Difference In Onset Time Research Articles

Evaluation of Dexmedetomidine with Tiletamine-Zolazepam for Snow Leopard (Panthera uncia) Immobilization.

This study describes two different doses of dexmedetomidine combined with tiletamine-zolazepam (TZ) for anesthesia in snow leopards (Panthera uncia). A total of 11 adult snow leopards were anesthetized in Xining City, Qinghai Province, China from November 2019 to June 2023. We recorded the onset time, anesthesia duration, head-up time, and walking time. Vital signs were recorded every 5 min during anesthesia. Arterial blood gas analysis was performed approximately 20 min after the onset of anesthesia by collecting blood from the femoral artery. All results were presented as mean±SD. There were no significant differences in onset time, anesthesia duration, head-up time, and walking time between the two anesthesia protocols. Heart rate, respiratory rate, body temperature, and blood pressure had a gradual decreasing trend, and blood oxygen saturation gradually increased. Our results suggest that using dexmedetomidine at doses of 21.25±1.38 μg/kg to 30.95±1.13 μg/kg combined with TZ at 2.07±0.08 mg/kg to 2.13±0.15 mg/kg can provide safe and effective anesthesia for snow leopards.

Characterization of Chronotypes Using the Symbolic Aggregate apprXimation (SAX) on Actigraphy Data.

In this study, we discuss an efficient approach to characterizing chronotypes using Symbolic Aggregate approXimation (SAX) on actigraphy data. Actigraphy, a non-invasive monitoring of human rest/activity cycles, provides valuable insights into sleep-wake behaviors and circadian rhythms. However, the high dimensionality of actigraphy data poses significant challenges in storage, processing, and analysis. To address these challenges, we applied the SAX algorithm to transform continuous time-series actigraphy data into a symbolic representation, enabling dimensionality reduction while preserving essential patterns. We analyzed actigraphy data from the National Health and Nutrition Examination Survey (NHANES) database, covering over 10,000 individuals, and used unsupervised clustering to identify distinct chronotype patterns. The SAX transformation facilitated the application of machine learning techniques, revealing five chronotype clusters characterized by differences in activity onset, resolution, and intensity. Age distribution analysis showed biases towards specific age groups within the clusters, highlighting the relationship between age and chronotype. Key findings include age-related Chronotype variations with younger individuals exhibiting delayed chronotypes with significant differences in sleep onset (SOT) and wake time (WT) compared to older adults, suggesting a phase delay in sleep patterns as age decreases and activity transition dynamics where clusters showed distinct patterns in winding up and winding down periods, providing insights into the dynamics of activity transitions. This study demonstrates the efficiency and effectiveness of SAX in processing large-scale actigraphy data, enabling robust chronotype characterization that can inform personalized healthcare and public health initiatives. Further exploration of SAX integration with other biometric measures could deepen our understanding of human circadian biology and its impact on health and behavior.

Yinqiao Sanhuang Paste Combined with Traditional Chinese Medicine Plaster for the Intervention of Drug Rash Induced by Targeted Therapy in Lung Cancer

Objective: To observe the efficacy and safety of Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster in treating drug rash caused by targeted therapy in lung cancer. Methods: A total of 100 lung cancer patients treated at our hospital from January 2021 to December 2023 were selected and randomly divided into an observation group and a control group, with 50 patients in each group. The control group received conventional medication, while the observation group was treated with Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster. The clinical symptom improvement and adverse reactions in both groups were observed. Results: The effective rate in the control group was 80.00%, while in the observation group, it was 96.00%, with a statistically significant difference between the two groups (P < 0.05). The onset time, duration, and significant effect time in the control group were (2.41 ± 0.29) days, (4.42 ± 1.21) days, and (5.45 ± 0.29) days, respectively; in the observation group, they were (2.44 ± 0.21) days, (4.28 ± 1.11) days, and (5.57 ± 1.01) days, respectively. There was no statistically significant difference in the total onset time and total duration between the two groups (P > 0.05). The incidence of adverse reactions in the control group was 28.00%, higher than the observation group’s 10.00% (P < 0.05). Conclusion: Yinqiao Sanhuang Paste combined with traditional Chinese medicine plaster can effectively reduce the symptoms of drug rash induced by targeted therapy in lung cancer and lower the incidence of adverse reactions, indicating good clinical application value.

