[1H NMR based metabolomics study of bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model].
The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.


Case Report: An Acute Chikungunya Infection and a Recent Secondary Dengue Infection in a Peripartum Case in Ecuador.
Dengue virus (DENV) and chikungunya virus (CHIKV) are transmitted by the same mosquito vectors and now co-circulate in many parts of the world; however, coinfections and serial infections are not often diagnosed or reported. A 38-week pregnant woman was admitted to the hospital with a diagnosis of suspected DENV and CHIKV in southern coastal Ecuador. The pregnancy was complicated by mild polyhydramnios and fetal tachycardia, and a healthy newborn was born. The patient was positive for a recent secondary DENV infection (Immunoglobulin M and Immunoglobulin G positive) and an acute CHIKV infection (real-time reverse transcriptase polymerase chain reaction positive) (Asian genotype). The newborn was not tested for either virus. This case resulted in a benign clinical course with a favorable pregnancy outcome.


Electrophysiology Reveals the Neural Dynamics of Naturalistic Auditory Language Processing: Event-Related Potentials Reflect Continuous Model Updates.
The recent trend away from ANOVA-based analyses places experimental investigations into the neurobiology of cognition in more naturalistic and ecologically valid designs within reach. Using mixed-effects models for epoch-based regression, we demonstrate the feasibility of examining event-related potentials (ERPs), and in particular the N400, to study the neural dynamics of human auditory language processing in a naturalistic setting. Despite the large variability between trials during naturalistic stimulation, we replicated previous findings from the literature: the effects of frequency, animacy, and word order and find previously unexplored interaction effects. This suggests a new perspective on ERPs, namely, as a continuous modulation reflecting continuous stimulation instead of a series of discrete and essentially sequential processes locked to discrete events.


Photoswitchable dynamic combinatorial libraries: coupling azobenzene photoisomerization with hydrazone exchange.
The novel azobenzene-based monomer 1 was prepared, equipped with the necessary functionality to undergo simultaneous dynamic exchange processes: hydrazone exchange and photoisomerization. Acid-promoted hydrolysis of the azobenzene building block produced a dynamic combinatorial library of cyclic oligomers, while multibuilding block libraries were also generated upon addition of proline-based monomers. Libraries equilibrated under thermal conditions were dominated by trans isomers of the azobenzene macrocycles, whereas light-induced isomerization resulted in a conformational change of the library members to their corresponding cis-azo form. In the presence of a pentaproline template, a slower rate of thermal relaxation of the cis-azobenzene species 1(c) was observed, resulting in stabilization and amplification of this receptor due to favorable binding interactions. The facile identification and application of such photoswitchable receptors have the potential to allow for greater control over molecular recognition events.


Capacitance-Based Biosensor for the Measurement of Total Loss of L-Amino Acids in Human Serum during Hemodialysis.
In this paper, we present a biosensor based on a gold nanoparticle (AuNP)-modified Pt electrode with an adjusted membrane containing cross-linked L-amino acid oxidase for the detection and quantification of total L-amino acids. The designed biosensor was tested and characterized using the capacitance-based principle, capacitance measurements after electrode polarization, disconnection from the circuit, and addition of the respective amount of the analyte. The method was implemented using the capacitive and catalytic properties of the Pt/AuNP electrode; nanostructures were able to store electric charge while at the same time catalyzing the oxidation of the redox reaction intermediate H2O2. In this way, the Pt/AuNP layer was charged after the addition of analytes, allowing for much more accurate measurements for samples with low amino acid concentrations. The combined biosensor electrode with the capacitance-based measurement method resulted in high sensitivity and a low limit of detection (LOD) for hydrogen peroxide (4.15 μC/μM and 0.86 μM, respectively) and high sensitivity, a low LOD, and a wide linear range for L-amino acids (0.73 μC/μM, 5.5 μM and 25-1500 μM, respectively). The designed biosensor was applied to measure the relative loss of amino acids in patients undergoing renal replacement therapy by analyzing amino acid levels in diluted serum samples before and after entering/leaving the hemodialysis apparatus. In general, the designed biosensor in conjunction with the proposed capacitance-based method was clinically tested and could also be applied for the detection of other analytes using analyte-specific oxidases.


Comparison of two random-effects methods of meta-analysis.
Two studies compared the Schmidt-Hunter method of meta-analysis (J. E. Hunter & F. L. Schmidt, 1990) with the method described by L. V. Hedges and J. L. Vevea (1998). Study 1 evaluated estimates of rho, sigmarho, and resulting credibility intervals for both models through Monte Carlo methods. Results showed slight differences between the 2 methods. In Study 2, a reanalysis of published meta-analyses using both methods with several artifact distributions showed that although both choice of technique and type of correction could matter, the technique of meta-analysis used is less influential on the study outcome than is the choice of artifact correction.


Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression.
The genome (genes), epigenome, and environment work together from the earliest stages of human life to produce a phenotype of human health or disease. Epigenetic modifications, including among other things: DNA methylation, modifications of histones and chromatin structure, as well as functions of noncoding RNA, are coresponsible for specific patterns of gene expression. This refers also to mental disorders, including depressive disorders. Early childhood experiences accompanied by severe stressors (considered a risk factor for depression in adult life) are linked with changes in gene expression. They include genes involved in a response to stress (hypothalamic-pituitary-adrenal axis, HPA), associated with autonomic nervous system hyperactivity and with cortical, and subcortical processes of neuroplasticity and neurodegeneration. These are, among others: gene encoding glucocorticoid receptor, FK506 binding protein 5 gene (FKBP5), gene encoding arginine vasopressin and oestrogen receptor alpha, 5-hydroxy-tryptamine transporter gene (SLC6A4), and gene encoding brain-derived neurotrophic factor. How about personality? Can the experiences unique to every human being, the history of his or her development and gene-environment interactions, through epigenetic mechanisms, shape the features of our personality? Can we pass on these features to future generations? Hence, is the risk of depression inherent in our biological nature? Can we change our destiny?


Targeting Ribosomal Frameshifting as an Antiviral Strategy: From HIV-1 to SARS-CoV-2.
Treatment of HIV-1 has largely involved targeting viral enzymes using a cocktail of inhibitors. However, resistance to these inhibitors and toxicity in the long term have pushed the field to identify new therapeutic targets. To that end, -1 programmed ribosomal frameshifting (-1 PRF) has gained attention as a potential node for therapeutic intervention. In this process, a ribosome moves one nucleotide backward in the course of translating a mRNA, revealing a new reading frame for protein synthesis. In HIV-1, -1 PRF allows the virus to regulate the ratios of enzymatic and structural proteins as needed for correct viral particle assembly. Two RNA structural elements are central to -1 PRF in HIV: a slippery sequence and a highly conserved stable hairpin called the HIV-1 frameshifting stimulatory signal (FSS). Dysregulation of -1 PRF is deleterious for the virus. Thus, -1 PRF is an attractive target for new antiviral development. It is important to note that HIV-1 is not the only virus exploiting -1 PRF for regulating production of its proteins. Coronaviruses, including the COVID-19 pandemic virus SARS-CoV-2, also rely on -1 PRF. In SARS-CoV-2 and other coronaviruses, -1 PRF is required for synthesis of RNA-dependent RNA polymerase and several other nonstructural proteins. Coronaviruses employ a more complex RNA structural element for regulating -1 PRF called a pseudoknot. The purpose of this Account is primarily to review the development of molecules targeting HIV-1 -1 PRF. These approaches are case studies illustrating how the entire pipeline from screening to the generation of high-affinity leads might be implemented. We consider both target-based and function-based screening, with a particular focus on our group's approach beginning with a resin-bound dynamic combinatorial library (RBDCL) screen. We then used rational design approaches to optimize binding affinity, selectivity, and cellular bioavailability. Our tactic is, to the best of our knowledge, the only study resulting in compounds that bind specifically to the HIV-1 FSS RNA and reduce infectivity of laboratory and drug-resistant strains of HIV-1 in human cells. Lessons learned from strategies targeting -1 PRF HIV-1 might provide solutions in the development of antivirals in areas of unmet medical need. This includes the development of new frameshift-altering therapies for SARS-CoV-2, approaches to which are very recently beginning to appear.


Review. Specificity in pollination and consequences for postmating reproductive isolation in deceptive Mediterranean orchids.
The type of reproductive isolation prevalent in the initial stages of species divergence can affect the nature and rate of emergence of additional reproductive barriers that subsequently strengthen isolation between species. Different groups of Mediterranean deceptive orchids are characterized by different levels of pollinator specificity. Whereas food-deceptive orchid species show weak pollinator specificity, the sexually deceptive Ophrys species display a more specialized pollination strategy. Comparative analyses reveal that orchids with high pollinator specificity mostly rely on premating reproductive barriers and have very little postmating isolation. In this group, a shift to a novel pollinator achieved by modifying the odour bouquet may represent the main isolation mechanism involved in speciation. By contrast, orchids with weak premating isolation, such as generalized food-deceptive orchids, show strong evidence for intrinsic postmating reproductive barriers, particularly for late-acting postzygotic barriers such as hybrid sterility. In such species, chromosomal differences may have played a key role in species isolation, although strong postmating-prezygotic isolation has also evolved in these orchids. Molecular analyses of hybrid zones indicate that the types and strength of reproductive barriers in deceptive orchids with contrasting premating isolation mechanisms directly affect the rate and evolutionary consequences of hybridization and the nature of species differentiation.


[Chondroid syringoma].
This is a retrospective monocentric stydy of all the cases diagnosed at our department over a period of 10 years. The study included seven male patients. All patients presented with a single painless skin lesion of about 1,5 cm on the face, lasting for 14 months on average. In all cases, treatment was surgical and the outcome satisfactory. Chondroid syringoma is a benign sweat gland tumor. This lesion is electively located in the craniofacial area, made of a subcutaneous painless tumor measuring from 0.5 to 3 cm. Diagnosis can always be confirmed by histology which shows tubuloalveolar and gland like structures with two or more cuboidal cell lines in a fibroadipoid or chondroid stroma that is positively stained for Alcian blue. Mixed tumors have a slow course; their progress to malignancy is rare but possible. The best treatment remains surgical allowing a histological diagnosis with a control of the lesion edges.


