The ferric iron chelator 2,2'-dipyridyl attenuates basilar artery vasospasm and improves neurological function after subarachnoid hemorrhage in rabbits.

We investigated the efficacy of the ferrous iron (Fe(2+)) chelator 2,2'-dipyridyl (DP) to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH). Thirty-six New Zealand white rabbits were randomly assigned to four groups: untreated control, SAH, SAH + dimethyl sulfoxide (DMSO) vehicle, and SAH + DP. SAH was induced by injection of autologous blood into the cisterna magna and then DP or vehicle was infused into the cistern magna for 5 days (20 mg/kg/day or an equal volume of DMSO). Neurological deficit score (NDS) was used to assess neurological function and cerebral angiography to measure basilar artery (BA) diameter following SAH. TUNEL staining was used to detect BA endothelial cell apoptosis, and immunohistochemistry and Western blotting to assess changes in caspase-3 protein levels 5 days post-SAH. The SAH + DP group had a significantly larger mean BA diameter and lower mean NDS post-SAH compared to the SAH + DMSO and SAH groups (p < 0.05). TUNEL-positive cell numbers and caspase-3 levels were significantly reduced in BA endothelial cells of the SAH + DP group as compared to the SAH and SAH + DMSO groups (p < 0.05). The iron chelator DP reduced vasospasm and neurological sequelae in rabbits, likely by chelating the Fe(2+) in oxyhemoglobin and reducing oxidative stress-induced endothelial cell apoptosis.

PEGDA hydrogel microspheres with encapsulated salt for versatile control of protein crystallization.

Due to their biocompatibility and adjustable chemical structure and morphology, hydrogels have great potential in many applications, and can be used to enhance protein crystal quality and crystallization efficiency, contributing to biomedicine manufacturing. Monodispersed PEGDA hydrogel microspheres (HMSs) were synthesized using a Lego-inspired microfluidic device. The generated droplets were then UV polymerized, partially hydrolyzed with 0.1 M NaOH solution to improve their absorption capacity, and soaked in a buffer solution containing 0, 0.5, 1, 2, and 4 M NaCl. Salt-loaded HMSs were used as the medium for the enhanced crystallization of hen egg white lysozyme from aqueous solutions. Different supersaturations were achieved in the protein solutions by releasing NaCl of different concentrations from HMSs, as confirmed by electrical conductivity measurements. HMSs with or without NaCl can both provide heterogeneous nucleation sites due to their nano-porous structure and wrinkled surface. The addition of NaCl-loaded HMSs to the protein solution can also increase or decrease the supersaturation in the whole solution or locally near the HMS, leading to controllable nucleation time and crystal size distribution dependent on the NaCl concentration loaded into HMSs.

Binding profiles for 954 Drosophila and C. elegans transcription factors reveal tissue specific regulatory relationships.

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here we present the culmination of the modERN (model organism Encyclopedia of Regulatory Networks) consortium that systematically assayed TF binding events in vivo in two major model organisms, Drosophila melanogaster (fly) and Caenorhabditis elegans (worm). We describe key features of these datasets, comprising 604 TFs identifying 3.6M sites in the fly and 350 TFs identifying 0.9 M sites in the worm. Applying a machine learning model to these data identifies sets of TFs with a prominent role in promoting target gene expression in specific cell types. TF binding data are available through the ENCODE Data Coordinating Center and at https://epic.gs.washington.edu/modERNresource, which provides access to processed and summary data, as well as widgets to probe cell type-specific TF-target relationships. These data are a rich resource that should fuel investigations into TF function during development.

The importance of low IQ to early diagnosis of autism.

