Miracle-dz/UniFAR-FTUs huggingface dataset:
Spousal relationship satisfaction following acquired brain injury: The role of insight and socio-emotional skill

Spousal relationships following brain injury are particularly vulnerable to strain and breakdown. Changes in personality and socio-emotional processing and behaviour have been implicated as causal factors. We examined spousal relationship satisfaction following an acquired brain injury to one partner. Couples affected by chronic pain and a group of healthy couples were used for comparison and control. Compared to healthy controls current satisfaction was poorer in the brain injury couples, and satisfaction with the relationship had reduced from pre to post-injury. We found an especially important role for empathy, which differentiated between the groups in terms of functioning and insight.
Macrophages and Myeloid Dendritic Cells Lose T Cell–Stimulating Function in Simian Immunodeficiency Virus Infection Associated with Diminished IL-12 and IFN-α Production

Impaired T cell responses are a defining characteristic of HIV infection, but the extent to which altered mononuclear phagocyte function contributes to this defect is unclear. We show that mononuclear phagocytes enriched from rhesus macaque lymph nodes have suppressed ability to stimulate CD4 T cell proliferation and IFN-γ release after acute SIV infection. When individual populations were isolated, myeloid dendritic cells (mDC) and macrophages but not plasmacytoid DC (pDC) had suppressed capacity to stimulate CD4 T cell proliferation, with macrophage function declining as infection progressed. Macrophages, but not pDC or mDC, had suppressed capacity to induce IFN-γ release from CD4 T cells in acute infection, even after stimulation with virus-encoded TLR7/8 ligand. Changes in expression of costimulatory molecules did not explain loss of function postinfection. Conversely, pDC and mDC had marked loss of IFN-α and IL-12 production, respectively, and macrophages lost production of both cytokines. In T cell cocultures without TLR7/8 ligand, macrophages were the primary source of IL-12, which was profoundly suppressed postinfection and correlated with loss of IFN-γ release by T cells. TLR7/8-stimulated pDC, mDC and macrophages all produced IL-12 in T cell cocultures, which was suppressed in chronic infection. Supplementing IL-12 enhanced mDC-driven IFN-γ release from T cells, and IL-12 and IFN-α together restored function in TLR7/8-activated macrophages. These findings reveal loss of macrophage and mDC T cell–stimulating function in lymph nodes of SIV-infected rhesus macaques associated with diminished IL-12 and IFN-α production that may be a factor in AIDS immunopathogenesis.
Genetic aspects of lactation curves.

Parameters of lactation curves were defined by a gamma-type function for 113,705 lactations from the California Dairy Herd Improvement Association. Heritabilities and genetic correlations were estimated from a mixed-model analysis of paternal half sisters for first, second, third, and later lactations. Daily milk production on day 6 postpartum was estimated from production at first test-day to reduce the percentage of atypical lactations to less than 1% instead of an expectation of 30% without estimating production for day 6. The natural logarithm of the gamma-type function was ln(yt) = ln(a) + b ln(t) - ct, where yt was daily milk production in the tth week and ln(a), b, and c were coefficients. Persistency (c-(b+1)), week of peak yield (b/c), peak yield (a(b/c)be-b), and coefficient of determination were estimated from coefficients for each lactation. Heritabilities in first lactation were: ln(a) . 10 +/- . 01, b . 06 +/- . 01, c . 14 +/- . 02, persistency . 02 +/- . 01, week of peak yield . 02 +/- . 01, peak yield . 23 +/- . 02, and determination . 03 +/- . 01. Heritabilities for later lactations were similar. Cows in first lactation had lower ln(a), lower peak yield, lower c, greater persistency, and took longer to reach peak yield than did cows in later lactations. Genetic and phenotypic correlations indicated that selection for increased peak yield would be associated with increased ln(a), b, and c without changing persistency or week of peak yield.
Toll-like receptor 9 polymorphism is associated with increased Epstein–Barr virus and Cytomegalovirus acquisition in HIV-exposed infants

