Fast slow folding of an outer membrane porin.

In comparison to globular proteins, the spontaneous folding and insertion of ß-barrel membrane proteins are surprisingly slow, typically occurring on the order of minutes. Using single-molecule Förster resonance energy transfer to report on the folding of fluorescently labeled outer membrane protein G we measured the real-time insertion of a ß-barrel membrane protein from an unfolded state. Folding events were rare and fast (<20 ms), occurring immediately upon arrival at the membrane. This combination of infrequent, but rapid, folding resolves this apparent dichotomy between slow ensemble kinetics and the typical timescales of biomolecular folding.

Multi-environment association study highlights candidate genes for robust agronomic quantitative trait loci in a novel worldwide Capsicum core collection.

Investigating crop diversity through genome-wide association studies (GWAS) on core collections helps in deciphering the genetic determinants of complex quantitative traits. Using the G2P-SOL project world collection of 10 038 wild and cultivated Capsicum accessions from 10 major genebanks, we assembled a core collection of 423 accessions representing the known genetic diversity. Since complex traits are often highly dependent upon environmental variables and genotype-by-environment (G × E) interactions, multi-environment GWAS with a 10 195-marker genotypic matrix were conducted on a highly diverse subset of 350 Capsicum annuum accessions, extensively phenotyped in up to six independent trials from five climatically differing countries. Environment-specific and multi-environment quantitative trait loci (QTLs) were detected for 23 diverse agronomic traits. We identified 97 candidate genes potentially implicated in 53 of the most robust and high-confidence QTLs for fruit flavor, color, size, and shape traits, and for plant productivity, vigor, and earliness traits. Investigating the genetic architecture of agronomic traits in this way will assist the development of genetic markers and pave the way for marker-assisted selection. The G2P-SOL pepper core collection will be available upon request as a unique and universal resource for further exploitation in future gene discovery and marker-assisted breeding efforts by the pepper community.

The Interictal Suppression Hypothesis in focal epilepsy: network-level supporting evidence.

Why are people with focal epilepsy not continuously having seizures? Previous neuronal signalling work has implicated gamma-aminobutyric acid balance as integral to seizure generation and termination, but is a high-level distributed brain network involved in suppressing seizures? Recent intracranial electrographic evidence has suggested that seizure-onset zones have increased inward connectivity that could be associated with interictal suppression of seizure activity. Accordingly, we hypothesize that seizure-onset zones are actively suppressed by the rest of the brain network during interictal states. Full testing of this hypothesis would require collaboration across multiple domains of neuroscience. We focused on partially testing this hypothesis at the electrographic network level within 81 individuals with drug-resistant focal epilepsy undergoing presurgical evaluation. We used intracranial electrographic resting-state and neurostimulation recordings to evaluate the network connectivity of seizure onset, early propagation and non-involved zones. We then used diffusion imaging to acquire estimates of white-matter connectivity to evaluate structure-function coupling effects on connectivity findings. Finally, we generated a resting-state classification model to assist clinicians in detecting seizure-onset and propagation zones without the need for multiple ictal recordings. Our findings indicate that seizure onset and early propagation zones demonstrate markedly increased inwards connectivity and decreased outwards connectivity using both resting-state (one-way ANOVA, P-value = 3.13 × 10-13) and neurostimulation analyses to evaluate evoked responses (one-way ANOVA, P-value = 2.5 × 10-3). When controlling for the distance between regions, the difference between inwards and outwards connectivity remained stable up to 80 mm between brain connections (two-way repeated measures ANOVA, group effect P-value of 2.6 × 10-12). Structure-function coupling analyses revealed that seizure-onset zones exhibit abnormally enhanced coupling (hypercoupling) of surrounding regions compared to presumably healthy tissue (two-way repeated measures ANOVA, interaction effect P-value of 9.76 × 10-21). Using these observations, our support vector classification models achieved a maximum held-out testing set accuracy of 92.0 ± 2.2% to classify early propagation and seizure-onset zones. These results suggest that seizure-onset zones are actively segregated and suppressed by a widespread brain network. Furthermore, this electrographically observed functional suppression is disproportionate to any observed structural connectivity alterations of the seizure-onset zones. These findings have implications for the identification of seizure-onset zones using only brief electrographic recordings to reduce patient morbidity and augment the presurgical evaluation of drug-resistant epilepsy. Further testing of the interictal suppression hypothesis can provide insight into potential new resective, ablative and neuromodulation approaches to improve surgical success rates in those suffering from drug-resistant focal epilepsy.

