bluuebunny/crossref_metadata_2025 huggingface dataset:
P29 Manuka honey downregulates IL-4-induced CCL26 via activation of the aryl hydrocarbon receptor
Authors: Alangari Abdullah A , Ashoori Matin Dokht , Alwan Wisam , Stockinger Brigitta , Barker Jonathan N   , Wincent Emma , Di Meglio Paola 
Published: July 2023

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that regulates skin homeostasis. AHR activation by physiological ligands (e.g. indoles originated from host or microbial metabolism of tryptophan) leads to the expression of cytochrome P450 (CYP) enzymes, such as CYP1A1 and has anti-inflammatory effects in animal models and clinical samples of psoriasis and atopic dermatitis. Manuka honey (MH) is a complex nutritional material with antimicrobial, antioxidant and anti-inflammatory activity. We have previously shown that MH downregulates interleukin (IL)-4-induced CCL26 expression in immortalized keratinocytes. Recent studies suggest that MH contains potential AhR ligands, including indoles. Thus, we hypothesize that its anti-inflammatory effect may be mediated, at least partially, via AhR activation. Here, we treated HaCaT keratinocytes, either stably transfected with an empty vector (EV-HaCaT) or in which AhR had been stably silenced (AhR-silenced HaCaT), or primary normal human epithelial keratinocytes (NHEK) with 2% MH for 24 h and measured gene expression by reverse transcriptase quantitative polymerase chain reaction. We detected a 15.4-fold upregulation of CYP1A1 in EV-HaCaTs, which was significantly reduced (P ≤ 0.001) in AhR-silenced cells. Pretreatment with the AhR antagonist CH223191 significantly (P ≤ 0.0001) abrogated this effect. Similar findings were observed in NHEKs. In vivo epicutaneous treatment of Cyp1a1Cre × R26ReYFP reporter mice with pure MH significantly (P < 0.0001) induced CYP1A1 expression compared with Vaseline. Treatment of HaCaT with 2% MH significantly decreased (P < 0.0001) baseline CYP1A1 enzymatic activity at 3 and 6 h but increased it after 12 h, suggesting that MH may activate the AhR through both direct and indirect means. Importantly, MH downregulation of IL-4-induced CCL26 mRNA and protein was abrogated in AhR-silenced HaCaTs and by pretreatment with CH223191. Finally, MH significantly (P < 0.0001) upregulated filaggrin (FLG) expression in NHEKs in an AhR-dependent manner. In conclusion, MH activates AhR, both in vitro and in vivo, thereby providing a mechanism of its IL-4-induced CCL26 downregulation and upregulation of FLG expression. Taken together, our data show that the AhR-activating properties of MH could have broader clinical implications in a range of skin inflammatory conditions.
P32 Restoring the ageing skin barrier in vitro
Authors: Garcha Priya , Jones Eleri , Shelley Jennifer , Caley Matthew
Published: July 2023

The skin provides an essential barrier to the body. As we age, the make-up of this barrier changes, with a reduction of stratum corneum lipids. This loss of lipids as we age can lead to the formation of dry and easily damaged skin, allowing for water loss from the skin surface. One mechanism for this reduction in stratum corneum lipids is dysfunctional lipid transport. To investigate lipid transport within the skin we have developed a two-dimensional high-throughput cholesterol transport assay. Using this assay we have screened 200 naturally occurring compounds and 800 plant extracts to determine their ability to improve cholesterol transport. We identified seven compounds that were able to increase cholesterol transport with no cellular toxicity. Three compounds were selected for further testing in three-dimensional (3D) organotypic skin models with or without defects in cholesterol transport and stratum corneum lipids. Three-dimensional organotypic skin models were grown for 7 days before daily treatment with either dimethyl sulfoxide or 1 µmol L–1 of the selected compound for an additional 7 days. Immunofluorescent staining was conducted to assess skin differentiation (K14, K10, TGM1), proliferation (Ki67), basement membrane (laminin α3) and stratum corneum lipids (Nile red). We have developed a 2D screening and 3D testing platform to assess compounds and drugs for their effect on cholesterol transport. Compounds that can target cholesterol transport within keratinocytes could be a beneficial treatment to help improve the ageing skin barrier, improving dry and damaged skin.
Eocene palynoflora from the La Marcelina Formation, Patagonia, Argentina
Authors: Noetinger Sol , Aramendía Inés , Pujana Roberto R , García Massini Juan L , Barreda Viviana D
Published: July 2023

Southern Patagonia contains several Eocene fossiliferous deposits that have only been superficially explored and studied. One of these corresponds to the La Marcelina Formation with outcrops in the south-western slope of the Deseado Massif, Santa Cruz Province, Argentina. No detailed palynological studies have been performed so far in this unit. Here we estimate the age, palaeoenvironment, and climatic conditions based on the analysis of terrestrially derived spores, algae cysts, and pollen grains. The recovered association supports an Eocene age and concurs with a mixed flora, including Gondwanan and Neotropical elements, dominated by Podocarpaceae, Nothofagaceae, and Proteaceae, and that probably developed under a temperate and humid climate. Overall, these results expand our understanding of the composition of Eocene floras from the highest latitudes of South America, as well as provide new evidence of past paleoclimates for the area.
New insights into risk variables associated with gas embolism in loggerhead sea turtles (Caretta caretta) caught in trawls and gillnets
Authors: Garcia-Parraga Daniel , Crespo-Picazo Jose Luis , Sterba-Boatwright Blair , Marco Vicente , Muñoz-Baquero Marta , Robinson Nathan J , Stacy Brian , Fahlman Andreas
Published: July 2023

