Miracle-dz/UniFAR-FTUs huggingface dataset:
Treated effect of silymarin on vascular function of aged rats: Dependant on nitric oxide pathway

Abstract Context: Aging leads to endothelial dysfunction and vascular stiffness which are the main causes of many cardiovascular diseases. Previous reports have shown that the cell protective effect of silymarin (SM) is dependent on its antioxidant properties. Objectives: We investigated the effect of SM on vascular functions of aged rats and the involvement of nitric oxide or cyclooxygenase (COX) activity in this effect. Materials and methods: Isolated rat aortas were obtained from 22-month old rats. Each ring was incubated with SM (50 mg/L), SM/l-nitro-arginine methyl ester (100 μM, l-NAME) or SM/indomethacin (10 μM, INDO) in tissue bath. Three- to four-month-old rats were used as young controls. Endothelium-intact rings were precontracted with α-receptor agonist phenylephrine (0.001–30 µM) or voltage-dependent high potassium (40 mM), endothelium dependent/independent relaxant responses were obtained using acetylcholine (0.001–30 µM) and sodium nitroprusside (0.0001–3 µM), respectively. Results: Aging increased phenylephrine sensitivity (6.45 ± 0.08; 6.88 ± 0.09) and decreased KCl contraction (882 ± 118.4; 499 ± 80.4). SM treatment decreased the Emax of both agents (548 ± 109; 223 ± 48.9). Aging deteriorated acetylcholine relaxation (93.9 ± 2.09; 72.0 ± 2.56) and SM improved the response (86.3 ± 1.90). l-NAME prevented the SM effect whereas INDO was ineffective. Discussion and Conclusion: Immediate SM treatment partially restored endothelial dysfunction and vascular tone in aging. The possible mechanism might not be mediated by prostacyclin or the COX pathway in acute administration; the nitric oxide pathway and calcium antagonistic features of SM relate to its action on the vessel.
Young women with polycystic liver disease respond best to somatostatin analogues: a pooled analysis of individual patient data.

BACKGROUND & AIMS Clinical trials have shown that in patients with polycystic liver disease (PLD), short-term treatment with somatostatin analogues (SAs) reduces liver volumes by 4.5%-5.9%, compared with placebo. However, the effects of SA therapy vary among individuals. We collected data from individual patients with PLD to identify subgroups that benefit most from SA therapy. METHODS We analyzed data from 107 patients with PLD from 3 randomized placebo-controlled trials (67 received SAs, 52 received placebo). We used multiple linear regression analysis to determine the effects of SAs based on patients' age, sex, baseline liver volume, and diagnosis (autosomal dominant polycystic liver or kidney disease). The primary outcome was change in liver volume after 6-12 months of treatment. RESULTS The effects of SA therapy did not differ significantly among patients with different diagnoses or baseline liver volumes; the overall difference in liver volume between groups receiving SAs therapy vs placebo was 5.3% (P < .001). Among subjects given placebo, young women (48 years old or younger) had the greatest increase in polycystic liver volume (4.8%; 95% confidence interval: 2.2%-7.4%), and mean liver volumes did not increase in older women and men. Women 48 years old or younger had a greater response to therapy (a reduction in liver volume of 8.0% compared with placebo; P < .001) than older women (a reduction in liver volume of 4.1% compared with placebo; P = .022). CONCLUSIONS Based on a pooled analysis of data from individual patients with PLD, treatment with somatostatin analogues is equally effective for patients with autosomal dominant polycystic kidney disease or polycystic liver disease; efficacy does not depend on size of the polycystic liver. Young female patients appear to have the greatest benefit from 6-12 months of SA therapy, which might avert the progressive course of the disease in this specific group.
Penicillin‐induced potentiation of glycine receptor‐operated choride current in rat ventro‐medial hypothalamic neurones

