tRNA Methylation Is a Global Determinant of Bacterial Multi-drug Resistance.
Gram-negative bacteria are intrinsically resistant to drugs because of their double-membrane envelope structure that acts as a permeability barrier and as an anchor for efflux pumps. Antibiotics are blocked and expelled from cells and cannot reach high-enough intracellular concentrations to exert a therapeutic effect. Efforts to target one membrane protein at a time have been ineffective. Here, we show that m1G37-tRNA methylation determines the synthesis of a multitude of membrane proteins via its control of translation at proline codons near the start of open reading frames. Decreases in m1G37 levels in Escherichia coli and Salmonella impair membrane structure and sensitize these bacteria to multiple classes of antibiotics, rendering them incapable of developing resistance or persistence. Codon engineering of membrane-associated genes reduces their translational dependence on m1G37 and confers resistance. These findings highlight the potential of tRNA methylation in codon-specific translation to control the development of multi-drug resistance in Gram-negative bacteria.


Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease.
The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease. Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure. In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes. In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.


Differences in Health Care Expenditures Among Non-Latino Whites and Asian Subgroups Vary Along the Distribution of the Expenditures.
Using a nationally representative sample from the 2013 to 2016 Medical Expenditure Panel Survey, we examined differences among non-Latino Whites and Asian subgroups (Asian Indians, Chinese, Filipinos, and other Asians) across distributions of total health care expenditures and out-of-pocket (OOP) expenditures. For total health care expenditures, differences between Asian and White adults persisted throughout the distribution, but the magnitude of the difference was larger at no or low levels of expenditures than at high expenditure levels. A similar pattern was observed in OOP expenditures, but the magnitude of the difference was substantially larger at low levels of expenditures. The extent of the difference varied by Asian subgroup, but this trend persisted across all the subgroups. Similar trends were observed by nativity and limited English proficiency. Our findings suggest that differences in health care expenditures between Whites and Asians are more pronounced at low expenditure levels.


Friendship closeness inventory: development and psychometric evaluation.
This study developed a psychometrically sound measure of closeness in Australian men's (n = 59) and women's (n = 77) same-sex friendships, the Friendship Closeness Inventory. Subscales were developed to measure both masculine and feminine styles of closeness in three domains of Emotional Closeness, Behavioural Closeness, and Cognitive Closeness. The inventory was subjected to reliability checks which supported the reliability of each scale, and factor analyses which supported the 3-factor design. Correlations among ratings on subscales suggested that the affective, behavioural, and cognitive dimensions are distinguishable but related components of friendship. Group comparisons indicated that women rated themselves closer to their same-sex friends on the affective dimension than men. Researchers have suggested that sex-role socialisation may partly account for sex differences in self-ratings of emotional expressiveness in friendships. There were no significant differences between men's and women's ratings on the behavioural and cognitive aspects of friendships. The cognitive element may need further exploration in further scale development as it measures only one aspect of cognitive closeness: the perceived influence of friends. Pending further validation, the inventory appears potentially useful for research exploring affective, behavioural, and cognitive elements of young men's and women's friendships.


Unmasking emotion: exposure duration and emotional engagement.
Effects of exposure duration on emotional reactivity were investigated in two experiments that parametrically varied the duration of exposure to affective pictures from 25-6000 ms in the presence or absence of a visual mask. Evaluative, facial, autonomic, and cortical responses were measured. Results demonstrated that, in the absence of a visual mask (Experiment 1), emotional content modulated evaluative ratings, cortical, autonomic, and facial changes even with very brief exposures, and there was little evidence that emotional engagement increased with longer exposure. When information persistence was reduced by a visual mask (Experiment 2), differences as a function of hedonic content were absent for all measures when exposure duration was 25 ms but statistically reliable when exposure duration was 80 ms. Between 25-80 ms, individual differences in discriminability were critical in observing affective reactions to masked pictures.


[Primary squamous cell carcinoma of the ovary].
A 61-year-old woman underwent laparotomy because of a right ovarian cyst 25 cm in diameter and clinically benign. Unexpectedly, a workup showed primary squamous cell carcinoma of the ovary. The patient received adjuvant radiation therapy. Follow-ups have not revealed any signs of relapse. The histogenesis of this rare tumor is uncertain, but the diagnosis is important because the prognosis and the response to adjuvant therapy of primary ovarian squamous cell carcinoma is probably worse than for other ovarian epithelial carcinomas.


Respondent reactions to sensitive questions.
WE ADMINISTERED DEBRIEFING PROBES TO gauge respondent discomfort in reaction to sensitive questions. These probes assessed respondents' own reactions to being asked to report on substance use (subjective discomfort), as well as their beliefs about the reaction of others (projective discomfort). We investigated whether a sample of men from the general population were more uncomfortable with questions about drug use than a sample of men who have sex with men (MSM) surveyed from the same city (Chicago). We also investigated whether those who disclosed drug use on the survey experienced higher levels of discomfort. Contrary to opinions often expressed as research ethics committee (REC) recommendations, questions about drug use do not generate much subjective discomfort. MSM did not differ from the general population with respect to subjective discomfort. General population males did, however, report higher levels of "drug specific" projective discomfort. Respondents disclosing recent drug use reported higher levels of subjective discomfort. Implications for the REC practice, researcher and REC education, and directions for future research are discussed.


Thoracoabdominal endaortectomy in case of type B aortic dissection.
Despite remarkable progress in both, diagnostic and therapeutic development in treating aortic dissections, this continues to be one of the most severe vascular disorders and is subject to high mortality rates. While aortic dissections of Type A can be treated surgically today, in the majority of patients with Type B dissections hypotensive treatment is the method of choice, providing a better chance of survival and the effective prevention of aneurysm formation and rupture at the site of the intimal tear. However in certain cases, Type B dissection generates either isthmic aneurysm formation, or, with distal progression, may result in long segmental thoracic, thoraco-abdominal or abdominal deterioration of the aorta and its side branches. The spinal, visceral, renal and lower limb ischemia threatens the viability of these organs and hypotensive medication may enhance this risk. Emergency diagnostic work-up and selective surgical reconstruction could lead to reduced mortality. In our department we have undertaken 33 thoracoabdominal endoaortectomies with meticulous reconstruction of renal and visceral orifices. The mortality rate in this subgroup of patients was 6%. Based on our experience with Type B aortic dissections we recommend open "endoaortectomy" in selected cases in order to improve the long-term outcome.


Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model.
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks. BCAA supplementation significantly improved hepatic steatosis, inflammation, fibrosis, and tumors in Ath+HF mice at 68 weeks. GeneChip analysis demonstrated the significant resolution of pro-fibrotic gene expression by BCAA supplementation. The anti-fibrotic effect of BCAA was confirmed further using platelet-derived growth factor C transgenic mice, which develop hepatic fibrosis and tumors. In vitro, BCAA restored the transforming growth factor (TGF)-β1-stimulated expression of pro-fibrotic genes in hepatic stellate cells (HSC). In hepatocytes, BCAA restored TGF-β1-induced apoptosis, lipogenesis, and Wnt/β-Catenin signaling, and inhibited the transformation of WB-F344 rat liver epithelial stem-like cells. BCAA repressed the promoter activity of TGFβ1R1 by inhibiting the expression of the transcription factor NFY and histone acetyltransferase p300. Interestingly, the inhibitory effect of BCAA on TGF-β1 signaling was mTORC1 activity-dependent, suggesting the presence of negative feedback regulation from mTORC1 to TGF-β1 signaling. Thus, BCAA induce an anti-fibrotic effect in HSC, prevent apoptosis in hepatocytes, and decrease the incidence of HCC; therefore, BCAA supplementation would be beneficial for patients with advanced liver fibrosis with a high risk of HCC.


Crystallization and preliminary crystallographic analysis of an esterase with a novel domain from the hyperthermophile Thermotoga maritima.
A predicted esterase (EstA) with an unusual new domain from the hyperthermophilic bacterium Thermotoga maritima has been cloned and overexpressed in Escherichia coli. The purified protein was crystallized by the hanging-drop vapour-diffusion technique in the presence of lithium sulfate and polyethylene glycol 8000. Selenomethionine-substituted EstA crystals were obtained under the same conditions and three different-wavelength data sets were collected to 2.6 A resolution. The crystal belongs to space group H32, with unit-cell parameters a = b = 130.2, c = 306.2 A. There are two molecules in the asymmetric unit, with a V(M) of 2.9 A3 Da(-1) and 58% solvent content.


High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment.
Spatial navigation is essential for everyday life and relies on complex network-level interactions. Recent evidence suggests that transcranial direct current stimulation (tDCS) can influence the activity of large-scale functional brain networks. We characterized brain-wide changes in functional network segregation (i.e. the balance of within vs. between-network connectivity strength) induced by high-definition (HD) tDCS in older adults with mild cognitive impairment (MCI) during virtual spatial navigation. Twenty patients with MCI and 22 cognitively intact older adults (healthy controls-HC) underwent functional magnetic resonance imaging following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right parietal cortex (center anode at P2) and delivered 2 mA for 20 min. Compared to HC, MCI patients showed lower brain-wide network segregation following sham HD-tDCS. However, following active HD-tDCS, MCI patients' network segregation increased to levels similar to those in HC, suggesting functional normalization. Follow-up analyses indicated that the increase in network segregation for MCI patients was driven by HD-tDCS effects on the "high-level"/association brain networks, in particular the dorsal-attention and default-mode networks. HD-tDCS over the right parietal cortex may normalize the segregation/integration balance of association networks during spatial navigation in MCI patients, highlighting its potential to restore brain activity in Alzheimer's disease.