Tissue and blood gas embolism (GE) associated with fisheries bycatch are likely a widespread, yet underestimated, cause of sea turtle mortality. Here, we evaluated risk factors associated with tissue and blood GE in loggerhead turtles caught incidentally by trawl and gillnet fisheries on the Valencian coastline of Spain. Of 413 turtles (303 caught by trawl, 110 by gillnet fisheries), 54% (n = 222) exhibited GE. For sea turtles caught in trawls, the probability and severity of GE increased with trawl depth and turtle body mass. In addition, trawl depth and the GE score together explained the probability of mortality (P[mortality]) following recompression therapy. Specifically, a turtle with a GE score of 3 caught in a trawl deployed at 110 m had a P[mortality] of ~50%. For turtles caught in gillnets, no risk variables were significantly correlated with either the P[GE] or GE score. However, gillnet depth or GE score, separately, explained P[mortality], and a turtle caught at 45 m or with a GE score between 3 and 4 had a P[mortality] of 50%. Differences in the fishery characteristics precluded direct comparison of GE risk and mortality between these gear types. Although P[mortality] is expected to be significantly higher in untreated turtles released at sea, our findings can improve estimates of sea turtle mortality associated with trawls and gillnets, and help guide associate conservation efforts.
Imaging for implementation of heart failure guidelines
Authors: Nagueh Sherif F , Nabi Faisal , Chang Su Min , Al-Mallah Mouaz , Shah Dipan J , Bhimaraj Arvind
Published: July 2023

The classification of heart failure with implications for pharmacological therapeutic interventions rests on defining ejection fraction (EF) which is an imaging parameter. Imaging can provide diagnostic clues as to aetiology of heart failure; it can also guide and help assess response to treatment. Echocardiography, CMR, cardiac computed tomography, positron emission tomography, and Tc 99 m pyrophosphate scanning provide information about the aetiology of heart failure. Further, echocardiography plays the primary role in the evaluation of LV diastolic function and the estimation of left ventricular (LV) filling pressures both at rest and with exercise during diastolic stress testing. Heart failure guidelines recognize four stages (A, B, C, and D) for heart failure. Cardiac imaging along with risk factors and clinical status is needed for identifying these stages. There are joint societal echocardiographic guidelines by American Society of Echocardiography (ASE) of Echocardiography and European Association of Cardiovascular Imaging that are applicable to the imaging of heart failure patients. There are also separate guidelines for the evaluation of patients being considered for LV assist device implantation and for multimodality imaging of patients with heart failure and preserved EF. Cardiac catheterization is needed in patients whose haemodynamic status is uncertain after clinical and echocardiographic evaluation and to evaluate for coronary artery disease. Myocardial biopsy can identify the presence of myocarditis or specific infiltrative diseases when the findings by non-invasive imaging are not conclusive.
Case report of culture-negative endocarditis in lupus nephritis
Authors: Khandait Harshwardhan , Ong Cheng Ken , Javaid Ayesha , Sandhu Rav
Published: July 2023

Background

Cardiovascular involvement is frequent in systemic lupus erythematosus (SLE). Valvular abnormalities are increasingly being recognized with the advent of echocardiography.

Case summary

We present a case of a 46-year-old lady who presented to the emergency department with upper limb ischaemia. On examination, she had poor dentition and a short systolic murmur on auscultation. A blood workup revealed a diagnosis of SLE. Further investigations showed vegetations on the mitral valve. Initially, an infective endocarditis (IE) diagnosis was made, which was treated with antibiotics. High-dose steroids and immunosuppressants were initiated due to her clinical deterioration and biopsy-proven lupus nephritis. She improved clinically before being discharged home.

Discussion

It can be difficult to distinguish between IE and Libman–Sacks endocarditis (LSE), especially in the setting of risk factors for both. Antibiotics and immunosuppressants might be started simultaneously in these cases. A multidisciplinary team is required to manage challenging cases of culture-negative endocarditis. Procalcitonin may have a role in differentiating bacterial endocarditis and LSE.
Drivers and consequences of bacteriophage host range
Authors: Holtappels Dominique , Alfenas-Zerbini Poliane , Koskella Britt
Published: July 2023

Bacteriophages are obligate parasites of bacteria characterized by the breadth of hosts that they can infect. This “host range” depends on the genotypes and morphologies of the phage and the bacterial host, but also on the environment in which they are interacting. Understanding phage host range is critical to predicting the impacts of these parasites in their natural host communities and their utility as therapeutic agents, but is also key to predicting how phages evolve and in doing so drive evolutionary change in their host populations, including through movement of genes among unrelated bacterial genomes. Here, we explore the drivers of phage infection and host range from the molecular underpinnings of the phage–host interaction to the ecological context in which they occur. We further evaluate the importance of intrinsic, transient, and environmental drivers shaping phage infection and replication, and discuss how each influences host range over evolutionary time. The host range of phages has great consequences in phage-based application strategies, as well as natural community dynamics, and we therefore highlight both recent developments and key open questions in the field as phage-based therapeutics come back into focus.
Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans
Authors: Bell Avery Davis , Chou Han Ting , Valencia Francisco , Paaby Annalise B
Published: July 2023

