[Application of an amphiphilic bonder in a goat model to increase the femoral cement-bone adhesion in cemented hip arthroplasty].
Cemented revision of femoral components in total hip arthroplasty has shown high rates of early loosening due to reduced micro- and macroretention of the cement to the endostal bone stock. Enhanced stability can be reached by an amphiphilic bonder, which offers a covalent bonding of the hydrophobic cement to the hydrophilic bone. The aim of this study is to evaluate the biocompatibility of such a bonder and its effects on the mechanical stability of cemented hip arthroplasty stems in vivo. Total cemented hip arthroplasties were performed in 20 sheep. In the verum group (n = 10) the implant bed was preconditioned by application of the bonder prior to femoral stem implantation. To study the biocompatibility around the bone-cement interface fluorescent marking of osteoblasts was applied in vivo throughout the observation period of 9 months. Native X-rays of the hip joints were obtained immediately after implantation and after euthanasia. The bone-cement interface was examined histologically. All stems of the verum group showed firm bonding of cement to bone in manual testing, while in 7 of the 10 controls the stems with adherent cement could be easily pulled out off the bony implant bed. This was coherent with significantly higher rates of progredient radiolucent lines and soft-tissue interpositions between bone and cement in the control group. The bonder was biocompatible. When preconditioned with an amphiphilic bonder, cemented stems showed a markedly higher adhesive strength to the cancellous bone without signs of inflammation or neoplasia. This procedure might offer enhanced longevity of cemented femoral revision stems in hip arthroplasty.


Psychological distress, intimate partner violence and substance use in a representative sample from Mexico: A structural equation model.
Intimate Partner Violence (IPV) is a public health concern associated with multiple adverse health outcomes, including psychological distress (PD). To assess the association of IPV and psychological distress, and the mediation of tobacco and alcohol consumption in a national representative sample from Mexico. Data from the Encuesta Nacional de Consumo de Drogas, Tabaco y Alcohol (ENCODAT) were analyzed. The sample included 34,864 people between the ages of 12 and 65 with a partner. Using Structural Equation Modeling (SEM), the association between IPV, use alcohol, tobacco and psychological distress was measured. The population was composed of women (51.9%) and men (48.1%); 15.1% (women = 18.2% and men = 11.9%) reported IPV in the last year. The prevalence of psychological distress in the last year was 3.3%, being 3.8% in women, and 2.7% in men. Results from the SEM in women indicated a direct positive effect of the IPV construct on psychological distress (β = 0.298, p < 0.01); these findings confirmed that IPV tended to systematically increase psychological distress. Likewise, the presence of IPV increased the consumption of tobacco (β = 0.077, p < 0.01) and alcohol (β = 0.072, p < 0.01). The SEM results in men showed that alcohol and tobacco consumption tended to increase in the presence of IPV (β = 0.121, p < 0.01, and β = 0.086, p < 0.01, respectively), and in turn, alcohol consumption and tobacco tended to increase psychological distress (β = 0.024, p < 0.01, and β = 0.025, p < 0.01, respectively). This study indicated that in women, IPV had a direct effect on psychological distress and on alcohol and tobacco consumption. Meanwhile in men, alcohol and tobacco consumption had a mediating effect between IPV and psychological distress. The empirical findings of this study will contribute toward the design of public health policies for the prevention and attention of IPV, alcohol and tobacco consumption, and consequently address the mental health consequences derived from these problems.


Pyruvate dehydrogenase complex (PDC) export from the mitochondrial matrix.
Studies on mitochondria protein import had revealed in detail molecular mechanisms of how peptides and proteins could be selectively targeted and translocated across membrane bound organelles. The opposite process of mitochondrial export, while known to occur in various aspects of cellular physiology and pathology, is less well understood. Two very recent reports have indicated that a large mitochondrial matrix protein complex, the pyruvate dehydrogenase complex (PDC) (or its component subunits), could be exported to the lysosomes and the nucleus, respectively. In the case of the latter, evidence was presented to suggest that the entire complex of 8-10 MDa could translocate in its entirety from the mitochondrial matrix to the nucleus upon mitogenic or stress stimuli. We discuss these findings in perspective to what is currently known about the processes of transport in and out of the mitochondrion.


