Linking Immigrants with Nutrition Knowledge (Project LINK): An Innovative Approach to Improve Cultural Competence in Dietetic Education.

Linking Immigrants with Nutrition Knowledge (Project LINK) was a service-learning cultural competence training programme completed by undergraduate dietetic students enrolled in the University of Saskatchewan's (USASK) nutrition and dietetic programme.This paper evaluates the impact of participation in the programme on students' cultural competence. We conducted a cross-sectional survey and qualitative analysis of reflective essays of 107 participants of Project LINK from 2011 to 2014. Cumulative logistic regression models assessed the impact of the intervention on students' cultural competencies. The Akaike information criterion compared models and Spearman correlation coefficient identified possible correlation among pre- and post-intervention data points. Student reflective essays were analyzed by inductive thematic analysis.All cultural competencies improved comparing pre- and post-participation in Project LINK. Odds of increasing one level of student knowledge were 110 times of that prior to Project LINK. Comparing student competencies before and after Project LINK, the odds of increasing one level of students' skills were six times greater, five times greater for increasing one level of students' ability to interact or encounter, and 2.8 times greater for increasing one level of students' attitude.The results of this study indicate Project LINK has successfully increased cultural competence and underscores the importance of combining opportunities for practical experience in addition to classroom-based training on cultural competence.

Some Drugs Have Two Faces: Paradoxical Colitis in a Patient with Psoriatic Arthritis Previously Treated with Etanercept and IL-17 Inhibitors.

Tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) inhibitors are among the most potent treatments for inflammatory arthropathies including rheumatoid arthritis, psoriasis, and spondyloarthropathies. The availability of these biologic agents have revolutionized the management of these conditions and improved patient outcomes. Though generally safe, these biologics may contribute to the induction or exacerbation of colitis. This paradoxical colitis has been observed in patients on TNF-α inhibitor etanercept and IL-17 inhibitors (secukinumab and ixekizumab). We report a case of a 46-year-old female with psoriasis and psoriatic arthritis who presented with gastrointestinal symptoms after treatment with etanercept and IL-17 inhibitors. She was later diagnosed with paradoxical indeterminate colitis that was masked and treated by subsequent biologics given for her RA and psoriatic arthritis. In this report, we will discuss the importance of considering paradoxical colitis in the differential diagnosis for patients even several years after TNF-α/IL-17 inhibitor initiation and explain why careful consideration must be made when initiating these colitis-inducing agents to treat patients with inflammatory disorders.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.

Thyroid hormone receptor alpha modulates fibrogenesis in hepatic stellate cells.

OBJECTIVE: Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells (HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly affect development, growth, cell differentiation and metabolism through activation of TH receptor α and/or ß (TRα/ß). Here, we evaluated the influence of TH in hepatic fibrogenesis. DESIGN: Human liver tissue was obtained from explanted livers following transplantation. TRα-deficient (TRα-KO) and wild-type (WT) mice were fed a control or a profibrogenic methionine-choline deficient (MCD) diet. Liver tissue was assessed by qRT-PCR for fibrogenic gene expression. In vitro, HSC were treated with TGFß in the presence or absence of T3. HSC with stable TRα knockdown and TRα deficient mouse embryonic fibroblasts (MEF) were used to determine receptor-specific function. Activation of HSC and MEF was assessed using the wound healing assay, Western blotting, and qRT-PCR. RESULTS: TRα and TRß expression is downregulated in the liver during hepatic fibrogenesis in humans and mice. TRα represents the dominant isoform in HSC. In vitro, T3 blunted TGFß-induced expression of fibrogenic genes in HSC and abrogated wound healing by modulating TGFß signalling, which depended on TRα presence. In vivo, TRα-KO enhanced MCD diet-induced liver fibrogenesis. CONCLUSION: These observations indicate that TH action in non-parenchymal cells is highly relevant. The interaction of TRα with TH regulates the phenotype of HSC via the TGFß signalling pathway. Thus, the TH-TR axis may be a valuable target for future therapy of liver fibrosis.

DGKα/ζ inhibitors combine with PD-1 checkpoint therapy to promote T cell-mediated antitumor immunity.