What do you learn from a single cue? Dimensional reweighting and cue reassociation from experience with a newly unreliable phonetic cue

In language comprehension, we use perceptual cues to infer meanings. Some of these cues reside on perceptual dimensions. For example, the difference between bear and pear is cued by a difference in voice onset time (VOT), which is a continuous perceptual dimension. The present paper asks whether, and when, experience with a single value on a dimension behaving unexpectedly is used by the learner to reweight the whole dimension. We show that learners reweight the whole VOT dimension when exposed to a single VOT value (e.g., 45 ms) and provided with feedback indicating that the speaker intended to produce a /b/ 50% of the time and a /p/ the other 50% of the time. Importantly, dimensional reweighting occurs only if 1) the 50/50 feedback is unexpected for the VOT value, and 2) there is another dimension that is predictive of feedback. When no predictive dimension is available, listeners reassociate the experienced VOT value with the more surprising outcome but do not downweight the entire VOT dimension. These results provide support for perceptual representations of speech sounds that combine cues and dimensions, for viewing perceptual learning in speech as a combination of error-driven cue reassociation and dimensional reweighting, and for considering dimensional reweighting to be reallocation of attention that occurs only when there is evidence that reallocating attention would improve prediction accuracy (Harmon, Z., Idemaru, K., & Kapatsinski, V. 2019. Learning mechanisms in cue reweighting. Cognition, 189, 76–88.).

Onset time, duration of action, and intubating conditions after mivacurium in elderly and younger patients.

The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults. This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 μg kg-1 and propofol 1.5-2.5 mg kg-1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg-1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively. No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness. No difference in onset time of mivacurium 0.2 mg kg-1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions.

Changes in Fingertip Cold-Induced Vasodilatation (Hunting Reaction) on Acute Exposure to Altitude.

Fossati, Alexandre, and Aleid C. J. Ruijs. Changes in fingertip cold-induced vasodilatation (hunting reaction) on acute exposure to altitude. High Alt Med Biol. 25:212-217, 2024. Objective: Cold-induced vasodilation (CIVD) of the extremities is an interesting part of human physiology. Although the physiology of the CIVD reaction remains unknown, there are indications that hypoxia influences our CIVD reaction. The objective of this study is to measure the influence of acute hypoxia on the CIVD reaction of the fingertips. Methods: The CIVD reaction was measured using immersion of one hand in a water bath of 0°C in 12 healthy volunteers at low (1,235 m) and high (3,800 m) altitude during 35 minutes. High altitude was reached by a 20-minute cable car ride. Testing was performed indoors (room temperature, 22-25°C) at both altitudes. Data analysis was performed measuring the parameters of the CIVD reaction. Differences were found using the paired Student's t-test. Results: There was no significant difference in baseline finger temperature, onset time, peak time, and frequency of the CIVD reaction. However, at high altitude, maximum temperature and amplitude were significantly higher, slope was steeper, and minimum temperature was lower. Conclusion: We did not find evidence for a diminished CIVD reaction at high altitude due to hypoxia.

Effects of global warming on drought onset in China

This study investigated the effects of warming on the drought onset in China using meteorological data and soil moisture data from 1980 to 2020. The variation characteristics of drought onset time and onset speed were analyzed systematically. The differences in drought onset time and onset speed during the period 1995–2020 and the period 1980–1994 were compared, and possible impact factors were analyzed. Results indicated that the spatial distribution of drought onset time decreased with an increase in regional wetness in China. In arid regions, onset time at 73 % of sites was over 35 days, and about 13 % was among 60–90 days. In semi-arid and sub-humid regions, the onset time was 25–40 days, and in humid regions, it was 20–30 days. After 1994, namely the significant temperature rise period, the onset time has remarkably shortened in parts of the southern Northeast, North China, the eastern Northwest, the western Southwest, the middle of Tibet, the lower reaches of the Yangtze River, and the coastal region of South China. The shortening was most obvious in sub-humid regions. The greater the warming magnitude, the wetter the region, the faster the drought onset speed. Drought onset speed (γ) was higher in the southern humid region than that in the northern region, and γ for southern Northeast China, northern North China, and eastern Northwest China was higher than that for the rest of North China. After 1994, drought onset speed was accelerated in most regions, especially in the semi-arid and sub-humid regions with precipitation in the range of 300–600 mm. Under the combined effect of increased evapotranspiration and reduced precipitation, the region has been the hot spot with increased drought speed after obvious warming in China.

