Hepatocellular adenomas with severe intra-abdominal bleeding, related to an underlying coagulation disorder: a case report.

BACKGROUND: Hepatocellular adenoma is a rare benign liver tumor. Typically, hepatocellular adenomas are solitary and are found in young women who use estrogen-containing contraceptives. The occurrence of multiple hepatocellular adenoma has been linked to higher body mass index, and as the prevalence of overweight increases, multiple hepatocellular adenomas are seen more often. An hepatocellular adenoma does not always necessitate treatment, as they can regress under conservative strategies. In incidental cases, an adenoma presents owing to bleeding, which is mostly self-limiting. If it is not, embolization of hepatic involved vessels is indicated. CASE PRESENTATION: In this case report, we discuss a 42-year old Caucasian woman with multiple hepatocellular bleeds, treated by multiple endovascular procedures. After the first embolization of an adenoma in the right liver lobe, a second bleed occurred in the left lobe, necessitating additional endovascular intervention. During admittance, treatment was complicated by pulmonary embolism and a pneumonia. During follow-up, our patient was diagnosed with antiphospholipid syndrome. CONCLUSION: Hepatocellular adenoma is a rare diagnosis that requires centralized expertise. This particular case illustrates the complexity of treatment strategies for associated intra-abdominal bleeding and possible complications. Although liver adenoma is often an incidental finding, it can also result in significant morbidity. Centralization of treatment leads to expertise in managing complex treatment strategies.

Naïve information aggregation in human social learning.

To glean accurate information from social networks, people should distinguish evidence from hearsay. For example, when testimony depends on others' beliefs as much as on first-hand information, there is a danger of evidence becoming inflated or ignored as it passes from person to person. We compare human inferences with an idealized rational account that anticipates and adjusts for these dependencies by evaluating peers' communications with respect to the underlying communication pathways. We report on three multi-player experiments examining the dynamics of both mixed human-artificial and all-human social networks. Our analyses suggest that most human inferences are best described by a naïve learning account that is insensitive to known or inferred dependencies between network peers. Consequently, we find that simulated social learners that assume their peers behave rationally make systematic judgment errors when reasoning on the basis of actual human communications. We suggest human groups learn collectively through naïve signaling and aggregation that is computationally efficient and surprisingly robust. Overall, our results challenge the idea that everyday social inference is well captured by idealized rational accounts and provide insight into the conditions under which collective wisdom can emerge from social interactions.

Urodynamic changes in mice with experimental autoimmune encephalomyelitis correlate with neurological impairment.

AIMS: Neurogenic bladder dysfunction is a major issue in Multiple Sclerosis (MS). High intravesical pressure should be treated early. Available therapies are insufficient and there is need for drug development and investigation of pathogenesis. Experimental Autoimmune Encephalomyelitis (EAE) in rodents is a well validated model to study MS. Previous research has shown that these animals develop urinary symptoms. However, from clinical studies, we know that symptoms do not necessarily reflect changes in bladder pressure. This paper aims to provide a complete overview of urodynamic changes in a model for detrusor overactivity in MS. METHODS: Female C57Bl/6J mice, injected with MOG35-55 and control mice, injected with vehicle (Complete Freund's adjuvant), were monitored daily for neurologic symptoms. Within 1 month after symptom development, mice were used for cystometry or histology of the bladder. RESULTS: Increasing disease score correlated with increased micturition frequency, basal pressure, and average pressure, and with a decrease in functional bladder capacity, voiding amplitude, and maximum pressure. CONCLUSIONS: This paper provides a detailed description of bladder function in C57Bl/6J mice with Myelin Oligodendrocyte Glycoprotein peptide (MOG35-55 ) induced EAE. This EAE model induces detrusor overactivity in close relationship to neurological impairment. EAE in mice is a suitable model to study detrusor overactivity in MS. Neurourol. Urodynam. 35:450-456, 2016. © 2015 Wiley Periodicals, Inc.

TRP channels in lower urinary tract dysfunction.

