Changes In Function Research Articles

Relationship of Perivascular Space Markers With Incident Dementia in Cerebral Small Vessel Disease.

Recent studies, using diffusion tensor image analysis along the perivascular space (DTI-ALPS), suggest impaired perivascular space (PVS) function in cerebral small vessel disease, but they were cross-sectional, making inferences on causality difficult. We determined associations between impaired PVS, measured using DTI-ALPS and PVS volume, and cognition and incident dementia. In patients with lacunar stroke and confluent white matter hyperintensities, without dementia at baseline, recruited prospectively in a single center, magnetic resonance imaging was performed annually for 3 years, and cognitive assessments, including global, memory, executive function, and processing speed, were performed annually for 5 years. We determined associations between DTI-ALPS and PVS volume with cerebral small vessel disease imaging markers (white matter hyperintensity volume, lacunes, and microbleeds) at baseline and with changes in imaging markers. We determined whether DTI-ALPS and PVS volume at baseline and change over 3 years predicted incident dementia. Analyses were controlled for conventional diffusion tensor image metrics using 2 markers (median mean diffusivity [MD] and peak width of skeletonized MD) and adjusted for age, sex, and vascular risk factors. A total of 120 patients, mean age 70.0 years and 65.0% male, were included. DTI-ALPS declined over 3 years, while no change in PVS volume was found. Neither DTI-ALPS nor PVS volume was associated with cerebral small vessel disease imaging marker progression. Baseline DTI-ALPS was associated with changes in global cognition (β=0.142, P=0.032), executive function (β=0.287, P=0.027), and long-term memory (β=0.228, P=0.027). Higher DTI-ALPS at baseline predicted a lower risk of dementia (hazard ratio, 0.328 [0.183-0.588]; P<0.001), and this remained significant after including median MD as a covariate (hazard ratio, 0.290 [0.139-0.602]; P<0.001). Change in DTI-ALPS predicted dementia conversion (hazard ratio, 0.630 [0.428-0.964]; P=0.048), but when peak width of skeletonized MD and median MD were entered as covariates, the association was not significant. There was no association between baseline PVS volume, or PVS change over 3 years, and conversion to dementia. DTI-ALPS predicts future dementia risk in patients with lacunar strokes and confluent white matter hyperintensities. However, the weakening of the association between change in DTI-ALPS and incident dementia after controlling for peak width of skeletonized MD and median MD suggests part of the signal may represent conventional diffusion tensor image metrics. PVS volume is not a predictor of future dementia risk.

Hemodialysis Patients with High-Flow Arteriovenous Fistulas: An Evaluation of the Impact on Cardiac Function.

: Patients undergoing hemodialysis often experience changes in cardiac function when they have a high-flow arteriovenous fistula (AVF). This study aimed to assess the effect of high-flow AVFs on cardiac function in patients undergoing hemodialysis. : A longitudinal study was conducted on hemodialysis patients with high-flow AVFs. Echocardiographic parameters, such as left ventricular ejection fraction (LVEF), left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD), right ventricular end-diastolic dimension (RVEDD), inferior vena cava diameter (IVCD), systolic blood pressure, and diastolic blood pressure, were measured and compared before and after AVF creation. : One hundred hemodialysis patients with high-flow AVFs (mean age: 55.95±13.39 years, mean body mass index: 24.71±3.43 kg/m²) were studied. LVEF significantly decreased (51.10%±5.39% to 47.50%±5.79%), while LAD, LVEDD, and IVCD significantly increased after AVF creation (P<0.05). Systolic (132.49±16.42 mmHg to 146.60±17.43 mmHg) and diastolic (79.98±8.40 mmHg to 83.33±9.68 mmHg) blood pressure substantially rose post-fistularization (P<0.001). Notably, LVEF reduction was more significant in brachio-cephalic AVFs (46.29%±4.24%) compared to distal radio-cephalic or snuffbox AVFs (49.17%±7.15%) (P=0.014). : High-flow AVFs can significantly affect echocardiographic parameters in hemodialysis patients, thereby increasing the risk of cardiac failure. Close cardiac monitoring may be necessary for early intervention. Distal AVFs may be preferable in patients with decreased cardiac function.

Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function.