Identification of key miRNA-gene pairs in gastric cancer through integrated analysis of mRNA and miRNA microarray.
Nowadays, the current bioinformatic methods have been increasingly applied in the field of oncological research. In this study, we expect a better understanding of the molecular mechanism of gastric cancer from the bioinformatic methods. By systematically addressing the differential expression of microRNAs (miRNAs) and mRNAs between gastric cancer specimens and normal gastric specimens with the application of bioinformatics tools, A total of 206 DEGs and 38 DEMs were identified. The Gene Ontology (GO) analysis of Annotation, Visualization and Integrated Discovery (DAVID) database revealed that the differentially expressed genes (DEGs) were significantly enriched in biological process, molecular function and cellular component, while Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed DEGs were significantly enriched in 8 signal pathways. The miRNA-gene regulatory network was constructed based on 385 miRNA-gene (DEM-DEG) pairs, consisting of 35 miRNAs and 107 target genes. In the regulatory network, the top 5 up-regulated genes were Transmembrane Protease, Serine 11B (TMPRSS11B), regulator of G protein signaling 1 (RGS1), cysteine rich angiogenic inducer 61 (CYR61), inhibin subunit beta A (INHBA), syntrophin gamma 1 (SNTG1), and the top 5 down-regulated genes were tumor necrosis factor receptor superfamily, member 19 (TNFRSF19), pleckstrin homology domain containing B2 (PLEKHB2), Tax1 binding protein 3 (TAX1BP3), presenilin enhancer, gamma-secretase subunit (PSENEN), NME/NM23 nucleoside diphosphate kinase 3 (NME3). Based on the gastric cancer patient database from Kaplan-Meier Plotter tools, we found that 8 of 10 genes with most significant changes in the miRNA-gene regulatory network possessed a prognostic value for survival time of gastric cancer patients. Patients with higher level of RGS1, PLEKHB2, TAX1BP3 and PSENEN in gastric cancer had a longer survival time compared with the patients with lower level of these genes. On the contrary, patients with higher level of INHBA, SNTG1, TNFRSF19 and NME3 were found associated with a shorter survival time. In conclusion, our findings provided several potential targets regarding gastric cancer, which may result in a new strategy to treat gastric cancer from a system rather than a single-gene perspective.


Assessment of three placement techniques for individualized positioning of the tip of the tracheal tube in children under the age of 4 years.
Accurate positioning of the tip of the tracheal tube (tube tip) is challenging in young children. Prevalent clinical methods include placement of intubation depth marks, palpation of the tube cuff in the suprasternal notch, or deliberate mainstem intubation with subsequent withdrawal. To compare the predictability of tube tip positions, variability of the resulting positions in relation to the carina was determined applying the three techniques in each patient. In 68 healthy children aged ≤4 years, intubation was performed with an age-adapted, high-volume low-pressure cuffed tube adjusting the imprinted depth mark to the level of the vocal cords. The tube tip-to-carina distance was measured endoscopically. Thereafter, placements using (I) cuff palpation in the suprasternal notch and (II) auscultation to determine change in breath sounds during withdrawal after bronchial mainstem intubation were completed in random order. Tube tip position above the carina was higher when using depth marks (mean = 36.8 mm) compared with cuff palpation in the suprasternal notch (mean = 19.0 mm). Variability, expressed as sd, was lowest with the mainstem intubation technique (5.2 mm) followed by the cuff palpation (7.4 mm) and the depth mark technique (11.2 mm) (P < 0.005). Auscultation after deliberate mainstem intubation and cuff palpation resulted in a tube tip position above the carina that was shorter and more predictable than placement of the tube using depth markings.


Feasibility and safety of targeting mitochondria for cancer therapy - preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor.
Mitochondria are key tumor drivers, but their suitability as a therapeutic target is unknown. Here, we report on the preclinical characterization of Gamitrinib (GA mitochondrial matrix inhibitor), a first-in-class anticancer agent that couples the Heat Shock Protein-90 (Hsp90) inhibitor 17-allylamino-geldanamycin (17-AAG) to the mitochondrial-targeting moiety, triphenylphosphonium. Formulated as a stable (≥24 weeks at -20°C) injectable suspension produced by microfluidization (<200 nm particle size), Gamitrinib (>99.5% purity) is heavily bound to plasma proteins (>99%), has intrinsic clearance from liver microsomes of 3.30 mL/min/g and minimally penetrates a Caco-2 intestinal monolayer. Compared to 17-AAG, Gamitrinib has slower clearance (85.6 ± 5.8 mL/min/kg), longer t1/2 (12.2 ± 1.55 h), mean AUC0-t of 783.1 ± 71.3 h∙ng/mL, and unique metabolism without generation of 17-AG. Concentrations of Gamitrinib that trigger tumor cell killing (IC50 ~1-4 µM) do not affect cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2B6, CYP2C8 or ion channel conductance (Nav1.5, Kv4.3/KChIP2, Cav1.2, Kv1.5, KCNQ1/mink, HCN4, Kir2). Twice weekly IV administration of Gamitrinib to Sprague-Dawley rats or beagle dogs for up to 36 d is feasible. At dose levels of up to 5 (rats)- and 12 (dogs)-fold higher than therapeutically effective doses in mice (10 mg/kg), Gamitrinib treatment is unremarkable in dogs with no alterations in clinical-chemistry parameters, heart function, or tissue histology, and causes occasional inflammation at the infusion site and mild elevation of serum urea nitrogen in rats (≥10 mg/kg/dose). Therefore, targeting mitochondria for cancer therapy is feasible and well tolerated. A publicly funded, first-in-human phase I clinical trial of Gamitrinib in patients with advanced cancer is ongoing (ClinicalTrials.gov NCT04827810).


Evaluation of ultrasonic scattering for different cortical bone porosities and excitation frequencies: A numerical study.
Quantitative ultrasound is a promising and relative recent method for the assessment of bone. In this work, the interaction of ultrasound with the porosity of cortical bone is investigated for different frequencies. Emphasis is given on the study of complex scattering effects induced by the propagation of an ultrasonic wave in osseous tissues. Numerical models of cortical bone are established with a porosity of 0, 5 and 10% corresponding to healthy homogeneous bone, healthy inhomogeneous bone and normal ageing, respectively. Different excitation frequencies are applied in the range 0.2-1 MHz. The scattering amplitude and the acoustic pressure are calculated for multiple angles and receiving positions focusing on the backward direction. The results indicate that the application of higher frequencies can better distinguish changes in the energy distribution in the backward direction due to alterations of the cortical porosity.


Sensitive detection of tetracyclines using europium-sensitized fluorescence with EDTA as co-ligand and cetyltrimethylammonium chloride as surfactant.
The determination of tetracyclines (TC) in aqueous solutions, based on europium-sensitized fluorescence, has been improved using EDTA as co-ligand and cetyltrimethylammonium chloride as surfactant. The method involves working in slightly alkaline solutions with the formation of a new chelate where the lanthanide ion is bound to the beta-diketone group. The method is about 6 times more sensitive than that with the Eu-TC-Triton system and LODs are 2.5 x 10(-10), 5 x 10(-10), 1.5 x 10(-9) and 2 x 10(-9) mol l-1 for TC, oxytetracycline, chlortetracycline and doxycycline, respectively. The method has been applied to the determination of TC in calf serum without sample pretreatment. The mean recovery was close to 102% and the lowest concentration attainable in serum samples was better than 0.1 microgram ml-1.


Spatiotemporal adaptive evolution of an MHC immune gene in a frog-fungus disease system.
Genetic diversity of major histocompatibility complex (MHC) genes is linked to reduced pathogen susceptibility in amphibians, but few studies also examine broad spatial and temporal patterns of MHC and neutral genetic diversity. Here, we characterized range-wide MHC diversity in the Northern leopard frog, Rana pipiens, a species found throughout North America that is experiencing disease-related declines. We used previously sequenced neutral markers (mitochondrial DNA and microsatellites), sequenced an expressed MHC class IIß gene fragment, and measured infection prevalence and intensity of the global fungal pathogen Batrachochytrium dendrobatidis (Bd) across 14 populations. Four populations were sampled across two decades, enabling temporal comparisons of selection and demography. We recovered 37 unique MHC alleles, including 17 that were shared across populations. Phylogenetic and population genetic patterns between MHC and neutral markers were incongruent, and five MHC codon positions associated with peptide binding were under positive selection. MHC heterozygosity, but not neutral marker heterozygosity, was a significant factor explaining spatial patterns of Bd prevalence, whereas only environmental variables predicted Bd intensity. MHC allelic richness (AR) decreased significantly over time but microsatellite-based AR did not, highlighting a loss of functional immunogenetic diversity that may be associated with Bd selective pressures. MHC supertype 4 was significantly associated with an elevated risk of Bd infection, whereas one supertype 2 allele was associated with a nearly significant reduced risk of Bd. Taken together, these results provide evidence that positive selection contributes to MHC class IIß evolution in R. pipiens and suggest that functional MHC differences across populations may contribute to disease adaptation.


Potential animal models of seasonal affective disorder.
Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions.


Histamine-induced chloride channels in apical membrane of isolated rabbit parietal cells.
The electrical properties of the apical membrane of isolated rabbit parietal cells were studied using the patch-clamp technique. The apical membrane of the parietal cells plated on Matrigel and maintained in culture conditions was identified by lectin-binding studies. Cell-attached and excised inside-out patches from 10(-4) M cimetidine-treated parietal cells infrequently contained Cl- channels (9% of the patches). A single class of voltage-dependent outwardly rectifying Cl- channels with 24 +/- 1-pS conductance was observed in 75% of the patches from cells stimulated (acid secreting) by 10(-4) M histamine. Other anions passed through these channels with a permeability sequence of I- (1.2) greater than Br- (1.1) greater than or equal to Cl- (1.0) greater than NO3- (0.7) greater than SO4(2-) (0.1), but there was a very low permeability for Na+ or K+ (PCl-/PNa+ or PCl-/PK+ greater than 5). In inside-out patch configurations the Cl- channel was insensitive to Ba2+ and stilbene derivatives but was inhibited by diphenylamine-2-carboxylic acid in a manner characteristic of a reversible open-channel blocker. It is concluded that H2-receptor agonist stimulation of acid secretion by rabbit parietal cells activates Cl- channels in the apical cell membrane.


