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Abstract Oxidative stress is a key contributor to AD pathology. However, the earliest role of pre-plaque neuronal oxidative stress, remains elusive. Using laser microdissected hippocampal neurons extracted from McGill-R-Thy1-APP transgenic rats we found that intraneuronal amyloid beta (iAβ)-burdened neurons had increased expression of genes related to oxidative stress and DNA damage responses including Ercc2, Fancc, Sod2, Gsr, and Idh1. DNA damage was further evidenced by increased neuronal levels of XPD (Ercc2) and γH2AX foci, indicative of DNA double stranded breaks (DSBs), and by increased expression of Ercc6, Rad51, and Fen1, and decreased Sirt6 in hippocampal homogenates. We also found increased expression of synaptic plasticity genes (Grin2b (NR2B), CamkIIα, Bdnf, c-fos, and Homer1A) and increased protein levels of TOP2β. Our findings indicate that early accumulation of iAβ, prior to Aβ plaques, is accompanied by incipient oxidative stress and DSBs that may arise directly from oxidative stress or from maladaptive synaptic plasticity.

OBJECTIVES:. To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. DESIGN:. Prospective cohort study. SETTING:. Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. PATIENTS:. Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. INTERVENTIONS:. All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. MEASUREMENTS AND MAIN RESULTS:. Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5–15.7%) in band 1, 28.1% (95% CI, 21.3–35.8%) in band 2, and 49.4% (95% CI, 41.4–57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. CONCLUSIONS:. Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.

Category: Midfoot/Forefoot; Trauma Introduction/Purpose: Anecdotal evidence suggests patients who require midfoot fusion following initial open reduction and internal fixation (ORIF) for Lisfranc injury fare worse than those treated with an index arthrodesis, despite an identical final construct. Substantial data has been generated to understand optimal initial treatment of Lisfranc injuries; however, no data exists comparing the primary arthrodesis (PA) and secondary fusion (SA) populations. The purpose of this study was to compare radiographic and patient reported outcomes (PROs) of patients who underwent PA versus SA following ORIF of their Lisfranc injury. Methods: We retrospectively identified skeletally mature patients from an academic level 1 trauma center treated for midfoot injuries between 2002-2022. We identified 232 patients (234 feet) with Lisfranc injuries. A total of 65 patients underwent a fusion procedure and were included in our cohort. Demographic data, treatment, radiographic outcomes, and PROs were recorded. Patients who underwent PA as index treatment of their Lisfranc injury were compared to those who underwent index ORIF and subsequent SA. We used a composite primary outcome for comparison which included: the development of adjacent midfoot arthrosis, midfoot collapse, or mal/nonunion. Secondary outcomes were PROMIS measures of physical function (PF) and pain interference (PI). Descriptive statistics, chi-squared, and independent sample t-tests were employed for analysis. Multivariable analysis was utilized to determine the contribution of confounders on outcome. Logistic regression was used to ascertain effects of index treatment on outcome probability. Results: 42 underwent index PA (18%); 23 SAs were required (12.3% of index ORIFs). Average follow-up was 4.3 years (0.3- 18.2y). Mean age at fusion was 48.3 years; average time from index to fusion was 3.1 years (SD 5.29y). Poor radiographic outcomes were noted in 2 PA patient (5.3%) compared to 5 SA (27.8%, p=0.02). Logistic regression indicated those requiring SA were 6.9 times more likely to exhibit poor radiographic outcomes (p=0.03). A non-significant trend demonstrated higher PF and lower PI scores after index PA versus primary ORIF and SA (42.5 vs 39.0, p=0.17; 56.3 vs. 61.6, p=0.06). There was otherwise no difference in PROs between groups. Logistic regression revealed no significant prediction of PROs by treatment. Post-hoc power analysis indicated 32% power to detect PRO differences. Conclusion: While this study does not reveal robust evidence to advocate for primary fusion of every Lisfranc, results may suggest a suboptimal outcome if a patient requires SA after index ORIF compared to PA. This may be in part to effects of repeat surgery. Findings should prompt further larger scale investigations to better elucidate the merits of a single surgery approach, and warrant consideration of how to predict who might be at risk to require SA so to advocate for PA as their index procedure.