&NA; Polymorphisms in the Toll-like receptor 9 1635 locus have been associated with HIV-1 acquisition and progression. Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) acquisition were compared between Kenyan HIV-exposed infants by 1635 genotype. Having one or more copies of the 1635A allele was associated with increased CMV acquisition in HIV-infected infants (42 vs. 11%, P = 0.03) and increased risk of EBV acquisition in HIV-exposed uninfected infants (hazard ratio = 4.2, P = 0.02) compared with 1635GG. In addition, 1635A was associated with 0.4 log10 copies/ml lower median EBV levels in HIV-infected infants (P = 0.03). These data suggest a potentially important role for this locus in primary herpesvirus infection.
Stability and Activity in Sputum of G10KHc, a Potent Anti‐Pseudomonas Antimicrobial Peptide

G10KHc, a specifically targeted antimicrobial peptide developed in our laboratory, has shown rapid and selective killing activity against Pseudomonas aeruginosa in culture medium. Because of the major role played by this pathogen in cystic fibrosis, we sought to evaluate the utility of G10KHc under more physiologic conditions in vitro. In the current study, we found that robust G10KHc activity could be maintained in expectorated sputum if serine protease‐dependant digestion associated with this fluid was inhibited, either by chemical antagonists or by the construction of a d‐amino acid enantiomer of G10KHc. Further investigations revealed that specifically targeted antimicrobial peptide activity in sputum could be further enhanced when samples were treated with a combination of peptide and recombinant human DNase. Our results illustrate the importance of investigating combination therapy to treat cystic fibrosis, especially if protease‐sensitive peptide‐based agents, such as G10KHc, are to be developed as alternatives to, or in conjunction with, conventional small‐molecule antibiotics.
The Adaptor Protein Shb Binds to Tyrosine 1175 in Vascular Endothelial Growth Factor (VEGF) Receptor-2 and Regulates VEGF-dependent Cellular Migration*

Previous studies have shown that the adaptor protein Shb is involved in receptor tyrosine kinase signaling. In this study, we demonstrate that Shb is phosphorylated in an Src-dependent manner upon vascular endothelial growth factor (VEGF) stimulation using porcine aortic endothelial cells expressing the human VEGF receptor 2 (VEGFR-2) (KDR). In co-immunoprecipitation experiments, we could detect an interaction between Shb and the VEGFR-2 in human telomerase-immortalized microvascular endothelial cells. Furthermore, in a glutathione S-transferase pull-down assay, the Src homology 2 domain of Shb was shown to interact with phosphorylated tyrosine 1175 in the C-terminal tail of VEGFR-2. VEGF-induced Shb phosphorylation was lost in porcine aortic endothelial cells expressing a chimeric murine VEGFR-2 (Flk-1) with a mutation at the corresponding position. Shb expression was specifically decreased by 80%, in a transient manner, by using the short interfering RNA technique. Reduced Shb expression led to a loss of stimulation of phosphatidylinositol 3-kinase, phosphorylation of focal adhesion kinase at tyrosine 576, the generation of focal adhesions, and stress fiber formation in response to VEGF. Furthermore, we show that VEGF-induced migration is inhibited in Shb short interfering RNA-treated cells. Our data demonstrate that Shb is important for VEGF signaling in endothelial cells. This is achieved by Shb binding to tyrosine 1175 in the VEGFR-2, which regulates VEGF-induced formation of focal adhesions and cell migration, of which the latter occurs in a phosphatidylinositol 3-kinase-dependent manner.
Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis / chronic fatigue syndrome: another pathway that may be associated with coronary artery disease and neuroprogression in depression.

BACKGROUND Major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are two disorders accompanied by an upregulation of the inflammatory and oxidative and nitrosative (IO&NS) pathways and a decreased antioxidant status. Moreover, depression is accompanied by disorders in inflammatory and neuroprogressive (IN-PRO) pathways. METHODS This study examines whole blood glutathione peroxidase (GPX) in depression and in ME/CFS; GPX is an enzyme that reduces hydroperoxides by oxidizing glutathione and consequently protects the cells from oxidative damage. Blood was sampled in 39 patients with depression, 40 patients with ME/CFS and 24 normal volunteers. Whole blood was analysed for GPX activity using the Ransel assay (Randox). Severity of illness was measured by means of the Hamilton Depression Rating Scale (HDRS) and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF scale). RESULTS We found that whole blood GPX activity was significantly (p=0.001) lower in depressed patients than in normal controls and that there were no significant differences between ME/CFS and controls. In depression and ME/CFS, there were significant and inverse relationships between GPX activity and the FF items, depressed mood and autonomic symptoms. In depression, there were significant and negative correlations between whole blood GPX and the HDRS score and autonomic symptoms. DISCUSSION The results show that lowered whole blood GPX activity contributes to the lowered antioxidant status in depression. Since GPX activity is a predictor of neuroprogression and coronary artery disease (CAD), lowered GPX activity in depression contributes to the IN-PRO pathways and the comorbidity between depression and CAD. Our results suggest that patients with depression would benefit from Ebselen or a supplementation with glutathione, N-Acetyl-l-Cysteine and selenium.
[Surgical removal of pulmonary metastasis: prospective study in 182 patients].