Cell-dependent differential cellular uptake of PNA, peptides, and PNA-peptide conjugates.
Peptide nucleic acid (PNA) oligomers were conjugated to cell-penetrating peptides: pAnt, a 17-residue fragment of the Drosophila protein Antennapedia, and pTat, a 14-amino acid fragment of HIV protein Tat. A 14-mer PNA was attached to the peptide by disulfide linkage or by maleimide coupling. The uptake of (directly or indirectly, via biotin) fluorescein-labeled peptides, PNAs, or PNA-peptide conjugates was studied by fluorescence microscopy, confocal laser scanning microscopy, and fluorometry in five cell types. In SK-BR-3, HeLa, and IMR-90 cells, the PNA-peptide conjugates and a T1, backbone-modified PNA were readily taken up (2 microM). The PNA was almost exclusively confined to vesicular compartments in the cytosol. However, the IMR-90 cells also showed a weak diffuse staining of the cytoplasm. In the U937 cells, we observed a very weak and exclusively vesicular staining with the PNA-peptide conjugates and the T(lys)-modified PNA. No evident uptake of the unmodified PNA was seen. In H9 cells, both peptides and the PNA-peptide conjugates quickly associated with the membrane, followed by a weak intracellular staining. A cytotoxic effect resulting in artificial staining of the cells was observed with fluoresceinated peptides and PNA-peptide conjugates at concentrations above 5-10 microM, depending on cell type and incubation time. We conclude that uptake of PNAs in many cell types can be achieved either by conjugating to certain peptides or simply by charging the PNA backbone using lysine PNA units. The uptake is time, temperature, and concentration dependent and mainly endocytotic. Our results also show that proper controls for cytotoxicity should always be carried out to avoid misinterpretation of visual data.


Acute myocardial infarction therapy using calycosin and tanshinone co-loaded; mitochondrion-targeted tetrapeptide and cyclic arginyl-glycyl-aspartic acid peptide co-modified lipid-polymer hybrid nano-system: preparation, characterization, and anti myocardial infarction activity assessment.
Acute myocardial infarction (AMI) is one of the most common ischemic heart diseases. However, lack of sufficient drug concentration (in the ischemic heart) is the major factor of treatment failure. It is urgent for researchers to engineer novel drug delivery systems to enhance the targeted delivery of cardioprotective agents. The aim of the present study was to investigate the anti-AMI ability of calycosin (CAL) and tanshinone (TAN) co-loaded; mitochondrion-targeted tetrapeptide (MTP) and cyclic arginyl-glycyl-aspartic acid (RGD) peptide co-modified nano-system.: We prepared CAL and TAN combined lipid-polymer hybrid nano-system, and RGD was modified to the system to achieve RGD-CAL/TAN NS. MTP-131 was conjugated with PEG and modified onto the nanoparticles to achieve dual ligands co-modified MTP/RGD-CAL/TAN NS. The physicochemical properties of nano-systems were characterized. The AMI therapy ability of the systems was investigated in AMI rats' model. The size of MTP/RGD-CAL/TAN NS was 170.2 ± 5.6 nm, with a surface charge of -18.9 ± 1.9 mV. The area under the curve (AUC) and blood circulation half-life (T1/2) of MTP/RGD-CAL/TAN NS was 178.86 ± 6.62 μg·min/mL and 0.47 h, respectively. MTP/RGD-CAL/TAN NS exhibited the most significant infarct size reduction effect of 22.9%. MTP/RGD-CAL/TAN NS exhibited the highest heart accumulation and best infarct size reduction effect, which could be used as a promising system for efficient treatment of cardiovascular diseases.


Sister chromatid exchange induction and the course of DNA duplication, two mechanisms of sister chromatid exchange induction by ENU and the role of BrdU.
The aims of the present study were to establish the following: (i) the course of sister chromatid exchange (SCE) induction by ethylnitrosourea (ENU) in the first, second and third divisions as a function of the exposure time; (ii) the persistence of SCE-inducing lesions and the determination of whether or not they are always involved in SCE formation; (iii) the effect of bromodeoxyuridine (BrdU) incorporation on the induction and persistence of SCE. Three-way differential staining of sister chromatids in murine bone marrow cells in vivo was used in the present study. The results indicate the following: (i) SCE induction in each cell division depends on the course of DNA duplication, suggesting that SCE occurs at the replication fork; (ii) the cell population under study could be considered synchronous and had a cell cycle duration of nearly 9 h; (iii) in the second and third cell divisions ENU preferentially induced SCE in the cycle in which the exposure occurred; (iv) lesions induced by exposure to ENU did not cause SCE at the same site in subsequent divisions; (v) ENU was also capable of producing a long-lasting induction of SCE in BrdU-unsubstituted DNA; (vi) the sensitivity to SCE induction by the mutagen increases nearly proportionally to BrdU incorporation into DNA.


Optimizing suicide gene therapy for head and neck cancer.
An effective "suicide gene" therapy strategy in experimental studies has been the use of the herpes simplex virus thymidine kinase gene (HSV-tk) to sensitize tumors to the cytotoxic effects of ganciclovir administration. Previous studies using this model have focused on utilizing maximal viral titers and high levels of ganciclovir that are not compatible with human dosing. Because of the high ganciclovir doses and the maximal viral titers, this strategy has limited application to actual clinical scenarios. In the following studies the authors investigate tumor regression in an oral squamous cell carcinoma animal model as a function of variable adenoviral titers and more physiologic ganciclovir dosing. Using adenoviral titers ranging from 1 x 10(8) to 2 x 10(9) plaque forming units (pfu) to treat oral tumors, they found no statistical difference in tumor regression among the different viral doses, despite differences in mitotic activity. Each treatment group, however, demonstrated a significant effect on tumor regression when compared with controls. Furthermore, the authors were able to reduce the level of ganciclovir administration to 10 mg/kg twice daily from established levels of 100 to 150 mg/kg twice daily while maintaining significant tumor responses to the HSV-tk therapy. Mean survival of animals treated with this lower ganciclovir dose was significantly higher than in controls and was equal to established means based on previous studies using higher ganciclovir doses. The optimization of this suicide gene therapy strategy is imperative in order to minimize theoretical and known viral and ganciclovir toxicities while establishing a foundation upon which to design appropriate and effective clinical trials.


Integration of late-enhanced MRI and electroanatomical mapping for substrate ablation of poorly tolerated ventricular tachycardia.
We describe the case of a patient with a poorly tolerated ventricular tachycardia (VT) in which a substrate ablation was performed. The ablation was guided by the integrated images of the scar obtained by MRI and electro-anatomical mapping. This combined technique can make substrate ablation more accurate and may have a role in the ablation of unmappable VT.


Computed tomography manifestations of tricuspid regurgitation.
Six patients undergoing dynamic contrast enhanced abdominal computed tomography (CT) for upper abdominal symptoms and signs are described. Each patient demonstrated early, intense opacification of the inferior vena cava (IVC) and hepatic veins, exceeding that in the aorta on scans through the upper abdomen. Opacification of the IVC returned to normal on more caudal slices. All six patients were found to have echocardiographically proven tricuspid regurgitation (TR). It is suggested that this sign occurs in patients with TR due to direct reflux of contrast from the right atrium into the IVC during protracted bolus injection. Additional CT findings included patchy parenchymal liver enhancement in four patients and ascites in five. Recognition of this simple sign may direct the clinician to a cardiac aetiology for upper abdominal symptoms and signs.


[Tendons: inflammatory and degenerative pathology].
Tendons may be affected by a variety of pathologic conditions, including those caused by overuse and inflammatory diseases. Sonography is a very sensitive means of detecting tendonous pathology because of its spatial resolution and its comparative and dynamic capabilities. Moreover its wide availability makes it the preferred first-line imaging modality in these cases. This paper reviews the inflammatory and degenerative conditions that may involve the tendons and their sonographic appearances.


[Goblet cell carcinoid of the appendix].
Appendiceal goblet cell carcinoids are mixed tumors including neuroendocrine cells and intestinal type of goblet cells. Compared to typical carcinoids, goblet cell carcinoids are malignant tumors with degree of malignity differing from case to case. Carcinoid syndrom is not present. There is poor prognosis in larger tumors. Appendectomy is a sufficient therapeutical approach in small tumors, hemicolectomy should be performed in larger ones. There is limited experience with chemotherapy in metastasizing tumors and sporadic with somatostatin analogues.


Toward an asthma patient-reported outcome measure for use in digital remote monitoring.
To develop and test a patient-reported outcome measure (PROM) for suitability in digital remote asthma symptom monitoring to identify uncontrolled asthma. We modified a 5-item PROM that does not require a license, the asthma control measure (ACM), from a one-month to one-week lookback period, and evaluated it using the 5-item asthma control questionnaire (ACQ-5). We recruited subjects with asthma through MTurk, an online platform. In a sample of 498 subjects, the ACM identified uncontrolled asthma with sensitivity 0.99 and specificity 0.65. The two measures correlated with r = 0.81. The ACM modified to a weekly lookback period can differentiate patients with well-controlled asthma from those with uncontrolled asthma. This PROM does not require a license and can be used in digital remote monitoring interventions.


Isolation and Characterization of Concanavalin A-labeled Plasma Membranes of Carrot Protoplasts.
The plasma membranes of protoplasts released from carrot suspension culture cells were labeled with [(14)C]acetyl-concanavalin A. After homogenization a single labeled membrane fraction was isolated in a continuous isopycnic Renografin gradient. The labeled membranes peaked at an apparent density of 1.14 grams per cubic centimeter between the Golgi fraction at a density of 1.11 grams per cubic centimeter as determined by latent IDPase activity and the mitochondria at a density of 1.16 grams per cubic centimeter as determined by the cytochrome c oxidase activity. This method provided a very discrete peak of putative plasma membrane. On discontinuous Renografin gradients a relatively pure fraction of labeled plasma membranes could be readily isolated at the 1.122 to 1.146 grams per cubic centimeter interface. The labeled fraction was enriched in both an ATPase (pH 6.5) and a glucan synthetase with a pH optimum of 6.5 whose activity was promoted by magnesium and cellobiose. Enzyme activities were not altered by the membrane label.


