Production of recombinant His-tagged triple-FLAG peptide in Brevibacillus choshinensis and its utilization as an easy-to-remove affinity peptide.
Triple-FLAG (3 × FLAG)-tagged proteins can be affinity purified through binding to an anti-FLAG antibody and competitive elution with excess free 3 × FLAG peptide. To expand the availability of the 3 × FLAG purification system, we produced a recombinant His-tagged 3 × FLAG peptide in Brevibacillus choshinensis. The screening of connecting linkers between His-tag and the 3 × FLAG peptide, culture containers, and culture media showed that the His-tagged 3 × FLAG peptide with an LA linker was most expressed in 2SY medium using a baffled shake flask. The peptide was affinity-purified to give a yield of about 25 mg/L of culture. The peptide was effective for eluting 3 × FLAG-tagged α-amylase from anti-FLAG magnetic beads. Finally, the peptide remaining in the amylase fraction was removed by His-tag affinity purification. These results show that the recombinant His-tagged 3 × FLAG peptide can function as an easy-to-remove affinity peptide in the 3 × FLAG purification system.


AL Amyloidosis: Current Chemotherapy and Immune Therapy Treatment Strategies: JACC: CardioOncology State-of-the-Art Review.
Immunoglobulin light chain (AL) amyloidosis is an incurable plasma cell disorder characterized by deposition of fibrils of misfolded immunoglobulin free light chains (FLC) in target organs, leading to failure. Cardiac involvement is common in AL amyloidosis and represents the single most adverse prognostic feature. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to arrest the process of amyloid deposition and preserve organ function. The clinical use of molecularly targeted drugs, such as proteasome inhibitors and immunomodulatory agents, monoclonal antibodies such as daratumumab, and risk-adjusted autologous stem cell transplant in eligible patients, has radically changed the natural history of AL amyloidosis. Here, we review the state-of-the-art treatment landscape in AL amyloidosis with an eye toward future therapeutic venues to impact the outcome of this devastating illness.


Photophysical Properties and Heterogeneous Photoredox Catalytic Activities of Ru(bpy)3 @InBTB Metal-Organic Framework (MOF).
Metal-organic frameworks (MOFs) with negatively charged frameworks are suitable for selectively encapsulating cationic guest ions via a cation-exchange process. Encapsulating photoactive [RuL3 ]2+ polypyridine complexes into the preorganized mesoscale channels of a MOF is a good method for stabilizing the excited states of the complexes. Three new RuL3 @InBTB MOFs were prepared by encapsulating cationic [Ru(bpy)3 ]2+ (bpy=2,2'-bipyridine), [Ru(phen)3 ]2+ (phen=1,10-phenanthroline), and [Ru(bpz)3 ]2+ (bpz=2,2'-bipyrazine) into the mesopores of a three-dimensional (3D) InBTB MOF (H3 BTB=1,3,5-benzenetribenzoic acid). The photophysical properties of the resulting materials were investigated by photoluminescence (PL) analysis. The photoredox catalytic activities were also investigated for the aza-Henry reaction, hydrogenation of dimethyl maleate, and decomposition of methyl orange under visible light irradiation at room temperature. RuL3 @InBTB MOFs were found to be very stable and highly recyclable photoredox catalytic systems.


Evaluation of seven different enzyme-linked immunosorbent assays for serodiagnosis of Staphylococcus aureus bacteremia.
Serologic assays for Staphylococcus aureus antibodies were evaluated regarding their ability to differentiate between uncomplicated and complicated S. aureus bacteremia, between S. aureus and non-S. aureus bacteremia, and between S. aureus and non-S. aureus endocarditis. Enzyme-linked immunosorbent assays (ELISAs) were performed to measure Ig G antibodies against seven S. aureus antigens (peptidoglycan, teichoic acid, S. aureus ultrasonicate, whole S. aureus cells, alpha-toxin, lipase and capsular polysaccharide) in 129 patients with S. aureus bacteremia (including 51 with endocarditis), 78 patients with non-S. aureus bacteremia (including 27 with endocarditis) and 100 febrile non-bacteremic controls. Whole-cell ELISA was the most sensitive assay. The specificity of all assays was low. Two different combinations of ELISAs for whole cells, teichoic acid,alpha-toxin, lipase and capsular polysaccharide did distinguish between S. aureus and non-S. aureus endocarditis, but not between uncomplicated and complicated S. aureus bacteremia.


Psychosocial factors significantly predict driving self-regulation in Australian older adults.
This study aimed to investigate: (i) whether attitudes and beliefs about driving predict older adults' driving self-regulation, and how much variance in self-regulation can be explained by these factors; and (ii) if driving confidence is controlled, whether attitudes and beliefs remain significant independent predictors of driving self-regulation. The present study examined the psychosocial factors that underlie driving self-regulation in 277 older adults within Australia. Participants completed standardised questionnaires about their driving, attitudes, belief and use of driving self-regulation. Driving confidence, affective and instrumental attitude, and perceived behavioural control were all significant predictors of driving self-regulation. The combination of these factors accounted for 56% of the variance in driving self-regulation. Driving self-regulation is a complex behaviour influenced by a wide range of psychosocial factors. Improved understanding of these factors could inform strategies to improve older driver safety and influence the advice that people receive.


Polymorphonuclear leukocyte dysfunction in children with recurrent otitis media.
Depressed PMN chemotactic responsiveness was observed in 17.5% of 97 patients studied, depressed PMN bactericidal activity in 23.3% of 30 patients, and depressed PMN chemiluminescence activity in 15.8% of 19 patients. Depressed chemotactic


The Need for Governance by Experimentation: The Case of Biofuels.
The policies of the European Union concerning the development of biofuels can be termed a lock-in. Biofuels were initially hailed as a green, sustainability technology. However evidence to the contrary quickly emerged. The European Commission proposed to alter its policies to accommodate for these effects but met with fierce resistance from a considerable number of member states who have an economic interest in these first generation biofuels. In this paper I argue that such a lock-in might have been avoided if an experimental approach to governance had been adopted. Existing approaches such as anticipation and niche management either do not reduce uncertainty sufficiently or fail to explicitly address conflicts between values motivating political and economic support for new technologies. In this paper, I suggest to apply an experimental framework to the development of sustainable biobased technologies. Such an approach builds on insights from adaptive management and transition management in that it has the stimulation of learning effects at its core. I argue that these learning effects should occur on the actual impacts of new technologies, on the institutionalisation of new technologies and most specifically on the norms and values that underly policies supporting new technologies. This approach can be relevant for other emerging technologies.


An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation.
Foreign protein antigens must be broken down within endosomes or lysosomes to generate suitable peptides that will form complexes with class II major histocompatibility complex molecules for presentation to T cells. However, it is not known which proteases are required for antigen processing. To investigate this, we exposed a domain of the microbial tetanus toxin antigen (TTCF) to disrupted lysosomes that had been purified from a human B-cell line. Here we show that the dominant processing activity is not one of the known lysosomal cathepsins, which are generally believed to be the principal enzymes involved in antigen processing, but is instead an asparagine-specific cysteine endopeptidase. This enzyme seems similar or identical to a mammalian homologue of the legumain/haemoglobinase asparaginyl endopeptidases found originally in plants and parasites. We designed competitive peptide inhibitors of B-cell asparaginyl endopeptidase (AEP) that specifically block its proteolytic activity and inhibit processing of TTCF in vitro. In vivo, these inhibitors slow TTCF presentation to T cells, whereas preprocessing of TTCF with AEP accelerates its presentation, indicating that this enzyme performs a key step in TTCF processing. We also show that N-glycosylation of asparagine residues blocks AEP action in vitro. This indicates that N-glycosylation could eliminate sites of processing by AEP in mammalian proteins, allowing preferential processing of microbial antigens.


Implementing a computer software system.
A great deal of time and energy goes into deciding what software computer system to purchase for the nursing department. Too often following purchase, we think our work is over, when in reality, the most critical phase is starting--installing the system. This article discusses critical responsibilities of both nurse administrators and installers during implementation of the system.


Gaze-based assistive technology in daily activities in children with severe physical impairments-An intervention study.
To establish the impact of a gaze-based assistive technology (AT) intervention on activity repertoire, autonomous use, and goal attainment in children with severe physical impairments, and to examine parents' satisfaction with the gaze-based AT and with services related to the gaze-based AT intervention. Non-experimental multiple case study with before, after, and follow-up design. Ten children with severe physical impairments without speaking ability (aged 1-15 years) participated in gaze-based AT intervention for 9-10 months, during which period the gaze-based AT was implemented in daily activities. Repertoire of computer activities increased for seven children. All children had sustained usage of gaze-based AT in daily activities at follow-up, all had attained goals, and parents' satisfaction with the AT and with services was high. The gaze-based AT intervention was effective in guiding parents and teachers to continue supporting the children to perform activities with the AT after the intervention program.


Flat clathrin lattices are linked to metastatic potential in colorectal cancer.
Clathrin assembles at the cells' plasma membrane in a multitude of clathrin-coated structures (CCSs). Among these are flat clathrin lattices (FCLs), alternative clathrin structures that have been found in specific cell types, including cancer cells. Here we show that these structures are also present in different colorectal cancer (CRC) cell lines, and that they are extremely stable with lifetimes longer than 8 h. By combining cell models representative of CRC metastasis with advanced fluorescence imaging and analysis, we discovered that the metastatic potential of CRC is associated with an aberrant membranous clathrin distribution, resulting in a higher prevalence of FCLs in cells with a higher metastatic potential. These findings suggest that clathrin organization might play an important yet unexplored role in cancer metastasis.


