Associations of brain-derived neurotrophic factor rs6265 polymorphism and cognitive function in breast cancer survivors from a cross-sectional study.

BACKGROUND: Breast cancer survivors (BCS) often complain of cancer-related cognitive impairment (CRCI) during and even months after completing primary cancer treatments, particularly chemotherapy. The etiology of CRCI is unknown, but associations of CRCI with germline genetic polymorphisms have been reported, including Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism. The current study investigated the associations of specific BDNF rs6265 with CRCI. METHODS: Cancer-related cognitive impairment was assessed using subjective reports of cognitive symptoms (the version 1.0, 8-item short-forms of the Patient-Reported Outcomes Measurement Information System®) and computerized objective cognitive function scores (CANTAB®). BDNF rs6265 genotypes were determined from buccal swabs. The associations of specific BDNF rs6265 with CRCI were examined by either one-way analysis of variance or the Kruskal-Wallis test followed by post hoc tests and rank-based regression analysis. RESULTS: We examined 356 female BCS. The mean (SD) age was 55.6 (9.8) years old, the median (IQR) years since cancer diagnosis were 4.0 (6.0), and 331 (92.7%) were self-described as White. BCS carrying the Met/Met genotype showed poorer results on 'visual episodic memory and new learning' and 'spatial working memory and executive function.' This relationship was observed regardless of prior chemotherapy. CONCLUSION: Our findings suggest that carrying the BDNF rs6265 Met/Met genotype increases the risk for CRCI in BCS. These results are foundational in nature and provide important information to identify mechanisms underpinning CRCI.

Serum Phosphorus as a Driver of Skeletal Morbidity in Fibrous Dysplasia.

CONTEXT: Fibrous dysplasia (FD) results in fractures, pain, and deformities. Abnormal osteoprogenitor cells overproduce FGF23, leading to hyperphosphaturia in most patients and frank hypophosphatemia in a subset. Studies suggest hypophosphatemia is associated with increased FD-related morbidity. However, the relationship between phosphorus and skeletal complications has not been investigated, and the optimal therapeutic target has not been determined. OBJECTIVE: Characterize the impact of serum phosphorus on FD-related morbidity and identify levels associated with increased skeletal complications. METHODS: Natural history study with 240 subjects at a clinical research center who had ≥1 fasting phosphorus level, determined as age- and sex-adjusted Z-scores. Subjects were categorized based on frank hypophosphatemia (Z-score ≤ -2; n = 48); low-normophosphatemia (> -2 to ≤ -1; n = 66); and high-normophosphatemia (> -1 to ≤ 2; n = 125). Main outcomes were fractures, orthopedic surgeries, and scoliosis. RESULTS: Subjects with frank and low-normophosphatemia had increased fracture and surgery rates vs high-normophosphatemia. The prevalence of moderate to severe scoliosis was similarly higher in the frank and low-normophosphatemia groups. In a subanalysis of patients matched for Skeletal Burden Score ≥35, fracture and surgery rates remained higher in the frank hypophosphatemia group, suggesting association between phosphorus and skeletal complications is not explained by differences in FD burden alone. CONCLUSION: Both frank hypophosphatemia and low-normophosphatemia are associated with increased FD-related complications. This supports FGF23-mediated hypophosphatemia as a driver of skeletal morbidity, which may impact a larger proportion of the FD/McCune-Albright syndrome population than previously recognized. These findings enable clinicians to identify at-risk patients and will inform development of prospective studies to determine optimal therapeutic targets.

Smartphone Augmented Reality Outperforms Conventional CT Guidance for Composite Ablation Margins in Phantom Models.