A Series of Oral Lesions Presenting to an Otolaryngology Department.
This study was performed to assess the incidence and intraoral distribution of different mucosal lesions in a representative population. Retrospective review of clinical notes and assessment of histology reports of patients were performed, who presented with different oral lesions to University Hospital Galway, between January 2007 and December 2008.Of the 106 histology reports evaluated, 94 were identified as benign lesions while 12 were malignant lesions. 96 of these patients were referred from G.P services, 6 patients were referred from other departments while 4 patients came through emergency department by self referral. The numbers and incidence of the commonest lesions in order of frequency were chronic inflammation 20 (18.8%), papilloma 19 (17.1%), fibroma 09 (8.4%), mucocele 09 (8.4%) and leukoplakia 08 (7.5%).We concluded that majority of the presented oral lesions are benign (88.%). Chronic inflammation (18.8%) is the commonest benign oral lesion and all white lesions which represents 34% of oral lesions are not true leukoplakia.


Cation-π Complexes of Silver Studied with Photodissociation and Velocity-Map Imaging.
Ag+(aromatic) ion-molecule complexes of benzene, toluene, or furan are generated in the gas phase by laser vaporization in a supersonic expansion. These ions are mass selected in a time-of-flight spectrometer and studied with ultraviolet laser photodissociation and photofragment imaging. UV laser excitation results in dissociative charge transfer (DCT) for these ions, producing neutral silver atom and the respective aromatic cation as the photofragments. Velocity-map imaging and slice imaging techniques are employed to investigate the kinetic energy release in these photodissociation processes. In each case, DCT produces significant kinetic energy, and evidence is also found for excitation of the internal rovibrational degrees of freedom for the molecular cations. Analysis of the kinetic energy release together with the known ionization energies of silver and the molecular ligands provides new information on the cation-π bond energies.


Using visual art and collaborative reflection to explore medical attitudes toward vulnerable persons.
Vulnerable persons often face stigma-related barriers while seeking health care. Innovative education and professional development methods are needed to help change this. We describe an interdisciplinary group workshop designed around a discomfiting oil portrait, intended to trigger provocative conversations among health care students and practitioners, and we present our mixed methods analysis of participant reflections. After the workshop, participants were significantly more likely to endorse the statements that the observation and interpretive skills involved in viewing visual art are relevant to patient care and that visual art should be used in medical education to improve students' observational skills, narrative skills, and empathy with their patients. Subsequent to the workshop, significantly more participants agreed that art interpretation should be required curriculum for health care students. Qualitative comments from two groups from two different education and professional contexts were examined for themes; conversations focused on issues of power, body image/self-esteem, and lessons for clinical practice. We argue that difficult conversations about affective responses to vulnerable persons are possible in a collaborative context using well-chosen works of visual art that can stand in for a patient.


Proteomic biomarkers for blast neurotrauma: targeting cerebral edema, inflammation, and neuronal death cascades.
Proteomics for blast traumatic brain injury (bTBI) research represents an exciting new approach that can greatly help to address the complex pathology of this condition. Antibody-based platforms, antibody microarrays (AbMA), and reverse capture protein microarrays (RCPM) can complement the classical methods based on 2D gel electrophoresis and mass spectrometry (2DGE/MS). These new technologies can address problematic issues, such as sample complexity, sensitivity, quantitation, reproducibility, and analysis time, which are typically associated with 2DGE/MS. Combined with bioinformatics analysis and interpretation of primary microarray data, these methods will generate a new level of understanding about bTBI at the level of systems biology. As biological and clinical knowledge and the availability of these systems become more widely established, we expect that AbMA and RCPM will be used routinely in clinical diagnostics, and also for following therapeutic progress. At the technical level, we anticipate that these platforms will evolve to accommodate comprehensive, high-speed, label-free analysis on a human proteome-wide scale.


Evaluation of the effects of subgingival injection of Simvastatin on space re-opening after orthodontic space closure in adults.
Background. This clinical trial evaluated the effect of Simvastatin on space re-opening after orthodontic space closure and its effect on the gingival index (GI) and clinical attachment loss (CAL). Methods. 16 females, 25-40 years old, with spaces between anterior mandibular teeth due to chronic periodontitis were participated in this study. The patients were randomly divided into control and experimental groups. In the experimental group, 1.2% Simvastatin gel and in the control group, 0.9% sodium chloride as a placebo was injected into the pocket depth of the six anterior teeth. The amount of space reopening, GI and CAL were measured. Results. No serious complications were observed during interventions and follow-up periods. Space re-opening was significantly reduced in patients receiving Simvastatin (P < 0.001). Moreover, GI reduction was significantly greater in Sim-vastatin group compared to the control group (P < 0.001). However, CAL did not demonstrate a significant difference between the groups. Conclusion. Simvastatin may decrease space re-opening after orthodontic space closure in human anterior teeth.


Reduction in age of puberty in gilts consuming melatonin during decreasing or increasing daylength.
Two experiments were conducted to determine whether oral administration of melatonin alters the onset of puberty in gilts during naturally increasing or decreasing daylength. In Exp. 1, 20 crossbred prepubertal gilts weighing 77.5 +/- .5 kg at 171.8 +/- 1.0 d of age were assigned randomly to receive either a daily oral dose of 3 mg of melatonin (MEL) or ethanol vehicle (ETH) at 1530 from August 31 to December 1, 1987 (decreasing daylength). Gilts were exposed to mature boars for 20 min thrice weekly and blood samples were collected twice weekly. Serum concentrations of progesterone were used to establish age at puberty and length of estrous cycle. In Exp. 2, 20 crossbred prepubertal gilts weighing 67.7 +/- .7 kg at 143.8 +/- 1.1 d of age received either MEL or ETH treatment from February 1 to May 15, 1988 (increasing daylength). Age of puberty was less in gilts that received MEL than in gilts that received ETH in both Exp. 1 (198 +/- 3 vs 228 +/- 7 d; P less than .01) and Exp. 2 (183.8 +/- 2.7 d vs 194.3 +/- 3.3 d; P less than .05). Gilts that received MEL reached puberty at a lighter weight than gilts that received ETH in Exp. 1 (95.6 +/- 2.1 vs 112.4 +/- 3.9 kg; P less than .01) and Exp. 2 (88.1 +/- 1.5 vs 96.0 +/- 1.8 kg; P less than .01). Serum concentrations of LH and FSH, length of estrous cycles, and percentage of muscle of carcasses were similar between MEL and ETH gilts.(ABSTRACT TRUNCATED AT 250 WORDS)


Infrared atmospheric transmission of laser radiation.
Calculations have been made of the monochromatic transmission of HF, HCI, HBr, and DF laser radiations between 2400 cm(-1) and 3500 cm(-1) for nonhomogeneous atmospheric slant paths. Aerosol extinction, continuum molecular absorption, and line absorption are included in the computations. An approximate Voigt profile has been used to express mixed Doppler-Lorentz line broadening. HF P(2)(8) and DF P(2)(8) lines are chosen from among the presently operational cw chemical lasers for detailed studies. Their transmission characteristics at different altitudes are compared with those of CO and CO(2) lasers. Comparisons of these transmittance calculations with the theoretical calculations of McClatchey and Selby and experimental results have been made, and reasons for the discrepancies are discussed.


Correlates of the caregiving process in multiple sclerosis.
This study sought to identify predictors of general health, mood, family, and life satisfaction for spousal caregivers of persons with multiple sclerosis. Cross-sectional data were obtained through structured interviews with 34 husbands and 27 wives of the disabled individuals. Results of the hierarchical regression analyses indicated that objective burden, subjective burden, and perceived uncertainty about the illness situation accounted for the largest proportion of variance in caregivers' general health, mood, family and life satisfaction. Perceived social support explained an additional small, but significant proportion in caregivers' general health, mood, and family satisfaction. Contrary to expectation, family coping did not significantly explain any variance in caregiver outcome measures.


Light intensity modulation in a thermal medium.
The intensity of a low power He-Ne laser beam was modulated in a thermal medium consisting of a slab of lead glass by temperature fluctuations caused by the absorption of light from a higher power argon laser. Close agreement between experiment and analytical calculations has been obtained. This type of modulation permits the detection of small temperature fluctuations in materials that are partially transmitting to a low power laser.


Rottlerin induces a transformed phenotype in human keratinocytes.
PKCdelta plays a fundamental role in cell cycle control. Consistent with its proposed tumour suppressor function, ras transfection of the human keratinocyte cell line HaCaT results in a loss of PKCdelta expression mediated by TGFalpha (Exp. Cell Res., 219, 299, 1995). To get more insight into the role of PKCdelta in keratinocytes, we investigated the effects of Rottlerin, a specific inhibitor of protein kinase Cdelta, in HaCaT cells. After Rottlerin treatment, HaCaT cells lost their cobble-stone morphology and displayed a spindle-shaped, fibroblastic phenotype. Additionally, the establishment of cell-cell contacts was prevented. This was caused by an internalization of E-cadherin and beta-catenin as assessed by immunofluorescence. A similar phenotype was observed in the presence of a neutralizing anti-E-cadherin antibody. Rottlerin-treated HaCaT cells proliferated like transformed cells in a three-dimensional cell culture system. We therefore conclude that PKCdelta is involved in mediating cell-cell contacts via E-cadherin and hence regulates differentiation in HaCaT cells.


Manganese effects on the human neuroblastoma cell line SK-ER3.
SK-ER3 cells were recently demonstrated to represent a valuable model for the study of estrogen-inducible differentiation of neural cells in culture. This system may constitute an important tool also for the analysis of the effects of neurotoxic drugs. The present study demonstrates that short term exposure to Mn causes increased proliferation rate of SK-ER3 cells regardless of their differentiation. Long term treatment causes cell death in undifferentiated cells at concentrations of the metal as low as 100 nM. When the cells are differentiated with estrogens, death is observed only with a Mn concentration two orders of magnitude higher. Measurement of neurite extension and quantitation of tyrosine hydroxylase content after long-term exposure to the metal allow the conclusion that Mn does not alter the state of differentiation of SK-ER3 cells induced by the treatment with the hormone. The study underlines the importance of studying the effect of Mn in proliferating neural cells and demonstrates the toxic role of micromolar concentrations of the metal in fully differentiated neural cells. Since other authors produced evidence of effects of the metal on cell death and proliferation only at millimolar concentrations, and none described its proliferative activity, the model utilized in the present study seems to be of particular interest.