Effects of moxibustion on cognition and activities of daily living in post-stroke cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.
Post-stroke cognitive impairment (PSCI) imposes a huge burden on patients and society as a whole; however, unequivocally effective treatments for PSCI are still lacking. Therefore, the exploration of effective and safe non-pharmacological treatment modalities for PSCI is a key imperative. Moxibustion has been widely used for cognitive rehabilitation; however, there is a paucity of systematic reviews of the available evidence. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that investigated the effectiveness of moxibustion for treatment of PSCI to provide evidence base for the treatment of PSCI with moxibustion. To evaluate the efficacy of moxibustion in improving cognitive function and activities of daily living (ADLs) in patients with PSCI. Systematic review and meta-analysis of RCTs. Patients with a clinical diagnosis of PSCI. Relevant studies published in English or Chinese were retrieved from ten databases until December 2021. RCTs that assessed the efficacy of moxibustion on cognitive functioning and ADL in patients with PSCI were included. Two reviewers independently identified the trials and extracted the data. Risk-of-bias was assessed using the Cochrane Risk of Bias Tool. Cochrane's Review Manager (RevMan 5.4) software was used for the meta-analysis. Eighteen RCTs (1290 participants) qualified the inclusion criteria and were included. Compared with the control group, the addition of moxibustion significantly improved the cognitive function, evaluated using the Montreal Cognitive Assessment (MoCA) [pooled mean difference (MD): 2.27, 95% CI: 1.98, 2.55, I2 = 22%]. The pooled MD of Mini-Mental State Examination (MMSE) score was 1.85 (95% CI: 1.56, 2.15, I2 = 26%), and the pooled odds ratios (OR) total effective rate was 4.74 (95% CI: 2.55, 8.80, I2 = 0%) (p < 0.05 for all). Moxibustion also significantly improved ADL, assessed using Modified Barthel Index (MBI) (pooled MD = 4.10, 95% CI: 2.10 to 6.10, I2 = 0%) and Barthel Index (pooled MD: 8.63, 95% CI: 7.47, 9.79, I2 = 5%) (p < 0.05 for all). Compared with control group, the addition of moxibustion significantly improved the cognition and ADL of patients with PSCI. Nurses can incorporate moxibustion into the rehabilitation nursing of PSCI.


Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial.
Endometriosis-associated chronic pelvic pain (EACPP) presents with an intense inflammatory reaction. Melatonin has emerged as an important analgesic, antioxidant, and antiinflammatory agent. This trial investigates the effects of melatonin compared with a placebo on EACPP, brain-derived neurotrophic factor (BDNF) level, and sleep quality. Forty females, aged 18 to 45 years, were randomized into the placebo (n = 20) or melatonin (10 mg) (n = 20) treatment groups for a period of 8 weeks. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on daily pain, dysmenorrhea, dysuria, and dyschezia (analysis of variance, P < 0.01 for all analyses). Post hoc analysis showed that compared with placebo, the treatment reduced daily pain scores by 39.80% (95% confidence interval [CI] 12.88-43.01%) and dysmenorrhea by 38.01% (95% CI 15.96-49.15%). Melatonin improved sleep quality, reduced the risk of using an analgesic by 80%, and reduced BNDF levels independently of its effect on pain. This study provides additional evidence regarding the analgesic effects of melatonin on EACPP and melatonin's ability to improve sleep quality. Additionally, the study revealed that melatonin modulates the secretion of BDNF and pain through distinct mechanisms.


Ammonium Bicarbonate Addition Improves the Detection of Proteins by Desorption Electrospray Ionization Mass Spectrometry.
The analysis of protein by desorption electrospray ionization mass spectrometry (DESI-MS) is considered impractical due to a mass-dependent loss in sensitivity with increase in protein molecular weights. With the addition of ammonium bicarbonate to the DESI-MS analysis the sensitivity towards proteins by DESI was improved. The signal to noise ratio (S/N) improvement for a variety of proteins increased between 2- to 3-fold relative to solvent systems containing formic acid and more than seven times relative to aqueous methanol spray solvents. Three methods for ammonium bicarbonate addition during DESI-MS were investigated. The additive delivered improvements in S/N whether it was mixed with the analyte prior to sample deposition, applied over pre-prepared samples, or simply added to the desorption spray solvent. The improvement correlated well with protein pI but not with protein size. Other ammonium or bicarbonate salts did not produce similar improvements in S/N, nor was this improvement in S/N observed for ESI of the same samples. As was previously described for ESI, DESI also caused extensive protein unfolding upon the addition of ammonium bicarbonate. Graphical Abstract .


Effects of inhibitors of lipid synthesis on the replication of Rous sarcoma virus. A specific effect of cerulenin on the processing of major non-glycosylated viral structural proteins.
The effects of two inhibitors of lipid biosynthesis on the replication of Rous sarcoma virus Prague C strain in chick embryo fibroblasts have been examined in media containing delipidated serum. 25-Hydroxycholestetate into sterols, had no effect on the formation of infectious virions or on the synthesis and processing of intracellular virion proteins. Cerulenin strongly inhibited [1(-14C)]acetate incorporation into fatty acids and partially inhibited its incorporation into sterols in chick embryo cells. Rous sarcoma virus production as measured by focus formation and by the production of [35S]methionine-labeled virions was strongly inhibited within 5 h after cerulenin addition to infected cultures. Examinatin of extracts of these cells revealed the accumulation of the 76 000 dalton precursor (Pr76) of the major non-glycosylated virion structural proteins, p27, p19, p15 and p12. The failure to process the 76 000 dalton precursor was coincident in time with the decrease in viron production. Neither whole serum nor mixtures of fatty acids plus cholesterol were able to reverse the effects of cerulenin.


Aurora kinases: shining lights on the therapeutic horizon?
The Aurora kinases have been implicated in tumorigenesis and are important regulators of diverse cell cycle events, ranging from the entry into mitosis, centrosome function, mitotic spindle formation, chromosome biorientation and segregation, and cytokinesis. The recent identification of novel binding partners and key downstream effectors, together with new small-molecule inhibitors that display efficacy against tumours, heralds an upsurge of interest in these critical kinases. This review details new developments in the field and analyses the potential of Aurora kinases as anticancer targets.


High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life.
Children with eczema and sensitization to foods are recommended skin care and, if food allergy is proven by challenge, an elimination diet. For most children the diet period is transient, but the process behind tolerance development and the influence of decreased allergen exposure is not fully known. The aim of the study was to investigate the effect of elimination diet on serum and salivary antibodies and to identify immunological parameters related to the ability to tolerate foods. Eighty-nine children, below 2 yr of age, with eczema and suspected food allergy were included. Recommended treatment was skin care to all children, and 60 children had a period of elimination diet. At 4(1/2) yr of age, the children were divided into two groups, based on if they had been able to introduce the eliminated foods, or not. Serum and salivary antibodies were analyzed with enzyme-linked immunosorbent assay and UniCAP before and after a 6-wk treatment period and at 4(1/2) yr of age. Children sensitized to egg and/or milk that could eat and drink the offending foods at 4(1/2) yr of age, had higher levels of Immunoglobulin G(4) antibodies to ovalbumin and beta-lactoglobulin and also higher IgG(4)/Immunoglobulin E ratios on inclusion in the study, than those who had to eliminate egg and/or milk from their diet, beyond 4(1/2) yr of age. The highest IgG(4)/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative skin prick test on inclusion. The 6-wk treatment period did not significantly affect the levels of serum and salivary antibodies. In conclusion, eczematous, food sensitized infants with high levels of IgG(4) and high ratios of IgG(4)/IgE antibodies to food allergens are more likely to consume these foods at 4(1/2) yr than infants with low levels and ratios.


Hemispheric activity of 40 Hz EEG during recall of emotional events: differences between low and high hypnotizables.
This study evaluates individual differences in hypnotizability as reflected in waking-state hemispheric engagement during recollection of 3 positively and 3 negatively valenced personal life events. The State-Trait Anxiety Inventory, Maudsley Personality Inventory, Tellegen Absorption Scale and Harvard Group Scale of Hypnotic Susceptibility (Form A) were administered. Electromyogram (EMG) and bilateral electroencephalogram (EEG) activities within the 40-Hz band were recorded during rest and task conditions in 22 high and 21 low hypnotizable women. Self-report rating scores for vividness of visual imagery and emotional feeling of the material recalled were evaluated. The 40-Hz EMG amplitude and both hemisphere 40-Hz EEG densities were obtained. A 40-Hz EEG ratio, as a measure of hemispheric asymmetry, and a hemispheric specificity index were also computed. High hypnotizables showed significantly lower 40-Hz EEG density than low hypnotizables in all experimental conditions. The relationship between lateralization of 40-Hz EEG and emotional processing was moderated by hypnotizability. High hypnotizables, with respect to rest condition, showed an increase of density over both left and right hemispheres during two of the three positive emotional tasks, while they showed a depressed activity over the left and an increased activity over the right during negative emotional tasks. Low hypnotizables, on the other hand, did not exhibit differential hemispheric patterns that could be attributed to different emotional valences. The high group showed greater hemispheric specificity in the predicted direction than the low group. High subjects exhibited greater ratings of absorptive ability and emotional feeling than low subjects. Anxiety and EMG levels did not differ between groups. EMG was dependent on the type of emotion which showed greater activity in the negative emotion condition compared with the positive one.


A novel method for drug-target interaction prediction based on graph transformers model.
Drug-target interactions (DTIs) prediction becomes more and more important for accelerating drug research and drug repositioning. Drug-target interaction network is a typical model for DTIs prediction. As many different types of relationships exist between drug and target, drug-target interaction network can be used for modeling drug-target interaction relationship. Recent works on drug-target interaction network are mostly concentrate on drug node or target node and neglecting the relationships between drug-target. We propose a novel prediction method for modeling the relationship between drug and target independently. Firstly, we use different level relationships of drugs and targets to construct feature of drug-target interaction. Then, we use line graph to model drug-target interaction. After that, we introduce graph transformer network to predict drug-target interaction. This method introduces a line graph to model the relationship between drug and target. After transforming drug-target interactions from links to nodes, a graph transformer network is used to accomplish the task of predicting drug-target interactions.