PURPOSE: To develop and evaluate a smartphone augmented reality (AR) system for a large 50-mm liver tumor ablation with treatment planning for composite overlapping ablation zones. MATERIALS AND METHODS: A smartphone AR application was developed to display tumor, probe, projected probe paths, ablated zones, and real-time percentage of the ablated target tumor volume. Fiducial markers were attached to phantoms and an ablation probe hub for tracking. The system was evaluated with tissue-mimicking thermochromic phantoms and gel phantoms. Four interventional radiologists performed 2 trials each of 3 probe insertions per trial using AR guidance versus computed tomography (CT) guidance approaches in 2 gel phantoms. Insertion points and optimal probe paths were predetermined. On Gel Phantom 2, serial ablated zones were saved and continuously displayed after each probe placement/adjustment, enabling feedback and iterative planning. The percentages of tumor ablated for AR guidance versus CT guidance, and with versus without display of recorded ablated zones, were compared among interventional radiologists with pairwise t-tests. RESULTS: The means of percentages of tumor ablated for CT freehand and AR guidance were 36% ± 7 and 47% ± 4 (P = .004), respectively. The mean composite percentages of tumor ablated for AR guidance were 43% ± 1 (without) and 50% ± 2 (with display of ablation zone) (P = .033). There was no strong correlation between AR-guided percentage of ablation and years of experience (r < 0.5), whereas there was a strong correlation between CT-guided percentage of ablation and years of experience (r > 0.9). CONCLUSIONS: A smartphone AR guidance system for dynamic iterative large liver tumor ablation was accurate, performed better than conventional CT guidance, especially for less experienced interventional radiologists, and enhanced more standardized performance across experience levels for ablation of a 50-mm tumor.

Correlates of frailty in older female cancer survivors.

INTRODUCTION: Cancer survivors are at risk of frailty because of cancer and its treatment. Understanding the factors that increase the risk of frailty is an important aspect of cancer care for the development of interventions to prevent or manage frailty, thus improving cancer survival and overall quality of life of cancer survivors. This study aimed to identify demographic, clinical, and psychosocial correlates of frailty in older, female cancer survivors. MATERIALS AND METHODS: This is a sub-study focusing on the exploratory aim of a larger cross-sectional study (NURS-IIR-IUSCC-0748). A total of 213 female cancer survivors aged 59-87 years old were included from the parent study in the current analysis. Frailty, the primary outcome, was measured using the Tilburg Frailty Indicator scale. The independent variables were age, relationship status, clinical stage of cancer, treatment type, comorbidity, depression, affect, optimism, stress, and social support. Stepwise linear regression modeling identified the independent variables that were significantly associated with frailty. RESULTS: The final regression model revealed that high patient-reported stress and depression, comorbidity, not being married or living with a partner, and low positive affect were significantly associated with worsening frailty in this population. DISCUSSION: Understanding the context of frailty is important for the design of interventions that target factors known to be associated with frailty in older cancer survivors. Further validation with a larger and a more diverse sample from a broad spectrum of sociodemographic and clinical population would fully account for the multiple independent variables influencing frailty in cancer survivors.

Research Progress and Prospect of Stimuli-Responsive Lignin Functional Materials.

As the world's second most abundant renewable natural phenolic polymer after cellulose, lignin is an extremely complex, amorphous, highly cross-linked class of aromatic polyphenolic macromolecules. Due to its special aromatic structure, lignin is considered to be one of the most suitable candidates to replace fossil materials, thus the research on lignin functional materials has received extensive attention. Because lignin has stimuli-sensitive groups such as phenolic hydroxyl, hydroxyl, and carboxyl, the preparation of stimuli-responsive lignin-based functional materials by combining lignin with some stimuli-responsive polymers is a current research hotspot. Therefore, this article will review the research progress of stimuli-responsive lignin-based functional materials in order to guide the subsequent work. Firstly, we elaborate the source and preparation of lignin and various types of lignin pretreatment methods. We then sort out and discuss the preparation of lignin stimulus-responsive functional materials according to different stimuli (pH, light, temperature, ions, etc.). Finally, we further envision the scope and potential value of lignin stimulus-responsive functional materials for applications in actuators, optical coding, optical switches, solar photothermal converters, tissue engineering, and biomedicine.