Biphasic effects of cannabis and cannabinoid therapy on pain severity, anxiety, and sleep disturbance: a scoping review.

INTRODUCTION: Cannabinoids are being used by patients to help with chronic pain management and to address the 2 primary chronic pain comorbidities of anxiety and sleep disturbance. It is necessary to understand the biphasic effects of cannabinoids to improve treatment of this symptom triad. METHODS: A scoping review was conducted to identify whether biphasic effects of cannabinoids on pain severity, anxiolysis, and sleep disturbance have been reported. The search included the Embase, Biosis, and Medline databases of clinical literature published between 1970 and 2021. The inclusion criteria were (1) adults more than 18 years of age, (2) data or discussion of dose effects associated with U-shaped or linear dose responses, and (3) measurements of pain and/or anxiety and/or sleep disturbance. Data were extracted by 2 independent reviewers (with a third reviewer used as a tiebreaker) and subjected to a thematic analysis. RESULTS: After the database search and study eligibility assessment, 44 publications met the final criteria for review. Eighteen publications that specifically provided information on dose response were included in the final synthesis: 9 related to pain outcomes, 7 measuring anxiety, and 2 reporting sleep effects. CONCLUSIONS: This scoping review reports on biphasic effects of cannabinoids related to pain, sleep, and anxiety. Dose-response relationships are present, but we found gaps in the current literature with regard to biphasic effects of cannabinoids in humans. There is a lack of prospective research in humans exploring this specific relationship.

Global range expansion history of pepper (Capsicum spp.) revealed by over 10,000 genebank accessions.

Genebanks collect and preserve vast collections of plants and detailed passport information, with the aim of preserving genetic diversity for conservation and breeding. Genetic characterization of such collections has the potential to elucidate the genetic histories of important crops, use marker-trait associations to identify loci controlling traits of interest, search for loci undergoing selection, and contribute to genebank management by identifying taxonomic misassignments and duplicates. We conducted a genomic scan with genotyping by sequencing (GBS) derived single nucleotide polymorphisms (SNPs) of 10,038 pepper (Capsicum spp.) accessions from worldwide genebanks and investigated the recent history of this iconic staple. Genomic data detected up to 1,618 duplicate accessions within and between genebanks and showed that taxonomic ambiguity and misclassification often involve interspecific hybrids that are difficult to classify morphologically. We deeply interrogated the genetic diversity of the commonly consumed Capsicum annuum to investigate its history, finding that the kinds of peppers collected in broad regions across the globe overlap considerably. The method ReMIXTURE-using genetic data to quantify the similarity between the complement of peppers from a focal region and those from other regions-was developed to supplement traditional population genetic analyses. The results reflect a vision of pepper as a highly desirable and tradable cultural commodity, spreading rapidly throughout the globe along major maritime and terrestrial trade routes. Marker associations and possible selective sweeps affecting traits such as pungency were observed, and these traits were shown to be distributed nonuniformly across the globe, suggesting that human preferences exerted a primary influence over domesticated pepper genetic structure.

Real-Time Monitoring and Control of Nanoparticle Formation.

Methods capable of controlling synthesis at the level of an individual nanoparticle are a key step toward improved reproducibility and scalability in engineering complex nanomaterials. To address this, we combine the spatially patterned activation of the photoreductant sodium pyruvate with interferometric scattering microscopy to achieve fast, label-free monitoring and control of hundreds of gold nanoparticles in real time. Individual particle growth kinetics are well-described by a two-step nucleation-autocatalysis model but with a distribution of individual rate constants that change with reaction conditions.