The interaction of a trypsin-dependent neutral protease and its inhibitor found in tumour cells. Analysis of complex kinetic data involved in a thiol-disulphide exchange mechanism.
Ehrlich ascites tumour cells contain a granule-derived zymogen which on trypsin activation yields a collegenolytic neutral protease. The preparation of the granule fraction by subcellular fractionation procedure results in the preparation of a second fraction referred to as the post-granule supernatant fraction. The post-granule supernatant fraction contains a latent form of the granule-derived neutral protease and an excess of cytoplasmic inhibitor for this enzyme. The inhibitor of neutral protease is also capable of inhibiting trypsin and in each case the chemical mechanism of enzyme.inhibitor complex formation has been shown to be a reversible thiol-disulphide exchange. The post-granule supernatant fraction exhibited complex kinetic data when the interactions between the inhibitor, the latent enzymes and trypsin were examined simultaneously by incremental analysis. The data were interpreted and quantitatively analysed by computer analysis. It was demonstrated that the conventional types of analysis could not have provided meaningful interpretations of the experimental data provided by these complex-interacting systems.


Women's quality of life in the premenopausal and postmenopausal periods.
The purpose of this research was to determine the relationship between menopausal symptoms and quality of life in women in the pre and postmenopausal periods. METHODS AND INSTRUMENTS: All 171 women in the climacteric period who registered at the Pamukkale University Education and Research Hospital Obstetrics and Gynecology Clinic between January and July 2001 were included in the study. A questionnaire asking for sociodemographic information, complaints related to the climacteric period, and HRT use, as well as the WHOQOL brief, were used in order to obtain data. One hundred of the women who participated in the study were premenopausal and 71 were postmenopausal and the mean age was 47.39 (SD=6.65). No significant difference was found in pre and postmenopausal women in the comparison of their quality of physical life, psychological, social relationships and environment scores (p>0.05). The physical quality of life scores for those without vasomotor complaints in the pre and postmenopausal periods were significantly higher in those with a high educational level and women who had been menopausal between 1-5 years and more than 10 years (p<0.05). Age and HRT use in postmenopausal women were not found to affect quality of life scores (p>0.05). We did not find any significant difference in the quality of life of pre and postmenopausal women.


Acetyl group for proper protection of β-sugar-amino acids used in SPPS.
The synthesis of D-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc-GlcAPC(Ac)-OH, β-SAAs consisting of only 4-5 synthetic steps. Their active ester and amide bond formation with glycine methyl ester (H-Gly-OMe) was completed and monitored by 1H NMR. The stability of the pyranoid OHs protecting the acetyl groups was investigated under three different Fmoc cleavage conditions and was found to be satisfactory even at high piperidine concentration (e.g. 40%). We designed a SPPS protocol using Fmoc-GlcAPC(Ac)-OH to produce model peptides Gly-β-SAA-Gly as well as Gly-β-SAA-β-SAA-Gly with high coupling efficiency. The products were deacetylated using the Zemplén method, which allows the hydrophilicity of a building block and/or chimera to be fine-tuned, even after the polypeptide chain has already been synthesized.


Silencing of dopamine receptor D5 inhibits the browning of 3T3-L1 adipocytes and ATP-consuming futile cycles in C2C12 muscle cells.
As a part of the catecholamines, dopamine receptors (DRs) have not been extensively studied like β3-AR in the thermogenesis process. The present study investigates the effect of DRD5 in browning events and ATP-consuming futile cycles. siRNA technology, qPCR, immunoblot analysis, immunofluorescence, and staining methods were used to investigate the effect of DRD5 on 3T3-L1 and C2C12 cells. siDdr5 increased lipogenesis-associated effectors, and adipogenesis markers while reducing the expression of beige fat effectors. ATP-consuming futile cycle markers were also reduced following the siDrd5. On the contrary, pharmacological activation of DRD5 stimulated these effectors. Our mechanistic studies elucidated that DRD5 mediates fat browning via the cAMP-PKA-p38 MAPK signalling pathway in 3T3-L1 cells as well as the cAMP-SERCA-RyR pathway for the ATP-consuming futile cycles in both cells. siDrd5 positively regulates browning and ATP-consuming futile cycles, and understanding its functions will provide insights into novel strategies to treat obesity.


Determination of the pesticide carbaryl and its photodegradation kinetics in natural waters by flow injection-direct chemiluminescence detection.
A novel flow injection-chemiluminescence method for the quantitative assay of the pesticide carbaryl in environmental samples is presented. The determination is based on the CL-emission generated by the oxidation of the pesticide with potassium permanganate. The linear response of CL-emission versus concentration is valid in the range from 0.01 to 1.0 microg mL(-1), yielding detection limits (S/N=3) as low as 14.8 ng mL(-1). The method shows high reproducibility (R.S.D.=2.29%, n=10) and is subject to minor interferences from various organic and inorganic species likely to be found in natural waters. The suggested method is rapid and capable to be fully automated, thus resulting to a method of satisfactory sampling throughput, with low detection limits and efficient precision for routine analysis. The use of this technique to a new application of direct chemiluminescence involving the determination of carbaryl photodegradation in natural waters was successfully accomplished.


Association of squamous cell carcinoma of the larynx and chronic lymphoid leukemia.
The association of squamous cell carcinoma of the larynx and chronic lymphocytic leukemia (CLL) is exceptional. We report an observation of this association and present the therapeutic problems as well as the effects on prognosis. Direct laryngoscopy showed a tumor of the right hemilarynx, with the biopsy concluding in moderately differentiated keratinizing squamous cell carcinoma. The patient had a total laryngectomy, with bilateral lymph node evidement. The anatomopathological examination of the operative specimen demonstrated infiltration of the larynx and squamous cell carcinoma adenopathies and CLL. It was decided to monitor the chronic lymphoid leukemia, classified as Binet stage B. The synchronous or metachronous onset of a second cancer in a patient with CLL is more frequent than in the general population. The synchronous association of squamous cell carcinoma of the larynx and CLL has been described only rarely. The therapeutic strategy should focus first on the cancer with the shortest survival rate. The prognosis is more negative in an association of cervicofacial squamous cell carcinoma and leukemia than in a single cervicofacial cancer.


Switch on and switch off phenomenon of liver gluconeogenic function in lamprey (Lampetra fluviatilis L.) under the influence of season and temperature.
The potential activity of pyruvate carboxylase in lamprey liver is the same as in mammals. However, at certain stages of the life cycle this reaction does not take place because of ATP deficiency in mitochondria. Energy charge potential of liver cells ranges from 0.76 to 0.11 throughout a year. Heat adaptation of lampreys leads to a rapid increase of the ATP level and of the NAD+/NADH ratio in liver. The intensity of gluconeogenesis and glycogen levels are also enhanced. Cold reacclimation reverses the effect. A scheme accounting for the temperature changes in energy status of hepatocytes has been proposed.


Assembly of N,N-disubstituted hydrazines and 1-aryl-1H-indazoles via copper-catalyzed coupling reactions.
CuI-catalyzed coupling of N-acyl-N'-substituted hydrazines with aryl iodides takes place at 60-90 °C to afford N-acyl-N',N'-disubstituted hydrazines regioselectively and thereby gives a facile method for assembling N,N-diaryl hydrazines. N-Acyl-N'-substituted hydrazines can also react with 2-bromoarylcarbonylic compounds at 60-125 °C under the catalysis of CuI/4-hydroxy-l-proline to provide 1-aryl-1H-indazoles.


Protocol for the generation of HIV-1 genomic RNA with altered levels of N 6-methyladenosine.
N 6-methyladenosine (m6A) modification of human immunodeficiency virus type 1 (HIV-1) RNA plays a critical role in regulating viral replication and evasion of innate immunity. Here, we describe a protocol for the production of HIV-1 with altered m6A levels by manipulating the expression of m6A demethylases in HIV-1 producer cells. RNA from purified virions is analyzed by northern blot and dot blot for m6A levels prior to use in downstream assays to determine the function of m6A modification of viral RNA. For complete details on the use and execution of this protocol, please refer to Chen et al. (2021).


Differences in the binding of drugs to plasma proteins from newborn and adult man. I.
The binding of various drugs to plasma proteins from adult and cord plasma was determined by equilibrium dialysis. For almost all the drugs binding to cord plasma was lower than to plasma from adults. No evidence was found that the difference in binding was due to the different protein concentration in cord and adult plasma or to an influence of substances in ultrafiltrates of the plasmas.


Influences of subanesthetic isoflurane on ventilatory control in humans.
The purpose of this study was to quantify in humans the effects of subanesthetic isoflurane on the ventilatory control system, in particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isoflurane wash-in upon sustained hypoxic steady-state ventilation, and the ventilatory response at the onset of 20 min of isocapnic hypoxia. Study 1: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set (apneic threshold). Study 2: The ventilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min after the induction of isocapnic hypoxia, were studied in 11 healthy volunteers. Study 3: The ventilatory responses to a step decrease in end-tidal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 breaths; duration of hypoxia 20 min) were assessed in eight healthy volunteers at 0, 0.1, and 0.2 MAC isoflurane. Values are reported as means +/- SF. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 l.min-1.mmHg-1 (isoflurane; P < 0.01). The central carbon dioxide sensitivities (control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 l.min-1.mmHg-1) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0.2 mmHg) did not differ between treatments. Study 2: Within 30 s of exposure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 l.min-1 (hypoxia, isoflurane). Study 3: At the initiation of hypoxia ventilation increased by 7.7 +/- 1.4 (control), 4.1 +/- 0.8 (0.1 MAC; P < 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P < 0.05 vs. control) l.min-1. The subsequent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0.5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P < 0.05 vs. control) l.min-1. There was a good correlation between the acute hypoxic response and the hypoxic ventilatory decrease (r = 0.9; P < 0.001). The results of all three studies indicate a selective and profound effect of subanesthetic isoflurane on the peripheral chemoreflex loop at the site of the peripheral chemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.


Prenatal diagnosis of Pallister-Killian syndrome.
We describe a case of Pallister-Killian syndrome ascertained by routine amniocentesis as i(12p). The i(12p) was also found in 4 tissues of the aborted fetus, where various degrees of mosaicism 46/47 + i(12p) were seen. Although autopsy showed no major malformations, some of the minor anomalies of Pallister-Killian syndrome were found.


