Miracle-dz/UniFAR-FTUs huggingface dataset:
Extradural block. Confirmation of the injection site by X‐ray monitoring

X‐ray monitoring was used to confirm the accuracy of extradural block in 100 patients who attended the Pain Relief Clinic for treatment of a variety of different conditions. A Tuohy needle was introduced by the central or paramedian approach and conventional physical signs, notably loss of resistance, used to identify entry into the estradural space. A radio‐opaque dye was introduced prior to the analgesic solution, to display the injection site. X‐ray screening confirmed the accuracy of the block in 83 patients, but unexpectedly in 17 the point of the needle was either just outside the spinal canal or only partly in the extradural space. There was no difficulty in correcting the needle position with the X‐ray facilities available. Imprecise needle siting is only partially explained by technical problems. Imprecise siting of the needle may be responsible for at least some cases of inadequate analgesia or unexpected complications. In our view X‐ray confirmation of site is essential for difficult extradural blocks, or when neurolytic solutions are introduced into the spinal canal. It may also be useful in teaching and research.
Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies

Background: It is unclear whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressant drugs reduce the risk of suicide in people with depression. We explored the association between exposure to SSRIs and risk of suicide completion or attempt. Methods: We conducted a systematic review of observational studies that reported completed or attempted suicide in depressed individuals who were exposed to SSRIs compared with those who were not exposed to antidepressants. We assessed the overall risk of completed or attempted suicide. Results: Eight studies involving more than 200 000 patients with moderate or severe depression were included in the meta-analysis. Although exposure to SSRIs increased the risk of completed or attempted suicide among adolescents (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.51–2.44), the risk was decreased among adults (OR 0.57, 95% CI 0.47–0.70). Among people aged 65 or more years, exposure to SSRIs had a protective effect (OR 0.46, 95% CI 0.27–0.79). Sensitivity analyses did not change these findings. In particular, for studies that used completed suicide as an outcome, exposure to SSRIs was associated with increased risk among adolescents (OR 5.81, 95% CI 1.57–21.51) and decreased risk among adults (OR 0.66, 95% CI 0.52–0.83) and older people (OR 0.53, 95% CI 0.26–1.06). Interpretation: Based on data from observational studies, use of SSRIs may be associated with a reduced risk of suicide in adults with depression. Among adolescents, use of SSRIs may increase suicidality.
On the symmetry of periodontal disease.

BACKGROUND/AIM Symmetry is a common feature of biological systems, and can be observed in multiple aspects of the human body. The purpose of this study was to estimate the impact of symmetry on variance observed in intraoral topographic distribution patterns of chronic periodontitis. METHOD This analysis was performed on a data set from 56 subjects, including clinical and microbiological variables, recorded at the mesial and distal aspect of every tooth in the entire dentition. The impact of contralateral conditions was determined on the level of the site, the tooth, and the quadrant. RESULTS Significant correlations were detected between probing depths, recession, attachment levels, total cultivable bacterial counts and the plaque index recorded on the right and left side on all levels of analysis. The odds for bleeding on sampling, as well as for the presence of P. intermedia/nigrescens and A. actinomycetemcomitans increased significantly if the respective contralateral site was positive for the same parameter. In combining ipsilateral and contralateral parameters into the analysis it could be shown in several instances that this contralateral effect was stronger than the impact of other, ipsilateral factors. As an example, the odds for bleeding on sampling increased up to 10 fold if the contralateral site was bleeding, whereas the ipsilateral total cultivable count, determined at the same site, explained less than 30% of the variation in the bleeding tendency. CONCLUSION These findings support the view that the development of periodontal disease in any site cannot be explained by the influence of local detrimental factors alone.
Curcumin Modulates miR‐19/PTEN/AKT/p53 Axis to Suppress Bisphenol A‐induced MCF‐7 Breast Cancer Cell Proliferation

