Evaluation of the impact of guideline communication from the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services among US healthcare providers: COVID-19 prevention counselling guidance.

AIM: To evaluate healthcare provider awareness and uptake of the Centers for Medicare & Medicaid Services (CMS) billing for coronavirus disease 2019 (COVID-19) prevention counselling and the delivery of prevention counselling to patients awaiting severe acute respiratory syndrome coronavirus 2 test results. DESIGN: Cross sectional survey of US-based healthcare providers in February 2021. METHODS: Analysis of associations with healthcare provider-reported awareness of CMS prevention counselling guidance and billing with provider type, specialty, and work setting. RESULTS: A total of 1919 healthcare providers responded to the survey. Overall, 38% (726/1919) of providers reported awareness of available CMS reimbursement for COVID-19 patient counselling and 29% (465/1614) of CMS billing-eligible providers reported billing for this counselling. Among physicians, those aware of CMS guidance were significantly more likely to bill (58%) versus those unaware (10%). Among RNSights respondents eligible for CMS billing (n = 114), 31% of those aware of the guidance reported billing as compared to 0% of those not aware.

A Reaching Performance Scale for 2 Wolf Motor Function Test Items.

OBJECTIVE: To adapt the Reaching Performance Scale for Stroke (RPSS) for the Wolf Motor Function Test (WMFT) "Lift Can" (Can) and "Hand to Box" (Box) items. DESIGN: Retrospective analysis of video-recorded WMFT assessment performed by 3 raters on 2 occasions. SETTING: Not applicable. PARTICIPANTS: Participants (N=29) with mild to moderate upper extremity impairment less than 3 months after stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Inter- and intra-rater agreement, concurrent validity of WMFT-RPSS. RESULTS: Mean ± SD inter-rater Gwet's agreement coefficient (AC2) was 0.61±0.05 for Can WMFT-RPSS and 0.56 (0.03) for Box. Mean ± SD intra-rater AC2 for Can was 0.63±0.05 and 0.70±0.04 for Box. WMFT-RPSS Can and Box scores correlated with log mean WMFT time (C, -0.73; B, -0.48), Functional Ability Scale (C, 0.87; B, 0.62), Upper Extremity Fugl-Meyer Motor Score (C, 0.69; B, 0.51), and item movement rate (C, 0.74; B, 0.71) (P<.05 for all). Mean ± SD WMFT-RPSS score across the 29 participants was 12.7±3.5 for Can (max score, 19) and 11.4±3.0 for Box (max score, 16). CONCLUSIONS: WMFT-RPSS demonstrated moderate intra-rater and weak-to-moderate inter-rater agreement for individuals with mild-moderate impairment. For construct validity, Can and Box WMFT-RPSS were significantly correlated with 4 standardized measures. Average WMFT-RPSS scores revealed that some participants may have relied on compensatory movements to complete the task, a revelation not discernable from movement rate alone. The WMFT-RPSS is potentially useful as a valid and reliable tool to examine longitudinal changes in movement quality after stroke.

Outcomes of Patients Hospitalized for Severe Acute Alcoholic Hepatitis.

OBJECTIVES: Severe acute alcoholic hepatitis is a serious condition in individuals who consume significant quantities of alcohol. We aimed to identify risk factors for short-term mortality with this illness. METHODS: Patients with severe acute alcoholic hepatitis admitted to our academic medical center from 2010 to 2012 were identified. Demographic features, laboratory values, and patient outcomes were recorded. In-hospital mortality and transfer to inpatient hospice were combined to calculate overall inpatient mortality. RESULTS: A total of 251 hospitalizations of 191 patients were identified. The average age was 43.1 years (standard deviation 9.55). Most patients were men (80.6%). Compared with all adult patients admitted to internal medicine services during the same period, patients self-reporting Native American and Hispanic race/ethnicity were overrepresented (11.1% vs 34.0% and 14.8% vs 27.7%, χ2 P < 0.0001). In-hospital mortality was 20.3%. Another 10% of patients were transferred to inpatient hospice facilities. In the multivariate analysis, higher overall inpatient mortality was associated with an admission bilirubin >20 mg/dL (odds ratio 4.59). Of the patients, 11.9% were readmitted with a complication within 30 days-most commonly septic shock. Of the readmitted patients, the overall inpatient mortality was 86.2%. CONCLUSIONS: This study confirms the severity of illness among patients with severe acute alcoholic hepatitis. Patients with the highest total bilirubin levels on admission had the highest overall inpatient mortality. Readmission was a strong predictor of overall in-hospital mortality.