Programmed cell death protein 1 (PD-1) immune checkpoint blockade therapy has revolutionized cancer treatment. Although PD-1 blockade is effective in a subset of patients with cancer, many fail to respond because of either primary or acquired resistance. Thus, next-generation strategies are needed to expand the depth and breadth of clinical responses. Toward this end, we designed a human primary T cell phenotypic high-throughput screening strategy to identify small molecules with distinct and complementary mechanisms of action to PD-1 checkpoint blockade. Through these efforts, we selected and optimized a chemical series that showed robust potentiation of T cell activation and combinatorial activity with αPD-1 blockade. Target identification was facilitated by chemical proteomic profiling with a lipid-based photoaffinity probe, which displayed enhanced binding to diacylglycerol kinase α (DGKα) in the presence of the active compound, a phenomenon that correlated with the translocation of DGKα to the plasma membrane. We further found that optimized leads within this chemical series were potent and selective inhibitors of both DGKα and DGKζ, lipid kinases that constitute an intracellular T cell checkpoint that blunts T cell signaling through diacylglycerol metabolism. We show that dual DGKα/ζ inhibition amplified suboptimal T cell receptor signaling mediated by low-affinity antigen presentation and low major histocompatibility complex class I expression on tumor cells, both hallmarks of resistance to PD-1 blockade. In addition, DGKα/ζ inhibitors combined with αPD-1 therapy to elicit robust tumor regression in syngeneic mouse tumor models. Together, these findings support targeting DGKα/ζ as a next-generation T cell immune checkpoint strategy.

The Process Model of Stigmatized Loss: Identity-Threatened Experiences of Bereaved Mothers.

Despite almost one-third of women suffering from the loss of a baby through miscarriage, stillbirth, or infant loss, it is surprising how little research examines how such loss affects the identity and stigmas experienced by these individuals. Through in-depth, semi-structured interviews with bereaved mothers (in particular, mothers who lost a baby during pregnancy or within one year after birth), this research sheds light on the bereaved mother's experiences after loss. Specifically, this research applies the identity-threat model of stigma to showcase the process of stigmatized loss. Based on our findings, we also introduce the process model of stigmatized loss that can apply to all types of stigmatized loss. Key themes emerged as we explored stigmatized loss discourses. These include situational cues that trigger stigma, identity-based responses that aim to preserve both a baby's and mother's identity, as well as nonvolitional and volitional responses that help restore control and reconstruct identity. Additionally, other themes revolve around positive and negative outcomes stemming from avoiding stigmatized identity activation and identification of triggers that initiate a recursive process through stigmatized baby loss. Importantly, stigma can be perceived as both an identity threat (negative) and an identity confirmation (positive). Findings inform theory and practice alike.

SARS-CoV-2 infections in patients enrolled on the Children's Oncology Group standard-risk B-cell acute lymphoblastic leukemia trial, AALL1731.

Hematologic malignancy is a risk factor for severe coronavirus disease 2019 (COVID-19) in adults; however, data specific to children with leukemia are limited. High-quality infectious adverse event data from the ongoing Children's Oncology Group (COG) standard-risk B acute lymphoblastic leukemia/lymphoma (ALL/LLy) trial, AALL1731, were analyzed to provide a disease-specific estimate of SARS-CoV-2 infection outcomes in pediatric ALL. Of 253 patients with reported infections, the majority (77.1%) were asymptomatic or mildly symptomatic (CTCAE grade 1/2) and there was a single COVID-19-related death. These data suggest SARS-CoV-2 infection does not confer substantial morbidity among young patients with B-lymphoblastic leukemia/lymphoma (B-ALL/LLy).

Performance of a Large Language Model on Practice Questions for the Neonatal Board Examination.

This Diagnostic/Prognostic Study evaluates the performance of a large language model in generating answers to practice questions for the neonatal-perinatal board examination.

AFX unibody stent graft: Effective and safe for the treatment of severe aorto-iliac occlusive disease.

