Monte Carlo modelling of large scale NORM sources using MCNP.
The representative Monte Carlo modelling of large scale planar sources (for comparison to external environmental radiation fields) is undertaken using substantial diameter and thin profile planar cylindrical sources. The relative impact of source extent, soil thickness and sky-shine are investigated to guide decisions relating to representative geometries. In addition, the impact of source to detector distance on the nature of the detector response, for a range of source sizes, has been investigated. These investigations, using an MCNP based model, indicate a soil cylinder of greater than 20 m diameter and of no less than 50 cm depth/height, combined with a 20 m deep sky section above the soil cylinder, are needed to representatively model the semi-infinite plane of uniformly distributed NORM sources. Initial investigation of the effect of detector placement indicate that smaller source sizes may be used to achieve a representative response at shorter source to detector distances.


Surgical treatment and lymphedema.
Lymphedema is a serious and disabling complication of the treatment of breast carcinoma. This is related directly to the removal of axillary lymph nodes. Because lymph node status is the single most important predictor of outcome, it is necessary to obtain accurate information. Whereas breast conservation has become the preferred approach for treating early breast carcinoma, the accompanying axillary dissection continues to cause morbidity. The history of the operations for breast carcinoma is reviewed, and the anatomy, techniques, and complications of axillary lymphadenectomy are described. Data to support the necessity for accurate axillary staging is presented, and results of noninvasive axillary staging approaches are discussed. The technique and value of sentinel node biopsy are presented. Axillary lymphadenectomy is required where lymph node metastases are present to accomplish local control, improve survival, and provide information for staging to plan adjunctive therapy. Noninvasive techniques do not yet provide high enough sensitivity to assess the status of the axilla. The sentinel lymph node biopsy is a technique that can identify those patients who require axillary lymphadenectomy. Screening mammography has been responsible for down-staging the size of detected breast carcinomas, so that the axillary dissection may be omitted in small carcinomas of favorable histologic type. For carcinomas in which the probability of axillary metastases exists, by using the sentinel lymph node biopsy, axillary dissections can be avoided when results are negative, and the risk of lymphedema can be reduced.


Mutational analysis using next generation sequencing in pediatric thyroid cancer reveals BRAF and fusion oncogenes are common.
We previously described mutation rates of BRAFV600E, RAS, RET-PTC and PAX8-PPARγ in pediatric subjects with well-differentiated thyroid cancer (WDTC). We expanded the cohort adding next-generation sequencing (NGS) and assessed genotype-phenotype correlations. Single-center retrospective cohort examining thyroidectomy tissue blocks from consecutive pediatric WDTC patients between 2001 and 2015. Tissues were analyzed at Quest Diagnostics for BRAF, RAS mutations, RET-PTC and PAX8-PPARγ, and additional fusions, using standalone and NGS tests. WDTC included papillary (PTC), follicular (FTC) and follicular-variant PTC (FVPTC). We genotyped 46 samples (36 females). Mean age at diagnosis was 14.7 years and the cohort comprised of mostly Hispanic (60.9%) and Caucasian (26.1%) patients. Mean follow-up was 3.5 years. Genetic alterations (GA) were noted in 69.6%, with BRAFV600E (n = 11), and RET-PTC (n = 8) detected only in PTC. GA were detected in 2/7 FTC (1 PAX8-PPARγ, 1 NRAS) and 6/10 FVPTC (3 PAX8-PPARγ, 1 STRN-ALK, 1 BRAFK601E, 1 NRAS). Patients with BRAFV600E were predominantly Hispanic (81.8%) and >15 years (81.8%), whereas 87.5% RET-PTC and 50% other-fusions occurred in patients ≤15 years (p = 0.044). Of the 29 PTC patients, 82.8% had GA: BRAFV600E (37.9%), RET-PTC (27.6%), 17.2% other fusion-oncogenes (2 -ALK, 3 -NTRK). Non-RET fusions had the highest vascular invasion (100%, p = 0.042 vs RET-PTC) and frequent lymphatic invasion (80%). GA were most common in PTC with cervical metastasis. BRAFV600E was the most common single mutation, especially in older and Hispanic adolescents. All fusions combined are more common than BRAFV600E. NGS reveals a genetic basis in most pediatric WDTC, which may have implications for the role of molecular testing and systemic therapy.


Effects of distraction using virtual reality glasses during lumbar punctures in adolescents with cancer.
To determine the effects of virtual reality (VR) glasses on adolescents with cancer undergoing lumbar punctures (LPs). Pilot study using an experimental, control group design. In-hospital oncology clinic. 30 adolescents with cancer (17 in the VR and 13 in the control group) undergoing frequent LPs. Subjects were randomly assigned to groups. Both groups received standard intervention during the LP, but the experimental group also wore VR glasses and watched a video. Following the LP, both groups rated their pain using a visual analog scale (VAS) and were interviewed to evaluate their experience. Pain, subjective evaluation of experience. Although VAS pain scores were not statistically different between the two groups (p = 0.77), VAS scores tended to be lower in the VR group (median VAS of 7.0, range 0-48) than in the control group (median VAS of 9.0, range 0-59). 77% of subjects in the experimental group said the VR glasses helped to distract them from the LP. VR glasses are a feasible, age-appropriate, nonpharmacologic adjunct to conventional care in managing the pain associated with LPs in adolescents. The clinical application of various age-appropriate distracters to reduce pain in adolescents undergoing painful procedures should be explored.


Assay of 2-hydroxyputrescine in various regions of rat brain by gas chromatography-mass spectrometry.
2-Hydroxyputrescine in seven regions of single rat brains was measured with a sensitive, specific assay by gas chromatography-mass spectrometry. The regions were the cerebral cortex, cerebellum, medulla oblongata, hypothalamus, striatum, hippocampus, and midbrain. The level of 2-hydroxyputrescine was very high in the cerebral cortex and cerebellum, high in the medulla oblongata, hypothalamus, and hippocampus, and low in the striatum and midbrain. The level of 2-hydroxyputrescine in the cerebellum was significantly higher than in the striatum and midbrain.


[Short-term and long-term clinical study of the absence of nutritional syndromes, body weight increase, blood serum parameters, and return to work of patients gastrectomized using a special surgical technique. III].
Short- and long-term clinical results obtained following the employment of a surgical technique used for gastric resection, and described in two previous notes, are presented. Nutritional syndromes were not observed and body weight increased. These findings, coupled with the blood serum data and the fact that patients fully resumed their work, are compared with the less satisfactory results obtained with the techniques of Balfour and Reichel-Polya.


Endocannabinoid system and aggression across animal species.
This narrative review article summarizes the current state of knowledge regarding the relationship between the endocannabinoid system (ECS) and aggression across multiple vertebrate species. Experimental evidence indicates that acute administration of phytocannabinoids, synthetic cannabinoids, and the pharmacological enhancement of endocannabinoid signaling decreases aggressive behavior in several animal models. However, research on the chronic effects of cannabinoids on animal aggression has yielded inconsistent findings, indicating a need for further investigation. Cannabinoid receptors, particularly cannabinoid receptor type 1, appear to be an important part of the endogenous mechanism involved in the dampening of aggressive behavior. Overall, this review underscores the importance of the ECS in regulating aggressive behavior and provides a foundation for future research in this area.


A new technique for primary hepatocyte expansion in vitro.
The current application for many potential cell-based treatments for liver failure is limited by the low availability of mature functional hepatocytes. Although adult hepatocytes have a remarkable ability to proliferate in vivo, attempts to proliferate adult hepatocytes in vitro have been less successful. In this study, we investigated the effect of coculture cell type on the proliferative response and the functional activities of hepatocytes. We show, for the first time, a robust proliferative response of primary adult rat hepatocytes when cocultured with mouse 3T3-J2 fibroblasts. Hepatocytes cultured at low density on growth-arrested 3T3-J2 fibroblast feeder layers underwent significantly higher proliferation rates than when cultured on feeder layers made of four other cell types. Increasing colony size correlated with an increase in hepatocellular functions. The proliferating hepatocytes retained their morphologic, phenotypic, and functional characteristics. Using a cell patterning technique, we found that 3T3-J2 fibroblasts stimulate DNA synthesis in hepatocytes by short-range heterotypic cell-cell interactions. When hepatocytes that proliferated in cocultures were harvested and further subcultured either on 3T3-J2 fibroblast feeders or in the collagen sandwich configuration, their behavior was similar to that of freshly isolated hepatocytes. We conclude that adult rat hepatocytes can proliferate in vitro in a coculture cell type-dependent manner, and can be serially propagated by coculturing with 3T3-J2 fibroblasts while maintaining their differentiated characteristics. Our results also suggest that one of the major reasons for the functional differences in hepatocyte cocultures may be due to the different proliferative responses of hepatocytes as a function of coculture cell type. This study provides new insights in the roles of coculture cell types and cell-cell interactions in the modulation of hepatic proliferation and function.


Biological effects of chrysotile after SO2 sorption. II. Effects on alveolar macrophages and red blood cells.
An experimental study has been carried out using different biological and biochemical in vivo and in vitro tests for assessing the toxicity of natural UICC (A) chrysotile and SO2-sorbed UICC (A) chrysotile and for detecting a possible synergistic effect. For in vivo studies, rabbits received an intratracheal injection of chrysotile fibers suspended in physiological saline (PS). The control group received only PS; all animals were sacrificed after 68 hr. The alveolar free cells were harvested by pulmonary lavage. The results have shown that chrysotile induces a decrease in the free cell population but there was no significant difference in the number of viable cells or in the nature of cells harvested between the two chrysotile groups. Enzymatic activities of the alveolar macrophages from animals injected with SO2-sorbed chrysotile showed a significant increase of the enzymes LDH and acid phosphatases. The LDH increase could be related to the affinity of the enzyme regarding some chemical forms of SO2. In vitro studies using alveolar macrophages harvested by pulmonary lavage have shown no differences between the two chrysotile groups when cell viability and enzyme release were studied. The toxic effect was due to chrysotile fibers (decrease of 38% in cell viability and increase in cellular enzyme release when compared with control). When rabbit red blood cells were used, both natural and SO2 chrysotile fibers showed the same hemolytic activity. The failure to detect high differences between the two chrysotile groups may be related to the chemical form of sorbed SO2.