GlycoMapsDB: a database of the accessible conformational space of glycosidic linkages.
Conformational energy maps of the glycosidic linkages are a valuable resource to gain information about preferred conformations and flexibility of carbohydrates. Here we present GlycoMapsDB, a new database containing more than 2500 calculated conformational maps for a variety of di- to pentasaccharide fragments contained in N- and O-glycans. Oligosaccharides representing branchpoints of N-glycans are included in the set of fragments, thus the influence of neighbouring residues is reflected in the conformational maps. During refinement of new crystal structures, maps contained in GlycoMapsDB can serve as a valuable resource to check whether the torsion values of a glycosidic linkage are located in an 'allowed' region similar to the Ramachandran plot analysis for proteins. This might help to improve the structural quality of the glycan data contained in the Protein Data Bank (PDB). A link between GlycoMapsDB and the PDB has been established so that the glycosidic torsions of all glycans contained in the PDB can be retrieved and compared to calculated data. The service is available at www.glycosciences.de/modeling/glycomapsdb/.


Evaluation of dairy products available on the Polish market in the context of nutrient profiles. Clear arguments for reformulation of foodstuffs
Dairy products, which are one of the main groups of products in the diet, are expected to have high nutritional value. The development of food technology often involves changing the nutritional parameters of foodstuffs. The aim of this study was to determine the nutritional value of dairy products, in the context of nutrient profiles. The tested products included yoghurts, yoghurt drinks, kefir, cream cheeses and milk desserts available on the Polish market, basing on the information from unit product packaging. The average sugar content in the group of all products was 11 g/100 g. Milk desserts contained the largest amount of sugar (average 14.7 g/100g), whereas kefir – the smallest amount (average 6 g/100 g) (p <0.0001). Yoghurts and yoghurt drinks intended for children had higher sugar content than products for the general population (14.4 g vs. 10.5 g/100 g) (p <0.0001). As many as 75% of products were sweetened. Taking into account the natural content of lactose, the estimated amount of added sugar ranged from 6.9 - 12.3 g/100 g. The average fat content in the group of all products amounted to 3.8 g/100 g. In the view of WHO profiles, 71% of products exceeded the permissible sugar content (≤ 10 g/100 g) and 36% exceeded the permissible content of saturated fatty acids (≤ 2 g/100 g). Using more liberal profiles developed by the food industry, the proportion of such products was smaller, but still quite high (34% in case of sugar and 26% in case of saturated fatty acids). In terms of the sugar content, according to regulation introduced in Poland, only 29% of the analyzed dairy products could be offer for children at schools. Among them there are all natural (not sweetened) yoghurts and kefir and only 6% of other sweetened products. There is a justified need for the reformulation of dairy products, especially in terms of added sugar.


Dynamic effective mass of granular media and the attenuation of structure-borne sound.
We report a theoretical and experimental investigation into the fundamental physics of why loose granular media are effective deadeners of structure-borne sound. Here, we demonstrate that a measurement of the effective mass, M(omega), of the granular medium is a sensitive and direct way to answer the question: what is the specific mechanism whereby acoustic energy is transformed into heat? Specifically, we apply this understanding to the case of the flexural resonances of a rectangular bar with a grain-filled cavity within it. The pore space in the granular medium is air of varying humidity. The dominant features of M(omega) are a sharp resonance and a broad background, which we analyze within the context of simple models. We find that: (a) on a fundamental level, dampening of acoustic modes is dominated by adsorbed films of water at grain-grain contacts, not by global viscous dampening or by attenuation within the grains. (b) These systems may be understood, qualitatively, in terms of a height-dependent and diameter-dependent effective sound speed [approximately 100-300 (m.s-1)] and an effective viscosity [approximately 5x10(4) Poise]. (c) There is an acoustic Janssen effect in the sense that, at any frequency, and depending on the method of sample preparation, approximately one-half of the effective mass is borne by the side walls of the cavity and one-half by the bottom. (d) There is a monotonically increasing effect of humidity on the dampening of the fundamental resonance within the granular medium which translates to a nonmonotonic, but predictable, variation in dampening within the grain-loaded bar.


Further evidence of association between two NET single-nucleotide polymorphisms with ADHD.
The norepinephrine transporter (NET) gene is an attractive candidate gene for attention-deficit hyperactivity disorder (ADHD). Noradrenergic systems are critical to higher brain functions such as attention and executive function, which are defective in ADHD. The clinical efficacy of medications that target NET also supports its role in the etiology of ADHD. Here, we have applied a dense mapping strategy to capture all genetic variations within the NET gene in a large number of ADHD families (474 trios). As a result, we found association of the same alleles from two single-nucleotide polymorphisms (rs3785143 and rs11568324) previously identified in another large-scale ADHD genetic study (International Multisite ADHD Geneproject). Furthermore, the effect sizes were consistent across both studies. This is the first time that identical alleles of NET from different studies were implicated, and thus our report provides further evidence that the NET gene is involved in the etiology of ADHD.


Continuity conditions for Q-Bézier curves of degree n.
As a new method of representing curves, Q-Bézier curves not only exhibit the beneficial properties of Bézier curves but also allow effective shape adjustment by changing multiple shape parameters. In order to resolve the problem of not being able to construct complex curves using a single curve, we study the geometric continuity conditions for Q-Bézier curves of degree n. Following the analysis of basis functions and terminal properties of Q-Bézier curves of degree n, the continuity conditions of [Formula: see text] and [Formula: see text] between two adjacent Q-Bézier curves are proposed. In addition, we discuss the specific steps of smooth continuity for Q-Bézier curves and analyze the influence rules of shape parameters for Q-Bézier curves. The modeling examples show that the proposed method is effective and easy to achieve, making it useful for constructing complex curves for engineering design.


RIFLE: a Phase II trial of stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer.
Currently, the prognosis for metastatic colorectal cancer (mCRC) still remains poor. The management of mCRC has become manifold because of the varied advances in the systemic and topical treatment approaches. For patients with limited number of metastases, radical local therapy plus systemic therapy can be a good choice to achieve long-term tumor control. In this study, we aimed to explore the efficacy and safety of the combination of fruquintinib, tislelizumab, and stereotactic ablative radiotherapy (SABR) in mCRC (RIFLE study). RIFLE was designed as a single-center, single-arm, prospective Phase II clinical trial. A total of 68 mCRC patients who have failed the first-line standard treatment will be recruited in the safety run-in phase (n = 6) and the expansion phase (n = 62), respectively. Eligible patients will receive SABR followed by fruquintinib (5 mg, d1-14, once every day) and tislelizumab (200 mg, d1, once every 3 weeks) within 2 weeks from completion of radiation. The expansion phase starts when the safety of the treatment is determined (dose limiting toxicity occur in no more than one-sixth of patients in the run-in phase). The primary end point is the objective response rate. The secondary end points include the disease control rate, duration of response, 3-year progression-free survival rate, 3-year overall survival rate, and toxicity. The results of this trial will provide a novel insight into SABR in combination with PD-1 antibody and vascular endothelial growth factor receptor inhibitor in the systematic treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients. NCT04948034 (ClinicalTrials.gov).


Shoulder arthroscopy combined to hardware removal in proximal humeral fractures: a series of 58 cases with a mean follow-up of 2 years.
Proximal humerus fractures are common injuries. Locking plates and anterograde medullary nails are the two most common fixation devices used when open reduction and internal fixation (ORIF) is indicated. Complications related to fracture and to hardware are numerous, especially shoulder stiffness. The goal of this study is to report the clinical outcomes of gleno-humeral arthroscopic arthrolysis combined with hardware removal. A total of 58 patients (25 men, 33 women) with a mean age of 58 years (24-79) were reviewed retrospectively. Forty of them were active workers (5 heavy workers), and 18 were retired. A total of 24 fractures were reported after sport accident, 26 after domestic accident, and 8 after high energy trauma. Thirty-four patients with 3 or 4 part fractures (fracture through the anatomic neck and tuberosities), 20 patients with two part (displaced surgical neck) fracture and 4 cases of fracture of the tuberosities were operated. We combined a gleno-humeral arthrolysis by arthroscopy and a removal of the hardware using the previous incision for the plate or by arthroscopy for the nail. The average follow-up was 23 months (range 6-60). Pain in Constant Murley score (CS) increased from 7.3 ± 3.8 points preoperatively to 13 ± 2.76 points post-operatively (p < 0.05). CS increased from 36.8 ± 12.25 points to 68.45 ± 15.24 points. Subjective shoulder value (SSV) score increased from 45.8 ± 16.6 to 78.23 ± 14.74. A gain in all active range of motion was reported (forward flexion: 37.6°, abduction: 39.5°, external rotation: 24.3°, internal rotation: from L5-S1 to T12-L1). Gleno-humeral arthrolysis by arthroscopy combined with hardware removal after proximal humerus ORIF in one step is safe and beneficial for post-traumatic stiffness of the shoulder. It provides significant pain relief and increase of range of motion and allows to treat associated articular pathology.


Leukemia as a second malignancy.
To study the occurrence of leukemia as a second malignancy following various primary solid and hematological malignancies. Total 11 cases of leukemia presenting as a second malignancy were studied over a period of 15 years from 1990 to 2005. The primary malignancies included carcinoma breast (4), multiple myeloma (3) and one each of Hodgkin's lymphoma, mediastinal germ cell tumor, papillary carcinoma thyroid and myxopapillary ependymoma. Ten patients had received chemotherapy with combination radiotherapy in six patients. The commonest type of leukemia was AML-M2. The cyogenetic test results were available in three cases. The secondary leukemia showed aggressive behaviour and all patients on follow-up died within a period of one month. The risk benefit ratio of chemotherapy and radiotherapy should be considered before starting the patients on treatment. A high degree of suspicion and follow up with hematological parameters is required for therapy related complications.


DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers.
A shift between two dimer conformations has been proposed for the transcription factor STAT1 (signal transducer and activator of transcription 1) which links DNA binding of the parallel dimer to tyrosine dephosphorylation of the antiparallel dimer as two consecutive and important steps in interferon- γ (IFNγ)-mediated signalling. However, neither the kinetics nor the molecular mechanisms involved in this conformational transition have been determined so far. Our results demonstrated that the dissociation of dimers into monomers and their subsequent re-association into newly formed tyrosine-phosphorylated dimers is a relatively slow process as compared to the fast release from high-affinity DNA-binding sites, termed GAS (gamma-activated sequence). In addition, we noted an inhibitory effect of GAS binding on the exchange rate of protomers, indicating that DNA binding substantially impedes the recombination of dimeric STAT1. Furthermore, we found that reciprocal aminoterminal interactions between two STAT1 molecules are not required for the interchange of protomers, as an oligomerization-deficient point mutant displayed similar interdimeric exchange kinetics as the wild-type molecule. Our results demonstrate that DNA binding impairs the oscillation rate between STAT1 conformers. Furthermore, these data suggest that the rapid release from high-affinity GAS sites is not a rate-limiting step in IFNγ-mediated signal transduction. Further investigations are needed to decipher the physiological significance of the observed dissociation/re-association process of STAT1 dimers.


Redistribution of metal ions to control low density lipoprotein oxidation in Ham's F10 medium.
The study of cell-mediated low density lipoprotein (LDL) oxidation has traditionally been undertaken using Ham's F10 media due to its high metal content and low levels of antioxidants. Although there has been no acknowledged change to this media in recent years by the suppliers, Ham's F10 medium has been found to be extremely inconsistent in its promotion of LDL oxidation in the absence of cells. This variability contrasts with the relatively consistent rates of THP-1 cell-mediated LDL oxidation. This study has now shown that the variability in cell-free LDL oxidation is medium-dependent and not an artefact of experimental protocol. It presents evidence that suggests the variable rates of cell-free LDL oxidation are caused by iron auto-oxidation during storage of the Ham's F10 medium. The medium can be standardized by removal of all transition metals, by treatment with Chelex, before the addition of known amounts of iron or copper. This treatment generates a cell culture medium that only allows very slow LDL oxidation in the absence of cells.


iVI-TD-DFT: An iterative vector interaction method for exterior/interior roots of TD-DFT.
The recently proposed iterative vector interaction (iVI) method for large Hermitian eigenvalue problems (Huang et al., J. Comput. Chem. 2017, 38, 2481) is extended to generalized eigenvalue problems, HC = SCE, with the metric S being either positive definite or not. Although, it works with a fixed-dimensional search subspace, iVI can converge quickly and monotonically from above to the exact exterior/interior roots. The algorithms are further specialized to nonrelativistic and relativistic time-dependent density functional theories (TD-DFT) by taking the orbital Hessian as the metric (i.e., the inverse TD-DFT eigenvalue problem) and incorporating explicitly the paired structure into the trial vectors. The efficacy of iVI-TD-DFT is demonstrated by various examples. © 2018 Wiley Periodicals, Inc.


Seasonal Pacing - Match Importance Affects Activity in Professional Soccer.
This research explores the influence of match importance on player activity in professional soccer. Therefore, we used an observational approach and analyzed 1,211 matches of German Bundesliga and 2nd Bundesliga. The importance measurement employed is based on post season consequences of teams involved in a match. This means, if a match result could potentially influence the final rank, and this rank would lead to different consequences for a team, such as qualification for Champions League opposed to qualification for Europe League, then this match is classified as important; otherwise not. Activity was quantified by TOTAL DISTANCE COVERED, SPRINTS, FAST RUNS, DUELS, FOULS and ATTEMPTS. Running parameters were recorded using a semi-automatic optical tracking system, while technical variables were collected by professional data loggers. Based on our importance classification, low important matches occurred at the beginning of round 29. A two-way ANOVA indicates significantly increased FAST RUNS (+4%, d = 0.3), DUELS (+16%, d = 1.0) and FOULS (+36%, d = 1.2) in important matches compared to low important ones. For FAST RUNS and FOULS, this effect only exists in Bundesliga. A comparison of the two leagues show that TOTAL DISTANCE COVERED (+3%, d = 0.9), SPRINTS (+25%, d = 1.4) and FAST RUNS (+15%, d = 1.4) are higher compared to 2nd Bundesliga, whilst FOULS is less in Bundesliga (-7%, d = 0.3). No difference in player activity was found between matches at the beginning of a season (round 1-6) and at the end of a season (round 29-34). We conclude that match importance influences player activity in German professional soccer. The most reasonable explanation is a conscious or unconscious pacing strategy, motivated by preserving abilities or preventing injury. Since this tendency mainly exists in Bundesliga, this may suggest that more skilled players show a higher awareness for the need of pacing.


Pirarubicin-based versus doxorubicin-based osteosarcoma chemotherapy.
To conduct a retrospective evaluation of tetrahydropyranyladriamycin (PIR)-based combination chemotherapy for osteosarcomas in comparison with doxorubicin (DOX)-based regimens to determine differences in response and toxicities between DOX- and PIR-containing regimens. Toxicities and response rates of the 2 anthracyclines given as combination chemotherapy were assessed in patients with osteosarcoma, with 19 patients receiving PIR-based and 11 receiving DOX-based regimens. The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up. Adverse effects such as mucositis and diarrhea were also less pronounced in the PIR cohort. PIR-based combination chemotherapy might be a useful and safe chemotherapeutic strategy for osteosarcomas compared with DOX regimens. Further assessment is necessary to confirm the safety and efficacy of this treatment.


Angioplasty for arteriovenous grafts and fistulae.
The technique of percutaneous transluminal angioplasty (PTA) has become routinely used in the management of hemodialysis access dysfunction. It is used for the management of problems that affect both AVF and grafts. In the case of fistulae, it is used for treatment of early failure caused by juxta-anastomotic stenosis and late failure related to venous stenosis. In the case of AVGs, it is used primarily for the management of venous stenosis secondary to neointimal hyperplasia. The technique has been shown to be safe, easily performed, and effective. Details of the procedure, supplies used, complications and their management, and results are reviewed in detail.


Cell volume regulation in liver.
The maintenance of liver cell volume in isotonic extracellular fluid requires the continuous supply of energy: sodium is extruded in exchange for potassium by the sodium/potassium ATPase, conductive potassium efflux creates a cell-negative membrane potential, which expelles chloride through conductive pathways. Thus, the various organic substances accumulated within the cell are osmotically counterbalanced in large part by the large difference of chloride concentration across the cell membrane. Impairment of energy supply leads to dissipation of ion gradients, depolarization and cell swelling. However, even in the presence of ouabain the liver cell can extrude ions by furosemide-sensitive transport in intracellular vesicles and subsequent exocytosis. In isotonic extracellular fluid cell swelling may follow an increase in extracellular potassium concentration, which impairs potassium efflux and depolarizes the cell membrane leading to chloride accumulation. Replacement of extracellular chloride with impermeable anions leads to cell shrinkage. During excessive sodium-coupled entry of amino acids and subsequent stimulation of sodium/potassium-ATPase by increase in intracellular sodium activity, an increase in cell volume is blunted by activation of potassium channels, which maintain cell membrane potential and allow for loss of cellular potassium. Cell swelling induced by exposure of liver cells to hypotonic extracellular fluid is followed by regulatory volume decrease (RVD), cell shrinkage induced by reexposure to isotonic perfusate is followed by regulatory volume increase (RVI). Available evidence suggests that RVD is accomplished by activation of potassium channels, hyperpolarization and subsequent extrusion of chloride along with potassium, and that RVI depends on the activation of sodium hydrogen ion exchange with subsequent activation of sodium/potassium-ATPase leading to the respective accumulation of potassium and bicarbonate. In addition, exposure of liver to anisotonic perfusates alters glycogen degradation, glycolysis and probably urea formation, which are enhanced by exposure to hypertonic perfusates and depressed by hypotonic perfusates.


The mechanism underlying T cell help for induction of an antigen-specific in vivo humoral immune response to intact Streptococcus pneumoniae is dependent on the type of antigen.
Little is known concerning the role of T cells in regulating an anti-polysaccharide Ig response to an intact pathogen. We previously reported that the in vivo Ig responses to Streptococcus pneumoniae (strain R36A), specific for pneumococcal surface protein A (PspA) and for the phosphorylcholine (PC) determinant of C-polysaccharide, were both dependent on TCR-alphabeta(+) T cells and B7-dependent costimulation, although only PspA-specific memory was generated. In this report, we show that the T cell help underlying these two Ag-specific Ig responses is distinct. Using H-Y-specific T cell transgenic mice made "nonleaky" by crossing with mice genetically deficient for TCR-alpha, we demonstrate that the T cell help for the anti-PC, in contrast to the anti-PspA, response is TCR-nonspecific and occurs normally in the absence of germinal center formation, although it is still dependent on B7-dependent costimulation. Consistent with these data, we demonstrate, using cathepsin S(-/-) mice, that although the anti-PC response is largely dependent on CD4(+) T cells, there is a reduced (or lack of) dependence, relative to the anti-PspA response, on the generation of new peptide-MHC class II complexes. In this regard, the T cell help for an optimal anti-PC response is delivered more rapidly than that required for an optimal anti-PspA response. Collectively, these data demonstrate a novel accelerated TCR-nonspecific B7-dependent form of T cell help for augmenting a polysaccharide-specific Ig response to an intact bacterium without the generation of memory.


CO2 capture in different carbon materials.
In this work, the CO(2) capture capacity of different types of carbon nanofibers (platelet, fishbone, and ribbon) and amorphous carbon have been measured at 26 °C as at different pressures. The results showed that the more graphitic carbon materials adsorbed less CO(2) than more amorphous materials. Then, the aim was to improve the CO(2) adsorption capacity of the carbon materials by increasing the porosity during the chemical activation process. After chemical activation process, the amorphous carbon and platelet CNFs increased the CO(2) adsorption capacity 1.6 times, whereas fishbone and ribbon CNFs increased their CO(2) adsorption capacity 1.1 and 8.2 times, respectively. This increase of CO(2) adsorption capacity after chemical activation was due to an increase of BET surface area and pore volume in all carbon materials. Finally, the CO(2) adsorption isotherms showed that activated amorphous carbon exhibited the best CO(2) capture capacity with 72.0 wt % of CO(2) at 26 °C and 8 bar.