Brain-Derived Neurotrophic Factor rs6265 polymorphism is associated with severe cancer-related fatigue and neuropathic pain in female cancer survivors.

PURPOSE: This study examined the relationships between a single-nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) rs6265 and psychoneurological (PN) symptoms in female cancer survivors. METHODS: This secondary analysis examined 393 study participants. In addition to demographic variables, self-reported PN symptom scores (anxiety, bodily pain, depression, fatigue, neuropathic pain, and sleep disturbance) were collected using the Patient-Reported Outcomes Measurement Information System and 36-Item Short-Form Health Survey. Buccal swab samples were collected to obtain genotypes for BDNF rs6265 (Val/Val, Val/Met, or Met/Met). The PN symptom scores were compared across genotypes, and the relationships were examined using a regression model. We also explored correlations between different symptoms within each genotype. RESULTS: Participants with the Met/Met genotype reported significantly worse cancer-related fatigue and neuropathic pain, which was confirmed by rank-based regression analysis. In addition, cancer-related fatigue was correlated with other PN symptoms, particularly depression. These correlations were stronger in study participants with the Met/Met genotype than those with other genotypes. CONCLUSION: Our study suggests that female cancer survivors with the Met/Met genotype of BDNF rs6265 are likely to experience worse cancer-related fatigue and neuropathic pain and that cancer-related fatigue is a good predictor of co-occurring PN symptoms in this population. IMPLICATIONS FOR CANCER SURVIVORS: Our findings advance the scientific community's understanding of cancer-related PN symptoms experienced by female cancer survivors, especially the unique role of BDNF rs6265 polymorphism in these symptoms. Our findings offer valuable insights for clinical practice that the symptom experience among female cancer survivors may vary based on BDNF genotypes.

CT radiomics for differentiating fat poor angiomyolipoma from clear cell renal cell carcinoma: Systematic review and meta-analysis.

PURPOSE: Differentiation of fat-poor angiomyolipoma (fp-AMLs) from renal cell carcinoma (RCC) is often not possible from just visual interpretation of conventional cross-sectional imaging, typically requiring biopsy or surgery for diagnostic confirmation. However, radiomics has the potential to characterize renal masses without the need for invasive procedures. Here, we conducted a systematic review on the accuracy of CT radiomics in distinguishing fp-AMLs from RCCs. METHODS: We conducted a search using PubMed/MEDLINE, Google Scholar, Cochrane Library, Embase, and Web of Science for studies published from January 2011-2022 that utilized CT radiomics to discriminate between fp-AMLs and RCCs. A random-effects model was applied for the meta-analysis according to the heterogeneity level. Furthermore, subgroup analyses (group 1: RCCs vs. fp-AML, and group 2: ccRCC vs. fp-AML), and quality assessment were also conducted to explore the possible effect of interstudy differences. To evaluate CT radiomics performance, the pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were assessed. This study is registered with PROSPERO (CRD42022311034). RESULTS: Our literature search identified 10 studies with 1456 lesions in 1437 patients. Pooled sensitivity was 0.779 [95% CI: 0.562-0.907] and 0.817 [95% CI: 0.663-0.910] for groups 1 and 2, respectively. Pooled specificity was 0.933 [95% CI: 0.814-0.978]and 0.926 [95% CI: 0.854-0.964] for groups 1 and 2, respectively. Also, our findings showed higher sensitivity and specificity of 0.858 [95% CI: 0.742-0.927] and 0.886 [95% CI: 0.819-0.930] for detecting ccRCC from fp-AML in the unenhanced phase of CT scan as compared to the corticomedullary and nephrogenic phases of CT scan. CONCLUSION: This study suggested that radiomic features derived from CT has high sensitivity and specificity in differentiating RCCs vs. fp-AML, particularly in detecting ccRCCs vs. fp-AML. Also, an unenhanced CT scan showed the highest specificity and sensitivity as compared to contrast CT scan phases. Differentiating between fp-AML and RCC often is not possible without biopsy or surgery; radiomics has the potential to obviate these invasive procedures due to its high diagnostic accuracy.