Atrichia with papular lesions: electron microscopic observations of cystic lesions.
Atrichia with papular lesions is a rare inherited skin disorder characterized by congenital atrichia with numerous papules. We describe a 27-year-old woman with atrichia, who had numerous papules on her scalp, nape, and axillae. Histologically, many keratinous cysts were seen in the middermis of a skin specimen from the nape. Electron microscopy showed that the developing keratinocytes in the walls of some cysts were rich in glycogen granules and had epidermoid keratinization with formation of keratohyaline granules and that laminated bodies were formed before keratinization. Langerhans cells were often seen in the walls of the cysts. In addition, a broad glassy vitreous layer surrounded the cyst wall. From these findings, it was suggested that the cystic lesions might have originated from immature or incomplete hair follicles. In particular, the structure of the cyst wall corresponded well to infundibular and/or isthmal portions of the outer root sheath of the hair follicle.


Oxidative stress induced by copper and iron complexes with 8-hydroxyquinoline derivatives causes paraptotic death of HeLa cancer cells.
Here, we report the antiproliferative/cytotoxic properties of 8-hydroxyquinoline (8-HQ) derivatives on HeLa cells in the presence of transition metal ions (Cu(2+), Fe(3+), Co(2+), Ni(2+)). Two series of ligands were tested, the arylvinylquinolinic L1-L8 and the arylethylenequinolinic L9-L16, which can all interact with metal ions by virtue of the N,O donor set of 8-HQ; however, only L9-L16 are flexible enough to bind the metal in a multidentate fashion, thus exploiting the additional donor functions. L1-L16 were tested for their cytotoxicity on HeLa cancer cells, both in the absence and in the presence of copper. Among them, the symmetric L14 exhibits the highest differential activity between the ligand alone (IC50 = 23.7 μM) and its copper complex (IC50 = 1.8 μM). This latter, besides causing a significant reduction of cell viability, is associated with a considerable accumulation of the metal inside the cells. Metal accumulation is also observed when the cells are incubated with L14 complexed with other late transition metal ions (Fe(3+), Co(2+), Ni(2+)), although the biological response of HeLa cells is different. In fact, while Ni/L14 and Co/L14 exert a cytostatic effect, both Cu/L14 and Fe/L14 trigger a caspase-independent paraptotic process, which results from the induction of a severe oxidative stress and the unfolded protein response.


Identifying the Factors Related to Depressive Symptoms Amongst Community-Dwelling Older Adults with Mild Cognitive Impairment.
High-level depressive symptoms have been reported in individuals with mild cognitive impairment (MCI), resulting in increased risk of progression to dementia. However, studies investigating the correlates of depressive symptoms among this population are scarce. This study aimed to investigate the significant socio-demographic, lifestyle-related and disease-related correlates of depressive symptoms among this cohort. Cross-sectional data were obtained from a sample of 154 Chinese community-dwelling older adults with MCI. MCI subjects were screened by the Montreal Cognitive Assessment. Depressive symptoms were measured by the Geriatric Depression Scale. Possible correlates of depressive symptoms in individuals with MCI were explored by multiple linear regressions. The prevalence of depressive symptoms among Chinese older adults with MCI was 31.8%. In multiple regression analysis, poor perceived positive social interaction, small social network, low level of physical activity, poor functional status, subjective memory complaint, and poor health perception were correlated with depressive symptoms. The findings highlight that depressive symptoms are sufficient to warrant evaluation and management in older adults with MCI. Addressing social isolation, assisting this vulnerable group in functional and physical activities, and cultivating a positive perception towards cognitive and physical health are highly prioritized treatment targets among individuals with MCI.


New light-focusing fibers made by a continuous process.
A new continuous manufacturing process for light-focusing glass fibers has been developed using fast ion-exchange in a special double crucible. By use of this new process, new low-loss optical fibers with a transmission loss of 20 dB/km at wavelengths between 0.81 microm and 0.85 microm and a transmission capacity of more than a few Gbit/sec for 1 km were fabricated from low-loss bulk glass prepared by an improved raw powder refinement technique and by clean melting.


Stratospheric temperature measurement with scanning Fabry-Perot interferometer for wind retrieval from mobile Rayleigh Doppler lidar.
Temperature detection remains challenging in the low stratosphere, where the Rayleigh integration lidar is perturbed by aerosol contamination and ozone absorption while the rotational Raman lidar is suffered from its low scattering cross section. To correct the impacts of temperature on the Rayleigh Doppler lidar, a high spectral resolution lidar (HSRL) based on cavity scanning Fabry-Perot Interferometer (FPI) is developed. By considering the effect of the laser spectral width, Doppler broadening of the molecular backscatter, divergence of the light beam and mirror defects of the FPI, a well-behaved transmission function is proved to show the principle of HSRL in detail. Analysis of the statistical error of the HSRL is carried out in the data processing. A temperature lidar using both HSRL and Rayleigh integration techniques is incorporated into the Rayleigh Doppler wind lidar. Simultaneous wind and temperature detection is carried out based on the combined system at Delhi (37.371°N, 97.374°E; 2850 m above the sea level) in Qinghai province, China. Lower Stratosphere temperature has been measured using HSRL between 18 and 50 km with temporal resolution of 2000 seconds. The statistical error of the derived temperatures is between 0.2 and 9.2 K. The temperature profile retrieved from the HSRL and wind profile from the Rayleigh Doppler lidar show good agreement with the radiosonde data. Specifically, the max temperature deviation between the HSRL and radiosonde is 4.7 K from 18 km to 36 km, and it is 2.7 K between the HSRL and Rayleigh integration lidar from 27 km to 34 km.


The treatment of menopausal symptoms by traditional Chinese medicine in Asian countries.
Menopausal symptoms (or climacteric syndrome) refer to a series of symptoms that occur during the perimenopausal and early postmenopausal period. About 80% of women will have various degrees of menopausal symptoms, and most of them need associated treatment. Asian women are more inclined to choose traditional Chinese medicine (TCM) in terms of therapeutic method, and menopausal hormone therapy has low acceptance because the women have been misinformed about the side effects of hormones. Therefore, TCM is used for menopausal symptoms in women in most Asian countries, including China, Japan, Vietnam, and South Korea. In the basic theory of TCM, the menopause is classified as the Kidney deficiency and imbalance of Yin and Yang; therefore, the treatment methods in either Chinese patent medicine or Chinese herbal medicine are aimed at supplementing the Kidney function and rebalancing Yin and Yang. It is believed that TCM treatment is suitable for patients with mild or moderate menopausal symptoms. The incidence rate of adverse reactions in terms of breast tenderness and irregular vaginal bleeding is lower than that of hormone therapy. However, there are few randomized, double-blind, placebo-controlled studies on TCM treatment of menopausal syndrome. Future studies should be undertaken to confirm its merits.


[Clinicopathological characteristics and prognostic analysis of bilateral primary breast cancer].
The aim of this study is to explore the clinicopathological characteristics, diagnosis, multidiscipline therapy and prognosis of bilateral primary breast cancer (BPBC). Clinical data of 133 patients with BPBC seen in Cancer Institute and Hospital of Tianjin Medical University from January 2005 to December 2008 were retrospectively analyzed and compared with those of 266 patients with unilateral primary breast cancer (UPBC). BPBC accounted for 2.08% of all breast cancer cases. Compared with UPBC, BPBC patients had earlier menarche, more postmenopause disease and fewer fertility(P<0.05). The T stage, pathological type, histological grade and tumor stage of the second tumor in BPBC patients were significantly different from those in UPBC cases (P<0.05). The ER and HER-2 status of both the two tumors in BPBC and the PR status of the second tumor in BPBC were also significantly different from those in UPBC(P<0.05). Besides, the menopause status when the first tumor happened and the lymph node metastasis status when the second tumor occurred were independent prognostic factors. There was no significant difference between the five-year disease free survival rates of UPBC and BPBC (79.3% and 72.8%, P>0.05), but the 5-year overall survival rates of UPBC and BPBC had significant difference(89.8% and 84.9%, P=0.02). The prognosis of UPBC and BPBC has significant differences. If the patient is premenopause when the first tumor occurs or had more than ten metastatic axillary lymph nodes in patient with the second one, she has a poorer prognosis. The pationts who underwent unilateral breast radical mastectomy have an increased risk of contralateral breast cancer. In order to have early detection, diagnosis and treatment, we should strengthen the follow-up of the high risk patients.


New Species and New Records of Buellia (Lichenized Ascomycetes) from Jeju Province, South Korea.
A new species and 2 new records of lichen genus Buellia were discovered from Chuja-do Island in Jeju Province during a recent floristic survey: B. chujana X. Y. Wang, S. Y. Kondr., L. Lőkös & J.-S. Hur sp. nov., B. halonia (Ach.) Tuck., and B. mamillana (Tuck.) W. A. Weber. The new species is characterized by a brown, areolate thallus, the presence of perlatolic acid, and a saxicolous habitat. Together with previously recorded species, 10 Buellia species were confirmed from Jeju-do Island. Among these species, 3 growing in the exposed rocky area contained xanthone (yellowish lichen thallus, UV + orange), indicating that production of xanthone in this genus might be a defense strategy against the harm of UV light. Although the genus Buellia has been thoroughly studied in Korea before, novel species have been discovered continuously, and large species diversity has been found in this crustose genus, even from a small rocky island. This study indicates that the coastal area harbors a vast number of crustose lichen species, and there is great potential to discover unknown lichens in the coastal rocky area in Korea.


