Oxetin, a new antimetabolite from an actinomycete. Fermentation, isolation, structure and biological activity.
A new amino acid-antimetabolite, oxetin, was isolated from a fermentation broth of a Streptomyces sp. OM-2317, a soil isolate. The chemical structure was elucidated as (2R,3S)-3-amino-2-oxetane carboxylic acid by analysis of the spectral data and by X-ray diffraction methods. The antibiotic is the first natural product possessing an oxetane ring. Certain microorganisms were inhibited by oxetin only when cultivated in minimal media. The inhibitory action was reversed by several amino acids such as L-isoleucine, L-methionine, L-valine and L-glutamine. It also exhibited herbicidal activity and inhibited glutamine synthetase from spinach leaves.


Functional imaging of cerebrovascular activities in small animals using high-resolution photoacoustic tomography.
Photoacoustic imaging (PAI) is a noninvasive, nonionizing modality based on the differences in light absorption of various biological tissues. PAI utilizes the endogenous contrast characteristics of traditional optical imaging, while benefiting from high spatial resolution of the ultrasound imaging. A PAI system was developed to reconstruct the two-dimensional cross section image and to visualize the cerebrovascular activities of mouse in vivo. The spatial resolution of the PAI system was determined to be 0.110 mm by a two-point-source phantom with the Rayleigh criterion. The potential applications of the system were clearly demonstrated by successfully mapping a traumatic lesion in the mouse brain cerebral cortex, by its ability to monitor physiological changes in the brain due to carotid ligation and drug stimulation, and two-dimensional sliced images of a traumatic mouse brain at different depths were also provided. Our experimental results indicate that PAI has the potential for studying of traumatic brain injury and physiological functions of the brain.


Morph-specific fecundity and egg size in the female-dimorphic damselfly Ischnura senegalensis.
Females of coenagrionid damselflies exhibit color dimorphism, consisting of an andromorph and a gynomorph. This study compared reproductive traits between the female morphs in both field-captured and laboratory-reared females of the female-dimorphic damselfly Ischnura senegalensis. No difference was found in the onset of egg development between the morphs. The andromorphs developed significantly smaller mature eggs and had significantly more immature eggs than the gynomorphs. These results suggest that the andromorphs are r-strategists (high fecundity with small eggs), whereas the gynomorphs are K-strategists (low fecundity with large eggs). Fecundity and egg size might determine the quantity and quality of the offspring, respectively, indicating that morph-specific reproductive traits would contribute to the overall fitness of each female morph, and consequently be key factors affecting morph frequency in a population.


Memory Fidelity Reveals Qualitative Changes in Interactions Between Items in Visual Working Memory.
Memory for objects in a display sometimes reveals attraction-the objects are remembered as more similar to one another than they actually were-and sometimes reveals repulsion-the objects are remembered as more different from one another. The conditions that lead to these opposing memory biases are poorly understood; there is no theoretical framework that explains these contrasting dynamics. In three experiments (each N = 30 adults), we demonstrate that memory fidelity provides a unifying dimension that accommodates the existence of both types of visual working memory interactions. We show that either attraction or repulsion can arise simply as a function of manipulations of memory fidelity. We also demonstrate that subjective ratings of fidelity predict the presence of attraction or repulsion on a trial-by-trial basis. We discuss how these results bear on computational models of visual working memory and contextualize these results within the literature of attraction and repulsion effects in long-term memory and perception.


The six-year results of a combined surgical and endovascular repair for thoracoabdominal aortic aneurysm involving the visceral arteries.
The authors report a case of a combined endovascular and open repair (hybrid procedure) for a mycotic thoracoabdominal aneurysm (TAAA) including its 6-year result. A 72-year-old man with diabetes mellitus, old brain infarction and moderate aortic stenosis was transferred to the hospital because of obstinate fever and back pain, The initial computed tomography (CT) scan revealed giant (TAAA), and from the laboratory findings, the white blood cell and C-reactive protein (CRP) were significantly elevated 12,400/mm3 and 23.9 mg/dL respectively. Based on the CT and laboratory findings, a mycotic TAAA was highly suspected. After the remission of inflammation, graft replacement with reconstruction of celiac trunk (CA) and superior mesenteric artery (SMA) was performed via spiral incision under extracorporeal circulation. two months after the first operation, the patient complained about his back pain again. CT showed a pseudoaneurysm which formed at the distal anastomotic site. A hybrid procedure was deemed to be the most appropriate for such patient who needs a second operation. First bilateral renal artery bypass (ilio-renal artery bypass) were done using the saphenous vein grafts (SVGs). Following bypass grafting to renal arteries, endovascular aneurysm repair was performed with handmade stent-graft which was fabricated using a self-expanding "Z" stent and woven Dacron graft. The postoperative course was uneventful, and follow-up CT showed the aneurysm to have shrunk with no endoleaks. At six months after hybrid procedure, the shrinkage of the aneurysm sac and the patency of the graft to renal arteries were confirmed by a CT scan. A hybrid procedure is considered to be useful and feasible for the poor surgical candidate with severe comorbidities, hostile abdomen and a complex anatomy. The long-term results of this hybrid procedure is considered to be promising.


Simulation analysis of the effect of single-chamber double-line pipe jacking through different soil materials on surface uplift and subsidence.
This article is based on the relocation project of the 330 kV overhead line in Xi'an, China. In this paper, the soil settlement under different jacking depths was calculated by using the modified Peck's formula. Meanwhile, by modeling in ABAQUS, the jacking process of a single-chamber double-line large diameter pipeline under different soil conditions was simulated, and the ground deformation data under the different simulated working conditions were obtained. The results of the two methods were compared with the construction monitoring results, and it was found that the finite element simulation results were closer to the actual results. The control variable method was used in the analysis of the surface soil deformation law to analyze the effect of different soil parameters and pipe jacking depths on surface soil deformation. Finally, the best soil conditions applicable to single-chamber double-line large diameter pipe jacking construction were obtained through comparative analysis. The results show that (1) when using double-line construction, the maximum surface settlement under different soil conditions is located 11-15 m from the centerline of the soil above the pipeline, the minimum settlement location is inside the isolation pile, and with the increase in jacking distance, the settlement at the same section of the surface will gradually decrease and finally produce a small uplift. (2) In the first jacking, the settlement of powder clay is the largest, and the maximum settlement points in the surface section are more distributed. The maximum settlement value is approximately 11.66 mm. The settlement of powder soil is the smallest but produces a certain uplift deformation, and its maximum settlement is more concentrated in the surface section. After the comparison of deformation and soil parameters, loess-like soil is more suitable for single-compartment double-line large diameter pipe jacking construction. (3) When the top pipe burial depth changes, the greater the burial depth is, the smaller the settlement but the greater the lateral influence range. In the soil parameters, the modulus of elasticity only changes 3 MPa, and the settlement change value is approximately 5 mm. By changing the parameters, it can be obtained that the larger the modulus of elasticity of the soil is, the smaller its deformation. The larger the internal friction angle of the soil is, the smaller its deformation, but the maximum value of settlement change is only 1.7 mm, which means that the change in the internal friction angle has little effect on the soil deformation.


Evidence based practice of chronic pain.
The patients with chronic pain are increasingly reporting to the physicians for its management. Chronic pain are associated with head, neck and shoulder pain, spinal pain, pain in the joints and extremities, complex regional pain syndrome and phantom pain. The chronic pain is being managed worldwide. The different specialty of medicine is producing a lot of evidence through the published literature but the same is not being published in the field of chronic pain management. Though some evidence is being reported as to different aspects of pain management from different parts of the world but same is lacking from Indian subcontinent. This is in contrast to much done clinical work in this field as well. We present here the available evidence in relation to chronic pain management.


A Case of Left Groin Lymphocele Postoperatively.
Many surgical procedures may injure lymphatic channels unexpectedly, such as lymph node dissections, transplantations, and vessel reconstructions, and will lead to iatrogenic lymphatic leakage. We hereby present a case of postoperative lymphocele diagnosed more precisely by single-photon emission computed tomography (SPECT)/CT fusion imaging.


MicroRNA 214 inhibits adipocyte enhancer-binding protein 1 activity and increases the sensitivity of chemotherapy in colorectal cancer.
The present study aimed to analyze adipocyte enhancer-binding protein 1 (AEBP1) expression in colorectal cancer (CRC), with a focus on its possible molecular mechanisms, in order to provide novel insight into the clinical treatment of CRC. Immunohistochemistry (IHC) was used to detect AEBP1 expression in 62 CRC tissues. Kaplan-Meier survival curves were used to analyze AEBP1 expression and the postoperative disease-free survival (DFS) and overall survival (OS) rates of CRC patients. HT-29 cells were treated with oxaliplatin to detect cell proliferation and apoptosis following a Cell Counting kit-8. Through bioinformatics prediction, microRNA 214 (miR214) was identified as an upstream microRNA of AEBP1 that regulates its expression. IHC revealed that the expression of AEBP1 in CRC tissues was significantly higher than that in adjacent healthy tissues, and that it is associated with Tumor-Node-Metastasis stage, recurrence and metastasis. The DFS and OS rates of patients with a low AEBP1 expression were significantly higher than those in patients with a high expression (P<0.05). Following depletion of AEBP1 and treatment with oxaliplatin, the HT-29 cell proliferation was lower than that of the blank control and the negative control groups. However, the cell apoptosis rate was higher than that of the control group at 72 h (P<0.05). Bioinformatics prediction revealed that miR-214 is negatively associated with AEBP1 expression, and co-transfection and luciferase report gene tests revealed that AEBP1 is a target gene of miR-214. Therefore, AEBP1 may become a novel treatment for CRC patients with chemoresistance and may act through the upstream miR-214 to participate in the progression of a tumor.