PURPOSE The present study evaluates the results of surgical treatment of lung metastases, as well as attempts to identify subgroups of patients who would benefit the most from the operation. CASE AND METHODS This is a prospective analysis of patients with history of neoplasia, submitted to resection of pulmonary nodules, with the diagnosis or suspicion of metastases. The 182 patients were operated upon through a lateral thoracotomy. RESULTS The patients submitted to pulmonary resection for suspected metastases showed no malignant tissue in 34 patients (18.6%), and in six patients (3.2%) were diagnosed a second lung primary tumor. Overall survival of the patients was 28% at 56 months, and disease-free survival was 9%. Multivariate analysis showed that disease free interval (p = 0.002), complete resection (p = 0.039), and number of malignant nodules resected (p = 0.016) significantly affected overall survival. Disease-free survival was affected only by complete resection (p = 0.0001) and number of malignant nodules resected (p = 0.004). CONCLUSION Resection of pulmonary metastasis improve survival in a selected group of patients. More studies are necessary to define the value of other therapies in the results of survival in resected pulmonary metastasis.
Atypical activation of dendritic cells by Plasmodium falciparum

Significance With more than 200 million cases per year worldwide and more than 400,000 deaths, mostly affecting children in sub-Saharan Africa, malaria is still one of the most prevalent infectious diseases. Infection with the malaria parasite Plasmodium falciparum is characterized by high inflammation but also the failure of the immune system to form efficient memory, leading to recurring infections. No efficient vaccine is available to date. Here we have studied the response of dendritic cells (DCs), an essential cell type in the orchestration of immune and vaccine responses. We found that P. falciparum induces a distinct transcriptional profile compared with a classical inflammatory stimulus in primary human DCs, leading to a highly atypical response, which may contribute to parasite immune evasion during malaria. Dendritic cells (DCs) are activated by pathogens to initiate and shape immune responses. We found that the activation of DCs by Plasmodium falciparum, the main causative agent of human malaria, induces a highly unusual phenotype by which DCs up-regulate costimulatory molecules and secretion of chemokines, but not of cytokines typical of inflammatory responses (IL-1β, IL-6, IL-10, TNF). Similar results were obtained with DCs obtained from malaria-naïve US donors and malaria-experienced donors from Mali. Contact-dependent cross-talk between the main DC subsets, plasmacytoid and myeloid DCs (mDCs) was necessary for increased chemokine and IFN-α secretion in response to the parasite. Despite the absence of inflammatory cytokine secretion, mDCs incubated with P. falciparum-infected erythrocytes activated antigen-specific naïve CD4+ T cells to proliferate and secrete Th1-like cytokines. This unexpected response of human mDCs to P. falciparum exhibited a transcriptional program distinct from a classical LPS response, pointing to unique P. falciparum-induced activation pathways that may explain the uncharacteristic immune response to malaria.
Does Sickle Cell Disease Protect Against Diabetes Mellitus?: Cross-sectional study.

OBJECTIVES The co-existence of diabetes mellitus (DM) and sickle cell disease (SCD) is rare. This study aimed to explore whether SCD patients have the same DM prevalence as the general population in a country with a high prevalence of DM. METHODS This cross-sectional study included all SCD adult patients admitted to Salmaniya Medical Complex, Bahrain, between 2003 and 2010 (n = 2,204). A random sample (n = 520) was taken to establish the prevalence of DM. Laboratory records were examined to determine the presence of DM. RESULTS There were 376 SCD patients with complete records; of these, 24 (6.4%) had DM. The age- and sex-standardised prevalence of DM was 8.3%. CONCLUSION While the prevalence of DM in SCD patients in Bahrain was high, it was lower than expected in this population. SCD may have a protective effect towards DM development. However, the impact of these two conditions on vascular diseases suggest a need for screening and aggressive treatment in this population.
Lack of Trophic Pancreatic Effects in Humans With Long-term Administration of Ximelagatran