Breast cancer is the most common cancer in women. Bisphenol A (BPA), as a known endocrine disrupter, is closely related to the development of breast cancer. Curcumin has been clinically used in chemopreventation and treatment of cancer; however, it remains unknown whether microRNAs are involved in curcumin‐mediated protection from BPA‐associated promotive effects on breast cancer. In the present study, we showed that BPA exhibited estrogenic activity by increasing the proliferation of estrogen‐receptor‐positive MCF‐7 human breast cancer cells and triggering transition of the cells from G1 to S phase. Curcumin inhibited the proliferative effects of BPA on MCF‐7 cells. Meanwhile, BPA‐induced upregulation of oncogenic miR‐19a and miR‐19b, and the dysregulated expression of miR‐19‐related downstream proteins, including PTEN, p‐AKT, p‐MDM2, p53, and proliferating cell nuclear antigen, were reversed by curcumin. Furthermore, the important role of miR‐19 in BPA‐mediated MCF‐7 cell proliferation was also illustrated. These results suggest for the first time that curcumin modulates miR‐19/PTEN/AKT/p53 axis to exhibit its protective effects against BPA‐associated breast cancer promotion. Findings from this study could provide new insights into the molecular mechanisms by which BPA exerts its breast‐cancer‐promoting effect as well as its target intervention. Copyright © 2014 John Wiley & Sons, Ltd.
Indices of Leukocyte Infiltration and Muscle Recovery After Eccentric Contraction‐Induced Injury in Young and Adult Male Mice

The movement of leukocytes (e.g., neutrophils and macrophages) into skeletal muscle is a critical response after a sports-related injury. Age could influence this response. The major objectives of the study were to determine whether there is a relationship between age and the degree of (1) leukocyte response and (2) muscle recovery. The left plantarflexor muscles of 42 young and adult male mice underwent eccentric contractions, which can cause injury. After 1 or 5 days, leukocyte infiltration and muscle recovery were assessed in the soleus or medial gastrocnemius muscles. No relationship between age and leukocyte infiltration was found (P = .36). Neutrophils, but not macrophages, were detected at 1-day recovery. A significant relationship between age and muscle recovery was detected (P = .0498), suggesting that muscle recovery may be decreased with increased age.
Evaluation of POSSUM and P-POSSUM scoring systems for predicting the mortality in elective neurosurgical patients

A simple way of evaluating surgical outcomes is to compare mortality and morbidity. Such comparisons may be misleading without a proper case mix. The POSSUM scoring system was developed to overcome this problem. The score can be used to derive predictive mortality and morbidity for surgical procedures. POSSUM and a modified version P-POSSUM have been evaluated in various groups of surgical patients for the accuracy of predicting mortality. These scoring systems have not been evaluated in neurosurgical patients. Thus, we tried to evaluate the usefulness of POSSUM and P-POSSUM scoring systems in neurosurgical patients in predicting in-hospital mortality. POSSUM physiological and operative variables were collected from all neurosurgical patients undergoing elective craniotomy, from April 2005 to Feb 2006. In-hospital mortality was obtained from the hospital mortality register. The physiological score, operative score, POSSUM predicted mortality rate and P-POSSUM predicted mortality rate were calculated using a calculator. The observed number of deaths was compared against the predicted deaths. A total of 285 patients with a mean age of 38 ± 15 years were studied. Overall observed mortality was nine patients (3.16%). The mortality predicted by the P-POSSUM model was also nine patients (3.16%). Mortality predicted by POSSUM was poor with predicted deaths in 31 patients (11%). The difference between observed and predicted deaths at different risk levels was not significant with P-POSSUM (p = 0.424) and was significantly different with POSSUM score (p < 0.001). P-POSSUM scoring system was highly accurate in predicting the overall mortality in neurosurgical patients. In contrast, POSSUM score was not useful for prediction of mortality.
Response to an aerobic training intervention in young adults depends on ponderal index at birth