Some individuals can flexibly adapt to life's changing demands while others, in particular those with Autism Spectrum Disorder (ASD), find it challenging. The origin of early individual differences in cognitive abilities, the putative tools with which to navigate novel information in life, including in infants later diagnosed with ASD remains unexplored. Moreover, the role of intelligence quotient (IQ) vis-à-vis core features of autism remains debated. We systematically investigate the contribution of early IQ in future autism outcomes in an extremely large, population-based study of 8000 newborns, infants, and toddlers from the US between 2 and 68 months with over 15,000 cross-sectional and longitudinal assessments, and for whom autism outcomes are ascertained or ruled out by about 2-4 years. This population is representative of subjects involved in the National Institutes of Health (NIH)-funded research, mainly on atypical development, in the US. Analyses using predetermined age bins showed that IQ scores are consistently lower in ASD relative to typically developing (TD) children at all ages (p < 0.001), and IQ significantly correlates with social, non-social, and total Calibrated Severity Scores (CSS) on the Autism Diagnostic Observation Schedule (ADOS) (p<0.01). Lower IQ is associated with greater autistic impairments. Note, verbal IQ (VIQ) is no better than the full-scale IQ to predict ASD cases. These findings raise new, compelling questions about potential atypical brain circuitry affecting performance in both verbal and nonverbal abilities and preceding an ASD diagnosis. This study is the first to establish prospectively that low early IQ is a major feature of ASD in early childhood. LAY SUMMARY: The role of IQ scores in autism remains debated. We systematically investigate the contribution of early IQ in an extremely large study of 8,000 children between 2 and 68 months with autism outcomes by about 2-4 years. We show that IQ scores are consistently lower in ASD relative to TD children. This study is the first to establish prospectively that low early IQ is a predictor for ASD diagnosis in early childhood.

Comparison of 18F-FDG PET/CT imaging with different dual time 18F-FDG PET/CT with forced diuresis in clinical diagnosis of prostate cancer.

The aim of this study was to compare the capability of different dual time (interval 1, 2, 3, or 4 hours) 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) with forced diuresis to diagnose prostate cancer (PCa). A retrospective review of 273 male patients from March 2009 to June 2019, with any focal 18F-FDG uptake in the prostate gland during PET/CT imaging. Early PET/CT imaging was performed 60 minutes after FDG injection. Delayed imaging was performed 1 to 4 hours after diuretic injection. For prostate lesions with increased 18F-FDG uptake, a spheroid-shaped volume of interest was drawn, including the entire lesion, and the maximum standard uptake value (SUVmax) of the lesion was measured. The SUVmax > 2.5 after delayed imaging and the retention index > 15% were used as the diagnostic criteria for PET/CT in the diagnosis of PCa. Otherwise, it was diagnosed as the benign prostate disease. The final diagnosis was based on histological examination, associated imaging studies, or/and clinical follow-up. The results of inter-group comparison showed that the SUVmax of 1-, 2-, 3-, and 4-hour delayed imaging after diuresis in PCa group was significantly higher than that in control group (P < .05), but there was no statistical difference in SUVmax of early imaging between PCa and control group (P > .05). And the retention index of PCa group that delayed 1, 2, 3, and 4 hours after diuresis were significantly higher than those of control group, respectively (P < .05). The diagnostic sensitivity of imaging delayed 1, 2, 3, and 4 hours after diuresis was 68.8%, 81.2%, 85.7 %, and 71.4%, the specificity was 52.5%, 74.5%, 70.6%, and 65.0%, and the accuracy was respectively 58.2%, 77.4%, 76.4%, and 67.6%, the positive predictive values were 44.0%, 68.9%, 64.3%, and 58.8%, and the negative predictive value were 75.6%, 85.4%, 88.9%, and 76.5%, respectively. 18F-FDG PET/CT imaging as an imaging tool lacks certain specificity in the diagnosis of PCa, regardless of whether the imaging is delayed. The main advantage of delayed diuretic imaging in PCa is that it can significantly improve the sensitivity, especially the diagnostic effect delayed 2 hours after diuresis is better.

A pure invasive cribriform carcinoma of the breast with bone metastasis if untreated for thirteen years: a case report and literature review.

