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Objective: Lower socioeconomic status (SES) is a risk factor for poorer pain-related outcomes. Further, the neighborhood environments of disadvantaged communities can create a milieu of increased stress and deprivation that adversely affects pain-related and other health outcomes. Socioenvironmental variables such as the Area Deprivation Index, which ranks neighborhoods based on socioeconomic factors could be used to capture environmental aspects associated with poor pain outcomes. However, it is unclear whether the ADI could be used as a risk assessment tool in addition to individual-level SES. Methods: The current study investigated whether neighborhood-level disadvantage impacts knee pain-related outcomes above sociodemographic measures. Participants were 188 community-dwelling adults who self-identified as non-Hispanic Black or non-Hispanic White and reported knee pain. Area Deprivation Index (ADI; measure of neighborhood-level disadvantage) state deciles were derived for each participant. Participants reported educational attainment and annual household income as measures of SES, and completed several measures of pain and function: Short-form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, and Graded Chronic Pain Scale were completed, and movement-evoked pain was assessed following the Short Physical Performance Battery. Hierarchical linear regression analyses were used to assess whether environmental and sociodemographic measures (i.e., ADI 80/20 [80% least disadvantaged and 20% most disadvantaged]; education/income, race) were associated with pain-related clinical outcomes. Results: Living in the most deprived neighborhood was associated with poorer clinical knee pain-related outcomes compared to living in less deprived neighborhoods (ps < 0.05). Study site, age, BMI, education, and income explained 11.3–28.5% of the variance across all of the individual pain-related outcomes. However, the ADI accounted for 2.5–4.2% additional variance across multiple pain-related outcomes. Conclusion: The ADI accounted for a significant amount of variance in pain-related outcomes beyond the control variables including education and income. Further, the effect of ADI was similar to or higher than the effect of age and BMI. While the effect of neighborhood environment was modest, a neighborhood-level socioenvironmental variable like ADI might be used by clinicians and researchers to improve the characterization of patients' risk profile for chronic pain outcomes. [ABSTRACT FROM AUTHOR]

Advances in the spatiotemporal resolution and field-of-view of neuroimaging tools are driving mesoscale studies for translational neuroscience. On October 10, 2023, the Center for Mesoscale Mapping (CMM) at the Massachusetts General Hospital (MGH) Athinoula A. Martinos Center for Biomedical Imaging and the Massachusetts Institute of Technology (MIT) Health Sciences Technology based Neuroimaging Training Program (NTP) hosted a symposium exploring the state-of-the-art in this rapidly growing area of research. "Mesoscale Brain Mapping: Bridging Scales and Modalities in Neuroimaging" brought together researchers who use a broad range of imaging techniques to study brain structure and function at the convergence of the microscopic and macroscopic scales. The day-long event centered on areas in which the CMM has established expertise, including the development of emerging technologies and their application to clinical translational needs and basic neuroscience questions. The in-person symposium welcomed more than 150 attendees, including 57 faculty members, 61 postdoctoral fellows, 35 students, and four industry professionals, who represented institutions at the local, regional, and international levels. The symposium also served the training goals of both the CMM and the NTP. The event content, organization, and format were planned collaboratively by the faculty and trainees. Many CMM faculty presented or participated in a panel discussion, thus contributing to the dissemination of both the technologies they have developed under the auspices of the CMM and the findings they have obtained using those technologies. NTP trainees who benefited from the symposium included those who helped to organize the symposium and/or presented posters and gave "flash" oral presentations. In addition to gaining experience from presenting their work, they had opportunities throughout the day to engage in one-on-one discussions with visiting scientists and other faculty, potentially opening the door to future collaborations. The symposium presentations provided a deep exploration of the many technological advances enabling progress in structural and functional mesoscale brain imaging. Finally, students worked closely with the presenting faculty to develop this report summarizing the content of the symposium and putting it in the broader context of the current state of the field to share with the scientific community. We note that the references cited here include conference abstracts corresponding to the symposium poster presentations. [ABSTRACT FROM AUTHOR]

The early diversification of tetrapods into terrestrial environments involved adaptations of their locomotor apparatus that allowed for weight support and propulsion on heterogeneous surfaces. Many lineages subsequently returned to the water, while others conquered the aerial environment, further diversifying under the physical constraints of locomoting through continuous fluid media. While many studies have explored the relationship between locomotion in continuous fluids and body mass, none have focused on how continuous fluid media have impacted the macroevolutionary patterns of limb shape diversity.We investigated whether mammals that left terrestrial environments to use air and water as their main locomotor environment experienced constraints on the morphological evolution of their forelimb, assessing their degree of morphological disparity and convergence. We gathered a comprehensive sample of more than 800 species that cover the extant family‐level diversity of mammals, using linear measurements of the forelimb skeleton to determine its shape and size.Among mammals, fully aquatic groups have the most disparate forelimb shapes, possibly due to the many different functional roles performed by flippers or the relaxation of constraints on within‐flipper bone proportions. Air‐based locomotion, in contrast, is linked to restricted forelimb shape diversity. Bats and gliding mammals exhibit similar morphological patterns that have resulted in partial phenotypic convergence, mostly involving the elongation of the proximal forelimb segments.Thus, whereas aquatic locomotion drives forelimb shape diversification, aerial locomotion constrains forelimb diversity. These results demonstrate that locomotion in continuous fluid media can either facilitate or limit morphological diversity and more broadly that locomotor environments have fostered the morphological and functional evolution of mammalian forelimbs. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6‐dependent opioids while on CYP2D6‐inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6‐dependent opioids utilizing electronic health records data from the University of Florida Health (2015–2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine‐treated patients exposed to CYP2D6‐inhibitor antidepressants (n = 7,043) had a higher crude rate of pain‐related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6‐inhibitor antidepressant‐exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27–2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control. [ABSTRACT FROM AUTHOR]

Context The real world efficacy and tolerabiltiy of NTRK inhibitor larotrectinib has not yet been reported in the literature although trial data has shown promising results. Objective We report a retrospective analysis of patients with thyroid cancer harboring NTRK fusions who underwent treatment with larotrectinib. Methods A single-institution, retrospective case series of patients with NTRK fusion-positive thyroid cancers treated with neurotrophic tyrosine receptor kinase (NTRK) inhibitors from January 1, 2007, to January 1, 2023, was performed. This study was conducted at a single academic tertiary referral center. Patients with confirmed NTRK -fusion thyroid cancer who received larotrectinib were included. Larotrectinib was administered in accordance with clinical judgment from oncology providers. The primary end point was progression-free survival (PFS). Results Eight patients with NTRK fusion-positive thyroid cancer treated with larotrectinib were identified: 4 with papillary thyroid cancer (PTC) (50%), 3 with poorly differentiated thyroid cancer (PDTC) (38%), and 1 with anaplastic thyroid cancer (ATC) (12%). The median PFS (mPFS) for all patients was 24.7 months (95% CI, 11.3-38.1). mPFS in PTC was higher than PDTC (34.6 months [24.7-48.7 months] vs 17.5 [7.1-21.1 months]; P =.017). The median overall survival (OS) was 43.8 months (29.8-56.8 months) overall. The single patient with ATC had a PFS and OS of 23 months. Two patients remained on treatment/alive at data cutoff, with a duration of response of 33.5 months and a median follow-up of 52 months. Patients achieved 1 complete response (12%), 6 partial responses (75%), and 1 stable disease (12%). Conclusion In this single-institution cohort of patients with NTRK fusion-positive thyroid cancer, NTRK inhibition led to an mPFS of 25 months, with survival surpassing historic benchmarks for ATC and PDTC. [ABSTRACT FROM AUTHOR]

