Low Activity Research Articles

Effect of Different Kharif Paddy Straw Management Options and Different Levels of Nitrogen on Soil Dehydrogenase and Urease Activity

A field experiment was conducted during rabi 2020-21, at Regional Agricultural Research Station, Polasa, Jagtial, PJTSAU to study soil dehydrogenase and urease activity as influenced by different kharif paddy straw management options and nitrogen levels. The results reveal that dehydrogenase and urease activity of soil was significantly influenced by paddy straw management options and activity was increased with crop duration up to 60 DAT and decreased after harvest. Dehydrogenase activity was reduced after burning (1.93 mg TPF produced g-1 soil d-1) as compared to the initial values (2.34 mg TPF produced g-1 soil d-1). The highest dehydrogenase activity of 3.74 and 3.54 mg TPF produced g-1 soil d-1 was recorded at 60 DAT in paddy straw incorporation with phosphorus and incorporation without phosphorus and decreased to 3.36 and 3.03 mg TPF produced g-1 soil d-1 after harvest respectively. Soil urease activity was showed an increasing trend with crop duration up to 60 DAT and then declined. Maximum activity of 3.05, 4.84, 5.17 mg NH4+ released g-1 soil h-1 was observed at 60 DAT under paddy straw burning, paddy straw incorporation with phosphorus incorporation without phosphorus respectively. Paddy straw incorporation with phosphorus recorded higher urease activity and paddy straw burning recorded lower urease activity at all the intervals of crop growth. The effect of nitrogen levels on soil urease activity was found to be significant. Soil urease was highest with 120% RDN followed by 115% RDN, followed by 110% RDN, followed by 100% RDN and the similar trend was observed at all the intervals of crop growth.

Toxicokinetic Profiles and Potential Endocrine Disruption Effects at the Reproductive Level Promoted by Siloxanes Used in Consumer Products.

Siloxanes, commonly known as silicones, are polymeric compounds made up of silicon and oxygen atoms bonded together alternately. Within this group of substances are linear methyl-siloxanes and cyclic methyl-siloxanes, with octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) being the most produced and used industrially. Due to their versatility, high production volume, stability, and local presence in environmental matrices and biological fluids such as breast milk, fat, and plasma, siloxanes have been considered persistent organic pollutants, representing a public health problem. This represents a public health concern, especially when different investigations have reported potential endocrine effects at the reproductive level in experimental animals exposed to D4 and D5. The objective of this study was to review the potential reproductive and endocrine effects derived from siloxanes present in personal care products (PCPs). The results of the literature review confirmed that D4 and D5 were the most used siloxanes as additives in PCP because they improve the emollient properties of the cosmetic and the physical appearance of hair and skin. Similarly the toxicological effects of siloxanes, particularly D4, D5, and D6 included significant endocrine disruption, reproductive toxicity, and liver toxicity. Studies in SD and F-344 rats, commonly used to assess these effects, have shown that D4 has low estrogenic activity, binding to ER-α receptors, whereas D5 does not bind to estrogen receptors. D4 exposure has been associated with increased uterine weight and estrous cycle alterations, leading to prolonged exposure to estrogens, which raises the risk of endometrial hyperproliferation and carcinogenesis. Recent research highlights that D5 exposure disrupts follicle growth, endometrial receptivity, and steroidogenesis, resulting in infertility and hormonal imbalances, potentially causing disorders like endometriosis and increased cancer risk. Chronic exposure to D5 has been linked to the development of uterine endometrial adenocarcinoma, with higher doses further elevating this risk.

Investigation on Polyether Sulfone Toughening Epoxy Vitrimer: Curing and Dynamic Properties.