WNT-Conditioned Mechanism of Exit from Postchemotherapy Shock of Differentiated Tumour Cells.
the present study aims to prove or disprove the hypothesis that the state of copy number aberration (CNA) activation of WNT signalling pathway genes accounts for the ability of differentiated tumour cells to emerge from postchemotherapy shock. In the first step, the CNA genetic landscape of breast cancer cell lines BT-474, BT-549, MDA-MB-231, MDA-MD-468, MCF7, SK-BR-3 and T47D, which were obtained from ATCC, was examined to rank cell cultures according to the degree of ectopic activation of the WNT signalling pathway. Then two lines of T47D with ectopic activation and BT-474 without activation were selected. The differentiated EpCAM+CD44-CD24-/+ cells of these lines were subjected to IL6 de-differentiation with formation of mammospheres on the background of cisplatin and WNT signalling inhibitor ICG-001. it was found that T47D cells with ectopic WNT signalling activation after cisplatin exposure were dedifferentiated to form mammospheres while BT-474 cells without ectopic WNT-signalling activation did not form mammospheres. The dedifferentiation of T47D cells after cisplatin exposure was completely suppressed by the WNT signalling inhibitor ICG-001. Separately, ICG-001 reduced, but did not abolish, the ability to dedifferentiate in both cell lines. these data support the hypothesis that the emergence of differentiated tumour cells from postchemotherapy shock after chemotherapy is due to ectopic activation of WNT signalling pathway genes.


A rare occurrence of peripheral ossifying fibroma in the first decade of life and its management.
Localised growths are commonly seen on the gingiva. Many of these enlargements are considered to be reactive rather than neoplastic in nature. Clinically, differentiating one from the other as a specific entity is often not possible. Clinical knowledge and histopathological examination is needed to positively identify the lesion. The peripheral ossifying fibroma is one such lesion. We report a rare case in a 10-year-old female patient with a peripheral ossifying fibroma in the mandible exhibiting a significant increase in size within a short duration of 6 months.


Oases: robust de novo RNA-seq assembly across the dynamic range of expression levels.
High-throughput sequencing has made the analysis of new model organisms more affordable. Although assembling a new genome can still be costly and difficult, it is possible to use RNA-seq to sequence mRNA. In the absence of a known genome, it is necessary to assemble these sequences de novo, taking into account possible alternative isoforms and the dynamic range of expression values. We present a software package named Oases designed to heuristically assemble RNA-seq reads in the absence of a reference genome, across a broad spectrum of expression values and in presence of alternative isoforms. It achieves this by using an array of hash lengths, a dynamic filtering of noise, a robust resolution of alternative splicing events and the efficient merging of multiple assemblies. It was tested on human and mouse RNA-seq data and is shown to improve significantly on the transABySS and Trinity de novo transcriptome assemblers. Oases is freely available under the GPL license at www.ebi.ac.uk/~zerbino/oases/.


Patient-reported health-related quality of life from a randomized, placebo-controlled phase 2 trial of zuranolone in adults with major depressive disorder.
Major depressive disorder (MDD), a disabling, potentially life-threatening condition, negatively affects health-related quality of life (HRQoL). This secondary analysis aimed to understand the impact of the neuroactive steroid zuranolone on HRQoL using the Short Form-36v2 Health Survey (SF-36v2). Adult patients with MDD and 17-item Hamilton Rating Scale for Depression total score ≥22 were randomized 1:1 to receive zuranolone 30 mg or placebo for 2 weeks, with 4 weeks follow-up. SF-36v2 scores were assessed at Day 15 across 8 domains (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and 2 summary scores (Physical and Mental Component), using a mixed-effects model for repeated measures. Correlations between SF-36v2 scores and clinician-reported efficacy endpoints were assessed using Pearson's correlation. Eighty-nine patients were treated with zuranolone 30 mg (n = 45) or placebo (n = 44). In zuranolone-treated patients, HRQoL improved across all SF-36v2 domains and summary scores at Day 15. Improvements exceeding established minimally important difference thresholds were observed in Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health scores. Improvements in General Health, Vitality, Mental Health, and Mental Component Summary were statistically significant versus placebo (p ≤ 0.025). Clinician-rated endpoints negatively correlated with SF-36v2 scores. The small unipolar depression sample may not be representative of all US MDD patients. HRQoL measures could be impacted by factors unrelated to depression. Zuranolone-treated patients reported rapid and significant improvements in HRQoL versus placebo at Day 15. HRQoL improvements correlated with improvements in clinician-rated assessments. clinicaltrials.gov:NCT03000530; https://clinicaltrials.gov/ct2/show/NCT03000530.


Layered double hydroxides, an effective nanomaterial to remove phosphorus from wastewater: Performance, mechanism, factors and reusability.
Systematic understanding of phosphorus adsorption performance, mechanism, factors and reusability of layered double hydroxides (LDH) remains limited. Thus, iron (Fe), calcium (Ca) and magnesium (Mg)-based LDH (FeCa-LDH and FeMg-LDH), were synthesized with a co-precipitation method to improve phosphorus removal efficiency during the wastewater treatment process. Both FeCa-LDH and FeMg-LDH showed a considerable ability to remove phosphorus in wastewater. When the phosphorus concentration was 10 mg/L, the removal efficiency reached 99 % (FeCa-LDH: 1 min) and 82 % (FeMg-LDH: 10 min), respectively. The phosphorus removal mechanism was observed to be electrostatic adsorption, coordination reaction and anionic exchange, which was more evident at pH = 10 for FeCa-LDH. Co-occurrence anions that affected phosphorus removal efficiency, were observed in the following order: HCO3- > CO32- ≈ NO3- > SO42-. After five adsorption-desorption cycles, phosphorus removal efficiency was still up to 85 % (FeCa-LDH) and 42 % (FeMg-LDH), respectively. Together, the present findings suggest that LDHs were high-performance, strongly-stable and reusable phosphorus adsorbents.


[Malignant syndrome in burned children. Nosologic and therapeutic approach].
A malignant syndrome was observed in 7 children less than 3 years old; the extent of burn was between 5 and 25 p. cent. This syndrome appeared between the second and the fifth days. It was characterized by fever, autonomic disorders and finally coma. The clinical, biological and anatomical features look like the syndrome of Reye. The use of dopamine before coma allowed healing.


A case of heavy chain disease: diagnosis and monitoring using assays of immunoglobulin heavy and light chains.
Heavy chain diseases (HCD) are uncommon. We report the first use of recently developed analytical techniques for the assay of immunoglobulin heavy and light chains in the diagnosis and monitoring of a patient with gamma-HCD.


Statistical optimization of microalgae Pavlova lutheri cultivation conditions and its fermentation conditions by yeast, Candida rugopelliculosa.
In this study, sequential strategy based design was applied to optimize the microalgae, Pavlova lutheri mass culture conditions and fermentation conditions of the cultured algae by proteolytic yeast Candidia rugopelliculosa to obtain small peptide chains. This optimization of culture and fermentation conditions by response surface methodology (RSM) finally leads to effective purification of a bioactive peptide MPGPLSPL (793.01 Da) with hydroxyl radical scavenging activity. Collectively, these results indicated that microalgae P. lutheri can enhance the hydroxyl radical inhibiting effect through protein hydrolysis process under RSM optimal condition.


Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in evaluation of inflammation in non-dialysis patients with end-stage renal disease (ESRD).
Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to be associated with inflammation in end-stage renal disease (ESRD) receiving dialysis. However, the value of NLR and PLR in non-dialysis patients with ESRD remains unclear. Among 611 non-dialysis patients with ESRD in The First Affiliated Hospital of University of South China (2012-2018), we compared NLR and PLR in patients with high-sensitivity C-reactive protein (hs-CRP) levels of ≤3 mg/L vs. > 3 mg/L. Correlation of NLR and PLR to hs-CRP, PCT, ferritin were analyzed. Receiver operating characteristics (ROC) analysis was used for estimating sensitivity and specificity of NLR and PLR. NLR was higher in the patients with high hs-CRP levels (> 3 mg/L), compared to patients with low hs-CRP levels (≤ 3 mg/L) [5.74 (3.54-9.01) vs. 3.96 (2.86-5.85), p < 0.0001]. Additionally, PLR was higher in high hs-CRP group than in low group [175.28 (116.67-252.26) vs. 140.65 (110.51-235.17), p = 0.022]. In the current study, NLR and PLR were both positively correlated with hs-CRP (rs = 0.377, p = 0.000 for NLR; rs = 0.161, p = 0.001 for PLR), PCT, leukocytes, neutrophils, platelets, and age. NLR or PLR with a cut-off value of 5.07 or 163.80 indicated sensitivity and specificity were 65.67 and 66.37% (AUC = 0.69) or 57.21 and 57.52% (AUC = 0.55), respectively. NLR or PLR was positively correlated with hs-CRP in non-dialysis patients with ESRD. NLR might be better for identifying inflammation than PLR in this population.


Actin, tubulin and H4 histone genes in three species of hypotrichous ciliated protozoa.
In hypotrichous ciliated protozoa, genes are transcribed in the macronucleus where the genome consists of 'gene-sized' linear DNA molecules. We have isolated clones of actin, tubulin and H4 histone macronuclear genes from Oxytricha nova, Stylonychia lemnae and Euplotes crassus in an effort to determine if they possess molecules of similar size for a given coding function, and also to determine the size range of non-coding DNA present on these molecules. Our results indicate that while the length of their non-coding DNA can vary slightly, both between different hypotrichs and within the gene family of a single organism, actin and tubulin macronuclear molecules are similarly sized. The sizes observed for these molecules support the hypothesis that each macronuclear molecule encodes a single gene. However, the H4 histone macronuclear molecules show a much wider size range and generally are much longer than necessary to encode the H4 histone. We therefore sequenced a 1700-bp H4 histone macronuclear molecule from O. nova to determine if it might possibly encode additional gene products. Sequence data reveals the presence of nine open reading frames (ORFs) greater than 100 bp in length; however, Northern hybridization analysis of the products of this DNA molecule reveals only a single transcript.


Effects of complement gene-set polygenic risk score on brain volume and cortical measures in patients with psychotic disorders and healthy controls.
Multiple genome-wide association studies of schizophrenia have reported associations between genetic variants within the MHC region and disease risk, an association that has been partially accounted for by alleles of the complement component 4 (C4) gene. Following on previous findings of association between both C4 and other complement-related variants and memory function, we tested the hypothesis that polygenic scores calculated based on identified schizophrenia risk alleles within the "complement" system would be broadly associated with memory function and associated brain structure. We tested this using a polygenic risk score (PRS) calculated for complement genes, but excluding C4 variants. Higher complement-based PRS scores were observed to be associated with lower memory scores for the sample as a whole (N = 620, F change = 8.25; p = .004). A significant association between higher PRS and lower hippocampal volume was also observed (N = 216, R2 change = 0.016, p = .015). However, after correcting for further testing of association with the more general indices of cortical thickness, surface area or total brain volume, none of which were associated with complement, the association with hippocampal volume became non-significant. A post-hoc analysis of hippocampal subfields suggested an association between complement PRS and several hippocampal subfields, findings that appeared to be particularly driven by the patient sample. In conclusion, our study yielded suggestive evidence of association between complement-based schizophrenia PRS and variation in memory function and hippocampal volume.


