The relationship of insects to the deterioration of stored grain by fungi.
The data presented tests the hypothesis that knowledge of basic biological relationships between insects and fungi in the stored grain ecosystem can open new paths for management of the system. Evidence indicates: (1) some storage insect species are disseminators of storage fungi and some are exterminators; (2) some storage fungi attract storage insects and promote their population increases and other repel and secrete toxins harmful to insects; (3) certain morphophysiologic, biochemical similarities of fungi and the early developmental stages of insects suggest that new protective chemicals, 'insecticidal fungicides', could be designed or specifically sought. A specific example of a naturally occurring compound with dual action, sorbic acid (2,4-hexadienoic acid), is given and its effect on both insects and fungi is discussed. Sorbic acid is the only compound in the U.S. presently labelled by the FDA (Food and Drug Administration) as GRAS (Generally Regarded as Safe) and registered by the EPA (Environmental Protection Agency) for use on grain (maize) in storage.


Localization of an RNA-binding domain in the nucleocapsid protein of the coronavirus mouse hepatitis virus.
The interaction between the nucleocapsid (N) protein of mouse hepatitis virus (MHV) and RNA was studied in an effort to define portions of the N molecule that participate in binding to RNA. N mRNAs transcribed from SP6 and T7 vectors were translated in a rabbit reticulocyte lysate. Analysis of synthesized N protein in a nondenaturing gel system showed that it bound in vitro to an endogenous RNA in the reticulocyte lysate but not to its own mRNA. A set of deletion mutants was constructed in order to localize the RNA-binding activity of the N protein. It was found that removal of as much as 135 amino-terminal or 57 carboxy-terminal amino acids from the molecule had little or no effect on RNA binding. Moreover, deletion mutants lacking both termini still retained RNA-binding ability. By contrast, internal deletions or truncations extending beyond these two limits effectively abolished RNA binding by N protein. Thus, the RNA-binding region of N has been mapped to the second (central) of the three structural domains of the molecule.


Characterization of different tumor antigens present in cells transformed by simian virus 40.
In addition to large T and small t antigens, cells transformed by simian virus 40 (SV40) commonly contain other proteins which specifically immunoprecipitate with SV40 anti-T serum and which are not detected in untransformed cells. The additional tumor antigens (T-Ags) fall into two groups: those having a close structural relationship with normal SV40 T-Ags, and those unrelated to large T and small t. The latter are probably nonviral T-Ags (NVT-Ags). The NVT-Ags comprise a family of proteins of molecular weight 50,000-55,000. Fingerprint analysis shows that NVT-Ags have few if any peptides in common with large T or small t, and that they lack the amino terminal tryptic peptide and the peptides unique to small t. NVT-Ags from different species have different fingerprints, but those isolated from different transformants of the same cell line are identical. The size of NVT is unaltered in cells transformed by mutants of SV40 with deletions in the region 0.60-0.55 map units. The mRNA for NVT does not hybridize to SV40 DNA. The other forms of T-Ag isolated from transformed cells fall into three classes: shortened forms of large T (truncated large T); multiple species of T-Ag with molecular weights very similar to, but distinct from, those of normal large T (large T doublets and triplets); and elongated forms of large T (super T). These proteins all contain the normal amino terminus of SV40 T-Ags, and the truncated forms of large T lack peptides from the carboxy terminal half of large T. One species of super T (molecular weight 130,000) contains only those methionine tryptic peptides present in normal large T, although it may contain some peptides in more than one copy.


Antimicrobial stewardship programs in the Intensive Care Unit in patients with infections caused by multidrug-resistant Gram-negative bacilli.
Antimicrobial stewardship programs (ASPs) have been shown to be effective and safe, contributing to reducing and adjusting antimicrobial use in clinical practice. Such programs not only reduce antibiotic selection pressure and therefore the selection of multidrug-resistant strains, but also reduce the potential deleterious effects for individual patients and even improve the prognosis by adjusting the choice of drug and dosage, and lessening the risk of adverse effects and interactions. Gram-negative bacilli (GNB), particularly multidrug-resistant strains (MDR-GNB), represent the main infectious problem in the Intensive Care Unit (ICU), and are therefore a target for ASPs. The present review provides an update on the relationship between ASPs and MDR-GNB.


Risk factors and visual results in cases of LASIK flap repositioning due to folds or dislocation: case series and literature review.
The presence of a corneal flap is a hallmark of laser in situ keratomileusis (LASIK), which offers advantages in terms of speed of visual recovery; however, it also carries the risk of postoperative flap displacement. We conducted a retrospective review of all consecutive eyes on which LASIK was performed by one single surgeon at an ophthalmological institute in Colombia between May 2005 and January 2011, looking for eyes that required flap repositioning. Demographic data, preoperative refraction, hinge position, and visual outcomes following flap repositioning were evaluated. A literature review on the subject was also conducted. We found 37 eyes on which flap repositioning was performed-12 eyes (32.4 %) with subluxation and 25 eyes (67.6 %) with folds; 21 eyes (56.8 %) had a temporal hinge and 16 eyes (43.2 %) had a superior hinge. With regard to the total number of eyes on which LASIK was performed (2,595), the overall incidence was 1.4 %. Sixteen out of 2,093 eyes (0.8 %) with a superior hinge and 21 out of 502 eyes (4.2 %) with a temporal hinge had flap-related postoperative complications (p < 0.00). A final best-corrected visual acuity (BCVA) between 20/20 and 20/25 was found in 75.7 % and a final BCVA between 20/30 and 20/40 was found in 21.6 %. Only one eye had less than 20/40 (previous amblyopia). From the eight eyes with a BCVA between 20/30 and 20/40, three had residual microstriae and one had corneal haze. Six eyes (16.2 %) lost two or more lines of BCVA. Flap subluxation or folds requiring flap repositioning were significantly more frequent when a temporal hinge was used.


Keratinocyte damage in vitiligo.
Light and electron-microscopic studies were performed on the amelanotic and adjacent normal-appearing skin in patients with vitiligo. The amelanotic skin revealed complete loss of pigment and absence of melanocytes. In addition to severe degenerative changes of melanocytes, varying degree of damage was also seen in the keratinocytes of normal-appearing skin adjacent to amelanotic skin.


Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination.
Di-monoubiquitination of the FANCI-FANCD2 (ID2) complex is a central and crucial step for the repair of DNA interstrand crosslinks via the Fanconi anaemia pathway. While FANCD2 ubiquitination precedes FANCI ubiquitination, FANCD2 is also deubiquitinated at a faster rate than FANCI, which can result in a FANCI-ubiquitinated ID2 complex (IUb D2). Here, we present a 4.1 Å cryo-EM structure of IUb D2 complex bound to double-stranded DNA. We show that this complex, like ID2Ub and IUb D2Ub , is also in the closed ID2 conformation and clamps on DNA. The target lysine of FANCD2 (K561) becomes fully exposed in the IUb D2-DNA structure and is thus primed for ubiquitination. Similarly, FANCI's target lysine (K523) is also primed for ubiquitination in the ID2Ub -DNA complex. The IUb D2-DNA complex exhibits deubiquitination resistance, conferred by the presence of DNA and FANCD2. ID2Ub -DNA, on the other hand, can be efficiently deubiquitinated by USP1-UAF1, unless further ubiquitination on FANCI occurs. Therefore, FANCI ubiquitination effectively maintains FANCD2 ubiquitination in two ways: it prevents excessive FANCD2 deubiquitination within an IUb D2Ub -DNA complex, and it enables re-ubiquitination of FANCD2 within a transient, closed-on-DNA, IUb D2 complex.


A sparse QSRR model for predicting retention indices of essential oils based on robust screening approach.
A robust screening approach and a sparse quantitative structure-retention relationship (QSRR) model for predicting retention indices (RIs) of 169 constituents of essential oils is proposed. The proposed approach is represented in two steps. First, dimension reduction was performed using the proposed modified robust sure independence screening (MR-SIS) method. Second, prediction of RIs was made using the proposed robust sparse QSRR with smoothly clipped absolute deviation (SCAD) penalty (RSQSRR). The RSQSRR model was internally and externally validated based on [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], Y-randomization test, [Formula: see text], [Formula: see text], and the applicability domain. The validation results indicate that the model is robust and not due to chance correlation. The descriptor selection and prediction performance of the RSQSRR for training dataset outperform the other two used modelling methods. The RSQSRR shows the highest [Formula: see text], [Formula: see text], and [Formula: see text], and the lowest [Formula: see text]. For the test dataset, the RSQSRR shows a high external validation value ([Formula: see text]), and a low value of [Formula: see text] compared with the other methods, indicating its higher predictive ability. In conclusion, the results reveal that the proposed RSQSRR is an efficient approach for modelling high dimensional QSRRs and the method is useful for the estimation of RIs of essential oils that have not been experimentally tested.


The Most Logical Approach to Improve CAR T Cell Therapy.
Combinational antigen recognition is the most logical way to improve the safety of cancer therapy. CAR T cells therapy, combined with synthetic biology, protein engineering, and bioinformatics, can perform advanced computations to enhance tumor targeting specificity.


The Importance of Neighborhood Context and Gender on International Students' Fear of Crime in Istanbul.
Although fear of crime is an important issue for international students in a host country, this issue has not been explored in Turkey. The current study aims to fill this gap with data from a sample of 377 international students from a large urban university in Istanbul. The current study applies the incivilities thesis to fear of crime by including individual-level variables, perceived safety, and the perceived crime problem in Istanbul. The structural equation model (SEM) results show that social and physical incivilities do not mediate the relationship between international students' demographic characteristics and fear of crime. The findings indicate that gender is one of the important variables shaping internationals students' fear of crime and the perceived crime problem in Istanbul. By highlighting the importance of investigating international students' fear of crime, the study has important implications for stakeholders in host societies.