Though natural systems harbor genetic and phenotypic variation, research in model organisms is often restricted to a reference strain. Focusing on a reference strain yields a great depth of knowledge but potentially at the cost of breadth of understanding. Furthermore, tools developed in the reference context may introduce bias when applied to other strains, posing challenges to defining the scope of variation within model systems. Here, we evaluate how genetic differences among 5 wild Caenorhabditis elegans strains affect gene expression and its quantification, in general and after induction of the RNA interference (RNAi) response. Across strains, 34% of genes were differentially expressed in the control condition, including 411 genes that were not expressed at all in at least 1 strain; 49 of these were unexpressed in reference strain N2. Reference genome mapping bias caused limited concern: despite hyperdiverse hotspots throughout the genome, 92% of variably expressed genes were robust to mapping issues. The transcriptional response to RNAi was highly strain- and target-gene-specific and did not correlate with RNAi efficiency, as the 2 RNAi-insensitive strains showed more differentially expressed genes following RNAi treatment than the RNAi-sensitive reference strain. We conclude that gene expression, generally and in response to RNAi, differs across C. elegans strains such that the choice of strain may meaningfully influence scientific inferences. Finally, we introduce a resource for querying gene expression variation in this dataset at https://wildworm.biosci.gatech.edu/rnai/.
An Open-Source Photogrammetry Workflow for Reconstructing 3D Models
Authors: Zhang C , Maga A M
Published: July 2023

Synopsis

Acquiring accurate 3D biological models efficiently and economically is important for morphological data collection and analysis in organismal biology. In recent years, structure-from-motion (SFM) photogrammetry has become increasingly popular in biological research due to its flexibility and being relatively low cost. SFM photogrammetry registers 2D images for reconstructing camera positions as the basis for 3D modeling and texturing. However, most studies of organismal biology still relied on commercial software to reconstruct the 3D model from photographs, which impeded the adoption of this workflow in our field due the blocking issues such as cost and affordability. Also, prior investigations in photogrammetry did not sufficiently assess the geometric accuracy of the models reconstructed. Consequently, this study has two goals. First, we presented an affordable and highly flexible SFM photogrammetry pipeline based on the open-source package OpenDroneMap (ODM) and its user interface WebODM. Second, we assessed the geometric accuracy of the photogrammetric models acquired from the ODM pipeline by comparing them to the models acquired via microCT scanning, the de facto method to image skeleton. Our sample comprised 15 Aplodontia rufa (mountain beaver) skulls. Using models derived from microCT scans of the samples as reference, our results showed that the geometry of the models derived from ODM was sufficiently accurate for gross metric and morphometric analysis as the measurement errors are usually around or below 2%, and morphometric analysis captured consistent patterns of shape variations in both modalities. However, subtle but distinct differences between the photogrammetric and microCT-derived 3D models could affect the landmark placement, which in return affected the downstream shape analysis, especially when the variance within a sample is relatively small. At the minimum, we strongly advise not combining 3D models derived from these two modalities for geometric morphometric analysis. Our findings can be indictive of similar issues in other SFM photogrammetry tools since the underlying pipelines are similar. We recommend that users run a pilot test of geometric accuracy before using photogrammetric models for morphometric analysis. For the research community, we provide detailed guidance on using our pipeline for building 3D models from photographs.
Identifying contributors to disparities in patient access of online medical records: examining the role of clinician encouragement
Authors: Sisk Bryan A , Lin Sunny , Balls-Berry Joyce (Joy) E , Servin Argentina E , Mack Jennifer W
Published: July 2023

Objective

The aim of this study was to understand the influence of clinician encouragement and sociodemographic factors on whether patients access online electronic medical records (EMR).

Materials and Methods

We analyzed 3279 responses from the Health Information National Trends Survey 5 cycle 4 survey, a cross-sectional, nationally representative survey administered by the National Cancer Institute. Frequencies and weighted proportions were calculated to compare clinical encouragement and access to their online EMR. Using multivariate logistic regression, we identified factors associated with online EMR use and clinician encouragement.

Results

In 2020, an estimated 42% of US adults accessed their online EMR and 51% were encouraged by clinicians to access their online EMR. In multivariate regression, respondents who accessed EMR were more likely to have received clinician encouragement (odds ratio [OR], 10.3; 95% confidence interval [CI], 7.7–14.0), college education or higher (OR, 1.9; 95% CI, 1.4–2.7), history of cancer (OR, 1.5; 95% CI, 1.0–2.3), and history of chronic disease (OR, 2.3; 95% CI, 1.7–3.2). Male and Hispanic respondents were less likely to have accessed EMR than female and non-Hispanic White respondents (OR, 0.6; 95% CI, 0.5–0.8, and OR, 0.5; 95% CI, 0.3–0.8, respectively). Respondents receiving encouragement from clinicians were more likely to be female (OR, 1.7; 95% CI, 1.3–2.3), have college education (OR, 1.5; 95% CI, 1.1–2.0), history of cancer (OR, 1.8; 95% CI, 1.3–2.5), and greater income levels (OR, 1.8–3.6).

Discussion

Clinician encouragement of patient EMR use is strongly associated with patients accessing EMR, and there are disparities in who receives clinician encouragement related to education, income, sex, and ethnicity.

Conclusions

Clinicians have an important role to ensure that all patients benefit from online EMR use.
Enhancing the nutritive value of canola meal for broiler chickens through enzymatic modifications
Authors: Niu Yanxing , Rogiewicz Anna , Patterson Rob , Slominski Bogdan A
Published: July 2023

