Plasma long non-coding RNAs (lncRNAs) serve as potential biomarkers for predicting breast cancer.

OBJECTIVE: Recent studies have suggested that lncRNAs play important regulatory roles in occurrence and progression of many cancers including breast cancer. However, only a small number of lncRNAs have proved to be related to breast cancer. Moreover, the effect of lncRNAs on breast cancer is yet unclear. We aimed at examining whether the expression level of these lncRNAs in our breast cancer patients could be different to normal people, and whether these lncRNAs could serve as potential biomarkers for the diagnosis of breast cancer. PATIENTS AND METHODS: We selected twelve lncRNAs as the research targets, which were previously found to be abnormally expressed in plasma of other cancers. The expression levels of these lncRNAs were measured by Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) and compared between breast cancer patients and normal people. RESULTS: The expression levels of plasma lncRNAs (H19, HOTAIR, and RP11-445H22.4) are found to increase significantly in breast cancer patients. The expression levels of other 9 lncRNAs were no significant changed compared with normal people. CONCLUSIONS: lncRNAs may be related to the occurrence of breast cancer and serve as potential biomarkers for its diagnosis.

The protective effect of lidocaine on lipopolysaccharide-induced acute lung injury in rats through NF-κB and p38 MAPK signaling pathway and excessive inflammatory responses.

OBJECTIVE: Acute lung injury is a severe disease with a high rate of mortality, leading to more important illness. We aimed at exploring the protective role and potential mechanisms of lidocaine on lipopolysaccharide (LPS)-induced acute lung injury (ALI). MATERIALS AND METHODS: Sprague Dawley (SD) rats were randomly assigned to control group receiving 0.9% saline solution, LPS group treated with 4 mg/kg LPS i.p., LPS + lidocaine(treated with 4 mg/kg LPS i.p. followed by giving 1 mg/kg, 3 mg/kg, 5 mg/kg of lidocaine i.v.). Lung specimens and the bronchoalveolar lavage fluid (BALF) were collected for histopathological examination and biochemical analyze 12 h after LPS induction. The cytokines expression of TNF-α, IL-6 and MCP-1 was measured by ELISA. In addition, the malondialdehyde (MDA) content, the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in lung tissues were also detected using ELISA. The protein expressions of p38, p-p38, p65, p-p65 and IκB were analyzed by Western blot. RESULTS: The results indicated that after lidocaine treatment was able to decrease significantly wet-to-dry (W/D) ratio and ameliorate the histopathologic damage. Additionally, total protein content and the number of leukocytes in BALF significantly decreased. ELISA result indicated that the levels of TNF-α, IL-6 and MCP-1 in BALF were markedly suppressed. Meanwhile, the activities of T-AOC and SOD in lung tissues significantly increased, while the content of MDA significantly decreased after treatment with lidocaine. Moreover, Western blot suggested that lidocaine inhibited phosphorylation of NF-κB p65 and p38 MAPK. CONCLUSIONS: Therefore, lidocaine could ameliorate the LPS-induced lung injury via NF-κB/p38 MAPK signaling and excessive inflammatory responses, providing a potential for becoming the anti-inflammatory agent against lung injury.

Effects of sevoflurane post-conditioning in cerebral ischemia-reperfusion injury via TLR4/NF-κB pathway in rats.

OBJECTIVE: The aim of the study was to investigate the anti-inflammatory effect of sevoflurane post-conditioning on cerebral ischemia-reperfusion injury in rats. MATERIALS AND METHODS: Thirty Sprague Dawley (SD) rats were randomly divided into 3 groups: sham operation group (Sham), ischemia/reperfusion injury (I/R) group and sevoflurane post-conditioning group (Se). Hematoxylin-eosin (HE) staining was used to observe the inflammatory response in the brain tissue. The levels of TNF-α, IL-1ß, IL-6 in serum were measured by ELISA. The mRNA and protein expression of TLR4 and NF-κB p65 were detected by RT-PCR and Western blot in the brain tissue. RESULTS: The post-conditioning of sevoflurane decreased the level of inflammatory reaction in ischemic-reperfusion rat cerebral infarction area and reduced the levels of pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6 in rats with ischemia-reperfusion injury. In addition, after treatment with sevoflurane, the mRNA and protein expression of TLR4 and NF-κBp65 in TLR4/NF-κB pathway was inhibited. CONCLUSIONS: Sevoflurane post-conditioning can decrease the inflammatory reaction in cerebral infarct area induced by cerebral ischemia-reperfusion injury in rats. The neuroprotective effect mechanism of sevoflurane may be related to TLR4/NF-κB signaling pathway.

