Significant Decline Research Articles

Exposure to zinc oxide nanoparticles induced reproductive toxicities in male Sprague Dawley rats

BackgroundThis research delves into the reproductive toxicology of zinc oxide nanoparticles (ZnO-NPs) in male Sprague Dawley rats. It specifically examines the repercussions of Zn accumulation in the testes, alterations in testosterone levels, and histopathological changes in the gonadal tissues. AimsThe primary objective of this study is to elucidate the extent of reproductive toxicity induced by ZnO-NPs in male Sprague Dawley rats. The investigation aims to contribute to a deeper understanding of the potential endocrine and reproductive disruptions caused by ZnO-NPs exposure. MethodsCharacterization techniques including SEM-EDX and XRD affirmed the characteristic nature of ZnO-NPs. Twenty-five healthy post weaning rats (200–250 g) were intraperitoneally exposed to different concentrations of ZnO-NPs @ 10 or 20 or 30 mg/kg BW for 28 days on alternate days. ResultsResults showed significant dose dependent decline in the body weight and testicular somatic index of rats. It also showed significant dose dependent accumulation of Zn in testis with increasing dose of ZnO-NPs. Conversely, serum testosterone level and sperm count were reduced with increasing dose of ZnO-NPs. Histological results showed dose dependent abnormalities i.e., vacuolization, edema, hemorrhage, destruction of seminiferous tubules, loss of germ cells and necrosis in rat testis. ConclusionThe findings of this study clearly indicate that high doses of zinc oxide nanoparticles (ZnO-NPs) can adversely affect the structural integrity and functional efficacy of the male reproductive system. Given these results, it becomes crucial to implement stringent precautionary measures in the utilization of ZnO-NPs, particularly in cosmetics and other relevant sectors. Such measures are imperative to mitigate the toxicological impact of ZnO-NPs on the male reproductive system and potentially on other related physiological functions. This study underscores the need for regulatory vigilance and safety assessments in the application of nanotechnology to safeguard human health.

Beneficial Effects of Natural Alkaloids from Berberis glaucocarpa as Antidiabetic Agents: An In Vitro, In Silico, and In Vivo Approach.

Diabetes, also known as diabetes mellitus (DM), is a metabolic disorder characterized by an abnormal rise in blood sugar (glucose) levels brought on by a complete or partial lack of insulin secretion along with corresponding changes in the metabolism of lipids, proteins, and carbohydrates. It has been reported that medicinal plants play a pivotal role in the treatment of various ailments such as diabetes mellitus, dyslipidemia, and hypertension. The current study involved exploring the acute toxicity and in vivo antidiabetic activity of berberine (WA1), palmatine (WA2), and 8-trichloromethyl dihydroberberine (WA3) previously isolated from Berberis glaucocarpa Stapf using a streptozotocin (STZ)-induced diabetic rat model. Body weight and blood glucose level were assessed on a day interval for 4 weeks. Biochemical parameters, antioxidant enzymes, and oxidative stress markers were also determined. In an acute toxicity profile, the WA1, WA2, and WA3 were determined to be nontoxic up to 500 mg/kg (b.w). After the second and third weeks of treatment (14 and 21 days), the blood glucose levels in the WA1-, WA2-, and WA3-treated groups were significantly lower than those in the diabetic control group (476.81 ± 8.65 mg/dL, n = 8, P < 0.001). On the 21st day, there was a decrease in the blood glucose level and the results obtained were 176.33 ± 4.69, 197.21 ± 4.80, and 161.99 ± 4.75 mg/dL (n = 8, P < 0.001) for WA1, WA2, and WA3 at 12 mg/kg, respectively, as opposed to the diabetic control group (482.87 ± 7.11 mg/dL, n = 8, P < 0.001). Upon comparison with the diabetic group at the end of the study (28 days), a substantial drop in the glucose level of WA3 at 12 mg/kg (110.56 ± 4.11 mg/dL, n = 8, P < 0.001) was observed that was almost near the values of the normal control group. The treated groups (WA1, WA2, and WA3) treated with the samples displayed a significant decline in the levels of HbA1c. Treatment of the samples dramatically lowered the lipid level profile. In groups treated with samples, plasma levels of triglycerides, total cholesterol, and LDL were significantly lowered [F (5, 42) = 100.6, n = 8, P < 0.001]; these levels were also significantly decreased [F (5, 42) = 129.6 and 91.17, n = 8, P < 0.001]. In contrast to the diabetes group, all treated groups had significantly higher HDL levels [F (5, 42) = 15.46, n = 8, P < 0.001]. As a result, hypolipidemic activity was anticipated in the samples. In addition to that, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was considerably elevated in the groups treated with the sample compared to the diabetic control group (n = 8, P < 0.001).