Sound Level Changes the Auditory Cortical Activation Detected with Functional Near-Infrared Spectroscopy.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is a viable non-invasive technique for functional neuroimaging in the cochlear implant (CI) population; however, the effects of acoustic stimulus features on the fNIRS signal have not been thoroughly examined. This study examined the effect of stimulus level on fNIRS responses in adults with normal hearing or bilateral CIs. We hypothesized that fNIRS responses would correlate with both stimulus level and subjective loudness ratings, but that the correlation would be weaker with CIs due to the compression of acoustic input to electric output. METHODS: Thirteen adults with bilateral CIs and 16 with normal hearing (NH) completed the study. Signal-correlated noise, a speech-shaped noise modulated by the temporal envelope of speech stimuli, was used to determine the effect of stimulus level in an unintelligible speech-like stimulus between the range of soft to loud speech. Cortical activity in the left hemisphere was recorded. RESULTS: Results indicated a positive correlation of cortical activation in the left superior temporal gyrus with stimulus level in both NH and CI listeners with an additional correlation between cortical activity and perceived loudness for the CI group. The results are consistent with the literature and our hypothesis. CONCLUSIONS: These results support the potential of fNIRS to examine auditory stimulus level effects at a group level and the importance of controlling for stimulus level and loudness in speech recognition studies. Further research is needed to better understand cortical activation patterns for speech recognition as a function of both stimulus presentation level and perceived loudness.

High-frequency spinal cord stimulation (10 kHz) alters sensory function and nerve fiber density in painful diabetic neuropathy: a pilot prospective open-label study.

OBJECTIVE: Spinal cord stimulation at 10 kHz has provided effective pain relief and improved function in painful diabetic peripheral neuropathy. This study aims to confirm the clinical outcomes for 10-kHz spinal cord stimulation treatment of painful diabetic peripheral neuropathy and explore its impact on objective quantitative measures of nerve pathology and function. METHODS: This single-academic center, prospective, open-label, observational study examined the pain relief success of 10-kHz spinal cord stimulation in patients >18 years of age with diabetic peripheral neuropathy. Patients underwent skin biopsies to measure intra-epidermal nerve fiber densities and corneal confocal microscopy measurements before implantation and at the 3-, 6-, and 12-month follow-up visits. Numerical rating scale for pain, visual analog scale, neuropathy pain scale, Short Form-36, and Neuropen (pin prick and monofilament) assessments were also conducted. RESULTS: Eight patients met the criteria and were enrolled in the study. A successful trial was achieved in 7 subjects, and 6 completed the study. Significant pain relief (P < .001) was achieved at all follow-up visits. Neurological assessments showed reduced numbers of "absent" responses and increased "normal" responses from baseline to 12 months. Both proximal and distal intra-epidermal nerve fiber densities were higher at 12 months than at baseline (P < .01). Confocal microscopy measurements showed a steady increase in nerve density from baseline (188.8% increase at 12 months; P = .029). CONCLUSIONS: We observed pain relief and improvements in sensory function after stimulation that were accompanied by increases in lower-limb intra-epidermal nerve fiber density and corneal nerve density. Further evaluation with a blinded and controlled study is needed to confirm the preliminary findings in this study.

Nurse rostering with fatigue modelling : Incorporating a validated sleep model with biological variations in nurse rostering.

We use a real Nurse Rostering Problem and a validated model of human sleep to formulate the Nurse Rostering Problem with Fatigue. The fatigue modelling includes individual biologies, thus enabling personalised schedules for every nurse. We create an approximation of the sleep model in the form of a look-up table, enabling its incorporation into nurse rostering. The problem is solved using an algorithm that combines Mixed-Integer Programming and Constraint Programming with a Large Neighbourhood Search. A post-processing algorithm deals with errors, to produce feasible rosters minimising global fatigue. The results demonstrate the realism of protecting nurses from highly fatiguing schedules and ensuring the alertness of staff. We further demonstrate how minimally increased staffing levels enable lower fatigue, and find evidence to suggest biological complementarity among staff can be used to reduce fatigue. We also demonstrate how tailoring shifts to nurses' biology reduces the overall fatigue of the team, which means managers must grapple with the issue of fairness in rostering.

