Stripping versus ligation of vas deferens in microscopic denervation of spermatic cord in men with chronic orchialgia: A multicenter study.

BACKGROUND: Microdenervation of the spermatic cord (MSCD) is an effective treatment modality for men with intractable scrotal content pain. For patients not interested in preserving fertility, some centers advocate ligation of the vas during denervation, while others prefer stripping of the vas deferens to preserve the vasal artery, hence preserving vasculature to the testis and possibly decreasing post-operative congestion pain. OBJECTIVE: To compare outcomes of patients with chronic orchialgia, who underwent MSCD by either stripping or ligating the vas deferens. MATERIALS AND METHODS: A retrospective chart review of 85 patients who underwent MSCD from 2017-2023 was performed. Patients' demographics including history of prior surgical procedures were recorded. Response to surgery was evaluated as either complete resolution of pain, partial resolution of pain, or no improvement in pain. RESULTS: Eighty-five patients underwent MSCD with a median (interquartile range, IQR) age of 36 (25.5-46.5) years and median duration of pain of 16 (6-31) months. Thirty-seven patients underwent stripping of vas, while 48 underwent ligation of vas during MSCD. Median follow up was 12 months. Twenty-one (43.5%) patients had prior inguinal scrotal surgery in the ligation group compared to 5 (13.5%) in the stripping group, p = 0.003. The etiology of pain was similar between the groups. The response to MSCD between the two groups was similar, 67.6% of patients who underwent stripping had complete resolution of pain versus 66.7% of those who had ligation (p = 0.968), with similar rates of post-operative complications (p-value = 0.132). CONCLUSIONS: In men with intractable chronic scrotal content pain with no interest in preserving fertility, ligation, or stripping of the vas deferens yields similar outcomes with regard to pain resolution. Both techniques are safe with no reports of any testicular atrophy.

Urine microbes and predictive metagenomic profiles associate with abnormalities in sperm parameters: implications for male subfertility.

OBJECTIVE: To explore the taxonomic and predicted functional relationship between the urine microbiome and alterations of semen analysis (SA) parameters. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Men presenting for fertility evaluation or men presenting for vasectomy consultation with proven biological paternity were recruited and stratified on the basis of alterations, or lack thereof, in SA parameters. MAIN OUTCOME MEASURE: Changes in the functional and taxonomic urine microbiome profiles of participants with or without alterations in SA parameters. RESULTS: Seventy-three participants were included in our study. Men with abnormal sperm motility (N = 27) showed a nearly 50-fold higher abundance of Dialister micraerophilus compared with those with normal sperm motility (N = 46). This relationship persisted on canonical correlational analysis (r = 0.439). Men with abnormal sperm concentration (N = 20) showed a lower abundance of Enterococcus faecalis and Staphylococcus aureus, compared with those with normal sperm concentration (N = 53). The urine of participants with impaired sperm motility demonstrated dramatic differences in predictive functional profiles in pathways involved in oxidation-reduction balance and cell longevity. CONCLUSIONS: Our findings underscore differences in the urinary microbiome and abnormalities in semen parameters, especially sperm motility. By incorporating predictive functional profiling, we also highlight possible mechanisms that may drive the observed differences in sperm parameters.

Semen microbiota are dramatically altered in men with abnormal sperm parameters.

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

Can ChatGPT Aid Clinicians in Educating Patients on the Surgical Management of Glaucoma?

