Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in scleral collagen organization in murine chronic experimental glaucoma.

PURPOSE The organization of scleral collagen helps to determine the eye's biomechanical response to intraocular pressure (IOP), and may therefore be important in glaucoma. This study provides a quantitative assessment of changes in scleral collagen fibril organization in bead-induced murine experimental glaucoma. METHODS Wide-angle X-ray scattering was used to study the effect of bead-induced glaucoma on posterior scleral collagen organization in one eye of 12 CD1 mice, with untreated fellow eyes serving as controls. Three collagen parameters were measured: the local preferred fibril directions, the degree of collagen anisotropy, and the total fibrillar collagen content. RESULTS The mouse sclera featured a largely circumferential orientation of fibrillar collagen with respect to the optic nerve head canal. Localized alteration to fibril orientations was evident in the inferior peripapillary sclera of bead-treated eyes. Collagen anisotropy was significantly (P<0.05) reduced in bead-treated eyes in the superior peripapillary (Treated: 43±8%; CONTROL 49±6%) and midposterior (Treated: 39±4%; CONTROL 43±4%) sclera, and in the peripapillary region overall (Treated: 43±6%; CONTROL 47±3%). No significant differences in total collagen content were found between groups. CONCLUSIONS Spatial changes in collagen fibril anisotropy occur in the posterior sclera of mice with bead-induced chronic IOP elevation and axonal damage. These results support the idea that dynamic changes in scleral form and structure play a role in the development of experimental glaucoma in mice, and potentially in human glaucoma.
TRIF and IRF-3 Binding to the TNF Promoter Results in Macrophage TNF Dysregulation and Steatosis Induced by Chronic Ethanol1

Chronic ethanol (EtOH) abuse results in the development of steatosis, alcoholic hepatitis, and cirrhosis. Augmented TNF-α production by macrophages and Kupffer cells and signaling via the p55 TNF receptor have been shown to be critical for these effects of chronic EtOH; however, the molecular mechanisms leading to augmented TNF-α production remain unclear. Using cell culture models and in vivo studies we demonstrate that chronic EtOH results in increased TNF-α transcription, which is independent of NF-κB. Using reporter assays and chromatin immunoprecipitation we found that this increased transcription is due to increased IRF-3 binding to and transactivation of the TNF promoter. As IRF-3 is downstream from the TLR4 adaptor TIR-domain-containing adapter-inducing IFN-β (Trif), we demonstrate that macrophages from Trif−/− mice are resistant to this dysregulation of TNF-α transcription by EtOH in vitro as well as EtOH-induced steatosis and TNF dysregulation in vivo. These data demonstrate that the Trif/IRF-3 pathway is a target to ameliorate liver dysfunction associated with chronic EtOH.
Oral supplementation with superoxide dismutase in Standardbred trotters in training: a double-blind placebo-controlled study.

REASONS FOR PERFORMING STUDY Intense physical exercise produces an excess of reactive oxygen species which can disturb the antioxidant/oxidant balance of the horse in training. Several classes of antioxidant dietary compounds have been suggested to provide health benefits and there is evidence that consumption of these products leads to a reduction in the expression of various pro-inflammatory and/or oxidative stress biomarkers. The recent development of a new galenic system allows the oral delivery of the antioxidant enzyme: superoxide dismutase (SOD). This has been developed from a specific melon variety with a particularly high SOD activity. OBJECTIVES To study the influence of an oral supplementation with an encapsulated melon rich in SOD on muscular and antioxidant balance variables in a population of Standardbreds in training. METHODS Twenty-four Standardbreds in training were paired by age, sex and training level. They were randomly split into 2 groups: SOD group (520 iu/day) and placebo group. At the beginning of the study (T0) and after 30 days (T30) and 60 days (T60) of supplementation, physiological response during a standardised exercise test, plasma muscular enzymes at rest and post exercise (creatine kinase), oxidative stress markers (erythrocyte SOD) and blood resistance to haemolysis (KRL test) were assessed. Analysis of variance of time, treatment and interaction time x treatment was calculated. RESULTS Between T0 and T60, in contrast with placebo group, a significant increase in the plasma resistance to haemolysis in the SOD group was observed and it was significantly higher (P < 0.05) in the SOD group than in the placebo group on T60. Between T0 and T60, resting CK remained constant in SOD group whereas a significant increase in plasma CK in the placebo group was observed. On T60, the CK level was significantly lower (P < 0.05) in SOD group than in the placebo group. CONCLUSIONS These results suggest that oral SOD supplementation might increase blood resistance to haemolysis and reduce the increase in muscular membrane permeability induced by training.
Antemortem Prediction of Braak Stage