Identification of GNAS Variants in Circulating Cell-Free DNA from Patients with Fibrous Dysplasia/McCune Albright Syndrome.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic bone and endocrine disorder. Although most variants affect the GNAS R201 codon, obtaining a genetic diagnosis is difficult because not all cells harbor the variant, and an invasive biopsy may be required. We explored the presence of GNAS p.R201 variants in blood circulating cell free DNA (ccfDNA) using sensitive techniques of digital droplet polymerase chain reaction (PCR) (ddPCR) and competitive allele-specific TaqMan PCR (castPCR) in an effort to improve the genetic diagnosis of FD/MAS. We isolated ccfDNA from the plasma of 66 patients with a wide range of disease severity and performed both ddPCR and castPCR mutation analysis to search for GNAS p.R201H or R201C variants. We detected R201 variants in ccfDNA samples of 41 of 66 (62.1%) patients by either castPCR or ddPCR, and 45 of 66 (68.2%) of patients if the techniques were combined. Variant detection was more likely in patients with more severe disease. Skeletal disease burden score (SBS) was significantly higher in patients who had detectable variants, and SBS was a predictor of variant allele frequency. By ddPCR analysis, patients aged ≤30 years had higher detection rates, and higher variant allele frequencies, independent of disease burden. We detected variant DNA in only one patient with monostotic FD by ddPCR only. In summary, we have demonstrated that ccfDNA containing variant GNAS can be isolated from the plasma of patients with FD/MAS and that ddPCR and castPCR methods have similar variant detection rates. This methodology represents an important potential advancement in diagnosis for patients with FD/MAS, especially those younger than 30 years or with more severe disease. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Views of IRB members regarding phase 1 pediatric oncology trials.

There is significant debate over whether phase 1 pediatric oncology trials are ethical and approvable. We thus surveyed IRB members to answer four questions. First, do IRB members think the potential medical benefits of average phase 1 pediatric oncology trials justify the risks? Second, do they think these trials are ethically appropriate? Third, do they think these trials are approvable? Fourth, how do the views of IRB members on the first two questions compare to the views of the US public? Of the 80 respondents who answered the test questions correctly, 18.8% stated that the potential medical benefits of average phase 1 pediatric oncology trials outweigh the risks, 32.5% stated that the potential medical benefits and risks are about equal, and 48.8% stated that the risks outweigh the potential medical benefits. Compared to the general public, IRB members were significantly more likely to think the risks outweigh the potential medical benefits (p = 0.01). Finally, 68.8% of IRB members indicated that average phase 1 pediatric oncology trials are approvable, and 56.3% indicated that these trials are appropriate in children. These findings suggest two-thirds of IRB members believe average phase 1 pediatric oncology trials are approvable. Yet, almost half regard the risks as outweighing the potential medical benefits and almost half think these trials are inappropriate. These findings raise important questions regarding why IRB members and the general public evaluate the same risk/benefit profile differently, and whether it is possible to reconcile the two perspectives.

CT radiomics for differentiating oncocytoma from renal cell carcinomas: Systematic review and meta-analysis.