OBJECTIVES: The primary objective of this study was to determine the primary, assisted primary and secondary patency rates of the Endologix AFX stent-graft in patients considered high risk for open surgery with complex aorto-iliac occlusive disease. The secondary objective was to determine 30-day major adverse cardiovascular and cerebrovascular events. METHODS: A retrospective review was undertaken of clinical records of 38 patients who underwent AFX stent-graft placement for aorto-iliac occlusive disease from 2016 to 2019. Patient data was de-identified and entered into a REDcap secure database. Descriptive statistical analysis (means and standard deviations) and Kaplan-Meier survival curves were created to determine the duration of patency of the AFX stent-graft system. RESULTS: Primary patency rates at 6, 12 and 24 months were 92%, 92% and 84%, respectively. Assisted primary patency rates at these times were 100%, 100% and 93% with secondary patency of 100% maintained throughout. The incidence of 30-day major adverse cardiovascular and cerebrovascular events was 8% and major adverse limb events was 3%. One death unrelated to the AFX device occurred during the study period though outside of the 30-day peri-operative period. CONCLUSIONS: Primary, assisted primary and secondary patency rates of AFX stent-grafts, when used to treat aorto-iliac occlusive disease, are high. This study supports the use of the AFX stent-graft for the endovascular treatment of complex aorto-iliac occlusive disease as an alternative to other endovascular options as well as a safe alternative to open aorto-iliac or aorto-femoral bypass in patients who are at high risk for open procedures.

Split Spinal Cord Malformation Fed by Bilateral, Enlarged Radiculopial Arteries.

Anatomical variations of the spinal cord are seen in many manifestations; one rare variant that does not stem from a neural tube defect is known as a split cord malformation (SCM). In this variation, a deviation from normal development causes the spinal cord to divide into two hemicords, typically in the lumbar region. In the case described here, a SCM was observed with large, bilateral, radiculopial arteries. To our knowledge, such large vessels in conjunction with a SCM has not previously been documented in the literature. Such variants could be problematic during surgical approaches to the lumbar spine. Herein, we report the case and discuss the development of the findings with relevant clinical applications.

Minimal residual disease predicts outcomes in KMT2A-rearranged but not KMT2A-germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631.

We measured minimal residual disease (MRD) by multiparameter flow cytometry at three time points (TP) in 117 infants with KMT2A (lysine [K]-specific methyltransferase 2A)-rearranged and 58 with KMT2A-germline acute lymphoblastic leukemia (ALL) on Children's Oncology Group AALL0631 study. For KMT2A-rearranged patients, 3-year event-free survival (EFS) by MRD-positive (≥0.01%) versus MRD-negative (<0.01%) was: TP1: 25% (±6%) versus 49% (±7%; p = .0009); TP2: 21% (±8%) versus 47% (±7%; p < .0001); and TP3: 22% (±14%) versus 51% (±6%; p = .0178). For KMT2A-germline patients, 3-year EFS was: TP1: 88% (±12%) versus 87% (±5%; p = .73); TP2: 100% versus 88% (±5%; p = .24); and TP3: 100% versus 87% (±5%; p = .53). MRD was a strong independent outcome predictor in KMT2A-rearranged, but not KMT2A-germline infant ALL.

National Needs Assessment of Utilization of Common Newborn Clinical Decision Support Tools.

OBJECTIVE: Clinical decision support tools (CDSTs) are common in neonatology, but utilization is rarely examined. We examined the utilization of four CDSTs in newborn care. STUDY DESIGN: A 72-field needs assessment was developed. It was distributed to listservs encompassing trainees, nurse practitioners, hospitalists, and attendings. At the conclusion of data collection, responses were downloaded and analyzed. RESULTS: We received 339 fully completed questionnaires. BiliTool and the Early-Onset Sepsis (EOS) tool were used by > 90% of respondents, the Bronchopulmonary Dysplasia tool by 39%, and the Extremely Preterm Birth tool by 72%. Common reasons CDSTs did not impact clinical care included lack of electronic health record integration, lack of confidence in prediction accuracy, and unhelpful predictions. CONCLUSION: From a national sample of neonatal care providers, there is frequent but variable use of four CDSTs. Understanding the factors that contribute to tool utility is vital prior to development and implementation. KEY POINTS: · Clinical decision support tools are common in medicine.. · There is a varied use of neonatal CDST.. · Understanding the use of CDST is vital for future development..

Incidence and Trends of High Tibial Osteotomy and Unicompartmental Knee Arthroplasty Over the Past Decade: A Lost Art.