Specific triacylglycerol, diacylglycerol, and lyso-phosphatidylcholine species for the prediction of type 2 diabetes: a ~ 16-year prospective study in Chinese.
Bioactive lipids play an important role in insulin secretion and sensitivity, contributing to the pathophysiology of type 2 diabetes (T2D). This study aimed to identify novel lipid species associated with incident T2D in a nested case-control study within a long-term prospective Chinese community-based cohort with a median follow-up of ~ 16 years. Plasma samples from 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) were first analyzed using untargeted lipidomics. Potential predictive lipid species selected by the Boruta analysis were then verified by targeted lipidomics. The associations between these lipid species and incident T2D were assessed. Effects of novel lipid species on insulin secretion in mouse islets were investigated. Boruta analysis identified 16 potential lipid species. After adjustment for body mass index (BMI), triacylglycerol/high-density lipoprotein (TG/HDL) ratio and the presence of prediabetes, triacylglycerol (TG) 12:0_18:2_22:6, TG 16:0_11:1_18:2, TG 49:0, TG 51:1 and diacylglycerol (DG) 18:2_22:6 were independently associated with increased T2D risk, whereas lyso-phosphatidylcholine (LPC) O-16:0, LPC P-16:0, LPC O-18:0 and LPC 18:1 were independently associated with decreased T2D risk. Addition of the identified lipid species to the clinical prediction model, comprised of BMI, TG/HDL ratio and the presence of prediabetes, achieved a 3.8% improvement in the area under the receiver operating characteristics curve (AUROC) (p = 0.0026). Further functional study revealed that, LPC O-16:0 and LPC O-18:0 significantly potentiated glucose induced insulin secretion (GSIS) in a dose-dependent manner, whereas neither DG 18:2_22:6 nor TG 12:0_18:2_22:6 had any effect on GSIS. Addition of the lipid species substantially improved the prediction of T2D beyond the model based on clinical risk factors. Decreased levels of LPC O-16:0 and LPC O-18:0 may contribute to the development of T2D via reduced insulin secretion.


RNA interference in vitro and in vivo using a novel chitosan/siRNA nanoparticle system.
This work introduces a novel chitosan-based siRNA nanoparticle delivery system for RNA interference in vitro and in vivo. The formation of interpolyelectrolyte complexes between siRNA duplexes (21-mers) and chitosan polymer into nanoparticles, ranging from 40 to 600 nm, was shown using atomic force microscopy and photon correlation spectroscopy. Rapid uptake (1 h) of Cy5-labeled nanoparticles into NIH 3T3 cells, followed by accumulation over a 24 h period, was visualized using fluorescence microscopy. Nanoparticle-mediated knockdown of endogenous enhanced green fluorescent protein (EGFP) was demonstrated in both H1299 human lung carcinoma cells and murine peritoneal macrophages (77.9% and 89.3% reduction in EGFP fluorescence, respectively). In addition, Western analysis showed approximately 90% reduced expression of BCR/ABL-1 leukemia fusion protein while BCR expression was unaffected in K562 (Ph(+)) cells after transfection using nanoparticles containing siRNA specific to the BCR/ABL-1 junction sequence. Effective in vivo RNA interference was achieved in bronchiole epithelial cells of transgenic EGFP mice after nasal administration of chitosan/siRNA formulations (37% and 43% reduction compared to mismatch and untreated control, respectively). These findings highlight the potential application of this novel chitosan-based system in RNA-mediated therapy of systemic and mucosal disease.


Pathological alterations of ependyma and choroid plexus after experimental cerebral infection of mice with Sendai virus.
The effects of intracerebral inoculation of Sendai virus into young adult mice were investigated by immunofluorescence, light, and electron microscopy. Immunofluorescence of virus-specific antigens was maximal on the third day after inoculation, revealing infection of leptomeninges, ependyma, and choroid plexus. Histologically, meningitis, ependymitis, and choroiditis occurred between the second and third days. The choroiditis was associated with formation of vacuoles within the cytoplasm of epithelial cells. The vacuoles reached diameters up to 50 micrometer. The ubiquitous vacuolization of plexus epithelia resulted in a honeycomb-like pattern. Opaque viral inclusions were visible within the cytoplasm of choroidal and ependymal epithelium as well as in mononuclear inflammatory cells. On electron microscopy, they were composed of intracytoplasmic nucleocapsid accumulations. Viria lay free between microvilli of plexus epithelial cells, and budding virus structures were observed at cellular surfaces. Occasionally, complete viria occurred in the cytoplasm of plexus epithelial cells and were surrounded by a unit membrane from which they appeared to arise by budding. The formation of this small cavity can be interpreted as the first stage of vacuole formation.


Evidence that NMDA receptors mediate the responses of putative RVLM presympathetic neurons to vagal afferent stimulation in rats.
Experiments were performed in 25 urethane-anaesthetized male Sprague-Dawley rats. Forty-six RVLM neurons were identified as putative presympathetic neurons according to their arterial baroreceptor reflex related properties, i.e. they were inhibited by stimulation of the aortic nerve; silenced by elevation of blood pressure and had a cardiac cycle related rhythm of spontaneous discharge. Responses of these neurons to tripled square wave stimulation of vagal afferents was tested by means of peristimulus time histograms. In addition to a long-lasting inhibition (I2), some neurons had one (P0) or two excitatory peaks (P1 and P2), and there was a short-lasting inhibition (I1) between P1 and P2. After microinjection of CPP (0.1 microl, 50 mM) into the NTS, the inhibitory responses were blocked, but the excitatory peaks were not affected; in the CVLM, CPP microinjection of the same dose had a similar effect on the responses elicited by vagal afferent stimulation in 15 of the 24 neurons tested. No detectable effects were observed in 9 neurons. However, intravenously administered ketamine attenuated or abolished these responses, either inhibitory or excitatory, in a dose dependent way. These results suggest: (1) an NMDA mechanism is involved in both the inhibitory and the excitatory responses. For the inhibitory responses, the involvement is both in the NTS and in the CVLM; for the excitatory responses, it is probably in the RVLM. (2) There may be a direct excitatory amino acid (EAA) pathway from the NTS to the RVLM.


Effect of antioxidant-enriched diets on glutathione redox status in tissue homogenates and mitochondria of the senescence-accelerated mouse.
The main purpose of this study was to investigate whether consumption of diets enriched in antioxidants attenuates the level of oxidative stress in the senescence-accelerated mouse (SAM). In separate and independent studies, two different dietary mixtures, one enriched with vitamin E, vitamin C, L-carnitine, and lipoic acid (Diet I) and another diet including vitamins E and C and 13 additional ingredients containing micronutrients with bioflavonoids, polyphenols, and carotenoids (Diet II), were fed for 8 and 10 months, respectively. The amounts of glutathione (GSH) and glutathione disulfides (GSSG) and GSH:GSSG ratios were determined in plasma, tissue homogenates, and mitochondria isolated from five different tissues of SAM (P8) mice. Both diets had a reductive effect in plasma; however Diet I had relatively little effect on the glutathione redox status in tissue homogenates or mitochondria. Remarkably, Diet II caused a large increase in the amount of glutathione and a marked reductive shift in glutathione redox state in mitochondria. Overall, the effects of Diet II were tissue and gender specific. Results indicated that the glutathione redox state in mitochondria and tissues can be altered by supplemental intake of a relatively complex mixture of dietary antioxidants that contains substances known to induce phase 2 enzymes, glutathione, and antioxidant defenses. Whether corresponding attenuations occur in age-associated deleterious changes in physiological functions or life span remains unknown.


Nuclear localization of P-glycoprotein is responsible for protection of the nucleus from doxorubicin in the resistant LoVo cell line.
The high expression of P-glycoprotein (P-gp) belongs to one of the most important factors causing multidrug-resistant (MDR) of cancer cells. P-gp is primarily associated with plasma membrane; however, small fraction of that protein is present in the nuclear envelope. Such phenomenon is observed in cancer cells and may result in the selection of MDR cells as the secondary tumor and/or resistant metastasis that significantly shorten patient survival rate. Here, we confirmed nuclear localization of P-gp in resistant LoVo cells and demonstrated its impact on doxorubicin efflux from the nucleus to cytoplasm. Furthermore, we showed that P-gp located at the nuclear envelope might have a different glycoside chain when compared to the form located in the cytoplasm. It suggests that the glycoside chain plays a role in the intracellular trafficking of P-gp and may decide about the destination place in the cell.


Effect of diazoxide on capacitance vessels.
Haemodynamic changes after an i.v. bolus of diazoxide 300 mg were studied in 11 hypertensive subjects. A hypotensive effect due to a fall in total peripheral vascular resistance was found in all of them, but changes in the peripheral circulation were less regular. A uniform change in forearm blood volume, blood flow, vascular resistance and venous distensibility was not found after diazoxide. This is interpreted as being due to a reflex increase in sympathetic activity, which counteracts the direct vasodilator action of the drug.


TP53-induced glycolysis and apoptosis regulator (TIGAR) ameliorates lysosomal damage in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-mediated mouse model of Parkinson's disease.
The progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) correlates with rupture of lysosome in Parkinson's disease (PD). It has been found that TP53-induced glycolysis and apoptosis regulator (TIGAR) has been attributed to the regulation of metabolic pathways and neuroprotective effect. In the present study, we showed in a mouse model that 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) caused lysosomal damage and DA neurons loss in the SNpc. MPTP only induced SP1-mediated TIGAR upregulation in the early stage of neurotoxin-induced pathology, and this compensatory mechanism was not enough to maintain normal lysosomal function. MPTP significantly decreased the levels of NADPH and GSH, and the effects were ameliorated by the expression of exogenous TIGAR but execerbated by knockdown of TIAGR. TIGAR or NADPH alleviated oxidative stress, rescued lysosomal dysfunction and attenuated DA neurons degeneration. Overexpression of TIGAR or NADPH supplement inhibited MPP+-mediated reactive oxygen species (ROS), lysosomal membrane permeabilization (LMP) and autophagic flux impairment in PC12 cells. Together, these findings suggest that TIGAR reduces MPTP-mediated oxidative stress, lysosomal depletion and DA neuron damage.


LINGO-1 and its role in CNS repair.
LINGO-1 is selectively expressed in the CNS on both oligodendrocyte precursor cells (OPCs) and neurons. Its expression is developmentally regulated in the normal CNS, as well as up-regulated in human or rat models of neuropathologies. LINGO-1 functions as a negative regulator of oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration. Across diverse animal CNS disease models, targeted LINGO-1 inhibition was found to promote neuron and oligodendrocyte survival, axon regeneration, oligodendrocyte differentiation, remyelination and improved functional recovery. The targeted inhibition of LINGO-1 therefore presents a novel therapeutic approach for the treatment of neurological diseases.


