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The high kinetic inductance of niobium nitride (NbN) thin films can be used for an implementation of compact on-chip inductances in cryoelectronic circuits. Here, for the first time, we demonstrate the implementation of a hybrid superconducting technology that includes the fabrication of standard aluminum submicron Josephson junctions and the NbN atomic layer deposition process. As an example, we fabricated and characterized a single and array of Al Josephson junctions together with NbN interconnections. The main Al Josephson junction parameters as well as NbN superconducting properties are in a good agreement with the values obtained by our standard fabrication process. The combination of technological processes for the NbN layers with Al Josephson junction allows implementing a new generation of innovative superconducting devices for different applications. [ABSTRACT FROM AUTHOR]

TIME is a mm-wavelength grating spectrometer array that will map fluctuations of the 157.7-μm emission line of singly ionized carbon ([CII]) during the epoch of reionization (redshift z∼ 5-9). Sixty transition-edge sensor (TES) bolometers populate the output arc of each of the 32 spectrometers, for a total of 1920 detectors. Each bolometer consists of gold absorber on a ∼ 3 × 3 mm silicon nitride micro-mesh suspended near the corners by 1 × 1 × 500 μm silicon nitride legs targeting a photon-noise-dominated NEP ∼1×10-17W/Hz. Hafnium films are explored as a lower-Tc alternative to Ti (500 mK) for TIME TESs, allowing thicker support legs for improved yield. Hf Tc is shown to vary between 250 and 450 mK when varying the resident Ar pressure during deposition. Magnetic shielding designs and simulations are presented for the TIME first-stage SQUIDs. Total axial field suppression is predicted to be 5×107. [ABSTRACT FROM AUTHOR]

Background: The objective was to assess whether intraoral bone augmentation procedures have an impact on the patient's plasma levels of circulating nucleic acids, exosomes, miRNA levels and caspase activities. The null hypothesis was tested, that no significant differences between the two groups will be found., Methods: In this prospective randomized controlled clinical trial 35 systemically healthy non-smoking participants were randomly allocated using sealed envelopes by a blinded clinician not involved in the clinical setting. Plasma samples were collected preoperatively and 3 times postoperatively (immediately, 5 weeks and 4 months postoperatively). The test group consisted of twenty-five patients who received allogeneic bone grafting material and the control group of ten patients who received autologous bone grafts. Levels of cell-free DNA (cfDNA) and microRNAs (miR-21, miR-27a, miR-218) were quantified by real-time PCR, caspase activities and exosome concentrations were determined by ELISA., Results: Statistical evaluation reveled a significantly higher exosome level before surgery (p = 0.013) and the first postsurgical sample (p = 0.017) in the control group compared to the test group. The levels of miR-27a and miR-218 significantly differed between the plasma samples before surgery and after surgery in both groups. The levels of miR-21 only significantly differed between the pre- and postsurgical plasma samples in the test group, but not in the control group. All patients completed the study, no adverse events were recorded., Conclusions: Our data show the diagnostic potential of the plasma levels of miR-27a, miR-218 and miR-21 in detecting changes in bone metabolism after alveolar bone augmentation. Our very promising results indicate that there might be a high diagnostic potential in evaluating the plasma levels of the before mentioned miRNAs in order to detect bone resorption activities before they become clinically relevant. Trial registration Ethical commission of the Ärztekammer Hamburg, Germany (PV5211) on 11/03/2016 as well as by the German Registry of Clinical Studies (DRKS 00,013,010) on 30/07/2018 ( http://apps.who.int/trialsearch/ )., (© 2022. The Author(s).)

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220  GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8  μK&#95;{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r&#95;{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

We aimed to identify a specific microRNA (miRNA) pattern to determine diagnostic and prognostic value in plasma exosomes of hepatocellular carcinoma (HCC) patients. A two-stage study was carried out: exosomal miRNAs were quantified in plasma of HCC patients and healthy individuals by PCR-based microarray cards containing 45 different miRNAs (training cohort). Then, four deregulated miRNAs (miR-16, miR-146a, miR-192, and miR-221) were quantified in the validation analysis using exosomes derived from 85 HCC patients, 50 liver cirrhosis patients, and 20 healthy individuals. Exosomal miR-146a ( p = 0.0001), miR-192 ( p = 0.002) and miR-221 ( p = 0.032) were upregulated only in HCC patients. Repeated 10-fold cross validation showed that miR-146a differentiated HCC from liver cirrhosis patients with AUC of 0.80 ± 0.14 (sensitivity: 81 ± 13%, specificity: 58 ± 22%) in a logistic regression model. High miR-192 presence is associated with poor overall survival (OS) in all HCC patients ( p = 0.027) and was predictor of OS in HCC patients in an uni- and multivariate Cox regression model. Moreover, decreased miR-16 levels correlated with OS in liver cirrhosis patients ( p = 0.034). Our results emphasized that exosomes secreted into the plasma carry differentially expressed miRNAs of which in particular, miR-192, miR-146, and miR-16 are promising diagnostic and prognostic markers for both HCC and liver cirrhosis patients.