Improved Diagnostic Confidence Imparted by Radiologists in Radiology Reports After Educational Interventions on Reporting Styles.

Background Radiology reports are important medico-legal documents facilitating communication between radiologists and referring doctors. Language clarity and precision are crucial for effective communication in these reports. Radiology reporting has changed with the evolution of imaging technology, prompting the adoption of precise terminology. Diagnostic certainty phrases (DCPs) play an important role in communicating diagnostic confidence in radiology reports. Objective The aim of this study was to evaluate the use of DCPs in radiology reports, before and after targeted educational interventions. Materials and methods The study was approved by the Aga Khan University Hospital's Ethical Review Committee and includes cross-sectional radiology reports. It involved three cycles of retrospective evaluation, with educational interventions in between to improve the use of DCPs. Results The study found a dynamic shift in the use of DCPs during the three cycles. Initially, intermediate-certainty phrases prevailed, followed by an increase in high-certainty phrases and a drop in low-certainty phrases. Later cycles showed a significant decline in DCPs and an increase in the use of definitive language. Across all subspecialties, there was a consistent decrease in intermediate- and low-certainty DCPs. Conclusion The study validates the transformative impact of educational interventions on the use of DCPs in radiology reports. The radiology reports frequently used DCPs with intermediate to low diagnostic certainty with improvement in the subsequent cycles of the study after educational interventions. It emphasizes the significance of continuing education to ensure the use of precise nomenclature.

Analisis Penerimaan Pajak dan Retribusi Kota Medan Serta Hubungannya dengan Pelayanan Publik di Kota Medan dalam Meningkatakan Taraf Hidup Masyaratkat Kota Medan dari Segi Ekonomi

The aim of this research is to determine and analyze the growth of PAD (Regional Original Income) in Medan City at the Medan City Regional Tax and Levy Management Agency and to determine the influence of Tax and Levy Revenue on Public Services in Medan City. This research uses a descriptive single case study approach, which aims to collect, compile, classify and interpret data to provide an accurate picture of the nature of individuals, groups, conditions and symptoms in a society. Research results from the Regional Tax and Levy Management Agency for Medan City, the Ministry of Finance, and literature studies show that tax and levy revenue in Medan City has not reached the target for the last three periods. Public services in Medan City have experienced a significant decline, influenced by poor budget factors in revenue and allocation, as seen from the decline in Regional Original Income (PAD) over the last three years.

Trends in Urogynecology-Transvaginal Mesh Surgery in Germany.

Pelvic organ prolapse constitutes a prevalent condition associated with a considerable impact on the quality of life. The utilization of transvaginal mesh surgery for managing POP has been a subject of extensive debate. Globally, trends in TVM surgery experienced significant shifts subsequent to warnings issued by the FDA. This study aims to explore temporal patterns in transvaginal mesh surgery in the German healthcare system. A comprehensive analysis was conducted on in-patient data from the German Federal Statistical Office spanning 2006 to 2021. A total of 1,150,811 operations, each associated with specific codes, were incorporated into the study. Linear regression analysis was employed to delineate discernible trends. The trends in transvaginal mesh surgery within the anterior compartment exhibited relative stability (p = 0.147); however, a significant decline was noted in all other compartments (posterior: p < 0.001, enterocele surgery: p < 0.001). A subtle increasing trend was observed for uterine-preserving transvaginal mesh surgery (p = 0.045). Surgical trends over the specified timeframe demonstrate how POP management has evolved globally. Notably, despite observed fluctuations, transvaginal mesh surgery remains a viable option, particularly for specific cases with a high risk of relapse and contraindications to alternative surgical approaches.

Anti-oncogenic Potential and Inflammation Modulatory Response of Green Synthesized Biocompatible Silver Nanoparticles.

