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The Selective Serotonin 5-HT2A Receptor Agonist (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents
No full textPsychedelics have emerged as a promising treatment for mental health disease, and the therapeutic potential of psilocybin and lysergic acid diethylamide (LSD) is presently being pursued in numerous clinical trials. This has prompted a search for novel agents with more specific pharmacological activities than the rather promiscuous classical psychedelics. Here we present the detailed pharmacological characterization of one such compound, LPH-5 [(S)-3-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)piperidine]. LPH-5 was found to be a potent partial agonist at the 5-HT2A receptor (5-HT2AR) with pronounced selectivity for 5-HT2AR over the related 5-HT2BR and 5-HT2CR in a range of functional assays. LPH-5 dose-dependently induced head-twitch responses (HTR) as well as robust acute and persistent antidepressant-like effects in rats. These results suggest that selective 5-HT2AR activation holds antidepressant potential and indicate that this activity component is key for the therapeutics effects of classical psychedelics
Reduction in Opioid Requirements Following Changes to Regional Anesthesia for Patients Undergoing Total Knee Arthroplasty
Get PDFBackground: Newer analgesic techniques to reduce opioid use and pain after total knee arthroplasty (TKA) include preoperative cryoneurolysis, adductor canal block (ACB), and local anesthetic infiltration between the popliteal artery and capsule of the knee (iPACK) block. The purpose of this study was to evaluate whether changing the regional analgesic from ropivacaine to liposomal bupivacaine would provide superior pain relief and reduce opioid requirements at 2 and 12 weeks following TKA. Methods: We conducted a retrospective medical records review of 140 consecutive patients who underwent primary TKA at a single site and received ACB with ropivacaine (multimodal-ropivacaine [MM-R] group, n = 70) or ACB/iPACK with liposomal bupivacaine (multimodal-liposomal bupivacaine [MM-LB] group, n = 70). The primary outcomes were the morphine milligram equivalent (MME) of filled opioid prescriptions at discharge and during the first 12 weeks after TKA, as well as the Knee injury and Osteoarthritis Outcome Score and the Patient-Reported Outcomes Measurement Information System pain intensity and pain interference scores at 2 and 12 weeks postsurgery. Results: The median MMEs for discharge opioid prescriptions and all opioid prescriptions were, respectively,65% (P \u3c 0.0001) and 48% (P \u3c 0.0001) lower for patients in the MM-LB group vs the MM-R group. The MM-LB group had significantly better patient-reported outcomes 2 weeks after TKA compared to the MM-R group. Conclusion: Compared with ropivacaine-based regional analgesia, liposomal bupivacaine–based regional analgesia in the context of a modern multimodal pain regimen may reduce opioid requirements and improve patient-reported outcomes during acute and short-term recovery after TKA
Chronic administration of a cannabis-derived mixture at an antihyperalgesic dose does not significantly enhance hepatotoxicity or the development of metabolic dysfunction-associated steatohepatitis in male mice
Get PDFCannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic pathology following chronic administration of a cannabinoid mixture (NEPE14) at a dose equivalent to one previously demonstrating antihyperalgesic effects in rats. The effects of NEPE14 were investigated in a mouse model of MASH produced by feeding a Western diet rich in fat and simple sugars. After 24 weeks of NEPE14 administration, there was no hepatotoxicity in mice receiving the control diet and no significant exacerbation of MASH in mice receiving the Western diet. In conclusion, no chronic liver toxicity was observed, but there was also no evidence for protection against MASH by this product
Kresenda Raasch Interview
Get PDFThis interview with Kresenda Raasch was conducted by Chandler Smith on May 26, 2025. Interview transcribed by John Gore.https://digitalscholar.lsuhsc.edu/oral_hist/1007/thumbnail.jp
Description and Consistency of In-Game Pitching Kinetics\u27 Relationship With Ball Velocity
No full textBaseball pitchers commonly suffer shoulder and elbow injuries. Previous research on the relationship between pitch velocity and upper extremity kinetics has been limited to laboratory settings, but recent strides in markerless motion capture have allowed analysis of in-game baseball pitching biomechanics. Therefore, our purpose was to provide normative data of in-game pitching kinetics and assess the relationships between pitch velocity and shoulder and elbow kinetics. Data from 183 college pitchers were included in this retrospective analysis of in-game college baseball games. Multilevel models were used to assess the relationships between pitch velocity and kinetics. ICCs were used to assess the intrapitcher relationship between kinetics across multiple outings. The inclusion of random slopes did not meaningfully reduce intrapitcher throwing arm kinetic variance. Additionally, the intrapitcher relationship between throwing arm kinetics and ball velocity did not remain constant across multiple outings. Pitch velocity and in-game throwing arm kinetics did not have a strong intrapitcher relationship, which is different than the results of previous laboratory analyses. Intrapitcher relationship between fastball velocity and throwing arm kinetics does not remain consistent across multiple outings. Additionally, this study provides normative in-game kinetic data for baseball pitching
