[Laser-assisted angioplasty in chronic obliterative arteriopathies of the lower limbs. The authors' personal experience].
The laser represents one of the most interesting new methods of vascular surgery. As for laser-assisted angioplasty, the major clinical experience has come with Nd: Yag and Argon lasers. The authors comment on the 1989-1992 series of cases consisting of 51 arteries recanalized with a Nd:Yag laser--the patients were 42 men and 9 women, their mean age being 56.6 years. Four iliac obliterations, 36 femoropopliteal and 11 popliteotibial obliterations were treated surgically, according to the single anatomical radiologic circumstances. The immediate results showed 41 recanalizations (80.4%) 3 perforations (5.9%), 6 dissections (11.8%) and 2 distal emboli (3.9%). The long-term results, with a follow-up period ranging 6 months to 4 years (average: 1.8 years), were investigated with seriated c.w. Doppler, Doppler US and digital venous angiography and showed, in 34 examined patients, 22 patencies (64.7%), 8 stenoses > 50% (23.5%) and 3 occlusions (11.8%). These findings prove the value of laser-assisted--both percutaneous and surgical--angioplasty in the treatment of arterial occlusions both alone and combined with surgery. The results, whose positivity comes also from an eclectic interaction with surgery, and mostly from a systematic enhancement of the laser channel with balloon angioplasty, could be markedly improved upon by means of more selective and effective equipment.


Enhanced oral bioavailability of linagliptin by the influence of gallic acid and ellagic acid in male Wistar albino rats: involvement of p-glycoprotein inhibition.
Background Linagliptin is an antidiabetic drug used for the treatment of type-2 diabetes. The oral bioavailability of linagliptin is low (29.5%) due to its first pass metabolism in the intestine and liver. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. Gallic acid and ellagic acid have been reported to inhibit p-glycoprotein (p-gp) and enhance the bioavailability of p-gp substrate drugs. Hence, the purpose of the study was to evaluate the effect of gallic acid and ellagic acid on intestinal transport and bioavailability of linagliptin, a p-gp substrate in diabetic rats. Methods The intestinal transport of linagliptin was assessed by conducting an in situ single-pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study in diabetic rats. Results After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of linagliptin was observed at the ileum part of the rat intestine. A significant improvement in the peak serum concentration (Cmax) and area under the serum concentration time profile (AUC), AUMC, AUCtotal and decrease in clearance were observed in rats pretreated with gallic acid and ellagic acid. Conclusions This study demonstrates that gallic acid and ellagic acids increase the bioavailability of oral linagliptin in rats due to the inhibition of p-gp. These animal data need to be confirmed in a clinical setting to determine whether linagliptin dosing should be adjusted when given concomitantly with these phytochemicals or gallic acid/ellagic acid-containing dietary supplements.


Genetic determinants of nonmodulating hypertension.
We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C-344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student t test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and chi2 analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235 TT and angiotensin-converting enzyme DD showed further reduction (P=0.0377) when compared with angiotensinogen 235 TT alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 -344 TT genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235 TT significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95% confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme DD was combined with angiotensinogen 235 TT, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.


Critical structure-function determinants within the N-terminal region of pulmonary surfactant protein SP-B.
Surfactant protein SP-B is absolutely required for the surface activity of pulmonary surfactant and postnatal lung function. The results of a previous study indicated that the N-terminal segment of SP-B, comprising residues 1-9, is specifically required for surface activity, and suggested that prolines 2, 4, and 6 as well as tryptophan 9, may constitute essential structural motifs for protein function. In this work, we assessed the role of these two motifs in promoting the formation and maintenance of surface-active films. Three synthetic peptides were synthesized including a peptide corresponding to the N-terminal 37 amino acids of native SP-B and two variants in which prolines 2, 4, 6, or tryptophan 9 were substituted by alanines. All three synthetic peptides were surface-active, as expected from their amphipathic structure. The peptides were also able to insert into dipalmitoylphosphatidylcholine/palmitoyloleoylphosphatidylglycerol (7:3 w/w ratio) monolayers preformed at pressures >30 mN/m, indicating that they perturb and insert into membranes. Substitution of alanine for tryptophan at position 9 significantly decreased both the rate of adsorption/insertion of the peptide into the interface and reinsertion of surface-active material excluded from the film during successive compression-expansion cycles. Substitution of alanines for prolines at positions 2, 4, and 6 did not produce substantial changes in the rate of adsorption/insertion; however, reinsertion of surface-active material into the expanding interface film was not as effective as in the presence of the nativelike peptide. These results suggest that W9 is critical for optimal interface affinity, whereas prolines may promote a conformation that facilitates rapid insertion of the peptide into phospholipid monolayers compressed to the highest pressures during compression-expansion cycling.


Is nodule size an independent predictor of thyroid malignancy?
A decision to proceed with thyroidectomy or to perform more extensive thyroidectomy based on nodule size is controversial. It was our hypothesis that larger nodules are more likely to be malignant, and, as a result, nodule size may be useful for guiding operative decision making. Data was obtained from a prospectively maintained database for patients with nodular thyroid disease evaluated from 1990 to 2007. Logistic regression analysis was performed to determine if there was a significant relationship between nodule size and malignancy based on final pathology. The relationship of nodule size and malignancy was further evaluated for specific diagnostic categories of fine needle aspiration biopsy (FNAB). 1023 patients were evaluated for nodular thyroid disease and 676 underwent thyroidectomy. Mean size was 4.4 +/- 2.4 cm for benign and 3.3 +/- 2.2 cm for malignant nodules (P < .05). The size of benign and malignant nodules, as a function of FNAB, was not significantly different. Increasing nodule size was not predictive of thyroid malignancy suggesting that it should not be used in lieu of FNAB for therapeutic decision making.


Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects.
Coronary endothelial dysfunction is an early marker of coronary artery disease (CAD) but its noninvasive assessment is limited. We tested the hypothesis that diffuse patchy heterogeneous resting myocardial perfusion by noninvasive cardiac PET, quantified objectively by Markovian homogeneity analysis, or its improvement during dipyridamole stress, is a predictor of even mild stress perfusion abnormalities, consistent with coronary microvascular dysfunction as an early marker of CAD. Rest-dipyridamole PET with (82)Rb was performed on 1,034 consecutive subjects for possible CAD or follow-up, for second opinion on revascularization procedures, or for screening because of risk factors and on 50 healthy control subjects. Objective, automated software quantified myocardial PET perfusion images for (i) patchy diffuse perfusion heterogeneity by Markovian homogeneity analysis separately from, independently of, and around significant localized regional perfusion defects; (ii) size and severity of localized regional perfusion defects caused by flow-limiting stenosis; and (iii) the graded base-to-apex longitudinal perfusion gradient due to early diffuse CAD without flow-limiting stenosis. History of vascular risk factors was obtained for all subjects. Resting myocardial perfusion heterogeneity with a homogeneity index outside 1 SD of healthy reference subjects and its improvement with dipyridamole correlated closely with CAD documented by stress-induced regional myocardial perfusion abnormalities outside 1 SD independently of other risk factors by multivariate logistic regression analysis (P < 0.001), by multivariate linear regression analysis (P < 0.001), and by chi(2) analysis (P < 0.001). The relative odds ratios of having stress-induced myocardial perfusion abnormalities for a resting homogeneity index outside 1 SD of healthy reference subjects was highly predictive and substantially greater than for standard risk factors. Patchy heterogeneous resting myocardial perfusion by noninvasive cardiac PET quantified objectively using Markovian homogeneity analysis, and its improvement after dipyridamole, are powerful independent predictors of even mild stress-induced perfusion abnormalities, more than standard risk factors, consistent with coronary microvascular dysfunction as an early marker of preclinical CAD for potential preventive treatment.


Nefro-urological mortality causes in Jerez de los Caballeros (Badajoz) in the nineteenth century.
The causes of mortality from nefro-urologic diseases in Jerez de los Caballeros (Badajoz) during the nineteenth century will be our object of study. We have analyzed the death registry books of the parishes in Jerez. The percentage of deaths from nefro-urologic diseases compared to other pathologies is 0.8%, being most affected males in age ranges from 25-34 and 65-75 years of age. The months with the highest mortality were July, December and January. Due to the deficient death registrations in the first decades of the century, the results should be taken with caution.


Saccade-vergence interactions in macaques. I. Test of the omnipause Multiply Model.
Horizontal vergence eye movements are movements in opposite directions used to change fixation between far and near targets. The occurrence of a saccade during vergence causes vergence velocity to be transiently enhanced. The goal of this study was to test in the monkey the previously described Multiply Model (Zee et al. 1992) that holds that, in humans, the speeding of vergence during a saccade may be the result of the disinhibition of a subgroup of vergence-related neurons by the saccadic omnipause neurons (OPNs). In agreement with the Multiply Model: 1) the onset of the enhancement was closely related to saccadic onset, and thus linked to the onset of the OPN pause; 2) the magnitude of the vergence velocity enhancement was strongly dependent on saccade-vergence timing. Contrary to the Multiply Model: 1) the peak of the vergence velocity enhancement was dependent on saccadic peak velocity; 2) the dependency on saccadic peak velocity was not the indirect result of a dependency on saccadic duration and therefore on the duration of the OPN pause; 3) the decline of the vergence enhancement, identified by the time of the peak of the enhancement velocity, occurred too early to be linked to the end of the OPN pause; 4) vergence enhancement had a saccadic-like peak-velocity/size main sequence. Overall, the evidence is incompatible with the OPN Multiply hypothesis of vergence enhancement. Alternative models are described in an accompanying paper.


