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Background: Congenital tibial dysplasia is a severe pediatric condition that classically results in a persistent pseudarthrosis. A majority of these cases are associated with neurofibromatosis type I (NF1), a genetic disorder in which inactivation of the NF1 gene leads to overactivity of the Ras-MEK-MAPK (mitogen-activated protein kinase) signaling pathway. We therefore hypothesized that pharmaceutical inhibition of MEK-MAPK may be a beneficial therapeutic strategy. Methods: In vitro methods were used to demonstrate a role for the MEK inhibitor PD0325901 in promoting osteogenic differentiation in Nf1-/- calvarial osteoblasts. Local applications of rhBMP-2 and/or PD0325901 were then tested in a mouse model of NF1 tibial pseudarthrosis featuring localized double inactivation of the Nf1 gene in a fracture. Mice received no treatment, PD0325901 (10 mg/kg/day from two days before fracture to ten days after fracture), rhBMP-2 (10 µg), or a combination of rhBMP-2 and PD0325901. Results: Animals treated with the delivery vehicle alone, PD0325901, rhBMP-2, or the PD0325901 + rhBMP-2 combination showed union rates of 0%, 8%, 69% (p < 0.01), or 80% (p < 0.01), respectively, at twenty-one days after fracture. Mice treated with the rhBMP-2 + PD0325901 combination displayed a callus volume sixfold greater than the vehicle controls and twofold greater than the group receiving rhBMP-2 alone. Although MEK inhibition combined with rhBMP-2 led to increases in bone formation and union, the proportion of fibrous tissue in the callus was not significantly reduced. Conclusions: The data suggest that MEK inhibition can promote bone formation in combination with rhBMP-2 in the context of an NF1 pseudarthrosis. However, PD0325901 did not promote substantive bone anabolism in the absence of an exogenous anabolic stimulus and did not suppress fibrosis. Clinical Relevance: This study examines a signaling pathway-based approach to treating poor bone healing in a model of NF1 pseudarthrosis. [ABSTRACT FROM AUTHOR]

Background: There is limited previous research that has examined level of Alzheimer's disease (AD) knowledge and misconceptions using a structured questionnaire across a range of samples. To address this gap, the current study investigated knowledge, knowledge gaps, and misconceptions about AD in a sample of noncarers, caregivers, and individuals with AD.Method: A modified version of the Alzheimer's Disease Knowledge (ADK) test was administered to 13 carers, 20 noncarer older adults, and 10 people with AD. Two sets of analyses were undertaken, first to identify group differences in the amount of knowledge reported by each group and second, to determine the nature of people's understanding of AD.Results: Overall level of knowledge in the 3 groups was quite poor. Although carers had significantly greater AD knowledge than noncarers or patients, carers correctly answered approximately 50% of items only. Relative to noncarers and AD patients, carers demonstrated a higher number of commonly held correct beliefs than participants in the other 2 groups, who held relatively few correct beliefs. All 3 groups had some misconceptions about AD.Conclusions: These findings suggest not only that education programs targeting the elderly community in general and AD patients specifically may be needed, but also that carer knowledge of AD could be further improved. Future educational interventions could be tailored to address the knowledge needs of each of the groups identified in this study. In particular, the need to address misconceptions and knowledge gaps shared by more than 1 group should be a priorit [ABSTRACT FROM AUTHOR]

Studies the uselessness of therapeutic shoes with customized cork or prefabricated inserts in preventing foot reulceration. Comparison of therapeutic shoes with the normal shoes; Occurrence of ulcers in patients lacking protective sensation; Need for multilayered or multidurometer inserts with patient-specific modifications in treating foot reulceration.

Objective: The chronic impact of acetylcholinesterase inhibitors and other toxicants on Gulf War (GW) veterans' health symptoms is unclear., Methods: Building on reports of adverse neuropsychological outcomes in GW pesticide applicators exposed to pesticides and pyridostigmine bromide, we now report on health symptoms in this group., Results: In adjusted analyses, applicators with high exposures/impact to pesticides reported significantly more symptoms (18/34 symptoms) than applicators with lower exposures/impact and were more likely to meet modified Kansas and CDC Gulf War Illness criteria. The high pyridostigmine bromide exposure/impact group was 3 times more likely to report irregular heart rates. With regard to specific pesticide types, fly baits, pest strips, and delousers were the most associated with increased health symptom reporting., Conclusions: These results suggest that GW veterans with high acetylcholinesterase inhibitor and organochlorine exposures are most at risk for chronic health symptoms., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another., Methods: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival., Results: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy., Conclusions: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Competing Interests: The authors declare no conflicts of interest.

