Repeatability of MRI Biomarkers in Nonalcoholic Fatty Liver Disease: The NIMBLE Consortium.

Background There is a need for reliable noninvasive methods for diagnosing and monitoring nonalcoholic fatty liver disease (NAFLD). Thus, the multidisciplinary Non-invasive Biomarkers of Metabolic Liver disease (NIMBLE) consortium was formed to identify and advance the regulatory qualification of NAFLD imaging biomarkers. Purpose To determine the different-day same-scanner repeatability coefficient of liver MRI biomarkers in patients with NAFLD at risk for steatohepatitis. Materials and Methods NIMBLE 1.2 is a prospective, observational, single-center short-term cross-sectional study (October 2021 to June 2022) in adults with NAFLD across a spectrum of low, intermediate, and high likelihood of advanced fibrosis as determined according to the fibrosis based on four factors (FIB-4) index. Participants underwent up to seven MRI examinations across two visits less than or equal to 7 days apart. Standardized imaging protocols were implemented with six MRI scanners from three vendors at both 1.5 T and 3 T, with central analysis of the data performed by an independent reading center (University of California, San Diego). Trained analysts, who were blinded to clinical data, measured the MRI proton density fat fraction (PDFF), liver stiffness at MR elastography (MRE), and visceral adipose tissue (VAT) for each participant. Point estimates and CIs were calculated using χ2 distribution and statistical modeling for pooled repeatability measures. Results A total of 17 participants (mean age, 58 years ± 8.5 [SD]; 10 female) were included, of which seven (41.2%), six (35.3%), and four (23.5%) participants had a low, intermediate, or high likelihood of advanced fibrosis, respectively. The different-day same-scanner mean measurements were 13%-14% for PDFF, 6.6 L for VAT, and 3.15 kPa for two-dimensional MRE stiffness. The different-day same-scanner repeatability coefficients were 0.22 L (95% CI: 0.17, 0.29) for VAT, 0.75 kPa (95% CI: 0.6, 0.99) for MRE stiffness, 1.19% (95% CI: 0.96, 1.61) for MRI PDFF using magnitude reconstruction, 1.56% (95% CI: 1.26, 2.07) for MRI PDFF using complex reconstruction, and 19.7% (95% CI: 15.8, 26.2) for three-dimensional MRE shear modulus. Conclusion This preliminary study suggests that thresholds of 1.2%-1.6%, 0.22 L, and 0.75 kPa for MRI PDFF, VAT, and MRE, respectively, should be used to discern measurement error from real change in patients with NAFLD. ClinicalTrials.gov registration no. NCT05081427 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kozaka and Matsui in this issue.

Percutaneous image-guided cryoablation of painful metastases involving bone: multicenter trial.

BACKGROUND: This study sought to describe the results of a single-arm multicenter clinical trial using image-guided percutaneous cryoablation for the palliation of painful metastatic tumors involving bone. METHODS: Over a 44-month period, 61 adult patients with 1 or 2 painful bone metastases with a score of 4 or more on a scale of 0 to 10 (≥4/10) worst pain in a 24-hour period who had failed or refused conventional treatment were treated with percutaneous image-guided cryoablation. Patient pain and quality of life was measured using the Brief Pain Inventory prior to treatment, 1 and 4 days after the procedure, weekly for 4 weeks, and every 2 weeks thereafter for a total of 6 months. Patient analgesic use was also recorded at these same follow-up intervals. Complications were monitored. Analysis of the primary endpoint was undertaken via paired comparison procedures. RESULTS: A total of 69 treated tumors ranged in size from 1 to 11 cm. Prior to cryoablation, the mean score for worst pain in a 24-hour period was 7.1/10 with a range of 4/10 to 10/10. At 1, 4, 8, and 24 weeks after treatment, the mean score for worst pain in a 24-hour period decreased to 5.1/10 (P < .0001), 4.0/10 (P < .0001), 3.6/10 (P < .0001), and 1.4/10 (P < .0001), respectively. One of 61 (2%) patients had a major complication with osteomyelitis at the site of ablation. CONCLUSIONS: Percutaneous cryoablation is a safe, effective, and durable method for palliation of pain due to metastatic disease involving bone.