Surgery versus endoscopic cauterization in patients with third or fourth branchial pouch sinuses: A systematic review.
To systematically review the current literature on treatment of third and fourth branchial pouch sinuses with endoscopic cauterization, including chemocauterization and electrocauterization, in comparison to surgical treatment. PubMed, Embase, and the Cochrane Library. We conducted a systematic search. Studies reporting original study data were included. After assessing the directness of evidence and risk of bias, studies with a low directness of evidence or a high risk of bias were excluded from analysis. Cumulative success rates after initial and recurrent treatments were calculated for both methods. A meta-analysis was conducted comparing the success rate of electrocauterization and surgery. A total of 2,263 articles were retrieved, of which seven retrospective and one prospective article were eligible for analysis. The cumulative success rate after primary treatment with cauterization ranged from 66.7% to 100%, and ranged from 77.8% to 100% after a second cauterization. The cumulative success rate after the first surgical treatment ranged from 50% to 100% and was 100% after the second surgical attempt. Meta-analysis on electrocauterization showed a nonsignificant risk ratio of 1.35 (95% confidence interval: 0.78-2.33). The effectiveness of cauterization in preventing recurrence seems to be comparable to surgical treatment. However, we suggest endoscopic cauterization as the treatment of choice for third and fourth branchial pouch sinuses because of the lower morbidity rate.


[Neonatal infection with Stenotrophomonas maltophilia (2 case studies)].
Stenotrophomonas maltophilia (S.M.) is a Gram-negative bacillus, naturally resistant to cephalosporins and carbapenems, which can colonize different sites and may be responsible for serious infections for which treatment is a real challenge. We report 2 cases of nosocomial S.M. infection in 2 hospitalized newborns in the neonatal intensive care unit. CASE 1: A 3-day-old newborn presented with infection beginning in the respiratory system, treated with ciprofloxacin, and complicated by septicemia, resulting in death. CASE 2: An 11-day-old newborn presented with brain S.M. suppuration: empyema and multiple abscesses were treated successfully with the combination of amikacin and chloramphenicol with good progression in the short and medium terms. Some epidemiological studies report that S.M. is the second Gram-negative bacillus responsible for nosocomial infection after Klebsiella pneumoniae. While the respiratory location of the bacterium is typical, cerebral parenchyma damage is rare in the newborn. The treatment remains very delicate and difficult because of this bacterium's drug multiresistance. These 2 cases of infection caused by S.M. including respiratory tract infection with bacteremia and cerebral suppuration in newborns have broadened the spectrum of diseases caused by this organism and are a reminder of the emergence of this organism and its natural resistance to several antibiotics.


Infant sleep and temperament characteristics in association with maternal postpartum depression.
Aim of this study was to examine the association between infant temperament and sleep characteristics and postpartum depressive symptoms among mothers. Research data were collected at the baseline (2nd -4th days postpartum) and the follow-up (6-8 weeks postpartum), Slovak version of the (EPDS) was used, along with questions focused on perceived sleeping problems of an infant, and temperament Linear regression models were employed. Two public hospital sites in Slovakia. 204 women participated in both time points (mean age 30.9 ± 4.8, age range: 20-44; 78.9% vaginal births; 56.9% primiparas). Significant differences in the EPDS scores were found according to infant sleeping problems (p ≤ 0.05) and duration of infant night sleep (p ≤ 0.01). Both night sleep and day sleep duration were significant predictors for the level of postpartum depression symptoms at the 6-8 weeks follow-up in the linear regression model after adjusting for confounding variables (β= -0.13; 95%CI: -3.04;-0.01; β= -0.15; 95%CI: -3.02;-0.28, total explained variance 39.0%). Infant temperament characteristics have not been found significant predictors of postpartum depression symptoms in this study. Significant differences in depression levels were found among postpartum women according to perceived sleeping problems of infant, and the duration of infant night sleep. It is important to focus more attention on the role of infant sleeping problems as a possible risk factor for the increased occurrence of postpartum depressive symptoms.


Cytochemical profile of human haematopoietic biopsy cells and derived cell lines.
Twenty-three human haematopoietic cell lines, normal and mitogen stimulated peripheral blood lymphocytes and tumour material from fresh leukaemias, myelomas and lymphomas were investigated with a panel of cytochemical reactions. Normal and mitogen stimulated lymphocytes, non-neoplastic lymphoblastoid cell lines (LCL), lymphoma lines with B-lymphocyte characteristics, chronic lymphocytic leukaemia and fresh lymphocytic lymphomas reacted weakly or negatively with all stains. T-lymphocyte acute leukaemia lines were PAS and alpha-naphtyl acetate esterase positive. Myeloma lines and fresh myelomas were strongly beta-glucoronidase positive. A histiocytic lymphoma cell line was strongly esterase positive with naphtol AS-D acetate esterase inhibited by NaF. The three fresh histiocytic lymphomas, however, reacted as the lymphocytic lymphomas suggesting a lymphoid origin. A myeloid leukaemia line was strongly positive for acid phsophatase. No major disagreement was noted between the reactivity of established neoplastic lines and the corresponding fresh biopsy cells indicating an unaltered qualitative expression of enzyme production after prolonged in vitro culture.


Induction of donor-specific unresponsiveness to rat cardiac allograft by donor leukocytes and cyclosporine.
Many recent reports have emphasized the importance of donor antigens in the induction of allograft tolerance. This study examines the effect of pretransplant infusion of 10(8) donor leukocytes (DL) combined with peritransplant cyclosporine (CsA) on W/F cardiac allograft survival in Lewis rats. Peritransplant recipient treatment consisted of CsA 20 mg/kg given i.m. on days 0, +1, and +2 relative to heart transplantation. Lewis recipients, 5-8 per group, were pretreated with 10(8) DL with or without peritransplant CsA. A single DL transfusion on day -3 or day -7 prior to transplantation significantly prolonged the mean survival time (MST) of W/F hearts from 7.0 +/- 0.9 days in controls to 12.2 +/- 4.5 days and 12.4 +/- 1.0 days (P less than 0.01), respectively. Two DL infusions on days -7 and -3 or on days -14 and -7 prolonged the MST to 10.6 +/- 1.3 days (P less than 0.02) and 16.4 +/- 2.8 days (P less than 0.001), respectively. The administration of peritransplant CsA alone significantly prolonged W/F heart allograft survival to 43.1 +/- 2.7 days. When pretransplant DL transfusion on day -3 was combined with CsA treatment, 4/8 animals maintained their grafts indefinitely (greater than 100 days). Similarly, DL infusion on day -7 with peritransplant CsA led to indefinite graft survival in 3/5 animals. Administration of DL on days -7 and -3 combined with CsA resulted in indefinite graft survival (greater than 100 days) in 4/6 animals. Transfusion of DL on day -3 alone or in combination with peritransplant CsA, had no effect on a third-party (ACI) heart allograft survival prolongation compared with appropriate controls. To define the underlying mechanisms responsible for donor-specific unresponsiveness in this model, pooled sera and unseparated spleen cells were passively transferred from recipients of long-term cardiac allografts to syngeneic rats receiving donor-type (W/F) or third-party (ACI) cardiac allografts. Transfer of serum (1 ml on days 0, and 1, 0.5 ml on days +2, +3, and +4) from ungrafted recipients of DL on days -14 and -7 led to significant donor graft survival of 9.8 +/- 0.4 days (P less than 0.02) in unmodified hosts. Similarly, passive transfer of serum obtained at 20 and 100 days after transplantation significantly prolonged the MST of donor-type hearts in syngeneic untreated hosts to 11.3 +/- 0.8 and 10.0 +/- 1.1 days, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


Anlotinib plus chemotherapy for T790M-negative EGFR-mutant non-sqNSCLC resistant to TKIs: A multicenter phase 1b/2 trial.
This multicenter phase 1b/2 trial aimed to explore the maximum tolerated dose (MTD), activity, and safety of anlotinib plus chemotherapy in patients with T790M-negative epidermal growth factor receptor (EGFR)-mutant advanced nonsquamous non-small cell lung cancer (NSCLC) after resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). In the phase 1b stage, patients received anlotinib (8/10/12 mg, days 1-14) combined with cisplatin (75 mg/m2 , day 1) or carboplatin (AUC = 5, day 1) plus pemetrexed (500 mg/m2 , day 1) for a 3-week cycle based on a 3 + 3 dose-escalation design. In the phase 2 single-arm stage, anlotinib was administered at MTD combined with platinum plus pemetrexed for four cycles, followed by anlotinib maintenance therapy. The primary endpoint of the phase 2 stage was progression-free survival (PFS). The study was prematurely terminated due to slow accrual after 19 patients had been enrolled between January 18, 2019, and March 21, 2021. The MTD of anlotinib was 12 mg. The median PFS was 5.75 (95% confidence interval, 4.37-7.52) months. The objective response rate was 47.4% (95% confidence interval, 24.5%-71.1%). In the 12 mg group, seven (58.3%) patients experienced grade 3-4 treatment-related adverse events, and the most common ones were hypertension (6 [50.0%]), decreased platelet count (2 [16.7%]), and hypertriglyceridemia (1 [8.3%]). No treatment-related deaths occurred. Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M-negative EGFR-mutant advanced nonsquamous NSCLC after progression on first- or second-generation EGFR TKIs.


Contemporary outcomes of mitral valve replacement in octogenarians.
We aimed to determine the outcomes of contemporary mitral valve replacement (MVR) in octogenarians, for rational treatment selection in a patient cohort. Between 2007 and 2018, 656 consecutive MVRs were performed. Among these cases, 109 patients were aged 80 years or older, and 547 patients were younger than 80 years. Isolated MVRs were performed in 211 patients, of whom 36 were aged 80 years or older. Perioperative mortality and complications were compared between the two groups, adjusted by propensity score. In-hospital mortality of the entire MVR (<80: 26 [4.8%] vs. ≥80: 6 [5.5%], p = .81) and isolated MVR (<80: 6 [3.4%] vs. ≥80: 1 [2.8%], p > .99) groups were similar. Age >80 years did not influence in-hospital mortality (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.36-3.14, p = .9), stroke (HR, 1.12; 95% CI, 0.19-6.71, p = .9), hemodialysis (HR, 1.44; 95% CI, 0.45-4.66, p = .54), or prolonged ventilation (HR, 1.61; 95% CI, 0.81-3.23, p = .18), but influenced the incidence of reopening for bleeding (HR, 3.97; 95% CI, 1.11-14.19, p = .03). Cox proportional hazard model results showed that age >80 years did not affect cardiac death (HR, 1.45, 95% CI: 0.67-3.12, p = .35), bleeding events (HR, 1.89, 95% CI: 0.84-4.27, p = .13), or stroke (HR, 1.51, 95% CI: 0.54-4.21, p = .44) during the follow-up period. The perioperative and follow-up outcomes of MVR in octogenarians were not inferior to those of younger patients. We should not hesitate to conduct MVR on the grounds of old age.


