SARS-CoV-2 wastewater surveillance at two university campuses: lessons learned and insights on intervention strategies for public health guidance.

Wastewater surveillance has been a tool for public health officials throughout the COVID-19 pandemic. Universities established pandemic response committees to facilitate safe learning for students, faculty, and staff. These committees met to analyze both wastewater and clinical data to propose mitigation strategies to limit the spread of COVID-19. This paper reviews the initial efforts of utilizing campus data inclusive of wastewater surveillance for SARS-CoV-2 RNA concentrations, clinical case data from university response teams, and mitigation strategies from Grand Valley State University in West Michigan (population 21,648 students) and Oakland University in East Michigan (population 18,552 students) from November 2020 to April 2022. Wastewater positivity rates for both universities ranged from 32.8 to 46.8%. Peak viral signals for both universities directly corresponded to variant points of entry within the campus populations from 2021 to 2022. It was found that the organization of clinical case data and variability of wastewater testing data were large barriers for both universities to effectively understand disease dynamics within the university population. We review the initial efforts of onboarding wastewater surveillance and provide direction for structuring ongoing surveillance workflows and future epidemic response strategies based on those that led to reduced viral signals in campus wastewater.

An eosinophil peroxidase activity assay predicts acute exacerbations in post-operative chronic rhinosinusitis.

KEY POINTS: EPX activity has been correlated with eCRS diagnosis and baseline disease severity. Herein, EPX activity is shown to correlate with post-operative antibiotic and steroid use in CRS. EPX activity has potential to act as a prognostic biomarker of CRS disease severity and control.

A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum.

OBJECTIVES: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. MATERIALS AND METHODS: Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). RESULTS: VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. CONCLUSIONS: This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Whole-Body Sweat Rate Prediction: Outdoor Running and Cycling Exercise.

Our aim was to develop and validate separate whole-body sweat rate prediction equations for moderate to high intensity outdoor cycling and running, using simple measured or estimated activity and environmental inputs. Across two collection sites in Australia, 182 outdoor running trials, and 158 outdoor cycling trials were completed at a wet-bulb globe temperature ranging from ~15 to ~29˚C, with ~60-min whole-body sweat rates measured in each trial. Data were randomly separated into model development (running: 120; cycling: 100 trials) and validation groups (running: 62; cycling: 58 trials), enabling proprietary prediction models to be developed and then validated. Running and cycling models were also developed and tested when locally measured environmental conditions were substituted with participant subjective ratings for black globe temperature, wind speed, and humidity. The mean absolute error for predicted sweating rate was 0.03 and 0.02 L·h-1 for running and cycling models, respectively. The 95% confidence intervals for running (+0.44 and -0.38 L·h-1) and cycling (+0.45 and -0.42 L·h-1) were within acceptable limits for an equivalent change in total body mass over 3 h of ±2%. The individual variance in observed sweating described by the predictive models was 77% and 60% for running and cycling, respectively. Substituting measured environmental variables with subjective assessments of climatic characteristics reduced the variation in observed sweating described by the running model by up to ~25%, but only by ~2% for the cycling model. These prediction models are publicly accessible (https://sweatratecalculator.com) and can guide individualized hydration management in advance of outdoor running and cycling.

Provincial Intra-Action Review of the COVID-19 Vaccination Programme: Opportunities to Improve Vaccine Response in North Kivu, Democratic Republic of Congo.

