[Study on the situation of antiretroviral therapy against HIV/AIDS in Henan province based on the CD4+ T cells count and virus load].
To analyze the CD4(+) T cells and virus load in HIV/AIDS affected population and to evaluate the HIV/AIDS antiretroviral therapy programs in Henan province. "Henan HIV/AIDS Testing Laboratory Network Database" was used to collect the data on CD4(+) T cells and virus load (VL) value and corresponding information in HIV/AIDS population of Henan in 2009. Cross-sectional studies was used to study the constituent ratio of CD4(+) T cells and virus load value in individuals who had not received antiretroviral-treated (ART) and had joined first-line ART between the year of 2005 to 2008 among HIV/AIDS population of Henan. As to these people living with HIV/AIDS that had not received ART in the first half and the second half year of 2009, the constituent ratio of individuals whose CD4(+) T cells were less than 200 cells/µl both accounted for more than 20% (χ(2) = 2.059, P = 0.151). The constituent ratio of individuals whose CD4(+) T cells were in 200 - 350 cells/µl and more than 350 cells/µl increased from 27.61% to 29.41% (χ(2) = 4.636, P = 0.031) and decreased from 51.49% to 48.60% (χ(2) = 9.767, P = 0.002), respectively. Meanwhile, we saw 34.53% and 19.65% of the patients whose virus load was > 10 000 copy/ml and > 30 000 copy/ml in this population. Patients that joined first-line ART during 2005 - 2008 showed the following results: the longer of the therapy time, the higher constituent ratio of individuals whose CD4(+) T cells were more than 350 cells/µl (χ(2) = 148.689, P < 0.001) and the lower constituent ratio of individuals of whose CD4(+) T cells were less than 200 cells/µl (χ(2) = 46.686, P < 0.001). Simultaneously, the lower constituent ratio of individuals whose viral load was less than 500 copy/ml (χ(2) = 9.066, P = 0.003) and the higher constituent ratio of individuals whose virus load was more than 10 000 copy/ml (χ(2) = 6.597, P = 0.010). Significant curative effect had been achieved in AIDS first-line ART of Henan, but along with the increasing treatment time, the risk of treatment failure also increased. Drug resistance test and changing of treatment protocols were needed. To reach better and more efficient effects on therapy, factors as more detections and investments on ART, expanding the scope of treatment etc. were needed on those people living with HIV/AIDS that had not received ART.


Potentiation of mitogenic activity of platelet-derived growth factor by physiological concentrations of insulin via the MAP kinase cascade in rat A10 vascular smooth muscle cells.
Hyperinsulinemia has been shown to be associated with diabetic angiopathy. Migration and proliferation of vascular smooth muscle cells (VSMC) are the processes required for the development of atherosclerosis. In this study, we attempted to determine whether insulin affects mitogenic signaling induced by platelet-derived growth factor (PDGF) in a rat VSMC cell line (A10 cells). PDGF stimulated DNA synthesis which was totally dependent on Ras, because transfection of dominant negative Ras resulted in complete loss of PDGF-stimulated DNA synthesis. Initiation of DNA synthesis was preceded by activation of Raf-1, MEK and MAP kinases (Erk 1 and Erk2). Treatment of the cells with PD98059, an inhibitor of MAPK kinase (MEK) attenuated but did not abolish PDGF-stimulated DNA synthesis, suggesting that MAPK is required but not essential for DNA synthesis. PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70 S6Kinase (p70S6K) in a wortmannin-sensitive manner. Rapamycin, an inhibitor of p70S6K, markedly suppressed DNA synthesis. Low concentrations of insulin (1-10 nmol/l) alone showed little mitogenic activity and no significant effect on MAPK activity. However, the presence of insulin enhanced both DNA synthesis and MAPK activation by PDGF. The enhancing effect of insulin was not seen in cells treated with PD98059. Insulin was without effect on PDGF-stimulated activations of protein kinase B (Akt/PKB) and p70S6K. We conclude that insulin, at pathophysiologically relevant concentrations, potentiates the PDGF-stimulated DNA synthesis, at least in part, by potentiating activation of the MAPK cascade. These results are consistent with the notion that hyperinsulinemia is a risk factor for the development of atherosclerosis.


Absorption of tretinoin in rats and rabbits following oral and dermal application.
To assess the teratogenic potential of Airol cream (0.05% tretinoin, CAS 302-79-4), plasma concentrations were compared after repeated dermal applications of the maximum dose which could be applied reliably and after oral administration of the highest non-teratogenic dose. The test preparation was applied dermally in two equal portions to rats and rabbits at 2 g/animal/d (equivalent to a tretinoin dose of 3.7 mg/kg/d) and at 6 g/kg/d (equivalent to 3 mg tretinoin/kg/d), respectively. After a single oral administration of 2 mg/kg, Cmax and AUC for tretinoin in rat plasma were 285 +/- 14.6 ng/ml and 595 +/- 123 ng h/ml, respectively. Corresponding values for the rabbit were 78.4 +/- 16.9 ng/ml and 126 +/- 25.4 ng h/ml. In both species, plasma concentrations of tretinoin after dermal application were consistently below the assay quantification limit (< 5 ng/ml and < 2 ng/ml for rat and rabbit, respectively), despite marked irritation of the skin. Thus repeated topical application of the test preparation produced plasma concentration of tretinoin which were well below the plasma concentrations produced by a non-teratogenic oral dose of 2 mg/kg in the rat and rabbit.


Pathology of lung transplantation.
The International Society for Heart and Lung Transplantation has a standardized nomenclature for the evaluation of lung allografts. Rejection of the lung allograft is divided into acute and chronic forms. Acute cellular rejection is characterized by perivascular accumulations of mononuclear cells and eosinophils; bronchiolar inflammation is also included in the grading scheme. Acute antibody-mediated rejection in lung allografts is not well defined. Chronic rejection is manifest by fibrous scarring narrowing the lumen of bronchioles, arteries, and veins. The diagnosis of rejection requires the exclusion of infection and other pathology in the allograft.


[Danish studies of acute treatment after initiation of emergency departments].
In Denmark, hospitals in these years reorganize the overall acute treatment of patients with the aim of providing better quality of treatment during several common interventions. This paper presents a status of the limited number of Danish studies, which have examined the acute care and knowledge about the planned interventions in the emergency departments. The new concept for the reception and treatment of emergency patients opens up new areas of research in a Danish context. The number of preliminary published results that have been presented by Danish acute conferences testify this.


Differences in various biochemical and clinical parameters with respect to family history of Non Communicable Diseases in fourth year MBBS students of Karachi, Pakistan.
To observe the differences of various biochemical and clinical parameters with respect to Family History (FH) of Non-communicable Diseases (NCDs) in fourth year Bachelor of Medicine, Bachelor of Surgery (MBBS) students. This observational study was conducted at Baqai Institute of Diabetology & Endocrinology from December 2013 to January 2014. Total 50 medical students from Dow University of Health Sciences (DUHS) participated in the study. Statistical Package for Social Sciences (SPSS) version 13 was used to analyze the data. For cross tabulation and mean comparison z-test and t test were applied. Out of 50 subjects, there were 26 (52%) females. Mean age of the study population was 21.56 ± 0.90 years. Mean serum cholesterol levels with positive FH of NCDs was significantly higher than negative FH of NCDs (p=0.005). Mean value of low density lipoprotein (LDL) of positive family history of NCDs was found higher than those with negative FH (p=0.006) being statistically significant. The insulin levels in subjects with positive FH of NCDs were higher than subjects with negative FH of NCDs (p=0.685). However, serum leptin and plasma renin showed no significant difference with the negative FH of NCDs being higher compared to positive FH of NCDs (p=0.068) and (p=0.884) respectively. However, Waist circumference, Body mass index and central obesity in subjects with positive FH of NCDs shows increasing trend but no statistically significant difference (p > 0.05) was observed. In our study of various biochemical and clinical parameters with respect to FH of NCDs, Serum Cholesterol and LDL levels were observed higher and statistically significant.


Efficacy of computer technology-based HIV prevention interventions: a meta-analysis.
To conduct a meta-analysis of computer technology-based HIV prevention behavioral interventions aimed at increasing condom use among a variety of at-risk populations. Systematic review and meta-analysis of existing published and unpublished studies testing computer-based interventions. Meta-analytic techniques were used to compute and aggregate effect sizes for 12 randomized controlled trials that met inclusion criteria. Variables that had the potential to moderate intervention efficacy were also tested. The overall mean weighted effect size for condom use was d = 0.259 (95% confidence interval = 0.201, 0.317; Z = 8.74, P < 0.001; N = 4639), indicating a statistically significant impact of the interventions. This effect size compares favorably to previously tested interventions delivered by human facilitators. Statistically significant effect sizes were also found for frequency of sexual behavior, number of partners, and incident sexually transmitted diseases. In addition, interventions were significantly more efficacious when they were directed at men or women (versus mixed sex groups), utilized individualized tailoring, used a Stages of Change model, and had more intervention sessions. Computer technology-based HIV prevention interventions have similar efficacy to more traditional human-delivered interventions. Given their low cost to deliver, ability to customize intervention content, and flexible dissemination channels, they hold much promise for the future of HIV prevention.


Merging of the photocatalysis and copper catalysis in metal-organic frameworks for oxidative C-C bond formation.
The direct formation of new C-C bonds through photocatalytic oxidative coupling from low reactive sp3 C-H bonds using environmentally benign and cheap oxygen as oxidant is an important area in sustainable chemistry. By incorporating the photoredox catalyst [SiW11O39Ru(H2O)]5- into the pores of Cu-based metal-organic frameworks, a new approach for merging Cu-catalysis/Ru-photocatalysis within one single MOF was achieved. The direct CuII-O-W(Ru) bridges made the two metal catalyses being synergetic, enabling the application on the catalysis of the oxidative coupling C-C bond formation from acetophenones and N-phenyl-tetrahydroisoquinoline with excellent conversion and size-selectivity. The method takes advantage of visible light photoredox catalysis to generate iminium ion intermediate from N-phenyl-tetrahydroisoquinoline under mild conditions and the easy combination with Cu-catalyzed activation of nucleophiles. Control catalytic experiments using similar Cu-based sheets but with the photoredox catalytic anions embedded was also investigated for comparison.