Conservation of Wild Food Plants and Their Potential for Combatting Food Insecurity in Kenya as Exemplified by the Drylands of Kitui County.
Wild food plants are important resources for people living in dry areas of Kenya. A botanical inventory of vascular plants of Kitui county was compiled from specimens collected during field investigations in Kitui county, at the East African (EA) herbarium and from literature reporting on plants of Kitui county. To obtain an inventory of wild edible plants found in Kitui county, literature reporting on wild edible plants of Kenya were searched and combined with the use reports obtained from field surveys in Kitui county. A total of 199 wild plants found in Kitui county have the potential of being utilized as foods in different ways. Plant species growing either as trees or shrubs (83 species) and herbs (36 species) are the dominant life forms while the best represented plant families are Leguminosae (25 species) and Malvaceae (17 species). Fruits (124 reports) and leaves (56 reports) are the common plant parts collected for food. Fruits (120 species) and vegetables (44 species) are the common wild food types in Kitui county. Further studies on species distribution are necessary to address conservation concerns that may threaten such plants.


New pregnane glycosides from Stelmatocrypton khasianum.
Four new pregnane glycosides, stelmatocryptonoside A, B, C, and D (1-4), were isolated from the stems of Stelmatocrypton khasianum. On the basis of chemical and spectral data, the structures of 1-4 were established as 3beta, 16alpha-dihydroxy-pregn-5-en-20-one-16-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside; 3beta, 20-dihydroxy-pregn-5-en-20-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-(1-->2)-beta-D-digitalopyranoside; 3beta, 16alpha-dihydroxy-pregn-5-en-20-one-16-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside; and 3beta, 16alpha-dihydroxy-pregn-5-en-20-one-16-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside. This is the first report of pregnane glycosides with sugar chains linked at C-16 of the aglycone.


Boron carbonitride nanofibers: synthesis, characterization, and photoluminescence properties.
Large-scale highly aligned boron carbonitride (BCN) nanofibers with controllable orientations and chemical compositions were synthesized directly on nickel substrates from a gas mixture of N2, H2, CH4, and B2H6 by plasma-enhanced hot filament chemical vapor deposition. The morphology of the BCN nanofibers was examined by scanning electron microscopy, the microstructures were studied by high-resolution transmission electron microscopy, and the bonding states as well as chemical compositions were determined by electron energy loss spectroscopy. To our knowledge, this is the first report on the photoluminescent properties of BCN nanofibers that shows that they are interesting blue- and violet-light-emitting materials with tunable wavelengths. Further studies on field electron emission suggest that BCN nanofibers are also promising candidates for field emission sources.


WITHDRAWN: Unlimited possibilities to use Сladophora (Chlorophyta, Ulvophyceae, Cladophorales) biomass in agriculture and aquaculture with profit for the environment and humanity.
This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been withdrawn at the request of the Publisher for legal reasons related to Elsevier's policy on Geographic Sanctions (https://www.elsevier.com/about/policies/trade-sanctions).


Melaleuca rugulosa (Link) Craven Tannins: Appraisal of anti-inflammatory, radical scavenging activities, and molecular modeling studies.
Genus Melaleuca or tea tree species are well known to be an important source of biological active oils and extracts. The biological significance appears in their usage for treatment of several clinical disorder owing to their traditional uses as anti-inflammatory, antibacterial, antifungal, and cytotoxic activities. Our study aimed to investigate the metabolic profile of the M. rugulosa polyphenol-rich fraction along with determination of its anti-inflammatory potential, free radical scavenging and antiaging activities supported with virtual understanding of the mode of action using molecular modeling strategy. The anti-inflammatory activity of the phenolic rich fraction was investigated through measuring its inhibitory activity against inflammatory mediators viz tumor necrosing factor receptor-2 (TNF-α) and cyclooxygenases 1/2 (COX-1/2) in a cell free and cell-based assays. Moreover, the radical scavenging activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and β-carotene assays, while the antiaging activity in anti-elastase, anti-collagenase, and anti-tyrosinase inhibitory assays. Finally, the biological findings were supported with molecular docking study using MOE software. The chromatographic purification of the polyphenol-rich fraction of Melaleuca rugulosa (Link) Craven afforded fourteen phytoconstituents (1-14). The anti-inflammatory gauging experiments demonstrated inhibition of inflammatory-linked enzymes COX-1/2 and the TNF-α at low μg/mL levels in the enzyme-based assays. Further investigation of the underlying mechanism was inferred from the quantification of protein levels and gene expression in the lipopolysaccharide (LPS)-activated murine macrophages (RAW264.7) in vitro model. The results revealed the reduction of protein synthesis of COX-1/2 and TNF-α with the down regulation of gene expression. The cell free in vitro radical scavenging assessment of the polyphenol-rich fraction revealed a significant DPPH reduction, peroxyl radicals scavenging, and β-carotene peroxidation inhibition. Besides, the polyphenol-rich fraction showed a considerable inhibition of the skin aging-related enzymes as elastase, collagenase, and tyrosinase. Ultimately, the computational molecular modelling studies uncovered the potential binding poses and relevant molecular interactions of the identified polyphenols with their targeted enzymes. Particularly, terflavin C (8) which showed a favorable binding pose at the elastase binding pocket, while rosmarinic acid (14) demonstrated the best binding pose at the COX-2 catalytic domain. In short, natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions. Natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions.


BNT162b2-elicited neutralization of Delta plus, Lambda, Mu, B.1.1.519, and Theta SARS-CoV-2 variants.
BNT162b2-elicited human sera neutralize the currently dominant Delta SARS-CoV-2 variant. Here, we report the ability of 20 human sera, drawn 2 or 4 weeks after two doses of BNT162b2, to neutralize USA-WA1/2020 SARS-CoV-2 bearing variant spikes from Delta plus (Delta-AY.1, Delta-AY.2), Delta-∆144 (Delta with the Y144 deletion of the Alpha variant), Lambda, B.1.1.519, Theta, and Mu lineage viruses. Geometric mean plaque reduction neutralization titers against Delta-AY.1, Delta-AY.2, and Mu viruses are slightly lower than against USA-WA1/2020, but all sera neutralize the variant viruses to titers of ≥80, and neutralization titers against the Delta-∆144, Lambda, B.1.1.519 and Theta variants not significantly reduced relative to those against USA-WA1/2020. The susceptibility of Delta plus, Lambda, B.1.1.519, Theta, Mu, and other variants to neutralization by the sera indicates that antigenic change has not led to virus escape from vaccine-elicited neutralizing antibodies and supports ongoing mass immunization with BNT162b2 to control the variants and to minimize the emergence of new variants.


Major Adverse Cardiovascular Events After Colchicine Administration Before Percutaneous Coronary Intervention: Follow-Up of the Colchicine-PCI Trial.
Periprocedural inflammation is associated with major adverse cardiovascular events in patients who undergo percutaneous coronary intervention (PCI). In the contemporary era, 5% to 10% of patients develop restenosis, and in the acute coronary syndrome cohort, there remains a 20% major adverse cardiovascular events rate at 3 years, half of which are culprit-lesion related. In patients at risk of restenosis, colchicine has been shown to reduce restenosis when started within 24 hours of PCI and continued for 6 months thereafter, compared with placebo. The Colchicine-PCI trial, which randomized patients to a 1-time loading dose of colchicine or placebo 1 to 2 hours before PCI, showed a dampening of the inflammatory response to PCI but no difference in postprocedural myocardial injury. On mean follow-up of 3.3 years, the incidence of major adverse cardiovascular events did not differ between colchicine and placebo groups (32.5% vs 34.9%; hazard ratio 0.95 [0.68 to 1.34]).


The establishment of a cytomegalovirus -specific CD8+ T-cell threshold by kinetic modeling for the prediction of post-hemopoietic stem cell transplant reactivation.
The dynamic interaction between the CMV virus and host immune response remains obscure, thus hindering the diagnosis and therapeutic management of patients with HSCT. The current diagnosis of CMV viremia depends on viral load estimation. Medical intervention based on viral load, can be unnecessary or poorly timed for many patients. Here we examined the clinical features and blood samples of patients with HSCT and assessed the CMV reactivation kinetics and corresponding CMV antigen-specific T-cell response in individual patients based on a peptide pool stimulation T-cell assay, which showed that CMV-specific CD8+ T cells were more suitable to be a diagnosis indicator for suppressing CMV reactivation. Using ROC analysis, we defined and verified a CMV-specific CD8+ T-cell counts threshold (925 cells/106 PBMCs) as an indicator of CMV reactivation post-HSCT, and suggested that use of this threshold would provide more accurate guidance for prompt medication and better management of CMV infection post-HSCT.


Carabid Beetle Assemblages (Coleoptera: Carabidae) in a Seminatural Grassland and the Adjacent Old Beech Forest in Northeast Japan.
The decline and disappearance of seminatural grasslands in Japan have caused a reduction in plant and animal species inhabiting such grasslands. We aimed to understand the assemblage structure, species diversity, and distribution of carabid beetles in traditionally managed seminatural grasslands, by comparing with the adjacent old beech forest. We investigated the carabid beetle assemblages in a seminatural grassland maintained by prescribed burning and annual mowing, and the adjacent old beech forest in Yamagata Prefecture, northeast Japan. We recorded several forest species along with open habitat species and habitat generalists in the grassland, suggesting that forest species may utilize the adjacent grasslands as temporary habitats. Cluster analysis showed that the assemblage structure of carabid beetles in the grassland differed from that in the beech forest. There were no clear differences in the carabid assemblages between the burned grassland sites and the grassland sites mowed in July after burning. This suggests that the annual mowing had little influence on the response of grassland carabid species in parts of the grassland. We recorded Harpalus roninus (Coleoptera: Carabidae), a rare carabid species in Japan, indicating that this beetle can be a characteristic of the studied grassland. Redundancy analysis showed that the eight abundant grassland species were associated with canopy openness, grass height, and understory vegetation cover, whereas the five most common species recorded from the beech forest were associated with litter depth and soil moisture.


