Influence of particle shape on plasma protein adsorption and macrophage uptake.
The purpose of this study was to evaluate the plasma protein adsorption behavior onto different LIPOMER nanoparticles, especially looking for the first time, if the particle shape affects the protein adsorption pattern. The potential in vivo fate is discussed and compared with previous in vivo animal studies. The two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used for identification of adsorbed plasma proteins. Qualitative similar patterns were obtained from the protein adsorption analysis and four apolipoproteins with considerable quantitative differences were identified. Besides the quantitative differences in the adsorbed apolipoproteins, in vitro uptake in the human macrophage cell line U-937 of histocytic lymphoma organ revealed significantly lower uptake of the irregular glycerol monostearate LIPOMER nanoparticles. Therefore, protein adsorption does not seem to play a role in the splenotropic behavior in the sense, that adsorption of opsonins, especially spleen-specific opsonins are required for the uptake. The splenotropic uptake might be favored because all LIPOMER nanoparticles did not adsorb opsonins at all, mediating competitive uptake by liver macrophages. Differences in the in vivo uptake by the spleen were attributed to differences in particle shape with potential super position effect by the quantitative differences in the adsorbed proteins.


Suppression of microtubule dynamics by epothilone B is associated with mitotic arrest.
The epothilones are a group of novel microtubule-targeted, antimitotic compounds that have a paclitaxel-like, assembly enhancing effect on tubulin in vitro as well as in cultured cells. We hypothesize that epothilones induce mitotic arrest by suppressing microtubule dynamics. To test this hypothesis, we used MCF7 cells stably transfected with GFP-alpha-tubulin to analyze microtubule dynamics at three concentrations of epothilone B, one that induced no mitotic arrest (0.2 nM, 20 h), one that induced one-third maximal mitotic arrest (IC(33,) 2 nM, 20 h), and one that induced half-maximal mitotic arrest (IC(50,) 3.5 nM, 20 h). We found that epothilone B suppressed microtubule dynamics in a concentration-dependent manner coincident with mitotic block. At 0.2 nM epothilone B, dynamics were not significantly altered. At 2 nM epothilone B (IC(33)), the mean growth and shortening rates were decreased by 38 and 27%, respectively. Dynamicity was decreased by 47%. At the IC(50), 80% of the cells had nearly complete stabilization of microtubule dynamics, and no anaphase or telophase figures were observed. Comparison of the effects of epothilone B on microtubule dynamics with those of paclitaxel indicated that both drugs alter the same microtubule dynamic parameters to a similar extent. At the IC(50) for mitotic arrest, dynamicity was reduced by 54% by paclitaxel compared with 62% for epothilone B. In 65% of the cells treated with paclitaxel, the microtubules were completely stabilized. Thus, the effects of epothilone B on microtubule dynamics are remarkably similar to those of paclitaxel, suggesting that both drugs induce mitotic block by a similar mechanism.


Approaches to Dispersing Medical Biofilms.
Biofilm-associated infections pose a complex problem to the medical community, in that residence within the protection of a biofilm affords pathogens greatly increased tolerances to antibiotics and antimicrobials, as well as protection from the host immune response. This results in highly recalcitrant, chronic infections and high rates of morbidity and mortality. Since as much as 80% of human bacterial infections are biofilm-associated, many researchers have begun investigating therapies that specifically target the biofilm architecture, thereby dispersing the microbial cells into their more vulnerable, planktonic mode of life. This review addresses the current state of research into medical biofilm dispersal. We focus on three major classes of dispersal agents: enzymes (including proteases, deoxyribonucleases, and glycoside hydrolases), antibiofilm peptides, and dispersal molecules (including dispersal signals, anti-matrix molecules, and sequestration molecules). Throughout our discussion, we provide detailed lists and summaries of some of the most prominent and extensively researched dispersal agents that have shown promise against the biofilms of clinically relevant pathogens, and we catalog which specific microorganisms they have been shown to be effective against. Lastly, we discuss some of the main hurdles to development of biofilm dispersal agents, and contemplate what needs to be done to overcome them.


Indolocarbazole-Based Photo-Crosslinkable Hole-Transporting Layer for Efficient Solution-Processed Organic Light-Emitting Diodes.
We designed and synthesized a new indolocarbazole-based polymer, poly(N,N-diphenyl(5,11-dihexylindolo[3,2,1-jk]carbazol-2-yl)amine) (PICA), for solution-processed organic light-emitting diodes (OLEDs). The highest occupied and lowest unoccupied molecular orbital energy levels of this polymer, -5.25 and -2.46 eV, respectively, are suitable for hole transport from the anode to the emissive layer. PICA was photo-crosslinked by UV irradiation with ethane-1,2-diyl bis(4-azido-2,3,5,6-tetrafluorobenzoate) (FPA) as the photoinitiator. Successful crosslinking was confirmed by a decreased intensity in the azide-stretching FT-IR peak and solvent test with toluene (a suitable solvent for PICA). The PICA film photo-crosslinked with 3 wt% FPA showed enhanced solvent resistance (90%) compared to the non-crosslinked neat PICA film (<20%). Moreover, OLED devices using PICA-based hole-transporting layers exhibited better device performance (EQE/LE/PE: 8.88%/12.97/8.12 in red devices, 10.84%/38.47 cd/A/25.06 lm/W in green devices) than those using poly-TPD:FPA. We demonstrated that the photo-crosslinked PICA can be applied as a hole-transporting layer in solution-processed OLEDs.


Effect of SSRI and calcium channel blockers on depression symptoms and cognitive function in elderly persons treated for hypertension: three city cohort study.
ABSTRACTBackground:Emerging genetic, ex-vivo, and clinical trial evidence indicates that calcium channel blockers (CCB) can improve mood and cognitive function. The objective of this study was to examine the effect of selective serotonin reuptake inhibitor (SSRI) therapy augmented with CCB on depression and cognitive decline in an elderly population with hypertension. Prospective study of 296 persons treated with SSRI and antihypertensive drugs. Baseline and two year clinic assessments were used to categorize participants as users of SSRI + CCB (n = 53) or users of SSRI + other antihypertensives (n = 243). Clinic visits were performed up to four times in a ten-year period to assess depression and cognitive function. The sample mean age was 75.2 ± 5.47 years and 78% of participants were female. At two year follow-up there was a significant group by time interaction showing lower Center for Epidemiological Studies-Depression (CESD) scores in the SSRI + CCB group, F(1,291) = 4.13, p = 0.043, η2p = 0.014. Over ten-years follow-up, SSRI + CCB use was associated with improved general cognitive function (Mini-Mental State Examination: β = 0.97; 95% CI 0.14 to 1.81, p = 0.023) and immediate visual memory (Boston Visual Retention Test: β = 0.69; 95% CI 0.06 to 1.32, p = 0.033). The findings provide general population evidence that SSRI augmentation with CCB may improve depression and cognitive function.


Type-I prenyl protease function is required in the male germline of Drosophila melanogaster.
Many proteins require the addition of a hydrophobic prenyl anchor (prenylation) for proper trafficking and localization in the cell. Prenyl proteases play critical roles in modifying proteins for membrane anchorage. The type I prenyl protease has a defined function in yeast (Ste24p/Afc1p) where it modifies a mating pheromone, and in humans (Zmpste24) where it has been implicated in a disease of premature aging. Despite these apparently very different biological processes, the type I prenyl protease gene is highly conserved, encoded by a single gene in a wide range of animal and plant groups. A notable exception is Drosophila melanogaster, where the gene encoding the type I prenyl protease has undergone an unprecedented series of duplications in the genome, resulting in five distinct paralogs, three of which are organized in a tandem array, and demonstrate high conservation, particularly in the vicinity of the active site of the enzyme. We have undertaken targeted deletion to remove the three tandem paralogs from the genome. The result is a male fertility defect, manifesting late in spermatogenesis. Our results also show that the ancestral type I prenyl protease gene in Drosophila is under strong purifying selection, while the more recent replicates are evolving rapidly. Our rescue data support a role for the rapidly evolving tandem paralogs in the male germline. We propose that potential targets for the male-specific type I prenyl proteases include proteins involved in the very dramatic cytoskeletal remodeling events required for spermatid maturation.


Is positive thinking in anticipation of a performance situation better than distraction? An experimental study in preadolescents.
The current study compares the effects of experimentally induced positive anticipatory thinking and distraction in preadolescents aged 12-13. Eighty-seven participants were instructed to either engage in positive anticipatory thoughts or perform a distraction task while preparing to perform a sporting activity in front of their peers. Results revealed that trait social anxiety was associated with more negative estimates of sport performance and catastrophic thoughts relating to the impending sport activity. Additionally, compared to children who distracted, children in the positive anticipation condition showed significantly increased anxiety levels, more catastrophic thoughts and more negative predictions of sport performance and appearance, although these effects did not appear to interact with trait social anxiety. Finally, no significant manipulation effect on participants' observable behavior was found. The findings further highlight the utility of distracting from an impending, anxiety-provoking situation to keep anxious feelings to a low level.


Cocultures of GFP(+) -granule cells with GFP(-) -pyramidal cells and interneurons for the study of mossy fiber neurotransmission with paired recordings.
Synaptic transmission of the granule cells (GCs) via their axons, the mossy fibers (MFs), is traditionally studied on acutely prepared or cultured slices. Usually, extracellular, bulk or minimal stimulation is used to evoke transmitter release from MF terminals, while recording from their postsynaptic target cells, the pyramidal cells and interneurons of CA3. However, the ideal method to assess MF neurotransmission, the simultaneous recording of a presynaptic GC and one of its target cells, is extremely difficult to achieve using slices. Alternatively, cultures of GCs establishing autapses have been developed, but in these, GCs do not contact their natural targets. We developed cocultures of GCs, dissociated from transgenic GFP(+) rats, with pyramidal cells and interneurons of CA3, dissociated from wild-type rats, and confirmed the expression of cell-specific markers by immunofluorescence. We conducted recordings of GFP(+) -GCs synaptically connected with their GFP(-) -target cells, and demonstrate that synaptic transmission and its plasticity have the signature of transmission of MF. Besides being strongly depressed by activation of mGluRs, high frequency activation of GC-to-pyramidal cells synapses undergo LTP, while GC-to-interneuron synapses undergo LTD. This coculture method allows a high reproducibility of recording connected pairs of identified cells, constituting a valuable tool to study MF transmission, as well as different combinations of identifiable pre- and postsynaptic cells.