The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy.

Objectives: Cell-free DNA (cfDNA) harboring mutations has been found in patients with diseases. Experimental studies have shown that cfDNA can be transmitted, leading to transformations in the host. In the present study, we evaluated whether bone allograft material contains cfDNA and whether this foreign cfDNA can be released into the patient's blood circulation., Materials and Methods: Plasma samples were collected preoperatively and postoperatively on the same day, at 5 weeks, and 4 months from 25 women who received bone allograft material (test group) from male donors and from 10 women who were treated with autologous graft (control group, only pre- and postoperative samples were collected). DNA was quantified and characterized in bone material and plasma samples by quantitative PCR with primers specific for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Y chromosome and gel electrophoresis. DNA in bone material was digested by different concentrations of DNase I., Results: We detected between 1 and 1.8 μg cfDNA fragments at a length around 601 base pairs (bp) and smaller in each 100 mg allograft. Treatment of the allograft with DNase I completely degraded the longer but not the shorter DNA 90-bp fragments. Y-DNA was not detected in the patients' bloodstream at any time during the treatment and follow-up, but elevated levels of circulating cfDNA could be measured immediately postoperatively., Conclusions: Our results suggest that a transmission of DNA from allografts used for alveolar ridge reconstruction in humans is unlikely. The observed increase in circulating cfDNA in allograft and autograft patients immediately postoperatively may be elicited by the surgical procedure., Clinical Relevance: The results support the safety of allograft materials. The results suggest that human allograft materials seem not to release DNA into the blood since we did not measure Y-DNA with our technique.

Long noncoding RNAs (lncRNAs) are frequently precursor RNAs of microRNAs (miRNAs) or act as competing endogenous RNAs (ceRNAs) to interact with miRNAs. To better understand the shared impact of lncRNAs and miRNAs in the regulatory post-transcriptional network, we focused here on the relationships between (a) lncRNA H19 and miR-675, (b) NEAT1 and miR-204, and (c) HOTAIR and miR-331 in plasma of early breast cancer (BC) patients. We quantified each RNA in plasma samples of 63 BC patients and 10 healthy women by quantitative real-time PCR. In cell culture experiments, the influence of these noncoding RNAs (ncRNAs) on proliferation and apoptosis of BC cell line MCF-7 was examined. Plasma levels of H19 (P = 0.030), NEAT1 (P = 0.030), and miR-331 (P = 0.012) were deregulated in BC patients compared with healthy women. In both cohorts, the concentrations of H19 correlated with those of miR-675 (P = 0.0001). Higher H19 (P = 0.001) along with lower miR-675 (P = 0.007) levels and higher miR-204 (P = 0.017) along with lower NEAT1 (P = 0.030) levels were detected in plasma of HER2-positive patients compared with the other BC subgroups. Whereas the expression of HOTAIR was below the detection level, miR-331 levels correlated with nodal status (P = 0.002) and recurrence (P = 0.012). In cell culture experiments, a competitive impact on cell proliferation and apoptosis by these ncRNAs was also documented. Our findings describe a relationship of the plasma levels of H19/miR-675 and NEAT1/miR-204 in the different BC subtypes; in addition, they reveal an interplay between these lncRNAs and miRNAs in the regulatory network in MCF-7 cells, which should also be considered in the search for new diagnostic and therapeutic markers., (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency. MLPA was exclusively suitable for cfDNA extracted from serum. Serum from 72 patients (84.7%) could be analyzed. Thirty-five patients (48.6%) had presence of CNV in cfDNA. The median CNV count in patients with presence of CNV was 2. Predominantly, CNV were located in the genes CDH1, ZFHX3, RIPK2 and PTEN in 15 patients (20.8%), 12 patients (16.7%), 9 patients (12.5%) and 7 patients (9.7%), respectively. CNV in TSG1, RAD21, KIAA0196, ANXA7 and TMPRSS2 were associated with presence of variant UCB histology ( p = 0.029, 0.029, 0.029, 0.029, 0.043, respectively). Furthermore, CNV in miR-15a, CDH1 and ZFHX3 were associated with presence of incidental prostate cancer ( p = 0.023, 0.003, 0.025, respectively). Patients with CNV in KLF5, ZFHX3 and CDH1 had reduced cancer-specific survival, compared to patients without CNV in these genes (pairwise p = 0.028, 0.026, 0.044, respectively). MLPA represents an efficient method for the detection of CNV among numerous genes on various chromosomal regions. CNV in specific genes seem to be associated with aggressive UCB biologic features and presence of incidental prostate cancer, and may have a negative impact on cancer-specific survival., Competing Interests: CONFLICTS OF INTEREST T.H., director of J Innuscreen GmbH, provided the PME free-circulating DNA Extraction kits free of charge. H.S. received the SALSA MLPA probemix X049-A1 kits from MRC Holland, Amsterdam, The Netherlands, free of charge. No potential conflicts of interest were disclosed by the other authors.