On the Safety of Implanted Breast Prostheses in Accidental Impacts.
The employment of breast silicone implants, both in aesthetic and reconstructive medicine, is widespread thanks to their recognized biocompatibility and durability. Some critical situations, for example, in the case of accidental impacts, may induce concerns by potential patients about their use. Dynamic tests reproducing frontal impacts at speeds up to 90 km/h, with anthropomorphic dummies carrying 330 cc prostheses and wearing safety belts, were conducted. Tests showed a significant probability of internal gel loss following implant damage at the highest speed. Moreover, considering that prostheses may remain implanted for many years, the effects of accelerated aging at 37 °C, 60 °C, 75 °C and 90 °C in physiological solution were also investigated. Tensile tests of the shell material and compressive tests of the full prosthesis showed evidence of variation in the prostheses' mechanical characteristics after aging, which affects their stiffness, deformability and strength. These results stress the importance of medical investigations for possible damages of the implanted prostheses in the case of an accident.


Role of Spatial Constraints of Brønsted Acid Sites for Adsorption and Surface Reactions of Linear Pentenes.
The Brønsted acid sites of H-ZSM-5 and ferrierite reversibly adsborb linear pentenes via hydrogen bonding, rapidly isomerizing the double bond. On H-ZSM-5, dimerization of adsorbed pentenes occurs at a slower rate and leads to pentyl ester covalently bound to the surface. Pentene adsorbed on zeolites with narrower pores, such as ferrierite, remained stable in a hydrogen-bonded state even up to 423 K. Comparing the differential heat of adsorption of 2-pentene on silicalite and ferrierite allowed for the determination of the enthalpy difference between physically adsorbed pentene in ZSM-5 and the localized hydrogen-bonded π-complex at Brønsted acid sites, -36 kJ/mol. The activation energy (35 kJ/mol) for dimerization is almost identical to this enthalpy difference, suggesting that the rate-determining step is associated either with the mobilization of π-bonded 2-pentene or with the equally large activation barrier to form an alkoxy group via a carbenium-ion transition state. In a closed system, the dimerization rate is first order in the concentration of the π-complex that is both in equilibrium with the mobile pentene phase and in production of the carbenium ion that reacts with the mobile pentene. Overall, the alkoxy group is -41 ± 7 kJ/mol more stable than physisorbed pentene, establishing a series of energetically well-separated groups of reactive surface species.


Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements.
CD1d-expressing cells present lipid Ag to CD1d-restricted NKT cells, which play an important role in immune regulation and tumor rejection. Lymphoid enhancer-binding factor-1 (LEF-1) is one of the regulators of the Wnt signaling pathway, which is a powerful regulator in cellular growth, differentiation, and transformation. There is little evidence connecting Wnt signaling to CD1d expression. In this study, we have identified LEF-1 as a regulator of the expression of the gene encoding the human CD1d molecule (CD1D). We found that LEF-1 binds specifically to the CD1D promoter. Overexpression of LEF-1 in K562 or Jurkat cells suppresses CD1D promoter activity and downregulates endogenous CD1D transcripts, whereas knockdown of LEF-1 using LEF-1-specific small interfering RNA increases CD1D transcripts in K562 and Jurkat cells but there are different levels of surface CD1d on these two cell types. Chromatin immunoprecipitation showed that the endogenous LEF-1 is situated at the CD1D promoter and interacts with histone deacetylase-1 to facilitate the transcriptional repressor activity. Knockdown of LEF-1 using small interfering RNA potentiates an acetylation state of histone H3/H4, supporting the notion that LEF-1 acts as a transcriptional repressor for the CD1D gene. Our finding links LEF-1 to CD1D and suggests a role of Wnt signaling in the regulation of the human CD1D gene.


Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma.
In a prospective phase I/II clinical study, we treated eight patients suffering from recurrent glioblastoma multiform with stereotactically guided intratumoral convection-enhanced delivery of an HSV-1-tk gene-bearing liposomal vector and systemic ganciclovir. Noninvasive identification of target tissue together with assessment of vector-distribution volume and the effects of gene therapy were achieved using magnetic resonance imaging and positron emission tomography. The treatment was tolerated well without major side effects. In two of eight patients, we observed a greater than 50% reduction of tumor volume and in six of eight patients focal treatment effects. Intracerebral infusion of contrast medium before vector application displayed substantial inhomogeneity of tissue staining indicating the need of test infusions to monitor the mechanical distribution of vectors. Visualization of therapeutic effects on tumor metabolism and documentation of gene expression using positron emission tomography indicated that molecular imaging technology appears to be essential for the further development of biological treatment strategies.


Autophagic marker MAP1LC3B expression levels are associated with carotid atherosclerosis symptomatology.
The mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques). 80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools. Several genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5-fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system-related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients. Carotid atherosclerotic plaques in which MAP1LC3B is underexpressed would not be able to benefit from MAP1LC3B-associated autophagy. This may lead to accumulation of dead cells at lesion site with subsequent plaque destabilization leading to cerebrovascular events. Identified biomarkers and network interactions may represent novel targets for development of treatments against plaque destabilization and thus for the prevention of cerebrovascular events.


Multimorbid disease trajectories for people with periodontitis.
Periodontitis is a multifactorial condition linked to increased risk of systemic diseases. This study aimed to identify disease trajectories of people with periodontitis using the process mining technique as a heuristic approach. A total of 188,863 participants from the UK Biobank cohort were included. Self-reported oral health indicators (bleeding gums, painful gums, loose teeth) were surrogates for periodontitis at baseline. Systemic disease diagnoses and dates formed the process mining event log. Relative risk (RR) of systemic diseases, disease trajectories, and Cox proportional hazard ratio models for mortality were compared to age- and sex-matched controls who did not report a history of periodontitis. Participants with loose teeth had shorter median time to most systemic diseases, and crude RR was increased for several diseases including cardiovascular disease (crude RR: 1.15, 95% CI: 1.03-1.28), hypertension (crude RR: 1.14, 95% CI: 1.05-1.24), and depression (crude RR: 1.33, 95% CI: 1.09-1.61). Participants with loose teeth had increased RR for 20 disease trajectories, though these were not significant after adjustments. Participants with bleeding/painful gums had similar disease trajectories as those of matched controls. Self-reported periodontitis may be associated with early and frequent multimorbidity development, though further evidence is required to confirm this hypothesis. People with periodontitis should be informed of the risks of disease progression and be targeted in prevention initiatives.


Lipid studies in primary gout.
Serum total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride were measured in three groups of male patients with primary gout. The groups were defined by the presence of 0, 1, or more than 1 coexisting medical conditions or cardiac risk factors (coronary heart disease, hypertension, diabetes, proteinuria, overweight). Mean values of total, LDL, and HDL cholesterol were lower in patients with one or more associated conditions than in those with none. By contrast, triglyceride levels were significantly higher and exceeded the desirable range. Distributions of individual values of all lipid parameters except triglycerides were similar along the three groups. Triglyceride values, however, were significantly higher in patients with multiple complications. Observed differences in lipid values could not be correlated with patient age or type of nature of medication received. High triglycerides and LDL cholesterol are not a feature of uncomplicated gout in men. HDL cholesterol tends to be normal and triglyceride mildly elevated. Only in patients with two or three associated medical conditions are high triglycerides or low HDL cholesterol common. Our results suggest that these findings are independently related to concurrent disease and that gout is not necessarily in itself a risk factor for cardiovascular or diabetic disease.


Altered production of PGE2, IL-1 beta and TNF-alpha by peripheral blood monocytes from HIV-positive individuals at early stages of HIV infection.
We analyzed the in vitro synthesis and release of PGE2, IL-1 beta, and TNF-alpha by peripheral blood monocytes from HIV-infected injection drug users at the early clinical stages of HIV infection. We investigated whether there is a concomitant altered production of PGE2 and proinflammatory cytokines by HIV-positive monocytes. We also evaluated T-cell subsets and lymphocyte transformation response to pokeweed mitogen (PWM) in HIV-positive patients and healthy controls. PGE2 and IL-1 beta levels in supernatants from monocyte cultures were determined by radioimmunoassay (RIA), and TNF-alpha by enzyme immunoassay (EIA). Monocytes from asymptomatic HIV-positive individuals produced spontaneous and significantly increased quantities of PGE2, IL-1 beta, and TNF-alpha. Concomitant increased production of PGE2 and IL-1 beta by monocytes from HIV-positive asymptomatic patients was significantly associated with low CD4+ T-cell numbers (< 500 cells/mm3). We also found a strong association between spontaneous and concomitantly increased production of PGE2 and cytokines by monocytes from asymptomatic HIV-positive individuals and a low lymphocyte transformation response to PWM. Further studies are necessary to establish whether this altered production of PGE2 and proinflammatory cytokines by monocytes from HIV-positive individuals might play a role in the mechanisms involved in the progressive impairment of cell-mediated immunity in HIV infection.


Mesenchimal stem cells in oral medicine: an overview.
This review aims to address the procedures and indications, required for the application of the mesenchymal stem cells treatment strategy of regenerative dentistry. Mesenchymal stem cells have rarely been used in this field; conversely, experience from other clinical fields and basic research seems to recommend the suitability of this scope of application. We reviewed 31 out of 206 articles on Web of Science, Scopus, PubMed, etc. The main purpose of this paper is a short review of the literature evaluating the application of stem cells in regenerative dentistry, their ability to get a multilineage differentiation and to introduce a safe and useful alternative way of harvesting and selection. The most common derivation of stem cells used for regenerative dentistry is from the adipose tissue. There are conditions in which the levy adipose cannot be easily achieved, or where large amounts of injectables are not needed. For this purpose, the possibility of selecting stromal stem cells directly from the lax subcutaneous connective tissue preferably of the head region would allow a technical simplification and a greater homology in tissues. .


