Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular complications after renal transplantation.

BACKGROUND Vascular complications in renal transplant recipients are uncommon but important causes of graft dysfunction and graft loss after kidney transplantation. OBJECTIVES To document vascular complications that occurred following kidney transplantations in order to assess the incidence of these complications at our center as well as to identify possible treatment approach. METHODS 103 kidney transplantations were performed in the period from 1 January 2008 to 31 December 2009. All patients after kidney transplantation underwent ultrasound examination (included colour Doppler flow and duplex Doppler ultrasound) immediately after surgery--especially in condition of anuria, then regularly according to an internal schedule and always in patients with worsened graft function. RESULTS We detected renal vein thrombosis in 3 cases (2.9%), artery thrombosis in 4 cases (3.9%), one time intrarenal pseudoaneurysm (1%) and renal artery stenosis in 10 patients (9.7%). There was no extrarenal pseudoaneurysm or arteriovenous fistula in our group of patients. CONCLUSION The incidence of vascular complications in our department correlates with the incidence of these complications referred in literature. We confirmed the importance of established immediate diagnosis and fast intervention once the diagnosis of vascular complication is established (Fig. 8, Ref. 12). Full Text in free PDF www.bmj. sk.
Bridging the treatment gap: the primary care perspective

The Darlington heart failure service model, part of the South Durham Heart Failure Network, was devised to overcome barriers to accurate diagnosis and effective management of heart failure. It involves rapid diagnosis of left ventricular systolic dysfunction (LVSD) and ongoing heart failure management. A weekly one stop diagnostic clinic, run by a general practitioner (GP) specialist and a heart failure nurse, is jointly funded by the primary care trust and the South Durham NHS Trust. If LVSD is confirmed, a management plan is formulated which includes patient education and initiation of evidence based treatment. The heart failure nursing service is invaluable in bridging the gap between primary and secondary care. Local guidelines, together with continuing education of GPs and practice nurses, and the new General Medical Services contract, should further increase the uptake of evidence based treatments at target doses.
Characterization of the Netrin/RGMa receptor neogenin in neurogenic regions of the mouse and human adult forebrain

In the adult rodent forebrain, astrocyte‐like neural stem cells reside within the subventricular zone (SVZ) and give rise to progenitors and neuroblasts, which then undergo chain migration along the rostral migratory stream (RMS) to the olfactory bulb, where they mature into fully functional interneurons. Neurogenesis also occurs in the adult human SVZ, where neural precursors similar to the rodent astrocyte‐like stem cell and neuroblast have been identified. A migratory pathway equivalent to the rodent RMS has also recently been described for the human forebrain. In the embryo, the guidance receptor neogenin and its ligands netrin‐1 and RGMa regulate important neurogenic processes, including differentiation and migration. We show in this study that neogenin is expressed on neural stem cells (B cells), progenitor cells (C cells), and neuroblasts (A cells) in the adult mouse SVZ and RMS. We also show that netrin‐1 and RGMa are ideally placed within the neurogenic niche to activate neogenin function. Moreover, we find that neogenin and RGMa are also present in the neurogenic regions of the human adult forebrain. We show that neogenin is localized to cells displaying stem cell (B cell)‐like characteristics within the adult human SVZ and RMS and that RGMa is expressed by the same or a closely apposed cell population. This study supports the hypothesis that, as in the embryo, neogenin regulates fundamental signalling pathways important for neurogenesis in the adult mouse and human forebrain. J. Comp. Neurol. 518:3237–3253, 2010. © 2010 Wiley‐Liss, Inc.
The spatial relationship of gamma-aminobutyric acid (GABA) neurons and gonadotropin-releasing hormone (GnRH) neurons in larval and adult sea lamprey, Petromyzon marinus.

