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The extracellular matrix is suggested to play a role in neurogenesis, but it is unclear what role integrin signalling may play in the developing neuroepithelium. Here, in chick, Long et al. show that expression of constitutively active integrin beta-1 enhances neurogenesis via a novel Wnt7 and decorin pathway.

Abstract Introduction The number of older adults who are cancer survivors is rapidly growing. Evidence is needed to inform interventions to support successful aging among older adults (including older adult cancer survivors). Active engagement with life, that is, spending time with family and/or close friends, may be related to health outcomes, but this concept remains understudied. Methods We used survey data to assess active engagement among older adults (ages 50 + years) from seven mid-Atlantic US states (n = 2,914), and geocoded their residence to collect collected measures of community availability of social interaction. Outcomes were physical and mental health-related quality of life (HRQoL), assessed with the SF-12. We used multivariable, multilevel linear regression to evaluate relationships between social interactions (i.e., “active engagement with life,” or visiting with family and/or friends at least once per week and having at least three close friends, and community-level availability, measured with census tract-level park land and walkability and with county-level availability of social associations) and HRQoL. Finally, we explored differences in these relationships by recent cancer survivorship. Results Overall, 1,518 (52.3%) participants were actively engaged. Active engagement was associated with higher physical HRQoL (estimate = 0.94, standard error [SE] = 0.46, p = .04) and mental HRQoL (estimate = 2.10, SE = 0.46, p

This study investigated how prospective elementary teachers view themselves as learners of mathematics and science during their last year in a teacher preparation program at an American university. Using drawing and reflections as the method for collecting data, prospective teachers were prompted to draw themselves and reflect on learning mathematics and draw themselves and reflect on learning science prior to and after their mathematics and science methods courses. Drawings (n = 147) were coded according to the presence or absence of several themes including physical objects, teachers, students, and environment. The drawings and reflections indicated that the experience of participating in mathematics and science methods courses taught from a social constructivist perspective positively impacted prospective teachers' conceptions of themselves as learners and in ways consistent with current research-based pedagogies. The research study described here proposes that prospective teachers' learning experiences in mathematics and science methods classes might impact how they will teach mathematics and science in their future elementary classrooms.

ObjectiveTo examine the association of older adults’ loneliness, life satisfaction, and other psychological stressors and resources with oral health status.MethodsThis study merged 2018 data from the Health and Retirement Study (HRS) CORE survey with the HRS-Dental Module, and Psychosocial and Lifestyle Questionnaire–Panel A “Leave Behind” surveys (HRS-LB)(N = 418). Dental Module outcomes of interest were self-rated oral health status (SROH), and oral health-related quality of life (OHQOL). Older adults reported on loneliness, life satisfaction, perceived age, social status, control, mastery, and chronic stressors. Three distinct profiles based on the distribution of loneliness and life satisfaction were previously identified in the combined HRS and HRS-LB study population (N = 4,703) using latent class analysis (LCA). Class A:“Not Lonely/Satisfied” adults had the fewest psychosocial risk factors and most resources; Class C:“Lonely/Unsatisfied” adults exhibited the opposite profile (most risk factors, fewest resources); Class B:“Lonely/Satisfied” adults exhibited loneliness with favorable life satisfaction. Regression models examined associations between LCA classes and fair/poor SROH and the OHQOL scale score and individual items, after adjusting for socio-demographics.ResultsAbout 13% of older adults experienced loneliness, and about 16% reported low life satisfaction. About one-quarter (28%) of older adults reported fair/poor SROH, and they experienced more psychosocial risk factors than their counterparts with better oral health status. Nearly half the older adults were categorized in Class A:“Not Lonely/Satisfied” (n = 201), and about one-quarter each in Class B:“Lonely/Satisfied” (n = 103) and Class C:“Lonely/Unsatisfied” (n = 112). In fully adjusted models, Class B older adults had 1.81 (1.11–2.96) times greater odds of fair/poor SROH, and Class C had 4.64 (2.78–7.73) times greater odds of fair/poor SROH than Class A. Fully adjusted linear regression model results indicated a gradient by LCA class. OHQOL varied; Class A older adults had the best (lowest) OHQOL score (mean = 8.22, 4.37–12.10), Class B scored in the middle (mean = 12.00, 7.61–16.50), while Class C had the worst (highest) OHQOL score (mean = 16.20, 11.80–20.60).ConclusionLoneliness, as a defining characteristic distinguishing three latent classes of older adults, was associated with more risk factors and poorer oral health outcomes. Loneliness, life satisfaction, perceived age, social status, control, mastery, and chronic stressors vary widely for older adults and matter for oral health and OHQOL.

