Mixed occupancy: the crystal structure of scheelite-type LiLu[MoO4]2.

Coarse colorless single crystals of lithium lutetium bis-[orthomolybdate(VI)], LiLu[MoO4]2, were obtained as a by-product from a reaction aimed at lithium derivatives of lutetium molybdate. The title compound crystallizes in the scheelite structure type (tetra-gonal, space group I41/a) with two formula units per unit cell. The Wyckoff position 4b (site symmetry ) comprises a mixed occupancy of Li+ and Lu3+ cations in a 1:1 ratio. In comparison with a previous powder X-ray study [Cheng et al. (2015 ▸). Dalton Trans. 44, 18078-18089.] all atoms were refined with anisotropic displacement parameters.

Evolution of Telehealth Program to Meet Current Needs of Post-Acute and Long-Term Care Communities.

This article describes a telehealth program initially created to reduce transfers to acute care from the nursing home and its evolution into a robust program that includes Behavioral Health, a Medical Director program, and telenursing.

Declining antibody affinity over time after human vaccination with a Plasmodium falciparum merozoite vaccine candidate.

Maintaining high affinity antibodies after vaccination may be important for long-lasting immunity to malaria, but data on induction and kinetics of affinity is lacking. In a Phase 1 malaria vaccine trial, antibody affinity increased following a second vaccination but declined substantially over 12-months, suggesting poor maintenance of high affinity antibodies.

Exploring adolescent girls and young women's PrEP-user profiles: qualitative insights into differentiated PrEP delivery platform selection and engagement in Cape Town, South Africa.

INTRODUCTION: Adolescent girls and young women (AGYW), a priority population for HIV prevention in Africa, show high interest but difficulty in sustained effective use of pre-exposure prophylaxis (PrEP). With ongoing PrEP scale-up focused on increasing access, it is important to understand what influences AGYW's choice of PrEP delivery platforms. METHODS: The POWER implementation study in Cape Town provided PrEP between 2017 and 2020 to AGYW (16-25 years) from four differentiated delivery platforms: mobile clinic, government facility, courier delivery or community-based youth club. Healthcare providers at government and mobile clinics provided PrEP (initiation and refills) as part of comprehensive, integrated sexual and reproductive health services. Courier and youth club platforms provided light-touch PrEP refill services incorporating rapid HIV self-testing. We conducted in-depth interviews with a purposive sample of AGYW who had ≥3 months of PrEP-use and accessed ≥2 PrEP delivery platforms. The thematic analysis explored AGYW's preferences, decision-making and habits related to PrEP access to inform market segmentation. RESULTS: We interviewed 26 AGYW (median age 20) PrEP-users between November 2020 and March 2021. AGYW PrEP-users reported accessing different services with, 24 accessing mobile clinics, 17 courier delivery, 9 government health facilities and 6 youth clubs for their PrEP refills. Qualitative findings highlighted four potential behavioural profiles. The "Social PrEP-user" preferred PrEP delivery in peer spaces, such as youth clubs or adolescent-friendly mobile clinics, seeking affirmation and social support for continued PrEP use. The "Convenient PrEP-user" favoured PrEP delivery at easily accessible locations, providing quick (courier) or integrated contraception-PrEP refill visits (mobile and government clinic). The "Independent PrEP-user" preferred PrEP delivery that offered control over delivery times that fit into their schedule, such as the courier service. The "Discreet PrEP-user" highly valued privacy regarding their PrEP use (courier delivery) and avoided delivery options where unintentional disclosure was evident (youth club). Comfort with HIV self-testing had minimal influence on PrEP delivery choice. CONCLUSIONS: Market segmentation of AGYW characterizes different types of PrEP-users and has the potential to enhance tailored messaging and campaigns to reach specific segments, with the aim of improving sustained PrEP use and HIV prevention benefits.

Characterizing the opioidergic mechanisms of repetitive transcranial magnetic stimulation-induced analgesia: a randomized controlled trial.

ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of ß-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.