Enzymatic modification of canola meal (CM) is a potential method to enhance its nutritional value as it can depolymerize nonstarch polysaccharides (NSP) and mitigate its potential antinutritive properties. Based on the previous studies, pectinase A (PA), pectinase B (PB), xylanase B (XB), and invertase (Inv) were used for the enzymatic modifications. The highest NSP depolymerization ratio was obtained when 4 g/kg of each PA, PB, and XB, and 0.2 g/kg of Inv were used during 48 h incubation at 40 °C. In the current study, changes in pH, simple sugars, sucrose, oligosaccharides, and NSP contents during the enzymatic modification (CM+E) of CM were measured and compared to Control (CM) without enzymes addition or with the addition of bacteriostat sodium azide (CM+E+NaN3). The results showed that spontaneous fermentation occurred during incubation. After incubation, the pH of the slurry decreased, lactic acid was produced, phytate disappeared, and the concentration of simple sugars decreased substantially. The NSP of the slurry was progressively depolymerized by the enzyme blend. The chemical composition and nutritive value of enzymatically-modified CM (ECM) were evaluated. Ross 308 broilers were randomly assigned to 18 cages of six birds each for the standardized ileal amino acid digestibility (SIAAD) and nitrogen-corrected apparent metabolizable energy (AMEn) assay. A corn/soybean meal-based basal diet formulated to meet Ross 308 breeder recommendations and two test diets contained 70% of the basal diet and 30% of CM or ECM, respectively, were fed to Ross 308 from 13 to 17 d of age. No difference was observed between SIAAD of CM and ECM. The AMEn value of ECM was 2118.0 kcal/kg on a dry matter basis which was 30.9% greater (P < 0.05) than the CM.
Survival in sporadic ALS is associated with lower p62 burden in the spinal cord
Authors: Pinkerton Monica , Lourenco Guinevere , Pacheco Maria Torres , Halliday Glenda M , Kiernan Matthew C , Tan Rachel H
Published: July 2023

The autophagy marker p62 appears as a consistent component of pathological aggregates in amyotrophic lateral sclerosis (ALS) and its modulation to facilitate protein degradation has been proposed as a potential therapeutic target. Importantly, recent studies have implicated diffuse phosphorylated TDP-43 inclusions that are immuno-negative for p62 in more rapid disease, highlighting the need for better understanding of p62 involvement in ALS pathogenesis. The present study set out to assess p62 pathology in the motor neurons of 31 patients with sporadic ALS that had either a short (<2 years) or longer (4–7 years) disease duration to determine its association with pTDP-43 pathology, motor neuron loss, and survival in sporadic disease. Our results identified significantly more cytoplasmic p62 aggregates in the spinal cord of patients with a shorter survival. Disease duration demonstrated a negative association with p62 burden and density of remaining motor neurons in the spinal cord, suggesting that survival in sporadic ALS is associated with the successful clearance of lower motor neurons with p62 aggregates. These findings implicate the autophagy pathway in ALS survival and provide support for further study of p62 as a potential prognostic biomarker in ALS.
Comparison of Administrative Database-Derived and Hospital-Derived Data for Monitoring Blood Culture Use in the Pediatric Intensive Care Unit
Authors: Xiao Shaoming , Woods-Hill Charlotte Z , Koontz Danielle , Thurm Cary , Richardson Troy , Milstone Aaron M , Colantuoni Elizabeth ,   The Bright STAR Authorship Group, Elaine-Marie Albert J , Zerr Danielle M , Foster Charles B , Ezetendu Chidiebere , Hauger Sarmistha B , Dallefeld Samantha H , Sandora Thomas J , Priebe Gregory P , Tadphale Sachin D , Hysmith Nicholas D , Nolt Dawn , Kirby Aileen L , Toltzis Philip , Clayton Jason A , Agulnik Asya , Wolf Joshua , Newland Jason G , Lin John C , Steffen Katherine M , Schwenk Hayden T , Flaherty Brian F , Larsen Gitte Y , Coffin Susan E , Fainberg Nina A , Linam William M , Smith Craig M , Kociolek Larry K , Hong Sue J , Miller Marlene R , Xie Anping , Fackler James C
Published: July 2023

Background

Optimizing blood culture practices requires monitoring of culture use. Collecting culture data from electronic medical records can be resource intensive. Our objective was to determine whether administrative data could serve as a data source to measure blood culture use in pediatric intensive care units (PICUs).

Methods

Using data from a national diagnostic stewardship collaborative to reduce blood culture use in PICUs, we compared the monthly number of blood cultures and patient-days collected from sites (site-derived) and the Pediatric Health Information System (PHIS, administrative-derived), an administrative data warehouse, for 11 participating sites. The collaborative’s reduction in blood culture use was compared using administrative-derived and site-derived data.

Results

Across all sites and months, the median of the monthly relative blood culture rate (ratio of administrative- to site-derived data) was 0.96 (Q1: 0.77, Q3: 1.24). The administrative-derived data produced an estimate of blood culture reduction over time that was attenuated toward the null compared with site-derived data.

Conclusions

Administrative data on blood culture use from the PHIS database correlates unpredictably with hospital-derived PICU data. The limitations of administrative billing data should be carefully considered before use for ICU-specific data.
Surgical management of deep dermatophytosis in a patient with CARD9 deficiency
Authors: El Maati Maha , Berjaou Zakia , Hammouch Zaineb , Khachani Kenza , Moustakbal Iliass , Meziane Meryem , Ismaili Nadia , Benzekri Laila , Aoufi Sara , Mazouz Samir , Senouci Karima
Published: July 2023

Deep dermatophytosis is a dermal infection caused by Dermatophytes. It can cause deeper dermal dermatophytosis, Majocchi’s granuloma, dermatophytic pseudomycetoma or a widespread infection. CARD9 deficiency is a known risk factor in the Mediterranean region, first reported in 1964 in Morocco. We report a case of 23-year-old man with a scarring alopecia who presented with subcutaneous abscesses topped off with a large ringworm infection. Mycotic analysis revealed a Trichophyton Rubrum deep dermatophytosis. The molecular study revealed a CARD9 mutation confirming dermatophytosis with parotid and lymph nodes involvement. The patient underwent successful drainage surgery of the abscesses alongside medical treatment including antifungal agents and he was discharged after an uneventful postoperative course.
(20) DUAL EFFECT OF A SEROTONIN AND DOPAMINE REUPTAKE INHIBITOR (IP2018), AND THE SEARCH FOR A DEPRESSIVE RAT MODEL WITH ERECTILE DYSFUNCTION
Authors: Simon G Comerma Steffensen , Eugenio Gutierrez , Rafael Fais , Dan Peters , Claus Olesen , Prof. Gregers Wegener , Prof. Ulf Simonsen
Published: July 2023

Objectives

We investigated whether an amine transport inhibitor, IP2018, improves depression and erectile function in the same dose range.