Objectives: Cervical cancer screening rates have stagnated, but self-sampling modalities have the potential to increase uptake. This study compares the test characteristics of self-sampled high-risk human papillomavirus (hrHPV) tests with clinician-collected hrHPV tests in average-risk (i.e., undergoing routine screening) and high-risk patients (i.e., receiving follow-up after abnormal screening results). Methods: In this cross-sectional study, a relatively small cohort of average-risk (n?=?35) and high-risk (n?=?12) participants completed both clinician-collected and self-sampled hrHPV testing, along with a brief phone survey. We assessed hrHPV positivity, concordance, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity across both methods (for types 16, 18, or other hrHPV). We also explored the relationship between test concordance and sociodemographic/behavioral factors. Results: Among average-risk participants, hrHPV positivity was 6% for both test methods (i.e., hrHPV-positive cases: n?=?2), resulting in reported concordance, PPV, NPV, sensitivity, and specificity of 100%. Among high-risk participants, hrHPV positivity was 100% for clinician-collected tests but only 67% for self-sampled tests, showing varied concordance and sensitivity. Concordance was not associated with sociodemographic or behavioral factors. Conclusions: Self-sampled hrHPV testing demonstrated high accuracy for average-risk patients in this exploratory study. However, its performance was less consistent in high-risk patients who had already received an abnormal screening result, which could be attributed to spontaneous viral clearance over time. The limited number of participants, particularly HPV-positive cases, suggests caution in interpreting these results. Further research with larger cohorts is necessary to validate these findings and to explore the integration of self-sampled hrHPV testing into routine clinical care, particularly for patients with a history of cervical abnormalities. Clinical Trial Registration: NCT04591977, NCT04585243.

Introduction: To characterize the impact of rural patients’ travel time to obtain healthcare on their reported utilization of preventive healthcare services and personal health outcomes. Methods: Online survey data from rural adults ages 50+ years living in the Northeastern United States were collected from February to August 2021. Study measures included self-reported travel time to obtain healthcare, use of preventive healthcare, and health outcomes. The associations between travel time with use of preventive care and health outcomes were assessed using linear, Poisson, and logistic regression analyses controlling for demographic variables. Results: Our study population included 1052 rural adults, with a mean travel time of 18.5 min (range: 0-60). Travel time was greater for racial/ethnic minority participants and for higher-income participants (both P

Background: Chin-on-chest deformity is a rare and severely disabling condition characterized by kyphotic deformity in the cervicothoracic spine. To treat this deformity, various osteotomy techniques were described. Methods: A comprehensive literature search of biomedical databases including MEDLINE (via PubMed), Scopus (via Elsevier), Embase (via Elsevier), and Cochrane Library in English from 1/1/1990 to 3/31/2022 was conducted using a combination of text and Medical Subject Headings (MeSH). Results: The final analysis included 16 studies. All the studies were assigned a level of evidence of four. Except for two articles, all of the articles were non-comparative studies. A total of 288 patients were included in this review. Of the 288 patients, 107 underwent posterior column extension osteotomy (PCEO), 108 underwent pedicle subtraction osteotomy (PSO), and 33 underwent vertebral column resection osteotomy (VCRO). The most common osteotomy level in fifteen of the studies was C7/T1. The studies included in this review described several techniques for cervical sagittal balance correction. The range of preoperative and postoperative visual analogue scale (VAS) scores was 5.5–8.6 to 1.7–4.91, respectively. The range of preoperative and postoperative neck disability index (NDI) was 34.2–65.4 to 22.1–51.3, respectively. The most common complications were upper extremity paresthesia and hand numbness through the C8 dermatome distribution. Conclusions: Corrective osteotomies provide satisfactory results in patients with chin-on-chest deformity; however, the quality of the included studies limits the evidence.

Abstract Purpose Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity. Methods A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers. Results In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery. Discussion This study provides important insights into patients’ views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients.