Structural and functional evidence for discrete exit pathways that connect the canine sinoatrial node and atria.

Surface electrode recordings cannot delineate the activation within the human or canine sinoatrial node (SAN) because they are intramural structures. Thus, the site of origin of excitation and conduction pathway(s) within the SAN of these mammals remains unknown. Canine right atrial preparations (n=7) were optically mapped. The SAN 3D structure and protein expression were mapped using immunohistochemistry. SAN optical action potentials had diastolic depolarization and multiple upstroke components that corresponded to the separate excitations of the node and surface atrial layers. Pacing-induced SAN exit block eliminated atrial optical action potential components but retained SAN optical action potential components. Excitation originated in the SAN (cycle length, 557+/-72 ms) and slowly spread (1.2 to 14 cm/sec) within the SAN, failing to directly excite the crista terminalis and intraatrial septum. After a 49+/-22 ms conduction delay within the SAN, excitation reached the atrial myocardium via superior and/or inferior sinoatrial exit pathways 8.8+/-3.2 mm from the leading pacemaker site. The ellipsoidal 13.7+/-2.8/4.9+/-0.6 mm SAN structure was functionally insulated from the atrium. This insulation coincided with connexin43-negative regions at the borders of the node, connective tissue, and coronary arteries. During normal sinus rhythm, the canine SAN is functionally insulated from the surrounding atrial myocardium except for 2 (or more) narrow superior and inferior sinoatrial exit pathways separated by 12.8+/-4.1 mm. Conduction failure in these sinoatrial exit pathways leads to SAN exit block and is a modulator of heart rate.

Spontaneous Ca waves in ventricular myocytes from failing hearts depend on Ca(2+)-calmodulin-dependent protein kinase II.

Increased cardiac ryanodine receptor (RyR)-dependent diastolic SR Ca leak is present in heart failure and in conditions when adrenergic tone is high. Increasing Ca leak from the SR could result in spontaneous Ca wave (SCaW) formation. SCaWs activate the inward Na/Ca exchanger (NCX) current causing a delayed afterdepolarization (DAD), potentially leading to arrhythmia. Here we examine SCaWs in ventricular myocytes isolated from failing and healthy rabbit hearts. Myocytes from healthy hearts did not exhibit SCaWs under baseline conditions versus 43% of those exposed to isoproterenol (ISO). This ISO-induced increase in activity was reversed by inhibition of Ca-calmodulin-dependent protein kinase II (CaMKII) by KN93. Inhibition of cAMP-dependent protein kinase (PKA) by H89 had no observed effect. Of myocytes treated with forskolin 50% showed SCaW activity, attributable to a large increase in SR Ca load ([Ca](SRT)) versus control. At similar [Ca](SRT) (121muM) myocytes treated with ISO plus KN93 had significantly fewer SCaWs versus those treated with ISO or ISO plus H89 (0.2+/-0.28 vs. 1.1+/-0.28 and 1.29+/-0.39 SCaWs cell(-)(1), respectively). In myocytes isolated from failing hearts ISO induced an increase in the percentage of cells generating SCaWs vs. baseline (74% vs. 11%) with no increase in [Ca](SRT). Inhibiting CaMKII reversed this effect (14%). At similar [Ca](SRT) (71microM) myocytes treated with ISO or ISO plus H89 had significantly more SCaWs per cell vs. untreated (2.5+/-0.5; 1.6+/-0.7 vs. 0.36+/-0.3, respectively). Treatment with ISO plus KN93 completely abolished this effect. The evidence suggests the ISO-dependent increase in SCaW activity in both healthy and failing myocytes is CaMKII-dependent, implicating CaMKII in arrhythmogenesis.

Design and synthesis of trivalent ligands targeting opioid, cholecystokinin, and melanocortin receptors for the treatment of pain.