In this study we examined the spatial relationship of GABA-containing and GnRH-containing neurons by immunocytochemistry and in situ hybridization in larval and adult brains of sea lamprey, Petromyzon marinus. In immunocytochemical studies, GABA-containing neurons were detected early in lamprey development, by day 20 post-fertilization. At this time point, one population of GABA-containing neurons was visualized in the hypothalamus and preoptic area, and another population was located in the olfactory bulb of the telencephalon. By day 30 after fertilization, after the GABA neurons were detected, GnRH-containing neurons were visualized in the preoptic area/rostral hypothalamus region, adjacent to the GABA-containing neurons in the wall of the third ventricle. Similarly, in adult lamprey brains distinct populations of both GABA- and GnRH-containing neurons were located in the hypothalamus adjacent to the third ventricle. To further establish a proximate relationship between GABA and GnRH, the mRNA for glutamate decarboxylase (GAD), the enzyme catalyzing GABA synthesis from glutamate, and GnRH were examined by in situ hybridization in the brains of larval lamprey. These studies also showed that GnRH and GAD are produced in cell populations in and around the third ventricle of the hypothalamus. This close spatial relationship of GABA neurons and GnRH neurons provides a basis for a regulatory role of GABA on GnRH neurons in the sea lamprey.
Early Evolution of the Human Immunodeficiency Virus Type 1 Subtype C Epidemic in Rural Malawi

ABSTRACT We have tracked the early years of the evolution of the human immunodeficiency virus type 1 (HIV-1) epidemic in a rural district of central east Africa from the first documented introductions of subtypes A, D, and C to the present predominance of subtype C. The earliest subtype C sequences ever reported are described. Blood samples were collected on filter papers from 1981 to 1984 and from 1987 to 1989 from more than 44,000 individuals living in two areas of Karonga District, Malawi. These samples included HIV-1-positive samples from 200 people. In 1982 to 1984, HIV-1 subtypes A, C, and D were all present, though in small numbers. By 1987 to 1989, 152 (90%) of a total of 168 sequences were subtype C and AC, AD, and DC recombinants had emerged. Four of the subtype C sequences from 1983 to 1984 were closely related and were found at the base of a large cluster of low diversity that by the late 1980s accounted for 40% of C sequences. The other two early C sequences fell into a separate and more diverse cluster. Three other clusters containing sequences from the late 1980s were identified. Each cluster contained at least one sample from a person who had recently arrived in the district. From 18 HIV-1-positive spouse pairs, 12 very closely related pairs of sequences were identified. We conclude that there were multiple introductions of HIV-1 with limited spread, followed by explosive growth of a subtype C cluster, probably arising from a single introduction in or before 1983.
Corneal resistance to shear force after UVA-riboflavin cross-linking.

PURPOSE We evaluated whether UVA-riboflavin collagen cross-linking (CXL) increases transverse stromal shear moduli ex vivo, whether the shear moduli are greater in the anterior compared to the posterior stroma, and whether the shear moduli are affected by CXL. METHODS The resistance to unidirectional transverse shear of human (n = 18) and porcine (n = 42) corneas was measured in a custom engineered biaxial biomechanical setup at different hydrations. The corneas were separated into untreated, riboflavin solution-treated, and CXL-treated groups. The depth dependency of shear moduli within groups was assessed in femtosecond laser cut sheets. Dry weights were obtained for solids correction. RESULTS In porcine full-thickness buttons and 300 μm anterior sheets, a significantly increased unidirectional transverse shear modulus was detected in riboflavin-treated and CXL-treated groups compared to the respective untreated groups. There was no significant difference in shear modulus between riboflavin- and CXL-treated groups. In all groups, the shear moduli were greater in the anterior sheets compared to posterior sheets. Similar results were detected in human corneas. CONCLUSIONS A method for unidirectional transverse shear resistance measurement was developed. The shear moduli were greater in the anterior compared to the posterior sheets. Increase in shear moduli was observed in the riboflavin and CXL groups compared to the untreated group, indicating that the immediate effects of the riboflavin or CXL treatment may be due partly to ground substance/dextran-5-phosphate interaction.
CXCR4 Expression Determines Functional Activity of Bone Marrow–Derived Mononuclear Cells for Therapeutic Neovascularization in Acute Ischemia