Improved genome assembly and pan-genome provide key insights into eggplant domestication and breeding.

Eggplant (Solanum melongena L.) is an important horticultural crop and one of the most widely grown vegetables from the Solanaceae family. It was domesticated from a wild, prickly progenitor carrying small, round, non-anthocyanic fruits. We obtained a novel, highly contiguous genome assembly of the eggplant '67/3' reference line, by Hi-C retrofitting of a previously released short read- and optical mapping-based assembly. The sizes of the 12 chromosomes and the fraction of anchored genes in the improved assembly were comparable to those of a chromosome-level assembly. We resequenced 23 accessions of S. melongena representative of the worldwide phenotypic, geographic, and genetic diversity of the species, and one each from the closely related species Solanum insanum and Solanum incanum. The eggplant pan-genome contained approximately 51.5 additional megabases and 816 additional genes compared with the reference genome, while the pan-plastome showed little genetic variation. We identified 53 selective sweeps related to fruit color, prickliness, and fruit shape in the nuclear genome, highlighting selection leading to the emergence of present-day S. melongena cultivars from its wild ancestors. Candidate genes underlying the selective sweeps included a MYBL1 repressor and CHALCONE ISOMERASE (for fruit color), homologs of Arabidopsis GLABRA1 and GLABROUS INFLORESCENCE STEMS2 (for prickliness), and orthologs of tomato FW2.2, OVATE, LOCULE NUMBER/WUSCHEL, SUPPRESSOR OF OVATE, and CELL SIZE REGULATOR (for fruit size/shape), further suggesting that selection for the latter trait relied on a common set of orthologous genes in tomato and eggplant.

Impact of Patient Portal Messaging Reminders with Self-Scheduling Option on Influenza Vaccination Rates: a Prospective, Randomized Trial.

BACKGROUND: Patient portal messages have been used in a variety of ways to facilitate improved communication between provider and patient. These platforms have shown promise in many ways for improving various health outcomes and overall communication between patient and provider. OBJECTIVE: Assess the impact of automated portal reminder messages and self-scheduling options on increasing rates of annual influenza vaccination. DESIGN: This is a prospective, randomized, controlled study. PARTICIPANTS: All patients who receive their primary care through an ambulatory primary care clinic at a large, multidisciplinary, academic health center. INTERVENTIONS: One group of patients received a portal message reminder to undergo influenza vaccination. A second group received the same message with instructions to self-schedule the vaccination appointment. A third group received no portal message (control). MAIN MEASURES: Rates of influenza vaccination in each group for previously unvaccinated patients in the 2019-2020 influenza season. KEY RESULTS: For the group receiving the message with self-scheduling option (n=5408), the in-study vaccination rate was significantly greater than the group receiving no message (n=5621) (15.7% vs. 13.5%; p=0.002). For the group receiving a message alone (without self-scheduling) (n=5699), the in-study vaccination rate was significantly greater than the group receiving no message (15.1% vs. 13.5%; p=0.01). There was no significant difference in vaccination rate between the two intervention groups receiving messages (15.7% vs. 15.1%; p=0.549). CONCLUSIONS: Portal messaging reminders increase annual influenza vaccination rates, but the addition of a self-scheduling option did not further increase rates. KEY WORDS: vaccination patient portal messaging influenza.

Functional localization of audiovisual speech using near infrared spectroscopy.