Lower urinary tract dysfunction (LUTd) represents a major healthcare problem. Although it is mostly not lethal, associated social disturbance, medical costs, loss of productivity and especially diminished quality of life should not be underestimated. Although more than 15% of people suffer from a form of LUTd to some extent, pathophysiology often remains obscure. In the past 20 years, transient receptor potential (TRP) channels have become increasingly important in this field of research. These intriguing ion channels are believed to be the main molecular sensors that generate bladder sensation. Therefore, they are intensely pursued as new drug targets for both curative and symptomatic treatment of different forms of LUTd. TRPV1 was the first of its class to be investigated. Actually, even before this channel was cloned, it had already been targeted in the bladder, with clinical trials of intravesical capsaicin instillations. Several other polymodally gated TRP channels, particularly TRPM8, TRPA1 and TRPV4, also appear to play a prominent role in bladder (patho)physiology. With this review, we provide a brief overview of current knowledge on the role of these TRP channels in LUTd and their potential as molecular targets for treatment.

Tunable chiral spin texture in magnetic domain-walls.

Magnetic domain-walls (DWs) with a preferred chirality exhibit very efficient current-driven motion. Since structural inversion asymmetry (SIA) is required for their stability, the observation of chiral domain walls in highly symmetric Pt/Co/Pt is intriguing. Here, we tune the layer asymmetry in this system and observe, by current-assisted DW depinning experiments, a small chiral field which sensitively changes. Moreover, we convincingly link the observed efficiency of DW motion to the DW texture, using DW resistance as a direct probe for the internal orientation of the DW under the influence of in-plane fields. The very delicate effect of capping layer thickness on the chiral field allows for its accurate control, which is important in designing novel materials for optimal spin-orbit-torque-driven DW motion.

Domain wall depinning governed by the spin Hall effect.

Perpendicularly magnetized materials have attracted significant interest owing to their high anisotropy, which gives rise to extremely narrow, nanosized domain walls. As a result, the recently studied current-induced domain wall motion (CIDWM) in these materials promises to enable a new class of data, memory and logic devices. Here we propose the spin Hall effect as an alternative mechanism for CIDWM. We are able to carefully tune the net spin Hall current in depinning experiments on Pt/Co/Pt nanowires, offering unique control over CIDWM. Furthermore, we determine that the depinning efficiency is intimately related to the internal structure of the domain wall, which we control by the application of small fields along the nanowire. This manifestation of CIDWM offers an attractive degree of freedom for manipulating domain wall motion by charge currents, and sheds light on the existence of contradicting reports on CIDWM in perpendicularly magnetized materials.

Shift registers based on magnetic domain wall ratchets with perpendicular anisotropy.

The movement of magnetic domain walls can be used to build a device known as a shift register, which has applications in memory and logic circuits. However, the application of magnetic domain wall shift registers has been hindered by geometrical restrictions, by randomness in domain wall displacement and by the need for high current densities or rotating magnetic fields. Here, we propose a new approach in which the energy landscape experienced by the domain walls is engineered to favour a unidirectional ratchet-like propagation. The domain walls are defined between domains with an out-of-plane (perpendicular) magnetization, which allows us to route domain walls along arbitrary in-plane paths using a time-varying applied magnetic field with fixed orientation. In addition, this ratchet-like motion causes the domain walls to lock to discrete positions along these paths, which is useful for digital devices. As a proof-of-principle experiment we demonstrate the continuous propagation of two domain walls along a closed-loop path in a platinum/cobalt/platinum strip.

Electric-field control of domain wall motion in perpendicularly magnetized materials.

Domain wall motion in materials exhibiting perpendicular magnetic anisotropy has been the subject of intensive research because of its large potential for future spintronic devices. Recently, it has been shown that perpendicular anisotropy of thin films can be influenced by electric fields. Voltage-controlled magnetic switching has already been realized, which is envisioned to lead to low-power logic and memory devices. Here we demonstrate a radically new application of this effect, namely control of domain wall motion by electric fields. We show that an applied voltage perpendicular to a Co or CoB wire can significantly increase or decrease domain wall velocities. Velocity modification over an order of magnitude is demonstrated (from 0.4 to 4 µm s(-1)), providing a first step towards electrical control of domain wall devices. This opens up possibilities of real-time and local control of domain wall motion by electric fields at extremely low power cost.

Tunable resistivity of individual magnetic domain walls.

Despite the relevance of current-induced magnetic domain wall (DW) motion for new spintronics applications, the exact details of the current-domain wall interaction are not yet understood. A property intimately related to this interaction is the intrinsic DW resistivity. Here, we investigate experimentally how the resistivity inside a DW depends on the wall width Δ, which is tuned using focused ion beam irradiation of Pt/Co/Pt strips. We observe the nucleation of individual DWs with Kerr microscopy, and measure resistance changes in real time. A 1/Δ(2) dependence of DW resistivity is found, compatible with Levy-Zhang theory. Also quantitative agreement with theory is found by taking full account of the current flowing through each individual layer inside the multilayer stack.