It has been known that co-administration of morphine with either cholecystokinin (CCK) receptor or melanocortin (MC) receptor antagonists enhance morphine's analgesic efficacy by reducing serious side effects such as tolerance and addiction. Considering these synergistic effects, we have designed trivalent ligands in which all three different pharmacophores for opioid, CCK, and MC receptors are combined in such a way as to conserve their own topographical pharmacophore structures. These ligands, excluding the cyclic compound, were synthesized by solid phase synthesis using Rink-amide resin under microwave assistance in very high yields. These trivalent ligands bind to their respective receptors well demonstrating that the topographical pharmacophore structures for the three receptors were retained for receptor binding. Ligand 10 was a lead compound to show the best biological activities at all three receptors.

Hepatic iron overload in children with sickle cell anemia on chronic transfusion therapy.

Hepatic iron overload is a serious complication of chronic transfusion therapy in patients with sickle cell disease (SCD). No firm consensus has been reached with regard to correlation between hepatic iron content (HIC) and variables including age, number of transfusions, and serum iron makers. Also, the role of HIC in determining hepatic injury is not well established. There is scarcity of data on chronically transfused children with SCD and no other confounding liver pathology. We aimed to further explore relationships between these variables in a cohort of children with SCD on chronic transfusion therapy naive to chelation. Liver biopsies obtained before starting chelation therapy from 27 children with sickle cell anemia receiving chronic transfusion therapy were evaluated for histologic scoring and determination of HIC. Average serum ferritin and iron saturation values were determined for 6 months before biopsy. Duration and total volume of transfusion were obtained from the medical records. All children were negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Mean age at biopsy was 10.95+/-3.34 years. Mean duration and total volume of transfusions were 50.0+/-26.6 months and 17.4+/-9.6 L, respectively. Pearson product-moment bivariate correlation coefficients indicated significant correlations between HIC and histologic iron score, serum ferritin, iron saturation, age, and transfusion volume. After adjusting for transfusion volume, a significant correlation was only seen between HIC and transfusion volume. Mean HIC was 21.8+/-10.4 mg/g dry weight, with fibrosis observed in 10 patients and lobular inflammation in 9. HIC was higher in biopsies with fibrosis (28.2+/-3.8 mg/g) than biopsies without fibrosis (17.6+/-18.3 mg/g; P=0.012). HIC did not differ between biopsies with lobular inflammation (25.5+/-4.0 mg/g) and biopsies without inflammation (19.9+/-2.5 mg/g; P=0.22). These findings show that transfusion volume provides more insight on hepatic iron overload than serum iron markers.

Effects of exercise on quality of life in women living with breast cancer: a systematic review.

The goal of this systematic review was to examine the effect of exercise on quality of life (QOL) in women living with breast cancer. Data bases searched were MEDLINE, EMBASE, CINAHL, PubMed, and PEDro. Keywords were "breast cancer and quality of life" in combination with "exercise" or "physical activity" (with associated Mesh terms). Limits were English or French language. Included studies were independently reviewed for methodological quality (van Tulder et al.) and assigned a level of evidence (Centre for Evidence-Based Medicine). Nine relevant randomized controlled trials were included: four of moderate methodological quality and five of high methodological quality. There was strong evidence that exercise positively influences QOL in women living with breast cancer. Exercise can be an effective strategy to improve QOL in women living with breast cancer. Future research is necessary to determine optimal exercise types and parameters.

Impact of Psychiatric Hospitalization on Trust, Disclosure and Working Alliance with the Outpatient Psychiatric Provider: A Pilot Survey Study.