BACKGROUND: Radiomics is a type of quantitative analysis that provides a more objective approach to detecting tumor subtypes using medical imaging. The goal of this paper is to conduct a comprehensive assessment of the literature on computed tomography (CT) radiomics for distinguishing renal cell carcinomas (RCCs) from oncocytoma. METHODS: From February 15th 2012 to 2022, we conducted a broad search of the current literature using the PubMed/MEDLINE, Google scholar, Cochrane Library, Embase, and Web of Science. A meta-analysis of radiomics studies concentrating on discriminating between oncocytoma and RCCs was performed, and the risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies method. The pooled sensitivity, specificity, and diagnostic odds ratio were evaluated via a random-effects model, which was applied for the meta-analysis. This study is registered with PROSPERO (CRD42022311575). RESULTS: After screening the search results, we identified 6 studies that utilized radiomics to distinguish oncocytoma from other renal tumors; there were a total of 1064 lesions in 1049 patients (288 oncocytoma lesions vs 776 RCCs lesions). The meta-analysis found substantial heterogeneity among the included studies, with pooled sensitivity and specificity of 0.818 [0.619-0.926] and 0.808 [0.537-0.938], for detecting different subtypes of RCCs (clear cell RCC, chromophobe RCC, and papillary RCC) from oncocytoma. Also, a pooled sensitivity and specificity of 0.83 [0.498-0.960] and 0.92 [0.825-0.965], respectively, was found in detecting oncocytoma from chromophobe RCC specifically. CONCLUSIONS: According to this study, CT radiomics has a high degree of accuracy in distinguishing RCCs from RO, including chromophobe RCCs from RO. Radiomics algorithms have the potential to improve diagnosis in scenarios that have traditionally been ambiguous. However, in order for this modality to be implemented in the clinical setting, standardization of image acquisition and segmentation protocols as well as inter-institutional sharing of software is warranted.

Infigratinib Reduces Fibroblast Growth Factor 23 (FGF23) and Increases Blood Phosphate in Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by ectopic production of fibroblast growth factor 23 (FGF23) by phosphaturic mesenchymal tumors (PMTs). Acting on renal tubule cells, excess FGF23 decreases phosphate reabsorption and 1,25-dihydroxy-vitamin D (1,25D) production, leading to hypophosphatemia, impaired bone mineralization, pain, and fractures. Fibronectin 1-fibroblast growth factor receptor 1 (FN1-FGFR1) gene fusions have been identified as possible drivers in up to 40% of resected PMTs. Based on the presumptive role of FGFR1 signaling by chimeric FN1-FGFR1 proteins, the effectiveness of infigratinib, a FGFR1-3 tyrosine kinase inhibitor, was studied in an open-label, single-center, phase 2 trial. The primary endpoint was persistent normalization of blood phosphate and FGF23 after discontinuation. Four adults with TIO (two nonlocalized, two nonresectable PMTs) were treated with daily infigratinib for up to 24 weeks. All patients had a favorable biochemical response that included reduction in intact FGF23, and normalization of blood phosphate and 1,25D. However, these effects disappeared after drug discontinuation with biochemistries returning to baseline; no patients entered biochemical remission. In the two patients with identifiable tumors, 68Gallium (68Ga)-DOTATATE and 18Fluoride (18F)-Fluorodeoxyglucose (FDG) PET/CT scans showed a decrease in PMT activity without change in tumor size. Patients experienced mild to moderate, treatment-related, dose-limiting adverse events (AEs), but no serious AEs. Three patients had dose interruptions due to AEs; one patient continued on a low dose for the entire 24 weeks and one patient stopped therapy at 17 weeks due to an AE. The study closed early due to a failure to meet the primary endpoint and a higher-than-expected incidence of ocular AEs. Infigratinib treatment lowered FGF23, increased blood phosphate, and suppressed PMT activity, confirming the role of FGFR signaling in PMT pathogenesis. However, treatment-related AEs at efficacy doses and disease persistence on discontinuation support restricting the use of infigratinib to patients with life-limiting metastatic PMTs. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Acceptable Risks in Pediatric Research: Views of the US Public.

