Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction.
To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR). Thirty-four women with FGR diagnosed at <34.0 weeks were recruited. Serum angiogenic marker levels were estimated within 6 hours of a diagnosis of FGR. A receiver operating characteristic curve was used to determine the threshold of the sFlt-1/PlGF ratio to predict adverse outcomes. We used multivariable logistic regression analysis to examine the association between the sFlt-1/PlGF ratio and adverse outcomes. Finally, we used Kaplan-Meier analysis and the log-rank test to assess the probability of delay in delivery. Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25-72.8) was associated with adverse maternal and neonatal outcomes. A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR.


Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain.
Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for clinical pain therapy.


Successful recovery of sensation loss in upper brachial plexus injuries.
Injuries of the upper trunk of the brachial plexus may trigger motor and sensory deficits. There exists a growing body of literature with respect to the reconstruction of motor deficits in upper trunk brachial plexus injuries by using nerve transfers; albeit to date, very few old reports have focused on the reconstruction of sensory loss resulting from upper trunk injuries. In this case series, we review six cases (five males and one female) with upper trunk brachial plexus injuries undergoing sensory nerve transfers. Sensory reconstruction was carried out by using transfer of the ulnar to the median nerves, innervating adjacent aspects of the little and ring fingers (the fourth web space) and adjacent aspects of the thumb and the index finger (the first web space), respectively. The mean age of our six patients was 30.5 ± 9 years old (range 20-45). The mean time interval between the injury and subsequent surgery was 6.6 ± 1.8 months (range 5-10). Five patients achieved S3 or S3+ in both the thumb and the index finger while the sixth one regained S2+ in the index finger while also achieving S3 in the thumb according to the Highet-Zachary system scoring scale. These results suggest that nerve transfers can achieve satisfactory outcomes in patients having sensory reconstruction after upper brachial plexus injuries, and thus, we lay emphasis on reviving the use of sensory nerve transfer techniques in such patients.


Expression of HLA-B27 causes loss of migratory dendritic cells in a rat model of spondylarthritis.
In rats transgenic for human HLA-B27 and β(2) -microglobulin (B27-transgenic rats), colitis and peripheral inflammation develop spontaneously. Therefore, B27-transgenic rats provide a model of spondylarthritis. Because inflammation in these rats requires CD4+ T lymphocytes and involves intestinal pathology, we hypothesized that dendritic cells (DCs) that migrate from the intestine and control CD4+ T cell differentiation would be aberrant in B27-transgenic rats. Migrating intestinal lymph DCs were collected via thoracic duct cannulation from B27-transgenic and control (HLA-B7-transgenic or nontransgenic) rats. The phenotypes of these DCs and of mesenteric lymph node DCs were assessed by flow cytometry. The ability of DCs to differentiate from bone marrow precursors in vitro was also assessed. Lymph DCs showed increased activation and, strikingly, lacked the specific DC population that is important for maintaining tolerance to self-antigens. This population of DCs was also depleted from the mesenteric lymph nodes of B27-transgenic rats. Furthermore, in vitro culture of DCs from bone marrow precursors revealed a defect in the ability of B27-transgenic rats to produce DCs of the migratory phenotype, although the DCs that were generated induced enhanced interleukin-17 (IL-17) production from naive CD4+ T cells. We describe 2 different mechanisms by which HLA-B27 may contribute to inflammatory disease: increased apoptotic death of B27-transgenic DCs that normally function to maintain immunologic tolerance and enhanced IL-17 production from CD4+ T cells stimulated by the surviving B27-transgenic DCs.


Decreased endemic malaria in Suriname: moving towards elimination.
Suriname has moved from being the country with the highest annual parasite index in the Americas to one on the threshold of elimination. The progress toward elimination in the stable populations of Suriname between 2000 and 2015 is reviewed. Data was obtained from the Medical Mission and the Ministry of Health Malaria Programme case-reporting systems, and analysed with a focus on disease burden and differentiation of the disease geographically, by malaria species, age, gender, ethnicity, incidence and gametocytaemia. Between 2000 and 2015 there were 57,811 locally acquired cases of malaria in the stable populations of Suriname. A significant reduction in indigenous malaria cases was observed from 2006 to 2015. The number of imported malaria cases saw a relative increase compared to the number of autochthonous cases. In 2015 over 95% of the cases reported in stable communities are imported, mainly from neighbouring French Guiana, a department of France. The overall decline in malaria case incidence followed the mass-distribution of free long-lasting insecticide-impregnated mosquito nets and increased awareness building efforts, improved access to malaria services as a result of the introduction of Rapid Diagnostic Tests and the implementation of active case detection in high risk areas. In addition, improved management of Plasmodium falciparum infections was achieved with the introduction of artemisinin combination therapy. The existence of a network of policlinics in the interior ran by Medical Mission, for the indigenous population, allowed the rapid implementation of the strategy in stable communities. The success of malaria control in Suriname indicates that the availability at local level, of prompt and adequate prevention, diagnosis and treatment is a key requirement for the elimination of malaria.


Effects of Kudingcha Nanoparticles in Hyperlipidaemic Rats Induced by a High Fat Diet.
The herbal medicine Kudingcha has a bitter taste and low bioavailability for lipid reduction. To improve the bioavailability and ameliorate the compliance, we prepared Kudingcha nanoparticles and investigated their effect in hyperlipidaemic rats. In addition, the safety and lipid-lowering mechanism of the Kudingcha nanoparticles were examined. Kudingcha nanoparticles were prepared by ionotropic gelation and spray-drying. Seventy rats were randomly assigned into eight groups: a normal fat diet group (NF), a high-fat group (HF), a spontaneous recovery group (SR), a Kudingcha group (KDC), a blank nanoparticle group (B-N), and a Kudingcha nanoparticle groups (low, medium and high doses). All groups (except for the normal fat diet group) were fed a high-fat diet to establish hyperlipidaemia. Different interventions were administered to the treatment groups for four weeks. Serum lipids were measured using commercially available kits according to the recommended protocols. Liver morphology and histopathology were examined by a light microscope. The mRNA and protein levels of TLR4 and NF-κB were determined by RT-PCR and Western blotting, respectively. In addition, acute toxicity was evaluated by the LD50 test. The Kudingcha nanoparticles were spherical and had a smooth surface. The size distribution of the nanoparticles was 100-600 nm. Acute toxicity results revealed that the Kudingcha nanoparticles were a non-toxic substance. Compared with regular Kudingcha, TG and TC decreased distinctly in the Kudingcha nanoparticles, especially for the moderate and high dose groups (p<0.05). Moreover, the Kudingcha nanoparticles were superior in lowering body, liver and adipose tissue weights compared to Kudingcha (p<0.05). With respect to antioxidant properties, the nanoparticles also revealed an outstanding impact on serum SOD and MDA. In addition, liver morphology and histology in the moderate and high dose nanoparticle groups were similar to those in the normal group. Finally, the mRNA and protein expression levels of TLR4 and NF-κB in the liver tissue of the nanoparticle groups were significantly upregulated compared with the KDC group (p<0.05). Based on these results, we conclude that Kudingcha nanoparticles are a potent lipid-lowering agent and may have a potential role in the treatment of hyperlipidaemia and fatty liver disease.


Optimization of hydrophilic interaction LC by univariate and multivariate methods and its combination with salting-out liquid-liquid extraction for the determination of antihypertensive drugs in the environmental waters.
Hydrophilic interaction LC for the separation of four antihypertensive drugs was optimized by both univariate and multivariate methods. The column efficiency, resolution, and separation time were used as the three assessment parameters. The best separation condition of 97% ACN with 3% aqueous buffer containing 50 mM ammonium acetate at a pH of 3.0 was obtained by the two optimization methods. The multivariate optimization, orthogonal array design herein, was demonstrated to be a little tedious, but afforded a much better understanding of underlying separation factors. The content of ACN in the mobile phase contributed most significantly to separation. Furthermore, sample diluent and injection volume were found to influence the chromatographic performance. To match the hydrophilic interaction LC mobile phase, a proper sample pretreatment method, salting-out liquid-liquid extraction, in which ACN was the extractant, was chosen. Since reserpine was unstable under both acidic and alkaline conditions, it was not studied in this part. The optimal salting-out liquid-liquid extraction parameters were as follows: 400 μL ACN was added to 1 mL sample solution containing 500 mg NH4 Cl at a pH of 14.0. The linearity ranged from 0.01 to 1.00 μg/mL with r(2) > 0.9937. The LODs were between 1.9 and 2.5 ng/mL. The developed method was applied to the environmental water sample with good performance.


[Emerging azole antifungals].
Azoles have maintained a key role in the treatment of invasive fungal infections which have a growing importance, especially in immunocompromised patients. Because of its good activity and safety, fluconazole has becoming the treatment of choice for invasive candidiasis, except those caused by Candida glabrata and C. krusei. In contrast, itraconazole which is active against Aspergillus sp has limited use for the treatment of invasive mould infections due to the high variability of its bioavailibility. Voriconazole is active against a broad range of fungal pathogens including Aspergillus sp and other molds, except Zygomycetes. Voriconazole is used as first-line therapy for invasive aspergillosis and for infections caused by Fusarium and Scedosporium. It is available in both oral and intravenous administration. Posaconazole has similar in vitro activity but currently only the oral form is available. Its main indication is refractory aspergillosis or intolerance to previous treatment. Posaconzole will be very useful for long-term therapy of zygomycetes infections.