1 Effects of penicillin G (PCN) on glycine (Gly)‐evoked Cl− current (IGly) were investigated in acutely dissociated rat ventro‐medial hypothalamic (VMH) neurones by the whole cell mode of patch clamp technique. 2 When PCN was applied simultaneously with Gly, PCN depressed IGly like a Cl− channel blocker. 3 The PCN‐induced blocking action was clearly observed at a low PCN concentration (30 u), while the maximal blockade was achieved by 600 u (units per 10 ml) PCN. 4 When tested solution containing both PCN and Gly was quickly substituted with one containing Gly only, a new rebound‐like transient current (IT) which also passed through Cl− channel, was elicited. 5 The peak amplitude of IT induced by PCN at concentrations higher than 100 u was greater than that induced by glycine alone. We termed this phenomenon PCN‐induced potentiation of IGly. In all cells tested, PCN potentiated IGly. 6 At a lower PCN concentration below 30 u, IT generation was not clear in the presence of 10−5 m γ‐aminobutyric acid. With PCN a higher concentration than 300 u, IT amplitude was treater than that of the original peak IGly. This was observed in 18 neurones out of 21. The maximal amplitude of the IT was achieved with 600 u PCN.
Magnetically Targeted Viral Envelopes: A PET Investigation of Initial Biodistribution

Gene and drug therapy for organ-specific diseases in part depends on the efficient delivery to a particular region of the body. We examined the biodistribution of a viral envelope commonly used as a nanoscale gene delivery vehicle using positron emission tomography (PET) and investigated the magnetic alteration of its biodistribution. Iron oxide nanoparticles and 18F-fluoride were encapsulated by hemagglutinating virus of Japan envelopes (HVJ-Es). HVJ-Es were then injected intravenously in the rat and imaged dynamically using high-resolution PET. Control subjects received injections of encapsulated materials alone. For magnetic targeting, permanent magnets were fixed on the head during the scan. Based on the quantitative analysis of PET images, HVJ-Es accumulated in the liver and spleen and activity remained higher than control subjects for 2 h. Histological sections of the liver confirmed imaging findings. Pixel-wise activity patterns on coregistered PET images of the head showed a significantly different pattern for the subjects receiving magnetic targeting as compared to all control groups. Imaging demonstrated the initial biodistribution of a viral envelope within the rodent by providing quantitative behavior over time and in specific anatomical regions. Magnetic force altered the biodistribution of the viral envelope to a target structure, and could enable region-specific delivery of therapeutic vehicles noninvasively.
Protein C Concentrations Correlate with Organ Dysfunction and Predict Outcome Independent of the Presence of Sepsis

Background:Characterizing the evolution of protein C concentrations in critically ill patients may help in identifying high risk groups and potential therapeutic targets. The authors investigated the time courses of protein C concentrations and their relation to the presence of sepsis, organ dysfunction/failure, and outcome. Methods:This observational cohort study, in a university hospital surgical intensive care unit (ICU), included 312 consecutive patients with an estimated ICU length of stay more than 48 h. Plasma protein C concentrations and parameters of organ dysfunction were measured daily until discharge or death. Results:Protein C concentrations were below the lower limit of normal in 50.6% of patients (n = 158) on admission and decreased to a nadir within 3–4 days after admission before almost normalizing by 2 weeks thereafter, irrespective of the presence of sepsis, sex, source and type of admission, and type of surgery. The minimum protein C concentration was lower in patients with severe sepsis/septic shock (n = 54) than in those with sepsis (n = 63) and those who never had sepsis (n = 195), and was negatively correlated to the maximum Sequential Organ Failure Assessment score (R2 = 0.345, P < 0.001). Protein C levels were lower in nonsurvivors (n = 46; 14.7%) than in survivors, especially in the first 4 days after admission. In a multivariable analysis with ICU mortality as the dependent variable, a minimum protein C concentration less than 45% was an independent risk factor for ICU death. Conclusions:In critically ill surgical patients, protein C concentrations were generally low, associated with organ dysfunction/failure, and independently associated with a higher risk of ICU mortality.
Colonic transit time in long-term dialysis patients.