Estimating Latent Variable Interactions With Non-Normal Observed Data: A Comparison of Four Approaches.
A Monte Carlo simulation was conducted to investigate the robustness of four latent variable interaction modeling approaches (Constrained Product Indicator [CPI], Generalized Appended Product Indicator [GAPI], Unconstrained Product Indicator [UPI], and Latent Moderated Structural Equations [LMS]) under high degrees of non-normality of the observed exogenous variables. Results showed that the CPI and LMS approaches yielded biased estimates of the interaction effect when the exogenous variables were highly non-normal. When the violation of non-normality was not severe (normal; symmetric with excess kurtosis < 1), the LMS approach yielded the most efficient estimates of the latent interaction effect with the highest statistical power. In highly non-normal conditions, the GAPI and UPI approaches with ML estimation yielded unbiased latent interaction effect estimates, with acceptable actual Type-I error rates for both the Wald and likelihood ratio tests of interaction effect at N ≥ 500. An empirical example illustrated the use of the four approaches in testing a latent variable interaction between academic self-efficacy and positive family role models in the prediction of academic performance.


Chromosomal localization of angiotensin II type 1 receptor isoforms in the rat.
The cDNA sequences of two different isoforms of the rat angiotensin II type 1 receptors, AT1A and AT1B, have been reported. A single set of polymerase chain reaction primers was used to amplify sequence from both AT1A and AT1B from rat genomic DNA. Genomic DNA from a panel of rat x mouse somatic hybrid cell lines which had been characterized as to the rat chromosomal content was then amplified with these primers. The amplified products from rat AT1A and AT1B were distinguished from each other and those of the mouse by the use of differential restriction patterns. Using this method, AT1A was localized to rat chromosome 17 and AT1B to rat chromosome 2.


Causal associations of cytokines and growth factors with cholelithiasis: a bidirectional Mendelian randomization study.
It has been reported that patients with cholelithiasis may have changes in levels of cytokines and growth factors, while their causal relationships were still unclear. This study was a bidirectional Mendelian randomization (MR) study. Datasets of 41 circulation cytokines and growth factors and the data on cholelithiasis were obtained. Six steps of strict instrumental variable filtration were set, and inverse-variance weighted analysis, MR-Egger regression, and weighted median test were used to identify the causal relationships. Benjamini-Hochberg method was used to adjust the P-values. After adjustments of P-values, four cytokines and growth factors were still causally associated with cholelithiasis significantly: interleukin 2 receptor alpha (adjusted P: 4.59E-02), interleukin 8 (adjusted P: 1.09E-02), monocyte-specific chemokine 3 (adjusted P: 2.73E-04), and stem cell factor (adjusted P: 2.73E-04). In the reverse MR analysis, no significant causal relationship was detected after adjustment. Four cytokines and growth factors, including interleukin 2 receptor alpha, interleukin 8, monocyte-specific chemokine 3, and stem cell factor, were proven to relate to cholelithiasis causally and unidirectionally.


Intimacy of the neuroeffector junction and resistance to alpha-adrenoceptor-blockade of the neurogenic contractile response in vasa deferentia from guinea pig and rat.
The effect of phentolamine on the neurogenic contractile response in vasa deferentia from rat and guinea pig was studied during Wallerian degeneration. This response was also investigated after partial denervation (surgery or chemical sympathectomy by guanethidine treatment) in vasa deferentia from guinea pig. During Wallerian degeneration the response showed a gradual increase in sensitivity to phentolamine and was abolished in the late stages. The neurogenic contractile response of the partially denervated vas deferens was blocked by low concentrations of phentolamine. It is concluded that decreased intimacy of the neuroeffector junctions leads to increased susceptibility to alpha-adrenoceptor blockade of the contractile response to nerve stimulation. It is further concluded that the motor transmission in the vas deferens is essentially adrenergic. The resistance to alpha-adrenoceptor blockade of the initial phase of the contractile response to nerve stimulation of intact vasa deferentia from guinea pig and rat might well be explained by the "proximity theory" of Dale & Gaddum although participation of supplementary mediators cannot be excluded.


The indirect mechanism of action of the trifluoroacetyl peptides on elastase. Enzymatic and 19F NMR studies.
Trifluoroacetyl (CF3CO) dipeptide anilides are potent reversible inhibitors of elastase. Their 19F NMR spectra in the presence of the enzyme correspond therefore to slow chemical exchange. Their characteristics are very similar to those previously reported for other CF3CO-peptides. This should correspond to a single binding mode, in which the CF3CO group lies in a specific site in close contact with protein protons. Elastase, irreversibly inhibited by alkylation of Ser-195 with phenylsulfonyl fluoride derivatives, binds the CF3CO-Ala-containing dipeptide anilides still more tightly than the native enzyme. It no longer binds the dipeptide anilides containing a bulky CF3CO-Lys group, suggesting a location of the CF3CO site near the S1 subsite. On the other hand, the chemical shift of the CF3CO 19F resonance in the complex is the only NMR property affected by the enzyme sulfonylation, the T1 and nuclear Overhauser effect values being unmodified as compared to those in the complexes with the native enzyme. The observation of the NMR characteristics of elastases inhibited by phenylsulfonyl groups substituted with fluorine shows that complexation with CF3CO-peptides induces a change of conformation of the catalytic site which should correspond to a displacement of His-57 toward the ortho position of the phenylsulfonyl ring. Such a transconformation is not observed with corresponding acetylated peptides. The phenylsulfonyl fluoride derivatives are still able to react with elastase in the presence of a large excess of CF3CO-peptides. In such conditions the rate of inactivation is much slower but still at least 5% of that measured in the absence of the reversible inhibitors. This residual activity is hardly compatible with the presence of two exclusive modes of interaction of the CF3CO-peptides with native elastase. On the contrary, these observations are better interpreted by a single and identical mode of binding of the peptide to the native and sulfonylated enzymes. According to this mode of binding, the reversible inhibition of elastase by CF3CO-peptides should correspond to an indirect mechanism by which a change of conformation at the active site results in a reduced catalytic activity.


Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers.
An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor beta-2 (RARbeta-2), CDH13 (H-cadherin), p16(INK4a) (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens. In addition, we also analyzed sputum samples from 30 never smokers for methylation of these genes. Our major findings are: (i) At least one gene was methylated in one or more specimens from 48% of the smokers. However, methylation was statistically significant less frequently in never smokers compared to smokers. (ii) In general, methylation occurred more frequently in samples from the central airways (sputum, bronchial brushes) compared to the peripheral airways (BAL) and only occasionally in the oropharynx. (iii) RARbeta-2 was the most frequently methylated gene, whereas the frequency of methylation for the other genes was lower. (iv) Data from sputum samples and bronchial brushes were comparable. Our findings suggest that detection of methylation should be investigated as an intermediate marker for lung cancer risk assessment and response to chemopreventive regimens.


The nutritional value of some processed meat products in Malaysia.
Per capita consumption of meat and meat products in Malaysia more than doubled from 15.70 kg in 1970 to 35.71 kg in 1990. This increase in meat consumption is mainly due to the rapid development and wide acceptance of value added meat and poultry products amongst Malaysian consumers. Meat products such as burgers, sausages, hotdogs and nuggets are widely accepted and consumed by all ethnic groups at home as well as in the fast food restaurants. The significant expansion of the fast food industry and the increase consumption of processed meat products makes it necessary for a re-evaluation of the nutritional quality of popular meat products currently available in the market. This review paper described the quality of some processed meat products, their proximate composition, meat quality, use of non meat proteins and binders, and the use of additives in the formulation of burgers, frankfurters, nuggets, bologna, chicken and beef balls. Preliminary results on the protein efficiency ratio of local meat products seemed favourable but this study is limited to only one laboratory. In vivo and in vitro protein digestibility studies indicated high values on the digestibility of locally manufactured meat products. Proximate analysis of the raw materials used in the formulation of such products showed many with high fat and low protein contents being utilized. The meat content was lower than the minimum amount stated by the food regulation. This paper concludes that due to lack of information and studies on the nutritional composition of processed meat products, concerned bodies should take positive steps to generate reliable data to elucidate the actual nutritional composition of such products. It is also observed that many by-products from the animal industry from non-conventional sources are increasingly being utilized in the manufacture of processed meat product.


[Precision medicine : a required approach for the general internist].
The general internist cannot be a passive bystander of the anticipated medical revolution induced by precision medicine. This latter aims to improve the predictive and/or clinical course of an individual by integrating all biological, genetic, environmental, phenotypic and psychosocial knowledge of a person. In this article, national and international initiatives in the field of precision medicine are discussed as well as the potential financial, ethical and limitations of personalized medicine. The question is not to know if precision medicine will be part of everyday life but rather to integrate early the general internist in multidisciplinary teams to ensure optimal information and shared-decision process with patients and individuals.


Muscle strength and gait speed rather than lean mass are better indicators for poor cognitive function in older men.
We aimed to examine muscle strength, function and mass in relation to cognition in older men. This cross-sectional data-set included 292 men aged ≥60 yr. Handgrip strength (kg) was measured by dynamometry, gait speed by 4-metre walk (m/s) and appendicular lean mass (kg) by dual-energy x-ray absorptiometry. Cognition was assessed across four domains: psychomotor function, attention, visual learning and working memory. Composite scores for overall cognition were calculated. Bivariate analyses indicated that handgrip strength and gait speed were positively associated with cognitive function. After accounting for confounders, positive associations between individual muscle (or physical) measures and cognitive performance were sustained for handgrip strength and psychomotor function, gait speed and psychomotor function, gait speed and attention, handgrip strength and overall cognition, and gait speed and overall cognition. In multivariable models, handgrip strength and gait speed independently predicted psychomotor function and overall cognition. No associations were detected between lean mass and cognition after adjusting for confounders. Thus, low muscle strength and slower gait speed, rather than low lean mass, were associated with poor cognition in older men.