Serial studies on the evolution of drug resistance in malaria in an area of east Africa: findings from 1979 up to 1986.
Observations, previously reported for 1979-82, have been continued up to 1986 on the development of drug resistance in P. falciparum in the North Mara area of Tanzania, where a chloroquine chemosuppression campaign was attempted from 1977 to 1982. The WHO micro in-vitro test for chloroquine and other drugs was used. Because of the large number of tests done, each test was characterized by the mean minimum inhibitory concentrations (MIC) of drug needed to prevent schizont development instead of counting the numbers of schizonts. The MIC for chloroquine has risen progressively each year but changes in the findings of in-vivo tests were less dramatic possibly due to the effects of immunity. Resistance to amodiaquine has followed that to chloroquine at a lower level, and in the last years the MIC for quinine has risen. Sporadic resistance to mefloquine was found and, by in-vivo test, to sulphadoxine-pyrimethamine. Possible factors in the evolution of drug resistance are discussed together with implications for the future.


Bone mineral density and body composition in adult patients with cystic fibrosis.
Cystic fibrosis is a multisystem disease characterised by chronic pulmonary sepsis and malnutrition. To ascertain whether osteoporosis is a feature of cystic fibrosis in adult patients, total body and regional bone mineral density (BMD) was measured in a group of eight men and eight women aged 17-42 years. Total body and regional BMD (lumbar spine L2-L4, femoral neck, trochanteric, and Ward's triangle), as well as total body fat and lean mass, were measured by dual energy x ray absorptiometry. A range of biochemical, lifestyle, and anthropometric variables was also assessed. Patients with cystic fibrosis had significantly reduced bone density at all sites compared with normal young adults. The mean reductions ranged from 7% at Ward's triangle to 13% at the trochanter. Body mass index (BMI) was positively correlated with BMD at four sites and disease severity negatively correlated with BMD at two sites. Other biochemical and anthropometric variables were not predictive of bone density. Total body fat mass was reduced by 30% compared with normal young adults. Bone density is decreased in adult patients with cystic fibrosis and BMI and disease severity are independent predictors of bone density.


[Avicenna--a great physician and thinker].
AVICENNA (980-1037), whose full name was Abu Ali al-Husayn ibn Abd-Allah ibn Sina, was the most renowned and influential medical man and philosopher of the medieval Islam. Over a three hundred of Avicenna's works have survived, ranging from encyclopedic treatments to short treatleses and covering apart from medicine, philosophy and science, religious, linguistic, and literary matters. He wrote some works in Persian, of which the Danishnama-yl 'Ala'i ("The Book of Science Dedicated to Ala's Dawla") is the most important. Most of his works, however, are in Arabic. His chief medical work is Al-Qanun fi't-tibb ("The Canon of Medicine"), a synthesis of Greek and Arabic medicine also includes his own clinical observations and views on scientific method. The most detailed philosophical work is the voluminous al-Shifa' ("The Healing"). Al-Najat ("The Deliverance") is largely a summary of al-Shifa', although there are some deviations. Al-Isharat wa al-Tanbihat ("The Directives and Remarks") gives the quintessence of Avicenna's philosophy, sometimes in an aphoristic style, and concludes with an expression of his mystical esoteric views, a part that relates to certain symbolic narratives which he also wrote.


Single drop solution electrode glow discharge for plasma assisted-chemical vapor generation: sensitive detection of zinc and cadmium in limited amounts of samples.
A simple and sensitive approach is proposed and evaluated for determination of ultratrace Zn and Cd in limited amounts of samples or tens of cells based on a novel single drop (5-20 μL) solution electrode glow discharge assisted-chemical vapor generation technique. Volatile species of Zn and Cd were immediately generated and separated from the liquid phase for transporting to atomic fluorescence or atomic mass spectrometric detectors for their determination only using hydrogen when the glow discharge was ignited between the surface of a liquid drop and the tip of a tungsten electrode. Limits of detection are better than 0.01 μg L(-1) (0.2 pg) for Cd and 0.1 μg L(-1) (2 pg) for Zn, respectively, and comparable or better than the previously reported results due to only a 20 μL sampling volume required, which makes the proposed technique convenient for the determination of Zn and Cd in limited amounts of samples or even only tens of cells. The proposed method not only retains the advantages of conventional chemical vapor generation but also provides several unique advantages, including better sensitivity, lower sample and power consumption, higher chemical vapor generation efficiencies and simpler setup, as well as greener analytical chemistry. The utility of this technique was demonstrated by the determination of ultratrace Cd and Zn in several single human hair samples, Certified Reference Materials GBW07601a (human hair powder) and paramecium cells.