[Secondary tumoral pleurisy].
WHEN THE PRIMARY CANCER IS KNOWN: Secondary tumoral pleurisy can develop at any stage in the evolution of a neoplastic disease and its diagnosis is easy when the primitive cancer is known. Cytological analysis of the pleural liquid and/or biopsy often provides material and the slides can then be compared with those of the primitive cancer and a relationship established. However, a probabilistic diagnosis should not be in haste, without anatomopathological confirmation, since the causes of pleurisy in a cancer patient are varied. WHEN THE PRIMARY CANCER IS NOT KNOWN: The most difficult situation is that when the pleurisy is revelatory of a neoplastic disease. In this case, explorations should be limited to a few essential examinations guided by the clinical profile, without being tempted to carrying out exhaustive explorations of the primitive cancer, which would not change the prognosis. Before such explorations, it is essential to obtain a precise pleural diagnosis, and for this, the indication for a pleuroscopy must be easily and rapidly accessible. FROM A THERAPEUTIC POINT OF VIEW: Once the diagnosis of pleurisy has be established, treatment is in two parts, associated or not: local treatment consisting in pleural sympysis and general treatment (chemotherapy or even hormone therapy, adapted to the primitive neoplasia). Pleural sympysis is often performed using talc, either during the pleuroscopy (talc insufflated under visual control), or during thoracic draining (talc slurry).


Construction of FGF21 knockout mouse models by the CRISPR/Cas9 system.
Fibroblast growth factors (FGFs) are multifunctional signal molecules between cells, regulating the various physiological functions of the organism. FGF21 is a regulatory factor of the FGF family and has been postulated to play important roles in hair follicle development and hair follicle growth cycle. To evaluate the roles of FGF21, we had established a FGF21 knockout mouse model, using the CRISPR/Cas9 technology. We had constructed a FGF21 targeting vector and microinjected it with Cas9 mRNA and gRNA into fertilized ova of FVB mice. The gRNA was designed to target the exon 1 of the endogenous mouse FGF21 gene. Three lines of Fgf21 -/- mice were obtained from these experiments, and confirmed to harbor Fgf21 -/- genotypes and null expression phenotype, using DNA sequencing, qRT-PCR and Western blotting. FGF21 mRNA and FGF21 protein were not detected in tissues of these Fgf21 -/- mice. Depilation and histochemistry analyses showed that the Fgf21 -/- mice had lower body weight, slower hair regrowth and poorer hair quantities and smaller hair follicles diameters, as compared to WT mice. The Fgf21 -/- mice reported here could provide a useful genetic model for future studies of FGF21 functions in hair follicle development and hair follicle growth cycle.


Diamond nanoparticles coating for in-tube solid-phase microextraction to detect polycyclic aromatic hydrocarbons.
Diamond nanoparticles were coated onto stainless steel wires as a extraction material, then it was filled into a poly(ether ether ketone) tube for in-tube solid-phase microextraction. Coupled with high-performance liquid chromatography, the extraction tube was evaluated with different types of analytes including polycyclic aromatic hydrocarbons, estrogens and plasticizers. As the coating, diamond nanoparticles exhibited greater extraction capacity for hydrophobic analytes. Several polycyclic aromatic hydrocarbons were used as model analytes, four main extraction and desorption factors were optimized, including sampling volume, sampling rate, methanol content in sample and desorption time. A sensitive analysis method was established with wide linear range (0.016-20 μg/L), good correlation coefficients (0.9991-0.9997), low limits of detection (0.005-0.020 μg/L), low limits of quantitation (0.016-0.070 μg/L) and high enrichment factors (305-2396). Relative standard deviations for intra- and interday were less than 2.4% (n = 3) and 8.4% (n = 3), respectively. Durability and chemical stability were satisfactory with relative standard deviations less than 7.9% (n = 3). Finally, the method has been successfully applied to the detection of polycyclic aromatic hydrocarbons in real samples.


Method for rapid identification and differentiation of the species of the Mycobacterium chelonae complex based on 16S-23S rRNA gene internal transcribed spacer PCR-restriction analysis.
Members of the Mycobacterium chelonae complex (MCC), including M. immunogenum, M. chelonae, and M. abscessus, have been associated with nosocomial infections and occupational hypersensitivity pneumonitis due to metalworking fluid (MWF) exposures. In order to minimize these health hazards, an effective and rapid assay for detection of MCC species and differentiation of MCC species from other species of rapidly growing mycobacteria (RGM) and from one another is warranted. Here we report such a method, based on the variable 16S-23S rRNA gene internal transcribed spacer (ITS) region. Mycobacterium genus-specific primers derived from highly conserved sequences in the ITS region and the flanking 16S rRNA gene were used. Specificity of the primers was verified using the MCC member species, 11 non-MCC RGM species, 3 slow-growing mycobacterial (SGM) species (two strains each), and 19 field isolates, including 18 MCC isolates (from in-use MWF) and one non-MCC isolate (from reverse osmosis water). The ITS amplicon size of M. immunogenum varied from those of M. chelonae and M. abscessus. Sequencing of the approximately 250-bp-long ITS amplicons of the three MCC member species showed differences in 24 to 34 bases, thereby yielding variable deduced restriction maps. ITS PCR-restriction analysis using the in silico-selected restriction enzyme MaeII or HphI differentiated the three MCC members from one another and from other RGM and SGM species without sequencing. The enzyme MaeII discriminated all three member species; however, HphI could only differentiate M. immunogenum from M. chelonae and M. abscessus. Use of an optimized rapid DNA template preparation step based on direct cell lysis in the PCR tube added to the simplicity and adaptability of the developed assay.


Carrots, Not Sticks: Adverse Impact and Wellness Programs.
The purpose of this study was to determine if wellness programs are likely to produce an adverse impact in various protected groups and to determine what features of the program may contribute to adverse impact. Using a nationally representative sample of US adults, we examined the proportions of protected groups that would be expected to encounter adverse impact using various health factors such as weight, blood pressure, and cholesterol levels. The results of this study indicate that disincentive-based programs pose a high risk of differentially selecting protected groups into program categories. This is especially true for members of multiple protected classes. We suggest organizations carefully consider both the type of program and the health factors incorporated into their wellness efforts and use incentives rather than disincentives to encourage health promotion.


Nursing staff's and physicians' acquisition of competences and attitudes to interprofessional education and interprofessional collaboration in pediatrics.
Interprofessional education (IPE) is deemed essential for interprofessional collaboration (IPC) in healthcare systems. IPC has positive effects for both patients and healthcare professionals. Especially in pediatrics, IPC is paramount for adequate care of patients and their families though there is a lack of data on the attitudes towards IPE and IPC and acquisition of respective competences in pediatric nursing and medical staff. Frequencies of interactions and attitudes towards IPE and IPC, with a focus on acquisition of competences for IPE and IPC, of nurses (N = 79) and physicians (N = 70) in a large pediatric university hospital were evaluated with an online questionnaire. All participants worked as part of interprofessional teams, mostly consisting of nurses and physicians. The majority (94.9% (n = 75) of nurses and 100% (n = 70) of physicians) highly valued IPC. Medical doctors acquired most competences important for IPC during day-to-day work and reported a substantial lack of IPE. Nursing staff on the other hand did report significant interprofessional education during their training as well as ongoing interprofessional learning during day-to-day work. Nurses also appreciated IPE more. Even though IPC is commonly reported in nurses and physicians working at a large pediatric university hospital there is a lack of structured IPE. A focus should be on IPE for nurses and physicians to enable them to effectively collaborate together. Political and local initiatives for IPE are gaining momentum but still need to be established nationally and internationally.


Polysaccharides from Angelica and Astragalus exert hepatoprotective effects against carbon-tetrachloride-induced intoxication in mice.
This study aimed to investigate the effects of polysaccharide from Angelica and Astragalus (AAP) on carbon tetrachloride (CCl4) induced liver damage in mice. A total of 120 Kunming mice were randomly distributed among 6 groups comprising (i) the normal control mice, (ii) the CCl4 treatment group, (iii) the bifendate treatment group, (iv) the AAP treatment group, (v) the Angelica sinensis polysaccharide (ASP) treatment group, and (vi) the Astragalus membranaceus polysaccharide (AMP) treatment group. AAP, ASP and AMP were administered to mice treated with CCl4. The activities of alanine transaminase (ALT) and aspartate transaminase (AST) in the serum, and superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver tissues were quantified, as well as the liver index. Hepatic histological changes were observed by staining liver sections with hematoxylin and eosin. Our results show that bifendate, AAP, ASP, and AMP significantly decreased the activities of MDA, AST, and ALT, and enhanced the activity of SOD in CCl4-treated mice. Bifendate, AAP, ASP, and AMP consistently ameliorated the liver injuries induced with CCl4. Notably, the hepatoprotective effect of AAP was stronger than that of bifendate, ASP, or AMP. In addition, AAP alleviated liver inflammation and decreased the liver indexes of mice induced with CCl4. These effects were at least partly due to the antioxidant properties of AAP in scavenging free radicals to ameliorate oxidative stress and to inhibit lipid peroxidation.


Is it advisable to perform radiosurgery for EGFR-TKI-controlled brain metastases? A retrospective study of the role of radiosurgery in lung cancer treatment.
Given the availability of TKIs with high central nervous system efficacy, the question arises as to whether upfront SRS provides additional clinical benefits. The goal of this study was to characterize the clinical outcomes of SRS as salvage therapy for TKI-uncontrolled BMs. This retrospective study included EGFR-mutant NSCLC patients presenting BMs at the time of primary tumor diagnosis. BMs were categorized into three subgroups, referred to as "Nature of TKI-treated BMs", "TKI-controlled brain metastases ± SRS", and "SRS salvage therapy". The first subgroup analysis characterized the effects of TKIs on tumor behavior. In the second subgroup, we compared outcomes of TKI-controlled BMs treated with TKI alone versus those treated with combined TKI-SRS therapy. The third subgroup characterized the outcomes of TKI-uncontrolled BMs treated with SRS as salvage therapy Clinical outcomes include local and distant tumor control. This study included 106 patients with a total of 683 BMs. TKI treatment achieved control in 63% of local tumors at 24 months. Among the TKI-controlled BMs, local tumor control was significantly higher in the combined TKI-SRS group (93%) than in the TKI-alone group (65%) at 24 months (p < 0.001). No differences were observed between the two groups in terms of distant tumor control (p = 0.832). In dealing with TKI-uncontrolled BMs, salvage SRS achieved local tumor control in 58% of BMs at 24 months. While upfront TKI alone proved highly effective in BM control, this study also demonstrated the outcomes of SRS when implemented concurrently with TKI or as salvage therapy for TKI-uncontrolled BMs. This study also presents a strategy of the precise timing and targeting of SRS to lesions in progression.