Aims: In the present intervention study, low-velocity-loss (LVL) versus high-velocity-loss (HVL) thresholds in the squat and bench press were compared for changes in muscle strength, power, and hypertrophy. Methods: Strength-trained volunteers (7♀ and 9♂; age: 27.2 [3.4] y; height: 174.6 [8.0] cm; body mass: 75.3 [10.1] kg) were randomized into an LVL or HVL threshold group (LVL n = 3♀ + 5♂, and HVL n = 4♀ + 4♂). Training took place 3 times per week over 6 weeks (loads: ∼75%–90% of 1-repetition maximum [1RM]). The thresholds of LVLs and HVLs were set at 20% and 40% of maximal velocity, respectively, for the squat, and at 30% and 60%, respectively, for the bench press. Before and after the intervention, 1RM, leg press power, and squat jump were tested. The load (∼45% of 1RM) corresponding to 1-m/s velocity was assessed in all sessions for both exercises. In addition, the thickness of the vastus lateralis and triceps brachii and body composition (dual-energy X-ray absorptiometry [DEXA]) were measured. Results: Squat and bench-press 1RM increased similarly in both groups by 7% to 11% (SD: 4%–6%, P <.05). No group differences were observed for changes in jump height, leg press power, or DEXA lean mass. However, HVL showed a small increase in muscle thickness of the vastus lateralis compared with LVL (6 ± 6% [95% CI] group difference, P <.05). Conclusion: For strength-trained individuals, high-volume lower-velocity-loss thresholds were as effective as higher thresholds for improvements in 1RM strength; but local hypertrophy was seemingly elicited faster with higher velocity-loss thresholds. [ABSTRACT FROM AUTHOR]

Pathological disruption of Nucleocytoplasmic Transport (NCT), such as the mis-localization of nuclear pore complex proteins (Nups), nuclear transport receptors, Ran-GTPase, and RanGAP1, are seen in both animal models and in familial and sporadic forms of amyotrophic lateral sclerosis (ALS), frontal temporal dementia and frontal temporal lobar degeneration (FTD\FTLD), and Alzheimer's and Alzheimer's Related Dementias (AD/ADRD). However, the question of whether these alterations represent a primary cause, or a downstream consequence of disease is unclear, and what upstream factors may account for these defects are unknown. Here, we report four key findings that shed light on the upstream causal role of Importin-β-specific nuclear transport defects in disease onset. First, taking advantage of two novel mouse models of NEMF neurodegeneration (NemfR86S and NemfR487G) that recapitulate many cellular and biochemical aspects of neurodegenerative diseases, we find an Importin-β-specific nuclear import block. Second, we observe cytoplasmic mis-localization and aggregation of multiple proteins implicated in the pathogenesis of ALS/FTD and AD/ADRD, including TDP43, Importin-β, RanGap1, and Ran. These findings are further supported by a pathological interaction between Importin-β and the mutant NEMFR86S protein in cytoplasmic accumulations. Third, we identify similar transcriptional dysregulation in key genes associated with neurodegenerative disease. Lastly, we show that even transient pharmaceutical inhibition of Importin-β in both mouse and human neuronal and non-neuronal cells induces key proteinopathies and transcriptional alterations seen in our mouse models and in neurodegeneration. Our convergent results between mouse and human neuronal and non-neuronal cellular biology provide mechanistic evidence that many of the mis-localized proteins and dysregulated transcriptional events seen in multiple neurodegenerative diseases may in fact arise primarily from a primary upstream defect in Importin- β nuclear import. These findings have critical implications for investigating how sporadic forms of neurodegeneration may arise from presently unidentified genetic and environmental perturbations in Importin-β function. Author summary: Neurodegenerative diseases are common disorders of aging, resulting in both motor and cognitive defects and premature death. Nucleocytoplasmic transport defects have been implicated in various forms of neurodegeneration including Alzheimer's and Related Dementias and Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here, we describe nuclear transport defects in two mouse models with genetic mutations in Nuclear Export Mediator Factor (NEMF). We have found that these mice exhibit defects in nucleocytoplasmic transport, specifically in the nuclear import of proteins which are regulated through the Importin-β pathway. In addition, the two mutations result in very different ages of onset and progression of both disease and transport defects, mimicking the variation seen in genetic forms of human neurodegenerative diseases. They also recapitulate common pathologies and transcriptional alterations found in patients and are therefore a unique animal model of neurodegeneration. These findings are important because they point towards a potentially common pathway for disease development between rarer genetic and common sporadic forms of neurodegeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phthalates and their replacements have been implicated as developmental toxicants. Young children may be exposed to phthalates/replacements when using skin care products (SCPs). OBJECTIVES: Our objective is to assess the associations between use of SCPs and children’s urinary phthalate/replacement metabolite concentrations. METHODS: Children (4–8 years old) from the Environmental Influences on Child Health Outcomes-Fetal Growth Study (ECHO-FGS) cohort provided spot urine samples from 2017 to 2019, and mothers were queried about children’s SCP use in the past 24 h (푛=906). Concentrations of 16 urinary phthalate/replacement metabolites were determined by liquid chromatography–tandem mass spectrometry (푛=630). We used linear regression to estimate the child’s use of different SCPs as individual predictors of urinary phthalate/replacement metabolites, adjusted for urinary specific gravity, age, sex assigned at birth, body mass index, and self-reported race/ethnic identity, as well as maternal education, and season of specimen collection. We created self-organizing maps (SOM) to group children into “exposure profiles” that reflect discovered patterns of use for multiple SCPs. RESULTS: Children had lotions applied (43.0%) frequently, but “2-in-1” hair-care products (7.5%), sunscreens (5.9%), and oils (4.3%) infrequently. Use of lotions was associated with 1.17-fold [95% confidence interval (CI): 1.00, 1.34] greater mono-benzyl phthalate and oils with 2.86-fold (95% CI: 1.89, 4.31) greater monoethyl phthalate (MEP), 1.43-fold (95% CI: 1.09, 1.90) greater monobutyl phthalate (MBP), and 1.40-fold (95% CI: 1.22, 1.61) greater low-molecular-weight phthalates (LMW). Use of 2-in-1 haircare products was associated with 0.84-fold (95% CI: 0.72, 0.97) and 0.78-fold (95% CI: 0.62, 0.98) lesser mono(3-carboxypropyl) phthalate (MCPP) and MBP, respectively. Child’s race/ethnic identity modified the associations of lotions with LMW, oils with MEP and LMW, sunscreen with MCPP, ointments with MEP, and hair conditioner with MCPP. SOM identified four distinct SCP-use exposure scenarios (i.e., profiles) within our population that predicted 1.09-fold (95% CI: 1.03, 1.15) greater mono-carboxy isononyl phthalate, 1.31-fold (95% CI: 0.98, 1.77) greater mono-2-ethyl-5-hydroxyhexyl terephthalate, 1.13-fold (95% CI: 0.99, 1.29) greater monoethylhexyl phthalate, and 1.04-fold (95% CI: 1.00, 1.09) greater diethylhexyl phthalate. DISCUSSION: We found that reported SCP use was associated with urinary phthalate/replacement metabolites in young children. These results may inform policymakers, clinicians, and parents to help limit children’s exposure to developmental toxicants. [ABSTRACT FROM AUTHOR]