The Impact of Lumbar Spine Disease and Deformity on Total Hip Arthroplasty Outcomes.
Concurrent spine and hip disease is common. Spinal deformities can restrict lumbar range of motion and lumbar lordosis, leading to pelvic obliquity and increased pelvic tilt. A comprehensive preoperative workup and component templating ensure appropriate compensation for altered pelvic parameters for implantation of components according to functional positioning. Pelvic obliquity from scoliosis must be measured to calculate appropriate leg length. Cup positioning should be templated on standing radiograph to limit impingement from cup malposition. In spinal deformity, the optimal position of the cup that accommodates pelvic parameters and limits impingement may lie outside the classic parameters of the safe zone.


Evaluation of a delayed-type hypersensitivity test for the diagnosis of Brucella abortus infection in cattle.
The delayed-type hypersensitivity (DTH) test was used to diagnose brucellosis in two cows experimentally induced with brucellosis, and 176 dairy cows from a farm suspected of brucellosis. DTH test results were compared with results of the milk ring test, the serum agglutination test, the complement fixation test and the Coombs test. Cows positive in the DTH test and in one of the other tests were examined bacteriologically. In experimentally infected animals the DTH test was positive 10 days after infection, 1-4 weeks before serologic tests indicated brucellosis. Although the DTH test was positive during the whole experiment, on the one occasion when serologic titres were high, it was negative. Of the 176 dairy cows, 45 were positive in one or more serologic tests. In twelve cows (29%) the diagnosis was inconclusive because they were positive in only one of the serologic tests. In these cases the DTH test confirmed the infection. Three cows with high serologic response tested negative in the DTH test. B. abortus was isolated from 13 of 15 cows examined. We conclude that when serologic results are ambiguous, the DTH test is a useful additional technique for diagnosing brucellosis.


Reproductive history, sexual behavior and use of contraception in women with epilepsy.
Women with epilepsy experience more pregnancy-related risks than do their healthy peers. Guidelines recommend highly effective contraception. However, their contraceptive practices remain unknown. We conducted a cross-sectional questionnaire study among reproductive-age women (18-44 years) with epilepsy presenting for routine, outpatient visits to an urban, academic medical center. Our questionnaire, in English or Spanish, included demographic characteristics, reproductive history, antiepileptic drug use, sexual behavior and contraception. Participants had a mean age of 32 years (S.D.=8), 32% spoke Spanish and described themselves as Hispanic. Participants reported a wide range of educational attainment, insurance payor and income. About half of the participants reported at least one pregnancy, and 50% of the 181 pregnancies reported were unplanned. Among the 53% who reported intercourse in the last month, 74% used contraception, 15% were pregnant, 5% did not want to use contraception, 3% sought pregnancy and 3% had hysterectomy. Of those using contraception, 53% used highly effective methods (sterilization, intrauterine device, hormonal pill, patch and injection), and 47% used less effective methods (condom, withdrawal, rhythm and spermicide). Among the 21 participants using hormonal methods, six concomitantly took enzyme-inducing antiepileptic drugs potentially increasing susceptibility to pregnancy. In this sample of women with epilepsy about half reported prior pregnancies; 50% were unplanned. Of those using contraception, only 53% used a highly effective method. Future studies should determine generalizability of these findings and explore reasons for inadequate family planning in women with epilepsy.


The lncRNA Ftx/miR-382-5p/Nrg1 axis improves the inflammation response of microglia and spinal cord injury repair.
During spinal cord injury (SCI), a quick and sustained decline of Neuregulin-1 (Nrg1) has been observed, exerting a significant positive effect in modulating the proliferation of astrocytes and the formation of glial scars within the damaged spinal cord. In this study, we revealed the abnormal downregulation of lncRNA Ftx and Nrg1 and upregulation of miR-382-5p after SCI, which contributed to the inflammatory response in microglial cells and affected SCI repair. Ftx overexpression was significantly reduced, and Ftx knockdown further promoted LPS effects on the inflammatory factors, indicating that lncRNA Ftx might affect the microglial inflammatory response. miR-382-5p targeted both lncRNA Ftx and Nrg1, and lncRNA Ftx competed with Nrg1 for miR-382-5p binding to act as a ceRNA, therefore counteracting miR-382-5p-mediated inhibition of Nrg1. miR-382-5p overexpression was significantly enhanced, and Nrg1 overexpression attenuated LPS effects on inflammatory factors within the microglia. Under LPS stimulation, the effects of Ftx overexpression were significantly reversed by overexpression of miR-382-5p, and the effects of miR-382-5p overexpression were significantly reversed by Nrg1 overexpression. In summary, the lncRNA Ftx/miR-382-5p/Nrg1 axis improves the inflammation response of the microglia, which might improve SCI repair.


Age-related changes of the concentrations of select elements in the prostates of Japanese.
To elucidate compositional changes of the prostate with aging, the authors investigated age-related changes of elements in the prostates and the relationships among their elements using Japanese and Thai. After ordinary dissections by students at Nara Medical University and Chiang Mai University were finished, the prostates were resected from the subjects. Fifty-seven Japanese subjects ranged in age from 65 to 101 years (average age = 82.5 +/- 7.8 years), whereas 13 Thai subjects ranged in age from 43 to 86 years (average age = 67.9 +/- 11.9 years). After ashing with nitric acid and perchloric acid, element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that although there were no significant correlations between age and seven element contents, such as Ca, P, S, Mg, Zn, Fe, and Na, in the prostates of Japanese, high contents of Ca (>5 mg/g) and P (>4 mg/g) were contained in one fourth of the prostates of Japanese over 70 years of age. In the prostates of Thai, a significant direct correlation was found between age and Ca content, but it was not found between age and the other element contents, such as P, S, Mg, Zn, Fe, and Na. Regarding the relationships among their elements, extremely significant direct correlations were found among the contents of Ca, P, Mg, Zn, and Na in the prostates of Japanese. In the prostates of Thai, significant direct correlations were found among the contents of Ca, Mg, and Zn, but no significant correlations were found between Ca and P contents and between P and Mg contents. Regarding the relationships among their elements, there were differences between the prostates of Japanese and Thai. To examine whether element contents changed in prostatic hypertrophy, the transverse width of the Japanese prostates was measured. No significant correlations were found between the transverse width and element contents, such as Ca, P, S, Mg, Zn, Fe, and Na, in the Japanese prostates. Therefore, it is unlikely that the increase of elements results in prostatic hypertrophy.


Anticipatory consonant-to-vowel coarticulation in the production of VCV sequences in Italian.
The study of the spatio-temporal interactions between contiguous segments in speech is a means for a better understanding of how segments are serially organized. This research explores the relation between a vowel and the following consonant by studying the anticipatory C-to-V coarticulatory effects by means of electropalatography. The materials were 'VCV utterances produced in isolation and in connected speech by three Italian speakers, with /a/ and /i/ as vowels and the coronals /t, d, l, z, integral of/ as intervocalic consonants. The results show that the consonants affect both the vocal tract configuration of the preceding vowel and its acoustic duration. The spatial effects increase from laterals to stops to fricatives. The tongue body position is raised during /a/ and lowered during /i/. The effects are much larger for /a/ than for /i/ and larger in connected speech than in isolated words. As for temporal coarticulatory effects, the data indicate that vowels tend to be shorter before /integral of/ than before /z/, and shorter before /t/ than before /d/ than before /l/. Spatial and temporal measurements of change in tongue body contact from vowel to the consonantal closure/constriction suggest that the consonants differ among each other in the dynamics as well as in the timing of their gestures, with ampler/longer movements (e.g., for /integral of/) starting earlier than smaller/shorter movements (e.g., for /d/ or /l/). These patterns result in smaller differences between the durations of the total VC sequences than between the individual durations of V or C segments, and suggest that intersegmental organization between vowels and following consonants may have the rhythmic function of reducing the variability of vowel-to-vowel temporal intervals.


Lympho-epithelioid cellular lymphoma (Lennert's lymphoma): a case report.
A patient with Lennert's lymphoma (malignant lymphoma with a high content of epithelioid histiocytes) is described. The case is unique in that hepatosplenomegaly was the presenting feature, the diagnosis was made on bone marrow biopsy and the disorder appears to have run a benign course.


Antimicrobial susceptibility of Haemophilus influenzae among children in Beijing, China, 1999-2000.
A study on the nasopharyngeal carriage and antimicrobial susceptibility of Haemophilus influenza among children was conducted in Beijing Children's Hospital from April to May 2000. The study included 292 children between 1 and 60 mo of age with acute upper respiratory tract infection. Nasopharyngeal swabs from these patients were cultured, and 105 Haemophilus influenzae strains were isolated, 3 of which were type b. Antibiotic susceptibility of the strains was determined using disk diffusion and E-tests and the results compared with those of isolates from children with pneumonia in 1999. The carriage rate of Haemophilus influenzae was 36.0% (105/292). It was found that 4.8% and 1.0% of isolates were resistant to ampicillin and cefaclor, respectively, and 5.7%, 16.2% and 77.1% were resistant to chloramphenicol, tetracycline, and sulphamethoxazole/trimethoprim, respectively. Amoxicillin/clavulanic acid, cefuroxime, ceftriaxone, azithromycin, and clarithromycin were uniformly active to all strains. Compared with the data from 1999, there was a significant increase in resistance to tetracycline (from 12.7% in 1999 to 16.2%) and sulphamethoxazole/trimethoprim (from 40.5% in 1999 to 77.1%). H. influenzae isolates from outpatients in Beijing Children's Hospital had low ampicillin resistance and were sensitive to amoxicillin/clavulanic acid. Sulphamethoxazole/ trimethoprim resistance rates increased rapidly compared with those in the 1999 data. Further surveillance investigations are important for the choice of empiric therapy of acute respiratory tract infection.