[Effect of larval feeding and imaginal supplementary nutrition on the degree of autogeny and fertility of Culex pipiens molestus mosquitoes at different periods of the year].
Studies of ovogenesis of C. p. molestus at different food regimes (water, sugar, blood) have shown that in winter the imaginal feeding with carbohydrates nearly twice increases the degree of autogenity and fecundity of these mosquitoes. In warm seasons the carbohydratous feeding does not affect the autogenity but increases the fecundity of females and maturation of their ovaries. Poor larval feeding decreases only slightly the autogenity and sharply decreases the fecundity of females. Blood feeding favours the maturation of ovaries in most members of C. p. molestus and the growth of their fecundity.


Streptococcus mutans serotypes and collagen-binding proteins Cnm/Cbm in children with caries analysed by PCR.
Streptococcus mutans, a primary bacterium associated with dental caries, has four known clinical serotypes (c, e, fand k). Certain serotypes, the presence of multiple serotypes and strains with collagen-binding proteins (CBP, Cnm and Cbm) have been linked with systemic disease. Evaluation of S mutans serotype distribution and caries association is needed in the United States. The purpose of this study was to evaluate the prevalence of S mutans serotypes from two cohorts of African-American children in rural Alabama using three sample types (saliva, plaque and individual S mutans isolates) by PCR detection for association with caries. Detection of CBP was also performed by PCR. In total, 129 children were evaluated and overall prevalence of serotypes were: serotype c(98%), e(26%), f(7%) and k(52%). Serotype c was statistically associated with higher caries scores in older children (P < 0.001) and serotype k was statistically more likely in females (P = 0.004). Fourteen per cent of children had CBP. Thirteen S mutans isolates from five children tested positive for both CBP. This study is the first to report on the prevalence of S mutans serotypes in a US population using the PCR-based approach. The frequency of serotype k in this study is the highest reported in any population, illustrating the need for further study to determine the prevalence of this clinically relevant serotype in the US. This is the first study to report S mutans isolates with both Cnm and Cbm in the same strain, and further analysis is needed to determine the clinical significance of these strains.


Value of leukocyte alkaline phosphatase and other leukocyte parameters in diagnosis of neonatal infection.
Various leukocyte parameters, i.e., leukocyte alkaline phosphatase (LAP) activity, absolute segmented polymorphonuclear count (segs), absolute band count and bands/segs ratio were studied in 15 full-term newborns with bacterial infections, 15 full-term newborns with bacterial infections, 15 full-term newborns with viral illnesses, and 10 age- and weight-matched control newborns. Mean LAP scores were 87.5 in the control group, 160.3 in newborns with viral illnesses, and 232.7 in newborns with bacterial infections. The differences between each group were statistically significant. The mean band count and bands/segs ratio were 65.6/mm3 and 0.013 in the control group; 842/mm3 and 0.18 in newborns with viral illnesses, and 2,207/mm3 and 0.37 in newborns with bacterial infections. LAP was more sensitive than other parameters in distinguishing the three groups. The data indicate that an LAP score of greater than 200, a band count of greater than 500/mm3 and a bands/segs ratio of greater than 0.3 are highly suggestive of bacterial infection.


Non-LTR R2 element evolutionary patterns: phylogenetic incongruences, rapid radiation and the maintenance of multiple lineages.
Retrotransposons of the R2 superclade specifically insert within the 28S ribosomal gene. They have been isolated from a variety of metazoan genomes and were found vertically inherited even if their phylogeny does not always agree with that of the host species. This was explained with the diversification/extinction of paralogous lineages, being proved the absence of horizontal transfer. We here analyze the widest available collection of R2 sequences, either newly isolated from recently sequenced genomes or drawn from public databases, in a phylogenetic framework. Results are congruent with previous analyses, but new important issues emerge. First, the N-terminal end of the R2-B clade protein, so far unknown, presents a new zinc fingers configuration. Second, the phylogenetic pattern is consistent with an ancient, rapid radiation of R2 lineages: being the estimated time of R2 origin (850-600 Million years ago) placed just before the metazoan Cambrian explosion, the wide element diversity and the incongruence with the host phylogeny could be attributable to the sudden expansion of available niches represented by host's 28S ribosomal genes. Finally, we detect instances of coexisting multiple R2 lineages showing a non-random phylogenetic pattern, strongly similar to that of the "library" model known for tandem repeats: a collection of R2s were present in the ancestral genome and then differentially activated/repressed in the derived species. Models for activation/repression as well as mechanisms for sequence maintenance are also discussed within this framework.


Role of SDF-1α/CXCR4 signaling pathway in clinicopathological features and prognosis of patients with nasopharyngeal carcinoma.
The present study aims to explore the role of stromal cell-derived factor-1α (SDF-1α)/stromal cell-derived factor receptor-4 (CXCR4) signaling pathway to the clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). From January 2009 to December 2010, 102 patients with NPC and 80 patients with chronic nasopharyngitis were enrolled for the study. Immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting were employed to determine the expressions of SDF-1α and CXCR4 proteins in NPC tissues and chronic nasopharyngitis tissues. Chi-square test was conducted to analyze the associations of the expressions of SDF-1α and CXCR4 proteins with the clinicopathological features of NPC patients. Spearman rank correlation analysis was used to analyze the correlation between the SDF-1α protein expression and CXCR4 protein expression. The mRNA and protein expressions of SDF-1α and CXCR4 in NPC tissues were significantly higher than those in chronic nasopharyngitis tissues. The expressions of SDF-1α and CXCR4 proteins showed associations with T staging, N staging, tumor node metastasis (TNM) staging, skull base invasion, and cervical lymph node metastasis of NPC patients. Compared with NPC patients showing negative expressions of SDF-1α and CXCR4 proteins, those with positive expressions of SDF-1α and CXCR4 proteins had a significantly shorter survival time. SDF-1α protein, CXCR4 protein, EBV-IgG status, T staging, N staging, TNM staging, skull base invasion, and cervical lymph node metastasis were independent risk factors for the prognosis of NPC. The findings indicated that SDF-1α/CXCR4 signaling pathway might be associated with the clinicopathological features and prognosis of patients with NPC.


Sequence of a 17 kDa vacuolar H(+)-ATPase proteolipid subunit from insect midgut and Malpighian tubules.
A 0.4 kb polymerase chain reaction (PCR) product obtained from cDNA made from the midgut and Malpighian tubules of fifth instar larvae of Heliothis virescens was used to screen a larval midgut and Malpighian tubules cDNA library. Four clones were obtained, one of 1.9 kb and others of 1.4 kb. The 1.9 kb clone encodes a 17.2 kDa protein which is highly homologous to other vacuolar ATPases proteolipids. Putative N-glycosylation and DCCD binding sites were observed at amino acid residues 83 and 139, respectively.


Interferon treatment in acute hepatitis B infection with prolonged course.
Interferon treatment (3.0 x 10(6) units of human leucocyte interferon) was initiated in a 64-year-old woman with acute hepatitis B infection showing a prolonged course. A decline in serum bilirubin, HBsAg and DNA polymerase activity started during the 10-day period of interferon treatment, and 4 weeks after start of treatment the liver function tests were quite normal. It is possible that the interferon treatment had a beneficial influence on the clinical course of the illness and may be worth trying also in acute fulminant cases of viral hepatitis.


Administration of porcine interleukin-3 induces increased levels of blood eosinophils.
Increasing resistance to anthelmintic drugs indicates a vital need to develop alternative strategies to control helminth infections. Interleukin-3 (IL-3) is a multilineage hematopoietic growth regulator produced by activated T lymphocytes in response to infection. In helminth infections, eosinophils play an important role in the elimination of parasites through their recruitment of inflammatory cells and the release of granules. The ability of IL-3 to stimulate the development of eosinophils makes it a particularly important candidate for therapeutic use to protect against parasites. To enable the role of IL-3 in the development, growth, and differentiation of porcine eosinophils to be elucidated, recombinant IL-3 (rPoIL-3) was expressed and purified. As the amino acid sequence identities between porcine IL-3 and other reported species were quite low ( approximately 39% between human and pig), an assessment of the in vitro activity of rPoIL-3 was made. The culture of porcine bone marrow (BM) cells with rPoIL-3 stimulated the proliferation of SWC3a(hi) myeloid cells, conA rming that rPoIL-3 acted as a hematopoietic cell growth factor. Since rPoIL-3 stimulated the development of myeloid cells in culture, the in vivo potential to produce elevated eosinophil proportions was assessed. In vivo administration of rPoIL-3 induced a signiA cant increase in the number of eosinophils in blood. These results suggest that rPoIL-3 is a potent inducer of eosinophils in swine and supports the inclusion of rPoIL-3 in therapeutic strategies.


Identification of Rickettsia conorii infection by polymerase chain reaction in a soldier returning from Somalia.
A soldier developed characteristic manifestations of boutonneuse fever shortly after leaving Somalia. Rickettsial DNA was detected in a biopsy sample of the tache noire by a polymerase chain reaction (PCR) in which primers derived from the 190-kD antigen gene of Rickettsia rickettsii were used. The source of this DNA was identified as Rickettsia conorii by restriction fragment length polymorphism (RFLP) analysis of the PCR product. R. conorii was also isolated from the skin biopsy specimen. The patient did not develop a significant increase in specific antibodies, as assessed by indirect fluorescent antibody testing, until several weeks after the onset of symptoms. This case demonstrates that the PCR/RFLP technique can be used for the direct identification of rickettsiae from clinical specimens. To our knowledge, this is the first confirmed case of R. conorii infection in Somalia.


Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells.
Mechanisms mediating adult enteric neurogenesis are largely unknown. Using inflammation-associated neurogenesis models and a transgenic approach, we aimed to understand the cell-source for new neurons in infectious and inflammatory colitis. Dextran sodium sulfate (DSS) and Citrobacter rodentium colitis (CC) was induced in adult mice and colonic neurons were quantified. Sox2GFP and PLP1GFP mice confirmed the cell-type specificity of these markers. Sox2CreER:YFP and PLP1creER:tdT mice were used to determine the fate of these cells after colitis. Sox2 expression was investigated in colonic neurons of human patients with Clostridium difficile or ulcerative colitis. Both DSS and CC led to increased colonic neurons. Following colitis in adult Sox2CreER:YFP mice, YFP initially expressed predominantly by glia becomes expressed by neurons following colitis, without observable DNA replication. Similarly in PLP1CreER:tdT mice, PLP1 cells that co-express S100b but not RET also give rise to neurons following colitis. In human colitis, Sox2-expressing neurons increase from 1-2% to an average 14% in colitis. The new neurons predominantly express calretinin, thus appear to be excitatory. These results suggest that colitis promotes rapid enteric neurogenesis in adult mice and humans through differentiation of Sox2- and PLP1-expressing cells, which represent enteric glia and/or neural progenitors. Further defining neurogenesis will improve understanding and treatment of injury-associated intestinal motility/sensory disorders.


[Argiopine, argiopinines and pseudoargiopinines--blockers of the glutamate receptors in hippocampal neurons].
Several homologous low-molecular weight compounds were purified from venom of spider Argiope lobata. They selectively blocked ionic currents elicited by glutamate and its agonist kainate in the membrane of isolated hippocampal neurons of rat. Three groups of these compounds--argiopine, argiopinines and pseudoargiopinines, blocked glutamate- and kainate-activated ionic currents in a voltage-dependent manner, acting preferentially on agonist-activated ionic channels. These compounds did not change the Kd values for both agonists. The blocking action was partially reversible for argiopine and poorly reversible for other compounds. Rate constants for the interaction of toxins with membrane receptors were estimated from the dependences of two-component kinetics of the blocking action and its recovery on toxin concentrations. Argiopine, argiopinines and pseudoargiopinines may be useful tools for further electrophysiological and biochemical investigation of the mammalian CNS glutamate receptors.


Body composition changes were related to nutrient intakes in elderly men but elderly women had a higher prevalence of sarcopenic obesity in a population of Korean adults.
In this study, we examined the relationship between sarcopenic obesity (SO) and nutrition status, according to sex in Korean adults who were 60 years or older. Body composition was categorized as SO, sarcopenic nonobesity, nonsarcopenic obesity, and nonsarcopenic nonobesity. Obesity was defined by body mass index. Sarcopenia was defined as an appendicular skeletal muscle mass divided by weight (Wt) of less than 1 SD below the sex-specific mean for young adults. Subjects included 1433 subjects (658 men and 775 women) who were 60 years or older and who participated in the fifth Korea National Health and Nutritional Examination Survey 2010. Sarcopenic obesity was more prevalent in women (31.3%) than in men (19.6%). Individuals with SO had significantly higher fasting insulin, homeostasis model assessment of insulin resistance (male: 3.2 ± 1.4, female: 3.4 ± 2.1), and triglycerides (male: 167.3 ± 90.6 mg/dL, female: 160.7 ± 85.0 mg/dL). High-density lipoprotein was under the normal criteria (50 mg/dL) in women. Intake of nutrients associated with muscle loss (protein, vitamin D, calcium, and vitamin C) was significantly different among the male but not the female groups. Although protein intake was normal, calcium and vitamin D intakes were insufficient in all groups. In conclusion, body composition changes were related to nutrient intakes in elderly (60 years or older) men but not elderly women. Women had a higher prevalence of SO than did men, suggesting that early nutritional intervention in elderly women may help them address age-associated body composition changes.


Dental fracture fragment attachment: fracture model and luting agent comparisons.
The purpose of this study was twofold: 1. To compare two different research models for simulating a traumatic anterior tooth fracture: the blunt trauma method (standard method) and an AL2O3 sectioning method (experimental method). 2. To compare the bond strength of tooth fragments bonded with resin modified glass ionomer vs. a light cured composite resin. Two hundred bovine incisors were used in the study and kept in plain tap water throughout. The study consisted of five basic steps: 1. Fracture of the teeth by either blunt trauma (chisel and hammer) or AL2O3 sectioning disc. 2. Luting of the fractured fragments back to the teeth using either a composite resin or resin modified glass ionomer. 3. Thermocycling of the repaired teeth. 4. Dislodging the teeth to determine the strength of repair. 5. Determination of fracture type. One-way ANOVA revealed a statistically significant difference in the forces required to fracture the resin modified glass ionomer and composite resin regardless of whether the teeth were originally fractured with the blunt force method (p=0.030) or the disc sectioning method (p=.001). One-way ANOVA also revealed a statistically significant difference between the forces required for fracture by blunt trauma and the disc fracture techniques with the resin modified glass ionomer group (p=0.000345). However, there was no significant difference when the two techniques were compared for the composite resin (p= 0.2941). 1. The resin modified glass ionomer was significantly stronger than the composite resin when both the blunt trauma and the disc fracture techniques were employed. 2. The study's results do not support substituting the ease of the AL2O3 disc for the more time-consuming blunt trauma method.


Integrating Artificial Intelligence and Wearable IoT System in Long-Term Care Environments.
With the rapid advancement of information and communication technology (ICT), big data, and artificial intelligence (AI), intelligent healthcare systems have emerged, including the integration of healthcare systems with capital, the introduction of healthcare systems into long-term care institutions, and the integration of measurement data for care or exposure. These systems provide comprehensive communication and home exposure reports and enable the involvement of rehabilitation specialists and other experts. Silver technology enables the realization of health management in long-term care services, workplace care, and health applications, facilitating disease prevention and control, improving disease management, reducing home isolation, alleviating family burden in terms of nursing, and promoting health and disease control. Research and development efforts in forward-looking cross-domain precision health technology, system construction, testing, and integration are carried out. This integrated project consists of two main components. The Integrated Intelligent Long-Term Care Service Management System focuses on building a personalized care service system for the elderly, encompassing health, nutrition, diet, and health education aspects. The Wearable Internet of Things Care System primarily supports the development of portable physiological signal detection devices and electronic fences.


[If it's not only itching or burning: management of sexually transmitted infections (part 2].
In this second part about sexually transmitted infections (STI) we focus on the commonest pathogens related with genital ulcer disease, including Herpes simplex virus, Treponema pallidum and Chlamydia trachomatis. As most of these pathogens can cause long-term sequelae if left untreated it is of upmost importance to be familiar with the clinical manifestations and current diagnostic and therapeutic management. Most recent published international guidelines are reviewed to provide an updated overview.


In vitro anti-tumour and cyto-selective effects of coumarin-3-carboxylic acid and three of its hydroxylated derivatives, along with their silver-based complexes, using human epithelial carcinoma cell lines.
The chemotherapeutic potential of coumarin-3-carboxylic acid (C-3-COOH) and a series of three hydroxylated coumarin-3-carboxylic acid ligands, namely 6-hydroxy-coumarin-3-carboxylic acid (6-OH-C-3-COOH), 7-hydroxy-coumarin-3-carboxylic acid (7-OH-C-3-COOH) and 8-hydroxy-coumarin-3-carboxylic acid (8-OH-C-3-COOH), along with their corresponding silver-based complexes, namely 6-hydroxycoumarin-3-carboxylatosilver (6-OH-C-COO-Ag), 7-hydroxycoumarin-3-carboxylatosilver (7-OH-C-COO-Ag) and 8-hydroxycoumarin-3-carboxylatosilver (8-OH-C-COO-Ag), was determined using two human-derived carcinoma (A-498 and Hep-G2), along with two non-carcinoma human-derived cell lines (CHANG and HK-2). All of the ligands and their silver complexes induced a concentration-dependent cytotoxic effect. Furthermore, hydroxylation of C-3-COOH and its subsequent complexation with silver led to the production of a series of compounds with dramatically enhanced cytotoxicity, with 6-OH-C-3-COO-Ag having the greatest activity. Additionally, all of the metal-based complexes were selectively cytotoxic to both carcinoma-derived cell lines, relative to normal renal and hepatic cells. In comparative studies with cisplatin, and based on the IC(50) values obtained with Hep-G2 cells, it appeared that the coumarin-silver complexes were between 2 and 5.5 times more cytotoxic than cisplatin. All of the coumarin-silver complexes inhibited DNA synthesis, which did not appear to be mediated through intercalation. Furthermore, results obtained from Ames tests showed that all of the test agents and their phase I metabolites were non-mutagenic. Taken together, these findings suggest that both hydroxylation particularly in the 6th position and complexation with silver, served to significantly augment the cytotoxic properties of C-3-COOH, to yield a compound which acts as a cyto-selective agent, as it is a significant killer of cancer, relative to normal cells. We suggest that this group of compounds may have a therapeutic role to play in the successful treatment and management of cancer in man.


Knowledge, attitude and practices about animal bites and rabies in general community--a multi-centric study.
Rabies a disease as old as our civilization, continues to be the most feared of all communicable diseases. Despite the availability the state-of-the-art tools which ensure near cent percent protection against rabies, India is the largest contributant to rabies mortality in the world. A multicentric study was carried out from April 2001 to September 2002 with the objective of assessing the knowledge, attitudes, beliefs and practices (KAP) about animal bites and rabies in the general community. The proforma for interviewing the general community was developed and used after field testing. The study was carried out at six selected centres across the country viz. Delhi, Hyderabad, Raipur, Jamnagar, Coonoor and Rajahmundry and was co-ordinated by National Institute of Communicable Diseases (NICD), Delhi, after thorough briefing of designated nodal officers. A total of 1129 (male: female :: 48.5: 51.5) persons in the age group of 18 to 80 years were interviewed in this study. Of these about 751% of the individuals had attended school at some level and rest were illiterates. 68.7% people had heard about rabies. In 60.7% of cases the community associates rabies with dog bite only. Knowledge about appropriate wound toilet was found to be inadequate. Only 360 (31.9%0/) people felt that washing the wound with soap and water was the best option. Application of indigenous products like chillies (11.4%), turmeric (5.6%), lime (6.8%), kerosene oil (2.3%), herbal paste (4.2%) etc was suggested along with visit to occult medicine practitioner (1.5%) as part of the bite wound management. People were not aware of number of injections needed for treatment of animal bites. Multiple reasons viz negligence and ignorance 354 (31.4%), fear of multiple painful injections 365 (32.3%), expensive treatment 169 (15%) and long course requiring daily visits to anti-rabies clinics 73 (6.5%) were cited as reasons for non-compliance of treatment. KAP study suggests that there is need to create awareness amongst the masses regarding epidemiology of the disease and merits of prompt and appropriate post exposure treatment through enhanced IEC activities.


Changes in thyroid hormone and thyrotrophin in the serum and thyroid glands of developing genetically obese male and female Zucker rats.
In a first experiment, serum thyroxine (T4), 3,5,3'-triiodothyronine (T3) and thyrotrophin (TSH) concentrations as well as thyroid gland T4 and T3 contents were measured in developing lean and obese Zucker male and female rats of 4-16 weeks of age. The rats were bred in our laboratory and always treated in sex-matched pairs of one lean and one obese rat from the same litter. Serum T4 was not different in any phenotype/sex group at 4 weeks. In male rats, it became progressively lower (27 and 37% at 12 and 16 weeks respectively) in obese than in lean rats. In females, similar levels of serum T4 were maintained in both obese and lean developing rats. Serum T3 was similar in obese and lean male 4-week-old rats whereas it was lower (28%) in obese than in lean females. It became progressively lower (39 and 49% at 12 and 16 weeks respectively) in obese than in lean developing male rats. In females, lower levels of serum T3 were maintained (25 and 43% at 12 and 16 weeks respectively) in obese than in lean rats. Serum TSH was not different in any phenotype/sex group at 4 weeks. It rose in both obese and lean male rats with age, but became progressively lower (33 and 23% at 12 and 16 weeks respectively) in obese compared with lean rats. In females, similar levels of serum TSH were maintained in both obese and lean developing rats. Thyroid gland weight was not different in any phenotype/sex group at 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)


Survival analyses of different treatment modalities and clinical stage for hypopharyngeal carcinoma.
We investigated the effects of different treatment modalities and clinical stage for hypopharyngeal carcinoma (HPC) patients. Between February 2004 and December 2012, 167 HPC patients were reviewed. We calculated overall survival (OS), progression-free survival (PFS), local failure-free survival (LFFS), regional failure-free survival (RFFS), and distant metastasis failure-free survival (DMFFS) using the Kaplan-Meier method and compared various survival outcomes between definitive chemoradiotherapy (CRT) and surgery-based therapy (SBT). There were no significant differences in baseline characteristics between SBT (n = 102) and definitive CRT (n = 65) groups. The 5-year rates of OS (59.7% vs. 24.0%, p < 0.0001) and PFS (49.9% vs. 22.6%, p = 0.0002) were significantly better in patients who received SBT than in those who received definitive CRT. The SBT group also obtained better LFFS (p < 0.0001), RFFS (p = 0.0479), and DMFFS (p = 0.0110). We did similar analyses by different T-classification (T1-2, T3, and T4) and found that SBT had better OS (p < 0.0001 and p = 0.0020), PFS (p < 0.0001 and p = 0.0513), LFFS (p = 0.0002 and p = 0.0075), RFFS (p = 0.1949 and p = 0.0826), and DMFFS (p = 0.0248 and p = 0.0436) in the T4 and T1-2 subgroups but similar OS (p = 0.9598), PFS (p = 0.5052), RFFS (p = 0.9648), and DMFFS (p = 0.8239) in T3 patients. Analyses by different overall stages revealed no differences between definitive CRT and SBT for stage III patients but significantly better results for stage IV patients who received SBT. SBT can obtain significant survival benefits when compared with definitive CRT for the whole cohort of patients. Definitive CRT has similar survival outcomes compared with SBT only for T3 tumors or overall stage III disease.


Ziprasidone overdose: cases recorded in the database of Pfizer-Spain and literature review.
Ziprasidone is an atypical antipsychotic with a highly specific receptorbinding profile that has been shown to be effective for both positive and negative symptoms of schizophrenia. The agent has been associated with a low frequency of extrapyramidal symptoms and sedative and anticholinergic effects. Four cases of acute ziprasidone overdose were recorded in the database of the department of pharmacovigilance of Pfizer-Spain from January 2003 (when ziprasidone was first marketed in Spain) to October 2004. The doses taken were 780, 1120, 4400, and 4480 mg. In two cases, an excessive ingestion of other drugs such as benzodiazepines and sedative hypnotics was also noted. None of the four cases showed cardiac adverse effects, and the QTc interval was within the normal range in all patients. No relevant neurologic clinical signs were observed, except for mild drowsiness in three cases. Evaluation of these four cases, as well as review of the literature, showed that an overdose of ziprasidone alone, in patients without risk factors that contraindicate its use, is relatively safe.


Growth- and stress-related defects associated with wall hypoacetylation are strigolactone-dependent.
Mutants affected in the Arabidopsis TBL29/ESK1 xylan O-acetyltransferase display a strong reduction in total wall O-acetylation accompanied by a dwarfed plant stature, collapsed xylem morphology, and enhanced freezing tolerance. A newly identified tbl29/esk1 suppressor mutation reduces the expression of the MAX4 gene, affecting the biosynthesis of methyl carlactonoate (MeCLA), an active strigolactone (SL). Genetic and biochemical evidence suggests that blocking the biosynthesis of this SL is sufficient to recover all developmental and stress-related defects associated with the TBL29/ESK1 loss of function without affecting its direct effect-reduced wall O-acetylation. Altered levels of the MAX4 SL biosynthetic gene, reduced branch number, and higher levels of MeCLA, were also found in tbl29/esk1 plants consistent with a constitutive activation of the SL pathway. These results suggest that the reduction in O-acetyl substituents in xylan is not directly responsible for the observed tbl29/esk1 phenotypes. Alternatively, plants may perceive defects in the structure of wall polymers and/or wall architecture activating the SL hormonal pathway as a compensatory mechanism.


Insight into active sites of nitrogen-doped carbon catalyst by stochastic collision electrochemistry.
Identifying the active sites of electrocatalysts is important for catalyst design. However, determining the specific active sites of catalysts is still a challenge. Herein, we demonstrate that stochastic collision electrochemistry could be used as a simple but efficient method for identifying the active sites of electrocatalysts, which can overcome the problems caused by the considerable difference between the giant geometric area and the limited exposure of active sites when using traditional cyclic voltammetry. To validate the method, the oxygen reduction reaction and ascorbic acid electrooxidation with the as-synthesized nitrogen-doped carbon catalysts were selected as model reactions. The results show that the pyridinic N dominates the reactivity of the oxygen reduction reaction while the CO functional group is the active site for ascorbic acid oxidation, which could not be identified by cyclic voltammetry with the ensemble drop-casting method. This manuscript demonstrates a new method for identifying the active sites of electrocatalysts, essentially enriching the methodology for identifying active sites.


Functional MDR1 polymorphisms (G2677T and C3435T) and TCF4 mutations in colorectal tumors with high microsatellite instability.
The multidrug resistance 1 (MDRI) gene and transcription factor 4(TCF4) gene are suggested to be involved in the WNT signalling pathway, the most important pathway altered in colorectal cancer. Mutations in both genes have been identified and associated with colorectal tumors exhibiting high microsatellite instability (MSI-H). In this study, we report on the distribution of functional polymorphisms in the MDR] gene and somatic frameshift mutations in the TCF4 gene coding mononucleotide repetition in 62 MSI-H colorectal tumors. Somatic frameshift mutations in(of) the TCF4 gene were identified in 24/62 (39%) of the studied MSI-H tumors. The estimated allele frequencies of functional polymorphisms in(of) exon 21 (2677 G>T, Ala893Ser) and exon 26(3435 C>T, Ilel 142I1e) of the MDR] gene were 0.42 and 0.46 in the controls and 0.54 (p=0.035) and 0.60 (p=0.017) in the MSI-H tumors. However, the allele frequency of both functional MDR] polymorphisms did not significantly differ between MSI-H tumors with TCF4 mutations and those without. These results support the involvement of the MDRI gene in the tumorgenesis of MSI-H tumors and also suggest that functional polymorphisms in the MDRI gene and mutations in the TCF4 gene are likely to occur independently in MSI-H tumors.


A pilot study for the detection of FLT3-ITD mutation frequency in 25 Iraqi patients with acute lymphoid leukemia in 2 Iraqi hospitals.
This study was conducted to evaluate the frequency of FLT3-ITD mutation in acute lymphoid leukemia (ALL) patients using conventional polymerase chain reaction (PCR) in Iraq, and to correlate this mutation with prognostic parameters of patients. A total of 25 individuals were enrolled (16 children with ALL and 9 adult with ALL), attending 2 teaching hospitals in Baghdad. Hematological investigations including complete blood picture, and bone marrow aspiration were performed. FLT3-ITD mutation was detected utilizing conventional PCR technology using specific primers. Two of 25 ALL patients (8%) showed a mutated band of FLT3-ITD mutation representing 12.5% of pediatric patients, and all the other ALL cases showed the absence of this mutation. These cases were an 8-year-old girl and a 7-year-old boy, L2 subtype, who had achieved complete hematological remission throughout the study. In conclusion, FLT3-ITD mutation was found in 2 morphologically appearing pediatric ALL patients that was higher than previously reported worldwide. Bilineage cases could not be excluded owing to absence of flow cytometer analysis. A larger number of Iraqi ALL patients confirmed by flow cytometer is necessary to evaluate the prognostic effect of this mutation in pediatric age group, especially FLT3 tyrosine kinase inhibitors might represent a promising target in ALL patients and can be used as minimal residual disease marker.


