Additional records for Stenosagolanewtoni Park & Carlton, 2013 (Staphylinidae: Pselaphinae: Faronitae), with notes on aedeagal morphology.
The purpose of this short note is to identify morphospecies sp. 0471 of the Hope River Forest Fragmentation Project. It is Stenosagolanewtoni Park & Carlton, 2013. The material listed herein raises the number of published specimen records for Stenosagolanewtoni from 2 to 51. All additional 49 specimens are fully winged males, collected in flight intercept traps (FITs), from the South Island of New Zealand. Examination of the new material has resulted in the detection of an error in the original description of Stenosagolanewtoni, whereby the mirror image of the aedeagus was inadvertently illustrated. It is not a case of genitalic antisymmetry.


Sensitivity analysis for matched pair analysis of binary data: From worst case to average case analysis.
In matched observational studies where treatment assignment is not randomized, sensitivity analysis helps investigators determine how sensitive their estimated treatment effect is to some unmeasured confounder. The standard approach calibrates the sensitivity analysis according to the worst case bias in a pair. This approach will result in a conservative sensitivity analysis if the worst case bias does not hold in every pair. In this paper, we show that for binary data, the standard approach can be calibrated in terms of the average bias in a pair rather than worst case bias. When the worst case bias and average bias differ, the average bias interpretation results in a less conservative sensitivity analysis and more power. In many studies, the average case calibration may also carry a more natural interpretation than the worst case calibration and may also allow researchers to incorporate additional data to establish an empirical basis with which to calibrate a sensitivity analysis. We illustrate this with a study of the effects of cellphone use on the incidence of automobile accidents. Finally, we extend the average case calibration to the sensitivity analysis of confidence intervals for attributable effects.


Structure of colloidal gels during microchannel flow.
We investigate the structure and flow behavior of colloidal gels in microchannels using confocal microscopy. Silica particles are first coated with a cationic polyelectrolyte and then flocculated by the addition of an anionic polyelectrolyte. In the quiescent state, the suspension is an isotropic and homogeneous gel. Under shear flow, the suspension contains dense clusters that yield at intercluster boundaries, resulting in network breakup at high shear rates. These structural changes coincide with a transition from pluglike flow at low pressures to fluidlike flow at high pressures.


Acute intoxications among Turkish children.
The aim of this study was to investigate characteristics, outcomes and clinical features of acute intoxications among children in Van region of Turkey. All cases with a diagnosis of acute intoxication admitted to the Pediatric Emergency Department of the Yüzüncü Yıl University of Van from June 1, 2010 to November 30, 2011 were evaluated. We retrospectively examined the medical records for demographical and etiological characteristics of patients below 17 years of age. A total of 239 intoxications were recorded. The majority of patients were under 5 years of age. Pharmaceutical agents were identified in 137 (57.3%) patients. Antidepressants with a majority of tricyclic antidepressants were the most common drugs (29.9%). Non-pharmaceutical agents were identified in 102 (42.6%) patients, 38.2% of which were insecticides-pesticides following by plants (25.4%) and carbon monoxide (17.6%). The majority (93.8%) of cases were accidental poisonings. Fourteen cases of intoxications occurred as suicide attempts and 85.7% (N.=12) of those patients were girls. Of all cases, gastric lavage was performed in 36.4% and activated charcoal administration in 53%. After hospitalization, only 23 (9.6%) of all patients received specific treatment besides symptomatic treatment. Specific treatments involved hemodialysis and antidotes such as biperiden, ethanol, atropine, neostigmine and pralidoxime. During the study period, one patient died due to acute intoxication of pesticide. The mortality rate was 0.4%. Our study revealed that pharmaceuticals were the most common cause of acute intoxications. While, insecticides-pesticides and plants were the leading non-pharmaceutic agents. Our data is important because it is one of few original reports on children with intoxication in Eastern Turkey.


Climatically-mediated landcover change: impacts on Brazilian territory.
In the face of climate change threats, governments are drawing attention to policies for mitigating its effects on biodiversity. However, the lack of distribution data makes predictions at species level a difficult task, mainly in regions of higher biodiversity. To overcome this problem, we use native landcover as a surrogate biodiversity, because it can represent specialized habitat for species, and investigate the effects of future climate change on Brazilian biomes. We characterize the climatic niches of native landcover and use ecological niche modeling to predict the potential distribution under current and future climate scenarios. Our results highlight expansion of the distribution of open vegetation and the contraction of closed forests. Drier Brazilian biomes, like Caatinga and Cerrado, are predicted to expand their distributions, being the most resistant to climate change impacts. However, these would also be affected by losses of their closed forest enclaves and their habitat-specific or endemic species. Replacement by open vegetation and overall reductions are a considerable risk for closed forest, threatening Amazon and Atlantic forest biomes. Here, we evidence the impacts of climate change on Brazilian biomes, and draw attention to the necessity for management and attenuation plans to guarantee the future of Brazilian biodiversity.


Linear response approach to active Brownian particles in time-varying activity fields.
In a theoretical and simulation study, active Brownian particles (ABPs) in three-dimensional bulk systems are exposed to time-varying sinusoidal activity waves that are running through the system. A linear response (Green-Kubo) formalism is applied to derive fully analytical expressions for the torque-free polarization profiles of non-interacting particles. The activity waves induce fluxes that strongly depend on the particle size and may be employed to de-mix mixtures of ABPs or to drive the particles into selected areas of the system. Three-dimensional Langevin dynamics simulations are carried out to verify the accuracy of the linear response formalism, which is shown to work best when the particles are small (i.e., highly Brownian) or operating at low activity levels.


Stem cells isolated from human dental follicles have osteogenic potential.
Stem cells isolated from human dental follicles as a potential cell source for bone-tissue engineering were examined for correcting a critical bone defect. Impacted third molars were collected and single cell-derived cell populations were cultivated in growth medium. Single cell-derived cell lines were examined in terms of cell shape, gene expression patterns, differentiation capacity in vitro, and osteogenic potential in vivo. Three distinct cell populations were identified with different morphologies, patterns of gene expression, and differentiation capacity. All 3 cell populations promoted bone formation when transplanted into surgically created critical-size defects in immunodeficient rat calvaria, compared with control animals without cell transplantation, although one of these populations showed a weak capacity for osteogenetic differentiation in vitro. Human dental follicle can derive at least 3 unique cell populations in culture, all of which promote bone formation in vivo.


From atomistic simulation to the dynamics, structure and helical network formation of dendronized polymers: the Janus chain model.
It is the purpose of this paper to establish a bottom-up multiscale approach for dendronized polymers. Based on our understanding of the phenomenology of an atomistic model for this class of polymers, we introduce a "Janus chain" (JC) model which adds a vectorial degree of freedom (Janus vector)--related to the sectorial amphiphilicity--to each segment of the linear backbone of a (classical) uncharged, semiflexible, and multibead chain representation of a polymer. The JC features induced polymeric curvature and ultimately triggers complexation. JC parameters related to the topology and chemical details are obtained from the atomistic level. Available experimental observations including the formation of superstructures and double helical conformations are well reproduced by the JC model. JC is efficiently solved via Brownian dynamics simulation and can be seen as a member of a universality class which is one (two) level(s) above the magnetic (semiflexible) chain model. It therefore should allow to model not only dendronized polymers but also structures belonging to the same class-exhibiting induced (or spontaneous) curvature--such as single stranded DNA and actin filaments.


Evaluation of biochemical and immunological parameters in patients with lung cancer by discrimination analysis.
Data obtained by biochemical and immunological tests in a group of healthy blood donors and a group of patients with lung cancer were subjected to discrimination analysis in order to find the minimum possible combination of methods which permit reliable differentiation of the two groups., It was revealed that the lymphocyte transformation after stimulation with PHA, the formation of E rosettes and the plasma level of glycoproteins permit complete differentiation between the group of patients and healthy controls. Based on the above three tests discrimination rules can be defined. If 52.73249--0.45913.ROS--0.40752. TRLY + 0.02790 GP greater than or equal to 0, the investigated subject can be included in the group of patients, when the values are smaller, the subject is healthy.


Jet lag in athletes after eastward and westward time-zone transition.
In healthy male top athletes several functions were measured after either a westbound flight over six time-zones (WEST: Frankfurt-Atlanta; n = 13) or an eastbound flight over eight time-zones (EAST: Munich-Osaka; n = 6). Under either condition the athletes performed two standardized exercise training units in the morning and in the afternoon within 24 h, investigations were done as controls in Germany and on day 1, 4, 6, and 11, after arrival. The primary aim of the study was to evaluate the effect of time-zone transitions on the 24h profiles of blood pressure (BP) and heart rate (HR) using an ambulatory BP device (SpaceLabs 90207), for up to 11 d after arrival at the destination. As additional parameters, we studied jet-lag symptoms, training performance, and training coordination by using visual analog scales. Finally, oral temperature and grip strength were measured, and saliva samples were analyzed for cortisol and melatonin. The study showed that all functions were disturbed on the first day after arrival at the destination, jet-lag symptoms remained until day 5-6 after WEST and day 7 after EAST, training performance was worst within the first 4 d after WEST. In accordance with earlier reports, cortisol, melatonin, body temperature, and grip strength were affected in their 24h profiles and additionally modified by the training units. Surprisingly, BP and HR were not only affected on the first day but also the time-zone transition led to an increase in BP after WEST and a decrease in BP after EAST. However, the training units seemed to influence the BP profile more than the time-zone transitions. HR rhythm was affected by both time-zone transitions and exercise. It is concluded that not only jet-lag symptoms but also alterations in physiological functions should be considered to occur in highly competitive athletes due to time-zone transition and, therefore, an appropriate time of reentrainment is recommended.


Role of ileorectal anastomosis in the treatment of ulcerative colitis and familial polyposis.
A 25-year experience with 109 patients treated with ileorectal anastomosis over 147 patients observed for ulcerative colitis and 25 patients undergoing the same surgical procedure for familial polyposis, is reported. Excellent functional results were obtained, associated to satisfactory ones with respect to inflammatory recurrence and cancer development in the rectal stump. Of 86 patients with ulcerative colitis who were followed-up, only 7 (8.1%) required proctectomy at long-term for a severe inflammatory recurrence, and 4 (4.6%) have developed a cancer in the following 3 to 20 years. Of the 17 followed-up patients, over the 25 operated for familial polyposis, only 1 (5.8%) has developed a cancer between 3 and 20 years. It is concluded that ileorectal anastomosis with a close follow-up still plays a major role because is an easier surgical procedure as compared to ileoanal anastomosis, with excellent functional results, a shorter hospitalization and mainly a lower number of severe complications, which are presently burdening the results of ileoanal anastomosis.