Abstract We examined the extent to which tauopathy distribution, as determined by Braak staging, might be predicted by various risk factors in older individuals. The Swedish Twin Registry provided extensive information on neuropsychological function, lifestyle, and cardiovascular risk factors of 128 patients for whom autopsy data including Braak staging were available. Logistic regression was used to develop a prognostic model that targeted discrimination between Braak stages 0 to II and III to VI. The analysis showed that Braak stages III to VI were significantly predicted by having 1 or more APOE &egr;4 alleles, older age, high total cholesterol, absence of diabetes and cardiovascular disease, and poorer scores on the Wechsler Adult Intelligence Score Information test, verbal fluency, and recognition memory but better verbal recall. The algorithm predicted Braak stages III to VI well (receiver-operating characteristic area under curve, 0.897; 95% confidence interval, 0.842–0.951). Using a cutoff of 50% risk or more, the sensitivity was 85%, the specificity was 70%, and the negative predictive value was 69%. This study demonstrates that tauopathy distribution can be accurately predicted using a combination of antemortem patient data. These results provide further insight into tauopathy development and AD-related disease mechanisms and suggest a prognostic model that predicts the spread of neurofibrillary tangles above the transentorhinal stage.
Does arterial recanalization improve outcome in carotid territory stroke?

BACKGROUND AND PURPOSE We sought to determine whether early (< 8 hours) or delayed (8 to 24 hours) recanalization after stroke may be an independent variable in the improvement of clinical outcome in patients with occlusion of the middle cerebral artery. METHODS We prospectively studied 77 patients by combined Scandinavian Stroke Scale score at admission, repeated computed tomography and angiography before and after thrombolytic treatment at < 8 hours after stroke onset, and transcranial Doppler ultrasound 24 hours later. We tested an association between clinical and neuroradiological baseline characteristics, recanalization, and outcome as assessed by the modified Rankin Scale 4 weeks after stroke and determined the effect of recanalization on mortality and good outcome (Rankin Scale grades 0 to 3) by multiple logistic regression analyses. RESULTS Recanalization rates at 8 and 24 hours after stroke correlated with sites of occlusion (middle cerebral artery branch, 73% and 73%, trunk, 27% and 38%, respectively; intracranial internal carotid artery bifurcation, 14% and 14%; P = .002), collaterals (good, 43% and 51%, respectively; scarce, 17% and 19%, respectively; P = .01), and Scandinavian Stroke Scale score at admission (P = .002). Six of 6 patients with delayed recanalization had good outcomes. Recanalization at < 8 hours after symptom onset had no independent predictive value for good outcome (P = .69). Recanalization at 24 hours increased the proportion of good outcomes from 23% to 75% in a subgroup of patients. Recanalization did not independently affect mortality (P > .15). CONCLUSIONS Even if delayed, arterial recanalization may improve clinical outcome in a subgroup of patients with middle cerebral artery occlusion.
The squamous variant of eccrine porocarcinoma: a clinicopathological study of 21 cases