Visual cues are especially vital for hearing impaired individuals such as cochlear implant (CI) users to understand speech in noise. Functional Near Infrared Spectroscopy (fNIRS) is a light-based imaging technology that is ideally suited for measuring the brain activity of CI users due to its compatibility with both the ferromagnetic and electrical components of these implants. In a preliminary step toward better elucidating the behavioral and neural correlates of audiovisual (AV) speech integration in CI users, we designed a speech-in-noise task and measured the extent to which 24 normal hearing individuals could integrate the audio of spoken monosyllabic words with the corresponding visual signals of a female speaker. In our behavioral task, we found that audiovisual pairings provided average improvements of 103% and 197% over auditory-alone listening conditions in -6 and -9 dB signal-to-noise ratios consisting of multi-talker background noise. In an fNIRS task using similar stimuli, we measured activity during auditory-only listening, visual-only lipreading, and AV listening conditions. We identified cortical activity in all three conditions over regions of middle and superior temporal cortex typically associated with speech processing and audiovisual integration. In addition, three channels active during the lipreading condition showed uncorrected correlations associated with behavioral measures of audiovisual gain as well as with the McGurk effect. Further work focusing primarily on the regions of interest identified in this study could test how AV speech integration may differ for CI users who rely on this mechanism for daily communication.

Cortical Morphology in Autism: Findings from a Cortical Shape-Adaptive Approach to Local Gyrification Indexing.

It has been challenging to elucidate the differences in brain structure that underlie behavioral features of autism. Prior studies have begun to identify patterns of changes in autism across multiple structural indices, including cortical thickness, local gyrification, and sulcal depth. However, common approaches to local gyrification indexing used in prior studies have been limited by low spatial resolution relative to functional brain topography. In this study, we analyze the aforementioned structural indices, utilizing a new method of local gyrification indexing that quantifies this index adaptively in relation to specific sulci/gyri, improving interpretation with respect to functional organization. Our sample included n = 115 autistic and n = 254 neurotypical participants aged 5-54, and we investigated structural patterns by group, age, and autism-related behaviors. Differing structural patterns by group emerged in many regions, with age moderating group differences particularly in frontal and limbic regions. There were also several regions, particularly in sensory areas, in which one or more of the structural indices of interest either positively or negatively covaried with autism-related behaviors. Given the advantages of this approach, future studies may benefit from its application in hypothesis-driven examinations of specific brain regions and/or longitudinal studies to assess brain development in autism.

Cross-disorder comparison of sensory over-responsivity in chronic tic disorders and obsessive-compulsive disorder.

BACKGROUND: Sensory over-responsivity (SOR) refers to excessively intense and/or prolonged behavioral responses to environmental stimuli typically perceived as non-aversive. SOR is prevalent in several neurodevelopmental disorders, including chronic tic disorders (CTDs) and obsessive-compulsive disorder (OCD). Few studies have examined the extent and clinical correlates of SOR across disorders, limiting insights into the phenomenon's transdiagnostic clinical and biological relevance. Such cross-disorder comparisons are of particular interest for CTDs and OCD given their frequent co-occurrence. OBJECTIVE: We sought to compare the magnitude of SOR between adults with CTD and adults with OCD and to identify the clinical factors most strongly associated with SOR across these disorders. METHODS: We enrolled 207 age- and sex-matched participants across four diagnostic categories: CTD without OCD (designated "CTD/OCD-"; n = 37), CTD with OCD ("CTD/OCD+"; n = 32), OCD without tic disorder ("OCD"; n = 69), and healthy controls (n = 69). Participants completed a self-report battery of rating scales assessing SOR (Sensory Gating Inventory, SGI), obsessive-compulsive symptoms (Dimensional Obsessive-Compulsive Scale, DOCS), inattention and hyperactivity (Adult ADHD Self-Report Screening Scale for DSM-5, ASRS-5), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire-9). CTD participants were also administered the Yale Global Tic Severity Scale (YGTSS). To examine between-group differences in SOR, we compared SGI score across all groups and between pairs of groups. To examine the relationship of SOR with other clinical factors, we performed multivariable linear regression. RESULTS: CTD/OCD-, CTD/OCD+, and OCD participants were 86.7%, 87.6%, and 89.5%, respectively, more likely to have higher SGI total scores than healthy controls. SGI total score did not differ between CTD/OCD-, CTD/OCD+, and OCD groups. In the regression model of log-transformed SGI total score, OCD diagnosis, DOCS score, and ASRS-5 score each contributed significantly to model goodness-of-fit, whereas CTD diagnosis and YGTSS total tic score did not. CONCLUSION: SOR is prevalent in adults with CTD and in adults with OCD but does not significantly differ in magnitude between these disorders. Across CTD, OCD, and healthy control adult populations, SOR is independently associated with both obsessive-compulsive and ADHD symptoms, suggesting a transdiagnostic relationship between these sensory and psychiatric manifestations. Future cross-disorder, longitudinal, and translational research is needed to clarify the role and prognostic import of SOR in CTDs, OCD, and other neurodevelopmental disorders.