Methods

The dose-dependent effect of IP2018 in mouse models for depression, the mouse-forced swim test (mFST) and mouse-tail suspension test (mTST), is reported. In male Wistar, Sprague Dawley and the depressive rats (Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL)), increases in intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured, and the ratio ICP/MAP was used as a measure of erectile function. We investigated whether IP2018 induces changes in ICP/flow and whether IP2018 facilitates suboptimal increases in ICP induced by cavernosal nerve electrical stimulation. The late procedure was performed in the rest of the rats to evaluate their erectile function.

Results

We found that infusion of IP2018 dose-dependently improved mFST and was more potent than citalopram. At the same time, higher doses of IP2018 were required to obtain effect in the mTST model, and IP2018 was equipotent to citalopram. Infusion of low doses of IP2018 dose-dependently increased the number and the duration of spontaneous erections. At the highest dose of IP2018, the increases in the number and duration of spontaneous erections were similar to the effect of the lowest dose, and the increases in flow were 5 times higher. IP2018 (1-30 μM) caused small relaxations in isolated corpus cavernosum strips. FSL and FRL rats showed a diminished ICP/MAP compared to Sprague Dawley control rats.

Conclusions

IP2018 is more potent or has a similar effect to the well-known antidepressant drug citalopram in mouse models for depression. The potent effect of IP2018 on erectile function in anaesthetized rats suggests that IP2018 in the same dose range has positive effects on both depression and erectile function. FSL/FRL rats appear to allow the study of drug effects on both depression and sexual function in one animal model.

Conflicts of Interest

There is no conflict of interest.
(118) THE MECHANISM OF ACTION OF PHOSPHODIESTERASE TYPE 5 INHIBITORS IN PREVENTING MYOFIBROBLAST TRANSFORMATION IN IN VITRO MODELS OF PEYRONIE’S DISEASE
Authors: Sophie L Harding , Dr. Marcus M Ilg , Dr. Alice R Lapthorn , Prof. Selim Cellek , Prof. David J Ralph
Published: July 2023

Objectives

Peyronie’s disease (PD) is a fibrotic disorder of the penis, where a fibrous plaque forms in the tunica albuginea (TA), leading to pain, penile deformity, and erectile dysfunction. There is currently no effective medical treatment available. The transformation of fibroblasts into myofibroblasts is a key event in the pathophysiology of PD and previous work has shown that phosphodiesterase type 5 inhibitors (PDE5i) can prevent this transformation in vitro and prevent PD development in vivo. This study aims to identify the molecular mechanism of the anti-myofibroblast action of PDE5i.

Methods

Primary fibroblasts were isolated from the TA of patients undergoing corrective surgery for PD. Myofibroblast transformation was determined utilizing an In-cell ELISA assay by quantifying the expression of α-smooth muscle actin in response to 10 ng/mL TGF-β1. Concentration response curves (CRCs) were generated to confirm the anti-fibrotic action of PDE5i, and in the presence and absence of pharmacological inhibitors to identify molecular components involved in the mechanism of action of PDE5i. Three biological and three technical replicates were generated, and statistical significance determined using unpaired Students’ t-test.

Results

TGF-β1 receptor inhibitor SB-505124 and PDE5i vardenafil abrogated TGF-β1-induced myofibroblast transformation with an IC50 of 0.29 ± 0.07 μM and 10.15 ± 3.53 μM, respectively. At 1 μM, protein kinase G inhibitor KT5823 did not prevent the antifibrotic action of vardenafil. The cAMP analog 8-Br-cAMP and PDE3i cilostamide abrogated TGF-β1-induced myofibroblast transformation with an IC50 of 6.88 ± 14.29 μM, and 14.05 ± 1.63 μM, respectively. In the presence of 1 μM KT5720, a protein kinase A inhibitor, the antifibrotic effect of vardenafil was significantly reduced.

Conclusions

These results suggest that PDE5i prevent TGF-β1-induced transformation of myofibroblasts not through PKG, but through the PDE3/cAMP/PKA pathway. Although such an interaction has been shown in other fibroblasts, this is the first demonstration in PD fibroblasts.

Conflicts of Interest

No known conflicts of interest.
(201) PENILE PROSTHESIS INSERTION POST-PRIAPISM: SATISFACTION GUARANTEED?
Authors: Dr. Aisling Looney , Katy Naylor , Dr. Chloe Mount , Fiona Holden , Dr. Mark Johnson , Prof. David Ralph , Dr. Philippa Sangster
Published: July 2023

Objectives

Penile prosthesis (PP) insertion is recommended for patients with ischaemic priapism of long duration in order to restore erectile function; but little has been published regarding quality of life (QOL) for those with implants post-priapism. This the largest study to date assessing QOL outcomes in these patients.

Methods

Within our department, 167 patients had a PP inserted following priapism between 2002-2022. We identified 42 patients that had PPs inserted for priapism between 2007-2021. Clinical and demographic details were recorded on an electronic log. Of these 42, 18 (43%) were contactable and agreeable to email or telephone questionnaire. The validated Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire was administered and responses were recorded. Two additional questions were asked regarding regret over PP insertion and feelings regarding their future with a PP.