Introduction  The relationship between inpatient psychiatric experience and subsequent outpatient psychiatric care remains highly understudied. We conducted a voluntary, anonymous, self-report, pilot survey study to explore the impact of current or recent psychiatric hospitalization on patients' ability to trust their outpatient psychiatric providers, particularly with respect to the disclosure of symptoms such as suicidal thoughts. Methods  A survey was conducted in a psychiatry practice-based research network (PBRN) of six outpatient community psychiatry clinic sites within four regional agencies and at an adult inpatient psychiatry unit of a tertiary-care academic hospital in the Cleveland area. We asked patients to record characteristics of their hospitalization, perceived changes in attitudes, and complete a working alliance inventory. Sixty-two surveys were collected. Results  Most respondents had high working alliance scores with their outpatient providers and a low prevalence of coercive experiences during hospitalization. A minority (15%) experienced a reduction in trust with their outpatient provider. Nonetheless, a substantial percentage of respondents expressed a lower likelihood of disclosing various concerning psychiatric symptoms and behaviors to their outpatient provider. Thirty-six percent reported they are less likely to disclose thoughts of harming self. Percentages for subjects reporting a reduced likelihood of disclosing thoughts of harming others, hearing voices, not taking medications as prescribed, and substance use ranged from 21-29%. At the same time, there were also trust-enhancing effects: a substantial number of patients reported an increase in their ability to trust psychiatric providers and an increase in the likelihood of disclosure of psychiatric symptoms. Exploratory analyses revealed significant associations of gender, race, outpatient provider involvement in hospitalization, and involvement of police during admission with trust, disclosure, and working alliance. Conclusion  Even with a high therapeutic alliance and low perceived coercion during inpatient psychiatric hospitalization, the experience can lead to a disruption of trust and transparency with the outpatient psychiatrist in a considerable proportion of patients.

Who Starts the Conversation and Who Receives Preexposure Prophylaxis (PrEP)? A Brief Online Survey of Medical Providers' PrEP Practices.

Uptake of preexposure prophylaxis (PrEP) has been slow, but is increasing. Although PrEP is indicated for many patients, it has been concentrated among men who have sex with men (MSM). Awareness of PrEP is limited among non-MSM individuals, and among some MSM. As such, individuals at risk for HIV who are unaware of PrEP must rely on their medical providers to initiate conversations about PrEP. Members of a national professional organization of HIV specialists with prescribing privileges, including physicians, nurse practitioners, and physician assistants, participated in an online survey ( n = 342) to characterize their PrEP prescribing behaviors and the demographic membership of their PrEP patients. Results indicated that when discussing PrEP with their patients, providers who more frequently initiated these conversations had a higher percentage of non-MSM patients in their PrEP caseload (e.g., women, people who inject drugs, transgender patients). Encouraging providers to initiate discussions about PrEP with their patients and helping them locate support to offset the cost may help increase uptake, particularly among at-risk patients who are underrepresented in PrEP adoption.

Quality-of-life valuations of advanced breast cancer by New Zealand women.

OBJECTIVES: To obtain health-related quality-of-life (HR-QOL) valuations (or 'utilities') from New Zealand women for four health states representative of advanced (metastatic) breast cancer, suitable for use in cost-utility analysis, and to compare four valuation methodologies. METHODS: Written case descriptions of four health states representative of advanced breast cancer (hormonal therapy, chemotherapy, radiotherapy and hypercalcaemia) were developed in consultation with nine oncology professionals. Time trade-off (TTO) and visual analogue scale (VAS) valuations were obtained via interviews from a sample of 50 women, aged 25-69 years, randomly selected from the New Zealand general public and through informal networks. Representations of the four health states on the EQ-5D health state classification system were also obtained from the respondents and later valued using New Zealand and UK EQ-5D social tariffs. RESULTS: The four valuation methods ranked the four states' mean valuations identically: hormonal therapy > chemotherapy > or = radiotherapy > hypercalcaemia. All methods except the TTO distinguished between chemotherapy and radiotherapy. In order of the VAS and TTO methods and the EQ-5D with NZ and UK tariffs, respectively, the valuations [mean (95% CI)] were: hormonal therapy 0.54 (0.48, 0.59); 0.65 (0.57, 0.73); 0.54 (0.51, 0.58); 0.60 (0.54, 0.65); chemotherapy 0.46 (0.41, 0.51); 0.49 (0.40, 0.57); 0.48 (0.43, 0.53); 0.51 (0.43, 0.59); radiotherapy for severe bone pain 0.35 (0.30, 0.40); 0.45 (0.37, 0.54); 0.31 (0.27, 0.35); 0.25 (0.18, 0.33); and moderate to severe hypercalcaemia 0.13 (0.09, 0.17); -0.17 (-0.29, -0.05); -0.05 (-0.07, -0.03); -0.52 (-0.56, -0.48). The four valuation methods gave similar results for chemotherapy, but for the three other states the TTO valuations differed from those obtained from the VAS method and the NZ and UK EQ-5D tariffs. There were significant pairwise correlations between the four methods across all four health states, although the valuation for hypercalcaemia obtained from the UK EQ-5D tariff was very low compared with the three other methods, and the VAS valuation was positive rather than negative. CONCLUSION: Our study suggests that women in the New Zealand general public are able to consistently evaluate and value case descriptions of advanced breast cancer using either direct methods (VAS or TTO) or the EQ-5D health state classification system. Some of the valuations elicited using the four methods differ quantitatively, especially for hypercalcaemia. As our sample size was modest (50) and it turned out to be unrepresentative of the New Zealand female population, this study serves as a pilot study.