BACKGROUND Constipation is a frequent health concern for long-term dialysis patients. The increased incidence of constipation in long-term dialysis patients is based mainly on self-reported data. Our aim is to investigate this problem objectively by using colonic transit time in long-term hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS Segmental and total colonic transit time studies measured by means of radiopaque markers were conducted in 56 HD patients, 63 CAPD patients, and 25 healthy control subjects. Segmental colonic transit times were calculated separately for 3 segments of the colon (right, left, and rectosigmoid) and total transit time, which was the sum of all 3 segment times. RESULTS Colonic transit time was significantly prolonged in HD patients (43.0 +/- 22.2 versus 32.7 +/- 13.7 hours in CAPD patients and 24.3 +/- 11.9 hours in controls; P < 0.001). Increased colonic transit times in the right and rectosigmoid segments, but not the left segment, contributed to the prolongation in total colonic transit time. Age and interdialytic weight gain correlated well with prolongation of total and segmental colonic transit times in HD patients (P < 0.01). Diabetes and female sex in all groups were associated with longer total and segmental colonic transit times, but this trend was not statistically significant. CONCLUSION Total, right segmental, and rectosigmoid segmental colonic transit times are prolonged in long-term HD patients compared with CAPD patients and healthy controls. We believe colonic transit time measurement is helpful to tailor therapy because it helps define the pathogenesis of constipation.
Estimation of Locomotion Speed and Directions Changes to Control a Vehicle Using Neural Signals from the Motor Cortex of Rat

We have developed a brain-machine interface (BMI) in the form of a small vehicle, which we call the RatCar. In this system, we implanted wire electrodes in the motor cortices of rat's brain to continuously record neural signals. We applied a linear model to estimate the locomotion state (e.g., speed and directions) of a rat using a weighted summation model for the neural firing rates. With this information, we then determined the approximate movement of a rat. Although the estimation is still imprecise, results suggest that our model is able to control the system to some degree. In this paper, we give an overview of our system and describe the methods used, which include continuous neural recording, spike detection and a discrimination algorithm, and a locomotion estimation model minimizes the square error of the locomotion speed and changes in direction
Pain and other symptoms after different treatment modalities of breast cancer.

PURPOSE The aim of this study was to analyse the risk factors that predispose women to chronic symptoms related to the treatment of breast cancer. PATIENTS AND METHODS A questionnaire was sent to 569 women who had undergone modified radical mastectomies with axillary evacuation (MRM) or breast resection with axillary evacuation (BCT). RESULTS Pain, paraesthesias and strange sensations were reported by half of the patients. The chronic pain slightly affected the daily lives of about 50% of the patients and moderately or more the daily lives of about 25% of the patients. Pain was reported significantly more often after BCT than after MRM both in the breast scar (BS) and in the ipsilateral arm (IA). The patients with chronic pain were significantly younger and had larger primary tumours. Postoperative complications increased the incidence of chronic pain in the IA. The highest incidence of pain in the IA was reported by patients who had had both radio- and chemotherapy. The fact that the incidence of pain (IA) had a significant correlation with the incidence of paraesthesias, oedema, strange sensations and muscle weakness may be an indication of nerve injury. CONCLUSIONS Chronic pain was more common after breast-conserving surgery than after radical surgery. Surgical complications and postoperative radiotherapy and chemotherapy increased the risk of chronic pain and other symptoms. Modifications in the treatment protocol and preclusion of postoperative complications may be necessary in order to minimize chronic treatment-related symptoms.
Cultural perspectives in feeding difficulty in Taiwanese elderly with dementia.

