Normal Function Research Articles

<i>Congenital Analbuminemia</i>

Congenital analbuminemia (CAA) is a rare autosomal recessive disorder, characterized by the absence or very low level of serum albumin (human serum albumin/HSA) as a result of defect on chromosome 4 which encodes albumin. It is defined as albumin level <1 g/l with normal liver function and the absence of protein loss.1,2 Estimated CAA prevalence is less than 1 in 1 million.A 10-year-old boy suffered from generalized edema that got worsened since last month. The patient had been misdiagnosed with nephrotic syndrome 2 years earlier, and then became protein-losing enteropathy. Neither cough nor diarrhea were reported. The patient had history of food allergy. Physical examination showed moderately ill condition, Glasgow Coma Scale (GCS) score E4 V5 M6, blood pressure 90/50 mmHg, pulse 120 x/min, respiratory rate 30x/min, palpebral edema, shifting dullness, undulation (+), with nonpitting edema on the extremities. Laboratory findings: leukocytosis (neutrophilia), peripheral blood smear showed hypochromic microcytic anisositosis erythrocyte. AAT serum 246 mg/dl, GGT serum: 88 U/l, iron serum 28 µg/dl, TIBC 411 µg/dl, transferrin saturation 7%, total IgE 775,90 U/ml. Serum Protein Electrophoresis (SPE) results were hypoalbuminemia (1,4 g/dl), hypogammaglobulinemia (0,21 g/dl), and total protein 2,91 g/dl. Chest X-ray showed pneumonia with minimal right pleural effusion. Overestimation of serum albumin level was caused by alpha and beta globulin that were detected as albumin in bromocresol green (BCG) methods. CAA aggravated with by allergy caused malnutrition in this patient. These data support the diagnosis of CAA with sepsis and iron deficiency anemia. Suggestion for the management consist of blood culture, procalcitonin level measurement, inguinal lymph node biopsy, DNA sequence analysis, also analysis of pleural and ascites fluid.

Evaluation of split renal dysfunction using radiomics based on magnetic resonance diffusion-weighted imaging.

Accurate and noninvasive assessment of split renal dysfunction is crucial, while there is lack of corresponding method clinically. To investigate the feasibility of using diffusion-weighted imaging (DWI)-based radiomics models to evaluate split renal dysfunction. We enrolled patients with impaired and normal renal function undergoing renal DWI examination. Glomerular filtration rate (GFR, mL/min) was measured using 99mTc-DTPA scintigraphy, which is reference standard of GFR measurement. The kidneys were classified into normal (GFR ≥40), mildly impaired (20≤ GFR<40), moderately impaired (10≤ GFR<20), and severely impaired (GFR<10) renal function groups. Optimized subsets of radiomics features were selected from renal DWI images and radiomics scores (Rad-score) calculated to discriminate groups with different renal function. The radiomics model (Rad-score based) was developed in a training cohort and validated in a test cohort. Evaluations were conducted on the discrimination, calibration, and clinical application of the method. The final analysis included 330 kidneys. Logistic regression was used to develop three radiomics models, model A, B, and C, which were used to distinguish normal from impaired, mild from moderate, and moderate from severe renal function, respectively. The area under the curve of the three models were 0.822, 0.704, and 0.887 in the training cohort and 0.843, 0.717, and 0.897 in the test cohort, respectively, indicating efficient discrimination performance. DWI-based radiomics models have potential for evaluating split renal dysfunction and discriminating between normal and impaired renal function groups and their subgroups.

A novel mutation of DNA2 regulates neuronal cell membrane potential and epileptogenesis.