BACKGROUND AND OBJECTIVES: Critics argue that it is unethical to expose children to research risks for the benefit of others, whereas many regulations permit "net-risk" pediatric research but only when the risks are minimal. In the present survey, we assessed whether the US public agrees with these views and whether the US public's views regarding the acceptability of net-risk pediatric research are influenced by its social value. METHODS: A 15-minute survey of a nationally representative sample of US adults. Participants were randomly assigned to 1 of 4 hypothetical scenarios involving procedures that pose increasing levels of risk. To assess whether respondents' views on the acceptability of the risks is influenced by the social value of the research, in each of the 4 scenarios we described the respective procedure being used in 3 studies with increasing levels of social value. RESULTS: A total 1658 of the 2508 individuals who were sent the survey link participated (response rate = 66.1%). Approximately 91% approved of a research blood draw in minors, and ∼69% approved of a research bone marrow biopsy. The proportion who indicated that the respective procedure was acceptable increased as the study's social value increased. This effect was significantly stronger for studies which pose greater risks compared with studies with lower risks (P < .001). CONCLUSIONS: The vast majority of the US public supports net-risk pediatric research that poses minimal risk, and a majority supports net-risk pediatric research that poses somewhat greater risks, provided it has high social value. These findings offer important information for assessing when it is acceptable to conduct net-risk pediatric research.

PTH and FGF23 Exert Interdependent Effects on Renal Phosphate Handling: Evidence From Patients With Hypoparathyroidism and Hyperphosphatemic Familial Tumoral Calcinosis Treated With Synthetic Human PTH 1-34.

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) both influence blood phosphate levels by regulating urinary phosphate reabsorption. Clinical data suggest that adequate renal phosphate handling requires the presence of both FGF23 and PTH, but robust evidence is lacking. To investigate whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with hypoparathyroidism, which features high blood phosphate in spite of concomitant FGF23 elevation, and 1 patient with hyperphosphatemic familial tumoral calcinosis (HFTC), characterized by deficient intact FGF23 action and resulting hyperphosphatemia, were treated with synthetic human PTH 1-34 (hPTH 1-34). Biochemical parameters, including blood phosphate, calcium, intact FGF23 (iFGF23), nephrogenic cAMP, 1,25(OH)2 vitamin D (1,25D), and tubular reabsorption of phosphate (TRP), were measured at baseline and after hPTH 1-34 treatment. In patients with hypoparathyroidism, administration of hPTH 1-34 increased nephrogenic cAMP, which resulted in serum phosphate normalization followed by a significant decrease in iFGF23. TRP initially decreased and returned to baseline. In the patient with HFTC, hPTH 1-34 administration also increased nephrogenic cAMP, but this did not produce changes in phosphate or TRP. No changes in calcium were observed in any of the studied patients, although prolonged hPTH 1-34 treatment did induce supraphysiologic 1,25D levels in the patient with HFTC. Our results indicate that PTH and FGF23 effects on phosphate regulation are interdependent and both are required to adequately regulate renal phosphate handling. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

Breeding a Soybean Cultivar Heinong 531 with Peking-Type Cyst Nematode Resistance, Enhanced Yield, and High Seed-Oil Contents.

Soybean cyst nematode (SCN) is a destructive threat to soybean production. It is economically important to develop a new SCN-resistant soybean cultivar with high yield and other good agronomic traits. In this study, a yellow-seed-coated and yellow-hilum-pigmented cultivar Heinong 531 belonging to maturity group I was developed by a pedigree breeding method through a test-cross between a female parental SCN-resistant soybean cultivar Pengdou 158 and a male parental line F1 (high-yield but SCN-susceptible Hefeng 55 × SCN-resistant Kangxian 12). Heinong 531 was evaluated for SCN resistance in both SCN-infested field and autoclaved soil inoculated with hatched second-stage juveniles of SCN HG Type 0. The results indicated that SCN development at all stages in Heinong 531 was suppressed and the female index was only 1.6 to 5.6%. Heinong 531 as well as Pengdou 158 and Kangxian 12 were identified as carrying the Peking-type resistance with both rhg1-a GmSNAP18 and Rhg4 GmSHMT08 genes. In the 2-year regional trials, the average yield of Heinong 531 reached 2805.0 kg/ha, and the 1-year production trial demonstrated an average yield of 2,751.5 kg/ha with yield increase of >12.0% when compared with the local cultivars. The average seed-fat (oil) contents of Heinong 531 reached up to 22.3%. The Peking-type SCN-resistant Heilong 531 with enhanced yield and high seed-oil contents was released in China in June 2021 with the certified number of 'Heishendou 20210004'. These agronomic traits make Heinong 531 a good prospect in a wide attempt to control SCN in the main soybean-producing areas of Northeast China.