While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions, including maintaining vascular integrity and T helper cell differentiation, meaning that platelets are central to both immune responses and immune quiescence. Clinical data have shown an association between low platelet counts (thrombocytopenia) and immune dysfunction in patients with sepsis and extracorporeal membrane oxygenation, further implicating platelets as more holistic immune regulators, but studies of platelet immune functions in nondisease contexts have had limited study. We used in vivo models of thrombocytopenia and in vitro models of platelet and monocyte interactions, as well as RNA-seq and ATAC-seq (assay for transposase-accessible chromatin with sequencing), to mechanistically determine how resting platelet and monocyte interactions immune program monocytes. Circulating platelets and monocytes interact in a CD47-dependent manner to regulate monocyte metabolism, histone methylation, and gene expression. Resting platelet-monocyte interactions limit TLR (toll-like receptor) signaling responses in healthy conditions in an innate immune training-like manner. In both human patients with sepsis and mouse sepsis models, thrombocytopenia exacerbated monocyte immune dysfunction, including increased cytokine production. Thrombocytopenia immune programs monocytes in a manner that may lead to immune dysfunction in the context of sepsis. This is the first demonstration that sterile, endogenous cell interactions between resting platelets and monocytes regulate monocyte metabolism and pathogen responses, demonstrating platelets to be immune rheostats in both health and disease.

Testing pulmonary physiology in ventilated non-human primates.

Animal models of respiratory viral infections are essential for investigating disease pathogenesis and the efficacy of antivirals and vaccine candidates. A major limitation in the research of respiratory diseases in animal models is correlating clinically relevant changes in pulmonary physiology with cellular and molecular mechanistic studies. Few animal models have captured and correlated physiologic changes in lung function and immune response within same experiment, which is critical given the heterogeneous nature of lung disease due to viral infections. In ventilated human patients, pulmonary physiology testing can be used to not only capture oxygenation, ventilation, but also pulmonary mechanics to yield quantitative measures of lung function and scalar tracings of flow-volume and pressure-volume loops. Application of this protocol during mechanical ventilation in non-human (NHP) models would represent a major advance in respiratory viral disease research. We have applied and optimized a human pulmonary physiology testing protocol to ventilated pigtail macaques (Macaca nemestrina) at baseline and 5 days after influenza A (IAV) viral inoculation. The NHPs manifested clinical disease with hypothermia and loss of body weight. Declines in lung function were striking with a 66%-81% decline in P/F ratio, a measure of oxygenation reflecting the ratio of partial pressure of oxygen in arterial blood (PaO2 ) to the fraction of inspiratory oxygen concentration (FiO2 ). There was also a 16%-45% decline in lung compliance. We describe a new approach to performing pulmonary physiology testing protocol in non-human primates to better capture quantitative correlates of respiratory disease and demonstrate protection by therapeutics and vaccines.

Single‐Layer Carbon Nitride as an Efficient Metal‐Free Organic Electron‐Transport Material with a Tunable Work Function

AbstractSingle‐layer carbon nitride (SLCN) is introduced as a metal‐free organic electron transport material (ETL) for organic solar cells, delivering a performance comparable to that of the benchmark nanocrystalline ZnO. SLCN is produced in the form of stable aqueous inks and can serve as an efficient electron transport layer for three different types of active layers, showing high stability to photodegradation. A lower conductivity of SLCN films as compared to ZnO is counter‐balanced by their higher transparency and lower light scattering losses. The SLCN ETL provides a unique opportunity to tune the work function from ca. −4.1 to −4.6 eV by varying the annealing temperature due to partial thermal oxidation of the SLCN film. The PL band position follows the oxidation‐induced changes of the work function allowing PL properties of SLCN to be used to predict the PV efficiency. The 2D structure of SLCN coupled with unique structural and compositional variability, and tunability of the work function show a high promise for emerging organic PV devices.

Stereotactic Radiation Therapy in Early Non–Small Cell Lung Cancer and Interstitial Lung Disease