Mesial temporal lobe epilepsy (MTLE) is one of the most intractable epilepsies. Previously, we reported that mitochondrial DNA deletions were associated with epileptogenesis. While the underlying mechanism of mitochondrial DNA deletions during epileptogenesis remain unknown. In this study, a novel somatic mutation of DNA2 gene was identified in the hippocampal tissue of two MTLE patients carrying mitochondrial DNA deletions, and this mutation decreased the full-length expression of DNA2 protein significantly, aborting its normal functions. Then, we knocked down the DNA2 protein in zebrafish, and we demonstrated that zebrafish with DNA2 deficiency showed decreased expression of mitochondrial complex II-IV, and exhibited hallmarks of epileptic seizures, including abnormal development of the zebrafish and epileptiform discharge signals in brain, compared to the Cas9-control group. Moreover, our cell-based assays showed that DNA2 deletion resulted in accumulated mitochondrial DNA damage, abnormal oxidative phosphorylation and decreased ATP production in cells. Inadequate ATP generation in cells lead to declined Na+, K+-ATPase activity and change of cell membrane potential. Together, these disorders caused by DNA2 depletion increased cell apoptosis and inhibited the differentiation of SH-SY5Y into branched neuronal phenotype. In conclusion, DNA2 deficiency regulated the cell membrane potential via affecting ATP production by mitochondria and Na+, K+-ATPase activity, and also affected neuronal cell growth and differentiation. These disorders caused by DNA2 dysfunction are important causes of epilepsy. In summary, we are the first to report the pathogenic somatic mutation of DNA2 gene in the patients with MTLE disease, and we uncovered the mechanism of DNA2 regulating the epilepsy. This study provides new insight into the pathogenesis of epilepsy and underscore the value of DNA2 in epilepsy.

Therapeutic targeting of TP53 nonsense mutations in cancer.

Mutations in the TP53 tumor suppressor gene occur with high prevalence in a wide range of human tumors. A significant fraction of these mutations (around 10%) are nonsense mutations, creating a premature termination codon (PTC) that leads to the expression of truncated inactive p53 protein. Induction of translational readthrough across a PTC in nonsense mutant TP53 allows the production of full-length protein and potentially restoration of normal p53 function. Aminoglycoside antibiotics and a number of novel compounds have been shown to induce full-length p53 in tumor cells carrying various TP53 nonsense mutations. Full-length p53 protein generated by translational readthrough retains the capacity to transactivate p53 target genes and trigger tumor cell death. These findings raise hopes for efficient therapy of TP53 nonsense mutant tumors in the future.

A study on the application of radiomics based on cardiac MR non-enhanced cine sequence in the early diagnosis of hypertensive heart disease

BackgroundThe prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension.Methods132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity.ResultsThe feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively.ConclusionsRadiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD.

Influence of intersignaling crosstalk on the intracellular localization of YAP/TAZ in lung cells.

A cell is a dynamic system in which various processes occur simultaneously. In particular, intra- and intercellular signaling pathway crosstalk has a significant impact on a cell's life cycle, differentiation, proliferation, growth, regeneration, and, consequently, on the normal functioning of an entire organ. Hippo signaling and YAP/TAZ nucleocytoplasmic shuttling play a pivotal role in normal development, homeostasis, and tissue regeneration, particularly in lung cells. Intersignaling communication has a significant impact on the core components of the Hippo pathway and on YAP/TAZ localization. This review describes the crosstalk between Hippo signaling and key lung signaling pathways (WNT, SHH, TGFβ, Notch, Rho, and mTOR) using lung cells as an example and highlights the remaining unanswered questions.

THE RELATIONSHIP OF FAMILY EATING PATTERNS WITH THE INCIDENCE OF OBESITY IN SCHOOL CHILDREN AT RT. 006 RW. 069 KELURAHAN 16 ULU PALEMBANG

Background: Obesity is a pathological condition, namely the accumulation of excess fat than is required for normal body function. However, there are still many opinions in society that think that obese children are healthy. Objective: This research aims to analyze the relationship between family diet and the incidence of obesity in school children in RT 006 RW. 069 Subdistrict 16 Ulu Palembang. Methodology: The research method is collecting data by direct interviews with respondents and analyzing the data. Results: There were 75% of respondents adopting eating patterns that were not good for their children and 25% of respondents adopting eating patterns that were good for their children. Conclusion: This research shows a p value of 0.016, meaning there is a relationship between eating patterns and incidents. obesity in children with an OR of 8.31, meaning that children who adopt poor eating patterns have an 8.31 chance of experiencing obesity.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines.

Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

Addressing the unspoken: sexual dysfunction in men with systemic lupus erythematosus, a call to action for rheumatologists.