Poor fetal growth is associated with later-life changes in adult body composition and decrements in muscle strength and morphology. Few studies have investigated the association of poor fetal growth with whole-body exercise. The purpose of this study was to investigate the association of poor fetal growth with the maximal oxygen consumption (VO2max), lactate levels during exercise and the response to aerobic training. Thirty-six college-aged men and women (aged 20.8 ± 0.3 years), born to term (37–42 weeks gestation), were recruited to participate in an 8-week training program. Participants comprised two groups, high ponderal index (HIGHPI) and low ponderal index (LOWPI) (n = 18/group), identified as falling above and below the 10th percentile of the ponderal index (g/cm3)-for-gestational age distribution, respectively. The HIGHPI and LOWPI were matched pair-wise on age, sex, body mass index and pre-study physical activity patterns. The LOWPI and HIGHPI did not differ significantly before training, after training or with a change (Δ) in training VO2max (l/min or ml/min kg/fat-free mass (FFM)). However, LOWPI had significantly lower pre-training lactate levels at similar levels of relative work output (P = 0.016), and significantly smaller decreases in lactate at a fixed level of absolute work after training (P = 0.044). These differences were independent of pre-training aerobic fitness, the change in fitness with training, diet and fuel substrate choice. The lower lactate of untrained LOWPI subjects during exercise could reflect metabolic reprograming due to intrauterine growth restriction, or could be secondary to muscle morphological and/or fiber-type distribution changes that also associate with poor fetal growth.
A novel dithiol amide CB3 attenuates allergic airway disease through negative regulation of p38 mitogen-activated protein kinase.

RATIONALE Cellular redox homeostasis altered by excessive production of reactive oxygen species (ROS) and weakening of the antioxidant defense leads to oxidative stress. Oxidative stress is characterized as a decrease in glutathione/glutathione disulfide (GSH/GSSG) and the triggering of a number of the redox-sensitive signaling cascades. Recent studies have demonstrated that ROS play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. OBJECTIVES Here we characterized for the first time the protective properties of a new hydrophobic thiol compound, N-acetyl cysteine proline cysteine amide (CB3), in allergic airway diseases. METHODS We used ovalbumin (OVA)-inhaled mice to evaluate the role of CB3 as an antiinflammatory reagent and to determine its molecular signaling activity in allergic airways. MEASUREMENTS AND MAIN RESULTS The administration of CB3 (1-50 mg/kg) to OVA-inhaled mice restored the decreased GSH levels, enhanced IL-10 expression, and significantly reduced the increase of Th2 cytokines and OVA-specific IgE. CB3 decreased the number of inflammatory cells and airway hyperresponsiveness in the lungs. We also found that the administration of CB3 dramatically decreased the nuclear translocation of the nuclear factor-κB (NF-κB) and the phosphorylation of p38 mitogen-activated protein kinases (MAPKs) in lungs after OVA inhalation. In addition, allergen-induced airway inflammation and hyperresponsiveness were substantially reduced by the administration of inhibitors of NF-κB and p38 MAPK, BAY 11-7085, and SB 239063, respectively. CONCLUSIONS These results suggest that CB3 attenuates allergic airway disease by up-regulation of GSH levels as well as inhibition of NF-κB and p38 MAPK activity.
Approaches to Investigating Impaired Cognition in Schizophrenia: A Paradigm Shift

There has been a growing interest in cognitive deficits in schizophrenia in recent years. The use of traditional clinical neuropsychological measures of cognition in schizophrenia has the advantages of normative data and standardized administration, and remains the standard for cognitive assessment in clinical practice. However for the investigation of cognition in schizophrenia these methods have critical limitations in their ability to measure specific cognitive processes. In this paper we discuss solutions to these interpretive and measurement issues that can be provided by measures derived from experimental cognitive psychology. We suggest that the use of these measures will increasingly become the preferred approach to the investigation of the nature, neurobiology and genetics of impaired cognition in schizophrenia in the coming years.
The Decrease in the V˙O2 Slow Component Induced by Prior Exercise Does Not Affect the Time to Exhaustion