Background: Low levels of COVID-19 vaccination coverage in many countries prompted the use of rapid assessments to characterize barriers to vaccination and identify corrective measures. The World Health Organization recommended the use of intra-action reviews (IARs) to identify best practices, gaps, and lessons learned to make real-time improvements to the COVID-19 vaccination response. Objective: The Democratic Republic of the Congo (DRC) implemented a national IAR in July 2021 that was poorly attended by the provincial health level, where vaccination activities are planned and implemented. To bridge this gap, we proposed sub-national IARs focused on COVID-19 vaccine program implementation at the provincial level. Methods: Using the WHO methodology, we organized a four-day provincial IAR workshop and invited national, provincial and health zone Ministry of Health (MoH) representatives and private and non-governmental organizations involved in the provincial COVID-19 vaccination response. Participants were divided into six groups based on their expertise, affiliation, and role within the health system to assess and identify lessons learned, challenges and the solutions within each of the six technical areas: (1) coordination, planning and monitoring; (2) service delivery; (3) risk communication and community engagement; (4) adverse effects following immunization (AEFI); (5) logistics; (6) and data management, monitoring and evaluation. Results: The first provincial COVID-19 IAR was conducted in Goma, North Kivu, from January 19-22, 2022. A total of 56 participants came from provincial and health zone offices, and non-governmental organizations. Through work group discussions, they identified best practices, challenges, and lessons learned, and made recommendations to improve implementation of vaccination activities and reach coverage targets. Activities were proposed to operationalize recommendations and address challenges to improve the provincial response. Conclusion: This provincial IAR was a useful tool for reviewing progress and areas of improvement, while evaluating aspects of the COVID-19 vaccine rollout. It provided a means to share information with vaccination partners on areas of intervention, tailored to the local context.

Articulated ankle-foot-orthosis improves inter-limb propulsion symmetry during walking adaptability task post-stroke.

BACKGROUND: Community ambulation involves complex walking adaptability tasks such as stepping over obstacles or taking long steps, which require adequate propulsion generation by the trailing leg. Individuals post-stroke often have an increased reliance on their trailing nonparetic leg and favor leading with their paretic leg, which can limit mobility. Ankle-foot-orthoses are prescribed to address common deficits post-stroke such as foot drop and ankle instability. However, it is not clear if walking with an ankle-foot-orthosis improves inter-limb propulsion symmetry during adaptability tasks. This study sought to examine this hypothesis. METHODS: Individuals post-stroke (n = 9) that were previously prescribed a custom fabricated plantarflexion-stop articulated ankle-foot-orthosis participated. Participants performed steady-state walking and adaptability tasks overground with and without their orthosis. The adaptability tasks included obstacle crossing and long-step tasks, leading with both their paretic and nonparetic leg. Inter-limb propulsion symmetry was calculated using trailing limb ground-reaction-forces. FINDINGS: During the obstacle crossing task, ankle-foot-orthosis use resulted in a significant improvement in inter-limb propulsion symmetry. The orthosis also improved ankle dorsiflexion during stance, reduced knee hyperextension, increased gastrocnemius muscle activity, and increased peak paretic leg ankle plantarflexor moment. In contrast, there were no differences in propulsion symmetry during steady-state walking and taking a long-step when using the orthosis. INTERPRETATION: Plantarflexion-stop articulated ankle-foot-orthoses can improve propulsion symmetry during obstacle crossing tasks in individuals post-stroke, promoting paretic leg use and reduced reliance on the nonparetic leg.

Reaction Rate and Stereoselectivity Enhancement in Glycosidations with O-Glycosyl Trihaloacetimidate Donors due to Catalysis by a Lewis Acid-Nitrile Cooperative Effect.

Activation of O-glycosyl trihaloacetimidate glycosyl donors with AuCl3 as a catalyst and pivalonitrile (tBuCN) as a ligand led to excellent glycosidation results in terms of yield and anomeric selectivity. In this way, various ß-d-gluco- and ß-d-galactopyranosides were obtained conveniently and efficiently. Experimental studies and density functional theory (DFT) calculations, in order to elucidate the reaction course, support formation of the tBuCN-AuCl2-OR(H)+ AuCl4- complex as a decisive intermediate in the glycosidation event. Proton transfer from this acceptor complex to the imidate nitrogen leads to donor activation. In this way, guided by the C-2 configuration of the glycosyl donor, the alignment of the acceptor complex enforces the stereoselective ß-glycoside formation in an intramolecular fashion, thus promoting also a fast reaction course. The high stereocontrol of this novel 'Lewis acid-nitrile cooperative effect' is independent of the glycosyl donor anomeric configuration and without the support of neighboring group or remote group participation. The power of the methodology is shown by a successful glycoalkaloid solamargine synthesis.

Feasibility of implementing an integrated long-term database to advance ecosystem-based management in the Laurentian Great Lakes basin.

The North American Great Lakes have been experiencing dramatic change during the past half-century, highlighting the need for holistic, ecosystem-based approaches to management. To assess interest in ecosystem-based management (EBM), including the value of a comprehensive public database that could serve as a repository for the numerous physical, chemical, and biological monitoring Great Lakes datasets that exist, a two-day workshop was organized, which was attended by 40+ Great Lakes researchers, managers, and stakeholders. While we learned during the workshop that EBM is not an explicit mission of many of the participating research, monitoring, and management agencies, most have been conducting research or monitoring activities that can support EBM. These contributions have ranged from single-resource (-sector) management to considering the ecosystem holistically in a decision-making framework. Workshop participants also identified impediments to implementing EBM, including: 1) high anticipated costs; 2) a lack of EBM success stories to garner agency buy-in; and 3) difficulty in establishing common objectives among groups with different mandates (e.g., water quality vs. fisheries production). We discussed as a group solutions to overcome these impediments, including construction of a comprehensive, research-ready database, a prototype of which was presented at the workshop. We collectively felt that such a database would offer a cost-effective means to support EBM approaches by facilitating research that could help identify useful ecosystem indicators and management targets and allow for management strategy evaluations that account for risk and uncertainty when contemplating future decision-making.

Pathogenicity, Host Resistance, and Genetic Diversity of Fusarium Species under Controlled Conditions from Soybean in Canada.

Fusarium spp. are commonly associated with the root rot complex of soybean (Glycine max). Previous surveys identified six common Fusarium species from Manitoba, including F. oxysporum, F. redolens, F. graminearum, F. solani, F. avenaceum, and F. acuminatum. This study aimed to determine their pathogenicity, assess host resistance, and evaluate the genetic diversity of Fusarium spp. isolated from Canada. The pathogenicity of these species was tested on two soybean cultivars, 'Akras' (moderately resistant) and 'B150Y1' (susceptible), under greenhouse conditions. The aggressiveness of the fungal isolates varied, with root rot severities ranging from 1.5 to 3.3 on a 0-4 scale. Subsequently, the six species were used to screen a panel of 20 Canadian soybean cultivars for resistance in a greenhouse. Cluster and principal component analyses were conducted based on the same traits used in the pathogenicity study. Two cultivars, 'P15T46R2' and 'B150Y1', were consistently found to be tolerant to F. oxysporum, F. redolens, F. graminearum, and F. solani. To investigate the incidence and prevalence of Fusarium spp. in Canada, fungi were isolated from 106 soybean fields surveyed across Manitoba, Saskatchewan, Ontario, and Quebec. Eighty-three Fusarium isolates were evaluated based on morphology and with multiple PCR primers, and phylogenetic analyses indicated their diversity across the major soybean production regions of Canada. Overall, this study contributes valuable insights into host resistance and the pathogenicity and genetic diversity of Fusarium spp. in Canadian soybean fields.

Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher z-transformed correlation coefficients (hereafter, z differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted P values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of z differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted P value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of z differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted P value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; P value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024 Supplemental material is available for this article.

Safety of mapping the motor networks in the spinal cord using penetrating microelectrodes in Yucatan minipigs.

OBJECTIVE: The goal of this study was to assess the safety of mapping spinal cord locomotor networks using penetrating stimulation microelectrodes in Yucatan minipigs (YMPs) as a clinically translational animal model. METHODS: Eleven YMPs were trained to walk up and down a straight line. Motion capture was performed, and electromyographic (EMG) activity of hindlimb muscles was recorded during overground walking. The YMPs underwent a laminectomy and durotomy to expose the lumbar spinal cord. Using an ultrasound-guided stereotaxic frame, microelectrodes were inserted into the spinal cord in 8 animals. Pial cuts were made to prevent tissue dimpling before microelectrode insertion. Different locations within the lumbar enlargement were electrically stimulated to map the locomotor networks. The remaining 3 YMPs served as sham controls, receiving the laminectomy, durotomy, and pial cuts but not microelectrode insertion. The Porcine Thoracic Injury Behavioral Scale (PTIBS) and hindlimb reflex assessment results were recorded for 4 weeks postoperatively. Overground gait kinematics and hindlimb EMG activity were recorded again at weeks 3 and 4 postoperatively and compared with preoperative measures. The animals were euthanized at the end of week 4, and the lumbar spinal cords were extracted and preserved for immunohistochemical analysis. RESULTS: All YMPs showed transient deficits in hindlimb function postoperatively. Except for 1 YMP in the experimental group, all animals regained normal ambulation and balance (PTIBS score 10) at the end of weeks 3 and 4. One animal in the experimental group showed gait and balance deficits by week 4 (PTIBS score 4). This animal was excluded from the kinematics and EMG analyses. Overground gait kinematic measures and EMG activity showed no significant (p > 0.05) differences between preoperative and postoperative values, and between the experimental and sham groups. Less than 5% of electrode tracks were visible in the tissue analysis of the animals in the experimental group. There was no statistically significant difference in damage caused by pial cuts between the experimental and sham groups. Tissue damage due to the pial cuts was more frequently observed in immunohistochemical analyses than microelectrode tracks. CONCLUSIONS: These findings suggest that mapping spinal locomotor networks in porcine models can be performed safely, without lasting damage to the spinal cord.

Behind the Scenes: Facilitators and Barriers to Developing State Scarce Resource Allocation Plans for the COVID-19 Pandemic.

BACKGROUND: In response to COVID-19, many states revised, developed, or attempted to develop plans to allocate scarce critical care resources in the event that crisis standards of care were triggered. No prior analysis has assessed this plan development process, including whether plans were successfully adopted. RESEARCH QUESTION: How did states develop or revise scarce resource allocation plans during the COVID-19 pandemic, and what were the barriers and facilitators to their development and adoption at the state level? STUDY DESIGN AND METHODS: Plan authors and state leaders completed a semi-structured interview February to September 2022. Interview transcripts were qualitatively analyzed for themes related to plan development and adoption according to the principles of grounded theory. RESULTS: Thirty-six participants from 34 states completed an interview, from states distributed across all US regions. Among participants' states with plans that existed prior to 2020 (n = 24), 17 were revised and adopted in response to COVID-19. Six states wrote a plan de novo, with the remaining states failing to develop or adopt a plan. Thirteen states continued to revise their plans in response to disability or aging bias complaints or to respond to evolving needs. Many participants expressed that urgency in the early days of the pandemic prevented an ideal development process. Facilitators of successful plan development and adoption include: coordination or support from the state department of health and existing relationships with key community partners, including aging and disability rights groups and minoritized communities. Barriers include lack of perceived political interest in a plan and development during a public health emergency. INTERPRETATION: To avoid repeating mistakes from the early days of the COVID-19 response, states should develop or revise plans with community engagement and consider maintaining a standing committee with diverse membership and content expertise to periodically review plans and advise state officials on pandemic preparedness.

A pressure-jump EPR system to monitor millisecond conformational exchange rates of spin-labeled proteins.

Site-directed spin labeling electron paramagnetic resonance (SDSL-EPR) using nitroxide spin labels is a well-established technology for mapping site-specific secondary and tertiary structure and for monitoring conformational changes in proteins of any degree of complexity, including membrane proteins, with high sensitivity. SDSL-EPR also provides information on protein dynamics in the time scale of ps-µs using continuous wave lineshape analysis and spin lattice relaxation time methods. However, the functionally important time domain of µs-ms, corresponding to large-scale protein motions, is inaccessible to those methods. To extend SDSL-EPR to the longer time domain, the perturbation method of pressure-jump relaxation is implemented. Here, we describe a complete high-pressure EPR system at Q-band for both static pressure and millisecond-timescale pressure-jump measurements on spin-labeled proteins. The instrument enables pressure jumps both up and down from any holding pressure, ranging from atmospheric pressure to the maximum pressure capacity of the system components (~3500 bar). To demonstrate the utility of the system, we characterize a local folding-unfolding equilibrium of T4 lysozyme. The results illustrate the ability of the system to measure thermodynamic and kinetic parameters of protein conformational exchange on the millisecond timescale.

Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone.

BACKGROUND: Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression. METHODS: Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis. FINDINGS: ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone. INTERPRETATION: Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer. FUNDING: Prostate Cancer Research and the Mark Foundation For Cancer Research, the Medical Research Council and Prostate Cancer UK.

Chemokine CCL19 and Its Receptors CCR7 and CCRL1 in Chronic Rhinosinusitis.

Background: CCL19 has been shown to predict disease severity in COVID-19 and treatment response in rheumatoid arthritis. CCL19 can exert both pro- and anti-inflammatory effects and is elevated in chronic rhinosinusitis (CRS). However, its role in CRS remains unknown. This study sought to determine the transcriptional changes in CCL19, its receptors, and associated cytokines and their association with disease severity in CRS. Methods: A clinical database of control subjects and patients with CRS was examined. Lund-Kennedy, Lund-Mackay, Sinonasal Outcomes Test 22 (SNOT-22), and rhinosinusitis disability index (RSDI) scores were collected at enrollment. mRNA was extracted from sinonasal tissues and subjected to multiplex gene expression analysis. Gene transcript differences between patients with CRS and controls were compared and correlated with disease severity metrics. Immunohistochemical analyses of CCL19, CCR7, and CCRL1 were conducted to compare differences in protein expression between cohorts. A subgroup analysis was performed to compare transcriptional and protein expression difference between patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls. Results: Thirty-eight subjects (control group, n=7; CRS group, n=31) were included in this study. CCRL1 (p=0.0093) and CCR7 (p=0.017) levels were significantly elevated in CRS compared to those in controls. CCL19 (p=0.038) and CCR7 (p=0.0097) levels were elevated in CRSwNP and CCRL1 was elevated in CRSsNP (p=0.0004). CCR7 expression was significantly elevated in sinonasal epithelial cells in CRSwNP (p=0.04). CCL19 expression was positively correlated with TNFA expression (p<0.0002). CCL19 and CCR7 expression was positively correlated with SNOT-22 and RSDI scores (p<0.05). Conclusion: CCL19 and CCR7 may modulate TNF-α-driven pro-inflammatory signaling and contribute to increased disease severity in CRS. Mechanistic studies are required to further elucidate the role of CCRL1 in CRS.

(What's the story) morning glory? MRI findings in morning glory disc anomaly.

PURPOSE: Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in our tertiary pediatric center. METHODS: A retrospective review was performed of fundoscopically-diagnosed cases of MGDA, that had been referred for MRI. All MRI studies were scrutinized for orbital and other intracranial abnormalities known to occur in association with MGDA. RESULTS: 18 of 19 cases of MGDA showed three characteristic MRI findings: funnel-shaped morphology of the posterior optic disc, abnormal soft tissue associated with the retrobulbar optic nerve, and effacement of adjacent subarachnoid spaces. The ipsilateral (intraorbital) optic nerve was larger in one patient and smaller in six. The ipsilateral optic chiasm was larger in two patients and smaller in one. CONCLUSION: This study represents a comprehensive radiological-led investigation into MGDA. It describes the most frequently-encountered MRI findings in MGDA and emphasizes the importance of MRI in this cohort, i.e., in distinguishing MGDA from other posterior globe abnormalities, in assessing the visual pathway, and in screening for associated intracranial abnormalities - skull base/cerebral, vascular, and facial. It hypothesizes neurocristopathy as an underlying cause of MGDA and its associations. Caliber abnormalities of the ipsilateral optic nerve and chiasm are a frequent finding in MGDA. Optic pathway enlargement should not be labeled "glioma". (239/250).

The Impact of Health Coaching on Weight and Physical Activity in Obese Adults: A Randomized Control Trial.

Health Coaching (HC) is an evidence-based, patient-centered approach to assisting individuals in achieving their health-related goals. Studies have generally shown positive effects of HC on weight loss in obese adults. However, limitations do exist, that if addressed would further clarify HC's viability as a clinical, obesity treatment approach. To examine the effects of HC on weight loss, moderate-to-vigorous physical activity (MVPA), and psychosocial constructs in obese adults. A randomized control trial with 44 [Mean body mass index (BMI) 36.5] middle-aged, White adults. Participants were randomly assigned to HC (n = 22) or control (n = 22) groups. A certified health coach provided bi-weekly, in-person and telehealth HC for 12 weeks. Percent excess weight loss was 15.7% in HC vs. 2.5% in controls (p< .001). The change in MVPA was significantly greater in HC (+50.3 min/wk) vs controls (+7.1 min/wk). Psychosocial constructs also changed more favorably in HC than controls. Health coaching is an effective approach for weight loss in obese adults. The results of this study support the consideration of HC as a treatment option for obese adults looking to lose weight.

Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a limited number of known driver mutations but considerable cancer cell heterogeneity. Phosphoproteomics provides a direct read-out of aberrant signaling and the resultant clinically relevant phenotype. Mass spectrometry (MS)-based proteomics and phosphoproteomics were applied to 42 PDAC tumors. Data encompassed over 19 936 phosphoserine or phosphothreonine (pS/T; in 5412 phosphoproteins) and 1208 phosphotyrosine (pY; in 501 phosphoproteins) sites and a total of 3756 proteins. Proteome data identified three distinct subtypes with tumor intrinsic and stromal features. Subsequently, three phospho-subtypes were apparent: two tumor intrinsic (Phos1/2) and one stromal (Phos3), resembling known PDAC molecular subtypes. Kinase activity was analyzed by the Integrative iNferred Kinase Activity (INKA) scoring. Phospho-subtypes displayed differential phosphorylation signals and kinase activity, such as FGR and GSK3 activation in Phos1, SRC kinase family and EPHA2 in Phos2, and EGFR, INSR, MET, ABL1, HIPK1, JAK, and PRKCD in Phos3. Kinase activity analysis of an external PDAC cohort supported our findings and underscored the importance of PI3K/AKT and ERK pathways, among others. Interestingly, unfavorable patient prognosis correlated with higher RTK, PAK2, STK10, and CDK7 activity and high proliferation, whereas long survival was associated with MYLK and PTK6 activity, which was previously unknown. Subtype-associated activity profiles can guide therapeutic combination approaches in tumor and stroma-enriched tissues, and emphasize the critical role of parallel signaling pathways. In addition, kinase activity profiling identifies potential disease markers with prognostic significance.

Intraductal magnetic resonance imaging of cholangiocarcinoma - a practical possibility.

Intraductal T2 mapping based on a catheter receiver is proposed as a method of visualizing the extent of intraductal and periductal cholangiocarcinoma (CCA). Compared to external receivers, internal receivers provide locally enhanced signal-to-noise ratios by virtue of their lower field-of-view for body noise, allowing smaller voxels and higher resolution. However, inherent radial sensitivity variation and segmentation for patient safety both distort image brightness. We discuss simulated T2 weighted images and T2 maps, and in vitro images obtained using a thin film catheter receiver of a freshly resected liver specimen containing a polypoid intraductal tumor from a patient with CCA. T2 mapping provides a simple method of compensating non-uniform signal reception patterns of catheter receivers, allowing the visualization of tumor extent without contrast enhancement and potentially quantitative tissue characterization. Potential advantages and disadvantages of in vivo intraductal imaging are considered.

Qualitative Analysis of Decision to Pursue Electrical Brain Stimulation by Patients With Drug-Resistant Epilepsy and Their Caregivers.

Background and Objectives: To understand why patients with drug-resistant epilepsy (DRE) pursue invasive electrical brain stimulation (EBS). Methods: We interviewed patients with DRE (n = 20) and their caregivers about their experiences in pursuing EBS approximately 1 year post device implant. Inductive analysis was applied to identify key motivating factors. Results: The cohort included participants aged from teens to 50s with deep brain stimulation, vagus nerve stimulation, responsive neurostimulation, and chronic subthreshold cortical stimulation. Patients' motivations included (1) improved quality of life (2) intolerability of antiseizure medications, (3) desperation, and (4) patient-family dynamics. Both patients and caregivers described a desire to alleviate burdens of the other. Patient apprehensions about EBS focused on invasiveness and the presence of electrodes in the brain. Previous experiences with invasive monitoring and the ability to see hardware in person during clinical visits influenced patients' comfort in proceeding with EBS. Despite realistic expectations for modest and delayed benefits, patients held out hope for an exceptionally positive outcome. Discussion: Our findings describe the motivations and decision-making process for patients with DRE who pursue invasive EBS. Patients balance feelings of desperation, personal goals, frustration with medication side effects, fears about surgery, and potential pressure from concerned caregivers. These factors together with the sense that patients have exhausted therapeutic alternatives may explain the limited decisional ambivalence observed in this cohort. These themes highlight opportunities for epilepsy care teams to support patient decision-making processes.