Interannual Variability in the Onset Time Distribution of the Open Water in the Kara Sea

Abstract Open water in ice-covered oceans is an essential condition for shipping and resource exploitation. We investigate the interannual and spatial variations of the open water onset time in the Kara Sea (KS) and the underlying mechanisms through analyzing satellite-based observations and model simulation results. The empirical orthogonal function (EOF) analysis on the satellite sea ice concentration during 1979–2020 reveals two primary spatial distribution patterns of the open water onset time. The first mode EOF1 shows the coherent advance or delay of the open water onset time within the KS, which is consistent with the multiyear-averaged state. The second mode EOF2 exhibits a seesaw pattern between the southwest and middle regions, which represents the regional difference of the open water onset time within the KS. In 1997 with significant anomaly in EOF2, analysis of the model simulation reveals that the strong easterly wind-induced ice transport is the main reason for the earlier opening in the middle region and delayed opening in the southwestern region. When compared with the multiyear-averaged state, this dynamic process causes a noticeable redistribution of local sea ice in the early melting season (May to June), with much more ice in the southwestern region, thence influences the regional onset time of open water. A similar situation also occurred in the years 1985, 2001, and 2004, as these years presented stronger easterly wind energy accumulated over May to June, which cause earlier opening in the middle region and later opening in the southwestern region. Significance Statement Variability of the open water in the Arctic Ocean has a significant impact on climate and ecosystem variability and also human activities. This study focuses on understanding why the onset time of open water was asynchronous over the Kara Sea. Generally, the open water first forms in the western region of the Kara Sea under the influences of warm inflow from the Barents Sea and river runoff. However, when strong easterly winds prevail across the whole region at the beginning of the melting season, sea ice is transported from east to west, resulting in the advanced opening in the middle and delayed opening in the southwest regions. This finding points out that wind can combine with surface and lateral heat fluxes to influence the interannual variability in the distribution of the open water onset time in the Kara Sea.

Passenger muscle responses in emergency braking events with reclined seating

Emergency braking can generate forward displacement that may influence the effectiveness of protection in collisions, especially for passengers. The development of automated vehicles has enabled the diversification and rationalization of sitting positions, including reclined seating. However, the passenger response in pre-crash scenarios in reclined seating differs from that in standard seating, which poses different requirements for biofidelic human body models (HBMs) to evaluate passenger injuries in collisions. This study conducted emergency braking trials in vehicles at an initial velocity of 80 km/h. Five volunteers were exposed to approximately 1 g manual emergency braking (MEB), and the muscle responses at the front passenger seat with backrest angles of 25°, 45°, and 65° were recorded. The electromyography obtained from 14 muscles of the neck, torso, and lower extremity were normalized using maximum voluntary contractions (MVCs). In the quiet sitting phase, the activity levels were low (< 5% MVC) in all muscles for the three sitting positions. During emergency braking, the muscles are activated to restrict the body motion. There were differences in muscle amplitude and onset time in different backrest angles, with higher muscle activity levels in most muscles in a reclined sitting position. In particular, the sternocleidomastoid, rectus abdominis, and vastus medialis showed different patterns in the peak and steady-state phases. We found that the tibialis anterior was consistently activated at a lower level in all sitting postures (< 8% MVC), which indicates limited support of the shank for the body. The data provided in the paper are presented in corridors and intended for use in the development and validation of HBMs with active muscle models to simulate evasive maneuvers that potentially occur before a crash in the reclined sitting position.

Intrathecal dexamethasone-bupivacaine combination with bupivacaine alone in spinal anesthesia for cesarean delivery.