Diglycidyl ether of bisphenol A crosslinking with glutaric anhydride is used to form the conventional "covalent adaptive network", polyether sulfone (PES) by coiling and aggregating on the adaptive network is used to significantly increase the uncured resin viscosity for improving the processability of epoxy resin, but inevitably affecting the curing reaction and dynamic transesterification reaction. This study investigates the crucial roles of PES in curing dynamics and stress relaxation behavior. The results indicate that although PES does not directly participate in the crosslinking reaction of polyester-based epoxy vitrimers. Moreover, the isothermal curing studies reveal that the addition of PES can greatly bring forward the reaction rate peak from conversion α = 0.6 to α = 0.2, meaning that the curing mechanism transfers from chemical control to diffusion control. Dynamic property analysis shows that the addition of PES significantly accelerates stress relaxation, especially at lower temperatures, leading to low viscous flow activation energy Eτ and relatively insensitive stress relaxation behavior to temperature. Introducing PES into vitrimer resin greatly improves crosslinking density (2.31×10⁴molm- 3), enhancing glass transition temperature (82.68°C), tensile strength (68.66MPa), and fracture toughness (6.25%). Additionally, the modified vitrimer resin exhibits satisfying shape memory performance and reprocessing capability.

Dual Metallosalen-based Covalent Organic Frameworks for Artificial Photosynthetic Diluted CO2 Reduction.

Directly converting CO2 in flue gas using artificial photosynthetic technology represents a promising green approach for CO2 resource utilization. However, it remains a great challenge to achieve efficient reduction of CO2 from flue gas due to the decreased activity of photocatalysts in diluted CO2 atmosphere. Herein, we designed and synthesized a series of dual metallosalen-based covalent organic frameworks (MM-Salen-COFs, M: Zn, Ni, Cu) for artificial photosynthetic diluted CO2 reduction and confirmed their advantage in comparison to that of single metal M-Salen-COFs. As a results, the ZnZn-Salen-COF with dual Zn sites exhibits a prominent visible-light-driven CO2-to-CO conversion rate of 150.9 μmol g-1 h-1 under pure CO2 atmosphere, which is ~6 times higher than that of single metal Zn-Salen-COF. Notably, the dual metal ZnZn-Salen-COF still displays efficient CO2 conversion activity of 102.1 μmol g-1 h-1 under diluted CO2 atmosphere from simulated flue gas conditions (15% CO2), which is a record high activity among COFs- and MOFs-based photocatalysts under the same reaction conditions. Further investigations and theoretical calculations suggest that the synergistic effect between the neighboring dual metal sites in the ZnZn-Salen-COF facilitates low concentration CO2 adsorption and activation, thereby lowering the energy barrier of the rate-determining step.

Microencapsulation of Bifidobacterium lactis and Lactobacillus plantarum within a Novel Polysaccharide-Based Core-Shell Formulation: Improving Probiotic Viability and Mucoadhesion.

Probiotics health benefits are hampered by long-term storage, gastrointestinal transit, and lack of adequate colonization within the colon. To this end, we have designed a core-shell structure that features an acid resistant core formulation with low water activity composed of alginate, hydroxypropyl methyl cellulose, and gellan gum (AHG) and a mucoadhesive shell made from chemically modified carboxymethyl chitosan with polyethylenimine (PEI-CMC). The structure of the core-shell microparticles was examined using scanning electron microscopy, and rheological measurements confirmed the improved ionic interactions between the core and the shell using the PEI-modified CMC. Simulated release from core-shell microparticles using polystyrene beads showed preferential release under intestinal conditions. PEI-CMC coating yielded improvements in mucoadhesion that was consistent with a positive shift in surface charge of the particles. Ex vivo studies using Bifidobacterium lactis probiotic bacteria demonstrated a 1.1 × 105-fold improvement in bacterial viability with encapsulation under storage conditions of high humidity and temperature (30 °C). When exposed to simulated gastric fluid, encapsulation increased the probiotic viability by 3.0 × 102-fold. In vivo studies utilizing bioluminescent Lactobacillus plantarum in mice revealed that encapsulation extended the duration of the signal within the gut and resulted in higher plate counts in suspensions isolated from the cecum. Conversely, we observed an abrupt loss of signal in the gut of the free probiotic. In conclusion, this core-shell system is suitable for improving probiotic shelf life and maximizing delivery to and retention by the colon.