Are five-view plain films of the cervical spine unreliable? A prospective evaluation in blunt trauma patients with altered mental status.
Clearing the cervical spine in a time-sensitive fashion is difficult. We hypothesized that admission computed tomographic scan of the occiput to T1 (CTS) with multiplanar reformatted images will replace five-view (odontoid, anteroposterior, lateral, and oblique) plain films of the cervical spine (CSX) in the initial evaluation of blunt trauma patients with altered mental status. Between January and July 2001, all patients aged 16 years or older with altered mental status undergoing both CTS and CSX were prospectively entered into the study group. Attending physician interpretation defined the presence of cervical spine injury. Unstable fractures were defined as requiring surgical or halo stabilization. One thousand six patients met study criteria. One hundred sixteen patients had 172 cervical spine injuries (CSIs) (fracture and subluxation). CSX missed 90 of 172 (52.3%) CSIs in 65 of 172 (56.0%) patients. Anatomically, CSX failed to identify 14 of 15 occipital fractures (93.3%), 17 of 36 (47.2%) C1-3 fractures, and 59 of 121 (48.8%) C4-T1 CSIs. CSX failed to identify 5 of 29 (17.2%) patients with unstable CSIs. CTS failed to diagnose 3 of 172 (1.7%) CSIs that were stable (spinous process fractures at C6-7). Two patients exhibited spinal cord injury without radiologic abnormality missed by both modalities. CTS had a sensitivity of 97.4%, a specificity of 100%, a prevalence of 11.5%, a positive predictive value of 100%, and a negative predictive value of 99.7%. CSX had a sensitivity of 44.0%, a specificity of 100%, a prevalence of 11.5%, a positive predictive value of 100%, and a negative predictive value of 93.2%. CTS outperformed five-view CSX in a group of patients with altered mental status or distracting injuries. Five-view CSX failed to diagnose 52.3% of cervical spine fractures identified by CTS. Five-view CSX failed to diagnose five patients with unstable cervical fractures and failed to identify 93.3% of patients with occipital condyle fractures.


Efficacy of totally laparoscopic distal gastrectomy for gastric cancer in elderly patients.
Elderly patients are often considered as high-risk for major abdominal surgery due to reduced functional reserve and increased comorbidities. We herein evaluated the efficacy of totally laparoscopic distal gastrectomy (TLDG) in elderly patients with gastric cancer by measuring the postoperative systemic responses and postoperative analgesic consumption. A total of 102 patients with gastric cancer [57 who underwent TLDG and 45 who underwent laparoscopy-assisted distal gastrectomy (LADG)] were enrolled in this study. The patients were classified as elderly (aged ≥75 years) and non-elderly (aged <75 years) groups. The surgical outcome and postoperative analgesic consumption were evaluated. The elderly group exhibited a higher incidence of comorbidities and a longer postoperative hospital stay compared with those of younger patients, although there was no difference in the incidence of postoperative complications. In addition, the total consumption of additional analgesics until postoperative day 5 in patients who underwent TLDG was significantly lower compared with that in patients who underwent LADG in the elderly group; there was no such difference in the non-elderly group. The results suggested that TLDG was better for the management of postoperative pain in elderly patients with gastric cancer, who exhibit the highest mortality rates in the adult surgical population.


Expression of Semaphorin-3A and its receptors in endochondral ossification: potential role in skeletal development and innervation.
Bone tissue is densely innervated, and there is increasing evidence for a neural control of bone metabolism. Semaphorin-3A is a very important regulator of neuronal targeting in the peripheral nervous system as well as in angiogenesis, and knockout of the Semaphorin-3A gene induces abnormal bone and cartilage development. We analyzed the spatial and temporal expression patterns of Semaphorin-3A signaling molecules during endochondral ossification, in parallel with the establishment of innervation. We show that osteoblasts and chondrocytes differentiated in vitro express most members of the Semaphorin-3A signaling system (Semaphorin-3A, Neuropilin-1, and Plexins-A1 and -A2). In vitro, osteoclasts express most receptor chains but not the ligand. In situ, these molecules are all expressed in the periosteum and by resting, prehypertrophic and hypertrophic chondrocytes in ossification centers before the onset of neurovascular invasion. They are detected later in osteoblasts and also osteoclasts, with differences in intensity and regional distribution. Semaphorin-3A and Neuropilin-1 are also expressed in the bone marrow. Plexin-A3 is not expressed by bone cell lineages in vitro. It is detected early in the periosteum and hypertrophic chondrocytes. After the onset of ossification, this chain is restricted to a network of cell processes in close vicinity to the cells lining the trabeculae, similar to the pattern observed for neural markers at the same stages. After birth, while the density of innervation decreases, Plexin-A3 is strongly expressed by blood vessels on the ossification front. In conclusion, Semaphorin-3A signaling is present in bone and seems to precede or coincide at the temporal but also spatial level with the invasion of bone by blood vessels and nerve fibers. Expression patterns suggest Plexin-A3/Neuropilin-1 as a candidate receptor in target cells for the regulation of bone innervation by Semaphorin-3A.


Neural correlates of the individual emotional Stroop in borderline personality disorder.
Emotional dysregulation is a key feature of borderline personality disorder (BPD) with altered inhibitory functions having suggested as being crucial. The anterior cingulate cortex and further prefrontal brain regions are crucial for response inhibition. The regulation of emotions is ensured via inhibitory control over the amygdala. The present study aimed to investigate neural correlates of response inhibition in BPD by using an emotional Stroop paradigm extending the task to word stimuli which were related to stressful life events. Twenty BPD patients and 20 healthy controls underwent functional magnetic resonance imaging (fMRI) while performing the individual emotional Stroop task. A block design was used with the following word type conditions: neutral words, general negative words, and individual negative words. The individual negative words were recruited from a prior interview conducted with each participant. While BPD patients had overall slower reaction times in the Stroop task compared to healthy controls, there was no increased slowing with emotional interference. Controls exhibited significant fMRI blood oxygenation level-dependent signal increases in the anterior cingulate cortex as well as in frontal cortex contrasting generally negative vs. neutral and individual negative vs. neutral conditions, respectively. BPD patients did not show equivalent signal changes. These results provide further evidence for a dysfunctional network of brain areas in BPD, including the ACC and frontal brain regions. These areas are crucial for the regulation of stress and emotions, the core problems of BPD patients.


A Bayesian formulation of the Kalman filter applied to the estimation of individual pharmacokinetic parameters.
A general method of Bayesian forecasting employing the dynamic linear model has been adapted to the problem of estimating individual pharmacokinetic parameters. The Bayesian forecasting method incorporates an efficient Kalman filter algorithm for updating pharmacokinetic parameter estimates when further observations are made. The Kalman filter is more general and flexible than other Bayesian methods currently used and simulation studies have demonstrated its practicality for three different pharmacokinetic models. The method serves as the basis for a computer program for general clinical use.


[The oxLDL/β2GPI/β2GPI-Ab complex promotes the migration and the expression of inflammatory cytokines in human umbilical vein endothelial cells].
Objective To study the effects of the complex of oxidized low density lipoprotein/β2-glycoprotein I/β2-glycoprotein I antibodies (oxLDL/β2GPI/β2GPI-Ab) on the migration of human umbilical vein endothelial cells (HUVECs) and the expression of inflammatory cytokines, and their underlying Toll-like receptor (TLR4) pathway. Methods HUVECs were treated with oxLDL, oxLDL/β2GPI complex, oxLDL/β2GPI-Ab complex, oxLDL/β2GPI/β2GPI-Ab complex, or lipopolysaccharide (LPS) for a period of time in their corresponding groups. The migration of HUVECs was observed by the wound-healing assay. The mRNA and protein levels of TLR4 in HUVECs were detected by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The cells were pretreated with or without TAK-242 (the inhibitor of TLR4) 2 hours before stimulated by corresponding stimulus as described above. Then, the contents of monocyte chemotactic protein-1 (MCP-1), interleukin 1β (IL-1β) and IL-6 in cell culture supernatant were determined by ELISA, and their mRNAs were detected by qRT-PCR. Results The oxLDL/β2GPI/β2GPI-Ab complex promoted the migration of HUVECs effectively, and increased the expression of TLR4. The oxLDL/β2GPI/β2GPI-Ab complex increased the expressions of MCP-1, IL-1β, and IL-6. TAK-242 could reduce the effects of oxLDL/β2GPI/β2GPI-Ab complex. Conclusion The oxLDL/β2GPI/anti-β2GPI-Ab complex can promote the migration of HUVECs and the expression of related inflammatory cytokines, and TLR4 may be involved in this process.


The Hemarthrosis-Simulating Knee Model: A Useful Tool for Individualized Education in Patients with Hemophilia (GEFACET Study).
Hemophilic arthropathy is a major complication in patients with severe hemophilia. A plastic knee model has been developed for the therapeutic education of patients to promote improved care management and self-treatment skills. The objective of this study was to evaluate the impact of this hemarthrosis-simulating artificial knee (HSAK) on patients' knowledge of their disease and its treatment. In this observational study, the impact of HSAK was assessed during individualized education in patients with severe/moderately severe hemophilia A or B at seven hemophilia treatment centers in France. Participants provided written informed consent and completed questionnaires to assess knowledge of their disease (score range: 0-7) and knowledge of their treatment (score range: 0-4). Questionnaires were completed before, immediately after and 6 months after HSAK use. The scores obtained before and after the use of the HSAK were compared. The participants comprised 32 children, 29 teenagers, and 31 adults. The mean (SD) disease knowledge score increased significantly in all age groups of patients from 4.5 (2.0) to 5.9 (1.5; p<0.001) immediately after the training and remained unchanged at 6 months. Mean (SD) treatment knowledge scores were unchanged, but Wilcoxon signed rank testing showed a significant increase after the training course that was maintained at 6 months in children and teenagers. These findings suggest that an individualized training course can enhance the understanding of hemophilia in patients of all ages, especially in children and teenagers, and that the HSAK may assist in improving patients' management of their disease.


[Rupture of a congenital aneurysm of the sinus of Valsalva].
The ruptured aneurysm of the sinus of Valsalva is a rare congenital anomaly which we encountered in less then 1% of our surgical patients. We recently operated on a young girl suffering from this congenital malformation consisting of a 15 mm long fistula arising from the right coronary sinus and giving rise to a 6 cm aneurysm which dissected the interatrial septum as well as the posterolateral wall of the right atrium before rupturing into this cavity. Because of the unusual presentation of this malformation, which has never been described previously, we though worthwhile reporting this case in details. We also summarized the embryological, anatomopathological, clinical and surgical aspects discussed in the literature.