Adjustment of chest wall thickness of voxel phantom for numerical efficiency calibration of lung counters.
A modification method was implemented to adjust the chest wall thickness of human voxel phantom for the purpose of numerical efficiency calibration of lung counters. This method was based on two basic mathematical morphology operations (dilation and erosion) and combined with proper structure elements. The voxel model of LLNL torso phantom was used as a reference to validate the modification process. The chest wall was mathematically modified from the starting phantom with no overlay plate to the target with an overlay plate of 24-mm thickness. The influences of different structure elements on detection efficiency were discussed. When diamond or square structure elements were used, the calculated efficiency was overestimated or underestimated by ∼40 % for 17.5-keV photons, compared with that of target phantom. In contrast, it was shown a good agreement with a deviation of <3 % when the hybrid structure elements were adopted. A similar adjustment method can be used for 3D modification of human voxel phantom to keep the body's anatomical geometry without distortion during the adjustment process.


Visual field restorative rehabilitation after brain injury.
About 20%-30% of patients undergoing neurological rehabilitation report visual field defects, one of the most frequent of which is homonymous hemianopsia (loss of the same half of the visual field in both eyes). There is still no consensus as to whether homonymous hemianopsia is best treated in a restorative or compensatory manner. The aim of this review is to describe the effects of restorative rehabilitation, whose long-term efficacy is still being debated. We analyzed 56 articles describing the use of various techniques used to promote visual field recovery but concentrating on two approaches: "border training," which involves exercising vision at the edge of the damaged visual field, and "blindsight training," which is based on exercising unconscious perceptual functions in the mild of the blind hemifield where the scotoma is deep. Both techniques have been supported by functional imaging studies showing evidence of cortical rearrangement (plasticity) after rehabilitation. Although no formal meta-analysis was possible, the results of a semiquantitative evaluation suggested that the improvement in visual skills obtained is related to the type of training used: Border rehabilitation seems to improve the detection of visual stimuli, whereas blindsight rehabilitation seems to improve their processing. Finally, the addition of transcranial direct current stimulation seems to enhance the effects of visual field rehabilitation.


Comparison of two high-performance liquid chromatographic methods for monitoring plasma concentrations of haloperidol and reduced haloperidol.
Two high-performance liquid chromatographic methods for monitoring haloperidol (HAL) and reduced haloperidol (RHAL) plasma concentrations were compared. In one method ultraviolet detection and a C18 column were used (UV method); in the other method electrochemical detection and a CN-column were used (EC method). Both methods are accurate and precise. For plasma samples spiked with HAL or RHAL, an excellent correlation was observed between the concentrations of HAL and RHAL found with both methods (r < or = 0.99, p < 0.01). However, for plasma obtained from patients treated with HAL the correlation between the two methods was poor (r > or = 0.71, p < 0.01). The main reason for the discrepancy between the two methods is probably interference of comedications or their metabolites, mostly in the EC method. Although the quantitation limit of the UV method (2 ng/ml for HAL and RHAL) is higher than that of the EC method (0.5 ng/ml for HAL and RHAL), the UV method is to be preferred for monitoring plasma levels in psychiatric patients because there is less interference from comedication.


Intravenous glucose tolerance test in Macaca radiata radiata.
A reliable method for performing sensitive intravenous glucose tolerance tests in monkeys has been standardized. This helps in assessment of beta cell function. A normal curve for glucose disposal is constructed. A high variability in insulin levels is also documented.


Enterotoxin-encoding genes in Staphylococcus spp. from bulk goat milk.
Although Staphylococcus aureus has been implicated as the main Staphylococcus species causing human food poisoning, recent studies have shown that coagulase-negative Staphylococcus could also harbor enterotoxin-encoding genes. Such organisms are often present in goat milk and are the most important mastitis-causing agents. Therefore, this study aimed to investigate the occurrence of enterotoxin-encoding genes among coagulase-positive (CoPS) and coagulase-negative (CoNS) staphylococci isolated from raw goat milk produced in the semi-arid region of Paraiba, the most important region for goat milk production in Brazil. Enterotoxin-encoding genes were screened in 74 staphylococci isolates (30 CoPS and 44 CoNS) by polymerase chain reaction targeting the genes sea, seb, sec, sed, see, seg, seh, and sei. Enterotoxin-encoding genes were found in nine (12.2%) isolates, and four different genes (sea, sec, seg, and sei) were identified amongst the isolates. The most frequent genes were seg and sei, which were often found simultaneously in 44.5% of the isolates. The gene sec was the most frequent among the classical genes, and sea was found only in one isolate. All CoPS isolates (n=7) harboring enterotoxigenic genes were identified as S. aureus. The two coagulase-negative isolates were S. haemolyticus and S. hominis subsp. hominis and they harbored sei and sec genes, respectively. A higher frequency of enterotoxin-encoding genes was observed amongst CoPS (23.3%) than CoNS (4.5%) isolates (p<0.05), reinforcing the importance of S. aureus as a potential foodborne agent. However, the potential risk posed by CoNS in goat milk should not be ignored because it has a higher occurrence in goat milk and enterotoxin-encoding genes were detected in some isolates.


Influence of Martensite/Bainite Dual Phase-Content on the Mechanical Properties of EA4T High-Speed Axle Steel.
In this work, we have investigated the effect of martensite/bainite dual phase content on the mechanical properties of EA4T high-speed axle steel. For evaluation and control of the strength, ductility, and toughness of steel, the microstructure of lath martensite (LM) and granular bainite (GB) was clarified through an optical microscope (OM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM). Besides, the tensile fracture morphology was studied by scanning electron microscopy (SEM). For this purpose, this study conducted a quantitative analysis of the LM and GB fractions using the Pro Imaging software-2018 of OM. The remarkable effect of the LM/GB structure on mechanical properties is discussed. The results have shown that by increasing the volume fraction of the GB structure, the LM structure is refined and its microhardness and strength are improved. Meanwhile, the micro strength of LM follows the Hall-Petch relationship with the lath martensite packet size. Subsequently, the mechanical property prediction model of EA4T steel based on the LM/GB content was established by regression analysis of all experiment dates. When the LM fraction in the steel is about 40-70%, a superior combination of strength, ductility, and toughness can be obtained in EA4T steel.


Surface crystallization of amorphous solid water.
We demonstrate that the crystallization of thin, supported amorphous solid water layers is initiated at the water surface. This is concluded from the observation of sequential crystallization of amorphous water at the surface, in the bulk, and at the water-support interface. A surface nucleation model quantitatively reproduces the observed transformation kinetics at the three sites.


Glucocorticoids decrease the bioavailability of TGF-beta which leads to a reduced TGF-beta signaling in hepatic stellate cells.
Glucocorticoids bound to their receptors transmit information, which regulates numerous physiological and pathophysiological responses, amongst others glucose metabolism, wound healing, inflammation, and stress, either directly as transcription factors by binding DNA elements of target genes or indirectly by protein-protein interactions with other transcription factors. TGF-beta, a key factor in activation of hepatic stellate cells (HSC), induces production of extracellular matrix, this being a prerequisite for the development of liver fibrosis. Glucocorticoids and their receptors may provide a crosstalk with the TGF-beta-Smad signaling pathway by antagonizing TGF-beta effects. We studied the influence of glucocorticoids on the TGF-beta isoform and Smad mRNA expression, TGF-beta secretion, and signaling in activated HSC using gene-specific real-time PCR, ELISA, and transfection techniques. Dexamethasone treatment reduces TGF-beta mRNA transcription in a time-dependent manner. Activated HSC produce TGF-beta and secrete it into the cell culture medium. After dexamethasone treatment, TGF-beta secretion into the medium is reduced dose-dependently but restorable by mifepristone. Further, we found that reduced secretion of endogenous TGF-beta is accompanied by a reduced TGF-beta signal. Additionally, reporter gene analysis after adenoviral infection with a recombinant virus encoding a Smad-binding-element showed that TGF-beta-Smad signaling is significantly down-regulated by dexamethasone in primary HSC and CFSC, a HSC related cell line. Our data suggest that glucocorticoids inhibit TGF-beta expression, prevent TGF-beta from efficient secretion, and finally lead to reduced TGF-beta signaling in primary HSC.


Spurious level and phase noise improved Fourier domain mode-locked optoelectronic oscillator based on a self-injection-locking technique.
We propose and experimentally demonstrate a spurious level and phase noise improved Fourier domain mode-locked optoelectronic oscillator (FDML-OEO) based on a self-injection-locking (SIL) technique. The scheme applies a dual-loop FDML-OEO structure, in which a long optical fiber delay loop is used to injection-lock the OEO with a short oscillating optical fiber delay loop. SIL is achieved so long as the delay of the long loop is tuned at the integral multiple of the oscillation loop. The spur suppression ratio of the wideband linear frequency modulated (LFM) signal generated by the FDML-OEO can be improved by 14 dB under SIL. Furthermore, the modification of the spur suppression ratio depending on the injection power is also demonstrated. The phase noise of the proposed OEO is -127.5 dBc/Hz at 10 kHz offset, which is much improved comparing with a free-running OEO.


Assessment of Food Waste Prevention and Recycling Strategies Using a Multilayer Systems Approach.
Food waste (FW) generates large upstream and downstream emissions to the environment and unnecessarily consumes natural resources, potentially affecting future food security. The ecological impacts of FW can be addressed by the upstream strategies of FW prevention or by downstream strategies of FW recycling, including energy and nutrient recovery. While FW recycling is often prioritized in practice, the ecological implications of the two strategies remain poorly understood from a quantitative systems perspective. Here, we develop a multilayer systems framework and scenarios to quantify the implications of food waste strategies on national biomass, energy, and phosphorus (P) cycles, using Norway as a case study. We found that (i) avoidable food waste in Norway accounts for 17% of sold food; (ii) 10% of the avoidable food waste occurs at the consumption stage, while industry and retailers account for only 7%; (iii) the theoretical potential for systems-wide net process energy savings is 16% for FW prevention and 8% for FW recycling; (iv) the theoretical potential for systems-wide P savings is 21% for FW prevention and 9% for FW recycling; (v) while FW recycling results in exclusively domestic nutrient and energy savings, FW prevention leads to domestic and international savings due to large food imports; (vi) most effective is a combination of prevention and recycling, however, FW prevention reduces the potential for FW recycling and therefore needs to be prioritized to avoid potential overcapacities for FW recycling.