Different Attention Domains and Speech-in-Noise Performance: A Preliminary Study
No full textPurpose: The primary aim of this preliminary study was to explore the relationship between five attention domains, cognitive flexibility, and speech-in-noise (SIN) performance in both auditory-only (AO) and audiovisual (AV) modalities. Methods: Ten younger and 10 middle-aged adult participants who had standard pure-tone averages no greater than 15 dB HL completed the following three behavioral measures. The Multimodal Lexical Sentence Test for Adults (Kirk et al, 2012) was used to evaluate speech-in-noise performance in AO and AV modalities. Two lists of 12 sentences were presented at a fixed 0-dB signal-to-noise ratio for each of the AO and AV conditions. The Attention Processing Training test (Sohlberg and Mateer, 2005) was administered to each participant, presented bilaterally at 60 dB HL via insert earphones to assess five domains of attention: sustained attention (I), complex sustained attention (II), selective attention (III), divided attention (IV), and alternating attention (V). The Comprehensive Trail-Making Test, Second Edition (Reynolds, 2019) was administered to assess participants\u27 inhibitory control and cognitive flexibility, which are heavily influenced by attention. Results: Correlation and regression analyses of these sample data indicated a significant link between alternating attention and SIN performance in the auditory modality in the younger adults. This link was not observed in middle-aged adults, nor for audiovisual SIN performance. Conclusions: In this study sample, younger individuals with better alternating attention abilities were able to better use contextual information to understand speech in noisy situations without visual context support. The younger adults capitalized on their alternating attention capacities to improve their auditory-only SIN performance, whereas the middle-aged adults did not demonstrate this ability despite similar (sometimes better) alternating attention scores. Alternating attention was not used in the AV modality in either group, possibly due to the simultaneous demand of visual and auditory inputs
Robust and resilient hidden sequence decoding in noisy data with enhanced HMM and dynamic NN ensembles
No full textThe hidden Markov model (HMM) is a powerful tool for modeling sequential data in fields such as bioinformatics, speech recognition, natural language processing, and finance. However, sequential data are often noisy and incomplete, posing significant challenges for traditional HMMs. To address these issues, we propose a novel approach that integrates a Dynamic-Weighted Sequential Ensemble of Neural Network models (DWSE-NN) and an Enhanced Adaptive-HMM (EA-HMM). Our DWSE-NN framework reduces bias from previous ensemble predictions, while the EA-HMM, based on a modified Baum–Welch (MBW) and Posterior-Viterbi (PV) algorithm, dynamically adjusts transition and emission probabilities to achieve improved decoding accuracy and robustness. Our ensemble model demonstrates substantial improvements over Adaboosting sequential ensembles across multiple datasets and metrics. For instance, on Dataset 1, DWSE-RNN achieved 98.34% accuracy, 98.30% precision, 98.33% recall, and an F1 score of 98.25% under noisy test conditions, with a loss of 0.57, significantly surpassing Adaboost’s 74.18% accuracy, 80.47% precision, 74.18% recall, and 75.95% F1 score with a loss of 8.92. Similarly, on Dataset 2, DWSE-RNN outperformed Adaboost, achieving 89.02% accuracy and F1 score, compared to Adaboost’s 66.57% accuracy and 67.23% F1 score. On Dataset 3, DWSE-RNN maintained resilience, achieving 50.04% accuracy, 48.76% precision, 52.27% recall, and a 49.81% F1 score under noisy conditions, compared to Adaboost’s 33.85% accuracy and 34.05% F1 score. To further assess decoding performance, we introduce a ‘reconstruction loss’ metric, which evaluates how well the EA-HMM captures underlying state transitions and emission probabilities, compared to traditional HMM models. For instance, DWSE-DNN with the MBW and PV configuration demonstrated resilience with a reconstruction loss of 0.05 on Dataset D1, 0.07 on Dataset D2, and 0.10 on Dataset D3. These results validate our model’s robustness, making it highly suitable for applications requiring accurate and resilient sequence decoding in challenging data environments
Genotype distribution of human papillomavirus among women with cervical cancer stratified by HIV status in Tanzania