Living mammal groups exhibit rapid juvenile growth with a cessation of growth in adulthood1. Understanding the emergence of this pattern in the earliest mammaliaforms (mammals and their closest extinct relatives) is hindered by a paucity of fossils representing juvenile individuals. We report exceptionally complete juvenile and adult specimens of the Middle Jurassic docodontan Krusatodon, providing anatomical data and insights into the life history of early diverging mammaliaforms. We used synchrotron X-ray micro-computed tomography imaging of cementum growth increments in the teeth2–4 to provide evidence of pace of life in a Mesozoic mammaliaform. The adult was about 7 years and the juvenile 7 to 24 months of age at death and in the process of replacing its deciduous dentition with its final, adult generation. When analysed against a dataset of life history parameters for extant mammals5, the relative sequence of adult tooth eruption was already established in Krusatodon and in the range observed in extant mammals but this development was prolonged, taking place during a longer period as part of a significantly longer maximum lifespan than extant mammals of comparable adult body mass (156 g or less). Our findings suggest that early diverging mammaliaforms did not experience the same life histories as extant small-bodied mammals and the fundamental shift to faster growth over a shorter lifespan may not have taken place in mammaliaforms until during or after the Middle Jurassic.Juvenile and adult skeletons of Middle Jurassic Krusatodon from the Isle of Skye, Scotland, show that this mouse-sized mammaliaform had longer development and lifespan than modern mammals of similar mass. [ABSTRACT FROM AUTHOR]

Simple Summary: Pain is a common symptom that affects individuals with cancer. This study, using data from the National Health Interview Survey, explored how household income relates to chronic pain among cancer survivors. It found that lower-income survivors, those below 200% of the federal poverty level (FPL), were more likely to report chronic pain lasting at least 3 months and pain that significantly limited their daily activities. Compared to higher-income survivors (at least 400% FPL), those with lower incomes had higher odds of experiencing chronic pain and its impact on daily life. Additionally, opioid use for pain management was more common among lower-income survivors, while higher-income survivors tended to use alternative methods like yoga, chiropractic care, and physical therapy. This study emphasizes the need for targeted efforts to address healthcare disparities and improve pain management for all cancer survivors, regardless of their income level. Pain is a prevalent issue among cancer patients, yet its link with socioeconomic status has not been thoroughly examined. This study investigated chronic pain (lasting ≥3 months) and high-impact pain (chronic pain limiting activities) among cancer survivors based on household income relative to the federal poverty level (FPL), using data from the National Health Interview Survey (2019–2020). Of the 4585 participants with a history of solid cancers, 1649 (36.3%) reported chronic pain and 554 (12.6%) reported high-impact chronic pain. After adjustment, participants with incomes < 200% FPL had significantly higher odds of chronic pain (adjusted odds ratio [aOR]: 1.60, 95% CI: 1.25–2.05) and high-impact chronic pain (aOR: 1.73, 95% CI: 1.09–2.74) compared to those with incomes ≥ 400% FPL. Opioid use for chronic pain was most prevalent among those with incomes < 200% FPL (28.3%) compared to those with 200–399% (21.3%) and ≥400% (19.0%). Higher-income participants reported greater use of alternative pain management methods such as yoga (50.5%), chiropractic care (44.8%), and physical therapy (44.3%). This study highlights the association between household income and chronic pain outcomes among cancer survivors, emphasizing the necessity for targeted interventions to mitigate healthcare access disparities and improve pain management for all individuals affected by cancer. [ABSTRACT FROM AUTHOR]

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6‐guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT‐PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6‐impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6‐guided trial recommendations. The primary study outcome is the 3‐month absolute change in the composite pain intensity score assessed using Patient‐Reported Outcomes Measurement Information System (PROMIS) measures. Follow‐up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment. [ABSTRACT FROM AUTHOR]

Pork carcasses and meat may harbor Salmonella and may contaminate other products during harvest and fabrication. Sources of contamination include manure on hides, environmental contamination, ingredients from external sources, and lymph nodes. Swine lymph nodes are often incorporated into ground meat, as their anatomical location makes removal labor prohibitive. A sausage processing plant in the midwestern United States was sampled monthly (except for December) from May 2021 to April 2022 to enumerate Salmonella and Enterobacteriaceae (EB) throughout the sausage manufacturing process to determine high-risk stages and efficiency of existing in-plant interventions. Salmonella serotypes and antimicrobial susceptibility were evaluated on a subset of isolates recovered at the end phases of sausage production. In each collection, samples were taken from the carcasses of eight sows through 11 stages of sausage manufacturing. A total of 830 samples were cultured. Thirty-four Salmonella were isolated from the final three production stages; of these, there were eleven serotypes. Three isolates displayed resistance to ampicillin, whereas the remainder of the isolates were pan-susceptible to the antimicrobials tested. Salmonella and EB were significantly reduced (p < 0.001) by acid washes at different stages of production, and the results point to the beneficial effects of interventions to lessen Salmonella concentrations in retail products. [ABSTRACT FROM AUTHOR]

The nature of pharmacokinetic interactions between cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids and antidepressants among older nursing home residents is unclear. In this study of nursing home residents, concomitant use of CYP2D6-metabolized opioids with CYP2D6-inhibiting antidepressants was associated with higher adjusted rate ratios of worsening pain, pain-related hospitalization, pain-related emergency department visits, and opiate use disorder. These findings suggest the need for caution in prescribing these agents in older patients. Visual Abstract. Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents: The nature of pharmacokinetic interactions between cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids and antidepressants among older nursing home residents is unclear. In this study of nursing home residents, concomitant use of CYP2D6-metabolized opioids with CYP2D6-inhibiting antidepressants was associated with higher adjusted rate ratios of worsening pain, pain-related hospitalization, pain-related emergency department visits, and opiate use disorder. These findings suggest the need for caution in prescribing these agents in older patients. Background: Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents. Objective: To investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs). Design: Retrospective cohort study using a target trial emulation framework. Setting: 100% Medicare NH sample linked to Minimum Data Set (MDS) from 2010 to 2021. Participants: Long-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use. Intervention: Initiating CYP2D6-inhibiting versus CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for 1 day or more. Measurements: Clinical outcomes were worsening pain, physical function, and depression from baseline to quarterly MDS assessments and were analyzed using modified Poisson regression models. The ORAE outcomes included counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose and were analyzed with negative binomial or Poisson regression models. All models were adjusted for baseline covariates via inverse probability of treatment weighting. Results: Among 29 435 identified residents, use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher adjusted rate ratio of worsening pain (1.13 [95% CI, 1.09 to 1.17]) and higher adjusted incidence rate ratios of pain-related hospitalization (1.37 [CI, 1.19 to 1.59]), pain-related ED visit (1.49 [CI, 1.24 to 1.80]), and OUD (1.93 [CI, 1.37 to 2.73]), with no difference in physical function, depression, and opioid overdose. Limitation: Findings are generalizable to NH populations only. Conclusion: Use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with worsening pain and increased risk for most assessed ORAEs among older NH residents. Primary Funding Source: National Institute on Aging. [ABSTRACT FROM AUTHOR]

The Cenozoic stratigraphy of the Zagros records the ongoing collision between the Arabian and Eurasian Plates and the closure of NeoTethys. A Paleogene NW‐SE trending foreland basin was inherited from a Late Cretaceous precursor. Widespread progradation into the foredeep was a feature of both margins which, allied to ongoing tectonism, had by the late Eocene led to the narrowing and subsequent division of the foredeep into the Lurestan – Khuzestan and Lengeh Troughs, separated by the northward continuation of the rejuvenated Qatar‐Fars Arch. This sub‐division strongly influenced subsequent deposition and the petroleum geology of the area. In addition, the diachronous nature of the Arabian – Eurasian collision led to strong diachroneity in lithostratigraphic units along the length of the Zagros. Hence its petroleum geology is best understood within a regional sequence stratigraphic framework. This study identifies three tectono‐megasequences (TMS 10, TMS 11a, TMS 11b) and multiple depositional sequences. The Cenozoic contains a world class hydrocarbon province with prolific oil reservoirs in the Oligo‐Miocene Asmari Formation sealed by the evaporite‐dominated Gachsaran Formation, mostly contained within giant NW‐SE trending "whaleback" anticlines concentrated in the Dezful Embayment. Reservoirs in the SW are dominantly siliciclastic or comprise mixed siliciclastics and carbonates, whereas those to the east and NE are dominated by fractured carbonates. There remains untested potential in stratigraphic traps, especially in deeperwater sandstone reservoirs deposited along the SW margin of the foredeep. Late Miocene to Pliocene charge to the Asmari reservoirs was mostly from Aptian – Albian Kazhdumi Formation source rocks. In some fields, an additional component was from organic‐rich late Eocene to earliest Oligocene Pabdeh Formation source rocks confined to the narrowing Lurestan – Khuzestan Trough. Where mature, the latter source rock is also a potential unconventional reservoir target, although the prospective area is limited due to recent uplift and erosion. Deeper Jurassic source rocks contributed to the Cheshmeh Khush field in Dezful North. Silurian source rocks charged gas‐bearing structures in the Bandar Abbas region. [ABSTRACT FROM AUTHOR]

Introduction: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non–small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity‐modulated radiotherapy (IMRT). Methods: Patients with locally advanced non–small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90‐day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan–Meier method was used for progression‐free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. Results: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p <.001) and had higher Charlson Comorbidity Index scores (p =.02). The PBT group received a lower mean heart dose (p <.0001), left anterior descending artery V15 Gy (p =.001), mean lung dose (p =.008), and effective dose to immune circulating cells (p <.001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38–0.81; p =.002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37–0.81; p =.003). There was no difference in other G3+ toxicities, progression‐free survival, or overall survival. Conclusions: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed. The use of proton beam therapy in locally advanced non–small cell lung cancer is associated with fewer 90‐day acute hospitalizations, lower effective dose to immune circulating cells, and less grade 3+ lymphopenia compared with intensity‐modulated radiation therapy. [ABSTRACT FROM AUTHOR]

Background: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. Aim: The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m‐amph). Methods: Wistar rats were given 14 days of m‐amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low‐frequency stimulation (LFS) or continuous high‐frequency stimulation (HFS). Immediately after DBS, manic‐like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open‐field tests and fast‐scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. Results: M‐amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M‐amph increased DA reuptake time post‐sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. Conclusion: These results demonstrate that both VTA LFS and HFS DBS exert anti‐manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti‐manic effects. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate fetal biometrics as predictors of shoulder dystocia (SD) in a low-risk obstetrical population. Study Design Participants were enrolled as part of a U.S.-based prospective cohort study of fetal growth in low-risk singleton gestations (n = 2,802). Eligible women had liveborn singletons ≥2,500 g delivered vaginally. Sociodemographic, anthropometric, and pregnancy outcome data were abstracted by research staff. The diagnosis of SD was based on the recorded clinical impression of the delivering physician. Simple logistic regression models were used to examine associations between fetal biometrics and SD. Fetal biometric cut points, selected by Youden's J and clinical determination, were identified to optimize predictive capability. A final model for SD prediction was constructed using backward selection. Our dataset was randomly divided into training (60%) and test (40%) datasets for model building and internal validation. Results A total of 1,691 women (98.7%) had an uncomplicated vaginal delivery, while 23 (1.3%) experienced SD. There were no differences in sociodemographic or maternal anthropometrics between groups. Epidural anesthesia use was significantly more common (100 vs. 82.4%; p = 0.03) among women who experienced SD compared with those who did not. Amniotic fluid maximal vertical pocket was also significantly greater among SD cases (5.8 ± 1.7 vs. 5.1 ± 1.5 cm; odds ratio = 1.32 [95% confidence interval: 1.03,1.69]). Several fetal biometric measures were significantly associated with SD when dichotomized based on clinically selected cut-off points. A final prediction model was internally valid with an area under the curve of 0.90 (95% confidence interval: 0.81, 0.99). At a model probability of 1%, sensitivity (71.4%), specificity (77.5%), positive (3.5%), and negative predictive values (99.6%) did not indicate the ability of the model to predict SD in a clinically meaningful way. Conclusion Other than epidural anesthesia use, neither sociodemographic nor maternal anthropometrics were significantly associated with SD in this low-risk population. Both individually and in combination, fetal biometrics had limited ability to predict SD and lack clinical usefulness. Key Points SD unpredictable in low-risk women. Fetal biometry does not reliably predict SD. Epidural use associated with increased SD risk. SD prediction models clinically inefficient. [ABSTRACT FROM AUTHOR]

Smartwatches are a type of wearable device that enable continuous monitoring of an individual's activities and critical health metrics. As the number of older adults age 65+ continues to grow in the U.S. so does their usage of smartwatches, making it necessary to understand the real-world uptake and use of these devices to monitor health. In this study, older adults with a relatively high level of education and digital skills were provided with a smartwatch equipped with a mobile application (ROAMM) that was worn for a median of 14 days. Usability surveys were distributed, and a qualitative analysis was performed about participants' experience using the smartwatch and ROAMM application. Constructs from the Technology Acceptance Model and Consolidated Framework for Implementation Research were incorporated into in-depth interviews, which were recorded and transcribed. Data were analyzed using the constant comparative method. Interviews among 30 older adults revealed the following main themes: 1) familiarization with the device and adoption and acceptance, 2) factors encouraging usage, such as a doctor's endorsement or the appeal of tracking one's health, and 3) barriers to usage, such as insufficient education and training and the desire for additional functionality. Overall, participants found the smartwatch easy to use and were likely to continue using the device in a long-term study. Data generated from smartwatches have the potential to engage individuals about their health and could inspire them to participate more actively during clinical encounters. [ABSTRACT FROM AUTHOR]

Objectives: Studies examining electromyography (EMG)‐guided laryngeal onobotulinumtoxinA (BTxA) injection for chronic cough reveal promising efficacy, however, are limited by small cohorts and absent quantifiable outcomes. It further remains unclear if pulmonary disease limits efficacy, or if vagal motor neuropathy prognosticates response. We hypothesize BTxA injection results in qualitative improvement in cough, decrease in Cough Severity Index (CSI), no change in Voice Handicap Index‐10 (VHI‐10), and complication rates comparable to historical data. We also examine the correlation of pulmonary comorbidities and vocal fold hypomobility with treatment efficacy. Study Design: Retrospective review. Methods: Charts for patients receiving percutaneous adductor compartment BTxA injection for cough were reviewed for the binary outcome of patient‐reported presence or absence of improvement. Generalized estimating equations regression models were used to analyze the change in CSI (ΔCSI) and the correlation of ΔCSI with qualitative outcomes. Multivariable analyses were used to examine correlation of vocal fold hypomobility and pulmonary disease with qualitative outcomes and ΔCSI. Results: Forty‐seven patients underwent 197 BTxA injections from June 2012 to June 2022. A statistical proportion of 0.698 (0.599–0.813, p < 0.0001) or 69.8% of injections resulted in subjective improvement. Mean ΔCSI was −2.12 (0.22–4.02, p < 0.05), indicating overall improvement. With and without subjective improvement, estimated ΔCSI was −4.43 and +2.68, respectively (p < 0.0001). VHI‐10 did not change (0.69, p = 0.483). Neither pulmonary disease nor vocal fold hypomobility correlated with subjective improvement or ΔCSI. Dysphagia occurred following 15 (7.6%) injections with no aspiration pneumonia or hospitalization. Conclusions: BTxA injection to the laryngeal adductors may effectively treat cough with limited risk for serious complications. Level of Evidence: 4 Laryngoscope, 134:1749–1756, 2024 [ABSTRACT FROM AUTHOR]

Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell‐derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence‐like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR‐22‐3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence. Dysregulation of the SATB1‐MIR22‐GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence‐like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence‐induced neuroinflammation and reactive gliosis observed in both PD and normal aging. [ABSTRACT FROM AUTHOR]

Background: The immersive and interactive nature of virtual reality (VR) renders it a potential pedagogical approach for nursing education. A bottleneck for exploiting VR advantages has been the complexity of creating new experiences; however, recent advances with VR hardware and software enable novice users to create compelling experiences. Method: A case study describes an undergraduate nursing student with minimal technical skills using off-the-shelf VR software to create a pain management VR experience. Results: Using off-the-shelf hardware and software platforms eliminates the need to work with computer code. The team created a virtual environment and the objects in it through easy manipulation with click-and-drag techniques and by toggling simple settings. Conclusion: The insights gained from this case suggest nurse educators can create simple yet powerful VR experiences themselves, which can greatly enhance existing tools for nursing education. [J Nurs Educ. 2024;63(4):261–264.] [ABSTRACT FROM AUTHOR]

Background: The concordance between radiograph-derived Kellgren–Lawrence (KL) scores for knee osteoarthritis (KOA) and experimental and clinical pain and KOA-related physical function is conflicting. Objectives: We investigate whether the inclusion of dispositional traits reduces variability between KOA radiographic findings, experimental pain, clinical pain, and function in individuals with knee pain. Design: This study is a cross-sectional, secondary analysis of data collected from the UPLOAD-II study. Methods: Adults aged 45–85 years with and without knee pain were enrolled. Data collected included sociodemographics, knee radiographs, experimental pain, clinical pain and function, and trait affect. Vulnerable and protective dispositional traits were classified from combined positive and negative trait affect measures. KL scores were determined from the knee radiographs. Unadjusted and adjusted (age, sex, comorbidities, and body mass index) regression analyses were completed with SAS version 9.4 (Cary, NC, USA). Results: The study included 218 individuals with a mean age of 58 years, 63.6% women, and 48.2% non-Hispanic black adults. Dispositional traits were associated with the experimental pain measures. No association between radiographic KOA and experimental pain was observed. In a combined and adjusted analysis, dispositional traits were predictive of knee punctate pain temporal summation (p = 0.0382). Both dispositional traits and radiographic KOA scores independently and combined were predictive of Graded Chronic Pain Scale pain and function, and Western Ontario and McMaster University pain and function (p s ⩽ 0.01). Improvements in R 2 were noted across all models with the inclusion of dispositional traits. Conclusion: Consideration of dispositional traits reduces the variability between radiographic KOA and pain and function. Non-pathological and associated pain-related psychological factors and dispositional traits might serve as parsimonious proxy tools to improve clinical assessments. Registration: N/A. Plain language summary: Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function Significance • The concordance between radiographic knee osteoarthritis and experimental and clinical pain is conflicting. • Dispositional traits comprise the infrastructure from which an individual interprets and interacts with the environment and are predictive of sensory sensitivity, response to stress, psychopathology, and behavior. • Consideration of dispositional traits improves the congruence between knee osteoarthritis Kellgren-Lawrence scores, experimental pain, and clinical pain. [ABSTRACT FROM AUTHOR]

Background Limited evidence exists on the short- and long-term safety of discontinuing versus continuing chronic opioid therapy (COT) among patients with Alzheimer's disease and related dementias (ADRD). Methods This cohort study was conducted among 162,677 older residents with ADRD and receipt of COT using a 100% Medicare nursing home sample. Discontinuation of COT was defined as no opioid refills for ≥90 days. Primary outcomes were rates of pain-related hospitalisation, pain-related emergency department visit, injury, opioid use disorder (OUD) and opioid overdose (OD) measured by diagnosis codes at quarterly intervals during 1- and 2-year follow-ups. Poisson regression models were fit using generalised estimating equations with inverse probability of treatment weights to model quarterly outcome rates between residents who discontinued versus continued COT. Results The study sample consisted of 218,040 resident episodes with COT; of these episodes, 180,916 residents (83%) continued COT, whereas 37,124 residents (17%) subsequently discontinued COT. Discontinuing (vs. continuing) COT was associated with higher rates of all outcomes in the first quarter, but these associations attenuated over time. The adjusted rates of injury, OUD and OD were 0, 69 and 60% lower at the 1-year follow-up and 11, 81 and 79% lower at the 2-year follow-up, respectively, for residents who discontinued versus continued COT, with no difference in the adjusted rates of pain-related hospitalisations or emergency department visits. Conclusions The rates of adverse outcomes were higher in the first quarter but lower or non-differential at 1-year and 2-year follow-ups between COT discontinuers versus continuers among older residents with ADRD. [ABSTRACT FROM AUTHOR]