OBJECTIVE To investigate factors related to feeding difficulty that is shown in the interaction between nursing assistants and elderly residents with dementia. METHODS Forty-eight residents and 31 nursing assistants were observed during meal times in a congregate dining room of a Taiwanese nursing home specializing in dementia care. Residents' eating behaviors, the dining environment, interactions between the nursing assistant and the residents, and feeding strategies used by nursing assistants were observed. Nutritional data for residents were collected from medical charts. The EdFED Scale #2 and interviews of nursing assistants provided information about feeding difficulty. Interviews also provided data on strategies used to address feeding difficulties. FINDINGS The most frequent feeding difficulty was refusal to eat (37.5%). The strategies used by nursing assistants were limited. Nursing assistants stated they needed more training to address feeding difficulty in residents with dementia. CONCLUSIONS Future research should be focused on the interface between the residents and nursing assistants who must identify various feeding difficulties and select appropriate interventions. CLINICAL RELEVANCE Results might provide information that can be used to develop effective interventions and promote high-quality mealtime care in patients with dementia.
Stable microbial communities in the sponge Crambe crambe from inside and outside a polluted Mediterranean harbor

Marine sponges have been shown to harbor diverse microbial symbiont communities that play key roles in host functioning, yet little is known about how anthropogenic disturbances impact sponge-microbe interactions. The Mediterranean sponge Crambe crambe is known to accumulate heavy metals in polluted harbors. In this study, we investigated whether the microbiome of C. crambe differed between sponges inhabiting a polluted harbor in Blanes (Spain) and a nearby (<1 km) natural environment. Triplicate sponge and ambient seawater samples were collected from each site and the microbial composition of each sample was determined by 16S rRNA gene sequence analysis (Illumina Hi-Seq platform). No significant differences in the diversity or structure of microbial communities in C. crambe were detected between habitats, while a significant difference in community structure was observed in ambient seawater inside and outside of the polluted harbor. The microbiome of C. crambe was clearly differentiated from free-living seawater microbes and dominated by Proteobacteria, specifically a single betaproteobacterium that accounted for >86% of all sequence reads. These results indicate that sponge microbiomes exhibit greater stability and pollution tolerance than their free-living microbial counterparts, potentially mitigating the effects of pollutants on coastal marine communities.
A self-regulating template in human telomerase

Significance The telomerase enzyme is essential for maintaining the replicative capacity of highly prolific cells, such as stem cells and cancer, by synthesizing telomeric DNA onto chromosome ends. Telomerase functions as an RNA–protein complex with an integral telomerase RNA (TR) component. While the templates from all other reverse transcriptases (RTs) merely specify the sequence for nucleotide addition, we found that the human TR template is embedded with a single-residue pausing signal for regulating DNA synthesis. Mutation of this pausing signal alters the fundamental function of telomerase for synthesizing exact telomeric DNA repeats. This is the first instance, to our knowledge, of a single-residue pausing signal found in the RNA template of an RT. Telomerase is a specialized reverse transcriptase (RT) containing an intrinsic telomerase RNA (TR) component. It synthesizes telomeric DNA repeats, (GGTTAG)n in humans, by reiteratively copying a precisely defined, short template sequence from the integral TR. The specific mechanism of how the telomerase active site uses this short template region accurately and efficiently during processive DNA repeat synthesis has remained elusive. Here we report that the human TR template, in addition to specifying the DNA sequence, is embedded with a single-nucleotide signal to pause DNA synthesis. After the addition of a dT residue to the DNA primer, which is specified by the 49 rA residue in the template, telomerase extends the DNA primer with three additional nucleotides and then pauses DNA synthesis. This sequence-defined pause site coincides precisely with the helix paired region 1 (P1)-defined physical template boundary and precludes the incorporation of nontelomeric nucleotides from residues outside the template region. Furthermore, this sequence-defined pausing mechanism is a key determinant, in addition to the P1-defined template boundary, for generating the characteristic 6-nt ladder banding pattern of telomeric DNA products in vitro. In the absence of the pausing signal, telomerase stalls nucleotide addition at multiple sites along the template, generating DNA products with heterogeneous terminal repeat registers. Our findings demonstrate that this unique self-regulating mechanism of the human TR template is essential for high-fidelity synthesis of DNA repeats.
PoF based reliability prediction for cascaded H-bridge converter in drive application