Results

The median time to implant insertion post-priapism was 15 days. Of the 18 patients who responded, 16/18 (89%) were actively using their prosthesis. Half of these patients (9/18) had an inflatable device inserted primarily. The median duration of PP insertion was 36.5 months. No patients (0/18, 0%) regretted their decision to have a PP inserted at the time of priapism, and 13/18 (72%) would be satisfied living the remainder of their life with a PP. Regarding pleasure, 12/18 (67%) of respondents felt their PP was satisfactory half the time or more, and 76% (13/17 responses) felt their PP had met expectations. Of the 16 men who responded regarding partner satisfaction, 10 (63%) felt their partner was satisfied with the PP half the time or more.

Conclusions

PP insertion is a suitable surgical technique to maintain sexual function in select patients post-priapism. We demonstrated that the majority of men who underwent PP insertion post-priapism were satisfied with the results, and all would choose to have a PP inserted were they to return to their priapism event again.

Conflicts of Interest

Nil
(268) EARLY EXPERIENCE IN PENILE REHABILIATION AFTER RADICAL PROSTATECTOMY
Authors: Senad Bajramovic , Prof. Benjamin Kulovac , Prof. Damir Aganovic , Dr. Jasmin Alic , Hajrudin Spahovic , Nirvana Sabanovic Bajramovic
Published: July 2023

Objectives

The incidence rate of erectile dysfunction (ED) is reportedly as high as 30-90% after radical prostatectomy which seriously affects the patients' quality of life. Penile rehabilitation is defined as the use of any drug or device at or after radical prostatectomy to maximize erectile function recovery.

Methods

Prospective study in men who underwent open radical prostatectomy and who received penile rehabilitation after surgery. Highly motivated (group I) patient started treatment with 5 mg tadalafil on the fifth postoperative day and continued to receive every day, regardless of erectile function. Intracavernous injection of prostaglandin E1 was initiated at 1 month. Minimally motivated patients (group II) started PDE5i on demand only. Follow up evaluations were done at 3, 6, 12, 18 and 24 months. Patients filled in International Index of Erectile Function-5 (IIEF-5) questionnaires.

Results

Of 165 men who underwent open radical prostatectomy 48 patients met inclusion criteria, complied with the study medication, and had complete data for 24 months. A total of 12 patients (25%) underwent (undefined include also unilateral) nerve-sparing surgery (NSS), while 36 patients (75%) had bilateral nerve-sparing surgery. At 24 months, 30% of patients who underwent undefined nerve-sparing surgery and 60% of patients who underwent bilateral nerve-sparing surgery reported having sufficient erectile function for intercourse without using intracavernous injection or PDE5i on demand. At 24 months after surgery, the median IIEF-5 score was 13 (1-25) for the whole cohort, 7 (1-25) for patients who had undergone undefined nerve-sparing surgery and 16 (1-25) for patients who had undergone bilateral nerve-sparing surgery. Patients received ICI treatment had success early in the study period compared to patients taking PDE5i alone.

Conclusions

Proper selection of patients, NSS and postoperative counseling as well as patient’s motivations and expectations might explain inferior erectile function results following this surgery.

Conflicts of Interest

No conflicts.
(276) FEASIBILITY OF MINIMALLY INVASIVE, SAME-DAY INJECTION OF AUTOLOGOUS ADIPOSE-DERIVED STEM CELLS IN THE TREATMENT OF ERECTILE DYSFUNCTION
Authors: Prof. Mikkel Fode , Dr. Naomi Nadler , Prof. Lars Lund , Prof. Nessn Azawi
Published: July 2023

Objectives

To investigate feasibility, safety and efficacy of a new minimally invasive same-day method of autologous adipose derived stem cell (ADSC) transplantation in men suffering from erectile dysfunction (ED).

Methods

Prospective case series of 10 men with an IIEF-EF domain score < 17. The IIEF questionnaire was filled out at baseline and 1, 2 and 3 months after treatment. Side effects were assessed by investigations and interviews until 6 months after treatment. The myStem® X2 kit was used for preparation of ADSC: Adipose tissue was harvested from the patient himself under local anesthesia and immediately prepared and injected into the penis. Primary endpoints were feasibility and safety. Secondary outcomes included effects on ED and changes in the remaining IIEF domains.

Results

Ten men were included. Only one adverse event in the form of minor blue discoloration at the fat harvest site was registered. There were statistically significant improvements in IIEF-EF at one, two and three months after treatment compared to baseline with the median score increasing from 5.5 to 10.5, 10.5, and 10 respectively. Considering the individual patients, 3/10 men achieved an improvement equal to or greater than the minimal clinically important difference according to their baseline IIEF-EF score.

Conclusions

Our study confirms the feasibility and safety of this minimally invasive, same-day delivery of ADSC. Due to the design and size on the study, firm conclusions should not be drawn regarding efficacy, but the method seems worthy of further study.

Conflicts of Interest

Mikkel Fode is a speaker for Boston Scientific.
(270) CAN INTRAOPERATIVE NERVE MONITORING IMPROVE FUNCTIONAL OUTCOMES AFTER UNILATERAL- OR NON-NERVE-SPARING ROBOT-ASSISTED RADICAL PROSTATECTOMY?
Authors: Dr. Alexander B Nolsøe , Peter B Østergren , Dr. Henrik Jakobsen , Christian F S Jensen , Dr. Roar Rasmussen , Niels H Bruun , Prof. Jens Sønksen , Prof. Mikkel Fode
Published: July 2023

Objectives

Damage to the pudendal nerve that innervates the external urethral sphincter (EUS) is a factor in the development of urinary incontinence after robot-assisted radical prostatectomy (RARP). We aim to investigate whether nerve identification can prevent nerve damage with a subsequent positive effect on functional outcomes.