Biology and potentiality in biological control of Micraspis discolor (Fabricius) (Coleoptera: Coccinellidae).
Hosts influence on growth duration and abundance of coccinellid predators. Micraspis discolor (Fabricius) (Coleoptera: Coccinellidae) has been well known as both carnivorous and pollinivorous. Work was carried out as a series of laboratory-based influence of host species Aphis gossypii (Clover) (Hemiptera: Aphididae) and green rice leafhopper, Nephotettix sp. (Hemiptera: Cicadellidae) on M. discolors development and effect of rice growth stage on M. discolor adult preference. For field study, population of M. discolor was monitored in the rice fields throughout rice growing season for study on the relative abundance between M. discolor and hopper insects in each stage of rice growth. Results demonstrated that Nephotettix sp. was more suitably for larval growth of M. discolor than A. gossypii, with faster development time and higher larval survival. Regardless of host species, 4th larval instars were the most voracious. For feeding preference, results indicated the general preference by M. discolors adult for rice with pollen (reproductive stage) over rice without pollen (vegetative stage). In addition, female coccinellid showed feeding preference on rice pollen more than male. Consistent with the results of rice growth stage preference of adult, highest population abundance of M. discolor was found at reproductive stage of rice growth. All stages of M. discolor inhabited in rice fields, with the dominant group of adults. However, fluctuation pattern of M. discolor population synchronized with hopper insects in rice fields, population abundances of M. discolor did not related to population abundance of hopper insects.


Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract.
Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high-grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Here, we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than intramuscular (IM) delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16(+) cervical cancer (TC-1 luc). We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8(+) T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8(+) T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8(+) T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8(+) T-cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Our results support future clinical translation using cervicovaginal TA-HPV vaccination.


stk: An extendable Python framework for automated molecular and supramolecular structure assembly and discovery.
Computational software workflows are emerging as all-in-one solutions to speed up the discovery of new materials. Many computational approaches require the generation of realistic structural models for property prediction and candidate screening. However, molecular and supramolecular materials represent classes of materials with many potential applications for which there is no go-to database of existing structures or general protocol for generating structures. Here, we report a new version of the supramolecular toolkit, stk, an open-source, extendable, and modular Python framework for general structure generation of (supra)molecular structures. Our construction approach works on arbitrary building blocks and topologies and minimizes the input required from the user, making stk user-friendly and applicable to many material classes. This version of stk includes metal-containing structures and rotaxanes as well as general implementation and interface improvements. Additionally, this version includes built-in tools for exploring chemical space with an evolutionary algorithm and tools for database generation and visualization. The latest version of stk is freely available at github.com/lukasturcani/stk.


Quantum chemistry and experimental studies of hydrothermal destruction of Co-EDTA complexes.
Hydrothermal oxidation, a promising method for removal of cobalt radionuclides from EDTA-containing liquid radioactive waste streams, is in the focus of the present study. It has been demonstrated that Co(III)-EDTA complexes, which are very stable under normal conditions, undergo oxidation as a result of the electron transfer from the EDTA carboxyl group to Co(III) ions under elevated temperature. The electron transfer reaction follows the first-order rate law with an activation energy of 91.8 kJ/mol at рH 12 and time of Co(III) ions half-conversion of 0.2 s at 200 °C. The rate of EDTA oxidation is proportional to the concentration of Co(III) ions and solution pH. Based on quantum chemistry simulations, possible intermediate structures formed upon the electron transfer from EDTA to Co(III) ions have been suggested. It has been shown that the introduction of hydrogen peroxide provides a continuous generation of Co(III) ions and a sequential decarboxylation of the EDTA until complete degradation of the chelate structure. The pathways of cobalt immobilization have been clarified.


Implementation of an Intrahospital Transport Checklist for Emergency Department Admissions to Intensive Care.
Intrahospital transports (IHTs) are high-risk activities with the potential for adverse outcomes. Suboptimal care of a patient in our emergency department (ED) needing IHT to the pediatric intensive care unit (ICU) identified improvement opportunities. We describe implementing a novel checklist (Briefing ED-to-ICU Transport To Exit Ready: BETTER) for improving the IHT safety of pediatric ED patients admitted to the pediatric ICU. A multidisciplinary team used the Model for Improvement to create a key driver diagram and process map. An evidence-based IHT checklist was implemented on July 23, 2019 after multiple plan-do-study-act checklist revisions. The specific aim was a ≥80% checklist completion rate for 6 months and maintaining that rate for 6 months. An anonymous, voluntary survey of ED nurses and physicians, 9 months postimplementation, evaluated perceived improvements in IHT safety. The outcome measure was the proportion of IHT-related incident reports, per ED-to-pediatric ICU admission, comparing baseline (2-year preimplementation) and intervention (1-year postimplementation) periods. Balancing measures included a quantitative assessment for any throughput measure delays and a survey question on perceived delays. From July 23, 2019 to July 22, 2020, 335 (84%) of 400 ED-to-ICU admissions had completed IHT checklists. Ninety percent of survey respondents (84% response rate) agreed that the checklist improved IHT safety. The incident report rate was lower in the intervention period (0.5% versus 2.3%; P = 0.03), with special cause improvement on T-chart analysis. Balancing measures did not indicate any delays secondary to checklist implementation. This IHT checklist was feasible and associated with improvements in perceived safety and incident event reporting. Further studies are needed to assess generalizability.


Shock waves in high-energy materials: the initial chemical events in nitramine RDX.
We extend the reactive force field ReaxFF to describe the high energy nitramine RDX and use it with molecular dynamics (MD) to study its shock-induced chemistry. We studied shock propagation via nonequilibrium MD simulations at various collision velocities. We find that for high impact velocities (>6 km/s) the RDX molecules decompose and react to form a variety of small molecules in very short time scales (<3 ps). These products are consistent with those found experimentally at longer times. For lower velocities only NO2 is formed, also in agreement with experiments.


Medicine and the arts in the undergraduate medical curriculum at the University of Oslo Faculty of Medicine, Oslo, Norway.
The authors describe a course titled Medicine and the Arts, established in 1996, that is part of the first semester of the undergraduate medical curriculum at the University of Oslo Faculty of Medicine. The course comprises four two-hour seminars on literature, visual arts, architecture, and music. The core objectives of the course are to demonstrate how art can be a source of personal and professional development, and also how art represents a source of insight into patients' experiences and the social, cultural, and historical context of medical practice. The course emphasizes that art is ambiguous and many layered and that its interpretation requires sensitivity, engagement, imagination, and reflection. Fostering these skills is a major aim of the course because these skills are also essential for clinical competence and professional development. The course's seminars are integrated into the curriculum but are not compulsory. Although the topics covered by the course have not been explicitly addressed in the formal examination of students, there has been some discussion about doing so, which would be a signal that those topics are as important as others in the curriculum.


Identification of robust focus measure functions for the automated capturing of focused images from Ziehl-Neelsen stained sputum smear microscopy slide.
Capturing of the best-focused image using focus measure function (FMF) from a stack of images acquired at different focus distances is a crucial step in automatic microscopy development. Detection of bacilli present in Ziehl-Neelsen (ZN) stained sputum smears conventional microscope (CM) images is critical to disease diagnosis. Studies have revealed that the performances of FMFs are sensitive to image contents and background noise. In this article, 24 diverse FMFs were implemented on 31 stacks of CM's field of view images acquired from three different microscopes to determine the best-focused one. Seven FMFs achieved the accuracies of greater than 90%. Accuracy, focus error, and false maxima were calculated for each FMF, and overall score and ranking were also calculated for better interpretation. Preprocessing techniques such as filtering and image distortions (noise, contrast, saturation, illumination, etc.) were performed to evaluate the robustness of every FMF. Gaussian derivative, steerable filters, Tenengrad, and Hemli and Scherer's mean FMFs were identified as the most robust and accurate functions with the accuracy >90%. These FMFs have a relatively less focus error and false maxima rate. Full widths at half maximum of these four FMFs were also computed to determine their efficacy for the optimization process. These four FMFs can be implemented for automated capturing of the image from ZN-stained sputum smear slide. Gaussian derivative FMF can also be used effectively for both CM and fluorescence microscope's field of view image stacks to determine the best-focused one from each stack. © 2017 International Society for Advancement of Cytometry.


Digital Fillet Flaps: A Systematic Review.
Digital fillet flaps have a consistent vascular supply and provide durable soft-tissue coverage. Despite their readily available nature, their use in the foot remains limited. This systematic review was undertaken to determine the size defect that could be covered, the potential postoperative complications, and the durability of a digital fillet flap. Studies were eligible for inclusion if they involved use of the entire digit for soft-tissue coverage of defects of any etiology, reported complications, and had any length of follow-up time. A total of 9 studies met all the inclusion criteria, for a total of 34 patients with a combined mean age of 47.1 years and a combined mean follow-up time of 9.3 months. Complications consisted of continued infection and partial or total necrosis of the flap. Digital fillet flaps were able to cover defects up to a combined mean size of 15.6 cm2. Coverage was found to be best for forefoot ulcerations. The flaps had limited donor site morbidity and provided full coverage of exposed vital and osseous structures that was able to withstand forces applied during weight bearing, The procedure is simple and straightforward, reducing operating time and the need for more complex soft-tissue reconstructive procedures. Therapeutic, Level IV: Systematic review.


