Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit all?

In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

Feasibility and acceptability of remote smartphone cognitive testing in frontotemporal dementia research.

Introduction: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp). Methods: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [N = 101]; prodromal: 0.5 [N = 49]; symptomatic ≥1 [N = 51]; not measured [N = 13]) were asked to complete ALLFTD-mApp tests on their smartphone three times within 12 days. They completed smartphone familiarity and participation experience surveys. Results: It was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity was associated with poorer performance across several tests. Discussion: These findings suggest that the ALLFTD-mApp study protocol is feasible and acceptable for remote FTD research. HIGHLIGHTS: The ALLFTD Mobile App is a smartphone-based platform for remote, self-administered data collection.The ALLFTD Mobile App consists of a comprehensive battery of surveys and tests of executive functioning, memory, speech and language, and motor abilities.Remote digital data collection using the ALLFTD Mobile App was feasible in a multicenter research consortium that studies FTD. Data was collected in healthy controls and participants with a range of diagnoses, particularly FTD spectrum disorders.Remote digital data collection was well accepted by participants with a variety of diagnoses.

Top Ten Tips Palliative Care Clinicians Should Know About Managing Immune-Mediated Endocrine Toxicities in Cancer.

Immune checkpoint inhibitors (ICI), such as PD-1/PDL-1 and CTLA-4, have become widely used in the treatment of solid and hematological malignancies; their use and side effects are increasingly seen in the palliative care (PC) population. These drugs can result in immune-mediated endocrinopathies; the thyroid is the most common endocrine gland affected, but the pituitary, adrenals, and pancreas may be affected as well. Symptoms may be insidious and nonspecific. A high index of suspicion and routine laboratory monitoring allows for prompt diagnosis and treatment, which can significantly improve symptoms and increase quality of life. In this study, we present an approach to monitoring and initial management of ICI-induced endocrinopathies in the PC patient population.

Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS.

Many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), lead to the selective degeneration of discrete cell types in the CNS despite the ubiquitous expression of many genes linked to disease. Therapeutic advancement depends on understanding the unique cellular adaptations that underlie pathology of vulnerable cells in the context of disease-causing mutations. Here, we employ bacTRAP molecular profiling to elucidate cell type-specific molecular responses of cortical upper motor neurons in a preclinical ALS model. Using two bacTRAP mouse lines that label distinct vulnerable or resilient projection neuron populations in motor cortex, we show that the regulation of oxidative phosphorylation (Oxphos) pathways is a common response in both cell types. However, differences in the baseline expression of genes involved in Stem and the handling of reactive oxygen species likely lead to the selective degeneration of the vulnerable cells. These results provide a framework to identify cell-type-specific processes in neurodegenerative disease.

Serotonin receptor 4 in the hippocampus modulates mood and anxiety.

Serotonin receptor 4 (5-HT4R) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5-HT4R is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5-HT4R knockout mouse line to dissect the function of 5-HT4R in specific brain regions and cell types. We show that the loss of functional 5-HT4R specifically from excitatory neurons of hippocampus led to robust AD-like behavioral responses and an elevation in baseline anxiety. 5-HT4R was necessary to maintain the proper excitability of dentate gyrus (DG) granule cells and cell type-specific molecular profiling revealed a dysregulation of genes necessary for normal neural function and plasticity in cells lacking 5-HT4R. These adaptations were accompanied by an increase in the number of immature neurons in ventral, but not dorsal, dentate gyrus, indicating a broad impact of 5-HT4R loss on the local cellular environment. This study is the first to use conditional genetic targeting to demonstrate a direct role for hippocampal 5-HT4R signaling in modulating mood and anxiety. Our findings also underscore the need for cell type-based approaches to elucidate the complex action of neuromodulatory systems on distinct neural circuits.

Shoulder Position During Magnetic Resonance Arthrogram Significantly Affects Capsular Measurements.