Effect of low culture temperature on specific productivity and transcription level of anti-4-1BB antibody in recombinant Chinese hamster ovary cells.
Lowering the culture temperature has been suggested as a useful tool for improving the production of recombinant proteins in Chinese hamster ovary (CHO) cells. In an effort to improve anti-4-1BB antibody production in recombinant CHO (rCHO) cells, rCHO cells producing anti-4-1BB antibody (LGA31-56) were cultivated at three different temperatures, 30, 33, and 37 degrees C. Lowering the culture temperature led to suppressed cell growth, cell cycle arrest in G(0)/G(1) phase, and improved cell viability for a longer period. However, antibody production and q(Ab) were not increased at low culture temperature. The maximum antibody concentration and q(Ab) at 37 degrees C were 110.6 +/- 2.6 microg mL(-)(1) and 0.43 +/- 0.03 microg (10(6) cells h)(-)(1), respectively, whereas those at 30 degrees C were 28.3 +/- 3.8 microg mL(-)(1) and 0.44 +/- 0.07 (10(6) cells h)(-)(1), respectively. Northern blot analysis revealed that lowering the culture temperature did not increase the transcription level of heavy and light chains. These results were quite in contrast with the improved production of erythropoietin, which is expressed in the same CHO host and driven by the same CMV promoters, by lowering the temperature. Taken together, the results obtained imply that the beneficial effect of low culture temperature on recombinant protein production in rCHO cells is cell-line-specific.


Gender-specific association between childhood adversities and smoking in adulthood: findings from a population-based study.
To investigate gender-specific differences between individual adverse childhood experiences (ACEs) and smoking behaviours in adulthood; while controlling for several known risk factors, including adult health behaviours, adult mental health, adult socio-economic indicators and social support. Data were obtained from the 2010 Behavioral Risk Factor Surveillance System. The sample included 19,356 individuals (11,506 females and 7850 males) aged ≥18 years who were asked questions about their ACEs. Using logistic regression, the independent factors associated with ever smoking and current smoking were determined. Childhood physical abuse was associated with ever smoking for both males and females. Neither sexual abuse nor verbal abuse were significantly associated with ever smoking for males, but they were for females [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.13-1.63 and OR 1.14, 95% CI 1.02-1.27, respectively]. For both genders, childhood exposure to parental separation or divorce, household drug abuse or household problem drinking, were significantly associated with ever smoking. These findings underscore the need for future research that investigates gender-specific differences, and the possible mechanisms, linking individual ACEs and smoking behaviours.


Facile fabrication of glycosylated and PEGylated carbon nanotubes through the combination of mussel inspired chemistry and surface-initiated ATRP.
Surface modification of carbon nanotubes (CNTs) through controlled living polymerization has demonstrated to be a useful route for preparation of CNTs based polymer composites. However, surface oxidation of CNTs is often required to generate functional groups, which can be further utilized for immobilization of polymerization initiator and grafting polymers. The surface oxidation procedure is rather complex, high energy cost, low efficient and will destroy the structure of CNTs. Therefore, the development of simple and efficient strategies for preparation of CNTs based composites should be of great research interest and raised much attention recently. In this work, a novel mussel inspired strategy that combination of ATRP and ring-opening reaction has been developed for simultaneous preparation of glycosylated and PEGylated CNTs for the first time. CNTs were first coated with polydopamine (PDA) through self-polymerization of dopamine under alkaline aqueous solution. Then polymerization initiator was immobilized on CNT-PDA through simple esterification and amidation reaction to obtain CNT-PDA-Br. The PEGylated CNTs were synthesized through ATRP using CNT-PDA-Br as initiator and polyethylene glycol monoester acrylate and itaconic anhydride (IA) as the monomers. Finally, glucosamine was conjugated with IA via ring-opening reaction. The successful preparation of glycosylated and PEGylated CNTs (CNT-PDA-Poly(PEGMA-co-IA)-Glu) was confirmed by a number of characterization techniques in details. The obtained CNTs based composites showed improved aqueous dispersibility and desirable cytocompatibility, implying their biomedical application potential. As compared with the conventional covalent strategies, the mussel inspired method described in this work will not destroy the structure for introduction functional groups on the surface of CNTs, that can occur under rather mild experimental conditions, including room temperature, short reaction time and aqueous solution. On the other hand, the mussel inspired chemistry can also be used for surface modification of almost any materials regardless of their size, morphology and compositions. Therefore, we believe that the mussel inspired strategy should be a general method for fabrication of various polymer composites for different applications.


Safety and efficacy of a feed additive consisting of endo-β-1,4-xylanase produced by Komagataella phaffiiCGMCC 7.371 (VTR-xylanase) for all avian species, piglets (suckling and weaned) and minor growing porcine species (Victory Enzymes GmbH).
Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of endo-β-1,4-xylanase (VTR-xylanase) as a zootechnical feed additive for all avian species, piglets (suckling and weaned) and minor growing porcine species. VTR-xylanase is available in a powder and a liquid form and is produced by a genetically modified strain of Komagataella phaffii (CGMCC 7.371). The genetic modification of the production strain does not give rise to safety concerns. Viable cells of the production strain and its DNA were not detected in the final products. The additive does not pose any safety concern regarding the production strain. VTR xylanase (powder/liquid) produced by Komagataella phaffii CGMCC 7.371 is safe for all avian species, piglets and minor growing porcine species at the proposed conditions of use. The use of both forms of the additive under assessment in animal nutrition under the proposed conditions of use raises no safety concerns for consumers or for the environment. The liquid and powder formulations of VTR-xylanase are non-irritant to eyes but should be considered skin sensitisers. No conclusions can be drawn on the potential of the final formulations of the additive to be irritant to skin. Due to the proteinaceous nature of the active substance, the additive is a respiratory sensitiser. The additive has the potential to be efficacious in all laying birds and piglets (suckling and weaned) from all Suidae at 2,000 U/kg and in all other avian species/categories at 1,000 U/kg feed.


Characterization of the protein C activator Protac from the venom of the southern copperhead (Agkistrodon contortrix) snake.
A single chain glycopeptide with a molecular weight of approximately 37,000, an isoelectric point of 3.0 +/- 0.2 and a carbohydrate content of approximately 20% was isolated from the venom of the southern copperhead Agkistrodon contortrix contortrix. It was capable of converting zymogen protein C in plasma of man and various vertebrates into its activated form, a serine proteinase which exerts an anticoagulant effect. Conversion of the zymogen protein C into the active proteinase was demonstrated by measuring the prolongation of the activated partial thromboplastin time due to proteolytic degradation of factors Va and VIIIa by the activation product, as well as by direct measurement of the generated enzyme activity by means of a synthetic chromogenic substrate. Intravenous injection of the venom protein C activator into rabbits caused prolonged activated partial thromboplastin time. Repeated subcutaneous injections led to formation of an antibody which formed, with purified protein C activator as well as with crude A. contortrix venom, a precipitating complex devoid of protein C activator potency. As revealed by activity measurements and by immunodiffusion experiments, the venoms of various A. contortrix, A. bilineatus subspecies contain similar protein C activators.


Do nigro-striatal neurones possess a discrete dendritic modulatory mechanism? Electrophysiological evidence from the actions of amphetamine in brain slices.
Dopamine released from dendrites of nigrostriatal neurones in the substantia nigra exerts an inhibitory action on these cells. However, the spatio-temporal characteristics of the action of dendritic dopamine is still unclear. The aim of the present study was to investigate the responses of these neurones in the guinea-pig to amphetamine, applied locally in the region of the distal dendrites in pars reticulata. During intracellular recording in vitro it was found that amphetamine hyperpolarizes the membrane and causes a decrease in the input resistance, probably by increasing a potassium conductance. This response was resistant to blockade of sodium channels but sensitive to dopamine depletion by reserpine and alpha-methyl-p-tyrosine. The response showed tachyphylaxis and proved to be highly dependent on the site of administration of amphetamine. It is concluded that the release and action of dopamine occurs locally, in a heterogeneous pattern, within the dendritic field of nigrostriatal neurones. The possibility is discussed that this phenomenon underlies a modulatory mechanism, localized in dendrites.


Biodegradation of PCBs by ligninolytic fungi and characterization of the degradation products.
The aim of the present study was to compare the degrading capabilities of eight ligninolytic fungal representatives towards a technical mixture of polychlorinated biphenyls (Delor 103). Axenic cultures of the fungi, either in complex or N-limited liquid media, were spiked with the technical mixture of Delor 103. All of the fungal strains were able to degrade the pollutant significantly after 6weeks of incubation in both media. Outstanding results were achieved by the treatment with Pleurotus ostreatus, which removed 98.4% and 99.6% of the PCB mixture in complex and mineral media, respectively. This fungus was the only one capable of breaking down penta- and hexachlorinated biphenyls in the complex medium. Ecotoxicological assays performed with the luminescent bacterium Vibrio fischeri demonstrated that all of the fungal strains employed in this study were able to remove the toxicity only temporarily (e.g., after 28d of incubation), while P. ostreatus was capable of suppressing the toxicity associated to PCBs along the whole incubation period in both media. We also performed an extensive set of qualitative GC/MS analyses and chlorinated derivatives of hydroxy- and methoxy-biphenyls were detected along with monoaromatic structures, i.e. chlorobenzoic acids, chlorobenzaldehydes and chlorobenzyl alcohols. This results indicate that both intracellular (cytochrome P-450 monooxigenase, aryl-alcohol dehydrogenase and aryl-aldehyde dehydrogenase) and extracellular (ligninolytic enzymes) enzymatic systems could be involved in the biotransformation of PCB by ligninolytic fungi. The data from this work also document that the fungi are able to degrade further the main metabolites on the PCB pathway (i.e. chlorobenzoic acids) simultaneously with PCBs.


Late magnetic resonance imaging features of leukoencephalopathy in children with central nervous system tumours following high-dose methotrexate and neuraxis radiation therapy.
High-dose methotrexate (HDMTX) is used increasingly to treat children with central nervous system (CNS) tumours. Although the neuro-imaging features of leukoencephalopathy associated with systemic or intrathecal methotrexate administered after cranial radiation have been well described, the extent to which the sequencing of HDMTX prior to cranial radiation in infants and children predisposes to late neuroradiological features of leukoencephalopathy is unknown. This report describes the National Cancer Institute (NCI) toxicity grade of leukoencephalopathy based on magnetic resonance imaging (MRI) findings in all patients who survived 4 or more years after treatment on an earlier phase II study. These patients, with newly diagnosed CNS embryonal tumours, were in the age range 3.5-14.2 years (median 6.9 years) at diagnosis, and received four courses of pre-irradiation combination chemotherapy, including HDMTX 8 g/m(2). Following completion of the 'up-front' phase II study, all patients received conventionally fractionated whole brain doses of 36-50.4 Gy. The radiation dose and treatment volumes were determined individually according to the primary tumour location and results of extent of disease evaluations. The most recent MRI brain scans, obtained 4.0-10.5 years (median 6.5 years) after radiation therapy and comprising a minimum of T1, T1 following gadolinium and T2 sequences, were reviewed centrally to assess the neuroradiological grade of leukoencephalopathy, based on the NCI Common Terminology Criteria for Adverse Events, v3.0. Grade I changes (mild increase in subarachnoid space, and/or mild ventriculomegaly, and/or small/focal T2 hyperintensities) were evident in 8 of the 12 patients and grade II changes (moderate increase in subarachnoid space and/or moderate ventriculomegaly, and/or focal T2 hyperintensities extending to the centrum ovale) were found in the remaining 4. In conclusion, treatment with multiple courses of HDMTX prior to 36-50.4 Gy cranial radiation did not result in moderate to severe MRI features of leukoencephalopathy. Future studies in paediatric neuro-oncology patients, involving HDMTX combined with prospective neuropsychological evaluations appear justified.