Conformational plasticity is crucial for C3-RhoA complex formation by ARTT-loop.
ADP-ribosylation is an important post-translational protein modification catalyzed by bacterial toxins and eukaryotic endogenous ADP-ribosyltransferases. Bacterial binary toxins and C3-like toxins recognize and ADP-ribosylate actin Arg177 and RhoA Asn41, respectively. Structural and mutational studies have identified an ADP-ribosylating turn-turn loop (ARTT-loop) that has been implicated in substrate specificity and recognition, although it has not been verified. Recently, we determined the crystal structure of the C3 exoenzyme-RhoA complex. The complex structure shows how C3 recognizes Rho GTPase and provides the first structural evidence for RhoA recognition by the ARTT-loop. The complex formation mediated by the ARTT-loop is through the intrinsic plasticity of C3 and RhoA. C3 changes the conformations of both the phosphate nicotinamide-loop and the ARTT-loop by NAD(+) and RhoA binding, respectively. In contrast, RhoA changes the conformations of switch I and II regions upon C3 binding with a particular conformation, irrespective of the bound nucleotide (GTP or GDP).


Effect of theophylline on contrast material-nephropathy in patients with chronic renal insufficiency: controlled, randomized, double-blinded study.
To investigate whether the adenosine antagonist theophylline reduces the incidence of contrast material-induced nephropathy (serum creatinine level increase of at least 0.5 mg/dL [44.2 micromol/L] in 48 hours) in high-risk patients who have chronic renal insufficiency and have received at least 100 mL of contrast medium. One hundred patients with serum creatinine levels of 1.3 mg/dL (114.3 micromol/L) or greater were randomly assigned to intravenously receive 200 mg theophylline or saline 30 minutes before administration of 100 mL or more of low-osmolarity contrast medium arterially (72 [72%] patients) or intravenously (28 [28%] patients). Patients receiving theophylline and control subjects were comparable with regard to risk factors for contrast-induced nephropathy such as mean serum creatinine level before contrast medium administration (2.07 mg/dL +/- 0.94 [SD] [182.9 micromol/L +/- 83.1] vs 1.92 mg/dL +/- 0.76 [169.7 micromol/L +/- 67.2], respectively), amount of contrast medium (196.5 mL +/- 84.1 vs 216.6 mL +/- 95.0, respectively), and diabetes prevalence. Theophylline prophylaxis significantly reduced the incidence of contrast material-induced nephropathy (4% vs 16%; P =.046). With theophylline, the mean serum creatinine level decreased nonsignificantly 12 (1.98 mg/dL +/- 0.77 [175.0 micromol/L +/- 68.1]; P =.09), 24 (1.97 mg/dL +/- 0.75 [174.1 micromol/L +/- 68.1]; P =.99), and 48 (1.94 mg/dL +/- 0.77 [171.5 micromol/L +/- 68.1]; P =.99)(1.94 mg/dL +/- 0.77 [171.5 micromol/L +/- 68.1]; P =.99) hours after contrast medium administration. With a placebo, serum creatinine level significantly increased 24 hours after contrast medium administration (2.01 mg/dL +/- 0.89 [177.7 micromol/L +/- 78.7]; P =.006). Urinary N-acetyl-beta-glucosaminidase level did not change with theophylline administration but significantly (P =.034) increased 24 hours after contrast medium administration with the placebo. Prophylactic administration of 200 mg theophylline reduces the incidence of contrast material-induced nephropathy in patients with chronic renal insufficiency.


A clinical analysis of malignant schwannoma.
In this study, we reviewed the clinical features of 11 patients with malignant schwannoma who were treated in our institute. Five patients had coexistent von Recklinghausen's disease and one of them showed multifocal occurrence. Patients with the centrally located tumors had a poorer prognosis than those with the others. The overall 3-year survival rate was 36%; 40% in patients with von Recklinghausen's disease and 33% in the others. At the time of the last follow-up, 9 patients had died of the tumor, one continued to be tumor free, and one was alive with tumor. Postoperative local recurrence developed in 5 patients (45%); 4 out of 6 patients (67%) who underwent a marginal excision and one out of 3 (33%) who underwent primary amputation. There was no local recurrence in patients after a wide excision with at least 3 cm of normal tissue removed surrounding the tumor in all directions. Nine patients (82%) developed pulmonary metastasis. The effect of adjuvant chemotherapy was not clear in this study. The high risk of pulmonary metastasis in this disease indicates the necessity of more effective adjuvant chemotherapy.


Alkyl (Het)Arylsulfones from SuFEx Reagents via Photochemical S-F Bond Activation.
A visible light-induced S-F bond activation of sulfur fluoride exchange (SuFEx) reagents to generate alkyl sulfones is described. The method is free of transition metals and relies on the use of commercially available commodity chemicals. In addition, this method demonstrates the first photoredox functionalization of SuFEx reagents. The reaction has a diverse substrate scope, with applications in various aryl sulfonyl fluorides, both activated and unactivated alkenes.


[Spectroscopic investigation of magnetic field effects on radical reactions induced by laser excitation].
Dynamic spin chemistry, including magnetic field effects (MFE), magnetic isotope effects (MIE), CIDEP and CIDNP, has become a research area. In the present paper, the authors briefly introduced the development history and the spectroscopic research state of magnetic field effects for the radical reactions induced by laser excitation. The possible reasons for magnetic field effects of the radical reactions, theories for the conversion of singlet and triplet states, and mechanisms of magnetic field effects were explained and the recent development state of magnetic field effects for the radical reactions was also introduced to domestic scientists.


[Radiotherapy in vulvar cancer treatment].
To provide an actual review of radiotherapy in the treatment of vulvar carcinoma. A review article. Department of Oncology and Radiotherapy, University Hospital in Hradec Králové. A review article evaluating the application of ionizing radiation in the treatment of early and advanced vulvar carcinoma, based on the most significant previously published studies. Postoperative groin irradiation in patients with positive groin lymph-nodes improves local control, time to progression, and overall survival; especially in 2 positive nodes and in N2/3 initial findings. In case of positive inguinal nodes, radiotherapy of both groins and at least lower pelvic iliac node-chains should follow. Adjuvant irradiation of the primary remains controversial, except for positive resection margins where radiotherapy improves overall survival. Concurrent chemoradiotherapy seems to be appropriate primary treatment of advanced vulvar carcinomas, in attempt to avoid mutilating intervention or exenteration. Chemoradiation should be followed by subsequent surgery, including potential groin dissection in case of lymph-node involvement. Definitive chemoradiotherapy is of limited evidence, and radical dose escalation to the gross tumor is essential for its implementation. Modern radiotherapy techniques, especially with intensity modulation, are convenient for dose escalation.


Short-term cognitive behavioral partial hospital treatment: a pilot study.
Brief, cost-contained, and effective psychiatric treatments benefit patients and public health. This naturalistic pilot study examined the effectiveness of a 2-week, cognitive-behavioral therapy (CBT) oriented partial hospital program. Study participants were 57 patients with mood, anxiety, and/or personality disorders receiving treatment in a private psychiatric partial hospital (PH) setting. A flexible treatment model was used that adapts evidence-based CBT treatment interventions to the PH context with emphases on psychoeducation and skills training. Participants completed self-report measures at admission and after 1 and 2 weeks, to assess stabilization and functional improvements, with added attention to the acquisition of cognitive and behavioral skills. The data were analyzed using repeated measures analyses of variance and correlation. Participants reported a decrease in symptoms and negative thought patterns, improved satisfaction with life, and acquisition and use of cognitive and behavioral skills. Skill acquisition was correlated with symptom reduction, reduced negative thought patterns, and improved satisfaction with life. Results of this pilot study suggest that a 2-week PH program can be effective for a heterogeneous patient population with mood, anxiety, and/or personality disorders. These findings are promising given the prevalence of treatments of such brief duration in private sector PH programs subject to the managed care marketplace. Future studies are planned to test this flexible PH treatment model, with particular attention to the effectiveness of the CBT approach for the treatment of different disorders and to whether effectiveness is sustained at follow-up. Further study should also examine whether skill acquisition is a mechanism of change for symptom reduction and functional improvements.


Translocation of an 89-kDa periplasmic protein is associated with Holospora infection.
The symbiotic bacterium Holospora obtusa infects the macronucleus of the ciliate Paramecium caudatum. After ingestion by its host, an infectious form of Holospora with an electron-translucent tip passes through the host digestive vacuole and penetrates the macronuclear envelope with this tip. To investigate the underlying molecular mechanism of this process, we raised a monoclonal antibody against the tip-specific 89-kDa protein, sequenced this partially, and identified the corresponding complete gene. The deduced protein sequence carries two actin-binding motifs. Indirect immunofluorescence microscopy shows that during escape from the host digestive vacuole, the 89-kDa proteins translocates from the inside to the outside of the tip. When the bacterium invades the macronucleus, the 89-kDa protein is left behind at the entry point of the nuclear envelope. Transmission electron microscopy shows the formation of fine fibrous structures that co-localize with the antibody-labeled regions of the bacterium. Our findings suggest that the 89-kDa protein plays a role in Holospora's escape from the host digestive vacuole, the migration through the host cytoplasm, and the invasion into the macronucleus.


Chromosome-mediated OXA-48 carbapenemase in highly virulent Escherichia coli.
Bacteria multiresistant to antibiotics are widely supposed to be weakly virulent. However, the virulence traits of carbapenem-resistant Enterobacteriaceae have not been investigated. In this work, we investigated the virulence and resistance mechanism of an extraintestinal pathogenic Escherichia coli (ExPEC) strain (LEB15) that exhibited decreased susceptibility to carbapenems. The MICs were determined by a microdilution method. The β-lactamase-encoding gene was identified by PCR and sequencing, and the genetic environment was analysed by PFGE and PCR mapping. The genetic background was investigated by multilocus sequence typing (MLST). Virulence-factor-encoding genes and pathogenic islands (PAIs) were detected by multiplex PCR. Virulence was assessed in a mouse sepsis model. Strain LEB15 produced a chromosomal OXA-48 carbapenemase. The complete bla(OXA-48)-encoding Tn1999.2 transposon was inserted in the LEB15 chromosome. The strain belonged to an MLST cluster of emerging ExPEC strains (ST-127/ST-22). It had a high pathogenic score and eight PAIs (I536, II536, III536, IV536, VI536, I(CFT073), II(CFT073) and II(J96)) and induced an unusually high lethality in the mouse sepsis model. Strain LEB15 combines both an atypical broad accumulation of virulence factors, which confers a strong killer phenotype, and a decrease in susceptibility to carbapenems following the chromosomal acquisition of bla(OXA-48). This association of virulence and carbapenemase in E. coli strains might pose major problems in the future for E. coli infection management.