Activation of canonical Wnt pathway promotes proliferation of retinal stem cells derived from adult mouse ciliary margin.
Adult retinal stem cells represent a possible cell source for the treatment of retinal degeneration. However, only a small number of stem cells reside in the ciliary margin. The present study aimed to promote the proliferation of adult retinal stem cells via the Wnt signaling pathway. Ciliary margin cells from 8-week-old mice were dissociated and cultured to allow sphere colony formation. Wnt3a, a glycogen synthase kinase (GSK) 3 inhibitor, fibroblast growth factor (FGF) 2, and a FGF receptor inhibitor were then applied in the culture media. The primary spheres were dissociated to prepare either monolayer or secondary sphere cultures. Wnt3a increased the size of the primary spheres and the number of Ki-67-positive proliferating cells in monolayer culture. The Wnt3a-treated primary sphere cells were capable of self-renewal and gave rise to fourfold the number of secondary spheres compared with nontreated sphere cells. These cells also retained their multilineage potential to express several retinal markers under differentiating culture conditions. The Wnt3a-treated cells showed nuclear accumulation of beta-catenin, and a GSK3 inhibitor, SB216763, mimicked the mitogenic activity of Wnt3a. The proliferative effect of SB216763 was attenuated by an FGF receptor inhibitor but was enhanced by FGF2, with Ki-67-positive cells reaching over 70% of the total cells. Wnt3a and SB216763 promoted the proliferation of retinal stem cells, and this was partly dependent on FGF2 signaling. A combination of Wnt and FGF signaling may provide a therapeutic strategy for in vitro expansion or in vivo activation of adult retinal stem cells.


A Wearable Transient Pressure Sensor Made with MXene Nanosheets for Sensitive Broad-Range Human-Machine Interfacing.
Flexible and degradable pressure sensors have received tremendous attention for potential use in transient electronic skins, flexible displays, and intelligent robotics due to their portability, real-time sensing performance, flexibility, and decreased electronic waste and environmental impact. However, it remains a critical challenge to simultaneously achieve a high sensitivity, broad sensing range (up to 30 kPa), fast response, long-term durability, and robust environmental degradability to achieve full-scale biomonitoring and decreased electronic waste. MXenes, which are two-dimensional layered structures with a large specific surface area and high conductivity, are widely employed in electrochemical energy devices. Here, we present a highly sensitive, flexible, and degradable pressure sensor fabricated by sandwiching porous MXene-impregnated tissue paper between a biodegradable polylactic acid (PLA) thin sheet and an interdigitated electrode-coated PLA thin sheet. The flexible pressure sensor exhibits high sensitivity with a low detection limit (10.2 Pa), broad range (up to 30 kPa), fast response (11 ms), low power consumption (10-8 W), great reproducibility over 10 000 cycles, and excellent degradability. It can also be used to predict the potential health status of patients and act as an electronic skin (E-skin) for mapping tactile stimuli, suggesting potential in personal healthcare monitoring, clinical diagnosis, and next-generation artificial skins.


Evaluation of the vocal performance of children using a voice range profile index.
Voice range profiles (VRPs) were analyzed according to 11 frequency, intensity, and morphological characteristics for 94 normal children and 136 children with vocal fold pathologies (ages 6-11 years). Normative data are presented showing marked differences between the groups. Using a specific combination of the child's age, the highest vocal fundamental frequency, the lowest intensity, and the slope of the upper VRP contour, a Voice Range Profile Index for Children (VRPIc) may be constructed using discriminant analysis. It is shown how the VRPIc can be used to screen children for vocal disorder or to quantitatively assess the effectiveness of voice treatment. Since the group means of the VRPIc for healthy and dysphonic children are scaled to +10 and -10, respectively, the VRPIc enables the clinician to rate a child's vocal performance with reference to healthy and dysphonic children in general. The sensitivity and specificity of this method was found to be 90% and 83%, respectively.


Familial Clustering of Aortic Size, Aneurysms, and Dissections in the Community.
Ruptured aortic aneurysm and aortic dissections are potentially preventable disorders associated with high mortality. Screening of individuals at risk may translate into elective surgical interventions and lowered mortality. It is uncertain if the risk of aortic dilation of varying degrees aggregates within families. We investigated the risk of having thoracic and abdominal aortic sizes in the highest quartile (measured by computed tomography scans and indexed for body size) if at least 1 parent did so in the Framingham Heart Study cohorts, and estimated the incidence rates and hazard ratios of developing aortic aneurysm or dissection among first-degree relatives of those with aortic aneurysm or dissection, in comparison with age- and sex-matched controls (1:10 for aortic aneurysm and 1:100 for aortic dissection) using the Danish nationwide administrative registries. In the Framingham Heart Study, offspring (n=235) whose parent(s) had a sex- and age-standardized aortic size in the upper quartile had a multivariable-adjusted ≈3-fold increased odds ratio of belonging to the upper quartile themselves. In Denmark, a total of 68 939 individuals (mean age, 42 years) had a first-degree relative with aortic aneurysm and 7209 persons (mean age, 39 years) had a first-degree relative with aortic dissection. During an average follow-up of 7 years, first-degree relatives of patients with aortic aneurysm and dissection had a hazard ratio of 6.70 (95% CI, 5.96-7.52) for developing aortic aneurysm and a hazard ratio of 9.24 (95% CI, 5.53-15.44) for dissection in comparison with matched controls. These estimates remained unchanged on adjusting for several comorbidities, including prevalent hypertension, bicuspid aortic valve, and the Marfan syndrome. For both aortic aneurysm and dissections, the absolute event rates approached 1 per 1000 person-years for first-degree relatives versus 11 to 13 (aortic aneurysm) and 2 to 3 (aortic dissections) per 100 000 person-years among controls. Increased aortic size, a precursor of aortic aneurysm and a risk factor for dissection, clusters in families. The incidence rates of aortic aneurysm and dissections approach the incidence rates of other common cardiovascular conditions in first-degree relatives, supporting the use of systematic screening for these conditions.


Examining sufficiency and equity in the geographic distribution of physicians in Japan: a longitudinal study.
The objective of this study was to longitudinally examine the geographic distribution of physicians in Japan with adjustment for healthcare demand according to changes in population age structure. We examined trends in the number of physicians per 100 000 population in Japan's secondary medical areas (SMAs) from 2000 to 2014. Healthcare demand was adjusted using health expenditure per capita. Trends in the Gini coefficient and the number of SMAs with a low physician supply were analysed. A subgroup analysis was also conducted where SMAs were divided into 4 groups according to urban-rural classification and initial physician supply. The time-based changes in the Gini coefficient and the number of SMAs with a low physician supply indicated that the equity in physician distribution had worsened throughout the study period. The number of physicians per 100 000 population had seemingly increased in all groups, with increases of 22.9% and 34.5% in urban groups with higher and lower initial physician supply, respectively. However, after adjusting healthcare demand, physician supply decreased by 1.3% in the former group and increased by 3.5% in the latter group. Decreases were also observed in the rural groups, where the number of physicians decreased by 4.4% in the group with a higher initial physician supply and 7.6% in the group with a lower initial physician supply. Although the total number of physicians increased in Japan, demand-adjusted physician supply decreased in recent years in all areas except for urban areas with a lower initial physician supply. In addition, the equity of physician distribution had consistently deteriorated since 2000. The results indicate that failing to adjust healthcare demand will produce misleading results, and that there is a need for major reform of Japan's healthcare system to improve physician distribution.


The epidemiology of teen suicide: an examination of risk factors.
The information presented here is on the incidence of suicide in the United States and in other countries where reporting procedures are reliable. The problem of underreporting is discussed and put into perspective. Secular trends in suicide incidence are presented, and it is shown how these have varied a great deal for different age groups. Age, ethnic, and cultural differences in incidence are demonstrated, and explanatory theories for these differences are put forward. The phenomenon of cluster suicide is described, and possible explanations for this are discussed. The limitations of death certificate data and the advantages (and limitations) of the psychological autopsy method are presented. Results from previous psychological autopsy studies on epidemiologically sound samples are summarized. Results (preliminary) from a current psychological autopsy study on consecutive adolescent suicides in the New York Metropolitan area are presented. Family history data and diagnostic profiles of completed suicides are emphasized.


Beta-thalassemia mutations in Denizli province of Turkey.
Beta-thalassemia is one of the most common genetic disorders in Turkey as well as in several other Mediterranean countries presenting microcytosis and hemolytic anemia. The city of Denizli is located in the inner part of the Aegean geographical region of Turkey. The beta-thalassemia incidence in Denizli province is in between 2.6-3.7% reported by different researchers. According to our results; the IVS-1/nt-110 (G>A) is the most frequent mutation type in our province the same as other geographical regions of Turkey. Here we report also two HbD-Los Angeles/beta-thalassemia combinations, which are HbD-Los Angeles/codon 39 (C>T) and HbD-Los Angeles/IVS-1/nt-1 (G>A), respectively. In conclusion, our preliminary results show the heterogeneity of the beta-thalassemia mutations in the province of Denizli.


Decreased natural killer cell activity in patients with invasive cervical carcinoma.
The cell-mediated immunity in 21,12,14 and 12 patients with preinvasive, stage I and II invasive cervical carcinoma, and in controls respectively, was studied. Lymphocyte subpopulations were enumerated using specific monoclonal antibodies (moAbs) of the Leu series (Leu2, Leu3, Leu4, Leu11b, and Leu15). Double stain using fluorescein-isothiocyanate (FITC) conjugated Leu2 moAb and phycoerythrin (PE) conjugated Leu15 moAb was applied to distinguish cytotoxic T-cells from suppressor T-cells. A 4-hour 51Cr-release assay was used to measure natural killer (NK) cell activity. The results showed that there was no significant difference in lymphocyte subpopulations among these 4 studied groups. However, the NK activity tended to be lower in patients with invasive cervical carcinoma (stage I and II) especially at a high effector/target ratio of 100. It is therefore concluded that functional cytotoxicity assay is more informative in evaluating the status of cell-mediated immunity against tumors than the enumeration of lymphocyte subsets.


Aged men display blunted biorhythmic variation of muscle performance and physiological responses.
Aging is known to disrupt the "biological clock" that governs physiological variables at rest. This study sought to determine whether aged men demonstrated biorhythmic variation in muscle performance during resistance exercise and physiological responses to that stimulus. Ten aged (75.6 +/- 1.6 yr; mean +/- SE) men completed an isokinetic testing protocol of knee extensors and flexors at 0800, 1200, 1600, and 2000 h. Although time of day variation in peak torque was detectable, significant (P < or = 0.05) oscillation was established only in the knee flexors at 3.14 rad/s. Heart rate, blood pressure, and rectal temperature displayed no significant variation, but trends (P < 0.10) in oscillation of postexercise blood pressure and rectal temperature were noted. Temporal patterns in biorhythmic variation of muscle performance, as well as thermal and cardiovascular measures, emulated those observed in a previous study involving young men where the magnitude of variation was sufficient to achieve statistical significance. Similar to our earlier findings in young men, however, pre- and postexercise testosterone and cortisol concentrations demonstrated significant variation among aged men. These data confirm the blunting of biorhythmic variation in muscle performance and physiological variables, except for circulating hormones, in aged men.