Low Serum Alanine Aminotransferase Blood Activity Is Associated with Shortened Survival of Renal Cell Cancer Patients and Survivors: Retrospective Analysis of 1830 Patients

Background: Sarcopenia is characterized by a loss of muscle mass and function and is often associated with frailty, a syndrome linked to physical disability and shortened survival in various patient populations, including cancer patients. Low serum alanine aminotransferase (ALT) values, serving as a biomarker for sarcopenia, were previously associated with frailty and shortened survival in several cancers. In the current study, we aimed to test the association between low ALT and shorter survival in renal cell carcinoma (RCC) patients and survivors. Methods: This was a retrospective analysis of RCC patients and survivors, both in- and outpatients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. Results: We identified records of 3012 RCC patients. The cohort included 1830 patients (mean age 65.6 ± 13.3 years, 68% were men) of whom only 179 underwent surgical treatment. Out of the eligible cohort, 811 patients (44.3%) had ALT < 17 IU/L, with a mean ALT value of patients within the low-ALT group of 11.79 IU/L, while the mean value in the higher ALT level group was 24.44 IU/L (p < 0.001). Patients in the low-ALT group were older (67.9 vs. 63.7 years; p < 0.001) and had lower BMIs (26.6 vs. 28; p < 0.001). In addition, patients with low ALT had lower hemoglobin values (12.14 vs. 12.91 g/dL; p < 0.001), higher serum creatinine (1.49 vs. 1.14; p < 0.001) and higher platelet to lymphocyte ratios (178 vs. 156; p < 0.001). In a univariate analysis, low ALT levels were associated with a 72% increase in mortality (95% CI 1.46–2.02, p < 0.001). In a multivariate model controlled for age, gender, hemoglobin, platelets, LDH, neutrophil to lymphocyte ratios and platelet to lymphocyte ratios, low ALT levels were still associated with a 27% increase in mortality (HR = 1.27, 95% CI 1.08–1.51; p = 0.005). Conclusion. Low ALT values, associated with sarcopenia and frailty, are also associated with shortened survival in RCC patients, and survivors and could potentially be applied for optimizing individual treatment decisions.

EFFECTS OF SOCIOECONOMIC AND CLINICAL FACTORS ON TREATMENT ADHERENCE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASES PATIENT: FOCUS ON INHALATION THERAPY

Objective: Chronic obstructive pulmonary disease (COPD) refers to a persistent blockage of airflow that requires bronchodilator medication for the rest of one’s life. The goal of the treatment can only be met when the patient is adhering to the prescribed medicine. This study identifies and analyzes how clinical and socioeconomic factors affect COPD patients’ drug adherence to given therapy. The impact of our findings will reduce socioeconomic inequality in COPD management which will improve adherence to drugs and overall physical well-being. Methods: The hospital-based cross-sectional studies were conducted at the Department of TB and CD for 6 months in a tertiary care hospital. A total of 55 patients diagnosed with COPD participated in the study after signing the informed constant. The individual patients were interviewed using MMAS-8 and Kuppuswamy scale questionnaires. The data were analyzed by Chi-square test to determine the correlation between medication adherence and socioeconomic status in patients with COPD. Results: Among 55 COPD patients included in the study, their mean age was 62.2(+10.76) years. Out of the total participants: Significant associations between the medication adherence scale (MMRS-8) scores and the Kuppuswamy scale were found as p<0.0001, indicating that medication adherence was influenced by the patient’s socioeconomic status. In addition, the BORG scale which is used to measure exercise tolerance in COPD that found to have a significant correlation with an MMAS-8 score of p=0.03. Conclusion: Our study found that a person with low socioeconomic levels will have poor adherence to inhaler therapy, leading to poor health outcomes like exacerbation and low physical activity due to shortness of breath.