In birds, the quadrate connects the mandible and skull, and plays an important role in cranial kinesis. Avian quadrate morphology may therefore be assumed to have been influenced by selective pressures related to feeding ecology, yet large-scale variation in quadrate morphology and its potential relationship with ecology have never been quantitatively investigated. Here, we used geometric morphometrics and phylogenetic comparative methods to quantify morphological variation of the quadrate and its relationship with key ecological features across a wide phylogenetic sample. We found non-significant associations between quadrate shape and feeding ecology across different scales of phylogenetic comparison; indeed, allometry and phylogeny exhibit stronger relationships with quadrate shape than ecological features. We show that similar quadrate shapes are associated with widely varying dietary ecologies (one-to-many mapping), while divergent quadrate shapes are associated with similar dietary ecologies (many-to-one mapping). Moreover, we show that the avian quadrate evolves as an integrated unit and exhibits strong associations with the morphologies of neighbouring bones. Our results collectively illustrate that quadrate shape has evolved jointly with other elements of the avian kinetic system, with the major crown bird lineages exploring alternative quadrate morphologies, highlighting the potential diagnostic value of quadrate morphology in investigations of bird systematics. [ABSTRACT FROM AUTHOR]

Introduction: Twin gestations have greater nutritional demands than singleton gestations, yet dietary intakes of women with twin gestations have not been well described. Methods: In a prospective, multi-site US study of 148 women with dichorionic twin gestations (2012–2013), we examined longitudinal changes in diet across pregnancy. Women completed a food frequency questionnaire during each trimester of pregnancy. We examined changes in means of total energy and energy-adjusted dietary components using linear mixed effects models. Results: Mean energy intake (95% CI) across the three trimesters was 2010 kcal/day (1846, 2175), 2177 kcal/day (2005, 2349), 2253 kcal/day (2056, 2450), respectively (P = 0.01), whereas the Healthy Eating Index-2010 was 63.9 (62.1, 65.6), 64.5 (62.6, 66.3), 63.2 (61.1, 65.3), respectively (P = 0.53). Discussion: Women with twin gestations moderately increased total energy as pregnancy progressed, though dietary composition and quality remained unchanged. These findings highlight aspects of nutritional intake that may need to be improved among women carrying twins. Significance: What is Already Known about the Subject? Twin pregnancies have higher nutritional demands than singleton pregnancies. However, studies with longitudinal dietary data examining if, how, and at what points during gestation women may change their diets to support twin pregnancies have not been available. What this Study adds? Though total energy intake increased statistically significantly from the first to the third trimester, other aspects of diet remained stable across gestation. Similar to singleton pregnancies, diet quality was suboptimal among women pregnant with twins. [ABSTRACT FROM AUTHOR]

Livestock producers need new technologies to maintain the optimal health and well-being of their animals while minimizing the risks of propagating and disseminating pathogenic and antimicrobial-resistant bacteria to humans or other animals. Where possible, these interventions should contribute to the efficiency and profitability of animal production to avoid passing costs on to consumers. In this study, we examined the potential of nitroethane, 3-nitro-1-propionate, ethyl nitroacetate, taurine and L-cysteinesulfinic acid to modulate rumen methane production, a digestive inefficiency that results in the loss of up to 12% of the host's dietary energy intake and a major contributor of methane as a greenhouse gas to the atmosphere. The potential for these compounds to inhibit the foodborne pathogens, Escherichia coli O157:H7 and Salmonella Typhimurium DT104, was also tested. The results from the present study revealed that anaerobically grown O157:H7 and DT104 treated with the methanogenic inhibitor, ethyl nitroacetate, at concentrations of 3 and 9 mM had decreased (p < 0.05) mean specific growth rates of O157:H7 (by 22 to 36%) and of DT104 (by 16 to 26%) when compared to controls (0.823 and 0.886 h−1, respectively). The growth rates of O157:H7 and DT104 were decreased (p < 0.05) from controls by 31 to 73% and by 41 to 78% by α-lipoic acid, which we also found to inhibit in vitro rumen methanogenesis up to 66% (p < 0.05). Ethyl nitroacetate was mainly bacteriostatic, whereas 9 mM α-lipoic acid decreased (p < 0.05) maximal optical densities (measured at 600 nm) of O157:H7 and DT104 by 25 and 42% compared to controls (0.448 and 0.451, respectively). In the present study, the other oxidized nitro and organosulfur compounds were neither antimicrobial nor anti-methanogenic. [ABSTRACT FROM AUTHOR]

We use properties of a cyclic quadrilateral to find the inradius of an arbelos. [ABSTRACT FROM AUTHOR]

Background: Phthalates are ubiquitous anti-androgenic endocrine disrupting chemicals found in personal care products, medications, and many plastics. Studies have shown a racial disparity in phthalates exposure among U.S. women, which may also impact fetal development. Methods: We conducted a prospective cohort study of gestational exposure to a phthalates mixture in a racially-diverse population to determine their association with genital development. Mid-gestation (18–22 weeks) urine was collected from 152 women who self-identified as non-Hispanic Black and 158 women who self-identified as non-Hispanic White in Charleston, South Carolina between 2011 and 2014. We measured eight phthalate monoester metabolites in urine using liquid chromatography tandem-mass spectrometry. Mid-gestational penile dimensions were measured using ultrasound and anogenital distances were measured postnatally. We used Bayesian kernel machine regression to estimate the associations among the mixture of phthalate metabolites and mid-gestation penile dimensions and postnatal anogenital distance measures among singleton male (n = 179) and female (n = 131) infants, adjusted for urinary specific gravity, maternal age, body mass index, education level, cigarette smoking, and gestational age at enrollment or birth weight z-score. Results: We found a stronger association between greater phthalates and decreased anopenile distance among infants born to women who self-identified as Black. Mono (2-ethylhexyl) phthalate (MEHP) was the driving mixture component among Black women, and monobutyl phthalate (MBP) and monoethyl phthalate (MEP) were drivers among White women. We also identified a non-linear association between phthalates and lesser ultrasound penile volume among women who self-identified as Black with monoisobutyl phthalate (MiBP) and MBP being most important. We also found an association between greater phthalates and shorter anoclitoral distance among infants born to women who self-identified as Black, with MEP and monobenzyl phthalate (MBzP) contributing most to this association. Conclusion: Our results suggest a disparity in the association between gestational exposure to a mixture of phthalates and fetal genital development among women who self-identified as Black compared to White. [ABSTRACT FROM AUTHOR]