Optimal Timing for Secondary Reconstruction of Head and Neck Defects after Free Flap Failure.
Finite options exist to address free flap failure. There is a lack of consensus on the gold standard for secondary reconstruction in such cases. Herein, we determined the survival rate of a second flap following a total loss of an initial free flap during head and neck reconstructions and evaluated if there was a difference in the rate of secondary flap necrosis depending on the timing of reconstruction salvage. We retrospectively reviewed 1572 free flaps for head and neck reconstruction from 2010-2022. Patients who underwent secondary surgery with flaps after failure of primary free flap were included. Patients were divided into three groups based on the time for secondary flap reconstruction from the time of primary reconstruction (Group A, 0-5 days; Group B, 6-30 days; Group C, >30 days). We identified 64 cases of complete flap loss after primary reconstruction requiring secondary reconstruction. Pedicled flaps were used in 34.4% of the cases, while a second free flap was used in 65.6% of the cases. Overall, the flap failure rate for secondary reconstructions was 6.7% in Group A, 35.3% in Group B, and 6.7% in Group C (p=0.022). For free tissue transfer, the success rate of a secondary reconstruction was 92.3% in Group A, 28.57% in Group B, and 93.3% in Group C. We favor an early microsurgical reconstruction (≤5 days) following primary reconstruction in cases of free flap failure. If early reconstruction cannot be performed, a deferred reconstruction with free tissue transfer (>30 days) should be considered.


Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation.
Cell-cycle progression is regulated by cyclin-dependent kinases (CDKs). CDK1 and CDK2 can be also activated by noncyclin proteins named RINGO/Speedy, which were identified as inducers of the G2/M transition in Xenopus oocytes. However, it is unclear how XRINGO triggers M phase entry in oocytes. We show here that XRINGO-activated CDKs can phosphorylate specific residues in the regulatory domain of Myt1, a Wee1 family kinase that plays a key role in the G2 arrest of oocytes. We have identified three Ser that are major phosphoacceptor sites for CDK/XRINGO but are poorly phosphorylated by CDK/cyclin. Phosphorylation of these Ser inhibits Myt1 activity, whereas their mutation makes Myt1 resistant to inhibition by CDK/XRINGO. Our results demonstrate that XRINGO-activated CDKs have different substrate specificity than the CDK/cyclin complexes. We also describe a mechanism of Myt1 regulation based on site-specific phosphorylation, which is likely to mediate the induction of G2/M transition in oocytes by XRINGO.


An exon polymorphism of programmed cell death 1 gene is associated with both the susceptibility and thoracolumbar kyphosis severity of ankylosing spondylitis in a Chinese Han population.
Although human leukocyte antigen (HLA)-B27 gene is the major susceptible gene associated with ankylosing spondylitis (AS), it has been recognized that non-HLA-B27 genes also play key roles in the development of AS. The purpose of this study is to investigate whether a single nucleotide polymorphism (SNP) in the exon region of the programmed cell death 1 (PDCD-1) gene is associated with the susceptibility or the thoracolumbar kyphosis severity of AS in a Chinese Han population. A total of 255 AS patients between January 2008 and October 2012 were recruited in this study. Two hundred and three healthy patients were recruited as normal controls. According to the severity of thoracolumbar kyphosis, the AS patients were further divided into group A (patients with kyphosis <70°, n = 135) and group B (patients with kyphosis ≥70°, n = 120). One exon polymorphism, rs2227982 (C/T) of PDCD-1 gene, was selected for analysis. Genotyping was performed by TaqMan probe assays in all the subjects. There were significant differences of genotype distributions of rs2227982 between AS patients and normal controls. The frequency of the T allele was significantly higher in AS patients when compared with normal controls. The frequency of the T allele in group B was significantly higher than that in group A. Carriage of the TT genotype increased the risk of severe thoracolumbar kyphosis 1.9-fold in AS patients. Our study confirms a significant association between the SNP rs2227982 of PDCD-1 gene and the susceptibility of AS in a Chinese Han population. Moreover, the TT genotype is suggested to be associated with the severity of thoracolumbar kyphosis secondary to AS.


Dehydration of the lipid-protein microinterface on binding of phospholipase A2 to lipid bilayers.
A novel method is described to demonstrate inaccessibility to the bulk aqueous phase of the microinterface between pig pancreatic phospholipase A2 and lipid bilayers to which this protein is bound. The method is based on the fact that the fluorescence emission quantum yields of the tryptophan residue of the protein and of a 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) chromophore attached to a lipid are lower in water as compared to that in deuterated water. The fluorescence emission quantum yield of these chromophores is measured in water and in deuterated water under conditions where the protein is either bound or not bound to the surface of a lipid bilayer containing the dansyl chromophore. Under conditions where the protein is tightly bound to the surface of the bilayer, desolvation of both fluorophores abolishes the observed effect of deuterated water. The tryptophan residue in the bound phospholipase A2 also becomes inaccessible to fluorescence quenching by acrylamide or succinimide. Desolvation of the microinterface is observed only under conditions that are significant for the catalytic action of phospholipase A2 in the scooting mode and not in the hopping mode. Also, under similar conditions, binding of pro-phospholipase A2 to anionic vesicles does not cause dehydration of the microinterface. The mechanistic significance of these observations for lipid-protein interactions, in general, and for interfacial catalysis and interfacial activation, in particular, is discussed.


Evidence that prostaglandin synthesis inhibitors increase the concentration of sodium and chloride in rat renal medulla.
Thirty minutes after indomethacin (10 mg/kg, iv), a prostaglandin synthesis inhibitor, had been given to 10 rats, the Na concentration in renal papilla averaged 349 mEq/kg H2O, whereas it averaged only 181 in 14 "non-indomethacin" control rats (P less than 0.0001). Papillary plasma flow was closely similar in both groups. In a subsequent study, eight "indomethacin" rats had the same papillary flow as seven non-indomethacin rats but had a papillary Na concentration of 358 vs. 185 in the non-indomethacin controls (P less than 0.0001). In nine more rats, indomethacin increased Cl concentration in papillas by 66% (P less than 0.0001), while Na concentration increased 60% (P less than 0.0001). In eight other rats, micropuncture indicated that indomethacin does not greatly alter delivery of fluid out of late proximal tubule. Meclofenamate, another inhibitor, increased papillary Na just as much as indomethacin. Papillary urea is not changed with indomethacin. Thus, papillary Na concentration was almost twice as high in indomethacin rats, despite similar papillary plasma flow and late proximal flow. Apparently, inhibiting prostaglandin synthesis is associated with either a great increase in Na or Cl "pumping" or a great decrease in Na or Cl "leak" in either collecting duct or ascending limb, or in both. The collecting duct and papillary interstitial cells both synthesize prostaglandins, which seem to have a profound effect on medullary net Na transport.


Alterations of plasma membrane fatty acid composition modify the kinetics of Na+ current in cultured rat diencephalic neurons.
Properties of inward Na+ currents (INa) were examined in dissociated diencephalic neurons whose plasma membrane fatty acid composition had been altered. These neurons were grown in a defined medium supplemented with essential fatty acids (EFA) of either the w3 class (linolenic acid, 18:3w3) or the w6 class (linoleic acid, 18:2w6), which resulted in a two-fold increase in the plasma membrane phospholipid polyunsaturated fatty acid (PUFA) concentration. The properties of the inward INa of these neurons were compared with those of control neurons grown in the absence of any supplemented fatty acids. The INa of neurons supplemented with a non-essential fatty acid (NFA) of w9 class (oleic acid, 18:1w9) was also examined. Several properties have been modified to different degrees. The ratio of the amplitudes between the fast and the slow decay components as well as the time constant of the fast decay component changed consistently and reversibly with the membrane phospholipid PUFA composition. The current-voltage relationships, channel selectivity, rates of inactivation and recovery from inactivation did not change. Other parameters, such as time-to-peak and steady-state inactivation curves, have changed in EFA- and NFA-supplemented cultures and did not reverse completely. These findings demonstrate that the kinetics of INa can be modified by fatty acid supplementation. These effects can be correlated, in part, with alterations in plasma membrane phospholipid fatty acid composition.


Opportunities for improving brain cancer treatment outcomes through imaging-based mathematical modeling of the delivery of radiotherapy and immunotherapy.
Immunotherapy has become a fourth pillar in the treatment of brain tumors and, when combined with radiation therapy, may improve patient outcomes and reduce the neurotoxicity. As with other combination therapies, the identification of a treatment schedule that maximizes the synergistic effect of radiation- and immune-therapy is a fundamental challenge. Mechanism-based mathematical modeling is one promising approach to systematically investigate therapeutic combinations to maximize positive outcomes within a rigorous framework. However, successful clinical translation of model-generated combinations of treatment requires patient-specific data to allow the models to be meaningfully initialized and parameterized. Quantitative imaging techniques have emerged as a promising source of high quality, spatially and temporally resolved data for the development and validation of mathematical models. In this review, we will present approaches to personalize mechanism-based modeling frameworks with patient data, and then discuss how these techniques could be leveraged to improve brain cancer outcomes through patient-specific modeling and optimization of treatment strategies.


Lack of health insurance coverage among working-age adults, evidence from the Behavioral Risk Factor Surveillance System, 1993-2006.
To use data from the Behavioral Risk Factor Surveillance System (BRFSS) to examine trends in the lack of health insurance coverage among working-age US adults and to identify populations without coverage. The BRFSS data from 1993 to 2006 were analyzed. SUDAAN software was used to generate estimates of prevalence and corresponding standard errors, and logistic regression techniques were used to examine trends in the data. An estimated 18.59% of working adults (aged 18-64 years) did not have health insurance coverage in 2006. Trend in uninsurance remained somewhat stable from 1993 to 2000 (OR=1.01; 95% CI 1.00-1.02); however, it changed more rapidly from 2001 to 2006 (OR=1.03; 1.02-1.03). Similar patterns were observed from 2001 to 2006 for those <35 years of age, employed, Hispanics and those with less than or high school education. Effective approaches to reducing uninsurance and the consequences related to lack of coverage are needed in the face of increasing health disparities in the United States.


Publication rate of abstracts presented at the 2010 Canadian Ophthalmological Society Annual Meeting.
To evaluate the publication rate of submitted abstracts accepted for presentation at the 2010 Canadian Ophthalmological Society (COS) Annual Meeting in peer-reviewed journals. A retrospective analysis and literature search of abstracts presented at the 2010 COS Annual Meeting. Abstracts accepted as an oral presentation or poster from the 2010 COS Annual Meeting were tabulated by type of presentation (oral vs poster), subspecialty, study design, number of authors, and principal investigator's institution. A PubMed search was conducted for each abstract by key word, first author, and last author. The year of publication, journal, and impact factor were recorded for identified publications. Publication rate was calculated by type of presentation, subspecialty, study design, number of authors, and institution. A total of 175 abstracts were presented at the 2010 COS Annual Meeting. There were 105 oral (60%) and 70 poster (40%) presentations. The overall publication rate was 45.7%; 49.5% for oral presentations and 40.0% for posters. Cornea (57.6%) and public health (54.5%) had the highest publication rates of all subspecialties. Randomized control trials (71.4%) and cohort studies (70.0%) had higher publication rates than other study designs. Overall, 28.8% of abstracts were published in the Canadian Journal of Ophthalmology. The average impact factor of all publications was 2.73. Of abstracts presented at the 2010 COS Annual Meeting, 45.7% were published within 5 years after the conference. This publication rate is within the upper end of previously reported meeting publication rates for medical societies.