Dual Metallosalen‐based Covalent Organic Frameworks for Artificial Photosynthetic Diluted CO2 Reduction

Directly converting CO2 in flue gas using artificial photosynthetic technology represents a promising green approach for CO2 resource utilization. However, it remains a great challenge to achieve efficient reduction of CO2 from flue gas due to the decreased activity of photocatalysts in diluted CO2 atmosphere. Herein, we designed and synthesized a series of dual metallosalen‐based covalent organic frameworks (MM‐Salen‐COFs, M: Zn, Ni, Cu) for artificial photosynthetic diluted CO2 reduction and confirmed their advantage in comparison to that of single metal M‐Salen‐COFs. As a results, the ZnZn‐Salen‐COF with dual Zn sites exhibits a prominent visible‐light‐driven CO2‐to‐CO conversion rate of 150.9 μmol g−1 h−1 under pure CO2 atmosphere, which is ~6 times higher than that of single metal Zn‐Salen‐COF. Notably, the dual metal ZnZn‐Salen‐COF still displays efficient CO2 conversion activity of 102.1 μmol g−1 h−1 under diluted CO2 atmosphere from simulated flue gas conditions (15% CO2), which is a record high activity among COFs‐ and MOFs‐based photocatalysts under the same reaction conditions. Further investigations and theoretical calculations suggest that the synergistic effect between the neighboring dual metal sites in the ZnZn‐Salen‐COF facilitates low concentration CO2 adsorption and activation, thereby lowering the energy barrier of the rate‐determining step.

In vitro evaluation of Morinda lucida root extracts against multi-drug resistant bacterial pathogens isolated from diabetic foot ulcers

Background: The continuous rise in microbial resistance to orthodox antimicrobial drugs has led to the search for alternative sources with proven efficacy to solve the challenges of antimicrobial resistance (AMR). The preferred alternatives are plant sources, and this has led to the evaluation of constituents and potency of medicinal plants to provide scientific justification for their use. Methodology: The root of Morinda lucida plant was dug up from the ground, washed clean, and cut into smaller pieces and dried. The root was then ground into fine powder and extracted with water (aqueous), methanol, ethyl acetate and n-hexane. Multi-drug resistant (MDR) Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa were isolated from wound swab samples collected from patients with diabetic foot ulcers using conventional cultures, biochemical identification, and antimicrobial susceptibility tests. The phytochemical and proximate contents of the extracts were assessed by standard technique. The in vitro antimicrobial activities of the extracts were determined at a concentration of 200mg/ml of the extract using the agar well diffusion technique. The minimum inhibitory and bactericidal concentrations were determined by serial doubling dilution. The methanol extract time-kill assay was performed to determine the time of kill of the bactericidal concentration. Results: The phytochemical analysis showed that M. lucida root contains essential secondary metabolites such as flavonoids, alkaloids, tannin, saponin, glucosides, anthraquinone and quinine. The methanol and aqueous extracts showed higher in vitro antibacterial activity, producing the highest zone of inhibition of 27mm against S. aureus but a lower activity of 18mm with n-hexane extract against all isolates except S. aureus. The MIC ranges from 3.125mg/ ml and 25mg/ml. The time-kill assay of methanol extract at 2x and 3x MIC showed that bactericidal activity occurred within 0-8 hours of incubation, indicating high activity. Conclusion: The antibacterial potency of M. lucida root extract and the phytochemical components from this study shows that it can serve as a source of alternative antimicrobial agent that may be effective in the treatment MDR bacterial infections.

Activity concentrations of 60 Co, 137Cs and 241Am in sieved soil and soil inclusions from the «Taiga» peaceful nuclear explosions site

The article presents results of comparative study of 137Cs, 60Co, and 241Am activity concentrations in components of the soil samples collected in 2009 on the territory adjacent to the «Taiga» peaceful nuclear explosions site (the Perm region, Russia). The objective of the study was to identify differences between: 1) non fractionated native soil, 2) the soil passed through a sieve with a mesh size of 1.2 mm, and 3) the screened out coarse components. Measurements of the radionuclides activities in counting samples were performed using a semiconductor gamma spectrometer. Statistically significantly lower activity concentrations of 137Cs (factor of 1.2), 60Co (factor of 2.2) and 241Am (factor of 2.6) were found in the finely dispersed sieved fraction of soil compared to the native soil. On the opposite, in the solid radioactive inclusions selected from the screened out coarse fraction, the activity concentrations of 137Cs, 60Co and 241Am were significantly higher compared to those in the native soil. Especially large differences (up to a factor of 10 and more) between the native soil and radioactive inclusions were observed for the refractory and low-volatile 60Co and 241Am. Presumably, these radionuclides were concentrated predominantly in the glassy substance of the radioactive inclusions. For 137Cs, the unevenness in the contamination of different soil components was less pronounced. The results obtained will be used to standardize methods for assessing radioactive contamination of the territory at the sites of peaceful nuclear explosions