The interference of geographical changes of cancer risk in tumor etiology in Japan.
An attempt was made to elucidate the relation between various human neoplasias in their geneses by comparatively investigating the geographical changes of cancer risk either between 2 sexes with one neoplasia or between two neoplasias for each sex with the data of multiple local populations of Japan as well as of the world. Specific cancer death rates for 11 sites in 46 prefectures of Japan, 1969-1971, were used in the domestic study, and age-adjusted cancer incidence rates for the corresponding 11 sites in 40 selected cancer registration areas of the world were used in the international study. The relation between 2 cancer risks was analyzed by calculating a 1st order regression equation using log-transformed data sets. Results obtained are as follows: 1) both the domestic and international data sets confirmed positive correlations of a high degree between the male and the female cancer risks in 6 out of 7 cancer sites tested (esophagus, stomach, colon, rectum, liver and bladder). A positive intersex correlation was also observed in lung cancer with the international data, but not with the domestic one. It was indicated that the male and female populations of Japan as well as of the world were under the influence of a common risk modifier in the course of geographical changes of cancer risk for each of 6 neoplasias except lung cancer. 2) Intercancer correlation was lacking in 11 out of 23 cancer pairs in the domestic study, whereas all 22 intercancer correlations but one in the international study were found to be statistically significant. Further insight into the correlation data of the international study led to the conclusion that the observed combination of positive and negative correlation in the 22 cancer pairs were explainable in terms of the differential cancer risk changes of Western type and Non-Western type cancers due to the transition of life style between the Western extreme and the Non-Western extreme in the world. In contrast, a high proportion of non-correlations (11 out of 23 cancer pairs) and emergence of opposite or new correlations (3 out of 23 pairs) were observed in the domestic study, a finding which indicates that the domestic cancer risk modifier, as evidenced in the intersex correlation test, is site-specific, and is to be differentiated from the Westernization-sensitive cancer risk modifiers of the international study.(ABSTRACT TRUNCATED AT 400 WORDS)


Preliminary experience using an optimized three-point transformation algorithm for spatial registration of coordinate systems: a method of noninvasive localization using frame-based stereotactic guidance systems.
This study describes the use of an optimized three-point transformation algorithm to spatially cross-register a volumetric computerized tomographic scan or magnetic resonance image data set with the coordinate system of a stereotactic frame. This algorithm was tested for accuracy using a scanned phantom in which calculated targets, using the Brown-Roberts-Wells (BRW) frame picket-fence algorithm as a standard, could be compared to physical targets measured using a BRW arc and phantom. These target values were then compared to target values calculated with the optimized three-point algorithm. This method was used for target localization in 21 patients. Following this noninvasive localization method, the standard BRW stereotactic system was used for guidance. The application accuracy of this frameless localization technique was within the limits of the scan slice thickness in 16 of 21 cases, with an average error of 2.11 mm in an average scan slice thickness of 3.1 mm. Intracranial targets were successfully reached in all cases without morbidity or mortality. The algorithm can be customized to cross-register image data sets with the coordinate systems of a wide variety of stereotactic guidance systems. The method increases the convenience and flexibility of frame-based stereotactic guidance by providing a means of noninvasive localization that can be accomplished electively at a separate time from the guidance part of a stereotactic operative procedure.


Mining wastewater management and its effects on groundwater and ecosystems.
Large-scale mining activities have a huge impact on the environment. Determination of the size of the effect and monitoring it is vital. In this study, risk assessment studies in mining areas and the effect of mining on groundwater and ecosystems were investigated. Best management practices and risk assessment steps were determined, especially in areas with huge amounts of mining wastewater. The pollution of groundwater and its reaching humans is a risk of major importance. Our study showed, using many cases with different parameters and countries, that the management of mining wastewater is vital. Environmental impact assessments and monitoring studies must be carried out before operation and at the closure of the mine. Policies must be in place and ready to apply. Factors of climate, geology, ecology and human health must be considered over a long period. Currently, only the developed countries are applying policies and paying attention to the risk. International assessments and health risk assessments should be carried out according to international standards.


Clinical Significance of Pro-inflammatory Cytokines and Their Correlation with Disease Severity and Blood Coagulation in Septic Patients with Bacterial Co-infection.
To evaluate the clinical significance of pro-inflammatory cytokines for disease severity and coagulation in septic patients with bacterial co-infection. A total of 92 patients with sepsis admitted to intensive care unit (ICU) from January 2017 to August 2020 were enrolled and their clinical data were retrospectively analyzed. Forty-seven patients (51.1%) had a single infection by Klebsiella pneumoniae or Acinetobacter baumannii (single-infection group), and 45 patients (48.9%) were infected by both species (co-infection group). We compared the clinical characteristics and disease severity among the 92 patients. Disease severity was defined as ICU stay time and 30-day mortality. Plasma concentrations of pro-inflammatory cytokines and their correlation with disease severity and blood coagulation were analyzed. The 30-day mortality in the co-infection group (35.5%) was significantly higher than in the single-infection group (19.1%). The levels of IL-6 and TNF-α in the co-infection group were higher than in the single-infection group. Moreover, high levels of IL-6, IL-8, and TNF-α were positively correlated with disease severity (Spearman P value < 0.05). High levels of IL-6 and TNF-α were negatively correlated with the platelet count (Spearman P value < 0.05) and positively correlated with prothrombin time, and plasma levels of fibrin degradation product and D-dimer levels (Spearman P value < 0.05 for all). Septic patients with bacterial co-infection had increased plasma levels of pro-inflammatory cytokines. Furthermore, a positive correlation between high levels of pro-inflammatory cytokines and increased disease severity and depressed blood coagulation function for septic patients with co-infection was identified.


The Impact of Local Food Expenditure on School Foodservice Revenues.
Locally grown foods, through farm-to-school (FTS) activities, may be a key component to balancing foodservice budgets and alleviating financial constraints in school districts. Therefore, the purpose of this study is to examine the impact of local food expenditures on school foodservice revenues and earnings. We anticipated a positive impact of local food expenditures on foodservice revenues and earnings. Ordinary Least Squares (OLS) regression analysis was conducted using data from the 2013 US Department of Agriculture Farm to School Census. The questionnaire primarily asked all US public school districts about their FTS operations during 2011-2012 school year. Although our results initially showed a negative impact of local milk and nonmilk expenditures on foodservice revenues from food sales, when combined with revenues from the federal government, the impact is positive. The positive effect seems to hold when adding foodservice revenues from both food sales and federal funds. Our study found a similar pattern for foodservice earnings. This may indicate that competitive foods are still widely preferred in school districts. Revenue from the federal government is critical to maintain FTS activities viable to students and community members although federal funds and food sales may not cover total foodservice expenditures.


Homocysteine-induced impairment of insulin secretion from clonal pancreatic BRIN-BD11 beta-cells is not prevented by catalase.
Although detrimental effects of homocysteine attributed to homocysteine auto-oxidation and generation of hydrogen peroxide (H2O2) have been reported in various cell types, such actions have not been considered in pancreatic beta-cells. This study investigates the acute effects of homocysteine on beta-cell integrity and regulation, in particular, the role of H2O2 generated by auto-oxidation. Assessment of beta-cell function was examined during acute 20- or 40-minute incubations with homocysteine using clonal BRIN-BD11 beta-cells. Homocysteine (50-1000 micromol/L) inhibited basal and glucose-induced insulin secretion in a concentration-dependent manner. Insulinotropic responses to alanine, arginine, 2-ketoisocaproate, elevated Ca, tolbutamide, potassium chloride (KCl), forskolin, and phorbol 12-myristate 13-acetate were also significantly reduced by homocysteine. Likewise, preincubation with homocysteine caused a reduction in the insulinotropic responses to glucose and each of the secretagogues tested. Notably, excess catalase (100 microg/mL) in the buffer, although sufficient to remove homocysteine-derived H2O2, did not alleviate the detrimental effects of homocysteine. Collectively, these data suggest that homocysteine impairs insulin secretory function by mechanisms independent of H2O2 generation. Although homocysteine may give rise to reactive oxygen species, these observations indicate detrimental non-oxidative pancreatic beta-cell actions of homocysteine.


PTX1(ERGIC2)-VP22 fusion protein upregulates interferon-beta in prostate cancer cell line PC-3.
PTX1 is a gene identified by subtractive hybridization on the basis that it is expressed in normal prostate and not in prostate carcinoma. It is unrelated to the pituitary homeobox protein (Ptx1 or Pitx1), which regulates pituitary hormone gene expression, and its function is currently unknown. Recently, it was found to be a homolog of the yeast Erv41p, an endoplasmic reticulum (ER) resident protein involved in protein trafficking between ER and Golgi, and was renamed as ERGIC2. Ectopic expression of a partial sequence of PTX1 (Met84 - Leu225) as a VP22-fusion protein in prostate cancer cell line, PC-3, induced cellular senescence. Gene expression microarray analyses showed that interferon-beta (IFN-beta) and a number of IFN-inducible genes, among other genes, were upregulated by the PTX1-VP22 fusion protein. Upregulation of IFN-beta was confirmed by RTPCR and promoter-reporter assay. However, the upregulation of IFN-beta by the PTX1-VP22 fusion protein was not due to nuclear translocation of the PTX1 luminal domain.


Field Dynamic Balancing for Magnetically Suspended Turbomolecular Pump.
A field dynamic balancer is crucial to the applications of magnetically suspended turbomolecular pumps. Therefore, this paper presents a novel field dynamic balancing method based on autocentering control mode without any additional instrumentation. Firstly, the dynamics of the active magnetic bearing rotor system with unbalance are modeled. Through model analysis, it was found that making the rotor rotate around the geometric axis can improve the accuracy of dynamic balancing. Secondly, the relationship between the correcting masses and the synchronous currents based on the influence coefficient method is established. Then, an autocentering controller is designed to make the rotor rotate around the geometric axis. The synchronous currents can be detected and extracted by the current transducers to calculate the unbalance correction mass. Finally, the experimental results show that this novel field dynamic balancing method can effectively eliminate the majority of rotor unbalance. Compared with the original unbalance of a rotor, the synchronous current in the A-end has been reduced by 71.4% and the synchronous current in the B-end, by 90.8% with the proposed method.