Expression of GFP in nuclear transplants generated by transplantation of embryonic cell nuclei from GFP-transgenic fish into nonenucleated eggs of medaka, Oryzias latipes.
In order to investigate whether foreign genes can be used as genetic markers of donor nuclei in fish nuclear transplantation, expression of the GFP gene derived from donor nuclei was examined in nuclear transplants in medaka (Oryzias latipes). Embryonic nuclei were obtained from blastula embryos produced by crossing of transgenic fish of the wild-type strain heterozygous for the GFP gene with nontransgenic ones or by mutual crossing between transgenic fish. The GFP gene was driven by the promoter of the medaka elongation factor gene, EF-1alpha-A, which is known to induce GFP expression in many tissues except for the muscle in the transgenic fish. The nuclei were transplanted into nonenucleated unfertilized eggs of the orange-red strain. Adult nuclear transplants were successfully obtained at the rate of about 2% of the operated eggs. They were triploid and had no reproductive potential. The GFP gene was expressed in embryos, fry, and adults of nuclear transplants in a pattern similar to that in the transgenic fish. These results indicate that GFP is useful as a foreign genetic marker of donor nuclei in fish nuclear transplantation.


Epigenetic Changes in Host Ribosomal DNA Promoter Induced by an Asymptomatic Plant Virus Infection.
DNA cytosine methylation is one of the main epigenetic mechanisms in higher eukaryotes and is considered to play a key role in transcriptional gene silencing. In plants, cytosine methylation can occur in all sequence contexts (CG, CHG, and CHH), and its levels are controlled by multiple pathways, including de novo methylation, maintenance methylation, and demethylation. Modulation of DNA methylation represents a potentially robust mechanism to adjust gene expression following exposure to different stresses. However, the potential involvement of epigenetics in plant-virus interactions has been scarcely explored, especially with regard to RNA viruses. Here, we studied the impact of a symptomless viral infection on the epigenetic status of the host genome. We focused our attention on the interaction between Nicotiana benthamiana and Pelargonium line pattern virus (PLPV, family Tombusviridae), and analyzed cytosine methylation in the repetitive genomic element corresponding to ribosomal DNA (rDNA). Through a combination of bisulfite sequencing and RT-qPCR, we obtained data showing that PLPV infection gives rise to a reduction in methylation at CG sites of the rDNA promoter. Such a reduction correlated with an increase and decrease, respectively, in the expression levels of some key demethylases and of MET1, the DNA methyltransferase responsible for the maintenance of CG methylation. Hypomethylation of rDNA promoter was associated with a five-fold augmentation of rRNA precursor levels. The PLPV protein p37, reported as a suppressor of post-transcriptional gene silencing, did not lead to the same effects when expressed alone and, thus, it is unlikely to act as suppressor of transcriptional gene silencing. Collectively, the results suggest that PLPV infection as a whole is able to modulate host transcriptional activity through changes in the cytosine methylation pattern arising from misregulation of methyltransferases/demethylases balance.


[Morphogenesis of central and peripheral arteriopathies in the hypertensive rat. 2. Histochemical aspects].
Twenty-seven enzyme activities and five macromolecular complexes in central and peripheral arteries of the spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) 4, 20, 30 and 60 week-old rats were comparatively studied. Some of the four-week-old SHR (prehypertensive stage) showed several enzyme-cytochemical differences in comparison with WKY of the same age. In the adult SHR (20 to 60 weeks), the metabolic behaviour of different arterial segments was not uniform. Thus, the arteriopathy of elastic-type arteries was reflected by early and permanent activation of 5' nucleotidase and by the early increase (between 5 and 30 weeks) and later decrease (60th week) of esterase-and cholinesterase-activity. Peripheral arteriopathy was evidenced by hyperactivity and/or hypoactivity of glycogen-synthetase, glycogen-phosphorylase and monamine oxidase (in muscular-type arteries) and by early (5th week) and long lasting (60th week) hyperactivity of alcaline phosphatase (in arterioles). Some parameters were modified throughout the whole vasculature: increase in RNA, glycosaminoglycans, and glycoproteins, heightened lysosomal and dehydrogenase enzyme activities. Certain reported chemical modifications are discussed in connection with atherogenesis (carboxylic esterases and glycosaminoglycans) and peripheral tensiogenesis (5' nucleotidase, alcaline phosphatase, L-amino-peptidase, MAO).


Calcium Channel Opening Rather than the Release of ATP Causes the Apoptosis of Osteoblasts Induced by Overloaded Mechanical Stimulation.
Stress fracture is one of the most common overuse injuries in athletes. Overloaded mechanical stimulation is an important factor affecting stress fractures, but the mechanism is unclear. MC3T3-E1 cells and a polycaprolactone (PCL) scaffold were co-cultured, and finite element analysis (FEA) was used to analyze the load-carrying capability. Cell proliferation was investigated with CCK-8 assays. An alkaline phosphatase (AKP) activity assay was used to evaluate cell differentiation. Cell apoptosis was analyzed using Hoechst/ PI double-labeling, Caspase-3 activity and lactate dehydrogenase (LDH) activity assays. Realtime PCR and Western blotting were used to examine the gene and protein expression, respectively, of Caspase-3 and Caspase-9. Assays of the intracellular calcium with fluorescent probe technique and extracellular ATP with fluorometric assay kit were used to analyze the changes in the intracellular calcium concentration induced by calcium channel opening and the release of ATP, respectively, at different operation times. When the apparent strain reached 10000 µε, the strain scope of fber at levels greater than 4000 µε was 60%. Overloading for 4 days and operation times of 0.5 h and 2 h increased the cell number and AKP secretion. However, apoptosis genes were activated at the same time, and the operation time of 2 h had a significantly greater effect than 0.5 h. At 8 days, the cell numbers were greater for the operation time of 0.5 h than for 2 h, and the 2-h groups had the fastest apoptosis rate. Overloading for 1 day increased intracellular calcium levels and ATP release. The increase in intracellular calcium could be blocked by the addition of N-ethylmaleimide (NEM) or Hank's medium. Overloading for 8 days increased intracellular calcium levels but decreased extracellular ATP, and verapamil blocked the increase in intracellular calcium. We found that a simultaneous 'double effect' on osteoblasts was induced by overloading, which promoted cell proliferation, differentiation and apoptosis. Short-term overloading could open the cell membrane calcium channels and release calcium stores to elevate intracellular calcium levels, thereby promoting the proliferation and differentiation of cells to a greater extent than the effect of apoptosis. For long-term overloading, calcium channel opening in the membrane could lead to overloading of intracellular calcium levels, inducing an apoptosis effect that is greater than the effect on proliferation and differentiation.


Synthesis, structure and magnetism of new single molecule magnets composed of MnII2MnIII2 alkoxo-carboxylate bridged clusters capped by triethanolamine ligands.
A family of tetranuclear mixed-valent Mn(II)(2)/Mn(III)(2) complexes of type [Mn(4)(LH(2))(2)(LH)(2)(H(2)O)(x)(RCO(2))(2)](Y)2.nS has been synthesised and structurally characterised, where LH(3) = triethanolamine (N(CH(2)CH(2)OH)(3)), (R=CH(3), x=2, Y = CH(3)CO(2)-, n=2, S = H(2)O; 1), (R=C(6)H(5), x=0, Y=C(6)H(5)CO(2)-, n=1, S = CH(3)CN; 2), (R=C(2)H(5), x=0, Y=ClO(4)(-), n=0; 3). A common structural core was deduced from X-ray crystallography and consists of a rhomboidal (planar-diamond) array with two 7-coordinate Mn(II) "wingtip (w)" centres and two 6-coordinate Mn(III) "body (b)" centres. The Mn(III) ions are bridged to the Mn(II) ions by mu3-oxygen atoms from a deprotonated alcohol "arm" of each tridentate LH(2-) ligand and by mu2-oxygen atoms from each tetradentate LH(2)(-) ligand. The four nitrogen atoms from LH(2-) and LH(2)(-) groups, together with bridging and terminal carboxylates oxygens complete the outer coordination sites around the Mn atoms. A feature of these clusters is that they are linked together in the crystal lattice by hydrogen-bonding interactions involving a non-coordinated hydroxyl arm on each LH(2-) group. Detailed DC and AC magnetic susceptibility measurements and magnetisation isotherms have been made on the three complexes and show that intra-cluster ferromagnetic coupling is occurring between the S = 2 Mn(III) and S = 5/2 Mn(II) ions to yield S = 9 ground states. The g, J(bb) and J(wb) parameters have been deduced. Inter-cluster antiferromagnetic coupling was noted in and this influences the magnetisation versus field behaviour and the temperature and magnitude of the out-of-phase AC chi"M maxima in comparison to those observed for and. An Arrhenius plot of the reciprocal temperature of the maxima in chi"M obtained at different frequencies (10 to 1500 Hz), in the range 1.75 K to 4 K, against the natural logarithm of the magnetization relaxation rate (1/tau) yielded values of the activation energies and pre-exponential factors for two of these new tetranuclear single-molecule magnets (SMMs), and. The activation energies were compared with the potential energy barrier height, U, for magnetisation direction reversal (U = DS(2)) using the axial zero-field splitting parameter, D, deduced from the DC M/H isotherm analysis for these S = 9 species. The very small separation of S = 9 and 8 levels for these clusters highlights the limitations in the determination of D values from M/H data at low temperatures.