Background: As cancer-testis MAGE-A antigens are targets for tumor immunotherapy, it is important to study the regulation of their expression in cancers. This regulation appears to be rather complex and at the moment controversial. Although it is generally accepted that MAGE-A expression is controlled by epigenetics, the exact mechanisms of that control remain poorly understood., Methods: We analyzed the interplay of another cancer-testis gene, BORIS, and the transcription factors Ets-1 and Sp1 in the regulation of MAGE-A1 gene expression performing luciferase assays, quantitative real-time PCR, sodium bisulfite sequencing, chromatin immunoprecipitation assays and pull down experiments., Results: We detected that ectopically expressed BORIS could activate and demethylate both endogenous and methylated reporter MAGE-A1 promoter in MCF-7 and micrometastatic BCM1 cancer cell lines. Overexpression of Ets-1 could not further upregulate the promoter activity mediated by BORIS. Surprisingly, in co-transfection experiments we observed that Sp1 partly repressed the BORIS-mediated stimulation, while addition of Ets-1 expression plasmid abrogated the Sp1 mediated repression of MAGE-A1 promoter. Both BORIS and Sp1 interacted with the TATA binding protein (hTBP) suggesting the possibility of a competitive mechanism of action between BORIS and Sp1., Conclusions: Our findings show that BORIS and Sp1 have opposite effects on the regulation of MAGE-A1 gene expression. This differential regulation may be explained by direct protein-protein interaction of both factors or by interaction of MAGE-A1 promoter with BORIS alternatively spliced isoforms with different sequence specificity. We also show here that ectopic expression of BORIS can activate transcription from its own locus, inducing all its splice variants.

Trastuzumab and lapatinib are established treatments for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer with different mechanisms of action. The focus of this study is to investigate, whether altered expression levels of potentially relevant microRNAs (miRs) in serum are associated with response to trastuzumab or lapatinib. Circulating miR-21, miR-210, and miR-373 were quantified with TaqMan MicroRNA assays in serum of 127 HER2-postive breast cancer patients before and after neoadjuvant therapy and in 19 healthy controls. Patients received chemotherapy combined with either trastuzumab or lapatinib within the prospectively randomized Geparquinto trial. The association between miR levels and pathological response (pCR) to therapy and type of therapy was examined. Serum levels of miR-21 (p = 5.04e-08, p = 1.43e-10), miR-210 (p = 0.00151, p = 1.6e-05), and miR-373 (p = 7.87e-06, p = 1.75e-07) were significantly higher in patients before and after chemotherapy than in healthy women. Concentrations of miR-21 (p = 5.73e-08), miR-210 (p = 0.000724), and miR-373 (p = 0.00209) increased further after chemotherapy. A significant association of higher serum levels of miR-373 with advanced clinical tumor stage could be detected (p < 0.002). An association of miR-21 levels before (p = 0.0091) and after (p = 0.037) chemotherapy with overall survival of the patients could be detected, independent of type of anti-HER2 therapy. No association of circulating miRs with pCR was found. Our findings demonstrate a specific influence of neoadjuvant therapy on the serum levels of miR-21, miR-210, and miR-373 in breast cancer patients together with a prognostic value of miR-21.