Objective—Bone marrow–derived mononuclear cells (BMCs) improve the functional recovery after ischemia. However, BMCs comprise a heterogeneous mixture of cells, and it is not known which cell types are responsible for the induction of neovascularization after cell therapy. Because cell recruitment is critically dependent on the expression of the SDF-1-receptor CXCR4, we examined whether the expression of CXCR4 may identify a therapeutically active population of BMCs. Methods and Results—Human CXCR4+ and CXCR4− BMCs were sorted by magnetic beads. CXCR4+ BMCs showed a significantly higher invasion capacity under basal conditions and after SDF-1 stimulation. Hematopoietic or mesenchymal colony-forming capacity did not differ between CXCR4+ and CXCR4− BMCs. Injection of CXCR4+ BMCs in mice after induction of hindlimb ischemia significantly improved the recovery of perfusion compared to injection of CXCR4− BMCs. Likewise, capillary density was significantly increased in CXCR4+ BMC-treated mice. Because part of the beneficial effects of cell therapy were attributed to the release of paracrine effectors, we analyzed BMC supernatants for secreted factors. Importantly, supernatants of CXCR4+ BMCs were enriched in the proangiogenic cytokines HGF and PDGF-BB. Conclusion—CXCR4+ BMCs exhibit an increased therapeutic potential for blood flow recovery after acute ischemia. Mechanistically, their higher migratory capacity and their increased release of paracrine factors may contribute to enhanced tissue repair.
Proteolytic Processing of the Astrovirus Capsid

ABSTRACT To further characterize the nature of proteolytic processing of the astrovirus capsid, we infected Caco-2 cells with a high multiplicity of astrovirus without trypsin in the presence of 5 to 10% fetal calf serum. These infections were characterized by pulse-chase labeling with [35S]methionine, electron microscopy, gel electrophoresis of purified viral particles, and analysis of infectivity of such particles with and without added trypsin. Pulse-chase experiments showed that the astrovirus capsid protein was initially translated as an approximately 87-kDa protein. The 87-kDa capsid protein was rapidly converted intracellularly to a 79-kDa form which was found in smaller amounts in the cell supernatant. Purification by differential centrifugation yielded particles that appeared quite similar to trypsin-grown astrovirus particles by negatively stained electron microscopy. These particles were antigenically distinct from trypsin-treated virions as demonstrated by their various reactions with monoclonal antibodies in a solid-phase immunoassay. The purified trypsin-free particles were mainly composed of the 79-kDa capsid protein which was found to have an amino terminus at residue 71 of the entire open reading frame 2 (ORF2) product. The cleavage site was identified in a highly conserved region of the astrovirus ORF2 product. These trypsin-free particles were minimally infectious in cultured Caco-2 cells but became highly infectious (105-fold increase) after trypsin but not chymotrypsin treatment. This trypsin-enhanced infectivity correlated with conversion of the 79-kDa capsid protein to three smaller peptides of approximately 34, 29, and 26 kDa.
Short-term side effects of fractional photothermolysis.

OBJECTIVE To ascertain the immediate and short-term side effects of fractional photothermolysis for the treatment of a variety of skin disorders involving the face, neck, chest, and hands. METHODS Physician-administered questionnaires were given during 60 follow-up visits for fractional photothermolysis treatment for a variety of facial skin disorders in patients with skin types ranging from I to IV. The questionnaire addressed 14 possible side effects, pain, and limitation of social activities. In addition, all patients were asked about any additional side effects not mentioned in the survey. An analysis of the data was performed once 60 surveys had been collected. RESULTS All patients (100%) undergoing fractional photothermolysis had transient post-treatment erythema. Other frequently reported post-treatment side effects were transient and included facial edema (82%), dry skin (86.6%), flaking (60%), a few (one to three) small, superficial scratches (46.6%), pruritus (37%), and bronzing (26.6%). Other more rarely reported effects included transient increased sensitivity (10%) and acneiform eruption (10%). Most patients reported that the pain level was easily tolerated, with an average pain score of 4.6 on a scale of 10. Most patients (72%) reported limiting social engagements for an average of 2 days after treatment. There were no long-lasting adverse events noted in our survey. CONCLUSION Fractional photothermolysis to treat dermatologic conditions on the face, neck, chest, and hands is a well-tolerated and safe procedure with several immediate, and slightly delayed, post-treatment side effects. In our experience, these side effects were transient and limited to erythema, edema, dry skin, flaking skin, superficial scratches, pruritus, increased sensitivity, and acneiform eruption. Importantly, we did not see the development of post-treatment scarring, herpetic activation, hypopigmentation, hyperpigmentation, persistent erythema, persistent edema, or infection.
Differential Effects of Protein Kinase C, Ras, and Raf-1 Kinase on the Induction of the Cardiac B-type Natriuretic Peptide Gene through a Critical Promoter-proximal M-CAT Element*