Endoplasmic reticulum-associated degradation.
Secretory and transmembrane proteins enter the secretory pathway through the protein-conducting Sec61 channel in the membrane of the endoplasmic reticulum. In the endoplasmic reticulum, proteins fold, are frequently covalently modified, and oligomerize before they are packaged into transport vesicles that shuttle them to the Golgi complex. Proteins that misfold in the endoplasmic reticulum are selectively transported back across the endoplasmic reticulum membrane to the cytosol for degradation by proteasomes. Depending on the topology of the defect in the protein, cytosolic or lumenal chaperones are involved in its targeting to degradation. The export channel for misfolded proteins is likely also formed by Sec61p. Export may be powered by AAA-ATPases of the proteasome 19S regulatory particle or Cdc48p/p97. Exported proteins are frequently ubiquitylated prior to degradation and are escorted to the proteasome by polyubiquitin-binding proteins.


Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway.
Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin-bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells.


Multicultural psychology: bringing together gender and ethnicity.
This article suggests that just as gender studies should not proceed without consideration of the various contexts in which men and women behave, similarly multicultural psychology should recognize gender, among other characteristics in the populations examined. Focusing on ethnic group women, who are understudied, develops this theme. Two arguments are proposed: (a) that gender must be recognized as impinging on every aspect of psychological research and practice, and (b) that gender should be considered an aspect of culture, just as ethnicity now is. The literature in psychology is reviewed to demonstrate how erroneous beliefs and exclusion operate to minimize examination of ethnicity and gender. Finally, a call to advocacy is made for attention to complexity.


Highly elastic binders integrating polyrotaxanes for silicon microparticle anodes in lithium ion batteries.
Lithium-ion batteries with ever-increasing energy densities are needed for batteries for advanced devices and all-electric vehicles. Silicon has been highlighted as a promising anode material because of its superior specific capacity. During repeated charge-discharge cycles, silicon undergoes huge volume changes. This limits cycle life via particle pulverization and an unstable electrode-electrolyte interface, especially when the particle sizes are in the micrometer range. We show that the incorporation of 5 weight % polyrotaxane to conventional polyacrylic acid binder imparts extraordinary elasticity to the polymer network originating from the ring sliding motion of polyrotaxane. This binder combination keeps even pulverized silicon particles coalesced without disintegration, enabling stable cycle life for silicon microparticle anodes at commercial-level areal capacities.


Targeting mitochondrial dysfunctions in pancreatic cancer evokes new therapeutic opportunities.
Pancreatic cancer (PC) is a highly devastating neoplasm due to its irrepressible characteristics and propensity to override the available treatment strategies. Rapid prevalence and enormous severity of this cancer urgently demand the exploration of novel approaches for the development of effective therapeutic measures. Metabolic derangement is one of the hallmarks of cancers which restructures mitochondrial activities and biological pathways. Apart from their bioenergetic and biosynthetic functions, mitochondria are also implicated in a myriad of cellular functions including proliferation, differentiation, apoptosis, senescence, homeostasis, and other cell regulatory mechanisms. It has been noted that PC, like other types of cancers, exploits these activities in favor of tumor growth and survival by inducing mitochondrial dysfunctions such as mitochondrial-DNA mutation, metabolic enzyme modification, ROS generation, mitophagy, evasion of apoptosis, and mitochondrial biogenesis. During pancreatic carcinogenesis, a large number of onco-factors including Bcl-2 family proteins, NF-κB, HIFs, NRF2, NOX, MFNs, DRP1, DUSP6, Cyp-D, PARKIN, and others are dysregulated, resulting into reprogramming of metabolic pathways and cellular kinetics. Hence, targeted interventions in these metabolic derangements may present some effective anticancer approaches. The current review gives an insight into various mitochondrial disorders and their targetable molecules in PC which may provide certain novel opportunities in the pursuit of therapeutic development. Furthermore, we have also discussed certain treatment perspectives in PC based on specific mitochondrial activities.


VO2 kinetics in supra-anaerobic threshold constant tests allow the visualization and quantification of the O2 saving after cytochrome c oxidase inhibition by aerobic training or nitrate administration.
We tested whether the known cytochrome c oxidase (COX) inhibition by nitric oxide (NO) could be quantified by VO(2) kinetics during constant load supra-Anaerobic Threshold (AT) exercises in healthy trained or untrained subjects following aerobic training or nitrate administration. In cycle ergometer constant load exercises supra-AT, identified in previous incremental tests, VO(2) kinetics describe a double exponential curve, one rapid and one appreciably slower, allowing the area between them to be calculate in O(2) l. After training, with increased NO availability, this area decreases in inverse ratio to treatment efficacy. In fact, in 11 healthy subjects after aerobic training for 6-7 weeks, area was decreased on average by 51 %. In 11 untrained subjects, following the assumption of an NO donor, 20 mg isosorbide 5 mononitrate, area was decreased on average by 53 %. In conclusion, supra-AT VO(2) kinetics in constant load exercises permit the quantification of the inhibitory effect NO-dependent on COX after either physical training or nitrate assumption.


Embodied Processing at Six Linguistic Granularity Levels: A Consensus Paper.
Language processing is influenced by sensorimotor experiences. Here, we review behavioral evidence for embodied and grounded influences in language processing across six linguistic levels of granularity. We examine (a) sub-word features, discussing grounded influences on iconicity (systematic associations between word form and meaning); (b) words, discussing boundary conditions and generalizations for the simulation of color, sensory modality, and spatial position; (c) sentences, discussing boundary conditions and applications of action direction simulation; (d) texts, discussing how the teaching of simulation can improve comprehension in beginning readers; (e) conversations, discussing how multi-modal cues improve turn taking and alignment; and (f) text corpora, discussing how distributional semantic models can reveal how grounded and embodied knowledge is encoded in texts. These approaches are converging on a convincing account of the psychology of language, but at the same time, there are important criticisms of the embodied approach and of specific experimental paradigms. The surest way forward requires the adoption of a wide array of scientific methods. By providing complimentary evidence, a combination of multiple methods on various levels of granularity can help us gain a more complete understanding of the role of embodiment and grounding in language processing.


Persistently obese youth: interactions between parenting styles and feeding practices with child temperament.
To assess the interaction of parent and child characteristics with feeding practices and mealtime functioning. Longitudinal, predictive study comparing baseline characteristics with follow-up assessments. The caregivers of 52 persistently obese youth and 32 nonoverweight comparison youth completed measurements of child temperament, parental feeding practices, parenting styles, and interactions during mealtimes. Adolescents with persistent obesity were significantly more likely to be parented using problematic feeding practices when parents also reported difficult child temperaments. Additionally, adolescents with persistent obesity and difficult temperaments were significantly more likely to have lower levels of positive mealtime interactions. Persistently obese youth are at increased risk for problematic parental feeding practices and mealtime functioning, particularly when youth are described as having difficult temperaments. These results indicate that further investigations are needed to better understand the mechanisms linking parent and child characteristics with health-related behaviors for adolescents with obesity.


Effect of tea theaflavins and catechins on microvascular function.
Beneficial effects of flavonoid-rich black and green tea on macrocirculation have been well established. Theaflavins are unique to black tea as they are formed from catechins during the enzymatic oxidation of tea leaves. The study was performed to gain more insight into the effects of theaflavins on microcirculation and to compare effects with another important flavonoid class, the green tea derived catechins, which have been reported to improve vascular function. Twenty-four healthy subjects were included in a double-blind, placebo-controlled, randomised, cross-over study. On six different days, subjects received capsules with a single dose of catechins (500 mg), four varying doses of theaflavins (100 to 500 mg) or placebo. Microcirculation was assessed after each treatment by Pulse Amplitude Tonometry (EndoPAT) at baseline and 2, 4 and 6 h after test product intake. The EndoPAT reactive hyperemia response was improved by 500 mg catechins (reactive hyperemia index (RHI): 0.2; p = 0.04) and by 500 mg theaflavins (RHI: 0.19; p = 0.06) compared to placebo. Also, 300 mg theaflavins increased the RHI (0.28; p = 0.02), but no effects were observed at lower doses. The study suggests moderate effects of single doses of catechins and theaflavins on peripheral microcirculation.


RNA-Cholesterol Nanoparticles Function as Potent Immune Activators via TLR7 and TLR8.
The innate immune system senses viral and bacterial ribonucleic acid (RNA) via pattern recognition receptors (PRR) leading to subsequent activation of the immune system. One group of RNA sensors is formed by endosomal/lysosomal Toll-like receptors (TLR) such as TLR7 and TLR8. During viral or bacterial infection, immunostimulatory RNA is part of the pathogen reaching the endosomal/lysosomal compartment after cellular uptake. Synthetic single-stranded or double-stranded oligoribonucleotides (ORN) can mimic RNA from pathogens and are widely used as activating ligands for TLR7 and TLR8. However, one limitation in the use of synthetic ORN driven immune stimulation is the need for transfection reagents for RNA delivery into cells. Here we demonstrate that the conjugation of cholesterol to a double-stranded version of immunostimulatory RNA40 strongly enhanced RNA uptake into monocytes and plasmacytoid dendritic cells when compared to naked RNA. Cholesterol-conjugated RNA (RNA-chol) formed nanoparticles that were superior to RNA-liposomes complexes in regard to induction of type I interferon from human and murine plasmacytoid dendritic cells as well as proinflammatory cytokine production (e.g. TNF-α, IL12p70 or IL-6) in human monocytes. Furthermore, the RNA40-chol induced cytokines in human monocyte cultures supported TH1 and TFH cell differentiation underscoring a strong adjuvant function of RNA-chol nanoparticles for adaptive immune responses. In summary, cholesterol-conjugated immunostimulatory RNA forms nanoparticles and functions as a potent immune adjuvant in human and murine immune cells. It further simplifies the use of immunostimulatory RNA by avoiding the need for liposomal transfection reagents.


The effect of height on estimates of the change in BMI-based prevalence of childhood obesity.
Body mass index (BMI, body mass/height2) is biased toward height in children. Here we investigate how change in population height affected change in BMI-based estimates of the prevalence of overweight and obesity in Australian children. Height, weight, and percent body fat (%BF) were measured at ages 8, 10, and 12 years (1855 sets of measures). Age-specific relationships between BMI and height were derived, adjusting for %BF, to estimate the degree of height bias inherent in BMI. Then, from cross-sectional measurements recorded in 1985 (N = 2388) and 1995 (N = 2148) in 8, 10, and 12 year olds, changes in overweight/obesity prevalences were calculated before and after accounting for the BMI-height bias. Estimates of the effect of height on BMI following adjustment for %BF were similar across age groups and all were significant at p < 0.001. Referring to 12 year olds, at the same %BF for a 1% increase in height there was 0.77% (95% CI 0.55, 0.99) increase in BMI in boys, and 0.74% (0.28, 1.02) increase in girls. Between 1985 and 1995, mean height of 12-year-old boys and girls increased 3.9 and 3.2 cm, respectively. In 1985 unadjusted prevalences of combined overweight/obesity in boys and girls were 13.5% and 13.0%, respectively, and in 1995 were 24% and 24.5%. The latter values were reduced to 21.6% and 22.6% after adjusting for increased height. Previously reported increases in childhood overweight/obesity in Australia between 1985 and 1995 were likely to be moderately overestimated as a result of increased population height; suggesting that population height be taken into account in any pediatric investigation of changes in overweight/obesity prevalence over time.


Critical appraisal of randomized controlled trials of anemia correction in patients with renal failure.
Recent randomized controlled trials (RCTs) have reported risks and benefits in the correction of anemia using erythropoietin-stimulating agents (ESAs) in patients with predialysis chronic kidney disease (CKD) or end-stage renal disease. The purpose of this review is to critically appraise the RCTs most relevant to clinical decision-making. The Trial to Reduce cardiovascular Events with Aransep Therapy (TREAT) is the biggest and best designed RCT performed so far, enrolling 4038 diabetic patients with CKD in a double-blind, placebo-controlled trial. Comparing the high hemoglobin (Hb) darbopoietin group with placebo, it reported no difference in cardiac and renal outcomes, a significantly increased risk of stroke, and modest improvement in fatigue and transfusion rate. Meta-analysis demonstrated that correction of anemia with ESA was associated with a significantly increased risk of hypertension and vascular access clotting and an increased risk of death that approached statistical significance. Quality-of-life improvements appeared to maximize in the target Hb range of 10-12 g/dl. Treatment of renal anemia using ESAs to target Hb higher than 13 g/dl is harmful. Treatment of Hb below 9 g/dl provides substantial transfusion and quality-of-life benefits, but safety is unknown. Target Hb levels of 10-12 g/dl seem reasonable, but increasing ESA doses in hyporesponsive patients to achieve a specific target is not.


Posttraumatic stress symptoms during treatment in parents of children with cancer.
The conceptualization of childhood cancer and its treatment as traumatic has gained increasing support in the growing literature on medically related posttraumatic stress. Posttraumatic stress symptoms (PTSS) such as intrusive thoughts, physiologic arousal, and avoidance have been documented in mothers and fathers of childhood cancer survivors. In this study we investigated the presence of PTSS in parents of children currently in treatment and their association with treatment intensity and length of time since diagnosis. Mothers (N = 119) and fathers (N = 52) of children currently in treatment for a childhood malignancy completed questionnaire measures of PTSS. Outcomes on these measures were compared with a sample of parents of childhood cancer survivors from our hospital. Oncologist ratings of treatment intensity were obtained based on diagnosis, treatment modalities, and protocol number. All but one parent reported PTSS. Mean scores indicated moderate PTSS for both mothers and fathers. In families with two participating parents, nearly 80% had at least one parent with moderate-to-severe PTSS. There were minimal associations between PTSS and length of time since diagnosis. PTSS are common among parents of children currently undergoing cancer treatment. Trauma-informed psychosocial interventions can be used to help patients and families, including normalizing the experience as potentially traumatic and using evidence-based interventions that are emerging to facilitate long-term well-being.


Understanding limitations in sport 1 year after an Achilles tendon rupture: a multicentre analysis of 285 patients.
The purpose of this study was to determine patient-related and treatment-related predictors of superior and inferior function in sport and recreational activities 1 year after an Achilles tendon rupture. This study is based on a multicentre cohort from 4 previous randomised controlled trials. All the patients who had responded to the Foot and Ankle Outcome Score (FAOS) at the 1-year follow-up were included. All the patients had a clinically verified Achilles tendon rupture and patients who underwent surgery were treated within 96 h of the time of rupture. Patients were excluded in the event of a previous Achilles tendon rupture or the presence of other lifestyle diseases. The primary outcomes of the study were reported in the 20th and 80th percentiles of the FAOS subscale, function in sports and recreational activities. A total of 285 (84% men) patients with an average age of 40.0 (SD 8.4) years were included. Smoking increased the odds of superior self-reported FAOS sport and recreation [OR 4.59 (95% CI 1.58-13.32), p = 0.005] compared with non-smoking, while being female [OR 0.38 (95% CI 0.16-0.93), p = 0.035] and every increment of one unit in BMI [OR 0.89 (95% CI 0.81-0.99), p = 0.029] reduced the odds. No variable was statistically significant when attempting to predict which patients report inferior FAOS sport and recreation. The recovery of symmetry in heel-rise tests had no effect on 1-year FAOS sport and recreation. Patient-reported outcomes had a good-to-excellent explanatory capacity of superior and inferior 1-year function in sport and recreational activities (AUC = 0.87-0.93). BMI is a modifiable risk factor, which, when lowered, may be associated with less impairment in sports 1 year after an Achilles tendon rupture. Females appear to perceive more limitations than males. Unexpectedly, smokers experience less limitations in foot and ankle function. Patients who report no functional limitation in sport are characterised by an overall perception of adequate foot, ankle and Achilles function, despite not having recovered symmetry in the heel-rise test. I.


Herpesvirus, cytomegalovirus, human sperm and assisted fertilization.
The effect of viral particles on the motility of human sperm and the relationship between sperm and virus are of importance particularly in assisted fertilization. We incubated ejaculated sperm with or without seminal fluid with either herpes simplex virus type 2 (HSV2) or human cytomegalovirus (HCMV). For each experiment, 5 x 10(5) sperm were incubated with a viral load of between 10(4) and 10(6) plaque-forming units. We detected no apparent variations in the percentage of motile forms when sperm were incubated with either HSV2 or HCMV. Using a computer-aided semen analysis system, a slight difference was reported in the percentage of motile forms when seminal fluid-free sperm were incubated with HSV2 (57.18 versus 64.43 in the control). Although the mean amplitude of lateral head displacement and the curvilinear velocity were significantly higher in infected sperm, the difference in straight line velocity was not statistically significantly different. Few viral particles (HSV2 or HCMV) adhered to the sperm membrane in the presence of seminal fluid. However, more particles stuck when in the absence of seminal fluid, particularly with HSV2 (8% of sperm sections for HSV2; 4% for HCMV). The relationship between sperm and viruses depends on the type of virus present as well as the presence or absence of seminal fluid. Motility is not a good enough criterion on which to prove the presence of viral elements, either in the medium or on the sperm.


Comparison of the migration behavior of nanoparticles based on polyethylene glycol and silica using micellar electrokinetic chromatography.
Nanoparticles, spherical particles with diameters less than 100 nm, are promising theranostic devices for noninvasive diagnosis and therapy. In this study, nanoparticles composed of polyethylene glycol and silica were prepared, and their migration behavior was examined using capillary electrophoresis. The effects of the sodium dodecyl sulfate concentration in the electrolyte, the nanoparticle size, and the encapsulated molecule on the migration were examined. The addition of sodium dodecyl sulfate into the electrolyte had a significant effect on the electrophoretic mobility of polyethylene glycol nanoparticles, but a small effect on that of silica nanoparticles. As for the size effect, the mobility became a little faster for smaller nanoparticle sizes for both polyethylene glycol and silica nanoparticles. The encapsulated molecule affected the mobility of the nanoparticles through interactions between the encapsulated molecules and sodium dodecyl sulfate. We propose that the large effect of sodium dodecyl sulfate on the migration of the polyethylene glycol nanoparticles was due to the large spaces within the nanoparticles. These results indicate that nanoparticle migration is mainly determined by the nanoparticle components.


Transcription profile of a human breast cancer cell line expressing MMTV-like sequences.
It has been postulated that inflammation caused by certain viruses might result in cancer. Recently, it was shown that childhood lymphoblastic leukemia, breast and ovarian cancers express an interferon-related signature, providing support for this notion. We have previously shown that 38% of the sporadic breast cancers contain MMTV-like env gene sequences. To find out if the presence and expression of MMTV-like sequences correlated with an inflammatory phenotype, we have compared the expression profile of two sublines of MCF-7 cells, one containing the MMTV-like sequences (env+), the other one lacking them (env-). The results indicated that there were 47 differentially expressed genes between the two sublines. Among 27 upregulated genes in the env+ cells there were 7 interferon-related genes, 5 TNF-connected genes and 2 TGFbeta-related genes. These results suggest that the env+ cells were most likely responding to an infectious agent, and support the hypothesis that a viral infection may play a role in breast cancer pathogenesis.


Occult gallbladder carcinoma after laparoscopic cholecystectomy: a report of four cases.
Eighty-four patients underwent laparoscopic cholecystectomy (LC) from January through August 2006. Of these patients, 4 (4.7%) were found to have occult gallbladder carcinoma (GC) either during or after the procedure. Two of the patients were women and 2 were men. The mean age was 75.0 years. One patient had mucosal tumors, 2 had subserosal tumors, and 1 had a serosal lesion. One of the 2 patients with subserosal tumors underwent radical surgery. In a previous study, 0.83% (10 of 1,195) of patients who had undergone LC were found to have occult GC, either during of after the procedure. The prevalence of gallbladder carcinoma has recently been increasing. GC has been reported in 0.3% to 1.5% of patients who have undergone cholecystectomy. Since the introduction of laparoscopic surgery, the number of cholecystectomies being performed has increased, which may explain why occult GC seems to be occurring more frequently. The prognosis for GC is poor, and surgical resection is the only potentially curative treatment. However, GC is difficult to diagnose at an early stage and difficult to recognize even in the advanced stages. Fifteen percent to 30% of patients show no preoperative or intraoperative evidence of malignancy. Occult GC is also increasing. Because flat infiltrating GC and GC with cholecystitis and numerous stones are difficult to diagnose preoperatively, we recommend taking frozen sections from patients who are of advanced age (older than 70 years), have a long history of stones, or have a thickened gallbladder wall.


Progress in researches on the effect of acupuncture in antagonizing oxygen stress.
Oxidation and free radicals participate in the pathological process of multiple diseases in organisms, and acupuncture shows good effect in antagonizing oxygen stress (OS). This article reviews the effect of acupuncture in antagonizing oxygen stress and the mechanism of its anti-free radical effect in various diseases. The authors hold that acupuncture not only has a chain-blocking effect, but also has preventive and repairing effects of anti-oxidation. And anti-OS action is one of the important mechanisms of acupuncture.


Increase of methionine-aminopeptidase activity in hyperplastic Leydig cells of rat cryptorchid testis.
In order to elucidate the reasons for the increased methionine-aminopeptidase activity in the rat cryptorchid testis, a histochemical study was conducted on the changes in testicular aminopeptidase activities using various substrates after the cryptorchidism experimentally was induced with reference to the regenerated hepatic cells which appeared in the partially hepatectomized liver of rat. Methionine-aminopeptidase gradually increased in Leydig cells after cryptorchid was induced, whereas the enzyme activity decreased in regenerated hepatic cells. These histochemical observations were coincident with the data obtained by enzyme assay. The present study has clearly indicated that the increased methionine aminopeptidase activity was specific for hyperplastic and hypertrophic Leydig cells in the cryptorchid testis, but did not depend merely on cell hyperplasia.


Maternal folate status, but not that of vitamins B-12 or B-6, is associated with gestational age and preterm birth risk in a multiethnic Asian population.
Maternal folate, vitamin B-12, and vitamin B-6 concentrations during pregnancy have been shown to influence birth outcomes, but the evidence is inconclusive. We aimed to examine the associations of maternal B-vitamin status with gestational age, birth weight, and length in a birth cohort study in Singapore. Maternal blood samples (n = 999) collected during weeks 26-28 of gestation were assayed for plasma folate, vitamin B-12, and vitamin B-6 concentrations. Birth weight and gestational age data were obtained from hospital records, and other anthropometric variables were measured within 72 h after birth. Relations between B-vitamin status and birth outcomes were assessed by linear or logistic regression with adjustment for potential confounders. Median (IQR) plasma concentrations were 34.4 (24.5-44.6) nmol/L for folate, 209 (167-258) pmol/L for vitamin B-12, and 61.8 (25.9-113) nmol/L for vitamin B-6. We found that higher plasma folate concentrations were associated with a longer gestational age (0.12 wk per SD increase in folate; 95% CI: 0.02, 0.21) and tended to be associated with lower risk of all preterm birth (delivery at <37 wk of gestation; OR: 0.79; 95% CI: 0.63, 1.00) and spontaneous preterm birth (OR: 0.76; 95% CI: 0.56, 1.04). Overall, concentrations of maternal folate, vitamin B-12, and vitamin B-6 were not independently associated with birth weight or being born small for gestational age (SGA; birth weight <10th percentile for gestational age). Higher maternal folate concentrations during late pregnancy were associated with longer gestational age and tended to be associated with a lower risk of preterm birth in this multiethnic Asian population. In contrast, the results of our study suggested little or no benefit of higher folate concentrations for reducing the risk of SGA or of higher vitamin B-6 and vitamin B-12 concentrations for reducing the risk of preterm birth or SGA.


Materials and surface modification for tissue engineered vascular scaffolds.
Although vascular implantation has been used as an effective treatment for cardiovascular disease for many years, off-the-shelf and regenerable vascular scaffolds are still not available. Tissue engineers have tested various materials and methods of surface modification in the attempt to develop a scaffold that is more suitable for implantation. Extracellular matrix-based natural materials and biodegradable polymers, which are the focus of this review, are considered to be suitable materials for production of tissue-engineered vascular grafts. Various methods of surface modification that have been developed will also be introduced, their impacts will be summarized and assessed, and challenges for further research will briefly be discussed.


One-pot synthesis of substituted furans using Cu(OTf)(2)-catalyzed propargylation/cycloisomerization tandem reaction.
A convenient one-pot propargylation/cycloisomerization tandem process has been developed for the synthesis of substituted furans derivatives from 1,3-dicarbonyl compounds and enoxysilanes with propargylic alcohols or acetates using copper(II) triflate as a bifunctional catalyst. This method provides a flexible and rapid route to substituted furans.


Health and support service utilization patterns of American Indians and Alaska Natives diagnosed with HIV/AIDS.
The purpose of this analysis is twofold: to examine the types of health and support services provided by CARE Act funded providers to American Indians/Alaska Natives and to compare the characteristics and service utilization patterns for this group with those of individuals from other racial/ethnic groups. We present an analysis of the demographic characteristics, service utilization, and health outcomes of all HIV-infected clients who received services in five geographic areas at agencies that were funded through the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act. Standard chi-square tests were used to test for statistically significant differences (p <.05) between the demographic characteristics and service utilization patterns of matched pairs of HIV-positive American Indian/Native Alaskans with HIV-positive individuals of other racial and ethnic backgrounds. Individuals were matched on gender, age, insurance, AIDS diagnosis, and site. Other data examined include client characteristics (income, homelessness, HIV exposure category, and source of health care), health indicators (CDC-defined disease stage, CD4+ counts, substance abuse and psychiatric illness) and service utilization (medical care; mental health treatment/counseling; substance abuse treatment/counseling; case management; dental care; housing, food, emergency financial, and transportation assistance, and buddy/companion and client advocacy services). There were no statistically significant differences between the two groups for HIV exposure category, CD4 count, substance abuse problem, and being homeless and in their likelihood to receive medical care, mental health or substance abuse treatment/counseling, dental care, food, emergency financial, and transportation assistance, as well as buddy/companion and client advocacy services. They were more likely (55% vs. 46%) to receive case management services than the matched individuals from other racial/ethnic groups. They were also more likely to receive housing assistance (35% vs. 25%). The analysis provides evidence that when individuals are matched on key demographic and health characteristics, few differences remain between HIV-positive American Indians/Native Alaskans and other racial/ethnic groups. The two exceptions are case management and housing assistance. The significantly higher use of case management is not surprising, given the emphasis by American Indians/Alaska Natives on traditional Native American case management case management. In contrast, the significantly higher use of housing assistance by American Indians/Alaska Natives was unexpected. Exploring the potential need for housing assistance among all American Indians/Alaska Natives served by the Ryan White CARE Act needs to be considered.


Molecular characterization of a new begomovirus infecting Mirabilis jalapa in northern India.
Begomoviruses are whitefly-transmitted single-stranded DNA viruses that are responsible for considerable economic losses. A begomovirus, alphasatellite and betasatellite were characterized in a Mirabilis jalapa plant exhibiting severe leaf curling and mottling symptoms. The complete viral genome shared highest sequence identity of 87% with pedilanthus leaf curl virus (AM712436), reported from Pakistan. Additionally, the viral genome was 84% identical to that of chilli leaf curl India virus (KX951415) and 83% identical to that of tobacco curly shoot virus (GU1999584), which were previously reported to infect M. jalapa in India and China, respectively. Based on the ICTV criterion for begomovirus species demarcation (≥91% sequence identity for the complete genome), the virus represents a new species, for which we propose the name Mirabilis leaf curl virus. The alphasatellite and betasatellite sequences were similar to the corresponding sequences of ageratum yellow vein India alphasatellite (KU852743; 99% identity) and tomato leaf curl Patna betasatellite (HQ180394; 86% identity) sequences, respectively. This report describes a new begomovirus-satellite disease complex in M. jalapa.


Bradykinin does not acutely sensitize the reflex pressor response during hindlimb skeletal muscle stretch in decerebrate rats.
Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechanogated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that injection of bradykinin into the arterial supply of a hindlimb in decerebrate, unanesthetized rats would acutely augment (i.e., sensitize) the increase in blood pressure and renal sympathetic nerve activity during hindlimb muscle stretch to a greater extent in rats with a ligated femoral artery than in rats with a freely perfused femoral artery. The pressor response during static hindlimb muscle stretch was compared before and after hindlimb arterial injection of 0.5 µg of bradykinin. Injection of bradykinin increased blood pressure to a greater extent in "ligated" (n = 10) than "freely perfused" (n = 10) rats. The increase in blood pressure during hindlimb muscle stretch, however, was not different before vs. after bradykinin injection in freely perfused (14 ± 2 and 15 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.62) or ligated (15 ± 3 and 14 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.80) rats. Likewise, the increase in renal sympathetic nerve activity during stretch was not different before vs. after bradykinin injection in either group of rats. We conclude that bradykinin did not acutely sensitize the pressor response during hindlimb skeletal muscle stretch in freely perfused or ligated decerebrate rats.


Nurse staffing and patient outcomes in Veterans Affairs hospitals.
To assess characteristics and perceptions of nurses working in the Veterans Health Administration (VHA), comparing types of nursing personnel, to benchmark to prior studies across healthcare systems. Prior studies have shown relationships between positive registered nurse (RN) perceptions of the practice environment and patient outcomes. To date, no study has reported the comparison of RN perceptions of the practice environment in hospital nursing with those of non-RN nursing personnel. This study is the first to offer a more comprehensive look at perceptions of practice environment from the full range of the nursing work force and may shed light on issues such as the relationship of skill mix to nurse and patient outcomes. Cross-sectional observational study with a mailed survey administered to all nursing personnel in 125 VA Medical Centers between February and June 2003. Compared with other types of nursing personnel in the VHA, RNs are generally less positive about their practice environments. However, compared with RNs in other countries and particularly with other RNs in the United States (Pennsylvania), VHA RNs are generally more positive about their practice environment and express more job satisfaction. The nursing work force of the VHA has some unique characteristics. The practice environment for nurses in the VHA is relatively positive, and may indicate that the VHA, as a system, provides an environment that is more like magnet hospitals. This is significant for a public sector hospital system.


A novel genetic algorithm for designing mimetic peptides that interfere with the function of a target molecule.
We designed a new computer program (MIMETIC), which generates a series of peptides for interaction with a target peptide sequence. The genetic algorithm employed ranks the sequences obtained from one generation to the next by "goodness of fit" to the target. MIMETIC designed recognition peptides to various regions of HIV-1 reverse transcriptase. Among ten peptide candidates synthesized, three inhibited reverse transcription in vitro. TLMA2993 and PSTW1594 both targeted the connection domain of reverse transcriptase and ESLA2340 targeted the thumb domain.


Heart Transplant and Donors After Circulatory Death: A Clinical-Preclinical Systematic Review.
Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients awaiting transplantation. Expanding the donor pool is critically important. The use of hearts donated following circulatory death is one approach to increasing the number of available donor hearts. A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines utilizing Pubmed/MEDLINE and Embase. Articles including adult human studies and preclinical animal studies of heart transplantation following donation after circulatory death were included. Studies of pediatric populations or including organs other than heart were excluded. Clinical experience and preclinical studies are reviewed. Clinical experience with direct procurement, normothermic regional perfusion, and machine perfusion are included. Preclinical studies addressing organ function assessment and enhancement of performance of marginal organs through preischemic, procurement, preservation, and reperfusion maneuvers are included. Articles addressing the ethical considerations of thoracic transplantation following circulatory death are also reviewed. Heart transplantation utilizing organs procured following circulatory death is a promising method to increase the donor pool and offer life-saving transplantation to patients on the waitlist living with end-stage heart failure. There is robust ongoing preclinical and clinical research to optimize this technique and improve organ yield. There are also ongoing ethical considerations that must be addressed by consensus before wide adoption of this approach.


An international expansion in voluntary euthanasia/assisted dying: The implications for nursing.
To provide an update on the international position of assisted dying legislation and its implications for nursing policy. Assisted dying legislation has been introduced in health systems in Europe, North America and Australasia (Australia and New Zealand). Despite contributions in research literature, this remains focussed on medical practitioners, with limited acknowledgement of the need for policy development in nursing. There is a need for critical evaluation of this contemporary issue and the significance for nursing practice of the lack of unified nursing perspective and robust policy guidance is identified. An overview of the existing role of voluntary euthanasia/assisted dying with recent developments is provided and the resulting concerns for nurses regarding the scope of practice, role confusion and conflicting professional values is considered. Despite a long history of assisted dying and the continued expansion of these practices, limited and highly variable nursing policy highlights the lack of clear guidance available to nurses. The growing inclusion of nurse practitioners and recognition of registered nurse involvement in the care of individuals on an assisted dying pathway merits clearer support from regulatory authorities and professional organisations. Nurses are the most likely health professionals to be approached with questions regarding assisted dying; they are intimately involved in patient experiences and need to understand what is possible, expected and legal in terms of their scope of practice regarding assisted dying. Nursing regulators and professional representatives need to provide clear policy statements and guidance identifying the nursing role and recognising where protections and support are necessary.


Effects of surface sterilisation with green synthesised silver nanoparticles on Lamiaceae seeds.
Nanoparticles have been used in many areas of biotechnology. In this study, an alternative surface sterilisation method was established for plant tissue cultures. Silver nanoparticles synthesised via green synthesis were used for the surface sterilisation of Lamiaceae seeds (Salvia farinecae, Ocimum basilicum - Large Leaf Italian, Thymus vulgaris, Ocimum basilicum var. purpurascens). Water extracts of dried Alkanna tinctorum rhizomes and Syzygium aromaticum flowers were utilised in the bioreduction of silver ions. The seeds were exposed to 0, 1, 7, 14 and 28 day-old colloidal solutions of silver nanoparticles and their effects on germination and surface sterilisation were determined. Fresh (0 and 1 day-old) colloidal solutions of silver nanoparticles were found very effective on surface sterilisation (100%). Moreover, they showed no negative effect on both germination and morphology of plantlets. It was shown that silver nanoparticles can be used as a surface sterilisation agent and they have no adverse effects on seed germination and in vitro plantlet growth.


Expression of Lewis(x), sialylated Lewis(x), Lewis(a), and sialylated Lewis(a) antigens in human lung carcinoma.
One hundred and five cases of various human lung neoplasms were studied immunohistochemically using monoclonal antibodies recognizing the antigens, Le(x), sialylated Le(x) (SLEX), Le(a), and sialylated Le(a) (SLEA). Of the 92 lung cancers examined for antigen expression SLEX was detected in 57% (52 cases), Le(x) in 42% (39), SLEA in 36% (33), and Le(a) in 23% (21). None of these antigens were expressed in 9 tumor like lesions of the lung or the 4 other non-epithelial malignant lung tumors examined. Higher expression was seen in the 54 lung adenocarcinomas: SLEX in 72%, Le(x) in 48%, SLEA in 39%, and Le(a) in 24%. The type 2 carbohydrate antigens (SLEX and Le(x) were more prevalent than the type 1 antigens (SLEA and Le(a)) in lung adenocarcinoma tissues. In adenocarcinomas, SLEX was expressed in 71% (10/14) of the Le(b) patients, and in 100% (5/5) of the Le(a) patients. Unexpectedly, SLEX was not detected in 4 out of 5 Le(a-b-) patients tested. This suggests that the expression of the Le(x) antigens and the Le(a) antigens are related in lung adenocarcinoma. These antigens were less expressed in other types of lung cancers. Tissue sections obtained serially showed heterogeneity in the expression of these antigens, as evidenced by the concurrent presence of both SLEX and SLEA. These results indicate that SLEX is a useful tumor-associated marker for lung adenocarcinomas, and that terminal fucosylation and sialylation may be activated heterogeneously in these lung cancers.


Are patients in Western Turkey contented with healthcare services?: a quality assessment study.
The purpose of this study was to describe service quality as perceived by 1200 patients who had inpatient treatment at 3 hospitals in Istanbul: university, social security administration, and government. Patients were most satisfied with the helpful attitudes of personnel during check-in procedures, promptness and skill of nurses, overall service provided by physicians, speedy and skilled work of personnel in laboratories and X-ray rooms, and hospitals in general.


Endoplasmic reticulum stress inhibitor may substitute for sleeve gastrectomy to alleviate metabolic dysfunction-associated steatotic liver disease.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming the most common form of chronic liver disease worldwide. We explored the potential mechanisms responsible for the protective role of sleeve gastrectomy (SG) on MASLD in a high-fat diet (HFD) rat model. Rats were fed with HFD for 12 weeks to generate MASLD model that were subjected to SG or sham surgery. The endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (4-PBA) was injected intraperitoneally every day for 4 weeks after surgery to identify the impact of ERS. The MASLD rat model was generated successfully, as indicated by significant upregulation of metabolic parameters. Fibroblast growth factor 21 (FGF21) and ERS-related proteins were increased in HFD rats, while expression of fibroblast growth factor receptor 1 was decreased as expected. An HFD also induced swelling and blurring of the endoplasmic reticulum and mitochondria in hepatocytes, and the above transformation could be relieved by SG and 4-PBA. SG and an ERS inhibitor both inhibited MASLD, but their combined treatment had no additional benefit. Dysfunction of the FGF21 signaling pathway and hepatic steatosis and inflammation could be induced by an HFD, potentially causing MASLD. Bariatric surgery and ERS inhibition could alleviate MASLD by relieving ERS-mediated impairment of FGF21 signal transduction. These findings provide a new insight into the use of ERS inhibitors to treat MASLD, especially in patients who prefer to avoid surgery.


Bacterial agents and antibiotic resistance profiles of infections from different sites that occurred among patients at Debre Markos Referral Hospital, Ethiopia: a cross-sectional study.
In developing countries like Ethiopia, infections with antibiotic resistant bacteria become a real threat. Hence, monitoring of local level antimicrobial resistance profile is indispensable to contain the spread of drug resistant bacteria and intervene poor awareness on antimicrobial resistance. Therefore, this study aimed at determining bacterial and antibiotic resistance profiles of infections from different sites that occurred among patients. Retrospective data recorded were analyzed on culture and drug susceptibility test results at Debre Markos Referral Hospital which were performed from 2011 to 2014. Drug susceptibility tests were performed using disk-diffusion technique. Chi square test was computed to compare the proportion of bacterial isolates with patients' age and sex. Out of 575 clinical samples processed, 280 (48.7%) were culture positive for aerobic bacteria pathogens. Wound 238 (41.4%) and urine 108 (18.8%) were the most frequent samples processed. Overall, Staphylococcus aureus (S. aureus) was the predominant isolate 100 (31.5%) followed by Escherichia coli (E. coli) 39 (13.8%), Pseudomonas aeruginosa (P. aeruginosa) 30 (10.3%) and Salmonella spp. 25 (8.9%). P. aeruginosa was the most frequent isolate followed by S. aureus from ear infection. E. coli was the leading isolate followed by Klebsiella spp. from urinary tract infection. Salmonella and Shigella spp. were the most frequent isolates in stool in children below 5 years of age. Neisseria gonorrhoeae (N. gonorrhoeae) 16 (76.2%) was the most common isolate from urethral discharge. The overall multidrug-resistant Gram positive and Gram negative bacteria isolates were 113 (84.6%) and 96 (72.2%), respectively. Gram positive bacteria revealed resistance to cotrimoxazole (80%), gentamicin (83.1%), amoxicillin (85.1%), ampicillin (85.8%), penicillin (89.7%), clindamycin (93.2%) and erythromycin (90.9%). Gram negative bacteria showed resistance to cotrimoxazole (53.1%), amoxicillin (58.8%), ampicillin (70.4%), tetracycline (75.9%) and gentamicin (76.9%). Various bacterial infections linked with high levels of MDR bacteria pathogens are major health problems in the study area. Therefore, treatment of common bacterial infections in the study area needs to be guided by drug-susceptibility testing of isolates.


Analysis of influential factors of image reconstruction quality in structured illumination imaging and its application in laser microprocessing.
Due to the huge demand for higher resolution and stable imaging from fluorescent labeling biological systems and life systems, there has been much research and development of structured light illumination imaging (SIM). Despite this, further investigating the possible applications of SIM in other fields is still meaningful. In this paper, super-resolution observation of non-fluorescent samples by a SIM system under reflective illumination is analyzed. The simulation of SIM imaging and image reconstruction is carried out by using an open-source program, and the influences of the structural parameters of the illumination light (fringe direction, phase, and intensity uniformity of the cosine structured light), the optical parameters of the imaging system (selection of the optical transfer function) and the anti-vibration characteristics of the platform on the super-resolution imaging effect are studied. Finally, by optimizing the above influential factors according to simulation results, successful application of SIM in laser processing process monitoring is demonstrated in the experiment. We believe that our research results will provide some reference for the application of SIM in other similar scenarios.


Hypothyroid heart: myxoedema as a cause of reversible dilated cardiomyopathy.
Hypothyroidism may cause several cardiac manifestations including conduction abnormalities, pericardial effusion, decreased myocardial contractility and accelerated coronary atherosclerosis. Although cardiac output is reduced in hypothyroidism, frank heart failure (HF) is relatively rare because of the low peripheral oxygen demand. Several mechanisms have been postulated in hypothyroid-induced HF, including genomic as well as non-genomic actions of thyroid hormone. Dilated cardiomyopathy (DCM) of other aetiologies is usually progressive, and is associated with significant morbidity and mortality. We report a case of DCM associated with severe hypothyroidism with marked improvement on restoration of euthyroid state. Our case is unique in that the patient had no known risk factors for cardiac disease and experienced marked improvement despite being on minimal doses of HF medications, illustrating the relationship between hypothyroidism and development of left ventricular dysfunction, and its reversible nature with restoration of euthyroid status.


Oral and genital human herpesvirus 8 and human papillomavirus in heterosexual partners.
The purpose of this study was to verify a possible co-infection of human herpesvirus 8 (HHV-8) in commonly associated human papillomavirus (HPV) penile lesions and to determine the frequency of detection of these viruses in the oral mucosa of their female counterparts. Thirty-one male subjects underwent penile swabs from clinical HPV-related lesions. Their female counterparts underwent swabs of the vagina, uterine cervix, and oral mucosa. HPV and HHV-8 detection was performed by polymerase chain reaction using the consensus primers MY11/MY09 and KS1/KS2, respectively. HPV DNA was detected in 31/31 penile lesions. HPV DNA was also detected in 18/31 (58%) female genital brushings and 17/31 (54%) female oral brushings. HHV-8 DNA was detected in 1/31 (3.2%) male genital brushings and 3/31 (9.6%) female oral mucosa brushings. None of the female genital brushings were HHV-8 DNA-infected. Based upon the results of this study, co-infection between HPV and HHV-8 in malignant and pre-malignant penile lesions is an unlikely finding.


[Liver cirrhosis caused by alpha-1-antitrypsin deficiency].
The authors present 2 patients with cirrhosis of the liver associated with alpha-1-antitrypsin deficiency. The patients are two children (brother and sister aged 4 and 13). The manifestation of the disease in these two children was a prolonged neonatal icterus. The symptoms of a decompensated cirrhosis of the liver appeared at the age of 2 and 4 years. There were several attacks of obstructive bronchitis etiologically associated with the same cause. The boy died at the age of four of hepatic coma preceded by several bleedings from esophageal varices. Splenectomy was performed in the girl on account of distinct signs of hyperplenism and two and a half years later mesentericocaval shunt because of the extensive bleeding from esophageal varices and the fundus of the stomach. The diagnosis of alpha-1-antitrypsin deficiency was made on the basis of low values in the serum and on the basis of liver biopsö and findings of typical PAS positive inclusions in the endoplasmic reticulum of hepatocytes. The values of A1A parents are also lower. The finding of Pi phenotypification is significant--the SZ phenotype was found in two patients (brother and sister), which is seldom described in patients with cirrhosis of the liver.


School lunches in Japan: their contribution to healthier nutrient intake among elementary-school and junior high-school children.
The role of school lunches in diet quality has not been well studied. Here, we aimed to determine the contribution of school lunches to overall nutrient intake in Japanese schoolchildren. The study was conducted nationwide under a cross-sectional design. A non-consecutive, three-day diet record was performed on two school days and a non-school day separately. The prevalence of inadequate nutrient intake was estimated for intakes on one of the school days and the non-school day, and for daily habitual intake estimated by the best-power method. The relationship between food intake and nutrient intake adequacy was examined. Fourteen elementary and thirteen junior high schools in Japan. Elementary-school children (n 629) and junior high-school children (n 281). Intakes between the school and non-school days were significantly different for ≥60 % of nutrients. Almost all inadequacies were more prevalent on the non-school day. Regarding habitual intake, a high prevalence of inadequacy was observed for fat (29·9-47·7 %), dietary fibre (18·1-76·1 %) and salt (97·0-100 %). Inadequate habitual intake of vitamins and minerals (except Na) was infrequent in elementary-school children, but was observed in junior high-school children, particularly boys. School lunches appear to improve total diet quality, particularly intake of most vitamins and minerals in Japanese children. However, excess intakes of fat and salt and insufficient intake of dietary fibre were major problems in this population. The contribution of school lunches to improving the intakes of these three nutrients was considered insufficient.


Evolution of Carotid Surgical Practice in the last Decade.
Stroke units provide immediate care and appropriate intervention in the evolving stroke. The aims of this study were to review the practice of carotid endarterectomy (CEA) before and after the establishment of a Stroke Unit in St. James's Hospital. Prior to the introduction of the Stroke Unit, 263 CEA's were performed over a five-year period. 139/263 (53%) of these were for symptomatic disease. 229 were performed in the five years since. 179/229 (78%) of these were for symptomatic disease. The 30-day stroke and death rates were < 2% before the introduction of the Stroke Unit, and have remained unchanged. Since the introduction of the Stroke Unit, there has been a slight decrease in the overall number of CEA's performed with a 25% increase in the proportion of endarterectomies performed for symptomatic disease. Despite the reduction in surgery for asymptomatic disease the overall 30-day stroke and death rate remains excellent at 2/229 (2%).


The seroprevalence of Johne's disease in Georgia beef and dairy cull cattle.
Beef and dairy cattle serum samples, collected during 2000 at sale barns throughout Georgia, were obtained from the Georgia State Brucellosis Laboratory and were used to conduct a retrospective epidemiological study. Statistical samplings of 5,307 sera, from over 200,000 sera, were tested for antibodies to Mycobacterium avium ssp. paratuberculosis, (Johne's disease) using a commercial enzyme-linked immunosorbent assay test kit. An overall period seroprevalence in all classes of cattle tested was 4.73%. The period seroprevalence in dairy cattle was 9.58%, in beef cattle it was 3.95%, and in cattle of unknown breed it was 4.72%. It was concluded that the seroprevalence of Johne's disease in cull beef and dairy cattle in Georgia is economically significant.


Lipid management among individuals with inflammatory arthritis in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.
Objective Hyperlipidemia guidelines do not currently identify inflammatory arthritis (IA) as a cardiovascular disease (CVD) risk factor. We compared hyperlipidemia treatment of individuals with and without IA (rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis) in a large national cohort. Methods Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were classified as having IA (without diabetes or hypertension); diabetes (but no IA); hypertension (but no diabetes or IA); or no IA, diabetes, or hypertension. Multivariable logistic regression models examined the odds of medical treatment among those with hyperlipidemia. Results Thirty-nine participants had IA, 5423 had diabetes, 7534 had hypertension, and 5288 had no diabetes, hypertension, or IA. The fully adjusted odds of treatment were similar between participants with IA and those without IA, hypertension, or diabetes. Participants with diabetes and no IA and participants with hypertension and no IA were twice as likely to be treated for hyperlipidemia as those without IA, diabetes, or hypertension. Conclusion Despite their higher CVD risk, patients with IA were as likely to be treated for hyperlipidemia as those without diabetes, hypertension, or IA. Lipid guidelines should identify IA as a CVD risk factor to improve CVD risk optimization in IA.


Synthetic Cell-Based Sensors with Programmed Selectivity and Sensitivity.
Bacteria live in an ever changing environment and, to adapt their physiology, they have to sense the changes. Our current understanding of the mechanisms and elements involved in the detection and processing of these environmental signals grant us access to an array of genetic components able to process such information. As engineers can use different electronic components to build a circuit, we can rewire the cellular components to create digital logic and analogue gene circuits that will program cell behaviour in a designed manner in response to a specific stimulus. Here we present the methods and protocols for designing and implementing synthetic cell-based biosensors that use engineered genetic logic and analogue amplifying circuits to significantly increase selectivity and sensitivity, for example, for heavy metal ions in an aqueous environment. The approach is modular and can be readily applied to improving the sensing limit and performance of a range of microbial cell-based sensors to meet their real world detection requirement.


