Systematics and life cycles of four avian schistosomatids from Southern Cone of South America.

Relative to the numerous studies focused on mammalian schistosomes, fewer include avian schistosomatids particularly in the southern hemisphere. This is changing and current research emerging from the Neotropics shows a remarkable diversity of endemic taxa. To contribute to this effort, nine ducks (Spatula cyanoptera, S.versicolor, Netta peposaca), 12 swans (Cygnus melancoryphus) and 1,400 Physa spp. snails from Chile and Argentina were collected for adults and larval schistosomatids, respectively. Isolated schistosomatids were preserved for morphological and molecular analyses (28S and COI genes). Four different schistosomatid taxa were retrieved from birds: Trichobilharzia sp. in N. peposaca and S. cyanoptera that formed a clade; S.cyanoptera and S. versicolor hosted Trichobilharzia querquedulae; Cygnus melancoryphus hosted the nasal schistosomatid, Nasusbilharzia melancorhypha; and one visceral, Schistosomatidae gen. sp., which formed a clade with furcocercariae from Argentina and Chile from previous work. Of the physid snails, only one from Argentina had schistosomatid furcocercariae that based on molecular analyses grouped with T. querquedulae. This study represents the first description of adult schistosomatids from Chile as well as the elucidation of the life cycles of N.melancorhypha and T. querquedulae in Chile and Neotropics, respectively. Without well-preserved adults, the putative new genus Schistosomatidae gen. sp. could not be described, but its life cycle involves Chilina spp. and C. melancoryphus. Scanning electron microscopy of T. querquedulae revealed additional, undescribed morphological traits, highlighting its diagnostic importance. Authors stress the need for additional surveys of avian schistosomatids from the Neotropics to better understand their evolutionary history.

Genotypic diversity of Salmonella ser. Abortusequi isolates from Argentina.

BACKGROUND: Salmonella enterica subsp. enterica serovar Abortusequi (S. Abortusequi) is a serotype restricted to equines, which produces abortion outbreaks. Nowadays the disease is being reported in different countries including Argentina thus generating an important impact in the equine industry. Molecular characterization of the 95 kb virulence plasmid and the spvC gene of S. Abortusequi demonstrated their importance in the pathogenicity of the serotype. In the last decades, high clonality of S. Abortusequi was identified in Japan, Mongolia and Croatia. OBJECTIVES: The aim of this work was to characterize S. Abortusequi isolates obtained in Argentina between 2011 and 2016 by virulence-gene profiling and pulsed-field gel electrophoresis. STUDY DESIGN: Case report. METHODS: S. Abortusequi isolates were studied by virulence-gene profiling and pulsed-field gel electrophoresis. RESULTS: Four virulence profiles and nine pulsed-field gel electrophoresis pulsotypes were identified among the 27 isolates included in the study. Different strains were found in the same outbreak and/or farm suggesting the presence of different sources of infection or mutation of isolates. MAIN LIMITATIONS: The number of related and nonrelated strains. More isolates may be necessary for a more intensive study. CONCLUSIONS: Most strains presented the same virulence profile, being positive for all the studied genes except gipA and sopE1, which are involved in intestinal virulence. Only few isolates showed different results in the same outbreak or farm. Unlike other studies, our results demonstrate a considerable diversity of S. Abortusequi pulsed-field gel electrophoresis pulsotypes, which suggests that different sources of infection may be involved within the same outbreak.

Fast recovery of the pristine magnetic and structural phases in superconducting LaFeAsO0.89F0.11 by Mn/Fe substitution.

We report an experimental study on the effect of Mn impurities in the optimally doped [Formula: see text] compound. The results show that a very tiny amount of Mn, of the order of 0.1%, is enough to destroy superconductivity and to recover at low temperatures both the magnetic ground state and the orthorhombic structure of the pristine LaFeAsO parent compound. The results are discussed within a model where electron correlations enhance the Ruderman-Kittel-Kasuya-Yosida interaction among impurities.

Fast wide-volume functional imaging of engineered in vitro brain tissues.

