Quantum initial condition sampling for linearized density matrix dynamics: Vibrational pure dephasing of iodine in krypton matrices.
This paper reviews the linearized path integral approach for computing time dependent properties of systems that can be approximated using a mixed quantum-classical description. This approach is applied to studying vibrational pure dephasing of ground state molecular iodine in a rare gas matrix. The Feynman-Kleinert optimized harmonic approximation for the full system density operator is used to sample initial conditions for the bath degrees of freedom. This extremely efficient approach is compared to alternative initial condition sampling techniques at low temperatures where classical initial condition sampling yields dephasing rates that are nearly an order of magnitude too slow compared to quantum initial condition sampling and experimental results.


SAIDO learning as a cognitive intervention for dementia care: a preliminary study.
The purpose of this study was to examine the beneficial effects on cognitive function by a cognitive intervention program designed for dementia care called Learning Therapy in Japan and SAIDO Learning in the United States (hereinafter "SAIDO Learning," as appropriate). SAIDO Learning is a working memory training program that uses systematized basic problems in arithmetic and language, including reading aloud, as well as writing. Twenty-three nursing home residents with dementia were assigned as an intervention group, and another 24 people with dementia at another nursing home were assigned as a control group. Both nursing homes were operated by the same organization, and residents of both nursing homes received essentially the same nursing care. Thirteen and 6 subjects of the intervention and control groups, respectively, were clinically diagnosed as Alzheimer disease (AD). After the 6-month intervention, the participants with AD of the intervention group showed statistically significant improvement in cognitive function, as measured by the Mini-Mental State Examination (MMSE) compared with the control participants. In addition, post hoc analysis revealed that the Frontal Assessment Battery at Bedside (FAB) scores of the intervention group tended to improve after 6-month intervention. Based on MDS scores, improvements in total mood severity scores also were observed, but only in the intervention group of the participants with AD. These results suggest that SAIDO Learning is an effective cognitive intervention and is useful for dementia care. An additional outcome of this intervention, which has not yet been evaluated in detail, appears to be that it promotes greater positive engagement of a diversity of nursing home staff in the residents' individual progress and care needs.


Difference of allelotype between squamous cell carcinoma and adenocarcinoma of the lung.
We compared the frequency of loss of heterozygosity on all autosomal chromosomes among 41 squamous cell carcinomas and 119 adenocarcinomas, to analyze possible relationships of specific tumor suppressor gene(s) to each histological type. On the majority (28 of 36) of chromosomal arms tested, loss of heterozygosity was observed more frequently in squamous cell carcinomas than in adenocarcinomas; in nine of these locations (3p, 3q, 4q, 7p, 9q, 13q, 16q, 17p, and 21q), the frequency was statistically significant (3p, 3q, 4q, 9q, 13q, and 17p, P < 0.01; 7p, 16q, and 21q, P < 0.05, chi 2 test). In squamous cell carcinomas, the frequency of allelic loss on chromosome 9q (67%) fell between the frequencies of loss on chromosomes 3p (82%) or 17p (88%) and chromosome 13q (60%). On the other hand, in adenocarcinomas frequent loss of heterozygosity was observed on chromosomes 8q (32%), 9p (36%), 3p (40%), and 17p (51%). Furthermore, allelic losses on chromosomes 9p, 9q, and 13q tended to correlated with smoking. These results suggest that more genetic changes accumulate during tumorigenesis in squamous cell carcinomas than in adenocarcinomas and that unidentified tumor suppressor genes exist on chromosome 9q for squamous cell carcinoma and on chromosome 8q for adenocarcinoma of the lung. These differences may be related to differences in tumorigenic mechanisms, such as etiological factors, operating in the separate histologies.


[Study on turnaround time of biological analysis in urgent need in hospital laboratories].
We have assessed turnaround time (TAT) for urgent laboratory analysis. Twelve hospital laboratories participated to this study. All laboratories have organized a classification of a management system of urgent analyses. The TAT reporting were relatively homogeneous for 12 laboratories. We have defined TAT as time of specimen receipt in the laboratory to time of results reporting. This TAT divides into 4 groups: close to 50 minutes for analyses as TP, D-dimeres, CRP (C Protein Reactive), HCG, troponin, alcoholhemia, K, lipase; 35 minutes for the cytology of cerebrospinal fluid; 25 minutes for complete blood cell count and 15 minutes for blood gases. All laboratories have accepted to TAT as a quality indicator. Quality indicator data should be collected in time to identify and correct problems to implemente effective interventions and to standardize processes among clinical laboratories.


TVT-Exact and midurethral sling (SLING-IUFT) operative procedures: a randomized study.
The aim of the study is to compare results, effectiveness and complications of TVT exact and midurethral sling (SLING-IUFT) operations in the treatment of female stress urinary incontinence (SUI). A single center nonblind, randomized study of women with SUI who were randomized to TVT-Exact and SLING-IUFT was performed by one surgeon from April 2009 to April 2011. SUI was diagnosed on coughing and Valsalva test and urodynamics (cystometry and uroflowmetry) were assessed before operation and 1 year after surgery. This was a prospective randomized study. The follow up period was 12 months. 76 patients were operated using the TVT-Exact operation and 78 patients - using the SLING-IUFT operation. There was no statistically significant differences between groups for BMI, parity, menopausal status and prolapsed stage (no patients had cystocele greater than stage II). Mean operative time was significantly shorter in the SLING-IUFT group (19 ± 5.6 min.) compared with the TVT-Exact group (27 ± 7.1 min.). There were statistically significant differences in the effectiveness of both procedures: TVT-Exact - at 94.5% and SLING-IUFT - at 61.2% after one year. Hospital stay was statistically significantly shorter in the SLING-IUFT group (1. 2 ± 0.5 days) compared with the TVT-Exact group (3.5 ± 1.5 days). Statistically significantly fewer complications occurred in the SLING-IUFT group. the TVT-Exact and SLING-IUFT operations are both effective for surgical treatment of female stress urinary incontinence. The SLING-IUFT involved a shorter operation time and lower complications rate., the TVT-Exact procedure had statistically significantly more complications than the SLING-IUFT operation, but a higher effectiveness.


Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site.
Syndecan-1 is a developmentally regulated cell surface heparan sulfate proteoglycan (HSPG). It functions as a coreceptor for a variety of soluble and insoluble ligands and is implicated in several biological processes, including differentiation, cell migration, morphogenesis, and recently feeding behavior. The extracellular domain of syndecan-1 is proteolytically cleaved at a juxtamembrane site by tissue inhibitor of metalloprotease-3 (TIMP-3)-sensitive metalloproteinases in response to a variety of physiological stimulators and stress in a process known as shedding. Shedding converts syndecan-1 from a membrane-bound coreceptor into a soluble effector capable of binding the same ligands. We found that replacing syndecan-1 juxtamembrane amino acid residues A243-S-Q-S-L247 with human CD4 amino acid residues can completely block PMA-induced syndecan-1 ectodomain shedding. Furthermore, using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS), we identified the proteolytic cleavage site of syndecan-1 as amino acids A243 and S244, generated by constitutive and PMA-induced shedding from murine NMuMG cells. Finally, we show that basal cleavage of syndecan-1 utilizes the same in vivo site as the in vitro site. Indeed, as predicted, transgenic mice expressing the syndecan-1/CD4 cDNA do not shed the syndecan-1 ectodomain in vivo. These results suggest that the same cleavage site is utilized for basal syndecan-1 ectodomain shedding both in vitro from NMuMG and CHO cells and in vivo.


Working Memory Profiles in HIV-Exposed, Uninfected and HIV-Infected Children: A Comparison with Neurotypical Controls.
This study compared the working memory profiles of three groups of children, namely HIV-infected (HIV-I; n = 95), HIV-exposed, uninfected (HIV-EU; n = 86) and an HIV-unexposed, uninfected, (HIV-UU; n = 92) neurotypical control group. Working memory, an executive function, plays an important role in frontal lobe-controlled behaviors, such as motivation, planning, decision making, and social interaction, and is a strong predictor of academic success in school children. Memory impairments have been identified in HIV-I children, particularly in visuospatial processing. Verbal working memory has not been commonly investigated in this population, while it is unknown how the working memory profiles of HIV-EU children compare to their HIV-I and HIV-UU peers. Of interest was whether the working memory profiles of the HIV-EU children would be more similar to the HIV-I group or to the uninfected control group. The results revealed no significant differences in working memory performance between the HIV-I and HIV-EU groups. However, this does not mean that the etiology of the working memory deficits is the same in the two groups, as these groups showed important differences when compared to the control group. In comparison to the controls, the HIV-I group experienced difficulties with processing tasks irrespective of whether they drew on a verbal or visuospatial modality. This appears to stem from a generalized executive function deficit that also interferes with working memory. In the HIV-EU group, difficulties occurred with verbally based tasks, irrespective of whether they required storage or processing. For this group, the dual demands of complex processing and using a second language seem to result in demand exceeding capacity on verbal tasks. Both groups experienced the greatest difficulties with verbal processing tasks for these different reasons. Thus, disruption of different cognitive abilities could result in similar working memory profiles, as evidenced in this study. This has implications for the underlying developmental neurobiology of HIV-I and HIV-EU children, as well the choice of appropriate measures to assist affected children.


UV adaptation: Pigmentation and protection against overexposure.
The skin is known to adapt to UV exposures, that is become less sensitive to sunburn. Reported decreases in sensitivity vary widely from well over 10-fold down to a negligible 10%. This appears to depend importantly on the UV irradiation spectrum to which the skin adapts and on the UV irradiation spectrum that is used to test the sensitivity. The sensitivity is conventionally and generally assessed by the reciprocal of the minimal erythema dose (MED): the UV dose causing a just perceptible reddening of the skin after 8-24 hours. However, MED is much too subtle for everyday life: people will not notice a minimal reddening and commonly consider themselves sunburnt at considerably higher UV doses causing an intense reddening. Levels of adaptation of a well-tanned skin may be substantially higher at these more intense levels of reddening than MED levels. This expectation is based on the fact that people with a constitutively coloured skin may show moderate differences in MED compared with fair-skinned people but far less steep increases in reddening with overexposures to solar-simulated radiation (SSR). UVA exposure is known to enhance pigmentation and may thus be important in protection against overexposure to SSR.