A Method for Electrical Stimulus Artifact Removal Exploiting Neural Refractoriness: Validation by Contrasting Cathodic and Anodic Stimulation.

To present a novel method for removing stimulus transient that exploits the absolute refractory period of electrically excitable neural tissues. Electrical stimulation often generates significant signal artifacts that can obscure important physiological signals. Removal of the artifact and understanding latent information from these signals could provide objective measures of circuit engagement, potentially driving advancements in neuromodulation research and therapies. We conducted intracranial physiology studies on five consecutive patients with Parkinson's disease who underwent deep brain stimulation (DBS) surgery as part of their routine care. Monopolar stimuli (either cathodic or anodic) were delivered in pairs through the DBS electrode across a range of inter-stimulus intervals. Recordings from adjacent unused electrode contacts used broadband sampling and precise synchronization to generate a robust template for the stimulus transient during the absolute refractory period. These templates of stimulus transient were then subtracted from recordings at different intervals to extract and analyze the residual neural potentials. After artifact removal, the residual signals exhibited absolute and relative refractory periods with timing indicative of neural activity. Cathodic and anodic DBS pulses generated distinct patterns of local tissue activation, showing phase independence from the prior stimulus. The earliest detectable neural responses occurred at short peak latencies (ranging from 0.19 to 0.38 ms post-stimulus) and were completely or partially obscured by the stimulus artifact prior to removal. Cathodic stimuli produced stronger local tissue responses than anodic stimuli, aligning with clinical observations of lower activation thresholds for cathodic stimulation. However, cathodic and anodic pulses induced artifact patterns that were equivalent but opposite. The proposed artifact removal technique enhances prior approaches by allowing direct measurement of local tissue responses without requirements for stimulus polarity reversal, template scaling, or specialized filters. This approach could be integrated into future neuromodulation systems to visualize stimulus-evoked neural potentials that would otherwise be obscured by stimulus artifacts.

Penerapan Model Pembelajaran Contextual Teaching And Learning Untuk Meningkatkan Aktivitas Dan Hasil Belajar Administrasi Pajak Di SMKN 1 Sidikalang

This study overcomes the problem of low activity and learning outcomes of students in class XI AKL 1 SMK N 1 Sidikalang, consisting of 36 students. This study aims to improve activity and learning outcomes by using the Contextual Teaching and Learning model. Data were collected through activity observation sheets and learning outcomes tests, then analyzed quantitatively and qualitatively. 1) In cycle I, the first meeting showed an average of 27.77% active activities, then in cycle II, it increased with an average of 77.77% active activities. 2) The average pre-test score was 72.77% with 17 students (47.22%) complete, post-test cycle I 75% with 19 students (52.77%) complete, and post-test cycle II 85.27% with 32 students (88.88%) complete, meeting the success indicator ≥85%. In conclusion, the application of the Contextual Teaching and Learning model succeeded in improving student learning activities and outcomes.

Assessing functional suitability of a lyophilized formulation containing designed ankyrin repeat proteins for radionuclide imaging of HER2/neu overexpression in malignant tumors

Aim. To study in vitro and in vivo the functional suitability of 99mTc-labeled lyophilized formulation containing designed ankyrin repeat protein (DARPin) G3-(GGGS)3Cys for radionuclide imaging of HER2/neu overexpression in malignant tumors.Materials and methods. To create a targeted protein, a modified genetic construct with the sequence encoding DARPin G3-(GGGS)3Cys was used. To generate the experimental probe, we used a lyophilized formulation containing DARPin G3-(GGGS)3Cys with auxiliary substances and 99mTc sodium pertechnetate (500 MBq) incubated at 60 °C for 30 min. Radiochemical purity of 99mTc-G3-(GGGS)3Cys was analyzed by thin-layer radiochromatography. SKOV-3, BT-474, and DU-145 cell lines were used to test binding specificity in vitro. The dissociation constant was determined via a saturation binding assay on SKOV-3 cells with a range of protein concentrations from 0.2 to 40 nM. Nu/j mice bearing HER2-positive SKOV-3 xenografts and HER2-negative Ramos xenografts were used to evaluate the targeting properties and biodistribution.Results. A radiocomplex based on 99mTc and a lyophilized formulation with DARPin G3-(GGGS)3Cys was obtained with the radiochemical purity of more than 96%. Binding of 99mTc-G3-(GGGS)3Cys to the cells was specific (KD 3.9 ± 0.5 nM) and proportional to the level of HER2/neu expression in the cells. The uptake of 99mTc-G3-(GGGS)3Cys in SKOV-3 xenografts was significantly higher than in Ramos xenografts. 99mTc-G3-(GGGS)3Cys demonstrated rapid blood and renal clearance and had low activity in the salivary glands and stomach. Liver uptake was about 5–7%ID/g. In addition, 99mTc-G3-(GGGS)3Cys exhibited very low uptakes in the lungs, muscles, small intestine, and bones.Conclusion. The 99mTc-labeled lyophilized formulation with DARPin G3-(GGGS)3Cys is functionally suitable for imaging HER2/neu overexpression in tumors, as it binds specifically to the receptor, is stable in vivo, and has favorable biodistribution in organs and tissues. The radiocomplex based on 99mTc-G3-(GGGS)3Cys was obtained by a simple method with high radiochemical purity.

PLGA-PEG Nanoparticles Loaded with Cdc42 Inhibitor for Colorectal Cancer Targeted Therapy.

Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV-vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025-0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation.

6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation

Abstract Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None. Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(<1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was <0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A>G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS. Presentation: 6/1/2024

Maternal cortisol concentration is associated with reduced brain activation to infant cry and more intrusive parenting behavior

Previous research indicates that maternal cortisol function and maternal brain response to infant are each in turn related to variations in parenting behavior. However, little is known about how maternal cortisol and maternal brain function are associated, thus studying these two mechanisms together may improve our understanding of how maternal cortisol assessed during interactions with own infant is associated with brain response to infant cry. First-time mothers (N = 59) of infants aged 3–4 months old were recruited to participate. Mothers’ cortisol concentration was measured during a naturalistic interaction with their infant and their behavior was coded for two parenting behaviors-- maternal sensitivity and non-intrusiveness. In an fMRI session, mothers listened to their own infant and a control infant crying. Higher cortisol concentration was associated with more intrusive behavior. We found greater cortisol concentration was further associated with decreased activation in the brain to infant cry in the right precentral gyrus, the left culmen extending into the left inferior temporal gyrus and fusiform, two clusters in the superior temporal gyrus, and in the medial frontal gyrus. We also found that lower activation in these regions was associated with more intrusive maternal behavior. These data demonstrate the associations between maternal cortisol concentration and reduced brain activation to infant cry in both motor planning and auditory processing regions in predicting intrusive parenting behavior.