Comparison of Mechano- and PhotoATRP with ZnO Nanocrystals.
Zinc oxide (ZnO) was previously reported as an excellent cocatalyst for mechanically controlled atom transfer radical polymerization (mechanoATRP), but its photocatalytic properties in photoinduced ATRP (photoATRP) have been much less explored. Herein, well-defined ZnO nanocrystals were prepared via microwave-assisted synthesis and applied as a heterogeneous cocatalyst in mechano- and photoATRP. Both techniques yielded polymers with outstanding control over the molecular weight, but ZnO-cocatalyzed photoATRP was much faster than analogous mechanoATRP (conversion of 91% in 1 h vs 54% in 5 h). The kinetics of photoATRP was tuned by loadings of ZnO nanocrystals. PhotoATRP with ZnO did not require any excess of ligand versus Cu, in contrast to mechanoATRP, requiring an excess of ligand, acting as a reducing agent. ZnO-cocatalyzed photoATRP proceeded controllably without prior deoxygenation, since ZnO was involved in a cascade of reactions, leading to the rapid elimination of oxygen. The versatility and robustness of the technique were demonstrated for various (meth)acrylate monomers with good temporal control and preservation of end-group functionality, illustrated by the formation of tailored block copolymers.


Electron microscopic immunolocalization of a conserved sperm acrosomal antigen recognized by HS-63 monoclonal antibody.
HS-63 monoclonal antibody was shown to react with a sperm-specific acrosomal antigen from spermatozoa of a variety of mammalian species. Indirect immunofluorescence showed that HS-63 was associated with acrosome-intact sperm after sperm had been fixed with methanol. Electron microscopy (EM) was employed to determine the ultrastructural localization of this sperm antigen. When the immunogold labelled goat anti-mouse IgG was used as a probe, we demonstrated that HS-63 monoclonal antibody did not bind to the freshly prepared human spermatozoa. However, gold particles were observed in the intra-acrosomal region, when the spermatozoa had been pre-treated with 0.5% Triton X-100 prior to incubation with HS-63. We further observed that the immunogold did not stain the inner acrosome membrane when the spermatozoa became acrosome-reacted. A good correlation was obtained between the percentage of spermatozoa which did not react with HS-63 as determined by indirect immunofluorescence assay and that of acrosome-reacted spermatozoa as quantitated by electron microscopy. The results of this EM study were consistent with those obtained by indirect immunofluorescence assay and both indicated that HS-63 reacts only with the capacitated and acrosome-intact spermatozoa. Therefore, HS-63 monoclonal antibody is a useful probe for rapid evaluation of acrosomal status in human spermatozoa.


Weakly coupled lipid bilayer membranes on multistimuli-responsive poly(N-isopropylacrylamide) copolymer cushions.
Polymer-cushioned lipid bilayers are frequently used to mimic the native environment of cellular membranes in respect to the extracellular matrix and intracellular structures. With the aim to actively tune lipid membrane characteristics, we pursue the approach to use temperature and pH responsive polymer thin films of poly(N-isopropylacrylamide-co-carboxyacrylamide) (PNIPAAm-co-carboxyAAM) as cushions for supported lipid bilayers. A cationic lipid bilayer composed of dioleoylphosphatidylcholine (DOPC) and dioleoyltrimethylammoniumpropane (DOTAP) (9:1) was formed on top of the polymer thin film in a drying/rehydration process. Fluorescence recovery after photobleaching (FRAP) yielded higher lipid diffusion coefficients (6.3-9.6 μm(2) s(-1)) on polymer cushions in comparison to solid glass supports (3.0-5.9 μm(2) s(-1)). No correlation of the lipid mobility was found with the swelling state of (PNIPAAm-co-carboxyAAM), which is ascribed to restrained interfacial electrostatic interactions and dispersion forces. The results revealed a minimal coupling of the lipid bilayer with the polymer cushions, and thus, bilayers supported by (PNIPAAm-co-carboxyAAM) provide interesting opportunities for unperturbed lipid diffusion combined with control of transmembrane protein mobility due to the impact of a tunable frictional drag.


High PD-L1 expression is associated with a favorable prognosis in patients with esophageal squamous cell carcinoma undergoing postoperative adjuvant radiotherapy.
Previous results on the prognostic value of programmed death-ligand (PD-L)1 expression in patients with esophageal squamous cell carcinoma (ESCC) remain limited and conflicting. The present study aimed to determine whether PD-L1 expression status predicts prognosis in patients with ESCC, particularly in those undergoing different postoperative treatments. Immunohistochemical staining for PD-L1 was performed on surgical specimens that were obtained from 246 patients with ESCC, who underwent surgical treatment but did not undergo preoperative chemotherapy, radiotherapy, targeted therapy or immune therapy. The association of PD-L1 expression with the clinicopathological factors and the association of PD-L1 expression with survival of patients with ESCC, including subgroups of patients undergoing different postoperative treatments (surgery alone, surgery with adjuvant chemotherapy, surgery with adjuvant radiotherapy and surgery with adjuvant chemo-radiotherapy groups), were statistically analyzed. Positive PD-L1 expression was significantly associated with advanced tumor-node metastasis stage (P=0.022). Median overall survival (OS) time was compared between patients with positive PD-L1 expression and those with negative PD-L1 expression in the overall patient population. In patients who were treated with postoperative adjuvant radiotherapy, the prognosis was significantly improved in patients who were PD-L1-positive compared with those who were PD-L1-negative (P=0.046). In patients treated with adjuvant chemotherapy, median OS was poorer in patients with positive PD-L1 expression compared with those with negative PD-L1 expression. However, the difference was not significant. Multivariate Cox regression analysis demonstrated that PD-L1 expression status was not an independent prognostic factor in patients with ESCC. High PD-L1 expression was associated with a favorable prognosis in patients with ESCC undergoing postoperative adjuvant radiotherapy, and it was concluded that patients with positive PD-L1 expression might benefit from postoperative adjuvant radiotherapy.


Association between allergic rhinitis and despair, suicidal ideation, and suicide attempts in Korean adolescents: a nationally representative study of one million adolescents.
There is a lack of studies establishing the association between allergic rhinitis (AR) and despair, suicidal thinking, and suicide attempts in adolescents and children at a population level. This study aimed to investigate whether there are associations between allergic rhinitis and despair, suicidal thinking, and suicide attempts. The study utilized data from middle through high school adolescents from 2005-2021 who enrolled in the Korea Youth Risk Behavior Web-based Survey (KYRBS; 1,067,169). We assessed despair, suicidal thinking, and suicide attempts in the context of both non-atopic and atopic AR. Multivariable analysis was used to determine the association of variables. The prevalence of allergic rhinitis was 28.0%. 1,067,169 enrolled participants were included in the final analysis. There were 299,468 individuals with allergic rhinitis and 767,701 without. In the context of AR, adolescents were more likely to have despair [adjusted odds ratio (aOR), 1.16; 95% CI, 1.15-1.17], suicidal thoughts (aOR, 1.12; 95% CI, 1.11-1.13 for model 2), and suicide attempts (aOR, 1.13; 95% CI, 1.10-1.15 for model 2). Individuals with atopic AR were more likely in almost all measures to have despair, suicidal thinking, and suicide attempts than individuals with non-atopic AR. Females with AR were more likely to have suicide attempts and middle school students were more likely to have despair, suicidal thoughts, and suicide attempts. The results of this study warrant future studies investigating why AR is so closely associated with despair, suicidal ideation, and suicide attempts, with the goal of establishing suicide prevention strategies as well as improving overall mental health for adolescents.


Impaired PPARγ activation by cadmium exacerbates infection-induced lung injury.
Emerging data indicate an association between environmental heavy metal exposure and lung disease, including lower respiratory tract infections (LRTIs). Here, we show by single-cell RNA sequencing an increase in Pparg gene expression in lung macrophages from mice exposed to cadmium and/or infected with Streptococcus pneumoniae. However, the heavy metal cadmium or infection mediated an inhibitory posttranslational modification of peroxisome proliferator-activated receptor γ (PPARγ) to exacerbate LRTIs. Cadmium and infection increased ERK activation to regulate PPARγ degradation in monocyte-derived macrophages. Mice harboring a conditional deletion of Pparg in monocyte-derived macrophages had more severe S. pneumoniae infection after cadmium exposure, showed greater lung injury, and had increased mortality. Inhibition of ERK activation with BVD-523 protected mice from lung injury after cadmium exposure or infection. Moreover, individuals residing in areas of high air cadmium levels had increased cadmium concentration in their bronchoalveolar lavage (BAL) fluid, increased barrier dysfunction, and showed PPARγ inhibition that was mediated, at least in part, by ERK activation in isolated BAL cells. These observations suggest that impaired activation of PPARγ in monocyte-derived macrophages exacerbates lung injury and the severity of LRTIs.


Alcohol After Resistance Exercise Does Not Affect Muscle Power Recovery.
Levitt, DE, Idemudia, NO, Cregar, CM, Duplanty, AA, Hill, DW, and Vingren, JL. Alcohol after resistance exercise does not affect muscle power recovery. J Strength Cond Res 34(7): 1938-1944, 2020-The purpose of this study was to investigate the effect of alcohol consumed after heavy eccentric resistance exercise on measures of muscle power. After familiarization and an initial eccentric exercise bout to control for the "repeated-bout effect," 10 recreationally resistance-trained men completed 2 identical heavy eccentric squat bouts (4 sets of 10 repetitions at 110% of concentric 1-repetition maximum) 1 week apart. Each exercise bout was followed by ingestion of a beverage containing either alcohol (1.09 g ethanol·kg fat-free body mass) or no alcohol (placebo; volume of alcohol replaced with water). Vertical jump (VJ) peak power, VJ peak force, VJ jump height, change-of-direction ability (shuttle run), sprint acceleration (sprint test), and muscle soreness were measured before (PRE), 24 hours after (24H), and 48 hours after (48H) each eccentric exercise bout. Although the exercise bout resulted in significantly (p ≤ 0.05) decreased VJ peak power at 24H, significantly decreased VJ jump height at 24H, and significantly increased muscle soreness at 24H and 48H, consuming alcohol after the exercise bout did not affect any of the performance outcome measures. When consumed after a non-novel heavy eccentric resistance exercise bout, alcohol did not affect soreness or recovery of muscular power. Practitioners can use this information to advise their athletes with regard to responsible alcohol use after non-novel exercise. Although short-term anaerobic performance does not seem compromised as a result of acute postexercise alcohol ingestion, practitioners and athletes should be aware of potential long-term effects of such alcohol use.


Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency.
The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.


In-vitro safety and off-target profile of the anti-parasitic arylmethylaminosteroid 1o.
Parasite-mediated diseases like malaria and schistosomiasis are growing health problems worldwide and novel drug candidates are urgently needed. In this study, the in-vitro safety profile of steroid compound 1o (sc1o), effective against the parasites Plasmodium falciparum and Schistosoma mansoni with an IC50 value of 5 nM, was characterized. We assessed viability/proliferation, apoptosis and cell cycle tests to determine the cytotoxic profile of sc1o in cancer cells. The mutagenic potential was determined with the AMES test. To identify off-target effects we investigated whether sc1o interacts with safety-relevant molecules such as cytochrome P450 (CYP) enzymes, phosphodiesterases (PDE), histone deacteylases (HDAC) and human ether-a-go-go related gene (hERG). Furthermore, to predict the potential bioavailability of sc1o, its effect on Caco-2 cell barrier integrity, by measurement of the transepithelial electrical resistance (TEER), was determined. Sc1o at 25 µM reduced cell viability, probably through cell-cycle arrest, but did not induce apoptosis in cancer cells. No adverse off-target effects nor mutagenic potential of sc1o were observed. Furthermore, sc1o did not disturb the integrity of the cell barrier, but exhibited low membrane permeability, apparently due to cell adherence. In conclusion, sc1o up to 10 µM showed a good in-vitro safety profile.


Gastrointestinal complications after cardiac surgery.
Gastrointestinal (GI) complications after cardiac surgical procedures are infrequent but severe. Thirty-three GI complications were identified in 25 patients who underwent cardiac surgery during a 7-year period (2.0% incidence). The mortality rate for patients having these GI complications was 44%. Acute acalculous cholecystitis was the most lethal complication (86%). Acute pancreatitis was the most common complication (eight patients). Most patients responded well to conservative measures. Five patients had upper GI hemorrhage and three had lower GI bleeding that required more than 2 U of packed red blood cells. All patient conditions were diagnosed endoscopically and none necessitated operation. Of the remaining patients, one was operated on because of perforated duodenal ulcer, one because of perforated diverticulitis, and one because of pseudo-obstruction of the colon, and one patient underwent diagnostic laparotomy and showed negative results for presumed acalculous cholecystitis. Liver failure was fatal in all three patients in whom it occurred. GI complications correlated significantly with advanced age, prolonged bypass times, valve surgery, and the female sex. We conclude that septic GI complications--particularly acute acalculous cholecystitis and perforated viscus--after cardiac surgery are uncommon but lethal. Clinical features are often subtle, and a high index of suspicion is necessary for an early diagnosis and the institution of appropriate treatment.


Naturally occurring human parainfluenza type 3 viruses exhibit divergence in amino acid sequence of their fusion protein neutralization epitopes and cleavage sites.
Many human parainfluenza type 3 virus (PIV3) strains isolated from children with respiratory illness are resistant to neutralization by monoclonal antibodies (MAbs) which recognize epitopes in antigenic site A or B of the fusion (F) protein of the prototype 1957 PIV3 strain. The F protein genes of seven PIV3 clinical isolates were sequenced to determine whether their neutralization-resistant phenotypes were associated with specific differences in amino acids which are recognized by neutralizing MAbs. Several clinical strains which were resistant to neutralization by site A or B MAbs had amino acid differences at residues 398 or 73, respectively. These specific changes undoubtedly account for the neutralization-resistant phenotype of these isolates, since identical substitutions at residues 398 or 73 in MAb-selected escape mutants confer resistance to neutralization by site A or B MAbs. The existence of identical changes in naturally occurring and MAb-selected neutralization-resistant PIV3 strains raises the possibility that antigenically different strains may arise by immune selection during replication in partially immune children. Three of the seven clinical strains examined had differences in their F protein cleavage site sequence. Whereas the prototype PIV3 strain has the cleavage site sequence Arg-Thr-Lys-Arg, one clinical isolate had the sequence Arg-Thr-Arg-Arg and two isolates had the sequence Arg-Thr-Glu-Arg. The different cleavage site sequences of these viruses did not affect their level of replication in either continuous simian or bovine kidney cell monolayers (in the presence or absence of exogenous trypsin or plasmin) or in the upper or lower respiratory tract of rhesus monkeys. We conclude that two nonconsecutive basic residues within the F protein cleavage site are sufficient for efficient replication of human PIV3 in primates.


Ketotifen, a mast cell blocker improves sperm motility in asthenospermic infertile men.
This study aimed to evaluate the efficacy of ketotifen on sperm motility of asthenospermic infertile men. It is a prospective study designed in vivo. In this interventional experimental study, a total of 40 infertile couples with asthenospermic infertility factor undergoing assisted reproductive technology (ART) cycles were enrolled. The couples were randomly assigned to one of two groups at the starting of the cycle. In control group (n = 20), the men did not receive Ketotifen, while in experiment group (n = 20), the men received oraly ketotifen (1 mg Bid) for 2 months. Semen analysis, under optimal circumferences, was obtained prior to initiation of treatment. The second semen analysis was done 2-3 weeks after stopped ketotifen treatment and sperm motility was defined. Clinical pregnancy was identified as the presence of a fetal sac by vaginal ultrasound examination. All data are expressed as the mean ± standard error of mean (SEM). t test was used for comparing the data of the control and treated groups. The mean sperm motility increased significantly (from 16.7% to 21.4%) after ketotifen treatment (P < 0.001). This sperm motility improvement was more pronounced in the primary infertility cases (P < 0.003). The rate of pregnancy was 12.5% in infertile couples that their men receiving 1 mg/twice a day ketotifen. In 52% of infertile men's semen, the percentage of sperm motility was increased from 5% to 35% and this sperm motility improvement was also observed in 33% of necrospermia (0% motility) cases. These results suggest that ketotifen may represent as a novel therapeutic approach to improve sperm motility in the infertile men with cause of asthenospermia or necrospermia.


Revalidation: implications for senior nurses.
Revalidation replaces the current triennial self-declaration system of maintaining nurse registration. It involves a third-party affirmation process designed to improve public and patient confidence that nurses remain up to date by undertaking relevant professional development activities. While revalidation is ultimately the responsibility of individual nurses, senior nurses have an important facilitating role in ensuring that registrants can remain on the register and so continue to practise. This article outlines, from a practical perspective, the senior nurse's role and responsibilities in supporting registrants through each stage of the revalidation process.


Correlation between optics quality of multifocal intraocular lenses and visual acuity: tolerance to modulation transfer function decay.
To study the relationship between the optics quality of multifocal intraocular lenses (IOLs) and distance-corrected near, intermediate, and distance visual acuity to determine the degree to which optics quality must change to produce a significant difference in visual acuity. Fundación Oftalmológica del Mediterráneo, Valencia, Spain. Monocular distance-corrected visual acuity (decimal and logMAR) was measured at 4 m, 70 cm, and 30 cm under photopic and mesopic conditions in eyes with 1 of 3 multifocal IOL models. Visual acuity versus the "average modulation" of the IOL was assessed. The pupil diameter and patient age were similar between the 3 IOL groups (20 eyes each). A difference in average modulation (ie, optics quality) up to 15% did not produce significant differences in mean visual acuity between 2 groups; however, there was a significant difference in mean visual acuity between 2 groups when the average modulation values differed by at least 25%. The slope of the linear correlation between visual acuity and average modulation was 0.018 (r(2) = 0.91) under photopic conditions and 0.024 (r(2) = 0.089) under mesopic conditions. There was a strong linear correlation between IOL optics quality and visual acuity with distance correction under photopic conditions with a pupil of approximately 3.5 mm in a cohort in which the patient age was controlled. The correlation was similar under mesopic conditions. The eye's tolerance to modulation transfer function decay was approximately 15% of the average modulation value.


Hierarchical Ti3C2@TiO2 MXene hybrids with tunable interlayer distance for highly durable lithium-ion batteries.
To realize high-rate and long-term performance of rechargeable batteries, the most effective approach is to develop an advanced hybrid material with a stable structure and more reaction active sites. Recently, 2D MXenes have become an up-and-coming electrode owing to their high conductivity and large redox-active surface area. In this work, we firstly prepared Ti3C2 MXenes through the selective etching of silicon from Ti3SiC2 (MAX) using HF and an oxidant for highly durable lithium-ion batteries (LIBs). The interlayer distance of Ti3C2 MXenes can be controlled with the oxidizability of the oxidant and etching temperature. In addition, Ti3C2@TiO2 MXene hybrids with further expanded interlayer spacing were purposefully fabricated by a simple hydrothermal method. The hierarchical N-doped Ti3C2@TiO2 MXene hybrids show that the in situ synthesized nanoscale TiO2 particles are loaded homogeneously on the layered N-doped Ti3C2 surface. The interlayer distance of N-doped Ti3C2@TiO2 MXene can reach 12.77 Å when using HNO3 as the oxidant at room temperature. As an anode material, the N-doped Ti3C2@TiO2(HNO3-RT) hybrid displays a high reversible capacity of 302 mA h g-1 at 200 mA g-1 after 500 cycles and 154 mA h g-1 at 2000 mA g-1 after 1500 cycles, which indicates its long cycle lifetime and excellent stability in LIBs. This highly durable LIB anode performance is ascribed to synergetic contributions from the high capacitive contribution, high electrical conductivity, high-capacity of in situ formed nanoscale TiO2 and interlayer-expanded architecture of the N-doped Ti3C2@TiO2(HNO3-RT). This study provides a theoretical basis for the application of MXenes as high capacity anodes for advanced LIBs.