Postoperative pain management can be achieved by adjuvant medications during the analgesia procedure. The study investigated the effect of intrathecal dexamethasone-bupivacaine combination with bupivacaine alone in spinal anesthesia for cesarean delivery. This randomized, double-blind clinical examination included 50 females who had previously experienced a cesarean section. The participants were assigned randomly into two categories: the intervention group, received intrathecal bupivacaine-dexamethasone, and the control group, received intrathecal bupivacaine-normal saline. Levels of pain were evaluated using a 10 cm visual analog scale (VAS) at intervals of 30 minutes, 1 hour, 2 hours after the operation. The span of the sensory block and postoperative analgesia were assessed. The inclusion of intrathecal dexamethasone with bupivacaine resulted in a significant enhancement in the duration of pain relief during the intervention, lasting for an average of 473.4 ± 39.95 minutes (p<0.001). The duration of sensory and motor block analgesia in the intervention group was more than the control group (128.32 ± 7.30 vs. 92.84 ± 7.84) and (155.6±12.34 vs. 126.16±11.89), respectively (p<0.001). Pain score on the VAS scale at 30, 60, and 120 minutes was significantly lower in the intervention group (p<0.001). There was no difference in side effects and onset time between the study groups. The inclusion of intrathecal dexamethasone alongside bupivacaine has demonstrated enhancement in the duration of sensory block during spinal anesthesia. This improvement was observed without any alterations in the time it takes for the anesthesia to take effect and without any adverse effects during the postoperative period.

Endovenous laser treatment vs conventional surgery for great saphenous vein varicosities: A propensity score matching analysis.

Varicosis is a common venous condition, which is typically treated surgically. However, selection of the optimal surgical approach can be challenging. Previous studies comparing endovenous laser treatment (EVLT) and conventional surgery were retrospective and observational in nature and the results may therefore have been influenced by selection bias and the presence of other confounding factors. In this study, we used propensity score matching to reduce selection bias when comparing EVLT and conventional surgery for the treatment of varicose great saphenous veins. To compare the perioperative and postoperative outcomes of EVLT and conventional surgery in patients with great saphenous vein varicosis. We retrospectively reviewed the records of 1063 patients treated for primary varicosis of the great saphenous vein at the Second Affiliated Hospital of Xuzhou Medical University between January 2009 and December 2019. Among them, 56 patients were excluded owing to additional small saphenous varicose vein involvement, 81 owing to recurring varicose veins, 83 owing to complicated varicose veins (CEAP clinical classification C5-C6), and 6 owing to perioperative phlebitis. Finally, 772 patients were enrolled in this study. Standard demographic and clinicopathological data were collected from the medical records of the patients. For propensity score matching, 522 patients (261 who underwent EVLT and 261 who underwent conventional surgery) were randomly matched 1:1 by age, sex, onset time, smoking status, presence of diabetes, family history, stress therapy, C class, and the affected leg. Of the 772 patients included in the study, 467 underwent EVLT and 305 underwent conventional surgery. There were significant differences in age, onset time, smoking and diabetes status, and family history between the two groups. Following propensity score matching, no significant differences in patients' characteristics remained between the two groups. ELVT was associated with a shorter operation time and hospital stay than conventional surgery, both before and after propensity score matching. There were no differences in complications between the two groups after propensity score matching. Patients who underwent EVLT had a higher recurrence rate during the two-year follow-up period than those who underwent conventional surgery (33.33% vs 21.46%, χ2 = 11.506, P = 0.001), and a greater percentage of patients who underwent EVLT experienced pain one week after the procedure (39.85% vs 19.54%, P = 0.000). EVLT may not always be the best option for the treatment of great saphenous vein varicosis.