Gravitational lensing due to the large-scale distribution of matter in the cosmos distorts the primordial cosmic microwave background (CMB) and thereby induces new, small-scale B-mode polarization. This signal carries detailed information about the distribution of all the gravitating matter between the observer and CMB last scattering surface. We report the first direct evidence for polarization lensing based on purely CMB information, from using the four-point correlations of even- and odd-parity E- and B-mode polarization mapped over ∼30 square degrees of the sky measured by the POLARBEAR experiment. These data were analyzed using a blind analysis framework and checked for spurious systematic contamination using null tests and simulations. Evidence for the signal of polarization lensing and lensing B modes is found at 4.2σ (stat+sys) significance. The amplitude of matter fluctuations is measured with a precision of 27%, and is found to be consistent with the Lambda cold dark matter cosmological model. This measurement demonstrates a new technique, capable of mapping all gravitating matter in the Universe, sensitive to the sum of neutrino masses, and essential for cleaning the lensing B-mode signal in searches for primordial gravitational waves.

We reconstruct the gravitational lensing convergence signal from cosmic microwave background (CMB) polarization data taken by the Polarbear experiment and cross-correlate it with cosmic infrared background maps from the Herschel satellite. From the cross spectra, we obtain evidence for gravitational lensing of the CMB polarization at a statistical significance of 4.0σ and indication of the presence of a lensing B-mode signal at a significance of 2.3σ. We demonstrate that our results are not biased by instrumental and astrophysical systematic errors by performing null tests, checks with simulated and real data, and analytical calculations. This measurement of polarization lensing, made via the robust cross-correlation channel, not only reinforces POLARBEAR auto-correlation measurements, but also represents one of the early steps towards establishing CMB polarization lensing as a powerful new probe of cosmology and astrophysics.

MicroRNAs play a role in breast cancer development and progression by post-transcriptional repression of the expression of important genes, such as the tumor suppressor gene phosphatase and tensin homolog (PTEN). The focus of the current study was to examine the diagnostic potential of circulating cell-free microRNAs targeting PTEN in breast cancer. Our analyses were performed on preoperative serum samples of 102 patients with early breast cancer and a subset of 34 postoperative samples, as well as of 32 patients with benign breast disease and 53 healthy women. The relative concentrations of four circulating microRNAs (miR-19a, miR-20a, miR-21, and miR-214) in blood serum were measured by TaqMan MicroRNA assays. Levels of preoperative serum miR-20a and miR-21 were significantly higher in patients with breast cancer and benign disease than in healthy women (p = 0.0001), but only serum miR-214 could discriminate malignant from benign tumors and healthy controls (p = 0.0001) with an area under the curve of 0.878 and 0.883 in ROC analysis, respectively. Moreover, miR-214 levels significantly decreased in the postoperative serum samples (p = 0.0001) as compared to the preoperative samples. The comparison with the clinicopathologic data of the breast cancer patients showed that increased miR-214 levels were associated with a positive lymph node status (p = 0.039). Our data show that circulating, cell-free miR-214 has diagnostic potential in breast cancer as indicator of malignant disease and metastatic spread to regional lymph nodes. Since PTEN is an important target gene of miR-214, this finding could also have potential implications for therapeutic approaches.

High levels of DNA and RNA released by apoptotic and necrotic cells circulate in the blood of cancer patients. In the present study we determined the applicability of the quantification of nucleic acids and their genetic alterations as minimally invasive tool for breast cancer screening. The relative concentrations of DNA and RNA were determined in preoperative serum of 102 breast cancer patients, 32 patients with benign breast disease and 53 healthy women. The mean follow-up time of the cancer patients was 6.2 years. Loss of heterozygosity (LOH) at four polymorphic markers (D13S159, D13S280, D13S282 at region 13q31-33 and D10S1765 at PTEN region 10q23.31) was analyzed by PCR-based fluorescence microsatellite analyses using cell-free DNA. The serum levels of DNA (p = 0.016) and RNA (p = 0.001) could differentiate between healthy women and cancer patients, but could not discriminate malignant from benign breast lesions. A significant correlation of serum DNA with RNA levels was observed in all groups (p = 0.018). Increased serum DNA levels (but not RNA levels) in cancer patients were associated with a poorer overall (p = 0.021) and disease-free survival (p = 0.025). The occurrence of LOH at all markers significantly correlated with lymph node status (p = 0.026). In addition, the LOH frequency at D13S280 (p = 0.047) and D13S159 (p = 0.046) associated with overall and disease-free survival, respectively. In conclusion, the quantification of cell-free tumour DNA had diagnostic and prognostic values in breast cancer patients, and DNA loss at the region 13q31-33 may be an indication of lymphatic tumour cell spread.