Garden-path sentences and the diversity of their (mis)representations.
Previous studies have reliably shown that the initial misanalysis of garden-path sentences lingers even after the whole sentence is processed. However, other aspects of the resulting representation of these sentences are far from being clear. Some authors argue that comprehenders form a full analysis of the sentence which is faithful to the input and that the fact that the misanalysis lingers is due to an inhibition failure. Recently, it has been shown that comprehenders might not manage to create a coherent representation at all, at least in the case of more demanding garden-path structures. The aim of the current paper is to examine resulting representations of garden-path sentences in more detail. To do this, four self-paced reading experiments in Czech were conducted, which differed in the presentation mode (word-by-word and sentence-at-once) and comprehension question format (yes-no questions and open-ended questions). The experiments replicated effects typical for the lingering initial misanalysis, but provided mixed evidence for other aspects of resulting representations. In most cases, participants managed to build a coherent representation that was faithful to the input. However, both the quantitative and qualitative analysis of the results showed that comprehenders sometimes maintained multiple local interpretations at once or even failed to build a coherent representation of a garden-path sentence. Thus, we argue that resulting representations of garden-path sentences are in fact not uniform, but rather diverse, and they vary both in their faithfulness to the presented input and in their internal coherence.


EEG functional brain connectivity strengthens with age during attentional processing to faces in children.
Studying functional connectivity may generate clues to the maturational changes that occur in children, expressed by the dynamical organization of the functional network assessed by electroencephalographic recordings (EEG). In the present study, we compared the EEG functional connectivity pattern estimated by linear cross-correlations of the electrical brain activity of three groups of children (6, 8, and 10 years of age) while performing odd-ball tasks containing facial stimuli that are chosen considering their importance in socioemotional contexts in everyday life. On the first task, the children were asked to identify the sex of faces, on the second, the instruction was to identify the happy expressions of the faces. We estimated the stable correlation pattern (SCP) by the average cross-correlation matrix obtained separately for the resting state and the task conditions and quantified the similarity of these average matrices comparing the different conditions. The accuracy improved with higher age. Although the topology of the SCPs showed high similarity across all ages, the two older groups showed a higher correlation between regions associated with the attentional and face processing networks compared to the youngest group. Only in the youngest group, the similarity metric decreased during the sex condition. In general, correlation values strengthened with age and during task performance compared to rest. Our findings indicate that there is a spatially extended stable brain network organization in children like that reported in adults. Lower similarity scores between several regions in the youngest children might indicate a lesser ability to cope with tasks. The brain regions associated with the attention and face networks presented higher synchronization across regions with increasing age, modulated by task demands.


Generation of transgenic mice on an NOD/SCID background using the conventional microinjection technique.
Humanized mice, which refers to immunodeficient mice repopulated with the human immune system, are powerful tools for study in the field of immunology. It has been difficult, however, to generate these transgenic (Tg) mice directly from such strains as the NOD/SCID mouse. In this study, we describe a method developed by us for the generation of Tg mice on an NOD/SCID background. First, we obtained fertilized eggs efficiently by means of in vitro fertilization (IVF); then, we attempted to generate CAG-EGFP Tg mice on an NOD/SCID background, finding that delayed timing of the microinjection after the IVF improved the time to development of the two-cell-stage embryos and the obtainment of newborns. We successfully generated Tg mice and confirmed the germ-line transmission in the offspring. In conclusion, we established a novel system for directly generating transgenic mice on an NOD/SCID background. This novel system is expected to allow improved efficiency of the generation of humanized mice.


The advancement of multidimensional QSAR for novel drug discovery - where are we headed?
The Multidimensional quantitative structure-activity relationship (multidimensional-QSAR) method is one of the most popular computational methods employed to predict interesting biochemical properties of existing or hypothetical molecules. With continuous progress, the QSAR method has made remarkable success in various fields, such as medicinal chemistry, material science and predictive toxicology. Areas covered: In this review, the authors cover the basic elements of multidimensional -QSAR including model construction, validation and application. It includes and emphasizes the very recent developments of multidimensional -QSAR such as: HQSAR, G-QSAR, MIA-QSAR, multi-target QSAR. The advantages and disadvantages of each method are also discussed and typical examples of their application are detailed. Expert opinion: Although there are defects in multidimensional-QSAR modeling, it is still of enormous help to chemists, biologists and other researchers in various fields. In the authors' opinion, the latest more precise and feasible QSAR models should be further developed by integrating new descriptors, algorithms and other relevant computational techniques. Apart from being applied in traditional fields (e.g. lead optimization and predictive risk assessment), QSAR should be used more widely as a routine method in other emerging research fields including the modeling of nanoparticles(NPs), mixture toxicity and peptides.


Epidemic processes with immunization.
We study a model of directed percolation (DP) with immunization, i.e., with different probabilities for the first infection and subsequent infections. The immunization effect leads to an additional non-Markovian term in the corresponding field theoretical action. We consider immunization as a small perturbation around the DP fixed point in d<6, where the non-Markovian term is relevant. The immunization causes the system to be driven away from the neighborhood of the DP critical point. In order to investigate the dynamical critical behavior of the model, we consider the limits of low and high first-infection rate, while the second-infection rate remains constant at the DP critical value. Scaling arguments are applied to obtain an expression for the survival probability in both limits. The corresponding exponents are written in terms of the critical exponents for ordinary DP and DP with a wall. We find that the survival probability does not obey a power-law behavior, decaying instead as a stretched exponential in the low first-infection probability limit and to a constant in the high first-infection probability limit. The theoretical predictions are confirmed by optimized numerical simulations in 1+1 dimensions.


[Prevention of restenosis with a new modified fully-covered retrievable esophageal stent].
To observe and evaluate the effectiveness of a new modified fully-covered retrievable esophageal stent in preventing restenosis at the proximal end of the stent. From January 2008 to October 2011, 380 consecutive patients who underwent placement of a conventional stent or a new modified stent for benign or malignant dysphagia were divided into two groups: conventional stent group 193 patients (male 137, female 56) and modified stent group 187 patients (male 125, female 62). The granulation formation and restenosis rate one month after stenting were evaluated. Data such as patient demographics, outcomes and complications were collected. The results were statistically analyzed by Student t test, chi-squared test, Fisher's exact probability or rank sum test. A P-value less than 0.05 was considered statistically significant. All stents were successfully implanted. They were highly effective in palliating dysphagia. The dysphagia score decreased from 3 (1) to 0 (1) in conventional stent group (P < 0.01), and that from 4 (1) to 0 (1) in modified stent group (P < 0.01). The modified stent group were superior to the conventional stent group in severe granulation formation rate (0 vs 4.7% (9/193), P = 0.004) and restenosis rate (2.7% (5/187) vs 7.3% (14/193), P = 0.041) within one month after stenting, and the modified stent was easier to retrieve. Postoperative remission rate of dysphagia, and complications such as chest pain, bleeding, perforation, stent migration had no statistical differences between the two groups (all P > 0.05). The new modified fully-covered retrievable esophageal stent can significantly reduce granulation formation at the proximal end of the stent. Using of this stent seems to be a better choice in treating patient of dysphagia, with lower restenosis rate and easier to retrieve.


Role of eicosanoids in the cardiovascular system.
Cardiovascular eicosanoids are of significance in relation to regulation of hemostasis and flow under healthy and pathological conditions. In healthy subjects, TxA2 and PGI2 participate in the maintenance of vascular integrity in relation to vascular injury. In this respect, vascular eicosanoids can be regarded as constituents of a balancing system which favours platelet deaggregation in intact vessels but platelet aggregation in a injured vessel. Degenerative arterial disease, like e.g. atherosclerosis, disturbs the balance and favours platelet activation and adhesion to vascular surfaces. This may promote the development of platelets thrombi in the absence of vascular injury and lead to thrombosis.


Association of Low Blood Pressure, Low Bispectral Index and Low Minimum Alveolar Concentration of Anaesthetic during Surgery with Postoperative 30-day Mortality: A Systemic Review and Meta-Analysis.
The triple low state [low mean arterial pressure, low bispectral index (BIS) and a low minimum alveolar concentration (MAC)] fraction of anaesthetic during surgery) has been a controversial subject of interest in clinical practise. Previous retrospective studies have produced different conclusions on the association between a triple low state and postoperative 30-day mortality. This study was a systematic review of previous studies on the effects of the triple low state on postoperative 30-day mortality and a meta-analysis with a sample size larger than that of previous studies. After searching for relevant articles in the PubMed database as on 27 March 2017, we included studies that compared postoperative 30-day mortality between triple low and non-triple low groups. The identified articles were subjected to an initial screening using keywords 'low bispectral index', 'intraoperative hypotension' and 'low minimum alveolar concentration' according to the PRISMA Flow diagram (2009). After a full-text review, appropriate studies were finally included in our meta-analysis. All statistical analyses were performed using the R programme 3.3.2 and meta packages. Three retrospective cohort studies were included in the meta-analysis. The total number of subjects in the triple low and non-triple low groups was 29,402 and 17,428, respectively; the sample size was 46,830. We derived a hazard ratio (HR) of 1.09 [95% confidence interval (CI), 1.07-1.11)] for the fixed effect model and of 1.30 (95% CI, 1.04-1.07) for the random effect model. In the analysis of heterogeneity among the three studies, I2=95% was obtained (P<0.01). Thus, the values obtained from the random effect model were used; HR was 1.30 for the triple low group, indicating a 30% increase in the overall 30-day mortality. The present study demonstrated that patients exposed to the triple low state exhibit higher 30-day mortality rates than those not exposed to the triple low state.