Sexual dysfunction (SD) is highly prevalent and multifactorial; nevertheless, recent research has shed light on a notable phenomenon: male patients with systemic lupus erythematosus (SLE) exhibit an elevated prevalence of sexual function disorders compared with the general population. Despite this recognition, the precise nature and extent of this association remain incompletely understood. This comprehensive review aims to clarify the link by providing an overview of the fundamental components of normal male sexual function, delving into the pathogenesis of male SD and exploring the primary factors predisposing male SLE patients to SD. Additionally, the review offers insights into potential screening, diagnostic, and treatment strategies based on the current body of literature. A meticulous search of relevant literature was conducted using the PubMed and Google Scholar databases. Studies exploring the correlation between SLE and SD in both genders have revealed a nearly 2-fold increased risk of SD among individuals with SLE compared with healthy counterparts. Moreover, these studies suggest that male SLE patients may have a higher susceptibility to SD, with reported prevalence ranging from 12% to 68%, compared with 0% to 22% in healthy individuals. Male patients with SLE are influenced by a spectrum of pathological factors, including pharmacological, psychological, and disease-related determinants, which, through their intricate interplay, elevate the likelihood of developing SD. Healthcare professionals must remain vigilant in understanding the intricacies of human sexuality and its dysfunction, particularly in males with SLE. The objective is to establish effective and potentially standardized methods for promptly diagnosing and optimally managing SD, recognizing its significant impact on the quality of life for males living with SLE. The pivotal role of rheumatologists in initiating discussions about sexual health, diagnosing SD, investigating causes, and implementing tailored strategies is underscored as crucial in addressing this multifaceted issue.

Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19

BackgroundRenal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes.MethodsThis retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression.ResultsThe prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only.ConclusionsClinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.

Development and Characterization of Hemoglobin Microbubbles for Acoustic Blood Oxygen Level Dependent Imaging.

Oxygen levels in tissues and organs are crucial for their normal functioning, and approaches to monitor them non-invasively have wide biological and clinical applications. In this study, we developed a method of acoustically detecting oxygenation using contrast-enhanced ultrasound (CEUS) imaging. Our approach involved the use of specially designed hemoglobin-based microbubbles (HbMBs) that reversibly bind to oxygen and alter the state-dependent acoustic response. We confirmed that the bioactivity of hemoglobin remained intact after the microbubble shell was formed, and we did not observe any significant loss of heme. We conducted passive cavitation detection (PCD) experiments to confirm whether the acoustic properties of HbMBs vary based on the level of oxygen present. The experiments involved driving the HbMBs with a 1.1 MHz focused ultrasound transducer. Through the PCD data collected, we observed significant differences in the subharmonic and harmonic responses of the HbMBs when exposed to an oxygen-rich environment versus an oxygen-depleted one. We used a programmable ultrasound system to capture high-frame rate B mode videos of HbMBs in both oxy and deoxy conditions at the same time in a two-chambered flow phantom and observed that the mean pixel intensity of deoxygenated HbMB was greater than in the oxygenated state using B-mode imaging. Finally, we demonstrated that HbMBs can circulate in vivo and are detectable by a clinical ultrasound scanner. To summarize, our results indicate that CEUS imaging with HbMB has the potential to detect changes in tissue oxygenation and could be a valuable tool for clinical purposes in monitoring regional blood oxygen levels.

Outcomes of leadless pacemaker in chronic kidney disease patients: real-world data from the i-LEAPER registry