Personal characteristics, cooking at home and shopping frequency influence consumption.

This study examines how the consumption of fruits and vegetables is affected by home cooking habits and shopping patterns, including distance to patronized stores and frequency of shopping, in two low-income predominantly African American urban neighborhoods in New Orleans, Louisiana. In-person interviews were conducted in 2013 with 901 adult residents who identified themselves as the primary household shopper. Respondents were asked where and how often they shopped and answered a food frequency questionnaire. Addresses were geocoded and distances to the stores where respondents shopped were calculated. Multivariable logistic regression was used to examine the relationship between food consumption and personal factors, neighborhood factors and shopping habits. Consumption of daily servings of fresh produce increased by 3% for each additional trip to a grocery store, by 76% for shopping at a farmer's market, and by 38% for preparing food at home. Each additional trip to a convenience store increased the frequency of consumption of chips, candy and pastries by 3%. The distance from residence to the type of store patronized was not associated with consumption of produce or chips, candy or pastries. Shopping at full-service grocery stores, farmer's markets and cooking at home were positively associated with the consumption of fresh produce while shopping at convenience stores was associated with increased consumption of chips, candy and pastries. These findings are useful for designing programmatic interventions to increase fresh fruit and vegetable consumption among residents in low-income urban communities.

Palliative Care for American Indians and Alaska Natives: A Review of the Literature.

BACKGROUND: Little is known about optimal palliative and end-of-life care for American Indians and Alaska Natives (AIs/ANs). METHODS: We searched MEDLINE, the Cochrane library, EBSCOhost, (PsycINFO, CINAHL Complete), and the University of New Mexico (UNM) Health Sciences Library and Informatics Center Native Health Database for search terms related to palliative care and AIs/ANs as of December 1, 2015. We included English language, peer-reviewed articles describing palliative care projects, programs, or studies in AI/AN populations or communities. We excluded case series, opinion or reflection pieces, and dissertations and articles addressing Pacific Islanders. RESULTS: Our search strategy yielded 294 references, of which we included 10 publications. Study methods and outcome measures were heterogeneous, and many studies were small and/or subject to multiple biases. Common themes included the importance of culturally appropriate communication, multiple barriers to treatment, and less frequent use of advance directives than other populations. CONCLUSIONS: Heterogeneity of study types, population, and small sample sizes makes it hard to draw broad conclusions regarding the best way to care for AIs/ANs. More studies are needed to assess this important topic.

Appendiceal Adenocarcinoma Presenting as a Rectal Polyp.

Appendiceal adenocarcinoma typically presents as an incidentally noted appendiceal mass, or with symptoms of right lower quadrant pain that can mimic appendicitis, but local involvement of adjacent organs is uncommon, particularly as the presenting sign. We report on a case of a primary appendiceal cancer initially diagnosed as a rectal polyp based on its appearance in the rectal lumen. The management of the patient was in keeping with standard practice for a rectal polyp, and the diagnosis of appendiceal adenocarcinoma was made intraoperatively. The operative strategy had to be adjusted due to this unexpected finding. Although there are published cases of appendiceal adenocarcinoma inducing intussusception and thus mimicking a cecal polyp, there are no reports in the literature describing invasion of the appendix through the rectal wall and thus mimicking a rectal polyp. The patient is a 75-year-old female who presented with spontaneous hematochezia and, on colonoscopy, was noted to have a rectal polyp that appeared to be located within a diverticulum. When endoscopic mucosal resection was not successful, she was referred to colorectal surgery for a low anterior resection. Preoperative imaging was notable for an enlarged appendix adjacent to the rectum. Intraoperatively, the appendix was found to be densely adherent to the right lateral rectal wall. An en bloc resection of the distal sigmoid colon, proximal rectum and appendix was performed, with pathology demonstrating appendiceal adenocarcinoma that invaded through the rectal wall. The prognosis in this type of malignancy weighs heavily on whether or not perforation and spread throughout the peritoneal cavity have occurred. In this unusual presentation, an en bloc resection is required for a complete resection and to minimize the risk of peritoneal spread. Unusual appearing polyps do not always originate from the bowel wall. Abnormal radiographic findings adjacent to an area of gastrointestinal pathology may signify locally advanced disease from a surrounding organ that secondarily involves the gastrointestinal tract. These findings warrant further investigation prior to any intervention to ensure appropriate treatment.