The cardiac genes for the A- and B-type natriuretic peptides (ANP and BNP) are coordinately induced by growth promoters, such as α1-adrenergic receptor agonists (e.g. phenylephrine (PE)). Although inducible elements in the ANP gene have been identified, responsible elements in the BNP gene are unknown. In this study, reporter constructs transfected into neonatal rat ventricular myocytes showed that in the context of 2.5 kilobase pairs of native BNP 5′-flanking sequences, a 2-base pair mutation in a promoter-proximal M-CAT site (CATTCT) disrupted basal and PE-inducible transcription by more than 98%. Expression of constitutively active forms of Ras, Raf-1 kinase, and protein kinase C, all of which are activated by PE in cardiac myocytes, strongly stimulated BNP reporter expression. Isolated M-CAT elements conferred PE, protein kinase C, and Ras inducibility to a minimal BNP promoter, however, they did not confer Raf-1 inducibility. These results show that M-CAT elements can serve as targets for Ras-dependent, Raf-1-independent pathways, implying the involvement of c-Jun N-terminal kinase and/or p38 mitogen-activated protein kinases, but not extracellular signal-regulated protein kinase/mitogen-activated protein kinase. Moreover, the essential M-CAT element distinguishes the BNP gene from the ANP gene, which utilizes serum response elements and an Sp1-like sequence.
Adaptive evolution of voltage-gated sodium channels: The first 800 million years

Voltage-gated Na+-permeable (Nav) channels form the basis for electrical excitability in animals. Nav channels evolved from Ca2+ channels and were present in the common ancestor of choanoflagellates and animals, although this channel was likely permeable to both Na+ and Ca2+. Thus, like many other neuronal channels and receptors, Nav channels predated neurons. Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Approximately 500 Mya in early chordates Nav channels evolved a motif that allowed them to cluster at axon initial segments, 50 million years later with the evolution of myelin, Nav channels “capitalized” on this property and clustered at nodes of Ranvier. The enhancement of conduction velocity along with the evolution of jaws likely made early gnathostomes fierce predators and the dominant vertebrates in the ocean. Later in vertebrate evolution, the Nav channel gene family expanded in parallel in tetrapods and teleosts (∼9 to 10 genes in amniotes, 8 in teleosts). This expansion occurred during or after the late Devonian extinction, when teleosts and tetrapods each diversified in their respective habitats, and coincided with an increase in the number of telencephalic nuclei in both groups. The expansion of Nav channels may have allowed for more sophisticated neural computation and tailoring of Nav channel kinetics with potassium channel kinetics to enhance energy savings. Nav channels show adaptive sequence evolution for increasing diversity in communication signals (electric fish), in protection against lethal Nav channel toxins (snakes, newts, pufferfish, insects), and in specialized habitats (naked mole rats).
Binding of the protein kinase PKR to RNAs with secondary structure defects: role of the tandem A-G mismatch and noncontiguous helixes.

