Robotic transanal endoscopic microsurgery in benign rectal tumour

Aim

To present a case of resection of a rectal tumour by a transanal robotic approach.

Patient

A 58-year-old woman with a 3-cm tumour located 6 cm proximal to anal verge (uT1N0).

Results

We describe the details of the surgical technique. A complete resection with adequate margins was accomplished. The defect was closed with a running suture. Operation time was 180 min. There were no complications and the patient was discharged 24 h after surgery.

Conclusion

A complete resection of a rectal tumour by a robotic approach is feasible and safe. More studies are needed to clearly define the indications where this new approach can show clear advantages over other transanal resection approaches.     

Glucagonoma syndrome. Rapid response following arterial embolization of glucagonoma metastatic to the liver

Transcatheter arterial embolization was used to treat a patient with glucagonoma metastatic to the liver after chemotherapy failed. Rapid amelioration of the syndrome's manifestations followed.     

Clinical, histochemical, and ultrastructural correlation in septal endomyocardial biopsies from chronic chagasic patients: detection of early myocardial damage

In order to recognize early signs of myocardial damage, histologic, histochemical, and ultrastructural studies were performed on septal endomyocardial biopsy tissue obtained from 79 chronic chagasic patients and from 18 patients with atypical chest pain (control group). Abnormal biopsy findings were recognized in 9 of 16 (60%) chagasic patients with no clinical evidence of myocardial damage. In cases of segmental asynergy only, biopsies were abnormal in 18 of 19 patients. When signs of advanced myocardial damage were evidenced by clinical examination or ECGs, all biopsies were abnormal. Mitochondrial, nuclear, and cell membrane irregularities were consistent findings. A peculiar dilatation and filling of the T tubule system with a glycoprotein-like substance and a remarkable increase in monoamine oxidase activity were observed early in the disease and progressed in magnitude and frequency as myocardial damage became more evident by other diagnostic methods. Septal endomyocardial biopsy is a sensitive method for detection of early myocardial damage in chronic chagasic patients. Based on these findings, a modification of the currently used classification is proposed.     

Abortion in democratic Spain: the parliamentary political agenda 1979-2004

Since Spain's transition to democracy, abortion has been a public policy issue both inside and outside parliament. This paper describes the history of abortion law reform in Spain from 1979 to 2004 and analyses the discourse on abortion of members of the Spanish parliament by sex and political allegiance. The analysis is based on a retrospective study of the frequency of legislative initiatives and the prevalence of different arguments and positions in debates on abortion found through a systematic search of the parliamentary database. Little time was given to abortion in the parliamentary agenda compared to other women's issues such as violence against women. There were 229 bills and other parliamentary initiatives in that period, 60% initiated and led by pro-choice women. 143 female and 72 male parliamentarians took part in the debates. The inclusion of socio-economic grounds for legal abortion (64%), and making abortion on request legal in the first 12 weeks of pregnancy (60%) were the most frequent forms of law reform proposed, based most often on pro-women's rights arguments. Male and female members of anti-choice parties and most male members of other parties argued for fetal rights. Pro-choice parties tabled more bills than anti-choice parties but till now all reforms proposed since 1985 have been voted down.     

Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation

Ryanodine receptors (RyR) amplify activity-dependent calcium influx via calcium-induced calcium release. Calcium signals trigger postsynaptic pathways in hippocampal neurons that underlie synaptic plasticity, learning, and memory. Recent evidence supports a role of the RyR2 and RyR3 isoforms in these processes. Along with calcium signals, brain-derived neurotrophic factor (BDNF) is a key signaling molecule for hippocampal synaptic plasticity and spatial memory. Upon binding to specific TrkB receptors, BDNF initiates complex signaling pathways that modify synaptic structure and function. Here, we show that BDNF-induced remodeling of hippocampal dendritic spines required functional RyR. Additionally, incubation with BDNF enhanced the expression of RyR2, RyR3, and PKMζ, an atypical protein kinase C isoform with key roles in hippocampal memory consolidation. Consistent with their increased RyR protein content, BDNF-treated neurons generated larger RyR-mediated calcium signals than controls. Selective inhibition of RyR-mediated calcium release with inhibitory ryanodine concentrations prevented the PKMζ, RyR2, and RyR3 protein content enhancement induced by BDNF. Intrahippocampal injection of BDNF or training rats in a spatial memory task enhanced PKMζ, RyR2, RyR3, and BDNF hippocampal protein content, while injection of ryanodine at concentrations that stimulate RyR-mediated calcium release improved spatial memory learning and enhanced memory consolidation. We propose that RyR-generated calcium signals are key features of the complex neuronal plasticity processes induced by BDNF, which include increased expression of RyR2, RyR3, and PKMζ and the spine remodeling required for spatial memory formation.     

Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.Actin is critically involved in the regulation of neuronal polarization, differentiation, and growth of neuronal processes, cargo trafficking, and plasticity of synapses (1–3). Spectrin is an actin-binding protein that is important for the development and stabilization of axons and maintenance of neuronal polarization (4–6). In Caenorhabditis elegans, spectrin is important for the stability and integrity of axons under mechanical stress (4, 6) and for mechanosensation (6), and spectrin depletion results in axon breakage during animal locomotion (4). In Drosophila, spectrin has been shown to be involved in axonal path finding (7) and stabilization of presynaptic terminals (8). In mice, spectrin null mutations are embryonically lethal, and neurons with spectrin knockdown display defects in axonal initial segment assembly (5, 9, 10).Actin and spectrin form a 2D polygonal lattice structure underneath the membrane of erythrocytes (11). Recently, a novel form of actin–spectrin-based submembrane skeleton structure was discovered in neuronal axons (12) using superresolution STORM imaging (13, 14). This membrane-associated periodic skeleton (MPS) has been observed in both fixed and live cultured neurons (12, 15, 16) and in brain tissue sections (12). In this structure, short actin filaments are organized into repetitive, ring-like structures that wrap around the circumference of the axon with a periodicity of ∼190 nm; adjacent actin rings are connected by spectrin tetramers, and actin short filaments in the rings are capped by adducin (12). This structure also appears to organize other associated molecules, such as ankyrin and sodium channels, into a periodic distribution in axons (12, 16). During neuronal development, MPS originates from the axonal region proximal to the soma and propagates to distal axonal terminals (16). At a relatively late stage during development, specific isoforms of ankyrin and spectrin molecules, ankyrin-G and βIV spectrin, are recruited to the axon initial segment (AIS) (17, 18), and these molecules are also assembled into the MPS structure, adopting a similar periodic distribution (16, 19). As in the AIS, this periodic structure is also present in the nodes of Ranvier (20). This periodic skeletal structure has been shown to preferentially form in axons compared with dendrites in primary neuronal cultures: actin and spectrin typically form a long-range, periodic lattice structure throughout the entire axonal shaft, except for the very distal region near the growth cone, in essentially all observed axons. In contrast, such a periodic structure was observed in only a small fraction (∼10–30%) of dendrites and typically appeared as short, isolated patches in portions of these dendrites (16, 20). The local concentration of spectrin is a key determinant for the preferential formation of MPS in axons: in wild-type neurons, βII spectrin is enriched in axons, and artificially increasing the concentration of βII spectrin through overexpression is sufficient to induce the formation of MPS in all dendrites (16). Ankyrin-B appears to be an important regulator of this structure: in ankyrin-B knockout mice, βII spectrin becomes evenly distributed between axons and dendrites, leading to the formation of the long-range MPS structure in all dendrites (16) without perturbing the MPS structure in axons (16, 21).The ubiquitous expression of spectrin in the nervous systems of nearly all animal species (22) raises the questions of how widespread the MPS structure is in different nervous system cell types and distinct subcellular compartments and of how conserved this structure is across different animal species. A recent paper reports the presence of periodic actin structures in several nervous system cell types from rodents (23). Here we investigated these questions regarding the prevalence and conservation of the MPS structure by examining the distribution of spectrin in many different types of rodent neurons and glial cells and across a variety of organisms ranging from C. elegans to Homo sapiens. Furthermore, we examined the distribution of spectrin in presynaptic and postsynaptic compartments of axons and dendrites, respectively, to shed light on the relation between the MPS structure and synapses.     

Neutrophils extracellular traps damage Naegleria fowleri trophozoites opsonized with human IgG

Naegleria fowleri infects humans through the nasal mucosa causing a disease in the central nervous system known as primary amoebic meningoencephalitis (PAM). Polymorphonuclear cells (PMNs) play a critical role in the early phase of N. fowleri infection. Recently, a new biological defence mechanism called neutrophil extracellular traps (NETs) has been attracting attention. NETs are composed of nuclear DNA combined with histones and antibacterial proteins, and these structures are released from the cell to direct its antimicrobial attack. In this work, we evaluate the capacity of N. fowleri to induce the liberation of NETs by human PMN cells. Neutrophils were cocultured with unopsonized or IgG‐opsonized N. fowleri trophozoites. DNA, histone, myeloperoxidase (MPO) and neutrophil elastase (NE) were stained, and the formation of NETs was evaluated by confocal microscopy and by quantifying the levels of extracellular DNA. Our results showed N. fowleri induce the liberation of NETs including release of MPO and NE by human PMN cells as exposure interaction time is increased, but N. fowleri trophozoites evaded killing. However, when trophozoites were opsonized, they were susceptible to the neutrophils activity. Therefore, our study suggests that antibody‐mediated PMNs activation through NET formation may be crucial for antimicrobial responses against N. fowleri.     

Proteins synthesized in African swine fever virus-infected cells analyzed by two-dimensional gel electrophoresis

At least 74 acidic and 37 basic proteins are synthesized in African swine fever virus (ASFV)-infected monkey cells not detected in uninfected cells analyzed by two-dimensional gel electrophoresis. Essentially all the proteins synthesized early during infection are also observed at late times. The use of inhibitors such as cycloheximide and phosphonoacetate has led to the identification of 34 immediate early and 13 delayed early polypeptides. Therefore 64 proteins were classified as late polypeptides. Several ASFV-induced proteins are phosphorylated as proteins a1, a4, a20, a41, a48, a49, a51, a52, a55, a58, a67, b2, b12, b28, and b32.