Hypothermia has been recognized as a potential side effect of continuous hemofiltration, but the thermal energy loss within the extracorporeal circuit has not yet been quantified. The authors measured temperature decrease and thermal energy balance in vitro at different points within the extracorporeal circuit of the Acu-men (Fresenius Medical Care, Bad Homburg, Germany), a new device for continuous hemofiltration. The device employs a disposable cartridge with a pneumatic blood pump as the driving force for the blood. Furthermore, a volumetric balancing chamber is used to balance filtrate with replacement fluid. At a blood flow of 120 ml/min, a filtrate volume of 1.4 L/hr, and a replacement fluid temperature of 20 degrees C, temperature decreased from the beginning to the end of the extracorporeal circuit from 37.0 degrees C to 32.4 degrees C. This corresponds to a calculated in vitro thermal energy loss of 3,300 kJ/d. The in vivo thermal energy loss might be significantly less because of baroreceptor induced peripheral vasoconstriction, with reduced heat loss through the skin. The blood tubing contributed 26%, the hemofilter 31%, and the produced filtrate 43% to the negative thermal energy balance. Heat transmission within the volumetric balancing system of the Acu-men reduced the heat loss by 15%. Heating of replacement fluid to 30 degrees C, 37 degrees C, or 42 degrees C reduced the thermal energy loss by 22%, 48%, and 72%, respectively.

The management of patients with mammographic abnormalities is rapidly shifting from needle-localized surgical biopsy (NLB) to stereotactic core biopsy (SCB). The precise role of SCB in the management of nonpalpable breast cancer remains to be defined. The purpose of this study was to compare SCB to NLB in the diagnosis of mammographically detected breast cancer in women who underwent breast-conserving surgery. The records of all patients with nonpalpable breast cancer who underwent breast-conserving surgery from 1/1/95 to 6/1/97 were analyzed with respect to method of diagnosis, time interval from detection to diagnosis and breast-conserving surgery, volume of breast tissue excised, margin status and reexcision rate, number of surgical procedures, and total charges and costs per patient. During a 30-month period, 117 patients with nonpalpable breast cancer underwent breast-conserving surgery. The diagnosis was made by NLB in 69 patients and SCB in 48 patients. The time from detection to diagnosis and breast-conserving surgery was 1.7 +/- 0.5 and 8.1 +/- 1.2 days for SCB patients and 6. 8 +/- 1.3 and 16.9 +/- 2.3 days for NLB patients (P < 0.01). The volume of breast tissue removed was 117.9 +/- 5.6 cm3 for SCB patients versus 75.2 +/- 2.9 cm3 for NLB patients (P < 0.01). Three SCB patients (6%) had positive margins, while 38 NLB patients (55%) had positive margins (P < 0.01). Only 1 SCB patient (2%) was reexcised, while 34 NLB patients (50%) were reexcised (P < 0.01). Eighty-nine percent of SCB patients had a single surgical procedure compared to 39% of NLB patients (P < 0.001). Patients who underwent SCB had reduced total charges and total costs per patient compared to NLB patients ($11,700 +/- $554 and $3537 +/- $167 per SCB patient versus $15,654 +/- $706 and $4853 +/- $198 per NLB patient, P < 0. 0001). Stereotactic core biopsy shortens the time from detection at mammography to diagnosis and breast-conserving therapy, permits appropriate discussion of treatment alternatives, reduces the positive margin rate and reexcision rate, and may represent a significant cost savings in the management of nonpalpable breast cancer., (Copyright 1998 Academic Press.)