Emotion reactivity and regulation are associated with psychological functioning following the 2011 earthquake, tsunami, and nuclear crisis in Japan.

Frequent and successful use of cognitive reappraisal, an emotion regulation strategy that involves rethinking the meaning of an emotional event in order to change one's emotional response, has been linked in everyday life to positive outcomes such as higher well-being. Whether we should expect this association to be maintained in a strong, temporally and spatially close emotional context is an unexplored question that might have important implications for our understanding of emotion regulation and its relations to psychological functioning. In this study of members of the U. S. Embassy Tokyo community in the months following the March 2011 earthquake, tsunami, and nuclear crisis in Japan, self-reported use of cognitive reappraisal was not related to psychological functioning, but demonstrated success using cognitive reappraisal to decrease feelings of unpleasantness in response to disaster-related pictures on a performance-based task was associated with fewer symptoms of depression and posttraumatic stress. Moreover, emotional reactivity to these pictures was associated with greater symptomatology. These results suggest that situational intensity may be an important moderator of reappraisal and psychological functioning relationships.

Ultrasound elastography in children: establishing the normal range of muscle elasticity.

BACKGROUND: Ultrasound elastography allows assessment of tissue elasticity. To the best of our knowledge, the elastography appearance of muscles in normal children has not been described. OBJECTIVE: To determine the US elasticity of muscles in children at rest and following exercise. MATERIALS AND METHODS: Cine elastography of biceps brachii and rectus femoris muscles was obtained at rest and after exercise in 42 healthy children (23 males, 19 females; mean: 11.2 ± 4.4 years, range: 2-18 years). Elastography scores were assigned to each clip based on a five-point color scale. Mean elastography scores and standard deviations were calculated and resting and postexercise elastography scores were compared. RESULTS: Resting muscle elasticity was lower in the biceps brachii than in the rectus femoris (P = 0.008), and higher in the dominant than in the nondominant biceps brachii (P < 0.032). Rectus femoris elasticity was higher in males than females (P = 0.051). Postexercise muscle elasticity significantly increased in both the dominant and nondominant biceps brachii (P < 0.001) and in the rectus femoris (P < 0.001). There was no significant gender-related difference in postexercise muscle elasticity. Biceps brachii elasticity decreased and rectus femoris elasticity increased with increasing body mass index. Younger subjects had a greater change in muscle elasticity with exercise. CONCLUSION: Resting muscle elasticity in children is significantly lower in the biceps brachii than in the rectus femoris and in the nondominant biceps brachii than in the dominant biceps brachii. Elasticity significantly increases immediately postexercise in both muscle groups; resting differences between biceps brachii and rectus femoris elasticity, and dominant and nondominant biceps brachii elasticity, do not persist after exercise. The change in muscle elasticity with exercise is higher in younger children.

Inter-rater concordance of wound classifications in patients undergoing appendectomy.

BACKGROUND: Despite the widespread utilization of a four-stage wound classification system to risk-adjust operations for surgical site infection (SSI) rates, we are not aware of any study evaluating the definitions of the wound classes for clarity. We limited our study of wound classifications to appendectomies and posed the question whether different reviewers classify individual cases differently. METHODS: We evaluated the wound classifications of 105 consecutive appendectomies in our community hospital. Four reviewers graded retrospectively the wound classifications, first after reading the description of the appendix in the operative report and again after reading the pathology report. The wound classifications of the four reviewers were evaluated for concordance with the original operating room nurse (ORN) assignment. RESULTS: The kappa scores for inter-observer concordance of wound classifications among the four reviewers based on their interpretation of the operative report and the ORN who originally classified the operation ranged from 0.1028 to 0.1597. By conventional standards, this represents no better than "slight agreement" for any of the reviewers. We found that 19%, 50%, 94%, 95%, or 96% of our appendectomies would be considered "high risk," Class 3 or 4, operations depending on which rater classified the operation. The additional information contained in the pathology reports did not change the distribution of wound classifications of the four reviewers significantly. CONCLUSIONS: Our study demonstrated considerable differences in the distribution of wound classifications of appendectomies among our ORNs and retrospective reviewers. A review of the surgical literature supports our finding that the incision classification system utilized commonly lacks precision, at least in the rating of appendectomies. We recommend that further studies be performed to determine whether changes in the definitions of wound classes are warranted.

Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.

BACKGROUND: Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking. METHODS: We tested the anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal seizures. In addition, we evaluated the protective effects of postnatal day (P)10 LEV treatment on later-life kainic acid (KA)-induced seizure susceptibility and seizure-induced neuronal injury. Western blot and immunohistochemistry were used to assess the developmental regulation of SV2A in the rat and human brain. RESULTS: LEV pretreatment at P10 significantly decreased the cumulative duration of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA-induced seizures and neuronal loss were significantly diminished in rats previously treated with LEV. LEV target SV2A is present in both neonatal rat and human brain and increases steadily to adulthood. CONCLUSION: LEV suppressed acute seizures induced by perinatal hypoxia and diminished later-life seizure susceptibility and seizure-induced neuronal injury, providing evidence for disease modification. These results support consideration of a clinical trial of LEV in neonatal seizures.

Glutamate receptor 1 phosphorylation at serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability after early life seizures.

Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, and there are no treatments to prevent these sequelae. We showed previously that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of serine-831 (S831) and Serine 845 (S845) sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced posttranslational modifications may represent a novel therapeutic target. To unambiguously assess the contribution of these sites, we examined seizure susceptibility in wild-type mice versus transgenic knock-in mice with deficits in GluR1 S831 and S845 phosphorylation [GluR1 double-phosphomutant (GluR1 DPM) mice]. Phosphorylation of the GluR1 S831 and S845 sites was significantly increased in the hippocampus and cortex after a single episode of pentyleneterazol-induced seizures in postnatal day 7 (P7) wild-type mouse pups and that transgenic knock-in mice have a higher threshold and longer latencies to seizures. Like the rat, hypoxic seizures in P9 C57BL/6N wild-type mice resulted in transient increases in GluR1 S831 and GluR1 S845 phosphorylation in cortex and were associated with enhanced seizure susceptibility to later-life kainic-acid-induced seizures. In contrast, later-life seizure susceptibility after hypoxia-induced seizures was attenuated in GluR1 DPM mice, supporting a role for posttranslational modifications in seizure-induced network excitability. Finally, human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845, supporting the validation of this potential therapeutic target in human tissue.

The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR) pathway.

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures.

Prediction of fat-free mass and percentage of body fat in neonates using bioelectrical impedance analysis and anthropometric measures: validation against the PEA POD.

Accurate assessment of neonatal body composition is essential to studies investigating neonatal nutrition or developmental origins of obesity. Bioelectrical impedance analysis or bioimpedance analysis is inexpensive, non-invasive and portable, and is widely used in adults for the assessment of body composition. There are currently no prediction algorithms using bioimpedance analysis in neonates that have been directly validated against measurements of fat-free mass (FFM). The aim of the study was to evaluate the use of bioimpedance analysis for the estimation of FFM and percentage of body fat over the first 4 months of life in healthy infants born at term, and to compare these with estimations based on anthropometric measurements (weight and length) and with skinfolds. The present study was an observational study in seventy-seven infants. Body fat content of infants was assessed at birth, 6 weeks, 3 and 4·5 months of age by air displacement plethysmography, using the PEA POD body composition system. Bioimpedance analysis was performed at the same time and the data were used to develop and test prediction equations for FFM. The combination of weight+sex+length predicted FFM, with a bias of < 100 g and limits of agreement of 6-13 %. Before 3 months of age, bioimpedance analysis did not improve the prediction of FFM or body fat. At 3 and 4·5 months, the inclusion of impedance in prediction algorithms resulted in small improvements in prediction of FFM, reducing the bias to < 50 g and limits of agreement to < 9 %. Skinfold measurements performed poorly at all ages.

Preliminary clinical experience at 3 T with a 3D T2-weighted sequence compared with multiplanar 2D for evaluation of the female pelvis.