Objectives: Negative feedback regulation of pancreatic proteases controls pancreatic secretion in most species and pancreatic growth in rodents. Its mechanism involves the inhibition of intraluminal proteases, resulting in sustained elevation of plasma cholecystokinin (CCK) concentrations, producing a chronic trophic stimulus to the pancreas that leads to the formation of pancreatic nodules and adenomas. Ximelagatran, whose active form, melagatran, inhibits both thrombin and the serine protease trypsin, is under clinical development as an oral anticoagulant. Recent data indicate species differences in the expression of CCK receptor subtypes in the pancreas. CCK1 receptors are abundant in rat pancreas but are either absent or present at very low levels in human pancreas. As part of the clinical studies, we examined whether long-term ximelagatran administration causes CCK release and exerts possible trophic effects on the pancreas in humans. Methods: One hundred thirty patients requiring anticoagulation treatment for atrial fibrillation randomly received, in a double-blind fashion, either 36 mg oral ximelagatran twice daily or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0. Before enrollment and after 12 months of treatment, computed tomography scans of the pancreas were performed, and pancreas volumes were quantified using the summation-of-areas technique. Three months after the initiation of drug treatment, plasma CCK concentrations were measured by radioimmunoassay 120 minutes after the patients drank 240 mL of a mixed liquid meal (Ensure). Results: After 3 months of treatment, plasma CCK concentrations did not differ between the ximelagatran and warfarin groups, 15 ± 18 and 11 ± 17 pmol/L (X ± SD; P = 0.22), respectively. The initial average pancreas volumes were 82 ± 31 and 88 ± 28 mL in the ximelagatran and warfarin groups, respectively, and decreased to 70 ± 25 and 75 ± 28 mL, respectively, after 12 months of treatment. Although the decrease in pancreas volume with time was significant in each group (P = 0.0001), the magnitude of the volume reduction was similar in the 2 groups. Conclusion: In contrast to rats, in which long-term oral administration of ximelagatran stimulates pancreatic growth and adenoma formation, in humans, ximelagatran does not increase plasma CCK concentrations and has no demonstrable trophic effect on the human pancreas.
Coding-Based Data Broadcast Scheduling in On-Demand Broadcast

According to data broadcast, we can satisfy multiple requests for the same data item in a broadcast tick. However, there is no significant breakthrough in performance improvement until recently that some studies proposed to use network coding in data broadcast. After broadcasting an encoded packet which encodes a number of data items, multiple clients can retrieve different requested data items in a broadcast tick. This not only utilizes bandwidth more efficiently, but also improves system performance. In this work, we propose a generalized encoding framework to incorporate network coding into data scheduling algorithms for on-demand broadcast. In the framework, data scheduling can be formulated as a weighted maximum clique problem in a graph where the weight of the clique is defined according to the performance objectives of the applications. Under the proposed framework, existing data scheduling algorithms for on-demand broadcast can be migrated into their corresponding coding versions while preserving their original criteria in scheduling data items. Our simulation results using a number of representative scheduling algorithms show that significant performance improvement can be achieved with coding.
The effects of selective serotonin reuptake inhibitors and their metabolites on S-mephenytoin 4'-hydroxylase activity in human liver microsomes.

The inhibitory effects of four selective serotonin reuptake inhibitors (SSRIs), fluoxetine, sertraline, paroxetine and citalopram, and three metabolites (norfluoxetine, demethylcitalopram and didemethylcitalopram), on S-mephenytoin 4'-hydroxylation activities in human liver microsomes were studied. The 4'-hydroxylation of S-mephenytoin, a representative substrate toward CYP2C19, was competitively inhibited by all the SSRIs and their metabolites studied. The mean Ki values of fluoxetine, norfluoxetine, sertraline, paroxetine, citalopram, demethylcitalopram and didemethylcitalopram were 5.2, 1.1, 2.0, 7.5, 87.3, 55.8 and 7.7 microM, respectively. The findings suggest that some SSRIs and their metabolites with a low Ki value (e.g., fluoxetine, norfluoxetine) may reduce the clearance of drugs metabolized by this isoform of P450, thereby resulting in a possible drug-drug interaction, when administered simultaneously. In addition, SSRIs and their metabolites examined herein may be substrates toward CYP2C19.
Neurochemical gradients along monkey sensory cortical pathways: calbindin‐immunoreactive pyramidal neurons in layers II and III