The human interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an antiviral agent that is activated by long stretches of dsRNA. PKR can also be activated or repressed by a series of cellular and viral RNAs containing non-Watson-Crick motifs. PKR has a dsRNA-binding domain (dsRBD) that contains two tandem copies of the dsRNA-binding motif (dsRBM). In vitro selection experiments were carried out to search for RNAs capable of binding to a truncated version of PKR containing the dsRBD. RNA ligands were selected by binding to His6-tagged proteins and chromatography on nickel(II) nitrilotriacetic acid agarose. A series of RNAs was selected that bind either similar to or tighter than a model dsRNA stem loop. Examination of these RNAs by a variety of methods, including sequence comparison, free-energy minimization, structure mapping, boundary experiments, site-directed mutagenesis, and footprinting, revealed protein-binding sites composed of noncontiguous helices. In addition, selected RNAs contained tandem A-G mismatches (5'AG3'/3'GA5'), yet bound to the truncated protein with affinities similar to duplexes containing only Watson-Crick base pairs. The NMR structure of the tandem A-G mismatch in an RNA helix (rGGCAGGCC)2 reveals a global A-form helix with minor perturbations at the mismatch [Wu, M. , SantaLucia, J., Jr., and Turner, D. H. (1997) Biochemistry 36, 4449-4460]. This supports the notion that dsRBM-containing proteins can bind to RNAs with secondary structure defects as long as the RNA has an overall A-form geometry. In addition, selected RNAs are able to activate or repress wild-type PKR autophosphorylation as well as its phosphorylation of protein synthesis initiation factor eIF-2, suggesting full-length PKR can bind to and be regulated by RNAs containing a tandem A-G mismatch.
The Impact of Education and Acculturation on Nonverbal Neuropsychological Test Performance Among Latino/a Patients with Epilepsy

The present study examined the relationship between various sociocultural factors (e.g., acculturation, education), neurological variables (e.g., epilepsy duration and seizure frequency) and nonverbal neuropsychological (NP) test performance in a sample of 305 Latino/a and Non-Latino/a White adults with and without epilepsy. All participants completed nonverbal NP measures of visuospatial skills, memory, executive functioning, and psychomotor speed. An acculturation scale was administered to Spanish-speaking epilepsy patients and controls. Education was strongly correlated with performance on all but one of the nonverbal measures across the entire sample. Among Spanish-speaking Latino/a patients with epilepsy, level of acculturation to U.S. culture was associated with a measure of behavioral inflexibility (p < .05) and with a composite measure of nonverbal NP test performance (p < .05). Finally, the results of hierarchical regression models showed that sociocultural factors accounted for a greater proportion of variance in nonverbal NP test performance than did neurological factors. These results provide further evidence that sociocultural factors are strong predictors of NP test performance in clinical populations, even on nonverbal tests. Assessment of acculturation may be as critical as assessment of disease factors in interpreting cognitive performance in Latino/a individuals.
Identification of β‐amyrin and sophoradiol 24‐hydroxylase by expressed sequence tag mining and functional expression assay

Triterpenes exhibit a wide range of structural diversity produced by a sequence of biosynthetic reactions. Cyclization of oxidosqualene is the initial origin of structural diversity of skeletons in their biosynthesis, and subsequent regio‐ and stereospecific hydroxylation of the triterpene skeleton produces further structural diversity. The enzymes responsible for this hydroxylation were thought to be cytochrome P450‐dependent monooxygenase, although their cloning has not been reported. To mine these hydroxylases from cytochrome P450 genes, five genes (CYP71D8, CYP82A2, CYP82A3, CYP82A4 and CYP93E1) reported to be elicitor‐inducible genes in Glycine max expressed sequence tags (EST), were amplified by PCR, and screened for their ability to hydroxylate triterpenes (β‐amyrin or sophoradiol) by heterologous expression in the yeast Saccharomyces cerevisiae. Among them, CYP93E1 transformant showed hydroxylating activity on both substrates. The products were identified as olean‐12‐ene‐3β,24‐diol and soyasapogenol B, respectively, by GC‐MS. Co‐expression of CYP93E1 and β‐amyrin synthase in S. cerevisiae yielded olean‐12‐ene‐3β,24‐diol. This is the first identification of triterpene hydroxylase cDNA from any plant species. Successful identification of a β‐amyrin and sophoradiol 24‐hydroxylase from the inducible family of cytochrome P450 genes suggests that other triterpene hydroxylases belong to this family. In addition, substrate specificity with the obtained P450 hydroxylase indicates the two possible biosynthetic routes from triterpene‐monool to triterpene‐triol.