6953 Bridging the Gender Gap: Sexually Dimorphic Brain Responses in Distressing Low Sexual Desire

Abstract Disclosure: J. Tsoutsouki: None. N. Ertl: None. E.G. Mills: None. M.B. Wall: None. L. Thurston: None. L. Yang: None. S. Suladze: None. T. Hunjan: None. M. Phylactou: None. B. Patel: None. J. Howard: None. A. Abbara: None. D. Golmeier: None. A.N. Comninos: None. W.S. Dhillo: None. Background: Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects 10% of women and 8% of men. The established ‘top-down’ neurofunctional model of HSDD in women suggests that in response to erotic cues, excessive activation of higher-level cognitive brain regions (involved in introspection/self-monitoring) suppresses lower-level sexual brain centres, thereby impeding normal sexual function. By contrast, the neurodysfunction in men with HSDD remains to be fully characterised and crucially unlike in women, there are currently no licensed therapies. Herein, we report the first direct comparison of the neural bases of HSDD in women and men. Methods: 32 premenopausal women with HSDD [mean age±SD (y) 29.2±6.7] and 32 men with HSDD [age 37.9±8.6] underwent a task-based functional MRI (fMRI) measuring sexual brain activity during erotic versus control (exercise) videos. Participants completed psychometric questionnaires before and after the fMRI scan, providing functional relevance for the brain activity changes. Results: Women displayed significantly greater activation in higher-level cortical regions (e.g. inferior frontal gyrus, superior frontal gyrus) and lower-level limbic brain regions (e.g. amygdala, striatum, thalamus) in response to erotic videos, compared to the men. Lower activation in lower-limbic sexual regions in women correlated with more severe HSDD, which along with a hyperactivation in the inferior-frontal gyrus relative to the men, supports the ‘top-down’ mechanism underlying HSDD in women. By contrast, men exhibited lower activation in both higher-cortical and lower-limbic regions, but greater activation than the women in the visual cortex in response to erotic videos. Hence, a heightened sensitivity to visual erotic cues in men might not be effectively relayed to the limbic system. In women only, hypothalamic hyperactivation in response to erotic videos correlated with ‘increased heartbeat’ (r=0.5, P=0.001), and ‘tingling all over’ (r=0.6, P<0.001), while higher striatal activation correlated with feeling more ‘stimulated’ (r=0.4, P=0.001) and ‘genital tingling’ (r=0.6, P<0.001) on the psychometric questionnaires. Crucially, these findings were specific to erotic stimuli as no differences were identified in the control comparison (exercise>baseline contrast). Discussion: This is the first study to directly compare the neural bases of distressing low sexual desire in women and men. While supporting the ‘top-down’ mechanism of HSDD in women, it suggests a different neurodysfunctional process in men with HSDD, highlighting a potential functional disconnection between sensory/attention and sexual centres. Our findings have key clinical implications as they identify a sexual dimorphism in the neural bases of low sexual desire relevant to the escalating development of therapeutics for patients with HSDD. Presentation: 6/3/2024

Understanding the interaction forces between shield-triggered autoinjectors and skin: an in-depth noninvasive study

ABSTRACT Objective This noninvasive study aimed to understand the interaction between shield-triggered autoinjectors (AI) and skin at the point of activation, hypothesizing that the AI’s housing absorbs a significant amount of the user-applied force depending on shield design and skin characteristics. Methods Twenty-seven volunteers used a test device measuring applied force versus shield force and indentation depth relative to shield length (2,4,6,8 mm) in standing and sitting positions. Results Significant differences were found between applied and shield force for the different shield lengths. Shorter shields resulted in significantly lower force transfer coefficients, with means ranging from 0.72 for the 2 mm shield to 0.94 for the 8 mm shield. ANOVA revealed statistically significant factors (p < .05), including position and gender, with females generally having lower coefficient values. Indentation depth increased with higher forces and varied significantly between positions without significant shield length impact. Conclusion The findings confirm that an increase in shield length at the point of activation reduces skin friction with the housing, resulting in less force loss and a lower device activation force perceived by the user. Force loss can be further reduced by standing up. Understanding device-tissue interactions will support development of better AIs with fewer user failures.