This study presents a novel approach to synthesizing silver nanoparticles (Ag NPs) using a solution combustion synthesis (SCS) method with Catharanthus roseus (C. roseus) leaf extract. The NPs were thoroughly characterized through X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), Transmission electron microscopy (TEM), and Selected area electron diffraction (SAED), elucidating their crystal structure. Notably, the synthesized Ag NPs exhibited a significant dose-dependent decline in viability of the MDA-MB 231 breast cancer cell line, with an IC50 value of 13.3 μg/mL, underscoring their potential as potent anticancer agent. Beyond cytotoxicity, the study pioneers an investigation into the biocompatibility of Ag NPs by blood hemolsysis, providing critical insights into their safety and biomedical applicability. Furthermore, this research uncovers a distinctive facet of Ag NPs, revealing their inhibitory effects on the inflammatory enzyme secretory phospholipase A2 (sPLA2), a recognized biomarker for breast cancer. The demonstrated in vitro and in vivo inhibition of sPLA2 highlights the multifaceted potential of Ag NPs in not only targeting cancer cells but also modulating inflammatory responses associated with breast cancer, positioning the study at the forefront of advancements in nanomedicine and cancer therapeutics.

Assessment of Mediterranean diet adherence and comparison with Italian dietary guidelines: a study of over 10,000 adults from 2019 to 2022

Despite the many well-documented benefits of the Mediterranean diet (MD), many Mediterranean countries seem to be moving away from it. The aim of this study was to investigate the MD adherence in 10,916 adults who completed the validated Medi-Lite questionnaire from January 2019 to December 2022 in Italy, and to assess the consumption of its food groups by comparing them with current national dietary guidelines. The sample showed a good level of MD adherence (12 ± 2.5). However, from 2019 to 2022, a significant (p < 0.001) decline in the adherence level emerged. An overconsumption of fresh red meat, cheese and poultry compared to dietary guidelines was observed. In contrast, an under-consumption of vegetables, bread, legumes, fish and milk and dairy products emerged. In recent years, a decline in MD adherence was observed in Italy, probably determined by an excessive consumption of animal products.

Return to Play, Performance, and Earnings Analysis After Lumbar Disc Herniation in National Hockey League Players

Study Design Retrospective cohort study. Objective Professional hockey players have a high incidence of lumbar disc herniations (LDH). The purpose of this study was to determine the impact of LDH on the performance and financial earnings of National Hockey League (NHL) players. Methods NHL players who sustained a LDH were retrospectively reviewed utilizing an online database and a 2:1 matched control cohort. Player performance and game usage was compared at one- and three-season(s) pre- and post-injury season within the cohorts. Injured and matched players were divided into 3 groups based on the player’s adjusted index season salary. Results A total of 181 players were included, with 62 LDH players matched to 119 healthy controls. Return to play after LDH was 79%. The LDH cohort had fewer seasons played throughout their career compared to the matched group (12.5 ± 4.3 vs 14.2 ± 3.8; P = .031). At 1 season post-index, the LDH cohort had significantly fewer goals per 60 and points per 60 when compared to pre-index. At 3 seasons post-index, the LDH cohort exhibited a significant decline in time-on-ice per game played, goals per 60, and points per 60 compared to pre-index. Conclusion The majority of NHL players who sustained a LDH returned to play (79%) but had shorter careers overall and decreased performance outcomes when compared to matched cohorts at both 1 and 3 seasons post-injury.

Structural integrity of a submersible sea cage exposed to extreme oceanographic conditions

AbstractThis study focuses on the structural integrity analyses of a submersible cage with dimensions of 20 m in diameter and 10 m depth under extreme oceanographic conditions, including current speed of 0.5 and 1 m/s, combined with waves ranging from 2 to 5 m in height and a period of 7 s. Employing a dynamic simulation model based on finite elements, The study examines the stresses in the cage's pipes, as well as the tension in the bridle lines and mooring lines. Results indicate that submerging the cage leads to a reduction in peak tensions, with mooring lines experiencing a decrease of up to 32% and bridle lines experiencing a decrease of up to 59%. Furthermore, the stresses in the pipes exhibit a significant decline of up to 71.4%. These findings demonstrate that the submersible cage, when submerged, significantly reduces peak stresses, thereby decreasing the risk of structural loss or damage when the system is submerged.