Epiphytic lichens and bryophytes provide important habitat for microarthropods, yet little work has documented epiphytic microarthropod assemblages. Further, the response of epiphytes and their associated microarthropod communities to varying levels of forest disturbance and cutting intensity are not well known. We conducted a case study to provide an initial community description of epiphyte-dwelling microarthropods in Adirondack northern hardwoods, and to assess potential for impacts of aggregated and dispersed patterns of reserve tree retention to these communities. In total, 79 families of microarthropods were identified in the 0.14 m2 of samples. Late summer average daily maximum temperatures were 3.2 °C higher in the shelterwood, and three years following treatments the per-unit area dry weight of the bole-associated bryophyte Neckera pennata was 34 % lower in the shelterwood. Microarthropod richness and density were distinctly greater in epiphyte substrates at the base of trees, and were reduced in the shelterwood. Several indicator taxa were identified within the basal bryophytes in the reserve treatment, and in both bryophytes the microarthropod assemblages were more homogenous in the shelterwood. A few mobile and heavily sclerotized taxa persisted in shelterwood substrates, especially in the lichens which lacked 3-dimensional structure. This case study revealed a diverse community of microarthropods in northern hardwood forests that were structured by epiphyte type, height on tree and, potentially, by canopy removal, and suggests conservation value of aggregated tree retention when applying even-age regeneration methods with respect to epiphytic bryophytes, lichens, and their associated invertebrates.

The central role of RNAs in health and disease calls for robust tools to visualize RNAs in living systems through fluorescence microscopy. Live zebrafish embryos are a popular system to investigate multicellular complexity as disease models. However, RNA visualization approaches in whole organisms are notably underdeveloped. Here, we establish our RNA tagging and imaging platform Riboglow-FLIM for complex cellular imaging applications by systematically evaluating FLIM capabilities. We use adherent mammalian cells as models for RNA visualization. Additional complexity of analyzing RNAs in whole mammalian animals is achieved by injecting these cells into a zebrafish embryo system for cell-by-cell analysis in this model of multicellularity. We first evaluate all variable elements of Riboglow-FLIM quantitatively before assessing optimal use in whole animals. In this way, we demonstrate that a model noncoding RNA can be detected robustly and quantitatively inside live zebrafish embryos using a far-red Cy5-based variant of the Riboglow platform. We can clearly resolve cell-to-cell heterogeneity of different RNA populations by this methodology, promising applicability in diverse fields.

Abstract Objective: Empiric broad-spectrum antibiotic therapy is commonly prescribed for patients hospitalized with diabetic foot infections (DFI) and lower extremity osteomyelitis (OM). The primary objective was to evaluate the concordance between empiric antibiotic therapy, microbiologic results, and definitive antibiotic therapy with a focus on methicillin-resistant Staphylococcus aureus (MRSA) and resistant gram-negative organisms. The secondary objective was to evaluate the negative predictive values (NPV) of select risk factors for MRSA and resistant gram-negative organisms for microbiologic results with these organisms. Design: Retrospective cohort study. Setting: Safety-net health system in Ohio. Patients: Adults hospitalized and receiving antibiotic therapy for DFI or lower extremity OM in 2021. Results: For 259 unique patients, empiric therapies with activity against MRSA and resistant gram-negative organisms were administered to 224 (86.5%) and 217 (83.8%) patients, respectively. Definitive therapies with activity against MRSA and resistant gram-negative organisms were administered to 91 (35%) and 74 (28.6%) patients, respectively. Of 234 patients with microbiologic testing, 29 (12.4%) had positive cultures with MRSA and 41 (17.5%) with resistant gram-negative organisms. The NPVs of risk factors for MRSA and resistant gram-negative organisms for the absence of these organisms in culture were 91% and 85%, respectively. Conclusions: For patients hospitalized with DFI and lower extremity OM, our data suggest opportunities for substantial reductions in empiric therapies with activity against MRSA and resistant gram-negative organisms. The absence of risk factors for these organisms was reasonably good at predicting negative cultures with these organisms.