Methods

Men scheduled to unilateral- or non-nerve-sparing RARP were randomized (1:1) to standard RARP (CTRL) or intraoperative nerve monitoring (INT) via the PROPEP® system. Two electrodes are inserted in the EUS and the Maryland forceps convey an electric impulse. When a nerve innervating the EUS is located, an action potential is seen on the robot console screen. Subsequently, the area can be spared during dissection.

The primary outcome was the International Consultation on Incontinence Questionnaire (ICIQ) score at 12 months. Secondary endpoints included continence at 12 months defined as <8 grams on a 24-hour pads test or the use of 0 pads per day and the answer “never” to the first ICIQ question regarding incontinence frequency. Also, the international prostate symptom score (IPSS), the Erection Hardness Score (EHS), and sexual activity at 12 months. Outcomes were analyzed using regression with robust variance estimation.

Results

From 2018-2022, 100 men were randomized. A positive nerve signal was found in all the INT-group participants. There were no differences in baseline characteristics between the groups. ICIQ was 5.37 (INT) versus 5.66 (CTRL) (95% CI [-2.57;1.99], p=0.8). Continence was 63.4% (INT) vs. 63.4% (CTRL) (95% CI [-21.43;21.43], p= 1). IPSS score was 5.93 (INT) vs. 5.39 (CTRL) (95% CI [-0.91;1.98], p= 0.46). EHS score was 0.95 (INT) vs. 1.18 (CTRL) (95% CI [-0.73;0.29], p= 0.39). Sexual activity was 61% (INT) vs. 57.5% (CTRL) (95% CI [-18.5;25.5], p= 0.75).

Conclusions

Identification of the somatic nerves that innervate the EUS did not improve functional outcomes compared to standard RARP.

Conflicts of Interest

None of the Authors have any conflicts of interest to report.
(155) THE CLINICAL PROFILE OF MEN WITH PREMATURE EJACULATION AT PRESENTATION HAS CHANGED OVER THE LAST FIFTEEN YEARS: analysis froma longitudinalstudy
Authors: Dr. Luca Boeri , Dr. Edoardo Pozzi , Dr. Federico Belladelli , Dr. Giuseppe Fallara , Dr. Alessandro Bertini , Dr. Simone Cilio , Dr. Francesco Lanzaro , Dr. Luigi Candela , Dr. Christian Corsini , Dr. MAssimiliano Raffo , Ludovica Cella , Fausto Negri , Margherita Fanton , Dr. Paolo Capogrosso , Dr. Alessia Darma , Prof. Francesco Montorsi , Prof. Andrea Salonia
Published: July 2023

Objectives

Patient’s characteristics at first medical evaluation for a specific sexual dysfunction (SD) are strongly correlated to the public awareness towards the specific disease and the availability of novel treatments. We aimed to assess the clinical characteristics of patients presenting for premature ejaculation (PE) as their primary medical complaint over a 15-year time frame

Methods

Data from 257 heterosexual men seeking first medical help for primary PE between 2008 and 2022 were analysed. Clinical data and serum hormones were collected. At baseline all patients completed the IIEF, the Beck Inventory for Depression (BDI), and the Premature Ejaculation Diagnostic Tool (PEDT). Relationship status was categorized as: single vs. stable sexual relationship. Descriptive statistics and linear regression analyses were permformed.

Results

Of all, 182) (71%) patients reported erectile dysfunction (ED) according to IIEF-EF scores. Across the 15-year time frame, patient’s age at presentation significantly decreased over time (p<0.001). Furthermore, depressive symptoms at BDI (p<0.001) and PE severity as scored with the PEDT (p<0.001) linearly decreased. When segregating the whole cohort into 5-year groups, age at presentation decreased from 2008-2012 to 2013-2017 (p=0.04) and further decreased between 2018-2022 (p=0.01). Similarly, baseline BDI scores decreased from 2008-2012 to 2018-2022 (all p<0.001). PE severity at first assessment has decreased since 2017 (p<0.01). Patients more frequently asked for medical attention for PE between 2018-2022 compared to 2013-2017 and 2008-2012 (p<0.001).

Conclusions

This longitudinal study showed that PE patients characteristic at first presentation has significantly changed throughout the last 15 years. Of note, age, PE severity and depressive symptoms showed has decreased overtime. Men in a stable sexual relationship were more likely to seek medical attention for PE in recent years. These results probably reflect the increased public awareness of PE; therefore, patients request PE consultation at younger age, with initial symptoms and with fewer psychological bother related to this condition

Conflicts of Interest

NA
(244) PROSTATE CANCER PATIENTS’ EXPERIENCE OF SEXUAL DYSFUNCTION AND SUPPORT ACCORDING TO TREATMENT PATHWAY
Authors: William Kinnaird , Prof. Michael Kirby , Dr. Patricia Schartau , Prof. Valerie Jenkins , Dr. Stephen Allen , Prof. Heather Payne
Published: July 2023

Objectives

Sexual dysfunction (SD) is a common side effect of almost all prostate cancer (PCa) treatments. This study examined how men’s experience of sexual side effects and accessing information and support varied by treatment pathway.

Methods

An anonymous online survey was distributed via email, social media and peer-support groups in collaboration with the charity Prostate Cancer UK. Results were analysed by treatment pathway: Radical Prostatectomy (RP), Radiotherapy (RT), Androgen Deprivation Therapy (ADT) ± second line therapy (Androgen Receptor Targeted Agent, Chemotherapy, Radioisotope), and No Treatment (Active Surveillance, Watchful Waiting, Awaiting Treatment). Chi-square testing was used for categorical variable analysis.