A novel and faster method of manual grading to measure choroidal thickness using optical coherence tomography.

PurposeChoroidal thickness (CT) measurements are typically obtained from manual segmentation of optical coherence tomography (OCT) B-scans. This method is time-consuming. We aimed to describe a novel and faster technique to obtain CT measurements.Patients and methodsIn a prospective cohort study of 200 healthy eyes, Spectral-Domain OCT with enhanced depth imaging were performed with the Spectralis OCT using standardised imaging protocols. The OCT scans were independently graded by reading centre-certified graders. The standard method of manual adjustment of segmentation boundaries was performed. The new method consisted of adjusting the lower segmentation line to the choroid-scleral boundary to generate the combined choroid-retina thickness, and subtracting the original retinal thickness (RT) from it to measure CT. Mean CT in the respective Early Treatment Diabetic Retinopathy Study (ETDRS) subfields was measured via the two methods, and were compared with intraclass correlation coefficients (ICC) and Bland-Altman plots.ResultsThe mean central subfield CT was 324.4 µm using the original method, compared with 328.8 µm using the new method, with a mean difference of 4.5 µm (range: -14.0 to +4.0 µm; P<0.001), and ICC for agreement of 0.9996 (P<0.001). Similar comparability was achieved for mean CT across other ETDRS subfields, with mean differences ranging from 2.4 to 3.7 µm, and ICCs ranging from 0.9993 to 0.9995 (all P<0.001).ConclusionsMean CT can be measured by subtracting the original RT from the combined choroid-retina thickness. Only one segmentation line needs to be adjusted, instead of two, reducing time required for segmentation. This method is faster and reliable.

Isoflurane and sevoflurane affects Wnt/ß-catenin signaling pathways in hippocampal formation of neonatal rats.

OBJECTIVE: General anesthesia impairs spatial learning and memory in neonatal rats. The aim of this study was to investigate whether the Wnt pathway was involved in neonatal isoflurane and sevoflurane exposure-induced neurocognitive impairment. MATERIALS AND METHODS: Sprague-Dawley rats were randomly assigned to administration isoflurane or sevoflurane for 6 hours at postnatal 7 days. Wnt inhibitor XAV 939 was administrated 30 min before anesthesia. Morris water maze was used to test the learning and memory at 5-week and 10-week. Hematoxylin and Eosin (H&E) stain was performed to evaluation the neuronal death in the hippocampus. Quantitative Real-time PCR (q-PCR) and Western blot assays were used to measure mRNA and proteins expression levels of the Wnt3a, GSK 3ß and ß-catenin, respectively. RESULTS: The results showed that isoflurane or sevoflurane could significantly increase neonatal death and cell lost in the developing brain and the Wnt inhibitor could improve the cell degeneration. It demonstrated that isoflurane or sevoflurane could impair the P7 rats learning and memory capability, while these effects were reduced over time. When rats treated Wnt inhibitor at 30 min before anesthesia, the impairment of brain could relieve. q-PCR and Western blot demonstrated that isoflurane or sevoflurane affects expression levels of Wnt3a, GSK 3ß and ß-catenin. These results suggested that impairment of learning and memory in P7 rats may be related to the Wnt signaling pathway. CONCLUSIONS: The results suggested general anesthesia treatment led to increased brain cell degeneration and impaired learning and memory in P7 rats via Wnt signaling pathway.

Regional cerebellar volumes are related to early musical training and finger tapping performance.

The cerebellum has been associated with timing on the millisecond scale and with musical rhythm and beat processing. Early musical training (before age 7) is associated with enhanced rhythm synchronization performance and differences in cortical motor areas and the corpus callosum. In the present study, we examined the relationships between regional cerebellar volumes, early musical training, and timing performance. We tested adult musicians and non-musicians on a standard finger tapping task, and extracted cerebellar gray and white matter volumes using a novel multi-atlas automatic segmentation pipeline. We found that early-trained musicians had reduced volume in bilateral cerebellar white matter and right lobules IV, V and VI, compared to late-trained musicians. Strikingly, better timing performance, greater musical experience and an earlier age of start of musical training were associated with smaller cerebellar volumes. Better timing performance was specifically associated with smaller volumes of right lobule VI. Collectively, these findings support the sensitivity of the cerebellum to the age of initiation of musical training and suggest that lobule VI plays a role in timing. The smaller cerebellar volumes associated with musical training and timing performance may be a reflection of more efficiently implemented low-level timing and sensorimotor processes.