Reliability prediction is widely used in industry for estimating field-reliability of a system before empirical data are available for the system. The two branches of reliability prediction, statistical based method and physics-of-failure based method are adopted in different industry sectors to make full use of their different merits. However, for power converters in electric drive system, the operation conditions of devices change severely and rapidly due to the harsh environment and fast-changing load. The adverse conditions are not well modelled by the statistical based method. Recently, the Physics-of-Failure (PoF) method which models failure mechanism of component draws lots of attention in research of power electronics reliability. This paper evaluate reliability of a power converter in electric drive system with PoF analysis of IGBT. A fast-changing operation profile is defined to mimic real operation of a high power converter in electric drive system. The electro-thermal simulation of a 6.7MW power converter is conducted to obtain the thermal stresses on IGBT and DC-link Capacitor. The PoF analysis results show that load variation rather than the heavy load consumes most the lifetime of IGBT. It is suggested that thermal stress smoothing method is a cost-effective way to improve the system lifetime.
High-throughput transcriptome sequencing identifies candidate genetic modifiers of vulnerability to fetal alcohol spectrum disorders.

BACKGROUND Fetal alcohol spectrum disorders (FASD) is a leading cause of neurodevelopmental disability. Genetic factors can modify vulnerability to FASD, but these elements are poorly characterized. METHODS We performed high-throughput transcriptional profiling to identify gene candidates that could potentially modify vulnerability to ethanol's (EtOH's) neurotoxicity. We interrogated a unique genetic resource, neuroprogenitor cells from 2 closely related Gallus gallus lines having well-characterized robust or attenuated EtOH responses with respect to intracellular calcium mobilization and CaMKII/β-catenin-dependent apoptosis. Samples were not exposed to EtOH prior to analysis. RESULTS We identified 363 differentially expressed genes in neuroprogenitors from these 2 lines. Kyoto Encyclopedia of Genes and Genomes analysis revealed several gene clusters having significantly differential enrichment in gene expression. The largest and most significant cluster comprised ribosomal proteins (38 genes, p = 1.85 × 10(-47) ). Other significantly enriched gene clusters included metabolism (25 genes, p = 0.0098), oxidative phosphorylation (18 genes, p = 1.10 × 10(-11) ), spliceosome (13 genes, p = 7.02 × 10(-8) ), and protein processing in the endoplasmic reticulum (9 genes, p = 0.0011). Inspection of gene ontogeny (GO) terms identified 24 genes involved in the calcium/β-catenin signals that mediate EtOH's neurotoxicity in this model, including β-catenin itself and both calmodulin isoforms. CONCLUSIONS Four of the identified pathways with altered transcript abundance mediate the flow of cellular information from RNA to protein. Importantly, ribosome biogenesis also senses nucleolar stress and regulates p53-mediated apoptosis in neural crest. Human ribosomopathies produce craniofacial malformations and 11 known ribosomopathy genes were differentially expressed in this model of neural crest apoptosis. Rapid changes in ribosome expression are consistently observed in EtOH-treated mouse embryo neural folds, a model that is developmentally similar to ours. The recurring identification of ribosome biogenesis suggests it is a candidate modifier of EtOH vulnerability. These results highlight this approach's efficacy to formulate new, mechanistic hypotheses regarding EtOH's developmental damage.
Autonomous control of interlinking converters in hybrid AC-DC microgrids with energy storages

Coexistence of both ac and dc sub-grids in a hybrid microgrid is likely given that modern distributed sources can either be ac or dc. Linking these sub-grids are power converters, whose topological configuration should preferably be not too unconventional to avoid unnecessary compromises in reliability. The desired operating features should therefore be introduced to the interlinking converters through control design with overall system simplicity still preserved for industry relevance. This concern is now addressed here through the development of an appropriate scheme for controlling the interlinking converters, so as to achieve autonomous control for the overall hybrid microgrid. Features achieved include proportional active power sharing among the distributed sources based on their ratings and not placements within the hybrid microgrid, and proper reactive power sharing within the ac sub-grid. These findings are not previously achieved by other existing schemes, which almost always consider only an ac microgrid. The scheme can also be extended to include energy storages within the interlinking converters, as demonstrated through simulation and experiment.