We report a case of pure invasive cribriform carcinoma of the breast, which had been untreated for thirteen years, being found with bone metastasis at initial presentation, because distant metastasis is rarely found in this tumor. A fifty-nine-year-old postmenopausal woman presented with a large left breast mass. Although she had noticed a lump in a left breast thirteen years ago, she had not sought treatment. The tumor had enlarged gradually since from one year before and become ulcerated. The two enlarged axillary lymph nodes were also palpable. After two cycles of neoadjuvant chemotherapy, she underwent left radial mastectomy with a free skin graft. Emission computed tomography result has confirmed bone metastasis. The histological diagnosis of the tumor revealed the pure invasive cribriform carcinoma, since over than ninety percent of invasive tumor components showed a characteristic cribriform growth, and the remainder was tubular carcinoma. She has been well without evidence of tumor recurrence for seven years after surgery and several routine postoperative therapies. Although with favorable prognosis, pure invasive cribriform carcinoma is still possible to develop into the advanced (Stage four) breast cancer if untreated for a long time. However, the survival of this patient for free disease after several locoregional and systemic therapies maybe provide a supplement for invasive cribriform carcinoma's excellent prognosis.

Direct comparison of choline PET/CT and MRI in the diagnosis of lymph node metastases in patients with prostate cancer.

BACKGROUND: Lymph node detection in prostate cancer is challenging and critical to determine treatment policy. Choline PET/CT (positron emission tomography/computed tomography) and magnetic resonance imaging (MRI) have been used for the evaluation of lymph node metastasis in patients with prostate cancer for the past decade. However, only limited patients underwent direct comparison studies. PURPOSE: To evaluate the diagnostic performance of choline PET/CT compared with MRI imaging for detecting lymph node metastases in prostate cancer patients. MATERIAL AND METHODS: Relevant English-language articles published before February 2018 were searched in PubMed database, Embase database, and Cochrane Library databases search using the keywords: (Prostate Neoplasm OR Prostate Cancer OR prostate carcinoma) and (Lymph Node) and (PET/CT OR positron emission tomography/computed tomography) and (choline or 2-hydroxy-N,N,N-trimethylethanaminium) and (magnetic resonance imaging OR MRI). Articles were included that directly compare the diagnostic performance and clinical utility of choline PET/CT and MRI for detecting lymph node metastases in prostate cancer patients. Study quality was assessed with QUADAS criteria. Analyses were performed on a per patient and a per node basis. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated using Meta-Disc 1.4 software. Summary receiver-operating characteristic (SROC) curves constructed. RESULTS: A total of 362 patients from 8 studies involving fulfilled the inclusion criteria. On patient-based analysis, the pooled sensitivity, specificity, and DOR with a 95% confidence interval (CI) for choline PET/CT imaging were 0.59 (95%CI, 0.50-0.67), 0.92 (95%CI, 0.87-0.96), 17.37 (95%CI, 4.42-68.33), and for MRI imaging, they were 0.52 (95%CI, 0.44-0.61), 0.87 (95%CI, 0.81-0.92), 6.05 (95%CI, 3.09-11.85), respectively. On node-based, the corresponding values for choline PET/CT imaging were 0.51 (95%CI, 0.46-0.57), 0.99 (95%CI, 0.98-0.99), 65.55 (95%CI, 23.55-182.45), and for MRI imaging, they were 0.39 (95%CI, 0.34-0.44), 0.97 (95%CI, 0.96-0.97), 15.86 (95%CI, 8.96-28.05), respectively. CONCLUSION: Choline PET/CT performed better than MRI imaging in evaluating the lymph nodes metastasis of prostate cancer patients and had the potential to be broadly applied in clinical practice.

Evaluation of Visceral Adipose Tissue Oxygenation by Blood Oxygen Level-Dependent MRI in Zucker Diabetic Fatty Rats.