Amorphous cellulose nanofiber supercapacitors with voltage-charging performance.
The electric charge storage properties of amorphous cellulose nanofiber (ACF) supercapacitors with different metal carboxylate radicals (COOM; M: Na(I), Ca(II), Al(III)) was investigated in terms of charging/discharging behaviours, alternating current impedance analysis, and plane-wave-based first-principles density functional calculations. Na-ACF exhibited a higher storage effect than Ca- and Al-ACFs. The charge storage mechanism for an Na-ACF supercapacitor was proposed using an electric double layer model in a C12H17O11Na electrolyte with an electrical resistivity of 6.8 × 103 Ω cm, based on the migration of protonic soliton. The supercapacitor, which demonstrated fast charging upon voltage application, could illuminate a white LED for 7 s after charging with 10 mA at 18.5 V.


Less Invasive Reoperative Ventricular Assist Device Insertion for Patients With Patent Bypass Grafts.
We report our technique for left ventricular assist device insertion that is useful in patients with patent coronary artery bypass grafts or mediastinal adhesions from other previous surgeries. An inverted-T upper hemisternotomy is made at the level of the second or third intercostal space, and with the left sternal section retracted, dissection is carried along the chest wall into the left pleural space. The device is implanted in the left ventricular apex via a left thoracotomy in the fifth or sixth intercostal space. The outflow graft is routed through the left pleural space and anastomosed to the ascending aorta.


Ultrasound-assisted extraction, analysis and antioxidant activity of polysaccharide from the rinds of Garcinia mangostana L.
According to response surface methodology (RSM), the extraction conditions of ultrasound-assisted extraction of polysaccharide from the rinds of Garcinia mangostana L. (GMRP) were optimized and determined. The optimal conditions obtained through optimization were: the liquid to material ratio was 40 mL/g, ultrasonic power was 288 W and extraction time was 65 min. The average extraction rate of GMRP was 14.73%. Ac - GMRP was obtained by acetylation of GMRP, and the antioxidant activities of the two polysaccharides were compared in vitro. The results indicated that the antioxidant capacity of polysaccharide obtained after acetylation was significantly improved compared with that of GMRP. In conclusion, chemical modification of polysaccharide is an effective measure to improve its properties to a certain extent. Meanwhile, it implies that GMRP has great research value and potential.


Systematic individual differences in sleep homeostatic and circadian rhythm contributions to neurobehavioral impairment during sleep deprivation.
Individual differences in vulnerability to neurobehavioral performance impairment during sleep deprivation are considerable and represent a neurobiological trait. Genetic polymorphisms reported to be predictors have suggested the involvement of the homeostatic and circadian processes of sleep regulation in determining this trait. We applied mathematical and statistical modeling of these two processes to psychomotor vigilance performance and sleep physiological data from a laboratory study of repeated exposure to 36 h of total sleep deprivation in 9 healthy young adults. This served to quantify the respective contributions of individual differences in the two processes to the magnitudes of participants' individual vulnerabilities to sleep deprivation. For the homeostatic process, the standard deviation for individual differences was found to be about 60% as expressed relative to its group-average contribution to neurobehavioral performance impairment. The same was found for the circadian process. Across the span of the total sleep deprivation period, the group-average effect of the homeostatic process was twice as big as that of the circadian process. In absolute terms, therefore, the impact of the individual differences in the homeostatic process was twice as large as the impact of the individual differences in the circadian process in this study. These modeling results indicated that individualized applications of mathematical models predicting performance on the basis of a homeostatic and a circadian process should account for individual differences in both processes.


Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess.
The presence of endotoxemia in peripheral venous blood was evaluated in 88 patients with alcoholic cirrhosis (AC) and in 42 patients with non-alcoholic cirrhosis (NAC). The two groups did not differ significantly with respect to mean age, liver function tests, and incidence of esophageal varices or ascites. In addition, a group of 24 patients with no evidence of chronic liver disease but with acute exposure to large quantities of alcoholic beverages was investigated. Endotoxin was determined by using the Limulus lysate test. The assays were carried out in the plasma samples by both the dilution technique and the chloroform extraction method. Endotoxemia was found more frequently in patients with AC (67.3%) than in patients with NAC (45.5%, P less than 0.025). The prevalence of endotoxemia was not significantly higher in cirrhotics with ascites or esophageal varices when compared to the subgroup without ascites or esophageal varices. Of the 24 patients with no evidence of chronic liver disease investigated because of acute alcohol excess immediately before admission 11 (45.7%) were found to have endotoxin in the peripheral venous blood. In 7 of these patients a second blood sample was tested 5-8 days later and no endotoxin could be detected. The latter results suggest that heavy alcohol abuse leads to transient endotoxemia even in patients with no signs of chronic liver disease. The findings support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.


How Work-Family Research Can Finally Have an Impact in Organizations.
Although work-family research has mushroomed over the past several decades, an implementation gap persists in putting work-family research into practice. Because of this, work-family researchers have not made a significant impact in improving the lives of employees relative to the amount of research that has been conducted. The goal of this article is to clarify areas where implementation gaps between work-family research and practice are prevalent, discuss the importance of reducing these gaps, and make the case that both better and different research should be conducted. We recommend several alternative but complementary actions for the work-family researcher: (a) work with organizations to study their policy and practice implementation efforts, (b) focus on the impact of rapid technological advances that are blurring work-family boundaries, (c) conduct research to empower the individual to self-manage the work-family interface, and (d) engage in advocacy and collaborative policy research to change institutional contexts and break down silos. Increased partnerships between industrial-organizational (I-O) psychology practitioners and researchers from many industries and disciplines could break down silos that we see as limiting development of the field.


[STUDY OF PROTECTIVE ACTIVITY OF PROTEIN-CONTAINING ANTIGENS OF STREPTOCOCCUS PNEUMONIAE IN A HETEROLOGOUS SYSTEM].
Study protective activity of protein-containing antigens of pneumococcus, obtained from serotypes 6B, 10A, 14, 19F, 23F and 36R, against infection with heterologous strains of S. pneumoniae. S. pneumoniae strains of serotypes 3, 6B, 10A, 14, 19F, 23F and 36R, obtained from the collection of pneumococcus strains of Mechnikov RIVS, were used in the study. Protein-containing antigens of S. pneumoniae were isolated by acetone precipitations of supernatant fraction of culture medium. Protective activity of preparations of protein-containing antigens of pneumococcus as studied in experiments of active protection of BALb/c line mice. The data obtained give evidence, that protein-containing antigens of pneumococcus, isolated from serotypes 6B, 10A, 14, 19F and 23F, effectively protect animals from subsequent infection with a heterologous S. pneumoniae strain of serotype 3 No. 11/56. Protection was noted at a level from 80 to 100% (p ≤ 0.05). Similar protective effect was detected in another experiment in a group of mice, immunized with preparations of protein-containing antigens of pneumococcus, obtained from serotypes 6B and 36R, against infection with a heterologous S. pneumoniae strain of serotype 3 No. 11/56. Protection was noted at a level of 90% (p ≤ 0.05). The results of the experiments carried out allow to assume, that the main role in formation of cross-protection in experiments in animals is played by pneumococcus, proteins, that are a part of the studied preparations, and not polysaccharide antigens.


Plasmodesmata dynamics are coordinated by intracellular signaling pathways.
Membrane-lined channels called plasmodesmata (PD) connect the cytoplasts of adjacent plant cells across the cell wall, permitting intercellular movement of small molecules, proteins, and RNA. Recent genetic screens for mutants with altered PD transport identified genes suggesting that chloroplasts play crucial roles in coordinating PD transport. Complementing this discovery, studies manipulating expression of PD-localized proteins imply that changes in PD transport strongly impact chloroplast biology. Ongoing efforts to find genes that control root and stomatal development reveal the critical role of PD in enforcing tissue patterning, and newly discovered PD-localized proteins show that PD influence development, intracellular signaling, and defense against pathogens. Together, these studies demonstrate that PD function and formation are tightly integrated with plant physiology.


Reconstruction of cell lineage and spatiotemporal pattern formation of the mesoderm in the amphipod crustacean Orchestia cavimana.
Cell lineage studies in amphipods have revealed an early restriction of blastomere fate. The mesendodermal cell lineage is specified with the third cleavage of the egg. We took advantage of this stereotyped mode of development by fluorescently labeling the mesodermal precursors in embryos of Orchestia cavimana and followed the morphogenesis of the mesodermal cell layer through embryonic development. The mesoderm of the trunk segments is formed by a very regular and stereotypic cell division pattern of the mesoteloblasts and their segmental daughters. The head mesoderm in contrast is generated by cell movements and divisions out of a mesendodermal cell mass. Our reconstructions reveal the presence of three different domains within the trunk mesoderm of the later embryo. We distinguish a cell group median to the limbs, a major central population from which the limb mesoderm arises and a dorsolateral branch of mesodermal cells. Our detailed description of mesodermal development relates different precursor cell groups to distinct muscle groups of the embryo. A dorsoventral subdivision of mesoderm is prepatterned within the longitudinal mesodermal columns of the germ-band stage. This makes amphipods excellent crustacean models for studying mesodermal differentiation on a cellular and molecular level.


Fat quantification: Imaging methods and clinical applications in cancer.
Recently, the study of the relationship between lipid metabolism and cancer has evolved. The characteristics of intratumoral and peritumoral fat are distinct and changeable during cancer development. Subcutaneous and visceral adipose tissue are also associated with cancer prognosis. In non-invasive imaging, fat quantification parameters such as controlled attenuation parameter, fat volume fraction, and proton density fat fraction from different imaging methods complement conventional images by providing concrete fat information. Therefore, measuring the changes of fat content for further understanding of cancer characteristics has been applied in both research and clinical settings. In this review, the authors summarize imaging advances in fat quantification and highlight their clinical applications in cancer precaution, auxiliary diagnosis and classification, therapy response monitoring, and prognosis.