Domain-wall pinning by local control of anisotropy in Pt/Co/Pt strips.

We theoretically and experimentally analyze the pinning of a magnetic domain wall (DW) at engineered anisotropy variations in Pt/Co/Pt strips with perpendicular magnetic anisotropy. An analytical model is derived showing that a step in the anisotropy acts as an energy barrier for the DW. Quantitative measurements are performed showing that the anisotropy can be controlled by focused ion beam irradiation with Ga ions. This tool is used to experimentally study the field-induced switching of nanostrips which are locally irradiated. The boundary of the irradiated area indeed acts as a pinning barrier for the domain wall and the pinning strength increases with the anisotropy difference. Varying the thickness of the Co layer provides an additional way to tune the anisotropy, and it is shown that a thinner Co layer gives a higher starting anisotropy thereby allowing tunable DW pinning in a wider range of fields. Finally, we demonstrate that not only the anisotropy itself, but also the width of the anisotropy barrier can be tuned on the length scale of the domain wall.

The treatment of soft-tissue defects of the lower leg after a traumatic open tibial fracture.

The treatment of large soft-tissue defects of the lower leg remains a challenge. The timing of the operation, the most suitable type of tissue, and the decision between local or free flap coverage still remains under discussion. Fifty-two patients were treated with local or free flap coverage after a traumatic soft-tissue defect of the lower leg. We compared the results after treatment with local versus free flaps and fasciocutaneous flaps versus musculocutaneous flaps. In the case of primary reconstruction, we also compared the results regarding the timing of the operation: patients treated within 72 h after the trauma versus patients treated after 72 h. Thirty-five patients (67%) have been treated because of posttraumatic soft-tissue defects and, therefore, insufficient fracture coverage. Seventeen patients (33%) were treated because of a chronic osteomyelitis that arose after the trauma. In our study, we did not find a statistically significant difference between the postoperative complications of local and free flaps. A significant increase could be demonstrated in the number of revisions after treatment with a free flap. Treatment with a fasciocutaneous flap in the entire study group was associated with significantly more postoperative complications than treatment with a musculocutaneous flap. There was no significant difference in results after early or late flap coverage. Patients treated with local or free flaps achieved equal outcomes, except for the number of postoperative revisions in which local flaps required lesser revisions. Treatment with a musculocutaneous flap is preferable to treatment with a fasciocutaneous flap regarding postoperative complications. The timing of operation proved not to be a discriminating factor.

Partial silencing of the NEC1 gene results in early opening of anthers in Petunia hybrida.

The NEC1 gene, previously isolated from Petunia hybrida, is expressed at high levels in nectaries, and in a very localized fashion in stamens, particularly in the anther stomium cells and the upper part of the filament. To elucidate the function of the NEC1 gene, co-suppression was employed for down-regulation of NEC1 expression, and transposon insertion mutagenesis was used to knock out the NEC1 function. Among the transgenic plants and plants carrying dTph1 inserted in the NEC1 gene, an "early open anther" phenotype was observed. In this mutant phenotype, the anthers already open in young flower buds (1.8 cm) that still contain immature pollen, resulting in poor pollen quality and impaired pollen release. The results obtained indicate that NEC1 might be involved in the development of stomium cells, which are ruptured during the normal process of anther dehiscence to release mature pollen. Southern analysis revealed the presence of a highly homologous NEC1-like gene, named NEC2, in the P. hybrida genome. The presence of NEC2 was confirmed by segregation analysis and sequencing of genomic clones. The implications of these results and possible reasons why no visually obvious phenotype in nectaries could be produced by co-suppression or transposon insertion mutagenesis are discussed.

Sex determination in the monoecious species cucumber is confined to specific floral whorls.

In unisexual flowers, sex is determined by the selective repression of growth or the abortion of either male or female reproductive organs. The mechanism by which this process is controlled in plants is still poorly understood. Because it is known that the identity of reproductive organs in plants is controlled by homeotic genes belonging to the MADS box gene family, we analyzed floral homeotic mutants from cucumber, a species that bears both male and female flowers on the same individual. To study the characteristics of sex determination in more detail, we produced mutants similar to class A and C homeotic mutants from well-characterized hermaphrodite species such as Arabidopsis by ectopically expressing and suppressing the cucumber gene CUCUMBER MADS1 (CUM1). The cucumber mutant green petals (gp) corresponds to the previously characterized B mutants from several species and appeared to be caused by a deletion of 15 amino acid residues in the coding region of the class B MADS box gene CUM26. These homeotic mutants reveal two important concepts that govern sex determination in cucumber. First, the arrest of either male or female organ development is dependent on their positions in the flower and is not associated with their sexual identity. Second, the data presented here strongly suggest that the class C homeotic function is required for the position-dependent arrest of reproductive organs.