Patients with interstitial lung disease (ILD) and early-stage non-small cell lung cancer (NSCLC) have been reported to be at high risk of toxic effects after stereotactic ablative radiotherapy (SABR), but for many patients, there are limited alternative treatment options. To prospectively assess the benefits and toxic effects of SABR in this patient population. This prospective cohort study was conducted at 6 academic radiation oncology institutions, 5 in Canada and 1 in Scotland, with accrual between March 7, 2019, and January 12, 2022. Patients aged 18 years or older with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgical resection were enrolled. Patients were treated with SABR to a dose of 50 Gy in 5 fractions every other day. The study prespecified that SABR would be considered worthwhile if median overall survival-the primary end point-was longer than 1 year, with a grade 3 to 4 risk of toxic effects less than 35% and a grade 5 risk of toxic effects less than 15%. Secondary end points included toxic effects, progression-free survival (PFS), local control (LC), quality-of-life outcomes, and changes in pulmonary function. Intention-to-treat analysis was conducted. Thirty-nine patients enrolled and received SABR. Median age was 78 (IQR, 67-83) years and 59% (n = 23) were male. At baseline, 70% (26 of 37) of patients reported dyspnea, median forced expiratory volume in first second of expiration was 80% (IQR, 66%-90%) predicted, median forced vital capacity was 84% (IQR, 69%-94%) predicted, and median diffusion capacity of the lung for carbon monoxide was 49% (IQR, 38%-61%) predicted. Median follow-up was 19 (IQR, 14-25) months. Overall survival at 1 year was 79% (95%, CI 62%-89%; P < .001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Median PFS was 19 months (95% CI, 13-28 months), and 2-year LC was 92% (95% CI, 69%-98%). Adverse event rates (highest grade per patient) were grade 1 to 2: n = 12 (31%), grade 3: n = 4 (10%), grade 4: n = 0, and grade 5: n = 3 (7.7%, all due to respiratory deterioration). In this trial, use of SABR in patients with fibrotic ILD met the prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. ClinicalTrials.gov Identifier: NCT03485378.

Changes in right ventricular function and clinical outcomes following tricuspid transcatheter edge-to-edge repair.

Prognostic impact of post-procedural changes in right ventricular (RV) function after tricuspid transcatheter edge-to-edge repair (T-TEER) is still unclear. We investigated association of RV function and its post-procedural changes with clinical outcomes in patients undergoing T-TEER. We retrospectively analysed 204 patients who underwent T-TEER and echocardiographic follow-up at 3 months after T-TEER. RV function was assessed by RV fractional area change (RVFAC), and RV dysfunction was defined as RVFAC <35%. Patients with an increase in RVFAC from baseline to the follow-up were considered as RV responders. Patients were divided into four groups according to baseline RVFAC and the RV responder. The primary outcome was a composite of mortality and hospitalization due to heart failure within 1 year. Forty-five of 204 patients (22.1%) had RVFAC <35% at baseline, and 71 (34.8%) were RV responders. The association between the RV responder and the composite outcome had a significant interaction with RVFAC at baseline. Among patients with baseline RVFAC <35%, RV responders had a lower risk of the composite outcome than RV non-responders, while this association was not significant in those with baseline RVFAC ≥35%. Among patients with baseline RVFAC <35%, a smaller RV diameter and a greater reduction of tricuspid regurgitation were predictors for the RV responder. Post-procedural increase in RVFAC after T-TEER is associated with improved outcomes in patients with RV dysfunction. The factors related to the increase in RVFAC may support patient selection for T-TEER in patients with RV dysfunction.

MISSENSE MUTATIONS IN THE IRAK1 GENE ARE ASSOCIATED WITH AN INCREASED RISK OF SYSTEMIC LUPUS ERYTHEMATOSUS

Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation in humans. Missense SNPs can change protein structure and function. This study aimed to determine missense SNPs of the IRAK1 gene that can affect the amino acid sequence and lead to changes in protein structure and function, as well as their relationship as a risk factor for SLE. In this in silico method, several bioinformatics tools have been used to identify missense SNPs, including their properties and impacts, as well as their interaction networks with proteins. The tools used were PolyPhenv2, SIFT, PhD-SNP, PROVEAN, SNAP, Panthers, I-Mutant 3.0, and GeneMania. Four missense SNPs, rs11465830, rs1059702, rs1059703, and 10127175, were obtained from the NCBI SNP database. The SIFT test results showed that all the SNPs were tolerant. In the test results obtained using PolyPhen, the four SNPs were benign. The results of the probe test indicated that the four SNPs were neutral. When tested with SNAP, one SNP was neutral, and three others had an impact. In the PhD-SNP test, all SNPs were neutral. In the panther test, all SNPs were benign. The I-mutant assay showed that the four SNPs could decrease protein stability. Tests with GeneMania have reported that most interactions between genes were between IRAK1 and MYD88, and physical interactions were the most dominant form of interaction. Conclusion. rs10127175, rs11465830, rs1059702, and rs1059703 are missense SNPs in IRAK1, which can disrupt protein stability and be a risk factor for SLE. Keywords: IRAK1, SNP, Missense, Systemic Lupus Erythematosus

Alterations in metabolic pathways: a bridge between aging and weaker innate immune response.