Rationale and Objectives: Use of small focal spots with low x-ray tube currents may result in very long exposure times and thus result in motion blur in magnification mammography. The authors investigated the reduction in exposure time with increasing x-ray tube kVp and the corresponding decrease in perceived visibility of low-contrast objects in phantom images., Methods: Exposure times required to radiograph an RMI 156 phantom in a magnification geometry were measured as a function of x-ray tube kVp when operated under automatic exposure control. Magnification images of the RMI 156 phantom were obtained at x-ray tube voltages ranging from 28 to 34 kVp. Five radiology residents ranked the visibility of two borderline fibers and six borderline microcalcification specks using a 5-point scale ranging from excellent to barely visible., Results: Between 28 and 34 kVp, the density of the RMI phantom images was nearly constant with a mean value of 1.32 +/- 0.04. Increasing the x-ray tube voltage from 28 kVp to 34 kVp reduced the exposure time from 1.27 seconds to 0.66 seconds. Image quality at 30 and 32 kVp was not significantly worse than that achieved at 28 kVp. Increasing the x-ray tube voltage to 34 kVp, however, resulted in a statistically significant (P < 0.001) deterioration in the relative visibility of fibers and microcalcification specks., Conclusions: Magnification mammography performed at 32 kVp will decrease exposure times significantly and result in a microcalcification and fiber visibility that is similar to that achieved at 28 kVp.

Citing evidence that breast implant-related capsules resolve uneventfully, surgeons have elected to leave the capsules in place when implants are removed because capsulectomy adds both morbidity and expense to the procedure. However, recent clinical and histopathologic evidence suggests that uneventful resolution is not always the case, and several potential problems may arise from retained capsules after removal of the implant. Retained implant capsules may result in a spiculated mass suspicious for carcinoma, dense calcifications that obscure neighboring breast tissue on subsequent imaging studies, and cystic masses due to persistent serous effusion, expansile hematoma, or encapsulated silicone filled cysts. Furthermore, retained capsules are a reservoir of implant-related foreign material in the case of silicone gel-filled implants and textured implants promoting tissue ingrowth. To avoid complications from retained capsules, total capsulectomy or postoperative surveillance should be offered to patients.

In the bovine ovary, prorenin production by theca cells is known to be regulated by LH. In the present study the aim was to evaluate whether LH-stimulated prorenin production could be further modulated by intraovarian factors in vitro. Theca cells were isolated from bovine ovaries by enzymatic dispersion, purified over Percoll gradient and cultured under serum-free conditions with LH/8Br-cAMP in the absence or presence of different steroids and growth factors and the amount of prorenin secreted into the medium was measured. None of the steroids used (androstendione, estradiol, progesterone) influenced the basal or LH-stimulated prorenin production. In contrast, cytokines and growth factors, like TNF alpha, TGF alpha, TGF beta and bFGF proved to be important regulators of prorenin synthesis. Whereas TNF alpha, TGF alpha and bFGF significantly reduced the LH- and 8Br-cAMP-induced prorenin synthesis at a site distal to cAMP formation, addition of TGF beta led to a further increase in the amount of prorenin secreted into the medium. None of the agonists had an influence on prorenin production by itself. The observed effects of cytokines and growth factors seemed to be confined to prorenin production only, since cell number, cell viability and steroidogenic response were not at all influenced by the agonists. We conclude that, although LH appears to be the primary regulator of ovarian prorenin production, several paracrine/autocrine intraovarian factors may be involved in "finely tuning" the secretion of prorenin, which is necessary for maintaining the differentiated state of the follicle.

Clinically useful methods to identify and document the presence of foreign material in tissues surrounding breast implants are needed. Fourier transform infrared microspectroscopy is an ideal technique for examining tissue for the presence of implantable biomaterials. Because the spectroscopy is microscopically guided, the pathologist is assured that the obtained spectrum is from the region of interest in a tissue section. Scanning electron microscopy yields elemental data but cannot be used to identify compounds. Because each compound has a unique spectrum by Fourier transform infrared microspectroscopy, the spectrum obtained enables identification of the various foreign materials observed by light microscopy in tissues surrounding breast implants. Histopathology from implant capsules demonstrating a silicone gel-filled implant, a saline-filled textured implant, a polyurethane foam-covered gel-filled implant, a Dacron fixation patch, and a paraffin injection granuloma are presented with corresponding Fourier transform infrared microspectroscopy spectra.

Other than gynecomastia, bilateral breast masses in a male patient is an unusual occurrence. We present a case of fat necrosis presenting in a male veteran as bilateral palpable breast masses.

Approximately 1.5 million women in the United States currently have breast implants. The majority were placed for cosmetic augmentation, but 20% were placed for reconstruction after the loss or deformity of a breast. The augmented breast is a challenge to the mammographer. Many of the palpable and mammographically detected abnormalities in these patients are related to the implant itself. Since, however, there is breast tissue present with cosmetic augmentation, the full range of fibrocystic and neoplastic conditions that can affect the breast may be seen. The presence of the implant makes imaging the breast more difficult because the implant obscures the nearby breast tissue. This paper reviews the history and evolution of various breast prostheses. The surgical approaches to placement of implants and complications associated with their use will be discussed. Examples of concomitant pathologies and a review of imaging strategies will be given.