Selective Enhancement of Object Representations through Multisensory Integration.

Objects are the fundamental building blocks of how we create a representation of the external world. One major distinction among objects is between those that are animate versus those that are inanimate. In addition, many objects are specified by more than a single sense, yet the nature by which multisensory objects are represented by the brain remains poorly understood. Using representational similarity analysis of male and female human EEG signals, we show enhanced encoding of audiovisual objects when compared with their corresponding visual and auditory objects. Surprisingly, we discovered that the often-found processing advantages for animate objects were not evident under multisensory conditions. This was due to a greater neural enhancement of inanimate objects-which are more weakly encoded under unisensory conditions. Further analysis showed that the selective enhancement of inanimate audiovisual objects corresponded with an increase in shared representations across brain areas, suggesting that the enhancement was mediated by multisensory integration. Moreover, a distance-to-bound analysis provided critical links between neural findings and behavior. Improvements in neural decoding at the individual exemplar level for audiovisual inanimate objects predicted reaction time differences between multisensory and unisensory presentations during a Go/No-Go animate categorization task. Links between neural activity and behavioral measures were most evident at intervals of 100-200 ms and 350-500 ms after stimulus presentation, corresponding to time periods associated with sensory evidence accumulation and decision-making, respectively. Collectively, these findings provide key insights into a fundamental process the brain uses to maximize the information it captures across sensory systems to perform object recognition.SIGNIFICANCE STATEMENT Our world is filled with ever-changing sensory information that we are able to seamlessly transform into a coherent and meaningful perceptual experience. We accomplish this feat by combining different stimulus features into objects. However, despite the fact that these features span multiple senses, little is known about how the brain combines the various forms of sensory information into object representations. Here, we used EEG and machine learning to study how the brain processes auditory, visual, and audiovisual objects. Surprisingly, we found that nonliving (i.e., inanimate) objects, which are more difficult to process with one sense alone, benefited the most from engaging multiple senses.

Validation of an oncology-specific opioid risk calculator in cancer survivors.

BACKGROUND: Clinical guidelines recommend that providers risk-stratify patients with cancer before prescribing opioids. Prior research has demonstrated that a simple cancer opioid risk score might help identify to patients with cancer at the time of diagnosis with a high likelihood of long-term posttreatment opioid use. This current project validates this cancer opioid risk score in a generalizable, population-based cohort of elderly cancer survivors. METHODS: This study identified 44,932 Medicare beneficiaries with cancer who had received local therapy. Longitudinal opioid use was ascertained from Medicare Part D data. A risk score was calculated for each patient, and patients were categorized into low-, moderate-, and high-risk groups on the basis of the predicted probability of persistent opioid use. Model discrimination was assessed with receiver operating characteristic curves. RESULTS: In the study cohort, 5.2% of the patients were chronic opioid users 1 to 2 years after the initiation of cancer treatment. The majority of the patients (64%) were at low risk and had a 1.2% probability of long-term opioid use. Moderate-risk patients (33% of the cohort) had a 5.6% probability of long-term opioid use. High-risk patients (3.5% of the cohort) had a 75% probability of long-term opioid use. The opioid risk score had an area under the receiver operating characteristic curve of 0.869. CONCLUSIONS: This study found that a cancer opioid risk score could accurately identify individuals with a high likelihood of long-term opioid use in a large, generalizable cohort of cancer survivors. Future research should focus on the implementation of these scores into clinical practice and how this could affect prescriber behavior and patient outcomes. LAY SUMMARY: A novel 5-question clinical decision tool allows physicians treating patients with cancer to accurately predict which patients will persistently be using opioid medications after completing therapy.