Purα Repaired Expanded Hexanucleotide GGGGCC Repeat Noncoding RNA-Caused Neuronal Toxicity in Neuro-2a Cells.
Expanded hexanucleotide GGGGCC repeat in a noncoding region of C9ORF72 is the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, its molecular pathogenesis remains unclear. In our previous study, the expanded GGGGCC repeats have been shown to be sufficient to cause neurodegeneration. In order to investigate the further role of expanded GGGGCC repeats in the neuron, the normal r(GGGGCC)3 and mutant-type expanded r(GGGGCC)30 expression vectors were transfected into Neuro-2a cells. Cell proliferation, dendrite development, and the proteins' levels of microtubule-associated protein-2 (MAP2) and cyclin-dependent kinase-5 (CDK5) were used to evaluate the cell toxicity of GGGGCC repeats on Neuro-2a cells. The results were shown that expression of expanded GGGGCC repeats caused neuronal cell toxicity in Neuro-2a cells, enhanced the expression of pMAP2 and pCDK5. Moreover, overexpression of Purα repaired expanded GGGGCC repeat-inducing neuronal toxicity in Neuro-2a cells and reduced the expression of pMAP2 and pCDK5. In all, our findings suggested that the expanded GGGGCC repeats might cause neurodegeneration through destroyed neuron cells. And the GGGGCC repeat-induced neuronal cell toxicity was inhibited by upregulation of Purα. We inferred that Purα inhibits expanded GGGGCC repeat-inducing neurodegeneration, which might reveal a novel mechanism of neurodegenerative diseases ALS and FTD.


Cardiac energetics: significance of mitochondria.
The mitochondrial activity as the energy producing step during biological oxidation was observed at rest and its regulation by the energy consuming auxotonic contractile work, depending on the preload, afterload and beat rate in isolated superfused left guinea pig atria. The mitochondrial activity was measured by (1) continuous determination of the O2 uptake rate, (2) the rate of 14CO2 production from labelled glucose or FFA and (3) separate measurements of the atrial ATP-, ADP-, AMP-, CP- and NAD-concentrations, for determination of the energy state. Some results, with points of general interest, are reported and discussed, including this model, former studies about cardiac energetics and the efficiency of cardiac work, reviewed recently.


Oryeongsan (Wulingsan), a traditional Chinese herbal medicine, induces natriuresis and diuresis along with an inhibition of the renin-angiotensin-aldosterone system in rats.
Oryeongsan (ORS, Wulingsan), a formula composed of five herbal medicines, has long been used for the treatment of impairments of the regulation of body fluid homeostasis in China, Japan and Korea. The purpose of the present study was to test the effects of ORS on the renal function and the mechanisms involved in rats. Experiments were performed in rats caged individually. Renal function and plasma levels of renin activity and aldosterone concentration were measured. Treatment of ORS resulted in increases in urinary volume, excretion of Na(+), K(+), and Cl(-), and glomerular filtration rate, and decreases in urinary osmolality and Na(+) balance. Further, ORS decreased plasma renin activity and aldosterone concentration. An increase in urinay excretion of Na(+) was a function of glomerular filtration rate, while the increase in the day-time period was related with the increase in the ratio of urinary Na(+)/K(+). Therefore, the present results suggest that ORS induces diuresis and natriuresis via inhibition of the renin-angiotensin-aldosterone system in rats.


Determination of rate-constants as a method to describe passive expiration.
To describe the relaxed expiration by a two-compartment model, we introduced a gas/energy transfer between the lung compartment ( V(1)) and a second one ( V(2)). If V(2) were a real volume, the rate-constants (i.e. the flow/volume ratios) of the compartments would describe a real gas-exchange. Alternatively, if a viscoelastic behaviour of the lung or an energy-exchange between compartments was simulated, V(2) would become a "pseudo-volume". We studied nine mechanically ventilated subjects. Changes in volume were transduced by respiratory inductive plethysmography. The rate-constants were assumed (together with the initial volumes of the compartments) as parameters to fit the total volume [ V(1)( t)+ V(2)( t)]. Once the best fitting was performed using these "physiological" parameters, the system was directly identified and the compartments were independently analysed. The time profile of the second compartment showed a maximum that depended on the value of the rate-constants. Appropriate tests confirmed the reliability of our procedure. In conclusion, our analysis demonstrated that the energy/volume of the second compartment may increase at the beginning of expiration and then decrease, showing a maximum, even though the total curve can only be a decreasing one. In other words, the slowing down of the curve representing expiratory volume is due not only to the longer emptying of the second compartment, but also to the interaction between the two compartments. As presently proposed, this interaction can be represented by either a gas exchange between two actual volumes, or a mechanical energy transfer between the lung and the tissue compartment.


Examining Social Capital, Social Support, and Language Use in an Online Depression Forum: Social Network and Content Analysis.
The use of peer-to-peer online support groups and communities has grown into a social phenomenon. Many people use online support groups and communities to seek and provide social support. It is essential to examine how users' participation behaviors may contribute to different outcomes. This study aimed to (1) use the structural positions of online depression forum users in their reply network to predict received support and (2) examine their language use reflecting their health conditions. A total of 2061 users and their 62,274 replies posted on a depression forum from July 2004 to July 2014 were extracted using a web crawler written in Python. The content of the forum users' posts and replies and their reply patterns were examined. A social network analysis method was used to build the reply networks of users. The computerized text analysis method was used to measure features of the forum users' language styles. Forum users' bridging social capital (operationalized as network betweenness) was positively associated with the level of communication accommodation in their received replies (P=.04). Forum users' bonding social capital (operationalized as network constraint) was negatively associated with the level of communication accommodation in their received replies (P<.001). The forum users' change in their use of self-referent words and words expressing negative emotions were examined as linguistic proxies for their health conditions and mental states. The results revealed a general negative association between the number of received replies and the degree of decrease in the use of words expressing negative emotion (P=.007). The structural positions of online depression forum users in the reply network are associated with different participation outcomes in the users. Thus, receiving replies can be beneficial to online depression forum users.


Hypersexuality and Trauma: a mediation and moderation model from psychopathology to problematic sexual behavior.
. Hypersexuality is a clinical condition regarding the psychopathology of sexual behavior. In this study, we aimed to investigate the role of trauma, through the post-traumatic stress-disorder (PTSD), depression, shame and guilt on the hypersexual behavior. . Through an online platform, a convenience sample of 1025 subjects was recruited (females: n=731; 71.3%; males: 294; 28.7%; age: 29.62±10.90). Recruited subjects compiled a psychometric protocol composed by the Hypersexual Behavior Inventory (HBI) to assess hypersexuality, the International Trauma Questionnaire (ITQ) for PTSD, the Patient Health Questionnaire (PHQ-9) to evaluate depression and the State Shame and Guilt Scale (SSGS) for shame and guilt. Then a mediation/moderation model was performed for the data analysis. . There was a statistically significant direct effect of post-traumatic symptoms (ITQTotal) on hypersexual behavior (HBTotal). Furthermore, indirect effects were also statistically significant, providing support to the hypothesis that depression and guilt would be serial mediators of trauma-hypersexual behavior relations. The paths through depression and guilt have been found to be the most significant with moderate and high indirect effects on hypersexuality. Moreover, male gender, as covariate variable, is a relevant risk factor for hypersexual behavior. . We found the relationship between hypersexuality and trauma describing a possible etiological pathway mainly involving depression, shame and guilt. Hypersexuality can be considered as a reactive form of a major affective psychopathology representing a tip of the iceberg hiding the real issues of a suffering personality. Clinicians and researchers should therefore consider hypersexual behavior in the light of a symptomatic manifestation of a major psychopathology involving the affective aspects of personality.


Endovascular treatments for type Ib endoleaks after aorto-iliac aneurysms exclusion: mid-term results.
To report early and mid-term results of endovascular treatments for type Ib endoleaks (IbEL) after endovascular aneurysm repair (EVAR) for aorto-iliac aneurysms (AAA). Patients with IbEL after EVAR were retrospectively analyzed. Cases of IbEL treated in two centers from January 2009 to February 2017 were considered. Patients' demographics and comorbidities, interval between EVAR and IbEL diagnosis, type of endograft, site of sealing, oversize and length of iliac sealing zone, type of IbEL treatment were collected. Main endpoints were freedom from IbEL recurrence and freedom from reintervention. Thirty-five IbEL were treated in 29 patients (mean age: 76±7years; male: 100%). Mean time between EVAR and IbEL detection was 43±30months. IbEL was symptomatic in 4 (14%) and bilateral in 6 (21%). Endograft was bifurcated in 26 patients (90%) and aorto-uniiliac in 3 (10%). Distal landing zone was achieved in common and external iliac artery in 33 (94%) and 2 cases (6%), respectively. Mean oversize of endograft limb was 11±9%, mean length of sealing zone was 22±15 mm. Endovascular treatments included: 34 iliac extensions (8 cases [24%] with hypogastric artery coverage), and 1 embolization. Concomitant embolization of hypogastric artery was performed in 3 (9%) cases. Technical success was 100%, with no procedure-related complication. Considering patients with hypogastric exclusion, buttock claudication developed in 2/8 cases (25%). Mean follow-up was 20±19 months. Freedom from IbEL was 100% and no reintervention was necessity for IbEL during follow-up. At 12, 24 and 36 months, survival was 88%, 82% e 61%, respectively, with no IbEL-related death. IbEL can be easily managed by endovascular means, typically with distal extensions with landing zones in the common or external iliac artery. Mid-term results are favourable, with no recurrent IbEL or reintervention.