Get PDFBackground Cervical cancer (CC) is the leading cancer among women in Tanzania, especially among those between the ages of 15 and 44. The prevalence of high-risk Human papillomavirus (HR-HPV)-16/18 women in the general population at any given time is 3.3%. HR-HPVs 16 or 18 are the primary cause of CC. The distribution of HPV genotypes among women with CC according to HIV status is unknown in Tanzania. This study aimed to determine the HPV genotype distribution according to HIV status among women with CC in Tanzania. Methods This cross-sectional study was done at Ocean Road Cancer Institute (ORCI) in Tanzania among women with histologically confirmed CC. HIV serology testing was performed. Biopsy was taken from cervical lesions, and DNA was extracted. HPV DNA was amplified by using a previously validated multiplex HPV PCR assay targeting 14 high-risk HPV genotypes (16,18,30,31,33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) and two low‐risk HPV genotypes (6 and 11). Continuous variables were compared using either a student t-test or the Mann-Whitney U test. Fisher’s exact test was employed to compare discrete variables. A P-value less than 0.05 was considered statistically significant. Results We included 100 women with CC. The prevalence of HIV infection in this study was 42%. The prevalence of any HPV infection was 94%, ranging from 1–3 genotypes per woman. HPV. The median age for women living with HIV (WLWH) with CC patients was 45 years (IQR, 31–60), while the median age for HIV-uninfected women with CC patients was 57 years (IQR, 30–78). (p = 0.0001). WLWH and HIV-uninfected women had similar HPV prevalence, except for HPV 35, which was more common in WLWH. There was a trend of high prevalence of HPV 52 and HPV 58 in WLHH compared to HIV-uninfected women, but this difference was not statistically significant. The prevalence of HPV 16 and/or 18 infection in the entire sample was 85%. The combined prevalence of HPV 16 and/or 18 was 76% WLWH and 91% amongst HIV-uninfected women (p = 0.036).The majority of women (77.9%) had single-genotype HPV infection. There was no difference in the distribution of multiple or single HPV genotypes infection by HIV status (p = 0.25). Conclusion In this study, HIV positive women with CC presented at a significantly younger age (45 years) compared to the HIV-negative women (57 years). The prevalence of high-risk HPV is high among women with CC in Tanzania. Distribution of most high-risk HPV genotypes among women with CC was not significantly influenced by HIV status except for HPV 35, which appeared to be more in HIV positive women compared to HIV-negative women. While the majority of the high-risk HPV infections were with single HPV genotypes, the prevalence of multiple high-risk HPV infections was at 22%, with no significant difference between the two HIV statuses. A vaccination program that aptly targets HPV 16 and 18 could prevent up to 85% of CC cases in Tanzania, regardless of HIV. Keywords: Human papillomavirus, cervical cancer, HIV, Tanzania
Utility of the scratch collapse test for diagnosis of neurogenic thoracic outlet syndrome: Patient-reported outcomes after surgical treatment with at least 1 year follow-up
No full textINTRODUCTION: This study introduces the Scratch Collapse Test as a diagnostic tool for Neurogenic Thoracic Outlet Syndrome (NTOS) and analyzes and evaluates functional and patient-reported outcomes with at least one year of post-surgical follow-up. METHODS: Forty-four consecutive patients who underwent surgery for NTOS were reviewed. Patients were contacted at least one year postoperatively and assessed using standardized patient-reported outcome measures (PROMs), including Visual Analog Scale (VAS) for pain, Derkash classification, Disabilities of the Arm, Shoulder, and Hand (DASH) score, Michigan Hand Outcomes Questionnaire (MHQ), and Cervical Brachial Symptom Questionnaire (CBSQ). Data were analyzed using t-tests and linear regression models. RESULTS: The NTOS site of involvement was supraclavicular (SC) in 12 (27.3%) patients, infraclavicular (IC) in 16 (36.4%), and both (SC and IC) in 16 (36.4%). A distal compression site was treated in 20 (45.5%) patients. The overall success rate, as assessed through the Derkash classification, was 87.5%. The mean postoperative VAS score (2.6 + 3.2) was significantly improved from the preoperative VAS score (8.0 + 2.9). Mean postoperative DASH, MHQ, and CBSQ scores were 32.8 ± 21.8, 68.1 ± 26.5, and 39.2 ± 32.6, respectively. Multiple linear regression analysis showed that a longer duration of symptoms before surgery was the most significant factor for a higher mean postoperative VAS pain score. CONCLUSION: Longer time to surgery was associated with higher postoperative VAS pain scores, suggesting that earlier surgical intervention in NTOS patients may be beneficial. Higher VAS scores were significantly correlated with poorer postoperative mid-term outcomes as assessed through the DASH, MHQ, CBSQ scores, and Derkash classification