Critical percolation clusters in seven dimensions and on a complete graph.
We study critical bond percolation on a seven-dimensional hypercubic lattice with periodic boundary conditions (7D) and on the complete graph (CG) of finite volume (number of vertices) V. We numerically confirm that for both cases, the critical number density n(s,V) of clusters of size s obeys a scaling form n(s,V)∼s^{-τ}n[over ̃](s/V^{d_{f}^{*}}) with identical volume fractal dimension d_{f}^{*}=2/3 and exponent τ=1+1/d_{f}^{*}=5/2. We then classify occupied bonds into bridge bonds, which includes branch and junction bonds, and nonbridge bonds; a bridge bond is a branch bond if and only if its deletion produces at least one tree. Deleting branch bonds from percolation configurations produces leaf-free configurations, whereas deleting all bridge bonds leads to bridge-free configurations composed of blobs. It is shown that the fraction of nonbridge (biconnected) bonds vanishes, ρ_{n,CG}→0, for large CGs, but converges to a finite value, ρ_{n,7D}=0.0061931(7), for the 7D hypercube. Further, we observe that while the bridge-free dimension d_{bf}^{*}=1/3 holds for both the CG and 7D cases, the volume fractal dimensions of the leaf-free clusters are different: d_{lf,7D}^{*}=0.669(9)≈2/3 and d_{lf,CG}^{*}=0.3337(17)≈1/3. On the CG and in 7D, the whole, leaf-free, and bridge-free clusters all have the shortest-path volume fractal dimension d_{min}^{*}≈1/3, characterizing their graph diameters. We also study the behavior of the number and the size distribution of leaf-free and bridge-free clusters. For the number of clusters, we numerically find the number of leaf-free and bridge-free clusters on the CG scale as ∼lnV, while for 7D they scale as ∼V. For the size distribution, we find the behavior on the CG is governed by a modified Fisher exponent τ^{'}=1, while for leaf-free clusters in 7D, it is governed by Fisher exponent τ=5/2. The size distribution of bridge-free clusters in 7D displays two-scaling behavior with exponents τ=4 and τ^{'}=1. The probability distribution P(C_{1},V)dC_{1} of the largest cluster of size C_{1} for whole percolation configurations is observed to follow a single-variable function P[over ¯](x)dx, with x≡C_{1}/V^{d_{f}^{*}} for both CG and 7D. Up to a rescaling factor for the variable x, the probability functions for CG and 7D collapse on top of each other within the entire range of x. The analytical expressions in the x→0 and x→∞ limits are further confirmed. Our work demonstrates that the geometric structure of high-dimensional percolation clusters cannot be fully accounted for by their complete-graph counterparts.


Activation and detoxication of N-hydroxy-Trp-P-2 by glutathione and glutathione transferases.
The roles of non-enzymatic and enzymatic glutathione (GSH) conjugation in the activation and detoxication of 3-hydroxy-amino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) were studied in vitro. N-OH-Trp-P-2 is an active metabolite of 3-amino-1-methyl-5H-pyrido[4,3-d]indole (Trp-P-2), a mutagenic and carcinogenic heterocyclic amine. 3-Nitroso-1-methyl-5H-pyrido[4,3-b]indole (NO-Trp-P-2) reacted rapidly and non-enzymatically with GSH to form N-OH-Trp-P-2 and a small amount of two GSH conjugates (CN-1 and CN-2). On the other hand, non-enzymatic reaction of GSH with N-OH-Trp-P-2 was very slow, but the GSH conjugation with N-OH-Trp-P-2 was catalyzed by rat liver GSH transferase and a rat liver cytosol fraction to form three conjugates (CH-1, CH-2 and CH-3). The enzymatic conjugation was effectively inhibited by organic tin compounds which are known as powerful GSH transferase inhibitors. The conjugates were unstable enough to yield Trp-P-2 (from CN-1, CN-2 and CH-2) or N-OH-Trp-P-2 (from CH-3) on incubation at 37 degrees C for 30-60 min. Only CH-1 was stable under similar conditions. The mutagenicities of the GSH conjugates and the effects of GSH and GSH transferase were studied by using Salmonella typhimurium TA98 as the tester strain. The GSH conjugates except for CH-3 were completely detoxicated products, but CH-3 was found to be a more potent mutagen than N-OH-Trp-P-2. The mutagenicity of CH-3 seemed to be due to the direct action of the conjugate, and not to N-OH-Trp-P-2 formed from it.


Perioperative administration of propranolol to women undergoing ovarian cancer surgery: A pilot study.
This study was done to evaluate whether perioperative propranolol (ß-blocker) in ovarian cancer patients undergoing debulking surgery reduced perioperative tumor growth induced by surgical stress. This was a prospective randomized single institution analysis. The primary objective was to compare the changes in CA 125 level (changes between preoperation day 2 and postoperative day 7). As a study arm, patients received a low dose of propranolol 40 mg/day (4×10 mg) starting two days before surgery and 40 mg twice daily for three days following surgery. Twenty-two patients were enrolled and 16 were evaluable for efficacy. The drug was well tolerated. The mean decrease of CA 125 during the seven perioperative days was 83.1±8.9% in the propranolol group and 72.4±14.7% in the placebo group. The difference was statistically significant (P=0.044). The change of C-reactive protein, cortisol, and anxiety score (State-Trait Anxiety Inventory-X1) were not different between the two groups. This preliminary result is the first to directly test the role of perioperative propranolol on tumor growth. Even with the small sample size and short term use of the drug, perioperative propranolol was effective in reducing tumor burden (as measured by CA 125) suggesting its potential benefits in decreasing perioperative tumor growth.


Experimental charge density evidence for pnicogen bonding in a crystal of ammonium chloride.
Chemical binding in crystalline ammonium chloride, a simple inorganic salt with an unexpectedly complex bonding pattern, was studied by using a topological analysis of electron density function derived from high-resolution X-ray diffraction. Supported by periodic quantum chemical calculations, it provided experimental evidence for weak σ-hole bonds (1.5 kcal mol(-1) ) that involve ammonium cations in a crystal. Our results show this type of supramolecular interaction to be more numerous than has been found to date by using gas-phase calculations or statistical analysis of CSD.


Clinical Features in Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency: A Systematic Review.
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human AADC gene into the putamina has become available. This systematic review on PubMed, Scopus databases, and other sources is aimed at describing the AADC whole phenotypic spectrum in order to facilitate its early diagnosis. Literature reviews, original articles, retrospective and comparative studies, large case series, case reports, and short communications were considered. A database was set up using Microsoft Excel to collect clinical, molecular, biochemical, and therapeutic data. By analysing 261 patients from 41 papers with molecular and/or biochemical diagnosis of AADC deficiency for which individuality could be determined with certainty, we found symptom onset to occur in the first 6 months of life in 93% of cases. Hypotonia and developmental delay are cardinal signs, reported as present in 73.9% and 72% of cases, respectively. Oculogyric crises were seen in 67% of patients while hypokinesia in 42% and ptosis in 26%. Dysautonomic features have been revealed in 53% and gastrointestinal symptoms in 19% of cases. With 37% and 30% of patients reported being affected by sleep and behavioural disorders, it seems to be commoner than previously acknowledged. Although reporting bias cannot be excluded, there is still a need for comprehensive clinical descriptions of symptoms at onset and during follow-up. In fact, our review suggests that most of the neurological and extraneurological symptoms and signs reported, although quite frequent in this condition, are not pathognomonic, and therefore, ADCC deficiency can remain an underdiscovered disorder.


The expression of genes of the steroid-thyroid hormone receptor superfamily in central nervous system tumors.
We studied the expression of ten genes (encoding the receptors for glucocorticoid, mineralocorticoid, progesterone, androgen, estrogen, thyroid, retinoid acid, vitamin D) belonging to the steroid-thyroid hormone receptor superfamily (STRS) in 12 neuroepithelial tumors, 12 meningiomas and 2 human glioblastoma cell lines. Our method, based on the polymerase chain reaction, allowed the simultaneous amplification of cDNAs of the STRS genes. On average, 7 STRS genes were simultaneously expressed in each sample. Our study indicates that many STRS gene are commonly co-expressed in human CNS tumors. The importance of our results for the ongoing and proposed hormonal treatment trials is discussed.


Use of hybridoma-resident variant cell lines to study H-2Db/FMR-specific cytotoxic T cells.
An H-2Db heterozygous tumor cell line and a variant subclone bearing a mutant gene product were used to analyze the H-2Db specificity of cytotoxic T lymphocytes (CTL) generated during a Moloney murine sarcoma virus (MSV) infection. When the mutant cells were used as targets for MSV-specific CTL, the amount of cell lysis, compared with that seen with the nonmutant parental cells, was drastically decreased. However, cells of the mutant clones remained susceptible to allogeneic CTL specific for the nonmutant H-2Db molecule. The mutant cells also did not differ from the parent cells in their level of viral antigen expression. Biochemically the parental and mutant molecules were similar but not identical. The data indicate that minor alterations of the H-2 antigens caused by somatic mutation may prevent virus-infected cells from being recognized as targets by CTL.


Mania as a manifestation of end-stage renal disease.
A patient presented with mania as the primary psychiatric manifestation of end-stage renal disease. Previous descriptions of mania secondary to renal failure have been reported only in the 19th century literature. This case demonstrates that mania may arise due to endstage renal disease and that it should be included in the differential of secondary mania. Implications of this case on the pathophysiology of mania are discussed.


The development of bone mass and bone strength in the mandible of the female rat.
The present study provides baseline data for a number of mandibular growth dimensions, specially on bone mass and bone strength, that were collected between the 21st and the 180th days of postnatal life, which are intended as a reference for researchers designing experimental studies, specially on mandibular catch-up growth, and as an aid for clinicians who must evaluate results from published animal studies for validity and potential extrapolation to the human clinical situation. Fifty weanling female Wistar (Hsd:Wi) rats were fed ad libitum a diet previously shown to allow normal, undeformed mandibular growth. Five of them were randomly selected at different times between 21 and 180 d of life. Mandibular growth was estimated directly on the right hemimandible by taking measurements between anatomical points; mandibular bone mass (calcium mass) was estimated from the mg of calcium, determined by atomic absorption spectrophotometry, present in the ashes of the left hemimandible; and mechanical properties of the right hemimandible were determined using three-point bending mechanical test. Dimensions, bone calcium mass and bone strength of the female rat mandible increased linearly from day 21 to approximately day 90. Bone growth, as expected, was more than twice when assessed from bone weight than when derived from mandibular area, length or height when the parameters were expressed as the relative increase from the mean infant condition. The growth rate of the posterior part of the mandible (behind the third molar) was almost five times greater than that of the anterior part. The rates of growth of the studied parameters showed a marked decline after day 90. ANOVA indicated that no statistical differences were found between day 90 and day 120 values. It could be concluded that the female rat mandible attains its adult size, peak bone calcium mass and bone structural mechanical properties at some point between 90 and 120 d of postnatal life. Because of the extremely high positive correlation between mandibular bone calcium mass and both mandibular area and mandibular weight, it was possible to calculate the mandibular peak bone mass from the relations 7.69 mgCa/cm2 and 0.19 mgCa/mg bone.