Background: Incorporating social determinants of health (SDoH) into clinical decision-making can clarify disease causes, enhance care planning, and improve health outcomes. Nurse educators should know which strategies are most effective for teaching SDoH in bachelor of science in nursing (BSN) programs., Objective: This integrative review synthesizes the literature on familiarizing BSN students with SDoH and identifies effective teaching interventions for SDoH in these programs., Methods: The researchers searched CINAHL, PubMed, Web of Science, and ERIC databases, and 21 articles met the inclusion criteria. The PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines were followed for reporting., Results: The curriculum method, service learning, and international outreach experiences were frequently used teaching strategies. Qualitative evaluation was used to evaluate student outcomes., Conclusions: Nurse educators should be mindful of these strategies. Interdisciplinary teamwork can bolster students' understanding of disadvantaged populations while integrating SDoH in nursing curricula. Quantitative evaluations of learning outcomes are needed to determine teaching effectiveness., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Background: Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99m Tc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13 N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique., Methods: Accuracy was assessed in 34 participants who underwent dynamic 99m Tc-sestamibi SPECT and 13 N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99m Tc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio., Results: SPECT global MBF with splines showed good correlation with 13 N-ammonia positron emission tomography (r=0.81, P <0.001) and MFR estimates (r=0.74, P <0.001). Correlations were substantially weaker for standard reconstruction without splines (r=0.61, P <0.001 and r=0.34, P =0.07, for MBF and MFR, respectively). Reproducibility of global MBF estimates with splines in paired SPECT scans was good (r=0.77, P <0.001), while ordered subset expectation maximization without splines led to decreased MBF (r=0.68, P <0.001) and MFR correlations (r=0.33, P =0.3). There were no significant differences in MBF or MFR between the 2 reproducibility scans independently of the reconstruction algorithm ( P >0.05 for all)., Conclusions: MBF and MFR quantification using 99m Tc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13 N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation.

Background and Objectives: To review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians., Methods: A multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence., Results: Initial treatment with levodopa provides superior motor benefit compared to treatment with dopamine agonists, whereas levodopa is more likely than dopamine agonists to cause dyskinesia. The comparison of different formulations of dopamine agonists yielded little evidence that any one formulation or method of administration is superior. Long-acting forms of levodopa and levodopa with entacapone do not appear to differ in efficacy from immediate-release levodopa for motor symptoms in early disease. There is a higher risk of impulse control disorders associated with the use of dopamine agonists than levodopa. Recommendations on initial therapy for motor symptoms are provided to assist the clinician and patient in choosing between treatment options and to guide counseling, prescribing, and monitoring of efficacy and safety., (© 2021 American Academy of Neurology.)

Purpose: The purpose of the study was to compare a single two-dimensional image processing system (IMAGE) to underwater weighing (UWW) for measuring body volume (BV) and subsequently estimating body fat percentage (%Fat), fat mass (FM), and fat-free mass (FFM) via a 3-compartment (3C) model., Methods: A sample of participants age 18-39 yr was recruited for this study (n = 67, 47.8% female). BV was measured with UWW and predicted via the IMAGE software. The BV estimates from UWW (3CUWW) and IMAGE (3CIMAGE) were separately combined with constant total body water and body mass values for 3C model calculation of %Fat, FM, and FFM., Results: BV obtained from the IMAGE was 67.76 ± 12.19 and 67.72 ± 12.04 L from UWW, which was not significantly different (P = 0.578) and very largely correlated (r = 0.99, P < 0.001). When converted to %Fat (3CUWW = 21.01% ± 7.30%, 3CIMAGE = 21.08% ± 7.04%, P = 0.775), FM (3CUWW = 14.68 ± 5.15 kg, 3CIMAGE = 14.78 ± 5.08 kg, P = 0.578), and FFM (3CUWW = 57.00 ± 13.20 kg, 3CIMAGE = 56.90 ± 12.84 kg, P = 0.578) with the 3C model, no significant mean differences and very large correlations (r values ranged from 0.96 to 0.99) were observed. In addition, the standard error of estimate, total error, and 95% limits of agreement for all three metrics were small and considered acceptable., Conclusions: An IMAGE system provides valid estimates of BV that accurately estimates body composition in a 3C model., (Copyright © 2020 by the American College of Sports Medicine.)

Objectives: The aim of this study was to characterize national variation in radionuclide calibrator activity response to a single National Institute of Standards and Technology (NIST) traceable reference Ge source used as a surrogate for F at clinical PET centres in England using National Physical Laboratory approved techniques., Methods: Readings from 20 instruments at 13 centres using local F and Ge factor settings were recorded with the source located in vial and syringe positions. Ten repeat measurements were conducted to investigate repeatability using % coefficient of variability (COV). Comparison ratios to investigate accuracy were made between calibrator responses and decay-corrected NISTref reference activity for syringe and vial position measurements., Results: The maximum %COV was 0.79%, while 90, 95 and 80% of calibrators conformed to 5% accuracy for F syringe, Ge syringe and Ge vial position readings, respectively. We revealed a trend towards reduced bias in measurements using Veenstra devices for F and using Capintec devices for Ge factor settings., Conclusions: This study demonstrated good repeatability in local device measurements. In total, 70% of English calibrators tested and 88% of all measurements performed achieved 5% accuracy. While statistically significant bias was exhibited between different vendor equipment dependent upon radioisotope selected, our study recommends regular traceability checks for optimum instrument performance conducted within National Metrology Institutes guidelines.