The Cortisol and ACTH Response to Dex/CRH Testing in Women With and Without Perimenopausal Depression.

CONTEXT: Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD. OBJECTIVE: We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test. METHODS: Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing. RESULTS: No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women. CONCLUSION: Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions.

Do the Potential Medical Benefits of Phase 1 Pediatric Oncology Trials Justify the Risks? Views of the United States Public.

OBJECTIVES: To assess the US public's views on whether the potential medical benefits of phase 1 pediatric oncology trials justify the risks. STUDY DESIGN: Online survey of a nationally representative sample of US adults. Participants were presented with a hypothetical scenario in which they have a 10-year-old child with advanced cancer. They were then offered the option of giving their child supportive care or trying one more potential treatment, in the research or clinical care setting, which has the same risks and potential medical benefits as the average phase 1 pediatric oncology trial. We assessed what percentage of respondents thought the potential medical benefits justify the risks. RESULTS: In total, 1658 of the 2508 individuals who were sent the survey participated (response rate = 66.1%). Of those who passed all 3 test questions indicating understanding, 67.1% in the research scenario and 58.5% in the clinical care scenario regarded the potential medical benefits of an average phase 1 pediatric oncology trial as equal to or greater than the risks. In addition, 53.4% of respondents in the research scenario thought it was appropriate for researchers to conduct a study in children with these risks and potential medical benefits, and 46.9% stated they would enroll their own child in such a trial. CONCLUSIONS: A majority of the US public regards the potential medical benefits of average phase 1 pediatric oncology trials as justifying the risks. This finding suggests that these trials are ethically appropriate and approvable in patients who have no more effective treatment options. At the same time, a significant minority thought the potential medical benefits do not justify the risks, suggesting these trials should be approved only when they have significant social value. Moreover, approximately one-half of respondents regarded the trials as inappropriate and would not enroll their own child, underscoring the need for a rigorous informed consent process that accurately educates parents regarding the risks, potential medical benefits, and alternatives, so they can decide whether to enroll their child based on their own preferences and goals.

Effects of enriched environment on depression and anxiety-like behavior induced by early life stress: A comparison between different periods.

BACKGROUND: Brain development is a prolonged process and it is sensitive to the environment during critical periods. Stress in early life is believed to increase vulnerability to depression, while enriched environment (EE) has beneficial effects on neural plasticity and depression. In this study, we compared the therapeutic effect of EE during different periods on early life stress-induced depression, and investigated the role of brain-derived neurotrophic factor (BDNF) and protein kinase B (AKT) on the effect of EE. Plasma corticosterone level was also detected to evaluate the reactivity of hypothalamic-pituitary-adrenal axis. METHODS: C57BL/6 mice were subjected to a 4-h maternal separation (MS) procedure during postnatal days 2-21. After this separation, the mice were assigned to standard environment groups (SE), EE in the early period groups (3-8 weeks, EEE) and EE in the adult groups (8-13 weeks, EEA). Depression and anxiety behavior were evaluated at 14-weeks of age. The plasma corticosterone was quantified utilizing enzyme-linked immunosorbent assay. Hippocampus BDNF and AKT/p-AKT were detected using Western blotting. RESULTS: The results showed that MS increased depression and anxiety level, while EE in both intervention periods alleviated the symptoms of depression and anxiety. The EEE group showed better effects in terms of anhedonia and anxiety than the EEA group. The difference in despair behavior between the EEE and EEA groups was not significant. MS increased plasma corticosterone level, while EE decreased corticosterone level in both intervention periods. EE increased BDNF and p-AKT expression in the hippocampus, with stronger effects in the EEE group. CONCLUSION: EE during the early development period was more effective in alleviating depression and anxiety induced by early life stress. BDNF and AKT may play a significant role in the effect of EE, and further research is needed to explore the detailed neurobiological mechanisms.