The effect of early, intensive statin therapy on acute coronary syndrome: a meta-analysis of randomized controlled trials.
In addition to well-established secondary prevention benefits for atherosclerotic coronary artery disease, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are hypothesized to have short-term benefit in acute coronary syndrome (ACS), yet the data are inconsistent, with some trials underpowered to demonstrate therapeutic benefit. Our objective was to determine the effects of early, intensive statin therapy for ACS. Studies found in the PubMed, MEDLINE, EMBASE, BIOSIS, SciSearch, PASCAL, and International Pharmaceutical Abstracts (IPA) databases and the Cochrane Controlled Trials Register published between January 1974 and May 2006. Randomized controlled trials of statins begun within 14 days of hospitalization for ACS were included. Two investigators independently abstracted study quality, characteristics, and outcomes. Thirteen randomized controlled trials published before May 2006 were available, involving 17 963 adults (median number of patients, 135; median follow-up, 6 months). Early, intensive statin therapy for ACS decreased the rate of death and cardiovascular events over 2 years of follow-up (hazard ratio, 0.81 [95% confidence interval, 0.77-0.87]) (Q(3) = 58.54; P<.001; I(2) = 95%). Survival curves revealed that this benefit begins to occur between 4 and 12 months, achieving statistical significance by 12 months. There was no evidence of publication bias, and sensitivity analyses did not identify a dominating study or study characteristic. Early, intensive statin therapy reduces death and cardiovascular events after 4 months of treatment. The validity of this finding would be strengthened by an analysis of individual patient data.


Electro-Catalytic Activity of RuO2-IrO2-Ta2O5 Mixed Metal Oxide Prepared by Spray Thermal Decomposition for Alkaline Water Electrolysis.
Oxygen evolution reaction for alkaline water electrolysis was studied using various mixed metal oxide catalysts. Mixed metal oxide electrodes consisting of RuO2, IrO2, and Ta2O5 with various ratios on a titanium substrate were prepared by spray thermal decomposition. The crystallinity of the synthesized catalyst was investigated via X-ray diffraction, and the oxidation state of each component was determined using X-ray photoelectron spectroscopy (XPS). Surface morphology was investigated by scanning electron microscopy, and the roughness factor was determined by cyclic voltammetry (CV) in 1 M H2SO4. Electo-catalytic activity for oxygen evolution reaction was measured by cyclic voltammetry (CV) in 1 M KOH at room temperature, and it was found to be strongly dependent.on composition of catalyst. Among all electrodes tested, catalyst with a composition of Ru:Ir:Ta = 1:2:2.5 exhibited the highest current density of 100 mA cm(-2) at 1.67 V, corresponding to an overpotential of 0.44 V.


A health care plan for the student with diabetes.
This article presents a generic healthcare plan for the student with diabetes. This plan provides the basis for comprehensive assessment and subsequent interventions and evaluation for the student with diabetes in the care of the school nurse. For this plan to be useful, it must be tailored to the student's individual needs. Individual problems must be identified and addressed, resulting in an Individual Healthcare Plan (IHP). The IHP presented includes an emergency health plan for treatment of hypoglycemia; management of diabetes in schools, including glucose monitoring and insulin administration; education regarding diabetes; and psychosocial assessment of students with diabetes.


PVA/ChCl Deep Eutectic Polymer Blends for Transparent Strain Sensors with Antifreeze, Flexible, and Recyclable Properties.
Wearable elastic electronic devices have attracted tremendous attention due to their monitoring capabilities for human motion detection. In this work, a hydrogen bond acceptor quaternary ammonium salt, choline chloride (ChCl), has been used to fabricate deep eutectic polymer (DEP) blends with polyvinyl alcohol (PVA). The miscibility, molecular interaction, and physical properties of PVA/ChCl DEP blends were investigated systematically. It is demonstrated that the deep eutectic of PVA/ChCl can be obtained by simple solution blending, and the melting points of both PVA and ChCl are reduced respectively due to the strong hydrogen bond between PVA and ChCl. Due to the elasticity of the PVA/ChCl elastomer and the response of ChCl ions to temperature and humidity, the fabricated sensor showed stable and repeatable resistance changes upon strain, temperature, and humidity variations. We hypothesize that the DEP blend system has potential applications in functional composites and the final PVA/ChCl elastomer composites exhibited high transparent, antifreeze, and recyclable capability, which may be promising for applications in soft/flexible devices.


[Cervical spondylodiscitis].
Eighty patients were treated for spondylodiscitis with the cervical spine involved in nine cases. Conservative treatment was applied in seven cases with Minerva jacket and antibiotics, and surgical treatment was applied in severe, rapidly, progressive, complicated cases and in patients with involvement of nervous system (two cases). The good and satisfactory results in both group were similar. These results show that when the indications are properly established, both conservative and operative methods have satisfactory results.


Evidence for Anisotropic Electronic Coupling of Charge Transfer States in Weakly Interacting Organic Semiconductor Mixtures.
We present a comprehensive investigation of the charge-transfer (CT) effect in weakly interacting organic semiconductor mixtures. The donor-acceptor pair diindenoperylene (DIP) and N,N'-bis(2-ethylhexyl)-1,7-dicyanoperylene-3,4/9,10-bis(dicarboxyimide) (PDIR-CN2) has been chosen as a model system. A wide range of experimental methods was used in order to characterize the structural, optical, electronic, and device properties of the intermolecular interactions. By detailed analysis, we demonstrate that the partial CT in this weakly interacting mixture does not have a strong effect on the ground state and does not generate a hybrid orbital. We also find a strong CT transition in light absorption as well as in photo- and electroluminescence. By using different layer sequences and compositions, we are able to distinguish electronic coupling in-plane vs out-of-plane and, thus, characterize the anisotropy of the CT state. Finally, we discuss the impact of CT exciton generation on charge-carrier transport and on the efficiency of photovoltaic devices.


Wound drainage after plastic and reconstructive surgery of the breast.
Wound drains are often used after plastic and reconstructive surgery of the breast, in order to reduce potential complications. It is unclear whether there is any evidence to support this practice and we therefore undertook a systematic review of the best evidence available. To compare the safety and efficacy of the use of wound drains following elective plastic and reconstructive surgery procedures of the breast. For the first update of this review we searched the Cochrane Wounds Group Specialised Register (searched 4 March 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 2); Ovid MEDLINE (2012 to March 3 2015); Ovid MEDLINE (In-Process & Other Non-Indexed Citations March 3 2015); Ovid EMBASE (2012 to March 3 2015); and EBSCO CINAHL (2012 to March 4 2015). There were no restrictions on the basis of date or language of publication. Three review authors undertook independent screening of the search results. All randomised trials (RCTs) that compared the use of a wound drain with no wound drain following plastic and reconstructive surgery of the breast (breast augmentation, breast reduction and breast reconstruction) in women were eligible. Two review authors undertook independent data extraction of study characteristics, methodological quality and outcomes (e.g. infection, other wound complications, pain, and length of hospital stay). Risk of bias was assessed independently by two review authors. We calculated the risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals. Analysis was on an intention-to-treat basis. Three randomised trials were identified and included in the review out of 190 studies that were initially screened; all evaluated wound drainage after breast reduction surgery. No new trials were identified for this first update. In total there were 306 women in the three trials, and 505 breasts were studied (254 drained, and 251 who were not drained). Apart from a significantly shorter duration of hospital stay for those participants who did not have drains (MD 0.77; 95% CI 0.40 to 1.14), there was no statistically significant impact of the use of drains on outcomes. The limited evidence available shows no significant benefit of using post-operative wound drains in reduction mammoplasty, though hospital stay may be shorter when drains are not used. No data are available for breast augmentation or breast reconstruction, and this requires investigation.


[Protective effects of n-acetylcysteine against decabromodiphenyl ether-induced brain oxidative injury in mice].
To study the protective effects of N-acetylcysteine (NAC) against oxidative injury in the brain tissue of mice induced by decabromodiphenyl ether (PBDE-209) and the expression of mitogen activated protein kinase (MAPK)-related proteins in the hippocampus. Twenty-one male BALB/c mice were randomly divided into three groups with seven mice in each group: solvent control group, PBDE-209 group with gavage of 500 mg/kg PBDE-209, and PBDE-209 +NAC group which received intraperitoneal injection of 100 mg/kg NAC 0.5 h before exposure to PBDE-209. Mice were sacrificed 6 weeks after exposure. Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and glutathione (GSH) level in the cerebral cortex, hippocampus, cerebellum, and striatum, as well as the protein expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), p38 MAPK (p38), and phosphorylated p38 (p-p38) in the hippocampus, were determined by Western blot. Compared with the hippocampal and cerebellar levels of MDA in control group [(4.91±1.60) and (2.42±1.41) nmol/mg pro] and PBDE-209+NAC group [(6.16±1.03) and (2.83±0.85) nmol/mg pro], the MDA levels in PBDE-209 group [(12.12±6.39) and (4.24±1.15) nmol/mg pro] were significantly increased (P < 0.05). The striatum MDA level in PBDE-209 group [(12.92±4.30) nmol/mg pro] was significantly increased as compared with that of the control group [(4.05±2.23) nmol/mg pro] (P < 0.05). The hippocampal SOD activity of PBDE-209 group [(59.29±37.09) U/mg pro] was reduced significantly as compared with those of the control group [(93.28±21.75) U/mg pro] and PBDE-209+NAC group [(98.92±21.54) U/mgpro] (P < 0.05). The GSH levels in the cerebral cortex, striatum, and cerebellum in PBDE-209 group [(40.98±13.19), (24.46±11.30), and (3.55±1.55) mg GSH/g pro] were significantly reduced as compared with those of the control group [(75.79±26.51), (44.52±13.15) and (8.01±3.23) mg GSH/g pro] and the PBDE-209+NAC group [(89.86±28.39), (39.01±9.05) and (10.34±2.58) mg GSH/g pro] (P < 0.05). Western blot results showed that the ratios of p-p38/p38 and p-ERK/ERK in the hippocampus were significantly higher in the PBDE-209 group than in the control group and PBDE-209+NAC group (P < 0.05). Antioxidant NAC has a protective effect against PBDE-209-induced brain injury in mice to some extent, and reduces the expression of MAPK-related proteins.