PRCIS: ChatGPT can help health care providers automate the quality assessment of online health information, but it does not produce easier-to-understand responses compared with existing online health information. PURPOSE: To compare the readability of ChatGPT-generated health information about glaucoma surgery to existing material online and to evaluate ChatGPT's ability to analyze the quality of information found online about glaucoma surgery. METHODS: ChatGPT was asked to create patient handouts on glaucoma surgery using 7 independent prompts, aiming to generate sixth grade level reading material. Existing patient-targeted online health information about glaucoma surgery was selected from the top 50 search results of 3 search engines, excluding advertisements, blog posts, information intended for health professionals, irrelevant content, and duplicate links. Four validated tools were used to assess readability, and the readability of the ChatGPT-generated material was compared with the readability of existing online information. The DISCERN instrument was used for the quality assessment of online materials. The DISCERN instrument was also programmed to use ChatGPT to evaluate its ability to analyze quality. R software and descriptive statistics were used for data analysis. RESULTS: Thirty-five webpages were included. There was no difference between the reading level of online webpages (12th grade) and the reading level of ChatGPT-generated responses (11th grade), despite the ChatGPT prompts asking for simple language and a sixth grade reading level. The quality of health content was "fair," with only 5 resources receiving an "excellent" score. ChatGPT scored the quality of health resources with high precision ( r =0.725). CONCLUSIONS: Patient-targeted information on glaucoma surgery is beyond the reading level of the average patient, therefore at risk of not being understood, and is of subpar quality, per DISCERN tool scoring. ChatGPT did not generate documents at a lower reading level as prompted, but this tool can aid in automating the time-consuming and subjective process of quality assessment.

Application of Artificial Intelligence to Patient-Targeted Health Information on Kidney Stone Disease.

OBJECTIVE: The American Medical Association recommends health information to be written at a 6th grade level reading level. Our aim was to determine whether Artificial Intelligence can outperform the existing health information on kidney stone prevention and treatment. METHODS: The top 50 search results for "Kidney Stone Prevention" and "Kidney Stone Treatment" on Google, Bing, and Yahoo were selected. Duplicate webpages, advertisements, pages intended for health professionals such as science articles, links to videos, paid subscription pages, and links nonrelated to kidney stone prevention and/or treatment were excluded. Included pages were categorized into academic, hospital-affiliated, commercial, nonprofit foundations, and other. Quality and readability of webpages were evaluated using validated tools, and the reading level was descriptively compared with ChatGPT generated health information on kidney stone prevention and treatment. RESULTS: 50 webpages on kidney stone prevention and 49 on stone treatment were included in this study. The reading level was determined to equate to that of a 10th to 12th grade student. Quality was measured as "fair" with no pages scoring "excellent" and only 20% receiving a "good" quality. There was no significant difference between pages from academic, hospital-affiliated, commercial, and nonprofit foundation publications. The text generated by ChatGPT was considerably easier to understand with readability levels measured as low as 5th grade. CONCLUSIONS: The language used in existing information on kidney stone disease is of subpar quality and too complex to understand. Machine learning tools could aid in generating information that is comprehensible by the public.

The Use of Large Language Models to Generate Education Materials about Uveitis.

OBJECTIVE: To assess large language models in generating readable uveitis information and in improving the readability of online health information. DESIGN: Evaluation of technology. SUBJECTS: Not applicable. METHODS: ChatGPT and Bard were asked the following prompts: (prompt A) "considering that the average American reads at a 6th grade level, using the Flesch-Kincaid Grade Level (FKGL) formula, can you write patient-targeted health information on uveitis of around 6th grade level?" and (prompt B) "can you write patient-targeted health information on uveitis that is easy to understand by an average American?" Additionally, ChatGPT and Bard were asked the following prompt from the first-page results of Google when the term "uveitis" was searched: "Considering that the average American reads at a 6th grade level, using the FKGL formula, can you rewrite the following text to 6th grade level: [insert text]." The readability of each response was analyzed and compared using several metrics described below. MAIN OUTCOME MEASURES: The FKGL is a highly validated readability assessment tool that assigns a grade level to a given text, the total number of words, sentences, syllables, and complex words. Complex words were defined as those with > 2 syllables. RESULTS: ChatGPT and Bard generated responses with lower FKGL scores (i.e., easier to understand) in response to prompt A compared with prompt B. This was only significant for ChatGPT (P < 0.0001). The mean FKGL of responses to ChatGPT (6.3 ± 1.2) was significantly lower (P < 0.0001) than Bard 10.5 ± 0.8. ChatGPT responses also contained less complex words than Bard (P < 0.0001). Online health information on uveitis had a mean grade level of 11.0 ± 1.4. ChatGPT lowered the FKGL to 8.0 ± 1.0 (P < 0.0001) when asked to rewrite the content. Bard was not able to do so (mean FKGL of 11.1 ± 1.6). CONCLUSIONS: ChatGPT can aid clinicians in producing easier-to-understand health information on uveitis for patients compared with already-existing content. It can also help with reducing the difficulty of the language used for uveitis health information targeted for patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Patient-Directed Vasectomy Information: How Readable Is It?