Cognitive–achievement relations research has been instrumental in understanding the development of academic skills and learning difficulties. Most cognitive–achievement relations research has been conducted with large samples and represent average relations across the ability spectrum. A notable gap in the literature is whether these relations vary by cognitive ability levels (IQ). This study examined cognitive–achievement relations across different general ability levels (Low, Average, and High) to fill this gap. Based on Spearman’s Law of Diminishing Returns, it would be expected that general intelligence would be a stronger predictor of academic skills at lower levels of IQ, and more specific abilities would be stronger predictors of academic skills at higher levels of IQ. To test this, multi-group path analysis and structural equation modeling were used to examine whether integrated models of cognitive–reading relations are differentiated by IQ levels in the Woodcock–Johnson III and Woodcock–Johnson IV standardization samples. Global and broad cognitive abilities were used as predictors of basic reading skills and reading comprehension for elementary and secondary school students. The magnitude of prediction differed across ability groups in some cases, but not all. Importantly, the variance explained in basic reading skills and reading comprehension tended to be larger for the Low group compared to the Average and High groups. When variance accounted for by general intelligence was removed from the broad abilities, the effects of the broad abilities were similar across ability groups, but the indirect effects of g were higher for the Low group. Additionally, g had stronger relative effects on reading in the Low group, and broad abilities had stronger relative effects on reading in the Average and High groups. The implications and limitations of this study are discussed.

Adrenocortical carcinoma (ACC) is a rare but highly aggressive cancer with limited treatment options and poor survival for patients with advanced disease. An improved understanding of the transcriptional programs engaged in ACC will help direct rational, targeted therapies. Whereas activating mutations in Wnt/β-catenin signaling are frequently observed, the β-catenin-dependent transcriptional targets that promote tumor progression are poorly understood. To address this question, we analyzed ACC transcriptome data and identified a novel Wnt/β-catenin-associated signature in ACC enriched for the extracellular matrix (ECM) and predictive of poor survival. This suggested an oncogenic role for Wnt/β-catenin in regulating the ACC microenvironment. We further investigated the minor fibrillar collagen, collagen XI alpha 1 (COL11A1), and found that COL11A1 expression originates specifically from cancer cells and is strongly correlated with both Wnt/β-catenin activation and poor patient survival. Inhibition of constitutively active Wnt/β-catenin signaling in the human ACC cell line, NCI-H295R, significantly reduced the expression of COL11A1 and other ECM components and decreased cancer cell viability. To investigate the preclinical potential of Wnt/β-catenin inhibition in the adrenal microenvironment, we developed a minimally invasive orthotopic xenograft model of ACC and demonstrated that treatment with the newly developed Wnt/β-catenin:TBL1 inhibitor Tegavivint significantly reduced tumor growth. Together, our data support that the inhibition of aberrantly active Wnt/β-catenin disrupts transcriptional reprogramming of the microenvironment and reduces ACC growth and survival. Furthermore, this β-catenin-dependent oncogenic program can be therapeutically targeted with a newly developed Wnt/β-catenin inhibitor. These results show promise for the further clinical development of Wnt/β-catenin inhibitors in ACC and unveil a novel Wnt/β-catenin-regulated transcriptome.

Class IC antiarrhythmics are generally considered a safe means of treating many common arrhythmias such as atrial fibrillation (a-fib), atrial flutter (a-flutter), and paroxysmal supraventricular tachycardia (PSVT). Essentially, flecainide works by binding and blocking sodium channels more effectively at higher heart rates. However, this class of drugs is known to exhibit use dependence which could predispose patients to the development of malignant arrhythmias during episodes of tachycardia. In this case, we present a patient who was being treated with flecainide for a-fib who ultimately developed a wide complex tachycardia after her metoprolol was held.