[Chemical Constituents from Camellia oleifera Stem].
To study the chemical constituents of stem of Camellia oleifera. The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. Seven compounds were isolated from the stem of Camellia oleifera, whose structures were elucidated as (-) -pinoresinol (1), (-) -medioresinol (2), skullcapflavone II (3), betulinic acid (4), ursolic acid (5), 3-O-β-D-glucopyranosyl- (1 --> 2) -β-D-xylopyransoyl-(1 --> 3) -[β-D-glucopyranosyl- (1 --> 2)] -β-D-glucuronopyranosyl-22α-angeloyloxyolean-12-ene-15α,16α,28-triol (6) and oleanolic acid (7). Compounds 1 - 6 are isolated from this plant for the first time, and compounds 1 - 3 are isolated from this genus for the first time.


cDNA-derived amino acid sequence of rat mitochondrial 3-oxoacyl-CoA thiolase with no transient presequence: structural relationship with peroxisomal isozyme.
The sorting of homologous proteins between two separate intracellular organelles is a major unsolved problem. 3-Oxoacyl-CoA thiolase is localized in mitochondria and peroxisomes, and provides a good system for the study on the problem. Unlike most mitochondrial matrix proteins, mitochondrial 3-oxoacyl-CoA thiolase in rats is synthesized with no transient presequence and possess information for mitochondrial targeting and import in the mature protein. Two overlapping cDNA clones contained an open reading frame encoding a polypeptide of 397 amino acid residues (predicted Mr = 41,868), a 5' untranslated sequence of 164 bp, a 3' untranslated sequence of 264 bp and a poly(A) tract. The amino acid sequence of the mitochondrial thiolase is 37% identical with that of the mature portion of rat peroxisomal 3-oxoacyl-CoA thiolase precursor. These results suggest that the two thiolases have a common origin and obtained information for targeting to respective organelles during evolution. Two portions in the mitochondrial thiolase that may serve as a mitochondrial targeting signal are presented.


Ultrastructural investigation of Zimmermann-Laband syndrome.
Zimmermann-Laband syndrome (ZLS) is a very rare autosomal dominant inherited condition characterized by 3 major clinical findings of which gingival hyperplasia are always present. The great heterogenicity of the syndrome is illustrated by the numerous variable clinical findings described in the literature. The purpose of the study was to examine a patient diagnosed with ZLS and to describe possible new characteristics of this rare syndrome, including the ultrastructural morphology using a transmission electron microscope (TEM) of the gingival and dermal fibroblasts. The ultrastrucutral morphology as has not previously been described in the literature. Tissue was collected from the alveolar ridge and skin of the forearm for TEM. TEM studies indicated the presence of prominent fibroblasts situated among numerous regular dense connective tissue bundles. Genetic analysis showed a new chromosomal insertion, ins(12;8)(p11.2;q11.2q24.3), suggesting that the gene responsible for the syndrome lies on chromosome 8.


Dopamine signaling in the dorsal striatum is essential for motivated behaviors: lessons from dopamine-deficient mice.
Genetically engineered mice that lack tyrosine hydroxylase in all dopaminergic neurons become hypoactive and aphagic, and they starve by 4 weeks of age. However, they can be rescued by daily treatment with l-dopa, which restores activity and feeding for about 10 hours. Thus, these mice can be examined in both dopamine-depleted and dopamine-replete states. A series of behavioral experiments lead to the primary conclusion that in the dopamine-depleted state these mice are not motivated to engage in goal-directed behaviors. Nevertheless, they still have a preference for sucrose, they can learn the location of food rewards, and they can form a conditioned-place preference for drugs. Dopamine signaling can be restored to the striatum by several different viral gene-therapy procedures. Restoring dopamine signaling selectively to the dorsal striatum is sufficient to allow feeding, locomotion, and reward-based learning. The rescued mice appear to have normal motivation to engage in all goal-directed behaviors that have been tested. The results suggest that dopamine facilitates the output from dorsal striatum, which provides a permissive signal allowing feeding and other goal-directed behaviors.


FOUNDER-FLUSH SPECIATION IN DROSOPHILA PSEUDOOBSCURA: A LARGE-SCALE EXPERIMENT.
A founder-flush-crash model of speciation has been proposed that may particularly apply to island and other colonizations. Previous laboratory experiments testing the model have given inconsistent results. We have conducted a large experiment with Drosophila pseudoobscura designed to meet the essential postulates of the model and to separately test some of the postulates. Forty-five experimental and 12 control populations have been studied during seven successive founder-flush-crash cycles, or about 50 generations. Sexual isolation tests yield significantly positive assortative mating in a few tests between pairs of experimental populations. Populations with fewer founders (N = 1 or 3) yield more significant instances of assortative mating than those with more founders (n = 5, 7, or 9), and this difference becomes statistically significant for pooled data. Only one of 15 population pairs tested three times (generations 25, 32, and 46) shows positive assortative mating in all three tests. No significant assortative mating occurs between control populations, including highly inbred ones. We conclude that although founder events may occasionally lead to the evolution of assortative mating and hence to speciation, our results do not support the claim that the founder-flush-crash model identifies conditions very likely to result in speciation events.


Medial Collateral Ligament Deficiency of the Elbow Joint: A Computational Approach.
Computational elbow joint models, capable of simulating medial collateral ligament deficiency, can be extremely valuable tools for surgical planning and refinement of therapeutic strategies. The objective of this study was to investigate the effects of varying levels of medial collateral ligament deficiency on elbow joint stability using subject-specific computational models. Two elbow joint models were placed at the pronated forearm position and passively flexed by applying a vertical downward motion on humeral head. The models included three-dimensional bone geometries, multiple ligament bundles wrapped around the joint, and the discretized cartilage representation. Four different ligament conditions were simulated: All intact ligaments, isolated medial collateral ligament (MCL) anterior bundle deficiency, isolated MCL posterior bundle deficiency, and complete MCL deficiency. Minimal kinematic differences were observed for isolated anterior and posterior bundle deficient elbows. However, sectioning the entire MCL resulted in significant kinematic differences and induced substantial elbow instability. Joint contact areas were nearly similar for the intact and isolated posterior bundle deficiency. Minor differences were observed for the isolated anterior bundle deficiency, and major differences were observed for the entire MCL deficiency. Complete elbow dislocations were not observed for any ligament deficiency level. As expected, during isolated anterior bundle deficiency, the remaining posterior bundle experiences higher load and vice versa. Overall, the results indicate that either MCL anterior or posterior bundle can provide anterior elbow stability, but the anterior bundle has a somewhat bigger influence on joint kinematics and contact characteristics than posterior one. A study with a larger sample size could help to strengthen the conclusion and statistical significant.


Plasma Resolvin D2 to Leukotriene B4 Ratio Is Reduced in Diabetic Patients with Ischemic Stroke and Related to Prognosis.
Diabetes mellitus (DM) aggravates symptoms and prognosis of acute ischemic stroke (AIS), and inflammation plays an important role therein. Resolvin D2 (RvD2) is one of the specialized pro-resolving mediators (SPMs), while leukotriene B4 (LTB4) is a classic proinflammatory mediator. The ratio of RvD2 to LTB4 is an index of pro-resolving/proinflammatory balance. We aim to explore the role of RvD2/LTB4 ratio in ischemic stroke complicated with DM. The plasma levels of RvD2 and LTB4 were analyzed by enzyme immunoassay in stroke patients with DM (DM + AIS group) or without DM (nonDM+AIS group). Patients were followed up at 90 days after stroke onset, and modified Rankin Score (mRS) was assessed. The association of RvD2/LTB4 ratio with stroke severity and prognosis was also analyzed. The plasma levels of RvD2 were positively correlated to LTB4. The RvD2/LTB4 ratio in DM + AIS group was lower than that in the nonDM+AIS group. No correlation was found between the RvD2/LTB4 ratio and infarct size or NIHSS score. The RvD2/LTB4 ratio at baseline was significantly lower in the poor prognosis group (mRS ≥ 3) than that in the good prognosis group (mRS ≤ 2). Our study indicated that the balance between pro-resolving and proinflammatory mediators was impaired by diabetes in ischemic stroke. The RvD2/LTB4 ratio may serve as a biomarker of prognosis for ischemic stroke.


Case report-CARMAT: the first experience with the Aeson bioprosthetic total artificial heart as a bridge to transplantation in a case of post-infarction ventricular septal rupture.
Post-infarction ventricular septal defects remain one of the most feared complications after myocardial infarction with high mortality rates. In special cases, surgical or interventional treatment strategies are technically not feasible and do not always lead to a good outcome. A 58-year-old male patient in cardiogenic shock with a very large ventricular septal (VSD) defect (4.9 cm × 5 cm) due to myocardial infarction was presented in our department. Acute stabilization was achieved using peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Neither surgical nor interventional therapy was considered as a sufficient option due to the unsuitable anatomy of the VSD and the patient was listed for heart transplantation. After 2 weeks on ECMO, bleeding and infectious complications occurred. Due to organ shortage, urgent implantation of the bioprosthetic total artificial heart (TAH) Aeson device (CARMAT) remained the only useful strategy to achieve a mid- or long-term bridge to transplantation. After successful implantation and good recovery with the Aeson device, the patient was transplanted 4 weeks after implantation. Post-infarction ventricular septal defects are highly challenging and are commonly associated with a poor prognosis. The implantation of the new Aeson TAH device is a promising therapeutic option, allowing a safe and long-term bridging to heart transplantation.


Confirmation and discovery of maternal grandsires and great-grandsires in dairy cattle.
Selection, mating, and improvement of dairy animals have required accurate pedigrees. Genomic tools allow paternal ancestors to be easily confirmed or discovered because most sires are genotyped for many markers, but maternal ancestors are more difficult to discover because most female ancestors are not genotyped. Three methods to discover maternal grandsires (MGS) were developed and compared. Conflicts were counted one single nucleotide polymorphism (SNP) at a time between genotypes of the animal and potential MGS (duo method) or also using the sire's genotype (trio method). Alternatively, haplotypes of a potential MGS were matched to the animal's maternal haplotype, obtained by using linkage across loci (HAP method). The duo and trio methods can be performed as soon as a genotype is received because no imputation is required. The HAP method improved accuracy because genotypes with 2,683 (3 K) SNP were imputed to the 45,187 (50K) SNP used for genomic evaluation. The HAP method was tested using modified pedigrees with 5% of true MGS replaced by a random genotyped bull from the same birth year and 5% of MGS set to missing for 4,134 Holsteins, 552 Jerseys, and 142 Brown Swiss that had confirmed, genotyped sires. Those same animals were used to test the duo and trio methods, except that some animals had multiple genotypes and imputed dams were excluded. Accuracy measured how often the correct MGS was selected from among 12,152 genotyped Holstein, 2,265 Jersey, and 1,605 Brown Swiss potential MGS. Accuracies were 61, 60, and 65%, respectively, with the duo method; 95, 91, and 94% with the trio method; and 97, 95, and 97% with the HAP method. Accuracy of the duo method was poor (only 52% for animals genotyped with 3 K and 65% with 50K) because additional information from the paternal genotype is not used. Accuracy of the trio method was 97% with 50K but only 78% with 3K because the missing SNP were not imputed. Accuracy of the HAP method was 94% with 3 K genotypes, 98% with 50K, and 92% with nongenotyped, imputed dams. When the HAP method was extended to great-grandsires, the accuracy of maternal great-grandsire discovery was 92% for 652 Holsteins, 95% for 33 Jerseys, and 85% for 20 Brown Swiss. Accuracy was even higher using simulated genotypes. Because most dairy bulls over several generations have been genotyped, percentages of haplotypes shared with candidate males can accurately confirm, correct, or discover the sires, MGS, and even more distant ancestors of most animals.


Temporal dynamics and potential neural sources of goal conduciveness, control, and power appraisal.
A major emotion theory, the Component Process Model, predicts that emotion-antecedent appraisal proceeds sequentially (e.g., goal conduciveness>control>power appraisal). In a gambling task, feedback manipulated information about goal conduciveness (outcome: win, loss), control (perceived high and low control), and power appraisals (choice options to change the outcome). Using mean amplitudes of event-related potentials, we examine the sequential prediction of these appraisal criteria. Additionally, we apply source localization analysis to estimate the neural sources of the evoked components of interest. Early ERPs (230-300 ms) show main effects of goal conduciveness and power but no interaction effects suggesting goal obstructiveness assessment of task-relevant feedback information. Late ERPs (350-600 ms) reveal main effects of all appraisals and interaction effects representing the integration of all appraisal information. Source localization analysis suggests distinct neural sources for these appraisal criteria.


Molecular techniques drive cutting edge advancements in management of cutaneous T cell lymphoma.
Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective and standardized diagnostic and prognostic clinical tools. Currently, diagnosis of CTCL practically relies on clinical presentation, histopathology, and immunohistochemistry. These methods are collectively fraught with limitations in sensitivity and specificity. Fortunately, recent advances in flow cytometry, polymerase chain reaction, high throughput sequencing, and other molecular techniques have shown promise in improving diagnosis and treatment of CTCL. Examples of these advances include T cell receptor clonotyping via sequencing to detect CTCL earlier in the disease course and single-cell RNA sequencing to identify gene expression patterns that commonly drive CTCL pathogenesis. Experience with these techniques has afforded novel insights which may translate into enhanced diagnostic and therapeutic approaches for CTCL.


SF3B1 mutation is a poor prognostic indicator in luminal B and progesterone receptor-negative breast cancer patients.
The purpose of this study was to explore the relationship between SF3B1 mutations and the prognoses of patients with breast cancer. Clinical and SF3B1 mutation data from The Cancer Genome Atlas were analyzed. SF3B1 mutations were evaluated as prognostic factors in all breast cancer patients and specific subgroups through Cox regression and Kaplan-Meier analyses. We also investigated the relationship between traditional parameters and SF3B1 mutations. Receiver operating characteristics curves were used to analyze common risk factors for their sensitivity and specificity in predicting SF3B1 mutations. SF3B1 mutations were a poor prognostic factor in luminal B and progesterone receptor (PR)-negative breast cancer (P < 0.01). Age at diagnosis and estrogen receptor (ER) status were associated with SF3B1 mutations in all breast cancers (P < 0.01) and in luminal B and PR-negative subgroups (P < 0.01). The age at diagnosis and ER status combined had a higher sensitivity and specificity for predicting SF3B1 mutations than each factor alone. SF3B1 mutations are a poor prognostic factor in luminal B and PR-negative breast cancer patients. These mutations are significantly associated with age at diagnosis and ER status. SF3B1 mutations may therefore be a novel therapeutic target for breast cancer patients.


Three closely-related cyclohexanols (C35H27X2N3O3; X = F, Cl or Br): similar molecular structures but different crystal structures.
Three highly-substituted cyclohexanol derivatives have been prepared from 2-acetylpyridine and 4-halogenobenzaldehydes under mild conditions. (1RS,2SR,3SR,4RS,5RS)-3,5-Bis(4-fluorophenyl)-2,4-bis(pyridine-2-carbonyl)-1-(pyridin-2-yl)cyclohexanol, C35H27F2N3O3, (I), (1RS,2SR,3SR,4RS,5RS)-3,5-bis(4-chlorophenyl)-2,4-bis(pyridine-2-carbonyl)-1-(pyridin-2-yl)cyclohexanol acetone 0.951-solvate, C35H27Cl2N3O3·0.951C3H6O, (II), and (1RS,2SR,3SR,4RS,5RS)-3,5-bis(4-bromophenyl)-2,4-bis(pyridine-2-carbonyl)-1-(pyridin-2-yl)cyclohexanol, C35H27Br2N3O3, (III), all crystallize in different space groups, viz. Pbca, Fdd2 and P1, respectively. In compound (II), the acetone molecule is disordered over two sets of atomic sites having occupancies of 0.690 (13) and 0.261 (13). Each of the cyclohexanol molecules contains an intramolecular O-H···N hydrogen bond and their overall molecular conformations are fairly similar. The molecules of (I) are linked by two independent C-H···O hydrogen bonds to form a C(5)C(10)[R2(2)(15)] chain of rings, and those of (III) are linked by a combination of C-H···O and C-H···N hydrogen bonds, forming a chain of alternating R2(2)(16) and R2(2)(18) rings. The cyclohexanol molecules in (II) are linked by a single C-H···N hydrogen bond to form simple C(4) chains and these chains are linked by a π-π stacking interaction to form sheets, to which the disordered acetone molecules are weakly linked via a number of C-H···O contacts.


Comprehensive analysis of amino acid and nucleotide composition in eukaryotic genomes, comparing genes and pseudogenes.
Based on searches for disabled homologs to known proteins, we have identified a large population of pseudogenes in four sequenced eukaryotic genomes-the worm, yeast, fly and human (chromosomes 21 and 22 only). Each of our nearly 2500 pseudogenes is characterized by one or more disablements mid-domain, such as premature stops and frameshifts. Here, we perform a comprehensive survey of the amino acid and nucleotide composition of these pseudogenes in comparison to that of functional genes and intergenic DNA. We show that pseudogenes invariably have an amino acid composition intermediate between genes and translated intergenic DNA. Although the degree of intermediacy varies among the four organisms, in all cases, it is most evident for amino acid types that differ most in occurrence between genes and intergenic regions. The same intermediacy also applies to codon frequencies, especially in the worm and human. Moreover, the intermediate composition of pseudogenes applies even though the composition of the genes in the four organisms is markedly different, showing a strong correlation with the overall A/T content of the genomic sequence. Pseudogenes can be divided into 'ancient' and 'modern' subsets, based on the level of sequence identity with their closest matching homolog (within the same genome). Modern pseudogenes usually have a much closer sequence composition to genes than ancient pseudogenes. Collectively, our results indicate that the composition of pseudogenes that are under no selective constraints progressively drifts from that of coding DNA towards non-coding DNA. Therefore, we propose that the degree to which pseudogenes approach a random sequence composition may be useful in dating different sets of pseudogenes, as well as to assess the rate at which intergenic DNA accumulates mutations. Our compositional analyses with the interactive viewer are available over the web at http://genecensus.org/pseudogene.


Resonant femtosecond stimulated Raman spectroscopy with an intense actinic pump pulse: Application to conical intersections.
We theoretically investigate the feasibility of characterizing conical intersections with time-resolved resonant femtosecond stimulated Raman spectroscopy (FSRS) using an intense actinic pump pulse. We perform nonperturbative numerical simulations of FSRS signals for a three-electronic-state two-vibrational-mode model, which is inspired by the S2(ππ*)-S1(nπ*) conical intersection in pyrazine. Our results show that moderately strong actinic pulses increase the intensity of vibrational fingerprint lines in FSRS transients. They facilitate the extraction of useful spectroscopic information by enhancing peaks revealing the coupling and tuning modes of the conical intersection.


The Elekta Fraxion™ system is not suitable for maxillary fixation in canine conformal radiation therapy techniques.
In this prospective, exploratory study, we evaluated the positioning accuracy in a group of 15 dogs undergoing fractionated stereotactic radiotherapy for tumors affecting the head, using a modified human maxillary fixation device (Elekta Fraxion™ system). Positioning was assessed using on-board volumetric imaging, with a six-degrees-of-freedom image registration technique. Prior to treatment delivery, CBCT images were obtained and patient alignment was corrected, in both translational and rotational planes, using a six-degrees-of-freedom robotic patient positioning system (HexaPOD Evo RT System). The maximum angular inter-fraction motions observed were 6.1° (yaw), 10.9° (pitch), and 4.5° (roll). The mean systematic translational errors were 4.7, 2.6, and 2.3 mm, mean random translational errors were 3.0, 2.2, and 2.5 mm, and mean overall translational errors were 2.4, 0.7, and 2.3 mm in the cranial-caudal, lateral, and dorsal-ventral directions, respectively. The mean systematic rotational errors were 1.17°, 0.77°, and 1.43°, the mean rotational random errors were 1.65°, 1.46°, and 1.34° and the mean overall rotational errors were 0.56°, 0.22°, and 0.29° in the yaw, pitch, and roll directions, respectively. The mean error of the three-dimensional vector was 6.9 mm with a standard deviation of 3.8 mm. Ninety-five percent of the three-dimensional vectors were <14.8 mm. This study demonstrates that this maxillary fixation device relies on six-degrees-of-freedom registration and an ability to apply corrections using a six-degrees-of-freedom couch for accurate patient positioning and tumor targeting. Its use in conformal radiation therapy in dogs is not recommended.


Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat.
Reactive oxygen species (ROS) are essential for cellular signaling and response to stress. The level of ROS and the type of ROS determine the ability of cells to undergo cell death. Furthermore, dysregulation of the antioxidant pathways is associated with many diseases. It has become apparent that cell death can occur through different mechanisms leading to the classifications of different types of cell death such as apoptosis, ferroptosis, and necroptosis. ROS play essential roles in all forms of cell death, but it is only now coming into focus that ROS control and determine the type of cell death that occurs in any given cell. Indeed, ROS may act as a rheostat allowing different cell death mechanisms to be engaged and crosstalk with different cell death types. In this review, we will describe the ROS regulatory pathways and how they control different types of cell death under normal and disease states. We will also propose how ROS could provide a mechanism of crosstalk between cell death mechanisms and act as a rheostat determining the type of cell death.


A high-carbohydrate diet effects on the A allele of hepatic lipase polymorphism on the apoB100/apoAI ratio in young Chinese males.
Diet induces changes in plasma lipid profiles, and the plasma lipid profiles vary among different genetic backgrounds. The aim of this study was to investigate how a high-carbohydrate (high-CHO) diet interacts with hepatic lipase G-250A promoter polymorphism to affect the ratios of plasma lipids and apolipoproteins (apo) in a young Chinese population. Experiments were conducted on 56 university students. A stabilization diet was given for 7 days and a high-CHO diet was followed for 6 days. The diets used in this study were described by Song et al. and the following parameters were evaluated: total plasma triglyceride (TG), total plasma cholesterol (TC), plasma high-density lipoprotein cholesterol (HDL-C), plasma low-density lipoprotein cholesterol (LDL-C), apoB100 and apoAI. The plasma lipids and apoB100/apoAI ratios were also calculated and hepatic lipase G-250A polymorphism was analyzed. At baseline, no significant difference was detected for subjects with different genotypes and genders. All the parameters showed significant differences before and after the high-CHO diet, and these differences are gender-specific: after the high-CHO diet, the TG/HDL-C ratios significantly increased in females (GG genotype: P = 0.004; A carriers: P = 0.005). The TC/HDL-C ratios significantly decreased in GG genotype males (P = 0.007), A carrier males (P < 0.0001) and A carrier females (P = 0.016) and the LDL-C/HDL-C ratios significantly decreased in the GG genotype males (P = 0.011), A carrier males (P < 0.0001) and A carrier females (P = 0.001). However, comparing the apoB100/apoAI ratio before and after the high-CHO diet, a significant difference only existed in male A carriers (P = 0.009). The results of this study show that the high-CHO diet induces the positive effects on the lipid ratios in general, only except the TG/HDL-C ratio in females. Noticeably, the decreased apoB100/apoAI ratio is associated with the A allele of hepatic lipase G-250A polymorphism only in young Chinese males.


Investigation of `glitches' in the energy spectrum induced by single-crystal diamond compound X-ray refractive lenses.
Single-crystal diamond stands out among all the candidate materials that could be exploited to fabricate compound refractive lenses (CRLs) owing to its extremely stable properties. Among all related experimental features, beam divergence, χ-angles relative to the incoming beam in Eulerian geometry and different positions of the X-ray beam relative to the lens geometry may influence the transmission energy spectrum of CRLs. In addition, the orientation of the single-crystal diamond sample may also affect the glitches significantly. To verify these initial assumptions, two experiments, an energy scan and an ω-scan, were set up by employing a polished diamond plate consisting of five biconcave lenses. The results show that beam divergence does not affect the spectrum, nor do χ-angles when ω is set to zero. Nevertheless, different incident positions have an appreciable effect on the transmission spectrum, in particular the `strengths' of the glitches. This is attributed to absorption. The ω-scan setup is capable of determining the so-called orientation matrix, which may be used to predict both `energy positions' and `strengths' of the glitches.


Effect of recombinant human epidermal growth factor against cutaneous scar formation in murine full-thickness wound healing.
A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-beta(1) in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-beta(1), and mediating the formation of collagen.


Objective qualitative and quantitative assessment of blood flow with near-infrared angiography in microvascular anastomoses in the rat model.
Intraoperative near-infrared indocyanine-green (ICG) angiography enables the visualization of microvascular perfusion and may help in the early detection of complications. The purpose of the present study was to examine whether the effect of microvascular stenoses can be quantitatively assessed by analysis of ICG-angiography in a microvascular model. Graded stenoses and total vessel occlusion of the carotid, aorta, and femoral arteries were created in 25 Wistar rats. Stenoses were graded to reduce arterial flow by 25%, 50%, 75%, and 100% of baseline flow as measured by transit-time flowmeter analyzing the emission signal of the ICG detected and investigated by the mathematical software tool (FLOW 800). ICG angiography was performed to assess vessel perfusion and flow curves were analyzed and correlated with the stenosis rate. A total of 576 investigations were performed. The area under the curve (P < 0.001), first and second maximum (P < 0.001), and the maximum slope to the first maximum (P < 0.001) were found to be of high prognostic value in evaluating the different flow patterns. Differences were displayed in comparisons by the maximum intensity of the ICG-concentrations. The maximum slope to the second maximum was found to be predictive in selected vessel types, and specific changes of the flow curve were found to indicate compromised vascular flow. The FLOW 800 tool applied for ICG angiography has shown to be a quick and reliable method for assessing blood flow in vessels in this study. The dynamic assessment of the ICG signal allows reliable identification of microanastomotic complications with the described parameters.


Elastase and lactoferrin in gingival crevicular fluid: possible indicators of a granulocyte-associated specific host response.
Periodontitis affects a limited number of susceptible humans. The aim of this study was to determine whether there is a difference in the inflammatory reaction between patients with gingivitis and those with periodontitis. For this purpose the levels of elastase and lactoferrin were measured in gingival crevicular fluid (GCF) from three types of sites: i) inflamed sites in patients with gingivitis alone, inflamed sites both ii) with and iii) without tissue destruction in patients with periodontitis. Elastase activity, measured with a chromogenic substrate was significantly higher in the two types of sites in periodontitis patients. Lactoferrin levels, measured with ELISA were the same in the three types of sites. In vitro activation of granulocytes from healthy volunteers with Fc-receptor stimulation showed that the entire release of lactoferrin occurred immediately. In contrast, elastase release was time-dependent and continued throughout the experiment. Thus, the degranulation of the specific (lactoferrin) and azurophil granule (elastase) are under separate control and the two parameters can be combined in a ratio in order to characterize the granulocytes of a given patient. Assuming an immediate release of lactoferrin from the activated granulocytes in vivo, similar amounts of lactoferrin in the three types of sites can be regarded as reflecting similar numbers of granulocytes in the three types of sites. Consequently, a higher elastase activity in GCF from patients with periodontitis indicates a higher rate of release from the cells per se and a granulocyte-associated specific host response.


Erotic Feelings Towards Patients in the Psychotherapy Session: Investigating Their Relationship With the Characteristics of the Therapist, the Patient, and the Treatment.
Experiencing erotic feelings towards a patient is a fairly common occurrence, not pathological per se, during phases of psychotherapy. This study aims to analyze associations between, on the one hand, the presence in therapists of romantic attraction (RA), sexual attraction (SA), or flirting behavior (FB) toward patients and, on the other hand, a series of characteristics of therapist, patient, and treatment. Between April and June 2022, 547 psychotherapists completed an online survey investigating their affective and behavioral responses toward their most recently treated patient. Compared to female therapists, males showed significantly higher prevalence of SA alone (p < .001) or in combination with RA (p < .01), FB (p < .01), or both (p < .05). Multivariate adjusted regression models showed that RA was associated with patient age ≤40 years (OR:39.49 for age 18-29; OR:28.44 for age 30-39), male sex (OR:10.40), and diagnosis of mood disorder (OR:14.08). Furthermore, RA was associated with intense countertransference feelings of tenderness towards the patient (OR:79.77) and hostility towards significant figures in their life (OR: 77.93). SA was associated with the therapist's male sex/gender (OR: 16.14), psychoanalytic orientation (OR:13.34), post-license experience ≤20 years (OR:6.12 for 1-9 years; OR:6.08 for 10-19 years). Lastly, FB was associated with the therapist's male sex/gender (OR:16.94).


[Biosynthesis of a single peptide chain containing human chorionic gonadotropin beta and ovine common alpha subunits tandem].
hCG beta-oLH alpha chimeric cDNA was constructed by using overlapping PCR to contact the codons of C-terminal end of hCG beta with the codons of N-terminal end of oLH alpha, then it was subcloned into nuclear polyhedrosis virus (AcNPV) expression vector pVL1393 to construct expression vector pVL1393-hCG beta-oLH alpha. The insect cells (Sf9) were cotransfected by the expression vector pVL1393-hCG beta-oLH alpha and BaculoGold AcNPV linearized genomic DNA, and recombinant viruses AcNPV-hCG beta-oLH alpha were screened out by plaque assay. Further the insect cells were infected by the recombinant viruses, the recombinant hCG beta-oLH alpha was purified by immunoaffinity chromatography column coupling anti-hCG beta monoclonal antibody from the conditioned media of infected cells. The results of SDS-PAGE silver staining and western blotting showed that hCG beta-oLH alpha single peptide chain had apparent molecular weights of 40.5 kD and 38.0 kD under non-reducing and reducing conditions respectively, indicating the occurrence of disulfide bonds and significant tertiary structure in the single peptide chain. From the results of competitive inhibition of 125I-hCG beta binding we can conclude that the anti-hCG beta antibody-binding activity of hCG beta-oLH alpha chimera is lower than that of native hCG, but higher than that of native hCG beta. Therefore, we assume that the hCG beta-oLH alpha chimera should have potential application as a target antigen of anti-hCG fertility regulatory vaccine.