PURPOSE: To assess the quality and readability of online health information on vasectomy using validated readability and quality assessment tools. MATERIALS AND METHODS: The top 50 search results for "vasectomy" on Google, Bing, and Yahoo were selected. Duplicate links, advertisements, blog posts, paid webpages, and information intended for healthcare providers were excluded. Flesch Reading Ease score, Flesch-Kincaid Grade level, Gunning Fog Index, and Simple Measure of Gobbledygook (SMOG) index were used to assess readability, with optimal readability level for online health information established as being at sixth grade reading level. DISCERN Instrument and JAMA Benchmark were used to assess the quality of selected webpages. Inter-assessment score correlation and results by webpage type were analyzed. RESULTS: We analyzed 44 webpages, including 16 academic, 5 hospital-affiliated, 6 commercial, 13 non-profit health advocacy, and 4 uncategorized sources. The average readability of the evaluated webpages was at a 10th grade reading level as measured by the Flesch Kincaid Assessment tool, and an undergraduate reading level per the SMOG and Gunning Fog indices. Non-profit health advocacy webpages had the best reading level but still was not at the recommended level of grade 6 to 7. The overall DISCERN quality of the webpages was "fair", with non-profit health advocacy pages performing best. CONCLUSIONS: The assessed webpages offer education on vasectomy in a language that is too complex for the general population to understand. Furthermore, several sources for online health information, such as non-profits, outperformed webpages by academic institutions. Increased healthcare collaboration and dedication to producing quality online patient resources is necessary to address these shortcomings and build trust among patients to increase utilization of vasectomy and decrease decisional regret.

Potential primary prevention of Peyronie's disease post prostatectomy?-retrospective analysis of peri-operative multi-modal penile rehabilitation.

The surgical management of prostate cancer through radical prostatectomy has the potential to impact patients' sexual function, including erectile dysfunction and Peyronie's disease (PD). Historical data suggests the incidence of PD in post-prostatectomy patients is higher than in the general population at 15.9%. Our study objective was to measure the rate of the development of PD among patients that receive penile rehabilitation (PR) regimen prior to and immediately after radical prostatectomy. In this study, we retrospectively reviewed the charts of 581 patients who were diagnosed with prostate cancer, treated with radical prostatectomy, and engaged in a PR program. Patients with the diagnosis of PD prior to prostatectomy were excluded from this study. The PR program consists of daily tadalafil, L-citrulline, and weekly vacuum erectile device with the option of intracavernosal injections if patients fail to respond to the regular regimen. We found the incidence of PD to be 2.9%, suggesting that PR regimens programs may be associated with a reduced incidence of PD in post-prostatectomy patients. Ten (out of 17) patients were diagnosed with PD after 2 years of follow up. The return of erections was not statistically different among patients who developed PD and the rest of the patients. Prospective, multi-institutional trials will be required to elucidate whether PR can prevent the development of PD in this patient population.

Should I freeze my sperm?-readability and quality of health resources for sperm banking.

Background: Sperm banking refers to the collection and storage of sperm cells for future use. Despite the recommendations of major medical societies, sperm banking is not discussed sufficiently with patients at risk of future fertility. Majority of Americans utilize the internet regarding health information. The aim of this study is to assess the reading level and the quality of online health information on sperm banking. Methods: The top 50 search results from Google, Bing, and Yahoo were selected after searching for the term "sperm banking". Duplicate pages, advertisements, news and magazines, blog posts, videos, paid subscriptions, articles intended for health professionals, and non-related pages were excluded. Four validated readability and two quality assessment tools were used to score the text. Websites were divided into five categories: academic, hospital-affiliated, commercial, non-profit health advocacy, and non-categorized. Descriptive statistics, one sample t-test, and Pearson's correlation coefficient were used to analyze the data. Results: Forty-one webpages were included. The mean Flesch Reading Ease Score (FRES) for all pages was 46.9/100 and the mean reading level was 11th grade, compared to the recommended 6th grade level, across various assessment tools. Utilizing the DISCERN Instrument, quality of online health information was fair. Seven percent of pages received a "good" quality score and no pages received a score of "excellent". On average, 1.5 out of 4 criteria categorized by the JAMA Benchmark, a validated quality assessment tool, were met. The hospital-affiliated webpages received the best reading scores and commercial pages received the highest quality scores. Conclusions: Online health information on sperm banking available in English is of poor quality based on several quality assessment tools and at a reading level significantly higher than what is recommended. Further efforts are needed by providers and healthcare institutions to improve the quality of information available to patients.