A Randomised Controlled Trial to Evaluate the Effectiveness of Intrathecal Bupivacaine Combined with Different Adjuvants (Fentanyl, Clonidine and Dexmedetomidine) in Caesarean Section.

PURPOSE: The purpose of this study was to evaluate comparatively, in women undergoing caesarean section under spinal anesthesia, the effectiveness of hyperbaric bupivacaine combined with 3 different adjuvants (fentanyl, clonidine, and dexmedtomidine) on quality of blockade and maternal and neonatal repercussions. METHOD: 84 patients undergoing elective surgeries under spinal anesthesia were randomized into 4 groups of 21 each, gB, gBF, gBC and gBD. Patients in groups gb, gBF, gBC and gBD were given bupivacaine alone, bupivacaine plus fentanyl (15.0 µg), bupivacaine plus fentanyl plus clonidine (75 µg), and bupivacaine plus dexmedetomidine (10 µg), respectively. Hemodynamic parameters evaluated were the onset and level of sensory block, perioperative analgesia, degree and recovery time of motor block, duration of analgesia, sedation, and maternal-foetal repercussions. RESULTS: The onset of blockade was significantly faster in groups with adjuvants clonidine and dexmedetomidine compared with gB and gBF. Patients in Groups gB and gBF reported pain during the perioperative period. Duration of analgesia was significantly higher in Group gBD and was comparable to gBC and time to motor block recovery was significantly higher in Group gBD. Sedation was significant in Group gBD and gBC. CONCLUSION: Addition of dexmedetomidine and clonidine as adjuvants to hyperbaric bupivacaine provided adequate anesthesia and postoperative analgesia compared to fentanyl adjuvant without causing any significant side effects.

The role of musical training in emergent and event-based timing.

INTRODUCTION: Musical performance is thought to rely predominantly on event-based timing involving a clock-like neural process and an explicit internal representation of the time interval. Some aspects of musical performance may rely on emergent timing, which is established through the optimization of movement kinematics, and can be maintained without reference to any explicit representation of the time interval. We predicted that musical training would have its largest effect on event-based timing, supporting the dissociability of these timing processes and the dominance of event-based timing in musical performance. MATERIALS AND METHODS: We compared 22 musicians and 17 non-musicians on the prototypical event-based timing task of finger tapping and on the typically emergently timed task of circle drawing. For each task, participants first responded in synchrony with a metronome (Paced) and then responded at the same rate without the metronome (Unpaced). RESULTS: Analyses of the Unpaced phase revealed that non-musicians were more variable in their inter-response intervals for finger tapping compared to circle drawing. Musicians did not differ between the two tasks. Between groups, non-musicians were more variable than musicians for tapping but not for drawing. We were able to show that the differences were due to less timer variability in musicians on the tapping task. Correlational analyses of movement jerk and inter-response interval variability revealed a negative association for tapping and a positive association for drawing in non-musicians only. DISCUSSION: These results suggest that musical training affects temporal variability in tapping but not drawing. Additionally, musicians and non-musicians may be employing different movement strategies to maintain accurate timing in the two tasks. These findings add to our understanding of how musical training affects timing and support the dissociability of event-based and emergent timing modes.

Attentional requirements of walking according to the gait phase and onset of auditory stimuli.

A dual-task paradigm was used to examine the influence of an attention demanding cognitive task on each phase of gait. Twenty-three participants (aged 18-27) walked on a treadmill at a 20% increase of their self-selected speed, either alone or while performing a cognitive task. Muscle activity was measured with electromyography (iEMG) for eight muscles of the dominant leg. The cognitive task consisted of subtracting one (EASY) or seven (HARD) from orally presented numbers. Reaction time (RT) and accuracy were recorded. iEMG events were selected according to stimulus onset (0-150 ms, 150-300 ms and 300-450 ms) prior to phases of gait (double-leg stance, single-leg stance and swing). There was a decrease in iEMG amplitude of fibularis longus (p=.013) and a trend in the same direction for vastus lateralis (p=.065) while walking and performing the cognitive task. When stimulus onset was considered, iEMG of medial gastrocnemius (p=.021) and lateral gastrocnemius (p=.004) were reduced during single-leg stance, when stimuli occurred between 300 and 450 ms prior to this phase. Cognitive performance was affected by task difficulty (RT, accuracy) and by dual-task load (RT). Dual-task costs were observed in both the motor and the cognitive tasks, suggesting that walking requires attention. There was a specific moment (300 ms after stimulus onset) during single-leg stance when dual-task costs were most pronounced, corroborating supraspinal involvement in the control of normal walking. Time-based approaches should be considered when analyzing attentional demands of a dynamic task such as gait.