Results

A total of 654 adult participants met the inclusion criteria and were included in the analysis. Sexual activity was ‘fairly/very important’ to the majority of men irrespective of treatment group. Sexual dysfunction was wide-ranging and common across almost all pathways, with men on combinations of treatment reporting problems most frequently [Fig 1]. Participants whose disease management involved RP were significantly more likely to have had discussions about SD with a healthcare professional (HCP) than those managed with RT and/or ADT alone (80.1% vs 43.3%, p<.001). Those discussions were also significantly more likely to have led to a referral for specialist sexual support (49.1% vs 26.6%, p<.001). However, there was dissatisfaction across groups, with a only minority of participants reporting they were ‘told everything I needed to know’ about SD and rating their care as ‘adequate’ [Fig 1].

Conclusions

This study investigated a wide range of sexual problems across PCa treatment pathways. Findings suggest physical and psychological sexual side effects are common and distressing in all treatment groups. Men place high importance on sexual activity, but only a minority are satisfied with the information and support they receive. Unmet needs are greatest among men whose disease is managed in the oncological setting with RT and ADT.

Conflicts of Interest

Astellas Pharma Resaerch Grant UK-72-RG-41.
(251) BIOCHEMICAL PREDICTORS OF STRUCTURAL HYPOTHALAMUS-PITUITARY ABNORMALITIES DETECTED BY MAGNETIC RESONANCE IMAGING IN MEN WITH SECONDARY HYPOGONADISM
Authors: Dr. Sarah Cipriani , Dr. Tommaso Todisco , Dr. Nicola Ghiandai , Prof. Linda Vignozzi , Dr. Giovanni Corona , Prof. Mario Maggi , Prof. Giulia Rastrelli
Published: July 2023

Objectives

Organic conditions underlying secondary hypogonadism (SH) may be ascertained by magnetic resonance imaging (MRI) of the hypothalamic-pituitary region that could not be systematically proposed to each patient. Based upon limited evidence, the Endocrine Society (ES) guidelines suggest total testosterone (T) < 5.2 nmol/L to identify patients eligible for MRI. The study aims to identify markers and their best threshold value predicting pathological MRI findings in men with SH.

Methods

A consecutive series of 609 men seeking medical care for sexual dysfunction and with SH (total T < 10.5 nmol/L and LH ≤ 9.4 U/L) was retrospectively evaluated. An independent cohort of 50 men with SH was used as validation sample. 126 men in the exploratory sample and the whole validation sample underwent MRI.

Results

In the exploratory sample, patients with pathological MRI findings (n = 46) had significantly lower total T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate specific antigen (PSA) than men with normal MRI (n = 80). Receiver Operating Characteristics analysis showed that total T, LH, FSH and PSA are accurate in identifying men with pathologic MRI (accuracy: 0.62-0.68, all p < 0.05). The Youden index was used to detect the value with the best performance, corresponding to total T 6.1 nmol/L, LH 1.9 U/L, FSH 4.2 U/L and PSA 0.58 ng/mL. In the validation cohort, only total T ≤ 6.1 nmol/L and LH ≤ 1.9 U/L were confirmed as significant predictors of pathologic MRI.

Conclusions

In men with SH, total T ≤ 6.1 nmol/L or LH ≤ 1.9 U/L should arise the suspect of hypothalamus/pituitary structural abnormalities, deserving MRI evaluation.

Conflicts of Interest

none
(269) COMPARISON BETWEEN TWO DIFFERENT TECHNIQUES FOR THE TREATMENT OF PENILE PARAFFINOMA: AESTHETIC AND FUNCTIONAL OUTCOMES
Authors: Dr. Angelo di Giovanni , Dr. Alessandro Giordano , Dr. Carlo D'Alterio , Dr. Claudio Marino , Dr. Luigi Napolitano , Dr. Lorenzo Cirigliano , Dr. Claudia Mirone , Prof. Alessandro Palmieri , Dr. Massimiliano Creta , Dr. Roberto La Rocca , Dr. Marco Capece
Published: July 2023

Objectives

To evaluate the differences in terms of aesthetic and functional outcomes of two different surgical techniques in the treatment of penile paraffinoma.

Methods

From September 2018 to July 2022 we selected 9 patients with penile paraffinoma. Patients were then subdivided into 2 groups. In group 1 (G1), four patients underwent a paraffinoma excision and split thickness skin graft reconstruction in one stage. Inclusion criteria for G1: patients suffering penile paraffinoma with small scrotum size or scrotal involvement.

In group 2 (G2), five patients underwent 2-stages surgical technique: on the first stage we performed excision of paraffinoma and penile scrotalization. three-six month later during the second stage, a scrotoplasty was performed.

All participants were invited to complete two different questionnaires, the international index of erectile function (IIEF-5) and a 6-items questionnaire on the satisfaction of genital aesthetics. The questionnaires were delivered by email. Datas were collected up to one year after surgery and a statistical analysis using SPSS V 26.0 3.4.

Results

No statistical significant differences in terms of IIEF-5 were observed between G1 (20,5 IQR 19-21,25) and G2 (20 IQR 19-22) (p-value 0,49). Otherwise, a statistically significant difference (p-value <0,05) was recorded between G1-G2 in the 6-items questionnaires regarding the satisfaction of genital aesthetics (9,00 IQR 6,75-10,5 vs 13 IQR 4-11 respectively).

Conclusions

In our experience, in patients suffering from penile paraffinoma with no scrotal involvement, a dual stage technique with scrotoplasty is resulting in better aesthetic outcomes rather than a split thickness skin graft. However, a single stage technique, using a split thickness skin graft, also provides good clinical outcome, including acceptable cosmetic results, patient satisfaction, and sexual function. Therefore, in our opinion, both techniques should be considered to enable surgeons to choose from among them based on the patient's preoperative characteristics.

Conflicts of Interest

The Authors declair no conflict of interest.