions: In spite of the increasing affordability and portability of ultrasounds devices, there are still important barriers to the implementation of POCUS in resource-limited settings

Postoperative complications and waiting time for surgical intervention after radiologically guided drainage of intra-abdominal abscess in patients with Crohn’s disease

Postoperative complications; DrainageComplicacions postoperatòries; DrenatgeComplicaciones postoperatorias; DrenajeBackground In patients with active Crohn’s disease (CD), treatment of intra-abdominal abscess usually comprises antibiotics and radiologically guided percutaneous drainage (PD) preceding surgery. The aim of this study was to investigate the risk of postoperative complications and identify the optimal time interval for surgical intervention after PD. Methods A multicentre, international, retrospective cohort study was carried out. Details of patients with diagnosis of CD who underwent ultrasonography- or CT-guided PD were retrieved from hospital records using international classification of disease (ICD-10) diagnosis code for CD combined with procedure code for PD. Clinical variables were retrieved and the following outcomes were measured: 30-day postoperative overall complications, intra-abdominal septic complications, unplanned intraoperative adverse events, surgical-site infections, sepsis and pathological postoperative ileus, in addition to abscess recurrence. Patients were categorized into three groups according to the length of the interval from PD to surgery (1–14 days, 15–30 days and more than 30 days) for comparison of outcomes. Results The cohort comprised 335 CD patients with PD followed by surgery. Median age was 33 (i.q.r. 24–44) years, 152 (45.4 per cent) were females, and median disease duration was 9 (i.q.r. 3.6–15) years. Overall, the 30-day postoperative complications rate was 32.2 per cent and the mortality rate was 1.5 per cent. After adjustment for co-variables, older age (odds ratio 1.03 (95 per cent c.i. 1.01 to 1.06), P < 0.012), residual abscess after PD (odds ratio 0.374 (95 per cent c.i. 0.19 to 0.74), P < 0.014), smoking (odds ratio 1.89 (95 per cent c.i. 1.01 to 3.53), P = 0.049) and low serum albumin concentration (odds ratio 0.921 (95 per cent c.i. 0.89 to 0.96), P < 0.001) were associated with higher rates of postoperative complications. A short waiting interval, less than 2 weeks after PD, was associated with a high incidence of abscess recurrence (odds ratio 0.59 (95 per cent c.i. 0.36 to 0.96), P = 0.042). Conclusion Smoking, low serum albumin concentration and older age were significantly associated with postoperative complications. An interval of at least 2 weeks after successful PD correlated with reduced risk of abscess recurrence

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn’s Disease Might Be Associated With Increased Rates of Stoma Construction

Crohn’s disease; Abscess; StomaMalaltia de Crohn; Abscés; EstomaEnfermedad de Crohn; Absceso; EstomaBackground Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn’s disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

Background and objectivesObesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.Materials and methodsMale C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.ResultsLentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.ConclusionsCathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Stress biology:Complexity and multifariousness in health and disease

Preserving and regulating cellular homeostasis in the light of changing environmental conditions or developmental processes is of pivotal importance for single cellular and multicellular organisms alike. To counteract an imbalance in cellular homeostasis transcriptional programs evolved, called the heat shock response, unfolded protein response, and integrated stress response, that act cell-autonomously in most cells but in multicellular organisms are subjected to cell-nonautonomous regulation. These transcriptional programs downregulate the expression of most genes but increase the expression of heat shock genes, including genes encoding molecular chaperones and proteases, proteins involved in the repair of stress-induced damage to macromolecules and cellular structures. Sixty-one years after the discovery of the heat shock response by Ferruccio Ritossa, many aspects of stress biology are still enigmatic. Recent progress in the understanding of stress responses and molecular chaperones was reported at the 12th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment in the Old Town Alexandria, VA, USA from 28th to 31st of October 2023.</p