OBJECTIVE: This study aimed to investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation. METHODS: Five-week-old ZDF rats and Zucker lean (ZL) rats were fed a high-fat diet (HFD) for 18 weeks. A baseline BOLD-MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks. At sacrifice, BOLD-MRI scan, Hypoxyprobe-1 injection, and circulating T helper 17 (Th17), regulatory T (Treg) cells, and monocyte subtype flow cytometry analysis were performed. RESULTS: HFD feeding led to a significant increase in VAT BOLD-MRI R2* signals (20.14 ± 0.23 per second vs. 21.53 ± 0.20 per second; P = 0.012), an indicator for decreased oxygenation. R2* signal was significantly correlated with VAT pimonidazole adduct-positive area, insulin resistance, Th17 and Treg cells, CD43 + and CD43+ + monocyte subtypes, and VAT macrophage infiltration. Pioglitazone treatment improved the insulin resistance and was associated with a delayed progression of VAT oxygenation. CONCLUSIONS: This work demonstrated the feasibility of BOLD-MRI for detecting the VAT oxygenation status in ZDF rats, and the BOLD-MRI signals were associated with insulin resistance and systemic metaflammation in ZDF rats during the development of obesity.

Polysplenia Syndrome With Splenic and Skeletal Muscle Metastases From Thyroid Carcinoma Evaluated by FDG PET/CT: Case Report and Literature Review: A Care-Compliant Article.

Polysplenia syndrome (PSS) is a rare congenital abnormality. Metastases to spleen and skeletal muscle from differentiated thyroid cancer (DTC) are also extremely rare. Our case report aims to present an interesting case of PSS associated with splenic metastasis (SM) and skeletal muscle metastasis (SMM) from advanced papillary thyroid carcinoma which was evaluated on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). An 84-year-old Chinese man was admitted with the history of multiple enlarged masses in bilateral neck, right axillary, and inguinal areas for >2 months. The results of ultrasonography examination were highly suggestive of malignancy. The histological results of the following biopsy were consistent with papillary thyroid carcinoma with involvement of multiple regional lymph nodes. He was referred for an FDG PET/CT imaging to evaluate the situation. FDG PET/CT showed that an intense FDG-avid thyroid mass with widespread regional lymph node involvement and distant metastases in the body. Unexpected sites of metastases were detected in the spleens and skeletal muscles. Most interestingly, FDG PET/CT imaging also described the typical imaging findings of PSS including the 2 right-sided spleens, azygos and hemiazygos continuation of inferior vena cava (IVC), right-sided stomach, middle line liver, a short pancreas, preduodenal portal vein (PPV), and malrotation of gut. Whole body FDG PET/CT imaging can accurately evaluate the situation of DTC by detecting regional lymph node involvement, common and rare sites of distant metastases which are closely related to staging, management, and prognosis of this disease. Whole-body FDG PET/CT is also valuable in demonstrating the typical imaging features of PSS.

[Manifestations of PET/CT Imaging in Primary Central Nervous System Lymphoma].

OBJECTIVE: To investigate the PET/CT features of primary central nervous system lymphoma(PCNSL). METHODS: A retrospective analysis of PET/CT imaging manifestations and clinical data was performed in 4 PCNSL cases which were confirmed by surgery or stereotactic pathologic biopsy. RESULTS: The pathologic biopsy in 4 patients all showed diffuse large B cell lymphoma with a total of 8 lesions. All cases were performed with 18F-FDG PET/CT imaging except 1 patient simultaneously with 18F-FLT PET/CT imaging in the brain. Single lesion was found in 2 cases which both were located in the left frontal lobe. Multiple lesions were found in 2 cases, out of them 1 case located in the corpus callosum and the right lateral ventricle Angle, and the other 1 located in dual lateral ventricle and pineal region. In 18F-FDG PET/CT image, 4 patients were characterized by high metabolism, even higher than the surrounding brain tissue. The patient which underwent 18F-FLT PET/CT imaging was also presented with high metabolism and had better Target and non-target ratio(T/N). 3 cases with surrounded by edema and 2 cases with area of cystic necrosis. CONCLUSION: PCNSL are characterized by high metabolism in 18F-FDG PET/CT images and can better contrast with the surrounding normal brain. Combined use of other tracer such as 18F-FLT can improve the diagnostic value of PET/CT in PCNSL.

Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice.

AIM: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. MATERIALS & METHODS: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. RESULTS: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C(hi) monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. CONCLUSION: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.

[Magnetic resonance imaging and radiography for diagnosis of lower limb osteosarcoma: a comparative study].

OBJECTIVE: To investigate the diagnostic value of magnetic resonance imaging (MRI) for lower limb osteosarcoma by comparing the findings between X-ray and MRI. METHODS: Fifteen surgically or pathologically confirmed patients with lower limb osteosarcoma (11 males and 4 females) underwent both plain and enhanced MRI (with CT scanning in 4 cases) in addition to radiography, and the findings were compared. RESULTS: The diagnostic accuracy of both MRI and X-ray film was 100%. Compared with X-ray, MRI was capable of clear display of the lesion extent, perpendicular periosteal reaction, the two layers of Codman's triangle and the skip lesions. CONCLUSION: Plain X-ray film provides a convenient and practical diagnostic modality for lower limb osteosarcoma, but MRI has better performance in clearer display of the tumor range and identification of early-stage lesions.

[Diagnosis of lesions in the major abdominal blood vessels by three-dimensional dynamic contrast-enhanced magnetic resonance angiography].

OBJECTIVE: To elucidate the working principles of three-dimensional dynamic contrast-enhanced magnetic resonance angiography(3D DCE-MRA)and assess its value in the diagnosis of lesions in the major abdominal blood vessels. METHODS: The imaging data of 3D DCE-MRA and conventional MR examination in 32 cases of suspected major abdominal blood vessel diseases were obtained and analyzed retrospectively. RESULTS: The peak flow of contrast agents through the abdominal aorta at the level of renal artery occurred 17 to 23 s after the injections. Normal presentation was found in 3 cases, with clear images of the abdominal aorta and its branches. Abdominal aortic aneurysm was identified in 7 cases, where the involved segment of the aorta was irregularly broadened and the actual lumen of the abdominal aorta was displayed. Aortic dissection was found in 18 cases, and the intima, the double-lumen, and the position where the abdominal aortic branches originated could be seen with 12 entry sites and 16 re-entry sites. Atherosclerosis was found in 3 cases, with tortuous abdominal aorta whose lumen was morphologically irregular. One case was found with thrombosis in the left iliac vein which was not visualized. CONCLUSIONS: 3D DCE-MRA is a non-invasive alternative for conventional angiography and has significant importance in the diagnosis of lesions in major abdominal blood vessels.

Birt-Hogg-Dubé syndrome with clear cell renal cell carcinoma in a Chinese family.

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis that presents as a clinical triad including follicular hamartomas, renal neoplasms and lung cysts associated with an increased risk of pneumothorax. FLCN gene defects have been identified as being responsible for BHDS. We herein report the case of a 67-year-old woman with the full-blown BHDS phenotype, characterized by skin lesions, multiple lung bullae and renal neoplasms. In her family history, one of the patient's sons exhibited a similar phenotype, without renal neoplasms. Due to the relatively late age of onset of renal neoplasms among variable BHDS phenotypes, follow-up imaging is recommended for the son who has not yet developed renal neoplasms.

TrkC expression predicts favorable clinical outcome in invasive ductal carcinoma of breast independent of NT-3 expression.