Background: After failed nonoperative treatment, unicompartmental osteoarthritis can be treated surgically by either unicompartmental knee arthroplasty (UKA) or high tibial osteotomy (HTO). The purpose of this retrospective study is to analyze utilization and demographic trends of UKA and HTO relative to total knee arthroplasty (TKA) over the past decade. Methods: A retrospective review was conducted using the PearlDiver database. Patients that received a UKA or HTO were identified. Trend analyses of surgical procedure utilization were performed with the Mann-Kendall trend test. Demographic data and the rates of various comorbidities were also queried. Results: A total of 103,465 UKAs, 2183 HTOs, and 1,413,425 TKAs, between 2010 and 2021 quarter 1, were analyzed. Trend analyses revealed that relative to TKA utilization, UKA utilization significantly increased (P < .001) while HTO utilization significantly decreased (P < .001). The compound annual growth rate of UKA utilization relative to TKA was +5.16% from 2010 to 2017 but was -10.61% from 2018 to 2021, while that of HTO relative to TKA was -9.69% from 2010 to 2021. Demographic analyses demonstrated the UKA cohort (63.1) was significantly older than the HTO cohort (46.5) (P < .001). Additionally, there were significantly more female patients who underwent UKA than HTO (P < .001). Conclusions: The present study demonstrated that relative to TKA, UKA utilization increased from 2010 to 2017, with a subsequent decrease afterward, whereas HTO utilization decreased since 2010. Demographic differences exist between the 2 operations, with HTOs more commonly performed in younger male patients, and UKAs in older female patients. Level of Evidence: Level III.

Part II: Risk Factors for Stress Fractures in Female Military Recruits.

INTRODUCTION: Stress fractures (SFx) represent a significant proportion of injuries in military recruits internationally. Stress fractures disproportionately affect female recruits, a disparity that has similarly been consistently demonstrated in female athletes. Stress fractures result in medical morbidity, financial burden, and medical discharge from military service. This review presents current literature regarding SFx risk factors to identify and/or mitigate in this high-risk population. METHODS: A literature review was conducted using PubMed to find relevant articles. We utilized keywords stress fracture, military, recruits, female, risk factors, modifiable, non-modifiable, overuse, nutrition, and/or prevention. Articles older than 10 years (published before 2010) were not considered. Review articles were considered, but if a research article was cited by a review, the research was included directly. Articles with primary military data, members of the military as subjects, especially when female recruits were included, were strongly considered for inclusion in this review. RESULTS: Modifiable risk factors for SFx include nutritional deficiency, especially of iron, vitamin D, and possibly calcium, poor physical fitness, suboptimal training programming for injury development and recovery, load carriage, and military footwear. Non-modifiable risk factors include female sex, greater height, lower weight and body mass index in females but lower or higher weight and body mass index in males, lower body fat percentage, and lower bone mineral density. In addition, menstrual dysfunction, low energy availability, later age at menarche, and iron deficiency pose unique risks to female recruits. Preventive measures include leadership education, programs with recovery considerations, and risk factor screening. CONCLUSION: This review, Part II of a two-part series, guides multidisciplinary management of military recruits, especially females, who are at risk for developing SFx. Unique nuances of the military recruit require specific knowledge to reduce high incidence rates of injury internationally.

Part I: Background and Clinical Considerations for Stress Fractures in Female Military Recruits.

INTRODUCTION: Stress fractures (SFx) represent a significant proportion of musculoskeletal injuries in military recruits internationally. Incidence rates as high as 40% have been reported, varying by country and branch of military cohorts. Tibial SFx are the most common, followed by other lower extremity sites, and are related to the emphasis on running during training. SFx disproportionately affect female recruits, similarly to a disparity demonstrated in female athletes. METHODS: A literature review of articles relevant to our review was conducted using PubMed, utilizing keywords stress fracture, military, recruits, diagnosis, management, treatment, prevention, epidemiology, background, and/or female. Articles older than 10 years old (prior to 2010) were not considered. Review articles were considered, but if a research article was cited by a review, the research was included directly. Articles with primary military data, members of the military as subjects, especially when female recruits were included, were strongly considered for inclusion in this review. RESULTS: SFx can cause medical morbidity and financial burden and can require discharge from military service. SFx management in the military has cost the United States approximately $100 million annually, which may be underestimated due to lost duty hours or medical discharge with resulting compensation. However, SFx incidence rates have been demonstrated to be reducible with concerted efforts in military cohorts. CONCLUSION: This review, Part I of a two-part series, provides updated information for multidisciplinary management of SFx in female military recruits. There are many similarities to management in athletes, but unique nuances of the military recruit require specific knowledge to reduce the high incidence rates of injury.