Secretory production of erythropoietin and the extracellular domain of the erythropoietin receptor by Bacillus brevis: affinity purification and characterization.
Bacillus brevis secretes a large amount of cell wall proteins into the culture medium. For construction of Bacillus brevis expression-secretion vectors of human erythropoietin (EPO) and the extracellular domain of mouse erythropoietin receptor (sEPOR), cDNA for each mature form was inserted into a plasmid containing the promoter region and the signal-peptide encoding region of a cell wall protein. Culture supernatants of transformants were affinity purified using a monoclonal antibody-fixed gel for EPO and and EPO-fixed gel for sEPOR. The affinity purification efficiently removed unwanted proteins, giving samples with sufficiently high purity to analyze amino acid sequences of N-terminal regions and biological activities. Combination of this secretory production and affinity purification may facilitate isolation of a large amount of pure EPO and sEPOR, and is useful for further understanding the molecular mechanism of interaction between EPO and EPOR.


Giving patients their own records in general practice: experience of patients and staff.
Patients have reacted positively to seeing their medical records in a general practice which has a predominantly working class population in south east London. Most patients were familiar with the information in their records. Older people tended to avoid reading their notes. There have been few inaccuracies and unpleasant reactions reported, and few problems have arisen.


Novel role for NFAT3 in ERK-mediated regulation of CXCR4.
The G-protein coupled chemokine (C-X-C motif) receptor CXCR4 is linked to cancer, HIV, and WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome. While CXCR4 is reported to be overexpressed in multiple human cancer types and many hematological cancer cell lines, we have observed poor in vitro cell surface expression of CXCR4 in many solid tumor cell lines. We explore further the possible factors and pathways involved in regulating CXCR4 expression. Here, we showed that MEK-ERK signaling pathway and NFAT3 transcriptional factor plays a novel role in regulating CXCR4 expression. When cultured as 3D spheroids, HeyA8 ovarian tumor cells showed a dramatic increase in surface CXCR4 protein levels as well as mRNA transcripts. Furthermore, HeyA8 3D spheroids showed a decrease in phospho-ERK levels when compared to adherent cells. The treatment of adherent HeyA8 cells with an inhibitor of the MEK-ERK pathway, U0126, resulted in a significant increase in surface CXCR4 expression. Additional investigation using the PCR array assay comparing adherent to 3D spheroid showed a wide range of transcription factors being up-regulated, most notably a > 20 fold increase in NFAT3 transcription factor mRNA. Finally, chromatin immunoprecipitation (ChIP) analysis showed that direct binding of NFAT3 on the CXCR4 promoter corresponds to increased CXCR4 expression in HeyA8 ovarian cell line. Taken together, our results suggest that high phospho-ERK levels and NFAT3 expression plays a novel role in regulating CXCR4 expression.


Offspring of women with nonorganic psychosis: fear of strangers during the first year of life.
Fear of strangers ( FOS ) during the infant's first year was studied in 46 "high-risk" offspring of index mothers with a history of nonorganic psychosis and in 80 demographically similar control offspring. FOS was measured in the home by a standardized test at 1 year of age and by repeated interviews with the mother during the first year. As compared with controls, the total index group, and the subgroups of offspring of mothers with Schizophrenia and Cycloid Psychosis, significantly more often showed a total absence of FOS in the test at 1 year, as well as during the entire first year. FOS at 1 year was unrelated both to serious active psychiatric disturbance in index mothers during the infant's first year of life, and the infant's sex, in index and control groups.


The duality of health technology in chronic illness: how designers envision our future.
This essay critically explores the role of technological innovation in the constitution of chronic states and illness. Drawing on the co-construction of technology and society perspective, it focuses more specifically on the way in which innovation designers envisage the enhancement of the chronically ill and build certain kinds of socio-technical configuration to deal with chronic illness. Using the case of ;intelligent distance patient monitoring' as an illustration, the paper argues that technology creates as much as it solves the problem of chronic illness. Technology is recursively embedded in chronic illness and it generates dual effects: it constrains and sustains users' daily practices. Only by recognizing technology's duality and eventually transcending it will research and policy initiatives be able to deal creatively and responsibly with the design of our future health experiences.


Evaluation of salivary flow and drug interactions in patients with a diagnosis of diabetes mellitus.
Diabetes mellitus (DM) is one of the most common chronic diseases responsible for substantial loss on the quality of life in elderly. Oral manifestations in these patients include xerostomia and alterations in salivary flow and salivary pH. The aim of this study was to analyze the relationship between salivary flow, pH and medication. The sample consisted of 53 subjects aged 60 years and older, including 30 patients with a diagnosis of type 2 DM and 23 controls. Salivary flow was 1.066±0.814 mL/min in the control group and 0.955±0.606 mL/min in the DM group, with no significant difference between groups (P=0.588). There was a significant difference (P=0.045) in mean salivary pH (DM: 5.267±0.828; control: 5.783±0.951). Only 32.07% of the patients reported to remove their denture while sleeping. Three of 53 subjects using medications presented severe drug interactions. In summary, dentists must be able to make the diagnosis, to recognize all factors related to salivary alterations in DM, and to prescribe adequate treatment related to oral condition. Patients with DM presented salivary pH below normal reference values. It is important to advice patients to remove their denture while sleeping in order to prevent traumatic irritations and infections with Candida albicans. Potentially harmful cases of drug interactions have to be observed in elderly patient. Further studies focusing on the nature of drug interactions as the cause of adverse events such as xerostomia and increased salivary pH are needed.


[Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis].
To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC). Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota. Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora. Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.


Mitochondrial involvement in the point of no return in neuronal apoptosis.
Programmed cell death (PCD) contributes to development, maintenance, and pathology in various tissues, including the nervous system. Many molecular, biochemical, and genetic events occur within cells undergoing PCD. Some of these events are incompatible with long-term cell survival because they have irreversible, catastrophic consequences. The onset of such changes marks the point of no return, a decisive regulatory event termed 'the commitment-to-die.' In this review, we discuss events that underlie the commitment-to-die in nerve growth factor-deprivation-induced death of sympathetic neurons. Findings in this model system implicate the mitochondrion as an important site of regulation for the commitment-to-die in the presence or absence of caspase inhibition.


A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants.
To identify single nucleotide polymorphisms (SNPs) associated with clinical chorioamnionitis among preterm infants. We reanalyzed a genome-wide association study (GWAS) from preterm newborns at less than 30 weeks' gestation. Cases and control definitions were determined using administrative records. There were 213 clinical chorioamnionitis cases and 707 clinically uninfected controls. We compared demographic and clinical outcomes of cases and controls. We performed a GWAS and compared the distribution of SNPs from the background genes and from the immunome genes. We used a Wilcoxon's rank-sum test to compare the SNPs normalized odds ratio and used odds ratios and p-values to determine candidate genes. Infants affected by clinical chorioamnionitis were more likely to have periventricular leukomalacia, high-grade retinopathy, and high-grade intraventricular hemorrhage (IVH). Although a GWAS did not identify SNPs associated with clinical chorioamnionitis at the genome-wide significance level, a direct test on the exonic variants in the human immunome revealed their significant increase of risk in clinical chorioamnionitis. Among very preterm infants, clinical chorioamnionitis was associated with periventricular leukomalacia, high-grade retinopathy, and IVH. Our analysis of variants in the human immunome indicates an association with clinical chorioamnionitis in very preterm pregnancies.


Molecular mechanics and antibody binding in the structural analysis of polycyclic aromatic hydrocarbon-diol-epoxide--DNA adducts.
Analysis of polycyclic aromatic hydrocarbon (PAH)-DNA adducts using monoclonal antibodies raised against DNA that had been modified with (+-)-r-7-,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in an enzyme-linked immunosorbent assay, as well as analysis using human serum antibodies and antibodies raised in laboratory animals, have suggested the presence on these adducts of both common and unique immunological epitopes. The molecular mechanics studies reported here establish a model for the analysis of PAH-DNA adducts through the identification of energetically favored binding conformations and they further reveal structural alterations in DNA due to the presence of carcinogen adducts. The data explain the antibody reactivity patterns by defining different molecular presenting surfaces that are available for antibody binding. The preferred orientation of the aromatic portions of the adducts, which align either 3' or 5' in the minor groove, were found to be correlated with antibody reactivity patterns. Examination of the topographical characteristics of the adducts facilitated correlation of adduct-antibody recognition and adduct presenting surface. Significant differences were found between benzo[a]pyrene-diol-epoxide (BPDE)-DNA adducts, which align 5' in the minor groove, and benz[a]anthracene-diol-epoxide (BADE)-DNA and dibenz[a,c]anthracene-diol-epoxide-DNA adducts, which align 3' within the minor groove. Chrysene-diol-epoxide-DNA adducts were found to have only a weak preference for 5' alignment and therefore share topographical characteristics with both BPDE-DNA and BADE-DNA adducts.


Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse.
Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca2+ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca2+ pool and also recruited, in part, Ca2+ from extracellular environment via the opening of store-operated Ca2+ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca2+ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders.


Comparison of the clinical effects of zero-profile anchored spacer (ROI-C) and conventional cage-plate construct for the treatment of noncontiguous bilevel of cervical degenerative disc disease (CDDD): A minimum 2-year follow-up.
Comparing the clinical and radiographic outcomes in anterior cervical discectomy and fusion (ACDF) using a zero-profile anchored spacer (ROI-C) or a conventional cage-plate construct (CPC) for treating noncontiguous bilevel of cervical degenerative disc disease (CDDD).Overall, 46 patients with 2 noncontiguous segments of CDDD, treated with ACDF from January 2011 to October 2015, were included in this study. ROI-C was used in 22 patients (group A) and CPC in 24 patients (group B). The clinical and radiographic outcomes and complications were compared pre- and postoperatively. All patients were followed up for at least 24 months after surgery.No significant difference was found in fusion rate, cervical curvature, height of fused segment (FSDH), intraoperative blood loss, and Japanese Orthopaedic Association (JOA), and Neck Disability Index (NDI) scores between the 2 groups. Group A had a shorter operation time and significantly lower incidence of dysphagia (3 and 24 months postoperatively) than group B (P < .001 and P < .05, respectively). Moreover, group A had a higher loss of FSDH than group B, but with no difference between the 2 groups (P > .05). Two cages developed subsidence in group A (4.5%) and 2 adjacent levels developed degeneration in group B (2,8%).ACDF with ROI-C device was superior to CPC for noncontiguous bilevel of CDDD because it avoided postoperative dysphagia and required a shorter operation time. Moreover, the clinical outcomes were comparable. Prospective trials with larger samples and longer follow-up are required to confirm the results.