Relationship between pelvic sensations and lifetime exposure to receptive anal intercourse among people with prostates.

BACKGROUND: Despite the negative stigma on receptive anal intercourse (RAI), this behavior has a positive influence on individuals' sexual and relationship health. No large studies have previously looked at specific sensations experienced during RAI and how these sensations may change with experience. AIM: In this study we aimed to quantify commonly reported pelvic sensations during RAI and determine whether their presentation changes with increasing experience of RAI. METHODS: An internet survey was conducted on sensations felt during RAI among people with prostates from July 2022-January 2023. The survey content was developed based on a mixed-methods qualitative study and inquired about demographic and sexual histories as well as sensations (pleasure, pain, urinary, and bowel) experienced during RAI. We used descriptive statistics to describe demographic and sexual histories. All data were stratified by lifetime exposure to RAI. OUTCOMES: The primary outcomes assessed included the quantification of both the primary sensations experienced during RAI and the associated bother. RESULTS: In total, 975 participants completed the survey. The median age was 32 (range 18-78) years. The average age of first participation in RAI was 21 ± 6.6 years. Most respondents were having sex at least once a week (65%). Nine percent of respondents reported fewer than 10 experiences with RAI, 26% reported 11-50 RAI experiences, 32% reported 51-200 experiences, 16% reported 201-500 experiences, and 18% reported >500 experiences. As the number of experiences with RAI increased (from <10 to >500 exposures), the reported frequency of pleasurable sensation increased from 41% to 92% (P < .0001), whereas severe insertional pain and symptoms of bowel urgency decreased from 39% to 13% and from 21% to 6%, respectively (P < .0001). Urinary urgency sensation did not differ by lifetime RAI experience. CLINICAL IMPLICATIONS: Lifetime RAI exposure can be readily assessed and correlates not only with pelvic sensation but also many other aspects of sexual health. These results imply that the etiology of dissatisfaction with pleasure or anodyspareunia during RAI may differ by lifetime RAI exposure. STRENGTHS AND LIMITATIONS: This is the first study to our knowledge to assess pelvic sensations experienced during RAI among a large sample of individuals. This is a cross-sectional study, and we cannot conclude how pelvic sensations change over time among individuals. Internet-based participants may not be representative of clinical populations. CONCLUSION: Lifetime exposure to RAI is positively associated with pleasure and is negatively associated with pain and bowel urgency. Pelvic sensations experienced during RAI appear to be dependent on lifetime RAI exposure history regardless of age.

A middle-aged man with hyperandrogenic state.

Hyperandrogenism secondary to testicular cancer typically arises in patients in whom Leydig cell hyperplasia or neoplasia can be identified. Additionally, benign and malignant adrenocortical tumors can also present with signs and symptoms of hyperandrogenism. We report a case of a 40-year-old gentleman who experienced several months of weight gain, worsening gynecomastia, and mood changes secondary to high testosterone and estradiol levels. Workup initially was negative for testicular malignancy and positive for a benign-appearing lesion in the adrenal gland. Despite adrenalectomy, symptoms continued to persist and ultimately a testicular cancer without Leydig cell involvement was identified.

Effectiveness of Topical ρ-Kinase Inhibitors in Veterans with Severe Glaucoma on Maximally Tolerated Medical Therapy.

SIGNIFICANCE: The real-world pharmacological use of netarsudil shows that it can produce a clinically significant decrease in intraocular pressure for a small group of patients, even if they are already taking three or four other hypotensive glaucoma medication classes. PURPOSE: This study aimed to assess the effectiveness of netarsudil in reducing intraocular pressure among veterans with advanced glaucoma on maximally tolerated medical therapy. METHODS: All patients with glaucoma who received netarsudil between June 2018 and April 2020 from the West Los Angeles Veterans Administration Medical Center were reviewed. Inclusion criteria included a minimum of one intraocular pressure measurement in each of two time windows (within and after 4 months of netarsudil use). Exclusion criteria included medication nonadherence, change in treatment plan before post-treatment intraocular pressure could be obtained, corneal disease precluding reliable measurement, outside follow-up, and loss to follow-up. Intraocular pressure at baseline and that at two time windows were compared using analyses of variance. Relationships between intraocular pressure and number of baseline medications and concurrent statin therapy were evaluated. Netarsudil tolerability was reported. RESULTS: Of 200 patients prescribed netarsudil, 42 patients (eyes) met the enrollment criteria. The mean age of these patients was 75.7 years (95% confidence interval [CI], 73.0 to 78.4 years), 64% were of African descent, 79% had open-angle glaucoma, and the mean number of baseline medications was 3.7 (95% CI, 3.5 to 3.9). Baseline intraocular pressure of 17.2 mmHg (95% CI, 16.1 to 18.2 mmHg) decreased to 15.1 mmHg (95% CI, 14.0 to 16.2 mmHg; P < .001), and a reduction of >20% was seen in 30.9% of patient after 4 months of netarsudil therapy. Intraocular pressure reduction was not associated with number of baseline medications or systemic statin use. CONCLUSIONS: Netarsudil may produce a clinically significant intraocular pressure reduction in up to a third of the patients with advanced glaucoma already on maximally tolerated medical therapy.

Perioperative Antibiotic Use in Endoscopic Endonasal Skull Base Surgery.

Introduction Improved evidence-based guidelines on the optimal type and duration of antibiotics for patients undergoing endoscopic endonasal transsphenoidal surgery (EETS) are needed. We analyze the infectious complications among a large cohort of EETS patients undergoing a standardized regimen of cefazolin for 24 hours, followed by cephalexin for 7 days after surgery (clindamycin if penicillin/cephalosporin allergic). Methods A retrospective review of 132 EETS patients from 2018 to 2020 was conducted. Patient, tumor, and surgical characteristics were collected, along with infection rates. Multivariate logistic regression determined the variable(s) independently associated with infectious outcomes. Results Nearly all patients (99%) received postoperative antibiotics with 78% receiving cefazolin, 17% receiving cephalexin, 3% receiving clindamycin, and 2% receiving other antibiotics. Fifty-three patients (40%) had an intraoperative cerebrospinal fluid (CSF) leak, and three patients (2%) developed a postoperative CSF leak requiring surgical repair. Within 30 days, no patients developed meningitis. Five patients (4%) developed sinusitis, two patients (3%) developed pneumonia, and one patient (1%) developed cellulitis at a peripheral intravenous line. Two patients (2%) developed an allergy to cephalexin, requiring conservative management. After adjustment for comorbidities and operative factors, presence of postoperative infectious complications was independently associated with increased LOS ( ß = 3.7 days; p = 0.001). Conclusion Compared with reported findings in the literature, we report low rates of infectious complications and antibiotic intolerance, despite presence of a heavy burden of comorbidities and high intraoperative CSF leak rates among our cohort. These findings support our standardized 7-day perioperative antibiotic regimen.

Opiate Use After Endoscopic Endonasal Transsphenoidal Surgery.