Can teenage novel users perform as well as General Surgery residents upon initial exposure to a robotic surgical system simulator?
New techniques in minimally invasive and robotic surgical platforms require staged curricula to insure proficiency. Scant literature exists as to how much simulation should play a role in training those who have skills in advanced surgical technology. The abilities of novel users may help discriminate if surgically experienced users should start at a higher simulation level or if the tasks are too rudimentary. The study's purpose is to explore the ability of General Surgery residents to gain proficiency on the dVSS as compared to novel users. The hypothesis is that Surgery residents will have increased proficiency in skills acquisition as compared to naive users. Six General Surgery residents at a single institution were compared with six teenagers using metrics measured by the dVSS. Participants were given two 1-h sessions to achieve an MScoreTM in the 90th percentile on each of the five simulations. MScoreTM software compiles a variety of metrics including total time, number of attempts, and high score. Statistical analysis was run using Student's t test. Significance was set at p value <0.05. Total time, attempts, and high score were compared between the two groups. The General Surgery residents took significantly less Total Time to complete Pegboard 1 (PB1) (p = 0.043). No significant difference was evident between the two groups in the other four simulations across the same MScoreTM metrics. A focused look at the energy dissection task revealed that overall score might not be discriminant enough. Our findings indicate that prior medical knowledge or surgical experience does not significantly impact one's ability to acquire new skills on the dVSS. It is recommended that residency-training programs begin to include exposure to robotic technology.


Attention capture by abrupt onsets: re-visiting the priority tag model.
Abrupt onsets have been shown to strongly attract attention in a stimulus-driven, bottom-up manner. However, the precise mechanism that drives capture by onsets is still debated. According to the new object account, abrupt onsets capture attention because they signal the appearance of a new object. Yantis and Johnson (1990) used a visual search task and showed that up to four onsets can be automatically prioritized. However, in their study the number of onsets co-varied with the total number of items in the display, allowing for a possible confound between these two variables. In the present study, display size was fixed at eight items while the number of onsets was systematically varied between zero and eight. Experiment 1 showed a systematic increase in reactions times with increasing number of onsets. This increase was stronger when the target was an onset than when it was a no-onset item, a result that is best explained by a model according to which only one onset is automatically prioritized. Even when the onsets were marked in red (Experiment 2), nearly half of the participants continued to prioritize only one onset item. Only when onset and no-onset targets were blocked (Experiment 3), participants started to search selectively through the set of only the relevant target type. These results further support the finding that only one onset captures attention. Many bottom-up models of attention capture, like masking or saliency accounts, can efficiently explain this finding.


[Effects and mechanism of allogeneic platelet rich plasma on collagen synthesis in wound healing].
Objective: To investigate the effects and mechanism of allogeneic platelet rich plasma (PRP) on collagen in wound surface at different time. Methods: A total of 50 clean 7-week rats were selected for this study, including 10 rats for platelet-rich blood plasma preparation, 20 rats for PRP group and 20 rats for control group, 0.1 ml allogenic PRP and 0.1 ml saline were smeared respectively on wound surfaces of PRP and control group, wound regeneration and healing were examined. Cellular and histological morphology alteration was observed via Masson staining, type Ⅰ and type Ⅲ collagen protein and mRNA expression level were detected by Western blot and real-time PCR. T test was applied for comparison between two samples and one-way ANOVA was utilized for comparison between two groups. Results: The wound healing rate of PRP group was higher than that of control group on 3(rd,) 6(th,) 10(th) and 15(th) day (30.33±3.35 vs.18.35±2.04, 55.51±2.74 vs.36.83±2.34, 79.64±1.40 vs.56.92±1.44, 86.88±2.12 vs.65.80±1.76) after wound surface formation, there were statistic differences (t=13.66-50.48, all P<0.05). The wound collagen of PRP group form faster and coarser, and the fibers arrayed more densely in Masson staining. The protein expression of type Ⅰ collagen(1.92±0.09 vs.1.18±0.11) and type Ⅲ collagen(1.16±0.05 vs.0.74±0.11) of PRP group were higher than that of control group (t=22.99, P<0.01; t=17.62, P<0.05); the mRNA expression of type Ⅰ collagen(5.17±0.11 vs.1.79±0.18, 6.97±0.09 vs.1.96±0.08, 6.00±0.26 vs.2.10±0.05, 4.95±0.11 vs.3.58±0.09)and type Ⅲ collagen(2.35±0.08 vs.1.44±0.05, 3.08±0.05 vs.1.84±0.06, 3.48±0.07 vs.2.36±0.09, 4.42±0.07 vs.2.77±0.10) were higher than that of control group on 3(rd,) 6(th,) 10(th) and 15(th) day after wound surface formation, there were significant differences (t=43.37-188.37, all P<0.05). Conclusion: The allogeneic platelet rich plasma may promote fibroblasts secreted collagen by activated and releasing all kinds of growth factors, especially type Ⅰ and type Ⅲ collagen to accelerate the wound healing.


Application of low-frequency alternating current electric fields via interdigitated electrodes: effects on cellular viability, cytoplasmic calcium, and osteogenic differentiation of human adipose-derived stem cells.
Electric stimulation is known to initiate signaling pathways and provides a technique to enhance osteogenic differentiation of stem and/or progenitor cells. There are a variety of in vitro stimulation devices to apply electric fields to such cells. Herein, we describe and highlight the use of interdigitated electrodes to characterize signaling pathways and the effect of electric fields on the proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs). The advantage of the interdigitated electrode configuration is that cells can be easily imaged during short-term (acute) stimulation, and this identical configuration can be utilized for long-term (chronic) studies. Acute exposure of hASCs to alternating current (AC) sinusoidal electric fields of 1 Hz induced a dose-dependent increase in cytoplasmic calcium in response to electric field magnitude, as observed by fluorescence microscopy. hASCs that were chronically exposed to AC electric field treatment of 1 V/cm (4 h/day for 14 days, cultured in the osteogenic differentiation medium containing dexamethasone, ascorbic acid, and β-glycerol phosphate) displayed a significant increase in mineral deposition relative to unstimulated controls. This is the first study to evaluate the effects of sinusoidal AC electric fields on hASCs and to demonstrate that acute and chronic electric field exposure can significantly increase intracellular calcium signaling and the deposition of accreted calcium under osteogenic stimulation, respectively.


Is goal planning in rehabilitation effective? A systematic review.
To determine the evidence regarding the effectiveness of goal planning in clinical rehabilitation. Systematic review. MEDLINE, EMBASE, PsycINFO, CINAHL, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, American College of Physicians (ACP) Journal Club, and the Database of Abstracts of Reviews of Effects (DARE) were searched for randomized controlled trials on the therapeutic effectiveness of goal planning in the rehabilitation of adults with acquired disability. Studies were categorized by patient population and the clinical context of the study. Data were analysed using best-research synthesis, based on methodological quality determined by Physiotherapy Evidence Database (PEDro) scale scores. Nineteen studies were included in this review. Study populations in these papers included patients with neurological disorders, psychiatric disorders, musculoskeletal disorders, cardiovascular disorders, respiratory disorders and dietary/endocrine disorders. Six studies investigated the immediate effects of goal planning on patient behaviour. Thirteen studies investigated the effects of goal planning in the context of a rehabilitation programme lasting more than one week. Some limited evidence was identified that goal planning can influence patient adherence to treatment regimes and strong evidence that prescribed, specific, challenging goals can improve immediate patient performance in some specific clinical contexts. However, evidence regarding how these effects translated to improved outcomes following rehabilitation programmes was inconsistent. This review identified that while some studies demonstrated positive effects associated with goal planning in local contexts, the best available empirical evidence regarding the generalizable effectiveness of goal planning was inconsistent and compromised by methodological limitations.


Perceived Value of Holistic Needs Assessment in Supporting the Needs of Women With Breast Cancer.
Holistic needs assessments (HNAs) were designed to identify and support the physical, psychological, and social impacts of cancer, yet delivery methods vary significantly. The study aimed to explore views of HNAs from the perspectives of healthcare professionals and women with breast cancer, including how the HNA contributed to providing support. A qualitative case study approach was adopted, with 4 hospitals in England. Twenty-four women with cancer and 24 staff were recruited. Data from interviews, observations, and HNA-related documentation were compiled into cases around use of the HNA in each organization. Principles of framework analysis and Normalization Process Theory enabled identification of conclusions. The contribution of HNA to women's experiences of support was complex and dependent on various influences: (1) how the woman's own views and judgments influenced her perceptions of the assessment, (2) how the views of staff delivering the HNA influenced both their own approach to the assessment and patient views, and (3) the organizational context and culture. Apparent superficial implementation of HNAs seemed to facilitate organizational cultures of evidencing the actions of staff and achieving management targets. Women's views toward the HNA appeared paradoxical; most women perceived the HNA to be meaningful "in principle" but reported little benefit of the assessment, and some reported negative outcomes. Holistic needs assessment implementation in clinical settings requires a greater focus on quality over targets, and healthcare professional training should be centered around delivering HNAs in a meaningful way that prioritizes individual patient benefit.


Alveolar echinococcosis of the liver; studies on 60 operated cases.
During the years 1936 through 1978, 60 cases received surgical intervention for alveolar echinococcosis of the liver. The resectability and operative mortality rate were 64.0% (16/25) and 43.8% (7/16) before 1968, but 54.3% (19/35) and zero (0/19) thereafter. Establishment of clinical staging and criteria for justifying radical resection of a given lesion, combined with systematic evaluation of all hepatic vasculatures, contributed to improvement of the result. The long-term prognosis of the disease, unless resected, has been exclusively poor. A mass screening program, which became possible by the development of serologic tests, has covered a population of over 140,000 in the endemic area and been of value in detecting the disease in its early developmental stage. The disease should be recognized even in currently unaffected areas since the cestode has a fairly wide geographic distribution including the United States.


Inclusion of joint laxity, recurrent patellar dislocation, and short distal ulnae as a feature of Van Den Ende-Gupta syndrome: a case report.
Van Den Ende-Gupta Syndrome (VDEGS) is an extremely rare autosomal recessive syndrome with less than 20 reported families (approximately 40 patients) in the worldwide literature. We have assessed one consanguineous Saudi family with typical features of VDEGS. Two siblings were affected with almost identical features; including blepharophimosis, arachnodactyly, flexion contractures of the elbows, camptodactyly, slender ribs, hooked lateral clavicular ends, and bilateral radial head dislocations. Both patients had several unusual features; including joint laxity, flat feet, recurrent patellar dislocations, and bilateral short distal ulnae. Full sequencing of SCARF2 revealed a homozygous mutation c.773G > A (p. Cys258Tyr) in both affected children. The parents (both with no abnormalities) were heterozygous for the same mutation. Joint laxity, recurrent patellar dislocations, and short distal ulnae should be included as part of the clinical spectrum of VDEGS.