Validation of Varian's AAA algorithm with focus on lung treatments.
The objective of this study was to examine the accuracy of the Anisotropic Analytical Algorithm (AAA). A variety of different field configurations in homogeneous and in inhomogeneous media (lung geometry) was tested for the AAA algorithm. It was also tested against the present Pencil Beam Convolution (PBC) algorithm. Two dimensional (2D) dose distributions were measured for a variety of different field configurations in solid water with a 2D array of ion chambers. The dose distributions of patient specific treatment plans in selected transversal slices were measured in a Thorax lung phantom with Gafchromic dosimetry films. A Farmer ion chamber was used to check point doses in the Thorax phantom. The 2D dose distributions were evaluated with a gamma criterion of 3% in dose and 3 mm distance to agreement (DTA) for the 2D array measurements and for the film measurements. For AAA, all fields tested in homogeneous media fulfilled the criterion, except asymmetric fields with wedges and intensity modulated plans where deviations of 5 and 4%, respectively, were seen. Overall, the measured and calculated 2D dose distributions for AAA in the Thorax phantom showed good agreement -- both for 6 and 15 MV photons. More than 80% of the points in the high dose regions met the gamma criterion, though it failed at low doses and at gradients. For the PBC algorithm only 30-70% of the points met the gamma criterion. The AAA algorithm has been shown to be superior to the PBC algorithm in heterogeneous media, especially for 15 MV. For most treatment plans the deviations in the lung and the mediastinum regions are below 3%. However, the algorithm may underestimate the dose to the spinal cord by up to 7%.


Phosphoramidate ProTides of the anticancer agent FUDR successfully deliver the preformed bioactive monophosphate in cells and confer advantage over the parent nucleoside.
The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence of the current drugs on active transport and nucleoside kinase-mediated activation. They are also resistant to metabolic deactivation by phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR with variation in the aryl, ester, and amino acid regions. Notably, only certain ProTide motifs are successful in delivering the nucleoside monophosphate into intact cells. We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression.


Nephroprotective effect of persimmon leaves (Diospyros kaki L.f.) against CCl4-induced renal toxicity in Swiss Albino rats.
Diospyros kaki L.f. fruit and leaves are traditionally used for the treatment of hypertension, angina, internal hemorrhage, antithrombotic and anti-inflammatory effects.In the current study, the protective effects of ethyl acetate (Per-1), n-butanol (Per-2), and aqueous (Per-3) fractions of Diospyros kaki leaves against carbon tetrachloride (CCl4) induced nephrotoxicity in Swiss albino rats were tested. Animal were divided into nine groups; each group consists of six animals. The groups were : group I was untreated and kept as control, group II was treated with CCl4 only, group III (silymarin with CCl4); group IV (Per-1 100 mg/kg with CCl4);group V (Per-1 200 mg/kg with CCl4); group VI (Per-2 100 mg/kg with CCl4); group VII (Per-2 200 mg/kg with CCl4); group VIII (Per-3 100 mg/kg with CCl4); and group IX (Per-3 200 mg/kg with CCl4). Silymarin was used as standard drug. All tested fractions were found active (except Per-1 at low dose of 100 mg/kg) with significant value (p < 0.001) compared to CCl4 only group. Serum creatinine, malondialdehyde (MDA), and uric acid were significantly (p < 0.001) lowered in group VII-IX as compared to CCl4 only group. Similarly, total protein (TP) and non-protein sulfhydryls(NP-SH) level in kidney tissues were significantly (p < 0.001) elevated in the same groups compared to CCl4 only group. Further to check the cardio-protective potential, biochemical parameters such as LDH, creatine kinase, TP, MDA, and NP-SH levels in myocardial tissues were also estimated.These findings confirmed that the n-butanol and aqueous fractions are active and recommended for further bioactive phytoconstituents screening. Repeated column chromatography on silica gel G and sephadex-LH-20 of the active n-butanol fraction, four flavonoids were isolated. Based on the spectroscopic NMR data, compounds were identified as kaempferol (1), quercetin (2), astragalin (3), and rutin (4).


Interim Analysis of a Phase II study of epirubicin and paclitaxel as first-line therapy in patients with metastatic breast cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to be used routinely in clinical practice, has aroused considerable interest for its high single-agent activity in breast cancer and its novel mechanism of action. The 4' epimer of doxorubicin, epirubicin is an agent with high activity against breast cancer but a lower rate of toxic side effects, especially cardiotoxic events, than its parent compound. Although the paclitaxel/doxorubicin combination has yielded response rates between 63% and 94% in phase I/II studies, some severe cardiotoxic events were reported. The rationale for our study was to evaluate the paclitaxel/epirubicin combination, focusing mainly on cardiotoxicity. In all, 57 patients with metastatic breast cancer entered the study, 28% of whom had primary metastatic breast cancer with large tumors at the primary site. Half of the patients had received adjuvant chemotherapy. Study medication consisted of 60 mg/m2 epirubicin given intravenously over 1 hour, followed by paclitaxel 175 mg/m2 administered as a 3-hour intravenous infusion after premedication with steroids, antihistamines, and H2 antagonists. The main toxicity was neutropenia (World Health Organization toxicity index grade 3/4, 72%). Other hematologic side effects were rare and no febrile neutropenia was reported. Peripheral neuropathy, arthralgia, and myalgia were mild (only World Health Organization grade 1 and 2). All patients had alopecia. The paclitaxel dose was escalated to 200 mg/m2 in eight patients, four of whom received a further escalation to 225 mg/m2. Severe neutropenia necessitated dose reductions in eight patients. No cardiac adverse events were reported. Of 41 patients evaluable for response, seven had complete remissions and 21 had partial remissions (68%). An additional 12 patients (29%) had stable disease. The combination of paclitaxel 175 mg/m2 and epirubicin 60 mg/m2 can be administered safely to patients with metastatic breast cancer. Although response was not the primary end point of this trial, the response data are nonetheless encouraging and suggest that further evaluation of the role of this combination in the first-line treatment of metastatic breast cancer is warranted.


Pneumoperitoneum in repair of giant hernias and eventrations.
The common use of laparoscopy has made many surgeons familiar with the use of pneumoperitoneum. It is important to know the therapeutic advantage of this technique in the repair of giant hernias and eventrations where the viscera are forced out of the abdominal cavity.


State-of-the-Art Review of Electrospun Gelatin-Based Nanofiber Dressings for Wound Healing Applications.
Electrospun nanofiber materials have been considered as advanced dressing candidates in the perspective of wound healing and skin regeneration, originated from their high porosity and permeability to air and moisture, effective barrier performance of external pathogens, and fantastic extracellular matrix (ECM) fibril mimicking property. Gelatin is one of the most important natural biomaterials for the design and construction of electrospun nanofiber-based dressings, due to its excellent biocompatibility and biodegradability, and great exudate-absorbing capacity. Various crosslinking approaches including physical, chemical, and biological methods have been introduced to improve the mechanical stability of electrospun gelatin-based nanofiber mats. Some innovative electrospinning strategies, including blend electrospinning, emulsion electrospinning, and coaxial electrospinning, have been explored to improve the mechanical, physicochemical, and biological properties of gelatin-based nanofiber mats. Moreover, numerous bioactive components and therapeutic agents have been utilized to impart the electrospun gelatin-based nanofiber dressing materials with multiple functions, such as antimicrobial, anti-inflammation, antioxidation, hemostatic, and vascularization, as well as other healing-promoting capacities. Noticeably, electrospun gelatin-based nanofiber mats integrated with specific functions have been fabricated to treat some hard-healing wound types containing burn and diabetic wounds. This work provides a detailed review of electrospun gelatin-based nanofiber dressing materials without or with therapeutic agents for wound healing and skin regeneration applications.


Is pedophilia a sexual orientation?
In this article, I address the question of whether pedophilia in men can be construed as a male sexual orientation, and the implications for thinking of it in this way for scientific research, clinical practice, and public policy. I begin by defining pedophilia and sexual orientation, and then compare pedophilia (as a potential sexual orientation with regard to age) to sexual orientations with regard to gender (heterosexuality, bisexuality, and homosexuality), on the bases of age of onset, correlations with sexual and romantic behavior, and stability over time. I conclude with comments about the potential social and legal implications of conceptualizing pedophilia as a type of sexual orientation in males.


Tall tails: cryo-electron microscopy of phage tail DNA ejection conduits.
The majority of phages, viruses that infect prokaryotes, inject their genomic material into their host through a tubular assembly known as a tail. Despite the genomic diversity of tailed phages, only three morphological archetypes have been described: contractile tails of Myoviridae-like phages; short non-contractile tails of Podoviridae-like phages; and long and flexible non-contractile tails of Siphoviridae-like phages. While early cryo-electron microscopy (cryo-EM) work elucidated the organisation of the syringe-like injection mechanism of contractile tails, the intrinsic flexibility of the long non-contractile tails prevented high-resolution structural determination. In 2020, four cryo-EM structures of Siphoviridae-like tail tubes were solved and revealed common themes and divergences. The central tube is structurally conserved and homologous to the hexameric rings of the tail tube protein (TTP) also found in contractile tails, bacterial pyocins, and type VI secretion systems. The interior surface of the tube presents analogous motifs of negatively charged amino acids proposed to facilitate ratcheting of the DNA during genome ejection. The lack of a conformational change upon genome ejection implicates the tape measure protein in triggering genome release. A distinctive feature of Siphoviridae-like tails is their flexibility. This results from loose inter-ring connections that can asymmetrically stretch on one side to allow bending and flexing of the tube without breaking. The outer surface of the tube differs greatly and may be smooth or rugged due to additional Ig-like domains in TTP. Some of these variable domains may contribute to adsorption of the phage to prokaryotic and eukaryotic cell surfaces affecting tropism and virulence.


Endoplasmic Reticulum Stress Induction and ERK1/2 Activation Contribute to Nefazodone-Induced Toxicity in Hepatic Cells.
Nefazodone, an antagonist for the 5-hydroxytryptanine receptor, has been used for the treatment of depression. Acute liver injury has been documented to be associated with the use of nefazodone; however, the mechanisms of nefazodone-induced liver toxicity are not well defined. In this report, using biochemical and molecular analyses, we characterized the molecular mechanisms underlying the hepatotoxicity of nefazodone. We found that nefazodone induced endoplasmic reticulum (ER) stress in HepG2 cells, as the expression of typical ER stress markers, including CHOP, ATF-4, and p-eIF2α, was significantly increased, and splicing of XBP1 was observed. Nefazodone-suppressed protein secretion was evaluated using a Gaussia luciferase reporter assay that measures ER stress. The ER stress inhibitors (4-phenylbutyrate and salubrinal) and knockdown of ATF-4 gene attenuated nefazodone-induced ER stress and cytotoxicity. Nefazodone activated the MAPK signaling pathway, as indicated by increased phosphorylation of JNK, ERK1/2, and p38. Inhibition of ERK1/2 reduced ER stress caused by nefazodone. Taken together, our findings suggest that ER stress contributes to nefazodone-induced toxicity in HepG2 cells and that the MAPK signaling pathway plays an important role in ER stress.