Bacterial Infections After Liver Transplantation and the Role of Oral Selective Digestive Decontamination: A Retrospective Cohort Study.

BACKGROUND: Bacterial infections are common after liver transplantation (LT) and cause serious morbidity and mortality. In our center, prolonged selective digestive decontamination (SDD) is the standard of care, which may lead to a reduced number and severity of bacterial infections. The aim of the current study was to investigate bacterial infection rates, the causative pathogens, localization, and the possible influence of SDD within the first year after LT. METHODS: A retrospective single-center cohort study was performed. Patients within their first year after LT between 2012 and 2017 were included. Patients received SDD for 3 weeks immediately after LT. The type of infection, bacterial subtype, CSI classification, severity, and potential interventions were recorded. RESULTS: One hundred eighty-six patients were included in the study. Seventy-eight patients (41.9%) had a bacterial infection within the first year after LT. The most common types of infection were cholangitis (25.8%) and secondary infected abdominal fluid collections (25.3%). The most common bacteria were Gram-positive enterococcal- (36.5%) and Gram-negative enterobacterial species (34.2%). 35.5% of the infections occurred within the first month after LT, mainly caused by Gram-positive bacteria (76.7%). CONCLUSIONS: Cholangitis and infected abdominal fluid are the most common types of infection within one year after LT, mainly caused by enterococcal- and enterobacterial species. Within the first month after LT, infections were mostly caused by Gram-positive bacteria, which could be a consequence of protocol use of SDD. The results can be used for the choice of empirical antibiotic therapy based on the most common types of bacteria and the time frame after LT.

Personalized and Circuit-Based Transcranial Magnetic Stimulation: Evidence, Controversies, and Opportunities.

The development of neuroimaging methodologies to map brain connectivity has transformed our understanding of psychiatric disorders, the distributed effects of brain stimulation, and how transcranial magnetic stimulation can be best employed to target and ameliorate psychiatric symptoms. In parallel, neuroimaging research has revealed that higher-order brain regions such as the prefrontal cortex, which represent the most common therapeutic brain stimulation targets for psychiatric disorders, show some of the highest levels of interindividual variation in brain connectivity. These findings provide the rationale for personalized target site selection based on person-specific brain network architecture. Recent advances have made it possible to determine reproducible personalized targets with millimeter precision in clinically tractable acquisition times. These advances enable the potential advantages of spatially personalized transcranial magnetic stimulation targeting to be evaluated and translated to basic and clinical applications. In this review, we outline the motivation for target site personalization, preliminary support (mostly in depression), convergent evidence from other brain stimulation modalities, and generalizability beyond depression and the prefrontal cortex. We end by detailing methodological recommendations, controversies, and notable alternatives. Overall, while this research area appears highly promising, the value of personalized targeting remains unclear, and dedicated large prospective randomized clinical trials using validated methodology are critical.

High-pitch CT pulmonary angiography (CTPA) with ultra-low contrast medium volume for the detection of pulmonary embolism: a comparison with standard CTPA.