[2011 Shanghai customer satisfaction report of DSA/X-ray equipment's after-service].
To improve the manufacturer's medical equipment after-sale service, the fifth Shanghai zone customer satisfaction survey was launched by the end of 2011. The DSA/X-ray equipment was setup as an independent category for the first time. From the survey we can show that the DSA/X-ray equipment's CSI is higher than last year, the customer satisfaction scores of preventive maintenance and service contract are lower than others, and CSI of local brand is lower than imported brand.


Predictors of breath alcohol concentrations in college parties.
Alcohol use and subsequent consequences are harmful for individual college students. Other students and the university can also be negatively impacted by the consequences of alcohol use. A field-based study was used to assess the alcohol use environment at college parties. Researchers replicated a previous study by driving and walking a route to identify parties primarily on Thursday, Friday, and Saturday evenings between 9:00 PM and 1:00 AM across an academic year. Parties were randomly sampled. Hosts were asked for permission to enter the party at each sampled location. A census of partygoers was attempted at each party. Participants were asked to complete a brief survey and give a breath sample. All participants were recruited into a follow-up survey. Bivariate and multivariate analyses of individual-level and party-level factors associated with intoxication are presented. The research team identified 29 parties: 16 were approached, and 12 were surveyed. Overall, 112 participants were surveyed for a response rate of approximately 28.7% of partygoers. Controlling for demographic characteristics, consumption of shots of liquor/spirits was significantly associated with a five times greater risk for intoxication. Notably, drinking games were protective of breath alcohol concentration (BrAC) risk in this model. Individuals who reported engaging in drinking games were 74% less likely to report a BrAC above the U.S. legal limit, while controlling for underage drinking in the model. Several party characteristics were identified that increased overall BrAC at the parties, including whether the party was themed, if it was a Greek life party, and whether there were illicit drugs present. Notably, when intoxication is examined by gender and party theme, women are significantly more likely to be intoxicated at themed parties: 75% were above 0.08 at themed parties compared to 35% above 0.08 at non-themed parties. Field-based data collection methods can, and should, be modified to conduct needs assessment and evaluation of prevention programs on college campuses. The findings on this campus were different than the originally sampled campus. Prevention programs should target unique risks identified on each campus, and to respond to problematic party behaviors with comprehensive programming rather than policy-level bans.


Decreasing burned children's pain behavior: impacting the trauma of hydrotherapy.
We evaluated the effects of cartoon viewing with the use of a star feedback chart on two burned children's pain behavior during their physical therapy sessions. In addition, the degree to which the observational data corresponded with physical therapists' and mothers' ratings of the children's pain, fear, and cooperativeness was examined. Using a reversal single-subject design, the results showed that the children's pain behavior substantially decreased during experimental treatment sessions compared to their baseline levels. The rating scale data indicated that the physical therapist's and mother's rating of pain, anxiety, and cooperativeness were all correlated significantly with the observational data (p less than .05). The contributions of respondent and operant conditioning to the occurrence and treatment of pain behavior in burned children are discussed.


Scalable production of foam-like nickel-molybdenum coatings via plasma spraying as bifunctional electrocatalysts for water splitting.
Foam-like NiMo coatings were produced from an inexpensive mixture of Ni, Al, and Mo powders via atmospheric plasma spraying. The coatings were deposited onto stainless-steel meshes forming a highly porous network mainly composed of nanostructured Ni and highly active Ni4Mo. High material loading (200 mg cm-2) with large surface area (1769 cm2 per cm2) was achieved without compromising the foam-like characteristics. The coatings exhibited excellent activity towards both hydrogen evolution (HER) and oxygen evolution (OER) reactions in alkaline media. The HER active coating required an overpotential of 42 mV to reach a current density of -50 mA cm-2 with minimum degradation after a 24 h chronoamperometry test at -10 mA cm-2. Theoretical simulations showed that several crystal surfaces of Ni4Mo exhibit near optimum hydrogen adsorption energies and improved water dissociation that benefit the HER activity. The OER active coating also consisting of nanostructured Ni and Ni4Mo required only 310 mV to achieve a current density of 50 mA cm-2. The OER activity was maintained even after 48 h of continuous operation. We envisage that the development of scalable production techniques for Ni4Mo alloys will greatly benefit its usage in commercial alkaline water electrolysers.


Zebrafish Embryonic Slow Muscle Is a Rapid System for Genetic Analysis of Sarcomere Organization by CRISPR/Cas9, but Not NgAgo.
Zebrafish embryonic slow muscle cells, with their superficial localization and clear sarcomere organization, provide a useful model system for genetic analysis of muscle cell differentiation and sarcomere assembly. To develop a quick assay for testing CRISPR-mediated gene editing in slow muscles of zebrafish embryos, we targeted a red fluorescence protein (RFP) reporter gene specifically expressed in slow muscles of myomesin-3-RFP (Myom3-RFP) zebrafish embryos. We demonstrated that microinjection of RFP-sgRNA with Cas9 protein or Cas9 mRNA resulted in a mosaic pattern in loss of RFP expression in slow muscle fibers of the injected zebrafish embryos. To uncover gene functions in sarcomere organization, we targeted two endogenous genes, slow myosin heavy chain-1 (smyhc1) and heat shock protein 90 α1 (hsp90α1), which are specifically expressed in zebrafish muscle cells. We demonstrated that injection of Cas9 protein or mRNA with respective sgRNAs targeted to smyhc1 or hsp90a1 resulted in a mosaic pattern of myosin thick filament disruption in slow myofibers of the injected zebrafish embryos. Moreover, Myom3-RFP expression and M-line localization were also abolished in these defective myofibers. Given that zebrafish embryonic slow muscles are a rapid in vivo system for testing genome editing and uncovering gene functions in muscle cell differentiation, we investigated whether microinjection of Natronobacterium gregoryi Argonaute (NgAgo) system could induce genetic mutations and muscle defects in zebrafish embryos. Single-strand guide DNAs targeted to RFP, Smyhc1, or Hsp90α1 were injected with NgAgo mRNA into Myom3-RFP zebrafish embryos. Myom3-RFP expression was analyzed in the injected embryos. The results showed that, in contrast to the CRISPR/Cas9 system, injection of the NgAgo-gDNA system did not affect Myom3-RFP expression and sarcomere organization in myofibers of the injected embryos. Sequence analysis failed to detect genetic mutations at the target genes. Together, our studies demonstrate that zebrafish embryonic slow muscle is a rapid model for testing gene editing technologies in vivo and uncovering gene functions in muscle cell differentiation.


The beta 1 isoform of protein kinase C mediates the protective effects of epidermal growth factor on the dynamic assembly of F-actin cytoskeleton and normalization of calcium homeostasis in human colonic cells.
Using intestinal monolayers, we showed that F-actin cytoskeletal stabilization and Ca(2+) normalization contribute to epidermal growth factor (EGF)-mediated protection against oxidant injury. However, the intracellular mediator responsible for these protective effects remains unknown. Since the protein kinase C-beta1 (PKC-beta1) isoform is abundant in our naive (N) cells, we hypothesized that PKC-beta1 is essential to EGF protection. Monolayers of N Caco-2 cells were exposed to H(2)O(2) +/- EGF, PKC, or Ca(2+) modulators. Other cells were transfected to over-express PKC-beta1 or to inhibit its expression and then pretreated with low or high doses of EGF or a PKC activator, OAG (1-oleoyl-2-acetyl-sn-glycerol), before H(2)O(2). In N monolayers exposed to oxidant, pretreatment with EGF or PKC activators activated PKC-beta1, enhanced (45)Ca(2+) efflux, normalized Ca(2+), decreased monomeric G-actin, increased stable F-actin, and protected the cytoarchitecture of the actin. PKC inhibitors prevented these protective effects. Transfected cells stably over-expressing PKC-beta1 (+3.1-fold) but not N cell monolayers were protected from injury by even lower doses of EGF or OAG. EGF or OAG rapidly activated the over-expressed PKC-beta1. Antisense inhibition of PKC-beta1 expression (-90%) prevented all measures of EGF protection. Inhibitors of Ca(2+)-ATPase prevented EGF protection in N cells as well as protective synergism in transfected cells. EGF protects the assembly of the F-actin cytoskeleton in intestinal monolayers against oxidants in large part through the activation of PKC-beta1. EGF normalizes Ca(2+) by enhancing Ca(2+) efflux through PKC-beta1. We have identified novel biologic functions, protection of actin and Ca(2+) homeostasis, among the classical isoforms of PKC.


Imaging features of primary spinal osseous tumors and their value in clinical diagnosis.
This study explored the method of imaging diagnosis of primary spinal osseous tumors and the application value of imaging in clinical diagnosis. Sixty-nine patients with primary spinal osseous tumors who received treatment in Nankai Hospital from July 2016 to June 2017 were selected. All of them received X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) examinations to analyze the imaging features of the three examination methods. Sensitivity (Sen), specificity (Spe), positive predictive value (PV+), negative predictive value (PV-) and accuracy (Acc) were compared. The consistency of the three examination methods in diagnosing primary spinal osseous tumors was analyzed. Sen, Acc and PV- of the three examination methods in diagnosing spinal osseous tumors had obvious differences. MRI showed the highest Sen (P<0.05). MRI had relatively high consistency with CT scan in diagnosing primary spinal osseous tumors, and κ-value was 0.72. CT scan and X-ray had obvious difference in diagnosing primary spinal osseous tumors (P<0.05). The consistency between CT scan and X-ray in diagnosing primary spinal osseous tumors was relatively low, and κ-value was 0.47. MRI and X-ray had obvious difference in diagnosing primary spinal osseous tumors (P<0.05). The consistency between MRI and X-ray in diagnosing primary spinal osseous tumors was relatively low, and κ-value was 0.41. X-ray examination is easy to operate with high resolution. CT scan has obvious advantages in displaying lesions with complex structure, many of which locate in overlapping sites. MRI has more advantages and higher accuracy in judging the scope of the tumor. CT and MRI examinations have obviously higher efficacy than X-ray in diagnosing primary spinal osseous tumors. They are conducive in improving the accuracy of diagnosing primary spinal osseous tumors.


Usability of a Low-Cost Head Tracking Computer Access Method following Stroke.
Assistive technology devices for computer access can facilitate social reintegration and promote independence for people who have had a stroke. This work describes the exploration of the usefulness and acceptability of a new computer access device called the Nouse™ (Nose-as-mouse). The device uses standard webcam and video recognition algorithms to map the movement of the user's nose to a computer cursor, thereby allowing hands-free computer operation. Ten participants receiving in- or outpatient stroke rehabilitation completed a series of standardized and everyday computer tasks using the Nouse™ and then completed a device usability questionnaire. Task completion rates were high (90%) for computer activities only in the absence of time constraints. Most of the participants were satisfied with ease of use (70%) and liked using the Nouse™ (60%), indicating they could resume most of their usual computer activities apart from word-processing using the device. The findings suggest that hands-free computer access devices like the Nouse™ may be an option for people who experience upper motor impairment caused by stroke and are highly motivated to resume personal computing. More research is necessary to further evaluate the effectiveness of this technology, especially in relation to other computer access assistive technology devices.


Immunohistochemical expression of survivin in cutaneous sebaceous lesions.
Survivin is a member of the inhibitor of apoptosis family of proteins implicated in the inhibition of apoptosis and cell cycle control, both crucial in the progression to malignancy. Survivin overexpression has been demonstrated in numerous malignancies including cutaneous squamous cell carcinoma and melanoma. To date, there are no studies evaluating the expression of survivin in sebaceous neoplasms. Immunohistochemical expression of survivin was evaluated in a total of 20 extraocular sebaceous neoplasms: sebaceous hyperplasia (SH, 8), sebaceous adenoma (SA, 8), and sebaceous carcinoma (SC, 4). All the results were independently evaluated by a single dermatopathologist. Nuclear expression of survivin was present in 1.4% of lesional SH cells, 8.2% of SA cells, and 12.5% of SC cells. A significant difference in survivin expression with the Student t test was noted between SH and SA (P=0.01), SA and SC (P=0.05), and SH and SC (P=0.001). There is a statistically significant difference in survivin expression among SH, SA, and SC. These findings demonstrate the potential diagnostic utility of survivin, further assisting in the microscopic differentiation of benign and malignant sebaceous neoplasms. However, larger studies are needed to determine the significance of survivin expression as it relates to recurrence, metastatic potential, and outcome.


Oleh Hornykiewicz (1926-2020): Sixty Years since the Pioneering L-DOPA Application - One Year since the Death of the Pioneer.
Oleh Hornykiewicz was born on November 17, 1926 in Lamberg, Ukraine. After completing his studies in July 1951, he moved to the "Pharmacological Institute of the University of Vienna". In 1958, he started his research on centrally acting drugs at the same institute and came up with the idea of linking laboratory observations with animals with the basal ganglia of the human brain. Soon, Hornykiewicz initiated a new question: L-DOPA as a therapy for Parkinson's disease? Fortunately, after administration of this new drug, patients were able to perform motor activities which could not be prompted to any comparable degree by any known drug. In the following decades, initial fiction became an unavoidable fact. Dopamine, adapted and combined with carbidopa or benzerazide, has evolved into a drug that no longer recognizes the borders of countries and continents. Distinguished emeritus prof. Oleh Hornykiewicz died on May 26, 2020 at the age of 93 in Vienna, Austria. Unfortunately, despite everything he has done and deserved, the Nobel Prize was not received.


[Pathological complete response in advanced gastric carcinoma with lymph node metastasis treated with combination neoadjuvant chemotherapy comprising S-1 and cisplatin-a case report].
A 55-year-old man with melena was referred to our hospital with suspicion of pancreatic cancer. Upper gastrointestinal endoscopy revealed a type 3 tumor in the greater curvature of the pylorus invading the duodenum. Examination of biopsy specimens showed poorly differentiated adenocarcinoma. Abdominal computed tomography (CT) and positron emission tomography (PET)-CT revealed a gastric tumor in the antrum and regional lymph node metastases invading the pancreas, indicating clinical stage IIIB (cT3, N2, H0, P0, M0) disease. Following 2 courses of neoadjuvant chemotherapy with S-1 plus cisplatin( CDDP), distal gastrectomy with D2 lymphadenectomy was performed. Histological examination revealed no residual cancer cells in the surgically obtained stomach and lymph node specimens, suggesting a complete pathological response( Grade 3). The patient was treated with S-1 for 1 year after surgery. Currently, at 54 months after surgery, the patient is in good health without recurrence.


Inducible beta-lactamases: clinical and epidemiologic implications for use of newer cephalosporins.
The emergence of resistance to multiple beta-lactam antibiotics is a major problem in patients infected with organisms that characteristically produce inducible beta-lactamases--e.g., species of Pseudomonas, Enterobacter, Serratia, Citrobacter, indole-positive Proteus, and Providencia. Resistance has emerged in 14%-56% of patients infected with these organisms and treated with one of the newer cephalosporins. The emergence of resistance has been associated with clinical failure or relapse in 25%-75% of these patients. Combination therapy appears to have little impact on rates of resistance or its clinical consequences. Multiply resistant organisms have spread widely in some hospitals, and this trend has been correlated closely with the extent of use of the newer cephalosporins. The magnitude of the problem is frequently underestimated because many properly performed susceptibility tests fail to detect resistance when it is actually present and because some methods used to calculate rates minimize the impact of the emergence of resistance among organisms with inducible beta-lactamases.


New Compounds and Phase Selection of Nickel Sulfides via Oxidation State Control in Molten Hydroxides.
Molten salts are promising reaction media candidates for the discovery of novel materials; however, they offer little control over oxidation state compared to aqueous solutions. Here, we demonstrated that when two hydroxides are mixed, their melts become fluxes with tunable solubility, which are surprisingly powerful solvents for ternary chalcogenides and offer effective paths for crystal growth to new compounds. We report that precise control of the oxidation state of Ni is achievable in mixed molten LiOH/KOH to grow single crystals of all known ternary K-Ni-S compounds. It is also possible to access several new phases, including a new polytope of β-K2Ni3S4, as well as low-valence KNi4S2 and K4Ni9S11. KNi4S2 is a two-dimensional low-valence nickel-rich sulfide, and β-K2Ni3S4 has a hexagonal lattice. Moreover, using KNi4S2 as a template, we obtained a new layered binary Ni2S by topotactic deintercalation of K. The new binary Ni2S has a van der Waals gap and can function as a new host layer for intercalation chemistry, as demonstrated by the intercalation of LiOH between its layers. The oxidation states of low-valence KNi4S2 and Ni2S were studied using X-ray absorption spectroscopy and X-ray photoelectron spectroscopy. Density functional theory calculations showed large antibonding interactions at the Fermi level for both KNi4S2 and Ni2S, corresponding to the flat-bands with large Ni-dx2-y2 character.


Science to practice: will contrast agents for molecular imaging of angiogenesis help overcome the limitations of functional vascular imaging?
Schmieder and colleagues introduced a new molecular magnetic resonance (MR) probe with a promising lipophilic gadolinium chelate complex that provides high relaxivity. Results of in vivo experiments clearly demonstrate the excellence of the probe for longitudinally monitoring α(v)β(3) integrin expression in tumors. In addition, the authors have developed a robust nonrelaxometric analysis method with which to quantify the spatial distribution of molecular MR probes. In combination with a molecular probe targeting angiogenesis, this approach may be superior to functional vascular assessments. It has the potential to enable better detection of angiogenic regions in heterogeneous tumors and to improve the monitoring and individualization of antiangiogenic treatments.


Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems.
We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13- along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1 H Nuclear Magnetic Resonance (NMR), 1 H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12 ]6- , to be in equilibrium with monomers 1(R) 3- (relaxed) and 1(S) 3- (squeezed). Through simultaneous line-shape analysis of 1 H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R) 3- includes anticancer drug mitoxantrone (MTO2+ ) in its pocket to give stable binary complex [MTO⊂1]- (Kd =2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.


COVID-19 Pandemic: The Local Community Perceptions and Associated Risks in Guji Society, Southern Ethiopia.
To investigate local perceptions of the causes and prevention of the COVID-19 pandemic in Guji Society, West Guji Zone, Bule Hora district. The researcher conducted a qualitative study using in-depth interviews and key informant interviews, focus group discussions, and case study with 46 informants, of which 22 were women and 24 were men. The informants were recruited using purposive sampling. The data was analyzed by qualitative description. The findings indicate the wrath of Waaqaa (God), evil spirit attacks, Gadaa party's omen, the virus, and unknown forces are thought to be the causes of the virus. The local amelioration and prevention mechanisms reported by the informants were rituals of praying for God's mercy and social distancing, along with using face-masks, keeping hygiene, and getting vaccines. The local community's perceptions about the COVID-19 pandemic's causes and prevention methods are based on myths, assumptions, and belief systems that contradict medical science concepts and prevention methods. As a result, this scenario would result in potential risk factors like susceptibility to the virus, severe health complications, and psychological and socio-economic adverse impacts.


Quantitative Phase-Change Thermodynamics and Metastability of Perovskite-Phase Cesium Lead Iodide.
The perovskite phase of cesium lead iodide (α-CsPbI3 or "black" phase) possesses favorable optoelectronic properties for photovoltaic applications. However, the stable phase at room temperature is a nonfunctional "yellow" phase (δ-CsPbI3). Black-phase polycrystalline thin films are synthesized above 330 °C and rapidly quenched to room temperature, retaining their phase in a metastable state. Using differential scanning calorimetry, it is shown herein that the metastable state is maintained in the absence of moisture, up to a temperature of 100 °C, and a reversible phase-change enthalpy of 14.2 (±0.5) kJ/mol is observed. The presence of atmospheric moisture hastens the black-to-yellow conversion kinetics without significantly changing the enthalpy of the transition, indicating a catalytic effect, rather than a change in equilibrium due to water adduct formation. These results delineate the conditions for trapping the desired phase and highlight the significant magnitude of the entropic stabilization of this phase.