Pengaruh EPS, DPS, PBV, dan DER Terhadap Harga Saham(Closing Price) PT. Unilever Indonesia Tbk. Periode 2015-2022

Fast Moving Consumer Goods companies are one of the sources in realizing investment with the main sources of daily necessities, such as food, beverages, household products, and beauty products. However, it turns out that recently the share price of PT. Unilever Indonesia actually experienced a very significant decline. This study aims to determine the effect of EPS, DPS, PBV and DER on stock prices. This study uses a quantitative approach. The data used in this study is secondary data taken from the financial statements of PT. Unilever Indonesia Tbk for the 2015-2022 period. The data analysis used is multiple linear regression analysis using review. The results showed that partially the EPS variables have no effect on stock prices. While the DPS, PBV and DER variables had a positive effect on stock prices. The simultaneous results show that the EPS, DPS, PBV and DER variables affect stock prices.

Low Dose Amantadine and Escitalopram in Progressive Supranuclear Palsy and Multiple System Atrophy

Background: Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are less responsive to usual antiparkinsonian drugs. Purpose: To assess the treatment outcome of the combination of low-dose amantadine and escitalopram in the study population. Methods: A retrospective study of PSP and MSA patients from June 2021 to December 2022 treated with the dose of amantadine 100 mg and escitalopram 5 mg per day with a follow-up of 2 months at a tertiary care centre in India. The primary outcome measure was a change in the PSP and MSA severity rating scale scores, while cognition, neuropsychiatric symptoms and functionality scale scores were secondary outcomes on follow-up visits. Repeated measures ANOVA and Friedman rank test were used to analyse the data. Results: A total of 21 patients (8 PSP and 13 MSA), including 19 males, with a mean age of 72.84 years, were included. The mean total PSP rating scale score had a significant decline from baseline to week 2 and 8 ( p &lt; .001), along with the scores for limb symptoms ( p &lt; .001), ocular ( p = .001), history ( p = .003), gait ( p = .007), mentation ( p = .014) and bulbar ( p = .018) symptoms. Similarly, the mean score of the MSA rating scale significantly decreased on follow-up visits ( p &lt; .001). The cognition, functional disability and behavioural symptoms scores also had significant improvement with p &lt; .01. Conclusion: The PSP and MSA patients had clinically significant improvement with the combination treatment in both motor and non-motor domains. Further prospective trials for longer durations are needed to establish the effect size and stability of response.

Assault-related traumatic brain injury hospitalizations in Canada from 2010 to 2021: rates, trends and comorbidity

BackgroundTraumatic brain injury (TBI) is a major cause of morbidity and mortality globally. TBI is often associated with other physical or psychological issues resulting in high hospitalization costs. TBI incidence and recovery can vary with the external cause being intentional or unintentional. It is important to monitor the rates of TBI hospitalizations related to different external causes. This study examined the annual rate, comorbidity and length of stay associated with assault-related TBI hospitalizations and compare it with other external causes, by age and sex in Canada from 2010 to 2021.MethodsDischarge Database was used to extract cases of TBI (2010–2021). ICD-10-CA codes were used to classify all cases with TBI as per assault and other external causes (falls; transport; sport, physical activity and recreation; struck by). Additional variables, including age, sex, comorbidity and length of stay, were examined. Time trends were quantified using Joinpoint regression.ResultsThe average annual percent increase for all TBI hospitalizations from 2010 to 2021 was not significant at 0.1%. Females accounted for 35.8% of these TBI hospitalizations. From 2010 to 2021, assault-related TBI hospitalizations showed a significant annual decline of 4.1% for males and a significant increase of 1.2% for females. Increase in TBI hospitalizations related to falls showed an average annual percent increase of 1.4% for males and 2.2% for females. A significant decrease was observed for TBI hospitalizations related to the other three (transport, SPAR and struck by) external causes for both sexes from 2010 to 2021. Infants and children under 10 years of age had higher percentages of cases with comorbidities and higher length of stay for assault-related TBI hospitalizations.ConclusionsAssault-related TBI hospitalization rates decreased overall and among males, rates among females increased from 2010 to 2021. These results underscore the importance of targeted prevention efforts for TBI related to different external causes, age and sex, and continued surveillance to monitor the epidemiology of assault-related TBI.