Studies on the pathogenesis of ischemic cell injury. VII. Proton gradient and respiration of renal tissue cubes, renal mitochondrial and submitochondrial particles following ischemic cell injury.
Electron transport in tissue cubes, isolated mitochondria and submitochondria particles were examined as a function of ischemic time. It was found that electron transport remains active in all systems beyond the 2 hour ischemic time interval. The NADH stimulated respiration, however, declined after 2 hours of ischemia in ASU (Ammonia-Sephadex-Urea) particles followed by respiration with matrix-located dehydrogenases tested by substrates such as glutamate, alpha-ketoglutarate and pyruvate plus malate. Succinate dependent respiration remains active at control levels. In contrast proton gradient reveals changes in two phases: Phase A is characterized by gradually increasing gradient without valinomycin and by a rapidly declining gradient with valinomycin in the medium. Phase B is characterized by a declining proton gradient with or without valinomycin. It is suggested that the alteration of the proton gradient between 1 and 2 hours ischemia is an important factor contributing to irreversible cell injury.


Novel surface antigen based impedimetric immunosensor for detection of Salmonella typhimurium in water and juice samples.
A specific surface antigen, OmpD has been reported first time as a surface biomarker in the development of selective and sensitive immunosensor for detecting Salmonella typhimurium species. The OmpD surface antigen extraction was done from Salmonella typhimurium serovars, under the optimized growth conditions for its expression. Anti-OmpD antibodies were generated and used as detector probe in immunoassay format on graphene-graphene oxide (G-GO) modified screen printed carbon electrodes. The water samples were spiked with standard Salmonella typhimurium cells, and detection was done by measuring the change in impedimetric response of developed immunosensor to know the concentration of serovar Salmonella typhimurium. The developed immunosensor was able to specifically detect S. typhimurium in spiked water and juice samples with a sensitivity upto 10(1)CFUmL(-1), with high selectivity and very low cross-reactivity with other strains. This is the first report on the detection of Salmonella typhimurum species using a specific biomarker, OmpD. The developed technique could be very useful for the detection of nontyphoidal Salmonellosis and is also important from an epidemiological point of view.


Ficin: A protease extract with relevance in biotechnology and biocatalysis.
Due to the problems raised by the use of animal or microbial recombinant proteases, the use of proteases from vegetable origin is becoming increasingly popular.. Among them, sulfidryl proteases have a special interest. Ficin is an outstanding example of this kind of proteases. This paper aims to be to make a comprehensive review of the recent uses of this enzyme, including for example protein hydrolysis, the production of bioactive peptides and antibodies fragments (researchers point that ficin results are more reproducible than using other proteases), meat tenderization, milk coagulations in cheese making or peptide synthesis. Efforts to get industrial immobilized biocatalysts of the enzyme will be also described. The review shows the huge potential and brilliant prospect that this enzyme can have in the near future.


Adaptation of Essential Care for Every Baby educational program to improve infant outcomes in the context of Zika.
The outbreak and ongoing transmission of Zika virus provided an opportunity to strengthen essential newborn care and early childhood development systems through collaboration with the US Agency for International Development Applying Science to Strengthen and Improve Systems (USAID ASSIST). The objective was to create a system of sustainable training dissemination which improves newborn care-related quality indicators in the context of Zika. From 2018-19, USAID ASSIST supported a series of technical assistance visits by the American Academy of Pediatrics (AAP) in four Caribbean countries to strengthen the clinical capacity in care of children potentially affected by Zika through dissemination of Essential Care for Every Baby (ECEB), teaching QI methodology, coaching visits, and development of clinical care guidelines. ECEB was adapted to emphasize physical exam findings related to Zika. The first series of workshops were facilitated by AAP technical advisors and the second series were facilitated by the newly trained local champions. Quality of care was monitored with performance indicators at 134 health facilities. A repeated measures (pre-post) ANOVA was conducted, revealing significant pre-post knowledge gains [F(1) = 197.9, p < 0.001] on knowledge check scores. Certain performance indicators related to ECEB practices demonstrated significant changes and midline shift on the run chart in four countries. ECEB can be adapted to incorporate important local practices, causes of neonatal morbidity and mortality, and differing healthcare system structures, which, as one part of a larger technical assistance package, leads to improved performance of health systems.


Effects of preventive home visits on health care costs for ambulatory frail elders: a randomized controlled trial.
Reducing health care costs through preventive geriatric care has become a high priority in Japan. We analyzed data from a randomized controlled trial to examine the effects of a preventive home visit program on health care costs among ambulatory frail elders. Structured preventive home visits by nurses or care managers were provided to the visit group every 6 months over 2 years. The enrolled participants (N = 323) were randomly assigned to either the visit group (N = 161) or the control group (N = 162). We analyzed the health care costs, including the costs for hospitalizations and outpatient clinic utilization for participants who had health care insurance from the local government (N = 307). The visit group included 154 individuals in the visit group and 153 people in the control group. Total health care costs over the study period were not significantly different between groups, but at most monthly time points costs and those for outpatient clinic utilization in the visit group were lower than those in the control group. Hospitalizations, which accounted for more than ¥ 500,000 JPY per month, were less likely to occur more often among participants in the visit group (N = 71) than in the control group (N = 113) (OR = 0.63; p = 0.002). These results suggest that a preventive home visit program may reduce monthly health care costs, primarily by reducing hospitalization costs.


Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram-Positive Pathogens.
New 5-substituted vitamin E derivatives were semisynthesized, and their antibacterial activity against human Gram-positive and Gram-negative pathogens was evaluated. Several vitamin E analogues were active against methicillin-resistant Staphylococcus aureus (MRSA) and/or methicillin-resistant Staphylococcus epidermidis (MRSE); structure-activity relationships (SARs) are discussed. As a result, it is shown that the presence of a carboxylic acid function at the C-5 position and/or at the end of the side chain is crucial for the antibacterial activity. The bactericidal or bacteriostatic action of three compounds against MRSA and MRSE was confirmed in a time-kill kinetics study, and the cytotoxicity on human cells was evaluated. The preliminary mechanism study by confocal microscopy indicated that those vitamin E analogues led to bacterial cell death through membrane disruption.


Antioxidant enzyme activities and lipid peroxidation induced by eicosapentaenoic acid (EPA) in PC12 cells.
Eicosapentaenoic acid (EPA) is one of the major dietary polyunsaturated fatty acids and induces apoptosis in several cancer cells. In this study, the EPA induced lipid peroxidation and response of antioxidative enzymes have been investigated in rat pheochromocytoma PC12 cells to elucidate the mechanisms of apoptosis induced by the polyunsaturated fatty acid EPA. We have analyzed superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and glutathione (GSH) contents in PC12 cells after exposure to different concentrations of EPA. Lipid peroxidation was shown to increase in the presence of EPA as an indication of the oxidative damage. Lipid peroxidation was enhanced by EPA in a dose-dependent manner, and the loss of cell viability was partially reversed by vitamin E. In the case of antioxidant enzyme activities, SOD and GPX activities and GSH contents increased significantly at 50 micromol/L EPA and were respectively 2.41-fold (p < 0.01), 3.49-fold (p < 0.05), and 1.43-fold (p < 0.05) higher than controls. The CAT activity at 10 micromol/L had the highest value and was increased by 25.83% (p < 0.05) compared to control. The results suggest that in PC12 cells the mechanism of apoptosis induced by EPA may be partly due to lipid peroxidation.


Guns, violence, politics: the gyre widens.
Inter-related sustained upward trends in firearm purchasing, violence, and political extremism are converging to put the USA at risk for disaster and threaten our future as a democracy. This narrative review provides a critical assessment and call to action. It explores each trend separately, considers the effects of their likely and imminent convergence, and suggests possibilities for collective and individual action to prevent or at least reduce those effects.


Extracellular fluid expansion during parenteral refeeding.
Life emerged on our planet from a fluid environment which probably contained a similar concentration of sodium and other electrolytes to that of the extracellular fluid of mammals (1). The maintenance of the volume and composition (homeostasis) of this internal fluid surrounding all the body cells is essential for survival. Malnutrition and illness are associated with alterations in the distribution and in the renal handling of water and sodium within the body (2). Thus, an understanding of water and salt physiology is essential for the proper practice of nutritional support.


Needle stick injuries among nurses in sub-Saharan Africa.
Despite a heavy burden of HIV/AIDS and other blood borne infections, few studies have investigated needle stick injuries in sub-Saharan Africa. We conducted a cross-sectional study at Mulago national referral hospital in Kampala, Uganda, to assess the occurrence and risk factors of needle stick injuries among nurses and midwives. A total of 526 nurses and midwives involved in the direct day-to-day management of patients answered a questionnaire inquiring about occurrence of needle stick injuries and about potential predictors, including work experience, work load, working habits, training, and risk behaviour. A 57% of the nurses and midwives had experienced at least one needle stick injury in the last year. Only 18% had not experienced any such injury in their entire career. The rate of needle stick injuries was 4.2 per person-year. Multiple logistic regression analysis showed that the most important risk factor for needle stick injuries was lack of training on such injuries (OR 5.72, 95% CI 3.41-9.62). Other important risk factors included working for more than 40 h/week (OR 1.90, 95% CI 1.20-3.31), recapping needles most of the time (OR 1.78, 95% CI 1.11-2.86), and not using gloves when handling needles (OR 1.91, 95% CI 1.10-3.32). The study showed a high rate of needle stick injuries among nurses and midwives working in Uganda. The strongest predictor for needle stick injuries was lack of training. Other important risk factors were related to long working hours, working habits, and experience.


Use of n-butyl cyanoacrylate in abdominal and pelvic embolotherapy: indications and techniques, complications, and their management.
The purpose of this article is to describe the indications for use of n-butyl cyanoacrylate (NBCA) in abdominal and pelvic embolotherapy, appropriate techniques for NBCA embolotherapy, and NBCA-related complications and their management. NBCA embolotherapy is a feasible and effective method for treating a variety of abdominal and pelvic vascular lesions or tumors; however, the techniques suitable for each case and knowledge of NBCA-related complications are essential to achieve favorable outcomes.


Serum folates in young dairy heifers.
1. In the first trial, hourly blood samples were drawn during the light period (06.30-20.30 hours) from thirty-four dairy heifers in two groups of different ages. 2. Concentrations of serum folates were 8.2 (SE 0.1) ng/ml at the age of 18.2 (SE 0.6) d and 14.8 (SE 0.2) ng/ml at 120.7 (SE 2.9) d (P less than or equal to 0.001). 3. In the second trial, forty heifers were randomly assigned to a factorial experiment where age (2 weeks v. 4 months) and quantity of pteroylmonoglutamic acid injected intramuscularly (2.5, 5.0, 10.0 and 20.0 mg) were the two factors studied. Blood samples were taken immediately before injection and on days 1, 2, 3, 4, 7 and 10 after the injection. 4. Serum folates reached a maximum on day 1 after the injection of pteroylmonoglutamic acid. The response to the injection was different for the two age groups (P less than or equal to 0.0002); concentration of serum folates for 2-week-old heifers markedly increased, while in 4-month-old heifers the effect of a supplement of pteroylmonoglutamic acid was less marked. 5. These results might indicate a need for pteroylmonoglutamic acid in young animals during the development of rumen function.


Classic and reversal steps stapedotomy performed with CO2 laser: a comparative analysis.
The objective of this paper is to evaluate and compare hearing outcomes, intraoperative and postoperative complications and tinnitus characteristics, with particular regard to the effects of stapes surgery on the course of tinnitus. Two groups were evaluated: one group of patients were treated with classical stapedotomy and the second group was composed of patients who underwent reversal technique. Eighty-four patients aged between 22 and 62 years with otosclerosis were divided into two groups: group 1 (n = 49, 17 male, mean age 38, patients treated with classic stapedotomy) and group 2 (n = 35, 13 male, mean age 40, patients treated with reversal stapedotomy). Classical and reversal stapedotomy techniques were performed using CO2 laser; self-crimping titanium piston prosthesis were positioned in patients treated with reversal stapedotomy and classical stapedotomy. Preoperative and postoperative audiometric evaluation using pure tone audiometry (air-bone gap (ABG), bone-conduction thresholds and air-conduction thresholds). Tinnitus handicap inventory (THI) scale and intraoperative/postoperative complications were assessed in both groups. Wilcoxon's test and Friedman's test followed by post hoc analysis were used. There were no statistically significant differences in ABG, air conduction, bone conduction, and THI score variations after surgery between the two groups. Complications in both groups were not significant, and different. In conclusion, reversal and classic stapedotomies performed with CO2 laser can be considered efficient, safe and reliable techniques considering the hearing outcomes and complications recorded.


Are higher odontogenic infection severity scores associated with difficult intubations?
This study aimed to determine if there is a relation between odontogenic infection severity score (OISS) and difficult intubation at the time of surgical treatment for severe odontogenic infections (SOI). A secondary goal of this study was to determine the utility of OISS as a predictor of difficult intubations. This retrospective cohort study was composed of consecutive patients admitted and surgically treated in the operating room (OR) for SOIs. Patients with an OISS ≥ 5 were designated as Group 1 and < 5 Group 2. There was a statistically significant difference in difficult intubations between the two groups (p = 0.018). Patients with an OISS ≥ 5 were nearly four times more likely to be difficult intubations compared to patients with an OISS < 5 (OR 3.70, 95% CI 1.19-11.45). When OISS ≥ 5 was used to predict difficult intubation, the sensitivity was 69%, the specificity was 63%, the positive predictive value was 23%, and the negative predictive value was 93%. OISS ≥ 5 was associated with a higher prevalence of difficult intubations compared to an OISS < 5. OISS may provide clinically relevant data that can be used with established risk factors, laboratory values, and clinical judgment.


Cortical lesions interfere with behavioral recovery from unilateral substantia nigra lesions induced by brain grafts.
Effects of aspiration lesions of the cerebral cortex on the behavioral effects of intraventricular substantia nigra grafts were investigated. Apomorphine-induced rotational behavior consequent to unilateral lesions of the substantia nigra was used as a behavioral measure. Substantia nigra grafts reduced rotational behavior in animals with sham cortical lesions. Cortical lesions also decreased rotational behavior and, in these animals, no additional decrease in rotational behavior was induced by substantia nigra grafts. It is concluded that cortical lesions alter striatal circuitry so as to preclude a behavioral effect of substantia nigra grafts.


Large variation in availability of Maya food plant sources during ancient droughts.
Paleoclimatic evidence indicating a series of droughts in the Yucatan Peninsula during the Terminal Classic period suggests that climate change may have contributed to the disruption or collapse of Classic Maya polities. Although climate change cannot fully account for the multifaceted, political turmoil of the period, it is clear that droughts of strong magnitude could have limited food availability, potentially causing famine, migration, and societal decline. Maize was undoubtedly an important staple food of the ancient Maya, but a complete analysis of other food resources that would have been available during drought remains unresolved. Here, we assess drought resistance of all 497 indigenous food plant species documented in ethnographic, ethnobotanical, and botanical studies as having been used by the lowland Maya and classify the availability of these plant species and their edible components under various drought scenarios. Our analysis indicates availability of 83% of food plant species in short-term drought, but this percentage drops to 22% of food plant species available in moderate drought up to 1 y. During extreme drought, lasting several years, our analysis indicates availability of 11% of food plant species. Our results demonstrate a greater diversity of food sources beyond maize that would have been available to the Maya during climate disruption of the Terminal Classic period than has been previously acknowledged. While drought would have necessitated shifts in dietary patterns, the range of physiological drought responses for the available food plants would have allowed a continuing food supply under all but the most dire conditions.


Sodium thiosulfate treatment of tumoral calcinosis in patients with end-stage renal disease.
Three patients (2 male and 1 female) undergoing maintenance hemodialysis for more than 4 years with tumoral calcifications were treated by sodium thiosulfate. All patients had periarticular and soft tissue calcification. A considerable regression of calcified masses with concurrent clinical improvement was noted in 2 of the 3 patients.


Large-Scale Cellular Vehicle-to-Everything Deployments Based on 5G-Critical Challenges, Solutions, and Vision towards 6G: A Survey.
The proliferation of fifth-generation (5G) networks has opened up new opportunities for the deployment of cellular vehicle-to-everything (C-V2X) systems. However, the large-scale implementation of 5G-based C-V2X poses critical challenges requiring thorough investigation and resolution for successful deployment. This paper aims to identify and analyze the key challenges associated with the large-scale deployment of 5G-based C-V2X systems. In addition, we address obstacles and possible contradictions in the C-V2X standards caused by the special requirements. Moreover, we have introduced some quite influential C-V2X projects, which have influenced the widespread adoption of C-V2X technology in recent years. As the primary goal, this survey aims to provide valuable insights and summarize the current state of the field for researchers, industry professionals, and policymakers involved in the advancement of C-V2X. Furthermore, this paper presents relevant standardization aspects and visions for advanced 5G and 6G approaches to address some of the upcoming issues in mid-term timelines.


Giant cell arteritis and inflammatory bowel disease - Is there a connection? Results from a population-based study.
Giant cell arteritis (GCA) is an autoimmune disorder which primarily affects large vessels, whilst inflammatory bowel diseases (IBD) mainly target the gut. Co-existence of the two maladies has been reported sporadically in the literature; therefore the purpose of this study was to assess the authenticity of such an association in a large, cross-sectional study. Utilizing data derived from the Clalit Health Services' registry, the largest health maintenance organization in Israel, we compared the proportion of CD and UC in GCA patients with age- and gender-matched controls. Univariate analysis was performed using Chi-square and student t-test and a multivariate analysis was performed using a logistic regression model. The study included 3938 GCA patients and 21,623 age- and gender-matched controls. GCA patients had a significantly increased proportion of both CD and UC in comparison with controls (0.79% vs. 0.12% and 0.84% vs. 0.21%, P-value < .001, respectively). The strength of the association between GCA and IBD was negatively correlated with the patients' age; thus the association was more robust amongst middle-aged patients (ages 50-69, OR = 8.13) than in elderly patients (ages 70-85, OR = 3.81). The association between GCA and IBD remained significant when evaluated independently of confounding factors (OR = 2.63, P-value < .001). The probability that GCA patients also suffer from IBD is increased in comparison with age- and gender-matched controls. Our findings indicate that this association is more prominent in middle-aged patients (50-69 years of age). Screening for IBD amongst GCA patients in this age group may be warranted.


Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry.
We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]. At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge. NCT02306824.


Translating Guidelines for the Diagnosis and Management of Sports-Related Concussion Into Practice.
Sports injuries are a significant clinical and public health concern. There is a growing call to improve the translation of available evidence-based and expert-informed sports injury prevention interventions into sustained use in practice by physicians and others (eg, athletic trainers, coaches, and parents) who care for injured athletes. This article provides a brief overview of the current sport injury prevention implementation literature before focusing specifically on the translation of guidelines (including consensus and position statements) developed to assist physicians and others diagnose and manage athletes with sport-related concussion and the associated return-to-play decisions. The outcomes of more than 20 published studies indicate that physician, athletic trainer, coach, parent, and athlete knowledge, use of, and compliance with sport-related concussion guidelines are limited. More concerted, coordinated, and theory-informed efforts are required to facilitate the widespread dissemination, translation, and implementation of such guidelines. An example is provided of how implementation drivers could be used to inform the development of a comprehensive, multilevel implementation strategy targeting the individual, organizational, and system-level changes necessary to support the translation of available sport-related concussion guidelines in both the clinical and sports settings.


Insertion of 2-carboxysuccinate and tricarballylic acid fragments into cyclic-pseudopeptides: new antagonists for the human tachykinin NK-2 receptor.
A series of cyclic pseudopeptides were synthesized containing the sequence -Trp-Phe-(D)-PhePsiCH2NH-, the terminal ends of which were bound to 2-carboxy succinate or enantiomerically enriched tricarballylic acid to give the final cyclic structures. These two molecules and their subsequent derivatives were screened for h-NK2 receptor binding and functional antagonist activity on the rabbit urinary bladder.