[Toxoplasmosis in the Congo Republic. Seroepidemiological study].
Our study group, which was composed of over 2,500 subjects, aged between 0 and 65 years, came from different regions of Congo. The samples obtained were examined for the presence of IgG and IgM against Toxoplasma gondii. IgG were detected in about 33% of children over 9 years and in about 40% of adults. A study of IgM confirmed the early contact of children with the parasite (11% of positive samples for children between 4 and 9) and that of young women (5 to 7% positivity for subjects between 15 and 30). In spite of local variations, the extremely humid climate did not allow us to detect a difference based on the origin of the samples as furthermore there seems to be an ethnic factor involved. Among the different types of professions in our sample only farmers appear to be less frequently positive. Diet, as well as contact with animals do not seem to have an influence.


Intraventricular aneurysms--three case reports.
Three rare cases of purely intraventricular aneurysms are described, including a unique aneurysm in the fourth ventricle. A 30-year-old female, a 47-year-old male, and an 11-year-old girl presented with disturbance of consciousness due to massive intraventricular hemorrhage. Digital subtraction angiography revealed an idiopathic peripheral aneurysm in the fourth ventricle in the first patient, and aneurysms in the lateral ventricle associated with moyamoya disease in the latter two patients. The former two aneurysms were treated surgically and histologically confirmed to be pseudoaneurysms. The latter aneurysm disappeared spontaneously within 2 months after onset. The aneurysm in the lateral ventricle was resected via a parietal corticotomy with stereotactic insertion of an 8-Fr silicone tube to guide the approach route. This method was very useful because computerized neuronavigation was not available. The aneurysm in the fourth ventricle was resected via a midline suboccipital approach with C-1 laminectomy. Conservative treatment is usually recommended initially for patients with intraventricular aneurysm because spontaneous cure often occurs. We recommend direct surgery if the size of the aneurysm remains unchanged, because the risk of surgery has decreased recently owing to new techniques for neuronavigation.


Tumour volume is an independent predictor of prostate-specific antigen recurrence in patients undergoing radical prostatectomy for clinically localized prostate cancer.
Authors from the USA sought to establish the relationship between tumour volume, pathological stage and outcomes after radical prostatectomy. In a large series of patients they found that tumour volume was correlated directly with pathological stage, and that it was independently correlated with PSA recurrence. The authors suggested that tumour volume had a potential use for prognostication in patients undergoing radical prostatectomy. Two papers, one from the USA and one from Germany, advise a re-staging TUR in patients with superficial bladder cancer who are at high risk of early tumour progression. In a large series of patients they found that residual tumour after initial resection was commoner than might be expected, and that the second resection indicated the way to earlier radical treatment and a better prognosis. To establish the relationship between tumour volume (TV), pathological stage and outcome after radical prostatectomy (RP), as TV is theoretically an important variable in prostate cancer pathology, but to date it has not been routinely reported and its independent prognostic significance is not well defined. The study included 431 consecutive patients undergoing RP for clinically localized cancer, from January 2000 to January 2002, who had a pathological examination of totally submitted whole-mount processed RP specimens. In addition to Gleason grade, tumour stage and margin assessment by standard techniques, TV was determined by digital planimetry. The total TV or index TV, for cases with obvious discrete separate tumours, were correlated with pathological stage and prostate-specific antigen (PSA) recurrence. The mean (range) follow-up was 25.4 (6-51) months, and the mean TV for all patients was 3.28 (0.4-38.8) mL. There was a direct correlation between TV and pathological stage (P < 0.001). The TV for organ-confined and extraprostatic disease was 2.09 and 6.02 mL, respectively (P < 0.001). In a multivariate analysis, TV was an independent predictor of PSA recurrence (P = 0.04). The mean TV for patients with PSA recurrence vs no recurrence was 6.8 and 2.6 mL, respectively (P < 0.001). TV correlates directly with pathological stage in RP specimens; furthermore, it is independently correlated with PSA recurrence. TV has potential use for prognostication in patients undergoing RP, and may be combined with other well established clinical variables to aid in predicting outcomes.


Photoelastic analysis of stress distribution in different retention systems for facial prosthesis.
The aim of this study was to assess the behavior and stress distribution of 3 retention systems associated with implant for facial prosthesis by using the photoelasticity method. A photoelastic model was made from the replica of the orbital region on the left side of a dry skull with two 4-mm implants fixed in the superior orbital region. Three facial prosthetic retention systems were made for this study: O'ring, bar-clip, and magnets. The set (model/retention systems/prosthesis) was placed in a polariscope, and then traction began to be applied to the retention systems. The limit values for removal of the retention system were obtained by tests performed in an EMIC Universal test machine. The results were obtained by observation during the experiments and by photographic record of the stress behavior in the photoelastic model, resulting from the traction of the retention systems. In the magnet system, a lowest formation of fringes was verified both around and between the implants; in the O'ring system, the formation of photoelastic fringes was noted between the implants in the apical region; and in the bar-clip system, there was a greater concentration of colored fringes in the regions between the implants and cervical area. Based on the results obtained, it was concluded that the retention systems produced different stress distribution characteristics that, in general, were concentrated in the area around the implants, and the highest concentration of fringes, in increasing order, occurred in the retention systems of the magnets, O'ring, and bar-clip.


catena-Poly[[bis(thiocyanato-kappa N)cadmium(II)]-di-mu-thiourea-kappa(4)S:S].
The Cd(II) ion in the title complex, [Cd(SCN)(2)[SC(NH(2))(2)](2)](infinity), is situated at a centre of symmetry, and is bound to two N atoms belonging to thiocyanate groups and to four S atoms of bridging thiourea ligands. The structure consists of infinite chains of slightly distorted edge-shared Cd-centred octahedra. The bridging S atoms of two thiourea ligands comprise the common edge. Some thermal properties are described.


Mechanical and spatial determinants of cytoskeletal geodesic dome formation in cardiac fibroblasts.
This study tests the hypothesis that the cell cytoskeletal (CSK) network can rearrange from geodesic dome type structures to stress fibers in response to microenvironmental cues. The CSK geodesic domes are highly organized actin microarchitectures within the cell, consisting of ordered polygonal elements. We studied primary neonatal rat cardiac fibroblasts. The cues used to trigger the interconversion between the two CSK architectures (geodesic domes and stress fibers) included factors affecting spatial order and the degree of CSK tension in the cells. Microfabricated three-dimensional substrates with micrometre sized grooves and peaks were used to alter the spatial order of cell growth in culture. CSK tension was modified by 2,3-butanedione 2-monoxime (BDM), cytochalasin D and the hyphae of Candida albicans. CSK geodesic domes occurred spontaneously in about 20% of the neonatal rat cardiac fibroblasts used in this study. Microfabricated structured surfaces produced anisotropy in the cell CSK and effectively converted geodesic domes into stress fibers in a dose-dependent manner (dependence on the period of the features). Affectors of actin structure, inhibitors of CSK tension and cell motility, e.g. BDM, cytochalasin D and the hyphae of C. albicans, suppressed or eliminated the geodesic domes. Our data suggest that the geodesic domes, similar to actin stress fibers, require maintenance of CSK integrity and tension. However, microenvironments that promote structural anisotropy in tensed cells cause the transformation of the geodesic domes into stress fibers, consistent with topographic cell guidance and some previous CSK model predictions.


Evaluation of Physical Properties of Tissue Conditioning Materials as used in Functional Impression - A Lab Study.
The purpose of this study was to identify the basic physical properties of 3 commonly available tissue-conditioning materials to gain knowledge for their clinical use as impression materials. A total of 60 samples were prepared and each sample was mixed and prepared according to manufacture direction. Finally five specimens of each tissue conditioners were subjected for each of the above test at different time duration. The study showed that all the materials underwent water loss from the time of mixing to 24 hr & became hard. The plasticity of coecomfort & viscogel decreased from the time of mixing upto 1hr & 2hr respectively & again increased after that till 24 hrs, but the softone showed decreased plasticity after 30 min till 24hrs. Softone & coecomfort at 30 min showed better flow & more plasticity than that of viscogel. The dimensional accuracy of softone & viscogel at 30min is better than that of coecomfort. Thus softone at 30 min after mixing has better Dimensional accuracy, Plasticity and Flow; suitable for making functional impression then that of Coe-comfort and Viscogel. How to cite this article: Shylesh K B S, Hallikerimath R B, Rajeev V V, Ganesh S, Meenakshi S. Evaluation of Physical Properties of Tissue Conditioning Materials as used in Functional Impression - A Lab Study. J Int Oral Health 2013; 5(3):20-27.


Determination of the optical functions of transparent glasses by using spectroscopic ellipsometry.
Two-channel spectroscopic polarization-modulation ellipsometry measurements have been made on four different glasses (fused SiO(2), finely annealed BK-7, a lead-indium-phosphate glass, and a germanium-arsenic-selenium glass). We show that this technique is sensitive to thin surface layers and that these surface layers can be modeled by using the Bruggeman effective-medium theory with 50% glass and 50% voids. By correcting the experimental spectra for this surface layer, we determined the refractive index of the sample within an error of +/-0.002 in the transparent region. For wavelength regions where the material is normally opaque, the ellipsometric data can be corrected for this overlayer, thereby increasing the accuracy of the determination of both the refractive index and the extinction coefficient.