The DNA polymerase genes of several HMU-bacteriophages have similar group I introns with highly divergent open reading frames.
A previous report described the discovery of a group I, self-splicing intron in the DNA polymerase gene of the Bacillus subtilis bacteriophage SPO1 (1). In this study, the DNA polymerase genes of three close relatives of SPO1: SP82, 2C and phi e, were also found to be interrupted by an intron. All of these introns have group I secondary structures that are extremely similar to one another in primary sequence. Each is interrupted by an open reading frame (ORF) that, unlike the intron core or exon sequences, are highly diverged. Unlike the relatives of Escherichia coli bacteriophage T4, most of which do not have introns (2), this intron seems to be common among the relatives of SPO1.


Cre-mediated recombination in pituitary somatotropes.
We report a transgenic line with highly penetrant cre recombinase activity in the somatotrope cells of the anterior pituitary gland. Expression of the cre transgene is under the control of the locus control region of the human growth hormone gene cluster and the rat growth hormone promoter. Cre recombinase activity was assessed with two different lacZ reporter genes that require excision of a floxed stop sequence for expression: a chick beta-actin promoter with the CMV enhancer transgene and a ROSA26 knock-in. Cre activity is detectable in the developing pituitary after initiation of Gh transcription and persists through adulthood with high penetrance in Gh expressing cells and lower penetrance in lactotropes, a cell type that shares a common origin with somatotropes. This Gh-cre transgenic line is suitable for efficient, cell-specific deletion of floxed regions of genomic DNA in differentiated somatotropes and a subset of lactotrope cells of the anterior pituitary gland.


12 days of altitude exposure at 1800 m does not increase resting metabolic rate in elite rowers.
Four elite rowers completed a 12-day altitude training camp living at 1800 m, and training at 1800 m and 915 m, to assess changes in resting metabolic rate (RMR). RMR and body composition were assessed pre- and postcamp. Downward trends in RMR and body composition were observed postaltitude: absolute RMR (percent change: -5.2%), relative RMR (-4.6%), body mass (-1.2%), and fat mass (-4.1%). These variations are likely related to the hypoxic stimulus and an imbalance between training load and energy intake.


Chemoprevention in Lynch syndrome.
CAPP1 tested aspirin 600 mg/day and/or resistant starch 30 g/day in 200 adolescent FAP carriers. Aspirin treatment resulted in a non-significant reduction in polyp number and a significant reduction in polyp size among patients treated with aspirin for more than 1 year. CAPP2 RCT used the same interventions in 937 Lynch syndrome patients, the first RCT to have cancer prevention as the primary endpoint. Aspirin did not reduce the risk of colorectal neoplasia in a mean treatment period of 29 months but double blind post intervention follow-up has revealed 48 participants developed 53 CRCs. Per protocol analysis showed 63% fewer colon cancers with aspirin (p = 0.008) apparent from 4 years, with a similar effect on other LS cancers. Resistant starch was not beneficial at long term followup. CAPP3 will involve a double blind dose non-inferiority trial comparing 100, 300 or 600 mg daily in 3,000 gene carriers. We can now recommend aspirin in people at high risk of colorectal cancer.


Rab7 Is Associated with Poor Prognosis of Gastric Cancer and Promotes Proliferation, Invasion, and Migration of Gastric Cancer Cells.
BACKGROUND Rab7 belongs to the Ras oncogene family. Many studies have shown that its dysfunction is associated with many types of malignant tumors, but its effect on the pathogenesis of gastric cancer (GC) is still unknown. Therefore, we investigated the effect and mechanism of Rab7 in GC. MATERIAL AND METHODS The expression of Rab7 in GC and adjacent tissues was detected by immunohistochemistry, Western blot analysis, and qRT-PCR. The relationship of Rab7 with clinicopathological parameters and prognosis was analyzed. The expressions of Rab7, PI3K, and AKT in GC cells were assessed by Western blot. Overexpressed and silenced GC cell lines were constructed and AGS cells were treated with LY294002. The proliferation capacity of GC cells was detected by CCK8 assay, cell cycle changes were detected by flow cytometry, and the invasion and migration abilities of GC cells were assessed by transwell assay. RESULTS The expression of Rab7 was upregulated in the samples and cells, and was positively correlated with lymph node metastasis but negatively correlated with histological differentiation and clinical prognosis. In cell function experiments, overexpression of Rab7 induced the transition from S phase to G2 phase and promoted the proliferation, invasion, and migration of GC cells. Our assessment of the molecular mechanism showed that Rab7 promoted the phosphorylation of PI3K and AKT in GC cells. Incubation with the PI3K inhibitor Ly294002 impaired the enhanced effect of Rab7 overexpression on proliferation, migration, and invasion abilities of GC cells. These results show that the Rab7 affects GC cell progression by modulating the PI3K/AKT pathway. CONCLUSIONS Rab7 could be a prognostic biomarker and therapeutic target of the PI3K/AKT pathway in GC.


Effect of ω-9MUFAs in Fat Emulsion on Serum Interleukin-6 in Rats with Lipopolysaccharide-induced Lung Injury.
This study aimed to investigate how ω-9 MUFAs in fat emulsion affect serum IL-6 levels in rats with lipopolysaccharide (LPS)-induced lung injury. Research suggests that acute lung injury (ALI) develops acute respiratory distress syndrome (ARDS) due to the activation of many inflammatory factors. ALI may be treated by reducing inflammation. Fat emulsion is used in parenteral nutrition for critically ill patients to regulate the body's inflammatory response. It is mostly made up of ω-9 MUFAs (Clinoleic), which can regulate the inflammatory response. The effect of ω-9MUFAs on the secretion of IL-6 in ALI rats was studied in order to provide a basis for the rational use of fat emulsion in clinical practice and provide new ideas for the diagnosis and treatment of ALI. The control, model, and -9MUFAs groups consisted of 18 female Sprageue-Dawley (SD) young rats (180 ± 20 g). The SD young rats received normal saline and were not operated. LPS-induced ALI animals received tail vein injections of normal saline. SD young rats were first triggered with acute lung injury by LPS (3 mg/kg) and then injected with 3 mg/kg of ω-9MUFAs via the tail vein. The expression levels of IL-6, an activator of signal transduction transcription 3 (STAT3), transforming growth factor-β (TGF-β), and glycoprotein 130 (GP130) in serum and lung tissues were determined by ELISA and Western blot methods. Compared with the model group, the survival rate of rats in the ω-9 MUFAs group was significantly increased, and the difference was statistically significant (p<0.05). Compared with the model group, the lung pathology of rats in the ω-9 MUFAs group was significantly improved, and the expression levels of IL-6, TGF-β1, GP130, IL-1 and other proteins were significantly decreased. The difference was statistically significant (p<0.05). In LPS-induced lung injury, ω-9MUFAs may alleviate symptoms by inhibiting the IL-6/GP130/STAT3 pathway.


Prevalence and predictors of cardiac hypertrophy and dysfunction in patients with Type 2 diabetes.
The aim of the present study was to determine the prevalence and predictors of an abnormal echocardiogram in patients with Type 2 diabetes. Cardiac function and structure were rigorously assessed by comprehensive transthoracic echocardiographic techniques in 229 patients with Type 2 diabetes. Cardiovascular risk factors and diabetic complications were assessed, and predictors of an abnormal echocardiogram were identified using multivariate logistic regression analysis. An abnormal echocardiogram was present in 166 patients (72%). LVH (left ventricular hypertrophy) occurred in 116 patients (51%), and cardiac dysfunction was found in 146 patients (64%), of whom 109 had diastolic dysfunction alone and 37 had systolic+/-diastolic dysfunction. Independent predictors of an abnormal echocardiogram were obesity, age, the number of antihypertensive drugs used (all P<0.001) and creatinine clearance (P<0.05). The risk of an abnormal echocardiogram increased by 9% for each year over 50 years of age {OR (odds ratio), 1.09 [95% CI (confidence interval), 1.04-1.15]}, 3-fold if obesity was present [BMI (body mass index) >30; OR, 4.2 (95% CI, 1.9-9.0)] and by 80% for each antihypertensive agent used [OR, 1.8 (95% CI, 1.3-2.4) per agent]. In conclusion, an abnormal cardiac echocardiogram is common in patients with Type 2 diabetes. Importantly, although cardiac abnormalities can be predicted by traditional risk factors, such as age, obesity and renal function, the absence of micro- or macro-vascular complications does not predict a normal echocardiogram. We suggest that an echocardiogram identifies those with Type 2 diabetes at increased cardiovascular risk due to occult LVH and diastolic dysfunction, and this information may lead to more aggressive management of known risk factors in the clinic.


Real-time reverse transcription PCR-based sequencing-independent pathotyping of Eurasian avian influenza A viruses of subtype H7.
Low pathogenic avian influenza viruses (LPAIV) of the subtypes H5 and H7 are known to give rise to highly pathogenic (HP) phenotypes by spontaneous insertional mutations which convert a monobasic trypsin-sensitive endoproteolytical cleavage site (CS) within the hemagglutinin (HA) protein into a polybasic subtilisin-sensitive one. Sporadic outbreaks of notifiable LPAIV H7 infections are continuously recorded in Europe and in Asia, and some lineages showed zoonotic transmission. De novo generation of HPAIV H7 from LPAIV precursors has been reported several times over the past decade. Rapid differentiation between LP and HP H7 virus strains is required as a prerequisite to emplace appropriate control measures. Here, reverse transcription real-time PCR assays (RT-qPCR) were developed and evaluated that allow LP and HP pathotype identification and distinction by probe-assisted detection of the HACS. These new RT-qPCRs allow a sensitive and highly specific pathotype identification of Eurasian subtype H7 AIV in allantoic fluids as well as in diagnostic field samples. RT-qPCR assisted pathotyping presents a rapid and sensitive alternative to pathotyping by animal inoculation or nucleotide sequencing.


The Cl Functionalized Aluminum Nitride (AlN) and Aluminum Phosphide (AlP) Nanocone Sheets as Hydrogen Selenide (H2Se) Sensor: a Density Functional Investigation.
The adsorption of H2Se molecule on AlN-NCS and AlP-NCS surfaces were investigated by using of DFT calculations. The potentials of Cl-functionalized AlN-NCS and AlP-NCS for H2Se adsorption were examined. All processes of H2Se-adsorption on considered nanocone sheets were exothermic reactions. The calculated |Ead| amount of complex H2Se with AlP-NCS was higher than AlN-NCS. The functionalization of considered nanocone sheets with Cl atom increase |Ead| amount of H2Se. Results reveal that, obtained Ead amounts of considered nanocone sheets have linear relationships with corresponding orbital energy amounts. Finally, the novel nanocone sheets with higher efficiency to adsorption of H2Se can be proposed.