BACKGROUND: TrkC, a member of neurotrophin receptor family, functions not only as an oncogene, but also act as a tumor suppressor via a manner of dependence receptor in human malignant tumors. Little is known on the action of TrkC for the clinical prognosis and the progression of breast cancer according to the availability of its ligand NT-3. We sought to investigate the prognostic relevance of NT-3-TrkC axis in breast cancer and estimate its role during the process of breast cancer progression. METHODS: 236 cases of invasive ductal carcinoma (IDC), 60 pure ductal carcinoma in situ (DCIS) and 30 normal breast tissue (NBT) between 2004 and 2005 were included in the study. Spearman's rank correlation test was used to analyze the association of NT-3-TrkC expression and breast cancer progression. The Kaplan-Meier method and Cox proportional hazards model were performed to identify the relevant prognostic factors. RESULTS: 50.4% IDC tumors displayed absent or low TrkC expression, while 49.6% was high TrkC expression. TrkC expression was negatively associated with lymph node metastasis (P = 0.029) and tumor proliferation (P = 0.015). Patients with lower TrkC expressing tumors had a higher risk of recurrence (odds ratio, 0.401; 95% confidence interval, 0.207-0.778; P = 0.007). The layered analysis indicated that patients with high TrkC expression tumors had a favor disease-free survival whether NT-3 and TrkC were co-expressed or solitarily expressed in the tumor (P = 0.000). NT-3 was demonstrated to be not a predictor of IDC patients' prognosis. But NT-3 expression was inversely correlated with the progression of breast cancer (r = -0.341, P = 0.000), since more IDC tumors showed high NT-3 expression than DCIS tumors (51.7% vs. 25.9%), while no NBT showed high NT-3 expression, as well. CONCLUSION: The study indicates TrkC expression reduces tumor relapse independent of NT-3 availability in the IDC. Elevated NT-3 expression contributes to the progression of breast cancer.

Invasive cribriform carcinoma in a Chinese population: comparison with low-grade invasive ductal carcinoma-not otherwise specified.

Invasive cribriform carcinoma (ICC) and low-grade invasive ductal carcinoma (IDC) were recently considered to belong to a low-grade breast neoplasia family. However, none of publications has compared ICC and low-grade IDC at present. Meanwhile, in order to evaluate prognostic significance of clinicopathological characteristics of different cribriform contents in ICC and invasive breast cancer with less cribriform structures, a retrospective review of fifty-one cases of ICC and forty cases of invasive breast cancer with less cribriform pattern (less than fifty percent) was conducted in a Chinese population. Forty-nine cases of low-grade IDC without cribriform elements were selected as a control. ICC presented more favorable prognostic factors than those of invasive breast carcinoma with less cribriform pattern and low-grade IDC, such as smaller tumor size, less frequent axillary lymph node involvement, higher positive rate of estrogen receptor and/or progestogen receptor expression, and lower proliferation index. The expression of human epidermal growth factor receptor two in ICC and invasive breast cancer with less cribriform pattern was mostly negative. Pure ICC showed less frequency of axillary lymph node involvement, but not its number. The proliferation index in the pure type was lower, although the tumor size in these two types was not obviously different. Tumors contained cribriform structures had a more favorable prognosis than those with low-grade IDC. Considering the tumor biology, and the benign course of pure ICC studied, chemotherapy may not be indicated in the typical case.

[Clinical application of T2*GRE multiple echo sequence on articular cartilage disease in the knee].

OBJECTIVE: To evaluate the correlation between T2* relaxation time and the pathological changes in the knee joint of patients with osteoarthritis (OA) and analyze the changes of T2* relaxation time in early cartilage injury. METHODS: Sixty-two patients with OA in different phases underwent magnetic resonance imaging (MRI) of the knee and the articular cartilage T2* relaxation time was recorded, with 20 young healthy volunteers as the control group. RESULTS: Patients with mild OA showed significantly different T2* relaxation time for most of the articular cartilage from that of the healthy volunteers (P<0.05), but no such difference was found between serious OA group and the healthy volunteers. The change of T2* relaxation time of the cartilage was also associated with age, weight and body height, and the potential effects of other factors could not be excluded. CONCLUSION: The articular cartilage shows no obvious morphological changes in early OA of the knee, a stage characterized mostly by alterations of the tissue structure and compositions. Cartilage pathologies can be the most obvious on the weight-bearing surface of the medial condyle of the femur or in the patella. T2* relaxation time measurement can be helpful in the detection of early cartilage pathologies.