OBJECTIVE: To investigate the feasibility and image quality of high-pitch CT pulmonary angiography (CTPA) with reduced iodine volume in normal weight patients. METHODS: In total, 81 normal weight patients undergoing CTPA for suspected pulmonary arterial embolism were retrospectively included: 41 in high-pitch mode with 20 mL of contrast medium (CM); and 40 with normal pitch and 50 mL of CM. Subjective image quality was assessed and rated on a 3-point scale. For objective image quality, attenuation and noise values were measured in all pulmonary arteries from the trunk to segmental level. Contrast-to-noise ratio (CNR) was calculated. Radiation dose estimations were recorded. RESULTS: There were no statistically significant differences in patient and scan demographics between high-pitch and standard CTPA. Subjective image quality was rated good to excellent in over 90% of all exams with no significant group differences (p = 0.32). Median contrast opacification was lower in high-pitch CTPA (283.18 [216.06-368.67] HU, 386.81 [320.57-526.12] HU; p = 0.0001). CNR reached a minimum of eight in all segmented arteries, but was lower in high-pitch CTPA (8.79 [5.82-12.42], 11.01 [9.19-17.90]; p = 0.005). Median effective dose of high-pitch CTPA was lower (1.04 [0.72-1.27] mSv/mGy·cm; 1.49 [1.07-2.05] mSv/mGy·cm; p < 0.0001). CONCLUSION: High-pitch CTPA using ultra-low contrast volume (20 mL) rendered diagnostic images for the detection of pulmonary arterial embolism in most instances. Compared to standard CTPA, the high-pitch CTPA exams with drastically reduced contrast medium volume had also concomitantly reduced radiation exposure. However, objective image quality of high-pitch CTPA was worse, though likely still within acceptable limits for confident diagnosis. CLINICAL RELEVANCE: This study provides valuable insights on the performance of a high-pitch dual-source CTPA protocol, offering potential benefits in reducing contrast medium and radiation dose while maintaining sufficient image quality for accurate diagnosis in patients suspected of pulmonary embolism. KEY POINTS: • High-pitch CT pulmonary angiography (CTPA) with ultra-low volume of contrast medium and reduced radiation dose renders diagnostic examinations with comparable subjective image quality to standard CTPA in most patients. • Objective image quality of high-pitch CTPA is reduced compared to standard CTPA, but contrast opacification and contrast-to-noise ratio remain above diagnostic thresholds. • Challenges of high-pitch CTPA may potentially be encountered in patients with severe heart failure or when performing a Valsalva maneuver during the examination.

Comparisons of Accelerated Continuous and Intermittent Theta Burst Stimulation for Treatment-Resistant Depression and Suicidal Ideation.

BACKGROUND: Suicidal ideation is a substantial clinical challenge in treatment-resistant depression (TRD). Recent work demonstrated promising antidepressant effects in TRD patients with no or mild suicidal ideation using a specific protocol termed intermittent theta burst stimulation (iTBS). Here, we examined the clinical effects of accelerated schedules of iTBS and continuous TBS (cTBS) in patients with moderate to severe suicidal ideation. METHODS: Patients with TRD and moderate to severe suicidal ideation (n = 44) were randomly assigned to receive accelerated iTBS or cTBS treatment. Treatments were delivered in 10 daily TBS sessions (1800 pulses/session) for 5 consecutive days (total of 90,000 pulses). Neuronavigation was employed to target accelerated iTBS and cTBS to the left and right dorsolateral prefrontal cortex (DLPFC), respectively. Clinical outcomes were evaluated in a 4-week follow-up period. RESULTS: Accelerated cTBS was superior to iTBS in the management of suicidal ideation (pweek 1 = .027) and anxiety symptoms (pweek 1 = .01). Accelerated iTBS and cTBS were comparable in antidepressant effects (p < .001; accelerated cTBS: mean change at weeks 1, 3, 5 = 49.55%, 54.99%, 53.11%; accelerated iTBS: mean change at weeks 1, 3, 5 = 44.52%, 48.04%, 51.74%). No serious adverse events occurred during the trial. One patient withdrew due to hypomania. The most common adverse event was discomfort at the treatment site (22.73% in both groups). CONCLUSIONS: These findings provide the first evidence that accelerated schedules of left DLPFC iTBS and right DLPFC cTBS are comparably effective in managing antidepressant symptoms and indicate that right DLPFC cTBS is potentially superior in reducing suicidal ideation and anxiety symptoms.

Protocol to image and analyze hippocampal network dynamics in non-anesthetized mouse pups.

Two-photon calcium imaging is a powerful technique that has revolutionized our understanding of how neural circuit dynamics supports different behaviors and cognitive processes. However, performing imaging during development remains challenging. Here, we provide a protocol to image CA1 neurons in mouse pups as well as a pipeline of analysis to analyze and share the data. We describe steps for intracerebroventricular injection, cranial window surgery, two-photon calcium imaging, and analysis of imaging data. For complete details on the use and execution of this protocol, please refer to Dard et al.1 and Denis et al.2.