BACKGROUND: The literature on opiate use after endoscopic endonasal transsphenoidal surgery (EETS) is limited. OBJECTIVE: To determine the risk factors for higher opiate use following EETS and the quantity of opiates used after discharge. METHODS: A retrospective review of 144 patients undergoing EETS from July 2018 to July 2020 was conducted. Patient, tumor, and surgical factors were documented. Pain scores and medications used on postoperative days (POD) 0 and 1, and discharge prescriptions, were recorded. Opiate use was quantified using morphine milligram equivalents (MME) dose. Multiple linear regression determined risk factors independently associated with POD0 to 1 opiate use. RESULTS: On POD 0 to 1, mean pain score was 4.9/10 (standard deviation [SD] ± 2.0). Mean acetaminophen use was 3.4 tablets (SD ± 1.6; 650 mg per tablet). Mean opiate use was 35.6 MME (SD ± 36.3), equivalent to 4.7 tablets (SD ± 4.8) of oxycodone 5 mg. Multiple linear regression showed that current smokers required an additional 37.1 MME (P = .011), and patients with grade 3 intraoperative cerebrospinal fluid leaks required an additional 36.7 MME (P = .046) on POD0 to 1. On discharge, mean opiate prescription was 117.7 MME (SD ± 102.1), equivalent to 15.7 tablets (SD ± 13.6) of oxycodone 5 mg. Thirty-nine patients (27.1%) did not require prescriptions. Only 10 patients (6.9%) required opiate refill(s) within 30 days after surgery. CONCLUSION: Patients undergoing EETS have higher opiate needs compared to those undergoing endoscopic sinus surgery, although the overall requirements are still considered low. Independent risk factors associated with higher opiate use in the immediate postoperative period included current smokers and grade 3 intraoperative cerebrospinal fluid leaks.

Development of a Novel, Potentially Universal Machine Learning Algorithm for Prediction of Complications After Total Hip Arthroplasty.

BACKGROUND: As the prevalence of hip osteoarthritis increases, the number of total hip arthroplasty (THA) procedures performed is also projected to increase. Accurately risk-stratifying patients who undergo THA would be of great utility, given the significant cost and morbidity associated with developing perioperative complications. We aim to develop a novel machine learning (ML)-based ensemble algorithm for the prediction of major complications after THA, as well as compare its performance against standard benchmark ML methods. METHODS: This is a retrospective cohort study of 89,986 adults who underwent primary THA at any California-licensed hospital between 2015 and 2017. The primary outcome was major complications (eg infection, venous thromboembolism, cardiac complication, pulmonary complication). We developed a model predicting complication risk using AutoPrognosis, an automated ML framework that configures the optimally performing ensemble of ML-based prognostic models. We compared our model with logistic regression and standard benchmark ML models, assessing discrimination and calibration. RESULTS: There were 545 patients who had major complications (0.61%). Our novel algorithm was well-calibrated and improved risk prediction compared to logistic regression, as well as outperformed the other four standard benchmark ML algorithms. The variables most important for AutoPrognosis (eg malnutrition, dementia, cancer) differ from those that are most important for logistic regression (eg chronic atherosclerosis, renal failure, chronic obstructive pulmonary disease). CONCLUSION: We report a novel ensemble ML algorithm for the prediction of major complications after THA. It demonstrates superior risk prediction compared to logistic regression and other standard ML benchmark algorithms. By providing accurate prognostic information, this algorithm may facilitate more informed preoperative shared decision-making.

Oleic acid stimulates monoamine efflux through PPAR-α: Differential effects in diet-induced obesity.

Obesity continues to be a growing health concern around the world, and elevated levels of free fatty acids as a result of high-fat intake might play a role in neuroendocrine alterations leading to obesity. However, it is unclear how fatty acids affect neuroendocrine functions and energy metabolism. Since hypothalamic monoamines play a crucial role in regulating neuroendocrine functions relating to energy balance, we investigated the direct effects of oleic acid on hypothalamic monoamines and hypothesized that oleic acid would activate peroxisome proliferator-activated receptor alpha (PPAR-α), a nuclear transcription factor involved with fatty acid metabolism, to affect monoamines. We also hypothesized that this response would be subdued in diet-induced obesity (DIO). To test these hypotheses, hypothalami from Sprague Dawley and DIO rats were incubated with 0 (Control), 0.00132 mM, 0.132 mM, 1.32 mM oleic acid, 50 µM MK 886 (a selective PPAR- α antagonist), or oleic acid + MK 886 in Krebs Ringers Henseleit (KRH) solution. HPLC-EC was used to measure monoamine levels in perfusates. Oleic acid produced a significant increase in norepinephrine, dopamine, and serotonin levels in a dose-dependent manner, and incubation with MK886 blocked these effects. The effect of oleic acid on hypothalamic monoamines was attenuated in DIO rats. These findings suggest that PPARα probably plays an essential role in fatty acid sensing in the hypothalamus, by affecting monoamine efflux and DIO rats are resistant to the effects of oleic acid.