Background: Suspension syndrome describes a multifactorial cardio-circulatory collapse during passive hanging on a rope or in a harness system in a vertical or near-vertical position. The pathophysiology is still debated controversially. Aims: The International Commission for Mountain Emergency Medicine (ICAR MedCom) performed a scoping review to identify all articles with original epidemiological and medical data to understand the pathophysiology of suspension syndrome and develop updated recommendations for the definition, prevention, and management of suspension syndrome. Methods: A literature search was performed in PubMed, Embase, Web of Science and the Cochrane library. The bibliographies of the eligible articles for this review were additionally screened. Results: The online literature search yielded 210 articles, scanning of the references yielded another 30 articles. Finally, 23 articles were included into this work. Conclusions: Suspension Syndrome is a rare entity. A neurocardiogenic reflex may lead to bradycardia, arterial hypotension, loss of consciousness and cardiac arrest. Concomitant causes, such as pain from being suspended, traumatic injuries and accidental hypothermia may contribute to the development of the Suspension Syndrome. Preventive factors include using a well-fitting sit harness, which does not cause discomfort while being suspended, and activating the muscle pump of the legs. Expediting help to extricate the suspended person is key. In a peri-arrest situation, the person should be positioned supine and standard advanced life support should be initiated immediately. Reversible causes of cardiac arrest caused or aggravated by suspension syndrome, e.g., hyperkalaemia, pulmonary embolism, hypoxia, and hypothermia, should be considered. In the hospital, blood and further exams should assess organ injuries caused by suspension syndrome. [ABSTRACT FROM AUTHOR]

Introduction: The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer‐related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6‐guided opioid prescribing for patients with cancer and reported pilot outcome data. Methods: Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation‐effectiveness clinical trial and randomized to CYP2D6‐genotype‐guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient‐reported pain and symptom scores at baseline and up to 8 weeks, were assessed. Results: Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3–37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6‐genotype‐guided recommendations to change therapy (n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow‐up questionnaires (n = 48), there was no difference in change in mean composite pain score (−1.01 ± 2.1 vs. −0.41 ± 2.5; p = 0.19) or symptom severity at last follow‐up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm (n = 26) and genotype‐guided arm (n = 22), respectively. Conclusion: Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype‐guided recommendations was low, impacting assessment of pain‐related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success. [ABSTRACT FROM AUTHOR]

Background and Objectives Pain treatments and their efficacy have been studied extensively. Yet surprisingly little is known about the types of treatments, and combinations of treatments, that community-dwelling adults use to manage pain, as well as how treatment types are associated with individual characteristics and national-level context. To fill this gap, we evaluated self-reported pain treatment types among community-dwelling adults in the United States and Canada. We also assessed how treatment types correlate with individuals' pain levels, sociodemographic characteristics, and country of residence, and identified unique clusters of adults in terms of treatment combinations. Research Design and Methods We used the 2020 "Recovery and Resilience" United States–Canada general online survey with 2 041 U.S. and 2 072 Canadian community-dwelling adults. Respondents selected up to 10 pain treatment options including medication, physical therapy, exercise, etc. and an open-ended item was available for self-report of any additional treatments. Data were analyzed using descriptive, regression-based, and latent class analyses. Results Over-the-counter (OTC) medication was reported most frequently (by 55% of respondents, 95% CI 53%–56%), followed by "just living with pain" (41%, 95% CI 40%–43%) and exercise (40%, 95% CI 38%–41%). The modal response (29%) to the open-ended item was cannabis use. Pain was the most salient correlate, predicting a greater frequency of all pain treatments. Country differences were generally small; a notable exception was alcohol use, which was reported twice as often among U.S. versus Canadian adults. Individuals were grouped into 5 distinct clusters: 2 groups relied predominantly on medication (prescription or OTC), another favored exercise and other self-care approaches, one included adults "just living with" pain, and the cluster with the highest pain levels employed all modalities heavily. Discussion and Implications Our findings provide new insights into recent pain treatment strategies among North American adults and identify population subgroups with potentially unmet need for more adaptive and effective pain management. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate sensory and psychological differences in individuals with thumb carpometacarpal (CMC) and/or knee osteoarthritis (OA) pain. This secondary analysis focuses on comparing the effects of OA at large and small joints in community-dwelling adults.Patients and Methods: A total of 434 individuals were recruited from communities in Gainesville, FL and Birmingham, AL. Each participant completed health and clinical history questionnaires, quantitative sensory testing, and physical functional tests. Participants were divided into four groups based on their pain ("CMC pain" (n = 33), "knee pain" (n = 71), "CMC + knee pain" (n = 81), and "pain-free" controls (n = 60)). ANCOVAs were performed to identify significant differences in experimental pain and psychological variables across groups.Results: The "CMC + knee pain" group had lower pressure pain thresholds (lateral knee site, p < 0.01) and higher temporal summation of mechanical pain (knee, p < 0.01) when compared to "CMC pain" and "pain-free" groups. The "knee pain" group had lower heat pain tolerance at the forearm site (p = 0.02) and higher mechanical pain (p < 0.01) at both tested sites in comparison to the "CMC pain" group. Lastly, the "CMC + knee pain" group had the highest self-reported pain (p < 0.01) and disability (p < 0.01) compared to all other groups.Conclusion: Results suggest knee OA compounded with CMC OA increases disease impact and decreases emotional health compared to OA at either the CMC or knee joint alone. Results also support a relationship between the number of painful joints and enhanced widespread pain sensitivity. Measuring pain at sites other than the primary OA location is important and could contribute to more holistic treatment and prevention of OA progression. [ABSTRACT FROM AUTHOR]

Concern exists that the continued use of antibiotics in animal feeds may lead to an increased prevalence of resistant bacteria within the host animal's gastrointestinal tract. To evaluate the effect of chlortetracycline on the persistence of Salmonella enterica serotype Typhimurium within a diverse population of porcine cecal bacteria, we cultured a mixed population of cecal bacteria without or with added chlortetracycline. When grown at a 24 h vessel turnover rate, chlortetracycline-susceptible S. Typhimurium exhibited more than 2.5 times faster (p < 0.05) disappearance rates than theoretically expected (0.301 log10 colony-forming unit/mL per day) but did not differ whether treated or not with 55 mg of chlortetracycline/L. Chlortetracycline-resistant S. Typhimurium was not recovered from any of these cultures. When the mixed cultures were inoculated with a chlortetracycline-resistant S. Typhimurium, rates of disappearance were nearly two times slower (p < 0.05) than those observed earlier with chlortetracycline-susceptible S. Typhimurium, and cultures persisted at >2 log10 colony-forming units/mL for up to 14 days of treatment with 110 mg of chlortetracycline/L. Under the conditions of this study, chlortetracycline-resistant S. Typhimurium was competitively enabled to persist longer within the mixed populations of porcine gut bacteria than chlortetracycline-susceptible S. Typhimurium, regardless of the presence or absence of added chlortetracycline. [ABSTRACT FROM AUTHOR]