Alterations in stress cortisol reactivity in depressed preschoolers relative to psychiatric and no-disorder comparison groups.

BACKGROUND: Despite the robust and widely replicated finding of elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity in depressed adults, studies of depressed children have yielded ambiguous findings. Animal models of early depression and studies of children experiencing early psychosocial deprivation have suggested that alterations in HPA axis reactivity are evident in early "depressive-like" conditions. The current study is, to our knowledge, the first investigation of HPA axis reactivity in very young children with a clinical depressive syndrome for which content validity has been established. METHODS: Depressed, psychiatric, and no-disorder comparison children aged 3 through 5.6 years were studied for HPA axis reactivity in response to experimental psychosocial stressors. The children were diagnosed using a developmentally appropriate, structured psychiatric interview. Salivary cortisol was obtained at 3 time points during a laboratory assessment before and after stressors involving separation from the parent and frustrating tasks. RESULTS: Repeated measures of multivariate analysis of variance revealed a significant interaction between the diagnostic group and 2 cortisol percent change scores. Depressed preschoolers displayed a pattern of increasing cortisol levels throughout the assessment in response to both separation and frustration stressors. In contrast, both comparison groups showed decreasing cortisol levels in response to the separation stressor. All groups displayed increasing cortisol levels in response to frustrating tasks. Preschoolers with a presumptive melancholic depressive subtype displayed these alterations at a greater magnitude relative to comparison groups. CONCLUSIONS: To our knowledge, these findings are the first to demonstrate altered HPA axis reactivity in depressed preschoolers. These alterations are consistent with those described in depressed adults and in animal models of early depression. These findings provide evidence for possible continuity of HPA axis alterations in depressive disorders across the lifespan and are discussed in the context of prior studies of HPA axis reactivity in clinically depressed children and adolescents, suggesting that younger age and inpatient status are features associated with altered HPA axis reactivity.

Cardiac Transplantation in the New Era.

The prevalence of heart failure continues to rise due to the aging population and longer survival of people with conditions that lead to heart failure, eg, hypertension, diabetes, and coronary artery disease. Although medical therapy has had an important impact on survival of patients and improving quality of life, heart transplantation remains the definitive therapy for patients that eventually deteriorate. Since the first successful heart transplantation in 1967, significant improvements have been made regarding donor and recipient selection, surgical techniques, and postoperative care. However, the number of potential organ donors has not changed and the growing number of patients in need for transplantation has resulted an increase in waiting list time, and the need for mechanical support. To overcome this issue, the United Network for Organ Sharing implemented an allocation system to prioritize the sickest patients on the list to receive organs. Despite the careful selection of patients, pretransplant immunological screening, and multidrug immunosuppressive regimens, acute and chronic rejections occur and potentially limit graft and patient survival. Treatment for rejection largely depends on the type of rejection, the presence of hemodynamic compromise, and time after transplantation. The limiting factor for long-term graft survival is allograft vasculopathy, an immune-mediated process causing diffuse narrowing of the coronary arteries. Percutaneous coronary intervention and coronary artery bypass surgery are often not an option for this vasculopathy due to the lack of focal lesions, and retransplantation is the only option in appropriate patients.

Characteristics of depressed preschoolers with and without anhedonia: evidence for a melancholic depressive subtype in young children.