An immunoinformatics study on the spike protein of SARS-CoV-2 revealing potential epitopes as vaccine candidates.
The pandemic situation of SARS-CoV-2 infection has sparked global concern due to the disease COVID-19 caused by it. Since the first cluster of confirmed cases in China in December 2019, the infection has been reported across the continents and inflicted upon a substantial number of populations. This study is focused on immunoinformatics analyses of the SARS-CoV-2 spike glycoprotein (S protein) which is key for the viral attachment to human host cells. Computational analyses were carried out for the prediction of B-cell and T-cell (MHC class I and II) epitopes of S protein and the analyses were extended further for the prediction of their immunogenic properties. The interaction and binding affinity of T-cell epitopes with HLA-B7 were also investigated by molecular docking. Three distinct epitopes for vaccine design were predicted from the sequence of S protein. The potential B-cell epitope was KNHTSPDVDLG possessing the highest antigenicity score of 1.4039 among other B-cell epitopes. T-cell epitope for human MHC class I was VVVLSFELL with an antigenicity score of 1.0909 and binding ability to 29 MHC-I alleles. The predicted T-cell epitope for human MHC class II molecule was VVIGIVNNT with a corresponding 1.3063 antigenicity score, less digesting enzymes, and 7 MHC-II alleles binding ability. All these three peptides were predicted to be highly antigenic, non-allergenic, and non-toxic. Analyses of the physiochemical properties of these predicted epitopes indicate their stable nature for plausible vaccine design. Furthermore, molecular docking investigation between the MHC class-I epitopes and human HLA-B7 reflects the stable interaction with high affinity among them. The present study posits three potential epitopes of S protein of SARS-CoV-2 predicted by immunoinformatic methods based on their immunogenic properties and interactions with the host counterpart that can facilitate the development of vaccine against SARS-CoV-2. This study can act as the springboard for the future development of the COVID-19 vaccine.


Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome.
Basan syndrome is a rare autosomal dominant genodermatosis, characterized by rapidly healing congenital acral bullae, congenital milia and lack of fingerprints. A mutation in the SMARCAD1 gene was recently reported to cause Basan syndrome in one family. Here, we present a large Chinese family with Basan syndrome; some patients presented with hyperpigmentation and knuckle pads in addition to previously reported clinical manifestations. We used genome-wide linkage analysis and whole-genome sequencing (WGS) to identify the pathogenic gene in this unique pedigree. Genome-wide linkage analysis successfully mapped the candidate gene to 4p15.31-4p14 and 4q13.2-4q23. The maximal LOD score was 3.01. WGS in one patient identified a splice variant (c.378+1G>T) in the SMARCAD1 gene (NG_031945.1) that was confirmed by Sanger sequencing. Co-segregation of the variant was confirmed in this pedigree. The same variant was recently found to be associated with isolated adermatoglyphia (ADG) in another family, suggesting that this variant is causative for both Basan syndrome and autosomal dominant ADG (OMIM 136 000). This indicates that ADG and Basan syndrome may be the phenotypic variants of the same disease. Further studies should be performed to elucidate the pathogenic mechanisms induced by this variant. This report increases the phenotypic spectrum of Basan syndrome and furthers our understanding of the genetic basis of this disease. Our results also highlight the power of combining WGS and genome-wide linkage analysis in identifying causative genes in pedigrees with a genetic disorder.


Signs of chronic stress in women with recurrent candida vulvovaginitis.
The purpose of this study was to determine whether there is an association between recurrent vulvovaginal candida and chronic stress. Chronic stress affects the hypothalamus-pituitary-adrenal axis, which influences the immune function. Recurrent candida vulvovaginitis is increasing. Women with recurrent vulvovaginal candida (n = 35) and age-matched healthy control subjects (n = 35) collected saliva for the analysis of cortisol. Hormone analyses of blood samples and vulvovaginal examinations were performed. A questionnaire was completed. Morning rise cortisol level was significantly blunted among patients compared with control subjects (P < .002). Mean levels of salivary cortisol were lower the first 45 minutes after awakening in women with recurrent vulvovaginal candida, compared with control subjects. More patients than control subjects reported a history of condyloma, bacterial vaginosis, and herpes genitalis. No differences were seen between patients and control subjects regarding sexual hormone binding globulin, dihydroepiandrosterone, testosterone or Hemoglobin A1c. Morning rise salivary cortisol level is blunted in women with recurrent vulvovaginal candida, which indicates signs of chronic stress. The higher incidence of vulvovaginal infections in these women compared with control subjects may reflect impaired immunity, which may be due to chronic stress.


Altered expression of autophagy-related genes might contribute to glucocorticoid resistance in precursor B-cell-type acute lymphoblastic leukemia.
Autophagy is an evolutionarily conserved process playing an important role in tumor cell's resistance to chemotherapy. Response to glucocorticoid (GC) treatment is out of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL); however, only few data are available connecting GC response and role of autophagy. Our aim was to investigate whether altered expression of autophagy-related genes contributes to GC-resistant phenotype in GC-sensitive and GC-resistant precursor B-cell-type (PBC) ALL cells. Gene expression data were obtained from public database for 26 children diagnosed with PBC ALL either sensitive or resistant to in vitro prednisolone treatment. We have identified 36 autophagy-associated genes which were differently expressed, based on at least a twofold difference, GC-sensitive group as compared to GC-resistant one. Of the 36 genes, 10 were downregulated and 26 upregulated in the GC-resistant group. The average fold change values for the decreased and increased transcripts were -4.57 and 2.67, respectively. Our data imply that GC sensitivity might depend on the expression of several genes involved in regulation and execution of autophagy in a way that key autophagy inducers are downregulated while inhibitors of autophagy are upregulated in GC-resistant cells.


Influence of hydronium, sulfate, chloride and other non-carbonate ions on hydrogen generation by anaerobic corrosion of granular cast iron.
Permeable reactive barriers are successfully applied for the removal of various contaminants. The concomitant reduction of hydrogen ions and the subsequent formation of hydrogen gas by anaerobic corrosion lead to decreased pore volume filled with water and thus residence times, so called gas clogging. Long term column experiments were conducted to elucidate the impact of ubiquitous water constituents on the formation of hydrogen gas and potential passivation due to corrosion products. The collected gas volumes revealed a relation to the hydronium concentration (pH) but were only slightly increased in the presence of chloride and sulfate and not significantly influenced in the presence of phosphate, silicate, humic acid and ammonium compared to deionized water. Significant gas volumes within the reactive filling were verified by gravimetry. The presence of nitrate completely eliminated hydrogen formation by competition for electrons. Solid phase analyses revealed that neither chloride nor sulfate was incorporated in corrosion products in concentrations above 0.1 weight percent, and they did not alter the formation of mainly magnetite in comparison to deionized water.


A simple sore throat? Retropharyngeal emphysema secondary to free-basing cocaine.
A case of retropharyngeal emphysema associated with drug abuse is presented. Although chest symptoms of pneumomediastinum have been widely reported with substance abuse, pain localized to the neck is rarely described. In the present case, localized dysphagia was the only complaint, and no free air could be demonstrated within the thorax. For uncomplicated cervical emphysema or pneumomediastinum due to substance abuse, extensive workup may be unnecessary, and conservative therapy, including administration of 100% oxygen and observation is recommended if resolution is prompt.


Pain Characteristics in Patients with Inflammatory Bowel Disease: A Monocentric Cross-Sectional Study.
The abdominal pain common in inflammatory bowel disease [IBD] patients is traditionally associated with inflammation but may persist during clinical remission. Central sensitization [CS] has not previously been explored in these patients. This study aimed to determine the epidemiology of pain in IBD patients and to specify pain characteristics with particular attention to CS. This cross-sectional study included 200 patients; 67% had Crohn's disease [CD]. Pain was assessed using the McGill questionnaire, using the Douleur Neuropathique 4 [DN4] questionnaire and by clinical examination. Its impacts on quality of life, depression and anxiety were also assessed. Three-quarters of IBD patients complained of pain, including intermittent pain attacks, 62% reported abdominal pain and 17.5% had CS. The prevalence of pain [83.6% vs 59.1%; p < 0.001] and abdominal pain [68.7% vs 48.5%; p = 0.006] was higher in CD patients than in ulcerative colitis [UC] patients. Multivariate analysis confirmed that age [p = 0.02], sex [female] [p = 0.004] and CD [p = 0.005] were independent risk factors for pain. Pain intensity was greater in the case of CS (6 [5-3] vs 3 [1.5-5], p < 0.003) which significantly impaired quality of life [p < 0.003] compared with pain without CS. The prevalence of pain was high in IBD patients [≈75%] and higher in CD patients. Significant impacts on quality of life were confirmed. More than 25% of patients with abdominal pain described CS as responsible for more severe pain and worsened quality of life. NCT04488146.


Quasiparticle Properties under Interactions in Weyl and Nodal Line Semimetals.
The quasiparticle spectra of interacting Weyl and nodal-line semimetals on a cubic lattice are studied using the cluster perturbation theory. By tracking the spectral functions under interaction, we find that the Weyl points will move to and meet at a specific point in one Weyl semimetal model, while in the other Weyl semimetal model they are immobile. In the nodal-line semimetals, we find that the nodal line shrinks to a point and then disappears under interaction in one-nodal-line system. When we add another nodal line to this system, we find that the two nodal lines both shrink to specific points, but the disappearing processes of the two nodal lines are not synchronized. We argue that the nontrivial evolution of Weyl points and nodal lines under interaction is due to the presence of symmetry breaking order, e.g., a ferromagnetic moment, in the framework of mean field theory, whereas the stability of Weyl points under interaction is protected by symmetry. Among all these models, the spectral gap is finally opened when the interaction is strong enough.


Gastric tumorigenesis by a single dose of 4-(hydroxymethyl)benzenediazonium ion of Agaricus bisporus.
4-(Hydroxymethyl-benzenediazonium tetrafluoroborate was administered as a single intragastric instillation at 400 micrograms/g to Swiss albino mice. The treatment gave rise to glandular stomach tumours in incidences of 30% in females and 32% in males. Histopathologically, the tumours were classified as polypoid adenomas and adenocarcinomas. This diazonium ion is an ingredient of the cultivated mushroom of commerce, Agaricus bisporus. The implications are self-evident.