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Background: Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease (CVD). Patients with CKD have a high prevalence of atherosclerosis. However, CVD risk associated with CKD is not entirely explained by standard lipid profile or liver handling of cholesterol, as evidenced by the resistance to statin benefits seen in later stages of CKD. This study aims to detect changes in expression of cholesterol transport proteins in the setting of CKD, and to determine if such changes adversely affect lipid handling by macrophages, leading to cholesterol overload and atheromatous foam cell formation. Methods: THP-1 human macrophages (106/ml) were incubated for 18 h-24 h with plasma obtained from 10 CKD patients (7 male, 3 female) or 10 healthy control subjects (4 male, 6 female). CKD patients were not on dialysis and had not received renal transplant. Following incubation, mRNA was isolated and reverse transcribed. The resulting cDNA was subjected to quantitative real-time PCR using specific primers for ATP binding cassette transporter (ABC) A1 (cholesterol efflux protein) and CD36, (a scavenger receptor with the capacity to endocytose oxidized LDL). Results: PCR analysis showed that ABCA1 mRNA was reduced by 23 ± 5% (p < 0.0001) while CD36 mRNA was decreased by 36 ± 7% (p < 0.0001) in macrophages exposed to CKD plasma as compared to healthy control. Conclusions: These findings suggest a different mechanism of lipid dysregulation associated with CKD, which may explain the pathogenesis of elevated CVD risk in CKD and lack of response to statins. This mechanism, through pro atherogenic suppression of ABCA1, differs from our finding in autoimmune rheumatic diseases where, in addition to lowering of ABCA1, augmentation of CD36 was also observed. In CKD, a paradoxical decrease in CD36 could compromise macrophage clearance of lipids, increasing vulnerability to lipoprotein thrombi in the kidney. Further lowering of monocyte CD36 with statins, would be of little benefit if CD36 is already low in CKD. Defining changes in lipid handling in CKD could lead to novel, targeted CVD treatment approaches in the CKD population. [ABSTRACT FROM AUTHOR]

Presents a correction to the article 'Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist,' published in the September 2002 issue of the journal 'Nature Medicine.'

This study evaluated (a) whether chronic, medicated schizophrenia patients show deficits in emotion recognition compared to nonpatients, and (b) whether deficits in emotion recognition are related to poorer social competence. Two emotion recognition tests developed by S. L. Kerr and J. M. Neale (1993) and Benton's Test of Facial Recognition (A. Benton, M. VanAllen, K. Hamsher, & H. Levin, 1978) were given to patients with chronic schizophrenia and nonpatient controls. Patients' social skills, social adjustment, and symptomatology were assessed. Like Kerr and Neale's unmedicated patients, these patients performed worse than controls on both emotion recognition tests and the control test. For patients, facial perception was related to the chronicity of illness and social competence. Chronicity of illness may contribute to face perception deficits in schizophrenia, which may affect social competence. [ABSTRACT FROM AUTHOR]

Background and Objectives: Within frontotemporal dementia (FTD), the behavioral variant (bvFTD) characterized by frontal atrophy, and semantic behavioral variant (sbvFTD) characterized by right anterior temporal lobe (rATL) atrophy, present diagnostic challenges due to overlapping symptoms and neuroanatomy. Accurate differentiation is crucial for clinical trial inclusion targeting TDP-43 proteinopathies. This study investigated whether automated speech analysis can distinguish between FTD-related rATL and frontal atrophy, potentially offering a non-invasive diagnostic tool., Methods: In a cross-sectional design, we included 40 participants with FTD-related predominant frontal atrophy (n=16) or predominant rATL atrophy (n=24) and 22 healthy controls from the UCSF Memory and Aging Center. Using stepwise logistic regression and receiver operating characteristic (ROC) curve analysis, we analyzed 16 linguistic and acoustic features that were extracted automatically from audio-recorded picture description tasks. Neuroimaging data were analyzed using voxel-based morphometry to examine brain-behavior relationships of regional atrophy with the features selected in the regression models., Results: Logistic regression identified three features (content units, lexical frequency, familiarity) differentiating the overall FTD group from controls (AUC=.973), adjusted for age. Within the FTD group, five features (adpositions/total words ratio, arousal, syllable pause duration, restarts, words containing 'thing') differentiated frontal from rATL atrophy (AUC=.943). Neuroimaging analyses showed that semantic features (lexical frequency, content units, 'thing' words) were linked to bilateral inferior temporal lobe structures, speech and lexical features (syllable pause duration, adpositions/total words ratio) to bilateral inferior frontal gyri, and socio-emotional features (arousal) to areas known to mediate social cognition including the right insula and bilateral anterior temporal structures. As a composite score, this set of five features was uniquely associated with rATL atrophy., Discussion: Automated speech analysis effectively distinguished the overall FTD group from controls and differentiated between frontal and rATL atrophy. The neuroimaging findings for individual features highlight the neural basis of language impairments in these FTD variants, and when considered together, underscore the importance of utilizing features' combined power to identify impaired language patterns. Automated speech analysis could enhance early diagnosis and monitoring of FTD, offering a scalable, non-invasive alternative to traditional methods, particularly in resource-limited settings. Further research should aim to integrate automated speech analysis into multi-modal diagnostic frameworks.