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model.

The antitumor effects of small-sized liposomal Adriamycin (LADR) administered by various routes were investigated in rabbits bearing well-developed VX2 tumors in the mammary gland. Rabbits received s.c. or i.v., or s.c. combined with i.v., injections of LADR 6 weeks after tumor implantation. The i.v. route showed a significant inhibitory effect on breast tumors and distant metastases. In comparison, metastases in axillary and mediastinal lymph nodes were more efficiently inhibited after s.c. injection. LADR administered concurrently by both the i.v. and s.c. routes produced satisfactory therapeutic activities on both primary breast tumors and metastases in local-regional lymph nodes, lungs and liver, as shown by slowed growth rates, decreased mRNA expression of proliferating cell nuclear antigen, and extensive necrosis and apoptosis of tumor cells. It is concluded that small-sized LADR administered s.c. provides reliable efficacy on lymphatic metastases of breast cancer and that the addition of treatment by the s.c. route to that by the conventional i.v. route can be recommended as a promising procedure to enhance chemotherapeutic effects in patients with metastatic breast cancer.

Walking while memorizing: age-related differences in compensatory behavior.

This study investigated predictions of the life-span theory of selection, optimization, and compensation, focusing on different patterns of task priority during dual-task performance in younger and older adults. Cognitive (memorizing) and sensorimotor (walking a narrow track) performance were measured singly, concurrently, and when task difficulty was manipulated. Use of external aids was measured to provide another index of task priority. Before dual-task testing, participants received extensive training with each component task and external aid. Age differences in dual-task costs were greater in memory performance than walking, suggesting that older adults prioritized walking over memory. Further, when given a choice of compensatory external aids to use, older adults optimized walking, whereas younger adults optimized memory performance. The results have broad implications for systemic theories of cognitive and sensorimotor aging, and the costs and benefits of assistive devices and environmental support for older populations.

The role of inhibition in the regulation of sequential action.

We investigated the regulation of sequential action using a new paradigm. Participants learned a sequence of seven stimulus categories and then monitored for them during successive displays. All displays were instances of these categories, presented in pseudorandom order. On each trial, participants monitored for an instance of Category 1, pressed a key on a computer keyboard, then monitored for an instance of Category 2, pressed a key on the keyboard, and so on for all seven categories. Thus, a perfect trial contained exactly seven responses. Intrusion errors were classified as a function of ordinal distance from the current serial position (n). Fewer intrusion errors were made at near serial positions than at far ones, suggesting a gradient of lateral inhibition. In addition, more intrusions were made on n + 1 categories than n - 1 categories, suggesting greater availability of intended than completed goals. In accord with current models of sequential action, the results indicate lateral and self-inhibition as important mechanisms in regulation of sequential action.

Distractibility, circadian arousal, and aging: a boundary condition?

Two studies assessed the presence of a synchrony effect between peak circadian arousal and time of testing for both older and younger adults. Participants performed a reading aloud task that included distracting words that were either present or absent and, if present, were either thematically related or unrelated to the target text. As well, the distracting material was presented in either spatially predictable or unpredictable locations. In each experiment, older and younger adults were tested at optimal versus nonoptimal times. Both experiments showed age differences in susceptibility to distraction, replicating earlier findings (e.g., M. C. Carlson, L. Hasher, R. T. Zacks, & S. L. Connelly, 1995). Neither showed differences due to time of testing, suggesting a boundary condition for cognitive disruptions associated with circadian arousal patterns.

Age differences in the interpretation of misaligned "You-Are-Here" maps.

"You-Are-Here" (YAH) maps, common in shopping malls and office buildings, are difficult to interpret if not aligned with their surroundings. Younger and older adults made direction decisions after viewing simple maps representing a university campus. YAH arrows were either upright and coordinated with viewer position or contra-aligned 180 degrees. Contra-alignment caused subjects, especially older adults, to take more time and be less accurate. Women were slower on contra-aligned maps, although no less accurate, than men. The need to mentally realign such incongruent maps in order to make correct direction decisions can cause serious difficulty for older adults trying to navigate through large, complex environments.