PURPOSE: To determine whether change in shoulder position between internal rotation (IR) and external rotation (ER) during magnetic resonance arthrography (MRA) affects previously defined capsular measurements and to determine the utility of rotation in the diagnosis of instability. METHODS: A retrospective study was conducted of patients who received a shoulder MRA with humeral IR and ER views. Patients with an arthroscopically confirmed diagnosis of instability and those with clinically stable shoulders, no history of instability, and no MRA findings of instability were identified and compared. Humeral rotation, glenoid retroversion, humeral head subluxation, capsular length, and capsular area using axial sequences of IR and ER views were recorded. Analysis compared IR, ER, and Δ capsular measurements between groups using independent t tests and univariate and multivariate regression. RESULTS: Thirty-one subjects who were diagnosed with instability were included, along with 28 control subjects. Capsular length, capsular area, and humeral subluxations were significantly greater with ER compared with IR views (P < .001, P < .001, P < .001). Patients with instability displayed greater ER capsular length (P = .0006) and ER capsular area (P = .005) relative to controls. Multivariate logistic regression identified age, weight, sex, ER capsular length, and retroversion to be significant predictors of instability. ER capsular length independently predicts instability with 86% sensitivity and 84% specificity. Interobserver reliability using the intraclass correlation coefficient was rated good or excellent on all measurements. CONCLUSION: Variance in humeral rotation during shoulder MRA significantly affects capsular measurements. Rotational views increase the utility of capsular measurements when assessing for instability, particularly capsular length and capsular area. The implementation of ER positioning enhances the ability to examine capsular changes of the shoulder joint and can assist in the diagnosis of instability. LEVEL OF EVIDENCE: III, retrospective comparative study.

The effect of body mass index on internal rotation and function following anatomic and reverse total shoulder arthroplasty.

BACKGROUND: The exact relationship between body mass index (BMI) and internal rotation (IR) before and after total shoulder arthroplasty has not been studied to date. The purpose of this study was to determine the effects of BMI on the preoperative and postoperative shoulder range of motion and function in anatomic (aTSA) and reverse total shoulder arthroplasty (rTSA), and specifically how IR affects patient ability to perform IR-related activities of daily living (ADLs). METHODS: Patients from a prospective multicenter international shoulder arthroplasty registry who underwent primary rTSA (n=1171) and primary aTSA (n=883) were scored preoperatively and at latest follow-up (2-10 years, mean = 3 years) using the Simple Shoulder Test, University of California-Los Angeles shoulder score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Constant score, and Shoulder Pain and Disability Index patient-reported outcome measures (PROMs). Measured active abduction, forward flexion, IR, and active and passive external rotation were recorded, and BMI was evaluated as a predictor of motion and patient-reported outcomes. Patient responses to questions regarding the difficulty level of IR-related ADLs were studied. The relationships between BMI, IR, and ability to perform IR-related ADLs were quantified through analysis of variance with post hoc comparisons by Tukey honestly significant difference tests, where significance was denoted as P < .05. RESULTS: BMI was found to be inversely correlated with IR in patients undergoing both aTSA and rTSA, both preoperatively (P < .001 and P = .002) and postoperatively (P < .001 and P < .001). BMI affected the range of motion parameters of forward flexion abduction and external rotation but to a lesser extent than that of IR. Nonobese patients demonstrated significantly greater IR than overweight, obese, and morbidly obese patients postoperatively for aTSA (P < .001). For rTSA, nonobese patients had a significantly greater postoperative IR than obese and morbidly obese patients (P < .001 and P = .011, respectively). For both aTSA and rTSA patients, mean IR scores significantly differed between patients reporting normal function vs. patients reporting slight difficulty, considerable difficulty, or inability to perform IR-related ADLs. Increasing IR demonstrated a significant, positive correlation with all PROMs for both aTSA and rTSA patients (Pearson correlation, P < .001). CONCLUSIONS: BMI is an independent predictor of IR, even when controlling for age, gender, glenosphere size, and subscapularis repair. BMI was inversely correlated with the degree of IR, and decreased IR significantly negatively affected the ability to perform IR-related ADLs. CLINICAL RELEVANCE: Increasing BMI adversely affects shoulder ROM, particularly IR. IR is correlated with the ability to perform ADLs requiring IR in both aTSA and rTSA patients.

Intraoperative Identification of Clavicle Fracture Patterns: Do Clavicles Fail in a Predictable Pattern?

OBJECTIVES: To characterize the fracture pattern and pattern of fragmentation for displaced, midshaft clavicle fractures undergoing operative management. DESIGN: Prospective observational study. SETTING: Two institutions. Level 1 and Level 2 Trauma Centers. PATIENTS/PARTICIPANTS: Fifty-three patients who underwent operative repair of midshaft clavicle fracture. INTERVENTION: All clavicles were treated by operative open reduction internal fixation. MAIN OUTCOME MEASUREMENTS: All clavicles were categorized by the Robinson classification based on injury plain film bilateral upright clavicle radiographs. In addition, intraoperative fracture characteristics of fragment length and location were measured and recorded to evaluate the fracture pattern. All fractures were analyzed to determine the frequency of segmental comminution versus length-stable patterns, analyze characteristics of butterfly fragment size, number and location as well as the location of the cortical read for those length-stable fractures. RESULTS: Analysis revealed 55% were Robinson 2B2 based on preoperative radiographs. Length-stable, anatomic reduction was achievable in 83%. For those in which an anatomic cortical read was achievable, 97.7% had a read present in the posterior-superior aspect of the clavicle. CONCLUSIONS: Midshaft clavicle fractures that meet conventional criteria for operative repair occur in a predictable manner with butterfly fragments generated from anterior-inferior compression and simple fracture line generated from tension along the posterior-superior aspect of the clavicle. Understanding this pattern can assist in the in surgical planning.

Pitch count adherence and injury assessment of youth baseball in South Carolina.

INTRODUCTION: Overuse injury in youth overhead athletes remains a concern. The introduction of pitch count guidelines was designed to limit the number of pitches per game. South Carolina is considered a warm weather climate which has been proven to expose overhead athletes to higher risk for injury. The purpose of this study was to detect baseline rates of arm pain and sequelae (injury, surgery, impact on participation) among southern youth baseball/softball players to better counsel players, parents, coaches and league administration on the prevention of arm injury. METHODS: A survey was distributed to 14 pediatric practices within the South Carolina Pediatric Practice Research Network. The 2-page survey included 28 closed-ended and descriptive questions that investigated physical and psychosocial responses during and after play. Additional questions were conducted on adherence and understanding of USA Baseball guidelines and pitch counting behavior. RESULTS: Two hundred and seventy three surveys were completed by parents of baseball/softball players. The players' average age was 11.6 years, who played on an average of 1.78 teams/leagues for 5.2 months each year. Only 26% of baseball players answered "Sometimes", "Often" or "Always" to their arm hurting. Arm fatigue, older age, parent/coach frustration with play, and months played were statistically significantly associated with arm pain. The survey revealed 58.9% of families were familiar with pitch count guidelines. DISCUSSION: Arm pain is relatively prevalent among the South Carolina youth baseball community and worse in older players and experience fatigue. This survey found lower percentage of youth overhead athletes experiencing arm discomfort when compared to prior studies. It is important for warm weather climate athletes to abide by guidelines, as they are more susceptible to arm injury. Increased recognition, education and compliance with pitch count guidelines will help protect these youth athletes from overuse injury. LEVEL OF EVIDENCE: IV, Descriptive Epidemiology Study.

The Effect of Screw Design and Cortical Augmentation on Insertional Torque and Compression in Coracoid-Glenoid Fixation in a Sawbones Model.

PURPOSE: To compare screw insertional torque and coracoid-glenoid compression from 4 fixation techniques with different screw design parameters and cortical augmentation for the Latarjet procedure. METHODS: Simulated Latarjet procedures were performed with 4 fixation techniques using laminated polyurethane blocks with dimensions similar to the coracoid-glenoid construct. The groups included DePuy Synthes Mitek 3.5-mm partially threaded screws with top hats, Arthrex 3.75-mm fully threaded screws with a 2-hole plate, Arthrex 3.75-mm fully threaded screws, and Smith & Nephew 4.0-mm partially threaded screws. Screws were inserted using a digital torque-measuring screwdriver to determine maximum insertional torque. Pressure-sensitive film was used to measure the maximum contact pressure and the effective pressure distribution (EPD) between the coracoid and glenoid; the EPD represents the percentage of the film's surface area that experienced pressure greater than 10 MPa. One-way analysis of variance and post hoc tests were used for statistical analysis. RESULTS: Significant differences were found between the 4 fixation groups for each variable measured. The 2 cortically augmented systems produced significantly higher maximum insertional torque than the non-cortically augmented systems (P < .001 for both). The 3.75-mm screws with a 2-hole plate yielded significantly higher contact pressures than the 4.0-mm screws (P = .028). This group also had a high EPD, with a mean value more than double the values of the non-cortically augmented systems (P = .037 and P < .001). CONCLUSIONS: Cortically augmented fixation methods showed higher maximum insertional torque, maximum contact pressure, and EPD between the surfaces of the coracoid and glenoid in this Sawbones model. CLINICAL RELEVANCE: Various implants are available for the Latarjet procedure, but their biomechanical characteristics have not yet been fully elucidated. Graft fracture and nonunion represent 2 modes of failure that may be related to insertional torque and coracoid-glenoid compression. This study compared screw insertional torque and compression achieved using 4 fixation techniques with different screw design parameters and cortical augmentation in a Sawbones model.

Local drug delivery systems in the management of periodontitis: A scientific review.

Periodontitis (PD) is a microbial disease of tooth supporting tissues that results in progressive destruction of surrounding soft and hard tissues with eventual tooth mobility and exfoliation. Perioceutics, which includes the delivery of therapeutic agents via systemic and local means as an adjunct to mechanical therapy has revolutionized the arena of periodontal therapy. Selection of a right antimicrobial agent with appropriate route of drug administration is the key to successful periodontal therapy. Irrigating systems, fibers, gels, strips, films, microparticles, nanoparticles and low dose antimicrobial agents are some of the local drug delivery systems (LDDS) available in the field, which aims to deliver antimicrobial agents to sub-gingival diseased sites with minimal or no side-effects on other body sites. The present review aim to summarize the current state-of-the-art technology on LDDS in periodontal therapy ensuring the the practitioners are able to choose LDD agents which are custom made for a specific clinical condition.

Racial and sex disparities in utilization rates for shoulder arthroplasty in the United States disparities in shoulder arthroplasty.

PURPOSE: To investigate racial disparities in shoulder arthroplasty (SA), accounting for demographic factors such as sex and age. METHODS: Data for SAs (2011-2014) was queried from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. Population-adjusted SA utilization rates, racial and sex differences by age, length of stay, insurer, and comorbidities were calculated. RESULTS: Caucasians aged 45-64 are 54% more likely than African-Americans and 74% than Hispanics to receive surgery. For patients aged 65-84, the disparity is wider for African-Americans and narrower for Hispanics. CONCLUSIONS: Policymakers and physicians should focus on further national efforts to alleviate healthcare disparities.

Mettl14 Is Essential for Epitranscriptomic Regulation of Striatal Function and Learning.

N6-methyladenosine (m6A) regulates mRNA metabolism and translation, serving as an important source of post-transcriptional regulation. To date, the functional consequences of m6A deficiency within the adult brain have not been determined. To achieve m6A deficiency, we deleted Mettl14, an essential component of the m6A methyltransferase complex, in two related yet discrete mouse neuronal populations: striatonigral and striatopallidal. Mettl14 deletion reduced striatal m6A levels without altering cell numbers or morphology. Transcriptome-wide profiling of m6A-modified mRNAs in Mettl14-deleted striatum revealed downregulation of similar striatal mRNAs encoding neuron- and synapse-specific proteins in both neuronal types, but striatonigral and striatopallidal identity genes were uniquely downregulated in each respective manipulation. Upregulated mRNA species encoded non-neuron-specific proteins. These changes increased neuronal excitability, reduced spike frequency adaptation, and profoundly impaired striatal-mediated behaviors. Using viral-mediated, neuron-specific striatal Mettl14 deletion in adult mice, we further confirmed the significance of m6A in maintaining normal striatal function in the adult mouse.

Chronic oxycodone induces axonal degeneration in rat brain.

BACKGROUND: Chronic opioid therapy for non-malignant pain conditions has significantly increased over the last 15 years. Recently, the correlation between opioid analgesics and alternations in brain structure, such as leukoencephalopathy, axon demyelination, and white matter lesions, has been demonstrated in patients with a history of long-term use of prescription opioids. The exact mechanisms underlying the neurotoxic effect of opioids on the central nervous system are still not fully understood. We investigated the effect of chronic opioids using an animal model in which female rats were orally gavaged with 15 mg/kg of oxycodone every 24 h for 30 days. In addition we tested oxycodone, morphine and DAMGO in breast adenocarcinoma MCF7 cells, which are known to express the µ-opioid receptor. RESULTS: We observed several changes in the white matter of animals treated with oxycodone: deformation of axonal tracks, reduction in size of axonal fascicles, loss of myelin basic protein and accumulation of amyloid precursor protein beta (ß-APP), suggesting axonal damages by chronic oxycodone. Moreover, we demonstrated activation of pro-apoptotic machinery amid suppression of anti-apoptotic signaling in axonal tracks that correlated with activation of biomarkers of the integrated stress response (ISR) in these structures after oxycodone exposure. Using MCF7 cells, we observed induction of the ISR and pro-apoptotic signaling after opioid treatment. We showed that the ISR inhibitor, ISRIB, suppresses opioid-induced Bax and CHOP expression in MCF7 cells. CONCLUSIONS: Altogether, our data suggest that chronic opioid administration may cause neuronal degeneration by activation of the integrated stress response leading to induction of apoptotic signaling in neurons and also by promoting demyelination in CNS.

Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutation.

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphoproliferation, accumulation of double-negative T cells, hypergammaglobulinemia G and A, and autoimmune cytopenia. OBJECTIVES: Although mostly associated with FAS mutations, different genetic defects leading to impaired apoptosis have been described in patients with ALPS, including the FAS ligand gene (FASLG) in rare cases. Here we report on the first case of complete FAS ligand deficiency caused by a homozygous null mutant. METHODS: Double-negative T-cell counts and plasma IL-10 and FAS ligand concentrations were determined as ALPS markers. The FASLG gene was sequenced, and its expression was analyzed by means of Western blotting. FAS ligand function was assessed based on reactivation-induced cell death. RESULTS: We describe a patient born to consanguineous parents who presented with a severe form of ALPS caused by FASLG deficiency. Although the clinical presentation was compatible with a homozygous FAS mutation, FAS-induced apoptosis was normal, and plasma FAS ligand levels were not detectable. This patient carries a homozygous, germline, single-base-pair deletion in FASLG exon 1, leading to a premature stop codon (F87fs x95) and a complete defect in FASLG expression. The healthy parents were each heterozygous for the mutation, confirming its recessive trait. CONCLUSION: FAS ligand deficiency should be screened in patients presenting with ALPS features but lacking the usual markers, including plasma soluble FAS ligand and an in vitro apoptotic defect. An activation-induced cell death test could help in discrimination.

VAMP-associated protein B (VAPB) promotes breast tumor growth by modulation of Akt activity.

VAPB (VAMP- associated protein B) is an ER protein that regulates multiple biological functions. Although aberrant expression of VAPB is associated with breast cancer, its function in tumor cells is poorly understood. In this report, we provide evidence that VAPB regulates breast tumor cell proliferation and AKT activation. VAPB protein expression is elevated in primary and metastatic tumor specimens, and VAPB mRNA expression levels correlated negatively with patient survival in two large breast tumor datasets. Overexpression of VAPB in mammary epithelial cells increased cell growth, whereas VAPB knockdown in tumor cells inhibited cell proliferation in vitro and suppressed tumor growth in orthotopic mammary gland allografts. The growth regulation of mammary tumor cells controlled by VAPB appears to be mediated, at least in part, by modulation of AKT activity. Overexpression of VAPB in MCF10A-HER2 cells enhances phosphorylation of AKT. In contrast, knockdown of VAPB in MMTV-Neu tumor cells inhibited pAKT levels. Pharmacological inhibition of AKT significantly reduced three-dimensional spheroid growth induced by VAPB. Collectively, the genetic, functional and mechanistic analyses suggest a role of VAPB in tumor promotion in human breast cancer.

Prenatal diagnosis of LAD-I on cord blood by flowcytometry.

OBJECTIVES: To optimize a simple flowcytometric technique for Prenatal diagnosis (PND) for Leukocyte adhesions defect (LAD-I) on cordocentesis sample at 18 wk gestation. METHODS: Normal reference ranges for expression of CD18/CD11-integrins in neutrophils and lymphocytes at 18 wk of gestation were established by flowcytometry. PND for LAD-I was then performed on the cordocentesis samples in three 'at risk' pregnancies after ruling out maternal contamination. RESULTS: CD18 and CD11a expression on fetal lymphocytes were found to be the most useful parameters for PND of LAD-I. All the three fetuses tested showed normal expression of CD18/CD11-integrins and thus were unaffected. This was confirmed by testing the cord blood (CB) samples after delivery and normal growth and absence of serious infections on follow-up. CONCLUSIONS: Flowcytometry offers a rapid and sensitive technique for PND of LAD-I in the absence of facilities for molecular diagnosis. Obstetricians, even in developing countries with modest facilities, can offer considerable relief for the families.

Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium.

It is well known that tumor-derived proangiogenic factors induce neovascularization to facilitate tumor growth and malignant progression. However, the concept of "angiocrine" signaling, in which signals produced by endothelial cells elicit tumor cell responses distinct from vessel function, has been proposed, yet remains underinvestigated. Here, we report that angiocrine factors secreted from endothelium regulate tumor growth and motility. We found that Slit2, which is negatively regulated by endothelial EphA2 receptor, is one such tumor suppressive angiocrine factor. Slit2 activity is elevated in EphA2-deficient endothelium. Blocking Slit activity restored angiocrine-induced tumor growth/motility, whereas elevated Slit2 impaired growth/motility. To translate our findings to human cancer, we analyzed EphA2 and Slit2 expression in human cancer. EphA2 expression inversely correlated with Slit2 in the vasculature of invasive human ductal carcinoma samples. Moreover, analysis of large breast tumor data sets revealed that Slit2 correlated positively with overall and recurrence-free survival, providing clinical validation for the tumor suppressor function for Slit2 in human breast cancer. Together, these data support a novel, clinically relevant mechanism through which EphA2 represses Slit2 expression in endothelium to facilitate angiocrine-mediated tumor growth and motility by blocking a tumor suppressive signal.

A rare case of uterine leiomyosarcoma: a case report.

INTRODUCTION: Malignant change in a leiomyoma or uterine fibroid is termed leiomyosarcoma. It arises from smooth muscle of the uterus and is a rare tumor that accounts for 2% to 5% of all uterine malignancies. Very few cases are reported in the literature. Our patient did not have any history of genital bleeding, which is the usual presentation in uterine sarcoma. We report an original case report of an unusual presentation of this rare tumor arising from the uterus. CASE PRESENTATION: A 40-year-old nulliparous woman of South Indian origin presented with a mass in her abdomen for one year with a rapid increase in size over the previous three months. Tumor marker CA-125 was raised, and a computed tomography scan showed a mass arising from the pelvis. An exploratory laparotomy was performed and the histopathology report confirmed the diagnosis of uterine leiomyosarcoma. CONCLUSION: Because of their rarity, uterine sarcomas are not suitable for screening. Diagnosis is by histopathologic examination and surgery is the only treatment. The prognosis for women with uterine sarcoma primarily depends on the extent of disease at the time of diagnosis and the mitotic index.

DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation.

Diet-induced obesity (DIO) leads to inflammatory activation of macrophages in white adipose tissue (WAT) and subsequently to insulin resistance. PPARgamma agonists are antidiabetic agents known to suppress inflammatory macrophage activation and to induce expression of the triacylglycerol (TG) synthesis enzyme acyl CoA: diacylglycerol acyltransferase 1 (DGAT1) in WAT and in adipocytes. Here, we investigated in mice the relationship between macrophage lipid storage capacity and DIO-associated inflammatory macrophage activation. Mice overexpressing DGAT1 in both macrophages and adipocytes (referred to herein as aP2-Dgat1 mice) were more prone to DIO but were protected against inflammatory macrophage activation, macrophage accumulation in WAT, systemic inflammation, and insulin resistance. To assess the contribution of macrophage DGAT1 expression to this phenotype, we transplanted wild-type mice with aP2-Dgat1 BM. These mice developed DIO similar to that of control mice but retained the protection from WAT inflammation and insulin resistance seen in aP2-Dgat1 mice. In isolated macrophages, Dgat1 mRNA levels correlated directly with TG storage capacity and inversely with inflammatory activation by saturated fatty acids (FAs). Moreover, PPARgamma agonists increased macrophage Dgat1 mRNA levels, and the protective effects of these agonists against FA-induced inflammatory macrophage activation were absent in macrophages isolated from Dgat1-null mice. Thus, increasing DGAT1 expression in murine macrophages increases their capacity for TG storage, protects against FA-induced inflammatory activation, and is sufficient to reduce the inflammatory and metabolic consequences of DIO.