Objectives: To evaluate variables associated with loss of fixation of retrograde rami screws in the treatment of stress-positive minimally displaced lateral compression type 1 (LC1) injuries., Design: Retrospective comparative study., Setting: Level 1 trauma center., Patient Selection Criteria: Stress-positive minimally displaced (<1 cm) LC1 pelvic ring injuries treated with retrograde rami screws., Outcome Measures and Comparisons: Loss of fixation, defined as >5 mm of pelvic fracture displacement based on the radiographic tear-drop distance or >5 mm of implant displacement on follow-up radiographs; revision surgery for loss of fixation., Results: Thirty-eight patients with 40 retrograde rami screws were analyzed. Median patient age was 64 years (interquartile range 42.5-73.3 years), 71.1% (n = 27/38) were female, and 52.6% (n = 20/38) of injuries were secondary to low-energy mechanisms. Loss of fixation occurred in 17.5% (n = 7/40) of screws with 10% (n = 4/40) requiring revision surgery. On univariate analysis, patients who had a loss of fixation were more likely to have greater dynamic displacement on stress radiographs (22.0 vs. 15.2 mm; median difference 5.6 mm, confidence interval [CI] -19.2 to 10.3; P = 0.04), unicortical rami screws (71.4% vs. 9.1%; proportional difference 62.3%, CI 8.8%-22.6%; P = 0.001), and partially threaded rami screws (71.4% vs. 21.2%; proportional difference 50.2%, CI 10.0%-77.6%; P = 0.01). The remaining variables had no observed association ( P ≥ 0.05) with loss of fixation, including age, sex, body mass index, energy of injury mechanism, tobacco use, American Society of Anesthesiologist score, sacral fracture type, distal rami fractures, rami comminution, number of sacral screws, fully threaded sacral screws, transsacral screws, or rami screw diameter. On multivariate analysis, only unicortical rami screws ( P = 0.01) remained associated with loss of fixation., Conclusions: Retrograde rami screws had a high rate of loss of fixation in minimally displaced LC1 pelvic ring injuries, and this was associated with unicortical screws. These screws should be avoided when possible., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: None of the authors have financial conflicts of interest relevant to the content of this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Morphosyntactic assessments are important for characterizing individuals with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard tests are subject to examiner bias and often fail to differentiate between nfvPPA and logopenic variant PPA (lvPPA). Moreover, relevant neural signatures remain underexplored. Here, we leverage natural language processing tools to automatically capture morphosyntactic disturbances and their neuroanatomical correlates in 35 individuals with nfvPPA relative to 10 healthy controls (HC) and 26 individuals with lvPPA. Participants described a picture, and ensuing transcripts were analyzed via part-of-speech tagging to extract sentence-related features (e.g., subordinating and coordinating conjunctions), verbal-related features (e.g., tense markers), and nominal-related features (e.g., subjective and possessive pronouns). Gradient boosting machines were used to classify between groups using all features. We identified the most discriminant morphosyntactic marker via a feature importance algorithm and examined its neural correlates via voxel-based morphometry. Individuals with nfvPPA produced fewer morphosyntactic elements than the other two groups. Such features robustly discriminated them from both individuals with lvPPA and HCs with an AUC of .95 and .82, respectively. The most discriminatory feature corresponded to subordinating conjunctions was correlated with cortical atrophy within the left posterior inferior frontal gyrus across groups (p FWE  < .05). Automated morphosyntactic analysis can efficiently differentiate nfvPPA from lvPPA. Also, the most sensitive morphosyntactic markers correlate with a core atrophy region of nfvPPA. Our approach, thus, can contribute to a key challenge in PPA diagnosis., Competing Interests: Declaration of competing interest The authors report no disclosures relevant to the manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