Outcomes of epiretinal membrane surgery in highly myopic eyes: a case-control study.
To evaluate the outcomes of epiretinal membrane (ERM) surgery in highly myopic eyes and to compare them with those from non-highly myopic eyes. Retrospective nested case-control study from a cohort of 1776 consecutive patients (1776 eyes) who underwent surgery for ERM. Fifty-seven highly myopic eyes (with axial length longer than 26 mm) were included in the study group and were matched for preoperative visual acuity and duration of symptoms with 57 non-highly myopic control eyes selected from the same cohort. The best-corrected visual acuity (BCVA), the relationship between axial length and visual improvement, the central macular thickness (CMT) and the surgical complications were analysed. The mean axial length was 27.3±1.1 mm in highly myopic eyes and 23.1±1 mm in controls (p<0.001). At the 1-year final examination, the mean BCVA significantly improved from 0.62±0.23 logarithm of minimal angle of resolution (logMAR) to 0.27±0.21 logMAR in the study group (p<0.001) and from 0.61±0.22 logMAR to 0.25±0.15 logMAR in the control group (p<0.001). Similarly, the mean CMT significantly decreased in both groups (p<0.001). The two groups did not differ statistically in terms of visual and anatomical changes as well as surgical complications. There was no significant correlation between axial length and visual recovery. ERM surgery resulted in similar anatomical and functional outcomes in both groups. Longer axial length does not seem to affect visual improvement and the complication rate.


Clinical Factors Predictive for Intracranial Hemorrhage in Mild Head Injury.
Patients with mild head injuries, a GCS of 13-15, are at risk for intracranial hemorrhage. Clinical decision is needed to weigh between risks of intracranial hemorrhage and costs of the CT scan of the brain particularly those who are equivocal. This study aimed to find predictors for intracranial hemorrhage in patients with mild head injuries with a moderate risk of intracranial hemorrhage. We defined moderate risk of mild head injury as a GCS score of 13-15 accompanied by at least one symptom such as headache, vomiting, or amnesia or with alcohol intoxication. There were 153 patients who met the study criteria. Eighteen of the patients (11.76%) had intracranial hemorrhage. There were four independent factors associated with intracranial hemorrhage: history of hypertension, headache, loss of consciousness, and baseline GCS. The sensitivity for the presence of intracranial hemorrhage was 100% with the cutoff point for the GCS of 13. In conclusion, the independent factors associated with intracranial hemorrhage in patients with mild head injury who were determined to be at moderate risk for the condition included history of hypertension, headache, loss of consciousness, and baseline GCS score.


Platelet hyperaggregability to platelet activating factor (PAF) in non-ST elevation acute coronary syndromes.
It is known that myocardial ischaemia increases platelet aggregatory response to various agonists, ex vivo. We investigated the platelet aggregatory response to platelet activating factor (PAF), ex vivo, in patients with non-ST elevation acute coronary syndromes and determined the specificity and sensitivity of this response. Thirty-two consecutive patients with non-ST elevation acute coronary syndromes and 20 healthy volunteers were studied. Platelet aggregation in platelet-rich plasma was studied on the day of admission. The maximal aggregation achieved within 2 min after the addition of PAF (100 nM) was expressed as a percentage of 100% light transmission. PAF EC50 values were defined as the concentration that induces 50% of maximal aggregation. The PAF EC50 values of the non-ST elevation acute coronary syndromes patients were significantly lower compared to those of the controls (p < 0.0001). The maximal percentage of aggregation was also significantly higher (p < 0.0005). Ninety-one per cent of the patients were correctly classified using PAF EC50 values (specificity 90.0% and sensitivity 91.2%); the corresponding results using the maximal percentage of aggregation were 80% (specificity 70.0% and sensitivity 87.5%). The estimated values used as thresholds were 22.47 nM and 17.97 for the PAF EC50 and the maximal percentage of aggregation, respectively. The results of the present study suggest that platelet hyperaggregability to PAF, ex vivo, in non-ST elevation acute coronary syndromes is characterised by a high specificity and sensitivity, and thus it may represent a mechanism contributing to the pathophysiology of acute coronary syndromes.


Variability of the E2/NS1 region of Swedish hepatitis C virus strains and its correlation to genotypes.
Serum RNA was extracted from 5 Swedish patients infected with hepatitis C virus (HCV). The N-terminal part of the genomic region coding for the gp70 (E2/NS1), including the hypervariable domain of the E2 protein, was reverse transcribed and amplified by the polymerase chain reaction (PCR) using biotinylated primers. The amplicon was immobilized on magnetic polystyrene beads coated with streptavidine. Solid-state sequencing was carried out on the bound single-stranded DNA, after denaturation. The results of phylogenetic sequence analysis and calculated ratios of transition and transversion mutations showed that 4 of the strains clustered together with the USA prototype strains HCV-1 and HCV-H (genotype I), while 1 strain was close to the Japanese isolate HCV-J, and particularly to isolate HCV-BK (genotype II). Possible antigenic epitopes in the Swedish strains were mapped in the HVR region.


Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.
Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria.


Comparative analysis of biodiesel produced by acidic transesterification of lipid extracted from oleaginous yeast Rhodosporidium toruloides.
This study investigated the potential of oleaginous yeast Rhodosporidium toruloides strain (ATCC20409) for the sustainable production of microbial lipids as biodiesel feedstock and other economically important fatty acids in comparison to algal or plant-based biodiesel. The strain exhibited high lipid content (76% of dry cell weight biomass) through consolidated bioprocessing which was transesterified to produce biodiesel. Physico-chemical properties of the biodiesel produced showed that they were in accordance with ASTM standards, although few parameters such as acid value, calorific value and free fatty acid value differed to some extent, as also reported in plant-based/microalgal biodiesel. Fatty acid methyl esters analysis of biodiesel showed 50.18% unsaturated fatty acid and 49.81% saturated fatty acid. Total content of (monounsaturated fatty acid) MUFA was higher than (polyunsaturated fatty acid) PUFA, being 44.36% and 2.69%, respectively. Considering the yield and cost, lipid extracted from R. toruloides may become a promising alternative feed in biodiesel production.


The zinc finger SET domain gene Prdm14 is overexpressed in lymphoblastic lymphomas with retroviral insertions at Evi32.
AKXD recombinant inbred strains of mice have proven to be very useful in the identification of potential oncogenes and tumor suppressors involved in the development of lymphoid and myeloid malignancies. In these tumors, the hematopoietic insertion of an active AKV murine leukemia virus (MuLV) is associated with the onset of disease. Common sites of retroviral insertion (CIS) identify genes causally associated with the development or initiation of lymphoma. In the present study, we analyzed a previously uncharacterized CIS, Ecotropic Viral Integration Site 32 (Evi32), which is located on mouse chromosome 1. We analyzed candidate genes in the region to identify those involved in Evi32 mediated oncogenesis. Here we show that proviral insertion at Evi32 correlates with significant overexpression of a putative transcription factor, PR-domain containing 14 (Prdm14). Tumors with insertions at Evi32 are consistently lymphoid in nature. Prdm14 is normally expressed early in embryonic development with the highest expression in undifferentiated embryonic stem (ES) cells. This study implicates Prdm14 as a proto-oncogene involved in lymphoblastic lymphoma formation.


Potent Plasmodium falciparum gametocytocidal activity of diaminonaphthoquinones, lead antimalarial chemotypes identified in an antimalarial compound screen.
Forty percent of the world's population is threatened by malaria, which is caused by Plasmodium parasites and results in an estimated 200 million clinical cases and 650,000 deaths each year. Drug resistance has been reported for all commonly used antimalarials and has prompted screens to identify new drug candidates. However, many of these new candidates have not been evaluated against the parasite stage responsible for transmission, gametocytes. If Plasmodium falciparum gametocytes are not eliminated, patients continue to spread malaria for weeks after asexual parasite clearance. Asymptomatic individuals can also harbor gametocyte burdens sufficient for transmission, and a safe, effective gametocytocidal agent could also be used in community-wide malaria control programs. Here, we identify 15 small molecules with nanomolar activity against late-stage gametocytes. Fourteen are diaminonaphthoquinones (DANQs), and one is a 2-imino-benzo[d]imidazole (IBI). One of the DANQs identified, SJ000030570, is a lead antimalarial candidate. In contrast, 94% of the 650 compounds tested are inactive against late-stage gametocytes. Consistent with the ineffectiveness of most approved antimalarials against gametocytes, of the 19 novel compounds with activity against known anti-asexual-stage targets, only 3 had any strong effect on gametocyte viability. These data demonstrate the distinct biology of the transmission stages and emphasize the importance of screening for gametocytocidal activity. The potent gametocytocidal activity of DANQ and IBI coupled with their efficacy against asexual parasites provides leads for the development of antimalarials with the potential to prevent both the symptoms and the spread of malaria.


Clinical Characteristics of Early-Onset and Late-Onset Leigh Syndrome.
Background: Leigh syndrome (LS) is the most common pediatric mitochondrial diseases caused by MRC defect. LS patients typically have onset age before 2 years old and have various clinical features. The purpose of this study was to evaluate the various characteristics between the group that were early onset and late onset patients. Methods: The medical records of this study used records between 2006 and 2017 (N = 110). Clinical characteristics, diagnostic evaluations, and neuro image studying of LS were reviewed in our study. We statistically analyzed data from patients diagnosed with LS at our hospital by using subgroup analysis was performed to divide patients according to the onset age. Results: Among the patients, 89 patients (80.9%) had the onset age before 2 years old, and 21 patents (19.1%) had onset age after 2 years old. In subgroup analysis first clinical presentation age, diagnosis age and several onset symptoms in the clinical characteristics were statistically significant. Early onset age group showed delayed development and late onset age group showed motor weakness and ataxia. However, Diagnostics evaluation and MRI findings showed no significant differences. The clinical status monitored during the last visit showed statistically significant differences in the clinical severity. In the early onset age group clinical status was more severe than late onset age group. Conclusions: Although the onset of Leigh syndrome is known to be under 2 years, there are many late onset cases were existed more than expected. Early onset LS patients have poor prognosis compare with late onset LS patients. Therefore, the specific phenotype according to the age of onset should be well-observed. Onset of LS is important in predicting clinical severity or prognosis, and it is necessary to provide individualized treatment or follow-up protocols for each patient.


Unlike in Drosophila Meroistic Ovaries, hippo represses notch in Blattella germanica Panoistic ovaries, triggering the mitosis-endocycle switch in the follicular cells.
During insect oogenesis, the follicular epithelium undergoes both cell proliferation and apoptosis, thus modulating ovarian follicle growth. The Hippo pathway is key in these processes, and has been thoroughly studied in the meroistic ovaries of Drosophila melanogaster. However, nothing is known about the role of the Hippo pathway in primitive panoistic ovaries. This work examines the mRNA expression levels of the main components of the Hippo pathway in the panoistic ovary of the basal insect species Blattella germanica, and demonstrates the function of Hippo through RNAi. In Hippo-depleted specimens, the follicular cells of the basal ovarian follicles proliferate without arresting cytokinesis; the epithelium therefore becomes bilayered, impairing ovarian follicle growth. This phenotype is accompanied by long stalks between the ovarian follicles. In D. melanogaster loss of function of Notch determines that the stalk is not developed. With this in mind, we tested whether Hippo and Notch pathways are related in B. germanica. In Notch (only)-depleted females, no stalks were formed between the ovarian follicles. Simultaneous depletion of Hippo and Notch rescued partially the stalk to wild-type. Unlike in the meroistic ovaries of D. melanogaster, in panoistic ovaries the Hippo pathway appears to regulate follicular cell proliferation by acting as a repressor of Notch, triggering the switch from mitosis to the endocycle in the follicular cells. The phylogenetically basal position of B. germanica suggests that this might be the ancestral function of Hippo in insect ovaries.


Carbon source-dependent phosphorylation of hexokinase PII and its role in the glucose-signaling response in yeast.
The HXK2 gene is required for a variety of regulatory effects leading to an adaptation for fermentative metabolism in Saccharomyces cerevisiae. However, the molecular basis of the specific role of Hxk2p in these effects is still unclear. One important feature in order to understand the physiological function of hexokinase PH is that it is a phosphoprotein, since protein phosphorylation is essential in most metabolic signal transductions in eukaryotic cells. Here we show that Hxk2p exists in vivo in a dimeric-monomeric equilibrium which is affected by phosphorylation. Only the monomeric form appears phosphorylated, whereas the dimer does not. The reversible phosphorylation of Hxk2p is carbon source dependent, being more extensive on poor carbon sources such as galactose, raffinose, and ethanol. In vivo dephosphorylation of Hxk2p is promoted after addition of glucose. This effect is absent in glucose repression mutants cat80/grr1, hex2/reg1, and cid1/glc7. Treatment of a glucose crude extract from cid1-226 (glc7-T152K) mutant cells with lambda-phosphatase drastically reduces the presence of phosphoprotein, suggesting that CID1/GLC7 phosphatase together with its regulatory HEX2/REG1 subunit are involved in the dephosphorylation of the Hxk2p monomer. An HXK2 mutation encoding a serine-to-alanine change at position 15 [HXK2 (S15A)] was to clarify the in vivo function of the phosphorylation of hexokinase PII. In this mutant, where the Hxk2 protein is unable to undergo phosphorylation, the cells could not provide glucose repression of invertase. Glucose induction of HXT gene expression is also affected in cells expressing the mutated enzyme. Although we cannot rule out a defect in the metabolic state of the cell as the origin of these phenomena, our results suggest that the phosphorylation of hexokinase is essential in vivo for glucose signal transduction.


The role of pharmacy computer systems in preventing medication errors.
To describe the controversies and review the evidence about computer-aided prospective drug utilization review (PDUR) systems. MEDLINE search of the literature. Published studies of the effectiveness of computer-aided prescription screening. One randomized, controlled trial and four nonrandomized studies constitute the evidence base. The five studies are inconclusive with respect to whether computer-aided prescription screening causes health care providers to take action, either because of a no difference finding or because there was no comparison group. In the one randomized, controlled trial, a substantial number of actions were taken by the control group whose members did not receive alerts. No study evaluated the total effect of screening by in-store and payer (online) systems. Specific research recommendations are made to increase the evidence base. Limited and inconclusive evidence about whether these systems are effective and what system features are optimal may explain the wide variation among systems in terms of what problems are screened and may also explain clinicians' uncertainty about their value. A comprehensive national research agenda for reducing medical errors should include research on the effectiveness of computer-aided PDUR.


How the Innate Immune System Senses Trouble and Causes Trouble.
The innate immune system is the first line of defense in response to nonself and danger signals from microbial invasion or tissue injury. It is increasingly recognized that each organ uses unique sets of cells and molecules that orchestrate regional innate immunity. The cells that execute the task of innate immunity are many and consist of not only "professional" immune cells but also nonimmune cells, such as renal epithelial cells. Despite a high level of sophistication, deregulated innate immunity is common and contributes to a wide range of renal diseases, such as sepsis-induced kidney injury, GN, and allograft dysfunction. This review discusses how the innate immune system recognizes and responds to nonself and danger signals. In particular, the roles of renal epithelial cells that make them an integral part of the innate immune apparatus of the kidney are highlighted.