Arterial oxygen saturation in healthy newborns delivered at term in Cerro de Pasco (4340 m) and Lima (150 m).
High altitude is associated with both low pulse oxygen saturation at birth and more pre-term deliveries. The present study was performed to determine pulse oxygen saturation in newborns at term in Cerro de Pasco (4340 m) and Lima (150 m) to test the hypothesis that low pulse oxygen saturation at birth at high altitudes was not observed at term deliveries. The present study was designed to determine pulse oxygen saturation values through 1 minute to 24 hours and values of Apgar score at 1 and 5 minutes in newborns delivered at term in Cerro de Pasco (4340 m) and Lima (150 m). Pulse oxygen saturation was recorded in 39 newborns from Cerro de Pasco (4340 m) and 131 from Lima (150 m) at 1, 2, 3, 4, 5, 10, 15, 30 minutes and 1, 2, 8 and 24 hours after delivery. Apgar score was assessed at 1 and 5 minutes after birth. Neurological score was assessed at 24 h of birth by Dubowitz exam. Pulse oxygen saturation increased significantly from 1 to 15 min after birth at sea level and from 1 to 30 minutes at Cerro de Pasco. Thereafter, it increased slightly such that at 30 min at sea level and at 60 minutes in Cerro de Pasco it reached a plateau up to 24 hours after birth. At all times, pulse oxygen saturation was significantly higher at sea level than at high altitude (P < 0.01). At 1 minute of life, pulse oxygen saturation was 15% lower at high altitude than at sea level. Apgar score at 1 minute was significantly lower at high altitude (P < 0.05). Neurological score at 24 hours was also lower at high altitude than at sea level. Head circumference, and Apgar score at 5 minutes were similar at sea level and at high altitude (P:NS). Incidence of low birth-weight (<2500 g) at high altitude (5.4%) was similar to that observed at sea level (2.29%) (P:NS). Incidences of low pulse oxygen saturation (<30%), low Apgar score at first minute (<7) and low neurological score at 24 h (<19) were significantly higher at high altitude than at sea level (P < 0.0001; P < 0.0001; and P < 0.001, respectively). From these analyses may be concluded that pulse oxygen saturation at 4340 m was significantly low despite the fact that births occurred at term. Apgar scores at first minute and neurological scores were also lower at high altitudes.


The Evolving Mcart Multimodal Imaging Core: Establishing a Protocol for Computed Tomography and Echocardiography in the Rhesus Macaque to Perform Longitudinal Analysis of Radiation-Induced Organ Injury.
Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities that produce critical longitudinal data that can be analyzed for radiation-induced organ-specific injury to the lung and heart. The Medical Countermeasures Against Radiological Threats (MCART) consortium has a well established animal model research platform that includes nonhuman primate (NHP) models of the acute radiation syndrome and the delayed effects of acute radiation exposure. These models call for a definition of the latency, incidence, severity, duration, and resolution of different organ-specific radiation-induced subsyndromes. The pulmonary subsyndromes and cardiac effects are a pair of interdependent syndromes impacted by exposure to potentially lethal doses of radiation. Establishing a connection between these will reveal important information about their interaction and progression of injury and recovery. Herein, the authors demonstrate the use of CT and EC data in the rhesus macaque models to define delayed organ injury, thereby establishing: a) consistent and reliable methodology to assess radiation-induced damage to the lung and heart; b) an extensive database in normal age-matched NHP for key primary and secondary endpoints; c) identified problematic variables in imaging techniques and proposed solutions to maintain data integrity; and d) initiated longitudinal analysis of potentially lethal radiation-induced damage to the lung and heart.


Gonadotropin-releasing hormone receptor-mediated growth suppression of immortalized LbetaT2 gonadotrope and stable HEK293 cell lines.
Continuous administration of GnRH analogs results in an inhibition of tumor growth that may be mediated in part by direct activation of GnRH receptors (GnRHRs) expressed on tumor cells. However, it is not fully understood how the GnRHR mediates these growth effects. This study aimed to determine how the presence or absence of this receptor in different cell types might affect the ability of GnRH to directly mediate growth effects. We demonstrate that continuous treatment with GnRH or a GnRH agonist (GnRHA) induces an antiproliferative effect in a gonadotrope-derived cell line (LbetaT2) and also in HEK293 cells stably expressing either the rat or human GnRHR. The antiproliferative effect was time and dose dependent and was verified using [3H]thymidine incorporation, light microscopy, and analysis of cell number. Inhibition was specifically mediated via the GnRHR, as cotreatment of the GnRHR-expressing cell lines with a GnRH antagonist blocked the growth-suppressive effect induced by GnRHA treatment. Cell cycle analysis revealed that GnRHA-treated HEK/GnRHR cell lines induced an accumulation of cells in the G2/M phase, whereas a G0/G1 arrest was observed in LbetaT2 cells. GnRHA treatment also caused a small, but significant, increase in apoptotic cells. This study provides evidence for a direct role for the GnRHR in mediating antiproliferative events in two cell systems, neither of which was derived from extrapituitary reproductive tumors. The ability to induce these effects, regardless of the cell system involved, has implications regarding the use of GnRH analogs for the treatment of endocrine-related disorders and tumors.


A system for high-speed microinjection of adherent cells.
This paper reports on a semi-automated microrobotic system for adherent cell injection. Different from embryos/oocytes that have a spherical shape and regular morphology, adherent cells are flat with a thickness of a few micrometers and are highly irregular in morphology. Based on computer vision microscopy and motion control, the system coordinately controls a three-degrees-of-freedom microrobot and a precision XY stage, demonstrating an injection speed of 25 endothelial cells per minute with a survival rate of 95.7% and a success rate of 82.4% (n=1012). The system has a high degree of performance consistency. It is operator skill independent and immune from human fatigue, only requiring a human operator to select injection destinations through computer mouse clicking as the only operator intervention. The microrobotic system makes the injection of a large number of adherent cells practical for testing cellular responses to foreign molecules.


Expression and function of LFA-1 on A-NK and T-LAK cells: role in tumor target killing and migration into tumor tissue.
To study the role of the adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) in lymphokine-activated natural killer (A-NK) and mitogen-stimulated lymphokine-activated T killer (T-LAK) cell function, we evaluated the correlation between LFA-1 expression, as well as conjugate formation and cytotoxicity. Furthermore, the role of LFA-1 in the extravascular phase of migration of A-NK and T-LAK cells into B16 tumor tissue in vivo was studied. We demonstrate an 8-fold increased LFA-1 expression on 4-day-old A-NK and T-LAK cells compared to unstimulated spleen cells. Moreover, we demonstrate that while LFA-1 expression on T-LAK cells was strictly correlated to conjugate formation and cytotoxic capacity, A-NK cells showed a less clear correlation between LFA-1 expression and these functions. Interestingly, anti-CD11a alone did not inhibit cytotoxicity, anti-CD18 alone did only inhibit cytotoxicity moderately (25%) whereas anti-CD11a and anti-CD18 in combination almost abrogated cytotoxicity against tumor targets P815 and YAC-1. Finally we demonstrate that pre-incubation of T-LAK cells with anti-bodies to CD11a and CD18 in combination inhibited their migration into the B16 tumors by more than 50-60%. In contrast, this pretreatment did not inhibit A-NK cell migration. This difference could not be explained by differences between A-NK and T-LAK cells with respect to LFA-1 expression, turnover of antibody-receptor complexes or complement-mediated lysis induced by the anti-LFA-1 antibodies. We conclude that T-LAK cell binding to and lysis of tumor target cells and migration into the intercellular space of tumors depend strongly on the expression of LFA-1. In contrast, LFA-1 expression of A-NK cells showed a less clear correlation to these functions.


Combatting pain after orthopedic/trauma surgery- perioperative oral extended-release tapentadol vs. extended-release oxycodone/naloxone.
High post-operative pain scores after "minor" orthopedic/trauma surgery are in part attributed to inadequate prescription of opioid analgesics. Novel concepts aiming to achieve sufficient analgesia while minimizing opioid-related side effects by avoiding fluctuating plasma levels are based on perioperative oral administration of extended-release opioids beginning with the first dose pre-operatively. This is the first study to evaluate analgesic efficacy and side effect rates of extended-release tapentadol compared to oxycodone/naloxone following orthopedic/trauma surgery. This randomized, observer-blinded, active-controlled prospective clinical trial had 2 co-primary endpoints: (1) Analgesic efficacy: Mean pain level on a numeric rating scale (NRS) from 0 to 10 during exercise over 5 days. (2) Safety: Side effect sum score of the following events: Nausea, vomiting, constipation, sedation, vertigo, somnolence. The study was powered to detect superiority of tapentadol for at least one endpoint pending statistical proof of non-inferiority for both endpoints in a first step. Two hundred sixty-six trauma patients were randomized to receive either tapentadol (n = 133) or oxycodone/naloxone (n = 133). Analgesic efficacy: Mean (±SD) daily pain levels in the first five post-operative days were 2.8 ± 1.3 in both groups. Mean maximum pain intensity during exercise in the first 24 h after surgery was 3.8 ± 1.9 (tapentadol) and 3.8 ± 2.1 (oxycodone/naloxone). Statistically tapentadol was non-inferior but not superior to oxycodone/naloxone. Vomiting on day 1 occurred in 11%, constipation in 35% of the tapentadol patients and in 16% and 30% of the oxycodone/naloxone patients (p = 0.60 and 0.33), respectively. The incidence of sedation/ vertigo was <10%, that of somnolence <2% in both groups (p > 0.3, respectively). The sum score of side effect events was 51% in the tapentadol vs. 49% in the oxycodone/naloxone group; risk difference 3% [95% CI, -8 to 14%]; p = 0.6). Non-inferiority of tapentadol could not be concluded as the pre-defined non-inferiority margin was exceeded. With both concepts, mean maximum pain intensity during exercise within the first 24 h after orthopedic/trauma surgery was reduced to a score of <4. This analgesic efficacy came at the cost of mainly gastro-intestinal side effects. Thus, we now use a prophylaxis against nausea and vomiting and pre-emptive laxatives as part of these concepts. https://eudract.ema.europa.eu (EudraCT- Nr. 2011-003238-15 ); October 24th, 2012.