High-contrast osteochondral junction imaging using a 3D dual adiabatic inversion recovery-prepared ultrashort echo time cones sequence.

While conventional MRI sequences cannot visualize tissues from the osteochondral junction (OCJ) due to these tissues' short transverse T2 /T2 * relaxations, ultrashort echo time (UTE) sequences can overcome this limitation. A 2D UTE sequence with a dual adiabatic inversion recovery preparation (DIR-UTE) for selective imaging of short T2 tissues with high contrast has previously been developed, but high sensitivity to eddy currents and aliased out-of-slice excitation make it difficult to image the thin layer of the OCJ in vivo. Here, we combine the DIR scheme with a 3D UTE cones sequence for volumetric imaging of OCJ tissues in vivo, aiming to generate higher OCJ contrast compared with a recently developed single IR-prepared UTE sequence with a fat saturation module (IR-FS-UTE). All sequences were implemented on a 3-T clinical scanner. The DIR-UTE cones sequence combined a 3D UTE cones sequence with two narrow-band adiabatic IR preparation pulses centered on water and fat spectrum frequencies, respectively. The 3D DIR-UTE cones sequence was first applied to a phantom, then to the knees of four healthy volunteers and four patients diagnosed with osteoarthritis and compared with the IR-FS-UTE sequence. In both phantom and volunteer studies, the proposed DIR-UTE cones sequence showed much higher contrast for OCJ imaging than the IR-FS-UTE sequence did. The 3D DIR-UTE cones sequence showed a significantly higher contrast-to-noise ratio between the OCJ and subchondral bone fat (mean, standard deviation [SD]: 25.7 ± 2.3) and between the OCJ and superficial layers of cartilage (mean, SD: 22.2 ± 3.5) compared with the IR-FS-UTE sequence (mean, SD: 10.8 ± 2.5 and 16.3 ± 2.6, respectively). The 3D DIR-UTE cones sequence is feasible for imaging of the OCJ region of the knee in vivo and produces both high resolution and high contrast.

High contrast cartilaginous endplate imaging using a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence.

Ultrashort echo time (UTE) sequences can image tissues with transverse T 2 /T 2 * relaxations too short to be efficiently observed on routine clinical MRI sequences, such as the vertebral body cartilaginous endplate (CEP). Here, we describe a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence to highlight the CEP of vertebral bodies in comparison to the intervertebral disc (IVD) and bone marrow fat (BF) at 3 T. The IR-FS-UTE sequence used a 3D UTE sequence combined with an adiabatic IR preparation pulse centered in the middle of the water and fat peaks, while a fat saturation module was used to suppress the signal from fat. A slab-selective half pulse was used for signal excitation, and a 3D center-out cones trajectory was used for more efficient data sampling. The 3D IR-FS-UTE sequence was applied to an ex vivo human spine sample, as well as the spines of six healthy volunteers and of three patients with back pain. Bright continuous lines representing signal from CEP were found in healthy IVDs. The measured contrast-to-noise ratio was 18.5 ± 4.9 between the CEP and BF, and 20.3 ± 4.15 between the CEP and IVD for the six volunteers. Abnormal IVDs showed CEP discontinuity or irregularity in the sample and patient studies. In conclusion, the proposed 3D IR-FS-UTE sequence is feasible for imaging the vertebral body's CEP in vivo with high contrast.

Non-opioid Analgesics and Emerging Therapies.

Pain is a common and debilitating symptom of cancer. Cancer-related pain can occur at any point along the continuum from diagnosis to treatment to survivorship1. A systematic review published in 2016 estimated the prevalence of cancer pain to be 55% in those undergoing antineoplastic treatment, 66.4% in advanced cancer, and 39.3% in the post-treatment population. Thirty-eight percent of cancer patients in this pooled analysis experienced moderate to severe pain2.