Abstract Background Many children and their families are affected by premature birth. Yet, little is known about their healthcare access and adverse family impact during early childhood. This study aimed to (1) examine differences in healthcare access and adverse family impact among young children by prematurity status and (2) determine associations of healthcare access with adverse family impact among young children born prematurely. Methods This was a secondary analysis of cross-sectional 2016 and 2017 National Survey of Children’s Health data. The sample included 19,482 U.S. children ages 0–5 years including 242 very low birthweight (VLBW) and 2205 low birthweight and/or preterm (LBW/PTB) children. Prematurity status was defined by VLBW (i.e.,

Background: As a result of COVID-19, numerous adaptations were made to health care delivery, including comprehensive medication management (CMM) delivered in community pharmacies. Objective: Identify and describe the adaptations that have been made to the delivery of CMM among community pharmacies due to COVID-19. Methods: Community pharmacies participating in a CMM implementation and research initiative had regular coaching calls throughout COVID-19 and completed a survey of changes that occurred as a result of COVID-19. Coaching notes and survey results were summarized and mapped to the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) to systematically capture changes that occurred. Results: A number of reactive adaptations were made to CMM delivery as a result of COVID-19, including increased virtual or remote delivery of CMM, delaying CMM visits to allow pharmacies to provide care directly related to the pandemic including COVID-19 testing and vaccines, wearing personal protective equipment (PPE) in visits, new ways of obtaining clinical patient information, and shifting CMM staffing models. Conclusion: Adaptations that occurred to CMM during COVID-19 allowed pharmacists to continue to serve their patients and meet public health needs.

Summary: HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (CycK) and cyclin-dependent kinase 13 (CDK13) as a Nef-associated kinase complex. CycK/CDK13 phosphorylates the serine at position 360 (S360) in SERINC5, which is required for Nef downregulation of SERINC5 from the cell surface and its counteractivity of the SERINC5 antiviral activity. To understand the role of S360 phosphorylation, we generate chimeric proteins between CD8 and SERINC5 to study their response to Nef. Nef not only downregulates but, importantly, also binds to this chimera in an S360-dependent manner. Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.

Objectives:. Sepsis is a common cause of morbidity and mortality. A reliable, rapid, and early indicator can help improve efficiency of care and outcomes. To assess the IntelliSep test, a novel in vitro diagnostic that quantifies the state of immune activation by measuring the biophysical properties of leukocytes, as a rapid diagnostic for sepsis and a measure of severity of illness, as defined by Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation-II scores and the need for hospitalization. Design, Setting, SUBJECTS:. Adult patients presenting to two emergency departments in Baton Rouge, LA, with signs of infection (two of four systemic inflammatory response syndrome criteria, with at least one being aberration of temperature or WBC count) or suspicion of infection (a clinician order for culture of a body fluid), were prospectively enrolled. Sepsis status, per Sepsis-3 criteria, was determined through a 3-tiered retrospective and blinded adjudication process consisting of objective review, site-level clinician review, and final determination by independent physician adjudicators. MEASUREMENTS AND MAIN RESULTS:. Of 266 patients in the final analysis, those with sepsis had higher IntelliSep Index (median = 6.9; interquartile range, 6.1–7.6) than those adjudicated as not septic (median = 4.7; interquartile range, 3.7–5.9; p < 0.001), with an area under the receiver operating characteristic curve of 0.89 and 0.83 when compared with unanimous and forced adjudication standards, respectively. Patients with higher IntelliSep Index had higher Sequential Organ Failure Assessment (3 [interquartile range, 1–5] vs 1 [interquartile range, 0–2]; p < 0.001) and Acute Physiology and Chronic Health Evaluation-II (7 [interquartile range, 3.5–11.5] vs 5 [interquartile range, 2–9]; p < 0.05) and were more likely to be admitted to the hospital (83.6% vs 48.3%; p < 0.001) compared with those with lower IntelliSep Index. CONCLUSIONS:. In patients presenting to the emergency department with signs or suspicion of infection, the IntelliSep Index is a promising tool for the rapid diagnosis and risk stratification for sepsis.