Effects of combined use of droperidol with pentazocine and with fentanyl on pulmonary hemodynamics.
The effects of droperidol combined with pentazocine and with fentanyl on the pulmonary hemodynamics were investigated in intact dogs anesthetized with urethanechloralose, and the results were compared with those of each analgesic alone. Mean pulmonary arterial pressure and pulmonary driving pressure remained almost unchanged after droperidol and pentazocine. Pulmonary vascular resistance decreased significantly, and pulmonary vascular compliance and its radium tended to increase. These results indicate that droperidol counteracts the vasoconstrictive action of pentazocine on the pulmonary hemodynamics. On the contrary, almost all the parameters of the pulmonary hemodynamics after droperidol and fentanyl changed to similar directions to those after fentanyl alone. Droperidol seemed not to modify but to exaggerate the pulmonary circulatory effects of fentanyl.


[Mechanism of histone deacetylase inhibitor tubastatin A promoting autophagy of Legionella pneumophila infected RAW264.7 cells].
Objective To investigate the role of HDAC6 in the interference of Legionella pneumophila on the autophagy of macrophages and its mechanism. Methods RAW264.7 macrophages were treated with 10 μmol/L, 5 μmol/L, and 2.5 μmol/L tubastatin A (TubA). CCK-8 assay was used to detect the proliferative activity of RAW264.7 macrophages, and the half maximal inhibitory concentration (IC50) of TubA was determined. A model of RAW264.7 macrophages infected with Legionella pneumophila was established and divided into TubA free groups (further divided into cell control group, inactivated bacteria group, and live bacteria group) and TubA treatment groups (10 μmol/L, 5 μmol/L, 2.5 μmol/L, each further divided into cell control group, inactivated bacteria group, and live bacteria group). The cells were collected at 6, 12, 24, and 48 h after Legionella pneumophila infection. The bacterial proliferation assay was conducted to detect the proliferation of Legionella pneumophila in RAW264.7 macrophages; RAW264.7 macrophages were transfected with pmCherry-C1-EGFP-LC3B plasmid to detect autophagic flux changes in each group; real-time quantitative PCR and Western blot were used respectively to detect the mRNA and protein expression levels of histone deacetylase 6 (HDAC6), sequestosome 1(SQSTM1/P62), microtubule associated protein 1 light chain 3 (LC3), α-tubulin, valosin containing protein (p97/VCP), heat shock protein 90 (HSP90), HSP70, heat shock transcription factor 1 (HSF1), and filamentous actin (F-actin). Results IC50 of TubA was 50 μmol/L. Compared with those in the RAW264.7 normal control group, the proliferation of Legionella pneumophila in mouse macrophages was significantly reduced after the addition of TubA. In the groups without the HDAC6 inhibitor, the live bacteria group had a stronger inhibiting effect on autophagic flux than the inactivated bacteria group compared with the normal control group. In the TubA groups with the HDAC6 inhibitor, the green fluorescence bright spots decreased and the autophagic flux increased in the live bacteria group. After the RAW264.7 macrophages were treated with inactivated and live Legionella pneumophila for 6, 12, 24, and 48 h, the mRNA and protein expression levels of HDAC6, α-tubulin, p97-VCP, and P62 decreased in the TubA group interfered with the Legionella pneumophila compared with the RAW264.7 normal control group. Conclusion The interference of Legionella pneumophila on the autophagy of macrophages is associated with the signal pathways of HDAC6/P62/LC3B and HDAC6/p97/HSF1.


Prenatal growth of the human cerebral cortex: brainprint analysis.
To construct a series of flat maps (brainprints) that document the prenatal growth of human cerebral cortex and help identify sulcal landmarks for division of cortical regions of interest (ROIs) on mapped surfaces, the authors photographed and traced histologic whole-brain slices of 25 normal human fetal brains aged 18-42 weeks gestation. Brainprints of both cerebral hemispheres from each fetus were constructed with semiautomatic brain-mapping software, and each map was divided into five ROIs based on sulcal landmarks: frontal, parietal, insular, occipital, and temporal cortices. Surface areas of cerebral hemispheres and the five ROIs were estimated. Corrected for histologic shrinkage, brainprint estimates of human fetal cortical surface area were approximately twice those of previous estimates. Cortical lobe proportions at 18 weeks appeared to be unchanged to term. Surface area estimates correlated with fetal age, brain weight, and brain volume. This collection of cortical maps may guide future quantitative analyses of cerebral hemispheric growth in premature and term infants who undergo magnetic resonance imaging, which may, in turn, help predict neurobehavioral outcomes of early cortical damage.


Comprehensive typing of DR52 (DRB3)-associated DRB1 and DRB3 alleles by PCR-RFLP.
The DR52-associated DRB1 and DRB3 alleles were resolved by PCR-RFLP. Second exon was amplified using four primer pairs (groups 1-4) for DRB1 and a pair for DRB3 alleles. Except for three endonucleases, all others had either none or only one site for a specific amplified product. Group 1 primers amplify 10 DRB1 alleles (DRB1*0302, 1101, 1302, 1303, 1305, 1307, 1402, 1403, 1407 and 1409). All but one pair, DRB1*1402 from 1409, could be resolved using seven endonucleases (ApaI, SacII, FokI, AvaII, BsaAI, BsrBI and SfaNI). Group 2 consisted of four alleles (DRB1*1201, 1202, 1404 and 1411) that can be resolved along with co-amplified DRB1*0804 and 0806 using five endonucleases (AvaII, SacII, FokI, HaeII and RsaI). Group 3 primers amplify 15 DRB1 alleles (DRB1*0301, 0303, 1102, 1103, 1104, 1107, 1301, 1304, 1306, 1308, 1401, 1405, 1406, 1408 and 14-New), which can be resolved using nine enzymes (KpnI, AvaII, FokI, SacII, HaeII, BsrBI, SfaNI, DdeI and RsaI). BsrBI, a new endonuclease, can resolve DRB1*1301 from 1306 and the previously unresolved allele DRB1*1103 from 1104. DRB1*1410, co-amplified with DR4 group-specific primers, is resolved with PstI which cleaves all DR4 alleles but not DRB1*1410. All four DRB3 alleles (DRB3*0101, 0201, 0202 and 0301) and their heterozygotes are resolved using two endonucleases, RsaI and HphI. Thirty-four DR52-associated alleles and their heterozygotes can be unambiguously resolved, except for DRB1*1402 from 1409.(ABSTRACT TRUNCATED AT 250 WORDS)


Inferring nonlinear neuronal computation based on physiologically plausible inputs.
The computation represented by a sensory neuron's response to stimuli is constructed from an array of physiological processes both belonging to that neuron and inherited from its inputs. Although many of these physiological processes are known to be nonlinear, linear approximations are commonly used to describe the stimulus selectivity of sensory neurons (i.e., linear receptive fields). Here we present an approach for modeling sensory processing, termed the Nonlinear Input Model (NIM), which is based on the hypothesis that the dominant nonlinearities imposed by physiological mechanisms arise from rectification of a neuron's inputs. Incorporating such 'upstream nonlinearities' within the standard linear-nonlinear (LN) cascade modeling structure implicitly allows for the identification of multiple stimulus features driving a neuron's response, which become directly interpretable as either excitatory or inhibitory. Because its form is analogous to an integrate-and-fire neuron receiving excitatory and inhibitory inputs, model fitting can be guided by prior knowledge about the inputs to a given neuron, and elements of the resulting model can often result in specific physiological predictions. Furthermore, by providing an explicit probabilistic model with a relatively simple nonlinear structure, its parameters can be efficiently optimized and appropriately regularized. Parameter estimation is robust and efficient even with large numbers of model components and in the context of high-dimensional stimuli with complex statistical structure (e.g. natural stimuli). We describe detailed methods for estimating the model parameters, and illustrate the advantages of the NIM using a range of example sensory neurons in the visual and auditory systems. We thus present a modeling framework that can capture a broad range of nonlinear response functions while providing physiologically interpretable descriptions of neural computation.


[Life extension study on high-yield non-myeloablating bone marrow transplantation from young to old mice].
Tissue renewal is the known phenomenon, when the progeny of resident or circulated stem cells (SC) replaces the vanishing cells. The delivery of stem cells via circulation should result in stem cell homing and differentiation into wide variety of tissues and gives promise as therapy for many diseases of tissue failure including aging itself. To test this hypothesis, we created chimeric mice C57BL/6 by bone marrow (BM) transplantation from young 1.5 months old donors to 21.5-months old recipient mice of the same strain C57BL/6. We applied here the recently published new transplantation technique, which allows to get high scores of chimerism due to very high amount of transplanted cells (1.5 x 10(8) per mouse or 25% of its total BM count). In the earlier works only 1% of total BM count (about 5 x 10(6) cells per mouse) was usually transplanted to lethally irradiated mice, what excluded the possibility to apply this method for life extension. As a result of the modified technique implementation, the mean post-transplantation life (starting the 21.5 months old) of treated mice was 4.9 months versus 3.4 months for untreated mice. The difference in 1.5 months counts for 44% extension of mean post-transplantation life.


Is the MNA valid in different populations and across practice settings?
The MNA is a successful screening tool in geriatric medicine, but this success is in Europe or countries with Western health care practice settings. The MNA is not directly applicable in many ethnic groups or countries or those with non-Western cultural and dietary habits or health care systems. There is an increased prevalence of type 2 diabetes, the metabolic syndrome and obesity among the elderly; however, the MNA does not include questions or measures related to these or other important health conditions affected by nutritional status. This paper addresses the relevance of anthropometry and the impact of different clinical practice settings on the MNA and discusses the development of the Chinese Nutritional Screen (CNS) in China. If the MNA is to continue to be successful among groups of elderly around the world, then the MNA, CNS or similar instruments should be as country or culturally and ethnically specific as possible. The development of the CNS maintained the underlying assumptions and concept of the MNA but modified them for a country with diverse food and cultural habits and health care settings.