There are a wide variety of interbody devices available for use in transforaminal lumbar interbody fusion (TLIF). While traditionally these interbodies are bullet-shaped, crescent-shaped cages have become increasingly common. There is a paucity of literature comparing the effect of cage geometry with substratification for surgical approach (minimally invasive (MIS) vs. open). The aim of this study was to determine the effect of implant geometry, positioning, and surgical approach on the correction of different spinal alignment parameters in patients undergoing TLIF. A retrospective chart and imaging review was performed on 103 patients with a total of 131 instrumented segments performed by a single surgeon. Preoperative, initial postoperative, and final postoperative standing lateral lumbar radiographs were evaluated for lumbar lordosis (LL), segmental lordosis (SL), anterior disc height (ADH), and posterior disc height (PDH). Anterior-posterior implant positioning was recorded for initial and final postoperative radiographs. These measurements were compared among four groups: open bullet (OB), MIS bullet (MB), open crescent (OC), and MIS crescent (MC). SL increased in all groups by a mean of 2.9° at initial imaging and 2.2° at final imaging. The OC group had greater initial improvement in SL compared to the MB group (p = 0.02), though this effect was lost at final follow-up (p = 0.11). The OB and OC groups conferred greater initial improvement in ADH (p = 0.02; p = 0.04), while the OC group had greater final improvement in ADH compared to the MB and MC groups (p = 0.01; p = 0.01). The OC group had less initial improvement in PDH compared with the other groups (p = 0.03, p = 0.02, p < 0.01). The MB group provided greater final improvement in PDH compared with the MC and OC groups (p = 0.04, p = 0.01). Cage geometry, surgical approach, and implant position all demonstrated a statistically significant but clinically minor impact on segmental alignment for TLIF procedures.

Human enteroviruses are the most common human pathogen with over 300 distinct genotypes. Previous work with poliovirus has suggested that it is possible to generate antibody responses in humans and animals that can recognize members of multiple enterovirus species. However, cross protective immunity across multiple enteroviruses is not observed epidemiologically in humans. Here we investigated whether immunization of mice or baboons with inactivated poliovirus or enterovirus virus-like-particles (VLPs) vaccines generates antibody responses that can recognize enterovirus D68 or A71. We found that mice only generated antibodies specific for the antigen they were immunized with, and repeated immunization failed to generate cross-reactive antibody responses as measured by both ELISA and neutralization assay. Immunization of baboons with IPV failed to generate neutralizing antibody responses against enterovirus D68 or A71. These results suggest that a multivalent approach to enterovirus vaccination is necessary to protect against enterovirus disease in vulnerable populations.

Introduction: Rural adults are less likely to receive cancer screening than urban adults, likely due to systematic differences in community- and individual-level factors. The purpose of this study was to analyze the relative contributions of rurality, travel time, medical mistrust, and cancer fatalism in explaining uptake of clinical cancer prevention services. Methods: We conducted a secondary data analysis of 2019–2020 survey data from women, ages 45–65, in rural and urban counties in central Pennsylvania, examining rurality, travel time to a primary care provider, medical mistrust, and cancer fatalism, as well as uptake of guideline-recommended colorectal cancer screening, cervical cancer screening, and preventive check-up. Final models used multivariable logistic regression to assess the relationships among study variables, controlling for participant demographics. Results: Among 474 participants, 48.9 % resided in rural counties. Most participants had received clinical cancer prevention services (colorectal cancer screening: 55.4 %; cervical cancer screening: 82.8 %; preventive check-up in the last year: 75.4 %). Uptake of services was less common among participants with higher medical mistrust (colorectal cancer screening: adjusted odds ratio [aOR] = 0.87, 95 % confidence interval [CI] = 0.76–1.00; cervical cancer screening: aOR = 0.79, 95 % CI = 0.63–1.00; last-year check-up: aOR = 0.74, 95 % CI = 0.63–0.88). Conclusions: Patient attitudes, particularly medical mistrust, may contribute to rural/urban disparities in clinical cancer prevention among women. Community- and individual-level interventions are needed to improve cancer outcomes in rural areas.

Abstract Background Healthcare costs in the U.S. are high and variable, which can hinder access and impact health outcomes across communities. This study examined hospital‐ and county‐level characteristics to identify factors that explain geographic variation in prices for four cancer‐related procedures. Methods Data sources included Turquoise Health, which compiles publicly‐available price data from U.S. hospitals. We examined list prices for four procedures: abdominal ultrasound, diagnostic colonoscopy, brain MRI, and pelvis CT scan, which we linked to characteristics of hospitals (e.g., number of beds) and counties (e.g., metropolitan status). We used multilevel linear regression models to assess multivariable relationships between prices and hospital‐ and county‐level characteristics. Supplementary analyses repeated these models using procedures prices for commercial insurance plans. Results For each procedure, list prices varied across counties (intraclass correlation: abdominal ultrasound = 23.2%; colonoscopy = 17.1%; brain MRI = 37.2%; pelvis CT = 50.9%). List prices for each procedure were associated with hospital ownership (all p