Aging is a time-dependent progressive physiological process, which results in impaired immune system function. Age-related changes in immune function increase the susceptibility to many diseases such as infections, autoimmune diseases, and cancer. Different metabolic pathways including glycolysis, tricarboxylic acid cycle, amino acid metabolism, pentose phosphate pathway, fatty acid oxidation and fatty acid synthesis regulate the development, differentiation, and response of adaptive and innate immune cells. During aging all these pathways change in the immune cells. In addition to the changes in metabolic pathways, the function and structure of mitochondria also have changed in the immune cells. Thereby, we will review changes in the metabolism of different innate immune cells during the aging process.

Abstract B111: Mechanism-informed photochemical strategies to overcome fluid shear stress-induced platinum resistance in ovarian cancer

Abstract Background: Over 75% of patients with disseminated ovarian cancer develop resistance to platinum-based chemotherapies (carboplatin or cisplatin). Patients with a high volume of malignant ascites or excessive fluid buildup in the peritoneum are more likely to present with primary platinum-resistant disease. It is hypothesized that the physical forces generated by ascites may contribute to the dissemination and progression of ovarian cancer. Our research group has shown that fluid shear stress (FSS) induces carboplatin resistance and a motile and aggressive phenotype in monolayer cultures and 3D models for adherent ovarian cancer. In this study, the effects of FSS on treatment response to cisplatin and doxorubicin were examined. The latter is used to manage recurrent platinum-resistant disease. Changes in mitochondrial function under FSS as they relate to platinum resistance were also characterized. Finally, the use of photodynamic therapy (PDT), which utilizes 690 nm light and a clinical photosensitizer benzoporphyrin derivative (BPD) to locally generate cytotoxic reactive molecular species as a means of overcoming FSS-induced platinum resistance, was explored. Methods: Human epithelial ovarian adenocarcinoma cells OVCAR-3 and Caov-3 (ATCC) were cultured in tissue culture plates (static culture) or chamber slides (ibidi) connected to a perfusion pump for 48 h (flow rate: 0.11 mL/min, shear stress: 0.41 dyn/cm2). Cells in static and flow cultures were exposed to cisplatin, doxorubicin, BPD-PDT or combinations thereof and survival fractions were measured 72 h post-treatment. Mitochondrial membrane potential was measured using JC-1 fluorescence assay, and mitochondrial DNA (mtDNA) copy number was quantified using qPCR. ATP content per cell was measured with a CellTiterGlo luminescence assay. Results: OVCAR-3 and Caov-3 cells grown under FSS developed significant resistance to cisplatin. Specifically, 3.13 µM cisplatin induced a 50% decrease in the survival fraction in OVCAR-3 static cultures but failed to decrease the survival fraction under flow. In contrast to these findings with platins, no resistance to doxorubicin was observed under flow. Evaluation of the mitochondrial function revealed increased ATP content and mtDNA copy number in flow cultures, suggesting that increased mitochondrial activity may contribute to platinum resistance. Finally, low-dose BPD-PDT (IC10, 0.15 J/cm2) enhanced the efficacy of cisplatin in OVCAR-3 cells under flow, indicating that PDT is a viable strategy to sensitize tumors exposed to FSS to platinum-based chemotherapy. Conclusions: Our data suggest that ovarian cancer cells that acquired resistance to platinum due to FSS remain sensitive to doxorubicin. Changes in mitochondrial function, including increased ATP content per cell and mtDNA copy number, have been identified as potential contributing factors to platinum resistance under FSS. Finally, low-dose BPD-PDT can be used to re-sensitize cells to cisplatin and overcome platinum resistance. Citation Format: Marta Overchuk, Brittany P. Rickard, Justin Tulino, Frances S. Ligler, Imran Rizvi. Mechanism-informed photochemical strategies to overcome fluid shear stress-induced platinum resistance in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B111.

Impact of surgical lung biopsy on lung function and survival in patients with idiopathic pulmonary fibrosis in a multi-centre registry cohort.

Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis. Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non-SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre- and post-SLB. A total of 81 SLB patients and 468 non-SLB patients were included. In the SLB group, the post-biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p-values >0.07). In the pre-post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both). No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi-centre study of patients with IPF.

The neurological decline and psychological factors caused by coronavirus disease 2019 may be predictors of erectile dysfunction.