Suppression of cell expansion by ectopic expression of the Arabidopsis SUPERMAN gene in transgenic petunia and tobacco.

Molecular and genetic analyses have shown that the Arabidopsis thaliana gene SUPERMAN (SUP) has at least two functions in Arabidopsis flower development. SUP is necessary to control the correct distribution of cells with either a stamen or carpel fate, and is essential for proper outgrowth of the ovule outer integument. Both these functions indicate a role for SUP in cell proliferation. To study the function of the Arabidopsis SUP gene in more detail, we over-expressed the SUP gene in petunia and tobacco in a tissue-specific manner. The petunia FLORAL BINDING PROTEIN 1 (FBP1) gene promoter was used to restrict the expression of SUP to petals and stamens. The development of petals and stamens was severely affected in both petunia and tobacco plants over-expressing SUP. Petals remained small and did not unfold, resulting in closed flowers. Stamen filaments were thin and very short. Detailed analysis of these floral organs from the petunia transformants showed that cell expansion was dramatically reduced without affecting cell division. These results reveal a novel activity for SUP as a regulator of cell expansion.

NEC1, a novel gene, highly expressed in nectary tissue of Petunia hybrida.

To study the molecular regulation of nectary development, we cloned NEC1, a gene predominantly expressed in the nectaries of Petunia hybrida, by using the differential display RT-PCR technique. The secondary structure of the putative NEC1 protein is reminiscent of a transmembrane protein, indicating that the protein is incorporated into the cell membrane or the cytoplast membrane. Immunolocalization revealed that NEC1 protein is present in the nectaries. Northern blot analyses showed that NEC1 is highly expressed in nectary tissue and weakly in the stamen. GUS expression driven by the NEC1 promoter revealed GUS activity in the outer nectary parenchyma cells, the upper part of the filament and the anther stomium. The same expression pattern was observed in Brassica napus. GUS expression was observed as blue spots on the surface of very young nectaries that do not secrete nectar and do accumulate starch. GUS expression was highest in open flowers in which active secretion of nectar and starch hydrolysis had taken place. Ectopic expression of NEC1 resulted in transgenic plants that displayed a phenotype with leaves having 3-4 times more phloem bundles in mid-veins than the wild-type Petunia. The possible role of NEC1 gene in sugar metabolism and nectar secretion is discussed.

A petunia MADS box gene involved in the transition from vegetative to reproductive development.

We have identified a novel petunia MADS box gene, PETUNIA FLOWERING GENE (PFG), which is involved in the transition from vegetative to reproductive development. PFG is expressed in the entire plant except stamens, roots and seedlings. Highest expression levels of PFG are found in vegetative and inflorescence meristems. Inhibition of PFG expression in transgenic plants, using a cosuppression strategy, resulted in a unique nonflowering phenotype. Homozygous pfg cosuppression plants are blocked in the formation of inflorescences and maintain vegetative growth. In these mutants, the expression of both PFG and the MADS box gene FLORAL BINDING PROTEIN26 (FBP26), the putative petunia homolog of SQUAMOSA from Antirrhinum, are down-regulated. In hemizygous pfg cosuppression plants initially a few flowers are formed, after which the meristem reverts to the vegetative phase. This reverted phenotype suggests that PFG, besides being required for floral transition, is also required to maintain the reproductive identity after this transition. The position of PFG in the hierarchy of genes controlling floral meristem development was investigated using a double mutant of the floral meristem identity mutant aberrant leaf and flower (alf) and the pfg cosuppression mutant. This analysis revealed that the pfg cosuppression phenotype is epistatic to the alf mutant phenotype, indicating that PFG acts early in the transition to flowering. These results suggest that the petunia MADS box gene, PFG, functions as an inflorescence meristem identity gene required for the transition of the vegetative shoot apex to the reproductive phase and the maintenance of reproductive identity.

Arabidopsis STERILE APETALA, a multifunctional gene regulating inflorescence, flower, and ovule development.

