American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

Prospective correction of patient-specific respiratory motion in myocardial T1 and T2 mapping.

PURPOSE: Respiratory motion in cardiovascular MRI presents a challenging problem with many potential solutions. Current approaches require breath-holds, apply retrospective image registration, or significantly increase scan time by respiratory gating. Myocardial T1 and T2 mapping techniques are particularly sensitive to motion as they require multiple source images to be accurately aligned prior to the estimation of tissue relaxation. We propose a patient-specific prospective motion correction (PROCO) strategy that corrects respiratory motion on the fly with the goal of reducing the spatial variation of myocardial parametric mapping techniques. METHODS: A rapid, patient-specific training scan was performed to characterize respiration-induced motion of the heart relative to a diaphragmatic navigator, and a parametric mapping pulse sequence utilized the resulting motion model to prospectively update the scan plane in real-time. Midventricular short-axis T1 and T2 maps were acquired under breath-hold or free-breathing conditions with and without PROCO in 7 healthy volunteers and 3 patients. T1 and T2 were measured in 6 segments and compared to reference standard breath-hold measurements using Bland-Altman analysis. RESULTS: PROCO significantly reduced the spatial variation of parametric maps acquired during free-breathing, producing limits of agreement of -47.16 to 30.98 ms (T1 ) and -1.35 to 4.02 ms (T2 ), compared to -67.77 to 74.34 ms (T1 ) and -2.21 to 5.62 ms (T2 ) for free-breathing acquisition without PROCO. CONCLUSION: Patient-specific respiratory PROCO method significantly reduced the spatial variation of myocardial T1 and T2 mapping, while allowing for 100% efficient free-breathing acquisitions.

Clade I TGACG-Motif Binding Basic Leucine Zipper Transcription Factors Mediate BLADE-ON-PETIOLE-Dependent Regulation of Development.

Lateral organs formed by the shoot apical meristem (SAM) are separated from surrounding stem cells by regions of low growth called boundaries. Arabidopsis (Arabidopsis thaliana) BLADE-ON-PETIOLE1 (BOP1) and BOP2 represent a class of genes important for boundary patterning in land plants. Members of this family lack a DNA-binding domain and interact with TGACG-motif binding (TGA) basic Leu zipper (bZIP) transcription factors for recruitment to DNA. Here, we show that clade I bZIP transcription factors TGA1 and TGA4, previously associated with plant defense, are essential cofactors in BOP-dependent regulation of development. TGA1 and TGA4 are expressed at organ boundaries and function in the same genetic pathways as BOP1 and BOP2 required for SAM maintenance, flowering, and inflorescence architecture. Further, we show that clade I TGAs interact constitutively with BOP1 and BOP2, contributing to activation of ARABIDOPSIS THALIANA HOMEOBOX GENE1, which is needed for boundary establishment. These studies expand the functional repertoire of clade I TGA factors in development and defense.

Patient specific prospective respiratory motion correction for efficient, free-breathing cardiovascular MRI.

PURPOSE: To develop a patient-specific respiratory motion correction technique with true 100% acquisition efficiency. METHODS: A short training scan consisting of a series of single heartbeat images, each acquired with a preceding diaphragmatic navigator, was performed to fit a model relating the patient-specific 3D respiratory motion of the heart-to-diaphragm position. The resulting motion model was then used to update the imaging plane in real-time to correct for translational motion based on respiratory position provided by the navigator. The method was tested in a group of 11 volunteers with 5 separate free-breathing acquisitions: FB, no motion correction; FB-TF, free breathing with a linear tracking factor; Nav Gate, navigator gating; Nav Gate-TF, navigator gating with a tracking factor; and PROCO, prospective motion correction (proposed). Each acquisition lasted for 50 accepted heartbeats, where non-gated scans had a 100% acceptance rate, and gated scans accepted data only within a ±4 mm navigator window. Retrospective image registration was used to measure residual motion and determine the effectiveness of each method. RESULTS: PROCO reduced the range/RMSE of residual motion to 4.08 ± 1.4/0.90 ± 0.3 mm, compared to 10.78 ± 6.9/2.97 ± 2.2 mm for FB, 5.32 ± 2.92/1.24 ± 0.8 mm for FB-TF, 4.08 ± 1.6/0.93 ± 0.4 mm for Nav Gate, and 2.90 ± 1.0/0.63 ± 0.2 mm for Nav Gate-TF. Nav Gate and Nav Gate-TF reduced scan efficiency to 48.84 ± 9.31% and 54.54 ± 10.12%, respectively. CONCLUSION: PROCO successfully limited the residual motion in single-shot imaging to the level of traditional navigator gating while maintaining 100% acquisition efficiency.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE - EXECUTIVE SUMMARYComplete Appendix to Guidelines available at http://journals.aace.com.

OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Each Recommendation is based on a diligent review of the clinical evidence with transparent incorporation of subjective factors. RESULTS: The Executive Summary of this document contains 87 Recommendations of which 45 are Grade A (51.7%), 18 are Grade B (20.7%), 15 are Grade C (17.2%), and 9 (10.3%) are Grade D. These detailed, evidence-based recommendations allow for nuance-based clinical decision making that addresses multiple aspects of real-world medical care. The evidence base presented in the subsequent Appendix provides relevant supporting information for Executive Summary Recommendations. This update contains 695 citations of which 202 (29.1 %) are evidence level (EL) 1 (strong), 137 (19.7%) are EL 2 (intermediate), 119 (17.1%) are EL 3 (weak), and 237 (34.1%) are EL 4 (no clinical evidence). CONCLUSION: This CPG is a practical tool that endocrinologists, other healthcare professionals, regulatory bodies and health-related organizations can use to reduce the risks and consequences of dyslipidemia. It provides guidance on screening, risk assessment, and treatment recommendations for a range of patients with various lipid disorders. These recommendations emphasize the importance of treating low-density lipoprotein cholesterol (LDL-C) in some individuals to lower goals than previously recommended and support the measurement of coronary artery calcium scores and inflammatory markers to help stratify risk. Special consideration is given to patients with diabetes, familial hypercholesterolemia, women, and pediatric patients with dyslipidemia. Both clinical and cost-effectiveness data are provided to support treatment decisions. ABBREVIATIONS: A1C = hemoglobin A1C ACE = American College of Endocrinology ACS = acute coronary syndrome AHA = American Heart Association ASCVD = atherosclerotic cardiovascular disease ATP = Adult Treatment Panel apo = apolipoprotein BEL = best evidence level CKD = chronic kidney disease CPG = clinical practice guidelines CVA = cerebrovascular accident EL = evidence level FH = familial hypercholesterolemia HDL-C = high-density lipoprotein cholesterol HeFH = heterozygous familial hypercholesterolemia HIV = human immunodeficiency virus HoFH = homozygous familial hypercholesterolemia hsCRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol Lp-PLA2 = lipoprotein-associated phospholipase A2 MESA = Multi-Ethnic Study of Atherosclerosis MetS = metabolic syndrome MI = myocardial infarction NCEP = National Cholesterol Education Program PCOS = polycystic ovary syndrome PCSK9 = proprotein convertase subtilisin/kexin type 9 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus TG = triglycerides VLDL-C = very low-density lipoprotein cholesterol.

Tier-specific evolution of match performance characteristics in the English Premier League: it's getting tougher at the top.

This study investigated the evolution of physical and technical performances in the English Premier League (EPL), with special reference to league ranking. Match performance observations (n = 14,700) were collected using a multiple-camera computerised tracking system across seven consecutive EPL seasons (2006-07 to 2012-13). Final league rankings were classified into Tiers: (A) 1st-4th ranking (n = 2519), (B) 5th-8th ranking (n = 2965), (C) 9th-14th ranking (n = 4448) and (D) 15th-20th ranking (n = 4768). Teams in Tier B demonstrated moderate increases in high-intensity running distance while in ball possession from the 2006-07 to 2012-13 season (P < 0.001; effect size [ES]: 0.68), with Tiers A, C and D producing less pronounced increases across the same period (P < 0.005; ES: 0.26, 0.41 and 0.33, respectively). Large increases in sprint distance were observed from the 2006-07 to 2012-13 season for Tier B (P < 0.001; ES: 1.21), while only moderate increases were evident for Tiers A, C and D (P < 0.001; ES: 0.75, 0.97 and 0.84, respectively). Tier B demonstrated large increases in the number of passes performed and received in 2012-13 compared to 2006-07 (P < 0.001; ES: 1.32-1.53) with small-to-moderate increases in Tier A (P < 0.001; ES: 0.30-0.38), Tier C (P < 0.001; ES: 0.46-0.54) and Tier D (P < 0.001; ES: 0.69-0.87). The demarcation line between 4th (bottom of Tier A) and 5th ranking (top of Tier B) in the 2006-07 season was 8 points, but this decreased to just a single point in the 2012-13 season. The data demonstrate that physical and technical performances have evolved more in Tier B than any other Tier in the EPL and could indicate a narrowing of the performance gap between the top two Tiers.