From c-Fos to MMP-9: In control of synaptic plasticity to produce healthy and diseased mind, a personal view.
c-Fos is a component of AP-1 transcription factor. Three lines of evidence support pivotal role of c-Fos in learning and memory: (i) learning experience markedly enhances its expression; (ii) blocking od c-Fos impairs, while optogenetic activation of c-Fos expressing neurons supports learning and memory; (iii) c-Fos/AP-1 gene targets in activated neurons, encoding tissue inhibitor of metalloproteinases-1 (TIMP-1) and matrix metalloproteinase 9 (MMP- 9) play a major role in synaptic plasticity that underlies learning and memory. TIMP-1 and MMP-9 compose an extracellularly operating enzymatic system active locally around excitatory synapses to modulate their morphology, molecular content and efficacy. Animal studies have implicated MMP-9 in a variety of neuropsychiatric conditions, e.g., epileptogenesis, autism spectrum disorders, development of addiction, and depression. In humans, MMP-9 contributes to epilepsy, alcohol and cocaine addiction, Fragile X Syndrome, schizophrenia and bipolar disorder. In aggregate, all those conditions can be considered as reflecting either healthy or diseased mind.


Predicting the Features of Methane Adsorption in Large Pore Metal-Organic Frameworks for Energy Storage.
Currently, metal-organic frameworks (MOFs) are receiving significant attention as part of an international push to use their special properties in an extensive variety of energy applications. In particular, MOFs have exceptional potential for gas storage especially for methane and hydrogen for automobiles. However, using theoretical approaches to investigate this important problem presents various difficulties. Here we present the outcomes of a basic theoretical investigation into methane adsorption in large pore MOFs with the aim of capturing the unique features of this phenomenon. We have developed a pseudo one-dimensional statistical mechanical theory of adsorption of gas in a MOF with both narrow and large pores, which is solved exactly using a transfer matrix technique in the Osmotic Ensemble (OE). The theory effectively describes the distinctive features of adsorption of gas isotherms in MOFs. The characteristic forms of adsorption isotherms in MOFs reflect changes in structure caused by adsorption of gas and compressive stress. Of extraordinary importance for gas storage for energy applications, we find two regimes of Negative gas adsorption (NGA) where gas pressure causes the MOF to transform from the large pore to the narrow pore structure. These transformations can be induced by mechanical compression and conceivably used in an engine to discharge adsorbed gas from the MOF. The elements which govern NGA in MOFs with large pores are identified. Our study may help guide the difficult program of work for computer simulation studies of gas storage in MOFs with large pores.


Cosecretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets following stimulation or inhibition of beta-cell function.
The aim of this work was to simultaneously study the secretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets in vitro. For examination of stimulated beta-cells, nutrient secretagogues (16.7 mM glucose, 10 mM leucine + 2 mM glutamine), phosphodiesterase inhibition (5 mM theophylline), a sulphonylurea (0.5 microgram/ml glipizide), a non-nutrient amino acid (10 mM arginine), cholinergic stimulation (0.1 mM carbamylcholine) and insulinotropic peptides (0.1 microM vasoactive intestinal polypeptide and 0.1 microM glucagon), were used. For beta-cell suppression glucose phosphorylation inhibition (10 mM mannoheptulose), depletion of extracellular calcium, activation of the ATP-regulated K(+)-channel (0.5 mM diazoxide), adrenoreceptor stimulation (3 microM adrenaline), paracrine modulation (0.1 microM somatostatin), short-term treatment with a selective beta-cytotoxin (1.1 and 2.2 mM streptozotocin) and long-term treatment with a cytokine (25 U/ml interleukin-1 beta), were studied. The compounds with known effects on insulin secretion exerted their expected actions and this was paralleled by similar relative changes, with a possible exception for glucagon, in the IAPP secretion. The ratio of IAPP/insulin released did not change significantly under any of the tested experimental conditions, except for a slight increase following carbamylcholine stimulation. On a molar basis approx. 1% of IAPP was released when compared with insulin. These results are consistent with the hypothesis that the regulation of IAPP secretion from beta-cells of isolated rat pancreatic islets is essentially regulated by the same mechanisms as insulin secretion.


Iterative reconstruction can permit the use of lower X-ray tube current in CT coronary artery calcium scoring.
CT coronary artery calcium scoring (CACS) is additive to traditional risk factors for predicting future cardiac events but is associated with relatively high radiation doses. We assessed the feasibility of CACS radiation dose reduction using a lower tube current and iterative reconstruction (IR). Artificial noise was added to the raw data from 27 CACS studies from patients who were symptomatic to simulate lower tube current scanning (75, 50 and 25% original current). All studies were performed on the same CT scanner at 120 kVp. Data were reconstructed using filtered back projection [Quantum Denoising Software (QDS+)] and IR [adaptive iterative dose reduction three dimensional mild, standard and strong]. Agatston scores were independently measured by two readers. CACS percentile risk scores were calculated. At 75, 50 and 25% tube currents, all adaptive iterative dose reduction (AIDR) reconstructions decreased image noise relative to QDS+ (p < 0.05). All AIDR reconstructions resulted in small reductions in Agatston score relative to QDS+ at the standard tube current (p < 0.05). Agatston scores increased with QDS+ at 75, 50 and 25% tube current (p < 0.05), whereas no significant change was observed with AIDR mild at any tested tube current. No difference in the percentile risk score with AIDR mild at any tube current occurred compared with QDS+ at standard tube current (p > 0.05). Interobserver agreement for AIDR mild remained excellent even at 25% tube current (intraclass correlation coefficient 0.997). Up to 75% reduction in CACS tube current is feasible using AIDR mild. AIDR mild IR permits low tube current CACS whilst maintaining excellent intraobserver and interobserver variability and without altering risk classification.


On some roots of creativity.
The possibility has to be considered that the infant, in danger of overwhelming himself with his own excitement, forms object-representations in ways dictated by expediency. It is necessary for survival to establish in one's mind an all-powerful and loving object-representation that contains in it major parts of the self-representation. In fact, all the vital and affective functions are attributed to the parenting object and are used only under a "franchise-like" illusion. From infancy we are just like the "hypnotized" person or the patient who has received a placebo and carries out self-caring or self-soothing functions under the illusion that he/she is not doing it on their own but the transference object is doing it. In considering the challenge of creating a coherent self-representation within the amazing world of perceptions and affects, it can be readily seen that it is very easy to overwhelm oneself, even for an adult just trying to imagine it. It is most helpful to use Stern's suggestion that probably a sense of self emerges gradually from the consolidation of various nuclear clusters of self-views. He listed (1) a self-agency, representing the recognition of one's volition and capacity to act; (2) a sense of self-coherence, representing a sentience of what remains constant within one's own purveyance; (3) a sense of self-affectivity, representing the recognition of feelings, that is, the subjective aspect of affective living; and (4) a sense of self-history, representing a registration of continuity and a recognition of what "goes on being." In our perusal of what we can learn by confronting the alexithymia picture lessons from developmental psychobiology and direct observations of infant behavior, we get useful clues to the origins of creativity. The epigenetic history of affects and the development of affect tolerance show us how these functions evolve in the context of the interaction of the infant and mother. The success in containing one's own excitement and keeping one's affects in manageable intensity so that they are useful for information processing is made possible by congruent responses of the mothering parent. This situation prolongs the illusions of symbiosis and omnipotence to their optimal duration, permitting a period of guilt-free practicing of self-soothing and self-gratification. By not forcing the conscious recognition of mother's externality and the confrontation with one's own rage and helplessness, the mother helps the infant to avoid a premature formation of an "external" object-representation.(ABSTRACT TRUNCATED AT 400 WORDS)


Non-linear EEG synchronization during observation and execution of simple and complex sequential finger movements.
The main aim of this study was to examine the temporal aspects of neuronal changes during the observation and execution of simple and complex tasks to gain a greater understanding of the mirror neuron system's involvement in complex motor tasks. Eleven right-handed subjects observed simple and complex finger movement sequences. Electroencephalograms were recorded from 19 electrodes. Activity was considered in four frequency bands (8-10, 10-13, 13-20, and 20-30 Hz) using a new measure, synchronization likelihood. The results show that motor tasks of different levels of complexity did not have a significant influence on cortical synchronization. The results also provide additional indirect evidence for mirror neuron activity associated with intransitive tasks. Data are discussed in the light of recent findings from the cognitive and behavioral neuroscience literature.


Exploring the planning practices of nurse managers in the unit: a study of nurse managers in the greater Accra region.
Nurse managers' planning practices are essential to the practice of management in the unit, and the overall efficiency of the healthcare service delivery. This study aims to explore the planning practices of nurse managers in the Greater Accra Region, Ghana. A descriptive phenomenological design was employed to explore nurse managers' planning practices. In total, 15 nurse managers and 47 nurses from 19 primary and secondary hospitals of the Ghana Health Service and two specialized hospitals in the Greater Accra Region, Ghana, were involved in the study. Data were collected using semi-structured interview guides and probes. The findings suggested that plans were widely common to all the units of the hospitals and were considered satisfactory by nurse managers. However, most of these plans were not effectively utilized. Nurse managers had only fair knowledge about the planning process and were moderately involved and communicated ideas to colleagues in the process. Furthermore, nurse managers do not frequently share the vision neither do they even communicate expectations to achieve unit goals and objectives with subordinates. The research emphasizes the relevance of planning in healthcare management. It highlights the management practice of planning in the context of nurse managers and accentuates the values the healthcare system derives with effective planning practices.