The need for in vitro models that mimic the human brain to replace animal testing and allow high-throughput screening has driven scientists to develop new tools that reproduce tissue-like features on a chip. Three-dimensional (3D) in vitro cultures are emerging as an unmatched platform that preserves the complexity of cell-to-cell connections within a tissue, improves cell survival, and boosts neuronal differentiation. In this context, new and flexible imaging approaches are required to monitor the functional states of 3D networks. Herein, we propose an experimental model based on 3D neuronal networks in an alginate hydrogel, a tunable wide-volume imaging approach, and an efficient denoising algorithm to resolve, down to single cell resolution, the 3D activity of hundreds of neurons expressing the calcium sensor GCaMP6s. Furthermore, we implemented a 3D co-culture system mimicking the contiguous interfaces of distinct brain tissues such as the cortical-hippocampal interface. The analysis of the network activity of single and layered neuronal co-cultures revealed cell-type-specific activities and an organization of neuronal subpopulations that changed in the two culture configurations. Overall, our experimental platform represents a simple, powerful and cost-effective platform for developing and monitoring living 3D layered brain tissue on chip structures with high resolution and high throughput.

Superconductivity Emerging from an Electronic Phase Separation in the Charge Ordered Phase of RbFe_{2}As_{2}.

^{75}As, ^{87}Rb, and ^{85}Rb nuclear quadrupole resonance (NQR) and ^{87}Rb nuclear magnetic resonance measurements in a RbFe_{2}As_{2} iron-based superconductor are presented. We observe a marked broadening of the ^{75}As NQR spectrum below T_{0}≃140 K which is associated with the onset of a charge order in the FeAs planes. Below T_{0} we observe a power-law decrease in the ^{75}As nuclear spin-lattice relaxation rate down to T^{*}≃20 K. Below T^{*} the nuclei start to probe different dynamics owing to the different local electronic configurations induced by the charge order. A fraction of the nuclei probes spin dynamics associated with electrons approaching a localization while another fraction probes activated dynamics possibly associated with a pseudogap. These different trends are discussed in light of an orbital selective behavior expected for the electronic correlations.

Co-Release of GABA Does Not Occur at Glycinergic Synapses onto Lumbar Motoneurons in Juvenile Mice.

The fast inhibitory neurotransmitters glycine and GABA are co-localized in synaptic terminals of inhibitory interneurons in the spinal cord and co-released onto lumbar motoneurons in neonatal rats. We performed whole-cell voltage-clamp experiments on spinal cord preparations obtained from juvenile (P8-14) mice to determine whether inhibitory currents exhibited GABAergic components in motoneurons of animals of weight-bearing age. Subsequently we established whether or not GABA is co-released at glycinergic synapses onto motoneurons by determining if it conferred modulatory effects on the kinetics of glycinergic currents. Exponential fitting analysis showed that evoked and miniature inhibitory post-synaptic currents (IPSCs) were best-fitted with a single decay time constant. Responses recorded from connected interneuron-motoneuron pairs showed no effect of a benzodiazepine or a GABA(A) receptor antagonist. Similarly IPSCs evoked by extracellular stimulation and miniature IPSCs were not affected by either agent, indicating the absence of co-detection. Experimental manipulation of the relative content of pre-synaptic GABA and glycine conferred no effect on post-synaptic responses. It is thus unlikely that GABA is co-released in biologically relevant amounts at glycinergic synapses onto lumbar motoneurons in mice of this age.

Gurltia paralysans (Wolffhügel, 1933): description of adults and additional case reports of neurological diseases in three domestic cats from southern Chile.

Adults of Gurltia paralysans were obtained from veins of the spinal cord subarachnoid space from three domestic cats presenting with chronic paraparesis/paraplegia from rural areas of southern Chile. Four adult nematodes were collected (2 males and 2 females) were recovered from cat 1, 14 adult nematodes (12 females and 2 males) from cat 2, and 12 nematodes (10 females and 2 males) were collected from cat 3. Parasite induced lesions that compromised subarachnoid vein microvasculature at the thoracic, lumbar, sacral spinal cord segments extending to conus medularis. Female nematodes measured 25 mm long (range=25-30 mm) and 0.1mm wide. Male measured a mean of 16 mm length (range=13-18 mm) with a body diameter of 0.1mm (range=0.08-0.15 mm). The present study described structural features of G. paralysans, a rare parasite first reported in the 1930s, and provides additional reports on associated clinical and pathological findings in naturally infected domestic cats.

Persistent pulmonary hypertension of the newborn refractory to inhaled nitric oxide and prostacyclin, responsive to neuromuscular blockade.

Neonatal pulmonary hypertension refractory to high frequency ventilation (HFOV) and inhaled nitric oxide (iNO) is an occasional occurrence. We report a full-term neonate with severe pulmonary hypertension unresponsive to the treatment with HFOV and iNO, later associated with prostacyclin, who rapidly improved after the addition of vecuronium, a neuromuscular blocker.