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2015 EXECUTIVE SUMMARY.

This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

A persistent, symptomatic urinary tract infection with multiple "negative" urine cultures.

While urinary tract infections (UTIs) are often suspected on the basis of clinical symptoms and the finding of pyuria on urinalysis, the documentation of a bacterial UTI is based on the significant growth ofa uropathogen on an agar medium incubated at 35-37 degrees C. The recommended length of time for incubation has ranged from 24 to 48 hours. We present a case of a UTI associated with the slow-growing, gram-negative organism, Oligella ureolytica which was finally documented after incubation of an agar medium for more than 48 hours.

Evidence for adaptation of Rhagoletis pomonella (Diptera: Tephritidae) on large-thorn hawthorn, Crataegus macracantha, in Okanogan County, Washington State, USA.

The apple maggot fly, Rhagoletis pomonella (Walsh) (Diptera: Tephritidae), was introduced from eastern North America into western North America via infested apples (Malus domestica Borkhausen) about 44 yr ago, where it subsequently adapted to 2 hawthorn species, Crataegus douglasii Lindley and C. monogyna Jacquin. Here, we test whether R. pomonella has also adapted to large-thorn hawthorn, Crataegus macracantha Loddiges ex Loudon, in Okanogan County, Washington State, USA. In 2020, 2021, and 2022, fruit of C. macracantha were shown to ripen in late September and were infested at rates from 0.7% to 3.0%. In laboratory rearing studies, large-thorn hawthorn flies from C. macracantha eclosed on average 9-19 days later than apple flies from earlier ripening apple (August-early September), consistent with large-thorn hawthorn flies having adapted to the later fruiting phenology of its host. In a laboratory no-choice test, significantly fewer (64.8%) large-thorn hawthorn than apple flies visited apples. In choice tests, greater percentages of large-thorn hawthorn than apple flies resided on and oviposited into C. macracantha versus apple fruit. Large-thorn hawthorn flies were also smaller in size than apple flies. Our results provide further support for the recursive adaptation hypothesis that R. pomonella has rapidly and independently specialized phenologically and behaviorally to different novel hawthorn hosts since its introduction into the Pacific Northwest of the USA, potentially leading to host race formation.

Valuing adaptive programming: A study of resilience processes and outcomes.

Recent decades have seen a growth in theoretical frameworks focusing on systems, context and the dynamic interplay of multiple variables, stimulating interest in complementary research and programme evaluation methods. With resilience theory now emphasising the complex and dynamic nature of resilience capacities, processes and outcomes, resilience programming stands to benefit from approaches such as design-based research and realist research/evaluation. The aim of this collaborative (researcher/practitioner) study was to explore how such benefits can be achieved when programme theory spans individual, community and institutional outcomes, with a focus on the reciprocal processes involved in effecting change across the social system. The context of the research was a regional (Middle East and North Africa) project operating in contexts with an escalated risk of marginalised young people being drawn into illegal/harmful activity. The project's youth engagement and development approach combined participatory learning, skills training, and collective social action, adapted for diverse localities and during the COVID-19 crisis. Quantitative measures of individual and collective resilience were at the centre of a set of realist analyses evidencing systemic connections in changes to individual, collective and community resilience. Findings demonstrated the value, challenges and limitations of the applied research approach for adaptive, contextualised programming.

A Rare Case of Undifferentiated Rhabdoid Carcinoma of the Colon.

Rhabdoid carcinoma of the colon is a rare type of malignancy that belongs to the family of malignant rhabdoid tumors (MRTs). This is infrequently encountered in clinical settings therefore data regarding treatment is lacking. Herein we discuss an elderly female patient who presented with severe abdominal pain in the setting of a gastrointestinal perforation. Imaging showed a large mass in the transverse colon, which was found to be an undifferentiated carcinoma of the colon with rhabdoid features. We highlight this case to discuss the clinical course of the patient, thereby adding to the limited literature that is available, as well as review the few studies that have, thus far, documented this rare presentation.