Carboxylate Adsorption on Rutile TiO2(100): Role of Coulomb Repulsion, Relaxation, and Steric Hindrance.
Understanding the adsorption and photoactivity of acetic acid and trimethyl acetic acid on TiO2 surfaces is important for improving the performance of photocatalysts and dye-sensitized solar cells. Here we present a structural study of adsorption on rutile TiO2(100)-1 × 1 and -1 × 3 using Scanning Tunnelling Microscopy and Density Functional Theory calculations. Exposure of both terminations to acetic acid gives rise to a ×2 periodicity in the [001] direction (i.e., along Ti rows), with a majority ordered c(2 × 2) phase in the case of the 1 × 1 termination. The DFT calculations suggest that the preference of c(2 × 2) over the 2 × 1 periodicity found for TiO2(110)-1 × 1 can be attributed to an increase in interadsorbate Coulomb repulsion. Exposure of TiO2(100)-1 × 1 and -1 × 3 to trimethyl acetic acid gives rise to largely disordered structures due to steric effects, with quasi-order occurring in small areas and near step edges where these effects are reduced.


Cardiac Disorders Associated with Cellular Therapy and Novel Agents for Acute Leukemia.
Several novel strategies have emerged in the last decade as potential therapies for patients with chemorefractory lymphoproliferative diseases and acute leukemia. While these treatments include exciting drugs that dramatically change the landscape of treatment, the organ-toxicity profile associated with these therapies may be significant. This article focuses on cardiac disorders associated with chimeric antigen receptor T-cell (CAR-T) therapy, as well as with novel regimens for acute leukemia.


A novel technique for flat-embedding cryofixed plant specimens in LR white resin.
Acrylic LR White is used preferentially for many research applications because it possesses unique advantages over other commercially available resin types. LR White has low toxicity; its low viscosity and hydrophilic properties enable it to infiltrate specimens with comparative ease, and specimens embedded in LR White take up stains for light microscopy well and tend to retain superior antigenicity relative to other resins. These qualities make LR White a good choice for immunohistochemistry, light microscopy, and transmission electron microscopy. However, LR White does not heat-polymerize in the presence of oxygen, which precludes its use with many commercially available embedding molds. Furthermore, flat-embedding specimens in LR White is often an arduous task. Therefore, in this paper, we report on the development of novel flat-embedding chambers for use with LR White. Another goal of our studies was the rapid fixation of larger specimens. Chemical fixation was inadequate because of the time required for tissue infiltration, but cryofixation quickly and effectively immobilized intracellular organelles. Mean amyloplast positions differed in vertically oriented versus control specimens after chemical fixation, whereas no significant difference was observed after cryofixation. Furthermore, cryofixation provided acceptable preservation at the light microscopy level, even though our specimens were relatively larger. This underscores the utility of cryofixation for light microscopy determination of organelle positioning within plant cells.


Evaluation of the validity and reliability of the 10-meter walk test using a smartphone application among Japanese older adults.
Maintaining or improving regular walking speed can help extend healthy life expectancy and prevent frailty. The evaluation of walking speed can help individuals meet their daily exercise goals; therefore, it may be beneficial as a public health policy for residents to measure and evaluate their walking speed easily. This study aimed to verify the validity and reliability of a smartphone application for the 10-m walk test, measured in the general population. The study participants were men (n = 20) and women (n = 20) aged 65-85 years. The 10-m walk tests were performed at the usual walking speed, using the stopwatch function of a newly developed smartphone application. A total of three 10-m walk tests were performed simultaneously with the study participants and professional fitness instructors to evaluate the criterion-related validity and the test-retest reliability. A strong positive correlation was found in the criterion-related validity by the study participants and professional staff for the average of the three trials {r = 0.961 [95% confidence interval (CI) = 0.927, 0.979]}. The results revealed good reliability, with an intraclass correlation coefficient of 0.712 (95% CI = 0.571, 0.823). The smartphone application walking speed measurement method can be widely used by the general public and is useful for health promotion.


[Cranial acupuncture in the treatment of spasticity. Neurophysiological findings].
On the basis of a study of the innervation of the cutaneous areas stimulated in cranial acupuncture, a neurophysiological classification of the technique is proposed, considering the bulbar level as the first site of integration of the afferent vessels activated by cranial acupuncture.


Feeding ecology of the Green-cheeked parakeet (Pyrrhura molinae) in dry forests in western Brazil.
The genus Pyrrhura includes small to medium-sized parakeets, which inhabit both low and dry alongside tall rainforests, mainly in South America. Pyrrhura molinae is still common, year round, in the markedly seasonal forests of western Brazil. This parakeet, as well as most Neotropical parrots, continues to be poorly understood. Hence, in the present study I examined their foraging ecology both in a highly deciduous and in a semi-deciduous forest in western Brazil. In addition, I assessed the relationship between food resource production (flowers and fruits), and the diet of this parakeet. Pyrrhura molinae exhibited a flexible diet consisting of 16 tree species, from which it consumed flowers (three species), seeds (three species), fruit pulp or aril (four species), and both pulp and seeds (six species). Parakeets consumed a wide array of fleshy fruits in the semi-deciduous forest, especially Cecropia pachystachya catkins. Conversely, in the highly deciduous forest they extensively foraged for figs (70% of the diet), in addition to nectar and seeds from dry fruits. Ficus calyptroceras, besides being abundant, bore fruits year round, and was substantially used by parakeets every month. Potentially, by exploiting a diverse set of plant food resources, and particularly due to the substantial use of figs, asynchronously produced, Pyrrhura molinae persists during the long dry season in the markedly seasonal forests of western Brazil.


Microbiota and Obesity.
Obesity is globally the most prevalent nutritional disorder. Multifaceted therapeutic approaches are called for to halt the cascade from neonatal adiposity/high birth weight to childhood excessive weight gain/adult obesity with comorbidities. Recent experimental and clinical data provide one new target for interventions aiming to close this vicious circle: the microbiota. An aberrant gut microbiota, dysbiosis, induces immune and metabolic disturbances both locally and, consequent upon impaired gut barrier function, also systemic low-grade inflammation, which is causally linked to insulin resistance. The gut microecology could thus fill the gap between energy intake and expenditure by processing nutrients and regulating their access to and storage in the body, producing chemicals of hormonal nature and controlling the secretion of proinflammatory mediators locally and systemically. Conversely, being highly sensitive to environmental impacts, particularly to early feeding, the compositional development of the gut microbiota may prove the target of choice in efforts to reduce the risk of obesity. It has been demonstrated that a lower number of bifidobacteria precedes the development of obesity, and a dearth of butyrate-producing bacteria and an overall richness of bacteria increase the risk of metabolic disease; moreover, recognition that practices known to disrupt the early gut microbiota, e.g., cesarean section delivery and antibiotic exposure, contribute to obesity, encourages to pursue this line of research.


Mitochondrial DNA methylation is a predictor of immunotherapy response and prognosis in breast cancer: scRNA-seq and bulk-seq data insights.
Alterations in Mitochondrial DNA methylation (MTDM) exist in many tumors, but their role in breast cancer (BC) development remains unclear. We analyzed BC patient data by combining scRNA-seq and bulk sequencing. Weighted co-expression network analysis (WGCNA) of TCGA data identified mitochondrial DNA methylation (MTDM)-associated genes in BC. COX regression and LASSO regression were used to build prognostic models. The biological function of MTDM was assessed using various methods, such as signaling pathway enrichment analysis, copynumber karyotyping analysis, and quantitative analysis of the cell proliferation rate. We also evaluated MTDM-mediated alterations in the immune microenvironment using immune microenvironment, microsatellite instability, mutation, unsupervised clustering, malignant cell subtype differentiation, immune cell subtype differentiation, and cell-communication signature analyses. Finally, we performed cellular experiments to validate the role of the MTDM-associated prognostic gene NCAPD3 in BC. In this study, MTDM-associated prognostic models divided BC patients into high/low MTDM groups in TCGA/GEO datasets. The difference in survival time between the two groups was statistically significant (P<0.001). We found that high MTDM status was positively correlated with tumor cell proliferation. We analyzed the immune microenvironment and found that low-MTDM group had higher immune checkpoint gene expression/immune cell infiltration, which could lead to potential benefits from immunotherapy. In contrast, the high MTDM group had higher proliferation rates and levels of CD8+T cell exhaustion, which may be related to the secretion of GDF15 by malignant breast epithelial cells with a high MTDM status. Cellular experiments validated the role of the MTDM-associated prognostic gene NCAPD3 (the gene most positively correlated with epithelial malignant cell proliferation in the model) in BC. Knockdown of NCAPD3 significantly reduced the activity and proliferation of MDA-MB-231 and BCAP-37 cells, and significantly reduced their migration ability of BCAP-37 cell line. This study presented a holistic evaluation of the multifaceted roles of MTDM in BC. The analysis of MTDM levels not only enables the prediction of response to immunotherapy but also serves as an accurate prognostic indicator for patients with BC. These insightful discoveries provide novel perspectives on tumor immunity and have the potentially to revolutionize the diagnosis and treatment of BC.


Evolution of Yeast Consortia during the Fermentation of Kalamata Natural Black Olives upon Two Initial Acidification Treatments.
The objective of this study was to elucidate the yeast consortia structure and dynamics during Greek-style processing of Kalamata natural black olives in different brine solutions. Olives were subjected to spontaneous fermentation in 7% (w/v) NaCl brine solution (control treatment) or brine acidified with (a) 0.5% (v/v) vinegar, and (b) 0.1% (v/v) lactic acid at the onset of fermentation. Changes in microbial counts, pH, acidity, organic acids, sugars, and alcohols were analyzed for a period of 187 days. Yeast consortia diversity was evaluated at days 4, 34, 90, 140, and 187 of fermentation. A total of 260 isolates were characterized at sub-species level by rep-PCR genomic fingerprinting with the oligo-nucleotide primer (GTG)5. The characterization of yeast isolates at species level was performed by sequencing of the D1/D2 domain of 26S rRNA gene. Results showed that yeasts dominated the process presenting a relatively broad range of biodiversity composed of 11 genera and 21 species. No lactic acid bacteria (LAB) or Enterobacteriaceae could be enumerated after 20 and 10 days of fermentation, respectively. The dominant yeast species at the beginning were Aureobasidium pullulans for control and vinegar acidification treatments, and Candida naeodendra for lactic acid treatment. Between 34 and 140 days the dominant species were Candida boidinii, Candida molendinolei and Saccharomyces cerevisiae. In the end of fermentation the dominant species in all processes were C. boidinii and C. molendinolei, followed by Pichia manshurica and S. cerevisiae in lactic acid acidification treatment, P. manshurica in vinegar acidification treatment, and Pichia membranifaciens in control fermentation.