Aim: Squamous differentiation in eccrine porocarcinoma (EPC) is an unusual phenomenon that has rarely been reported in the literature. This study describes the clinical and pathological findings in a series of 21 cases of EPC showing extensive squamous differentiation. Methods: The H&E-stained sections, epithelial membrane antigen and carcinoembryonic antigen immunohistochemical stains were reviewed for each case. The following variables were examined: age, gender, race, site and size of the EPC. The prevalence of other cutaneous lesions and/or underlying systemic disease was also documented. Results: There was an almost equal gender distribution. Mean age was 61.5 years and the average tumour size was 46.5 mm. An inordinately large number (10/21, 48%) of EPCs occurred in black patients. The tumours were located at various sites with the extremities predominating (10/19, 53%). Seven patients developed other sun-induced skin tumours, three patients were renal transplant recipients, and two patients were HIV-positive, one of whom also suffered from albinism. Six of the 11 patients in whom follow-up was available had an adverse outcome: local recurrence developed in one patient, one patient developed nodal metastases, and one patient experienced both local recurrence and nodal metastases, and of the three patients who died of disease, two developed distant metastases. Conclusion: The findings suggest a possible role for ultraviolet radiation and chronic immunosuppression in the induction of malignant squamous differentiation in a subset of EPCs. Further reports on this histological variant of EPC are required to determine whether a pathogenetic link does indeed exist or whether these tumours simply represent a unique variant of squamous cell carcinoma with divergent acrosyringial differentiation.
Effects of Passive and Active Rest on Physiological Responses and Time Motion Characteristics in Different Small Sided Soccer Games

Abstract The purpose of this study was to investigate the effects of resting regimes on physiological responses and time motion characteristics between bouts during small sided games (SSGs) in young soccer players. Sixteen players (average age 16.87 ± 0.34 years; body height 176.69 ± 3.21 cm; body mass 62.40 ± 2.59 kg; training experience 3.75 ± 0.44 years) performed four bouts 2-a-side, 3-a-side and 4-a-side games with three minutes active (SSGar: Running at 70% of HRmax) and passive (SSGpr) rest between bouts at two-day intervals. The heart rate (HR) along with total distance covered in different speed zones - walking (W, 0-6.9 km·h-1), low-intensity running (LIR, 7.0-12.9 km·h-1), moderate-intensity running (MIR, 13.0-17.9 km·h-1) and high-intensity running (HIR, >18km·h-1), were monitored during all SSGs, whereas the rating of perceived exertion (RPE, CR-20) and venous blood lactate (La-) were determined at the end of the last bout of each SSG. The results demonstrated that all SSGpr elicited significantly higher physiological responses compared to SSGar in terms of the RPE and La- (p < 0.05). In addition, 2-a-side SSGpr induced significantly lower %HRmax responses and total distance covered than 2-a-side SSGar (p < 0.05). Moreover, the distance covered at HIR was significantly higher in 4-a-side SSGar than 4-side SSGpr. The results of this study indicate that both SSGs with passive and active rest can be used for soccer specific aerobic endurance training. Furthermore, all SSGs with active recovery should be performed in order to increase players and teams’ performance capacity for subsequent bouts.
THE PROBLEM OF TOBACCO ADDICTION: META-ANALYSIS OF BEHAVIOURAL TREATMENTS IN SPAIN

En este trabajo se presentan los resultados de un estudio meta-analitico sobre la efectividad de los programas multicomponentes en el tratamiento de sujetos con adiccion al tabaco. Una busqueda exhaustiva de la literatura nos permitio identificar 16 trabajos empiricos realizados en Espana entre 1980 y 1996, dando lugar a un total de 37 estudios independientes que recogian datos de 1.979 sujetos. Se definio como indice del tamano del efecto la diferencia media tipificada entre el pretest y el postest en los disenos de un solo grupo, mientras que en los disenos de dos grupos se definio como la diferencia entre los cambios medios del pretest al postest entre el grupo tratado y el de control. Los resultados mostraron una clara efectividad global de las intervenciones conductuales (d+ = 1.450), aunque se reduce a la mitad tras 18 meses de seguimiento (d+ = 0.637). Las tecnicas de autocontrol fueron las mas efectivas (d+ = 1.810). Se analiza la influencia de otras variables moderadoras de los resultados y se propone un modelo predictivo de la efectividad. Finalmente, se discuten las implicaciones teoricas y clinicas de los resultados.
Interleukin-1beta and thiobarbituric acid reactive substance (TBARS) levels after phase I periodontal therapy in patients with chronic periodontitis.