OBJECTIVE: The purpose of this article is to compare 3D T2-weighted sampling perfection with application-optimized contrast with different flip-angle evolutions (SPACE) with three-plane 2D turbo-spin echo (TSE) sequences for female pelvic imaging at 3 T. MATERIALS AND METHODS: Twenty women were imaged with 2D TSE and 3D SPACE sequences. Three radiologists independently assessed image quality, diagnostic quality, and artifacts; measured normal anatomic structures; evaluated pathologic abnormalities; and recorded interpretation time. Readers subsequently performed a side-by-side comparison, and their preferences were graded according to overall interpretation, sharpness of lesion edges, motion and other artifacts, uterine and cervical zonal anatomy distinction, identification of adnexal pathologic abnormalities, and distinction between fat and fluid. Quantitative comparison of relative signal intensity and relative tissue contrast was performed. RESULTS: The mean acquisition time of 3D SPACE was significantly shorter than that of 2D TSE (6 minutes 35 seconds vs 8 minutes 50 seconds; p < 0.005). Intrareader agreement between interpretations of 2D and 3D sequences was excellent. There were no significant differences among readers in detecting artifacts, normal structures, and pathologic abnormalities or in determining endometrial thickness, image quality, or interpretation time (p > 0.05). Except for distinctions between fat and fluid, the average reader score indicated a slight preference for the 3D sequence. Three-dimensional multiplanar reconstructions were helpful but not considered essential. Relative agreement between readers was moderate (r ≥ 0.4) to strong (r ≥ 0.7). The relative signal intensity was higher for fat and bladder fluid on the 3D sequence than on the 2D sequence (p = 0.014 and p = 0.018, respectively). Relative tissue contrast was higher for the 3D sequence (p < 0.05), with no significant difference in bladder or fat contrast (p = 0.31) but a trend toward more superior contrast on the 2D sequence. CONCLUSION: At 3 T, 3D SPACE has similar image quality and diagnostic quality with shorter scan time when compared with 2D TSE but with reduced contrast between fat and fluid.

Advances in magnetic resonance imaging of articular cartilage.

The pathology, assessment, and management of articular cartilage lesions of the hip and knee have been the subject of considerable attention in the recent orthopaedic literature. MRI has long been an important tool in the diagnosis and management of articular cartilage pathology, but detecting and interpreting early cartilaginous degeneration with this technology has been difficult. Biochemical-based MRI has been advocated to detect early cartilaginous degenerative changes and assess cartilage repair. Techniques such as T2 mapping, T1rho (ie, T1 in the rotating frame), sodium MRI, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) take advantage of changes in the complex biochemical composition of articular cartilage and may help detect morphologic cartilaginous changes earlier than does conventional MRI. Although the newer modalities have been used primarily in the research setting, their ability to assess the microstructure of articular cartilage may eventually enhance the diagnosis and management of osteoarthritis.

The clinically available NMDA receptor antagonist, memantine, exhibits relative safety in the developing rat brain.

The N-methyl-d-aspartate glutamate receptor (NMDAR) has been implicated in preterm brain injury (periventricular leukomalacia (PVL)) and represents a potential therapeutic target. However, the antagonist dizocilpine (MK-801) has been reported to increase constitutive neuronal apoptosis in the developing rat brain, limiting its clinical use in the developing brain. Memantine is another use-dependent NMDAR antagonist with shorter binding kinetics and has been demonstrated to be protective in a rat model of PVL, without effects on normal myelination or cortical growth. To further evaluate the safety of memantine in the developing brain, we demonstrate here that, in contrast to MK-801, memantine at neuroprotective doses does not increase neuronal constitutive apoptosis. In addition, there are no long-term alterations in the expression of NMDAR subunits, AMPAR subunits, and two markers of synaptogenesis, Synapsin-1 and PSD95. Evaluating clinically approved drugs in preclinical neonatal animal models of early brain development is an important prerequisite to considering them for clinical trial in preterm infants and early childhood.

MRI features of renal oncocytoma and chromophobe renal cell carcinoma.