This is an analysis of important aspects of health equity in caring for children and adolescents written by a multidisciplinary team from different medical centers. In this discussion for clinicians, we look at definitions of pediatric health equity and the enormous impact of social determinants of health in this area. Factors involved with pediatric healthcare disparities that are considered include race, ethnicity, gender, age, poverty, socioeconomic status, LGBT status, living in rural communities, housing instability, food insecurity, access to transportation, availability of healthcare professionals, the status of education, and employment as well as immigration. Additional issues involved with health equity in pediatrics that are reviewed will include the impact of the COVID-19 pandemic, behavioral health concepts, and the negative health effects of climate change. Recommendations that are presented include reflection of one's own attitudes on as well as an understanding of these topics, consideration of the role of various healthcare providers (i.e., community health workers, peer health navigators, others), the impact of behavioral health integration, and the need for well-conceived curricula as well as multi-faceted training programs in pediatric health equity at the undergraduate and postgraduate medical education levels. Furthermore, ongoing research in pediatric health equity is needed to scrutinize current concepts and stimulate the development of ideas with an ever-greater positive influence on the health of our beloved children. Clinicians caring for children can serve as champions for the optimal health of children and their families; in addition, these healthcare professionals are uniquely positioned in their daily work to understand the drivers of health inequities and to be advocates for optimal health equity in the 21st century for all children and adolescents., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Transforming acidic acid coiled-coil protein 3 (TACC3) and cytoskeleton associated protein 5 (cKAP5; or colonic hepatic tumor overexpressed gene, chTOG) are vital for spindle assembly and stabilization initiated through TACC3 Aurora-A kinase interaction. Here, TACC3 and cKAP5/chTOG localization with monospecific antibodies is investigated in eGFP-centrin-2- expressing mouse meiotic spermatocytes. Both proteins bind spermatocyte spindle poles but neither kinetochore nor interpolar microtubules, unlike in mitotic mouse fibroblasts or female meiotic oocyte spindles. Spermatocytes do not display a liquid-like spindle domain (LISD), although fusing them into maturing oocytes generates LISD-like TACC3 condensates around sperm chromatin but sparse microtubule assembly. Microtubule inhibitors do not reduce TACC3 and cKAP5/chTOG spindle pole binding. MLN 8237 Aurora-A kinase inhibitor removes TACC3, not cKAP5/chTOG, disrupting spindle organization, chromosome alignment, and impacting spindle pole γ-tubulin intensity. The LISD disruptor 1,6-hexanediol abolished TACC3 in spermatocytes, impacting spindle bipolarity and chromosome organization. Cold microtubule disassembly and rescue experiments in the presence of 1,6-hexanediol reinforce the concept that spermatocyte TACC3 spindle pole presence is not required for spindle pole microtubule assembly. Collectively, meiotic spermatocytes without a LISD localize TACC3 and cKAP5/chTOG exclusively at spindle poles to support meiotic spindle pole stabilization during male meiosis, different from either female meiosis or mitosis., (© 2024. The Author(s).)