Infection with the foodborne pathogen Campylobacter is the leading bacterial cause of human foodborne illness in the United States. The objectives of this experiment were to test the hypothesis that mixed microbial populations from the bovine rumen may be better at excluding Campylobacter than populations from freshly voided feces and to explore potential reasons as to why the rumen may be a less favorable environment for Campylobacter than feces. In an initial experiment, C. jejuni cultures inoculated without or with freshly collected bovine rumen fluid, bovine feces or their combination were cultured micro-aerobically for 48 h. Results revealed that C. jejuni grew at similar growth rates during the first 6 h of incubation regardless of whether inoculated with the rumen or fecal contents, with rates ranging from 0.178 to 0.222 h−1. However, C. jejuni counts (log10 colony-forming units/mL) at the end of the 48 h incubation were lowest in cultures inoculated with rumen fluid (5.73 log10 CFUs/mL), intermediate in cultures inoculated with feces or both feces and rumen fluid (7.16 and 6.36 log10 CFUs/mL) and highest in pure culture controls that had not been inoculated with the rumen or fecal contents (8.32 log10 CFUs/mL). In follow-up experiments intended to examine the potential effects of hydrogen and hydrogen-consuming methanogens on C. jejuni, freshly collected bovine feces, suspended in anaerobic buffer, were incubated anaerobically under either a 100% carbon dioxide or 50:50 carbon dioxide/hydrogen gas mix. While C. jejuni viability decreased <1 log10 CFUs/mL during incubation of the fecal suspensions, this did not differ whether under low or high hydrogen accumulations or whether the suspensions were treated without or with the mechanistically distinct methanogen inhibitors, 5 mM nitrate, 0.05 mM 2-bromosulfonate or 0.001 mM monensin. These results suggest that little if any competition between C. jejuni and hydrogen-consuming methanogens exists in the bovine intestine based on fecal incubations. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant chemotherapy (NAC) for breast cancer has the advantage of determining in vivo response to treatment, enabling more conservative surgery, and facilitating the understanding of tumor biology. Pathologic complete response (pCR) after NAC is a predictor of improved overall survival. However, some patients demonstrate a discordant response to NAC between the breast and axillary nodes. This study was designed to identify factors that correlate to achieving a breast pCR without an axillary node pCR following NAC and explore the potential clinical implications. Methods: The National Cancer Database was used to identify patients diagnosed with clinical T1-4, N1-3 breast cancer between 2004 and 2017. Patients underwent NAC followed surgical resection of the breast cancer and axillary node surgery. Multivariable analyses were used to identify clinical and pathologic factors associated with discordant pathologic response. Results: In total, 13,934 patients met the inclusion criteria. Of these, 4292 (30.8%) patients demonstrated a breast pCR without a corresponding axillary pCR on final pathology. After adjusting for covariates, factors associated with higher discordance between axillary response in our cohort of breast pCR patients included older age (≥ 54), treatment at a community facility, T1 tumors, HR-positive, HER2 negative, low-grade tumors, and cN2/3 disease. Conclusions: Discordance between breast and axillary pCR is not infrequent and may be related to a number of patient-related factors and tumor characteristics impacting nodal response to NAC. Further investigation into differing responses to NAC is warranted to better understand the mechanism of this phenomenon and to determine how these findings may influence treatment. [ABSTRACT FROM AUTHOR]

Objectives: To describe swallowing and feeding‐tube outcomes in patients with high‐risk oropharyngeal cancer treated with trimodality therapy (TMT), including transoral robotic surgery (TORS) and adjuvant chemoradiotherapy. Methods: A chart review was conducted on patients with HPV+ OPSCC receiving TMT with TORS at an academic medical center from March 2010 to March 2021. Data collected included demographics, treatment, feeding tube placement, functional oral intake scale (FOIS) scores, and swallowing‐language pathology (SLP) evaluations. Results: A total of 255 patients met selection criteria (mean age 61 years, 88% male). Following intraoperative nasogastric tube (NG) placement, 31% remained NG tube dependent after 3 weeks. A gastrostomy tube was placed in 19% of patients, and at 1 year after end‐of‐treatment (EOT), 3.5% overall remained tube‐dependent. Mean FOIS scores were 6.9 (SD = 0.3) at pre‐operative visit, 2.6 (1.8) at first post‐operative visit, and 5.5 (1.5) after EOT. In the subset of patients with follow‐up longer than 2 years (n = 118), the mean FOIS was 6.1 (SD = 1.3) at most recent visit. Clinical signs of aspiration/penetration were suspected on SLP evaluation in 18% of patients. These patients were subsequently evaluated with fiberoptic endoscopic evaluation of swallowing (FEES) and/or barium swallow study, which confirmed signs of aspiration in 2.7% of patients overall. Delayed NG tube removal after 3 weeks was predictive of (1) gastrostomy tube requirement and (2) clinical signs of aspiration on an SLP visit after EOT. Conclusions: Favorable functional and feeding‐tube outcomes are demonstrated in patients with HPV‐associated OPSCC undergoing TMT. In this single‐institution study, we found low rates of long‐term feeding tube dependence and high median FOIS following treatment. Review of routine SLP visits provides a detailed and easily accessible means for assessing swallowing function in this cohort. Level of Evidence: 4 Laryngoscope, 133:3013–3020, 2023 [ABSTRACT FROM AUTHOR]

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid‐related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid‐induced Respiratory Depression (CIP‐RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects. This was an observational study of 44 participants discharged home from the emergency department with an opioid prescription for acute pain and followed for 30 days. We found pain interference may predict opioid‐related falls or serious adverse effects within older, opioid‐treated patients. If validated, pain interference may prove to be a beneficial marker for risk stratification of older adults initiated on opioids for acute pain. [ABSTRACT FROM AUTHOR]

There is a high prevalence of chronic pain among middle-aged and older adults in the United States. Chronic life stressors have been shown to have detrimental consequences for myriad health conditions, including chronic pain. However, there is limited evidence on the types of chronic life stressors that affect middle-aged and older adults and how these stressors influence the chronic pain burden in this population. Moreover, the interaction between chronic life stressors and racial/ethnic identity remains poorly understood as it relates to chronic pain. The current analysis used the 2018 Health and Retirement Study to investigate relationships between chronic life stressors and odds to experience any chronic pain and high-impact chronic pain. Chronic life stressors were characterized, overall and by racial/ethnic identity, and the main and interaction effects were calculated to evaluate relationships between chronic life stressors, racial/ethnic identity, and odds of experiencing any chronic pain and high-impact chronic pain. Results indicate that in 2018, the most common chronic life stressor among middle-aged and older adults was dealing with their own health problems (68%), followed by dealing with the physical or emotional issues affecting a spouse or child (46%). Adjusted analyses showed that a higher total of chronic life stressors increased the odds of middle-aged and older adults experiencing any chronic pain and high-impact chronic pain. There were no significant interactions between the overall chronic life stress burden and racial/ethnic identity as a predictor of odds to experience any chronic pain or high-impact chronic pain, but significant interaction effects were found related to specific chronic life stressors. Findings underscore the significant impact of chronic life stressors on the chronic pain burden among middle-aged and older adults in the United States, which cut across racial/ethnic identity. [ABSTRACT FROM AUTHOR]

Drawing on research in mathematics and science education that has supported student higher-level thinking in K-12 classrooms, we sought to classify the ways of thinking and reasoning supported by robotics coding tasks. As part of a larger project, we examined coding tasks implemented in elementary school classrooms and analyzed ways of thinking and reasoning about coding supported by these tasks. From this analysis, we developed a framework for analyzing the cognitive demand of coding tasks that can be used to support researchers, curriculum developers, and teachers in supporting students' higher levels of thinking as they learn coding. [ABSTRACT FROM AUTHOR]