BACKGROUND Interleukin-1beta (IL-1beta), a potent stimulator of bone resorption, has been implicated in the pathogenesis of periodontal tissue destruction. There is also a clearly defined and substantial role for free radicals or reactive oxygen species in periodontal destruction. The thiobarbituric acid reactive substances (TBARS) is a commonly applied test to measure free radical activity. The aims of this study were to investigate the amount of crevicular IL-1beta, tissue TBARS levels, and the clinical status of patients with advanced chronic periodontitis and the effect of phase I periodontal therapy on these clinical parameters and measurements. METHODS Twenty-five chronic periodontitis and 25 healthy control (C) patients were selected for the study. Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) were recorded from each sampling area. Gingival crevicular fluid (GCF) sampling and clinical index scores were recorded at the initial examination (IE) and 6 weeks after phase I periodontal therapy (APT). Assays for GCF IL-1beta were carried out by enzyme-linked immunosorbent assay (ELISA). Gingival tissue samples were obtained from sites requiring periodontal flap surgery due to unresolved pockets to determine the tissue TBARS levels. The paired-samples t test was used to compare the IL-1beta levels and clinical parameters between IE and APT. The independent-samples t test was used to determine the significance of all parameters between IE and C, and between APT and C. The correlation among the IL-1beta levels, clinical parameters, and tissue TBARS levels was analyzed using the Pearson correlation. RESULTS The concentration of IL-1beta levels was not statistically different among IE, APT, and C groups, but the total amount of IL-1beta levels was statistically different among the 3 groups. While the levels of IL-1beta and the clinical parameters were reduced following phase I periodontal treatment, pretreatment IL-1beta, post-treatment IL-1beta, and TBARS levels were statistically higher in IE and APT groups than C specimens. Tissue TBARS levels in the APT group were statistically greater than controls. No correlations were noted between tissue TBARS levels and clinical parameters in the APT group. A positive statistical correlation was detected between the total IL-1beta and TBARS levels in the APT group. CONCLUSION These data suggest that the levels of crevicular IL-1beta and gingival tissue TBARS are closely associated with periodontal status. This relationship may be valuable in treating and monitoring periodontal disease progression.
Glutamate and its metabotropic receptor in Drosophila clock neuron circuits

Identification of the neurotransmitters in clock neurons is critical for understanding the circuitry of the neuronal network that controls the daily behavioral rhythms in Drosophila. Except for the neuropeptide pigment‐dispersing factor, no neurotransmitters have been clearly identified in the Drosophila clock neurons. Here we show that glutamate and its metabotropic receptor, DmGluRA, are components of the clock circuitry and modulate the rhythmic behavior pattern of Drosophila. The dorsal clock neurons, DN1s in the larval brain and some DN1s and DN3s in the adult brain, were immunolabeled with antibodies against Drosophila vesicular glutamate transporter (DvGluT), suggesting that they are glutamatergic. Because the DN1s may communicate with the primary pacemaker neurons, s‐LNvs, we tested glutamate responses of dissociated larval s‐LNvs by means of calcium imaging. Application of glutamate dose dependently decreased intracellular calcium in the s‐LNvs. Pharmacology of the response suggests the presence of DmGluRA on the s‐LNvs. Antibodies against DmGluRA labeled dissociated s‐LNvs and the LNv dendrites in the intact larval and adult brain. The role of metabotropic glutamate signaling was tested in behavior assays in transgenic larvae and flies with altered DmGluRA expression in the LNvs and other clock neurons. Larval photophobic behavior was enhanced in DmGluRA mutants. For adults, we could induce altered activity patterns in the dark phase under LD conditions and increase the period during constant darkness by knockdown of DmGluRA expression in LNvs. Our results suggest that a glutamate signal from some of the DNs modulates the rhythmic behavior pattern via DmGluRA on the LNvs in Drosophila. J. Comp. Neurol. 505:32–45, 2007. © 2007 Wiley‐Liss, Inc.
The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1.