Production deficiencies in free recall: a comparison of hyperactive, learning-disabled, and normal children.
Free recall of weakly categorizable words was compared in hyperactive (ADDH), reading-disabled, and normal boys. During a baseline trial, hyperactive boys recalled fewer words and showed less category organization than both reading-disabled and normal boys. Following a manipulation designed to encourage semantic encoding of words, hyperactive boys showed an immediate improvement in item recall and organization so that their free-recall performance was similar to that of reading-disabled and normal children. During later trials of a multiple-trial format, hyperactive boys recalled fewer words than did the reading-disabled and normal boys, despite maintaining equality in category organization. Rather than lacking the skill to use semantic organization as a strategy in free recall, hyperactive boys had difficulty in spontaneously generating the organizational strategy in response to instructions to remember and sustaining sufficient effort to task completion.


Investigating a continuous shear strain function for depth-dependent properties of native and tissue engineering cartilage using pixel-size data.
A previously developed novel imaging technique for determining the depth dependent properties of cartilage in simple shear is implemented. Shear displacement is determined from images of deformed lines photobleached on a sample, and shear strain is obtained from the derivative of the displacement. We investigated the feasibility of an alternative systematic approach to numerical differentiation for computing the shear strain that is based on fitting a continuous function to the shear displacement. Three models for a continuous shear displacement function are evaluated: polynomials, cubic splines, and non-parametric locally weighted scatter plot curves. Four independent approaches are then applied to identify the best-fit model and the accuracy of the first derivative. One approach is based on the Akaiki Information Criteria, and the Bayesian Information Criteria. The second is based on a method developed to smooth and differentiate digitized data from human motion. The third method is based on photobleaching a predefined circular area with a specific radius. Finally, we integrate the shear strain and compare it with the total shear deflection of the sample measured experimentally. Results show that 6th and 7th order polynomials are the best models for the shear displacement and its first derivative. In addition, failure of tissue-engineered cartilage, consistent with previous results, demonstrates the qualitative value of this imaging approach.


Thiopyrano[2,3-e]indol-2-ones: angelicin heteroanalogues with potent photoantiproliferative activity.
A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC(50) values at submicromolar level. This latter photoinduced a massive apoptosis and a remarkable photodamage to lipids and proteins. Although it did not intercalate DNA, it was able to cause photooxidation of DNA bases.


Evaluation of hepatic and thyroid responses in male Sprague Dawley rats for up to eighty-four days following seven days of dietary exposure to potassium perfluorooctanesulfonate.
In a prior 28-day dietary study in rats with 20 and 100 ppm K⁺ PFOS, activation of PPARα and CAR/PXR were concluded to be etiological factors in K⁺ PFOS-induced hepatomegaly and hepatic tumorigenesis. The objective of this study was to evaluate persistence/resolution of K⁺ PFOS-induced, liver-related effects in male Sprague Dawley rats following a 7-day dietary exposure to K⁺ PFOS at 20 or 100 ppm. Groups of 10 rats per treatment were observed on recovery Day(s) 1, 28, 56, and 84 following treatment. Changes consistent with hepatic PPARα and CAR/PXR activation noted on recovery Day 1 included: increased liver weight; decreased plasma cholesterol, alanine aminotransferase, and triglycerides; decreased liver DNA concentration and increased hepatocellular cytosolic CYP450 concentration; increased liver activity of acyl CoA oxidase, CYP4A, CYP2B, and CYP3A; increased liver proliferative index and decreased liver apoptotic index; decreased hepatocellular glycogen-induced vacuoles; increased centrilobular hepatocellular hypertrophy. Most effects resolved to control levels during recovery. Effects on plasma cholesterol, hepatocellular cytosolic CYP450 concentrations, liver apoptotic index, CYP3A, and centrilobular hepatocellular hypertrophy persisted through the end of the recovery period. Thyroid parameters (histology, apoptosis, and proliferation) were unaffected at all time points. Mean serum PFOS concentrations on recovery Day 1 were 39 and 140 μg/mL (20 ppm and 100 ppm K⁺ PFOS, respectively), decreasing to 4 and 26 μg/mL by recovery Day 84. Thus, hepatic effects in male rats resulting from K⁺ PFOS-induced activation of PPARα and CAR/PXR resolved slowly or were still present after 84-days following a 7-day dietary treatment, consistent with the slow elimination rate of PFOS.


Pain, Genes, and Function in the Post-Hip Fracture Period.
Post-hip fracture generalized pain can lead to a progressive decline in function and greater disability. The purpose of this study was to explore the factors that influence pain among older adults post-hip fracture, including genetic variability, and evaluate whether pain directly or indirectly influenced upper and lower extremity function. This was a secondary data analysis using data from the first 200 participants in a Baltimore Hip Study (BHS), BHS-7. Assessments were done at 2 months post-hip fracture and included age, sex, marital status, education, cognitive status, comorbidities, body mass index (BMI), upper and lower extremity function, single nucleotide polymorphisms (SNPs) from 10 candidate genes, and total areas of pain and pain intensity. Model testing was done using the AMOS statistical program. The full sample included 172 participants with an average age of 81. Fifty percent were female and the majority was Caucasian (93%). Model testing was done on 144 individuals who completed 2 month surveys. Across all models, age, cognition, and BMI were significantly associated with total areas of pain. Thirty SNPs from five genes (BDNF, FKBP5, NTRK2, NTRK3, and OXTR) were associated with areas of pain and/or pain intensity. Together, age, cognition, BMI, and the SNP from one of the five genes explained 25% of total areas of pain and 15% of pain intensity. Only age and cognition were significantly associated with lower extremity function, and only cognition was significantly associated with upper extremity function. The full model was partially supported in this study. Our genetic findings related to pain expand prior reports related to BDNF and NTRK2.


Erythrocyte membrane lysophospholipase activity in muscular dystrophy.
The membrane lysophospholipase activity of erythrocytes obtained from Duchenne muscular dystrophy patients was lower than that of erythrocytes from age-matched normal boys. On the other hand, the membrane enzyme activity of erythrocytes from myotonic dystrophy patients was not different from that of their age- and sex-matched controls. Dipyridamole (0.1 mM) and glycerol 3-phosphorylcholine (2 mM) had no significant effect on these enzyme activities. These results suggest that membrane lysophospholipid metabolism may be altered in Duchenne muscular dystrophy but not in myotonic dystrophy.


Novel inner filter effect-based near-infrared electrochemiluminescence sensor mediated by well-matched AgBr-nitrogen-doped Ti3C2 MXene and nonmetallic plasmon WO3•H2O.
The development of innovative and efficient strategy is of paramount importance for near-infrared (NIR) electrochemiluminescence (ECL) sensing, which can substantially promote ECL detection in a wide range of situations. Herein, the inner filter effect (IFE) strategy was designed to construct an ultrasensitive NIR ECL biosensor based on the well-matched AgBr nanocrystals (NCs) decorated nitrogen-doped Ti3C2 MXene nanocomposites (AgBr-N-Ti3C2) and hydrated defective tungsten oxide nanosheets (dWO3•H2O). Specifically, the AgBr-N-Ti3C2 nanocomposites displayed extremely effective NIR ECL emission because N-doping could accelerate electron transfer and boost the red-shift of the ECL spectrum. The nonmetallic plasmon dWO3•H2O was used as an absorber due to its facile tuning of the spectra overlap and higher molar extinction coefficients. Time-resolved emission decay curves proved that the decreased ECL intensity was ascribed to the IFE-based steady quenching mechanism. With the support of tetracycline (TC) aptamer and the complementary DNA chain, the fabricated NIR ECL-IFE biosensor performed a wide linear range of 100 nM ∼ 10 fM with a low detection limit of 2.2 fM (S/N = 3), and it exhibited excellent stability, sensitivity, and reproducibility, so as to be applied to real samples. This strategy opens a new avenue to constructing an efficient NIR ECL-IFE system and shows excellent practical potential in actual sample analysis.


High-Strength Physically Multi-Cross-Linked Chitosan Hydrogels and Aerogels for Removing Heavy-Metal Ions.
With the goal of improving the mechanical strength of chitosan hydrogels, gallic acid modified carboxymethyl chitosan/iron ion (GA-CMCS/FeIII) complex hydrogels were initially prepared via noncovalent interactions and metal coordination. 1H NMR, 13C NMR, and Fourier trantsform infrared spectra analysis confirmed the covalent reactions between CMCS and GA. The formation of GA-CMCS hydrogel occurred through electrostatic interactions, hydrogen bonds, and hydrophobic interactions. GA-CMCS/FeIII hydrogel (380 kPa) exhibited higher compressive strength than GA-CMCS hydrogel (315 kPa). In addition, GA-CMCS/FeIII aerogel displayed satisfactory mechanical strength (1.59 MPa) and high-efficiency adsorption capacities up to 97.15 mg/g for Pb2+, 99.75 mg/g for Cd2+, and 98.50 mg/g for Cu2+, respectively. In addition, both of the GA-CMCS and GA-CMCS/FeIII aerogel adsorbents exhibited satisfactory recyclability. The design of GA-CMCS and GA-CMCS/FeIII hydrogels and aerogels offers a new opportunity for the construction of physically multi-cross-linked systems with excellent mechanical properties.


Congenital heart disease combined with Arrhythmogenic Right Ventricular Cardiomyopathy: A CARE compliant case report and literature review.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiomyopathy disease discovered in 1994. Though there are advances in diagnosis of arrhythmogenic right ventricular cardiomyopathy, early diagnosis is still difficult especially when it is combined with other diseases with similar pathophysiologic changes, such as left to right shunt congenital heart disease (CHD). In this paper, we reported a case of CHD combined with ARVC. The patient was referred to us for chest tightness and shortness of breath after physical activities. His cardiac MRI indicated the possibility of arrhythmogenic right ventricular cardiomyopathy. He was diagnosed with a large atrial septal defect (ASD) through ultrasound examination. CHD ASD combined with arrhythmogenic right ventricular cardiomyopathy. The patient underwent occlusion of the ASD and he was followed-up closely. His symptoms were relieved a lot and the activity tolerance was elevated. CHD may accompany with arrhythmogenic right ventricular cardiomyopathy. Careful history collection and comprehensive examinations should be emphasized. We firmly believe that our work will be helpful for the medical practice of similar complicated cardiovascular diseases.