In previous studies decreases in the VO(2) slow component were observed after prior heavy exercise. The observed effects after prior low-intensity exercise were rather controversial. The purpose of the present study was to more thoroughly examine the effects of prior low-intensity exercise on the VO(2) slow component. Furthermore, it has been suggested that the VO(2) slow component may be a determinant of exercise tolerance. Therefore we tested the hypothesis whether an attenuated VO(2) slow component induced by prior exercise could affect the time to exhaustion. Ten subjects performed four exercise protocols consisting of heavy cycling exercise (95 % VO(2)peak) until exhaustion. This constant-load exercise was performed without prior exercise (protocol NPE), or was preceded by 6 min heavy cycling exercise (protocol 6HPE), 12 min low-intensity cycling exercise (protocol 12LPE) or 6 min low-intensity cycling exercise (protocol 6LPE). The VO(2) slow component quantified as Delta VO(2 (end-2)) (669 +/- 90 ml x min (-1) in NPE) was significantly reduced after heavy as well as low-intensity exercise (respectively 47 %, 29 % and 17 % in 6HPE, 12LPE and 6LPE). This reduction lead to a significantly lower end VO(2) in 6HPE and 12LPE. The time to exhaustion (594 +/- 139 s in NPE), however, was unaffected by prior exercise rejecting our hypothesis that the attenuated VO(2) slow component could improve the capability to sustain exercise performance.
Understanding proneurotrophin actions: Recent advances and challenges

Neurotrophins are initially synthesized as larger precursors (proneurotrophins), which undergo proteolytic cleavage to yield mature forms. Although the functions of the mature neurotrophins have been well established during neural development and in the adult nervous system, roles for the proneurotrophins in developmental and injury‐induced cell death, as well as in synaptic plasticity, have only recently been appreciated. Interestingly, both mature neurotrophins and proneurotrophins utilize dual‐receptor complexes to mediate their actions. The mature neurotrophin coreceptors consist of the Trk receptor tyrosine kinases and p75NTR, wherein Trk transduces survival and differentiative signaling, and p75NTR modulates the affinity and selectivity of Trk activation. On the other hand, proneurotrophins engage p75NTR and the structurally distinct coreceptor sortilin, to initiate p75NTR‐dependent signal transduction cascade. Although the specificity of mature neurotrophins vs. proneurotrophins actions is due in part to the formation of distinct coreceptor complexes, a number of recent studies highlight how different p75NTR‐mediated cellular actions are modulated. Here, we review emerging evidence for a novel transmembrane mechanism for ligand‐specific p75NTR activation and several mechanisms by which p75NTR‐dependent apoptotic and nonapoptotic responses can be selective activated. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010
Selective modes determine evolutionary rates, gene compactness and expression patterns in Brassica

It has been well documented that most nuclear protein-coding genes in organisms can be classified into two categories: positively selected genes (PSGs) and negatively selected genes (NSGs). The characteristics and evolutionary fates of different types of genes, however, have been poorly understood. In this study, the rates of nonsynonymous substitution (Ka ) and the rates of synonymous substitution (Ks ) were investigated by comparing the orthologs between the two sequenced Brassica species, Brassica rapa and Brassica oleracea, and the evolutionary rates, gene structures, expression patterns, and codon bias were compared between PSGs and NSGs. The resulting data show that PSGs have higher protein evolutionary rates, lower synonymous substitution rates, shorter gene length, fewer exons, higher functional specificity, lower expression level, higher tissue-specific expression and stronger codon bias than NSGs. Although the quantities and values are different, the relative features of PSGs and NSGs have been largely verified in the model species Arabidopsis. These data suggest that PSGs and NSGs differ not only under selective pressure (Ka /Ks ), but also in their evolutionary, structural and functional properties, indicating that selective modes may serve as a determinant factor for measuring evolutionary rates, gene compactness and expression patterns in Brassica.
Reduction of TSG101 protein has a negative impact on tumor cell growth