Pharmacological profile of delta 9-THC carbamate.
1-N,N-bis-(Dichloroethyl)carbamate-delta 9-THC (THC carbamate), a nitrogen mustard analog of delta 9-THC, was recently synthesized as a potential anti-tumor agent. The decrease in spontaneous activity, induction of hypothermia, and the antinociceptive properties of THC carbamate and delta 9-THC were compared. THC carbamate and delta 9-THC were administered by a number of peripheral routes as well as intraventricularly (ivt). THC carbamate lacked cannabinoid activity following peripheral administration, with the exception of iv administration which produced very weak cannabimimetic effects. In contrast, THC carbamate was equipotent to delta 9-THC in reducing rectal temperature by 3 degrees C, and 5 times less active in decreasing spontaneous activity following ivt administration. The apparent lack of central effects following peripheral administration might limit the effectiveness of THC carbamate as an anti-emetic agent, but its use as a site-directed alkylator (a receptor probe) holds promise.


Factors influencing tinnitus loudness and annoyance.
To evaluate the 2 major components of tinnitus severity, loudness and annoyance, and their degree of dependence on characteristics of tinnitus manifestation, history, and etiology. Cross-sectional survey performed during the first months of 2004. Nonclinical population. A total of 4995 members of the German Tinnitus League. Comprehensive screening questionnaire, including the Klockhoff and Lindblom loudness grading system and the miniversion of the Tinnitus Questionnaire. A moderate correlation of 0.45 was found between tinnitus loudness and annoyance. Both factors were generally higher in men, those older than 50 years, those with binaural and centrally perceived tinnitus, those with increased noise sensitivity, and those who had continuous tinnitus without interruptions. Tinnitus that lasted 12 months or less had a stronger influence on annoyance (odds ratio [OR], 1.96) than on loudness (OR, 0.45), whereas the contrary was found for tinnitus of more than 5 years' duration (ORs, 0.72 and 2.11, respectively). Loudness and annoyance were increased in subjects with coexisting hearing loss, vertigo, and hyperacusis. The impact of hyperacusis on annoyance was clearly stronger than on loudness (ORs, 21.91 vs 9.47). Several clinical factors of tinnitus influence perceived loudness and annoyance. Both are distinguishable components of tinnitus severity.


[Neovascularization in human coronary arteries with lesions of different severity].
Endothelial function can be modulated by growth factors produced by activated smooth muscle cells, inflammatory cells and plasma products that infiltrate the lesion. The aim of this study was to quantify neovessels in human coronary arteries with atherosclerotic lesions of different severity and analyze their relationship with inflammatory cell and plasma product infiltrates. We studied 60 coronary arteries from patients who underwent heart transplant. Cellular markers (smooth muscle cell, monocyte/macrophage), the presence thrombin/prothrombin and expression of vascular endothelial growth factor (VEGF) were analyzed and quantified by conventional histology, immunohistochemistry and image analysis techniques. Neovessels were detected in advanced lesions, and a positive correlation was observed with the degree of vessel remodeling, monocyte/macrophage infiltration and lipid deposition. Smooth muscle cells were the main producers of VEGF in both the intima and media layers of advanced lesions. In these lesions thrombin/prothrombin-positive areas colocalized with activated smooth muscle cells. The presence of neovessels in coronary arteries correlated with inflammatory cell infiltration, lipid deposition and thrombin/prothrombin content. VEGF expression was mainly associated with smooth muscle cells, indicating a key role of these cells in the modulation of endothelial cell function.


σ28-dependent small RNA regulation of flagella biosynthesis.
Flagella are important for bacterial motility as well as for pathogenesis. Synthesis of these structures is energy intensive and, while extensive transcriptional regulation has been described, little is known about the posttranscriptional regulation. Small RNAs (sRNAs) are widespread posttranscriptional regulators, most base pairing with mRNAs to affect their stability and/or translation. Here, we describe four UTR-derived sRNAs (UhpU, MotR, FliX and FlgO) whose expression is controlled by the flagella sigma factor σ28 (fliA) in Escherichia coli. Interestingly, the four sRNAs have varied effects on flagellin protein levels, flagella number and cell motility. UhpU, corresponding to the 3´ UTR of a metabolic gene, likely has hundreds of targets including a transcriptional regulator at the top flagella regulatory cascade connecting metabolism and flagella synthesis. Unlike most sRNAs, MotR and FliX base pair within the coding sequences of target mRNAs and act on ribosomal protein mRNAs connecting ribosome production and flagella synthesis. The study shows how sRNA-mediated regulation can overlay a complex network enabling nuanced control of flagella synthesis.


Renal Agenesis, Extramural Ectopic Ureter, and Nonfunctioning Urinary Bladder: A Difficult Clinical Case with an Innovative Approach.
Summary. A 7-month-old female Jack Russell Terrier weighing 4.6 kg was referred to a veterinary hospital for persistent urinary incontinence. Blood test results and vital signs were within the normal range. Computed tomography allowed the diagnosis of extramural ectopic ureter and unilateral renal agenesis. After the first neoureterocystostomy surgery, the dog had severe complications, such as hydroureter and hydronephrosis, so a second surgery was performed. A commercial ureteral stent was not an option, and it was decided to fabricate a homemade stent to avoid euthanasia. The stent used was a soft, DEHP-free PVC tube with a lumen of 3 × 4.1 mm and a length of approximately 40 mm that connected the ureter to the urinary bladder. Two years after surgery, the dog is in good general condition, and the results of regularly performed blood and urine tests are within the normal range for dogs.


Aspects of insulin resistance in urbanisation-related hypertension in Zimbabwe: a preliminary report.
Insulin resistance has been associated with essential hypertension, obesity and old age. Likewise high blood pressure has been observed to develop in some rural people who migrate to urban areas in developing countries like Zimbabwe. The pathogenesis of this urbanisation-related hypertension is still unknown. We therefore investigated aspects of insulin resistance in urbanisation-related hypertension in Zimbabwean blacks using oral glucose tolerance tests. Thirty normotensive subjects and 30 newly diagnosed hypertensive patients participated in this study. All subjects had blood pressures measured by random zero sphygmomanometry. Fasting blood samples were taken before a 75 g oral glucose load was given. Four other blood samples were subsequently collected at 30 minute intervals and determination of blood glucose and insulin levels was made. Fasting glucose (mmol/l) and fasting insulin (in microU/ml) levels were, respectively, 4.8 +/- 0.2 and 19 +/- 2 in hypertensive patients which were significantly higher than 4.0 +/- 0.2 and 13 +/- 1.6 in normotensive patients (P < 0.05). In addition the area under the insulin curve was significantly higher in hypertensive than in normotensive patients (P < 0.05). These findings suggest that insulin resistance may play a role in urbanisation-related hypertension.


Effect of Needle Size in Ultrasound-guided Core Needle Breast Biopsy: Comparison of 14-, 16-, and 18-Gauge Needles.
The aim of the present study was to assess the diagnostic accuracy of ultrasound-guided core needle biopsy (US-CNB) of breast lesions, comparing smaller needles (16- and 18-gauge) with the 14-gauge needle, and to analyze the lesion characteristics influencing US-CNB diagnostic performance. All the patients provided informed consent before the biopsy procedure. The data from breast lesions that had undergone US-CNB in our institution from January 2011 to January 2015 were retrospectively reviewed. The inclusion criterion was the surgical histopathologic examination findings of the entire lesion or radiologic follow-up data for ≥ 24 months. The exclusion criterion was the use of preoperative neoadjuvant therapy. The US-CNB results were compared with the surgical pathologic results or with the follow-up findings in the 3 needle size groups (14-, 16-, and 18-gauge). The needle size- and lesion characteristic-specific diagnostic accuracy parameters were evaluated. Statistical analysis was performed using a dedicated software program, and P ≤ .01 was considered significant. A total of 1118 US-CNB cases (1042 patients) were included. Of the 1118 cases, 630 (56.3%) were in the 14-gauge group, 136 (12.2%) in the 16-gauge, and 352 (31.5%) in the 18-gauge needle group. Surgery was performed on 800 lesions (71.6%). Of these, 619 were malignant, 77 were high risk, and 104 were benign. The remaining 318 lesions (28.4%) underwent follow-up imaging studies. All the lesions were stable and, therefore, were considered benign. No differences were observed in the diagnostic accuracy parameters among the 3 needle size groups (P > .01). The false-negative rate was greater for lesions < 10 mm (7.2%) (P < .01) but without statistically significant differences among the 3 gauges (P > .01). US-CNB performed with small needles (16 and 18 gauge) had the same diagnostic accuracy as that performed with 14-gauge needles, regardless of the lesion characteristics.


A new FT-IR method combined with multivariate analysis for the classification of vinegars from different raw materials and production processes.
Due to the diversity of vinegars on the market and the increase in demand, it is considered necessary to investigate and establish criteria for classifying them in order to obtain more information concerning their real origin. New spectroscopic techniques such us mid-infrared spectroscopy with Fourier transform (FT-IR) are capable of providing information in relation to these aspects. FT-IR combined with multivariate analysis has been used to classify vinegars according to the raw materials and production processes (with or without ageing in wood). Principal component analysis (PCA), partial least-squares discriminant analysis regression (PLS-DA) and stepwise linear discriminant analysis (SLDA) were used. The results obtained have been compared to those achieved using different analytical parameters (polyphenolic content, organic acids and volatile compounds). SLDA and PLS-DA results show the ability of mid-FT-IR spectra to discriminate among vinegars from different raw materials and with or without ageing in wood, with correct classification percentages similar to those obtained using different analytical parameters. The discriminative ability combined with other advantages (e.g. rapid and non-destructive analysis, low cost) makes this new FT-IR method a promising tool for the classification and/or differentiation of vinegars.