Prior research has revealed distinctive patterns of impaired language abilities across the three variants of Primary Progressive Aphasia (PPA): nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). However, little is known about whether, and to what extent, non-verbal cognitive abilities, such as processing speed, are impacted in PPA patients. This is because neuropsychological tests typically contain linguistic stimuli and require spoken output, being therefore sensitive to verbal deficits in aphasic patients. The aim of this study is to investigate potential differences in processing speed between PPA patients and healthy controls, and among the three PPA variants, using a brief non-verbal tablet-based task (Match) modeled after the WAIS-III digit symbol coding test, and to determine its neural correlates. Here, we compared performance on the Match task between PPA patients (n = 61) and healthy controls (n = 59) and across the three PPA variants. We correlated performance on Match with voxelwise gray and white matter volumes. We found that lvPPA and nfvPPA patients performed significantly worse on Match than healthy controls and svPPA patients. Worse performance on Match across PPA patients was associated with reduced gray matter volume in specific parts of the left middle frontal gyrus, superior parietal lobule, and precuneus, and reduced white matter volume in the left parietal lobe. To conclude, our behavioral findings reveal that processing speed is differentially impacted across the three PPA variants and provide support for the potential clinical utility of a tabled-based task (Match) to assess non-verbal cognition. In addition, our neuroimaging findings confirm the importance of a set of fronto-parietal regions that previous research has associated with processing speed and executive control. Finally, our behavioral and neuroimaging findings combined indicate that differences in processing speed are largely explained by the unequal distribution of atrophy in these fronto-parietal regions across the three PPA variants., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Malnutrition is a significant public health problem that affects many patients in inpatient settings. Timely identification and addressing malnutrition in an inpatient setting presents an opportunity to improve patient care and reduce costs. There is a clear link between malnutrition, increased length of hospital stay, higher risk of readmissions and infections, skin breakdown, and higher hospital costs due to complications., Methods: We conducted a quality improvement project to increase the number of times patients were accurately diagnosed and successfully coded as malnourished. We used the Define, Measure, Analyse, Intervene, Control (DMAIC) process to complete this project. Data were collected for nearly a year using the Epic Report Tool developed explicitly for the project. Initial data showed that our hospital performed at 20% of patients diagnosed as malnourished, while the industry standard was 33%. A multidisciplinary team of physicians, nurses and dietitians identified critical areas of improvement, including incomplete nutritional assessments by nurses, delayed evaluations by dietitians and lack of documentation by physicians. We addressed these issues by partnering with nurse managers to provide education and individual accountability for missed screenings, expanding dietitian workflows to include an in-person assessment within 24 hours of consultation, and updating physician note templates to include smart phrases that automatically inserted nutritional evaluations from registered dietitians into notes. We also worked with hospital executives and administration to increase buy-in from participating care team members., Results: Our interventions resulted in 100% of malnutrition screening tool being completed, 33% of patients being screened at risk of malnutrition, 98% of nutrition assessments being done within 24 hours of patient admission and 100% of providers documenting malnutrition findings., Conclusions: Our study found an immediate and significant increase in the number of times malnutrition was diagnosed and ultimately coded during billing with our interventions. This highlights the importance of timely identification and addressing malnutrition in an inpatient setting to improve patient care and reduce costs. The DMAIC process and multidisciplinary team approach proved to be effective in identifying and addressing the barriers to malnutrition diagnosis in our hospital setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite minimal coding and billing training, surgeons are frequently tasked with both in clinical practice. This often results in denials for reimbursement based on incorrect or insufficient documentation, and reduced collections for work performed. We sought to evaluate how to correct these deficits while improving reimbursement for the most frequently rejected procedures at a high-volume academic center., Study Design: Hospital billing data were analyzed for a 4-year period (2018 to 2021) to determine the CPT code denials with the largest overall cost. The denials were then stratified according to payor, reason for denial, and preventability. Assigned ICD-10 codes were categorized based on specificity as related to the procedure. The distribution of denials according to ICD-10 specificity was evaluated using the chi-square test., Results: A total of 8,833 denials representing $11,009,108 in billing were noted during the study period. The CPT code 44970 (laparoscopic appendectomy) was the code associated with the largest financial impact, representing 12.8% of the total denied amount ($1.41M). Of the 823 denials for CPT 44970, 93.3% were associated with nonspecific ICD-10 codes, whereas only 42.0% had been associated with procedure-specific ICD-10 codes. Of the patients with nonspecific codes, 80.7% of denials were due to criteria that could be remedied with supplemental information or timely filing, representing $1,059,968 in collections., Conclusions: This is the first study to systematically evaluate a pathway for using denial data to improve collections for work performed at a high-volume academic pediatric surgery practice. Using this methodology, targets for improvement in coding and/or documentation can be identified to improve the financial performance of a surgical department. This study also provides evidence that association with nonspecific diagnostic codes is correlated with initial denial of payment by insurance companies., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)