OBJECTIVE: The purpose of this study was to retrospectively describe the MRI features of the pathologically related entities renal oncocytoma and chromophobe renal cell carcinoma (RCC). MATERIALS AND METHODS: Twenty-eight cases of histologically proven renal oncocytoma and 15 of chromophobe RCC evaluated with preoperative MRI from January 2003 through June 2009 at our institution were independently reviewed for an array of MRI features by two radiologists blinded to the final histopathologic diagnosis. These features were tabulated and compared between chromophobe RCC and renal oncocytoma by use of the Mann-Whitney test and binary logistic regression. RESULTS: Renal oncocytoma and chromophobe RCC showed no significant difference in size or any of 16 qualitative imaging features (p = 0.0842-1.0, reader 1; p = 0.0611-1.0, reader 2). Microscopic fat, hemorrhage, cysts, infiltrative margins, perinephric fat invasion, renal vein invasion, enhancement homogeneity, and hypervascularity were each observed in less than 20% of cases by both readers. A central scar and segmental enhancement inversion (a recently described finding in which early contrast-enhanced images show relatively more enhanced and less enhanced intralesional components with inversion of their relative enhancement on later images) were observed by both readers in at least 10% of cases of both renal oncocytoma and of chromophobe RCC with no significant difference between the two entities (p = 0.2092-0.2960). CONCLUSION: We have presented the largest series to date of the MRI features of both renal oncocytoma and chromophobe RCC. These related entities exhibited similar findings, and no MRI features were reliable in distinguishing between them.

Utility of the apparent diffusion coefficient for distinguishing clear cell renal cell carcinoma of low and high nuclear grade.

OBJECTIVE: The purpose of our study was to assess the utility of the apparent diffusion coefficient (ADC) in distinguishing low-grade and high-grade clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The cases of 57 patients with pathologically proven ccRCC who underwent preoperative MRI, including diffusion-weighted imaging, were retrospectively assessed. ADC values were obtained from ADC maps calculated using b-value combinations of 0 and 400 s/mm² and of 0 and 800 s/mm² (hereafter referred to as ADC-400 and ADC-800). Lesions were also evaluated for an array of conventional MRI features. A single expert uropathologist reviewed all slides to determine nuclear grade. The utility of ADC for detecting high-grade ccRCC, alone and in combination with conventional MRI features, was assessed using receiver operating characteristic (ROC) analysis and binary logistic regression. RESULTS: ADC-400 and ADC-800 were significantly lower among high-grade than among low-grade ccRCC (2.24 ± 0.50 mm²/s vs 1.59 ± 0.57 mm²/s for ADC-400, p < 0.001; 1.85 ± 0.40 mm²/s vs 1.28 ± 0.48 mm²/s for ADC-800; p < 0.001). The area under the ROC curve for identifying high-grade ccRCC using ADC-400 and ADC-800 was 0.801 and 0.824 respectively (p = 0.606), with optimal thresholds, sensitivity, and specificity as follows: ADC-400: 2.17 mm²/s, 88.5%, 64.5% and ADC-800: 1.20 mm²/s, 65.4%, 96.0%. Using multivariate logistic regression, only necrosis (p = 0.0229) and perinephric fat invasion (p = 0.0160) were retained among conventional imaging features as independent risk factors for high-grade ccRCC. The accuracy of the logistic regression model for predicting high-grade ccRCC was significantly improved by inclusion of either ADC-400 (p = 0.0143) or ADC-800 (p = 0.015). CONCLUSION: ADC is significantly lower in high-grade ccRCC compared with low-grade ccRCC and increases the accuracy for detecting high-grade ccRCC compared with conventional MRI features alone.

d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila.

dTOR (target of rapamycin) and dFoxo respond to changes in the nutritional environment to induce a broad range of responses in multiple tissue types. Both dTOR and dFoxo have been demonstrated to control the rate of age-related decline in cardiac function. Here, we show that the Eif4e-binding protein (d4eBP) is sufficient to protect long-term cardiac function against age-related decline and that up-regulation of dEif4e is sufficient to recapitulate the effects of high dTOR or insulin signaling. We also provide evidence that d4eBP acts tissue-autonomously and downstream of dTOR and dFoxo in the myocardium, where it enhances cardiac stress resistance and maintains normal heart rate and myogenic rhythm. Another effector of dTOR and insulin signaling, dS6K, may influence cardiac aging nonautonomously through its activity in the insulin-producing cells, possibly by regulating dilp2 expression. Thus, elevating d4eBP activity in cardiac tissue represents an effective organ-specific means for slowing or reversing cardiac functional changes brought about by normal aging.