Comparison of aortic blood flow rotational direction in healthy volunteers and patients with bicuspid aortic valves using volumetric velocity-sensitive cardiovascular magnetic resonance imaging.

Background: The rotational direction (RD) of helical blood flow can be classified as either a clockwise (RD+) or counter-clockwise (RD-) flow. We hypothesized that this simple classification might not be sufficient for analysis in vivo and a simultaneous existence of RD+/- may occur. We utilized volumetric velocity-sensitive cardiovascular magnetic resonance imaging (4D flow MRI) to analyze rotational blood flow in the thoracic aorta. Methods: Forty volunteers (22 females; mean age, 41±16 years) and seventeen patients with bicuspid aortic valves (BAVs) (9 females; mean age, 42±14 years) were prospectively included. The RDs and the calculation of the rotating blood volumes (RBVs) in the thoracic aorta were performed using a pathline-projection strategy. Results: We could confirm a mainly clockwise RD in the ascending, descending aorta and in the aortic arch. Furthermore, we found a simultaneous existence of RD+/RD-. The RD+/--volume in the ascending aorta was significantly higher in BAV patients, the mean RD+/RD- percentage was approximately 80%/20% vs. 60%/40% in volunteers (P<0.01). The maximum RBV always occurred during systole. There was significantly more clockwise than counter-clockwise rotational flow in the ascending aorta (P<0.01) and the aortic arch (P<0.01), but no significant differences in the descending aorta (P=0.48). Conclusions: A simultaneous occurrence of RD+/RD- indicates that a simple categorization in either of both is insufficient to describe blood flow in vivo. Rotational flow in the ascending aorta and in the aortic arch differs significantly from flow in the descending aorta. BAV patients show significantly more clockwise rotating volume in the ascending aorta compared to healthy volunteers.

Design of a Soft Sensor Based on Long Short-Term Memory Artificial Neural Network (LSTM) for Wastewater Treatment Plants.

Assessment of wastewater effluent quality in terms of physicochemical and microbial parameters is a difficult task; therefore, an online method which combines the variables and represents a final value as the quality index could be used as a useful management tool for decision makers. However, conventional measurement methods often have limitations, such as time-consuming processes and high associated costs, which hinder efficient and practical monitoring. Therefore, this study presents an approach that underscores the importance of using both short- and long-term memory networks (LSTM) to enhance monitoring capabilities within wastewater treatment plants (WWTPs). The use of LSTM networks for soft sensor design is presented as a promising solution for accurate variable estimation to quantify effluent quality using the total chemical oxygen demand (TCOD) quality index. For the realization of this work, we first generated a dataset that describes the behavior of the activated sludge system in discrete time. Then, we developed a deep LSTM network structure as a basis for formulating the LSTM-based soft sensor model. The results demonstrate that this structure produces high-precision predictions for the concentrations of soluble X1 and solid X2 substrates in the wastewater treatment system. After hyperparameter optimization, the predictive capacity of the proposed model is optimized, with average values of performance metrics, mean square error (MSE), coefficient of determination (R2), and mean absolute percentage error (MAPE), of 23.38, 0.97, and 1.31 for X1, and 9.74, 0.93, and 1.89 for X2, respectively. According to the results, the proposed LSTM-based soft sensor can be a valuable tool for determining effluent quality index in wastewater treatment systems.

Functional dysconnectivity in youth depression: Systematic review, meta-analysis, and network-based integration.

Youth depression has been associated with heterogenous patterns of aberrant brain connectivity. To make sense of these divergent findings, we conducted a systematic review encompassing 19 resting-state fMRI seed-to-whole-brain studies (1400 participants, comprising 795 youths with major depression and 605 matched healthy controls). We incorporated separate meta-analyses of connectivity abnormalities across the levels of the most commonly seeded brain networks (default-mode and limbic networks) and, based on recent additions to the literature, an updated meta-analysis of amygdala dysconnectivity in youth depression. Our findings indicated broad and distributed findings at an anatomical level, which could not be captured by conventional meta-analyses in terms of spatial convergence. However, we were able to parse the complexity of region-to-region dysconnectivity by considering constituent regions as components of distributed canonical brain networks. This integration revealed dysconnectivity centred on central executive, default mode, salience, and limbic networks, converging with findings from the adult depression literature and suggesting similar neurobiological underpinnings of youth and adult depression.

CT-derived coronary artery calcium density is affected by regional lesion distribution and image reconstruction parameters.

PURPOSE: The prognostic relevance of coronary artery calcium (CAC) density, assessed from cardiac CT scans, is established. However, the influence of CAC distribution, volume, image reconstruction, and clinical factors on CAC density warrants further examination. METHODS: In this study, 120 patients underwent non-contrast ECG-gated cardiac CT scans using a prospectively defined CAC scoring protocol with 1-, 3-, and 5-mm thick image reconstructions, both with and without a 20% image overlap. We segmented CAC in all reconstructions and assessed the relationship between CAC density, volume, and number of detected calcifications/patient. RESULTS: Overall, 75/120 (63%) patients (66% men, mean age 63 ± 11 years) presented CAC across 342 segments. CAC density, CAC volume, and the number of detected calcifications decreased with increasing slice thickness (p < 0.001 for all); these effects were slightly reduced by image overlap (p < 0.001 for all). Higher CAC density correlated with greater CAC volume (ρ = 0.62; p < 0.001) and more calcified segments per person (ρ = 0.32; p = 0.006). Higher CAC density was also associated with lower patient weight (beta: -0.6, 95%CI: -1.1--0.1, p = 0.022) and increased high-density lipoprotein (HDL) levels (beta: 0.7, 95%CI: 0.0-1.4, p = 0.046). In a multivariable analysis adjusted for clinical covariates, lower CAC density was associated with broader CAC distribution (i.e., a higher number of calcified segments at a given CAC volume; beta-coefficient: -58.9; 95%CI: -84.7 to -33.1; p < 0.001). CONCLUSION: CAC density is significantly impacted by regional CAC distribution and image reconstruction, potentially confounding its prognostic value. Accounting for these factors may improve patient risk assessment, management, and cardiovascular health outcomes.

Physiological effects of PFAS exposure in seabird chicks: A multi-species study of thyroid hormone triiodothyronine, body condition and telomere length in South Western France.

There is growing evidence that poly and perfluoroalkyl substances (PFAS) exposure leads to the disruption of thyroid hormones including thyroxine (T4) and triiodothyronine (T3), and may affect telomeres, repetitive nucleotide sequences which protect chromosome ends. Many seabird species are long-lived top predators thus exhibit high contaminant levels, and PFAS-disrupting effects on their physiology have been documented especially in relation to the endocrine system in adults. On the contrary, studies on the developmental period (i.e., chicks), during which exposure to environmental contaminants may have a greater impact on physiological traits, remain scarce to this date. We carried out a multi-species study with the aim to assess whether and to which extent chicks of four gull species (herring gull, great and lesser black-backed gull, yellow-legged gull) in South Western France are contaminated by PFAS, and to bring further evidence about their potential physiological consequences. Linear PFOS showed concentrations of concern as it was generally >10 times higher than the other PFAS, and exceeded a threshold toxicity level (calculated from previous studies in birds) in almost all sampled chicks. Nonetheless, in herring gull male chicks, total T3 levels were significantly and negatively associated with perfluorodecanoate (PFDA) and perfluorododecanoate (PFDoDA) and positively associated with perfluorotetradecanoate (PFTeDA) in female chicks. Total T3 levels were also positively associated with PFDoDA in great black backed gull male chicks and with perfluorotridecanoate (PFTrDA) in lesser black backed gull chicks. In lesser and great black-backed gulls, both females and males showed significant negative associations between several PFAS and their body condition, and a positive association between telomere length and L-PFOS in the yellow-legged gull was also found. These results corroborate previous findings and need to be further explored as they suggest that PFAS may interfere with the physiological status of chicks during the developmental period, potentially inducing long-lasting consequences.

Rapid structural remodeling of peripheral taste neurons is independent of taste cell turnover.

Taste bud cells are constantly replaced in taste buds as old cells die and new cells migrate into the bud. The perception of taste relies on new taste bud cells integrating with existing neural circuitry, yet how these new cells connect with a taste ganglion neuron is unknown. Do taste ganglion neurons remodel to accommodate taste bud cell renewal? If so, how much of the structure of taste axons is fixed and how much remodels? Here, we measured the motility and branching of individual taste arbors (the portion of the axon innervating taste buds) in mice over time with two-photon in vivo microscopy. Terminal branches of taste arbors continuously and rapidly remodel within the taste bud. This remodeling is faster than predicted by taste bud cell renewal, with terminal branches added and lost concurrently. Surprisingly, blocking entry of new taste bud cells with chemotherapeutic agents revealed that remodeling of the terminal branches on taste arbors does not rely on the renewal of taste bud cells. Although terminal branch remodeling was fast and intrinsically controlled, no new arbors were added to taste buds, and few were lost over 100 days. Taste ganglion neurons maintain a stable number of arbors that are each capable of high-speed remodeling. We propose that terminal branch plasticity permits arbors to locate new taste bud cells, while stability of arbor number supports constancy in the degree of connectivity and function for each neuron over time.

Saline dry fixation for improved cell composition analysis using Raman spectroscopy.

Raman spectroscopy enables the label-free assessment of cellular composition. While live cell analysis is the most accurate approach for cellular Raman spectroscopy, the analysis of fixed cells has proved to be very useful, particularly in collaborative projects where samples need to be serially examined by different laboratories or stored and reanalyzed at a later date. However, many chemicals that are widely used for cell fixation directly affect cellular biomolecules, yielding Raman spectra with missing or altered information. In this article, we compared the suitability of dry-fixation with saline versus chemical fixatives. We compared the Raman spectroscopy of saline dry-fixed cells with the more commonly used formaldehyde and methanol fixation and found that dry-fixed cell spectra preserved more cellular information than either chemical fixative. We also assessed the stability of dry-fixed cells over time and found that they were stable for at least 5 months. Finally, a comparison of dry-fixed and live cell spectra revealed effects due to the hydration state of the cells since they were recovered upon rehydrating dry-fixed samples. Thus, for fixed cell Raman spectroscopy, we recommend dry-fixation with unbuffered saline as a superior method to formaldehyde or methanol fixation.

Rapid Vector-Based Peak Fitting and Resolution Enhancement for Correlation Analyses of Raman Hyperspectra.

Spectroscopic peak parameters are important since they provide information about the analyte under study. Besides obtaining these parameters, peak fitting also resolves overlapped peaks. Thus, the obtained parameters should permit the construction of a higher-resolution version of the original spectrum. However, peak fitting is not an easy task due to computational reasons and because the true nature of the analyte is often unknown. These difficulties are major impediments when large hyperspectral data sets need to be processed rapidly, such as for manufacturing process control. We have developed a novel and relatively fast two-part algorithm to perform peak fitting and resolution enhancement on such data sets. In the first part of the algorithm, estimates of the total number of bands and their parameters were obtained from a representative spectrum in the data set, using a combination of techniques. Starting with these parameter estimates, all the spectra were then iteratively and rapidly fitted with Gaussian bands, exploiting intrinsic features of the Gaussian distribution with vector operations. The best fits for each spectrum were retained. By reducing the obtained bandwidths and commensurately increasing their amplitudes, high-resolution spectra were constructed that greatly improved correlation-based analyses. We tested the performance of the algorithm on synthetic spectra to confirm that this method could recover the ground truth correlations between highly overlapped peaks. To assess effective peak resolution, the method was applied to low-resolution spectra of glucose and compared to results from high-resolution spectra. We then processed a larger spectral data set from mammalian cells, fixed with methanol or air drying, to demonstrate the resolution enhancement of the algorithm on complex spectra and the effects of resolution-enhanced spectra on two-dimensional correlation spectroscopy and principal component analyses. The results indicated that the algorithm would allow users to obtain high-resolution spectra relatively fast and permit the recovery of important aspects of the data's intrinsic correlation structure.

Analgesic efficacy of theta-burst stimulation for postoperative pain.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) may be a relevant method to assist postoperative pain. However, studies to date have only used conventional 10 Hz rTMS and targeted the DLPFC for postoperative pain. A more recent form of rTMS, termed intermittent Theta Burst Stimulation (iTBS), enables to increase cortical excitability in a short period of time. This preliminary double-blind, randomised, sham controlled study was designed to evaluate the efficacy of iTBS in postoperative care across two distinct stimulation targets. METHODS: A group of 45 patients post laparoscopic surgery were randomised to receive a single session of iTBS over either the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), or Sham stimulation (1:1:1 ratio). Outcome measurements were number of pump attempts, total anaesthetic volume used, and self-rated pain experience, assessed at 1 hour, 6 hours, 24 hours, and 48 hours post stimulation. All randomised patients were analysed (n = 15 in each group). RESULTS: Compared to Sham stimulation, DLPFC-iTBS reduced pump attempts at 6 (DLPFC = 0.73 ± 0.88, Sham = 2.36 ± 1.65, P = 0.031), 24 (DLPFC = 1.40 ± 1.24, Sham = 5.03 ± 3.87, P = 0.008), and 48 (DLPFC = 1.47 ± 1.41, Sham = 5.87 ± 4.34, P = 0.014) hours post-surgery, whereby M1 stimulation had no effect. No group effect was observed on total anaesthetics, which was mainly provided through the continuous administration of opioids at a set speed for each group. There was also no group or interaction effect on pain ratings. Pump attempts were positively associated with pain ratings in the DLPFC (r = 0.59, P = 0.02) and M1 (r = 0.56, P = 0.03) stimulation. CONCLUSIONS: Our findings show that iTBS to the DLPFC reduces pump attempts for additional anaesthetics following a laparoscopic surgery. However, reduced pump attempts by DLPFC stimulation did not translate into a significantly smaller volume of total anaesthetic, due to the continuous administration of opioids at a set speed for each group. SIGNIFICANCE: Our findings therefore provide preliminary evidence for iTBS targeting the DLPFC to be used to improve postoperative pain management.

Taste arbor structural variability analyzed across taste regions.

Taste ganglion neurons are functionally and molecularly diverse, but until recently morphological diversity was completely unexplored. Specifically, taste arbors (the portion of the neuron within the taste bud) vary in structure, but the reason for this variability is unclear. Here, we analyzed structural variability in taste arbors to determine which factors determine their morphological diversity. To characterize arbor morphology and its relationship to taste bud cells capable of transducing taste stimuli (taste-transducing cell) number and type, we utilized sparse cell genetic labeling of taste ganglion neurons in combination with whole-mount immunohistochemistry. Reconstruction of 151 taste arbors revealed variation in arbor size, complexity, and symmetry. Overall, taste arbors exist on a continuum of complexity, cannot be categorized into discrete morphological groups, and do not have stereotyped endings. Arbor size/complexity was not related to the size of the taste bud in which it was located or the type of taste-transducing cell contacted (membranes within 180 nm). Instead, arbors could be broadly categorized into three groups: large asymmetrical arbors contacting many taste-transducing cells, small symmetrical arbors contacting one or two taste-transducing cells, and unbranched arbors. Neurons with multiple arbors had arbors in more than one of these categories, indicating that this variability is not an intrinsic feature of neuron type. Instead, we speculate that arbor structure is determined primarily by nerve fiber remodeling in response to cell turnover and that large asymmetrical arbors represent a particularly plastic state.