Efficacy and Safety of a 0.1% Tacrolimus Nasal Ointment as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.
Hereditary hemorrhagic telangiectasia is a rare but ubiquitous genetic disease. Epistaxis is the most frequent and life-threatening manifestation and tacrolimus, an immunosuppressive agent, appears to be an interesting new treatment option because of its anti-angiogenic properties. Our objective was to evaluate, six weeks after the end of the treatment, the efficacy on the duration of nosebleeds of tacrolimus nasal ointment, administered for six weeks to patients with hereditary hemorrhagic telangiectasia complicated by nosebleeds, and we performed a prospective, multicenter, randomized, placebo-controlled, double-blinded, ratio 1:1 phase II study. Patients were recruited from three French Hereditary Hemorrhagic Telangiectasia (HHT) centers between May 2017 and August 2018, with a six-week follow-up, and we included people aged over 18 years, diagnosed with hereditary hemorrhagic telangiectasia and epistaxis (total duration > 30 min/6 weeks prior to inclusion). Tacrolimus ointment 0.1% was self-administered by the patients twice daily. About 0.1 g of product was to be administered in each nostril with a cotton swab. A total of 50 patients was randomized and treated. Mean epistaxis duration before and after treatment in the tacrolimus group were 324.64 and 249.14 min, respectively, and in the placebo group 224.69 and 188.14 min, respectively. Epistaxis duration improved in both groups, with no significant difference in our main objective comparing epistaxis before and after treatment (p = 0.77); however, there was a significant difference in evolution when comparing epistaxis before and during treatment (p = 0.04). Toxicity was low and no severe adverse events were reported. In conclusion, tacrolimus nasal ointment, administered for six weeks, did not improve epistaxis in HHT patients after the end of the treatment. However, the good tolerance, associated with a significant improvement in epistaxis duration during treatment, encouraged us to perform a phase 3 trial on a larger patient population with a main outcome of epistaxis duration during treatment and a longer treatment time.


Deregulation of linc-PINT in acute lymphoblastic leukemia is implicated in abnormal proliferation of leukemic cells.
Long Non-Coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. Several lncRNAs are involved in cell proliferation and are deregulated in several human tumors. Few lncRNAs have been described to play a role in Acute Lymphoblastic Leukemia (ALL). In this study, we carried out a genome wide lncRNA expression profiling in ALL samples and peripheral blood samples obtained from healthy donors. We detected 43 lncRNAs that were aberrantly expressed in ALL. Interestingly, among them, linc-PINT showed a significant downregulation in T and B-ALL. Re-expression of linc-PINT in ALL cells induced inhibition of leukemic cell growth that was associated with apoptosis induction and cell cycle arrest in G2/M phase. linc-PINT induced the transcription of HMOX1 which reduced the viability of ALL cells. Intriguingly, we observed that treatment with anti-tumoral epigenetic drugs like LBH-589 (Panobinostat) and Curcumin induced the expression of linc-PINT and HMOX1 in ALL. These results indicate that the downregulation of linc-PINT plays a relevant role in the pathogenesis of ALL, and linc-PINT re-expression may be one of the mechanisms exerted by epigenetic drugs to reduce cell proliferation in ALL.


The role of ZFX in non-small cell lung cancer development.
Zinc finger protein, X-linked (ZFX) is a transcription factor encoded by its gene on the mammalian X chromosome, and functions to control survival and activity of stem cells and lymphocytes. However, little is known about the role of ZFX in tumorigenesis. The function of ZFX in cell proliferation was investigated by the lentivirus-mediated short hairpin RNA interference (shRNA) approach in non-small cell lung cancer (NSCLC) cell culture lines. The expression profiles of ZFX in 49 pairs of tumors and corresponding matched adjacent normal tissues from NSCLC patients were examined by real-time PCR. The specific knockdown of ZFX by shRNA significantly inhibited cell viability and reduced colony formation of 95D cells. And ZFX silencing resulted in cell cycle arrest in G0/G1 phase. In addition, ZFX was overexpressed and correlated with lymph node metastasis in samples from 49 NSCLC patients. We reported for the first time that ZFX may play an important role in cell growth control and cell cycle progression of 95D cells. Furthermore, ZFX was overexpressed in samples of NSCLC and ZFX mRNA expression associated with lymph node metastasis. Therefore, our findings suggest that ZFX would be a potential target to development of therapies for NSCLC.


Differences in the utilization of glycerol and glucose by Mycobacterium phlei.
A basic difference was found in the kinetics of uptake and utilization of glucose and glycerol by washed suspensions of Mycobacterium phlei. With glucose, the rates of uptake, respiration, and assimilation were saturated at low external substrate concentration. With glycerol, these rates were found to increase with increasing substrate concentration and did not show saturation at any concentration tested. Qualitatively similar patterns were observed for cells grown on either glycerol or glucose. Above a saturation concentration, ratios of cell (14)C to CO(2) (14)C for uniformly labeled (14)C-glucose were constant at a value of 0.96. Glycerol-U-(14)C, on the other hand, yielded cell-(14)C/CO(2)-(14)C ratios which were highest at the lowest glycerol concentration tested, and decreased with increasing substrate concentration. The distribution of the glucose and glycerol carbons assimilated into M. phlei were qualitatively similar. Quantitatively, however, the uptake and assimilation of glycerol was far more rapid than that of glucose for all substrate concentrations employed. These quantitative differences in the utilization of glycerol and glucose could account for the increased content of nonessential lipid and polysaccharide found in glycerol-grown M. phlei.


Association between baseline levels of muscular strength and risk of stroke in later life: The Cooper Center Longitudinal Study.
Muscular strength is an important component of physical fitness. We evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged ≥65 years during follow-up. We included 7627 healthy adults (mean age = 43.9 years, 86.0% male) underwent a baseline physical examination between 1980 and 1989. Muscular strength was determined by 1-repetition maximum measures for bench press and leg press and categorized into age- and sex-specific tertiles for each measure. Cardiorespiratory fitness (CRF) was assessed via a maximal treadmill exercise test. Those enrolled in fee-for-service Medicare from 1999 to 2019 were included in the analyses. Associations between baseline strength and stroke outcomes were estimated using a modified Cox proportional hazards model. In a secondary analysis, we examined stroke risk by categories of CRF where Quintile 1 = low, Quintiles 2-3 = moderate, and Quintiles 4-5 = high CRF based on age and sex. After 70,072 person-years of Medicare follow-up, there were 1211 earliest indications of incident stroke. In multivariable analyses, the hazard ratio (95% confidence interval (95%CI)) for stroke across bench press categories were 1.0 (referent), 0.96 (0.83-1.11), and 0.89 (0.77-1.04), respectively (p trend = 0.14). The trend across categories of leg press was also non-significant (p trend = 0.79). Adjusted hazard ratio (95%CI) for stroke across ordered CRF categories were 1.0 (referent), 0.90 (0.71-1.13), and 0.72 (0.57-0.92) (p trend < 0.01). While meeting public health guidelines for muscular strengthening activities is likely to improve muscular strength as well as many health outcomes in older adults, performing such activities may not be helpful in preventing stroke. Conversely, meeting guidelines for aerobic activity is likely to improve CRF and lower stroke risk.


Low doses of recombinant interleukin-2 enhance delayed type hypersensitivity to PPD in mice infected with Mycobacterium bovis-BCG and fed a diet supplemented with vitamin A acetate.
Mice infected intravenously with high doses of M. bovis, strain BCG, showed a marked impairment of delayed-type hypersensitivity to PPD evaluated in vivo as skin test and in vitro as splenocyte blast transformation. Furthermore, this state of unresponsiveness is partially reversed either by the intraperitoneal injection of high doses of IL-2 or by feeding mice a diet supplemented with vitamin A acetate (VAA) at least 6 weeks before the BCG injection. This paper shows that low doses of recombinant IL-2 together with a supplementation of VAA in the diet at the moment of BCG infection is sufficient to induce in mice a positive skin reaction and blast transformation to PPD.


Isokinetic strength characteristics of the quadriceps femoris and hamstring muscles in high school students.
The purpose of this study was to determine the isokinetic strength of the quadriceps femoris and hamstring muscles in high school-aged students. Forty-seven 15- to 18-year-old high school volunteers served as subjects. Data were gathered on each subject by a questionnaire, lower extremity musculoskeletal assessment, and isokinetic testing of the two muscle groups at 60 degrees/sec and 180 degrees/sec. This study found no age effect on peak torque and no significant differences in peak torque between dominant and nondominant limbs. Significant differences (p less than .001) occurred between the isokinetic strength of male and female subjects. The average hamstring muscle to quadriceps femoris muscle torque ratio was 57 percent at 60 degrees/sec and 70 percent at 180 degrees/sec. A value of foot pounds of torque per kilogram of body weight was provided as a guideline for clinicians. This investigation supports several findings already reported for other age groups.


DMD antisense oligonucleotide mediated exon skipping efficiency correlates with flanking intron retention time and target position within the exon.
Mutations in the DMD gene are causative for Duchenne muscular dystrophy (DMD). Antisense oligonucleotide (AON) mediated exon skipping to restore disrupted dystrophin reading frame is a therapeutic approach that allows production of a shorter but functional protein. As DMD causing mutations can affect most of the 79 exons encoding dystrophin, a wide variety of AONs are needed to treat the patient population. Design of AONs is largely guided by trial-and-error, and it is yet unclear what defines the skippability of an exon. Here, we use a library of phosphorodiamidate morpholino oligomer (PMOs) AONs of similar physical properties to test the skippability of a large number of DMD exons. The DMD transcript is non-sequentially spliced, meaning that certain introns are retained longer in the transcript than downstream introns. We tested whether the relative intron retention time has a significant effect on AON efficiency, and found that targeting an out-of-frame exon flanked at its 5'-end by an intron that is retained in the transcript longer ('slow' intron) leads to overall higher exon skipping efficiency than when the 5'-end flanking intron is 'fast'. Regardless of splicing speed of flanking introns, we find that positioning an AON closer to the 5'-end of the target exon leads to higher exon skipping efficiency opposed to targeting an exons 3'-end. The data enclosed herein can be of use to guide future target selection and preferential AON binding sites for both DMD and other disease amenable by exon skipping therapies.


Immunohistochemical investigation of the human inner ear. Limitations and prospects.
The application of highly sensitive and specific immunohistochemical methods in routine light microscopy has been rewarded by a great many new observations. The essential underlying antigen-antibody reaction has allowed the recognition and identification of some unknown or unidentified components of the cell. Successful results are best achieved by means of reliable fixation and the use of frozen sections. Frozen sections of the human cochlea are, however, impaired by unavoidable damage to the tissues to be studied. The temporal bone has to be decalcified, resulting in a reduction of the range of suitable methods and an interference with a reliable interpretation of the results. The preservation of the specific antigenicity of the tissues is of paramount importance, allowing the detection of the investigated antigen by the antibody applied. The investigation of different fixatives and various methods of decalcification in tissues possessing some familiar and readily identifiable antigens has confirmed the immunohistochemical suitability of properly fixed and adequately decalcified human temporal bones. The present demonstration deals with some of the principal technical procedures and includes examples of their application for the study of the human inner ear. The goal of our research is the development of reliable immunohistochemical methods of fixation and decalcification to be employed in the study of specimens from patients with Ménière's disease, sudden deafness, progressive loss of hearing, genetic sensorineural syndromes, etc. This will lead to the extension of our knowledge of some unrecognized causes of sensorineural hearing loss.