Rationale and Objectives: Recent concern regarding possible adverse effects from silicone breast implants has increased the role of radiologists in assessing augmented breasts. The authors compare the commonly available imaging modalities in evaluating the intact silicone implant as well as free silicone in the adjacent tissue., Methods: A contrast resolution phantom and breast of veal phantom were tested. Fat was used as a reference material. The phantoms were imaged with xeromammography, film-screen mammography, ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Proton MRI spectroscopy also was performed on fat, silicone, water, and water/gelatin samples. The consensus of two radiologists determined whether free silicone was present., Results: CT and MRI provided the best images of the implant and the free silicone. Several features of MRI were useful: spin-density scans and the fast low-angle shot (FLASH) and fast imaging with steady-state precision (FISP) techniques provided excellent resolution, a consistent chemical shift artifact appeared around the silicone, and frequency selective pre-saturation techniques resulted in marked suppression of the silicone., Conclusion: Additional testing in a more realistic setting, breast coil design, and improvement of various MRI techniques, particularly the frequency selective pre-saturation techniques, all appear promising in evaluating breast implants, the presence of free silicone, and the adjacent tissues.

Metastatic disease to the breast is often an unexpected diagnosis in a female who presents with a breast mass. The most important factor suggesting the appropriate diagnosis is a history of cancer. Correlation of mammographic and ultrasonographic findings may also raise the possibility of a metastatic mass. A well-defined, noncalcified dense mass on film-screen mammography, which also shows low-level homogeneous echoes without posterior acoustic enhancement, suggests the diagnosis. It is important that the diagnosis be made by fine needle aspiration or excisional biopsy so as to expedite appropriate therapy.

The assessment of implant capsular contracture has been imprecise and vulnerable to observer bias. Attempts to measure capsules with instruments that measure implant deformability are influenced by surrounding breast tissue, subcutaneous fat, and skin. Xeromammography, B-mode ultrasound, and CT were employed in an effort to provide a noninvasive and accurate method of capsule assessment. Through two study phases, implants were placed bilaterally in a total of 21 rabbits. At 4 months, animals underwent radiologic assessment and were then sacrificed for direct implant capsule measurements. Mammographic measurements, more than ultrasound-derived measurements, strongly correlated with laboratory measures of capsular dimensions and deformability. Cross-table lateral mammographic views were more informative than traditional views, providing measures of diameter and height that both strongly correlated with laboratory measurements. CT is theoretically the most accurate method to assess contracture, but it is impractical because of expense and time requirements. The results indicate that radiologic assessment, in particular by xeromammography, of implant capsules is accurate, practical, and noninvasive. Mammography strongly correlates with laboratory measures of implant capsular contracture and therefore could be used in the clinical setting to assess capsular contracture.

Fluid mechanical steady-state laminar wall shear stresses of 30 dyne/cm2 (high stress) and less than 1 dyne/cm2 (low stress) have been applied for varying times to confluent cultures of bovine aortic endothelial cells (BAECs) by means of two parallel plate channel flow chambers in series. BAEC cultures not exposed to shear or flow (no stress) were also studied. A shear stress of 30 dyne/cm2 resulted in cellular elongation and alignment, changes that were largely complete by 24 hr. In experiments in which BAECs were incubated with 125I-labeled low-density lipoprotein for 2 or 24 hr in the presence of shear stress levels, 125I-LDL internalization at 24 hr was increased (p less than .05) in response to high-stress conditions. This increased uptake of 125I-LDL was observed in BAECs prealigned for 24 hr under high stress and in BAECs undergoing alignment in the presence of circulating 125I-LDL. BAECs were also exposed to shear stress for 24 hr in the presence of a lipoprotein-deficient circulating medium to maximize LDL receptor expression. Receptor-mediated 125I-LDL internalization and degradation measured immediately after shear stress were both significantly enhanced (p less than .01) in BAECs exposed to high stress. Furthermore, 125I-LDL binding studies at 4 degrees C revealed a significant increase (p less than .01) in specific 125I-LDL binding to BAECs exposed to high stress relative to those exposed to low or no stress. Nonspecific 125I-LDL endocytosis was not influenced by shear stress levels.(ABSTRACT TRUNCATED AT 250 WORDS)