Investment of palliative medicine in bridging the gap with academia: a call to action.

Palliative care and palliative medicine define a relatively new medical discipline that has arisen in response to the need for better approaches to caring for people with advanced life-limiting illnesses. For professional, managerial and cultural reasons, it has evolved largely outside of academic structures. As the discipline has matured, its needs for education, training, intellectual discourse, evidence development and new science have become more apparent. Traditional academia remains sceptical about the role of palliative medicine, and bastions of palliative medicine expertise in universities have been slow to develop. Yet the engagement of the academic sector in palliative medicine has distinct benefits: (1) promoting the exploration of the culture, humanities and science of the discipline; (2) generating evidence to support practice; (3) creating a legion of educators to train a palliative medicine workforce and to inform clinical colleagues of the role of palliative medicine; and (4) providing order and direction to the discipline's development. A roadmap leading to better engagement between palliative medicine and academia is needed. Examples of developments that could help bridge the two domains include: standardisation of terminology and clarification of boundaries of influence; focus on high-quality research that will generate robust evidence to support clinical decision-making; and clear definition of outcomes, with measures that are understandable across medical disciplines.

Meningomyelitis due to nematode infection in four cats.

Spinal cord parasitic migrations in cats are uncommon. This report describes four cases of chronic hindlimb paraparesis in cats associated with nematode infection. Complete neurologic, hematologic, serum chemistry and radiographic examination was performed on all animals. Computed tomographic (CT)-myelographic examination at the lumbar area in one cat showed a slight swelling of the spinal cord. Necropsy examination of the spinal cord revealed generalized edema and marked submeningeal hemorrhage at the thoracic region in three cats. On histopathologic examination, numerous sections of adult nematodes and eggs were present in histological sections of the affected spinal cord segments in all cats. The morphologic features of the nematode, location and appearance of the lesions suggest that the parasite responsible for the paralysis in these cats is Gurltia paralysans.

PNAEmu can significantly reduce Burkitt's lymphoma tumor burden in a SCID mice model: cells dissemination similar to the human disease.

In human Burkitt's Lymphoma (BL) BRG cells, a t(8;14) translocation, placing c-myc near the Emu enhancer of the H chain locus, causes tumor expansion. Earlier, we showed that a peptide nucleic acid complementary to the Emu sequence (PNAEmu), specifically inhibited the expression of translocated c-myc and impaired the growth of BRG cells-induced subcutaneous tumors in mice suffering from severe combined immunodeficiency (SCID). In this study, the therapeutic potential of PNAEmu was evaluated in a systemic mouse model. BRG-BL cells transfected with the luciferase gene were inoculated intravenously into SCID mice resulting in a preferential expansion, similar to the one of human adult patients, in the abdominal cavity, central nervous system and bone marrow. The mice were chronically injected intraperitoneally either with PNAEmu or with control PNA. The treatment was stopped when the control animals developed severe neurological symptoms. As detected both by inspection at necropsy and imaging, overall tumor growth in PNAEmu-treated mice decreased by >80%. Histological and immunohistochemical studies showed, only in PNAEmu-treated mice, a substantially reduced BL cell growth at the major sites of invasion and vast areas of necrosis in the lymphomatous tissues, with concomitant c-myc expression downregulation. Altogether, the data support the therapeutic potential of PNAEmu in human adult BL.

Pentameric concatenated (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) nicotinic acetylcholine receptors: subunit arrangement determines functional expression.