Phenotypic features of patients with congenital adrenal hypoplasia and glycerol kinase deficiency.
Two unrelated boys with congenital adrenal hypoplasia and glycerol kinase deficiency were found to have similar features, including characteristic facies, testicular abnormalities, short stature, psychomotor retardation, and muscular dystrophy. The resemblance of these boys to other patients described in the literature suggests that a distinct phenotypic syndrome occurs in children with congenital adrenal hypoplasia and glycerol kinase deficiency.


Biological evidence of imagery abilities: intraindividual differences.
This study extended motor imagery theories by establishing specificity and verification of expected brain activation patterns during imagery. Eighteen female participants screened with the Movement Imagery Questionnaire-3 (MIQ-3) as having good imagery abilities were scanned to determine the neural networks active during an arm rotation task. Four experimental conditions (i.e., KINESTHETIC, INTERNAL Perspective, EXTERNAL Perspective, and REST) were randomly presented (counterbalanced for condition) during three brain scans. Behaviorally, moderate interscale correlations were found between the MIQ-3 and Vividness of Movement Imagery Questionnaire-2, indicating relatedness between the questionnaires. Partially confirming our hypotheses, common and distinct brain activity provides initial biological validation for imagery abilities delineated in the MIQ-3: kinesthetic imagery activated motor-related areas, internal visual imagery activated inferior parietal lobule, and external visual imagery activated temporal, but no occipital areas. Lastly, inconsistent neuroanatomical intraindividual differences per condition were found. These findings relative to recent biological evidence of imagery abilities are highlighted.


Cortisol in Neonatal Mother's Milk Predicts Later Infant Social and Cognitive Functioning in Rhesus Monkeys.
Milk provides not only the building blocks for somatic development but also the hormonal signals that contribute to the biopsychological organization of the infant. Among mammals, glucocorticoids (GCs) in mother's milk have been associated with infant temperament. This study extended prior work to investigate rhesus monkey (Macaca mulatta) mother-infant dyads (N = 34) from birth through 8 months postpartum. Regression analysis revealed that cortisol concentrations in milk during the neonatal period predicted impulsivity on a cognitive task, but not global social behaviors, months later. During this time period, sex-differentiated social behavior emerged. For female infants, milk cortisol concentrations predicted total frequency of play. Collectively, these findings support and extend the "lactational programming" hypothesis on the impact of maternal-origin hormones ingested via milk.


Morphine-halothane interaction in rats.
The effects of morphine, halothane, and their various combinations on the purposeful movement (PM) response and the heart rate (HR) increase caused by noxious stimulation were studied in 250 rat experiments. Doses that block the PM and HR responses for the single agent and for combinations were determined with a probit procedure and compared with an isobolographic analysis. As was evidenced by the PM response, the combined anesthetic effect of morphine and halothane, with some deviations, may be defined as additive. It also was found that the combined administration of morphine and halothane results in an antagonism for suppression of the HR increase to noxious stimulation. Halothane antagonized morphine to a much greater extent than morphine to halothane.


Pseudomonas matsuisoli sp. nov., isolated from a soil sample.
An aerobic, Gram-stain-negative, rod-shaped and polar-flagellated bacterium, designated strain CC-MHH0089(T), was isolated from a soil sample taken on Matsu Island (Taiwan). Strain CC-MHH0089(T) grew at 15-30 °C and pH 5.0-10.0 and tolerated ≤8 % (w/v) NaCl. 16S rRNA gene sequence analysis showed high pairwise sequence similarity to Pseudomonas azotifigens 6H33b(T) (97.3 %) and Pseudomonas balearica SP1402(T) (96.7 %) and lower sequence similarity to other strains (<96.0 %). In DNA-DNA reassociation experiments, the relatedness of strain CC-MHH0089(T) to P. azotifigens JCM 12708(T) was 38.3 % (reciprocal value 19.5 %). Evolutionary trees reconstructed on the basis of 16S rRNA, gyrB and rpoB gene sequences revealed a varying phylogenetic neighbourhood of strain CC-MHH0089(T) with regard to the most closely related type strains. The predominant quinone system was ubiquinone 9 (Q-9) and the DNA G+C content was 63.6 mol%. The major fatty acids were C12 : 0, C16 : 0, C17 : 0, C19 : 0 cyclo ω8c and summed features 2 (C14 : 0 3-OH/iso-C16 : 1 I), 3 (C16 : 1ω7c/C16 : 1ω6c) and 8 (C18 : 1ω7c/C18 : 1ω6c). The major polar lipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. According to its distinct phylogenetic, phenotypic and chemotaxonomic features, strain CC-MHH0089(T) is proposed to represent a novel species within the genus Pseudomonas, for which the name Pseudomonas matsuisoli sp. nov. is proposed. The type strain is CC-MHH0089(T) ( = BCRC 80771(T) = JCM 30078(T)).


Adolescent suicidal behaviours: a population-based study of risk.
Reports of adolescent suicidal behaviour have generally derived from clinical settings but population-based studies are likely to provide a clearer epidemiological view. Non-fatal suicidal behaviours were studied in 1699 Australian 15- to 16-year-old secondary school students at 44 schools in the state of Victoria, Australia. Self-reported episodes of self-harm were characterized using items from the Beck Suicide Intent Scale. The 12 month weighted prevalence estimate for deliberate self-harm was 5.1%. The commonest forms were self-laceration (1.7%), self-poisoning (1.5%) and deliberate recklessness (1.8%). Self-poisoning and self-laceration were commoner in girls. The prevalence of 'true suicide attempts' was 0.2%. Most self-harmers did not perceive death as likely, plan self-harming episodes at length or inform others of the episodes. Psychiatric morbidity had the strongest association with self-harm, an association which held for all subtypes. Antisocial behaviour and substance abuse were associated with self-harm in girls but not boys. Sexual activity was independently associated with self-harm in both genders. Deliberate self-harm was common but the great majority of episodes were not 'true suicide attempts'. It is, therefore, possible that attributable mortality and morbidity may be greater in self-harmers without definite suicidal intent.


Causal role for an activated N-ras oncogene in the induction of tumorigenicity acquired by a human cell line.
ras oncogenes have been found in approximately 15% of the human tumors analyzed. However, a causal role for these genes in the tumorigenesis of human cells has yet to be shown. Tumorigenic late-passage PA-1 human teratocarcinoma cells (E-PA-1) contain an activated N-ras gene. In this report evidence is presented that nontumorigenic early passage revertant PA-1 cells (E-PA-1) contain only the germ-line protooncogene. Introduction by gene transfer of the activated L-PA-1 oncogene induces E-PA-1 cells to form tumors, suggesting that the activated N-ras oncogene has a causal role in the tumorigenesis of these cells.


Can endoscopic injection of epinephrine prevent surgery in gastroduodenal ulcer bleeding? An analysis of 107 cases.
Gastroduodenal ulcers are still a common cause of severe upper gastrointestinal bleeding. Endoscopy has gained popularity worldwide over conventional open surgery for the treatment of upper gastrointestinal bleeding. This study aims to assess the efficacy of endoscopic injection of epinephrine in the treatment of gastroduodenal ulcer bleeding. This study was conducted between March 2000 and March 2003. We analyzed 107 consecutive patients admitted to our department of trauma and emergency surgery with upper gastrointestinal bleeding. Endoscopy was performed on all 107 patients and bleeding ulcers were treated with injection of diluted epinephrine. Recurrent bleeding was seen in 21 patients (19.6%), all of whom underwent a second endoscopy. Four patients (3.7%) required a third endoscopy session and nine patients (8.5%) needed surgery after endoscopy failed. There were two mortalities (1.9%). The nine patients who required surgery and the two patients who died were all in the Forrest Ia and Ib groups of acute UGI hemorrhage. Endoscopic injection therapy with epinephrine reduces operation rates and can be used safely in adequate hemostasis of gastroduodenal ulcers.


Description of Process and Content of Online Dementia Coaching for Family Caregivers of Persons with Dementia.
Family caregivers of persons with dementia encounter resistance to care behaviors (RCBs). The purpose of this methods paper was to describe the process and content of six weekly 60-min caregiver coaching sessions delivered synchronously through an online platform to 26 family caregivers of persons with dementia. All session notes were analyzed for process; two coaching sessions from five purposely-selected participants were transcribed and analyzed thematically for content. The six sessions followed an overall pattern. The first session included the most teaching and goal-setting; the coaches also queried the family caregiver about the premorbid personality, work history, and interpersonal attributes of the person with dementia. Sessions two through five were the most active coaching sessions; previously suggested strategies were evaluated and tailored; caregivers also role-played with the coaches and developed scripts designed to curtail RCB. The sixth session served as a review of successful caregiver strategies and concluded the coaching relationship. Four primary content themes emerged in the coaching process: (1) education; (2) caregiver communication; (3) affirmation of the caregiver; and (4) individualized strategies. These four content categories were used throughout the coaching process and were interwoven with each other so that the participant knew why the behavior was occurring, how to verbally address it, how to use a strategy effectively, and affirmation of the result. The coaching process and content demonstrated alignment with person-centered practices and relationship-centered care.


Munc18-1 phosphorylation by protein kinase C potentiates vesicle pool replenishment in bovine chromaffin cells.
Activation of protein kinase C (PKC) after robust stimulation is necessary for vesicle pool replenishment in secretory cells. Here we studied the contribution of a prominent downstream PKC target, Munc18-1, to this process in bovine chromaffin cells. In these cells, both activation of endogenous PKC and overexpressing of Munc18-1 promote vesicle pool replenishment after an extensive stimulation. In order to study the physiological relevance of PKC-dependent Munc18-1 phosphorylation, we generated two Munc18-1 phospho-mutants; one that mimics a constitutively PKC-phosphorylated Munc18-1 (i.e. a phosphomimetic mutant; Munc18-1(S313D)) and a second that cannot be PKC-phosphorylated (Munc18-1(3A)). Overexpression of Munc18-1(3A) caused a significant decrease in vesicle pool replenishment following a depleting stimulation, while Munc18-1(S313D) caused a significant increase in vesicle pool replenishment. These findings suggested that the phosphorylation of Munc18-1 by PKC potentiates vesicle pool replenishment. This hypothesis was further strengthened by the finding that overexpression of wild type Munc18-1 in the presence of a PKC inhibitor caused a significant reduction in vesicle pool replenishment, similar to that observed with Munc18-1(3A). Moreover, overexpression of Munc18-1(S313D) in the presence of the PKC inhibitor partly alleviated this attenuation, elucidating Munc18-1's unique contribution to vesicle pool replenishment. Finally, we demonstrate that Munc18-1 promotes vesicle docking in a phosphorylation-independent manner. This is deduced from the findings that both the wild type and the two Munc18-1 phospho-mutants enhanced docking to the same extent in bovine chromaffin cells. We conclude that Munc18-1 facilitates docking in a PKC phosphorylation-independent manner, and that its phosphorylation by PKC potentiates vesicle pool replenishment following a depleting stimulation, at a post-docking stage.