Detection and Quantification of Mosaic Mutations in Disease Genes by Next-Generation Sequencing.
The identification of mosaicism is important in establishing a disease diagnosis, assessing recurrence risk, and genetic counseling. Next-generation sequencing (NGS) with deep sequence coverage enhances sensitivity and allows for accurate quantification of the level of mosaicism. NGS identifies low-level mosaicism that would be undetectable by conventional Sanger sequencing. A customized DNA probe library was used for capturing targeted genes, followed by deep NGS analysis. The mean coverage depth per base was approximately 800×. The NGS sequence data were analyzed for single-nucleotide variants and copy number variations. Mosaic mutations in 10 cases/families were detected and confirmed by NGS analysis. Mosaicism was identified for autosomal dominant (JAG1, COL3A1), autosomal recessive (PYGM), and X-linked (PHKA2, PDHA1, OTC, and SLC6A8) disorders. The mosaicism was identified either in one or more tissues from the probands or in a parent of an affected child. When analyzing data from patients with unusual testing results or inheritance patterns, it is important to further evaluate the possibility of mosaicism. Deep NGS analysis not only provides insights into the spectrum of mosaic mutations but also underlines the importance of the detection of mosaicism as an integral part of clinical molecular diagnosis and genetic counseling.


Experimental atherosclerosis in rabbits fed cholesterol-free diets. 13. Interaction of proteins and fat.
The atherogenic and cholesterolemic effects of animal protein vis-a-vis plant protein are well documented. Virtually all the studies were carried out using diets high in saturated fat, such as coconut oil. In order to determine if the same effects were seen with less saturated fat, we have compared atherogenic effects of an animal protein (casein) with those of a plant protein (soybean protein isolate) fed with partially hydrogenated soybean oil (PHS) (iodine value 72) or soybean oil (iodine value 134) as part of a cholesterol-free semipurified diet. After 6 months only rabbits fed casein-PHS exhibited elevated levels of plasma and liver cholesterol and triglycerides and atherosclerosis. Rabbits fed soy protein-PHS had slightly higher plasma cholesterol and triglycerides than did those fed soy protein and soybean oil, but values in both groups were in the normal range. The different effects of animal and plant protein on lipidemia and atherosclerosis can be influenced by dietary fat and appear to be dependent on fat saturation.


CCR3, CCR4, CCR5, and CXCR3 expression in peripheral blood CD4+ lymphocytes in gastric cancer patients.
CD4+(TH1, and TH2) cell groups in the point of view of chemokine receptor expression were considered in blood of stomach cancer patients. The percentage of blood CD4+ T cells expressing chemokine receptors (before and after gastrectomy) was determined by flow cytometry (Becton Dickinson, USA) using the following chemokine receptor antibodies: anti-CCR5, anti-CXCR3, anti-CCR3 and anti-CCR4. The means of CD4(+) CCR5(+) expressing cells was 1.23% ± 0.90, 0.83% ± 0.34 and 1.34% ± 0.74 in control, pre- and post-operation groups, respectively. CD4(+) CXCR3(+) expressing cells were 19.09% ± 8.4, 16.95% ± 5.71 and 25.08% ± 9.31, respectively. Similar pattern was seen for CD4(+) CCR3(+) and CD4(+) CCR4(+) expressing cells. Pearson correlation analysis shows no relationship between CCR3 and CCR4 expressions on TCD4 cells (r = 0.211, P = 0.126). The complex expression TH1 (CD4(+) CXCR3(+) CCR5(+)) receptors determined 1.14% ± 0.54 for control group, 0.86% ± 0.49 for pre-T and 1.57% ± 0.67 for post-T group. Moreover, the TH2 (CD4(+) CCR3(+) CCR4(+)) expression was 1.60% ± 1.05 for control group, 1.57% ± 0.83 for pre-T and 1.27% ± 0.66 for post-treatment group. Pearson correlation analysis shows that only the CCR3 and CCR5 expression was statistically correlated (r = 0.321, P = 0.018). Due to low expression of CCR5 in TH1 and CCR3 in TH2 cells, it seems that utility of these is extremely limited for clinical evaluation, but not scientific purpose. Moreover, considering the CXCR3 for TH1 cells and CCR4 expression for TH2 cells, due to considerable expression, may be practical.


[Surgical curriculum. A model from thoracic surgery].
There is a shortage of new surgeons in Germany. The blame for this is laid on poor working and training conditions in German hospitals. Professional associations suggest restructuring teaching plans to improve surgical education. The study conditions, postgraduate education, and surgical training in a thoracic surgical department are presented as a model curriculum. Surgical training can be structured. Curricula can be delineated for colleagues and applicants and comply with quality management standards. Clear and fair courses would improve surgical training and satisfy the expectations of contemporary surgeons.


[Study on quality of schistosomiasis knowledge questionnaire of primary pupils in Wuxing Farm School of Nanchang City].
To evaluate the quality of a questionnaire about schistosomiasis knowledge of the pupils in Wuxing Farm School in Nanchang City. The quality of the questionnaire about schistosomiasis knowledge was evaluated through reliability, validity, discrimination and some other indexes. The entire reliability of the survey was high with its split-half reliability of 0.68 and Cronbach alpha coefficient of 0.627. The content validity was good: the exploratory factor analysis revealed 5 common factors from 13 questionnaire items which could account for 58.3% of the total variance; the confirmatory factor analysis revealed that the construct validity of 13 questionnaire items was better than that of the whole questionnaire (17 items in total) (chi2 = 90.5, df = 65, GFI = 0.92, AGFI = 0.88, NFI = 0.58, CFI = 0.817, RMSEA = 0.049); the difficulty and the discrimination coefficients of the questionnaire were suitable, being 0.595 and 0.42 respectively. The questionnaire is qualified in general, but parts of the items need to be revised to perfect.


Formation of adenosine triphosphate from Pi and adenosine diphosphate by purified Ca-2+-adenosine triphosphatase.
Ca-2+-ATPase purified from sarcoplasmic reticulum of rabbit muscle forms a phsophoeznyme when exposed to inorganic phosphate in the presence of Mg-2+. On addition of ADP and Ca-2+ virtually all of the phosphate bound to the enzyme is transferred to form ATP. It has been shown previously and confirmed by us that (a) the purified ATPase contains one major polypeptide and about 30% phospholipids; (b) on removal of residual detergent by passage through Sephadex the enzyme forms vesicular membranes; and (c) these vesicles are leaky and incapable of accumulating Ca-2+. Our findings therefore indicate that we have observed ATP generation from ADP and P-i without the formation of an ion gradient across a membrane. We propose that the energy derived from ion-protein interaction drives the formation of ATP.


La- and Mn-doped cobalt spinel oxygen evolution catalyst for proton exchange membrane electrolysis.
Discovery of earth-abundant electrocatalysts to replace iridium for the oxygen evolution reaction (OER) in a proton exchange membrane water electrolyzer (PEMWE) represents a critical step in reducing the cost for green hydrogen production. We report a nanofibrous cobalt spinel catalyst codoped with lanthanum (La) and manganese (Mn) prepared from a zeolitic imidazolate framework embedded in electrospun polymer fiber. The catalyst demonstrated a low overpotential of 353 millivolts at 10 milliamperes per square centimeter and a low degradation for OER over 360 hours in acidic electrolyte. A PEMWE containing this catalyst at the anode demonstrated a current density of 2000 milliamperes per square centimeter at 2.47 volts (Nafion 115 membrane) or 4000 milliamperes per square centimeter at 3.00 volts (Nafion 212 membrane) and low degradation in an accelerated stress test.


Loci associated with adult stature also affect calf birth survival in cattle.
Understanding the underlying pleiotropic relationships among quantitative traits is necessary in order to predict correlated responses to artificial selection. The availability of large-scale next-generation sequence data in cattle has provided an opportunity to examine whether pleiotropy is responsible for overlapping QTL in multiple economic traits. In the present study, we examined QTL affecting cattle stillbirth, calf size, and adult stature located in the same genomic region. A genome scan using imputed whole genome sequence variants revealed one QTL with large effects on the service sire calving index (SCI), and body conformation index (BCI) at the same location (~39 Mb) on chromosome 6 in Nordic Red cattle. The targeted region was analyzed for SCI and BCI component traits. The QTL peak included LCORL and NCAPG genes, which had been reported to influence fetal growth and adult stature in several species. The QTL exhibited large effects on calf size and stature in Nordic Red cattle. Two deviant haplotypes (HAP1 and HAP2) were resolved which increased calf size at birth, and affected adult body conformation. However, the haplotypes also resulted in increased calving difficulties and calf mortality due to increased calf size at birth. Haplotype locations overlapped, however linkage disequilibrium (LD) between the sites was low, suggesting that two independent mutations were responsible for similar effects. The difference in prevalence between the two haplotypes in Nordic Red subpopulations suggested independent origins in different populations. Results of our study identified QTL with large effects on body conformation and service sire calving traits on chromosome 6 in cattle. We present robust evidence that variation at the LCORL and NCAPG locus affects calf size at birth and adult stature. We suggest the two deviant haplotypes within the QTL were due to two independent mutations.


Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in hepatocellular carcinoma.
KiSS-1 has been cloned as a human metastasis suppressor gene and an orphan G-protein-coupled receptor (hOT7T175) identified as the endogenous receptor of the KiSS-1 product. In the present study, we evaluated the clinical importance of KiSS-1 and hOT7T175 gene expression in hepatocellular carcinoma (HCC). The expression levels of KiSS-1, hOT7T175 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) messenger RNAs (mRNAs) were analyzed quantitatively by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 60 surgically resected HCCs. The KiSS-1/GAPDH and hOT7T175/GAPDH ratios of tumors were compared with clinicopathological findings. Loss of KiSS-1 mRNA expression was not detected in HCCs. The mean KiSS-1/GAPDH ratio did not change between non-cancerous cirrhotic livers and carcinomas. On the other hand, the average hOT7T175/GAPDH ratios increased from non-cancerous livers (0.08) to carcinomas (0.48). Overexpression of KiSS-1 and hOT7T175 genes was recognized in 6 tumors, which were in an advanced stage and showed poor survival. Overexpression of KiSS-1 and hOT7T175 genes was frequently observed and correlated with HCC progression; thus, the possibility that overexpressed KiSS-1 and hOT7T175 peptides mediate growth signals into cancer cells in HCCs is suggested.


Nuclear-localized CTEN is a novel transcriptional regulator and promotes cancer cell migration through its downstream target CDC27.
C-terminal tensin-like (CTEN) is a tensin family protein typically localized to the cytoplasmic side of focal adhesions, and primarily contributes to cell adhesion and migration. Elevated expression and nuclear accumulation of CTEN have been reported in several types of cancers and found to be associated with malignant behaviors. However, the function of nuclear CTEN remains elusive. In this study, we report for the first time that nuclear CTEN associates with chromatin DNA and occupies the region proximal to the transcription start site in several genes. The mRNA expression level of CTEN positively correlates with that of one of its putative target genes, cell division cycle protein 27 (CDC27), in a clinical colorectal cancer dataset, suggesting that CTEN may play a role in the regulation of CDC27 gene expression. Furthermore, we demonstrated that CTEN is recruited to the promoter region of the CDC27 gene and that the mRNA expression and promoter activity of CDC27 are both reduced when CTEN is downregulated. In addition, we found that enhanced nuclear accumulation of CTEN in HCT116 cells by overexpression of CTEN fused with nuclear localization signals increases CDC27 transcript levels and promoter activity. The increased nuclear-localized CTEN also significantly promotes cell migration, and the migratory ability is suppressed when CDC27 is knocked down. These results demonstrate that nuclear CTEN regulates CDC27 expression transcriptionally and promotes cell migration through CDC27. Our findings provide new insights into CTEN moonlighting in the nucleus as a DNA-associated protein and transcriptional regulator involved in modulating cancer cell migration.


Mechanisms and models of movement of protocells and bacteria in the early stages of evolution.
A review of the physicochemical models of the movement of protocells and bacteria was performed. The mechanisms of gliding and movement based on flagella are considered. Based on the models, the average speed of movement of protocells and bacteria was calculated. A physicochemical model of bacterial gliding was constructed. The efficiency of the process of converting the energy of ATP into the energy of motion is estimated. A review of models of movement with the help of flagella was performed. A model has been constructed for converting ATP energy into proton and sodium motive forces, which, in turn, are converted into energy of rotor rotation. The problem of the accuracy of operation of nanomachines, on the basis of which the directed movement of bacteria occurs, is discussed. The considered models can be applied to create nanomotors for medical purposes.


Theoretical study on the lithium-halogen exchange reaction of 1,1-dihaloalkenes with methyllithium and the nucleophilic substitution reaction of the resulting alpha-halo alkenyllithiums.
Transition structures for the lithium-bromine exchange reaction of 1,1-dibromoalkenes with methyllithium have been located by both the B3LYP and the MP2 levels of theory with the 6-31+G basis set. The reaction with methyllithium dimer gave similar results with lower activation energies. These calculations predict both the kinetic and the thermodynamic stereoselectivity correctly. That is, the sterically more constrained bromine atom of 1,1-dibromoalkenes was predominantly reacted with alkyllithium (dimer) in the kinetic condition. The intramolecular substitution reaction of 4,4-dibromo-3-methyl-3-pentenol in the presence of methyllithium has been investigated. After deprotonation of the alcohol and the lithium-bromine exchange reaction, the intramolecular substitution reaction occurs to give dihydrofuran in a concerted manner. The intermolecular substitution of alpha-chloro alkenyllithium with methyllithium was also studied for comparison. The formation of the indene derivative from 3-(o-bromophenyl)-1,1-dibromo-1-propene in the presence of methyllithium occurs in a similar manner. The lithium-bromine exchange reaction of bromobenzene with methyllithium occurs in an S(N)2 mechanism and the solvent plays an important role.


The incidence of proximal humeral fractures in New York State from 1990 through 2010 with an emphasis on operative management in patients aged 65 years or older.
Proximal humeral fractures are commonly encountered injuries. The development of locking plate technology and reverse shoulder arthroplasty may have changed the treatment patterns of these fractures. We used the Statewide Planning and Research Cooperative System database in New York State to determine the incidence of proximal humeral fractures from 1990 through 2010 and the choice of treatment: closed reduction-internal fixation, open reduction-internal fixation (ORIF), hemiarthroplasty (HA), or total shoulder arthroplasty (TSA). The population-adjusted incidence per 100,000 increased from 15.35 in 1990 to 19.4 in 2010 (P < .0001). In patients aged 65 years or older, the incidence increased from 78.9 in 1990 to 101.0 in 2010 (P < .0001). In 1990, 20.4% of proximal humeral fractures were treated operatively; in 2010, this increased to 28.6% (P < .0001). Closed reduction-internal fixation/ORIF accounted for 58.4% of operative cases in 1990, decreasing to 46.6% in 2001 and increasing to 59.4% in 2010. HA was used in 27.1% of operative cases in 1990, increasing to 41% in 2001 and decreasing to 29.4% in 2010. TSA was used in 6.4% of operative cases in 1990, decreasing to 1.5% in 2001 with an increase to 7.5% in 2010. The incidence of proximal humeral fractures in patients aged 65 or older increased by 28% between 1990 and 2010, and operative management increased by more than 40%. The use of ORIF increased between 2001 and 2010, corresponding with the use of locking plate technology. There was an associated decrease in HA. TSA increased between 2006 and 2010, corresponding to the use of reverse shoulder arthroplasty.


Analysis of improvement in performance and design parameters for enhancing resolution in an atmospheric scanning electron microscope.
The scanning electron microscope is used in various fields to go beyond diffraction limits of the optical microscope. However, the electron pathway should be conducted in a vacuum so as not to scatter electrons. The pretreatment of the sample is needed for use in the vacuum. To directly observe large and fully hydrophilic samples without pretreatment, the atmospheric scanning electron microscope (ASEM) is needed. We developed an electron filter unit and an electron detector unit for implementation of the ASEM. The key of the electron filter unit is that electrons are transmitted while air molecules remain untransmitted through the unit. The electron detector unit collected the backscattered electrons. We conducted experiments using the selected materials with Havar foil, carbon film and SiN film.


Possible influence on heart rate on tinnitus.
Assuming the possibility of the inner ear damage due to a hemodynamic imbalance essentially due to an abnormal vasomotor regulatory response, the possibility that heart rate (HR) has a correlation with the onset and/or the enhancement of tinnitus is hypothesized. In fact, recent studies have drawn the influence of other factors than blood pressure, in normotensive subjects, in taking part to the regulation of peripheral resistance, outlining the importance of both cardiac output (CO) - which is a function of heart rate (HR) and stroke volume (SV) and SV itself as a dynamic component to baroreflex control of muscle sympathetic nerve activity (MSNA). From this point of view, it could be possible that a condition of bradycardia can enhance tinnitus regardless of its cause, and conversely that a more elevated HR can be related to a relief of this symptom.


A needle-punched nonwoven experiment using cotton and polyester scraps to wrap preserved fruit.
This study investigates the use of cotton and polyester scraps to produce nonwoven fabrics via the needle-punching method in order to create packaging to preserve fruit. Firstly, the fiber properties were investigated. The needle-punching approach was then used to produce nonwovens, which underwent testing to determine their properties. The nonwovens were then used to create open-ended bags of two fabric types: perforated and non-perforated. These bags were used to wrap three different fruit types: Kimju guava, pear, and tomato. A color meter spectrophotometer was used to obtain the systematic color values for the fruits using C.I.E. LAB (L∗a∗b∗). The color values were obtained and used to compare color change (ΔE). The testing results for the effective length of the cotton and polyester fibers showed respective values of 20 mm and 33.7 mm, while the cotton fiber resolution was 3.42 denier. Three nonwoven fabrics were produced for analysis: cotton fibers, poly-cotton blends, and polyester fibers. Their respective weights per unit area were 82 g/m2, 96 g/m2, and 90 g/m2. It could be determined that the polyester nonwovens provided the most suitable physical properties, including thickness of 1.49 mm and air permeability of 160 cm3/s/cm2. The force required to rear the fabric in the longitudinal direction was 29.44 N, while in the transverse direction it was 24.532 N. The longitudinal and transverse breaks measured 236.844 and 220.448 mm, respectively. It was not possible to obtain results for the puncture test because the nonwoven fabric was too thin and weak. Testing of the fruit preservation qualities of the nonwoven protective wrappings over a ten-day duration revealed that perforated cotton was best for Kimju guava and tomato preservation, with the recorded color change (ΔE) indicating the superiority of this nonwoven fabric over the alternatives.


Randomized Clinical Trial of Endovascular Therapy for Acute Large Vessel Occlusion with Large Ischemic Core (RESCUE-Japan LIMIT): Rationale and Study Protocol.
Endovascular therapy is strongly recommended for acute cerebral large vessel occlusion (LVO) with an Alberta stroke program early computed tomography score (ASPECTS) ≥6 due to occlusion of the internal carotid artery or M1 segment of the middle cerebral artery. However, the effect of endovascular therapy for patients with a large ischemic core with an ASPECTS ≤5 (0-5) was not established. A multicenter, randomized, open-label, parallel-group trial was conducted to investigate the superiority of endovascular therapy over medical therapy without endovascular therapy for a large ischemic core with ASPECTS (3-5). Patients were randomly assigned to receive endovascular therapy or without endovascular therapy at a ratio of 1:1. The primary outcome was a moderate functional outcome, defined as a modified Rankin scale (mRS; scores ranging from 0 [no symptoms] to 6 [death]) ≤3 after 90 days. The secondary outcomes were defined as ordinal mRS, good functional outcome (mRS ≤2), excellent functional outcome (mRS ≤1), mRS shift analysis after 90 days, and early improvement of neurological findings at 48 hours. A total sample size of 200 was estimated to provide a power of 0.9 with a two-sided alpha of 0.05, for the primary outcome, considering a 15% dropout rate. This randomized clinical trial reported the applicability of endovascular therapy in patients with acute cerebral LVO with a large ischemic core.


A Quick and Comprehensive Guide to Differential Diagnosis of Neck and Back Pain: a Narrative Review.
The list of diagnostic options when approaching a patient with axial pain is impressively complex. Many offer limited diagnostic workups, but we could not find a truly comprehensive diagnostic guide to assist in the diagnostic evaluation. In this short paper, we briefly described a long list of medical conditions, each of which can manifest as back or neck pain, and whose prevalence ranges from common to very rare. We then proposed an algorithm for classifying them into subgroups. Further referral to diagnostic tests and specialist consultations, after assignment to one of those subgroups, could save time and unnecessary tests. We believe that this review and the proposed diagnostic algorithm can be valuable for medical education and for use in the primary care setting for the diagnostic evaluation of any type of back or neck pain in all patient groups.