BACKGROUND AND PURPOSE: alpha4 and beta2 nicotinic acetylcholine (ACh) receptor subunits expressed heterologously in Xenopus oocytes assemble into a mixed population of (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) receptors. In order to express these receptors separately in heterologous systems, we have engineered pentameric concatenated (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) receptors. EXPERIMENTAL APPROACH: alpha4 and beta2 subunits were concatenated by synthetic linkers into pentameric constructs to produce either (alpha4)(2)(beta2)(3) or (alpha4)(3)(beta2)(2) receptors. Using two-electrode voltage-clamp techniques, we examined the ability of the concatenated constructs to produce functional expression in Xenopus oocytes. Functional constructs were further characterized in respect to agonists, competitive antagonists, Ca2+ permeability, sensitivity to modulation by Zn2+ and sensitivity to up-regulation by chaperone protein 14-3-3. KEY RESULTS: We found that pentameric concatamers with a subunit arrangement of beta2_alpha4_beta2_alpha4_beta2 or beta2_alpha4_beta2_alpha4_alpha4 were stable and functional in Xenopus oocytes. By comparison, when alpha4 and beta2 were concatenated with a subunit order of beta2_beta2_alpha4_beta2_alpha4 or beta2_alpha4_alpha4_beta2_alpha4, functional expression in Xenopus oocytes was very low, even though the proteins were synthesized and stable. Both beta2_alpha4_beta2_alpha4_beta2 and beta2_alpha4_beta2_alpha4_alpha4 concatamers recapitulated the ACh concentration response curve, the sensitivity to Zn2+ modulation, Ca2+ permeability and the sensitivity to up-regulation by chaperone protein 14-3-3 of the corresponding non-linked (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) receptors respectively. Using these concatamers, we found that most alpha4beta2-preferring compounds studied, including A85380, 5I-A85380, cytisine, epibatidine, TC2559 and dihydro-beta-erythroidine, demonstrate stoichiometry-specific potencies and efficacies. CONCLUSIONS AND IMPLICATIONS: We concluded that the alpha4beta2 nicotinic ACh receptors produced with beta2_alpha4_beta2_alpha4_beta2 or beta2_alpha4_beta2_alpha4_alpha4 pentameric constructs are valid models of non-linked (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) receptors respectively.

Lymphangioma communicating with the excretory system.

Lymphangioma is a rare benign tumor caused by failure in the development of the lymphatic communicating system. The corresponding nomenclature is confusing. In recent years ''renal lymphangiectasia'' is the preferred name. Although this disease may occur in any site of the body, the neck (75%) and axillary area (20%) are the most common sites, and the kidney is occasionally involved. We report a case of lymphangioma communicating with the urinary system in a 61-year-old man diagnosed by CT scan treated with nephrectomy and histological confirmation.

First Italian consensus statement on diagnosis, prevention and treatment of cardiovascular complications in HIV-infected patients in the HAART era (2006).

The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens.

Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc.

In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Emu enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Emu sequences (PNAEmuwt), specifically blocks the expression of the c-myc oncogene under the Emu enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEmuwt was also able to block tumor growth in SCID mice inoculated with human BL cell lines. After subcutaneous inoculum in mice BL cells reproducibly form tumors. Both pre-treatment of BL cells with PNAEmuwt before inoculum and chronic intravenous administration of PNAEmuwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEmuwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEmumut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Emu enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.

Cetuximab for treatment of metastatic colorectal cancer.

In the past decade the median overall survival of patients with metastatic colorectal cancer has increased from 12 to more than 20 months, mostly due to the new chemotherapeutic agents, irinotecan and oxaliplatin. Most recently, targeted therapies, that inhibit specific cancer pathways and molecules, have shown promising results in the treatment of patients with metastatic colorectal cancer and other solid tumors. One of the most studied targets for anticancer therapy is the epidermal growth factor receptor (EGFR), which is overexpressed in a variety of malignancies. Cetuximab, an anti-EGFR chimeric monoclonal antibody, has shown clinically meaningful antitumor activity in patients with metastatic colorectal cancer in several clinical trials. Efforts of physicians and researchers are currently directed towards the identification of predictive factors (clinical or molecular) of clinical outcome, with the aim of both optimizing the therapeutic index and dealing with increasing costs of these new compounds.

Relationship between human mammaglobin mRNA expression in breast cancer tissue and clinico-pathologic features of the tumors.

Human mammaglobin (hMAM) has recently been recognized as a breast associated glycoprotein. Although the biological role of hMAM is unknown, it has been previously reported that hMAM gene expression is a marker of low biological and clinical aggressiveness of breast cancer (BC). In this study, 148 cases of BC tissues were investigated for hMAM mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). In order to evaluate its prognostic value, hMAM was correlated with age of patients, type and size of tumor, nodal stage, histologic grade, c-erbB-2 over expression, Ki67 labelling index, estrogen receptor (ER) status and progesterone receptor (PGR) status. Fisher's exact test was used to examine the association between different parameters and hMAM. hMAM was expressed in 138/148 (93%) of BC tissues examined. Among the 10 hMAM negative cases, 8 were invasive ductal carcinomas (microscopically higher G3 grade) and 2 infiltrating lobular carcinomas. We found a significant association (p = 0.020) between absence of hMAM mRNA and G3 histologic grade but not with any other prognostic parameters studied. The present study indicates that lack of hMAM expression is restricted to the BC with G3 grading. Further studies are needed to clarify the biological basis and the clinical significance of our results.