Anticancer effect of propranolol on diethylnitrosamine-induced hepatocellular carcinoma rat model.

Hepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non-selective β-blocker propranolol demonstrated antiproliferative activity in many cancer types. This investigation aimed to evaluate the anticancer effect of propranolol against DEN-induced HCC in rats. Thirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b.wt.) once a week for 10weeks, to induce HCC, and Group III (HCC/Prop); received DEN for 10weeks for HCC induction, then received 20 mg/kg b.wt. propranolol, intraperitoneally for four successive weeks. HCC was developed in rats' livers and confirmed via significant liver architecture changes, significantly elevated activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-fetoprotein (AFP), total- and direct-bilirubin (Bil), and a decline in albumin (ALB) level in serum. HCC group demonstrated elevated levels of malondialdehyde (MDA), nitric oxide (NO), HIF-1α, IL-8, NF-κB, PGE2, TGF-β1, VEGF, and CD8, but significant decline of GSH, and IL-10 level, with suppression of the antioxidant enzymes' activities. In addition, the gene expression of the hepatic inducible nitric oxide synthase (iNOS), and LAG-3 were up-regulated. Moreover, the protein expression of p-PKC was up-regulated, while that of PD-1 and PD-L1 were down-regulated in the liver tissues of the HCC group. However, propranolol ameliorated the investigated parameters in the HCC/Prop group. Propranolol exhibited an anticancer effect and thus can be considered as a promising treatment for HCC. Blocking of PD-1/PD-L1 and LAG-3 signals participated in the anti-tumor effect of propranolol on HCC.

Stable Levels of Antibodies Against Unrelated Toxoid Vaccines After COVID-19: COVID-19 Infection Does Not Affect Toxoid Vaccine Antibody Levels.

Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies. We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms. No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without. We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.

Repetitive magnetic stimuli over the motor cortex impair long-term consolidation of a balance task by suppressing up-regulation of intracortical inhibition

Introduction&#x0D; Recent findings have demonstrated that low-frequency repetitive magnetic stimulations (rTMS) over the primary motor cortex (M1) impaired short-term consolidation of a balance task, underscoring the causal connection between M1 and the consolidation of balancing skills (Egger et al., 2023). However, the underlying neural mechanisms induced by rTMS and whether these adaptations endure over an extended period, encompassing multiple acquisition sessions, remain insufficiently elucidated (Censor &amp; Cohen, 2011). So far, its is widely acknowledged that GABAergic processes play an important role for consolidation (Sanes &amp; Donoghue, 2000), at the same time, are affected by learning balance skills (Mouthon &amp; Taube, 2019; Taube et al., 2020). Therefore, the present study aimed to investigate the impact of rTMS on GABA-mediated short-interval intracortical inhibition (SICI) and to explore the role of M1 in the long-term consolidation of a balance task (i.e., across multiple acquisition sessions).&#x0D; Methods&#x0D; Thirty-one volunteers underwent six balance acquisition sessions on a rocker-board, each followed by either rTMS or sham rTMS based on group affiliation. During the first and last training session, SICI was measured twice; before the balance acquisition and after the application of rTMS or sham-rTMS to investigate potential short- and long-term adaptations in intracortical inhibition. Adaptations were assessed during the execution of the learned balance task and in a non-learning postural control task (i.e., stable upright stance).&#x0D; Results&#x0D; Regardless of group affiliation, all participants achieved comparable improvements within the balance acquisition sessions. However, consolidation varied between groups. In particular, between the third and the fourth acquisition session, as Tukey corrected post-hoc tests showed a significant decline in performance for the rTMS group (p = 0.006). Both short- (p = 0.014) and long-term (p = 0.038) adaptations in SICI were affected by rTMS: while the sham rTMS group upregulated SICI, rTMS led to reduced levels of inhibition. No neurophysiological effects were observed in the non-learning control task (upright stance).&#x0D; Discussion/Conclusion&#x0D; The interfering effect of rTMS on balance consolidation and on upregulation of SICI indicates that increased intracortical inhibition is an important mechanism to protect and engrave newly acquired motor memory. Importantly, adaptations in SICI were only apparent during the execution of the learned task.&#x0D; References&#x0D; Censor, N., &amp; Cohen, L. G. (2011). Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory. The Journal of Physiology, 589(1), 21-28. https://doi.org/10.1113/jphysiol.2010.198077&#x0D; Egger, S., Wälchli, M., Rüeger, E., &amp; Taube, W. (2023). Short-term balance consolidation relies on the primary motor cortex: A rTMS study. Scientific Reports, 13, Article 5169. https://doi.org/10.1038/s41598-023-32065-x&#x0D; Mouthon, A., &amp; Taube, W. (2019). Intracortical inhibition increases during postural task execution in response to balance training. Neuroscience, 401, 35-42. https://doi.org/10.1016/j.neuroscience.2019.01.007&#x0D; Sanes, J. N., &amp; Donoghue, J. P. (2000). Plasticity and primary motor cortex. Annual Review of Neuroscience, 23, 393-415. https://doi.org/10.1146/annurev.neuro.23.1.393&#x0D; Taube, W., Gollhofer, A., &amp; Lauber, B. (2020). Training-, muscle- and task-specific up- and downregulation of cortical inhibitory processes. The European Journal of Neuroscience, 51(6), 1428-1440. https://doi.org/10.1111/ejn.14538