Abstract Background Chronic kidney disease (CKD) represents a major risk factor for patients requiring transvenous pacemaker (TV-PM), resulting in a high rate of operative complications and PM-related infection rate (21.9% and 12.5%, respectively), with both complications parallels to severity of CKD. Moreover, TV leads represent an important concern for end-stage CKD patients, often needing vascular access patency for renal replacement therapy. In this setting leadless pacemakers (LPMs) represent an attractive alternative to TV-PM for their lower device-related infection rate and the absence of TV leads. To date, limited data on LPM safety and efficacy profile in CKD patients are available. Purpose to assess operative and long-term safety and efficacy of LPMs implantation in patients with different stages of CKD in the real-world setting. Methods Consecutive patients who underwent LPM implantation in 12 European centers joining the i-LEAPER registry were retrospectively enrolled. CKD stage was assessed according to CKD-EPI equation for eGFR. Patients with CKD stage G3a/b (N=245) and stage G4/G5 (N=67) were compared with patients with normal kidney function (NKF) (N=867). Primary safety endpoint was LPM-related major complications rate at implant and during follow-up (FU). Additionally, the rate of patients showing sub-optimal electrical performance (pacing threshold [PT] &amp;gt;1V@0.24ms) was compared between groups. Results 1179 patients were enrolled and followed for a median of 33 [IQR 24-47] months. When compared with the NKF group, patients with CKD stage G3a/b and stage G4/G5 showed a higher burden of cardiovascular comorbidities (Table 1). The choice of a LPM was mainly due to vascular concern in the CKD stage G4/G5 group, while a perceived highest infective risk was reported in CKD stage G3a/b group (Table 1). Major complication rate at implant and during FU did not differ between groups, regardless of renal impairment stage (Table 2). All-cause mortality incidence resulted higher in CKD stage G4/G5 group when compared with NKF group (17.9% vs 6.8%; HR 4.24; 95%CI 4.25-7.94, p&amp;lt;0.001) (Figure A). The rate of patients with PT&amp;gt;V1@0.24ms during FU did not differ between groups, not exceeding 13.8%, and therefore remaining consistent with historical data for LPM (Figure B). Conclusion In the real-world setting, LPM showed a remarkable safety and efficacy profile in CKD patients regardless of renal impairment stage that was comparable to NKF population. LPM should be considered as first choice in CKD patients requiring a PM.

Reversible acute heart failure induced by thyrotoxic cardiomyopathy: A case report.

Thyrotoxic cardiomyopathy is a rare but severe complication of thyrotoxicosis, leading to episodes of acute heart failure. This case report highlights a rare presentation of thyrotoxic cardiomyopathy with low-output heart failure, emphasizing the importance of early diagnosis and comprehensive management. The report aims to increase awareness among clinicians about the potential reversibility of this condition and the effective strategies for managing such complex cases. This patient presented with dyspnea and chest constriction, without any antecedent predisposing factors. Subsequently, the patient abruptly manifested symptoms indicative of acute heart failure during outpatient consultation. Electrocardiography revealed rapid atrial fibrillation with type A preexcitation syndrome, whereas cardiac ultrasonography demonstrated global cardiac enlargement with a diminished ejection fraction (EF). After a comprehensive evaluation, the patient was diagnosed with thyrotoxic cardiomyopathy, acute heart failure, and atrial fibrillation with preexcitation syndrome. Immediate interventions comprised diuretic administration, oxygen therapy, and antiarrhythmic agents, addressing acute heart failure concomitant with preexcitation syndrome. Following a fortnight of comprehensive therapeutic measures, the patient was discharged with a prescription for oral medications, notably methimazole. Following the intervention, the patient showed significant improvement with the resolution of heart failure symptoms and dyspnea, restoration of sinus rhythm, improved left ventricular ejection fraction (LVEF improved from 36% to 45%), and normalization of thyroid function. These outcomes underscore the efficacy of the intervention strategy and offer a hopeful prognosis for similar cases. Thyrotoxicosis may cause cardiomyopathy in patients with heart failure that manifests as dilated cardiac chambers. Clinicians should carefully screen patients for this reversible condition. Diagnosis requires a comprehensive assessment of various tests, and the therapeutic goal is to restore normal thyroid function.

Staged hybrid convergent procedure versus pulsed field ablation for pulmonary veins and posterior wall isolation in the treatment of atrial fibrillation