OBJECTIVE: This study investigated whether a melancholic subtype similar to that established in depressed adults can be identified in depressed preschool children. METHOD: A final group total of 156 preschool children between the ages of 3.0 and 5.6 years and their caregivers underwent a comprehensive psychiatric assessment that included a structured psychiatric interview modified for young children. The clinical characteristics of four study groups (N=156) were compared: depressed preschoolers with anhedonia, depressed preschoolers without anhedonia ("hedonic"), a psychiatric comparison group with DSM-IV attention deficit hyperactivity disorder and/or oppositional defiant disorder, and a healthy comparison group. RESULTS: Fifty-four depressed preschoolers were identified, and 57% of this depressed group was anhedonic, a symptom deemed to be highly developmentally and clinically significant when arising in the preschool period. The anhedonic depressed subgroup identified was characterized by greater depression severity, alterations in stress cortisol reactivity, increased family history of major depressive disorder, and increased frequency of psychomotor retardation as well as other melancholic symptoms, such as a lack of brightening in response to joyful events. CONCLUSIONS: The clinical characteristics of this depressed subgroup are consistent with those described in melancholic depressed adults and suggest that a melancholic depressed subtype can be manifest in children as young as age 3.

Modification of DSM-IV criteria for depressed preschool children.

OBJECTIVE: This study compared the severity of depression in preschoolers diagnosed by standard versus modified DSM-IV criteria for major depression. METHOD: A group of 145 preschoolers and their caregivers underwent a diagnostic assessment for preschool children. A factor analysis of depressive symptoms from the group was performed to derive a depression severity score. Scores were compared among four groups: standard DSM-IV major depression, modified DSM-IV major depression, DSM-IV attention deficit hyperactivity disorder and/or oppositional defiant disorder, and no disorder. RESULTS: A hierarchy in severity emerged, with significant differences among all four groups. Preschoolers meeting standard criteria displayed the highest severity, followed by those who met modified criteria. Both depressed groups had significantly higher severity than the two comparison groups. CONCLUSIONS: Standard DSM-IV criteria captured the most severely affected preschoolers, missing a substantial proportion of children with potentially clinically significant but less severe symptoms who were captured by modified DSM-IV criteria.

ThePreschool Feelings Checklist: a brief and sensitive screening measure for depression in young children.

OBJECTIVE: Childhood depression is widely underrecognized in primary health care settings. This phenomenon appears to increase with younger age. Evidence has been provided for a valid depressive syndrome among preschool children. Based on the need for the earliest possible identification of depression, the development of a brief screening measure to capture young children with markers of depression from these community settings was developed and tested. METHOD: A group of 174 preschool children underwent a comprehensive psychiatric assessment. The majority of this study group was ascertained from primary care settings using a 20-item checklist designed to capture depressive symptoms in young children. The assessment included the Diagnostic Interview Schedule for Children Version modified for young children and the Child Behavior Checklist. Ratings on the checklist were subsequently compared with these independent measures of psychopathology using several analytic strategies. RESULTS: The Preschool Feelings Checklist demonstrated high internal consistency, and 16 items showed strong associations with independent diagnostic measures of internalizing symptoms and major depressive disorder. The Preschool Feelings Checklist demonstrated high specificity and sensitivity for the identification of major depressive disorder at a cutoff score 3 or more. CONCLUSIONS: The Preschool Feelings Checklist is a brief and valid screening measure highly feasible for use in primary care settings. It demonstrated utility for the identification of preschoolers in need of formal mental health evaluation for depression.

Preschool major depressive disorder: preliminary validation for developmentally modified DSM-IV criteria.