A recessive mutation in the Arabidopsis STERILE APETALA (SAP) causes severe aberrations in inflorescence and flower and ovule development. In sap flowers, sepals are carpelloid, petals are short and narrow or absent, and anthers are degenerated. Megasporogenesis, the process of meiotic divisions preceding the female gametophyte formation, is arrested in sap ovules during or just after the first meiotic division. More severe aberrations were observed in double mutants between sap and mutant alleles of the floral homeotic gene APETALA2 (AP2) suggesting that both genes are involved in the initiation of female gametophyte development. Together with the organ identity gene AGAMOUS (AG) SAP is required for the maintenance of floral identity acting in a manner similar to APETALA1. In contrast to the outer two floral organs in sap mutant flowers, normal sepals and petals develop in ag/sap double mutants, indicating that SAP negatively regulates AG expression in the perianth whorls. This supposed cadastral function of SAP is supported by in situ hybridization experiments showing ectopic expression of AG in the sap mutant. We have cloned the SAP gene by transposon tagging and revealed that it encodes a novel protein with sequence motifs, that are also present in plant and animal transcription regulators. Consistent with the mutant phenotype, SAP is expressed in inflorescence and floral meristems, floral organ primordia, and ovules. Taken together, we propose that SAP belongs to a new class of transcription regulators essential for a number of processes in Arabidopsis flower development.

Multiple AGAMOUS homologs from cucumber and petunia differ in their ability to induce reproductive organ fate.

The C function in Arabidopsis, which specifies stamen and carpel identity, is represented by a single gene called AGAMOUS (AG). From both petunia and cucumber, two MADS box genes have been isolated. Both share a high degree of amino acid sequence identity with the Arabidopsis AG protein. Their roles in specifying stamen and carpel identity have been studied by ectopic expression in petunia, resulting in plants with different floral phenotypes. Cucumber MADS box gene 1 (CUM1) induced severe homeotic transformations of sepals into carpelloid structures and petals into stamens, which is similar to ectopic AG expression in Arabidopsis plants. Overexpression of the other cucumber AG homolog, CUM10, resulted in plants with partial transformations of the petals into antheroid structures, indicating that CUM10 is also able to promote floral organ identity. From the two petunia AG homologs pMADS3 and Floral Binding Protein gene 6 (FBP6), only pMADS3 was able to induce homeotic transformations of sepals and petals. Ectopic expression of both pMADS3 and FBP6, as occurrs in the petunia homeotic mutant blind, phenocopies the pMADS3 single overexpresser plants, indicating that there is no additive effect of concerted expression. This study demonstrates that in petunia and cucumber, multiple AG homologs exist, although they differ in their ability to induce reproductive organ fate.

Downregulation of ovule-specific MADS box genes from petunia results in maternally controlled defects in seed development.

A maternally determined seed defect has been obtained by downregulation of the petunia MADS box genes Floral Binding Protein 7 (FBP7) and FBP11. These genes have been previously shown to play central roles in the determination of ovule identity. Aberrant development of the seed coat and consequent degeneration of the endosperm have been observed in transgenic plants in which these two genes are downregulated by cosuppression. Analysis of the expression pattern of FBP7 and FBP11 and genetic analysis confirmed the maternal inheritance of the phenotype. The FBP7 promoter was cloned and fused to reporter genes. One of these reporter genes was the BARNASE gene for targeted cell ablation. Our results indicate that FBP7 promoter activity is restricted to the seed coat of developing seeds and that it is completely silent in the gametophytically derived tissues. The mutants used in this study provided a unique opportunity to investigate one of the poorly understood aspects of seed development: the interaction of embryo, endosperm, and maternal tissues.

Onychomatricoma.

BACKGROUND: Onychomatricoma is a rare benign tumor originating in the nail matrix. Only eight cases have been reported until now. OBJECTIVE: The clinical and histopathological features of this recently reported tumor will be described and its differential diagnoses outlined. A typical case of onychomatricoma is described in a 62-year-old white man. RESULTS: Clinically, onychomatricoma is characterized by: 1) a yellowish discoloration of a longitudinal segment of the nail plate with small splinter hemorrhages within the proximal portion of the nail; 2) a thickening with increased transversal curvature of the involved nail plate positively corresponding with the yellow discoloration; and 3) a matrix tumor consisting of multiple fine filiform projections that extend into the thickened nail plate. The treatment of onychomatricoma is complete excision of the tumor. CONCLUSION: Onychomatricoma is a new entity with clinical and histopathological features that are characteristic enough to make the correct diagnosis.