Abstract Background There are limited effective treatment options for persistent atrial fibrillation (AF) patients, with pulmonary veins (PV) isolation alone being considered suboptimal for many patients. Hybrid convergent ablation has been shown to improve clinical outcomes when compared to an endocardial-only radiofrequency (RF) strategy. Pulsed field ablation (PFA) has recently gained growing interest for its efficacy and safety profile in PV and posterior wall (PW) ablation. Objectives To compare clinical outcomes of hybrid convergent RF ablation versus endocardial PFA for PV and PW isolation in patients with persistent AF. Methods From July 2022, 86 persistent AF consecutive patients, receiving endocardial PFA of PV and PW (PFA group, N = 44) or receiving hybrid convergent RF ablation (Hybrid group, N = 42) at our institution were enrolled. Recurrence was defined as any atrial tachyarrhythmia following the 3-month blanking period. Results No differences were found between PFA and Hybrid groups regarding age (PFA 66.0±7.4 years vs Hybrid 63.9±10.6 years; p=0.193) and left atrial volume index (PFA 45.5 [36.7-57.2] ml/m² vs Hybrid 45.0 [39.2-59.7] ml/m²; p=0.920). Differences regarding left ventricular ejection fraction were borderline significant among groups (PFA 55.0 [49.5-62.0]% vs Hybrid 60.5 [52.3-65.0]%; p=0.048), both showing an overall normal LV function. There were no significant differences regarding AF duration (PFA 38.0 months [IQR: 19.2 to 99.0 months] vs Hybrid 70.0 months [IQR: 46.0 to 118.0 months]; p = 0.063). Redo ablation patients’ rate was higher in the hybrid group (PFA n=16, 36.4% vs Hybrid n=28, 66.6%; p&amp;lt;0.001). Procedure duration was Ionger in the hybrid group (179.9±60.1 minutes) compared to PFA endocardial ablation (PFA 106.2±30.7 minute; p&amp;lt;0.01). After a median follow-up of 233.0 [179.0–331.8] days, there was no difference in atrial tachyarrhythmias recurrence rate (PFA n=11, 25.0% vs Hybrid n=10, 23.8%; p=0.897); no difference in the antiarrhythmic drug use rate was found (PFA n=24, 54.5% vs Hybrid n=19, 45.2%; p=0.388). Conclusions PFA of PV and PW, compared with the hybrid convergent ablation strategy, is an endocardial-only, less invasive, and faster procedure. 6-month rhythm outcomes were similar in both groups.

Heart rate is an important predictor of pacing induced cardiomyopathy in a machine learning analysis

Abstract Background 10-20% of patients who have right ventricular pacing develop pacing induced cardiomyopathy (PICM). Home monitoring (HM) could identify patients developing PICM in real-time and facilitate echocardiographic confirmation, medication optimisation and if necessary cardiac resynchronisation therapy (CRT). Purpose To identify predictors of PICM using machine learning models. Methods Consecutive cases of patients who developed PICM (12) after dual chamber pacing were identified from our implant database and matched 4:1 with propensity matched controls who underwent pacing but did not develop PICM (48) (Table 1.) HM data from the 6 months prior to echocardiographic diagnosis of PICM was analysed. PICM was defined as (1) a deterioration in left ventricular (LV) ejection fraction (EF) of &amp;gt;10%, (2) to an EF of &amp;lt;45%, (3) with right ventricular (RV) pacing &amp;gt;20% and (4) the exclusion of alternative causes. Three types of ML models were generated (1) random forest, (2) extreme gradient boosted (XGBoost) (3) K-nearest neighbours algorithm (KNN), with 10-fold cross-validation. Results HM data were available for 12 PICM cases (75 ± 8 years, 72% male). PICM occurred at 2.0 ± 1.2 years. There was no difference between cases and controls in atrial pacing (8±15% vs 18±22% p=0.14), ventricular pacing (81±29% vs 85±24% p=0.62) or base rate (53±5bpm vs 53±5bpm p=0.80). Of the 34 RM features analysed, mean ventricular heart rate was identified as the most important predictor of PICM; area under curve with XG Boost 0.95, KNN 0.95, and random forest 0.86. Other RM features failed to add any more predictive power to the models. Mean ventricular rate was significantly higher in cases than controls (80±6 bpm vs 69±9 bpm p&amp;lt;0.001). Sensitivity analysis was performed to assess whether episodes of atrial fibrillation (AF) were responsible for the higher ventricular rates. After days of AF days were excluded, mean ventricular rate was still significantly higher in cases than controls (79± 6vs 69±9bpm p&amp;lt;0.001) (Figure 1). 10/12 patients had a subsequent CRT upgrade. No consistent pattern emerged in heart rate changes in the first 3 months after CRT upgrade. Conclusion In a group of patients with normal left ventricular function at implant, remotely monitored heart rate can predict early-onset PICM. Further work is required to understand when these heart rate differences emerge, and whether they improve with positive LV remodelling.Table 1.Figure 1.