18Fluorodeoxyglucose-positron emission tomography/computed tomography for differentiation of renal tumors in hereditary kidney cancer syndromes.

PURPOSE: To assess differences in FDG-PET/CT uptake among four subtypes of renal tumors: clear cell RCC (ccRCC), papillary type I and II RCC (pRCC), and oncocytoma. METHODS: This retrospective study investigated 33 patients with 98 hereditary renal tumors. Lesions greater than 1 cm and patients with a timeframe of less than 18 months between preoperative imaging and surgery were considered. FDG-PET/CT images were independently reviewed by two nuclear medicine physicians, blinded to clinical information. Volumetric lesion SUVmean was measured and used to calculate a target-to-background ratio respective to liver (TBR). The Shrout-Fleiss intra-class correlation coefficient was used to assess reliability between readers. A linear mixed effects model, accounting for within-patient correlations, was used to compare TBR values of primary renal lesions with and without distant metastasis. RESULTS: The time interval between imaging and surgery for all tumors had a median of 77 (Mean: 139; Range: 1-512) days. Intra-class reliability of mean TBR resulted in a mean κ score of 0.93, indicating strong agreement between the readers. The mixed model showed a significant difference in mean TBR among the subtypes (p < 0.0001). Pairwise comparison showed significant differences between pRCC type II and ccRCC (p < 0.0001), pRCC type II and pRCC type I (p = 0.0001), and pRCC type II and oncocytoma (p = 0.0016). Furthermore, a significant difference in FDG uptake was present between primary pRCC type II renal lesions with and without distant metastasis (p = 0.023). CONCLUSION: pRCC type II lesions demonstrated significantly higher FDG activity than ccRCC, pRCC type I, or oncocytoma. These findings indicate that FDG may prove useful in studying the metabolic activity of renal neoplasms, identifying lesions of highest clinical concern, and ultimately optimizing active surveillance, and personalizing management plans.

Comparison of Smartphone Augmented Reality, Smartglasses Augmented Reality, and 3D CBCT-guided Fluoroscopy Navigation for Percutaneous Needle Insertion: A Phantom Study.

PURPOSE: To compare needle placement performance using an augmented reality (AR) navigation platform implemented on smartphone or smartglasses devices to that of CBCT-guided fluoroscopy in a phantom. MATERIALS AND METHODS: An AR application was developed to display a planned percutaneous needle trajectory on the smartphone (iPhone7) and smartglasses (HoloLens1) devices in real time. Two AR-guided needle placement systems and CBCT-guided fluoroscopy with navigation software (XperGuide, Philips) were compared using an anthropomorphic phantom (CIRS, Norfolk, VA). Six interventional radiologists each performed 18 independent needle placements using smartphone (n = 6), smartglasses (n = 6), and XperGuide (n = 6) guidance. Placement error was defined as the distance from the needle tip to the target center. Placement time was recorded. For XperGuide, dose-area product (DAP, mGy*cm2) and fluoroscopy time (sec) were recorded. Statistical comparisons were made using a two-way repeated measures ANOVA. RESULTS: The placement error using the smartphone, smartglasses, or XperGuide was similar (3.98 ± 1.68 mm, 5.18 ± 3.84 mm, 4.13 ± 2.38 mm, respectively, p = 0.11). Compared to CBCT-guided fluoroscopy, the smartphone and smartglasses reduced placement time by 38% (p = 0.02) and 55% (p = 0.001), respectively. The DAP for insertion using XperGuide was 3086 ± 2920 mGy*cm2, and no intra-procedural radiation was required for augmented reality. CONCLUSIONS: Smartphone- and smartglasses-based augmented reality reduced needle placement time and radiation exposure while maintaining placement accuracy compared to a clinically validated needle navigation platform.