Objective:. To compare outcomes after bariatric surgery between Medicaid and non-Medicaid patients and assess whether differences in social determinants of health were associated with postoperative weight loss. Background:. The literature remains mixed on weight loss outcomes and healthcare utilization for Medicaid patients after bariatric surgery. It is unclear if social determinants of health geocoded at the neighborhood level are associated with outcomes. Methods:. Patients who underwent laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) from 2008 to 2017 and had ≥1 year of follow-up within a large health system were included. Baseline characteristics, 90-day and 1-year outcomes, and weight loss were compared between Medicaid and non-Medicaid patients. Area deprivation index (ADI), urbanicity, and walkability were analyzed at the neighborhood level. Median regression with percent total body weight (TBW) loss as the outcome was used to assess predictors of weight loss after surgery. Results:. Six hundred forty-seven patients met study criteria (191 Medicaid and 456 non-Medicaid). Medicaid patients had a higher 90-day readmission rate compared to non-Medicaid patients (19.9% vs 12.3%, P < 0.016). Weight loss was similar between Medicaid and non-Medicaid patients (23.1% vs 21.9% TBW loss, respectively; P = 0.266) at a median follow-up of 3.1 years. In adjusted analyses, Medicaid status, ADI, urbanicity, and walkability were not associated with weight loss outcomes. Conclusions:. Medicaid status and social determinants of health at the neighborhood level were not associated with weight loss outcomes after bariatric surgery. These findings suggest that if Medicaid patients are appropriately selected for bariatric surgery, they can achieve equivalent outcomes as non-Medicaid patients.

Exposure to prolonged stress is a major risk-factor for psychiatric disorders such as generalized anxiety and major depressive disorder. Human imaging studies have identified structural and functional abnormalities in the prefrontal cortex of subjects with depression and anxiety disorders, particularly Brodmann's area 25 (BA25). Further, deep brain stimulation of BA25 reduces symptoms of treatment-resistant depression. The rat homolog of BA25 is the infralimbic cortex (IL), which is critical for cognitive appraisal, executive function, and physiological stress reactivity. Previous studies indicate that the IL undergoes stress-induced changes in excitatory/inhibitory balance culminating in reduced activity of glutamate output neurons. However, the regulatory role of IL glutamate output in mood-related behaviors after chronic variable stress (CVS) is unknown. Here, we utilized a lentiviral-packaged small-interfering RNA to reduce translation of vesicular glutamate transporter 1 (vGluT1 siRNA), thereby constraining IL glutamate output. This viral-mediated gene transfer was used in conjunction with a quantitative anatomical analysis of cells expressing the stable immediate-early gene product FosB/ΔFosB, which accumulates in response to repeated neural activation. Through assessment of FosB/ΔFosB-expressing neurons across the frontal lobe in adult male rats, we mapped regions altered by chronic stress and determined the coordinating role of the IL in frontal cortical plasticity. Specifically, CVS-exposed rats had increased density of FosB/ΔFosB-expressing cells in the IL and decreased density in the insula. The latter effect was dependent on IL glutamate output. Next, we examined the interaction of CVS and reduced IL glutamate output in behavioral assays examining coping, anxiety-like behavior, associative learning, and nociception. IL glutamate knockdown decreased immobility during the forced swim test compared to GFP controls, both in rats exposed to CVS as well as rats without previous stress exposure. Further, vGluT1 siRNA prevented CVS-induced avoidance behaviors, while also reducing risk aversion and passive coping. Ultimately, this study identifies the necessity of IL glutamatergic output for regulating frontal cortical neural activity and behavior following chronic stress. These findings also highlight how disruption of excitatory/inhibitory balance within specific frontal cortical cell populations may impact neurobehavioral adaptation and lead to stress-related disorders.

Chemokines play important roles in homeostasis and inflammatory processes. While their roles in leukocyte recruitment are well-appreciated, chemokines play additional roles in the body, including mediating or regulating angiogenesis, tumor metastasis and wound healing. In this opinion article, we focus on the role of CXCR3 and its ligands in fibrotic processes. We emphasize differences of the effects of each ligand, CXCL9, CXCL10 and CXCL11, on fibroblasts in different tissues of the body. We include discussions of differences in signaling pathways that may account for protective or pro-fibrotic effects of each ligand in different experimental models and ex vivo analysis of human tissues. Our goal is to highlight potential reasons why there are disparate findings in different models, and to suggest ways in which this chemokine axis could be manipulated for the treatment of fibrosis.

Objective: T-box 1 (TBX1) has been identified as a genetic marker of beige adipose tissue. TBX1 is a mesodermal development transcription factor essential for tissue patterning and cell fate determination. However, whether it plays a role in the process of adipose beiging or how it functions in adipose tissue has not been reported. Here, we examined the function of TBX1 in adipose tissue as well as adipose-derived stem cells from mice and humans. Methods: Adipose-specific TBX1 transgenic (TBX1 AdipoTG) and adipose-specific TBX1 knockout (TBX1 AdipoKO) mice were generated to explore the function of TBX1 in the process of adipose beiging, metabolism and energy homeostasis in vivo. In vitro, we utilized a siRNA mediated approach to determine the function of TBX1 during adipogenesis in mouse and human stem cells. Results: Adipose-specific overexpression of TBX1 was not sufficient to fully induce beiging and prevent diet-induced obesity. However, adipose TBX1 expression was necessary to defend body temperature during cold through regulation of UCP1 and for maintaining β3-adrenergic sensitivity and glucose homeostasis in vivo. Loss of adipose TBX1 expression enhanced basal lipolysis and reduced the size of subcutaneous iWAT adipocytes. Reduction of TBX1 expression via siRNA significantly impaired adipogenesis of mouse stromal vascular cells but significantly enhanced adipogenesis in human adipose derived stem cells. Conclusions: Adipose expression of TBX1 is necessary, but not sufficient, to defend body temperature during cold via proper UCP1 expression. Adipose TBX1 expression was also required for proper insulin signaling in subcutaneous adipose as well as for maintaining β-adrenergic sensitivity, but overexpression of TBX1 was not sufficient to induce adipocyte beiging or to prevent diet-induced obesity. TBX1 expression is enriched in adipose stem cells in which it has contrasting effects on adipogenesis in mouse versus human cells. Collectively, these data demonstrate the importance of adipose TBX1 in the regulation of beige adipocyte function, energy homeostasis, and adipocyte development.

Although the trajectories of children's social skills have been examined across biological sexes, less research has examined these patterns for racially and ethnically diverse children in the United States. The purpose of this study was to estimate the longitudinal growth trajectories of social skills, while examining the influence of biological sex, race, and ethnic identities using an adaptation of the commonly used Social Skills Rating Scale. A large nationally representative sample of elementary school children in the United States were assessed annually from kindergarten through fifth grade (N = 11,792). Structural equation modeling was used to examine latent growth curve models of teacher-rated interpersonal skills and self-control. After finding evidence of longitudinal invariance, results suggested a quadratic growth pattern best represented the trajectories of social skills ratings. Teacher ratings for African American children demonstrated a moderate declining linear trajectory throughout elementary school when compared with White children (reference group) and their Asian and Hispanic peers. Children from families with higher socioeconomic status and girls showed moderate to large differences in social skills ratings in kindergarten and stronger growth across time. Implications of the findings with future directions for research are discussed.

Meat from oxidative skeletal muscle has a higher postmortem ultimate pH, which was originally thought to be a result from decreased antemortem glycogen stores. Therefore, we hypothesized that excess glycogen may not resolve the high ultimate pH of meat from oxidative muscles in ruminants and poultry. To test this hypothesis, an in vitro muscle glycolytic buffer system containing excess glycogen was used to compare glycolysis and pH decline of glycolytic and oxidative muscle from beef, lamb, chicken, and turkey. Glycogen concentration of both glycolytic and oxidative muscle homogenates was similar at 0 min and decreased significantly with time in all species tested. All homogenates contained residual glycogen at 1440 min, indicating glycogen was provided in excess. The ultimate pH of the oxidative muscle homogenates was significantly increased compared to the glycolytic muscle. The oxidative muscle also contained decreased lactate and decreased glucose 6-phosphate in all the species tested at 1440 min. Combined these data suggest that glycolysis and pH decline of oxidative muscles terminate prematurely at higher ultimate pH even in the presence of excess glycogen across livestock species. Additionally, the data indicated that the in vitro glycolytic buffer system can be used to study species specific meat quality problems in beef, lamb, chicken, and turkey.

Atrial fibrillation (AF) and heart failure (HF) are two common conditions that often coexist and predispose each to one another. AF increases hospitalization rates and overall mortality in patients with HF. The current available therapeutic options for AF in patients with HF are diverse and guidelines do not provide a clear consensus regarding the best management approach. To determine if catheter ablation for AF is superior to medical therapy alone in patients with coexisting HF, we conducted this systematic review and meta-analysis. The primary outcomes evaluated are left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores, 6-minute walk test (6MWT) distance, heart failure hospitalizations, and mortality. The results are presented as a mean difference for continuous outcome measures and odds ratios for dichotomous outcomes (using Mantel-Haenszel random effects model). 7 full texts met inclusion criteria, including 856 patients. AF catheter ablation was associated with a significant increase in LVEF (mean difference 6.8%; 95% CI: 3.5 – 10.1; P

Pancreatic cancer is characterized by an extensive desmoplastic stroma, the functional relevance of which is poorly understood. Activated fibroblasts are a prevalent component of the stroma, and traditionally, these cells have been considered as a homogenous population derived from pancreatic stellate cells. In this study, we highlight a previously unappreciated heterogeneity of the fibroblast population within the stroma. In particular, a subset of stromal fibroblasts has characteristics of mesenchymal stem cells (MSCs). MSCs are present in the normal pancreas as well as in the carcinomatous pancreas (CA-MSCs). Here, we determine that CA-MSCs have increased tumor-promoting function compared with MSCs in normal pancreas. This ability to promote tumor growth is associated with CA-MSCs’ unique ability to promote alternative macrophage polarization. Thus, our study identifies a previously uncharacterized cell population within the stroma and sheds light on tumor-promoting interactions between different components of the stroma. Significance: Targeting the stroma is emerging as a new paradigm in pancreatic cancer; however, efforts to that effect are hampered by our limited understanding of the nature and function of stromal components. Here, we uncover previously unappreciated heterogeneity within the stroma and identify interactions among stromal components that promote tumor growth and could be targeted therapeutically.

This paper describes the application of adaptive mesh methods to the numerical simulation of one and two-dimensional petroleum reservoir waterfloods. The method uses current information on the solution to adapt the mesh to the solution as the computation proceeds. It is shown that this leads to significant improvements in accuracy at a marginal increase in computational cost. Cet article décrit l'application des méthodes de maillages évolutifs à la simulation numérique dinjection d'eau à une ou deux dimensions dans des réservoirs pétroliers. La méthode utilise des informations disponibles sur la solution pour adapter le maillage à la solution pendant que se déroule le calcul. On montre que cela conduit à des améliorations significatives en ce qui concerne la précision avec une augmentation marginale du coût des calculs.

In a cross-sectional national study that included 972 operations with > 3 horses on 1/1/98 in 28 states in the USA, 8,417 fecal specimens were collected from horses and cultured to test for the presence of Salmonella spp. Operations were characterized as Salmonella spp-positive if at least one fecal specimen tested positive for Salmonella spp. Percentages of Salmonella spp-positive operations were computed by management and other factors (collected from operation-level questionnaires) that were hypothesized to be related to fecal shedding of Salmonella spp. A logistic-regression model was constructed to identify factors associated with horses? shedding Salmonella spp in feces on an operation. The odds of an operation being Salmonella spp positive increased as the number of resident horses increased. In addition, the following factors were found to be associated with increased odds of an operation being Salmonella spp positive: horses were used primarily for breeding; operation cleanliness was characterized as poor by the data collector; and new resident equids had been added to the operation without routine quarantine.