Since the outbreak of coronavirus disease 2019, it has had a serious impact on people's physical and mental health. However, in our clinical work, we have found that the erectile function of coronavirus disease 2019 patients with neurological decline was often seriously affected. To further explore the relationship between erectile dysfunction and neurological dysfunction caused by coronavirus disease 2019. We conducted a survey from August 2022 to February 2023 at the First Affiliated Hospital of Anhui Medical University and the Third People's Hospital of Linyi City. A total of 251 subjects with a history of coronavirus disease 2019 infection were included. Symptoms and changes in erectile function after the coronavirus disease 2019 infection were collected and assessed using the International Index of Erectile Function-5 scale and several targeted questions. In this study, we found that in patients infected with novel coronavirus, the proportion of erectile dysfunction was higher in those with neurological manifestations such as olfactory and taste impairment or psychological symptoms such as anxiety. We found that neurological decline and psychological factors were independent and significant risk factors for erectile dysfunction caused by coronavirus disease 2019. Patients with neurological damage or psychiatric symptoms are more likely to have erectile dysfunction, suggesting that the 2019 novel coronavirus may affect erectile function by damaging nerves. This provides a new insight into the mechanism of erectile dysfunction.

(155) The Erectile Restoration Registry: It MATTERS

Abstract Introduction Treatment methodology for erectile dysfunction can vary from surgeon to surgeon. The It MATTERS registry has been developed to align prospective, long-term, real-world outcomes with current clinical practice. It MATTERS is an immediate avenue (following market approval of a product) to collect and monitor real-world data on existing and future innovation, with respect to Boston Scientific’s penile prostheses (2- and 3-piece inflatable, and malleable), Rear Tip Extenders, surgical tools (sterile and non-sterile), accessories, kits, and all included components. This includes, but is not limited to, the Furlow Insertion Tool, Disposable Dilators, Sizers, Insertion Package (tubing passers), Proximal Tool, Quick Connect Assembly Tool, AMS Closing Tool, and the Deactivation Package. Objective Description of a real-world registry that evaluates erectile function, post-penile prosthesis implantation, over time. Methods It MATTERS is a single-arm, prospective, multi-center registry with follow-up occurring post-surgery and at 6 months, 12 months, and annually, thereafter. Subjects will serve as their own control; follow-up assessments will be compared to values collected at baseline. The registry is designed to capture the wide array of immediate, post-surgery follow-up schedules without dictating a specific visit cadence. Following signature of an informed consent, eligible subjects are treated with a Boston Scientific penile prosthesis. The registry will enroll over the lifetime of each device, allowing for up to 150 active subjects in follow-up, per device. Results Registry endpoints include measuring change in erectile function from baseline using the Erectile Function domain of the International Index of Erectile Function (IIEF-EF), change in depressive symptoms using the Patient Health Questionnaire (PHQ)-9, overall sexual function using the IIEF Total Score, and change in work productivity using the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH). Additional measures, amongst many, include patient-reported device satisfaction using a 5-point Likert scale and adverse events. For each penile prothesis group in the registry, a two-sided 95% confidence interval may be constructed for interpreting the change in IIEF-EF score over time compared to baseline. Descriptive statistics will summarize continuous and categorical variables. Currently, 51 penile prosthesis implants have been completed: Tactra™ Malleable Penile Prosthesis (n = 34), Spectra™ Concealable Penile Prosthesis (n = 9), and AMS Ambicor™ Inflatable Penile Prosthesis (2-piece; n = 8). Conclusions The It MATTERS registry builds on over 50 years of erectile dysfunction patient care and data. It will allow for the comparison of outcomes and clinical practice on legacy and new market-approved products, which will pave the way for future innovation and advancing patient care. Disclosure Yes, this is sponsored by industry/sponsor: Industry initiated, executed, and funded registry. All authors act as consultants, employees, or shareholders of Boston Scientific Corporation. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific Corporation.

Dynamics of IGF signalling during the ovulatory peak in women undergoing ovarian stimulation.

IGF signalling is known to affect human ovarian follicular function during growth and development. However, the role of the IGF system is unknown during the ovulatory peak, which is characterized by profound changes in granulosa cell (GCs) mitosis and function. How is the IGF system expressed and regulated during the midcycle surge in women? Follicular fluid (FF) and granulosa cells (GCs) were collected during the ovulatory peak from two specific time-points. One sample was obtained before oocyte pick up (OPU): before ovulation trigger (OT) (T = 0 h) or at 12, 17, or 32 h after OT, and one sample was obtained at OPU 36 h after OT. University hospital. Fifty women undergoing ovarian stimulation were included. Gene expression profiles were assessed by microarray analysis of GCs. IGF-related proteins in the FF were assessed by using immunoassays or by determination of activity with a proteinase assay. Expression of proteins promoting IGF activity (i.e., IGF2, PAPPA, and IRS1) together with proliferation markers were downregulated on a transcriptional level in GCs after OT, whereas proteins inhibiting the IGF signal (i.e., IGFBPs, IGF2R, and STC1) were upregulated. STC1 gene expression and protein levels were greatly upregulated after OT with a parallel steep downregulation of PAPP-A proteolytic activity. These data suggest that downregulation of IGF signalling mediated by increased STC1 expression is instrumental for the sudden cessation in GC proliferation and onset of differentiation during the ovulatory peak.