Phorbol esters reactivate Epstein-Barr virus (EBV) from latently infected cells via transcriptional activation of the viral immediate-early gene BZLF1. BZLF1 is a member of the extended AP-1 family of transcription factors that binds to specific BZLF1-binding motifs within early EBV promoters and to consensus AP-1 sites. Regulation of BZLF1's activity is achieved at the transcriptional level as well as through post-translational modifications. Recently, we reported that the transcriptional activity of BZLF1 is augmented by TPA [Baumann, M. , Mischak, H. , Dammeier, S. , Kolch, W. , Gires, O. , Pich, D. , Zeidler, R. , Delecluse, H. J. & Hammerschmidt, W. , (1998) J. Virol. 72, 8105-8114]. The increase of BZLF1's activity depends on a single serine residue (S186) that is phosphorylated by protein kinase C (PKC) in vitro and in vivo after stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA). Here, we identified RACK1 as a binding partner of BZLF1 in a yeast interaction trap assay. RACK stands for receptor of activated C-kinase and is involved in targeting activated PKCs and other signaling proteins. In vivo, RACK1 binds directly to the transactivation domain of BZLF1. Although a functional relationship between BZLF1 and PKC could be mediated by RACKs, RACK1 did not have a detectable effect on the phosphorylation status of BZLF1 in in vitro or in vivo phosphorylation assays. We suggest that RACK1 may act as a scaffolding protein on BZLF1 independently of activated PKCs.
Instrumented measurement of anterior knee laxity in patients with acute anterior cruciate ligament disruption

Instrumented anterior/posterior laxity measurements were performed on 138 patients evaluated within 2 weeks of injury with their first traumatic knee hemar throsis. All patients were tested with the MEDmetric Arthrometer model KT-1000 in a knee injury clinic. Seventy-five of the patients had knee arthroscopy. Thirty-three had arthrometer laxity tests under anes thesia. Eighty-seven percent of patients arthroscoped had anterior cruciate ligament (ACL) tears and 41 % had meniscus tears. One hundred twenty normal subjects were tested to establish normal anterior laxity values. Three tests were used to evaluate anterior laxity: anterior displacement between a 15 and 20 pound force (compliance index), anterior displacement with a 20 pound force, and an terior displacement with a high manually applied force. Displacement measurements in normal subjects re vealed a wide range of normal laxity with a small right knee-left knee difference. For example, the 20 pound anterior displacement range was 3 to 13.5 mm with a right knee-left knee difference (mean ± SD, 0.8 ± 0.7 mm). Eighty-eight percent of the normals had a right- left difference of less than 2 mm. In the 53 patients arthroscoped who had complete ACL tears, the anterior laxity measurements performed in the clinic were suggestive or diagnostic of pathologic anterior laxity in 50 patients.
Metabolic and endocrine changes induced by chronic heatexposure in broiler chickens : biological and endocrinological variables

Abstract: The present study was designed to investigate the effect of chronic heat exposure (32° constant) on plasma metabolites and hormone concentrations in broiler chickens. At 2 and 4 weeks of age, fifty-four male Shaver broiler chickens were allocated to one of three treatments: 22° ad lib. feeding (22AL), 32°ad lib. feeding (32AL) and 22°,pair-feeding with the 32AL group (22PF). Ambient temperature was kept constant at either 22 or 32° for 2 weeks. Plasma glucose, triacylglycerols, phospholipids, non-esterified fatty acids (NEFA), individual amino acids, uric acid, insulin, triiodothyronine (T3), thyroxine, corticosterone were determined. Sensitivity to exogenous insulin was also measured at 7 weeks of age. At 4 and 6 weeks of age, i.e. after 2 weeks at high ambient temperature, fasted 32AL chickens displayed similar concentrations of glucose and triacylglycerols to those of 22AL birds. When fed, 32AL chickens exhibited higher plasma levels of glucose and decreased concentrations of NEFAand amino acids. Feed restriction resulted in intermediate values. Concentrations of all plasmafree amino acids were decreased under heat exposure except for aspartic acid, glutamic acid andphenylalanine. At 6 weeks of age, plasma T3 was reduced irrespective of the nutritional state, while plasma corticosterone concentrations were increased in 32AL birds compared with 22AL birds. Heat exposure did not change plasma insulin concentration in either fasted or fed chickens. The 32AL chickens displayed significantly reduced sensitivity to exogenous insulin when fasted,but an enhanced response to insulin when fed, compared with both 22° groups. Such endocrinological changes could stimulate lipid accumulation through increased de novo lipogenesis, reduced lipolysis and enhanced amino acid catabolism under chronic heat exposure.