The organization of the chloroplast DNA in wheat and maize in the region containing the LS gene.
The DNAs of the plasmids pTac39 and pZmB1B, which contain the wheat chloroplast DNA BamHI fragment 2 and the maize chloroplast DNA BamHI fragment 9 respectively, were analysed by electron microscopy and by Northern blotting. Both plasmids contain the gene for the large subunit of ribulose bisphosphate carboxylase (LS gene). Comparison of the DNAs of the two species by partial denaturation and heteroduplex analysis shows extended homologies interspersed with a fine pattern of non-homology. On analysis of wheat-RNA X maize-DNA hybrids a region of non-homology at the 3' end of the LS mRNA of about 200 bases was found. Analysis of wheat DNA X RNA hybrids showed that the wheat LS mRNA contains 1700 +/- 50 bases and another hybrid, containing 2400 bases was also shown to occur in a position adjacent to that formed by the LS mRNA. Binding of Escherichia coli RNA polymerase and the start of transcription in vitro occurred at well-defined sites, which are located between or close to the positions where mRNA X DNA hybrids are found. A modified technique for the preparation and fractionation by electrophoresis of glyoxalated RNA is described.


Subpopulations of T lymphocytes in a patient with fulminant mycosis fungoides.
A patient with fulminant Mycosis fungoides was found to have a very high percentage of T lymphocytes with Fc receptors for IgG and a low percentage of T lymphocytes with Fc receptors for IgM. The total number of T lymphocytes was normal, but the in vitro function of the lymphocytes was depressed in short-term cultures, though not in cultures of 5 days' duration. T lymphocytes with Fc receptors for IgG are considered to have suppressor functions, and the immunological changes in this patient may be explained by an increased suppressor cell activity. Other investigators have proposed that the abnormal lymphocytes in Mycosis fungoides are T helper cells. After treatment with electron beam and transfer factor, our patient developed uraemia due to uric acid crystallization in the kidneys. This complication to the treatment given seems not to have been reported before.


Male fertility: Is spermiogenesis the critical step for answering biomedical issues?
Regarding male fertility, biomedical issues have opposite goals to treat infertility or develop contraceptive drugs. Recently, the identification of the molecular mechanisms involved in germ cell differentiation suggest that spermiogenesis has to be put at the crossroad to reach these goals. Concerning fertility issues, citizens in our modern world are schizophrenic. On one side, couples have the possibility to control conception; and on the other side, more and more couples suffer from the misfortune of being infertile. These two societal problems lead to intensive research and conflicting government policies. However, these opposing goals rely on a better understanding of germ cell differentiation.


[The preliminary exploration into regulating sub-health as preventive and therapeutic strategies for tumor].
The definition of sub-health was studied from the angle of tumor dormancy again. We believe it is necessary to further supplement the present definition, diagnosis criteria, and assessment means. The definition of sub-disease and the division of a disease into four development stages (health --> sub-health --> sub-disease --> disease) were also brought up. Furthermore, we believe that application of regulating sub-health as preventive and therapeutic strategies for tumor is an anti-cancer method with Chinese features, which enriches the modern theories of tumor prevention and therapy.


State of the Art Approach to the Classification of Epileptic Seizures and Epilepsies.
In the light of the latest knowledge acquired from clinical and laboratory research dealing with genetic, molecular biology and neuroimaging, existing classifications were successively revised by the International League Against Epilepsy (ILAE) in 2001, 2006, and 2010. In the latest classification established in 2010, proposals articulated radical changes in terms of concepts and definitions of the previously published classifications and put forward new classifications for epileptic seizures, epilepsies and electroclinical syndromes. This review refers to the changes of the new classification with their reasons and criticisms.


[van Bogaert-Bertrand spongy cerebral dystrophy].
We report on a male infant with spongy degeneration of the central nervous system (van Bogaert and Bertrand type), who died at the age of 7 months. The clinic as well as the diagnostic procedure are described, especially the importance of cranial computerized tomography for the diagnosis.


The role of eye and head movements in detecting information about fly balls.
The authors attempted to identify perceptual mechanisms that pick up information for initiating a run to catch fly balls and for judging their landing locations. Fly balls have been shown to be tracked with the eyes and head (R. R. D. Oudejans, C. F. Michaels, F. C. Bakker, & K. Davids, 1999). This raised the question of whether constraining eye and head movements of experienced baseball players by having them wear eye-movement-preventing goggles (eye movements would lead to losing sight of the ball) or a head-movement-preventing neck brace, or both, would limit their capacity (a) to start running in the correct direction and (b) to make correct judgments about the balls' landing locations. Restrictions had minimal effects on response accuracy, but response latency was affected. The goggles increased latency of both running and judging. Moreover, the neck brace decreased judgment time, particularly for difficult balls, suggesting that head stability is important for making judgments. High performance levels suggested that the perceptual system was flexible; that is, different parts of the system can perform the same function. The implications of these findings for perceptual mechanisms are discussed.


Dehydration of an ethanol/water azeotrope through alginate-DNA membranes cross-linked with metal ions by pervaporation.
To obtain high dehydration membranes for an ethanol/water azeotrope, dried blend membranes prepared from mixtures of sodium alginate (Alg-Na) and sodium deoxyribonucleate (DNA-Na) were cross-linked by immersing in a methanol solution of CaCl2 or MaCl2. In the dehydration of an ethanol/water azeotropic mixture by pervaporation, the effects of immersion time in methanol solution of CaCl2 or MaCl2 on the permeation rate and water/ethanol selectivity through Alg-DNA/Ca(2+) and Alg-DNA/Mg(2+) cross-linked membranes were investigated. Alg-DNA/Mg(2+) cross-linked membrane immersed for 12h in methanol solution of MaCl2 exhibited the highest water/ethanol selectivity. This results from depressed swelling of the membranes by formation of a cross-linked structure. However, excess immersion in solution containing cross-linker led to an increase in the hydrophobicity of cross-linked membrane. Therefore, the water/ethanol selectivity of Alg-DNA/Mg(2+) cross-linked membranes with an excess immersion in cross-linking solution was lowered. The relationship between the structure of Alg-DNA/Ca(2+) and Alg-DNA/Mg(2+) cross-linked membranes and their permeation and separation characteristics during pervaporation of an ethanol/water azeotropic mixture is discussed in detail.


Development of tactical deception from 4 to 8 years of age.
One hundred eighteen children, divided into three age groups (4-, 6-, and 8-year-olds) participated in a competitive game designed to explore advances in children's deceptive abilities. Success in the game required children to inhibit useful information or provide misinformation in their communication with an adult opponent. Age trends were evident for all dependent variables, including success at the task, strategic behaviours, and interview data. Four-year-olds were non-strategic and rarely successful, 6-year-olds were increasingly strategic and successful, and 8-year-olds were significantly more subtle in their strategies, more successful at the task, and more likely to verbalize an understanding of their opponent's expectations than younger age groups.


The effect of talker variability on word recognition in preschool children.
In a series of experiments, the authors investigated the effects of talker variability on children's word recognition. In Experiment 1, when stimuli were presented in the clear, 3- and 5-year-olds were less accurate at identifying words spoken by multiple talkers than those spoken by a single talker when the multiple-talker list was presented first. In Experiment 2, when words were presented in noise, 3-, 4-, and 5-year-olds again performed worse in the multiple-talker condition than in the single-talker condition, this time regardless of order; processing multiple talkers became easier with age. Experiment 3 showed that both children and adults were slower to repeat words from multiple-talker than those from single-talker lists. More important, children (but not adults) matched acoustic properties of the stimuli (specifically, duration). These results provide important new information about the development of talker normalization in speech perception and spoken word recognition.


Temporally contiguous pencast instruction promotes meaningful learning for dental and dental hygiene students in physiology.
Smartpens allow for the creation of computerized "pencasts" that combine voice narration with handwritten notes and illustrations. The purpose of this study was to test the effects of voluntary participation in extracurricular instruction with a pencast on student learning. Dental and dental hygiene students were given instruction in a complex physiological topic using lecture and static slides. An Internet link to a pencast that covered the complex topic in a more temporally contiguous fashion was also provided for voluntary review. The students were given a multiple-choice exam that consisted of retention and transfer test questions. Sixty-nine percent of the students who did not watch the pencast and 89 percent of the students who watched the pencast answered the retention test question correctly (p=0.08). Fifty-four percent of the students who did not watch the pencast and 90 percent of the students who watched the pencast answered the transfer test question correctly (p=0.005). This finding indicates that students who watched the pencast performed better on a transfer test, a measurement of meaningful learning, than students who received only the narrated instruction with static images. This supports the hypothesis that temporally contiguous instruction promotes more meaningful learning than lecture accompanied only by static slide images.


IoT Data Quality Assessment Framework Using Adaptive Weighted Estimation Fusion.
Timely data quality assessment has been shown to be crucial for the development of IoT-based applications. Different IoT applications' varying data quality requirements pose a challenge, as each application requires a unique data quality process. This creates scalability issues as the number of applications increases, and it also has financial implications, as it would require a separate data pipeline for each application. To address this challenge, this paper proposes a novel approach integrating fusion methods into end-to-end data quality assessment to cater to different applications within a single data pipeline. By using real-time and historical analytics, the study investigates the effects of each fusion method on the resulting data quality score and how this can be used to support different applications. The study results, based on two real-world datasets, indicate that Kalman fusion had a higher overall mean quality score than Adaptive weighted fusion and Naïve fusion. However, Kalman fusion also had a higher computational burden on the system. The proposed solution offers a flexible and efficient approach to addressing IoT applications' diverse data quality needs within a single data pipeline.


Envy, shame, and sadism.
In this article, envy is identified as a drive derivative, erupting as a definable behavior in the anal phase of psychosexual development, locating envy as first being experienced during the stage of self-development, separation/individuation. The aim of envy, as identified by the nature of the investment the subject makes in envied objects, is described as "aquisitiveness," or, following Klein, sadism, defined in terms of the subject wanting to incorporate the envied object, making the aim of envy narcissistic, that is, an aggrandizing of the self. The usual aim assigned to envy, destructiveness, is conceptualized as a defense against the cannibalistic hunger of envy, in response to the regulatory affect, shame. The dynamic of this defense accounts for the dyadic nature of the object of envy (as opposed to jealousy), supporting the "splitting" quality of this defense. This rendering of envy, shame, and sadism promotes the integration of narcissistic urges into normative psychosexual development and deepens an understanding of the splitting defense in pathological narcissism.