TSG101 was defined originally as a tumor‐suppressor gene, raising the expectation that absence of the encoded protein should lead to increased tumor cell growth and, perhaps, increased tumor cell aggressiveness. We have used the RNA interference (RNAi) technique to downregulate TSG101 in PC3 (prostate cancer) and MDA‐MB‐231 (breast cancer) cells. An approximately 85% selective downregulation at the protein level was achieved in both cell lines over a period of 12 days as detected by Western blotting. This treatment resulted in inhibition of tumor cell growth, with a decreased level of TSG101 causing partial cell cycle arrest at the G1/S boundary and a reduction in the rate at which cells passed from G2 through mitosis and back into G1. In both cell lines, the percentage of cells in S‐phase was reduced significantly at day 4 after the TSG101 siRNA transfection (27% vs. 41% in MDA‐MB‐231 cells; 22% vs. 39% in PC3 cells). Additionally, RNAi‐mediated downregulation of TSG101 reduced the colony formation capacities of both cancer cell lines. Rather more surprisingly, TSG101 downregulation affected the migratory activity of the MDA‐MB‐231 cells, independent of any effect on proliferation. Thus, in a Transwell assay, after 4‐hr incubation, 36.0% of control MDA‐MB‐231 cells had migrated to the lower chamber vs. 7.3% of TSG101‐downregulated cells (p < 0.001; scrambled control, 36.5%). These results show that the TSG101 gene does not comply with the usual characteristics of a tumor‐suppressor gene; rather, its expression may be necessary for activities associated with aspects of tumor progression. © 2004 Wiley‐Liss, Inc.
Thiamet G mediates neuroprotection in experimental stroke by modulating microglia/macrophage polarization and inhibiting NF-κB p65 signaling

Inflammatory responses are accountable for secondary injury induced by acute ischemic stroke (AIS). Previous studies indicated that O-GlcNAc modification (O-GlcNAcylation) is involved in the pathology of AIS, and increase of O-GlcNAcylation by glucosamine attenuated the brain damage after ischemia/reperfusion. Inhibition of β-N-acetylglucosaminidase (OGA) with thiamet G (TMG) is an alternative option for accumulating O-GlcNAcylated proteins. In this study, we investigate the neuroprotective effect of TMG in a mouse model of experimental stroke. Our results indicate that TMG administration either before or after middle cerebral artery occlusion (MCAO) surgery dramatically reduced infarct volume compared with that in untreated controls. TMG treatment ameliorated the neurological deficits and improved clinical outcomes in neurobehavioral tests by modulating the expression of pro-inflammatory and anti-inflammatory cytokines. Additionally, TMG administration reduced the number of Iba1+ cells in MCAO mice, decreased expression of the M1 markers, and increased expression of the M2 markers in vivo. In vitro, M1 polarization of BV2 cells was inhibited by TMG treatment. Moreover, TMG decreased the expression of iNOS and COX2 mainly by suppressing NF-κB p65 signaling. These results suggest that TMG exerts a neuroprotective effect and could be useful as an anti-inflammatory agent for ischemic stroke therapy.
Short‐term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to β‐adrenergic stimulation

Sprint interval training (SIT) and traditional endurance training elicit similar physiological adaptations. From the perspective of metabolic function, superior glucose regulation is a common characteristic of endurance‐trained adults. Accordingly, we have investigated the hypothesis that short‐term SIT will increase insulin sensitivity in sedentary/recreationally active humans. Thirty one healthy adults were randomly assigned to one of three conditions: (1) SIT (n= 12): six sessions of repeated (4–7) 30 s bouts of very high‐intensity cycle ergometer exercise over 14 days; (2) sedentary control (n= 10); (3) single‐bout SIT (n= 9): one session of 4 × 30 s cycle ergometer sprints. Insulin sensitivity was determined (hyperinsulinaemic euglycaemic clamp) prior to and 72 h following each intervention. Compared with baseline, and sedentary and single‐bout controls, SIT increased insulin sensitivity (glucose infusion rate: 6.3 ± 0.6 vs. 8.0 ± 0.8 mg kg−1 min−1; mean ±s.e.m.; P= 0.04). In a separate study, we investigated the effect of SIT on the thermogenic response to beta‐adrenergic receptor (β‐AR) stimulation, an important determinant of energy balance. Compared with baseline, and sedentary and single‐bout control groups, SIT did not affect resting energy expenditure (EE: ventilated hood technique; 6274 ± 226 vs. 6079 ± 297 kJ day−1; P= 0.51) or the thermogenic response to isoproterenol (6, 12 and 24 ng (kg fat‐free mass)−1 min−1: %ΔEE 11 ± 2, 14 ± 3, 23 ± 2 vs. 11 ± 1, 16 ± 2, 25 ± 3; P= 0.79). Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose, insulin, adiponectin, pigment epithelial‐derived factor, non‐esterified fatty acids or noradrenaline (all P > 0.05). Sixteen minutes of high‐intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to β‐AR stimulation.