Direct Interaction between Carcinoma Cells and Cancer Associated Fibroblasts for the Regulation of Cancer Invasion.
The tumor stroma acts as an essential microenvironment of the cancer cells, which includes many different types of non-cancerous cells and the extracellular matrix (ECM). Stromal fibroblasts (SFs) are the major cellular constituents of the tumor stroma and are often called cancer-associated fibroblasts (CAFs). They are often characterized by α-smooth muscle actin (αSMA) expression, which is indicative of the myofibroblast phenotype and strong contractility. These characteristics contribute to the remodeling and stiffening of the stromal ECM, thereby offering an appropriate field for cancer cell invasion. Importance of the tumor stroma in cancer progression has recently been highlighted. Moreover, several reports suggest that stromal fibroblasts interact with adjacent cancer cells through soluble factors, exosomes, or direct cell-cell adhesion to promote cancer cell invasion. In this review, current models of the regulation of cancer cell invasion by surrounding fibroblasts are summarized, including our recent work on the interaction between stromal fibroblasts and scirrhous gastric carcinoma (SGC) cells by using a three-dimensional (3D) culture system. Further mechanistic insights into the roles of the interaction between cancer cells and stromal fibroblasts in cancer invasion will be required to identify novel molecular targets for preventing cancer cell invasion.


Effects of age on testosterone responses to resistance exercise and musculoskeletal variables in men.
This study compared serum total testosterone (TT) and free testosterone (FT) responses of young (20-26 years, n = 8), middle-aged (38-53 years, n = 7), and older (59-72 years, n = 9) men to resistance exercise. We also examined the relationships between testosterone (T) levels and strength, bone mineral density (BMD), and body composition variables for each age group. Subjects were tested for isotonic muscular strength (1 repetition maximum [1RM]), BMD (dual-energy x-ray absorptiometry [DXA]) and body composition (DXA). Each group performed an acute exercise protocol (3 sets, 10 repetitions, 80% of 1RM, 6 exercises). Blood samples were obtained at baseline, immediately postexercise, and 15 minutes postexercise for the TT and FT assays. The older age group had significantly (p < 0.05) lower T levels than the young group, but each group exhibited an increase (p < 0.05) in TT and FT immediately postexercise. Total T and FT were significantly correlated (p < 0.05) with strength in middle-aged and older men and with bone-free lean tissue mass in older men. In conclusion, middle-aged and older men showed similar relative T responses to those of younger men to a single bout of high-intensity resistance exercise. However, T levels were related to strength and muscle mass only in middle-aged or older men. On a practical application level, older men can complete a high-intensity resistance exercise program resulting in spikes in T that may attenuate age-related muscle and BMD loss.


Separation of lipase-positive cells from suspensions of pancreas cells in an isokinetic gradient of Ficoll in tissue culture medium.
Lipase-positive cells were separated from suspensions of pancreas cells both by velocity sedimentation and by isopycnic sedimentation. Lipase-positive cells were 51.0 +/- 9.6% of the disaggregated pancreas cells in the starting sample suspension. The purest gradient fractions from experiments using velocity sedimentation for cell separation contained a mean of 98.8 +/- 0.6% lipase-positive cells. Cell separation using isopycnic centrifugation was less effective than cell separation using velocity sedimentation and resulted in a mean purity of only 89.8 +/- 6.8% lipase-positive cells. Lipase positivity was assessed using the Gomori technic with the conditions for fixation slightly modified to be suitable for disaggregated cells.


[Correlation between the changes of innate lymphoid cells in peripheral blood of systemic lupus erythematosus and its clinical significance].
Objective: To explore the function and role of innate lymphoid cells in the pathogenesis of systemic lupus erythematosus (SLE) at different disease activity levels. Methods: From Nov 2017 to May 2018, 40 patients with SLE and 15 age-matched healthy non-immune-related diseases controls were enrolled from Anhui provincial hospital. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, the patients were divided into active group (n=20) and remission group (n=20). The frequency of ILCs, B cells, CD4+T and CD8+T cells from peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. The subsets of ILCs in each group were compared with the subsets of B cells and T cell respectively. The levels of IL-4, IL-33 and IFN-γ in each group were tested by ELISA. Result: Compared with the control group, ILC1 percentage was significantly increased in SLE active group [(22.33%±2.52%) vs (14.56%±1.28%), P=0.018 1]; ILC2 percentage was decreased significantly in both remission group [(19.67%±1.83%) vs (42.48%±3.46%), P<0.000 1] and active group [(8.67%±0.83%) vs (19.67%±1.83%), P<0.000 1]; ILC3 percentage was decreased significantly in active group [(5.72%±1.08%) vs (14.35%±2.40%), P=0.001 3]. SLEDAI score was negatively correlated with the percentage of ILC2 (P=0.023 9) in all patients. The percentage of ILCs in the remission group (P=0.046 2) and activity group (P=0.003 7) were both increased significantly. Moreover, the percentage of ILC2 in active group was negatively correlated with CD4+T cells (P=0.030 8), and the serum IgG was negatively correlated with ILC2% in all patients (P=0.013 8). Compared with control group or remission group, the levels of IFN-γ (F=10.91, P=0.000 1) and IL-4 (F=6.046, P=0.004 7) in active group were remarkable higher. However, IL-33 was significantly reduced in active group (F=6.645, P=0.002 7). The percentage of ILC2 (r=0.154 3, P=0.028 8) and ILC3 (r=0.313 6, P=0.001 1) in all patients with SLE were positively correlated with the level of IL-4. Conclusion: The percentage of ILCs is related to disease activity, and ILCs play a "double-edged" role in the pathogenesis of SLE. Its function and mechanism are worth further exploration.


Genomic expressions of human T-lymphotropic virus (HTLV-I).
Human T-lymphocyte cell line termed MT-2 is producing persistently HTLV-I virion and has a strong potential to transform human T-lymphocytes when cocultivated. The virion of HTLV-I (MT-2) was isolated and its RNA was extracted to analyze the gene and gene products of HTLV-I. HTLV (MT-2) virion RNA was translated in a rabbit reticulocyte lysate system in vitro in which a gag precursor polyprotein (p53) and a putative gag-prt fusion protein (p76) were synthesized from a full length 35S RNA. The full length provirus, HTLV-I (MT-2), was molecularly cloned and its genomic expression was examined transiently and permanently by transfecting in human lymphoid and non-lymphoid cells. The cloned provirus expressed the same virological activities as observed in naturally occurring infection of the virus. A new protease gene of HTLV-I was found and its function of the gene product was studied.


[Dislocation fractures of the forearm. Galeazzi, Monteggia, and Essex-Lopresti injuries].
Combined forearm fractures are identified according to their location as Galeazzi, Monteggia, or Essex-Lopresti injuries. The feature common to these three forms is the combination of a forearm fracture with instability of the distal or proximal radioulnar joint. Appropriate management of the injury at an early stage is indispensable to achieve good functional results. Galeazzi fractures should initially be treated by open reduction and correct anatomy restored by plate osteosynthesis. Fixation of the distal radioulnar joint with Kirschner wires should be performed in cases of persistent dislocation or instability and limited to 6 weeks. Monteggia fractures should be surgically approached, taking care not to overlook possible additional injuries (radial head, coronoid process). Essex-Lopresti injuries are treated by surgical reconstruction of the radial head, and in cases of comminuted fractures by implanting a radial head prosthesis. Subsequent treatment entails at least 14 days immobilization in a supinated position using an upper arm cast. Early functional therapy should follow when all three forms of injuries have been treated.


[The treatment of scabies with oral ivermectin].
To evaluate the efficacy and safety of a single 200 mcg/Kg dose of ivermectine as compared with placebo in the treatment of scabies was settled. Fifty five patients with the diagnosis of scabies were randomized to a single oral dose of ivermectine or placebo. The study informed that 26 (79.3%) patients were cured with ivermectine on their first follow-up visit, as compared to only four (16%) in the placebo group (X2 = 77.07, p < 0.001). Overall, 37 of 50 (74%) patients treated with ivermectine cured, as compared to only four of 26 (16%) treated with placebo, this difference was still significant (X2 = 23.66, p < 0.001). We concluded that ivermectine is a safe and effective treatment for scabies.


Individual and group housing in N-type Ca2+ channel alpha1B subunit-deficient mice differently affect motor activity.
N-type Ca2+ channel alpha1B-deficient mice have increased activity (ambulation, repetitive behavior, and rearing combined), suggesting contribution by the N-type Ca2+ channel, localized in the plasma membrane and essential for neurotransmitter release, on motor activity. We evaluated the effect of a 6-wk postweaning period of either individual or group housing on the activity displayed in a novel environment with or without previous habituation. Without habituation, male homozygous alpha1B-deficient mice showed significantly higher activity than wild-type controls, with no influence of the housing condition. When habituated, hyperactivity was seen in individually housed but not group-housed homozygous alpha1B-deficient mice. The results indicate that controlling for housing condition can be important when phenotypically analyzing mutant mice.


Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of the Jak-STAT (signal transducer and activator of transcription cytokine) signaling pathway but may also regulate other pathways. At least in vitro, SOCS-1 inhibits the action of multiple cytokines. By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes. Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type. Individually, these cytokines did not induce cell death. The titration of the two cytokines suggested that this increased cell death was because of hypersensitivity to TNF. Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency. Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation. The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment. A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways. Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets. Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.