(046) Pattern of Sexual Activities among Pregnant Women Attending Antenatal Clinic

Abstract Introduction Sexuality is rarely discussed in many cultures even in clinical context. Sexual repression and abstinence are not uncommon among pregnant women due to several factors; some of which may be related to ignorance. The pattern of sexual activity in pregnancy with its associated changes and challenges remain poorly understood due to a complex interplay of bio-psycho-social factor. Objective This study demonstrates the pattern of sexual activities among pregnant women with associated changes resulting from pregnancy as well as perception and experiences of these women about sexual activities and function in pregnancy. Methods Pre-tested self-administered questionnaires were used to obtain data from women in second and third trimesters of uncomplicated pregnancies about their sexual activities before and during pregnancy as well as their perception about sexual activities in pregnancy. Results The study recruited 228 pregnant women aged 19 to 44years (Mean - 31.7years) with an average gestational age of 27.8weeks and most (93.8%) were singleton. Most of the respondents were married (97.4%) with tertiary level of education (87.9%). Majority (60.1%) were multiparous and most (96.5%) have commenced antenatal care. Majority (58.8%) reported only one lifetime sexual partner with mean age at coitarche of 23.6years. Only 1.3% have multiple sexual partners during the index pregnancy. Most (74.8%) had sexual activities at least once weekly prior pregnancy. During pregnancy however, only 48% had sexual activities at least once weekly, 25.3% had sexual activity less than once monthly, 5.8% had no sexual activity at all in pregnancy. Frequency of sexual activity in pregnancy was moderately associated with frequency before pregnancy (Pearson–0.428, p-0.000). Regarding changes in sexual activity and function associated with pregnancy; 53.5% reported a negative effect, 28.6% had improvement and 18% reported no change in frequency of sexual activities. Regarding sexual desire, 46.1% had reduction, 31.6% reported improvement and 22.3% reported no effect on their desire. For lubrication however, 39.5% had improvement, 31.2% reported reduction whereas 29.3% reported no change. Their overall satisfaction with their sexual function was reported as better in pregnancy m 43.7%, no change in 20.2% and reduction in 36.1%. Although 77.5% of respondents agreed that regular sexual activities can improve bonding with their partners, 64.3% of respondents were afraid of risk of injury to the baby, 58.8% were afraid of risk of infection, and 51.2% were afraid of bleeding in pregnancy and these fears were reported as reasons for their decision regarding sexual activities in pregnancy. Conclusions Marked reduction in frequency of sexual activities were reported in pregnancy; women who had infrequent intercourse prior pregnancy were more likely to have infrequent intercourse in pregnancy. Fear of injury to the baby, bleeding and infection were among the topmost reasons sexual activities were avoided in pregnancy. Education of pregnant women may reduce unnecessary abstinence and sexual repression in pregnancy and avoid its psychosocial consequences on these women and their partners. Disclosure No.