Arabidopsis basic leucine-zipper transcription factors TGA9 and TGA10 interact with floral glutaredoxins ROXY1 and ROXY2 and are redundantly required for anther development.

ROXY1 and ROXY2 are CC-type floral glutaredoxins with redundant functions in Arabidopsis (Arabidopsis thaliana) anther development. We show here that plants lacking the basic leucine-zipper transcription factors TGA9 and TGA10 have defects in male gametogenesis that are strikingly similar to those in roxy1 roxy2 mutants. In tga9 tga10 mutants, adaxial and abaxial anther lobe development is differentially affected, with early steps in anther development blocked in adaxial lobes and later steps affected in abaxial lobes. Distinct from roxy1 roxy2, microspore development in abaxial anther lobes proceeds to a later stage with the production of inviable pollen grains contained within nondehiscent anthers. Histological analysis shows multiple defects in the anther dehiscence program, including abnormal stability and lignification of the middle layer and defects in septum and stomium function. Compatible with these defects, TGA9 and TGA10 are expressed throughout early anther primordia but resolve to the middle and tapetum layers during meiosis of pollen mother cells. Several lines of evidence suggest that ROXY promotion of anther development is mediated in part by TGA9 and TGA10. First, TGA9 and TGA10 expression overlaps with ROXY1/2 during anther development. Second, TGA9/10 and ROXY1/2 operate downstream of SPOROCYTELESS/NOZZLE, where they positively regulate a common set of genes that contribute to tapetal development. Third, TGA9 and TGA10 directly interact with ROXY proteins in yeast and in plant cell nuclei. These findings suggest that activation of TGA9/10 transcription factors by ROXY-mediated modification of cysteine residues promotes anther development, thus broadening our understanding of how redox-regulated TGA factors function in plants.

Automated detection of critical findings in multi-parametric brain MRI using a system of 3D neural networks.

With the rapid growth and increasing use of brain MRI, there is an interest in automated image classification to aid human interpretation and improve workflow. We aimed to train a deep convolutional neural network and assess its performance in identifying abnormal brain MRIs and critical intracranial findings including acute infarction, acute hemorrhage and mass effect. A total of 13,215 clinical brain MRI studies were categorized to training (74%), validation (9%), internal testing (8%) and external testing (8%) datasets. Up to eight contrasts were included from each brain MRI and each image volume was reformatted to common resolution to accommodate for differences between scanners. Following reviewing the radiology reports, three neuroradiologists assigned each study to abnormal vs normal, and identified three critical findings including acute infarction, acute hemorrhage, and mass effect. A deep convolutional neural network was constructed by a combination of localization feature extraction (LFE) modules and global classifiers to identify the presence of 4 variables in brain MRIs including abnormal, acute infarction, acute hemorrhage and mass effect. Training, validation and testing sets were randomly defined on a patient basis. Training was performed on 9845 studies using balanced sampling to address class imbalance. Receiver operating characteristic (ROC) analysis was performed. The ROC analysis of our models for 1050 studies within our internal test data showed AUC/sensitivity/specificity of 0.91/83%/86% for normal versus abnormal brain MRI, 0.95/92%/88% for acute infarction, 0.90/89%/81% for acute hemorrhage, and 0.93/93%/85% for mass effect. For 1072 studies within our external test data, it showed AUC/sensitivity/specificity of 0.88/80%/80% for normal versus abnormal brain MRI, 0.97/90%/97% for acute infarction, 0.83/72%/88% for acute hemorrhage, and 0.87/79%/81% for mass effect. Our proposed deep convolutional network can accurately identify abnormal and critical intracranial findings on individual brain MRIs, while addressing the fact that some MR contrasts might not be available in individual studies.

Intensive diabetes therapy and body weight: focus on insulin detemir.

Weight gain can be a significant barrier to the treatment of diabetes. Insulin detemir is a basal insulin analog that can help patients move safely toward glycemic targets with less weight gain. This review discusses the potential adverse effects of, and hypothesis for, weight gain resulting from intensive insulin management of diabetes. In addition, an assessment of all weight change data from clinical trials and observational studies involving insulin detemir are presented. Finally, we discuss how the ability of insulin detemir to closely mimic endogenous insulin secretion leads to more predictable glycemic control with reduced weight gain and provides patients with a more acceptable method of achieving glycemic control.