Degenerative disorders of the carpus.
Degenerative arthritis of the human wrist follows specific patterns. The patterns do not change with time. Degenerative arthritis progresses within the framework of these patterns. Specific therapeutic approaches have been developed for the treatment of degenerative arthritis of the wrist, with an emphasis on maintaining painless range of motion and power function capability.


Chemokine Homeostasis in Healthy Volunteers and during Pancreatic and Colorectal Tumor Growth in Murine Models.
Chemokines are involved in the humoral regulation of body homeostasis. Changes in the blood level of chemokines were found in cancer, atherosclerosis, diabetes, and other systemic diseases. It is essential to distinguish the effects of co-morbid pathologies and cancer on the level of chemokines in the blood. We aimed to analyze, by multiplex cytometry, the levels of chemokines in the blood of healthy young volunteers as well as of intact mice and mice with CT26 colon and Pan02 pancreatic tumors. Two types of chemokines were identified both in human and murine plasmas: homeostatic ones, which were found in high concentrations (>100 pg/mL), and inducible ones, which can be undetectable or determined at very low levels (0−100 pg/mL). There was a high variability in the chemokine levels, both in healthy humans and mice. To analyze chemokine levels during tumor growth, C57BL/6 and BALB/c were inoculated with Pan02 or CT26 tumor cells, accordingly. The tumors significantly differed in the growth and the mortality of mice. However, the blood chemokine levels did not change in tumor-bearing mice until the very late stages. Taken collectively, blood chemokine level is highly variable and reflects in situ homeostasis. Care should be taken when considering chemokines as prognostic parameters or therapeutic targets in cancer.


2D Atomic Layers for CO2 Photoreduction.
Artificial photosynthesis can convert carbon dioxide into high value-added chemicals. However, due to the poor charge separation efficiency and CO2 activation ability, the conversion efficiency of photocatalytic CO2 reduction is greatly restricted. Ultrathin 2D photocatalyst emerges as an alternative to realize the higher CO2 reduction performance. In this review, the basic principle of CO2 photoreduction is introduced, and the types, advantages, and advances of 2D photocatalysts are reviewed in detail including metal oxides, metal chalcogenides, bismuth-based materials, MXene, metal-organic framework, and metal-free materials. Subsequently, the tactics for improving the performance of 2D photocatalysts are introduced in detail via the surface atomic configuration and electronic state tuning such as component tuning, crystal facet control, defect engineering, element doping, cocatalyst modification, polarization, and strain engineering. Finally, the concluding remarks and future development of 2D photocatalysts in CO2 reduction are prospected.


The Introduction of a Protocol for Esophageal Screening in Videofluoroscopic Swallowing Studies: Exploring Clinical Impacts and Barriers.
Esophageal screening is a valuable inclusion in videofluoroscopic swallowing studies (VFSSs). However, routine standardized esophageal screening does not always occur in clinical practice. This study introduced and evaluated an esophageal screening protocol at one Australian hospital. Radiology, gastroenterology, and speech-language pathology endorsed an esophageal screening protocol, which followed a timed 20-ml International Dysphagia Diet Standardisation Initiative Level 0 bolus from mouth to stomach in an upright anterior-posterior position. Measures exploring clinical impacts and barriers were recorded. Participants were compared with 100 consecutive VFSS patients prior to the introduction of the esophageal screening protocol. During the esophageal screening protocol trial, 163 VFSSs were conducted with recruited patients. Aspiration risk (29%, n = 47/163) and positioning limitation (3%, n = 5/163) were barriers to esophageal screening. Rates of esophageal screening significantly increased with the esophageal screening protocol (χ2 = 63.462, p < .001). There was no difference in radiation dose for patients who had esophageal screening and those who did not in the esophageal screening protocol group (U = 1689.000, p = .237). The VFSS team breached the esophageal screening protocol for some patients, when evaluating esophageal transit time (n = 28) and recommending gastroenterology referral (n = 6). There was no difference between groups for rates of gastroenterology consults (χ2 = 1.805, p = .188) or dysphagia procedures (χ2 = 1.951, p = .209). This study confirms that routine esophageal screening provides additional clinical information to assist holistic dysphagia management without adverse operational impacts. Further research with the multidisciplinary dysphagia team has commenced to continue to optimize and refine esophageal screening practice.


New Insight into GO, Cadmium(II), Phosphate Interaction and Its Role in GO Colloidal Behavior.
This study establishes the relationship between the graphene oxide (GO) colloidal behavior and the co-adsorption of Cd(II) and phosphate (P(V)) on GO. Results reveal that the interactions among GO, Cd(II), and P(V) exhibit a significant dependence on solution chemistry and addition sequences and that these interactions subsequently affect the GO colloidal behavior. The GO aggregation is pH-dependent at pH < 4.0 and depends apparently on the binding ability of Cd(II) to GO at pH > 4.0. When the components were added simultaneously, the presence of P(V) enhances the GO binding capacity toward Cd(II), confirmed by theoretical calculation, resulting in the greater destabilizing influence of Cd(II) + P(V) on GO than Cd(II) at pH 3.0-9.5, while the formation of Cd3(PO4)2 precipitate leads to a lower destabilizing influence of Cd(II) + P(V) on GO than Cd(II) at pH > 9.5. Both pH and addition sequence affect the destabilizing ability of Cd(II) + P(V). These new insights are expected to provide valuable information not only for the application of GO as a potential adsorbent in multicomponent systems for heavy metal ion and oxyanion co-removal but also for the fate and risk assessment of GO after serving as heavy metal ion and oxyanion carrier.


A meta-analysis of randomized controlled trials on levetiracetam in the treatment of pediatric patients with epilepsy.
To evaluate clinical efficacy, safety, and tolerability of levetiracetam as mono- or adjunctive therapy in the treatment of children and adolescents with epilepsy. We performed a meta-analysis of randomized controlled trials published from January 2007 to December 2016 in the databases Web of Science, Medline, Embase, Cochrane Library, and PubMed, Bing, Baidu, Google Scholar, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data. All of the studies eligible were compared for the efficacy, safety, and tolerability of levetiracetam with other antiepileptic drugs (AEDs) in epilepsy. Thirteen randomized controlled trials on a total of 1,013 patients met the inclusion criteria in present study. Compared with other AEDs (oxcarbazepine, valproate, sulthiame, carbamazepine, and placebo), we found that levetiracetam had a comparable seizure-free rate (RR 1.16, 95% CI 1.03-1.31; P=0.30). Regarding seizure-frequency reduction ≥50% from baseline, levetiracetam also seemed equivalent to other AEDs (RR 1.08, 95% CI 1.01-1.16; P=0.35). In spite of patients treated with levetiracetam having a lower incidence of side effects compared with patients treated with other AEDs (RR 0.90, 95% CI 0.77-1.06), the difference between them was minute and not statistically significant (P=0.22). Based on this meta-analysis, it seemed that levetiracetam had comparable effects concerning efficacy, tolerability, and adverse events. Nevertheless, 13 studies were insufficient to draw a conclusion that levetiracetam is effective as mono- and adjunctive therapy for all types of epilepsy syndromes and seizures. Larger-sample and more well-designed trials are needed to justify the widespread use of levetiracetam in the treatment of children and adolescents.


Exact results for anomalous transport in one-dimensional hamiltonian systems.
Anomalous transport in one-dimensional translation invariant hamiltonian systems with short range interactions is shown to belong in general to the Kardar-Parisi-Zhang universality class. Exact asymptotic forms for density-density and current-current time correlation functions and their Fourier transforms are given in terms of the Prähofer-Spohn scaling functions, obtained from their exact solution for the polynuclear growth model. The exponents of corrections to scaling are found as well, but not so the coefficients. Mode coupling theories developed previously are found to be adequate for weakly nonlinear chains but in need of corrections for strongly anharmonic interparticle potentials. A simple condition is given under which Kardar-Parisi-Zhang behavior does not apply, sound attenuation is only logarithmically superdiffusive, and heat conduction is more strongly superdiffusive than under Kardar-Parisi-Zhang behavior.


On the additive properties of the fat-shattering dimension.
The properties of the VC-dimension under various compositions are well-understood, but this is much less the case for classes of continuous functions. In this brief, we show that a commonly used scale-sensitive dimension, Vγ, is much less well-behaved under Minkowski summation than its VC cousin, while the fat-shattering dimension retains some compositional similarity to the VC-dimension. As an application, we analyze the fat-shattering dimension of trigonometric functions and series.


Seprase, a membrane-bound protease, alleviates the serum growth requirement of human breast cancer cells.
Seprase is a cell surface serine protease that is expressed to high levels by infiltrating ductal carcinomas of the breast but its function in malignancy is unknown. MDA-MB-435 (WT435) and MDA-MB-436 (WT436) human breast cancer cells express high levels of seprase as do the carcinoma cells in tumors of human breast cancer patients. To investigate its role in the pathobiology of breast cancer, seprase was specifically reduced in WT436 and WT435 cells by expression of antisense seprase cDNA. Decreased expression of seprase was confirmed in the antisense transfectants by zymography, immunoblotting, and fluorescence-activated cell sorting of cells labeled with antibody to seprase. Control-transfectants continued to express high levels of seprase. Seprase-deficient cells growing on type I collagen gels reveal a markedly different morphology than the parental or control-transfected cells that express high levels of seprase. The seprase-deficient cells grow in islands and aggregates of tightly attached cells while cells with high seprase expression grow as groups of separate individual cells. Interestingly, the aggregated growth of the seprase-deficient cells was not correlated with increased expression of E-cadherin. Seprase-deficient breast cancer cells also exhibit altered growth properties. Seprase-deficient cells and those with high seprase levels proliferate in serum-containing media. However, in serum-free medium seprase-deficient cells proliferate much more slowly than their seprase-expressing counterparts. These findings indicate that seprase promotes the aberrant growth of breast cancer cells by reducing their dependence on exogenous growth factors. Seprase may contribute to the pathogenesis of breast cancer by promoting growth of the primary tumor and by facilitating the growth of breast cancer cells in metastases at other sites of the body.