P.023 Review of imaging changes, cognitive decline, and dementia risk in cancer survivors after chemotherapy

Background: Cancer survival rates in Canada have been improving, leading to a steady increase in the number of survivors entering the typical ages of dementia onset. Yet, some cancer treatments (e.g. chemotherapy) are neurotoxic and adversely affect normal brain functioning. We conducted a review to examine changes observed in brain imaging and cognitive measures in survivorship, and long-term risk of dementia among cancer survivors. Methods: 91 Primary studies were selected from PubMed. Inclusion criteria were studies investigating the changes in brain imaging, cognition, and future dementia risk among adult survivors who received chemotherapy. Study quality was assessed based on 1) prospective, controlled design, 2) sample size, and 3) validated imaging and cognitive metrics. Results: Imaging studies identified MRI-based structural grey and white matter changes and functional network changes among survivors. Cognitive studies reported heterogeneous impairments in attention, memory, and executive function. In studies that examined dementia risk among cancer survivors, 67% reported lower risk of dementia, while 33% reported no association or a higher risk. Conclusions: While short-term cognitive impairment with associated changes on brain imaging is widely reported, findings concerning future or long-term cognitive impairment are mixed. Studies are warranted to identify potential connections between short-term and long-term cognitive function after cancer treatment.

Walnut-Derived Peptides Ameliorate Scopolamine-Induced Memory Impairments in a Mouse Model via Activation of Peroxisome Proliferator-Activated Receptor γ-Mediated Excitotoxicity.

We investigated the protective effect of walnut peptides and YVPFPLP (YP-7) on scopolamine-induced memory impairment in mice and β-amyloid (Aβ)-induced excitotoxic injury in primary hippocampal neurons, respectively. Additionally, the protective mechanism of YP-7 on neuronal excitotoxicity was explored. Mouse behavioral and hippocampal slice morphology experiments indicate that YP-7 improves the learning and memory abilities of cognitively impaired mice and protects synaptic integrity. Immunofluorescence, western blotting, and electrophysiological experiments on primary hippocampal neurons indicate that YP-7 inhibits neuronal damage caused by excessive excitation of neurons induced by Aβ. HT-22 cell treatment with peroxisome proliferator-activated receptor γ (PPARγ) activators and inhibitors showed that YP-7 activates PPARγ expression and maintains normal neuronal function by forming stable complexes with PPARγ to inhibit the extracellular regulated protein kinase pathway. Therefore, YP-7 can ameliorate glutamate-induced excitotoxicity and maintain neuronal signaling. This provides a theoretical basis for active peptides to ameliorate excitotoxicity and the development of functional foods.

Prevalence and risk factors of female sexual dysfunction in low-risk women attending gynecology clinic at Kasr Alainy hospital: a cross-sectional study

Background: In Egypt, research on female sexual dysfunction, a prevalent health issue, is insufficient. Sexual dysfunction can develop later in life following a period of normal sexual functioning, or it can be an issue from the beginning of sexual activity. Objective: The purpose of this research is to determine the prevalence of female sexual dysfunction and to look into potential risk factors that could lead to it in Egyptian women. Methodology: This cross-sectional clinic-based survey trial was carried out at the Kasr Alainy gynecology outpatient clinic. 400 women were enrolled in the research after giving their consent, and data was gathered using a structured questionnaire, in which each participant was asked the same questions in the same sequence and manner throughout the interview. The validated Arabic version of the World Health Organization Quality of Life Questionnaire-Brief, which was provided by female investigators, was given to the participants to complete. Results: Prevalence of female sexual dysfunction was 63% (252 females). Sexual dysfunction was statistically significantly higher among women aged between 35-45 years, with low educational level, no occupation, cases with low family income, residents of rural areas and duration of marriage &gt;10 years. We noted highly statistically significant association between sexual dysfunction and nullipara, previous episiotomy, repeated CS, circumcision and no contraception and vaginitis or cervicitis. Conclusion: Two thirds of women who visited the Kasr Alainy Hospital's gynecological outpatient clinic had female sexual dysfunction, a serious health issue that affected their quality of life.