Comparative proteomic investigation unravels the pathobiology of Mycobacterium fortuitum biofilm.
Biofilm formation by Mycobacterium fortuitum causes serious threats to human health due to its increased contribution to nosocomial infections. In this study, the first comprehensive global proteome analysis of M. fortuitum was reported under planktonic and biofilm growth states. A label-free Q Exactive Quadrupole-Orbitrap tandem mass spectrometry analysis was performed on the protein lysates. The differentially abundant proteins were functionally characterized and re-annotated using Blast2GO and CELLO2GO. Comparative analysis of the proteins among two growth states provided insights into the phenotypic switch, and fundamental pathways associated with pathobiology of M. fortuitum biofilm, such as lipid biosynthesis and quorum-sensing. Interaction network generated by the STRING database revealed associations between proteins that endure M. fortuitum during biofilm growth state. Hypothetical proteins were also studied to determine their functional alliance with the biofilm phenotype. CARD, VFDB, and PATRIC analysis further showed that the proteins upregulated in M. fortuitum biofilm exhibited antibiotic resistance, pathogenesis, and virulence. Heatmap and correlation analysis provided the biomarkers associated with the planktonic and biofilm growth of M. fortuitum. Proteome data was validated by qPCR analysis. Overall, the study provides insights into previously unexplored biochemical pathways that can be targeted by novel inhibitors, either for shortened treatment duration or for eliminating biofilm of M. fortuitum and related nontuberculous mycobacterial pathogens. KEY POINTS: • Proteomic analyses of M. fortuitum reveals novel biofilm markers. • Acetyl-CoA acetyltransferase acts as the phenotype transition switch. • The study offers drug targets to combat M. fortuitum biofilm infections.


Mesona chinensis polysaccharide/zein nanoparticles to improve the bioaccesibility and in vitro bioactivities of curcumin.
The aim of this study was to enhance the stability, bioaccesibility, and bioactivities of curcumin using a composite nanoparticle prepared from zein and Mesona chinensis polysaccharide (MCP). Curcumin-loaded nanoparticles (ZMC NPs) were prepared. ZMC NPs showed smooth spherical structure with a high encapsulation efficiency (94 %), a small average particle size (223 nm), and surface negative charge (-34.53 mV). Compared with free curcumin, encapsulated curcumin has been shown to have better environmental stability, higher antioxidant activity and bioaccesibility. The surface coating of zein NPs with MCP makes them more amenable to uptake by intestinal epithelial cells. Studies on in vitro antitumor activity of ZMC NPs showed that they could enter hepatocellular carcinoma cells, induce cell apoptosis, promote ROS production, and alter mitochondrial membrane potential, showing higher in vitro antitumor activity compared to free curcumin. These results may contribute to the development of novel curcumin oral delivery systems.


Report on 2nd Royan Institute International Summer School on developmental biology and stem cells Tehran, Iran, 17-22nd July 2011.
The 2nd Royan Institute International Summer School was built around the topic of stem cells and grounding in the discipline of developmental biology. The meeting provided not only direct transfer of technical and intellectual information, the normal process in scientific meetings, but was also a forum for the exchange of personal ideas of science as a creative pursuit. This summer school introduced aspiring young Iranian scientists to international researchers and exposed the latter to a rich culture that highly values learning and education, attested by the confident, intelligent young men and women who asked probing questions and who were eager to participate in the workshops. Hossein Baharvand's dedication and passion for science have led to an impressive record of national and international peer-reviewed publications and an increasing number of students who pursue science in Iran, and shows how the right people can create an environment where good science, good science education and motivation will flourish. This report summarizes some of the activities of the workshop in the Royan Institute and the impressions of the visiting scientists in the wider context of the scientific and cultural heritage of Iran.


Flow modulation comprehensive two-dimensional gas chromatography-mass spectrometry with a supersonic molecular beam.
A new approach of flow modulation comprehensive two-dimensional gas chromatography-mass spectrometry (GC x GC-MS) with supersonic molecular beam (SMB) and a quadrupole mass analyzer is presented. Flow modulation uniquely enables GC x GC-MS to be achieved even with the limited scan speed of quadrupole MS, and its 20 ml/min column flow rate is handled, splitless, by the SMB interface. Flow modulation GC x GC-SMB-MS shares all the major benefits of GC x GC and combines them with GC-MS including: (a) increased GC separation capability; (b) improved sensitivity via narrower GC peaks; (c) improved sensitivity through reduced matrix interference and chemical noise; (d) polarity and functional group sample information via the order of elution from the second polar column. In addition, GC x GC-SMB-MS is uniquely characterized by the features of GC-MS with SMB of enhanced and trustworthy molecular ion plus isotope abundance analysis (IAA) for improved sample identification and fast fly-through ion source response time. The combination of flow modulation GC x GC with GC-MS with SMB (supersonic GC-MS) was explored with complex matrices such as diesel fuel analysis and pesticide analysis in agricultural products.


Incidence of Spontaneous Resorption of Lumbar Disc Herniation: A Meta-analysis.
A meta-analysis. This study aimed to analyze the incidence of spontaneous resorption of lumbar disk herniation (LDH) after conservative treatment. The resorption of intervertebral disks has been more frequently reported, but there is a lack of reference to the probability of resorption. We strictly refer to the standard established in the PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) statement, comprehensively searched electronic databases using the terms related to the spontaneous resorption of LDH. Two reviewers independently evaluated the potential studies, extracted, and analyzed the enrolled data. Thirty-one studies with 2233 patients who received conservative treatment were included for this analysis. We found that the pooled overall incidence of disk resorption was 70.39%, 87.77% for disk sequestration, 66.91% for disk extrusion, 37.53% for disk protrusion, and 13.33% for disk bugle, respectively. The resorption incidence in of 25%≤ reduction of disk herniation (RDH) 50%, RDH≥50%, and RDH=100% were 40.19%, 43.62, and 36.89%. The resorption incidence was 66.98% in Japan, 61.66% in the United States, 83.52% in Korea, 60.68% in China, 78.30% in the UK, 56.70% in Italy, and 83.68% in Turkey, respectively. Subgroup analysis showed that there was no significant difference in resorption incidence among prospective, retrospective studies and randomized controlled trials (P=0.77), and there was no significant difference in evaluation method among qualitative and quantitative studies (P=0.05). The existing evidence shows that the overall resorption incidence of LDH was 70.39%, the resorption incidence of ruptured LDH is higher than that of contained LDH. There are significant differences in the resorption incidence among countries. The resorption process mainly occurred within 6 months of conservative treatment.


Center Line Slope Analysis in Two-Dimensional Electronic Spectroscopy.
Center line slope (CLS) analysis in 2D infrared spectroscopy has been extensively used to extract frequency-frequency correlation functions of vibrational transitions. We apply this concept to 2D electronic spectroscopy, where CLS is a measure of electronic gap fluctuations. The two domains, infrared and electronic, possess differences: In the infrared, the frequency fluctuations are classical, often slow and Gaussian. In contrast, electronic spectra are subject to fast spectral diffusion and affected by underdamped vibrational wavepackets in addition to Stokes shift. All these effects result in non-Gaussian peak profiles. Here, we extend CLS-analysis beyond Gaussian line shapes and test the developed methodology on a solvated molecule, zinc phthalocyanine. We find that CLS facilitates the interpretation of 2D electronic spectra by reducing their complexity to one dimension. In this way, CLS provides a highly sensitive measure of model parameters describing electronic-vibrational and electronic-solvent interaction.


Association between nickel exposure and body compositions in the United States: a population-based cross-sectional study.
Increasing body fat or decreasing muscle and bone mass were associated with worse health outcomes in the adult population. The effects of nickel exposure on body composition are not known. The aim of the current study was to investigate the relationship between urinary nickel levels and body compositions. Two thousand seven hundred sixty-two participants were included in the analysis from the National Health and Nutrition Examination Surveys of 2017-2018 after excluding participants who have missing data on urinary nickel and those with missing all body mass component data. We used weighted generalized linear models to explore the relationship between urinary nickel and body mass components under interpolating missing covariable values. Simultaneously, sensitivity analyses and subgroup analysis were conducted to verify stability of analysis result. Curve fitting and saturation effect analysis were used to explore the possible nonlinear relationship between urine nickel and body compositions. Among the 2,762 participants, the average urinary nickel level was 1.58 ug/L. The weighted generalized linear models, the sensitivity analyses and subgroup analyses found no significant linear relationship between urinary nickel and body compositions. For body weight, BMI, TLM, ALM, TRF, TOF and BMC, the urine nickel saturation effect values were 0.76, 0.74, 0.5, 0.67, 0.64, 0.48, and 0.45 ug/L, respectively. For each 1 ug/L rise in urinary nickel levels at levels below the turning point, body weight increases (β = 9.06, 95% CI = 2.75, 15.36, p = 0.01), BMI increases (β = 3.20, 95% CI = 1.36, 5.05, p = < 0.001), TLM decreases (β = -47.39, 95% CI = -97.38, 2.59, p = 0.06), ALM decreases (β = -37.25, 95% CI = -63.25, -11.24, p = 0.01), TRF increases (β = 20.68, 95% CI = 1.50, 39.86, p = 0.03), TOF increases (β = 57.92, 95% CI = -0.12, 115.95, p = 0.05), and BMC decreases (β = -6.84, 95% CI = -12.64, -1.04, p = 0.02). In summary, our study demonstrated that a dose-response relationship exists between urinary nickel and body compositions, with a low inflection point level of urinary nickel for the saturation effect.


Continued declining incidence and improved survival of progressive multifocal leukoencephalopathy in HIV/AIDS patients in the current era.
To evaluate the situation and perspectives of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected patients, we investigated changes in the incidence, causes, and long-term outcome of this disease in 72 acquired immunodeficiency syndrome (AIDS) patients who were diagnosed with PML from 1996 to 2011. Patients were classified according to the date of diagnosis in the first (1996-2000, n = 35), second (2001-2006, n = 26), and recent or third highly active antiretroviral therapy (HAART) period (2007-2011, n = 11). Overall, the incidence of PML decreased from 14.8 cases/1,000 patients/year in 1996 to 2.6 in 2005 and 0.8 in 2011, and nearly two-thirds of recent cases (64 %) were observed in HIV patients not attending clinical visits. The baseline median CD4+ count was higher in recently PML-diagnosed patients (77 vs. 86 vs. 101 cells/mm(3); p < 0.01), and this fact was associated with a cerebrospinal fluid (CSF) inflammatory profile (from 11 to 31 to 55 %, p = 0.007) and with a significantly longer survival (attributable death, 54 vs. 35 vs. 36 %, respectively, p < 0.01). Thus, the overall 1-year and 3-year survival rates were 55 and 50 %, respectively, increasing to 79 % at 1 year for patients with CD4+ count above 100 cells/mm(3) at diagnosis. In a Cox regression analysis, an older age (hazard ratio, HR 0.76), a baseline CD4+ count above 100 cells/mm(3) (HR 0.33), and a CSF inflammatory profile (HR 0.12) were significantly associated with a longer survival. The clinical presentation and outcome of PML in AIDS patients continue to change dramatically. Now, a declining incidence and long-term survival is observed.


Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas.
Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with < or =3 mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.


Association of dietary fatty acids and the incidence risk of cardiovascular disease in adults: the Tehran Lipid and Glucose Prospective Study.
Considering the inconsistent available findings regarding the cardioprotective effect of dietary fatty acid composition, we prospectively examined the feasible association between the dietary fatty acids and the cardiovascular disease (CVD) incidence in framework of the population-based Tehran Lipid and Glucose Study. A total of 2369 participants (19-70 years, 43.5% men) without CVD at baseline (2006-2008) were included and followed-up for 6.7 years. Fatty acids' dietary intake was estimated using a 168-item semi-quantitative food frequency questionnaire. The CVD incidence risk across tertiles of dietary fatty acids was predicted via Cox proportional hazards regression models. The average age and body mass index of the included population were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m2 at baseline. Over 6.7 years of follow-up, 79 cases of CVD were detected. The risk of CVD was lower in upper tertile of monounsaturated fatty acids, oleic acid, and docosahexaenoic acid + eicosapentaenoic acid among the tertiles. No significant associations were found between total fat, saturated and polyunsaturated fatty acids' intake, and CVD. Our results suggest that the dietary fatty acid composition might affect the incidence risk of CVD within the Iranian population.


A model for studying the effect of shear stress on interactions between vascular endothelial cells and smooth muscle cells.
Vascular endothelial cells (ECs) are constantly subjected to blood flow-induced shear stress and the influences of neighboring smooth muscle cells (SMCs). In the present study, a coculture flow system was developed to study the effect of shear stress on EC-SMC interactions. ECs and SMCs were separated by a porous membrane with only the EC side subjected to the flow condition. When ECs were exposed to a shear stress of 12 dynes/cm2 for 24 h, the cocultured SMCs tended to orient perpendicularly to the flow direction. This perpendicular orientation of the cocultured SMCs to flow direction was not observed when ECs were exposed to a shear stress of 2 dynes/cm2. Under the static condition, long and parallel actin bundles were observed in the central regions of the cocultured SMCs, whereas the actin filaments localized mainly at the periphery of the cocultured ECs. After 24 h of flow application, the cocultured ECs displayed very long, well-organized, parallel actin stress fibers aligned with the flow direction in the central regions of the cells. Immunostaining of platelet endothelial cell adhesion molecule-1 confirmed the elongation and alignment of the cocultured ECs with the flow direction. Coculture with SMCs under static condition induced EC gene expressions of growth-related oncogene-alpha and monocyte chemotactic protein-1, and shear stress was found to abolish these SMC-induced gene expressions. Our results suggest that shear stress may serve as a down-regulator for the pathophysiologically relevant gene expression in ECs cocultured with SMCs.


The relation between the blood benzodiazepine concentration and performance in suspected impaired drivers.
Several experimental studies have shown a negative influence of benzodiazepines on driving skills. The objective of this study is to study the relationship between the blood concentration of benzodiazepines and the influence on performance in field sobriety tests. A retrospective case file evaluation was conducted to select cases of drivers, tested positive for benzodiazepines only in the period from January 1999 to December 2004. Drivers were grouped into the categories sub therapeutic, therapeutic or elevated concentrations. The outcome of the tests (walking, walking after turn, nystagmus, Romberg's test, behavior, pupils and orientation) was binomial. A Chi square test was used to assess differences in proportions of the categorized cases. In total 171 cases were included. Observations of behavior (n=137; p<0.01), walking (n=109; p<0.01), walking after turn (n=89; p=0.02) and Romberg's test (n=88; p<0.05) were significantly related to the benzodiazepine concentration. There was no significant relation between benzodiazepine concentration and effect on pupil size, nystagmus or orientation. The results of our study indicate a relation between the concentration of benzodiazepines and the results of some performance tests. More effort is needed to standardize the tests and to determine the sensitivity and selectivity of the tests for benzodiazepines.


Porcine sebaceous cyst model: an inexpensive, reproducible skin surgery simulator.
Surgical simulators are an established part of surgical training and are regularly used as part of the objective structured assessment of technical skills. Specific artificial skin models representing cutaneous pathology are available, although they are expensive when compared with pigskin. The limitations of artificial skin models include their difficulty in representing lifelike cutaneous pathology. Our aim was to devise an inexpensive, reproducible surgical simulator that provides the most lifelike representation of the sebaceous cyst. materials and methods: Pigskin, either pig's feet/trotters or pork belly, was incised, and a paintball was inserted subcutaneously and fixed with cyanoacrylic glue. This model has regularly been used in cutaneous surgical courses that we have organized. Either adding more cyanoacrylic glue or allowing more time for the paint ball to absorb fluid from surrounding tissue can also adjust the degree of difficulty. The degree of correlation with lifelike cutaneous pathology is such that we recommend that all courses involved in basic skin surgery should consider using the porcine sebaceous cyst model when teaching excision of sebaceous cysts.


The contribution of cohort studies to prescribing research.
This paper highlights the main issues in the design, analysis and interpretation of cohort studies used in prescribing research.


From Xiaoke to diabetes mellitus: a review of the research progress in traditional Chinese medicine for diabetes mellitus treatment.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia resulting from insulin secretion defects or insulin resistance. The global incidence of DM has been gradually increasing due to improvements in living standards and changes in dietary habits, making it a major non-communicable disease that poses a significant threat to human health and life. The pathogenesis of DM remains incompletely understood till now, and current pharmacotherapeutic interventions are largely inadequate, resulting in relapses and severe adverse reactions. Although DM is not explicitly mentioned in traditional Chinese medicine (TCM) theory and clinical practice, it is often classified as "Xiaoke" due to similarities in etiology, pathogenesis, and symptoms. With its overall regulation, multiple targets, and personalized medication approach, TCM treatment can effectively alleviate the clinical manifestations of DM and prevent or treat its complications. Furthermore, TCM exhibits desirable therapeutic effects with minimal side effects and a favorable safety profile. This paper provides a comprehensive comparison and contrast of Xiaoke and DM by examining the involvement of TCM in their etiology, pathogenesis, treatment guidelines, and other relevant aspects based on classical literature and research reports. The current TCM experimental research on the treatment of DM by lowering blood glucose levels also be generalized. This innovative focus not only illuminates the role of TCM in DM treatment, but also underscores the potential of TCM in DM management.


Stigma, Social Support, and Substance Use in Diverse Men Who Have Sex With Men and Transgender Women Living with HIV in the US Southeast.
Human immunodeficiency virus (HIV) rates in the southeast United States are high and substance use is common among people living with HIV (PLWH). This study used baseline data from the weCare intervention study to examine factors associated with the use of alcohol, tobacco, and marijuana among racially and ethnically diverse young gay, bisexual, and other men who have sex with men (GBMSM) and transgender women in the southeast who were newly diagnosed as having HIV, not linked to care, out of care, and/or not virally suppressed. Self-reported data were collected from 196 GBMSM and transgender women living with HIV via Audio Computer-Assisted Self-Interview at enrollment. Measures assessed demographics; stigma; social support; basic and clinical service needs; HIV disclosure; social media use; and recent use of alcohol, tobacco, and marijuana. Logistic regression identified correlates of past 30-day substance use. In multivariable analysis, increased age and needing basic support services were associated with past 30-day tobacco, cigarette, electronic cigarette, and/or hookah use. Increased HIV-related stigma and needing basic support services were associated with past 30-day marijuana use. Being White and needing clinical support services were associated with infrequent or no past 30-day marijuana use. HIV-related stigma and needing basic support services were associated with substance use among GBMSM and transgender women living with HIV in the southeastern United States. Routine screening for basic needs could identify GBMSM and transgender women living with HIV at risk for substance use and offer insight into intervention leverage points.


Conjunctival Ultraviolet Autofluorescence as a Measure of Riboflavin and Ultraviolet and Accelerated Cross-Linking Exposure in Keratoconic Patients.
The study was performed to analyze the prevalence of the conjunctival ultraviolet autofluorescence (CUVAF) area in keratoconic eyes and changes caused by UVA-irradiation as a component of accelerated corneal cross-linking (aCXL). The study group involved 20 keratoconic patients subjected to aCXL surgery in one eye. The comparative group consisted of 111 age- and sex-matched patients with healthy corneas. The images of the anterior segment in both patient groups were taken using a Coroneo camera. In the study group the photos were taken before and immediately after the surgery, and 7 and 30 days following the procedure. Nasal and temporal autofluorescence area (AN+T) were significantly smaller in a keratoconic patients group compared to control group (p = 0.0001). Patients with the third stage of keratoconus had significantly higher AN+T (p = 0.0277) compared with individuals with lower stage keratoconus. No statistically significant CUVAF changes were observed after the aCXL procedure. In keratoconic patients with primary CUVAF undergoing aCXL, a temporary fast enlargement of the autofluorescence area was observed. The eyes undergoing the aCXL procedure showed no difference in the size of the CUVAF area but such patients should be in strict follow-up in order to reveal UV-related ocular surface diseases.


Systems biology strategy through integrating metabolomics and network pharmacology to reveal the mechanisms of Xiaopi Hewei Capsule improves functional dyspepsia.
Functional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 20-25 %. It seriously affects the quality life of patients. Xiaopi Hewei Capsule (XPHC) is a classic formula originated from the Chinese Miao minority. Clinical studies have demonstrated that XPHC can effectively alleviate the symptoms of FD, but the molecular mechanism has not been elucidated. The purpose of this work is to investigate the mechanism of XPHC on FD by integrating metabolomics and network pharmacology. The mice models of FD were established, and gastric emptying rate, small intestine propulsion rate, serum level of motilin and gastrin were evaluate to study the interventional effect of XPHC on FD. Next, a metabolomics strategy has been developed to screen differential metabolites and related metabolic pathways induced by XPHC. Then, prediction of active compounds, targets and pathways of XPHC in treating FD were carried out by commonly used network pharmacological method. Finally, two parts of the results were integrated to investigate therapeutic mechanism of XPHC on FD, which were preliminary validated based on molecular docking. Thus, twenty representative different metabolites and thirteen related pathways of XPHC in treating FD were identified. Most of these metabolites were restored using modulation after XPHC treatment. The results of the network pharmacology analysis showed ten crucial compounds and nine hub genes related to the treatment of FD with XPHC. The further integrated analysis focused on four key targets, such as albumin (ALB), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF) and roto-oncogene tyrosine-protein kinase Src (SRC), and three representative biomarkers such as citric acid, L-leucine and eicosapentaenoic acid. Furthermore, molecular docking results showed that ten bioactive compounds from XPHC have good binding interactions with the four key genes. The functional enrichment analysis indicated that the potential mechanism of XPHC in treating FD was mainly associated with energy metabolism, amino acid metabolism, lipid metabolism, inflammatory reactions and mucosal repair. Our work confirms that network pharmacology-integrated metabolomics strategyis a powerful means to reveal the therapeutic mechanisms of XPHC improves FD, which contribute its further scientific research.


Haemoglobin level and vascular access survival in haemodialysis patients.
A full correction of anaemia in haemodialysis (HD) patients may lead to an increased risk of vascular access (VA) failure. We studied the relationship between haemoglobin (Hb) level and VA survival. Incident patients between January 2000 and December 2002 with <1 month on HD were considered. The relative risk (RR) of access failure was evaluated in four different groups of patients divided according to their Hb level (<10, 10-12, 12-13 and >13 g/dl). Other factors possibly influencing VA survival were also considered: age, gender, diabetes, vascular disease, intact parathyroid hormone (iPTH) and treatment with an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB) or recombinant human erythropoeitin therapy. We studied 1254 patients (1057 with autologous fistulae, 75 grafts and 122 permanent catheters at admission). Based on Cox analysis, we found the next statistically significant RR of VA failure to be 2.3 times higher with grafts than with arterio-venous fistulae (AVFs) and 1.8 times higher in AVFs with Hb <10 g/dl than in AVFs of the next Hb group. There was no statistically significant difference in the RR of VA failure between patients with Hb 10-12 g/dl and those with Hb 12-13 g/dl or >13 g/dl. Diabetes (RR: 1.41, P = 0.06), age >65 years (RR: 1.32; P = 0.11) and iPTH (RR: 1.56; P = 0.01) were identified as predictive factors for VA failure; ACE inhibitors or ARB (RR: 0.69; P = 0.03) were found to be protective factors. In the studied population, the correction of Hb level to >12 g/dl was not associated with a higher incidence of VA thrombosis than in patients with Hb between 10 and 12 g/dl. ACE inhibitors or ARBs were found to be protective factors, and diabetes, age >65 years and iPTH >400 pg/ml were negative predictive factors for VA survival.


PSA course after definitive high-dose radiotherapy of localized prostate cancer.
After radical prostatectomy, PSA levels that reach near zero values in less than 14 days are associated with a favourable prognosis. The aim of this analysis was to investigate whether PSA also declines to near zero values after combined tele-brachytherapy. Forty-one patient, treated with combined tele-brachytherapy for prostate cancer, were followed for at least 2 years after treatment with repeated PSA measurements. PSA values <1.0 ng/ml were only reached after 15 months; near zero PSA levels were not reached until 18-24 months after treatment (median: 0.25 ng/ml). A PSA decline to near zero values occurs after definitive tele-brachytherapy, but it takes longer than after surgery (18-24 months).


Arsenic sorption onto laterite iron concretions: temperature effect.
We investigated arsenate and arsenite sorption onto laterite iron concretions (LIC) to test its suitability for use in the low-tech treatment of arsenic-bearing drinking water. Batch experiments on crushed LIC from Prestea, Ghana were conducted at a series of temperatures, ionic strengths, and pHs. The point of zero net charge on laterite iron concretion was determined by potentiometric titrations yielding an average pHp(ZNC) around 8.64. Experiments show that sorption capacity for both arsenite and arsenate increase with temperature. The equilibrium sorption capacity for arsenite was larger than that for arsenate over the 25 to 60 degrees C temperature range. A Langmuir model satisfactorily fits the arsenite and arsenate sorption isotherm data. Both arsenite and arsenate sorbed over the pH range of natural waters. Arsenite sorption increases with increasing solution pH to a maximum at pH 7, then decreases with further increase in solution pH. Arsenate sorption, on the other hand, shows little change with increasing solution pH. Increasing solution ionic strength 10-fold results in a slight increase in sorption. Ionic strength experiments show that an inner-sphere sorption mechanism is responsible for As (V) sorption on LIC, while As (III) sorption is by an outer-sphere mechanism. Gibbs free energy (DeltaG degrees) for arsenite and arsenate sorption onto LIC was calculated from Langmuir isotherms; the negative values agree with reaction spontaneity. The positive values of the standard enthalpy (DeltaH degrees) show the endothermic nature of arsenite and arsenate sorption onto LIC. Positive entropy (DeltaS degrees) values suggest the affinity of LIC for the arsenic species in solution. Analysis of the arsenic sorption data suggests that LIC can be used for low-tech natural-materials arsenic water treatment. Laterite iron concretions have a number of advantages for this use over commercial materials, including the ability to remove arsenic from waters with a wide range in pH, the ability to sorb both common arsenic aqueous species equally well, and cost less. Laterite iron concretion's positive sorption temperature dependence will enhance sorption in tropical climates, and more especially in areas where groundwater sources are related to geothermal springs.


Development and evaluation of self-microemulsifying liquid and granule formulations of Brucea javanica oil.
The aim of this study was to develop and characterize a self-microemulsifying drug delivery system (SMEDDS) of Brucea javanica oil (BJO) and transform the liquid formulation into solid granules. Solubility studies of BJO and pseudo-ternary phase diagrams were used to identify the most efficient self-emulsification region. A methyl thiazolyl tetrazolium (MTT) assay was performed to identify cell apoptosis. Antitumor activity studies were also employed to evaluate the BJO SMEDDS. The optimized BJO SMEDDS in liquid and granule formulations rapidly formed fine oil-in-water microemulsions with particle sizes <50 nm. Additionally, the MTT assay demonstrated that BJO SMEDDS had a significant effect on cancer cells, and antitumor activity studies showed remarkable inhibition of S180 tumors. The BJO SMEDDS, optimized to have good characteristics, was successfully transformed into solid granules by adsorbing onto crospovidone. The studies of the release of the BJO SMEDDS of liquid and granules in vitro suggested that the release of BJO was enhanced by the SMEDDS. These studies revealed that the new self-microemulsifying systems of liquid and granule forms might be promising strategies for the oral delivery of the poorly water-soluble drug BJO.


Characterization of the calcium-dependent proteolytic system in a mouse muscle cell line.
Many studies have demonstrated that the calcium-dependent proteolytic system (calpains and calpastatin) is involved in myoblast differentiation. It is also known that myogenic differentiation can be studied in vitro. In the present experiments, using a mouse muscle cell line (C2C12) we have analyzed both the sequences of appearance and the expression profiles of calpains 1, 2, 3 and calpastatin during the course of myoblast differentiation. Our results mainly show that the expression of ubiquitous calpains (calpain 1 and 2) and muscle-specific calpain (calpain 3) at the mRNAs level as well as at the protein level do not change significantly all along this biological process. In the same time, the specific inhibitor of ubiquitous calpains, calpastatin, presents a stable expression at mRNAs level as well as protein level, all along myoblast to myotube transition. A comparison with other myogenic cells is presented.


Developmental trajectories of alcohol and cannabis concurrent use in a nationally representative sample of United States youths.
Previous studies have identified common trajectories of single type substance use over the course of adolescence; however, no study to date has examined joint trajectories of cannabis and alcohol concurrent use. Given that expansion of legal cannabis has increased availability, it is important to understand patterns of concurrent use in adolescents and factors that place male and female youth at risk for harmful trajectories of concurrent use. The current study sought to identify joint trajectories of cannabis and alcohol use - and predictors of harmful use trajectories - among male and female adolescents. We used 4 waves of data from 6997 early adolescent participants (age 12-14 years at Wave 1) in the Population Assessment of Tobacco and Health, a nationally representative longitudinal study in the United States. Participants reported their cannabis and alcohol use reassessed yearly for 5 years (2013-2018). We used joint trajectory growth mixture modeling to identify trajectory groups as defined by changes in alcohol and cannabis use over time. Five classes of alcohol and cannabis concurrent use trajectories were identified. Both internalizing and externalizing symptoms at Wave 1 increased the odds of membership in trajectory groups characterized by more harmful use trajectories. Internalizing symptomatology was a stronger predictor of membership in escalating use trajectories among girls, whereas externalizing symptomatology stronger predictor among boys. These findings underscore the utility of jointly considering alcohol and cannabis use when describing common developmental trajectories of use and identifying risk factors for trajectories characterized by harmful use.


Varieties of dispositional essentialism about natural laws.
An important task for metaphysicians and philosophers of science is to account for laws of nature - in particular, how they distinguish themselves from 'mere' regularities, and the modal force they are endowed with, 'natural necessity'. Dispositional essentialism about laws (for short: 'essentialism') is roughly the view that laws distinguish themselves by being grounded in the essences of natural entities (e.g. kinds, properties). This paper does not primarily concern how essentialism compares to its main rivals - Humeanism and Armstrongeanism. Rather, it distinguishes and comparatively assesses various brands of essentialism - which mainly differ as to where exactly they take laws to find their essentialist sources (e.g. in particular entities, like electrons, or in larger pluralities of entities, or in the world as a whole), and what they take to be the targets of laws, namely what they apply to. Yet, this internal comparison is not unrelated to the more general debate about laws: the main criteria with which I compare these essentialist views concern how they can deal with some of the main objections faced by essentialism in general (the modal status it typically attributes to laws, which some think is too strong; and its alleged incapacity to account for the most 'general' laws, like conservation laws), and how they can keep what is arguably the main intuitive advantage of essentialism over its rivals (the fact that, on this view, things "govern themselves"). Thus, the paper also concerns the relative position of essentialism in the larger debate about laws - ultimately bringing support to it.


