Search

ABSTRACT: A chick assay was conducted to determine the effects of Zn source on performance and to establish a Zn relative bioavailability value (RBV) for a new source of Zn hydroxychloride. In the assay, 8-day-old chicks were fed a Zn-deficient soy protein concentrate diet supplemented with 0, 7, and 15 mg Zn/kg from feed grade ZnSO4 monohydrate for 14 d to establish a standard response curve. The same basal diet was supplemented with 3, 7, and 10 mg Zn/kg from a new Zn hydroxychloride (SAMZn). A second source of Zn hydroxychloride (IBZn) was supplemented at 10 mg Zn/kg as a direct comparison to the highest level of SAMZn. Weight gain increased (P < 0.05) with increasing Zn level, regardless of source. Weight gain of chicks fed 7 mg Zn/kg from SAMZn was not different (P > 0.05) from chicks fed 15 mg Zn/kg from ZnSO4. Weight gain was not different (P > 0.05) when comparing the 2 sources of Zn hydroxychloride supplemented at 10 mg Zn/kg. Tibia ash Zn and total tibia Zn were increased (P < 0.05) by all Zn sources and responded linearly (P < 0.05) to Zn supplementation from ZnSO4 and SAMZn. Total tibia Zn concentration was not different (P > 0.05) for chicks fed 10 mg Zn/kg from either source of Zn hydroxychloride. Multiple linear regression of total tibia Zn on supplemental Zn intake (R2 = 0.95) resulted in a RBV of 115% for SAMZn compared with ZnSO4 (set at 100%). The RBV of SAMZn was higher (P < 0.05) than ZnSO4. In conclusion, relative bioavailability of Zn (based on tibia Zn) in Zn hydroxychloride from SAMZn was higher than feed grade ZnSO4 based on multiple regression slope-ratio analysis and was similar to that of IBZn Zn hydroxychloride based on tibia Zn responses to 10 mg/kg supplemental dietary Zn.

Objectives: To evaluate a training program for non-specialist health care providers in a brief coaching intervention to improve positive airway pressure (PAP) usage in Veterans with sleep apnea. Methods: We conducted a national webinar training designed for non-specialist providers to implement a brief telephone coaching intervention to improve PAP adherence. The curriculum was crafted by experts in sleep medicine and behavioral sleep medicine based on principles of PAP desensitization. Providers who participated in this training were asked to complete evaluations at 30 days and 1 year. Results: Provider surveys indicated that most respondents had incorporated the intervention into their clinical practice and felt comfortable counseling patients about sleep apnea and adherence to PAP. Provider feedback suggested that future training programs should include refresher trainings, more training on PAP equipment specifics, and facilitated collaboration with local sleep medicine staff. Conclusions: This pilot training program demonstrated that a webinar format was a feasible method to increase training in PAP adherence among non-specialist health care providers. Innovation: Non-specialists can be trained as PAP coaches in webinar format, improving patients' access to effective strategies and support to be successful with PAP therapy.

The Gaia hypothesis posits that the Earth and its biosphere function as a single self-stabilizing system, but a key challenge is explaining how this could have arisen through Darwinian evolution. One theory is that of "selection by differential survival," in which a clade's extinction probability decreases with age as it accumulates adaptations resisting environmental disturbances. While this is hard to assess during early Earth history, we can assess whether this process operated among marine animal genera throughout the Phanerozoic. To that end, we analyzed time ranges of 36,117 extinct animal genera using fossil occurrence data from the Paleobiology Database in order to calculate marine metazoan extinction age selectivity, extinction rates, and speciation rates over the Phanerozoic. We identify four signatures of selection by differential survival: lower extinction rates among older lineages, heritability and taxonomically nested propagation of extinction resistance, reduced age selectivity during rare environmental perturbations, and differential extinction rather than speciation as the primary driver of the phenomenon. Evidence for this process at lower taxonomic levels also implies its possibility for life as a whole - indeed, the possibility of Gaia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized., Objectives: We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices., Methods: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and β-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes., Results: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 μg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 μg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: β = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283)., Conclusions: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Transformation of white adipose tissue (WAT) to a brown adipose tissue-like (BAT-like) phenotype has emerged as an attractive approach against obesity e.g. using g ß3 adrenergic receptor agonists. These could however, produce side-effects following systemic exposure. The present study explored the possibility of local use of CL-316,243 - a selective ß3 agonist - to circumvent this problem. Rats treated s.c. for 2 weeks (0.3 and 1 mg/kg) showed decreased inguinal fat pad (IFP) weight/volume, increased UCP-1 staining and expressed BAT-like features in H&E stained micrographs. Interscapular BAT increased in weight/volume. In contrast, local treatment into the IFP was not efficacious in terms of weight/volume, despite slight increases in UCP-1 staining and changes in histological features. After local treatment, the exposure of the IFP was lower than after systemic treatment. In turn higher local doses (0.5 and 5 mg/ml) were then tested which produced a strong trend for decreased volume of the IFP, a significant increase in UCP-1 staining, and also a decrease in adipocytes size but increased number. However, after this treatment the systemic exposure was in the same range as following systemic treatment. In conclusion, we saw no evidence for the possibility of converting inguinal WAT to a BAT-phenotype solely through local activation of ß3 receptors. This is in concert with our in vitro experiments which detected direct effects of PPARγ agonists at the gene/protein expression and functional level, but were unable to detect any effect of CL-316,243., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Kaposi sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL) with a poor prognosis in immunocompromised patients. However, it still lacks effective treatment which urgently requires the identification of novel therapeutic targets for PEL. Here, we report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated by KSHV in vitro and in vivo. The selective c-MET inhibitor, PF-2341066, can induce PEL apoptosis through cell cycle arrest and DNA damage, and suppress tumor progression in a xenograft murine model. By using microarray analysis, we identify many novel genes that are potentially controlled by HGF/c-MET within PEL cells. One of the downstream candidates, ribonucleoside-diphosphate reductase subunit M2 (RRM2), also displays the promising therapeutic value for PEL treatment. Our findings provide the framework for development of HGF/c-MET-focused therapy and implementation of clinical trials for PEL patients.

First responders routinely experience work-related events that meet the definition of a traumatic stressor. Despite the high exposure to traumatic events, prevalence rates of posttraumatic stress disorder (PTSD) are relatively low. This discrepancy points to the potential value of identifying factors that distinguish those traumatic stressors that produce ongoing traumatic stress symptoms from those that do not. The present study surveyed 181 first responders from rural settings. A repeated-measures design was used to compare characteristics of traumatic stressors that were or were not associated with ongoing PTSD symptoms. A factor analysis revealed that distressing events were characterized by chaos and resource limitations. Consistent with contemporary models, two mediational analyses revealed that each event characteristic predicted peritraumatic dissociation and posttraumatic cognitions, which in turn predicted PTSD symptoms. Moreover, the effect of each event characteristic on PTSD symptoms was partially mediated by these cognitive processes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To determine Canadian radiation oncologists' (ROs) views regarding the benefits, workload implications, and legal liability of the peer review quality assurance (QA) process., Methods and Materials: A 26-item anonymous survey was electronically distributed to all current practicing ROs in Canada through the Canadian Association of Radiation Oncologists membership to obtain their opinions regarding peer review., Results: The survey was completed by 145 (36%) of 404 ROs. Most (82%) reported their practice is moderately or very busy and more than two-thirds (69%) felt stressed by their workload. A peer review process is standard at 92% of respondents' institutions. The majority reported this consists of weekly meetings where ROs and other health care providers convene to review radiation treatment plans; some have tumor site-specific rounds while others have 1 meeting for all sites. Nearly all (97%) found this type of QA is beneficial for review of radical plans and 71% found it is beneficial for palliative plans. Incorporating peer review into their current work schedule for all sites was deemed by 37% of respondents to be not or slightly difficult, while 40% found it moderately difficult and 22% very or extremely difficult. The majority (91%) reported that creating a work code to document QA meetings would be helpful and 69% stated that extra resources such as scheduling protected time, designating other health care providers QA coordinators, and increasing overall RO manpower are needed to implement effective peer review. Over half (52%) felt documenting QA meeting minutes would increase legal liability., Conclusions: The majority of ROs who responded found that peer review is beneficial and participate in peer review for at least some of the tumor sites they treat. However, most stated that extra resources are required to effectively implement QA for all tumor sites in their current schedule., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: The frenetic pace of inpatient care on surgical services can create barriers to resident teaching of students. Students are often concerned that busy surgical residents will not be able to adequately evaluate their performance at the end of a clerkship., Objective: To determine whether the addition of a resident preceptor would increase the satisfaction of students rotating through the general surgery portion of the required third-year surgery clerkship., Study Design: Before implementing a resident preceptor model, third-year students rotating on general surgery were administered a 24-item web-based survey regarding their experience on the general surgery portion of the surgery clerkship. General surgery residents were similarly surveyed. A resident preceptor model was then introduced. Subsequent students and residents were surveyed. Presurveys and postsurveys were compared and mean responses analyzed., Results: The addition of a resident preceptor made students more comfortable with asking residents questions (p = 0.02), increased the time students felt was available for developing relationships with residents (p = 0.03), and improved the feeling that residents would be able to accurately evaluate the student's effectiveness as a team member (p = 0.05). The students felt resident teaching on afternoon rounds was increased with the resident preceptor model (p = 0.05). Residents reported spending more time teaching students on morning rounds (p = 0.03)., Conclusions: Implementation of a resident preceptor model resulted in significant improvement in medical students' perceptions of resident teaching effectiveness and ability to accurately evaluate a student's performance., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents-3/4 maximum tolerated dose (MTD)], Doxo [6 mg/kg (3/4 MTD)], or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67) and abundant intratumoral programmed cell death (cleaved caspase-3). Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM.

An experiment was conducted using 588 Hy-Line W-36 hens (68 wk of age) to evaluate if laying hens can be successfully molted by ad libitum feeding various levels of 3 sources of distillers dried grains with solubles (DDGS). Treatment 1 consisted of a 47% corn (C):47% soy hulls (SH) molt diet (C:SH) fed for 28 d (positive control). Treatments 2, 3, and 4 were molt diets containing 94% DDGS from the 3 sources fed for 28 d. Treatments 5, 6, and 7 were 32% C: 42% SH: 20% DDGS, from each of the 3 DDGS sources, also fed for 28 d. At the end of the 28-d molt period, all hens were fed a 16% CP corn-soybean meal layer diet. Body weight loss during the molt period was significantly greater (P < 0.05) for hens fed the C:SH diet (26%) than hens fed the diets containing DDGS, and the reduction in BW loss varied among DDGS sources. Feed intake was lower (P < 0.05) for the C:SH control treatment compared with most DDGS treatments. Hens fed the C:SH diet had egg production near 0% during the last 3 wk of the molt period. Hens on the other treatments did not have mean egg production below 17% during the molt period (wk 1 to 4), and the reduction in egg production varied among DDGS sources. Postmolt hen-day egg production (5-41 wk) did not significantly differ among treatments; however, egg mass and egg specific gravity were generally reduced (P < 0.05) for hens fed the 94% DDGS molt diets compared with hens fed the C:SH diet. This study showed that molt and postmolt performance responses varied among DDGS sources; however, none of the molt diets containing 20 to 94% DDGS yielded molt period reductions in BW or egg production similar to a 47% C: 47% SH diet., (Poultry Science Association Inc.)

Major determinants that influence negative outcome in cancer patients are the abilities of cancer cells to resist current therapies and to invade surrounding host tissue, consequently leading to local and metastatic dissemination. Hyaluronan (HA), a prominent constituent of the tumor microenvironment, not only provides structural support but also interacts with cell surface receptors, especially CD44, that influence cooperative signaling pathways leading to chemoresistance and invasiveness. CD147 (emmprin; basigin) is a member of the Ig superfamily that has also been strongly implicated in chemoresistance and invasiveness. CD147 both regulates HA synthesis and interacts with the HA receptors, CD44, and LYVE-1. Increased CD147 expression induces formation of multiprotein complexes containing CD44 (or LYVE-1) as well as members of the membrane-type matrix metalloproteinase, receptor tyrosine kinase, ABC drug transporter, or monocarboxylate transporter families, which become assembled in specialized lipid raft domains along with CD147 itself. In each case, multivalent HA-receptor interactions are essential for formation or stabilization of the lipid raft complexes and for downstream signaling pathways or transporter activities that are driven by these complexes. We conclude that cooperativity between HA, HA receptors, and CD147 may be a major driver of the interconnected pathways of invasiveness and chemoresistance widely critical to malignancy., (© 2014 Elsevier Inc. All rights reserved.)

Recent technological improvements have led to the widespread adoption of field portable energy dispersive X-ray fluorescence (FP-XRF) by governmental agencies, environmental consultancies and research institutions. FP-XRF units often include analysis modes specifically designed for the quantification of trace elements in soils. Using these modes, X-ray tube based FP-XRF units can offer almost "point and shoot" ease of use and results comparable to those of laboratory based instruments. Nevertheless, FP-XRF analysis is sensitive to spectral interferences as well as physical and chemical matrix effects which can result in decreased precision and accuracy. In this study, an X-ray tube-based FP-XRF analyser was used to determine trace (low ppm) concentrations of As in a floodplain soil. The effect of different sample preparation and analysis conditions on precision and accuracy were systematically evaluated. We propose strategies to minimise sources of error and maximise data precision and accuracy, achieving in situ limits of detection and precision of 6.8 ppm and 14.4%RSD, respectively for arsenic. We demonstrate that soil moisture, even in relatively dry soils, dramatically affects analytical performance with a signal loss of 37% recorded for arsenic at 20 wt% soil moisture relative to dry soil. We also highlight the importance of the use of certified reference materials and independent measurement methods to ensure accurate correction of field values., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background & Aims: The effect of adjuvant steroids in infants with biliary atresia (BA) is not clear and evidence of benefit is lacking., Methods: During the period Jan. 2000-Dec. 2011, 153 infants with isolated (CMV IgM-ve) BA underwent Kasai portoenterostomy (KPE) at<70 days. They were divided into three groups: LOW-dose steroid (from a previous randomized trial; starting prednisolone 2mg/kg/day, n=18), HIGH-dose steroid (starting prednisolone 5mg/kg/day, n=44), and NO steroid [n=72+19 placebo (from randomized trial)=91]. Outcome was assessed by early liver biochemistry, clearance of jaundice (<20 μmol/L), and actuarial native liver survival. Data are quoted as median (IQ range) and compared with non-parametric ANOVA, Chi or Log-rank tests as appropriate. p ≤ 0.05 was regarded as significant., Results: All three groups were comparable for age (ANOVA, p=0.31) and a surrogate marker of liver fibrosis [aspartate-aminotransferase index (APRi), ANOVA, p=0.67]. At 1 month post KPE, there was a significant reduction in bilirubin [58 (25-91) vs. 91 (52-145)μmol/L, p=0.0015], AST [118 (91-159) vs. 155 (108-193)IU/L, p=0.0015], and APRi [0.49 (0.28-0.89) vs. 0.82 (0.45-1.2), p=0.005] for HIGH vs. NO steroid. There was a significant increase in % clearance of jaundice with the use of steroids [47/91 (52%) vs. 12/18 (67%) vs. 29/44 (66%); steroids vs. no steroids, p=0.037]. There was no statistical difference in 4-year patient survival (96% vs. 94% vs. 95%) or native liver survival (4 year=46% vs. 50 vs. 57%)., Conclusions: The adjuvant use of prednisolone significantly improved early post-operative liver biochemistry (especially at the higher dose), and increased the proportion of infants who cleared their jaundice at 6 months post-KPE., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Pseudomembranous Aspergillus tracheobronchitis (PMATB) is a relatively uncommon form of invasive pulmonary aspergillosis. PMATB is characterized by necrosis and sloughing of the respiratory epithelium resulting from the invasion of the tracheobronchial mucosa by Aspergillus species. The prognosis for patients with PMATB and underlying immune compromise is poor, but existing data suggest that the outcome of PMATB occurring in patients without overt immune compromise is favorable. To investigate the clinical features and prognosis for immunocompetent patients with PMATB in the study center, 10 patients with histologically and microbiologically confirmed PMATB lacking overt immune compromise over a 9-year period were retrospectively identified. Although all patients ultimately received systemic antifungal therapy, 4 patients required mechanical ventilation and 3 patients died. This report indicates that PMATB occurring in immunocompetent patients may exhibit an aggressive course, with rapid progression of lung parenchymal involvement and a fatal outcome.

Objective: To investigate the degree of CHD awareness as well as symptom, risk factor, and treatment knowledge in a broad sample of cardiac inpatients, and to examine its sociodemographic, clinical and psychosocial correlates., Methods: 1308 CHD inpatients (351 [27.0%] female), recruited from 11 acute care sites in Ontario, participated in this cross-sectional study. Participants were provided with a survey which included a knowledge questionnaire among other measures, and clinical data were extracted from medical charts., Results: 855 (68.8%) respondents cited heart disease as the leading cause of death in men, versus only 458 (37.0%) in women. Participants with less than high school education (p<.001), an annual family income less than $50,000CAD (p=.022), low functional capacity (p=.042), who were currently smoking (p=.022), who had no family history of heart disease (p<.001), and who had a perception of low personal control (p=.033) had significantly lower CHD knowledge., Conclusions: Awareness of CHD is not optimal, especially among women, South Asians, and those of low socioeconomic status. CHD patients have a moderate level of disease knowledge overall, but greater education is needed., Practice Implications: Tailored educational approaches may be necessary for those of low socioeconomic status, particularly with regard to the nature of CHD, tests and treatments.

The study objective was to determine the feasibility of implementation of personal health records (PHRs) by case managers (CMs) in a Veterans Affairs Medical Center (VAMC) Continuity of Care (COC) Clinic, to ascertain the impact of PHRs on patient access to vital health information, and to assess the effect on provider-patient communication. One hundred and fifty patients and 8 nurse CMs in the general medicine COC Clinic at the Iowa City VAMC participated in a prospective cohort study in which an intervention, implementation of PHRs, was performed in one half of the patients, selected at random by their CMs. All participants responded to questions about their personal possession of documentation of vital health information. Initially, the majority of subjects possessed poor documentation of basic health information. At follow-up, significant differences occurred between the cohort with PHRs and the cohort without in their documentation of immunizations, allergies, medications, and operations.

Glucosinolates and their breakdown products (nitriles) have long been implicated as toxic factors when feeding rapeseed (Brassica napus) meals and crambe (Crambe abyssinica) meals to poultry. Accordingly, various methods have been developed to remove these compounds from the meals to enhance their value as feed supplements. Glucosinolates and nitriles were extracted from commercially processed, defatted crambe meal by washing with water or various solvent-water mixtures: 50% isopropanol, 50% acetone, or 50% ethanol. In addition, crambe seed was extruded and extracted in the laboratory with isopropanol or hexane. Water washing of commercially defatted meal proved to be the most effective method of extraction, removing 95% of the glucosinolates and nitriles. Meals were fed to 7-d-old broiler chicks at 10% of the diet for 14 d. Weight gain decreased (P < .05) in most groups; however a greater decrease (P < .01) was observed in birds fed meals with high glucosinolate content. Feed intake also decreased (P < .05) in most groups; consequently, feed efficiencies were similar for all groups. No changes in serum chemistries, triiodothyronine, thyroxine, or tissue lesions were associated with glucosinolate or nitrile intake. A relationship (P < .05, r = .74) was found between weight gain and glucosinolate intake. No correlation was found between feed intake and meal glucosinolate or nitrile concentrations.