We examined the distribution of neurons containing immunoreactivity for three calcium‐binding proteins, calbindin, parvalbumin and calretinin, as well as nonphosphorylated neurofilament protein, in cortical areas along the ventral and dorsal cortical visual pathways, and in ventrally‐directed somatosensory and auditory cortical pathways. Calbindin‐immunoreactive pyramidal neurons showed the most prominent regional differences. They were largely restricted to layers II and III and their number monotonically increased from the primary sensory areas to the anteroventral areas along the ventral visual pathway and along the ventrally‐directed somatosensory and auditory pathways. The number of calbindin‐immunoreactive pyramidal neurons in layers II and III also increased along the dorsal visual pathway, but the number in the last recognized stage of the dorsal visual pathway (area 7a) was significantly smaller than that at the corresponding stage in the ventral visual pathway (TE). The number of calbindin‐immunoreactive pyramidal neurons was highest in layers II and III of areas 35/36, TG, and TF/TH, which represent terminal cortical regions of the pathways. These results show neurochemical differences between cortical areas located at early and late stages along serial corticocortical pathways, as well as confirming differences between pyramidal neurons in the supragranular and infragranular layers.
Effect of Asian Sand Dust on Mucin Production in NCI-H292 Cells and Allergic Murine Model

Objective. To investigate the effect of Asian sand dust (ASD) on mucin production in human respiratory epithelial cells in vitro and in allergic murine nasal epithelial cells. Study Design. Controlled, in vitro. Setting. Academic research laboratory. Materials and Methods. Human NCI-H292 cells were treated with ASD and analyzed by immunostaining, reverse transcriptase–polymerase chain reaction for MUC5AC mRNA expression, and Periodic Acid Schiff (PAS) staining. Forty female BALB/c mice were classified into 4 groups. Two groups were sensitized with ovalbumin (OVA), and 1 of these was treated with ASD (ASD+OVA). The 2 nonsensitized groups were treated with ASD or saline. Then the murine nasal mucosal tissues were evaluated by hematoxylin and eosin (H&E) staining, PAS staining, and immunostaining for MUC5AC and transforming growth factor (TGF)-α proteins. Results. The numbers of MUC5AC-immunopositive NCI-H292 cells and PAS-positive NCI-H292 cells were significantly higher in the ASD-treated cells than in the control cells (P = .039 and P = .029, respectively). MUC5AC mRNA expression in the cells increased with increasing concentrations of ASD. In the murine nasal epithelial tissues, the numbers of eosinophils and PAS-positive cells were significantly higher in the ASD+OVA group than in the OVA group (H&E staining, P = .037; PAS staining, P = .019). At 2 weeks, the numbers of MUC5AC- and TGF-α–positive cells in the nasal epithelial tissue were significantly higher in the ASD+OVA group than in the OVA group (P = .031 and P = .033, respectively). Conclusion. ASD can induce mucin production in respiratory epithelial cells.
Inhibitory mechanisms that generate centre and surround properties in ON and OFF brisk‐sustained ganglion cells in the rabbit retina

• ON and OFF cells in the retina are excited by increases and decreases in visual contrast, respectively. ON and OFF brisk‐sustained ganglion cells (BSGCs) have antagonistic ‘centre‐surround’ receptive fields; a visual stimulus that excites the centre is inhibitory in the surround. Such lateral inhibition enhances sensitivity to contrast borders. • This study provides the first detailed comparison of visually evoked, excitatory and inhibitory synaptic inputs driving the centres and surrounds of ON and OFF BSGCs. • GABAergic lateral inhibition suppresses excitatory inputs to BSGCs presynaptically, via GABAC receptors at ON BSGCS and GABAA and GABAC receptors at OFF BSGCs. Feed‐forward glycinergic inhibition, driven through the ON pathway, contributes to centre but not surround responses in both cell types. • Centre excitation is mediated by AMPA receptors in ON BSGCs, and NMDA and AMPA receptors in OFF BSGCs. • The results reveal mechanistic differences in homologous neural circuits that perform a similar neural computation in the visual system.