Fungal infection in solid organ recipients.
In solid organ recipients, as with other immunosuppressed patients, infections by Candida spp. and Aspergillus spp. are the most frequent invasive mycoses. Infections by Cryptococcus spp. and fungi of the Mucorales order are less common. Infections by Fusarium spp. and Scedosporium spp. are very uncommon, except in patients undergoing hematopoietic stem cell transplant and patients with prolonged neutropenia. The risk factors for fungal infection are immunosuppression, surgery, viral co-infection, and environmental exposure. Diagnosis is challenging: blood culture is of little use, except in candidiasis and cryptococcosis, and the poor accuracy of antigen-based techniques, except in cryptococcosis, favors widespread use of empirical therapy. A delay in the initiation of therapy increases the already high mortality of these infections. The agents used to treat fungal infection are azoles, echinocandins, and lipid amphotericin. Administration depends on antifungal activity, drug-drug interactions with calcineurin inhibitors, and safety profiles (effects on grafts and other side effects).


In Vitro and In Vivo Anti-parasitic Activity of Sambucus ebulus and Feijoa sellowiana Extracts Silver Nanoparticles on Toxoplasma gondii Tachyzoites.
Current chemical treatments for toxoplasmosis have side effects, researchers are looking for herbal remedies with minimal side effects and the best effectiveness. This study aimed to evaluate the anti-toxoplasmic effects of silver nanoparticles based on Sambucus ebulus (Ag-NPs-S. ebulus) and Feijoa sellowiana (Ag-NPs-F. sellowiana) fruit extracts, in vitro and in vivo. Vero cells were treated with different concentrations (0.5, 1, 2, 5, 10, 20, 40 μg/mL) of extracts and pyrimethamine as a positive control. Vero cells were infected with T. gondii and treated with extracts. The infection index and intracellular proliferation of T. gondii were evaluated. The survival rate of infected mice with tachyzoites of T. gondii was examined after intraperitoneal injection of the extracts at a dose of 40 mg/kg/day for 5 days after infection. The Ag-NPs-S. ebulus and Ag-NPs-F. sellowiana, almost similar to pyrimethamine, reduced proliferation index when compared to untreated group. Also, high toxoplasmicidal activity was observed with Ag-NPs-S. ebulus extract. Mice in the treatment groups of Ag-NPs-S. ebulus and pyrimethamine achieved better results in terms of survival than the others. The results indicated that Ag-NPs-F. sellowiana and S. ebulus have a significant growth effect on T. gondii in vitro and in vivo. Ag-NPs-S. ebulus extract has a more lethal effect on the parasite than Ag-NPs-F. sellowiana. It is suggested that in future investigate the induction of Toxoplasma-infected cell apoptosis using nanoparticles.


Fate of human albumin microsphere and spherocyte radioaerosols in the human tracheobronchial tree.
Human albumin microspheres (99mTc-HAM; 7-25 microns) and spherocytes (99mTc-S; 4-4.5 mu) are particles used for lung mucociliary clearance (MCC) measurements. If radiolabelled HAM aerosols are sent through an airway model to a screen, they appear peripherally distributed, whereas S present a more central and homogeneous distribution. The radioscanning evaluation of particle sedimentation in saline-filled tubes shows quite a different behavior pattern for S, HAM, and surfactant-coated HAM (S-C HAM). In these experimental conditions, S-C HAM and HAM floating properties were better than those of S. This could be explained by physical-chemical factors. Looking for the fate of organic particles after inhalation, we performed multiple bronchial biopsies in seven bronchitic patients, 2 h following inhalation of HAM and S. Scanning electron microscopy revealed that most of S was floating on the mucus layer, while HAM appeared deeply imbedded inside the mucus and partially digested. The same study performed on three bronchitic patients after S-C HAM inhalation, shows that S-C HAM float like S. In vitro, the time-course of tryptic digestion is similar for HAM and for S. However, in vivo, the different location of each particle on the bronchial surface might lead to a different digestion by trypsin and by PZ-peptidase, which are dosable in pathologic mucus. In our opinion, if HAM are coated with surfactant, this should improve the mucus-HAM interaction, thus helping to control variability in lung radioaerosol MCC studies.


Conditions which favor the C1-fixation by mouse IgG1.
The capacity of mouse IgG1 to mediate activation of the classical complement pathway was reinvestigated with purified C1 and under various conditions. Monoclonal and polyclonal IgG1 antibodies to TNP, which failed to show a haemolytic activity on TNP-SRBC with low epitopic density at physiologic salt concentration, invariably restored their activity when reacted to TNP-SRBC with relatively higher epitopic density and at a reduced salt concentration. Unliganded, monomeric IgG1 too proved to possess an inherent C1-binding capacity, but the susceptibility to competing salt was extremely high. These results were seemingly in accordance with the reduced number of basic amino acids in the plausible C1-binding region of the molecule.


Tailoring the surface-oxygen defects of a tin dioxide support towards an enhanced electrocatalytic performance of platinum nanoparticles.
Tin-dioxide nanofacets (SnO2 NFs) are crystal-engineered so that oxygen defects on the maximal {113} surface are long-range ordered to give rise to a non-occupied defect band (DB) in the bandgap. SnO2 NFs-supported platinum-nanoparticles exhibit an enhanced ethanol-electrooxidation activity due to the promoted charge-transport via the DB at the metal-semiconductor interface.


Experimental evidence against the mitochondrial theory of aging. A study of isolated human skeletal muscle mitochondria.
The mitochondrial theory of aging was tested with optimised preparation techniques. Mitochondria were isolated from approximately 90 mg quadriceps muscle from healthy humans at age 70+ and 20+. The content of mitochondrial protein was approximately 10 mg g(-1) muscle and the yields were approximately 40%. The mitochondrial integrity was high as judged from the respiratory control and P/O ratios. No general membrane alterations or changes in the cytochrome contents were observed. BSA decreased the non-phosphorylating rates of respiration equally in both age groups. Thirteen different enzyme activities were assayed and normalised to protein content and citrate synthase activity. Most of the critical levels for detection of declines were <10%. In the 70+ group, the activity for fatty acid oxidation was decreased by approximately 20%. Two inherently low activities associated with oxidation of sarcoplasmic NADH were also decreased, probably related to the age change of fibre types. The remaining activities measured, e.g. those of pyruvate dehydrogenase, tricarboxylic acid cycle, respiratory chain, and ATP synthesis, were not observed to be lowered. Thus, the central bioenergetic systems appeared unaltered with age. The obvious discord with reported age declines of human skeletal muscle mitochondrial function is discussed. It is concluded that the present results are incompatible with the mitochondrial theory of aging.


[From bearing arms to nursing care].
Having benefited from professional redeployment that has fully met his expectations, a former soldier who has become a nurse shares with us his work in a medical/social organization with residents of areas facing job insecurity.


[A method for assessing reliability of different rates of morbidity with temporary disability in small contingents of workers].
Suggested is the technique for mathematical processing of morbidity data proceeding from the replacement of common indicators per 100 workers by partial derivatives proportional to the number of work days a year. Reliability of changes in transforming indicators has been evaluated by means of statistical processing of small parts through Fisher's function phi. The advantages of the proposed technique lie in the fact that it has become possible to obtain important information on morbidity rates for the limited amount of investigation data and to reveal correlation of workers' health status to unfavourable occupational factors.


PRCC reduces the sensitivity of cancer cells to DNA damage by inhibiting JNK and ATM/ATR pathways and results in a poor prognosis in hepatocellular carcinoma.
The proline rich mitotic checkpoint control factor (PRCC) is involved in the splicing process of pre-mRNA. This study aims to elucidate PRCC molecular function, regulatory mechanism and diagnostic value in hepatocellular carcinoma (HCC). The tissue microarray and serum samples from HCC patients were used to investigate the clinical value of PRCC. The biological function and molecular mechanism of PRCC were demonstrated by cell biology, biochemical and animal experiments. The relationship between PRCC and intratumoral heterogeneity (ITH) was analyzed by bioinformatics. PRCC was highly expressed in HCC tissues and related to the poor prognosis of HCC patients, its contents were elevated in the preoperative sera of HCC patients. PRCC exhibited high application potential as a substitute or adjuvant of alpha-fetoprotein (AFP) for clinical diagnosis of HCC. It had no significant effect on the proliferation of cancer cells, but could inhibit spheroid formation and metastasis of HCC cells in vitro and in vivo. The high ectopic expression of PRCC made cancer cells insensitive to DNA damage, and enhanced the heterogeneity of HCC cells by inhibiting the JNK/ATM/ATR/ATF2 axis. The HCC patients with high PRCC expression had high ITH, which corresponded to a short overall survival in patients. PRCC has high application potential as a substitute or adjuvant of AFP for clinical diagnosis of HCC. The high ectopic expression of PRCC not only caused HCC cells to resist to cell death induced by DNA damage, but also endowed cancer cells with numerous DNA mutations to become increasingly heterogeneous, finally leading to a poor prognosis in HCC patients. These data suggested PRCC could be a promising therapeutic target in HCC patients.


[IL-18 and TNF-α promote the expression of IL-18Rβ in 3T3-L1 adipocytes and RAW264.7 macrophages].
To explore the effects of interleukin 18 (IL-18) and tumor necrosis factor alpha (TNF-α) on the expression of IL-18 receptor beta (IL-18Rβ) in 3T3-L1 adipocytes and RAW264.7 macrophages. The level of IL-18Rβ was determined by reverse transcription PCR and Western blotting in both 3T3-L1 adipocytes and RAW264.7 macrophages after processed by different concentrations of IL-18 and TNF-α. The level of IL-18Rβ mRNA and protein significantly increased in 3T3-L1 adipocytes after treated with 10 ng/mL, 100 ng/mL TNF-α. The expression of IL-18Rβ was also raised in RAW264.7 macrophages after treated with 10 ng/mL, 100 ng/mL IL-18. IL-18Rβ could be up-regulated by IL-18 or TNF-α in 3T3-L1 adipocytes and RAW264.7 macrophages. IL-18 may be an important factor involved in the inflammation of adipose tissues in diabetes and obesity.