Risk-stratified follow-up for endometrial cancer (EC) is being introduced in many cancer centres; however, there appears to be diversity in the structure and availability of schemes across the UK. This study aimed to investigate clinicians’ and clinical specialist nurses’ (CNS) experiences of follow-up schemes for EC, including patient-initiated follow-up (PIFU), telephone follow-up (TFU) and clinician-led hospital follow-up (HFU). A mixed-methods study was conducted, consisting of an online questionnaire to CNSs, an audience survey of participants attending a national “Personalising Endometrial Cancer Follow-up” educational meeting, and qualitative semi-structured telephone interviews with clinicians involved in the follow-up of EC. Thematic analysis identified three main themes to describe clinicians’ views: appropriate patient selection; changing from HFU to PIFU schemes; and the future of EC follow-up schemes. Many participants reported that the COVID-19 pandemic impacted EC follow-up by accelerating the transition to PIFU/TFU. Overall, there was increasing support for non-HFU schemes for patients who have completed primary treatment of EC; however, barriers were identified for non-English-speaking patients and those who had communication challenges. Given the good long-term outcome associated with EC, greater focus is needed to develop resources to support patients post-treatment and individualise follow-up according to patients’ personal needs and preferences.

Abstract Background Cancer screening is suboptimal in rural areas, and interventions are needed to improve uptake. The Consolidated Framework for Implementation Research (CFIR) is a widely-used implementation science framework to optimize planning and delivery of evidence-based interventions, which may be particularly useful for screening promotion in rural areas. We examined the discussion of CFIR-defined domains and constructs in programs to improve cancer screening in rural areas. Methods We conducted a systematic search of research databases (e.g., Medline, CINAHL) to identify studies (published through November 2022) of cancer screening promotion programs delivered in rural areas in the United States. We identified 166 records, and 15 studies were included. Next, two reviewers used a standardized abstraction tool to conduct a critical scoping review of CFIR constructs in rural cancer screening promotion programs. Results Each study reported at least some CFIR domains and constructs, but studies varied in how they were reported. Broadly, constructs from the domains of Process, Intervention, and Outer setting were commonly reported, but constructs from the domains of Inner setting and Individuals were less commonly reported. The most common constructs were planning (100% of studies reporting), followed by adaptability, cosmopolitanism, and reflecting and evaluating (86.7% for each). No studies reported tension for change, self-efficacy, or opinion leader. Conclusions Leveraging CFIR in the planning and delivery of cancer screening promotion programs in rural areas can improve program implementation. Additional studies are needed to evaluate the impact of underutilized CFIR domains, i.e., Inner setting and Individuals, on cancer screening programs.

Abstract Phenological diversity in food resources prolongs foraging opportunities for consumers and buffers them against environmental disturbances. Such diversity is particularly important in forage fish such as Pacific herring (Clupea pallasii), which are foundational to coastal food webs and fisheries. While the importance of phenological diversity is well-known from contemporary studies, the extent to which different populations contribute to fisheries over long time scales is mostly unknown. In this study, we investigated the relative contributions of genetically and phenologically distinct herring populations to Indigenous Peoples’ food systems over multiple centuries, using ancient DNA extracted from archaeological herring bones. These bones were excavated from two Coast Salish archaeological sites (Burton Acres Shell Midden and Bay Street Shell Midden) in the Puget Sound region, USA. Using genetic stock identification from seven nuclear DNA markers, we showed that catches at the two sites in central Puget Sound were dominated by January–February and March–April spawners, which are the contemporary spawning groups in the vicinity of the sites. However, May spawners were detected in the older Burton Acres assemblage (dated to 910–685 cal BP), and a mixed stock analysis indicated that catches at this site consisted of multiple populations. These results suggest that Coast Salish ancestors used a portfolio of herring populations and benefited from the ecological resource wave created by different spawning groups of herring. This study of ancient DNA allowed us to glimpse into Indigenous traditional food and management systems, and it enabled us to investigate long-term patterns of biodiversity in an ecologically important forage fish species.

Millions of people worldwide suffer from low back pain and disability associated with intervertebral disc (IVD) degeneration. IVD degeneration is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and the annulus fibrosus (AF) fissures form, which often results in intervertebral disc herniation or disc space collapse and related clinical symptoms. Currently available options for treating intervertebral disc degeneration are symptoms control with therapy modalities, and/or medication, and/or surgical resection of the IVD with or without spinal fusion. As such, there is an urgent clinical demand for more effective disease-modifying treatments for this ubiquitous disorder, rather than the current paradigms focused only on symptom control. Hydrogels are unique biomaterials that have a variety of distinctive qualities, including (but not limited to) biocompatibility, highly adjustable mechanical characteristics, and most importantly, the capacity to absorb and retain water in a manner like that of native human nucleus pulposus tissue. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. In this review, we summarize the latest findings and developments in the application of hydrogel technology for the repair and regeneration of intervertebral discs.

In an attempt to isolate new probiotic bacteria, two Gram-variable, spore-forming, rod-shaped aerobic bacteria designated as strain A4 and A15 were isolated from the feces of Canada geese (Branta canadensis). Strain A4 was able to grow in high salt levels and exhibited lipase activity, while A15 did not propagate under these conditions. Both were positive for starch hydrolysis, and they inhibited the growth of Staphylococcus aureus. The strains of the 16S rRNA sequence shared only 94% similarity to previously identified Sporosarcina spp. The ANI (78.08%) and AAI (82.35%) between the two strains were less than the species threshold. Searches for the most similar genomes using the Mash/Minhash algorithm showed the nearest genome to strain A4 and A15 as Sporosarcina sp. P13 (distance of 21%) and S. newyorkensis (distance of 17%), respectively. Sporosarcina spp. strains A4 and A15 contain urease genes, and a fibronectin-binding protein gene indicates that these bacteria may bind to eukaryotic cells in host gastrointestinal tracts. Phenotypic and phylogenetic data, along with low dDDH, ANI, and AAI values for strains A4 and A15, indicate these bacteria are two novel isolates of the Sporosarcina genus: Sporosarcina sp. A4 sp. nov., type strain as Sporosarcina cascadiensis and Sporosarcina sp. A15 sp. nov., type strain Sporosarcina obsidiansis.

Introduction The rapid evolution of minimally invasive surgery has had a positive impact on patient outcomes; however, it is reported to be associated with work-related musculoskeletal symptoms (WMS) in surgeons. Currently there is no objective measure to monitor the physical and psychological impact of performing a live surgical procedure on the surgeon.Methods and analysis A single-arm observational study with the aim of developing a validated assessment tool to quantify the impact of surgery (open/laparoscopic/robotic-assisted) on the surgeon. Development and validation cohorts of major surgical cases of varying levels of complexity performed by consultant gynaecological and colorectal surgeons will be recruited. Recruited surgeons wear three Xsens DOT monitors (muscle activity) and an Actiheart monitor (heart rate). Salivary cortisol levels will be taken and questionnaires (WMS and State-Trait Anxiety Inventory) completed by the participants preoperatively and postoperatively. All the measures will be incorporated to produce a single score that will be called the 'S-IMPACT' score.Ethics and dissemination Ethical approval for this study has been granted by the East Midlands Leicester Central Research Ethics Committee REC ref 21/EM/0174. Results will be disseminated to the academic community through conference presentations and peer-reviewed journal publications. The S-IMPACT score developed within this study will be taken forward for use in definitive multicentre prospective randomised control trials.

(1) Background: Since first approved by the FDA, on-label and off-label usage of recombinant human bone morphogenetic protein 2 (rhBMP2) for spinal fusion surgeries has become widespread. While many studies have investigated the safety and efficacy of its use, as well as its economic impact, few have looked at the current trends in its on- and off-label use. The goal of this study is to evaluate the current trends of on- and off-label rhBMP2 use for spinal fusion surgery. (2) Methods: A deidentified survey was created and electronically distributed to members of two international spine societies. Surgeons were asked to report their demographic information, surgical experience, and current usage of rhBMP2. They were then presented with five spinal fusion procedures and asked to report if they use rhBMP2 for these indications in their current practice. Responses were stratified between rhBMP2 users vs. non-users and on-label vs. off-label use. Data were analyzed using chi-square with Fisher’s exact test for categorical data. (3) Results: A total of 146 respondents completed the survey with a response rate of 20.5%. There was no difference in overall rhBMP2 usage based on specialty, experience, or number of cases per year. Fellowship-trained surgeons and those who practice in the United States were more likely to use rhBMP2. Surgeons who were trained in the Southeast and Midwest regions reported the highest usage rates. rhBMP2 use was more common among fellowship-trained and US surgeons for ALIFs; non-US surgeons for multilevel anterior cervical discectomy and fusions; and fellowship-trained and orthopedic spine surgeons for lateral lumbar interbody fusions. Non-US surgeons were more likely to use rhBMP2 for off-label indications compared to surgeons from the US. (4) Conclusions: While various demographics of surgeons report different rates of rhBMP2 use, off-label use remains relatively commonplace amongst practicing spine surgeons.

Background Self-sampling for colorectal and cervical cancer screening can address the observed geographic disparities in cancer burden by alleviating barriers to screening participation, such as access to primary care. This preliminary study examines qualitative themes regarding cervical and colorectal cancer self-sampling screening tools among federally qualified health center clinical and administrative staff in underserved communities. Methods In-depth interviews were conducted with clinical or administrative employees (≥18 years of age) from FQHCs in rural and racially segregated counties in Pennsylvania. Data were managed and analyzed using QSR NVivo 12. Content analysis was used to identify themes about attitudes towards self-sampling for cancer screening. Results Eight interviews were conducted. Average participant age was 42 years old and 88% of participants were female. Participants indicated that a shared advantage for both colorectal and cervical cancer self-sampling tests was their potential to increase screening rates by simplifying the screening process and offering an alternative to those who decline traditional screening. A shared disadvantage to self-sampling was the potential for inaccurate sample collection, either through the test itself or the sample collection by the patient. Conclusions Self-sampling offers a promising solution to increase cervical and colorectal cancer screening in rural and racially segregated communities. This study’s findings can guide future research and interventions which integrate self-sampling screening into routine primary care practice.

Abstract Background Area-level measures are often used to approximate socioeconomic status (SES) when individual-level data are not available. However, no national studies have examined the validity of these measures in approximating individual-level SES. Methods Data came from ~ 3,471,000 participants in the Mortality Disparities in American Communities study, which links data from 2008 American Community Survey to National Death Index (through 2015). We calculated correlations, specificity, sensitivity, and odds ratios to summarize the concordance between individual-, census tract-, and county-level SES indicators (e.g., household income, college degree, unemployment). We estimated the association between each SES measure and mortality to illustrate the implications of misclassification for estimates of the SES-mortality association. Results Participants with high individual-level SES were more likely than other participants to live in high-SES areas. For example, individuals with high household incomes were more likely to live in census tracts (r = 0.232; odds ratio [OR] = 2.284) or counties (r = 0.157; OR = 1.325) whose median household income was above the US median. Across indicators, mortality was higher among low-SES groups (all p < .0001). Compared to county-level, census tract-level measures more closely approximated individual-level associations with mortality. Conclusions Moderate agreement emerged among binary indicators of SES across individual, census tract, and county levels, with increased precision for census tract compared to county measures when approximating individual-level values. When area level measures were used as proxies for individual SES, the SES-mortality associations were systematically underestimated. Studies using area-level SES proxies should use caution when selecting, analyzing, and interpreting associations with health outcomes.

Damage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In this proof-of-concept study, we developed a nanoparticle (NP) delivery system to efficiently deliver high- and low-solubility drug molecules. Nanoparticles of cellulose acetate and polycaprolactone-polyethylene glycol conjugated with 1-oxo-1H-pyrido [2,1-b][1,3]benzoxazole-3-carboxylic acid (PBC), a novel fluorescent dye, were prepared by the oil-in-water emulsion. Two drugs, a water insoluble indomethacin (IND) and a water soluble 4-aminopyridine (4-AP), were used to study their release patterns. Electron microscopy confirmed the spherical nature and rough surface of nanoparticles. The particle size analysis revealed a hydrodynamic radius ranging ~150–162 nm based on dynamic light scattering. Zeta potential increased with PBC conjugation implying their enhanced stability. IND encapsulation efficiency was almost 3-fold higher than 4-AP, with release lasting up to 4 days, signifying enhanced solubility, while the release of 4-AP continued for up to 7 days. Nanoparticles and their drug formulations did not show any apparent cytotoxicity and were taken up by human IVD nucleus pulposus cells. When injected into coccygeal mouse IVDs in vivo, the nanoparticles remained within the nucleus pulposus cells and the injection site of the nucleus pulposus and annulus fibrosus of the IVD. These fluorescent nano-formulations may serve as a platform technology to deliver therapeutic agents to IVDs and other tissues that require localized drug injections.

Lateral lumbar interbody fusion is an evolving procedure in spine surgery allowing for the placement of large interbody devices to achieve indirect decompression of segmental stenosis, deformity correction and high fusion rates through a minimally invasive approach. Traditionally, this technique has been performed in the lateral decubitus position. Many surgeons have adopted simultaneous posterior instrumentation in the lateral position to avoid patient repositioning; however, this technique presents several challenges and limitations. Recently, lateral interbody fusion in the prone position has been gaining in popularity due to the surgeon’s ability to perform simultaneous posterior instrumentation as well as decompression procedures and corrective osteotomies. Furthermore, the prone position allows improved correction of sagittal plane imbalance due to increased lumbar lordosis when prone on most operative tables used for spinal surgery. In this paper, we describe the evolution of the prone lateral approach for interbody fusion and present our experience with this technique. Case examples are included for illustration.

The production of biofuels, such as bioethanol from lignocellulosic biomass, is an important task within the sustainable energy concept. Understanding the metabolism of ethanologenic microorganisms for the consumption of sugar mixtures contained in lignocellulosic hydrolysates could allow the improvement of the fermentation process. In this study, the ethanologenic strain Escherichia coli MS04 was used to ferment hydrolysates from five different lignocellulosic agroindustrial wastes, which contained different glucose and xylose concentrations. The volumetric rates of glucose and xylose consumption and ethanol production depend on the initial concentration of glucose and xylose, concentrations of inhibitors, and the positive effect of acetate in the fermentation to ethanol. Ethanol yields above 80% and productivities up to 1.85 gEtOH/Lh were obtained. Furthermore, in all evaluations, a simultaneous co-consumption of glucose and xylose was observed. The effect of deleting the xyIR regulator was studied, concluding that it plays an important role in the metabolism of monosaccharides and in xylose consumption. Moreover, the importance of acetate was confirmed for the ethanologenic strain, showing the positive effect of acetate on the co-consumption rates of glucose and xylose in cultivation media and hydrolysates containing sugar mixtures.