Genome-Wide Association Studies for Striga asiatica Resistance in Tropical Maize.
Striga asiatica L. is a parasitic weed in cereal crops including maize leading to tremendous yield losses up to 100% under severe infestation. The available S. asiatica control methods include cultural control options such as uprooting and burning the Striga plants before they flower, field sanitation, crop rotation, intercropping, organic matter usage, improved fallows, and application of herbicides. Resource limitation among smallholder farmers renders almost all of the control methods impossible. Development and use of Striga resistant genotypes are seen as the most feasible management option. Marker identification formulates tools that are faster, cheaper, and easier to utilise in breeding for S. asiatica resistance which has low heritability. The objective of this study was to identify single nucleotide polymorphism (SNP) markers for Striga resistance using the genome-wide association study (GWAS). Genotyping by sequencing was done on tropical maize inbred lines followed by their evaluation for Striga resistance. Analysis of variance showed significant (p < 0.05) variation among evaluated genotypes for Striga resistance traits such as germination distance, germination percentage, haustoria root attachments, total Striga plants emerged, total biomass, and growth rate. There were also significant differences (p < 0.05) for cobs, leaves, stems, and roots weight. The broad sense heritability was fairly high (up to 61%) for most traits. The means for derived traits on stress tolerance indices were subjected to a t-test, and significant differences (p < 0.05) were found for leaves, stem, roots, shoots, and total biomass. The Manhattan plots from GWAS showed the presence of three SNP markers on chromosome numbers 5, 6, and 7 for total Striga plants emerged. The identified markers for resistance to S. asiatica should be validated and utilised to breed for Striga resistance in tropical maize.


Breast Feeding Is Associated with Postmenopausal Bone Loss: Findings from the Korea National Health and Nutrition Examination Survey.
Postmenopausal osteoporosis is a common disease which can cause various morbidity and economic burden. Lactation is known to cause a decline in bone mineral density (BMD), but there are controversies on whether decreased BMD is fully recovered after lactation and whether lactation duration has an influence on postmenopausal BMD. This study was conducted to see whether breastfeeding is associated with postmenopausal bone loss using a highly representative sample of Korean population. Retrospective cross sectional study was done using data collected from Korea National Health and Nutrition Examination Survey V. The study outcome was BMD measured with dual-energy X-ray absorptiometry and divided into 2 groups: normal or low BMD (T score<-1), and breastfeeding duration was categorized into 4 groups (never, 1st, 2nd, and 3rd tertile). Logistic regression analysis was done to examine the association between lactation duration and BMD. Among 1,694 postmenopausal women (mean age, 63.5±9.1), 85.71% were in low BMD group. Compared to never breastfeeding group, postmenopausal women with longer than 79 months of breastfeeding duration are more likely to have low BMD (adjusted risk ratio [ARR]=1.24; 95% confidence interval, 1.17 to 1.32). As the duration of breastfeeding increases, ARR and risk difference for low BMD also increases (P for trend=0.008). The study results showed that total breastfeeding duration was associated with postmenopausal low BMD. All women planning on breastfeeding should be aware of its risks and should take adequate dietary calcium and vitamin D before, during, and after breastfeeding.


[Research advances in association between childhood obesity and gut microbiota].
In recent years, more and more studies have noted the close association between gut microbiota and the development and progression of obesity. Gut microbiota may act on obesity by increasing energy intake, affecting the secretion of intestinal hormones, inducing chronic systemic inflammation, and producing insulin resistance. This article reviews the association between childhood obesity and gut microbiota, as well as possible mechanisms, in an attempt to provide a reference for the etiology, prevention and treatment of childhood obesity.


Reaching more children with vaccines in developing countries: key challenges of innovation and delivery.
As we reach the deadline for the United Nations fourth Millennium Development Goal to reduce child mortality, many inequalities in vaccine access still exist, particularly for children in developing countries. Here we discuss some of the barriers to vaccine access in these countries, as well as some of the innovative approaches that could address these. Finally, we discuss the need to create a global environment conducive to innovation directed at low-resource settings, aimed to ultimately increase vaccine coverage.


[Coagulation properties of erythrocyte derived membrane microparticles].
Membrane microparticles (MP) produced upon cell activation and/or damage possess coagulation activity, i.e. ability to accelerate blood clotting. They contain on their surface phosphatidylserine (PS), a substrate for assembling coagulation enzymatic complexes, and some of them tissue factor (TF), the initiator of clotting cascade reactions. In this study coagulation properties of MP derived from erythrocytes have been investigated. These MP were obtained from donor's erythrocytes activated with ionophore A23187 as well as from outdated erythrocyte concentrates for transfusion. MP were counted by flow cytometry. Coagulation activity of MP was examined by modified plasma recalcification assay. Involvement of PS and TF in this reaction was assessed using PS blocker lactadherin and anti-TF antibodies. TF activity in MP was measured by its ability to activate factor X in a chromogenic assay. Size of MP was evaluated by dynamic light scattering. Properties of erythrocyte MP were compared with previously characterized (using the same methodological approaches) MP derived from platelets and monocytic THP-1 cells, lacking and containing TF, respectively. Erythrocyte MP accelerated plasma clotting, but less actively than MP from platelets and MP from THP-1 cells, which demonstrated maximal activity. Lactadherin completely inhibited coagulation activity of all MP. Anti-TF antibodies did not affect clotting parameters in the presence of platelet and erythrocyte MP, but slowed clotting in the presence of MP from THP-1 cells. TF activity was not detected in erythrocyte and platelet MP, unlike MP from THP-1 cells expressing active TF. MP derived from erythrocytes were smaller than MP from platelets and THP-1 cells, with average diameter about 200 nm and 400 nm respectively. Thus, MP from erythrocyte possess less ability to accelerate plasma clotting in comparison with MP from platelet and THP-1 cells. The data obtained suggest that lesser coagulation activity of erythrocyte MP in comparison with MP from THP-1 cells is due to the absence of TF in erythrocyte MP (in contrast to MP from THP-1 cells) and to their smaller size, and in comparison with MP from platelets (which as erythrocyte MP do not express TF) is due to their smaller size only.


Altered pain perception in children with chronic tension-type headache: is this a sign of central sensitisation?
The aim of this article is to investigate if children (7-17 years) with frequent episodic tension-type headache (FETTH) or chronic TTH (CTTH) have an altered pain perception compared to healthy controls. We applied a pressure of five increasing intensities to m. trapezius and m. temporalis with a Somedic Algometer II. Visual analogue scale-score was rated and area under the curve (AUC) calculated. An average AUC in each person was used as an outcome variable in further univariate multiple linear regression analysis because factor analysis showed that AUC represents only one dimension underlying both muscles. Participants included 22 children with FETTH, 36 children with CTTH and 57 controls. The CTTH group had a significantly higher AUC compared to the control group ( P < 0.001). The FETTH group represented an intermediate state. AUC did not change with increasing age, headache years, headache intensity, headache frequency or sex. Children with CTTH show significantly increased pain sensitivity in a range of pressures compared to the FETTH group and the controls. Since AUC in m. trapezius and m. temporalis represents only one general latent tenderness, it might indicate that the altered pain perception is mainly due to central sensitisation.


An automated large-scale culture system of Plasmodium falciparum using tangential flow filtration for medium change.
Asexual stages and mature gametocytes of Plasmodium falciparum have been produced in a 500 ml suspension culture system containing 6-10% red cells. Medium change was automated and was accomplished using a tangential flow filtration unit. The rate of multiplication of the parasite (isolate NF 54) was consistently high when compared with static cultures and ranged from 6.4 X to 15.3 X per cycle in 8 experiments. Mature gametocytes were present in up to 2% of red cells in 14-day-old cultures. Only minor modifications would be required to further scale-up the volume of the culture.


A century of heroes.
For most of history, humanity just struggled to survive in an unforgiving environment. Only in the past century or so did we start to dominate nature and overrun the planet. Rather than defend outselves against nature, we began to realize, we needed to defend nature against ourselves. Thus was born the environmental movement. These pages recognize men and women who helped give us this awareness--and pointed the way to protecting the only home we have.


LLGL1 Regulates Gemcitabine Resistance by Modulating the ERK-SP1-OSMR Pathway in Pancreatic Ductal Adenocarcinoma.
Gemcitabine resistance is rapidly acquired by pancreatic ductal adenocarcinoma (PDAC) patients. Novel approaches that predict the gemcitabine response of patients and enhance gemcitabine chemosensitivity are important to improve patient survival. We aimed to identify genes as novel biomarkers to predict the gemcitabine response and the therapeutic targets to attenuate chemoresistance in PDAC cells. Genome-wide RNA interference screening was conducted to identify genes that regulated gemcitabine chemoresistance. A cell proliferation assay and a tumor formation assay were conducted to study the role of lethal giant larvae homolog 1 (LLGL1) in gemcitabine chemoresistance. Levels of LLGL1 and its regulating targets were measured by immunohistochemical staining in tumor tissues obtained from patients who received gemcitabine as a single therapeutic agent. A gene-expression microarray was conducted to identify the targets regulated by LLGL1. Silencing of LLGL1 markedly reduced the gemcitabine chemosensitivity in PDAC cells. Patients had significantly shorter survival (6 months) if they bore tumors expressing low LLGL1 level than tumors with high LLGL1 level (20 months) (hazard ratio, 0.1567; 95% CI, 0.05966-0.4117). Loss of LLGL1 promoted cytokine receptor oncostatin M receptor (OSMR) expression in PDAC cells that led to gemcitabine resistance, while knockdown of OSMR effectively rescued the chemoresistance phenotype. The LLGL1-OSMR regulatory pathway showed great clinical importance because low LLGL1 and high OSMR expressions were observed frequently in PDAC tissues. Silencing of LLGL1 induced phosphorylation of extracellular signal-regulated kinase 2 and specificity protein 1 (Sp1), promoted Sp1 (pThr453) binding at the OSMR promoter, and enhanced OSMR transcription. LLGL1 possessed a tumor-suppressor role as an inhibitor of chemoresistance by regulating OSMR-extracellular signal-regulated kinase 2/Sp1 signaling. The data sets generated and analyzed during the current study are available in the Gene Expression Omnibus repository (ID: GSE64681).


The role of checkpoint inhibitors immunotherapy in advanced non-small cell lung cancer in the elderly.
Immune checkpoint inhibition is a novel treatment modality that has brought a new hope to patients with advanced NSCLC. Several molecules targeting cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 receptor/programmed death ligand-1 (PD1/PD-L1) pathways are under evaluation in NSCLC and three of them are currently approved: nivolumab and atezolizumab for advanced NSCLC after prior chemotherapy and pembrolizumab for advanced NSCLC expressing PD-L1 ≥ 1% after at least one prior chemotherapy regimen and > 50% as a first-line response. Areas covered: To date, the efficacy and toxicity of immune checkpoint inhibitors in the elderly is unclear because available studies involved mainly a low number of elderly patients. In this paper, the authors discuss the frailty of the elderly patient and the challenges of choosing the best therapeutic strategy, focusing on the role of immune checkpoint inhibitors. Expert opinion: There are several outstanding goals that need to be met for the proper and safe use of immunotherapeutic drugs. In terms of the elderly, it is true that age-tailored clinical trials are needed to confirm the real impact of immunotherapy and harmonize the standard of care in this specific demographic.


Pharmacokinetics of recombinant human granulocyte colony-stimulating factor studied in the rat by a sandwich enzyme-linked immunosorbent assay.
A sandwich enzyme-linked immunosorbent assay for the measurement of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rat serum was developed using anti-rhG-CSF Fab'-horseradish peroxidase conjugate. This assay method measured rhG-CSF in rat serum with greater sensitivity than a bioassay. Also, a good agreement between enzyme-linked immunosorbent assay and bioassay was observed with rat serum samples after administration of rhG-CSF. The pharmacokinetics of rhG-CSF were investigated in male Sprague-Dawley rats using enzyme-linked immunosorbent assay at four different doses from 1 to 100 micrograms/kg. For i.v. administration, the serum rhG-CSF concentration-time curves were best described by a biexponential equation. Over the dose range studied, no changes in volume of distribution were observed. However, a reduction in rhG-CSF clearance and prolongation of half-life (beta) were noted as the dose of rhG-CSF increased. For s.c. administration, a markedly lower serum peak rhG-CSF concentration was observed, but after 2 to 3 hr, rhG-CSF concentration was higher than that following i.v. administration. Administration s.c. also caused nonlinear increases in the serum concentration. Bioavailability after s.c. administration was 0.509 to 0.704.


[Ventilator-associated pneumonia among premature infants <34 weeks' gestational age in neonatal intensive care unit in China: a multicenter study].
Objective: To investigate the incidence and pathogen distribution of ventilator-associated pneumonia (VAP) among preterm infants admitted to level Ⅲ neonatal intensive care units (NICU) in China. Method: A prospective study was conducted in 25 level Ⅲ NICU, enrolling all preterm infants <34 weeks gestational age admitted to the participating NICU within the first 7 days of life from May 2015 to April 2016. Chi-square test, t test and Mann-Whitney U test were used for statistical analysis. Result: A total of 7 918 patients were enrolled, within whom 4 623(58.4%) were males. The birth weight was (1 639±415) g and the gestational age was (31.4±2.0) weeks; 4 654(58.8%) infants required non-invasive mechanical ventilation and 2 154(27.2%) required intubation. Of all the mechanically ventilated patients, VAP occurred in 95 patients. The overall VAP rate was 7.0 episodes per 1 000 ventilator days, varying from 0 to 34.4 episodes per 1 000 ventilator days in different centers. The incidence of VAP was 9.6 and 6.0 per 1 000 ventilator days in children's hospitals and maternity-infant hospitals respectively, without significant differences (t=1.002, P=0.327). Gram-negative bacilli (76 strains, 91.6%) were the primary VAP microorganisms, mainly Acinetobacter baumannii (24 strains, 28.9%), Klebsiella pneumonia (23 strains, 27.7%), and Pseudomonas aeruginosa (10 strains, 12.0%). Conclusion: The incidence of VAP in China is similar to that in developed counties, with substantial variability in different NICU settings. More efforts are needed to monitor and evaluate the preventable factors associated with VAP and conduct interventions that could effectively reduce the occurrence of VAP.


Comparison of the expression patterns of newly identified zebrafish retinoic acid and retinoid X receptors.
Retinoic acid (RA) signaling is important for multiple aspects of embryonic development and tissue homeostasis. Heterodimers of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) transduce RA signaling. It is not yet clear how the diversity of receptor combinations relates to the diversity of functions for RA. The expression patterns of three zebrafish RARs and four RXRs were reported recently. Here, we identify an additional RAR, a zebrafish RARgamma paralog, and two additional RXRs, duplicates of the previously identified RXRalpha and RXRgamma. Thus, the zebrafish genome contains duplicates of each RAR and RXR gene. All zebrafish RAR and RXR paralogs have overlapping and distinct areas of expression, as might be expected for duplicate genes in the process of diverging in function. By representing what is potentially the complete set of zebrafish RARs and RXRs, this study provides a valuable reference for future functional studies of the individual zebrafish RARs and RXRs.


[Antibacterial activity of secondary metabolites from Aspergillus awamori F12 isolated from rhizospheric soil of Rhizophora stylosa Griff].
To identify Aspergillus awamori strain F12 isolated from rhizospheric soil of Rhizophora stylosa Griff and to characterize antibacterial compounds from the ethyl acetate extracts of its fermentation broth. Strain F12 was identified based on its morphological characters and internal transcribed spacer (ITS) sequence. Its secondary metabolites were purified by chromatography, and elucidated by mass spectroscopy, H-NMR, 13C-NMR and physicochemical characters. The antibacterial activities of these compounds were tested against Staphyloccocus aureus and Bacillus subtilis. Strain F12 was identified as Aspergillus awamori. Three compounds, including 1,4-dimethoxybenzene (1), emodin (2) and 3, 6-dibenzylpiperazine-2, 5-dione (3), were purified and elucidated from the ethyl acetate extracts of fermentation broth, among which compound 1 was first reported for the genus of Aspergillus. Compound 2 suppressed the growth of Staphyloccocus aureus and Bacillus subtilis with MIC values of 16 microg/mL and 32 microg/mL respectively, while the other two compounds have no effects on these bacteria. Aspergillus awamori strain F12 isolated from rhizospheric soil of Rhizophora stylosa Griff can produce 1, 4-dimethoxybenzene and emodin, among which the latter can suppress the growth of bacteria apparently.


Triglyceride-rich lipoproteins as agents of innate immunity.
Bacterial endotoxin (i.e., lipopolysaccharide [LPS]) elicits dramatic responses in the host, including elevated plasma lipid levels due to increased synthesis and secretion of triglyceride-rich lipoproteins by the liver and inhibition of lipoprotein lipase. This cytokine-induced hyperlipoproteinemia, clinically termed the "lipemia of sepsis," was customarily thought to involve the mobilization of lipid stores to fuel the host response to infection. However, because lipoproteins can also bind and neutralize LPS, we have long postulated that triglyceride-rich lipoproteins (very-low-density lipoproteins and chylomicrons) are also components of an innate, nonadaptive host immune response to infection. Recent research demonstrates the capacity of lipoproteins to bind LPS, protect against LPS-induced toxicity, and modulate the overall host response to this bacterial toxin.


The factors affecting plasma glutathione peroxidase and selenium in rheumatoid arthritis: a multiple linear regression analysis.
The reactive oxygen radicals are trapped by anti-oxidants, such as selenium containing glutathione peroxidase (GSHpx), which also can inhibit the oxygenation of arachidonic acid to pro-inflammatory prostaglandins and leukotrienes. We studied the levels of anti-oxidant glutathione peroxidase and selenium (in plasma) in 48 patients with rheumatoid arthritis (RA). In the multiple regression model, joint score had the highest explanatory value for serum selenium, and sulphasalazine treatment was the most significant variable contributing to GSHpx activity. The plasma GSHpx activity was not increased in RA patients in general, but was high in those taking sulphasalazine as compared with those not doing so (342.4 +/- 48.2 vs. 298.9 +/- 34.7 U/l, 95% confidence interval of difference from 17.9 to 69.1, p less than 0.002). The serum selenium levels correlated with clinical activity of the joint, disease measuring joint score.


Oslerus osleri tracheobronchitis: treatment with ivermectin in 4 dogs.
Oslerus osleri tracheobronchitis was diagnosed in 4 young dogs following endoscopic visualization of tracheal nodules and identification of larvae in airway cytologic samples. All dogs improved when ivermectin was administered (200-400 micrograms/kg body weight); however, most (3/4) required serial treatments in order to achieve long-term resolution of clinical signs.


The value of chemoprophylaxis against Enterococcus species in elective cholecystectomy: a randomized study of cefuroxime vs ampicillin-sulbactam.
Cephalosporins are widely used and considered to be effective as prophylaxis in biliary surgery. Nevertheless, they lack activity against enterococci. We conducted a study to compare the efficacy of ampicillin-sulbactam vs cefuroxime in preventing surgical site infections following elective cholecystectomy. A prospective randomized controlled trial. A major tertiary care hospital. Four hundred eighteen randomized patients (of 549 total), who from July 2002 to August 2004 underwent elective open or laparoscopic cholecystectomy with prospective assessment for development of surgical site infections for 1 month postoperatively. A single intravenous dose of 1.5 g of cefuroxime (group A, n = 207) or 3 g of ampicillin-sulbactam (group B, n = 211) was administered during induction of anesthesia. Bile and gallbladder mucosal cultures were taken intraoperatively from all patients. Number of postoperative surgical site infections. A postoperative surgical site infection was noted in 19 (4.5%) of 418 patients, 18 from group A and 1 from group B (P<.001). In the group that received cefuroxime, 15 (83.3%) of 18 surgical site infections were due to Enterococcus species. Intraoperative bactibilia as well as intraoperative gallbladder rupture were associated with surgical site infections (P<.001). A single dose of ampicillin-sulbactam favored better compared with cefuroxime for prevention of postoperative surgical site infections due to Enterococcus species after elective cholecystectomy. Ampicillin-sulbactam may be a better agent for antimicrobial prophylaxis in high-risk patients undergoing elective cholecystectomy, especially in a setting where the incidence of enterococcal infections is higher.