A MAS NMR study of the bacterial ABC transporter ArtMP.
ATP-binding cassette (ABC) transport systems facilitate the translocation of substances, like amino acids, across cell membranes energised by ATP hydrolysis. This work describes first structural studies on the ABC transporter ArtMP from Geobacillus stearothermophilus in native lipid environment by magic-angle spinning NMR spectroscopy. The 2D crystals of ArtMP and 3D crystals of isolated ArtP were prepared in different nucleotide-bound or -unbound states. From selectively (13)C,(15)N-labelled ArtP, several sequence-specific assignments were obtained, most of which could be transferred to spectra of ArtMP. Residues Tyr133 and Pro134 protrude directly into the ATP-binding pocket at the interface of the ArtP subunits, and hence, are sensitive monitors for structural changes during nucleotide binding and hydrolysis. Distinct sets of NMR shifts were obtained for ArtP with different phosphorylation states of the ligand. Indications were found for an asymmetric or inhomogeneous state of the ArtP dimer bound with triphosphorylated nucleotides. With this investigation, a model system was established for screening all functional states occurring in one ABC transporter in native lipid environment.


[Effect of various blood components and additive solutions on phytohemagglutinin (PHA)-induced lymphocyte proliferation].
The effect of red blood cells (RBC), fresh plasma (FP), fresh frozen plasma (FFP) and different storage solutions (e.g. CPDA-1, CPD, PAGGS-M, SAG-M, Adsol) on the immune response was investigated in human lymphocyte cultures. The inhibitory activity was measured by determining the effect of different components on the PHA-induced T-cell proliferation. Our results indicate that the inhibitory effect is caused by an as yet unidentified plasma factor (e.g. anti-idiotypic antibodies, soluble HLA-class I or II antigens). In contrast, pure RBC or blood storage solutions revealed only minimal effects on the T-cell response.


Reducing wrinkles and other signs of aging.
As the aging population increases so does the demand for more effective modalities to combat the ravages of skin aging. It is important for dermatology nurses to understand and be able to explain to patients the preventive measures for skin aging and what can be realistically expected from currently available treatments.


Assessing the validity of plasma phospholipid fatty acids as biomarkers of dairy fat intake using data from a randomized controlled intervention trial.
Plasma phospholipid pentadecanoic acid (C15:0), heptadecanoic acid (C17:0), and trans-palmitoleic acid (trans-C16:1n-7) are correlates of dairy fat intake. However, their relative concentrations may be influenced by other endogenous factors, such as liver fat content, and their validity as biomarkers of dairy fat intake has yet to be established. We investigated whether liver fat content modifies relations between concentrations of C15:0, C17:0, and trans-C16:1n-7 (alone and in combination with iso-C17:0) and known dairy fat intake in the context of a randomized controlled intervention study. We further examined the proportion of dairy fat intake explained by these fatty acids on their own and when considering liver fat content. We used data from a 12-wk intervention trial in which participants (n = 62) consumed diets limited in dairy (0.3 g/d of dairy fat), rich in low-fat dairy (8.7 g/d of dairy fat), or rich in full-fat dairy (28.5 g/d of dairy fat). We used linear regression models to examine relations between relative fatty acid concentrations and grams per day of dairy fat intake, liver fat percentage, and their interaction. Only trans-C16:1n-7 in isolation (β: 0.0004 ± 0.0002, P = 0.03) and combined with iso-C17:0 (β: 0.002 ± 0.0005, P < 0.0001) were consistently positively associated with dairy fat intake regardless of liver fat content. Trans-C16:1n-7 combined with iso-C17:0 also explained the greatest proportion of variation (35.4%) in dairy fat intake. C15:0 and C17:0 were not associated with dairy fat intake after adjusting for liver fat and were predicted to be higher in relation to increased dairy fat intake only among individuals with elevated liver fat. The potential for liver fat to affect relative plasma phospholipid concentrations of C15:0 and C17:0 raises questions about their validity as biomarkers of dairy fat intake. Of the fatty acid measures tested, trans-C16:1n-7 combined with iso-C17:0, especially with adjustment of liver fat, age, and sex, may provide the most robust estimate of dairy fat consumption.


Identification of a helix-turn-helix motif of Bacillus thermoglucosidasius HrcA essential for binding to the CIRCE element and thermostability of the HrcA-CIRCE complex, indicating a role as a thermosensor.
In the heat shock response of bacillary cells, HrcA repressor proteins negatively control the expression of the major heat shock genes, the groE and dnaK operons, by binding the CIRCE (controlling inverted repeat of chaperone expression) element. Studies on two critical but yet unresolved issues related to the structure and function of HrcA were performed using mainly the HrcA from the obligate thermophile Bacillus thermoglucosidasius KP1006. These two critical issues are (i) identifying the region at which HrcA binds to the CIRCE element and (ii) determining whether HrcA can play the role of a thermosensor. We identified the position of a helix-turn-helix (HTH) motif in B. thermoglucosidasius HrcA, which is typical of DNA-binding proteins, and indicated that two residues in the HTH motif are crucial for the binding of HrcA to the CIRCE element. Furthermore, we compared the thermostabilities of the HrcA-CIRCE complexes derived from Bacillus subtilis and B. thermoglucosidasius, which grow at vastly different ranges of temperature. The thermostability profiles of their HrcA-CIRCE complexes were quite consistent with the difference in the growth temperatures of B. thermoglucosidasius and B. subtilis and, thus, suggested that HrcA can function as a thermosensor to detect temperature changes in cells.


[A new approach to local ablation therapy for hepatocellular carcinoma--hand-assisted laparoscopic radio-frequency ablation].
We have developed a radio-frequency ablation using hand-assisted laparoscopic surgery (HALS-RFA) for hepatocellular carcinoma, and it applied for 10 patients who were difficult to be treated by common laparoscopic surgery (LS) from November 2001. The reasons for selection of HALS-RFA were severe adhesions in 3 patients, anatomical location at the hepatic dome in 3 patients, lesions adjacent to other organs or vasculatures in 3 patients, and co-operation for another organ in 1 patient. We compared efficacies of HALS to other ablation therapeutic techniques with LS and open surgery (OS). The average amount of bleeding was 85 ml in HALS, 14 ml in LS and 319 ml in OS. The amount of HALS was lesser than that of OS, but not significant. Post operative maximal CRP level was 3.2 mg/dl, 4.9 mg/dl and 10.5 mg/dl in HALS, LS, and OS, respectively, with a statistical significance between HALS and OS. Complications occurred in 2 out of 10 cases (20%) in HALS, 2 out of 62 cases (3.2%) in LS and 3 out of 9 cases (33%) in OS. Recurrence in the treated site was encountered in 1 out of 10 cases (10%) in HALS, 2 out of 62 cases (3.2%) in LS and none (0%) of OS. Based on these findings, we conclude that HALS-RFA seems to be a minimally invasive and highly effective treatment.


A Physical Perspective to the Inductive Function of Myelin-A Missing Piece of Neuroscience.
Starting from the inductance in neurons, two physical origins are discussed, which are the coil inductance of myelin and the piezoelectric effect of the cell membrane. The direct evidence of the coil inductance of myelin is the opposite spiraling phenomenon between adjacent myelin sheaths confirmed by previous studies. As for the piezoelectric effect of the cell membrane, which has been well-known in physics, the direct evidence is the mechanical wave accompany with action potential. Therefore, a more complete physical nature of neural signals is provided. In conventional neuroscience, the neural signal is a pure electrical signal. In our new theory, the neural signal is an energy pulse containing electrical, magnetic, and mechanical components. Such a physical understanding of the neural signal and neural systems significantly improve the knowledge of the neurons. On the one hand, we achieve a corrected neural circuit of an inductor-capacitor-capacitor (LCC) form, whose frequency response and electrical characteristics have been validated by previous studies and the modeling fitting of artifacts in our experiments. On the other hand, a number of phenomena observed in neural experiments are explained. In particular, they are the mechanism of magnetic nerve stimulations and ultrasound nerve stimulations, the MRI image contrast issue and Anode Break Excitation. At last, the biological function of myelin is summarized. It is to provide inductance in the process of neural signal, which can enhance the signal speed in peripheral nervous systems and provide frequency modulation function in central nervous systems.


[The new configuration of migratory exchanges between Mexico and the United States: the case of mid-sized cities in the state of Jalisco].
"Migration between the urban areas of the State of Jalisco and the United States has undergone profound transformations in the last twenty years. These are apparent in the recent decrease of the flow of first time migrants and the migration balance; the growing participation of women in this flow; and in the diversity of activities carried out by the migrants, both in their place of origin and in the United States.... Migration is translated by an important transfer of currency, mostly used for the support of the families of the migrants; by a shift in the activities of the migrants, from wages towards different forms of self-employment; and by the sway of the primary and secondary sectors of economy towards the tertiary sector, once the migrants reinstall themselves in their cities of origin." (SUMMARY IN ENG AND SPA)


Steady-state imaging with inhomogeneous magnetization transfer contrast using multiband radiofrequency pulses.
Inhomogeneous magnetization transfer (ihMT) is an emerging form of MRI contrast that may offer high specificity for myelinated tissue. Existing ihMT and pulsed MT sequences often use separate radiofrequency pulses for saturation and signal excitation. This study investigates the use of nonselective multiband radiofrequency pulses for simultaneous off-resonance saturation and on-resonance excitation specifically for generation of ihMT contrast within rapid steady-state pulse sequences. A matrix-based signal modeling approach was developed and applied for both balanced steady state free precession and spoiled gradient echo sequences, accounting specifically for multiband pulses. Phantom experiments were performed using a combination of balanced steady state free precession and spoiled gradient echo sequences, and compared with model fits. A human brain imaging exam was performed using balanced steady state free precession sequences to demonstrate the achieved contrast. A simple signal model derived assuming instantaneous radiofrequency pulses was shown to agree well with full integration of the governing equations and provided fits to phantom data for materials with strong ihMT contrast (PL161 root mean square error = 0.9%, and hair conditioner root mean square error = 2.4%). In vivo ihMT ratio images showed the expected white matter contrast that has been seen by other ihMT investigations, and the observed ihMT ratios corresponded well with predictions. ihMT contrast can be generated by integrating multiband radiofrequency pulses directly into both spoiled gradient echo and balanced steady state free precession sequences, and the presented signal modeling approach can be used to understand the acquired signals.