5105 Characterization Of Novel PHEX Variants In X-Linked Hypophosphatemic Rickets And Genotype-PHEX Activity Correlation

Abstract Disclosure: H. Wu: None. W. Zhao: None. X. Chen: None. L. Gao: None. C. Xu: None. J. Zhao: None. X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by mutations in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene. Till now, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX have not been fully determined. Here we summarized clinical features of 49 HR patients and detected 17 novel PHEX variants and 5 novel non-PHEX variants. Then we explored the pathogenesis of new-found variants from protein expression, glycosylation analysis, subcellular localization and endopeptidase activity. The results showed that missense variants (Q189H and X750R) slightly reduced protein expression without obviously altering the length and localization of the protein, while truncating variants significantly impaired the synthesis of PHEX and produced a shorter immature protein retained in cells. No evident correlation was observed between mutation types and clinical phenotypes. However, for the first time ever, we analyzed the relationship between PHEX activity and serum phosphorus level and found that patients with low PHEX activity tended to have severe hypophosphatemia and high rickets severity score (RSS). Then we established two new knock-in XLHR mouse models by introducing into mice two novel Phex variants (c.T1349C and c.C426G) found in patients using CRISPR/Cas9 technology. Both demonstrated the clinical manifestations of XLHR seen in the patients and PhexC426G mice showed more severe phenotype than PhexT[1]349C mice, which further confirmed the rationality of genotype-PHEX enzymatic activity correlation analysis. Therefore, our findings demonstrated that novel PHEX variants could disrupt protein function via affecting protein synthesis, post-translational modification, cellular trafficking and catalytic activity. Our study promoted the understanding of XLHR pathogenic mechanism and PHEX activity-phenotype correlation provided scientific support for precise diagnosis and treatment of XLHR. Presentation: 6/3/2024

7787 Primary Aldosteronism Medical Treatment Outcomes (PAMO): An International Consensus on Outcome Assessment Criteria and Multicentre Study

Abstract Disclosure: J. Yang: None. J. Burrello: None. J. Goi: None. T.A. Williams: None. W.F. Young: Consulting Fee; Self; Arena Pharmaceuticals, Inc.. Other; Self; Crinetics Pharmaceuticals. P.J. Fuller: None. P. Investigators: None. Primary aldosteronism (PA) is the most common endocrine cause of hypertension. Mineralocorticoid receptor antagonists, at adequate doses, lower blood pressure and cardiovascular risk in patients with PA. However, there is a lack of a standardized approach to medical therapy and subsequent outcomes assessment. We aimed to: 1) establish criteria for assessing outcomes of targeted medical treatment of PA, and 2) evaluate outcomes using these criteria across an international cohort. A panel of 31 PA experts from 31 centres across four continents used the Delphi method, including three rounds of online questionnaires, to reach consensus. Clinical data were then collected from consecutive patients with PA who started targeted medical treatment between 2016 and 2021 at the participating centres. Consensus was reached for six outcomes, including complete, partial, or absent biochemical response, and complete, partial, or absent clinical response. “Complete biochemical response” was defined as “correction of hypokalemia without potassium supplementation, and normalization of plasma renin activity or concentration”; while “absent biochemical response” was defined as “persistent hypokalemia and/or persistently suppressed or low plasma renin activity or concentration without change from baseline”. “Complete clinical response” was defined as “normal blood pressure without additional antihypertensive medications”; while “absent clinical response” was defined as “the same or increased blood pressure compared to before targeted treatment with same or more antihypertensive medications, not counting targeted therapy”. Of 1483 patients (mean age 52y, 48% female) from 28 centers, 232 (16%) had a complete clinical response, and 719 (49%) had a complete biochemical response at the most recent follow-up (median 29 months after treatment initiation). Compared to those with partial or absent clinical response, patients with complete clinical response had a significantly higher proportion of women and lower proportion with diabetes, stroke or left ventricular hypertrophy. They also had a significantly shorter duration of hypertension, lower BMI, higher eGFR and lower defined daily dose of antihypertensives at baseline. In contrast, these differences were not observed in those with a complete, partial or absent biochemical response. The defined daily dose of targeted therapy did not differ across the various response categories. In conclusion, we have established an international expert consensus for standardized criteria to evaluate the response to targeted medical treatment of PA, facilitate comparisons of outcome data and guide clinicians who manage PA. In a retrospective international cohort, less than half of medically-treated patients reached the established biochemical treatment targets. Further work is needed to increase the rate of complete response. Presentation: 6/3/2024