Do middle-aged patients with onset of idiopathic scoliosis before the age of 10 years who have reduced pulmonary function have a risk for rapid decline – a comparative study

Back groundKnowledge concerning pulmonary function in adult patients with onset of idiopathic scoliosis before age 10 is sparse. A long-term follow-up (FU, mean 26 years, > 12 years after treatment) of pulmonary function (PF) in patients treated with brace or surgery due to idiopathic scoliosis with onset before the age of 10 was earlier performed. To evaluate whether a more severe reduction in pulmonary function leads to more rapid deterioration within a four-year period, this study was performed.MethodsTwenty patients with the most reduced pulmonary function and 19 out of those with normal PF found at the long-term FU were reexamined 4 years later to evaluate further changes in pulmonary function. Patients underwent spirometry and arterial blood gas analysis and answered pulmonary symptom questionnaires.Results70% of the reduced pulmonary function group had undergone surgery vs. 26% of the normal group. The mean age (47 vs. 43 years) at this FU and curve size (37° vs. 35°) at the 26-year FU were similar. The decline in forced vital capacity (FVC) % of predicted was similar in both groups over the four-year period, from 67 to 65% in the reduced PF group vs. 96 to 94% in the normal PF group. The total lung capacity (TLC) % of predicted did not change over time in either group. No patient reported worsening dyspnea symptoms. Only one patient in the reduced PF group showed low arterial oxygen tension, 8.4 kPa, not signifying respiratory insufficiency.ConclusionThe age-related decline in FVC and TLC % of predicted did not differ between those with reduced and those with normal pulmonary function at the 26-year follow-up. Thus, these data do not infer increased rate of decline in the most deteriorated patients.

The effect of bachmann bundle pacing on diastolic function in patients with non-obstructive HCM

Abstract Background and Objective Patients with non-obstructive HCM (nHCM) have advanced diastolic dysfunction and atrial remodeling, leading to increased heart failure hospitalisations. The objective of this study was to evaluate the role of Bachmann bundle pacing (BBP) in diastolic filling compared to right atrial appendage pacing (RAAP). Methods Forty patients with symptomatic nHCM and normal LV function were prospectively enrolled from January 2021 to June 2023. Inclusion criteria included electrocardiographic evidence of inter-atrial delay, E/e’ &amp;gt; 15, and an indication for ICD implantation. BBP was attempted in twenty patients, others underwent RAAP. A Biotronik Selectra 3D 40-S sheath was used for BBP in patients in whom initial lead implantation was unsuccessful. BBP was defined based on P-wave morphology and fluoroscopic lead position. The RV lead was implanted in the RV apex in all patients and the AV delay was optimized based on diastolic filling period and E/e’. Devices were programmed in DDD mode. During follow up, diastolic function, functional capacity, atrial fibrillation, and heart failure hospitalisations were assessed in both groups. Results Among the forty patients (age 48.2+7.8 yrs, males 75%, ESC-SCD Risk 4.3+0.6%), the baseline P wave duration, E/A, E/e’ were 138.4+16.4 ms, 2.5+0.5, and 17.5+2.4, respectively. Six patients (15%) had a history of paroxysmal AF (3 each in BBP and RAAP groups). Of the 16 patients (80%) who underwent successful BBP, the Selectra 3D 40-S sheath was used in 8 patients (Figure 1, Panel A). During BBP, a bachmann bundle potential was recorded in 7 of 16 patients (43.8%) (Figure 1, Panel C). The pacing threshold (1.5+0.5@0.4ms vs. 0.9+0.3@0.4ms, p=0.026) was higher and the atrial sensing (1.8+0.4 vs. 3.3+0.6, p=0.002) was lower in the BBP group compared to the RAAP group at 4 weeks and 6 months of follow up. There was an acute rise in threshold (2.1@0.4 ms) in 1 BBP patient at 4 weeks of follow up. Patients in the BBP group had a reduction in P wave duration compared to the patients in the RAAP group (-22.5 + 5.4 vs. +5.6 + 3.2 ms, p&amp;lt;0.001). During follow up (11.4 + 3.4 months), there was a significant improvement in diastolic function (E/e’), functional capacity (NYHA Class) and reduction in NT-proBNP in the BBB group compared to the RAAP group (Figure 1). The percentage of atrial pacing was similar in both groups (BBP 73.2 + 7.8 vs. RAAP 78.5 + 9.1 %, p=0.219). The risk of atrial fibrillation/tachycardia (12.5% vs. 35.0%, p=0.022) and heart failure hospitalisations (6.3% vs. 20%, p=0.042) was lower in the BBP group compared with RAAP during follow up. Conclusions BBP is safe and effective in improving diastolic function, functional capacity and heart failure hospitalizations in patients with nHCM.BBP Pacing using Selectra 3D 40-S SheathChange in E/e', NYHA, and NT-pro BNP