Unravelling the neglected role of ultravioletradiation on stomata: A meta-analysis with implications for modelling ecosystem-climate interactions.

Stomata play a pivotal role in regulating gas exchange between plants and the atmosphere controlling water and carbon cycles. Accordingly, we investigated the impact of ultraviolet-B radiation, a neglected environmental factor varying with ongoing global change, on stomatal morphology and function by a Comprehensive Meta-Analysis. The overall UVeffect at the leaf level is to decrease stomatal conductance, stomatal aperture and stomatal size, although stomatal density was increased. The significant decline in stomatal conductance is marked (6% in trees and >10% in grasses and herbs) in short-term experiments, with more modest decreases noted in long-term UV studies. Short-term experiments in growth chambers are not representative of long-term field UV effects on stomatal conductance. Important consequences of altered stomatal function are hypothesized. In the short term, UV-mediated stomatal closure may reduce carbon uptake but also water loss through transpiration, thereby alleviating deleterious effects of drought. However, in the long term, complex changes in stomatal aperture, size, and density may reduce the carbon sequestration capacity of plants and increase vegetation and land surface temperatures, potentially exacerbating negative effects of drought and/or heatwaves. Therefore, the expected future strength of carbon sink capacity in high-UV regions is likely overestimated.

(290) Impact of Neoadjuvant Relugolix on Patient-Reported Sexual Function and Bother

Abstract Introduction Relugolix is an oral GnRH receptor antagonist used in combination with radiation therapy in the treatment of unfavorable prostate cancer. It has been shown to achieve rapid and profound testosterone suppression (total testosterone &amp;lt;20 ng/dL) without the need for bothersome injections. Such low testosterone levels may impact sexual functioning and perceptions. Objective Given the potential benefits of Relugolix over other androgen deprivation therapies (ADTs), this prospective study sought to assess neoadjuvant Relugolix-induced sexual dysfunction prior to the initiation of stereotactic body radiation therapy (SBRT). Methods Prospective, patient-reported data was collected from a male cohort diagnosed with localized prostate cancer and subsequently treated with neoadjuvant Relugolix and SBRT. Relugolix was initiated at least 2 months prior to SBRT. Sexual function and bother were assessed via the sexual domain of the validated Expanded Prostate Index Composite (EPIC-26) survey which includes five function questions (erections and orgasm) and one overall bother question. Individual scores ranged from 0-100 with higher scores reflecting improved function/less bother. EPIC-26 was collected for each patient at pre-Relugolix baseline and one hour prior to SBRT initiation. Individual items were evaluated for statistical significance (paired t-test, p &amp;lt; 0.05) and clinical significance by minimally important difference (MID, +/- 0.5 SD from baseline score). Results Between July 2021 and January 2023, 49 patients with localized prostate cancer were treated with neoadjuvant Relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) at Georgetown University Hospital per institutional protocol IRB 12-1775. The median age was 73 years. 27% of patients were black and 26.1% were obese (BMI ≥30 kg/m2). Patients initiated Relugolix at a median of 3.6 months prior to SBRT. 82% of patients had intermediate risk disease. All individual EPIC sexual function scores declined in a similar manner following neoadjuvant Relugolix therapy. These declines were both statistically and clinically significant. There was no statistically or clinically significant change in the EPIC sexual overall bother score. Conclusions In concordance with known side effects of ADT, neoadjuvant Relugolix was associated with a significant decline in self-reported sexual function. However, patients indicated only a minimal and non-significant increase in bother. Relugolix was well-tolerated as patients on Relugolix did not subjectively find their sexual dysfunction troublesome. Future investigations should compare outcomes while on Relugolix directly to GnRH agonist-induced sexual dysfunction. Disclosure No.

Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline

Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64–68 years; 5-year follow-up: n = 129) who underwent positron emission tomography with 11C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.

Incidence and outcomes of perioperative myocardial infarction associated with coronary artery bypass surgery

Perioperative myocardial infarction (PMI) after CABG can contribute to in-hospital morbidity and mortality, however, its clinical significance on long-term outcome, remains inadequately addressed. We studied both 30-day mortality and long-term effects of PMI in Icelandic CABG-patients. A retrospective nationwide-study on 1446 consecutive CABG-patients operated at Landspitali in Iceland 2002-2018 without evidence of preoperative myocardial infarction. PMI was defined as a tenfold elevetion in serum-CK-MB associated with new ECG changes or diagnostic imaging consistent with ischemia. Patients with PMI were compared to a reference group with uni- and multivariate analyses. Long-term and MACCE-free survival were estimated with the Kaplan-Meier method and logistic regression used to determine factors associated with PMI. The mean follow-up time was 8.3 years. Out of 1446 patients 78 (5.4%) were diagnosed with PMI (range: 0-15.5%) with a significant annual decline in the incidence of PMI (12.7%, p<0.001). Over the same period preoperative aspirin use increased by 22.3% (p<0.018). PMI patients had a higher rate of short-term complications and a 11.5% 30-day mortality rate compared to 0.4% for non-PMI patients. PMI was found to be a predictor of 30-day mortality (OR 15.44, 95% CI: 6.89-34.67). PMI patients had worse 5-year MACCE-free survival (69.2% vs. 84.7, p=0,01), although overall survival was comparable between the groups. Although PMI after CABG is associated with significantly higher rates of short-term complications and 30-day mortality, long-term survival was similar to the reference group. Therefore, the mortality risk attributable to PMI appears to diminish after the immediate postoperative period.

Impact of nutritional intervention on concurrent chemoradiotherapy outcomes in locally advanced esophageal cancer: A pharmacological perspective

Purpose: To determine the pharmacological implications of nutritional intervention and the occurrence of toxic side effects in patients with locally advanced esophageal cancer undergoing concurrent chemoradiotherapy.&#x0D; Methods: An extensive retrospective analysis of clinical data was carried out on individuals who received concurrent chemo-radiotherapy. 150 patients were included in the study, with 85 patients receiving nutritional management (intervention group) and 65 patients without nutritional support (control group). Assessments were conducted for Nutritional Risk Screening-2002 (NRS-2002) and patient-generated subjective global assessment (PG- SGA) scores, serum nutritional parameters, toxic side effects and treatment completion rates at 2, 4, and 6 weeks before and during chemo-radiotherapy.&#x0D; Results: After concurrent chemo-radiotherapy, intervention group exhibited significantly lower NRS2002 and PG- SGA scores compared to control group (p = 0.002 and 0.001, respectively). Intervention group had a statistically significant increase in PALB (p = 0.001) and ALB, while control group experienced a significant decline in ALB (albumin) and PALB (pre-albumin) levels. Grip strength also significantly decreased in control group compared to intervention group (p = 0.003). Intervention group showed a significantly lower incidence of radiation esophagitis. Moreover, a smaller proportion of patients in intervention group experienced interruptions or delays in radiotherapy compared to control group (95 % vs. 83.3 %).&#x0D; Conclusion: Nutritional intervention has a pharmacological impact on maintaining nutritional status, reducing treatment toxicities and improving the completion rates of chemo- radiotherapy in patients with locally advanced esophageal cancer. Further investigations and longer-term studies are warranted to shed more light on the potential impact of nutritional interventions on the overall survival rates of these patients