Objectives The benefits of minimally invasive surgery (MIS) for endometrial carcinoma (EC) are well established although the financial impact of robotic-assisted hysterectomy (RH) compared with laparoscopic hysterectomy (LH) is disputed.Design Retrospective cohort study.Setting English National Health Service hospitals 2011–2017/2018.Participants 35 304 women having a hysterectomy for EC identified from Hospital Episode Statistics.Primary and secondary outcome measures The primary outcome was the association between route of surgery on cost at intervention, 30, 90 and 365 days for women undergoing an open hysterectomy (OH) or MIS (LH/RH) for EC in England. The average marginal effect was calculated to compare RH versus OH and RH versus LH which adjusted for any differences in the characteristics of the surgical approaches. Secondary outcomes were to analyse costing data for each surgical approach by age, Charlson Comorbidity Index (CCI) and hospital MIS rate classification.Results A total of 35 304 procedures were performed, 20 405 (57.8%) were MIS (LH: 18 604 and RH: 1801), 14 291 (40.5%) OH. Mean cost for LH was significantly less than RH, whereas RH was significantly less than OH at intervention, 30, 90 and 365 days (p

We describe an unusual case of hyperacute hepatic failure following general anesthesia in a patient receiving a simultaneous kidney-pancreas transplant. Despite an aggressive evaluation of structural, immunological, viral, and toxicological causes, a definitive cause could not be elucidated. The patient required a liver transplant and suffered a protracted hospital course. We discuss the potential causes of fulminant hepatic failure and the perioperative anesthesia management of her subsequent liver transplantation. Resumo: Descrevemos um caso incomum de insuficiência hepática hiperaguda após a anestesia geral em uma paciente que recebeu um transplante simultâneo de rim-pâncreas. Apesar de uma avaliação agressiva das causas estruturais, imunológicas, virais e toxicológicas, uma causa definitiva não pôde ser identificada. A paciente precisou de um transplante de fígado que resultou em prolongamento da internação hospitalar. Discutimos as potenciais causas da insuficiência hepática fulminante e o manejo da anestesia no período perioperatório de seu subsequente transplante de fígado. Keywords: Liver failure, Kidney-pancreas transplant, Volatile agents, Liver transplant, Drug reaction, Isoflurane toxicity, Adverse drug reaction, Inhalational anesthesia, Palavras-chave: Insuficiência hepática, Transplante de rim-pâncreas, Agentes voláteis, Transplante de fígado, Reação medicamentosa, Toxicidade por isoflurano, Reação medicamentosa adversa, Anestesia inalatória

Abstract Background Studies evaluating the benefit of adding motivational interviewing (MI) to behavioral weight-loss programs (BWLPs) have yielded mixed findings. Methods The aims of this randomized controlled trial were to: (1) assess the efficacy of adding MI to a BWLP on weight loss and adherence among 135 individuals with overweight and obesity (77.8% female; mean BMI = 33.6 kg/m2) enrolled in a 12-week BWLP and (2) explore levels of importance, confidence, and readiness for change ratings. Results Participants, who were randomized to receive two MI sessions or two attention control sessions, were assessed at baseline, the end of the BWLP, and 6 months post BWLP. Both groups decreased their weight from baseline to the end of the BWLP; however, there was no weight change in either group when measured between baseline and 6 months post BWLP. We observed no group differences in importance, confidence, and readiness for change after each session. Conclusions We highlight some important lessons learned from the present trial that can be applied to MI + BWLP research. Participants may not have benefited from MI because they were already highly motivated to change, which highlights the importance of pretreatment assessment. Findings also suggest that treatment monitoring may help to enhance MI + BWLP efficacy by guiding a stepped-care approach that identifies individuals for whom additional MI sessions are needed, and when. A focus on refining elements of treatment remains an important direction. Trial registration ClinicalTrials.gov, Identifier: NCT02649634 . Retrospectively registered on 5 January 2016.