Pharmacological Treatment of Heart Failure with Preserved Ejection Fraction.
Heart failure with preserved ejection fraction is a socioeconomic burden in Japan as well as other developed countries. Diuretics are widely used to attenuate symptoms and signs of congestion in both heart failure with preserved and reduced ejection fraction, although their effects on long-term prognosis of both phenotypes of heart failure have not been demonstrated because of an ethical difficulty in designing a randomized and prospective clinical trial. Guidelines do not provide any guidance on therapy choice, and physicians blindly choose furosemide among loop diuretics in current clinical settings. However, several clinical studies have suggested that the effects of loop diuretics are not consistent, and that furosemide is not necessarily preferable as compared with other loop diuretics. We should pay attention to the choice of loop diuretics. Regarding the improvement of long-term prognosis, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, mineralocorticoid receptor blocker and β-blocker are proven effective for heart failure with reduced ejection fraction. However, none of these drugs have improved prognosis of heart failure with preserved ejection fraction in clinical trials. Observational studies and subanalysis of clinical trials suggest the benefits of these drugs in this phenotype of heart failure. All of clinical trials and observational studies present facts to us, and let us recognize that "one size fits all approach" may be a cause for a lack of evidence about the therapeutic strategy of heart failure with preserved ejection fraction until now. We have to make efforts to clarify characteristics of patients with heart failure and preserved ejection fraction to whom the administration of each drug provides benefits or do not.


A miniaturized solid-phase extraction adsorbent of calix[4]arene-functionalized graphene oxide/polydopamine-coated cellulose acetate for the analysis of aflatoxins in corn.
A calix[4]arene-functionalized graphene oxide/polydopamine-coated cellulose acetate adsorbent was fabricated for the pre-concentration of aflatoxins. The highly porous developed adsorbent does not produce the high backpressure that normally occurs in particle-packed cartridges and its large surface area helps to improve adsorption. The highly efficient adsorption of aflatoxins by the hybrid adsorbent is facilitated via hydrogen bonding and hydrophobic and π-π interactions. Polymerization time, amount of calix[4]arene-functionalized graphene oxide, type and volume of desorption solvent, sample pH, sample volume, and sample flow rate were optimized. The linearity of aflatoxin B1 was in the range of 0.01-10.0 μg/kg, aflatoxin B2 was in the range of 0.02-10.0 μg/kg and aflatoxin G1 and aflatoxin G2 were in the range of 0.050-10.0 μg/kg. The limits of detection were 0.01 μg/kg for aflatoxin B1, 0.02 μg/kg for aflatoxin B2 and 0.05 μg/kg for aflatoxin G1 and aflatoxin G2. The developed calix[4]arene-functionalized graphene oxide/polydopamine-coated cellulose acetate adsorbent was successfully utilized for the analysis of aflatoxins from corn samples and the extraction efficiency was satisfactory with obtained recoveries from 83.0 to 106.7%. Moreover, fabricated adsorbent is easy to prepare, inexpensive, and can be reused.


Violence against women in Mexico: conceptualization and program application.
Violence against women has been a problem in human cultures for centuries. This is still the case both in developed and in developing countries, but it is in developing countries where the problem is aggravated as the result of cultural norms that are tolerant of men exerting power over women and girls as a commonly accepted practice. This power is often put into practice through physical and psychological acts of violence. In Mexico, as in many other countries, there is a legal framework that protects women from such acts, yet in the case of Mexico it has not yet been translated into actual improvements in their lives. We present an overview of advances in legal remedies regarding violence towards females internationally and in Mexico. The fact that these advances per se do not lead to changes in social norms that tolerate violence against females is emphasized. Also presented is the experience of the Mexican Institute for Research on Family and Population (IMIFAP) with the design and implementation of programs that promote protective factors and changes in behaviors in such a way that violence is effectively prevented. These programs focus on the development of psychosocial skills and knowledge through participatory workshops that promote self reflection, and they are developed and evaluated before being then applied on a large scale in poverty-stricken communities. These workshops lead to more egalitarian relationships between genders. IMIFAP's programs address not only violence but also other areas are integrated such that the enablement of psychosocial skills is applied in the broader socio-cultural context, leading to healthier and economically more productive lives. These programs are derived from the Framework for Enabling Agentic Empowerment (FENAE), which enables choice and the development of agentic empowerment through integrating skills, knowledge, and the context in which people live.


Right sided descending and sigmoid colon: its embryological basis and clinical implications.
Anatomical variations of the colon are described by various authors, but the occurrence of right sided descending and sigmoid colon is rare and has not been reported. We found that the anomalous right-sided descending and sigmoid colon had four parts. The proximal segment of the first part consisted of the descending colon extending across the midline from the splenic flexure to the portion supplied by the left colic artery. The distal segment was supplied by the superior sigmoid artery. The second and third parts formed a loop in the right lumbar region anterior to the lumbar cecum. The fourth part was in the lesser pelvis, extending from right sacroiliac joint to the third sacral body. Parts two, three, and four were supplied by the inferior sigmoid artery, which arose from the right side of the inferior mesenteric artery. The ascending and transverse colon was normally placed. This is a rare anomaly that has not been reported so far in adults and is of immense importance to interventional radiologists and colorectal surgeons. The embryological basis of such an anomaly is defective fixation occurring as early as the 12th-17th week of intrauterine life.


Interfacial behavior of pulmonary surfactant preparations containing egg yolk lecithin.
Mammalian lungs are covered with lipid-protein complexes or pulmonary surfactants. In this work, which aimed towards the less expensive production of artificial pulmonary surfactants, we produced surfactants composed of egg yolk lecithin (eggPC), palmitic acid, and hexadecanol (= 0.30/0.35/0.35, mol/mol/mol ) containing different amounts of Hel 13-5 (NH2-KLLKLLLKLWLKLLKLLL-COOH) as a substitute for the proteins in native pulmonary surfactants. Surface pressure (π)-molecular area (A) and surface potential (DV)-A isotherms of the mixtures were measured via the Wilhelmy and ionizing (241)Am electrode methods, respectively. The interactions between the lipid components and Hel 13-5 led to variations in the surface pressure caused by the expulsion of fluid components from the surface. Furthermore, the π-A and DV-A isotherms featured large hysteresis loops for the surfactant that contained a small amount of Hel 13-5 during compression and successive expansion cycling. To elucidate the morphology, the phase behavior was visualized in situ at the air-water interface by means of fluorescence microscopy; the images suggested less effective interactions between Hel 13-5 and the unsaturated PC in eggPC despite the similarity of their monolayer properties.


The effect of electrical stimulation of the ear points on the plasma ACTH and GH level in humans.
The effect of electrical stimulation of the ear points on the plasma ACTH and GH level was investigated in healthy female subjects. Electrical stimulation by 20 pulses/sec for 20 min. induced an elevation of plasma GH; however, no changes were found in the plasma level of ACTH at 20 min. after the needle removal. The mechanism of action of electroacupuncture in inducing GH secretion may involve the brain endorphin, serotoninergic and catecholaminergic systems. The results obtained from the determination of ACTH suggest the conclusion that electroacupuncture did not induce stress and the increased level of GH may be due to specific effects of electrical stimulation on the neuroendocrine processes.


[What will determine the first-line treatment of a patient with rectal cancer?].
Treatment of a rectal cancer patient is devised by a multidisciplinary expert team. The first thing to be solved is whether a curative treatment, one slowing the progression of the disease, or a symptomatic treatment is aimed at. The extent of the disease is assessed by using whole body CT scan and MR imaging of the rectum. When aiming at curative treatment, the need for preoperative radiation therapy and the surgical technique is assessed on the basis of MRI and clinical examination. The patient's physical condition, associated diseases or pelvic radiotherapy previously applied due to other diseases may restrict the choice of treatment. In an advanced disease, cytostatic chemotherapy is usually the first-line therapy, unless the tumor is obstructing the bowel.


Leveraging Actinide Hydrolysis Chemistry for Targeted Th and U Separations using Amidoxime-Functionalized Poly(HIPE)s.
Polymerized high internal phase emulsions (poly(HIPE)s) are porous polymer monoliths whose synthesis can easily be tailored to allow incorporation of functional units. In this work, nitrile containing poly(HIPE)s have been prepared with either acrylonitrile (AN) or 4-cyanostyrene (4CS) comonomers. Post-synthetic modification of these nitrile-containing poly(HIPE)s yields their corresponding amidoximated analogues, which were studied for actinide uptake. These amidoxime-functionalized, porous polymers were shown to adsorb 95 % Th4+ species from aqueous solution within 30 minutes. In contrast to other amidoxime containing polymers the uptake of UO2 2+ in these poly(HIPE)s is lower under similar conditions. A critical analysis of actinide separations and high-energy X-ray scattering data provides insight into the polymers' selectivity, enabled by the uptake of multinuclear Th clusters.


Metal-Organic Framework (MOF)-Based Drug/Cargo Delivery and Cancer Therapy.
Metal-organic frameworks (MOFs)-an emerging class of hybrid porous materials built from metal ions or clusters bridged by organic linkers-have attracted increasing attention in recent years. The superior properties of MOFs, such as well-defined pore aperture, tailorable composition and structure, tunable size, versatile functionality, high agent loading, and improved biocompatibility, make them promising candidates as drug delivery hosts. Furthermore, scientists have made remarkable achievements in the field of nanomedical applications of MOFs, owing to their facile synthesis on the nanoscale and alternative functionalization via inclusion and surface chemistry. A brief introduction to the applications of MOFs in controlled drug/cargo delivery and cancer therapy that have been reported in recent years is provided here.


[Results of surgical treatment of coral nephrolithiasis].
A total of 98 patients (39 males and 59 females) with coral nephrolithiasis (CN) were divided into 3 groups depending on the variant of surgical treatment. The results were followed up for 5 years. Group 1 and 2 patients have undergone combined low-traumatic open surgery or low-invasive interventions (extracorporeal lithotripsy--ECL or percutaneous nephrometolapaxy--PN), group 3 patients--open surgery (pyelonephrolithotomy or section nephrolithotomy. It was found that the treatment was longest in group 1 and shortest in group 3, complications occurred most frequently in group 3 on section nephrolithotomy, least frequently in group 2. A significant decline of operated on kidney late after the treatment was observed in patients subjected to section nephrolithotomy. Thus, ECL and PN produce positive results in patients with CN (elimination of the stone with a minimal risk of residual concrements) in good long-term function of the operated on kidney.


Digital and advanced imaging in endodontics: a review.
This review provides an overview of digital radiography as it exists, including advanced imaging such as computed tomography (CT), cone beam volumetric imaging, and micro-CT as relevant to the practice of endodontics. An evidence-based approach to adoption of different imaging technologies is included to assist the practitioner with the selection process of imaging modalities. Commonly used imaging terminology is introduced, as well as the advantages and disadvantages of image processing. New image reconstruction techniques have been introduced that provide information three-dimensionally to the clinician for routine endodontic and surgical treatment planning. The age of three-dimensional imaging and image processing is here. Limitations and advantages of newly introduced imaging modalities are discussed briefly.


[Study on the influencing factors to cerebral stroke in a region with high prevalence rate of hypertension].
To investigate the influencing factors on cerebral stroke in Zhangwu county, Liaoning province, a region with high hypertension prevalence rate. By cluster sampling method, 5208 adults ( > 18y. ) from 11 villages of 6 towns were registered. General information, common risk factors of cerebral stroke about these persons was recorded. Blood pressure together with several biochemistry indicators was determined. Data were analyzed by SPSS 10.0 software. Standardized prevalence of cerebral stroke in this region was 3.10%, and the difference between males and females was significant. Prevalence rate was increasing with age. Multiple-factor analysis revealed that the incidence rate of cerebral stroke was related to high blood pressure, high diastolic pressure, pulse pressure, age, high-density lipoprotein cholesterol (HDL-C) and low-DL-C (LDL-C) level with OR values of 95% CI as 2.958 (1.783-4.907), 2.803 (1.934-4.062), 1.154 (1.056-1.261), 1.080 (1.063-1.097), 0.390 (0.235-0.647) and 1.422 (1.008-2.006) respectively. High blood pressure, in particular high diastolic pressure, pulse pressure and LDL-C level were main risk factors of cerebral stroke in Zhangwu countryside. However, HDL-C level was a protective factor. No new risk factors were discovered.


Intravenous immunoglobulin use in patients with toxic epidermal necrolysis and Stevens-Johnson syndrome.
Intravenous immunoglobulin (IVIg) has been proposed as a treatment for toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). A comprehensive search of the literature was conducted to examine the efficacy and safety of IVIg in TEN and SJS patients. Seventeen relevant articles (14 TEN, 3 SJS) were identified. Only three of the TEN studies and one of the SJS studies were prospective; retrospective studies were the most common study design published. Information regarding disease severity, IVIg use, response, and hospitalization were recorded and cumulated. Aggregate level statistics were calculated. The average IVIg doses used were 0.8 +/- 0.4 g/kg/day for a mean duration of 4.0 +/- 1.0 days in TEN patients and 0.8 +/- 0.2 g/kg/day for 3.4 +/- 1.0 days in SJS patients. The clinical experience of IVIg use in TEN and SJS patients was positive in most cases. However, more studies need to be conducted to confirm the benefit of IVIg use in patients with TEN or SJS.


Evaluation of Electrical Impedance as a Biomarker of Myostatin Inhibition in Wild Type and Muscular Dystrophy Mice.
Non-invasive and effort independent biomarkers are needed to better assess the effects of drug therapy on healthy muscle and that affected by muscular dystrophy (mdx). Here we evaluated the use of multi-frequency electrical impedance for this purpose with comparison to force and histological parameters. Eight wild-type (wt) and 10 mdx mice were treated weekly with RAP-031 activin type IIB receptor at a dose of 10 mg kg-1 twice weekly for 16 weeks; the investigators were blinded to treatment and disease status. At the completion of treatment, impedance measurements, in situ force measurements, and histology analyses were performed. As compared to untreated animals, RAP-031 wt and mdx treated mice had greater body mass (18% and 17%, p < 0.001 respectively) and muscle mass (25% p < 0.05 and 22% p < 0.001, respectively). The Cole impedance parameters in treated wt mice, showed a 24% lower central frequency (p < 0.05) and 19% higher resistance ratio (p < 0.05); no significant differences were observed in the mdx mice. These differences were consistent with those seen in maximum isometric force, which was greater in the wt animals (p < 0.05 at > 70 Hz), but not in the mdx animals. In contrast, maximum force normalized by muscle mass was unchanged in the wt animals and lower in the mdx animals by 21% (p < 0.01). Similarly, myofiber size was only non-significantly higher in treated versus untreated animals (8% p = 0.44 and 12% p = 0.31 for wt and mdx animals, respectively). Our findings demonstrate electrical impedance of muscle reproduce the functional and histological changes associated with myostatin pathway inhibition and do not reflect differences in muscle size or volume. This technique deserves further study in both animal and human therapeutic trials.


Language performance as a prognostic factor for developing Alzheimer's clinical syndrome and mild cognitive impairment: Results from the population-based HELIAD cohort.
There is limited research on the prognostic value of language tasks regarding mild cognitive impairment (MCI) and Alzheimer's clinical syndrome (ACS) development in the cognitively normal (CN) elderly, as well as MCI to ACS conversion. Participants were drawn from the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. Language performance was evaluated via verbal fluency [semantic (SVF) and phonemic (PVF)], confrontation naming [Boston Naming Test short form (BNTsf)], verbal comprehension, and repetition tasks. An additional language index was estimated using both verbal fluency tasks: SVF-PVF discrepancy. Cox proportional hazards analyses adjusted for important sociodemographic parameters (age, sex, education, main occupation, and socioeconomic status) and global cognitive status [Mini Mental State Examination score (MMSE)] were performed. A total of 959 CN and 118 MCI older (>64 years) individuals had follow-up investigations after a mean of ∼3 years. Regarding the CN group, each standard deviation increase in the composite language score reduced the risk of ACS and MCI by 49% (8-72%) and 32% (8-50%), respectively; better SVF and BNTsf performance were also independently associated with reduced risk of ACS and MCI. On the other hand, using the smaller MCI participant set, no language measurement was related to the risk of MCI to ACS conversion. Impaired language performance is associated with elevated risk of ACS and MCI development. Better SVF and BNTsf performance are associated with reduced risk of ACS and MCI in CN individuals, independent of age, sex, education, main occupation, socioeconomic status, and MMSE scores at baseline.


Lacrimal sac tumour presenting with blood-stained ocular discharge.
Malignant epithelial tumours of the lacrimal sac are uncommon. They can mimic chronic dacryocystitis or dacryostenosis to cause a delay in diagnosis. The presence of a medial canthal lump with blood-stained ocular discharge should arouse the suspicion of this diagnosis. The prognosis of lacrimal sac tumour is often guarded especially following tumour recurrence after incomplete resection. We report a patient with squamous cell carcinoma of the lacrimal sac to highlight its presentation and clinical course.


Solution conformation of Lewis a--derived selectin ligands is unaffected by anionic substituents at the 3'- and 6'-positions.
The selectins are a family of proteins that mediate leukocyte tethering and rolling along the vascular endothelium. E-, P-, and L-selectin recognize various derivatives of the Lewis(a) and Lewis(x) trisaccharides. The distribution of negative charges on the Lewis(a) and Lewis(x) oligosaccharides appears to be an important factor in their binding by the selectins. Previous work exploring this electrostatic dependence found that a series of synthetic anionic trisaccharides, 3'-sulfo, 3'-phospho, 6'-sulfo, and 3',6'-disulfo Lewis(a)-(Glc), exhibited differing selectin inhibitory efficacies. To explore the possibility that these differences arise from conformational differences between the sugars, the solution structures of these trisaccharides were determined using NMR and molecular dynamics simulations. Interproton distances and interglycosidic torsion angles were determined at 37 degrees C using NOESY buildup curves and 1D LRJ experiments, respectively. Data from both experiments agreed well with predictions made from 2000 picosecond unrestrained molecular dynamics simulations. We found that 3'-sulfation did not alter the core Lewis(a) conformation, a finding that reaffirms the results of previous study. In addition, we found that sulfation at the 6' position also leaves the trisaccharide conformation unperturbed. This is significant because the proximity of the 6'-sulfate group to the fucose ring might have altered the canonical Lewis (a) structure. The disulfate exhibited greater flexibility than the other derivatives in dynamics simulations, but not so much as to affect NOE and heteronuclear coupling constant measurements. Taken together, our findings support the use of Lewis(a) as a template onto which charged groups may be added without significantly altering the trisaccharide's structure.


Navigating patients with atopic dermatitis or chronic spontaneous urticaria during the COVID-19 pandemic.
A rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented pandemic. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical body has encountered major obstacles concerning disease management at different levels. Even though patients infected with this virus mainly present with respiratory symptoms, it has been associated with a plethora of well-documented cutaneous manifestations in the literature. However, little investigations have been conducted concerning COVID-19 and its impact on skin disorders mediated by type 2 inflammation leaving multiple dermatologists and other specialists perplexed by the lack of clinical guidelines or pathways. This review focuses on the effects of this pandemic in patients with skin disorders mediated by type 2 inflammation, specifically atopic dermatitis and chronic spontaneous urticaria. In addition, it will provide clinicians a guide on treatment and vaccination considerations for this stated set of patients.


Solitary colonic neurofibroma in a patient with transient segmental colitis: case report.
Neurofibromas of the large bowel are very rare and usually are part of the colonic involvement in neurofibromatosis type 1 (Nf1, von Recklinghausen's disease). Solitary neurofibromas of the colon are extremely rare. We describe a case of an isolated neurofibroma that was found in the large bowel of a patient who suffered from segmental colitis and presented with bloody diarrhea. A review of the literature is also included, concerning the disclosure of isolated neurofibromas in the gut and other body parts and the type of gastrointestinal involvement in von Recklinghausen's disease.


Computer use and habitual spinal posture in Australian adolescents.
Computer use is common in adolescents, and there is evidence that adolescent spinal posture alters during computer use. However, it is unknown if computer use and habitual postures are associated. The objective of this study was to evaluate associations between adolescent computer use and habitual postures. Eight hundred eighty-four adolescents (408 females, 476 males, mean age, 14.0 years, standard deviation, 0.2) completed a questionnaire assessing weekly computer use. Habitual spinal posture was assessed by photographic analysis while standing and sitting. Computer use was associated with adolescent habitual postures. In males, increased computer use was associated with increased head flexion and neck flexion. In females, increased computer use was associated with increased lumbar lordosis. The amount of weekly computer use was associated with changes in habitual spinal postures, and these depended on gender. These associations may result from temporary computer postures leading to adaptive neuromusculoskeletal changes, though further multivariate and longitudinal studies are needed to confirm causality. As some habitual posture changes may place a greater strain on the musculoskeletal system, computer use by adolescents should be viewed as a possible health concern.


Accurate adiabatic correction in the hydrogen molecule.
A new formalism for the accurate treatment of adiabatic effects in the hydrogen molecule is presented, in which the electronic wave function is expanded in the James-Coolidge basis functions. Systematic increase in the size of the basis set permits estimation of the accuracy. Numerical results for the adiabatic correction to the Born-Oppenheimer interaction energy reveal a relative precision of 10(-12) at an arbitrary internuclear distance. Such calculations have been performed for 88 internuclear distances in the range of 0 < R ⩽ 12 bohrs to construct the adiabatic correction potential and to solve the nuclear Schrödinger equation. Finally, the adiabatic correction to the dissociation energies of all rovibrational levels in H2, HD, HT, D2, DT, and T2 has been determined. For the ground state of H2 the estimated precision is 3 × 10(-7) cm(-1), which is almost three orders of magnitude higher than that of the best previous result. The achieved accuracy removes the adiabatic contribution from the overall error budget of the present day theoretical predictions for the rovibrational levels.


Reactive oxygen species serve as signals mediating glucose-stimulated somatostatin secretion from cultured rat gastric primary D-cells.
Somatostatin plays an important role in glucose homeostasis. It is normally secreted in response to glucose and ATP generation is believed to be the key transduction signal of glucose-stimulated somatostatin secretion (GSSS). However, in the present study, in cultured rat gastric primary D-cells, GSSS was accompanied by increases in cellular reactive oxygen species (ROS). GSSS is dependent on the cellular ROS and independently of the ATP production linked to glucose metabolism. The antioxidant, alpha-lipoic acid or catalase inhibitor, 3-aminotriazole can influence the intracellular calcium concentration and abolish or further elevate GSSS. It is suggested that ROS production may serve as a signal modulating the necessary Ca(2+) recruitment for GSSS. Since somatostatin is thought to exert broad regulatory functions on gastrointestinal physiology and nutrient intake, the interaction with ROS may lead to potential targets for mediating nutrition and energy homeostasis.


Aptamers selected against the unglycosylated EGFRvIII ectodomain and delivered intracellularly reduce membrane-bound EGFRvIII and induce apoptosis.
Epidermal growth factor receptor variant III (EGFRvIII) is a glycoprotein uniquely expressed in glioblastoma, but not in normal brain tissues. To develop targeted therapies for brain tumors, we selected RNA aptamers against the histidine-tagged EGFRvIII ectodomain, using an Escherichia coli system for protein expression and purification. Representative aptamer E21 has a dissociation constant (Kd) of 33x10(-9) m, and exhibits high affinity and specificity for EGFRvIII in ELISA and surface plasmon resonance assays. However, selected aptamers cannot bind the same protein expressed from eukaryotic cells because glycosylation, a post-translational modification present only in eukaryotic systems, significantly alters the structure of the target protein. By transfecting EGFRvIII aptamers into cells, we find that membrane-bound, glycosylated EGFRvIII is reduced and the percentage of cells undergoing apoptosis is increased. We postulate that transfected aptamers can interact with newly synthesized EGFRvIII, disrupt proper glycosylation, and reduce the amount of mature EGFRvIII reaching the cell surface. Our work establishes the feasibility of disrupting protein post-translational modifications in situ with aptamers. This finding is useful for elucidating the function of proteins of interest with various modifications, as well as dissecting signal transduction pathways.


Force control tasks with pure haptic feedback promote short-term focused attention.
Focused attention has great impact on our quality of life. Our learning, social skills and even happiness are closely intertwined with our capacity for focused attention. Attention promotion is replete with examples of training-induced increases in attention capability, most of which rely on visual and auditory stimulation. Pure haptic stimulation to increase attention capability is rarely found. We show that accurate force control tasks with pure haptic feedback enhance short-term focused attention. Participants were trained by a force control task in which information from visual and auditory channels was blocked, and only haptic feedback was provided. The trainees were asked to exert a target force within a pre-defined force tolerance for a specific duration. The tolerance was adaptively modified to different levels of difficulty to elicit full participant engagement. Three attention tests showed significant changes in different aspects of focused attention in participants who had been trained as compared with those who had not, thereby illustrating the role of haptic-based sensory-motor tasks in the promotion of short-term focused attention. The findings highlight the potential value of haptic stimuli in brain plasticity and serve as a new tool to extend existing computer games for cognitive enhancement.


Characterization of a rat model with temporomandibular joint osteoarthritis following a surgical anterior disc displacement.
This study has characterized a rat model with temporomandibular osteoarthritis (TMJ-OA) following a surgical anterior displacement of their articular disc (ADD). The well-established model of OA, induced by an intra-articular injection of complete Freund's adjuvant (CFA) into the TMJ, was used for comparison purposes. Male Wistar rats were assigned into two surgical groups, namely, ADD (anterior disc displacement) and sham-operated (surgical access, without ADD). Additional groups received an intra-articular infiltration of CFA (50 μl/site; 1:1 oil/saline emulsion), or the vehicle (0.9% NaCl). The separate experimental subgroups were euthanized at 15, 30 or 60 days and their left TMJs were collected for histological, immunohistochemistry and micro-CT analyses. The serum levels of IL-1β, IL-6 and TNF were analyzed. The fibrocartilage thicknesses were increased in the ADD groups at all of the analyzed time-points. In the CFA group, fibrocartilage thickenings were seen only in the posterior thirds at 15 days. The ADD group displayed an increase of the proteoglycan contents and ADAMTS5 immunopositivity in the fibrocartilage at 30 and 60 days, without any variations of the collagen contents or the osteoclast activation. Upon the micro-CT evaluation, the ADD group presented increments of their trabecular separations and bone surfaces, with reduced trabecular thicknesses and bone volumes, plus osteophyte formations and condyle flattenings, from 30 to 60 days. The IL-1β, TNF or IL-6 serum levels were undetectable. The surgical ADD in the rats led to long-term OA-like alterations, with typical structural and morphological derangements of the TMJ, representing a reliable experimental model to investigate the TMJ-OA-related mechanisms.


Structure and dynamics of the platelet integrin-binding C4 domain of von Willebrand factor.
Von Willebrand factor (VWF) is a key player in the regulation of hemostasis by promoting recruitment of platelets to sites of vascular injury. An array of 6 C domains forms the dimeric C-terminal VWF stem. Upon shear force activation, the stem adopts an open conformation allowing the adhesion of VWF to platelets and the vessel wall. To understand the underlying molecular mechanism and associated functional perturbations in disease-related variants, knowledge of high-resolution structures and dynamics of C domains is of paramount interest. Here, we present the solution structure of the VWF C4 domain, which binds to the platelet integrin and is therefore crucial for the VWF function. In the structure, we observed 5 intra- and inter-subdomain disulfide bridges, of which 1 is unique in the C4 domain. The structure further revealed an unusually hinged 2-subdomain arrangement. The hinge is confined to a very short segment around V2547 connecting the 2 subdomains. Together with 2 nearby inter-subdomain disulfide bridges, this hinge induces slow conformational changes and positional alternations of both subdomains with respect to each other. Furthermore, the structure demonstrates that a clinical gain-of-function VWF variant (Y2561) is more likely to have an effect on the arrangement of the C4 domain with neighboring domains rather than impairing platelet integrin binding.


Concomitant intrusive luxation and root fracture of a central incisor--report of a case.
A case of a 9-year-old boy who presented with intruded maxillary central incisors, one of which had also sustained a middle third root fracture, is reported. The root fracture was diagnosed after orthodontic extrusion was started, which resulted in separation of the apical and coronal fragments. The hypermobile coronal fragment was stabilised by passing a K file through a palatal access cavity into the root canal of the apical fragment. Orthodontic alignment was completed and the fractured incisors were restored with the file left in situ. At a 10-year follow-up, the incisors were clinically healthy and continued to satisfy aesthetic and functional demands.


[Vescio-renal reflux. Medical and surgical treatment (author's transl)].
Among 359 children with vesico-renal reflux, 191 were labeled as primary reflux. Of these, 144 had a follow up longer than 2 years. 44 children were treated medically, desapearing the reflux in 30 children (68%). 100 children (142 ureters) were operated upon with cesation of the reflux in 123 ureters (87%). The criteria for selecting the treatment and the way treatments were carried out are described.


Effective detoxification of hexavalent chromium using sulfate-crosslinked chitosan.
A sulfate-crosslinked chitosan (SCC) was prepared for effective detoxification of hexavalent chromium (Cr(VI)) from effluents. SCC was characterized using Fourier transform infrared, X-ray diffraction, scanning electron microscopy and energy dispersive X-ray studies. The maximum adsorption of Cr(VI) was observed at pH 6.0 with adsorption capacity of 157 mg/g in accordance with the Langmuir adsorption isotherm model. The adsorption process was found to follow the pseudo-second-order rate kinetics. From the study of various thermodynamic parameters (Gibbs energy, entropy and enthalpy changes), the adsorption capacity was found to decrease with increase in temperature. Column studies were carried out to obtain a breakthrough point of the adsorbent. The adsorbent was regenerated using sodium hydroxide with no change in the adsorption efficiency for up to 10 cycles. Effect of diverse ions on adsorption efficiency was studied and SCC was applied for Cr(VI) removal in synthetic effluents.


Mechanisms of renal disease in β-thalassemia.
Although advances in the care of patients with β-thalassemia translate into better patient survival, this success has allowed previously unrecognized complications to emerge, including several renal abnormalities. Clinical studies continue to show that mild tubular dysfunction and abnormalities in GFR are common in patients with β-thalassemia. Chronic anemia and iron overload are believed to lie behind these abnormalities. Nonprogressive increases in levels of serum creatinine have also been observed after exposure to some iron chelators. Longitudinal studies are needed to understand the true burden of renal dysfunction in patients with β-thalassemia.


Medical management of Cushing's disease: When and how?
Transsphenoidal surgery is the first-line treatment of Cushing's disease. However, medical treatment can be given in a high proportion of patients with this rare condition. This is especially the case in severe hypercortisolism for which medical treatment will be given for a short period of time to prepare the patient for surgery, or on a long-term basis after failed transsphenoidal surgery, or when waiting for the maximal beneficial effect of radiation techniques. These different situations all require that hypercortisolism be perfectly controlled. Severe hypercortisolism is frequently treated by a block and replace approach during which a substitutive treatment is given after the induction of adrenal insufficiency. Mild hypercortisolism, the most frequent situation, is usually treated with a titration approach with a progressive dose increase. This approach requires certainty of eucortisolism because patients may be treated for a prolonged period. This review details the main situations during which medical treatment should be considered, as well as the way in which to monitor them to avoid the long-term consequences of mild hypo- or hypercortisolism.


Financial cost of osteoarthritis in France. The "COART" France study.
Osteoarthritis is the most common musculoskeletal disease, with about 9-10 million patients in France including 4.6 million with symptoms. The objective of the COART France study is to evaluate the cost of osteoarthritis in France from the societal point of view and to compare the results to those obtained in 1993 using the same methodology. The cost of osteoarthritis was evaluated using the macroeconomic approach. Direct costs were estimated from healthcare resource use (physician visits, drug prescriptions, and hospital admissions) and indirect costs from doctor-prescribed sick-leave durations. Direct costs of osteoarthritis in 2002 exceeded 1.6 billion Euros, contributing about 1.7% of expenses of the French health insurance system, which covers all residents of France regardless of employment or documentation status. Hospital admissions were the greatest single contributor to direct costs, with more than 800 million Euros. Osteoarthritis led to 13 million physician visits, during which 570 million Euros worth of medications were prescribed. The 156% increase in direct medical costs compared to 1993 was chiefly related to an increase in the number of patients (+54%); the cost increase per patient was only 2.5% per year. Despite the large increase in the number of treated patients and the development of new costly medications, the rise in the cost of managing osteoarthritis seems well contained. The aging of the population, development of new technologies, and increasing patient expectations will probably govern the future economic impact of osteoarthritis, which remains a major public health burden.


Fully automated assay for total homocysteine, cysteine, cysteinylglycine, glutathione, cysteamine, and 2-mercaptopropionylglycine in plasma and urine.
We describe a 6-min HPLC method to measure the total concentrations of the most important thiols in plasma and urine--cysteine, homocysteine, cysteinylglycine, and glutathione--as well as the concentrations in plasma and urine, respectively, of cysteamine and 2-mercaptopropionylglycine, two compounds used to treat disorders of cysteine metabolism. Precolumn derivatization with bromobimane and reversed-phase HPLC were performed automatically by a sample processor. Throughput was up to 100 samples in 24 h. The within-run CV ranged from 0.9% to 3.4% and the between-run CV ranged from 1.5% to 6.1%. Analytical recovery was 97-107%, with little difference between plasma and urine samples. The detection limit was approximately 50 nmol/L for all the analytes studied. Thiol concentrations were determined in the plasma of 206 healthy donors and in the urine of 318 healthy donors distributed for age and sex. Mean values of plasma cysteine and homocysteine were significantly lower in infants (ages, <1 y) compared with other age groups (P <0.005). In adults, mean plasma homocysteine values were higher in males than in females (9.2 vs 6.7 micromol/L, P <0.0001) and in the 6- to 10-year-old group (P <0.05). Mean values for glutathione and cysteinylglycine were not sex- and age-dependent. In urine, both cysteine and homocysteine showed a wide range of variation.


Serum Mannose-Binding Lectin Levels Are Correlated with the Disease Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center Study.
Mannose-binding lectin (MBL) is a soluble pattern-recognition molecule, which plays a crucial role in the innate immune system and the activation of lectin complement pathway. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease affecting the small vasculatures and is characterized by the alteration of innate and adaptive immunity and complement activation. In this study, we investigated whether serum MBL is associated with disease activity of AAV, which was measured by ELISA. Associations between serum MBL and AAV-specific indices, as well as clinical and laboratory data were assessed using Kendall's tau. Among the 80 patients, 42 (52.5%), 21 (26.3), and 17 (21.3%) patients were classified as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), respectively. The median values of erythrocyte sedimentation rate, C-reactive protein, and serum MBL were 36.5 (normal range < 20) mm/h, 2.4 (normal range < 8) mg/dL, and 8.6 ng/mL, respectively. The median serum levels of MBL in MPA, GPA, and EGPA patients were 8.4, 9.3, and 8.2 ng/mL. Correlation analysis showed that serum MBL was associated with Birmingham Vasculitis Activity Score (BVAS) (R = 0.169, p = 0.027), but not with other AAV-specific indices and clinical and laboratory data. In addition, serum MBL was significantly associated with the pulmonary manifestation score based on BVAS (R = 0.247, p = 0.001). In summary, among the AAV-specific indices and clinical and laboratory variables analyzed, serum MBL is correlated with BVAS and pulmonary manifestation score based on the BVAS.


Roles of p53 and caspases in induction of apoptosis in MCF- 7 breast cancer cells treated with a methanolic extract of Nigella sativa seeds.
Nigella Sativa (NS) is an herb from the Ranunculaceae family that exhibits numerous medicinal properties and has been used as important constituent of many complementary and alternative medicines (CAMs). The ability of NS to kill cancer cells such as PC3, HeLa and hepatoma cells is well established. However, our understanding of the mode of death caused by NS remains nebulous. The objective of this study was to gain further insight into the mode and mechanism of death caused by NS in breast cancer MCF-7 cells. Human breast cancer cells (MCF-7) were treated with a methanolic extract of NS, and a dose- and time-dependent study was performed. The IC50 was calculated using a Cell Titer Blue® viability assay assay, and evidence for DNA fragmentation was obtained by fluorescence microscopy TUNEL assay. Gene expression was also profiled for a number of apoptosis-related genes (Caspase-3, -8, -9 and p53 genes) through qPCR. The IC50 of MCF-7 cells was 62.8 μL/mL. When MCF-7 cells were exposed to 50 μL/mL and 100 μL/mL NS for 24 h, 48 h and 72 h, microscopic examination (TUNEL assay) revealed a dose- and time-dependent increase in apoptosis. Similarly, the expression of the Caspase-3, -8, -9 and p53 genes increased significantly according to the dose and time. NS induced apoptosis in MCF-7 cells through both the p53 and caspase pathways. NS could potentially represent an alternative source of medicine for breast cancer therapy.


More than a 100-fold increase in immunoblot signals of laser-microdissected inclusion bodies with an excessive aggregation property by oligomeric actin interacting protein 2/D-lactate dehydrogenase protein 2.
We established a histobiochemical approach targeting micron-order inclusion bodies possessing extensive aggregation properties in situ by using a nonchemical denaturant (oligomeric actin interacting protein 2/d-lactate dehydrogenase protein 2 [Aip2p/Dld2p]) with the combinatorial method of laser-microdissection and immunoblot analysis. As a model, pick bodies were chosen and laser-microdissected from three different brain regions of two patients with Pick's disease. Initially, 500 to 2000 pick bodies were applied onto SDS-PAGE gels after boiling in Laemmli's sample buffer according to established immunoblotting procedures; however, only faint signals were obtained. Following negative results with chemical denaturants or detergent, including 6 M guanidine hydrochloride, 8 M urea, and 2% SDS, the laser-microdissected pick bodies were pretreated with oligomeric Aip2p/Dld2p, which possesses robust protein unfolding activity under biological conditions. Strikingly, only one pick body was sufficient to illustrate an immunoblot signal, indicating that pretreatment with oligomeric Aip2p/Dld2p enhanced the immunoblot sensitivity by more than 100-fold. Pretreatment with oligomeric Aip2p/Dld2p also allowed us to quantify the total protein content of pick bodies. Thus, use of oligomeric Aip2p/Dld2p significantly contributed toward the acquisition of information pertaining to the molecular profile of proteins possessing an extensive aggregation property, particularly in small amounts.


Spatial-Temporal Analysis of Air Pollution, Climate Change, and Total Mortality in 120 Cities of China, 2012-2013.
China has had a rapid increase in its economy over the past three decades. However, the economic boom came at a certain cost of depleting air quality. In the study, we aimed to examine the burden of air pollution and its association with climatic factors and health outcomes using data from Chinese national and city-level air quality and public health surveillance systems. City-level daily air pollution index (API, a sum weighted index of SO2, NO2, PM10, CO, and Ozone) in 120 cities in 2012 and 2013, and its association with climate factors were analyzed using multiple linear regression analysis, spatial autocorrelation analysis, and panel fixed models. City-level ecological association between annual average API and total mortality were examined using univariate and partial correlation analysis. Sensitivity analysis was conducted by taking the consideration of time-lag effect between exposures and outcomes. The results show that among the 120 cities, annual average API significantly increased from 2012 to 2013 (65.05 vs. 75.99, p < 0.0001). The highest average API was in winter, and the lowest in summer. A significantly spatial clustering of elevated API was observed, with the highest API in northwest China in 2012 and with the highest in east China in 2013. In 2012, 5 (4%) of the 120 cities had ≥60 days with API >100 (defined as "slightly polluted"), however, it increased to 21 cities (18%) that experienced API >100 for ≥60 days in 2013. Furthermore, 16 cities (13%) in 2012 and 35 (29%) in 2013 experienced a maximum API >300 (defined as "severely polluted"). API was negatively and significantly correlated with heat index, precipitation, and sunshine hours, but positively with air pressure. Cities with higher API concentrations had significantly higher total mortality rates than those with lower API. About a 4-7% of the variation in total mortality could be explained by the difference in API across the nation. In conclusion, the study highlights an increased trend of air pollution from 2012 to 2013 in China. The magnitude of air pollution varied by seasons and regions and correlated with climatic factors and total mortality across the country.