Search

BACKGROUND: Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants. It is not known whether parenteral nutrition (PN) administered during bone marrow transplantation (BMT) supports systemic antioxidant status. OBJECTIVE: The aims of the study were to determine 1) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone. DESIGN: Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose, amino acids, micronutrients, and lipid (120 kJ/d) or a solution containing only micronutrients (identical to those in standard PN) and a small amount of lipid (12 kJ/d). Plasma antioxidant status was measured before conditioning therapy and serially at days 1, 3, 7, 10, and 14 after BMT. RESULTS: Plasma glutathione (GSH) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy. Plasma cysteine concentrations were unchanged, whereas cystine concentrations increased. Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time. Plasma alpha-tocopherol concentrations were lower in patients given standard PN. There were no differences in other plasma antioxidants between groups. CONCLUSIONS: A significant decline in GSH-glutathione disulfide, cysteine-cystine, and vitamin E status occurs after chemotherapy and BMT. Standard PN does not improve antioxidant status compared with administration of micronutrients alone. Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: The 21st Century Cures Act mandates the immediate, electronic release of health information to patients. However, in the case of adolescents, special consideration is required to ensure that confidentiality is maintained. The detection of confidential content in clinical notes may support operational efforts to preserve adolescent confidentiality while implementing information sharing., Objectives: This study aimed to determine if a natural language processing (NLP) algorithm can identify confidential content in adolescent clinical progress notes., Methods: A total of 1,200 outpatient adolescent progress notes written between 2016 and 2019 were manually annotated to identify confidential content. Labeled sentences from this corpus were featurized and used to train a two-part logistic regression model, which provides both sentence-level and note-level probability estimates that a given text contains confidential content. This model was prospectively validated on a set of 240 progress notes written in May 2022. It was subsequently deployed in a pilot intervention to augment an ongoing operational effort to identify confidential content in progress notes. Note-level probability estimates were used to triage notes for review and sentence-level probability estimates were used to highlight high-risk portions of those notes to aid the manual reviewer., Results: The prevalence of notes containing confidential content was 21% (255/1,200) and 22% (53/240) in the train/test and validation cohorts, respectively. The ensemble logistic regression model achieved an area under the receiver operating characteristic of 90 and 88% in the test and validation cohorts, respectively. Its use in a pilot intervention identified outlier documentation practices and demonstrated efficiency gains over completely manual note review., Conclusion: An NLP algorithm can identify confidential content in progress notes with high accuracy. Its human-in-the-loop deployment in clinical operations augmented an ongoing operational effort to identify confidential content in adolescent progress notes. These findings suggest NLP may be used to support efforts to preserve adolescent confidentiality in the wake of the information blocking mandate., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The 21st Century Cures Act information blocking final rule mandated the immediate and electronic release of health care data in 2020. There is anecdotal concern that a significant amount of information is documented in notes that would breach adolescent confidentiality if released electronically to a guardian., Objectives: The purpose of this study was to quantify the prevalence of confidential information, based on California laws, within progress notes for adolescent patients that would be released electronically and assess differences in prevalence across patient demographics., Methods: This is a single-center retrospective chart review of outpatient progress notes written between January 1, 2016, and December 31, 2019, at a large suburban academic pediatric network. Notes were labeled into one of three confidential domains by five expert reviewers trained on a rubric defining confidential information for adolescents derived from California state law. Participants included a random sampling of eligible patients aged 12 to 17 years old at the time of note creation. Secondary analysis included prevalence of confidentiality across age, gender, language spoken, and patient race., Results: Of 1,200 manually reviewed notes, 255 notes (21.3%) (95% confidence interval: 19-24%) contained confidential information. There was a similar distribution among gender and age and a majority of English speaking (83.9%) and white or Caucasian patients (41.2%) in the cohort. Confidential information was more likely to be found in notes for females ( p  < 0.05) as well as for English-speaking patients ( p  < 0.05). Older patients had a higher probability of notes containing confidential information ( p  < 0.05)., Conclusion: This study demonstrates that there is a significant risk to breach adolescent confidentiality if historical progress notes are released electronically to proxies without further review or redaction. With increased sharing of health care data, there is a need to protect the privacy of the adolescents and prevent potential breaches of confidentiality., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: For caregivers of adolescents and young adults with severe cognitive deficits, or "diminished capacity," access to the medical record can be critical. However, this can be a challenge when utilizing the electronic health record (EHR) as information is often restricted in order to protect adolescent confidentiality. Having enhanced access for these proxies would be expected to improve engagement with the health system for the families of these medically complex adolescents and young adults., Objectives: To describe a process for granting full EHR access to proxies of adolescents with diminished capacity and young adults who are legally conserved while respecting regulations supporting adolescent confidentiality., Methods: The first step in this initiative was to define the "diminished capacity" access class for both adolescents and young adults. Once defined, workflows utilizing best practice alerts were developed to support clinicians in providing the appropriate documentation. In addition, processes were developed to minimize the possibility of erroneously activating the diminished capacity access class for any given patient. To enhance activation, a support tool was developed to identify patients who might meet the criteria for diminished capacity proxy access. Finally, outreach and educations were developed for providers and clinics to make them aware of this initiative., Results: Since activating this workflow, proxies of 138 adolescents and young adults have been granted the diminished capacity proxy access class. Approximately 54% are between 12 and 17 years with 46% 18 years and older. Proxies for both age groups have engaged with portal functionality at higher rates when compared to institutional rates of use by proxies of the general pediatric population., Conclusion: With this quality improvement initiative, we were able to enhance EHR access and engagement of families of some of the most complex adolescent and young adult patients without inadvertently compromising adolescent confidentiality., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Bone stress injuries (BSIs) are common in athletes. Risk factors for BSI may differ by skeletal anatomy and relative contribution of trabecular-rich and cortical-rich bone., Hypothesis: We hypothesized that Female Athlete Triad (Triad) risk factors would be more strongly associated with BSIs sustained at trabecular-rich versus cortical-rich skeletal sites., Study Design: Cohort study; Level of evidence, 2., Methods: The study population comprised 321 female National Collegiate Athletic Association Division I athletes participating in 16 sports from 2008 to 2014. Triad risk factors and a Triad cumulative risk score were assessed using responses to preparticipation examination and dual energy x-ray absorptiometry to measure lumbar spine and whole-body bone mineral density (BMD). Sports-related BSIs were diagnosed by a physician and confirmed radiologically. Athletes were grouped into those sustaining a subsequent trabecular-rich BSI, a subsequent cortical-rich BSI, and those without a BSI. Data were analyzed with multinomial logistic regression adjusted for participation in cross-country running versus other sports., Results: A total of 19 participants sustained a cortical-rich BSI (6%) and 10 sustained a trabecular-rich BSI (3%) over the course of collegiate sports participation. The Triad cumulative risk score was significantly related to both trabecular-rich and cortical-rich BSI. However, lower BMD and weight were associated with significantly greater risk for trabecular-rich than cortical-rich BSIs. For every value lower than 1 SD, the odds ratios (95% CIs) for trabecular-rich versus cortical-rich BSI were 3.08 (1.25-7.56) for spine BMD; 2.38 (1.22-4.64) for whole-body BMD; and 5.26 (1.48-18.70) for weight. Taller height was a significantly better predictor of cortical-rich than trabecular-rich BSI., Conclusion: The Triad cumulative risk score was significantly associated with both trabecular-rich and cortical-rich BSI, but Triad-related risk factors appeared more strongly related to trabecular-rich BSI. In particular, low BMD and low weight were associated with significantly higher increases in the risk of trabecular-rich BSI than cortical-rich BSI. These findings suggest Triad risk factors are more common in athletes sustaining BSI in trabecular-rich than cortical-rich locations., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.S.T. has received research support from DJO and Uniform Health Services. M.F. has received consulting fees from Ipsen Bioscience and honoraria from Fidia Pharma. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Purpose: The Female Athlete Triad (Triad) is common in female athletes. The Triad is caused by low-energy availability (EA), which is often difficult to measure and has been postulated to be associated with low-iron status. Here, we explore whether markers of low-iron status may be associated with indicators of low EA including Triad risk factors., Methods: A total of 239 female National Collegiate Athletic Association Division I athletes completed preparticipation examinations that included Triad risk factors, medication/supplement use, diagnosis of anemia, and elected to complete dual-energy x-ray absorptiometry scan to measure bone mineral density. The association of markers of low iron (defined as self-report of iron supplementation and/or history of anemia) with each component of the Triad risk assessment score was assessed by stratifying low-iron status across different levels of Triad risk category. Differences across iron status groups were assessed using Fisher exact testing., Results: Every component of the Triad risk assessment score excluding delayed menarche was associated with low-iron status. The proportion of women who reported low iron was 11.5% in the low-risk EA group compared with 50% in the moderate-risk and 66.7% in the high-risk EA groups (P = 0.02); respectively. These numbers were 11.6%, 25.0%, and 66.7% (P = 0.02) for body mass index; 9.7%, 16.7%, and 25.0% (P < 0.05) for oligomenorrhea; 10.3%, 45.5%, and 50.0% (P < 0.01) for bone mineral density; and 10.4%, 20.8%, and 30.8% (P = 0.03) for history of stress reaction or fracture. Lean/endurance athletes were more likely to have low-iron status than other athletes (15.5% vs 3.4%, P = 0.02)., Conclusions: Markers for low-iron status were associated with Triad risk factors. Our study suggests that female athletes with a history of anemia or iron supplementation may require further screening for low EA., (Copyright © 2021 by the American College of Sports Medicine.)

Introduction: The study objectives were to estimate plasma flunixin (FLU) pharmacokinetic parameters and milk depletion profiles for FLU and its metabolite (5-hydroxy flunixin; 5-OH) after subcutaneous (SC) and intravenous (IV) administration of single and multiple flunixin meglumine (FM) doses to non-lactating (nulliparous and pregnant does) and lactating dairy goats. Analytical methods (ELISA and UPLC-MS/MS) for quantifying plasma FLU concentrations were compared. The final objective was to use regulatory (FDA and EMA) methods to estimate milk withdrawal intervals following extra-label drug use in goats. Methods: FM was administered IV and SC to commercial dairy goats at 1.1 mg/kg for single and multiple doses. Plasma and milk samples were analyzed for FLU and 5-OH via UPLC-MS/MS. Plasma samples were also analyzed for FLU concentrations via ELISA. Using statistical approaches recommended by regulatory agencies, milk withdrawal intervals were estimated following FM extra-label use. Results: Following IV administration of a single FM dose, clearances were 127, 199, and 365 ml/kg/h for non-lactating (NL) pregnant does, NL nulliparous does, and lactating dairy does, respectively. Following multiple SC doses, clearance/ F was 199 ml/kg/h for lactating does. After IV administration of a single FM dose, terminal elimination half-lives were 4.08, 2.87, and 3.77 h for NL pregnant does, NL nulliparous does, and lactating dairy does, respectively. After multiple SC doses, the terminal elimination half-life was 3.03 h for lactating dairy does. No significant differences were noted for samples analyzed by UPLC-MS/MS or ELISA. Milk withdrawal intervals ranged from 36 to 60 h depending on the regulatory statistical method and dosage regimen. Conclusions: Subcutaneous administration of FM to goats results in similar plasma pharmacokinetic parameters as IV administration. ELISA analysis is an alternative method to UPLC-MS/MS for quantifying FLU concentrations in caprine plasma samples. Following FM extra-label administration to dairy goats, clinicians could consider 36-60 h milk withdrawal intervals., (Copyright © 2020 Smith, Marmulak, Angelos, Lin, Rowe, Carlson, Shelver, Lee and Tell.)

Purpose: Athletes in weight-bearing sports may benefit from higher bone mineral density (BMD). However, some athletes are at risk for impaired BMD with female athlete triad (Triad). The purpose of this study is to understand the influence of sports participation and Triad on BMD. We hypothesize that athletes in high-impact and multidirectional loading sports will have highest BMD, whereas nonimpact and low-impact sports will have lowest BMD. Triad risk factors are expected to reduce BMD values independent of sports participation., Methods: Two hundred thirty-nine female athletes participating in 16 collegiate sports completed dual-energy x-ray absorptiometry (DXA) scans to measure BMD z-scores of the lumbar spine (LS) and total body (TB). Height and weight were measured to calculate body mass index (BMI). Triad risk assessment variables were obtained from preparticipation examination. Mean BMD z-scores were compared between sports and by sport category (high-impact, multidirectional, low-impact, and nonimpact). Multivariable regression analyses were performed to identify differences of BMD z-scores accounting for Triad and body size/composition., Results: Athlete populations with lowest average BMD z-scores included synchronized swimming (LS, -0.34; TB, 0.21) swimming/diving (LS, 0.34; TB, -0.06), crew/rowing (LS, 0.27; TB, 0.62), and cross-country (LS, 0.29; TB, 0.91). Highest values were in gymnastics (LS, 1.96; TB, 1.37), volleyball (LS, 1.90; TB, 1.74), basketball (LS, 1.73; TB, 1.99), and softball (LS, 1.68; TB, 1.78). All Triad risk factors were associated with lower BMD z-scores in univariable analyses; only low BMI and oligomenorrhea/amenorrhea were associated in multivariable analyses (all P < 0.05). Accounting for Triad risk factors and body size/composition, high-impact sports were associated with higher LS and TB BMD z-scores and nonimpact sports with lower LS and TB BMD z-scores compared to low-impact sport (all P < 0.05)., Conclusions: Both sport type and Triad risk factors influence BMD. Athletes in low-impact and nonimpact sports and athletes with low BMI and oligomenorrhea/amenorrhea are at highest risk for reduced BMD.

Resistant starches are non-digestible starches that are fermented in the colon by microbiota. These carbohydrates are prebiotic and can be beneficial to consumer health. Many types of resistant starch exist with varying physical properties that may result in differences in fermentability. The objective of this research project was to compare potential prebiotic effects and fermentability of four novel resistant starches using an in vitro fermentation system and measuring changes in total gas production, pH, and formation of SCFAs (short chain fatty acids). Fecal donations were collected from seven healthy volunteers. Four novel resistant starches, modified potato starch (MPS), modified tapioca starch (MTS), and modified maize starches (MMS-1 and MMS-2), were analyzed and compared to polydextrose and short chain fructooligosaccharides (FOS) as controls. After twenty-four hours of fermentation, MPS and MTS responded similarly in gas production (74 mL; 70.6 mL respectively), pH (5.93; 5.93 respectively), and SCFA production (Acetate: 115; 124, Propionate: 21; 26, Butyrate: 29; 31 μmol/mL respectively). While MMS-1 had similar gas production and individual SCFA production, the pH was significantly higher (6.06). The fermentation of MMS-2 produced the least amount of gas (22 mL), with a higher pH (6.34), and lower acetate production (78.4 μmol/mL). All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs., Competing Interests: M.L.S. is an employee of Ingredion Incorporated. J.L.S., J.M.E. and J.L.C. declare no conflict of interest.

Prebiotic dietary fibers act as carbon sources for primary and secondary fermentation pathways in the colon, and support digestive health in many ways. Fructooligosaccharides, inulin, and galactooligosaccharides are universally agreed-upon prebiotics. The objective of this paper is to summarize the 8 most prominent health benefits of prebiotic dietary fibers that are due to their fermentability by colonic microbiota, as well as summarize the 8 categories of prebiotic dietary fibers that support these health benefits. Although not all categories exhibit similar effects in human studies, all of these categories promote digestive health due to their fermentability. Scientific and regulatory definitions of prebiotics differ greatly, although health benefits of these compounds are uniformly agreed upon to be due to their fermentability by gut microbiota. Scientific evidence suggests that 8 categories of compounds all exhibit health benefits related to their metabolism by colonic taxa.

Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential prebiotic effects and fermentability of five commonly consumed fibers using an in vitro fermentation system measuring changes in fecal microbiota, total gas production and formation of common SCFAs. Fecal donations were collected from three healthy volunteers. Materials analyzed included: pure beta-glucan, Oatwell (commercially available oat-bran containing 22% oat β-glucan), xylooligosaccharides (XOS), WholeFiber (dried chicory root containing inulin, pectin, and hemi/celluloses), and pure inulin. Oatwell had the highest production of propionate at 12 h (4.76 μmol/mL) compared to inulin, WholeFiber and XOS samples ( p < 0.03). Oatwell's effect was similar to those of the pure beta-glucan samples, both samples promoted the highest mean propionate production at 24 h. XOS resulted in a significant increase in the genus Bifidobacterium after 24 h of fermentation (0 h:0.67 OTUs (operational taxonomic unit); 24 h:5.22 OTUs; p = 0.038). Inulin and WholeFiber increased the beneficial genus Collinsella , consistent with findings in clinical studies. All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Purpose: To determine the effect of dimethylfumarate (DMF), an inducer of glutathione (GSH)-dependent detoxification, on intracellular GSH levels in cultured human retinal pigment epithelium (hRPE) cells, its mechanism of action, and its effect on hRPE cells subjected to oxidative injury., Methods: Established hRPE cell lines were treated with DMF and assayed by high-pressure liquid chromatography for intracellular and extracellular GSH levels. Quantification of gamma-glutamylcysteine synthetase (GLCL) was determined through northern and western blot analyses, and activity was measured. Effects of pretreatment with DMF on GSH redox status of hRPE cells was determined. Sensitivity of hRPE cells to oxidative stress was determined using tert-butylhydroperoxide as the oxidative agent., Results: Dimethylfumarate caused a transient decrease followed by a significant increase in intracellular GSH. Glutathione increased maximally at 24 hours with 100 to 200 microM DMF. The initial decrease could be accounted for by the formation of a DMF-GSH conjugate. Dimethylfumarate treatment increased the steady state mRNA expression of the regulatory subunit of GLCL, but no increase was seen for the catalytic subunit. However, protein levels were increased for both, and the catalytic activity of GLCL was also increased. Whereas the initial decrease in GSH made hRPE cells more susceptible to oxidative damage, pretreatment with DMF under conditions that increased intracellular GSH protected hRPE cells against oxidative damage., Conclusions: These results suggest a means by which the antioxidant capability of hRPE may be augmented without direct antioxidant supplementation. Specifically, a dietary compound that conjugates with GSH can induce GSH synthesis, increase GSH concentration, and improve protection by GSH-dependent detoxification pathways in hRPE. However, the early depletion of GSH before stimulated synthesis necessitates caution in prevention strategies using dietary inducers.

Little is known about the growth and differentiation of the primary oocyte in the sexually mature chicken or turkey hen. In this study, primary oocytes from turkey hens in egg production were examined by light and electron microscopy. Based on oocyte and germinal vesicle (GV) diameters and organelle morphology and distribution, the sequential development of the primary oocyte was divided into five stages. No Balbiani body was observed in Stage I oocytes (< 80 microns in diameter). Pleomorphic mitochondria were localized around the GV and multivesicular bodies were scattered in the ooplasm. By Stage II (81 to 150 microns), the Balbiani body was observed adjacent to the GV. Pleomorphic mitochondria, macrobodies, and smooth endoplasmic reticulum (SER) were associated with the Balbiani body. Lipid droplets were predominantly localized to the periphery of the oocyte. The Balbiani body was partially dispersed by Stage III (151 to 350 microns) and associated organelles appeared in clusters in the ooplasm. Golgi and SER were observed immediately subjacent to the oolemma. Stage IV oocytes (351 to 500 microns) were characterized by the absence of the Balbiani body, a more centrally located GV, and the redistribution of the mitochondria to the periphery of the oocyte. Throughout the ooplasm was vesicular SER. By Stage V (501 to 800 microns), zonation of the organelles was completed with the mitochondrial ring immediately subjacent to the oolemma and a concentric layer of lipid droplets subjacent to the mitochondrial ring. The GV was in the periphery of the oocyte. Organelle and inclusion redistribution and organelle pleomorphism were presumed to be reflective of increasing metabolic and transport requirements of the growing oocyte in the mature turkey hen.