(225) Female Sexual Function During the Last Trimester of Pregnancy

Abstract Introduction Since antiquity and until today, sexuality remains a taboo and complex subject, often little discussed either in private circles or with healthcare professionals. Although advertising and the media sometimes use it to attract attention, sexuality is still synonymous with the unknown, raising several interrogations. These concerns are accentuated during the onset of pregnancy and all the physical, psychological, and environmental upheavals associated with this physiological state. Objective This study aims to assess the changes in female sexual function during the third trimester of pregnancy Methods It is a cross-sectional online study that took place over 5 weeks starting March 1st, 2023. All low-risk singleton third-trimester pregnant and newly delivered women enrolled in the public and private prenatal care centers of the region were contacted through the institutions’ social media groups to be recruited. The online questionnaire was a 4-item Google form elaborated in concertation with the literature and included the validated translated version of the Female Sexual Function Index (FSFI). Results The study included 81 married participants (8% response rate). The median age of the participants was 30,4± 6,9 years and 65,4% of them were employed when pregnant. The mean pregnancy rate per participant was 2,7± 1,9 and 90% of the pregnancies were spontaneous. When questioned about their sexual life during the 3rd trimester of pregnancy, 68% of the participants report being uncomfortable when the subject of sexuality is on the table. Most of the respondents (78%) were unsatisfied with their couple's sexuality during pregnancy. A low sexual desire was reported in 84,0%, dyspareunia in 55,6% with a decrease in lubrification in 16,0%, and orgasm disorders in 17,3%. Secondary vaginismus was described by 12,3%. Partners initiated sexual intercourse according to 72,8% of the respondent. Sexual intercourses were mutually initiated in 27,2%. Pregnant women reported a change in their sexual life during the 3rd trimester in 96,3%: the 7th month of pregnancy is associated with less frequent (70,5%) and shorter (69,2%) penetrative intercourses with lower female sexual desire (48,7%). The 8th and 9th months are associated with lower sexual desire (80,8%; 94,9%), lower sexual pleasure (75,6%; 92,3%), and less frequent orgasms (67,9%; 82,1%) and penetrative intercourses (85,9%; 93,6%). Conclusions Our results suggest that the third trimester in singleton low-risk pregnancies is associated with severe impairment of the female sexual function in relation to less frequent and shorter penetrative intercourses, lower desire, and pleasure associated with a general sexual unsatisfaction. Disclosure No.

Thromboelastographic evaluation of the effectiveness of choline or CDP-choline treatment on endotoxin-induced hemostatic alterations in dogs

Sepsis/endotoxemia associates with coagulation abnormalities. We showed previously that exogenous choline treatment reversed the changes in platelet count and function as well as prevented disseminated intravascular coagulation (DIC) in endotoxemic dogs. The aim of this follow-up study was to evaluate the effect of treatment with choline or cytidine-5′-diphosphocholine (CDP-choline), a choline donor, on endotoxin-induced hemostatic alterations using thromboelastography (TEG). Dogs were randomized to six groups and received intravenously (iv) saline, choline (20 mg/kg) or CDP-choline (70 mg/kg) in the control groups, whereas endotoxin (0.1 mg/kg, iv) was used alone or in combination with choline or CDP-choline at the same doses in the treatment groups. TEG variables including R- and K-time (clot formation), maximum amplitude (MA) and α-angle (clot stability), G value (clot elasticity), and EPL, A, and LY30 (fibrinolysis), as well as overall assessment of coagulation (coagulation index - CI), were measured before and at 0.5–48 h after the treatments. TEG parameters did not change significantly in the control groups, except for CI parameter after choline administration. Endotoxemia resulted in increased R-time and A value (P < 0.05), decreased K-time (P < 0.05), α-angle (P < 0.001) and CI values (P < 0.01) at different time points. Treatment with either choline or CDP-choline attenuated or prevented completely the alterations in TEG parameters in endotoxemic dogs with CDP-choline being more effective. These results confirm and extend the effectiveness of choline or CDP-choline in endotoxemia by further demonstrating their efficacy in attenuating or preventing the altered viscoelastic properties of blood clot measured by TEG.

Effects of Verbal and Tactile Cues on Gluteal Force Production and Broad Jump Distance.

Verbal and tactile cues can increase muscle activity, force production, and kinematics. Several studies demonstrate the effects of verbal and tactile cues on upper extremity muscles, while relatively few examined lower extremity muscles, specifically the gluteals. Studies that observed changes in gluteal function from verbal and tactile cues examined muscle activity via electromyography rather than force production or functional activities such as jumping. The purpose of this study was to measure the effects of verbal and tactile cues on gluteal force production and broad jump distance. Cross-Sectional cohort. Gluteus maximus force production and broad jump distance were tested in forty-two healthy male and female university students at baseline and after verbal and tactile cues given in random order. Gluteus maximus force was measured using handheld dynamometry and reported in kilograms. Verbal cues included "push, push, push" before both tests. The examiner provided tactile cues to the gluteus maximus before force production testing, and the participant provided tactile cues to both gluteus maximus muscles before performing the broad jump. Performance on the broad jump was measured in centimeters. Descriptive statistics and test-retest reliability via Pearson correlation coefficients were calculated, differences in performance between sexes were analyzed with an independent t-test, and changes in force production and jump distance from baseline were analyzed using a one-way ANOVA. Mean gluteus maximus force production following verbal cues significantly increased (p = 0.000) by 13.48% (3.83 kg) compared to the control condition, while gluteal force production following the tactile cues was not significantly different. Broad jump distance following the verbal cues significantly increased (p = 0.000) 3.99% (7.71 cm) compared to the control condition and significantly increased (p = 0.000) by 2.95% (5.71 cm) following the tactile cues. There were no significant differences in performances between males and females. The test-retest reliability of all measurements was 0.97-0.99. Verbal cues significantly increased gluteus maximus force production and broad jump distance. Tactile cues significantly increased broad jump distance but had no significant effect on gluteus maximus force. These results have implications for clinical testing and athletic performance when gluteus maximus force and jump distance are concerned. 3.