OBJECTIVE: To investigate the validity of developmentally modified DSM-IV criteria for preschool major depressive disorder (MDD). METHOD: Subjects between the ages of 3.0 and 5.6 years were ascertained from community and clinical sites for a comprehensive assessment that included an age-appropriate psychiatric interview with the parent about the child. Minor developmental modifications to the formal DSM-IV MDD criteria were tested, including translations of symptoms to describe age-appropriate manifestations and setting aside the duration criterion. Preschool children who met modified criteria were compared with psychiatric and normal control groups. RESULTS: Validation for the modified criteria was supported by a specific and stable symptom constellation, social impairment, greater family histories of affective disorders, and higher child-reported symptoms of depression on an age-appropriate puppet interview. Preschool children with MDD displayed "typical" symptoms of depression, as well as vegetative signs. Standard DSM-IV criteria failed to capture 76% of children who met these modified criteria. CONCLUSIONS: Evidence that preschool children can manifest typical symptoms of MDD when age-adjusted symptoms states are assessed is provided. Findings also suggest that standard DSM-/V criteria may not be sufficiently sensitive for preschool children, as they failed to capture a substantial proportion of symptomatic children. Minor modifications to DSM-IV criteria are recommended to capture clinically significant preschool MDD.

The clinical picture of depression in preschool children.

OBJECTIVE: To investigate the clinical characteristics of depression in preschool children. METHOD: One hundred seventy-four subjects between the ages of 3.0 and 5.6 years were ascertained from community and clinical sites for a comprehensive assessment that included an age-appropriate psychiatric interview for parents. Modifications were made to the assessment of major depressive disorder (MDD) criteria so that age-appropriate manifestations of symptom states could be captured. Typical and "masked" symptoms of depression were investigated in three groups: depressed (who met all MDD criteria except duration criterion), those with nonaffective psychiatric disorders (who met criteria for attention-deficit/hyperactivity disorder and/or oppositional defiant disorder), and those who did not meet criteria for any psychiatric disorder. RESULTS: Depressed preschool children displayed "typical" symptoms and vegetative signs of depression more frequently than other nonaffective or "masked" symptoms. Anhedonia appeared to be a specific symptom and sadness/irritability appeared to be a sensitive symptom of preschool MDD. CONCLUSIONS: Clinicians should be alert to age-appropriate manifestations of typical MDD symptoms and vegetative signs when assessing preschool children for depression. "Masked" symptoms of depression occur in preschool children but do not predominate the clinical picture. Future studies specifically designed to investigate the specificity and sensitivity of the symptoms of preschool depression are now warranted.

Health-related quality of life after lung volume reduction surgery.

Many studies have demonstrated short-term physiologic benefits and improvements in various measures of health-related quality of life (HRQOL) after lung volume reduction surgery (LVRS). However, LVRS involves short-term risks of morbidity, disability, and mortality. Few reports describe the long-term effects of LVRS on patients with emphysema. Rational decision making about LVRS depends on whether the expected improvement in quality of life from LVRS outweighs the expected disability and morbidity and the potential mortality from the procedure. This report describes the HRQOL and survival outcomes of patients with emphysema after LVRS.

Monitoring the development of xenograft triple-negative breast cancer models using diffusion-weighted magnetic resonance imaging.

Evaluations of tumor growth rates and molecular biomarkers are traditionally used to assess new mouse models of human breast cancers. This study investigated the utility of diffusion weighted (DW)-magnetic resonance imaging (MRI) for evaluating cellular proliferation of new tumor models of triple-negative breast cancer, which may augment traditional analysis methods. Eleven human breast cancer cell lines were used to develop xenograft tumors in severe combined immunodeficient mice, with two of these cell lines exhibiting sufficient growth to be serially passaged. DW-MRI was performed to measure the distributions of the apparent diffusion coefficient (ADC) in these two tumor xenograft models, which showed a correlation with tumor growth rates and doubling times during each passage. The distributions of the ADC values were also correlated with expression of Ki67, a biomarker of cell proliferation, and hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor receptor-2 (VEGFR2), which are essential proteins involved in regulating aerobic glycolysis and angiogenesis that support tumor cell proliferation. Although phosphatase and tensin homolog (PTEN) levels were different between the two xenograft models, AKT levels did not differ nor did they correlate with tumor growth. This last result demonstrates the complexity of signaling protein pathways and the difficulty in interpreting the effects of protein expression on tumor cell proliferation. In contrast, DW-MRI may be a more direct assessment of tumor growth and cancer cell proliferation.