Quorum quenching: role in nature and applied developments.
Quorum sensing (QS) refers to the capacity of bacteria to monitor their population density and regulate gene expression accordingly: the QS-regulated processes deal with multicellular behaviors (e.g. growth and development of biofilm), horizontal gene transfer and host-microbe (symbiosis and pathogenesis) and microbe-microbe interactions. QS signaling requires the synthesis, exchange and perception of bacterial compounds, called autoinducers or QS signals (e.g. N-acylhomoserine lactones). The disruption of QS signaling, also termed quorum quenching (QQ), encompasses very diverse phenomena and mechanisms which are presented and discussed in this review. First, we surveyed the QS-signal diversity and QS-associated responses for a better understanding of the targets of the QQ phenomena that organisms have naturally evolved and are currently actively investigated in applied perspectives. Next the mechanisms, targets and molecular actors associated with QS interference are presented, with a special emphasis on the description of natural QQ enzymes and chemicals acting as QS inhibitors. Selected QQ paradigms are detailed to exemplify the mechanisms and biological roles of QS inhibition in microbe-microbe and host-microbe interactions. Finally, some QQ strategies are presented as promising tools in different fields such as medicine, aquaculture, crop production and anti-biofouling area.


Surface electromyography as a measure of trunk muscle activity in patients with spinal cord injury: a meta-analytic review.
Surface electromyography (SEMG) may be a sensitive marker for distinguishing the activity of trunk muscles, which are critical to functional mobility recovery in patients with spinal cord injury (SCI). This manuscript presents a systematic review and meta-analysis of the published literature on the effect of SEMG as a measure of trunk muscle activity in patients with SCI. A comprehensive search of the research literature included Pubmed, Medline, CNKI, WANFANG DATA, Web of Science, Elsevier, Wiley-Blackwell, Karger, OVID, and a review of reference lists within found articles. Case-control, cohort, and cross-sectional studies were included in the review. Eleven studies were included in this meta-analysis. Trunk muscle activities for the sitting condition were greater in patients with SCI than normal subjects. SEMG activity of trunk muscles for the sitting condition and posterior transfer was greater in patients with high level (HL)-SCI compared to those with low level (LL)-SCI. In addition, across studies, the level of trunk muscle activity for various difficulty settings was different for a given SCI group. This systematic review evaluated the value of trunk muscles for patients with SCI. We recommend use of SEMG as an assessment tool for improving the comparability and interpretability of trunk muscle activity of SCI therapeutic strategies.


Effect of Early Enteral Nutrition Support Combined with Chemotherapy on Related Complications and Immune Function of Patients after Radical Gastrectomy.
The purpose was to analyze the effect of early enteral nutrition (EEN) support combined with chemotherapy on related complications and immune function in patients after radical gastrectomy. 80 patients with gastric cancer treated in our hospital from March 2019 to March 2020 were selected as the research objects and divided into the experimental group and control group according to the random number table, with 40 cases in each group. The control group received chemotherapy only after surgery, while the experimental group received EEN on this basis. The total protein (TP), transferrin (TF), albumin (ALB), immune cells, and other indexes were measured in the two groups before and after treatment to analyze the effect of different treatment methods on the complications and immune function of patients after radical gastrectomy. There were no significant differences in gender ratio, average age, average BMI, pathological types, disease staging, and residence between the two groups (P > 0.05). The exhaust recovery time, total gastric tube drainage, fluid intake time, and hospitalization time in the experimental group were significantly lower than those in the control group (P < 0.05). There were no significant differences in the TP, TF, and ALB levels between the two groups before treatment (P > 0.05), and the TP, TF, and ALB levels in the experimental group were significantly higher than those in the control group after treatment (P < 0.05). The CD4+/CD8+, CD3+, and CD4+ levels in the experimental group after treatment were significantly higher than those in the control group (P < 0.001). After treatment, the growth hormone levels in both groups significantly increased (P < 0.001), and the growth hormone level in the experimental group was significantly higher than that in the control group (P < 0.001). There was no significant difference in the KPS scores between the two groups before treatment (P > 0.05), and the KPS score in the experimental group was significantly higher than that in the control group after treatment (P < 0.001). The incidence of postoperative complications in the experimental group was significantly lower than that in the control group (P < 0.05). EEN combined with chemotherapy is a reliable method to improve the immune function of patients after radical gastrectomy for gastric cancer, which plays an important role in improving the physical state of patients and reducing the incidence of complications. Therefore, its further research will help to establish a better treatment plan for such patients.


Genes and pathways correlated with heat stress responses and heat tolerance in maize kernels.
Global warming leads to frequent extreme weather, especially the extreme heat events, which threating the safety of maize production. Here we selected a pair of maize inbred lines, PF5411-1 and LH150, with significant differences in heat tolerance at kernel development stage. The two maize inbred lines were treated with heat stress at kernel development stage. Compared with the control groups, transcriptomic analysis identified 770 common up- and down-regulated genes between PF5411-1 and LH150 under heat stress conditions, and 41 putative TFs were predicted. Based on the interaction term of the two-factorial design, we also identified 6,744 differentially regulated genes between LH150 and PF5411-1, 111 common up-regulated and 141 common down-regulated genes were overlapped with the differentially regulated genes, respectively. Combined with proteins and metabolites data, several key pathways including seven differentially regulated genes were highly correlated with the heat tolerance of maize kernels. The first is the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway ko04141: protein processing in endoplasmic reticulum, four small heat shock protein (sHSP) genes were enriched in this pathway, participating with the process of ER-associated degradation (ERAD). The second one is the myricetin biosynthesis pathway, a differentially regulated protein, flavonoid 3',5'-hydroxylase [EC:22.214.171.124], catalyzed the synthesis of myricetin. The third one is the raffinose metabolic pathway, one differentially regulated gene encoded the raffinose synthase controlled the synthesis of raffinose, high level of raffinose enhances the heat tolerance of maize kernels. And the last one is the ethylene signaling pathway. Taken together, our work identifies many genes responded to heat stress in maize kernels, and finds out seven genes and four pathways highly correlated with heat tolerance of maize kernels.


Nanoscale Probing of Elastic-Electronic Response to Vacancy Motion in NiO Nanocrystals.
Measuring the diffusion of ions and vacancies at nanometer length scales is crucial to understanding fundamental mechanisms driving technologies as diverse as batteries, fuel cells, and memristors; yet such measurements remain extremely challenging. Here, we employ a multimodal scanning probe microscopy (SPM) technique to explore the interplay between electronic, elastic, and ionic processes via first-order reversal curve I-V measurements in conjunction with electrochemical strain microscopy (ESM). The technique is employed to investigate the diffusion of oxygen vacancies in model epitaxial nickel oxide (NiO) nanocrystals with resistive switching characteristics. Results indicate that opening of the ESM hysteresis loop is strongly correlated with changes to the resonant frequency, hinting that elastic changes stem from the motion of oxygen (or cation) vacancies in the probed volume of the SPM tip. These changes are further correlated to the current measured on each nanostructure, which shows a hysteresis loop opening at larger (∼2.5 V) voltage windows, suggesting the threshold field for vacancy migration. This study highlights the utility of local multimodal SPM in determining functional and chemical changes in nanoscale volumes in nanostructured NiO, with potential use to explore a wide variety of materials including phase-change memories and memristive devices in combination with site-correlated chemical imaging tools.


A new species of Masteria L. Koch, 1873 (Dipluridae: Masteriinae) from Guyana.
Mygalomorphs are a diverse spider group with primitive characteristics composed of the largest spider species in the world, however some species may be very small (Bond et al. 2012; Rogerio et al. 2013). The small spiders of the subfamily Masteriinae (Dipluridae, Mygalomorphae) can be found in Asia and South America (Raven 1981; Pedroso et al. 2015; WSC 2017). The subfamily is represented by two genera: Masteria L. Koch, 1873 and Striamea Raven, 1981. Masteria species can be identified by the following combination of characters: absence of cuspules in endites and labium; zero, two, six or eight eyes; and with or without paraembolic apophysis on the male palpal bulb (Raven 1981, 1985, 1991; Alayón 1995; Bertani et al. 2013; Pedroso et al. 2015). Currently, 24 species of Masteria are described, with 6 species found in South America: Masteria colombiensis, Raven, 1981 from Colombia; M. manauara Bertani, Cruz Oliveira 2013 and M. emboaba Pedroso, Baptista Bertani, 2015 from Brazil; M. cyclops (Simon 1889), M. tovarensis (Simon, 1889) and M. lucifuga (Simon, 1889) from Venezuela (WSC 2017). We document herein the first record and description of a new species of the genus Masteria from Guyana.


Mechanical brain injury: the sympathoadrenal response.
Catecholamine release was studied in cats as a function of injury severity in the fluid-percussion model of brain injury. Hyperglycemia was also studied as a function of catecholamine response and injury severity. Epinephrine (E) and norepinephrine (NE) increased as a function of injury. This increase was maximal at about a 3.0-atmosphere (atm) injury level and amounted to a 500-fold increase for E and 100-fold increase for NE. Both catecholamines increased maximally by 10 seconds postinjury. Glucose increased to about 350% of baseline at 500 seconds postinjury and also increased as a function of injury severity. Results suggested that the sympathoadrenal discharge was capable of a graded response which was maximal at about 3.0 atm. Associated with this increase were hypertensin, bradyarrhythmias, tachyarrhythmias, and hyperglycemia.


AZGP1P2/UBA1/RBM15 Cascade Mediates the Fate Determinations of Prostate Cancer Stem Cells and Promotes Therapeutic Effect of Docetaxel in Castration-Resistant Prostate Cancer via TPM1 m6A Modification.
Prostate cancer (PCa) is a common malignant tumor with high morbidity and mortality worldwide. The prostate cancer stem cell (PCSC) model provides novel insights into the pathogenesis of PCa and its therapeutic response. However, the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be elusive. In this study, we have explored the expression, function, and mechanism of AZGP1P2, a pseudogene of AZGP1, in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer (CRPC). We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs, while it was positively associated with progression-free interval. Upregulation of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their stemness. RNA pull-down associated with mass spectrometry analysis, co-immunoprecipitation assay, and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a "writer" of methyltransferase to form a compound. UBA1, an E1 ubiquitin-activating enzyme, contributed to RBM15 protein degradation via ubiquitination modification. Methylated RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A methylation. Furthermore, a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in vivo. Collectively, these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.