The multi‐factorial modes of action of urease in the pathogenesis of incontinence associated dermatitis

AbstractBackgroundIncontinence Associated Dermatitis (IAD) is a type of skin inflammation caused by chronic exposure to urine and/or faeces. Current treatment strategies involve creating a barrier between the skin and urine/faeces rather than targeting specific irritants. Urease expressing pathogens catalyse the conversion of urea, present in urine, into ammonia. The accumulation of ammonia causes an elevation in skin pH which is believed to activate faecal enzymes which damage skin, and opportunistic pathogens, which lead to secondary infections.ObjectivesTo develop a better, multi‐factorial model of IAD pathogenesis, including the effect of urease‐expressing bacteria on skin, mechanism of damage of urease and urease‐triggered activity of faecal enzymes and secondary pathogens. To study the effect of urease inhibition on preventing IAD skin damage.MethodsFive separate studies were made using ex vivo porcine skin and in vivo human skin models. Measurements of the change in skin barrier function were made using skin impedance, trans‐epidermal water loss (TEWL), stratum corneum moisture and pH. Skin was exposed to artificial urine, inoculated with various microbes, enzymes and chemicals to examine the influence of: 1) urease‐positive Proteus mirabilis 2) ammonia, 3) combination of P. mirabilis and a faecal enzyme, trypsin, 4) combination of P. mirabilis and opportunistic pathogens, Candida albicans and Staphylococcus aureus, 5) inhibition of urease using acetohydroxamic acid (AHA) on barrier function.ResultsThe urease‐mediated production of ammonia had two principal effects: it elevated skin pH and caused inflammation, leading to significant breakdown in skin (stratum corneum) barrier function. Urease was found to further increase the activity of faecal enzymes and opportunistic pathogens, due to elevated skin pH. The urease inhibitor, AHA, was shown to have significantly reduced damage to skin barrier function, measured as its electrical resistance.ConclusionsTargeted therapeutic strategies should be developed to prevent the manifestation of IAD, rather than creating a generic barrier between skin and urine/faeces. Urease has been identified as a crucial component in the manifestation of IAD, due to its role in the production of ammonia. Urease inhibition provides a promising therapeutic target to halt the progression of IAD.

Glycine Receptor β-Targeting Autoantibodies Contribute to the Pathology of Autoimmune Diseases.

Stiff-person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM) are rare neurologic disorders of the CNS. Until now, exclusive GlyRα subunit-binding autoantibodies with subsequent changes in function and surface numbers were reported. GlyR autoantibodies have also been described in patients with focal epilepsy. Autoimmune reactivity against the GlyRβ subunits has not yet been shown. Autoantibodies against GlyRα1 target the large extracellular N-terminal domain. This domain shares a high degree of sequence homology with GlyRβ making it not unlikely that GlyRβ-specific autoantibody (aAb) exist and contribute to the disease pathology. In this study, we investigated serum samples from 58 patients for aAb specifically detecting GlyRβ. Studies in microarray format, cell-based assays, and primary spinal cord neurons and spinal cord tissue immunohistochemistry were performed to determine specific GlyRβ binding and define aAb binding to distinct protein regions. Preadsorption approaches of aAbs using living cells and the purified extracellular receptor domain were further used. Finally, functional consequences for inhibitory neurotransmission upon GlyRβ aAb binding were resolved by whole-cell patch-clamp recordings. Among 58 samples investigated, cell-based assays, tissue analysis, and preadsorption approaches revealed 2 patients with high specificity for GlyRβ aAb. Quantitative protein cluster analysis demonstrated aAb binding to synaptic GlyRβ colocalized with the scaffold protein gephyrin independent of the presence of GlyRα1. At the functional level, binding of GlyRβ aAb from both patients to its target impair glycine efficacy. Our study establishes GlyRβ as novel target of aAb in patients with SPS/PERM. In contrast to exclusively GlyRα1-positive sera, which alter glycine potency, aAbs against GlyRβ impair receptor efficacy for the neurotransmitter glycine. Imaging and functional analyses showed that GlyRβ aAbs antagonize inhibitory neurotransmission by affecting receptor function rather than localization.