Changes in serum BDNF levels associated with moderate-intensity exercise in healthy young Japanese men.
The purpose of this study was to examine the influence of acute moderate-intensity exercise on serum brain-derived neurotrophic factor (BDNF) levels in healthy young Japanese men. BDNF is one of a family of neurotrophic factors involved in neuronal transmission, modulation and plasticity. Previous human-based studies have demonstrated that acute exercise leads to increases in BDNF; however, to date there has been no study conducted among Japanese male subjects. Forty young adult Japanese men (aged 24.1 ± 2.9 years) - reduced to a total of thirty three following subjection to exclusion criteria - performed 30 minutes of exercise at 60% of VO2max on a stationary bicycle. Serum BDNF was analyzed both before and after exercise. Eighteen of the total thirty three subjects demonstrated an increase in serum BDNF after exercise. However, on aggregate, the change in serum BDNF associated with exercise was not significant (p = .17). This is the first study to demonstrate that serum BDNF levels are not consistently increased by acute moderate-intensity exercise in Japanese men. It is likely that something in the lifestyle and/or environment of male Japanese subjects underlies the difference between our findings and studies conducted in other countries.


Therapy in stage I non-seminomatous testicular tumor. A critical review of current strategies.
Currently administered forms of treatment after orchiectomy of non-seminomatous testicular tumor include unilateral (modified) or bilateral (radical) retroperitoneal lymph node dissection (RLND), adjuvant chemotherapy with or without RLND, radiotherapy, and a watch policy with close follow-up ('wait and see'). As diagnostic techniques and therapy concepts improve and new results become accessible, an up-to-date appraisal of these strategies in view of accuracy of staging procedures, of risk of progression, and of morbidity of treatment is being attempted. Our own results of modified and radical RLND are presented. 4 of 55 patients (9.5%) relapsed within 2 years after modified RLND. 1 of 26 patients (Urological Clinic, Bonn) and 13 of 106 patients (Bonn Register of Testicular Tumor) relapsed within 2 years after radical RLND. Relapse rates are 4 and 13.4%, respectively. Correlation between pT stage and rate of progression was found to be significant (95 cases; alpha = 0.01). From data published in the literature and our own data, we conclude that modified RLND with close follow-up is still preferable to other strategy, for reasons of exact staging, low morbidity, and curativity for all patients in clinical stage I. Expected results from current trials on a 'wait and see' approach for patients with low risk of progression may alter this conclusion. The therapeutic advantage of adjuvant chemotherapy for patients with high risk of progression has yet to be demonstrated.


Vasculature-specific MRI reveals differential anti-angiogenic effects of a biomimetic peptide in an orthotopic breast cancer model.
Translational vasculature-specific MRI biomarkers were used to measure the effects of a novel anti-angiogenic biomimetic peptide in an orthotopic MDA-MB-231 human triple-negative breast cancer model at an early growth stage. In vivo diffusion-weighted and steady-state susceptibility contrast (SSC) MRI was performed pre-treatment and 2 weeks post-treatment in tumor volume-matched treatment and control groups (n = 5/group). Treatment response was measured by changes in tumor volume; baseline transverse relaxation time (T2); apparent diffusion coefficient (ADC); and SSC-MRI metrics of blood volume, vessel size, and vessel density. These vasculature-specific SSC-MRI biomarkers were compared to the more conventional, non-vascular biomarkers (tumor growth, ADC, and T2) in terms of their sensitivity to anti-angiogenic treatment response. After 2 weeks of peptide treatment, tumor growth inhibition was evident but not yet significant, and the changes in ADC or T2 were not significantly different between treated and control groups. In contrast, the vascular MRI biomarkers revealed a significant anti-angiogenic response to the peptide after 2 weeks—blood volume and vessel size decreased, and vessel density increased in treated tumors; the opposite was seen in control tumors. The MRI results were validated with histology—H&E staining showed no difference in tumor viability between groups, while peptide-treated tumors exhibited decreased vascularity. These results indicate that translational SSC-MRI biomarkers are able to detect the differential effects of anti-angiogenic therapy on the tumor vasculature before significant tumor growth inhibition or changes in tumor viability.


Comparison of diode laser trans-scleral cyclophotocoagulation versus implantation of a 350-mm2 Baerveldt glaucoma drainage device for the treatment of glaucoma in dogs (a retrospective study: 2010-2016).
To compare outcomes following trans-scleral cyclophotocoagulation (TSCP) and 350-mm2 Baerveldt implantation in the treatment of canine refractory glaucoma. Retrospective case study. Client owned dogs undergoing surgical treatment of glaucoma within a veterinary referral hospital. Eighty-six glaucoma surgeries were performed on 83 eyes (69 dogs) diagnosed with primary or secondary glaucoma. Medical records were retrieved, and baseline data, surgery, medications, intraocular pressures (IOPs), vision, and complications were extracted. Fifty-four eyes (44 dogs) were treated with TSCP and placement of an anterior chamber suture shunt; 28 eyes (24 dogs) were implanted with a Baerveldt glaucoma drainage device (GDD); and four eyes (4 dogs) underwent GDD implantation after failure of TSCP to manage IOP. Following TSCP, IOP control (<20 mmHg) and vision retention occurred in 81.5% and 42.6%, respectively, for 16.1 ± 1.36 months. Following GDD implantation, 71.4% maintained IOP <20 mmHg and 69.6% maintained vision for 11.0 ± 0.94 months. IOP control without loss of vision was more likely following Baerveldt implantation (17/28; 60.7%) than TSCP (19/54; 35.2%) (P = 0.027). One eye had functional vision restored following GDD placement. IOP control without adjunctive medications was more likely following Baerveldt implantation (P = 0.02). In this study, eyes treated with Baerveldt GDD implantation were more likely to maintain IOP control and retain vision compared to eyes treated with TSCP and placement of an anterior chamber suture shunt. Lack of formal randomization, inconsistencies in surgical techniques and TSCP protocols, and potential unmeasured confounders must be considered when extrapolating from this retrospective study.


Phylogeny and biogeography of the algal DMS-releasing enzyme in the global ocean.
Phytoplankton produce the volatile dimethyl sulfide (DMS), an important infochemical mediating microbial interactions, which is also emitted to the atmosphere and affecting the global climate. Albeit the enzymatic source for DMS in eukaryotes was elucidated, namely a DMSP lyase (DL) called Alma1, we still lack basic knowledge regarding its taxonomic distribution. We defined unique sequence motifs which enable the identification of DL homologs (DLHs) in model systems and environmental populations. We used these motifs to predict DLHs in diverse algae by analyzing hundreds of genomic and transcriptomic sequences from model systems under stress conditions and from environmental samples. Our findings show that the DL enzyme is more taxonomically widespread than previously thought, as it is encoded by known algal taxa as haptophytes and dinoflagellates, but also by chlorophytes, pelagophytes and diatoms, which were conventionally considered to lack the DL enzyme. By exploring the Tara Oceans database, we showed that DLHs are widespread across the oceans and are predominantly expressed by dinoflagellates. Certain dinoflagellate DLHs were differentially expressed between the euphotic and mesopelagic zones, suggesting a functional specialization and an involvement in the metabolic plasticity of mixotrophic dinoflagellates. In specific regions as the Southern Ocean, DLH expression by haptophytes and diatoms was correlated with environmental drivers such as nutrient availability. The expanded repertoire of putative DL enzymes from diverse microbial origins and geographic niches suggests new potential players in the marine sulfur cycle and provides a foundation to study the cellular function of the DL enzyme in marine microbes.


Isolation site influences virulence phenotype of serotype 14 Streptococcus pneumoniae strains belonging to multilocus sequence type 15.
Streptococcus pneumoniae is a diverse species causing invasive as well as localized infections that result in massive global morbidity and mortality. Strains vary markedly in pathogenic potential, but the molecular basis is obscured by the diversity and plasticity of the pneumococcal genome. We have previously reported that S. pneumoniae serotype 3 isolates belonging to the same multilocus sequence type (MLST) differed markedly in in vitro and in vivo phenotypes, in accordance with the clinical site of isolation, suggesting stable niche adaptation within a clonal lineage. In the present study, we have extended our analysis to serotype 14 clinical isolates from cases of sepsis or otitis media that belong to the same MLST (ST15). In a murine intranasal challenge model, five ST15 isolates (three from blood and two from ears) colonized the nasopharynx to similar extents. However, blood and ear isolates exhibited significant differences in bacterial loads in other host niches (lungs, ear, and brain) at both 24 and 72 h postchallenge. In spite of these differences, blood and ear isolates were present in the lungs at similar levels at 6 h postchallenge, suggesting that early immune responses may underpin the distinct virulence phenotypes. Transcriptional analysis of lung tissue from mice infected for 6 h with blood isolates versus ear isolates revealed 8 differentially expressed genes. Two of these were exclusively expressed in response to infection with the ear isolate. These results suggest a link between the differential capacities to elicit early innate immune responses and the distinct virulence phenotypes of clonally related S. pneumoniae strains.


A helix 1-extended hairpin ribozyme exhibits altered cleavage behavior in vitro.
The catalytic domain of a hairpin ribozyme was incorporated at the 3'-end of a 254-base antisense RNA directed against the RNA of human immunodeficiency virus type 1 (HIV-1), generating a hairpin ribozyme with a largely extended helix 1. In parallel, a catalytic antisense RNA based on a hammerhead ribozyme was directed toward the same cleavage motif in the HIV-1 target. Both ribozymes were expected to create identical cleavage products. Cleavage analysis in vitro confirmed that the hammerhead ribozyme delivered the expected cleavage products. However, the helix 1-extended hairpin ribozyme catalyzed additional RNA cleavage at several unexpected sites, which were mapped. Some of the 3' cleavage products had other nucleotides than G at their 5'-terminus, indicating that the helix 1-extended hairpin ribozyme was able to cleave bonds other than NpG+1. Inspection of the sequence context of the different cleavage sites suggested that unconventional helices 2 in combination with an asymmetric loop A consisting of up to 32 unpaired nucleotides in the substrate strand were formed. A second variant of a helix 1-extended hairpin ribozyme that differed in two nucleotides gave consistent results.


