Outcome of Monochorionic Monoamniotic Twin Reversed Arterial Perfusion Sequence Diagnosed in the First Trimester.

INTRODUCTION: The aim of this study is to evaluate the outcome of pregnancies complicated by monochorionic monoamniotic twin reversed arterial perfusion sequence (MOMA TRAP) diagnosed in the first trimester. METHODS: All patients diagnosed with MOMA TRAP sequence <14.0 weeks of gestation in a 10-year study period were retrospectively analyzed for intrauterine course and outcome. All patients were offered either expectant management or intrauterine intervention. Adverse outcome was defined as either intrauterine death (IUD), neonatal death or preterm birth <34.0 weeks of gestation. RESULTS: In the study period, 17 cases with MOMA TRAP sequence were diagnosed. Of these, 2 couples opted for termination of pregnancy. The remaining 15 were divided into 2 groups depending on the management: group A (n = 8) with expectant management and group B (n = 7) with intrauterine intervention. All fetuses in group A died before 20 weeks. Survival in group B was significantly better with 4/7 (57.1%) life births at a median of 39.6 weeks of gestation (p = 0.0256). The reasons for IUD in the 3 cases in group B were hemodynamic, strangulation, and bleeding complications during intervention. CONCLUSIONS: Intrauterine intervention in MOMA TRAP pregnancies significantly improves neonatal survival, although it is still associated with a substantial risk for IUD by hemodynamic complications or entanglement.

Forces during cellular uptake of viruses and nanoparticles at the ventral side.

Many intracellular pathogens, such as mammalian reovirus, mimic extracellular matrix motifs to specifically interact with the host membrane. Whether and how cell-matrix interactions influence virus particle uptake is unknown, as it is usually studied from the dorsal side. Here we show that the forces exerted at the ventral side of adherent cells during reovirus uptake exceed the binding strength of biotin-neutravidin anchoring viruses to a biofunctionalized substrate. Analysis of virus dissociation kinetics using the Bell model revealed mean forces higher than 30 pN per virus, preferentially applied in the cell periphery where close matrix contacts form. Utilizing 100 nm-sized nanoparticles decorated with integrin adhesion motifs, we demonstrate that the uptake forces scale with the adhesion energy, while actin/myosin inhibitions strongly reduce the uptake frequency, but not uptake kinetics. We hypothesize that particle adhesion and the push by the substrate provide the main driving forces for uptake.

ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12) Interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) Linking Iron Deficiency and Oxidative Stress Responses.

Plants grown under iron (Fe)-deficient conditions induce a set of genes that enhance the efficiency of Fe uptake by the roots. In Arabidopsis (Arabidopsis thaliana), the central regulator of this response is the basic helix-loop-helix transcription factor FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT). FIT activity is regulated by protein-protein interactions, which also serve to integrate external signals that stimulate and possibly inhibit Fe uptake. In the search of signaling components regulating FIT function, we identified ZINC FINGER OF ARABIDOPSIS THALIANA12 (ZAT12), an abiotic stress-induced transcription factor. ZAT12 interacted with FIT, dependent on the presence of the ethylene-responsive element-binding factor-associated amphiphilic repression motif. ZAT12 protein was found expressed in the root early differentiation zone, where its abundance was modulated in a root layer-specific manner. In the absence of ZAT12, FIT expression was upregulated, suggesting a negative effect of ZAT12 on Fe uptake. Consistently, zat12 loss-of-function mutants had higher Fe content than the wild type at sufficient Fe. We found that under Fe deficiency, hydrogen peroxide (H2O2) levels were enhanced in a FIT-dependent manner. FIT protein, in turn, was stabilized by H2O2 but only in the presence of ZAT12, showing that H2O2 serves as a signal for Fe deficiency responses. We propose that oxidative stress-induced ZAT12 functions as a negative regulator of Fe acquisition. A model where H2O2 mediates the negative regulation of plant responses to prolonged stress might be applicable to a variety of stress conditions.

Calcite Single Crystals as Hosts for Atomic-Scale Entrapment and Slow Release of Drugs.

Doxorubicin (DOX)/CaCO3 single crystals act as pH responsive drug carrier. A biomimetic approach demonstrates that calcite single crystals are able, during their growth in the presence of doxorubicin, to entrap drug molecules inside their lattice along specific crystallographic directions. Alterations in lattice dimensions and microstructural parameters are determined by means of high-resolution synchrotron powder diffraction measurements. Confocal microscopy confirms that doxorubicin is uniformly embedded in the crystal and is not simply adsorbed on the crystal surface. A slow release of DOX was obtained preferentially in the proximity of the crystals, targeting cancer cells.

Combined expression of KLK4, KLK5, KLK6, and KLK7 by ovarian cancer cells leads to decreased adhesion and paclitaxel-induced chemoresistance.

OBJECTIVE: Chemoresistance is a critical feature of advanced ovarian cancer with only 30% of patients surviving longer than 5 years. We have previously shown that four kallikrein-related (KLK) peptidases, KLK4, KLK5, KLK6 and KLK7 (KLK4-7), are implicated in peritoneal invasion and tumour growth, but underlying mechanisms were not identified. We also reported that KLK7 overexpression confers chemoresistance to paclitaxel, and cell survival via integrins. In this study, we further explored the functional consequenses of overexpression of all four KLKs (KLK4-7) simultaneously in the ovarian cancer cell line, OV-MZ-6, and its impact on integrin expression and signalling, cell adhesion and survival as contributors to chemoresistance and metastatic progression. METHODS: Quantitative gene and protein expression analyses, confocal microscopy, cell adhesion and chemosensitivity assays were performed. RESULTS: Expression of α5ß1/αvß3 integrins was downregulated upon combined stable KLK4-7 overexpression in OV-MZ-6 cells. Accordingly, the adhesion of these cells to vitronectin and fibronectin, the extracellular matrix binding proteins of α5ß1/αvß3 integrins and two predominant proteins of the peritoneal matrix, was decreased. KLK4-7-transfected cells were more resistant to paclitaxel (10-100 nmol/L: 38-54%), but not to carboplatin, which was associated with decreased apoptotic stimuli. However, the KLK4-7-induced paclitaxel resistance was not blocked by the MEK1/2 inhibitor, U0126. CONCLUSIONS: This study demonstrates that combined KLK4-7 expression by ovarian cancer cells promotes reduced integrin expression with consequently less cell-matrix attachment, and insensitivity to paclitaxel mediated by complex integrin and MAPK independent interactions, indicative of a malignant phenotype and disease progression suggesting a role for these KLKs in this process.

Lung perfusion analysis with dual energy CT in patients with suspected pulmonary embolism--influence of window settings on the diagnosis of underlying pathologies of perfusion defects.

PURPOSE: On lung perfusion analysis with dual energy CT (DECT) in patients with suspected pulmonary embolism (PE) commonly three patterns of perfusion defects (PD) are observed: wedge-shaped, circumscribed but not wedge-shaped, and patchy. We investigated the influence of different window settings on the identification of the underlying pathologies for these types of PD. MATERIALS AND METHODS: 3724 segments in 196 consecutive patients who underwent pulmonary DECT angiography for clinically suspected acute PE were analyzed. Iodine distribution in the lung parenchyma was calculated from the dual energy data and displayed as color map in axial, sagittal and coronal view. Afterwards, lung and angiography window were applied separately and assessed for pulmonary embolism and pathologies of the lung parenchyma. RESULTS: 1420 segments in 141 patients showed PD, of which 276 were wedge-shaped, 287 circumscribed and 857 patchy. Circumscribed PD were associated in 99% with interstitial or alveolar fluid collections and in 1% with located bullae. Patchy PD were associated in 65% with emphysematous or fibrotic changes, in 38% with diffuse infiltrations or interstitial fluid collections and in 0.2% with PE. The underlying pathologies for wedge-shaped PD were in 78% PE, in 3% tumors compressing pulmonary arteries, in another 3% located bullae and in further 3% infiltrations. 13% (n=15) of the segments in this group did not show vascular or parenchymal pathologies, but in 80% (n=10) of these cases patients had PE in another segment. Totally n=6 of wedge-shaped PD in 5 patients remained with unclear direct cause. CONCLUSION: Whereas patchy and circumscribed PD are almost exclusively associated with pathologies of the lung parenchyma, wedge-shaped PD are mostly associated with PE. For a small number of wedge-shaped PD the underlying cause cannot be detected with DECT. Very small peripherally situated micro-emboli may be discussed as a reason. However, prospective trials are needed to clarify the value of this finding.

Influence of the size of the hiatus on the rate of reherniation after laparoscopic fundoplication and refundopilication with mesh hiatoplasty.

BACKGROUND: Intrathoracic wrap migration is the most frequent morphological anatomic reason for failure of laparoscopic antireflux surgery (LARS). This study investigates whether the size of the esophageal hiatus is a factor in reherniation after LARS with mesh hiatoplasty and after primary failed hiatal closure. METHODS: Fifty-four patients who underwent a laparoscopic 270° Toupet fundoplication with simple sutured crura and posterior onlay of Parietex mesh prosthesis between October 2003 and June 2008 were evaluated with respect to the occurrence of postoperative intrathoracic wrap migration/reherniation. Indication for mesh hiatoplasty was a hiatus with a hiatal surface area (HSA) of at least 5.60 cm(2) or slippage after the first LARS. The integrity of repair was assessed using a barium swallow test. Cinematography was performed at a median of 25.6 months (3-63 months after operation) and was completed in 49 of 54 patients (90%). Follow-up was completed in 24 patients who underwent primary LARS (group A) and 25 patients who underwent a laparoscopic refundoplication (group B). RESULTS: In group A, the occurrence of postoperative wrap reherniation was diagnosed in 20.8% of the patients, compared to 40% in group B. In both groups only one patient with recurrent hiatal hernia was symptomatic. In group A, patients who developed a recurrent hernia had a larger HSA than patients without postoperative reherniation. There was a huge difference in the size of the HSA between symptomatic and asymptomatic patients with reherniation. In comparison, group B patients had HSA of similar size in all described cases. CONCLUSION: In primary intervention, recurrence of hiatal hernia is more likely the larger the HSA is. The size of the hiatus is a major contributing factor to the possibility of reherniation. After failed primary hiatal closure, the size of the hiatal defect is no marker for the possibility of reherniation.