Disseminated Histoplasmosis Presenting as Weight Loss and Hypercalcemia in a Renal Transplant Patient With Prior History of Subtotal Parathyroidectomy.
Hypercalcemia and weight loss in a renal transplant patient especially with history of parathyroidectomy raises concern for an underlying malignancy, fungal infections or granulomatous disease. We present a case of 45-year-old male with history of subtotal parathyroidectomy presented with severe persistent hypercalcemia, acute kidney injury (AKI) and significant weight loss. An extensive workup revealed disseminated histoplasmosis. Hypercalcemia (which was refractory to initial medical management) and other symptoms resolved after a few weeks of initiating the antifungal treatment.


[Outcome of surgical treatment for Graves's disease and a correlation between its clinical course and values of TSH receptor antibodies (TRAb)].
Two hundreds and sixteen patients with Graves' disease who underwent subtotal thyroidectomy at Ito Hospital during 1983 and 1984 were studied in order to known about the relationship between the prognosis and preoperative values of TRAb. There were 65 euthyroid patients (30.1%), 112 hypothyroid (51.8%), and 39 hyperthyroid (18.1%). No relationship between postoperative thyroid function and preoperative values of TRAb was observed. Postoperative values of TRAb were significantly higher in hyperthyroid group than in euthyroid group and hypothyroid group at any period. Postoperative values of TRAb were negative in about 90% of the patients of euthyroid group. On the other hand, negative postoperative values of TRAb were also observed in about 40% patients of hyperthyroid group. It is concluded that postoperative thyroid function could not be estimated from preoperative values of TRAb and much care is thought to be necessary to estimate the prognosis from postoperative values of TRAb.


A comparison of low IQ scores from the Reynolds Intellectual Assessment Scales and the Wechsler Adult Intelligence Scale-Third Edition.
Twenty people with suspected intellectual disability took the Reynolds Intellectual Assessment Scales (RIAS; C. R. Reynolds & R. W. Kamphaus, 1998) and the Wechsler Adult Intelligence Scale-3rd Edition (WAIS-III; D. Wechsler, 1997) to see if the 2 IQ tests produced comparable results. A t test showed that the RIAS Composite Intelligence Index scores were significantly higher than WAIS-III Full Scale IQ scores at the alpha level of .01. There was a significant difference between the RIAS Nonverbal Intelligence and WAIS-III Performance Scale, but there was no significant difference between the RIAS Verbal Intelligence Index and the WAIS-III Verbal Scale IQ. The results raise questions concerning test selection for diagnosing intellectual disability and the use of the correlation statistic for comparing intelligence tests.


Process, structural, and outcome quality indicators of nutritional care in nursing homes: a systematic review.
The quality of nursing homes (NHs) has attracted a lot of interest in recent years and is one of the most challenging issues for policy-makers. Nutritional care should be considered an important variable to be measured from the perspective of quality management. The aim of this systematic review is to describe the use of structural, process, and outcome indicators of nutritional care in NHs and the relationship among them. The literature search was carried out in Pubmed, Embase, Scopus, and Web of Science. A temporal filter was applied in order to select papers published in the last 10 years. All types of studies were included, with the exception of reviews, conference proceedings, editorials, and letters to the editor. Papers published in languages other than English, Italian, and Spanish were excluded. From the database search, 1063 potentially relevant studies were obtained. Of these, 19 full-text articles were considered eligible for the final synthesis. Most of the studies adopted an observational cross-sectional design. They generally assessed the quality of nutritional care using several indicators, usually including a mixture of many different structural, process, and outcome indicators. Only one of the 19 studies described the quality of care by comparing the results with the threshold values. Nine papers assessed the relationship between indicators and six of them described some significant associations-in the NHs that have a policy related to nutritional risk assessment or a suitable scale to weigh the residents, the prevalence or risk of malnutrition is lower. Finally, only four papers of these nine included risk adjustment. This could limit the comparability of the results. Our findings show that a consensus must be reached for defining a set of indicators and standards to improve quality in NHs. Establishing the relationship between structural, process, and outcome indicators is a challenge. There are grounds for investigating this theme by means of prospective longitudinal studies that take the risk adjustment into account.


Long-Range Inhibitor-Induced Conformational Regulation of Human IRE1α Endoribonuclease Activity.
Activation of the inositol-requiring enzyme-1 alpha (IRE1α) protein caused by endoplasmic reticulum stress results in the homodimerization of the N-terminal endoplasmic reticulum luminal domains, autophosphorylation of the cytoplasmic kinase domains, and conformational changes to the cytoplasmic endoribonuclease (RNase) domains, which render them functional and can lead to the splicing of X-box binding protein 1 (XBP 1) mRNA. Herein, we report the first crystal structures of the cytoplasmic portion of a human phosphorylated IRE1α dimer in complex with (R)-2-(3,4-dichlorobenzyl)-N-(4-methylbenzyl)-2,7-diazaspiro(4.5)decane-7-carboxamide, a novel, IRE1α-selective kinase inhibitor, and staurosporine, a broad spectrum kinase inhibitor. (R)-2-(3,4-dichlorobenzyl)-N-(4-methylbenzyl)-2,7-diazaspiro(4.5)decane-7-carboxamide inhibits both the kinase and RNase activities of IRE1α. The inhibitor interacts with the catalytic residues Lys599 and Glu612 and displaces the kinase activation loop to the DFG-out conformation. Inactivation of IRE1α RNase activity appears to be caused by a conformational change, whereby the αC helix is displaced, resulting in the rearrangement of the kinase domain-dimer interface and a rotation of the RNase domains away from each other. In contrast, staurosporine binds at the ATP-binding site of IRE1α, resulting in a dimer consistent with RNase active yeast Ire1 dimers. Activation of IRE1α RNase activity appears to be promoted by a network of hydrogen bond interactions between highly conserved residues across the RNase dimer interface that place key catalytic residues poised for reaction. These data implicate that the intermolecular interactions between conserved residues in the RNase domain are required for activity, and that the disruption of these interactions can be achieved pharmacologically by small molecule kinase domain inhibitors.


Coordinate expression of Cdc25B and ER-alpha is frequent in low-grade endometrioid endometrial carcinoma but uncommon in high-grade endometrioid and nonendometrioid carcinomas.
Overexpression of cdc25B, an important cell cycle regulator, has been shown to result in mammary gland hyperplasia in transgenic mice and to increase steroid hormone responsiveness as a direct coactivator of the estrogen receptor (ER). We investigated the potential role of cdc25B in the pathogenesis of endometrial carcinomas in conjunction with ER-alpha. We examined the expression of cdc25B and phosphorylated ER-alpha in 4 archived human specimens of normal endometrium; 7 endometrial hyperplasia with or without atypia; 32 endometrioid endometrial carcinoma (EEC), including 20 low-grade (grade 1) and 12 high-grade (grade 2 or 3) tumors; and 18 endometrial cancers with aggressive histological subtypes (uterine papillary serous carcinoma and clear cell carcinoma, UPSC/CCC) by immunohistochemistry with monoclonal antibodies. Expression of cdc25B and phosphorylated ER-alpha was increased in endometrial hyperplasia and atypical hyperplasia compared with normal secretory endometrium. Ninety percent (18 of 20) of the low-grade EEC expressed cdc25B at a high level, whereas only 42% (5 of 12) of the high-grade EEC did so (chi(2) = 8.7; P < 0.01). Sixty-five percent (13 of 20) of the low-grade EEC expressed phosphorylated ER-alpha at high levels, but only 17% (2 of 12) of high-grade EEC did so (chi(2) = 7.0; P < 0.01). Coordinate high-level expression of phosphorylated ER-alpha and cdc25B occurred in 65% (13 of 20) of low-grade EEC but in only 17% (2 of 12) of the high-grade EEC (chi(2) = 7.0; P < 0.01). In the UPSC/CCC tumors, only 22% (4 of 18) of the tumors expressed phosphorylated ER-alpha at high-levels. However, 83% (15 of 18) of these carcinomas showed high expression of cdc25B (chi(2) = 13.5; P < 0.01). The majority of the UPSC/CCC (15 of 18) did not show coordinate high expression of phosphorylated ER-alpha and cdc25B. Our findings show that in endometrial hyperplasia and low-grade EEC, coordinate increase in cdc25B and phosphorylated ER-alpha occurs. However, in UPSC/CCC, cdc25B is highly expressed without coordinate increase in phosphorylated ER-alpha. Cdc25B may play important roles in the development and progression of EEC and UPSC/CCC by different mechanisms.


Crystal and magnetic structures and physical properties of a new pyroxene NaMnGe2O6 synthesized under high pressure.
A new pyroxene compound, NaMnGe(2)O(6), has been synthesized at 3 GPa and 800 °C and fully characterized by X-ray single-crystal diffraction, neutron powder diffraction, and measurements of magnetization and specific heat. NaMnGe(2)O(6) crystallizes into a monoclinic C2/c structure with unit-cell parameters a = 9.859(2) Å, b = 8.7507(18) Å, c = 5.5724(11) Å, and β = 105.64(3)° at 153 K. A cooperative Jahn-Teller distortion is formed by an ordering of the longest Mn-O bonds between two neighboring octahedra along the chain direction. This feature distinguishes NaMnGe(2)O(6) from other pyroxene compounds without Jahn-Teller active cations and suggests that the Jahn-Teller distortion competes with the intrinsic local distortion in the pyroxene structure. No orbital order-disorder transition has been found up to 750 K. Like other alkali-metal pyroxenes with S > (1)/(2), NaMnGe(2)O(6) (S = 2) was found to undergo a long-range antiferromagnetic (AF) ordering at T(N) = 7 K due to intrachain and interchain exchange interactions. Due to the peculiar structural features and the corresponding magnetic coupling, the weak AF spin ordering gives way to a ferromagnetic-like state at a sufficiently high magnetic field. Specific-heat measurements demonstrated that a large portion of the magnetic entropy, >60%, has been removed above T(N) as a result of strong spin correlations within the quasi-one-dimensional Mn(3+)-spin chains. The Reitveld refinement of neutron powder diffraction data gives a commensurate magnetic structure defined by k = [0 0 0.5] with Mn moments aligned mainly along the c-axis with a small component along both a- and b-axes.