IL-10 Levels Differentially Regulate IFNg Signaling of CART19 and CART22

Introduction: CD19-directed CART (CART19) are highly effective in the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, some pts relapse with CD19 negative disease after CART19, which has led to the development of CD22-directed CART (CART22). While CART22 has produced 70% CR in CD19 negative ALL, this is lower than CART19 and there is less evidence for long-term disease control compared to CART19. Interestingly, toxicity patterns are different with CART22 pts experiencing a later and less severe CRS even at high disease burden. To better understand these differences in efficacy and toxicity we conducted comprehensive serum proteomic profiling on serial samples from pts treated with CART-19 or -22. Methods: Serial serum samples from pts enrolled on two clinical trials of the murine CART19 CTL019 (NCT01626495 &amp; NCT02906371) and CART22 (NCT02650414) were examined. Pts were categorized as having severe (Grade 3 or 4) or minimal CRS (Grade 1 or 2). All statistical analyses were performed using R (v4.2.2) and PRISM (v9). Differential expression analyses were performed between CART19 and CART22 pts. Significance was defined as an absolute fold change &amp;gt; 2, and a false discovery rate (FDR) &amp;lt; 0.05. All in vitro experiments were performed in triplicate. Two-tailed t tests were calculated. Results: 43 pts (CART19 N=26 and CART22 N=17) with 223 unique timepoints were included in this analysis. All CART22 pts had minimal CRS; 13 CART19 pts had minimal and 13 had severe CRS. Both cohorts had high disease burden prior to infusion (CART19 mean = 29.9%, CART22 mean=44.3%, p=0.19). All pts who received CART22 had previously received CD19 directed immunotherapy (CART19 N=16, blinatumomab N=1). At the pre-infusion timepoint, 12 proteins were significantly different between pts in the CART19 and CART22 cohorts. The protein most significantly differentially expressed in patients who subsequently underwent CART22 treatment was the anti-inflammatory cytokine IL-10. IL-10 levels were consistently elevated in patients who received CART22, surpassing levels at all observed timepoints, even when compared with patients treated with CART19 who developed severe CRS (See Fig 1). We therefore hypothesized the IL-10 levels may be impacting the efficacy and CRS associated with CART22. We next tested the impact of IL-10 on IFNγ as a surrogate marker of CRS in a series of in vitro experiments. CART-19 or -22 cells from the same donor were co-cultured with NALM-6 cells in the presence and absence of IL-10. Without IL-10 present, CART22 cells produced higher levels of IFNγ than CART19 cells (8959 vs 6395 pg/mL, p=0.005). Inversely, with IL-10 present, CART19 cells produced more IFNγ than CART22 cells (21006 vs 15157 pg/mL, p=0.05). We evaluated the length of immune synapse (IS) formation, the time between CART cell interaction and blast killing, using live-cell microscopy, and found that CART22 cells had a trend towards a prolonged IS formation relative to CART19 cells (median time to detachment 9.1 min vs. 3.5 min, p=ns). Finally, given the differences in time of onset of CRS following CART19 vs CART22, we looked at levels of IFNγ and its canonical responder CXCL9 between pts with minimal CRS only. As expected, we found a later peak of IFNγ in CART22 pts compared to CART19 pts (Figure 2). Interestingly, despite similar peaks in IFNγ, CXCL9 levels were higher in CART22 pts, implying dysregulation of the IFNγ/CXCL9 axes in CART22 but not CART19 pts. Conclusions: Comparing comprehensive serum proteomic profiling between CART19 and CART22 pts we make several novel observations. First, IL-10 levels are significantly higher in CART22 pts at pre-infusion, suggesting that previous immunotherapy has caused an upregulation of this anti-inflammatory cytokine. Second, we show that IL-10 levels have a differential impact on IFNγ levels in CART19 vs CART22 cells. This may impact both CRS associated with CART cells and efficacy and may contribute to observed differences in IFNγ and CXCL9 levels seen between the two patient populations. These findings are significant for the clinical translation of CART22 and other immunotherapies, as previous immunotherapy may lead to sustained alterations in the cytokine milieu. Furthermore, IL-10 is a targetable cytokine that could be modulated in future studies to improve efficacy of CART22.

Selectivity to acoustic features of human speech in the auditory cortex of the mouse

A better understanding of the neural mechanisms of speech processing can have a major impact in the development of strategies for language learning and in addressing disorders that affect speech comprehension. Technical limitations in research with human subjects hinder a comprehensive exploration of these processes, making animal models essential for advancing the characterization of how neural circuits make speech perception possible. Here, we investigated the mouse as a model organism for studying speech processing and explored whether distinct regions of the mouse auditory cortex are sensitive to specific acoustic features of speech. We found that mice can learn to categorize frequency-shifted human speech sounds based on differences in formant transitions (FT) and voice onset time (VOT). Moreover, neurons across various auditory cortical regions were selective to these speech features, with a higher proportion of speech-selective neurons in the dorso-posterior region. Last, many of these neurons displayed mixed-selectivity for both features, an attribute that was most common in dorsal regions of the auditory cortex. Our results demonstrate that the mouse serves as a valuable model for studying the detailed mechanisms of speech feature encoding and neural plasticity during speech-sound learning.

Clinical characteristics of adnexal torsion and role of ovarian sparing surgery: a clinical retrospective analysis.

To analyze the clinical characteristics and risk factors related to necrosis of adnexal torsion (AT) and improve the application of ovarian-sparing surgery (OSS). Data of 142 patients with 144 surgically confirmed AT lesions between October 2011 and December 2021 were retrospectively analyzed. The risk of torsion caused by tumors was higher than that caused by tumor-like lesions (p = 0.003). The incidence of right adnexal necrosis was higher than that of left adnexal necrosis (p = 0.03). There were no significant differences in adnexal necrosis or onset time (p = 0.29) between groups. The main risk factor for adnexal necrosis was the degree of torsion with a threshold of 510°. The size of adnexal mass and the degree of torsion increased linearly with age. The OSS rate was 59.7% for all patients, and 71.6% in the premenopausal women. No serious complications occurred in any of the patients. Age, histopathological type, adnexal size, degree of torsion, and pelvic anatomical structure are risk factors for AT and adnexal necrosis. There is no infinite correlation between adnexal necrosis and onset time. Adnexal size is the main risk factor for AT, and along with the risk of adnexal necrosis, increases with age. The degree of torsion is the main risk factor for adnexal necrosis, and torsional severity increases with age. OSS is safe and does not increase the incidence of postoperative complications.

Two non-familial cases of Galloway-Mowat syndrome carrying the homozygous mutations of WDR73 and TP53RK

Galloway–Mowat syndrome (GAMOS) is a rare hereditary disease manifested as a combination of nephrotic syndrome and central nervous system impairment. To date, many GAMOS cases attributed to various gene mutations have been reported such as WHAMM, NUP107, WDR73, OSGEP, and TP53RK. We detected two novel homozygous mutations of WDR73 ‘’NM_032856:c.G287A:p.R96K‘’ and TP53RK ‘’NM_033550:c.A193O:p.K65Q‘’ in two female kids of the consanguineous parents from different families using whole exome sequencing. Both patients almost manifested similar neurodegenerative phenotypes, including developmental delay, microcephaly, hypotonia, and brain atrophy on magnetic resonance imaging during infancy. WDR73-positive GAMOS case manifested a late-onset minimal nephrotic syndrome at the age 4 years while TP53RK-positive case presented nephrotic syndrome at the age 1 which progressed to steroid-resistant nephrotic syndrome due to lack of remission after 4-6 weeks of initial treatment with prednisone. Despite the brain abnormalities and the onset time difference of renal abnormalities, both patients are still alive. Given the heterogeneity of the renal phenotype among GAMOS types, accurate recognition of expanding spectrum of phenotype findings and regular renal function screening are necessary for an early diagnosis and timely treatment.

THU541 Impact Of Gender On Treatment Decisions And Outcome In Patients With Neuroendocrine Neoplasms

Abstract Disclosure: J. Beck: None. A. Siebenhüner: None. D. Wild: None. E.R. Christ: None. J. Refardt: None. Introduction/Background: Gender differences affect the treatment of several diseases in both male and female patients. However, the influence of gender on treatment decisions and outcome in neuroendocrine neoplasms (NENs) has scarcely been investigated. Aims: Comparison of tumor characteristics, treatment decisions and outcome of patients with NENs, stratified by gender. Material and Methods: Retrospective analysis of the SwissNET cohort involving NENs of gastroenteropancreatic, pulmonal or unknown origin from 07/14 – 09/21. Site of origin, tumor grading, time to first treatment, choice of treatment and overall survival was assessed. Results: 2329 patients were included in the analysis with 54% being male and 46% female patients. No significant difference in site of origin, tumor grading and staging was found between male and female patients. There was also no difference in time of symptoms onset until diagnosis and first treatment intervention. Surgery was performed in 66.3% of male and 71% of the female patients, p=0.016. Meanwhile, male patients received more often PRRT (22% vs 19.3%, p=0.007) and chemotherapy (15.9% vs 12.7%, p=0.032). Despite the similar tumor characteristics, the median overall survival of male patients was significantly lower compared to female patients (Male: 124.8 months, Female: 158.5 months, p&amp;lt;0.001). Interestingly, this difference was most pronounced in patients with lung NENs (Male: 142 months, Female: not reached) and cancer of unknown origin (Male: 18.5 months, Female: 35 months). Conclusions: Male gender seems to be a risk factor for worse outcome, specifically for lung NENs and NENs of unknown origin. The underlying mechanisms of these findings remain to be established. Presentation: Thursday, June 15, 2023

Mycophenolate mofetil increases the risk of diarrhea in allogeneic hematopoietic stem cell transplantation recipients.

Mycophenolate mofetil (MMF) was reported to be a main cause of diarrhea following organ transplantation. However, research on MMF-induced diarrhea following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently insufficient. This retrospective study examined the incidence of MMF-induced diarrhea among allo-HSCT recipients. Recipients were divided according to the receipt of MMF and the appearance of diarrhea. The differences in clinical information, MMF usage and trough concentrations, and the occurrence of diarrhea from the first day of conditioning treatment to 100 days after transplantation were analyzed. In total, 32.9% of the recipients reported diarrhea. The incidence rate of diarrhea was higher in the MMF group than in the non-MMF group (40.0% vs. 16.7%). MMF-induced diarrhea usually occurred within 9 days of MMF initiation and persisted for 7.27 ± 3.54 days. The average body weight, MMF daily dose, and MMF trough concentration were higher in patients with diarrhea. MMF increased the risk of diarrhea in allo-HSCT recipients, and the risk was related to the MMF dose and trough concentration. The difference in onset time could be a basis for identifying the cause of diarrhea in allo-HSCT recipients.

State-dependent modulation of low-threshold-current-regulated dendritic Ca2+ response in thalamic reticular neurons with extracellular electric fields

Deep brain stimulation (DBS) in thalamic reticular nucleus (TRN) neuron provides a novel treatment for drug-resistant epilepsy via the induced electrical field (EFs). However, the mechanisms underlying EF effects remain unclear. This paper investigated how EFs regulate low-threshold dendritic Ca2+ (dCa) response and thus contribute to the input–output relationship of TRN cell. Our results showed that EFs modulate firing modes differently in a neuronal state-dependent manner. At the depolarized state, EFs only regulate the spike timing of a somatic stimulus-evoked single action potential (AP) with less contribution in the regulation of dCa response but could induce the transition between a dendritic stimulus-evoked single AP and a tonic burst of APs via the moderate regulation of dCa response. At the hyperpolarized state, EFs have significant effects on the dCa response, which modulate the large dCa response-dependent burst discharge and even cause a transition from this type of burst discharge to a single AP with less dCa response. Moreover, EF effects on stimulation threshold of somatic spiking prominently depend on EF-regulated dCa responses and the onset time differences between the stimulus and EF give rise to the distinct effect in the EF regulation of dCa responses. Finally, the larger neuronal axial resistance tends to result in the dendritic stimulus-evoked dCa response independent of somatic state. Interestingly, in this case, the EF application could reproduce the similar somatic state-dependent dCa response to dendritic stimulus which occurs in the case of lower axial resistance. These results suggest that the influence of EF on neuronal activities depends on neuronal intrinsic properties, which provides insight into understanding how DBS in TRN neuron modulates epilepsy from the point of view of biophysics.

Evaluation of differential effects of CDP-choline and choline on parasympathetic activity and changes in choline levels with heart rate variability

Objective: Heart rate variability (HRV) is used to evaluate the autonomic activity of heartbeat. This study aimed to investigate the&#x0D; effects of cholinomimetic drugs cytidine diphosphate-choline (CDP-choline) and choline, on short-term HRV parameters.&#x0D; Materials and Methods: Animals were randomized into three groups; control (0.9% NaCl), choline (100 mg/kg), CDP-choline (400&#x0D; mg/kg). Electrocardiography recordings were obtained for 45-minutes after treatments with 15-minutes intervals. HRV analyses and&#x0D; total choline level measurements in serum and heart tissues were performed.&#x0D; Results: High frequency power and total power increased in treatment groups, while heart rates were decreased. Low frequency was&#x0D; decreased with choline while very low frequency power decreased with CDP-choline. Choline affected most of the HRV parameters&#x0D; in the first 15 minutes, while the effect of CDP-choline started within 30 minutes. Total choline levels were higher in both treatment&#x0D; groups than in the control while the levels were also higher in the choline group compared to CDP-choline group.&#x0D; Conclusion: This study showed that CDP-choline and choline treatments produced a rapid response to short-term HRV parameters,&#x0D; while increasing tissue choline levels. Moreover, the differences in effects and onset time between the drugs on HRV might be related&#x0D; to tissue choline concentration.

Layer-fMRI VASO with short stimuli and event-related designs at 7 T

Layers and columns are the dominant processing units in the human (neo)cortex at the mesoscopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical surface. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing complementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period and sub-millimeter resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials (∼20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimulus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.