Structural, Electrical, and Optical Properties of ZnO Film Used as Buffer Layer for CIGS Thin-Film Solar Cell.
The CuIn(x)Ga(1-x)Se2 (CIGS) using the solution-based fabrication method is attractive for thin film solar cells because of its possibilities for large-area and low-cost production. ZnO films between transparent conductive oxide (TCO) and the CdS films can improve the performances of CIGS thin-film solar cells. In this study, we investigated the characteristics of ZnO film between TCO and CIGS layers in a solar cell (AZO/ZnO/CdS/CIGS/Mo), which were deposited at various thicknesses to investigate the role of the films in CIGS solar cells. It was confirmed that the conversion efficiency of a CIGS solar cell depends on the ZnO film. For a ZnO film thickness of 80 nm, the highest power conversion efficiency that a solar cell achieved was J(sc) of 18.73 mA/cm2.


Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms.
Ischemic stroke is a leading cause of death worldwide. A key secondary cell death mechanism mediating neurological damage following the initial episode of ischemic stroke is the upregulation of endogenous neuroinflammatory processes to levels that destroy hypoxic tissue local to the area of insult, induce apoptosis, and initiate a feedback loop of inflammatory cascades that can expand the region of damage. Stem cell therapy has emerged as an experimental treatment for stroke, and accumulating evidence supports the therapeutic efficacy of stem cells to abrogate stroke-induced inflammation. In this review, we investigate clinically relevant stem cell types, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), very small embryonic-like stem cells (VSELs), neural stem cells (NSCs), extraembryonic stem cells, adipose tissue-derived stem cells, breast milk-derived stem cells, menstrual blood-derived stem cells, dental tissue-derived stem cells, induced pluripotent stem cells (iPSCs), teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N), c-mycER(TAM) modified NSCs (CTX0E03), and notch-transfected mesenchymal stromal cells (SB623), comparing their potential efficacy to sequester stroke-induced neuroinflammation and their feasibility as translational clinical cell sources. To this end, we highlight that MSCs, with a proven track record of safety and efficacy as a transplantable cell for hematologic diseases, stand as an attractive cell type that confers superior anti-inflammatory effects in stroke both in vitro and in vivo. That stem cells can mount a robust anti-inflammatory action against stroke complements the regenerative processes of cell replacement and neurotrophic factor secretion conventionally ascribed to cell-based therapy in neurological disorders.


Telomere Length: A Potential Biomarker for the Risk and Prognosis of Stroke.
Stroke is one of the leading causes of death and disability worldwide. Age is associated with increased risk of stroke, while telomere length shortening plays a pivotal role in the process of aging. Moreover, telomere length shortening is associated with many risk factors of stroke in addition to age. Accumulated evidence shows that short leukocyte telomere length is not only associated with stroke occurrence but also associated with post-stroke recovery in the elderly population. In this review, we aimed to summarize the association between leukocyte telomere length and stroke, and discuss that telomere length might serve as a potential biomarker to predict the risk and prognosis of stroke.


A phosphine-mediated conversion of azides into diazo compounds.
N2 the mild: Diazo compounds are extremely versatile intermediates for synthetic organic chemistry, but their synthesis can be challenging in the presence of delicate functional groups. The Staudinger ligation has inspired a mild method for the conversion of a broad range of azides into their diazo compound derivatives through an acyl triazene intermediate.


Renal biopsy in patients with systemic lupus erythematosus: Not just lupus glomerulonephritis!
Kidney biopsy is a mainstay in the diagnosis and management of renal disease in patients with systemic lupus erythematosus. Though biopsies from patients with lupus typically show various forms of immune complex glomerulonephritis, other pathologies are occasionally encountered, including unusual lupus-related nephropathies, other forms of autoimmune disease, and occasional renal disorders without any direct connection with lupus or autoimmunity. Electron microscopy is a powerful tool for detecting and classifying these unusual conditions, which frequently have important therapeutic and prognostic implications.


Histopathology and immunohistochemistry in distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma with very high proliferation index and with or without a starry-sky pattern: a comparative study with EBER and FISH.
Burkitt lymphoma (BL) is characterized by c-myc translocation and CD10+/bc-2-/bcl-6+ with a very high Ki-67 proliferation index (PI). Occasional diffuse large B-cell lymphomas may exhibit a very high PI with or without a starry-sky pattern (DLBCL-HPSS). We compared 28 consecutive BL and 16 DLBCL-HPSS cases in immunocompetent Taiwanese diagnosed by histopathologic examination and immunophenotyping and compared the results with results for Epstein-Barr virus-encoded messenger RNA (EBER) and fluorescence in situ hybridization (FISH). There were statistically significant differences in the expression of CD10 (28/28 vs 1/16), bcl-2 (3/28 vs 11/16), MUM1 (5/28 vs 15/16), a PI of 95.0% or more (27/28 vs 2/16), and combined CD10+/bcl-2-/bcl-6+ (24/28 vs 1/16) between BLs and DLBCL-HPSSs. Of the BLs, 7 (25%) of 28 and 26 (96%) of 27 were positive for EBER and c-myc rearrangement as compared with 0 of 16 and 1 (7%) of 15 DLBCL-HPSSs, respectively. We can confidently distinguish BL from DLBCL-HPSS by using histopathologic and immunohistochemical (CD10, bcl-2, bcl-6, Ki-67) methods without the aid of EBER and FISH in the great majority of cases.


[Clinical studies on topical hemostat Avitene in urological surgery].
Avitene (Microfibrillar Collagen Hemostat) is a new absorbable topical hemostatic agent, of which action mechanisms are platelet entrapment and activation of platelet clotting factors. It was used clinically on 11 patients for bleeding during urological surgery; bleeding from renal beds, resectional surfaces of kidney, urethras and floor of the pelvis, prostatic capsule and renal pelvis. The patients were 9 males and 2 females aged from 30 to 71 years old. Avitene was applied directly to the source of bleeding in a dry condition after the treatment of large vessel hemostasis. Pressure was applied to the area, and after 3 to 5 minutes, the excess of this material was removed. Avitene was successful in rapidly controlling bleeding in all the patients. No patient had secondary bleeding and complications attributed to the use of this material. This study indicates that Avitene is very effective as a topical hemostatic agent, particularly in urological surgery.


Metabolomic profiling of the effects of Curcumae rhizoma and Sparganii rhizome on stress-led blood stasis.
Blood stasis (BS) is a complex syndrome with blood flow retardation or cessation. The Traditional Chinese Medicine, Curcumae rhizome (CR) and Sparganii rhizome (SR), showed promising effects on this disease, and especially effective when used in combination. However, the detailed influence of the TCMs on the BSS disturbed metabolic pathways was still unclear. In this study, a BS model was constructed in SD rat and the TCMs were used individually or in combination to assess the effects. As a result, combination of CR and SR led to the improvement in hemorheology parameters of up to 80% in the BS model. Further analyzing using metabolomics showed several metabolic pathways, including center carbon metabolism, amino acid metabolism, etc., recovered to the normal levels after treatment. Informatively, tyrosine and thymidine exhibited potential importance in the BSS and its treatment process. From these results, the metabolic profiles of BS and the SR-CR treatment were provided, which may helpful for better understanding the BSS mechanism and the development of more effective therapies.


Assessing the First DataBank settlement: dramatic shake-up or status quo?
First DataBank (FDB) is the prescription drug industry's largest publisher of average wholesale price (AWP) data, which is used to derive drug prices at the consumer end of the U.S. drug distribution system. In 2006, FDB agreed to a tentative legal settlement after allegations it engaged in questionable activities that cost millions of consumers and third-party payers an extra $7 billion between August 2001 and March 2005. The potential impact of the proposed settlement is projected to be far-reaching; however, settlement details still require final approval by the court.


The yeast Saccharomyces cerevisiae as a genetic system for obtaining variants of poliovirus protease 2A.
The inducible expression of poliovirus protease 2A (2Apro) blocks the growth of Saccharomyces cerevisiae. A number of yeast colonies that grow after 2Apro induction have been isolated. The majority of these clones express 2Apro to control levels, suggesting that their ability to divide is not due to the loss of 2Apro gene inducibility. The sequences of the 2Apro genes isolated from 22 clones were determined. Most of the 2Apro sequences from these colonies contain point mutations in the poliovirus protease. The different variant protease sequences were transferred to an infectious poliovirus cDNA clone. Translation of genomic RNA obtained from these poliovirus mutants in cell-free systems revealed that some of them had defects in their ability to cleave P1-2A in cis. In addition, several of these variants cleaved the translation initiation factor eIF-4G inefficiently. Transfection of the RNA generated from the full-length poliovirus genomes mutated in 2Apro yielded five viable polioviruses with a small plaque phenotype. These five polioviruses efficiently cleaved p220 but showed defects in viral protein synthesis, transactivation of a leader-luciferase mRNA, and 3CD cleavage to 3C' and 3D'. All 2Apro mutant sequences, including those that did not yield viable viruses, were cloned in pTM1 vector under a T7 promoter. Only the 2Apro variants that have activity to cleave 3CD produced viable poliovirus. Our findings indicate that S. cerevisiae represents a useful system for obtaining poliovirus 2Apro variants that may provide further insight into the role of this protease during the poliovirus replication cycle.


Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers.
Allelic loss on the short arm of chromosome 3 is one of the most common events in the pathogenesis of lung cancer. The lactotransferrin gene (LTF, also referred to as the lactoferrin gene, LF) is located at 3p21.3 common eliminated region 1, which is frequently deleted in lung and other cancers. The expression of the LTF gene was absent in 16 (59%) of 27 small cell lung cancer cell lines, 33 (77%) of 43 nonsmall-cell lung cancer (NSCLC) cell lines and 7 (54%) of 13 primary NSCLC, while LTF mRNA was overexpressed in 3 (7%) of 43 NSCLC cell lines. Its expression was restored by treatment with 5-aza-2'-deoxycytidine (5-aza-dC), trichostatin A (TSA) or a combination of both in a subset of lung cancer cell lines without LTF expression. In addition, we found 8 different types of nucleotide substitutions and one frameshift mutation. These results indicate that the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer.