Zika Virus Is Not Uniquely Stable at Physiological Temperatures Compared to Other Flaviviruses.
Zika virus (ZIKV) is a flavivirus that has emerged as a global health threat due in part to its association with congenital abnormalities. Other globally relevant flaviviruses include dengue virus (DENV) and West Nile virus (WNV). High-resolution structures of ZIKV reveal many similarities to DENV and suggest some differences, including an extended glycan loop (D. Sirohi, Z. Chen, L. Sun, T. Klose, T. C. Pierson, et al., 352:467-470, 2016, http://dx.doi.org/10.1126/science.aaf5316) and unique interactions among envelope (E) protein residues that were proposed to confer increased virion stability and contribute mechanistically to the distinctive pathobiology of ZIKV (V. A. Kostyuchenko, E. X. Lim, S. Zhang, G. Fibriansah, T. S. Ng, et al., Nature 533:425-428, 2016, http://dx.doi.org/10.1038/nature17994). However, in the latter study, virus stability was inferred by measuring the loss of infectivity following a short incubation period. Here, we rigorously assessed the relative stability of ZIKV, DENV, and WNV by measuring changes in infectivity following prolonged incubation at physiological temperatures. At 37°C, the half-life of ZIKV was approximately twice as long as the half-life of DENV (11.8 and 5.2 h, respectively) but shorter than that of WNV (17.7 h). Incubation at 40°C accelerated the loss of ZIKV infectivity. Increasing virion maturation efficiency modestly increased ZIKV stability, as observed previously with WNV and DENV. Finally, mutations at E residues predicted to confer increased stability to ZIKV did not affect virion half-life. Our results demonstrate that ZIKV is not uniquely stable relative to other flaviviruses, suggesting that its unique pathobiology is explained by an alternative mechanism. Zika virus (ZIKV) belongs to the Flavivirus genus, which includes other clinically relevant mosquito-borne pathogens such as dengue virus (DENV) and West Nile virus (WNV). Historically, ZIKV infection was characterized by a self-limiting, mild disease, but recent outbreaks have been associated with severe clinical complications, including Guillain-Barré syndrome and microcephaly, which are atypical of other flavivirus infections. Moreover, ZIKV has been detected in saliva, urine, and semen, and it may be sexually transmitted. Analysis of a high-resolution cryo-electron microscopic reconstruction of ZIKV hypothesized that the unusual stability of this virus contributes to its distinctive pathobiology. Here, we directly compared the stability of ZIKV to that of other flaviviruses following prolonged incubation in solution at physiological temperatures. We found that the stability of multiple ZIKV strains, including those from recent outbreaks, is intermediate between that of DENV and WNV, suggesting an alternative explanation for the unique clinical manifestations of ZIKV infection.


Glucosylated pH-sensitive liposomes as potential drug delivery systems.
The inclusion of pH-sensitive components in liposome formulations can allow a more controlled and efficient release in response to low pH typical of some pathological tissues and/or subcellular compartments. On the other hand decorating the surface of liposomes with sugar moieties attributes to lipid vesicles specificity toward lectins, sugar-binding proteins overexpressed in many tumor tissues. A novel multifunctional pH-sensitive glucosylated amphiphile was synthesized and characterized as pure aggregate component and in mixtures with a natural phospholipid. The comparison of the properties of the new glucosylated amphiphile with respect to those of a previously described cationic structural analogue demonstrates that the pH-sensitivity can strongly affect drug release, lipid organization, as well as the exposure of the glucose residues on liposome surface and their ability to interact with Concanavalin A, a plant lectin used as model system.


Ancient, recurrent phage attacks and recombination shaped dynamic sequence-variable mosaics at the root of phytoplasma genome evolution.
Mobile genetic elements have impacted biological evolution across all studied organisms, but evidence for a role in evolutionary emergence of an entire phylogenetic clade has not been forthcoming. We suggest that mobile element predation played a formative role in emergence of the phytoplasma clade. Phytoplasmas are cell wall-less bacteria that cause numerous diseases in plants. Phylogenetic analyses indicate that these transkingdom parasites descended from Gram-positive walled bacteria, but events giving rise to the first phytoplasma have remained unknown. Previously we discovered a unique feature of phytoplasmal genome architecture, genes clustered in sequence-variable mosaics (SVMs), and suggested that such structures formed through recurrent, targeted attacks by mobile elements. In the present study, we discovered that cryptic prophage remnants, originating from phages in the order Caudovirales, formed SVMs and comprised exceptionally large percentages of the chromosomes of 'Candidatus Phytoplasma asteris'-related strains OYM and AYWB, occupying nearly all major nonsyntenic sections, and accounting for most of the size difference between the two genomes. The clustered phage remnants formed genomic islands exhibiting distinct DNA physical signatures, such as dinucleotide relative abundance and codon position GC values. Phytoplasma strain-specific genes identified as phage morons were located in hypervariable regions within individual SVMs, indicating that prophage remnants played important roles in generating phytoplasma genetic diversity. Because no SVM-like structures could be identified in genomes of ancestral relatives including Acholeplasma spp., we hypothesize that ancient phage attacks leading to SVM formation occurred after divergence of phytoplasmas from acholeplasmas, triggering evolution of the phytoplasma clade.


Is frequent attendance in primary care disease-specific?
Sociodemographic characteristics of frequent attenders in general practice are known. It is not known whether frequent attendance is linked to specific diseases. To investigate whether frequent consultation in primary care is related to specific morbidities and whether this relationship is influenced by the general practice which the patient attends. One-year survey of consultation data. Nine general practices in North Staffordshire, UK. 1000 adults aged 18 years and over who had consulted primary care at least once during the study year were randomly selected from each practice and grouped into frequent (high and very high), medium and low frequency consulters. Type of morbidity coded at each consultation and number of repeat consultations for each morbidity (based on Read Code Chapters). All morbidity Chapters were associated with frequent consultation. Frequent consultation was also associated with repeated consultation within most morbidities. Stronger associations were seen with mental disorders, blood disorders, circulatory disorders, digestive disorders, endocrine diseases and with causes of injury and poisoning. Some variation between practices in the morbidities associated with frequent consultation were apparent; particularly for skin diseases and unspecified conditions. Frequent consulters in primary care are not restricted to particular groups of morbidities. There is some aspect of frequent consultation that is a characteristic of individuals regardless of the symptoms with which they consult. Some morbidities are more prominent than others in this group of consulters, and this may help guide practice policies and future research into frequent consulters.


DIAGNOSIS AND TREATMENT OF PATIENTS WITH SINONASAL INVERTED PAPILLOMA.
The frequency of occurrence of inverted papilloma (IP) ranges from 0.4% to 7% of all neoplasms of the nasal cavity and paranasal sinuses. Inverted papilloma is a benign epithelial tumor that refers to Schneider's sinonasal papilloma. IP is usually diagnosed in the late stages in average, 1-4 years after the first appearance of sinonasal symptoms. The purpose of this study - to summarize the results of diagnosis and treatment of patients with sinonasal inverted papilloma, who underwent surgical treatment in our department. We evaluated 37 patients with histologically verified sinonasal IP from 2015 to 2019. 29 were men (78,4%), and 8 women (21,6%). Along with generally accepted clinical studies, all patients underwent CT and MRI of the paranasal sinuses. Using the results of CT and MRI images, all patients were classified according to the Krouse classification. We evaluated the postoperative period, the presence of complications. The main criteria for assessing the results of treatment were indicators of continued growth and recurrence of IP. Endonasal endoscopic approach was used in the surgical treatment of patients. IP occurred more common in the maxillary sinus - in 16 (43.2%) patients and in the ethmoid - in 15 (40.5%). In the frontal sinus or frontoethmoidal recess - in 5 (13.5%) of the examined patients. In one case (2.7%), the inverted papilloma originated from the sphenoid sinus. Based on the Krouse classification of IP, the following results were obtained: T1 stage was detected in 5 (13.5%) patients, T2 in 22 (59.5%), T3 in 7 (18.9%), T4 - in 3 (8.1%) examined patients. We have used endoscopic endonasal approach in its various options for the treatment of patients. Based on postoperative CT and MRI scans, continued growth was determined in 3 (8.1%) patients, while the average term for detecting was 4 months. IP recurrence was diagnosed in 7 (18.9%) patients, with an average time of recurrence 14 months. CT and MRI are mandatory examination methods in patients with inverted papilloma. Inverted papilloma most common was diagnosed at T2-T3 stages and found in the maxillary and ethmoid sinus. Recurrence of IP was diagnosed in 7 (18.9%) patients, with an average recurrent rate in 14 months. Surgical treatment with removal area of hyperostosis and laser destruction surrounding tissues is the method of choice.


Hepatic ENPP1 expression is induced in diabetic rabbits.
The ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an inhibitor of the insulin receptor. Variants of ENPP1 are associated with infantile arterial calcification, obesity, and insulin resistance. To study the functional relevance of this protein in vivo, we cloned rabbit ENPP1 and studied its regulation in experimentally induced diabetes mellitus. We amplified and sequenced the complete coding sequence of rabbit ENPP1 gene out of a liver cDNA library using redundant primers deduced from other species. Next, we performed quantitative PCR of ENPP1 to study the tissue distribution of ENPP1 expression and its regulation in an alloxan-dependent diabetes model. The putative rabbit ENPP1 protein contains 873 amino acids and is highly conserved when compared with human ENPP1 (90% amino acid identity). Particularly high levels of ENPP1 mRNA expression were found in adipose tissue. Quantitative PCR analysis revealed a significant upregulation of ENPP1 transcription in liver (p = 0.025) and brain (p = 0.034) of diabetic rabbits compared with controls. Hepatic ENPP1 expression is induced in diabetic rabbits when compared with controls. This approximately twofold upregulation of ENPP1 mRNA in rabbit liver parallels previous findings in patients with type 2 diabetes mellitus. We provide further molecular information about ENPP1 as a potential pharmacologic target and characterize its regulation in an insulin-dependent diabetes mellitus animal model.


Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.
The fidelity of intracellular signaling hinges on the organization of dynamic activity architectures. Spatial compartmentation was first proposed over 30 years ago to explain how diverse G protein-coupled receptors achieve specificity despite converging on a ubiquitous messenger, cyclic adenosine monophosphate (cAMP). However, the mechanisms responsible for spatially constraining this diffusible messenger remain elusive. Here, we reveal that the type I regulatory subunit of cAMP-dependent protein kinase (PKA), RIα, undergoes liquid-liquid phase separation (LLPS) as a function of cAMP signaling to form biomolecular condensates enriched in cAMP and PKA activity, critical for effective cAMP compartmentation. We further show that a PKA fusion oncoprotein associated with an atypical liver cancer potently blocks RIα LLPS and induces aberrant cAMP signaling. Loss of RIα LLPS in normal cells increases cell proliferation and induces cell transformation. Our work reveals LLPS as a principal organizer of signaling compartments and highlights the pathological consequences of dysregulating this activity architecture.


Influence of a neoglycolipid and its PEO-lipid moiety on the organization of phospholipid monolayers.
The surface properties of the neoglycolipid (GlcNAcE(3)G(28)) and of its PEO-lipid (E(3)G(28)) moiety mixed with phospholipids (dipalmitoylphosphatidylcholine, DPPC; distearoylphosphatidylcholine, DSPC; diarachidoylphosphatidylcholine, DAPC; and dibehenoylphosphatidylcholine, DBPC) were studied in Langmuir monolayers at various mixture compositions and surface pressures. The pi-A isotherms of the pure compounds revealed that because of the presence of the sugar group in its molecule, GlcNAcE(3)G(28) collapsed at a higher surface pressure and occupied a larger molecular area than the PEO-lipid moiety. It was also observed that the presence of the PEO-lipid (E(3)G(28)) in the mixtures triggered a strong alteration of both phospholipid pi-A isotherm profiles and surface diffraction spectra, an indication that the disordering of the initially structured phospholipid monolayers took place. Unlike E(3)G(28), GlcNAcE(3)G(28) did not disorganize phospholipid monolayers but generated a partial segregation of the film-forming components. The calculated excess free energies of mixing (DeltaG(exc)) for GlcNAcE(3)G(28)-phospholipid mixtures enabled us to predict the stability of such systems.


17 beta-estradiol induces somatostatin (SRIF) inhibition of prolactin release and regulates SRIF receptors in rat anterior pituitary cells.
The role of 17 beta-estradiol (E2) in the induction of an inhibitory effect of somatostatin (SRIF) on PRL release and in the regulation of SRIF receptors was analyzed in rat anterior pituitary cells. SRIF exerts a moderate inhibitory effect on basal PRL release from cultured pituitary cells prepared from normal rats. The inhibitory effect of SRIF was weakened when the cells were prepared from castrated rats, but was strengthened in cells from E2-treated rats. When cells from ovariectomized rats were cultured with charcoal-treated sera in the absence of E2, SRIF affected neither basal PRL release nor the increased PRL release elicited by TRH, (Bu)2cAMP, or vasoactive intestinal peptide. However, in cells cultured with E2 (10(-9) M) for more than 12 h, SRIF decreased basal as well as secretagogue-stimulated PRL release. Enhancement of both the sensitivity and magnitude of the inhibitory effect of SRIF appeared dependent upon the length of the preincubation and the E2 concentration. On the other hand, an inhibitory effect of SRIF on GH release was unaffected by castration, E2 administration in vivo, or E2 treatment in vitro. Dihydrotestosterone (10(-6) M) produced an effect similar to that of E2, but other steroids tested did not. Binding studies demonstrated that the specific binding of [125I-Tyr11]SRIF was saturable, with a Kd of 99 pM and a maximum binding capacity of 89.4 fmol/mg protein in pituitary membranes from control rats, and a Kd of 45 pM and a maximum binding capacity of 305.2 fmol/mg protein in membranes from rats primed with E2 for 4 weeks. Apparent Ki values for native SRIF in both membranes were similar. Treatment of pituitary cells with E2 for 8 days in vitro in culture produced a 2-fold increase in the number of binding sites. These results demonstrate that E2 acts on mammotrophs at the pituitary level, rendering them sensitive to SRIF, probably by increasing the number of SRIF receptor sites.


Risk factors associated with bovine tuberculosis and molecular characterization of Mycobacterium bovis strains in urban settings in Niger.
A retrospective and a longitudinal survey were carried out at the abattoir of Niamey. Results showed a highly significant difference in suspected tuberculosis (TB) gross lesions among different animal species (P < 0.0001). The proportion of carcasses with TB-like lesions was 0.19% among cattle, 0.11% among camels, 0.001% among sheep and 0.0006% among goats. In cattle, cows are significantly more affected than the other categories (P < 0.001). Also in cattle, TB-like lesions are mostly localized in the lungs (92.77%) followed by the lymph nodes (50.87%) and the liver (32.40%). The prevalence of gross lesions compatible with bovine TB (BTB) is strongly influenced by the season (P < 0.0001), is closely correlated with the origin of the animals (P < 0.001) and has a negative impact on the weight of affected animals (P < 0.0001). Sixty-two samples of suspected TB gross lesions were subject to microbiological analysis and molecular typing of strains. Mycobacterium bovis was identified in 18 animals showing five different spoligotypes, belonging to type 'African 1' previously identified in Central and West Africa. In addition, a profile (SB1982) not previously reported distinguished by the absence of spacers 3, 4, 9, 16, 22, 30 and 39-43 has been characterized in this study. To assess risk factors for BTB transmission, a questionnaire on animal husbandry practices, food habits, and clinical signs of TB in animals and humans was submitted to the heads of 1131 randomly selected households. The main risk factors identified are consumption of unpasteurized milk (91%) and lack of hygiene within households (32-74%). Clinical signs that could be attributed to TB were also reported both in humans and in animals of the households.


Interstitial Granulomatous Drug Reaction: A Case Report.
Interstitial granulomatous drug reaction (IGDR) is a rare inflammatory reaction of the skin with an unknown etiology. Here, we report the case of a 55-year-old female with a history of diabetes mellitus and hypertension who presented with an asymptomatic persistent skin lesion over the left breast for more than one year. Skin examination revealed a single non-scaly, sharply demarcated, erythematous annular patch. Skin biopsy showed epidermal atrophy and histiocytic infiltrate throughout the entire dermis, both interstitial and perivascular. The patient was diagnosed with IGDR. We decided not to change her medications because her chronic diseases were well-controlled on these medications; her skin lesion was asymptomatic, very mild, and localized to a small body area; and, lastly, IGDR is not associated with any complications in the future.


Effects of Tyr-MIF's family of peptides on immobilization stress-induced antinociception in rats.
The Tyr-MIF-1 family of peptides includes MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1, which have been isolated from bovine hypothalamus and cortex of human brain. Data in the literature suggest that peptides of Tyr-MIF-1's family have opioid-like and anti-opioid actions. All these peptides interact with opioid receptors and in addition bind to non-opiate sites specific for each of the peptides and able to inhibit the expression of some forms of stress-induced analgesia (SIA) in various species. To examined the effects of the Tyr-MIF-1's peptides on immobilization stress-induced antinociception. Tyr-MIF-1's peptides were given to male Wistar rats intraperitoneally before or after 1 hour of restraint. The changes in the mechanical nociceptive threshold of the animals were measured by the Randall-Selitto paw pressure test. Immobilization of the rats increased the pain threshold at least 1 h. Tyr-MIF-1's peptides have contrasting effects on immobilization stress-induced antinociception in paw-pressure test in rats. When administered before immobilization procedure they potentiated the immobilization stress-induced antinociception, while if given after immobilization, they reduced it. Antinociceptive effects of Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1 were reduced in condition of stress. Tyr-MIF-1's peptides exerted antiopioide effects under condition of stress in paw-pressure test. These antiopioide effects were more pronounced when peptides were injected after stress exposure.


Analytical solution of the correlation transport equation with static background: beyond diffuse correlation spectroscopy.
The correlation transport equation (CTE) is the natural generalization of the theory for diffusion correlation spectroscopy and represents a more precise model when dealing with measurements of particle movement in fluids or red blood cell flow in biological tissues. Unfortunately, the CTE is not methodically used due to the complexity of finding solutions. It is shown that actually a very simple modification of the theory/software for the solution of the radiative transport equation allows one to obtain exact solutions of the CTE. The presence of a static background is also taken into account and its influence on the CTE solutions is discussed. The proposed approach permits one to easily work beyond the diffusion regime and potentially for any optical and/or physiological value. The validity of the approach is demonstrated by using "gold standard" Monte Carlo simulations.


Identification of nanopeptide from HTLV-III, ARV-2 and LAVBRU envelope gp120 determining binding to T4 cell surface protein.
The information contained in the primary structure of HIV envelope gp120 determining its biological activity, was analyzed by the use of the informational spectrum method. The parameter determining the interaction between gp120 and T4 cell-surface protein was defined. On the basis of this data in the conserved region of gp120 from HTLV-III, LAVBRU and ARV-2, a nanopeptide NAKTIIVQL was identified as a potential binding domain which could be used as a component of an effective therapeutic agent or as a vaccine component.


Testosterone/Epitestosterone Ratios-Further Hints to Explain Hyperandrogenemia in Children with Autism.
Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as inhibition of epitestosterone on androgen activity was postulated. As in autism, a higher androgen activity was implied. We, therefore, suggested higher levels of T/E ratios of children with autism versus children with typical development. Urine probes of 22 girls with autism (BMI 18.7 ± 4.3; average age 12.3 ± 3.8 years) and a sample of 51 controls (BMI 17.0 ± 2.6; average age 11.9 ± 4 years), as well as 61 boys with autism (BMI 17.04 ± 2. average age 11.9 ± 2.5 years) and 61 control boys (BMI 17.0 ± 2.6; average age 11.1 ± 3.0 years), were analyzed with gas chromatography mass spectrometry. The average T/E ratio of all boys with autism was 2.5 ± 1.8 versus 2.4 ± 1.3 in boys with typical development, respectively. No significant difference between boys with autism versus boys with typical development could be detected (p = 0.977). In girls with autism, the average T/E ratio was 1.4 ± 0.9 versus 2.0 ± 1.4 in girls with typical development, whereby a significant difference could be detected (p = 0.0285). Further, polynomial analysis of the third degree were conducted, showing a dependence from age with reasonable coefficients of determination (0.075 < R2 < 0.22, all samples). As encompassing steroid hormone analysis are expensive and work-intensive, we hoped to find an easily applicable biomarker to support diagnostics in autism. However, as a relatively small sample of only 22 girls with autism were analyzed and menstrual cycle and pubertal status were only partly controllable through the matching of BMI and age, the question arises if it was an incidental finding. Nevertheless, one suggestion might be that epitestosterone has the effect of a competitive inhibition on the androgen receptor, which would probably help to explain the higher prevalence of autism in boys as compared to girls. Presumably, as no significant difference was detected in boys, this effect might not be as relevant from a steroid hormone perspective, and other effects such as altered 17/20-hydroxylase activity as previously shown in boys and girls with autism seem to have more relevance. Analysis of larger samples, including plenty of metabolites and enzymatic cascades, as well as the role of backdoor pathway activity of androgen synthesis of girls with autism, are demanded in order to validate current findings of altered steroid hormones in autism.


Effective One-Dimensional Coupling in the Highly Frustrated Square-Lattice Itinerant Magnet CaCo_{2-y}As_{2}.
Inelastic neutron scattering measurements on the itinerant antiferromagnet CaCo_{2-y}As_{2} at a temperature of 8 K reveal two orthogonal planes of scattering perpendicular to the Co square lattice in reciprocal space, demonstrating the presence of effective one-dimensional spin interactions. These results are shown to arise from near-perfect bond frustration within the J_{1}-J_{2} Heisenberg model on a square lattice with ferromagnetic J_{1} and hence indicate that the extensive previous experimental and theoretical study of the J_{1}-J_{2} Heisenberg model on local-moment square spin lattices should be expanded to include itinerant spin systems.


Flow cytophotometric and time-lapse cinematographic study of human cells infected by adenovirus type 2 wild-type and two DNA-negative temperature-sensitive mutants.
Flow cytophotometry and time-lapse cinematography were used to study viral DNA synthesis and alteration of the cellular DNA content of human cells infected by adenovirus type 2 wild-type and two DNA-negative temperature-sensitive mutants. Cell populations with DNA contents greater than 4n (where n represents the normal haploid DNA content of cells) were found after infection and their origin is discussed with regard to cell cycle changes, viral DNA replication and cell fusion or endomitosis.


A Clarion Call for Social Work Attention: Brothers and Sisters of Persons With Acquired Brain Injury in the United States.
This article presents a clarion call for increased social work attention to the needs of siblings of persons with acquired brain injury (ABI) in the United States. The article overviews how siblings are psychosocially affected, how they provide care to the injured brothers and sisters, and how they personally develop as a result of their experiences. The article highlights the fact that social workers and other professionals often overlook the needs of siblings of persons with ABI and makes an appeal for social workers to advance clinical practice and research to benefit this often neglected population.


Suppressor mutations for crs mutants of Bacillus subtilis.
Mutants of Bacillus subtilis which carried suppressor mutations for catabolite-resistance gene crsA47 were isolated from methylmethanesulfonate-treated cultures of GLU-47 (crsA47). The suppressor mutation, sca19, suppressed resistance of crsA47 mutant to glucose and other inhibitors of sporulation. Moreover, the suppressor mutation could restore the rate of growth and the level of IMP dehydrogenase and alkaline phosphatase of crsA47 mutant to the wild-type level. The scal19 mutation was also able to suppress catabolite resistance of other crs mutants. The map position of the sca19 mutation indicated that this mutation was an intergenic suppressor for the crs mutants. It was also found that an erythromycin-resistance mutation, eryl, could suppress the catabolite resistance of some of the crs mutants. Our results were discussed in relation to the importance of a proper state of metabolic activities and membrane functions during the initiation of sporulation.


Salicylaldehyde azine cluster formation observed by cold-spray ionization mass spectrometry.
We installed a cold-spray ionization (CSI) source on a mass spectrometer to investigate the self-assembly behavior of an aggregation-induced emission enhancement system. Using a CSI source and the three-dimensional platform, a self-assembly system of a salicylaldehyde azine (SAA) was studied in mixture solution. This method permitted the determination of the structural information of the solution state, which cannot be detected by conventional mass spectrometry. In addition to the [M+H](+) ion (M is the SAA molecule), many major ion clusters such as [2M+Na](+) at m/z 503, [3M+Na](+) at m/z 743, [4M+Na](+) at m/z 983 and higher order aggregates were observed in the CSI mass spectra. However, many fragment ions, with the exception of cluster ions, appeared with high abundance when the ESI ion source was used due to the desolvation chamber temperature, suggesting that some aggregation can be detected at low temperatures. To investigate the effect of solvent on the aggregation, the CSI-mass spectrometry (MS) experiments of SAA in absolute ethanol solution and ethanol/water (good/poor solvent) mixture solution were conducted. The most abundant ion peak was protonated SAA (m/z 241) in absolute ethanol, but many cluster ions and some multiple charged ion peaks were observed after adding a small amount of water into the ethanol solution. The results showed good agreement with that inferred by the combinational analysis of scanning electron microscope and fluorescence microscopy, indicating that CSI-MS is capable of providing self-assembly information of labile molecules in the solution state.


In silico high throughput mutagenesis and screening of signal peptides to mitigate N-terminal heterogeneity of recombinant monoclonal antibodies.
N-terminal heterogeneity resulting from non-uniform signal peptide (SP) cleavage can potentially affect biologics property attributes and result in extended product development timelines. Few studies are available on engineering SPs systematically to address miscleavage issues. Herein, we developed a novel high throughput computational pipeline capable of generating millions of SP mutant sequences that uses the SignalP 5.0 deep learning model to predict which of these mutants are likely to alleviate the N-terminal miscleavage in antibodies. We optimized the parameters to target mutating one or two amino acids at the C-terminus of 84 unique SPs, exhausting all theoretically possible combinations and resulting in a library of 296,077 unique wildtype and mutant signal peptides for in silico screening of each antibody. We applied this method to five antibodies against different targets, with various extent of miscleavage (2.3% to 100%) on their Lambda light chains. In each case, multiple SP mutants were generated, with miscleavage reduced to a non-detectable level and titers comparable with or better than that of the original SPs. Pairwise mutational analysis using an in silico library enriched with high-scoring mutants revealed patterns of amino acids at the C-terminus of SPs, providing insights beyond the "Heijne rule". To our knowledge, no similar approach that combines high throughput in silico mutagenesis and screening with SP cleavage prediction has been reported in the literature. This method can be applied to both the light chain and heavy chain of antibodies, regardless of their initial extent of miscleavage, provides optimized solutions for individual cases, and facilitates the development of antibody therapeutics.Abbreviations: Aa, amino acids; CHO, Chinese hamster ovary; CNN, convolutional neural network; CSscore, cleavage site score; CSV, comma-separated values; HC, heavy chain; HEK, human embryonic kidney; HPLC, high-performance liquid chromatography; IgG, immunoglobulin G; IGLV, immunoglobulin G Lambda variable; LC, light chain; LCMS, liquid chromatography-mass spectrometry; MS, mass spectrometry; PCR, polymerase chain reaction; PBS, phosphate-buffered saline; PEI, polyethylenimine; SP, signal peptide; SPase, signal peptidase; TCEP, tris(2-carboxyethyl) phosphine; TOF, time-of-flight.


Access-Selection Algorithm for Heterogeneous Wireless Networks Based on Uncertain Network Attribute Values.
A heterogeneous wireless network (HWN) environment contains many kinds of wireless networks, such as UMTS, LTE, and WLAN, where users move around within their coverage area. How to ensure mobile users select the most suitable network is a hot research topic for HWNs. Owing to the mobility of users, the interference of wireless signals, and the fluctuation of network status, the network attribute values obtained by mobile users are often uncertain. However, the traditional access-selection algorithms assume that mobile users can obtain accurate network attribute values, which makes users unable to access the most appropriate network. To solve this problem, this paper designs an access-selection algorithm for HWNs in the context of inaccurate network attribute values. First, the algorithm calculates the network attribute values based on the hesitant fuzzy theory, then calculates the weights of network attributes using the fuzzy analytic hierarchy process (FAHP), and finally sorts the candidate networks using the hesitant fuzzy technique for order preference by similarity to ideal solution (TOPSIS) method. The simulation results show that the proposed algorithm enables users to select the most suitable network to access under the inaccurate network attribute environment and obtain higher gains.


Detergent-mediated formation of polymer-supported phospholipid bilayers.
Supported phospholipid bilayers can be formed by established methods such as vesicle fusion and the Langmuir-Blodgett (LB) technique. However, challenges remain in regards to creating supported bilayers from various lipid compositions, using various support surfaces, and incorporating membrane proteins. Here we report a detergent removal method as an alternative means of supported bilayer formation. The process consists of three steps: (1) incubation of phospholipid-poly(ethylene glycol) (PEG)-grafted glass with lipid-detergent micelles; (2) detergent removal by washing the surface with vesicles; and (3) incubation with the vesicles to complete lipid adsorption. These procedures yielded fluid planar bilayers of zwitterionic lipids. Because fluid structures were not obtained by vesicle fusion, the detergent seemed necessary to produce the polymer-supported bilayers. While anionic phospholipids inhibited the attachment of fluid bilayers in the absence of calcium ions, supported bilayers with almost full mobility were obtained from lipid mixtures containing 10-20 mol % anionic lipids in the presence of calcium ions. The incorporation of the anionic lipids in the bulk-facing leaflet was demonstrated by the binding of dye-labeled annexin V.


Highly Oil-Repellent Thermoplastic Boundaries via Surface Delivery of CF3 Groups by Molecular Bottlebrush Additives.
We fabricated thermoplastic surfaces possessing extremely limited water and oil wettability without employment of long-chain perfluoroalkyl (LCPFA) substances. Namely, by taking advantage of the structure and behavior of original oleophobic perfluoropolyether (PFPE) methacrylate (PFM) molecular bottlebrush (MBB) additive we obtained polymeric surfaces with oil contact angles well above 80° and surface energy on the level of 10 mN/m. Those angles and surface energies are the highest and the lowest respective values reported to date for any bulk solid flat organic surface not containing LCPFA. We show experimentally and computationally that this remarkable oil repellency is attributed to migration of small quantities of the oleophobic MBB additives to the surface of the thermoplastics. Severe mismatch in the affinity between the densely grafted long side chains of MBB and a host matrix promotes stretching and densification of mobile side chains delivering the lowest surface energy functionalities (CF3) to the materials' boundary. Our studies demonstrate that PFM can be utilized as an effective low surface energy additive to conventional thermoplastic polymers, such as poly(methyl methacrylate) and Nylon-6. We show that films containing PFM achieve the level of oil repellency significantly higher than that of polytetrafluoroethylene (PTFE), a fully perfluorinated thermoplastic. The surface energy of the films is also significantly lower than that of PTFE, even at low concentrations of PFM additives.


Social and psychological differences between cancer and noncancer patients: cause or consequence of the disease?
83 female patients with breast tumors were interviewed prior to biopsy. The interview contained a psychological instrument measuring action control as an indicator for the patients' reaction to stress together with questions about the expected diagnosis. Using multiple-regression analysis we estimated the explained variance of the variables relating to the histological result of the biopsy. Since most of the patients gave a correct prognosis of the nature of their disease-this variable proved to be very important-most of the social psychological findings have to be interpreted as consequences rather than causes of cancer.


System-driven longitudinal follow-up of incidental imaging findings.
Increasing utilization of cross-sectional imaging has resulted in more clinically significant incidental findings being discovered. However, the current approach for handling these findings is commonly inconsistent and relies greatly on the efforts of individual clinicians. Making sure every actionable incidental finding is handled in a consistent and reliable manner can be difficult, especially for a large health system. We propose an approach to handling incidental findings aimed at improving patient follow-up rates, which involves implementing system-level processes that standardize the reporting of incidental findings, notification of clinicians and the patient, and centralized monitoring of longitudinal patient follow-up. We will lay out a general framework for standardized reporting of incidental findings by the radiologist using software integrated into the daily workflow. This should enable simultaneous notification of the ordering clinician, the patient's primary-care provider, and an incidental findings navigator. The navigator will "close the loop" by working with clinicians to notify the patient of the finding, coordinate patient follow-up, and document the finding and long-term follow-up. We hope this can serve as a basic framework to help large health systems design an incidental findings workflow to improve follow-up rates and reduce patient harm.


Unconjugated hyperbilirubinemia in patients with non-alcoholic fatty liver disease: a favorable endogenous response.
The clinical significance of increased frequency of unconjugated hyperbilirubinemia in patients with non-alcoholic fatty liver disease (NAFLD) is unknown. Serum bilirubin is an endogenous anti-oxidant, and oxidative stress plays an important role in the pathogenesis of NAFLD. In this study, we have documented 25.4% prevalence of unconjugated hyperbilirubinemia in 204 consecutive NAFLD patients. These patients had a significantly less severe liver disease on histopathology and/or fibroScan which may be attributed to anti-oxidant effect of bilirubin.


Artesunate drug-loaded 2D nano-shuttle landing on RBCs infected with malaria parasites.
Artesunic acid (AS0), a derivative of artemisinin, is recommended for the treatment of severe and complicated malaria, but its use is limited because of limitations such as a short half-life, non-specific targeting capability, low bioavailability, etc. To overcome these issues, a novel 2D inorganic delivery shuttle system for an AS0 drug to target the malarial host, red blood cells (RBCs), is explored by immobilizing AS0 into 2D metal hydroxides to form AS- (artesunate, the deprotonated form of artesunic acid) nanohybrid drugs. Haemolysis assay showed that the AS- nanohybrids not only are haemo-compatible but also target RBCs due to the electrostatic interaction and hydrogen bonding between RBCs and AS- nanohybrids. As clearly demonstrated by the subsequent parasite lactate dehydrogenase assay, the antimalarial effect of the AS- nanohybrids is determined to be 6 times more effective than that of intact AS0 against malaria. Therefore, the AS- nanohybrids with haemo-compatible 2D inorganic carriers could be the promising drug delivery systems for targeting the malarial host, RBCs.


The emotional needs of children in hospital.
Hospitalization of a child for physical reasons brings with it separation from parents, siblings and familiar surroundings, as well as the probability of subjection to frightening and painful procedures. Unless steps are taken to prevent or modify the resultant stress, behavioural disturbances may arise and may result in permanent damage to the developing personality.


Antiemetic efficacy of ondansetron and metoclopramide, both combined with corticosteroid, in malignant lymphoma patients receiving non-cisplatin chemotherapy.
The aim of the present study was to compare the antiemetic efficacy of ondansetron (OND) with metoclopramide (MCP), both combined with corticosteroid (CS) in patients with malignant lymphoma. A total of 109 patients with malignant lymphoma receiving their first series of non-cisplatin chemotherapy (CT) (CHOP or MOPP) were divided into prospective, randomized, open and parallel groups and analyzed at two hematological centres at university hospitals in Copenhagen, Denmark. The patients were randomized to receive one of the two following regimens; 1) OND 8 mg/methylprednisolone 80 mg i.v. before CT and OND 8 mg p.o. after 8 h and at bedtime. OND 8 mg tid days 2-3, and 8 mg tid prn days 4-5 and prednisolone 75-100 mg qds days 2-5 and 2) MCP 30 mg/metylprednisolone 80 mg i.v. before CT and MCP 20 mg p.r. after 4 and 8 h respectively. MCP 20 mg p.r. prn days 1-5 and prednisolone 75-100 mg qds days 2-5. In the acute phase OND/CS was superior to MCP/CS in the control of nausea and emesis, resulting in no emesis in 92% of the OND/CS treated group vs. 50% treated with MCP/CS (p < 0.001), and no nausea in 79% (OND/CS) vs. 42% (MCP/CS) (p < 0.001). The ultimate aim - neither nausea nor emesis - was reached in 77% (OND/CS) vs. 35% (MCP/CS) day 1 (p < 0.001). OND/CS is significantly better than MCP/CS in the control of delayed nausea, 81% (OND/CS) vs. 58% (MCP/CS) (p < 0.026). Both the OND/CS and MCP/CS regimens are highly effective in the control of delayed emesis, 94% (OND/CS) vs. 85% (MCP/CS) (p < 0.26). Adverse events were mild and experienced in 31% of the patients. In the OND/CS group 13% had constipation vs. 8% in the MCP/CS group. Nine percent treated with OND/CS had headaches compared to none treated with MCP/CS (p < 0.08). One extrapyramidal reaction was recorded in the MCP/CS group. In malignant lymphoma patients receiving moderately emetogenic CT, the combination of OND and CS was very effective and significantly better than low dose MCP and CS in the control of acute emesis, acute nausea and delayed nausea.


Cognitive profiles of patients with mild cognitive impairment or dementia in Alzheimer's or Parkinson's disease.
Alzheimer's disease (AD) and Parkinson's disease (PD) are associated with severe cognitive decline, but it is still unclear to what extent they become functionally more similar over time. We compared amnestic mild cognitively impaired (aMCI; n = 29) patients to mild cognitively impaired (MCI) PD patients (n = 25), and patients with AD (n = 34) to patients with PD dementia (PDD; n = 15) with respect to cognitive functioning and mood. aMCI patients were impaired in episodic memory, while MCI PD patients showed deficits in visuoconstruction and attention. AD and PDD patients showed comparable deficits on tests for language, attention and visuoconstruction. However, unlike PDD patients but similar to aMCI patients, AD patients showed a characteristic memory impairment, especially commission errors on recognition tasks, whereas PDD patients scored higher on the depressive mood questionnaire. In advanced stages of both diseases, the pattern of functional deficits associated with parietal and temporal lobe functions (attention, visuoconstruction and language) is similar. However, specific differences, already present in the early stage (recognition errors in AD, associated with mediobasal temporal lobe functioning, and depressed mood in PDD, associated with non-motor basal ganglia loops), are also observed in the late stage.


[Conversion of laparoscopic cholecystectomy].
Laparoscopic cholecystectomy is nowadays the method of choice in treatment of symptomatic cholecystolithiasis, despite the fact that some operations cannot be completed laparoscopically and are converted. In a group of 431 patients operated during the last two years the authors evaluate the causes and predispositions of conversion which was performed in 7.4%. A significantly higher risk was found in subjects above 65 years of age, in those with ultrasonographic signs of thickening of the gallbladder wall and patients with acute cholecystitis. The risk of conversion is not significantly influenced by the patient's sex, obesity, the condition after endoscopic retrograde cholangiopancreaticography, pancreatitis and a previous abdominal operation.


[Biomarkers of bone remodelling].
Bone is a frequent site for metastases patients with advanced solid tumors. Metastatic bone disease alters bone homeostasis and biochemical markers of bone turnover are studied in patients with cancer. These markers include bone matrix synthesis and degradation products, or enzymes expressed by osteoblasts or osteoclasts. Thus, the use of these biochemical markers of bone metabolism is being evaluated in screening for development of bone metastases, in predicting risk of skeletal-related events and survival in patients with bone metastases, and in monitoring response to antiresorptive therapy. Bone markers have potential to provide information, but their routine use in the clinic cannot be recommended yet.


A model for change to evidence-based practice.
To describe a model that guides nurses and other healthcare professionals through a systematic process for the change to evidence-based practice. The tremendous increases in clinical research and accessibility to research findings have prepared the way for the paradigm shift from traditional and intuition-driven practice to evidence-based practice. Although several models have emerged to guide practitioners in research utilization, practitioners continue to have difficulty synthesizing empirical and contextual evidence and integrating evidence-based changes into practice. The model is based on theoretical and research literature related to evidence-based practice, research utilization, standardized language, and change theory. In this model, practitioners are guided through the entire process of developing and integrating an evidence-based practice change. The model supports evidence-based practice changes derived from a combination of quantitative and qualitative data, clinical expertise, and contextual evidence. The model was developed using sources identified on searches of Medline, CINAHL, and systematic reviews available on the Internet. Review topics were focused on evidence-based medicine and nursing, research utilization, and change process. Other sources included clinical expertise and quality-improvement information. Practitioners need skills and resources to appraise, synthesize, and diffuse the best evidence into practice. Patient outcomes must reflect discipline-specific and interdisciplinary accountabilities. Collaboration between researchers and practitioners within and among disciplines will enhance the diffusion of evidence-based practice innovations.


Decreased intracellular pH is not due to increased H+ extrusion in preconditioned rat hearts.
Ischemic preconditioning reduces intracellular acidification during a subsequent, prolonged period of ischemia. This may reflect decreased anaerobic glycolysis or increased H+ efflux. To distinguish between these hypotheses, we monitored intracellular and extracellular pH during a sustained period of ischemia to determine whether the preconditioned hearts had increased H+ efflux compared with nonpreconditioned hearts. At the end of 20 min of ischemia, intracellular pH in nonpreconditioned hearts was 5.90 +/- 0.08 and extracellular pH was 5.51 +/- 0.21, whereas in preconditioned hearts, intracellular pH was 6.50 +/- 0.06 and extracellular pH was 6.62 +/- 0.06. To investigate whether an Na+/H+ exchange inhibitor would alter the reduced acidification during ischemia, we preconditioned hearts with and without dimethylamiloride (DMA). Intracellular pH during ischemia was similar in preconditioned hearts with and without DMA treatment (pH 6.42 +/- 0.02 vs. 6.45 +/- 0.03, respectively). These data do not support the hypothesis that enhanced proton efflux is responsible for the more alkaline intracellular pH during sustained ischemia in preconditioned hearts.


Glycosylated ectodomain of the human thyrotropin receptor induces antibodies capable of reacting with multiple blocking antibody epitopes.
Recently, we showed that the glycosylated ectodomain of the human thyrotropin receptor (hET-gp) reacts with autoantibodies from autoimmune thyroid disease (AITD) patients' sera. To better understand the effects of glycosylation of thyrotropin receptor (TSHR) in antibody induction, we immunized rabbits with hET-gp protein. The rabbits developed relatively high titers of antibodies with highly potent TSH binding inhibitory immunoglobulin (TBII) and thyroid stimulatory blocking antibody (TSBAb) activities. Both the hET-gp and a nonglycosylated ectodomain of the human TSHR (hETSHR) protein significantly reversed the TBII as well as TSBAb activity. Based on the ability of synthetic peptides to significantly reverse the functional activity of these rabbit antisera, we identified three discrete regions of the TSH R, represented by amino acids 202-221, 292-311 and 367-386, as TBII epitopes and four regions represented by amino acids 352-371, 367-386, 382-401 and 392-415 as TSBAb epitopes. These data demonstrate that rabbit antibodies that bind to amino acids 367-386 mediate their TSBAb activity by inhibiting the binding of TSH to TSHR; whereas, antibodies to regions 352-415, excluding aa 367-386, exert their TSBAb activity by affecting a step subsequent to TSH binding. Coincident with the elevation of TBII and TSBAb activity, serum total T4 levels declined and thus suggested that the antibodies exerted functional effects on thyroid in vivo. Together, these data demonstrate that glycosylated hET-gp protein is a more potent immunogen and it can induce a broader antibody response directed against multiple TBII and TSBAb epitopes.


Interatomic Coulombic decay in a heteroatomic rare gas cluster.
Interatomic decay in a heteroatomic rare gas cluster (NeAr) is studied in detail using ab initio electronic structure description and nuclear dynamics simulations. Decay widths of all possible interatomic decay processes are calculated by the recently developed method based on Green's function formalism. Kinetic energy spectra of the electrons emitted in the course of interatomic Coulombic decay (ICD) are simulated for a series of initial vibrational states of the neutral cluster. The effect of the nuclear dynamics on the ICD electron spectra is discussed.


Oesophageal achalasia: an argument for primary surgical management.
Achalasia is a primary oesophageal motility disorder resulting from damage to the ganglion cells of the myenteric plexus. Impaired relaxation of the lower oesophageal sphincter and aperistalsis causes its cardinal symptoms of dysphagia, chest pain and reflux-type symptoms. Management is somewhat controversial, with options including systemic and local pharmacotherapy, dilatation and oesophagomyotomy. We review the presentation, investigation and management of oesophageal achalasia and make an argument for primary surgical management. We performed a Medline search of the term 'achalasia', limiting the search to clinical trials and meta-analyses. We then selected articles based on their abstracts using four main criteria: previously unreported findings, previously unreported techniques, size of patient cohort and journal impact factor. References in selected articles were manually searched for other relevant articles. Achalasia has been managed using a variety of techniques including systemic and local pharmacotherapy, forced dilatation and oesophagomyotomy. Success rates vary widely between techniques. Mechanical disruption ofthe lower oesophageal sphincter is most successful. In achalasia, mechanical disruption of the lower oesophageal sphincter using forced dilatation or surgical myotomy offers the only realistic prospect of long-term symptom relief. Recent evidence suggests that previous medical treatment or dilatation makes oesophagomyotomy more difficult and increases the risk of complications. As the morbidity associated with surgery continues to decrease with improvements in minimal access techniques, the argument for primary management of achalasia with oesophagomyotomy becomes more compelling.


The Relationship Between Compassion Fatigue and Professional Self-Concept in Psychiatric Nurses.
The current study examined the relationship between compassion fatigue and professional self-concept in psychiatric nurses. Participants included 156 nurses working in a mental health and disorders hospital in Turkey. Data were collected via a sociodemographics form, the Compassion Fatigue subscale of the Professional Quality of Life Scale, and Professional Self-Concept Scale. Participants exhibited low levels of compassion fatigue and high levels of professional self-concept. A significant negative relationship was found between participants' mean compassion fatigue scores and mean professional satisfaction, professional competence, and professional self-concept scores (p < 0.05). Professional satisfaction, professional competence, and professional self-concept decreased with increasing compassion fatigue. Nurses should be provided emotional support through in-service training and effective communication to prevent burnout. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].


Impacts and potential mechanisms of fine particulate matter (PM2.5) on male testosterone biosynthesis disruption.
Exposure to PM2.5 is the most significant air pollutant for health risk. The testosterone level in male is vulnerable to environmental toxicants. In the past, researchers focused more attention on the impacts of PM2.5 on respiratory system, cardiovascular system, and nervous system, and few researchers focused attention on the reproductive system. Recent studies have reported that PM2.5 involved in male testosterone biosynthesis disruption, which is closely associated with male reproductive health. However, the underlying mechanisms by which PM2.5 causes testosterone biosynthesis disruption are still not clear. To better understand its potential mechanisms, we based on the existing scientific publications to critically and comprehensively reviewed the role and potential mechanisms of PM2.5 that are participated in testosterone biosynthesis in male. In this review, we summarized the potential mechanisms of PM2.5 triggering the change of testosterone level in male, which involve in oxidative stress, inflammatory response, ferroptosis, pyroptosis, autophagy and mitophagy, microRNAs (miRNAs), endoplasmic reticulum (ER) stress, and N6-methyladenosine (m6A) modification. It will provide new suggestions and ideas for prevention and treatment of testosterone biosynthesis disruption caused by PM2.5 for future research.


Descriptive analysis of flavor characteristics for black walnut cultivars.
Seven black walnut cultivars, Brown Nugget, Davidson, Emma K, Football, Sparks 127, Sparrow, and Tomboy, were evaluated by descriptive sensory analysis. Seven trained panelists developed a lexicon for the black walnuts and scored the intensities of the samples for 22 flavor attributes. Results showed that the 7 samples differed significantly (P ≤ 0.05) on 13 of the attributes. For the majority of the attributes, only Emma K differed from the rest of the cultivars by being characterized with lower scores for black walnut ID, overall nutty, nutty-grain-like, nutty-buttery, floral/fruity, oily, and overall sweet. That sample also was higher in acrid, burnt, fruity-dark, musty/earthy, rancid, and bitter attributes. The remaining 6 cultivars showed few differences in individual attribute ratings, but did show some differences when mapped using multivariate techniques. Future studies should include descriptive analysis of other black walnut varieties, both wild and commercial, that could be grown and harvested for production.


[Research advances of anti-CD40 monoclonal antibody].
CD40 and its receptor CD40L are a very important pair of co-stimulating molecule in immune response, which have extensive biological effects. After stimulating CD40 signal, it can exert corresponding function through MAPK (JNK, ERK, p38) pathway, PI3K cascade, as well as NF-κB and STAT. The CD40 signal is closely related to tumor immunity, this moleculer has already become targeted-molecule for cancer treatment. Recently, there have been many anti-CD40 monoclonal antibodies displaying good anti-cancer effect, among which CHIR-12.12, SGN-40 and CP-870, 893 developed rapidly and successively have entered clinical research stage. This review focuses the status of anti-CD40 monoclonal antibody, including distribution of CD40, physiological function of CD40, CD40 and tumor immunity, anti-CD40 monoclonal antibodies and so on.


Contact formation dynamics: Mapping chemical bond formation between a molecule and a metallic probe.
We present a study that maps out chemical bond formation between a Pt-inked probe and a single 1,3-cyclohexadiene (1,3-CHD) molecule on Si(100). By separating the mechanical and electronic contributions to the current during the approach to contact, we show that there are significant forces between the probe and the C=C of the molecule and we track the relaxation of the molecule, the emergence of a chemical bond feature in the LDOS, and the quenching of specific molecular vibrations during bond formation.


Inhibitory action of toxic compounds present in lignocellulosic hydrolysates on xylose to xylitol bioconversion by Candida guilliermondii.
The inhibitory action of acetic acid, ferulic acid, and syringaldehyde on metabolism of Candida guilliermondii yeast during xylose to xylitol bioconversion was evaluated. Assays were performed in buffered and nonbuffered semidefined medium containing xylose as main sugar (80.0 g/l), supplemented or not with acetic acid (0.8-2.6 g/l), ferulic acid (0.2-0.6 g/l), and/or syringaldehyde (0.3-0.8 g/l), according to a 2(3) full factorial design. Since only individual effects of the variables were observed, assays were performed in a next step in semidefined medium containing different concentrations of each toxic compound individually, for better understanding of their maximum concentration that can be present in the fermentation medium without affecting yeast metabolism. It was concluded that acetic acid, ferulic acid, and syringaldehyde are compounds that may affect Candida guilliermondii metabolism (mainly cell growth) during bioconversion of xylose to xylitol. Such results are of interest and reveal that complete removal of toxic compounds from the fermentation medium is not necessary to obtain efficient conversion of xylose to xylitol by Candida guilliermondii. Fermentation in buffered medium was also considered as an alternative to overcome the inhibition caused by these toxic compounds, mainly by acetic acid.


The Function and Mechanism of Lipid Molecules and Their Roles in The Diagnosis and Prognosis of Breast Cancer.
Lipids are essential components of cell structure and play important roles in signal transduction between cells and body metabolism. With the continuous development and innovation of lipidomics technology, many studies have shown that the relationship between lipids and cancer is steadily increasing, involving cancer occurrence, proliferation, migration, and apoptosis. Breast cancer has seriously affected the safety and quality of life of human beings worldwide and has become a significant public health problem in modern society, with an especially high incidence among women. Therefore, the issue has inspired scientific researchers to study the link between lipids and breast cancer. This article reviews the research progress of lipidomics, the biological characteristics of lipid molecules, and the relationship between some lipids and cancer drug resistance. Furthermore, this work summarizes the lipid molecules related to breast cancer diagnosis and prognosis, and then it clarifies their impact on the occurrence and development of breast cancer The discussion revolves around the current research hotspot long-chain non-coding RNAs (lncRNAs), summarizes and explains their impact on tumor lipid metabolism, and provides more scientific basis for future cancer research studies.


CTHRC1 facilitates bladder cancer cell proliferation and invasion through regulating the PI3K/Akt signaling pathway.
Emerging evidence has illustrated that Collagen triple helix repeat containing 1 (CTHRC1) is crucial for tumorigenesis and development. However, the effects of CTHRC1 on bladder cancer progression remain largely unclear. Here, we aim to investigate the function and mechanism of CTHRC1 in behaviors of bladder cancer cells in vitro and in vivo. Interference assays were applied to determine the biological functions of CTHRC1. The expression of CTHRC1 was examined by quantitative real time-PCR (qRT-PCR), Western blot and immunohistochemical (IHC) analysis. Effects of CTHRC1 on proliferation, migration and invasion were evaluated by CCK-8, colony formation, flow cytometry, EdU staining, wound healing, transwell and western blot assays. Bladder cancer cells transfected with sh-CTHRC1 were injected into nude mice to explore the effect of CTHRC1 on tumorigenesis in vivo. CTHRC1 expression was increased in bladder cancer tissues and cell lines compared with normal controls, and associated with advanced clinical stage and lymph node metastasis. Also, patients with high levels of CTHRC1 expression were found to have a poor prognosis. Knockdown of CTHRC1 alleviated bladder cancer cell proliferation, migration and invasion in vitro and impeded tumorigenesis in vivo. Moreover, mechanistic investigation indicated that CTHRC1 could regulate the PI3K/Akt signaling pathway. Our data demonstrated that CTHRC1 played an oncogenic role in bladder cancer by modulating the PI3K/Akt signaling pathway, which sheds novel light on diagnosis and treatment of bladder cancer.


Autoantibodies to steroidogenic enzymes in autoimmune polyglandular syndrome, Addison's disease, and premature ovarian failure.
Autoantibodies to steroidogenic enzymes, steroid 17 alpha-hydroxylase (17 alpha-OH), cytochrome P450 side-chain cleavage enzyme (P450scc), and steroid 21-hydroxylase (21-OH), were measured using specific and sensitive immunoprecipitation assays (IPAs) in patients with various forms of autoimmune adrenal disease. Autoantibodies to 17 alpha-OH were detected in 6 of 11 (55%) patients with autoimmune polyglandular syndrome (APS) type I, 8 of 24 (33%) patients with APS type II, 11 of 56 (20%) patients with adrenal cortex antibody (ACA; measured by immunofluorescence)-positive patients without Addison's disease, and only 3 of 64 (5%) patients with Addison's disease. Autoantibodies to P450scc were found at a prevalence similar to those to 17 alpha-OH: in 5 of 11 (45%) APS type I patients, 10 of 24 (42%) APS type II patients, 11 of 56 (20%) ACA-positive patients without Addison's disease, and only 6 of 64 (9%) patients of the Addison disease group. Autoantibodies to 21-OH were found in a majority of patients with APS type I (7 of 11;64%), APS type II (23 of 24; 96%), Addison's disease (41 of 64; 64%), and ACA-positive patients without Addison's disease (48 of 56; 86%). All sera that were positive for 17 alpha-OH or P450scc were also positive for 21-OH autoantibodies, except in 1 case. There was good agreement between the presence of ACA measured by immunofluorescence and 21-OH antibodies measured by IPA in all patient groups studied, and this indicates that 21-OH is a major autoantigen in adrenal autoimmune disease regardless of whether the disease presents as isolated Addison's disease or APS type I or type II. Autoantibodies to 17 alpha-OH and P450scc appeared to be the major components of the steroid-producing cell antibodies measured by immunofluorescence. No autoantibodies to 21-OH, 17 alpha-OH, or P450scc were detected in 17 sera from patients with premature ovarian failure without evidence of adrenal autoimmunity (as judged by immunofluorescence studies), except for 1 serum in which low levels of 17 alpha-OH antibodies were found. Overall, our studies indicate that 35S-labeled 17 alpha-OH, P450scc, and 21-OH can be used successfully in IPAs for their respective autoantibodies. Assays such as these may well be valuable in the immunological assessment of patients at risk for or suspected of adrenal autoimmunity.


Ribonucleic Acid Synthesis Associated with a Developmental Change in the Gametophyte of Pteridium aquilinum.
When bacteria are subjected to step-down conditions, there is an enhanced production of a messenger-type of RNA for a short time after the shift. A cultural shift, which appears to be similar to step-down, is described for gametophytes of Pteridium aquilinum. When the cultures are grown in white light, a population of rapidly dividing cells is produced, whereas in red light cell elongation predominates. If the cultures growing in white light are shifted to red light, a transition occurs which involves a rapid decrease in growth and nucleic acid synthesis. In particular, there is a marked decline in RNA synthesis for a short time following the shift and prior to the initiation of the new mode of growth. It appears that this observed change in RNA synthesis is related to the initiation of the new mode of growth.


[Lesions of the cortical part of the auditory analyzer in explosive injury].
A survey of 48 victims aged 19-36 years with explosive trauma and combined damage to the auditory system was conducted to assess the level of damage to nerve structures by analyzing the bioelectric activity of the cerebral cortex. All patients underwent electroencephalography (EEG). It is established that akubarotrauma of explosive genesis almost always leads to lesions of the function of the cortical part of the auditory analyzer. Desynchronized activity on the EEG after acubarotrauma is a favorable prognostic sign, indicating only functional disorders of the cortical part of the auditory analyzer. On the contrary, EEG changes of an organic type of cortical or stem nature are an unfavorable prognostic factor, usually accompanied by sensorineural hearing loss with prolonged and incomplete hearing recovery. Promising drugs for the treatment of otoneurological disorders are antihypoxants, in particular, derivatives of triazine indole, which affect the molecular mechanisms of hypoxia development.


Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios.
There is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN. This was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment. MCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66-0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone. MCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.


Case 229: Burn-related Global Ankylosis of Interphalangeal Joints with Associated Acroosteolysis.
History A 50-year-old woman presented with a 6-month history of polyarthralgia involving the left and right hands, wrists, elbows, ankles, and knees. Her pain was not associated with morning stiffness but did worsen over the course of the day. She denied experiencing fevers, chills, or mouth ulcers. She did not report paresthesias or blue discoloration of her fingers when they were exposed to cold. Her family history was remarkable for an aunt who died of systemic lupus erythematosus and for a brother with arthritis. Her medical history was remarkable for vitamin D deficiency, hypertension, and rehabilitation for burns. At clinical examination, she had mild tenderness to palpation of her joints, without associated erythema, swelling, or crepitus. Healed skin grafts were also noted. Blood chemistry tests revealed a rheumatoid factor of 8.5 IU/mL (normal range, 0-13.9 IU/mL), an erythrocyte sedimentation rate of 2 mm/hr (normal range, 0-40 mm/hr), and a C-reactive protein value of 0.4 mg/L (3.8 nmol/L) (normal range, 0-4.9 mg/L [0-46.7 nmol/L]). Antinuclear antibodies test results were negative. Radiography of the right and left hands was performed.


The incidence of immunofluorescence patterns and specific autoantibodies observed in autoimmune patients in a tertiary care centre.
Objectives: Testing for antinuclear antibodies (ANA) facilitates the diagnosis of autoimmune diseases (ADs). Here, we report an incidence of ANA positivity and its patterns by indirect immunofluorescence (IIF) and specific autoantibodies through immunodot assay. Methods: Sera from 993 patients presenting with various ADs were tested by IIF and immunodot assay. Results: ANAs were detected in 39.7%, of which speckled pattern was predominantly observed (50.8%). 56.8% of samples were positive on the immunodot assay with SSA Ro 60 antibody being the most prevalent (30.7%). Discussion: A significant correlation (p minor 0.0001) was observed between patterns and auto-antibodies. Coarse speckled (CS) and homogeneous were overly represented by antibodies SSA Ro 60 (13%) and nucleosomes (5.8%) respectively. Mi-2, PL-7, PL-12, and SP-100 were the rarest autoantibodies specificities found. Conclusions: The presence of a particular IIF pattern is predictive of a specific autoantibody in the sample. Association of IIF patterns and specific autoantibody are relevant for a more accurate diagnosis of disease.


Acute disseminated encephalomyelitis.
Acute disseminated encephalomyelitis (ADEM), which is classified as a demyelinating disease of the central nervous system (CNS), is a condition that may be regarded as a bridge linking neurology and the infectious diseases. According to the classic definition, ADEM is a monophasic disease that can arise spontaneously; in most cases, however, it is triggered by systemic viral infections or, more rarely, by vaccinations. As the most recent publications on this topic have shown, ADEM can present a relapsing course, being described as "recurrent" if the affected districts are always the same, or "multiphasic" if there is a dissemination in space and time of the lesions, together with a more or less marked association with polyradiculoneuritis. The clinical features and history of the disease create difficulties in differential diagnosis both with encephalomyelitis caused by infectious agents and with noninfectious inflammatory diseases (other demyelinating syndromes, vasculitis, nonvasculitic autoimmune encephalopathies). This paper describes the main features of ADEM, focusing in particular particular on the factors that influence its outcome and can guide the process of differential diagnosis.


Prosthetic rehabilitation of a patient with bilateral cleft lip and palate using osseointegrated implants and extracoronal resilient attachments: a case report.
This case study reports on the prosthetic rehabilitation of a patient with an unrepaired bilateral cleft lip and palate using osseointegrated implants, extracoronal resilient attachments, a combination of metal-ceramic cement-retained fixed partial restorations, and removable prosthesis. Preoperative clinical examination of a 32-year-old woman with bilateral cleft lip and palate revealed a large oronasal communication, hyperplastic soft tissue surrounding the hard palate defect, and a severely resorbed alveolar ridge. A maxillary obturator prosthesis supported by implants and retained with an extracoronal resilient attachment was designed to cover the oronasal communication in the hard palate and fulfill the patient's functional and aesthetic requirements. The patient has been wearing the prosthesis for 1 year. Her speech quality has greatly improved, and her aesthetic and functional expectations have been met.


Molecular diodes based on conjugated diblock co-oligomers.
This report describes synthesis and characterization of a molecular diode based upon a diblock conjugated oligomer system. This system consists of two conjugated blocks with opposite electronic demand. The molecular structure exhibits a built-in electronic asymmetry, much like a semiconductor p-n junction. Electrical measurements by scanning tunneling spectroscopy (STS) clearly revealed a pronounced rectifying effect. Definitive proof for the molecular nature of the rectifying effect in this conjugated diblock molecule is provided by control experiments with a structurally similar reference compound.


Immunoresolvents in asthma and allergic diseases: Review and update.
Asthma and allergic diseases are inflammatory conditions developed by excessive reaction of the immune system against normally harmless environmental substances. Although acute inflammation is necessary to eradicate the damaging agents, shifting to chronic inflammation can be potentially detrimental. Essential fatty-acids-derived immunoresolvents, namely, lipoxins, resolvins, protectins, and maresins, are anti-inflammatory compounds that are believed to have protective and beneficial effects in inflammatory disorders, including asthma and allergies. Accordingly, impaired biosynthesis and defective production of immunoresolvents could be involved in the development of chronic inflammation. In this review, recent evidence on the anti-inflam]matory effects of immunoresolvents, their enzymatic biosynthesis routes, as well as their receptors are discussed.


Anti-Inflammatory Potential of Ethyl Acetate Fraction of Moringa oleifera in Downregulating the NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated Macrophages.
In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway.


Particulate Projectiles Driven by Cavitation Bubbles.
The removal of surface-attached particles with cavitation bubbles is usually attributed to the jetting or shear stresses when bubbles collapse. In this Letter, we report an unexpected phenomenon that millimeter-sized spherical particles made of heavy metals (e.g., stainless steel), when initially resting on a fixed rigid substrate, are suddenly accelerated like projectiles through the production of nearby laser-induced cavitation bubbles of similar sizes. We show experimentally and theoretically that the motion of a particle with radius R_{p} is determined by the maximum bubble radius R_{b,max}, the initial distance from the laser focus to the center of the particle L_{0}, and the initial azimuth angle φ_{0}. We identify two dominant regimes for the particle's sudden acceleration, namely, the unsteady liquid inertia dominated regime and the bubble contact dominated regime, determined by R_{b,max}R_{p}/L_{0}^{2}. We find the nondimensional maximum vertical displacement of the particle follows the fourth power and the square power scaling laws for respective regimes, which is consistent with the experimental results. Our findings can be applied to nonintrusive particle manipulation from solid substrates in a liquid.


Pulmonary embolus.
Pulmonary embolism (PE) remains a common problem and can present with nonspecific symptoms and signs. Anticoagulation is the mainstay of management, the duration of which often depends on the clinical circumstances of the PE. The aim of this article is to review the epidemiology, clinical presentation, diagnosis, management and long-term complications of PE. The incidence of PE appears to be increasing worldwide. Common risk factors include recent surgery, trauma, malignancy and oestrogen exposure. Diagnosis relies on a combination of clinical findings, laboratory tests and radiological imaging, often incorporating clinical prediction tools. Objectively confirmed PE requires anticoagulation, usually with a direct oral anticoagulant (DOAC), of at least three months' duration, but indefinite anticoagulation is being considered increasingly because of the heightened risk for recurrence following anticoagulation cessation, and overall safety of DOACs. Chronic thromboembolic pulmonary hypertension is rare but associated with significant morbidity and mortality.


Vibrio parahaemolyticus becomes lethal to post-larvae shrimp via acquiring novel virulence factors.
As a severe emerging shrimp disease, TPD has heavily impacted the shrimp aquaculture industry and resulted in serious economic losses in China since spring 2020. This study aimed to identify the key virulent factors and related genes of the Vp TPD, for a better understanding of its pathogenicity of the novel highly lethal infectious pathogen, as well as its molecular epidemiological characteristics in China. The present study revealed that a novel protein, Vibrio high virulent protein-2 (MW >100 kDa), is responsible to the lethal virulence of V. parahaemolyticus to shrimp post-larvae. The results are essential for effectively diagnosing and monitoring novel pathogenic bacteria, like Vp TPD, in aquaculture shrimps and would be beneficial to the fisheries department in early warning of Vp TPD emergence and developing prevention strategies to reduce economic losses due to severe outbreaks of TPD. Elucidation of the key virulence genes and genomics of Vp TPD could also provide valuable information on the evolution and ecology of this emerging pathogen in aquaculture environments.


Glycoprotein synthesis in plants: I. Role of lipid intermediates.
The enzymic processes involved in glycoprotein synthesis have been studied using crude extracts obtained from developing cotyledons of Phaseolus vulgaris harvested at the time of active deposition of vicilin. Radioactivity from GDP-[(14)C]mannose can be incorporated by crude extracts into a single chloroform-methanol-soluble product as well as into insoluble product(s). Mannose is the sole (14)C-labeled constituent of the lipid. The kinetics of incorporation of (14)C, as determined by pulse and pulse-chase experiments using GDP-[(14)C]mannose, as well as direct incorporation from added [(14)C]mannolipid, shows that the mannolipid is an intermediate in the synthesis of the insoluble product(s). The characteristics of the mannolipid are consistent with it being a mannosyl phosphoryl polyprenol. The mannose is apparently attached to the lipid via a monophosphate linkage. Of the radioactivity in the insoluble product(s), about 20% is pronase-digestible during a "pulse experiment." After a chase with unlabeled GDP-mannose, about 40% is pronase-digestible; the other 60% is as yet uncharacterized. A radioactive product soluble in a mixture of chloroform-methanol-H(2)O can be extracted from the insoluble residue obtained during a pulse, but is no longer present after a chase. This product may be a lipid oligosaccharide, the final intermediate in glycoprotein synthesis. Data are presented on incorporation from UDP-N-[(14)C]acetylglucosamine into both chloroform-methanol-soluble and -insoluble product(s). The results are consistent with an involvement of lipid intermediates in the glycosylation of protein in this system, and support the concept that the mechanisms of glycoprotein synthesis in higher plants are similar to those which have been reported for mammalian systems.


KCNE2, a down-regulated gene identified by in silico analysis, suppressed proliferation of gastric cancer cells.
It is important to identify the differentially expressed gene in gastric cancer for elucidating the molecular mechanisms of tumorigenesis of stomach. Here, 38 genes differentially expressed genes between gastric cancer and normal gastric mucosa by in silico approaches. A potassium channel protein KCNE2, identified as a down-regulated gene in gastric cancer, was chosen for further study. We investigated the expression of KCNE2 in gastric cancer tissues and cell lines and examined the effect of KCNE2 on proliferation of gastric cancer. The expression of KCNE2 was markedly down-regulated in gastric cancer tissues and cell lines. Forced overexpression of KCNE2 suppressed the growth of SGC7901 cells and cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1. KCNE2 also inhibited SGC7901 cell growth in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that in silico analysis approaches could be used to identify cancer-related genes effectively. KCNE2, as a novel down-regulated gene in gastric cancer, suppressed cell proliferation and tumorigenesis of stomach.


Changes in the Strength of Lettuce Endosperm during Germination.
The forces required to puncture intact lettuce (Lactuca sativa) seed and pericarp, endosperm and embryo were measured by the Instron Universal Testing Machine. It required about 0.6 newton to puncture the endosperm in seeds imbibed in the dark at 6, 12 and 24 hours. Endosperm of seeds imbibed in the light or in dark with gibberellic acid required about 4.2 newtons at 6 and at 12 hours and only about 0.15 newton at 24 hours. Forces required to puncture embryo at all treatments and times remained constant at about 0.3 newton. Changes in the strength of the endosperm do not appear to be related directly to protrusion of the radicle.


Revisiting patient satisfaction following total knee arthroplasty: a longitudinal observational study.
Total knee arthroplasty (TKA) is the most common joint replacement surgery in Canada. Earlier Canadian work reported 1 in 5 TKA patients expressing dissatisfaction following surgery. A better understanding of satisfaction could guide program improvement. We investigated patient satisfaction post-TKA in British Columbia (BC). A cohort of 515 adult TKA patients was recruited from across BC. Survey data were collected preoperatively and at 6 and 12 months, supplemented by administrative health data. The primary outcome measure was patient satisfaction with outcomes. Potential satisfaction drivers included demographics, patient-reported health, quality of life, social support, comorbidities, and insurance status. Multivariable growth modeling was used to predict satisfaction at 6 months and change in satisfaction (6 to 12 months). We found dissatisfaction rates ("very dissatisfied", "dissatisfied" or "neutral") of 15% (6 months) and 16% (12 months). Across all health measures, improvements were seen post-surgery. The multivariable model suggests satisfaction at 6 months is predicted by: pre-operative pain, mental health and physical health (odds ratios (ORs) 2.65, 3.25 and 3.16), and change in pain level, baseline to 6 months (OR 2.31). Also, improvements in pain, mental health and physical health from 6 to 12 months predicted improvements in satisfaction (ORs 1.24, 1.30 and 1.55). TKA is an effective intervention for many patients and most report high levels of satisfaction. However, if the TKA does not deliver improvements in pain and physical health, we see a less satisfied patient. In addition, dissatisfied TKA patients typically see limited improvements in mental health.


Proteomics Analysis Identifies IRSp53 and Fascin as Critical for PRV Egress and Direct Cell-Cell Transmission.
Pseudorabies virus (PRV) has been widely used as a live trans-synaptic tracer for mapping neuronal circuits. Systematically identifying mature PRV virion proteomes and defining co-purified host proteins are necessary to fully understand the detailed mechanism underlying PRV transmission processes. Here, a PRV virion purification strategy based on sorting with flow cytometry is developed and the mature extracellular and intracellular PRV virion proteomes using LC coupled with MS/MS are characterized. In addition to viral proteins, a large number of host proteins are also identified, including proteins related to actin cytoskeletal dynamics and membrane protrusion. How many of these host proteins are true virion components are unknown and the majority of these may not be. Through functional analysis, it is found that IRSp53 and fascin are critical for the egress process and play a role in direct cell-cell transmission. Moreover, it is shown that CDC42 and Rac1 are also involved in the production of mature extracellular virions. The results suggest that the formation of the filopodia-like cytoskeleton and the rearrangement of the membrane, which are both associated with IRSp53 and fascin, may be important for the transmission of viruses used in neuronal tracing.


[Lipids in the process of synaptic vesicle exo- and endocytosis].
The phenomenon of synaptic transmission is based on the processes of synaptic vesicle exo- and endocytosis carried out with complex protein-dependent mechanisms. The SNARE-complex forming proteins (synaptobrevin, syntaxin, SNAP-25), synaptotagmin, Munc13, Munc18, NSF, alpha-SNAP are involved in exocytosis, while the synaptic vesicle endocytosis is mediated by another protein (clathrin, AP-2, epsin, endophilin, amphiphysin, dynamin, synaptojanin, Hsc70). In recent years, data on critical role of various lipids in exo- and encocytosis are collected. Most interesting results are received about significance of the cholesterol, phosphoinositides, phosphatidic and polynonsaturated fat acids in the exo-endocytosis cycle. Participation of lipid rafts in synaptic vesicle recycling is discussed. In this article, the data of the last years, including the authors' own data about role of some lipids and lipid-modifying enzimes in processes of exo- and endocytosis are presented.


Effectiveness of Video-Assisted Thoracoscopic Surgery in Undiagnosed Exudative Pleural Effusions.
Undiagnosed pleural effusions mostly require histologic studies for a definite diagnosis. In addition, malignant pleural effusions responsible for a significant part of exudative pleurisy need palliative therapy The purpose of our study is to research the effectiveness of video-assisted thoracoscopic surgery in definitive diagnosis and palliative treatment of unexplained non-parapneumonic exudative pleural effusions. The study included 263 patients with non-parapneumonic exudative pleurisy, which could not be diagnosed by an initial clinical, radiological, biochemical, microbiological, and cytological investigation in three centers. All patients underwent video-assisted thoracoscopic surgery for definitive diagnosis between January 2002 and January 2018. Patients' data were retrospectively analyzed in terms of age, gender, symptoms, previously diagnosed cancers, computerized tomography of chest findings, histopathological diagnosis, cytological diagnosis, morbidity, mortality, and success rates of the procedure. Patient groups from the three centers were divided into three groups according to the center of the patient. The groups were compared statistically in terms of cytologic diagnosis rates. The most common complaint was dysnea (66.5%). Of the 263 cases, 83 were previously diagnosed with cancer. The simple pleural effusion (66.5%) was the most frequent radiological finding. The success rate for definitive diagnosis was detected as 97%. Of all the cases, the rate of specific cytological diagnosis was detected to be 34%. The cytologic diagnosis rate was meaningfully lower in Group 1than in Groups2 and 3. The postoperative morbidity rate was detected as 9%. Video-assisted thoracic surgery is not only a rapid and effective diagnostic method, but also a palliative therapeutic method. We think that it should be used immediately after initial diagnostic thoracentesis in undiagnosed exudative PEin the less experienced centers.


Nucleotide binding to noncatalytic sites is essential for ATP-dependent stimulation and ADP-dependent inactivation of the chloroplast ATP synthase.
Light-dependent binding of labeled ADP and ATP to noncatalytic sites of chloroplast ATP synthase and the effect of light-exposed thylakoid membrane preincubation with ADP or ATP on ATPase activity were studied. ADP binding during the preincubation was shown to inactivate the chloroplast ATPase, whereas ATP binding caused its activation. The rate and equilibrium constants of ATPase inactivation and activation were close to those of ADP and ATP binding to a noncatalytic site, with K (d) values of 38 and 33 μM, respectively. It is suggested that ADP- or ATP-binding to one of the noncatalytic sites affects the ATPase activity of chloroplast ATP synthase through a mechanism that modulates tightness of ADP binding to a catalytic site.


Evaluation of WHO criteria for diagnosis of polycythemia vera: a prospective analysis.
We prospectively evaluated the accuracy of the 2007 World Health Organization (WHO) criteria for diagnosing polycythemia vera (PV), especially in "early-stage" patients. A total of 28 of 30 patients were diagnosed as PV owing to an elevated Cr-51 red cell mass (RCM), JAK2 positivity, and at least 1 minor criterion. A total of 18 PV patients did not meet the WHO criterion for an increased hemoglobin value and 8 did not meet the WHO criterion for an increased hematocrit value. Bone marrow morphology was very valuable for diagnosis. Low serum erythropoietin (EPO) values were specific for PV, but normal EPO values were found at presentation (20%). We recommend revision of the WHO criteria, especially to distinguish early-stage PV from essential thrombocythemia. Major criteria remain JAK2 positivity and increased red cell volume, but Cr-51 RCM is mandatory for patients who do not meet the defined elevated hemoglobin or hematocrit value (>18.5 g/dL and 60% in men and >16.5 g/dL and 56% in women, respectively). Minor criteria remain bone marrow histology or a low serum EPO value. For patients with a normal EPO value, marrow examination is mandatory for diagnostic confirmation. Because the therapies for myeloproliferative disorders differ, our data have major clinical implications.


Hypertelorism: interorbital growth, measurements, and pathogenetic considerations.
Normal pre- and post-natal changes in the interorbital distance are described. Causes of illusory hypertelorism include flat nasal bridge, epicanthic folds, exotropia, widely-spaced eyebrows, narrow palpebral fissures, and dystopia canthorum. Measurements of hypertelorism may involve soft tissues or bone, and a number of indices have also been proposed. Various types of measurements are evaluated and recommendations suggested. Possible pathogenetic mechanisms for hypertelorism include: early ossification of the lesser wings of the sphenoid; failure in nasal capsule development allowing the primitive brain vesicle to protrude into the space normally occupied by the capsule resulting in morphokinetic arrest in the position of the eyes; and disturbances of the cranial base in Apert syndrome. Associations with increased interorbital distance are also discussed: orofacial clefting, nonprotruding lipomas of the corpus callosum, calcification of the falx cerebri, duplication of the crista galli, wrinkling of the nose, and tissue tags of the nose. Finally, experimental models of hypertelorism in animals are discussed.


Reliability of Fossae Lumbales Laterales and Pelvic Incidence for Estimating Transsacral Corridors Assessed Using Reconstruction Computed Tomography.
The present study aimed to evaluate the effect of fossae lumbales laterales and pelvic incidence (PI) on transsacral corridors. Patients who underwent pelvic computed tomography (CT) during routine therapy in a single center between 2015 and 2020 were retrospectively reviewed. The patients' age and sex were documented during CT examination. Measurements were performed for both the upper and second sacral segments. Height and weight of the patients were determined using appropriate tools and body mass index (BMI) was calculated. Transsacral corridors were identified in true coronal and true sagittal planes and their width was determined as the maximum gap measured so that no screws could come out of the transacral corridors. PI was measured. Our study included 244 (57%) male and 184 (43%) female patients, who had a mean age of 49.3 ± 14.15 years (range, 18-89 years) and a mean BMI of 26.57 ± 2.38 kg/m2. No statistically significant correlation was found between the detection of the dimple sign in physical examination and the presence of an adequate corridor. The PI was statistically significantly higher in the patients with dimples (p < 0.001). PI of the female patients was higher than that of the male patients (p = 0.026). The correlation between PI and the existence of adequate corridors for S1 and S2 screws was not statistically significant (p = 0.858 and p = 0.129, respectively). On the relationship between the presence of adequate S1 and S2 corridors where transsacral screws could be sent, an inverse relationship was detected: if the S1 transsacral corridor was adequate, the S2 corridor was inadequate or vice versa. We could not obtain meaningful results on the use of the dimples of Venus or PI instead of CT to evaluate the adequacy of transverse corridors. Nevertheless, we confirmed that an increased PI was associated with the presence of dimples of Venus.


Metabolism of 14C-naphthalene in marine sediments.
Metabolism of 14C-naphthalene was studied in aerobic and anaerobic marine sediments from the Mumbai coast, India using a continuous flow-through system for 5 weeks. There was no volatilisation of naphthalene from anaerobic sediment. Naphthalene underwent more extensive mineralization in aerobic sediment (31.6% of the applied activity) than in anaerobic sediment (5% of the applied activity). No metabolite of naphthalene was present in sediments at the end of the incubation period.


[Vecuronium: onset of effect and intubation conditions in comparison to pancuronium and suxamethonium].
The onset of neuromuscular blockade following the i.v. injection of vecuronium and pancuronium 0.05, 0.08 or 0.1 mg/kg and suxamethonium 0.5 or 1.0 mg/kg was studied in 304 patients during induction of anaesthesia by means of the compound action potential derived from the adductor pollicis muscle, which was indirectly stimulated via the ulnar nerve. The intubation conditions 1-5 min after injection were assessed using a scoring system related to ease of laryngoscopy, movement of vocal cords and coughing, and reflex movements of extremities. Development of motor blockade was time- and dose-dependent. After administration of 0.1 mg/kg vecuronium, the actual maximum effect (more than 90% block) was established within 4 min; after 0.1 mg/kg pancuronium within 6 min and after 1.0 mg/kg suxamethonium within 2 min. Intubation conditions improved with time. After 0.1 mg/kg vecuronium atraumatic intubation was possible within 2 min and after 0.1 mg/kg pancuronium within 4 min. Following 1.0 mg/kg suxamethonium, optimum intubation conditions were achieved within 1 min. Although suxamethonium acts the fastest and tracheal intubation can be achieved within 0.5-1.0 min, its use involves certain side effects and disadvantages. Vecuronium acts considerably faster than pancuronium and good or excellent intubation conditions are present within 2 min. Suxamethonium is no longer the muscle relaxant of choice for intubation except for crash intubation, e.g., in patients with a full stomach.