Holographic fabricated photonic-crystal distributed-feedback quantum cascade laser with near-diffraction-limited beam quality.
We demonstrate the fabrication and characterization of photonic-crystal distributed-feedback quantum cascade laser emitting at 4.7 microm. The tilted rectangular-lattice PCDFB structure was defined using a multi-exposure of two-beam holographic lithography. The devices exhibit the near-diffraction-limited beam emission with the full width at half maximum of the far-field divergence angles about 4.5 degrees and 2.5 degrees for stripe widths of 55 microm and 95 microm, respectively. Single-mode emission with a side mode suppression ratio of approximately 20 dB is achieved in the temperature range (80-210 K). The single-facet output power is above 1 W for a 95 microm x 2.5 mm laser bar at 85 K in pulsed operation.


A fuzzy inference-based index for piped water supply service quality in a complex, low-income urban setting.
Sustainable Development Goal (SDG) 6 calls for universal access to safely managed drinking water services. We studied the evolution of the water supply service between January 2017 and December 2021 in the town of Uvira (South Kivu, Democratic Republic of the Congo) where large investments were made to improve the water supply infrastructure during this period, including a new 2,000-m3 tank, 56 community taps and 1,191 private taps. Across 16 geographic clusters in the town, we assessed water service accessibility, water quantity, continuity, and affordability, based on data provided by the construction team and the utility. We combined these dimensions into a single index ranging 0-100% according to rules defined using the fuzzy inference Mamdani method. Our results show that despite substantial increases in accessibility (i.e. proportion of households with a private tap or within 200 m of a community tap), overall service quality remained unsatisfactory, with a maximum index value of 38.1%, and worsened in many parts of the town due to limitations of the water production capacity after major flooding events and persistent electricity supply issues. The estimated amount of water supplied per user per day remained under 20 L during >95% of the observation period, with a decreasing trend. Pumps operated 58% of the time on average and the frequency of days without electricity supply increased over time. Our study highlights the important gap between upgrades in water supply infrastructure and improvements in the quality of service. The analysis of potential future scenarios for Uvira indicates that increasing production capacity is priority to improve overall service quality. Our results demonstrate that meeting SDG6 will be challenging in complex urban settings and will not only require sustained investments in water supply infrastructure but also in systems management and in energy supply.


Sensitivity to musical denotation and connotation in organic patients.
Musical segments convey at least two kinds of meaning: The "real-world" events referred to by lyrics and by occasions of performance constitute musical denotation: the formal expressive patterns suggested by such constituents as pitch, timbre, and intensity constitute musical connotation. To ascertain sensitivity to these musical facets among brain-injured patients, tests assessing appreciation of musical denotation and connotation were administered to unilaterally brain-injured subjects in the United States and Italy. On the musical denotation test, right hemisphere patients excelled on items where knowledge of lyrics was required; in contrast, anterior aphasics surpassed both posterior aphasics and right hemisphere patients on items where acquaintance with lyrics was unnecessary. On the musical connotation test, right hemisphere patients performed relatively better in matching sound patterns to temporally-sequenced designs than to gestalten; these patients also performed better than left hemisphere patients on a number of other dimensions. The relatively high performance of posterior aphasics on the connotation test, along with the lack of correlation between connotative and denotative scores received by aphasic patients, suggest a behavioral and neurological dissociation between the two forms of musical sensitivity.


Plant protein interactomes.
Protein-protein interactions are a critical element of biological systems, and the analysis of interaction partners can provide valuable hints about unknown functions of a protein. In recent years, several large-scale protein interaction studies have begun to unravel the complex networks through which plant proteins exert their functions. Two major classes of experimental approaches are used for protein interaction mapping: analysis of direct interactions using binary methods such as yeast two-hybrid or split ubiquitin, and analysis of protein complexes through affinity purification followed by mass spectrometry. In addition, bioinformatics predictions can suggest interactions that have evaded detection by other methods or those of proteins that have not been investigated. Here we review the major approaches to construct, analyze, use, and carry out quality control on plant protein interactome networks. We present experimental and computational approaches for large-scale mapping, methods for validation or smaller-scale functional studies, important bioinformatics resources, and findings from recently published large-scale plant interactome network maps.


Association between joint hypermobility, scoliosis, and cranial base anomalies in paediatric Osteogenesis imperfecta patients: a retrospective cross-sectional study.
Joint hypermobility is a common clinical characteristic of patients with Osteogenesis imperfecta (OI), a disorder with serious comorbidities of scoliosis and cranial base anomalies. This study aimed at evaluating how prevalent joint hypermobility is in paediatric OI patients, and to find out whether it serves as a potential predictive marker of the different spinal complications; scoliosis and craniovertebral anomalies (basilar impression and basilar invagination). In this cross-sectional one-center study we analysed retrospectively clinical patient records and radiographs of 47 OI patients, aged 1-19 years, some of whom were treated with bisphosphonates. Presence of joint hypermobility, scoliosis, and craniovertebral anomalies was recorded and possible connections between the phenomena were explored with correlation analysis. Joint hypermobility was found in 70% of the patients. Scoliosis and cranial base anomalies had developed in 26%. The presence of spinal complications was independent of the bisphosphonate treatment status and joint hypermobility. Scoliosis and craniovertebral anomalies are strongly associated in paediatric OI patients. Joint hypermobility that is much more common appears, however, to be a poor predictor.


Towards understanding the effect of fibrinogen interactions on fibrin gel structure.
Fibrin gelation involves the enzymatic conversion of the plasma protein fibrinogen to fibrin monomers which then polymerize to form the gel that is a major structural component of a blood clot. Because fibrinogen provides the material from which fibrin is made, it is generally regarded as promoting the gelation process. However, fibrinogen can bind to a site on a fibrin oligomer, preventing another fibrin oligomer from binding there, thus slowing the polymerization process. "Soluble fibrin oligomers," which are mixtures of fibrin and fibrinogen, are found in the blood plasma and serve as biomarkers for various clotting disorders, so understanding the interplay between fibrin and fibrinogen during fibrin polymerization may have medical importance. We present a kinetic gelation model of fibrin polymerization which accounts for the dual and antagonistic roles of fibrinogen. It builds on our earlier model of fibrin polymerization that proposed a novel mechanism for branch formation, which is a necessary component of gelation. This previous model captured salient experimental observations regarding the determinants of the structure of the gel, but did not include fibrinogen binding. Here, we add to that model reactions between fibrinogen and fibrin, so oligomers are now mixtures of fibrin and fibrinogen, and characterizing their dynamics leads to equations of substantially greater complexity than previously. Using a moment generating function approach, we derive a closed system of moment equations and we track their dynamics until the finite time blow-up of specific second moments indicates that a gel has formed. In simulations begun with an initial mixture of fibrin and fibrinogen monomers, a sufficiently high relative concentration of fibrinogen prevents gelation; the critical concentration increases with the branch formation rate. In simulations begun with only fibrinogen monomers that are converted to fibrin at a specified rate, the rates of conversion, fibrinogen binding to oligomers, and branch formation together determine whether a gel forms, how long it takes to form, and the structural properties of the gel that results.


Toxicity of Rhazya stricta to sheep.
The toxicity of Rhazya stricta leaves for Najdi sheep is described in 9 sheep assigned as untreated controls, Rhazya-treated at 0.25 g/kg/d and Rhazya-treated at 1 g/kg/d. The oral use of 1 g/kg/d caused body weight depression, ruminal bloat, diarrhea, dyspnea and weakness of the hind limbs. Enterohepatonephropathy, pulmonary congestion, hemorrhage and emphysema, lymphocytes in vital organs, and congestion of the blood vessels of the heart were associated with increases in serum AST and LDH, in elevated bilirubin and urea concentrations, and decreased total protein, albumin and calcium concentrations, and leucopenia and anemia.


High dose glargine alters the expression profiles of microRNAs in pancreatic cancer cells.
To investigate the effect of high dose glargine on the expression profiles of microRNAs in human pancreatic cancer cells. Real-time polymerase chain reaction array (RT-PCR) was applied to investigate miRNAs differentially expressed in Sw1990 cells treated with or without 100 IU/L glargine. Stem-loop RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-95 on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, apoptosis assay, Matrigel invasion and migration assay in Sw1990 and Panc-1 cells. Nude mice xenograft models with Sw1990 cells were built to investigate pancreatic cancer growth in vivo after transfection by the lentivirus pGLV3-GFP- miR-95. Ten miRNAs were significantly up-regulated and 2 miRNAs down-regulated in glargine treated Sw1990 cells when compared with non-treated cells (2.48-fold changes on average, P < 0.01). miR-95, miR-134 and miR-34c-3p are the top three miRNAs regulated by glargine (3.65-fold, 2.67-fold and 2.60-fold changes respectively, P < 0.01) in Sw1990 cells. Stem-loop RT-PCR confirmed that high dose glargine up-regulated the expression of miR-95 and miR-134 in both Sw1990 and Panc-1 cells. The most obvious change is the apparent increase of miR-95. Forced expression of miR-95 significantly increased cell proliferation (Sw1990: 2.510 ± 0.129 vs 2.305 ± 0.187, P < 0.05; Panc-1: 2.439 ± 0.211 vs 2.264 ± 0.117, P < 0.05), invasion (Sw1990: 67.90 ± 12.33 vs 47.30 ± 5.89, P < 0.01; Panc-1: 37.80 ± 8.93 vs 30.20 ± 5.14, P < 0.01), migration (Sw1990: 101 ± 6.00 vs 51.20 ± 8.34, P < 0.01; Panc-1: 91.80 ± 9.22 vs 81.50 ± 7.47, P < 0.01) and inhibited cell apoptosis (Sw1990: 22.05% ± 1.92% vs 40.32% ± 1.93%, P < 0.05; Panc-1: 20.17% ± 0.85% vs 45.60% ± 1.43%, P < 0.05) when compared with paired negative controls, whereas knockdown of miR-95 obtained the opposite effect. Nude mice xenograft models confirmed that miR-95 promoted the growth of pancreatic cancer in vivo when compared with negative control (tumor volume: 373.82 ± 23.67 mL vs 219.69 ± 17.82 mL, P < 0.05). These observations suggested that modulation of miRNA expression may be an important mechanism underlying the biological effects of glargine.


High-Throughput Fingerprinting of Rhizobial Free Fatty Acids by Chemical Thin-Film Deposition and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry.
Fatty acids (FAs) represent an important class of metabolites, impacting on membrane building blocks and signaling compounds in cellular regulatory networks. In nature, prokaryotes are characterized with the most impressing FA structural diversity and the highest relative content of free fatty acids (FFAs). In this context, nitrogen-fixing bacteria (order Rhizobiales), the symbionts of legumes, are particularly interesting. Indeed, the FA profiles influence the structure of rhizobial nodulation factors, required for successful infection of plant root. Although FA patterns can be assessed by gas chromatography-(GC-) and liquid chromatography-mass spectrometry (LC-MS), sample preparation for these methods is time-consuming and quantification suffers from compromised sensitivity, low stability of derivatives and artifacts. In contrast, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) represents an excellent platform for high-efficient metabolite fingerprinting, also applicable to FFAs. Therefore, here we propose a simple and straightforward protocol for high-throughput relative quantification of FFAs in rhizobia by combination of Langmuir technology and MALDI-TOF-MS featuring a high sensitivity, accuracy and precision of quantification. We describe a step-by-step procedure comprising rhizobia culturing, pre-cleaning, extraction, sample preparation, mass spectrometric analysis, data processing and post-processing. As a case study, a comparison of the FFA metabolomes of two rhizobia species-Rhizobium leguminosarum and Sinorhizobium meliloti, demonstrates the analytical potential of the protocol.


Increased innate and adaptive immune responses in induced sputum of young smokers.
It is known that chronic obstructive pulmonary disease (COPD) development process is imperceptible and can be asymptomatic for 20 or more years. It is of great importance to diagnose early inflammatory changes that can lead to COPD in young asymptomatic cigarette smokers. The aim of our study was to analyze the cell spectrum of induced sputum (IS) of young cigarette smokers, with emphasis on T-regulatory cells. A total of 20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled in the study. After lung function measurements were taken, we performed sputum induction and analyzed sputum cells. We evaluated the cell count of FOXP3-positive, CD4+ and CD8+ T lymphocytes by immunocytochemistry staining, and the cell count of macrophages and neutrophils by May-Grünwald Giemsa staining. Induced sputum of smokers contained a higher absolute amount of macrophages and neutrophils when compared to nonsmokers. FOXP3-positive cells in the sputum of young smokers showed a statistically significant increase when compared to nonsmokers. Induced sputum of COPD patients contained an increased absolute amount of neutrophils and FOXP3-positive Treg cells when compared to nonsmokers. Regression analysis showed that the amount of FOXP-3 positive cells, neutrophils and macrophages in the induced sputum was increasing with the number of pack years. This study demonstrates that young smokers have early inflammatory changes in their airways that not only initiate nonspecific mechanisms recruiting neutrophils, but also involve specific immune mechanisms with recruitment of T regulatory lymphocytes. The lymphocyte response is probably adaptive.


Quantifying the Metabolome of Pseudomonas taiwanensis VLB120: Evaluation of Hot and Cold Combined Quenching/Extraction Approaches.
Absolute quantification of free intracellular metabolites is a valuable tool in both pathway discovery and metabolic engineering. In this study, we conducted a comprehensive examination of different hot and cold combined quenching/extraction approaches to extract and quantify intracellular metabolites of Pseudomonas taiwanensis (P. taiwanensis) VLB120 to provide a useful reference data set of absolute intracellular metabolite concentrations. The suitability of commonly used metabolomics tools including a pressure driven fast filtration system followed by combined quenching/extraction techniques (such as cold methanol/acetonitrile/water, hot water, and boiling ethanol/water, as well as cold ethanol/water) were tested and evaluated for P. taiwanensis VLB120 metabolome analysis. In total 94 out of 107 detected intracellular metabolites were quantified using an isotope-ratio-based approach. The quantified metabolites include amino acids, nucleotides, central carbon metabolism intermediates, redox cofactors, and others. The acquired data demonstrate that the pressure driven fast filtration approach followed by boiling ethanol quenching/extraction is the most adequate technique for P. taiwanensis VLB120 metabolome analysis based on quenching efficiency, extraction yields of metabolites, and experimental reproducibility.


Psychological ill-being experienced by first-time mothers and their partners in pregnancy after abortion: a cohort study.
The psychological effects of abortion have been much discussed lately, with recently published studies indicating that induced abortion (IA) may, contrary to the general consensus, be contributing to psychological symptoms post-abortion. Using a cohort of first-time mothers, we assessed the likelihood of them experiencing psychological ill-being at the midpoint of their pregnancy, depending on their IA history. We also examined the psychological symptoms of their partners, the hypothesis being that ill-being in IA-experienced mothers might reflect onto their partners. Altogether 680 future first-time mothers (9.8% of whom had an IA history) and their partners were selected. Most mothers attended their 16 check-ups at maternity health clinics (MHC), where the family's physical and emotional well-being were checked. Several internationally validated questionnaires, which gauged psychological ill-being, were filled in at the 20th week of pregnancy. There were no significant differences between the study and the control group in terms of psychological ill-being during the pregnancy. The contribution of prior IA to psychological ill-being during the next pregnancy seems to be minimal. The availability of IA procedures, intensive MHC services in Finland, as well as this society's neutral attitude towards IA, may be among the reasons why the results are so positive for mothers who have previously undergone one or more IAs.


Functional and phenotypical studies of the Leu-4 (CD3)+, Leu-1 (CD5)- T lymphocyte.
A small T cell subpopulation expressing the phenotype Leu-5(CD2)+, Leu-4(CD3)+, Leu-1 (CD5)- can be found in peripheral blood and bone marrow of normal individuals. When these cells were sorted out by three colour immunofluorescence cell sorting and tested in limiting dilution assays, they were found to have lower frequencies of proliferating (9.0 +/- 5.6 times, n = 7) and of IL-2 producing cells (11.5 +/- 5.0 times n = 5), and a higher frequency of cytotoxic cells (3.1 +/- 2.6 times, n = 2) than T lymphocytes expressing the three markers. In peripheral blood lymphocytes, 1/3 of the CD3+, CD5- cells were positive for Leu-2a (CD8) while virtually all were negative for Leu-3a (CD4). Four colour flow cytometric analysis revealed a small subset of T cells positive for CD3 and negative for CD5, CD4 and CD8. Approximately 75% of the CD3+, CD5- cells were negative for Leu-7 and CD16 simultaneously. These results shed a light on the phenotype of T cells that escape killing by CD5 and complement in T cell depleted bone marrow and may explain why fewer residual T cells in the depleted marrow are detected by limiting dilution assays than by flow cytometric analysis.


Essential oil from Cymbopogon citratus exhibits "anti-aspergillosis" potential: in-silico molecular docking and in vitro studies.
Aspergillosis, has recently confounded some states of India. Due to major role in fungal cell wall synthesis, in the present study UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase were chosen as an appropriate sites to design drug. The objective of present study was molecular docking of lemon grass essential oil component citral and in vitro validation. GC-FID analysis was used to find out aromatic profile. For docking, Patch-dock analysis was used. Ligand Protein 2D and 3D Interactions were also studied. Drug likeliness, and toxicity profile were also studied. Docking analysis indicated effective binding of citral to UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase. In vitro validation was performed by fungal strain Aspergillus fumigatum. GC-FID profiling revealed the presence of citral as major bioactive compound. Interactions results indicated that, UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase enzymes and citral complexes forms hydrogen and hydrophobic interactions. Citral also depicted drug likeliness by LIPINSKY rule, sufficient level of bioactivity, drug likeliness and toxicity. In vitro results revealed that lemon grass oil was able to inhibit growth of fungal strains toxicity thus signifying its role as potent anti-fungal drug. The online version contains supplementary material available at 10.1186/s42269-022-00711-5.


Therapeutic donor insemination; a review of 440 cases.
Of 399 patients inseminated therapeutically with the semen of a donor, 303 became pregnant, the great majority of them within six months of the time inseminations were begun. The average number of inseminations was 6.2 and the average number of menstrual cycles over which they were carried out was 3.55. The greatest number of pregnancies occurred between the twelfth and the fifteenth day of the menstrual cycle. Seven patients had four pregnancies by this method, 17 had three and 59 had two. Emotional problems related to children of artificial insemination were far fewer than those associated with adoption.


Kleine-Levin syndrome ethiopathogenesis and treatment.
The complex of the symptoms of psychic disorders and of the disorders of sleep, appetite, and food intake often forms the basis of the clinical picture of a mental disease. However, it is only rarely conceived in a complex manner as a set of physiologically interdependent functions. A remarkable proof of the interdependence of these functions is their complex disorder, the Kleine-Levin syndrome. The first descriptions of the symptoms of the Kleine-Levin syndrome can be found in the studies of several authors published as early as at the turn of the century. In 1942, the syndrome was designated by Critchley and Hoffmann after Willi Kleine and Max Levin, who defined it precisely in 1925 and 1929. The syndrome of periodic hypersomnia, megaphagia, and psychic disorders, originally described only in young males, was later found in females as well; the original very strict criteria were gradually broadened and complemented to some extent. At present, the most commonly accepted criterion for the diagnosis of the Kleine-Levin syndrome is the existence of the combined sleep disorder (hypersomnia or insomnia lasting from days to weeks), food intake disorders (megaphagia or anorexia), and various psychic abnormalities accompanying or following the attacks of the affection. We term the syndrome typical if the sleep disorder appears in the form of hypersomnia, food disorder in the form of megaphagia, and if psychic abnormalities are clearly expressed. On the other hand, we term the syndrome atypical if one of the main symptoms is opposite. The incomplete syndrome consists of only two main symptoms. The attacks of the affection set on mostly suddenly, lasting from several days to several weeks, ending suddenly again. The interparoxysmal periods last from several days to several months, sometimes even to several years. The etiopathogenesis of the affection is still unknown. A number of reports indicate a disorder of the diencephalon, perhaps only of the hypothalamus. The pathological-anatomical findings following the death of persons suffering from the disorders of sleep and food intake and from psychic abnormalities mostly reveal lesions in the region of the third brain ventricle. The development of the typical syndrome is benign, however, and morphological studies are not available. The typical Kleine-Levin syndrome can hardly escape the attention of clinicians owing to the richness and clarity of symptoms. The atypical or discretely expressed forms, however, often remain unrecognized even after a detailed medical examination and may lead to diagnostic uncertainty.(ABSTRACT TRUNCATED AT 400 WORDS)


A High Strength Self-Healable Antibacterial and Anti-Inflammatory Supramolecular Polymer Hydrogel.
There is a significant cost to mitigate the infection and inflammation associated with the implantable medical devices. The development of effective antibacterial and anti-inflammatory biomaterials with novel mechanism of action has become an urgent task. In this study, a supramolecular polymer hydrogel is synthesized by the copolymerization of N-acryloyl glycinamide and 1-vinyl-1,2,4-triazole in the absence of any chemical crosslinker. The hydrogel network is crosslinked through the hydrogen bond interactions between dual amide motifs in the side chain of N-acryloyl glycinamide. The prepared hydrogels demonstrate excellent mechanical properties-high tensile strength (≈1.2 MPa), large stretchability (≈1300%), and outstanding compressive strength (≈11 MPa) at swelling equilibrium state. A simulation study elaborates the changes of hydrogen bond interactions when 1-vinyl-1,2,4-triazole is introduced into the gel network. It is demonstrated that the introduction of 1-vinyl-1,2,4-triazole endowes the supramolecular hydrogels with self-repairability, thermoplasticity, and reprocessability over a lower temperature range for 3D printing of different shapes and patterns under simplified thermomelting extrusion condition. In addition, these hydrogels exhibit antimicrobial and anti-inflammatory activities, and in vitro cytotoxicity assay and histological staining following in vivo implantation confirm the biocompatibility of the hydrogel. These hydrogels with integrated multifunctions hold promising potential as an injectable biomaterial for treating degenerated soft supporting tissues.


A serine phosphatase is involved in CD2-mediated activation of human T lymphocytes and natural killer cells.
We investigated early activation events after T cell triggering via the Ag receptor (TCR/CD3) complex as compared to activation via the CD2 surface molecule. To this end, resting peripheral human T lymphocytes were preincubated with 32P-orthophosphate and subsequently exposed to mitogenic mAb directed at either TCR/CD3 or CD2 for varying time periods. Cells were lysed and postnuclear lysates subjected to two-dimensional-gel electrophoresis (IEF and SDS-PAGE). As early as 10 min after stimulation through CD2, dephosphorylation of a cytosolic 19-kDa protein was observed. In contrast, this protein remained phosphorylated in unstimulated as well as CD3 activated T cells. Phosphoprotein (pp) 19 dephosphorylation was transient because, at later time points (2-4 h) after CD2 triggering, this protein was phosphorylated again. Phosphoaminoacid analysis indicated that pp19 is dephosphorylated on serine residues. Identical results were obtained using a CD2+ but TCR/CD3- human NK cell clone indicating that pp19 dephosphorylation occurs independent of surface expression of a TCR/CD3 complex. These data show that, in addition to protein phosphorylation events, serine dephosphorylation is involved in T cell triggering. More important, a selective signaling mechanism appears to be linked to T cell activation through the CD2 pathway.


Sustained production of spliced X-box binding protein 1 (XBP1) induces pancreatic beta cell dysfunction and apoptosis.
Pro-inflammatory cytokines involved in the pathogenesis of type 1 diabetes deplete endoplasmic reticulum (ER) Ca2+ stores, leading to ER-stress and beta cell apoptosis. However, the cytokine-induced ER-stress response in beta cells is atypical and characterised by induction of the pro-apoptotic PKR-like ER kinase (PERK)-C/EBP homologous protein (CHOP) branch of the unfolded protein response, but defective X-box binding protein 1 (XBP1) splicing and activating transcription factor 6 activation. The purpose of this study was to overexpress spliced/active Xbp1 (XBP1s) to increase beta cell resistance to cytokine-induced ER-stress and apoptosis. Xbp1s was overexpressed using adenoviruses and knocked down using small interference RNA in rat islet cells. In selected experiments, Xbp1 was also knocked down in FACS-purified rat beta cells and rat fibroblasts. Expression and production of XBP1s and key downstream genes and proteins was measured and beta cell function and viability were evaluated. Adenoviral-mediated overproduction of Xbp1s resulted in increased XBP1 activity and induction of several XBP1s target genes. Surprisingly, XBP1s overexpression impaired glucose-stimulated insulin secretion and increased beta cell apoptosis, whereas it protected fibroblasts against cell death induced by ER-stress. mRNA expression of Pdx1 and Mafa was inhibited in cells overproducing XBP1s, leading to decreased insulin expression. XBP1s knockdown partially restored cytokine/ER-stress-driven insulin and Pdx1 inhibition but had no effect on cytokine-induced ER-stress and apoptosis. XBP1 has a distinct inhibitory role in beta cell as compared with other cell types. Prolonged XBP1s production hampers beta cell function via inhibition of insulin, Pdx1 and Mafa expression, eventually leading to beta cell apoptosis.


Optimized development of sebaceous fingermarks on nonporous substrates with conformal columnar thin films.
A form of physical vapor deposition, called the conformal-evaporated-film-by-rotation (CEFR) method, was optimized for the conformal deposition of columnar thin films (CTFs) on sebaceous fingermarks. Relying on the surface topology of the fingermark, the CTF development technique is different from traditional development techniques. After the optimization of the development conditions, the CTF development technique was found to be superior to traditional development methods on several nonporous substrates: the smooth side of Scotch(®) Multitask, Gorilla(®) , and Scotch(®) Duct tapes; clear and black soft plastics; stained and sealed walnut and cherry woods; partial bloody fingermarks on stainless steel; and discharged cartridge casings. It was equally as good as other development techniques on other substrates, but worse on a few. The optimization study is expected to assist in designing a mobile CEFR apparatus capable of on-scene development of fingermarks.


Development of an atomic-force-microscope-based hanging-fiber rheometer for interfacial microrheology.
A new interfacial microrheology technique using atomic force microscope (AFM) as a force sensor is developed. The probe used for microrheology contains a long vertical glass fiber with one end glued onto a rectangular shaped cantilever beam and the other end immersed through a water-air interface. The motion of the modified cantilever can be accurately described by the Langevin equation for a damped harmonic oscillator, from which we obtain the friction coefficient xi of the glass fiber in contact with the water. It is found that xi contains two contributions. One is generated by the bulk fluid, which increases with the immersion length of the glass fiber. The other contribution comes from the contact line between the water-air interface and the glass fiber, which is obtained by an extrapolation of the measured xi at the limit of zero immersion length. The experiment thus demonstrates an application of AFM in the studies of interfacial microrheology and contact line dynamics.


A Case of Artificial Snow Foam induced Corneal Endotheliitis Followed up by Scheimpflug Densitometry.
The aim was to present a rare case of artificial snow foam induced corneal endotheliitis followed up by Scheimpflug Densitometry. A 15-year-old male complained of redness, tearing and reduced vision in the left eye after artificial snow foam entered his left eye 4 days before the presentation. Slit lamp examination of the same eye showed ciliary injection with corneal edema with no epithelial defect and endothelial lesion measuring 3 × 4 millimeters (mm) with large keratic precipitates (KP). Examining the left eye by the Scheimpflug densitometry of the Sirius device (CSO, Florence, Italy) showed plaque on the back of the cornea. Aqueous tab Polymerase chain reaction analysis (PCR) results for the affected eye had negative results for viral infection. Improvement of ocular symptoms occurred after treatment with topical steroid therapy. Scheimpflug densitometry showed disappearance of the saw-tooth protrusions on the back of the cornea with decreased reflectivity. Corneal endotheliitis can be triggered by chemical ocular trauma. The Scheimpflug densitometry examination may be a useful noninvasive method for reaching a clinical diagnosis of corneal endotheliitis and monitoring treatment effectiveness.


Factors affecting well-being in adults recently diagnosed with rheumatoid arthritis.
This article examines role stress, key psychosocial variables, and well-being in adults recently diagnosed with rheumatoid arthritis. Patients recently diagnosed with rheumatoid arthritis must often learn to balance disease and role-related responsibilities. This was cross-sectional, descriptive study ( N = 80). Data were analyzed using correlation coefficients and linear regression models. Participants were predominantly female (78%), married, and employed. Mean age and disease duration were 54.2 years and 24.2 months, respectively. The findings suggest that well-being is influenced by feelings of being self-efficacious and having balance in their roles and less to do with social support received from others.


Comparative analysis of DNA ploidy and proliferative index in fine needle aspirates of non-Hodgkin's lymphomas by image analysis and flow cytometry.
To determine the application of image analysis (IA) to fine needle aspiration (FNA) of non-Hodgkin's lymphomas, 78 cases, categorized according to the Working Formulation, were analyzed and compared with those analyzed by flow cytometry (FCM). Aspirated material was immediately fixed in either IA fixative (31 cases) or acetone, stored at -70 degrees C (47 cases) for periods up to 48 months and postfixed in IA fixative. IA assessed DNA index (DI), ploidy balance, degree of hyperdiploidy and proliferation index (PI). DNA index, % S + G2M and RNA index were obtained by acridine orange FCM. There were no significant differences in measured variables between fresh and stored cases. Statistically significant differences between low, intermediate and high grade lymphomas were present in all evaluated variables except DNA ploidy (DI) (P = .074) measured by IA. DI, however, showed a very high correlation with the DI obtained by FCM (r = .94). PIs, although generally lower, also had a high correlation with S + G2M (r = .85). We conclude that results obtained by IA were comparable to results by FCM and that frozen material can be used to retrospectively evaluate ploidy and proliferation. IA is especially suitable for the evaluation of low-volume specimens obtained by FNA.