Traumatic spinal cord injury (SCI) has devastating implications for patients, including a high predisposition for developing chronic pain distal to the site of injury. Chronic pain develops weeks to months after injury, consequently, patients are treated after irreparable changes have occurred. Nociceptors are central to chronic pain; however, the diversity of this cellular population presents challenges to understanding mechanisms and attributing pain modalities to specific cell types. To begin to address how peripheral sensory neurons below the injury level may contribute to the below-level pain reported by SCI patients, we examined SCI-induced changes in gene expression in lumbar dorsal root ganglia (DRG) below the site of injury. SCI was performed at the T10 vertebral level, with injury produced by a vessel clip with a closing pressure of 15 g for 1 min. Alterations in gene expression produce long-term sensory changes, therefore, we were interested in studying SCI-induced transcripts before the onset of chronic pain, which may trigger changes in downstream signaling pathways and ultimately facilitate the transmission of pain. To examine changes in the nociceptor subpopulation in DRG distal to the site of injury, we retrograde labeled sensory neurons projecting to the hairy hindpaw skin with fluorescent dye and collected the corresponding lumbar (L2–L6) DRG 4 days post-injury. Following dissociation, labeled neurons were purified by fluorescence-activated cell sorting (FACS). RNA was extracted from sorted sensory neurons of naïve, sham, or SCI mice and sequenced. Transcript abundances validated that the desired population of nociceptors were isolated. Cross-comparisons to data sets from similar studies confirmed, we were able to isolate our cells of interest and identify a unique pattern of gene expression within a subpopulation of neurons projecting to the hairy hindpaw skin. Differential gene expression analysis showed high expression levels and significant transcript changes 4 days post-injury in SCI cell populations relevant to the onset of chronic pain. Regulatory interrelationships predicted by pathway analysis implicated changes within the synaptogenesis signaling pathway as well as networks related to inflammatory signaling mechanisms, suggesting a role for synaptic plasticity and a correlation with pro-inflammatory signaling in the transition from acute to chronic pain.

Abstract Thousands of sequenced genomes are now publicly available capturing a significant amount of natural variation within plant species; yet, much of these data remain inaccessible to researchers without significant bioinformatics experience. Here, we present a webtool called ViVa (Visualizing Variation) which aims to empower any researcher to take advantage of the amazing genetic resource collected in the Arabidopsis thaliana 1001 Genomes Project (http://1001genomes.org). ViVa facilitates data mining on the gene, gene family, or gene network level. To test the utility and accessibility of ViVa, we assembled a team with a range of expertise within biology and bioinformatics to analyze the natural variation within the well‐studied nuclear auxin signaling pathway. Our analysis has provided further confirmation of existing knowledge and has also helped generate new hypotheses regarding this well‐studied pathway. These results highlight how natural variation could be used to generate and test hypotheses about less‐studied gene families and networks, especially when paired with biochemical and genetic characterization. ViVa is also readily extensible to databases of interspecific genetic variation in plants as well as other organisms, such as the 3,000 Rice Genomes Project ( http://snp-seek.irri.org/) and human genetic variation ( https://www.ncbi.nlm.nih.gov/clinvar/).

Cartilage injury occurs commonly in equine athletes, often precipitating posttraumatic osteoarthritis (PTOA). Orthobiologics such as autologous conditioned serum (ACS) and autologous protein solution (APS) may be useful in decreasing posttraumatic inflammation, thereby preventing PTOA. The objective of this study was to quantify cytokine concentrations in ACS and APS and evaluate the protective effects of ACS and APS on inflamed chondrocytes cultured in vitro. We hypothesized that the combination of platelet-derived growth factors (PDGF) and anti-inflammatory cytokines present in APS would be superior in decreasing the inflammatory and catabolic cascade in inflamed chondrocytes when compared to ACS in which platelets are excluded from the preparation. Chondrocytes were isolated from the cartilage of femoral trochlear ridges of 6 horses and cultured in 12-well transwell plates. Treatment groups included: (1) control, (2) APS (Pro-Stride; Owl Manor), and (3) ACS (IRAP II; Arthrex). Each group was unstimulated or stimulated with IL-1β and TNF-α for 48 h. The concentration of IL-1β, IL-6, TNF-α, MMP-3, MMP-13, and IL-10 was quantified using a fluorescent bead-based multiplex assay. IL-1Ra concentration was quantified using ELISA. APS and ACS both had significantly increased concentrations of IL-1Ra without a concurrent increase in IL-1β concentration. After 48 h of culture, media from chondrocytes treated with APS contained significantly increased concentrations of IL-1Ra and IL-10. APS-treated cultures had increased concentrations of IL-6. Overall, APS effectively concentrated IL-1Ra without an incubation period and media from APS-treated chondrocytes had increased concentrations of chondroprotective (IL-1Ra and IL-10) and modulatory (IL-6) cytokines, which may be beneficial in the treatment of inflammatory conditions such as PTOA.