Application of haptic feedback to robotic surgery.
Robotic surgical systems have greatly contributed to the advancement of minimally invasive endoscopic surgery. However, current robotic systems do not provide tactile or haptic feedback to the operating surgeon. Under certain circumstances, particularly with the manipulation of delicate tissues and suture materials, this may prove to be a significant irritation. We hypothesize that haptic feedback, in the form of sensory substitution, facilitates the performance of surgical knot tying. This preliminary study describes evidence that visual sensory substitution permits the surgeon to apply more consistent, precise, and greater tensions to fine suture materials without breakage during robot-assisted knot tying.


Abuse liability of electronic cigarettes in men who are experienced electronic cigarette users.
Most electronic cigarettes (e-cigs) aerosolize a nicotine-containing liquid that users inhale. Few experimental studies have examined e-cig abuse liability (the extent to which use of these products may lead to persistent and/or problematic use). In this study, 24 experienced male e-cig users completed 4 sessions that differed byproduct used: own e-cig (OWN), an eGo e-cig filled with participants' own brand/flavor liquid in 0 mg/mL nicotine (e-cig0), an eGo e-cig filled with the highest nicotine concentration available in participants' own brand/flavor (e-cighighest), and a U.S. Food and Drug Administration-approved nicotine inhaler (IN). Outcome measures included crossover point on the multiple-choice procedure, plasma nicotine delivery, and subjective effect profile. After 10 puffs, a significantly higher mean crossover point was observed for OWN at $1.35 (SD = 0.90) compared to e-cighighest at $0.88 (SD = 0.89), e-cig0 at $0.83 (SD = 0.79), and IN at $0.72 (SD = 0.84). Significant increases in mean plasma nicotine concentration were observed for OWN at 7.94 ng/mL (SD = 6.19) and e-cighighest at 7.51 ng/mL (SD = 5.39). Significant reductions in abstinence symptom suppression and higher ratings of satisfaction were observed for OWN and e-cighighest, with significantly less suppression and lower ratings of satisfaction for e-cig0 and IN. These findings suggest that human laboratory methods can be used to assess e-cig abuse liability and that nicotine-containing e-cigs have greater abuse liability than nicotine-free e-cigs and the IN. Potential regulations intended to limit e-cig abuse liability should be tested using these or similar procedures. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Detection limit analysis of optical fiber sensors based on interferometers with the Vernier-effect.
Vernier-effect has been widely employed in interferometer-based optical fiber sensors to improve the sensitivities greatly. However, the influence of the Vernier-effect on detection limit (DL) that is more important for evaluating the actual performance of the sensor has not been discussed. Two gas pressure fiber sensors (a typical Fabry-Perot interferometer-based sensor and a Vernier sensor) are used to compare the DL of them by experiments. Both the theoretical analysis and the experimental results show that, though the Vernier-effect magnifies the spectrum shift sensitivity, it also magnifies the value of the smallest detectable wavelength shift. As a result, the actual DL of the sensor is not improved by employing the Vernier-effect. If the contrast ratio of the Vernier envelope is not optimized enough for most of the reported sensors, the DL can even degenerate greatly.


Ophthalmologic findings in patients with non-surgically treated blowout fractures.
We evaluated the ocular and visual status in a group of patients with a non-surgically treated blowout fracture. Clinical examination with refraction, test of binocular function, and tear film evaluation was performed in 23 patients. These values were statistically correlated with the orbital volume measurements and ocular finding from the patient records at presentation. About 50% of the study group was symptomatic due to low visual acuity from refractive errors and decompensated phorias as a consequence of the blowout fracture. Several patients displayed changes in tear film production. There was no strong correlation between the measured parameters and orbital volume measurements. Patients with a non-surgically treated blowout fracture often display ocular and visual changes after discharge. A routine visual exam is advocated in all patients after the ocular status has stabilized after a blowout fracture.


Studies on the constituents of Cimicifuga foetida collected in Guizhou Province and their cytotoxic activities.
Two new triterpenoids and a chromone glycoside, namely, 24-epi-cimigenol-3-one (1), foetinoside (2), cimifugin-4'-O-[6″-feruloyl]-β-D-glucopyranoside (3), together with 18 known compounds, were isolated from the rhizomes of Cimicifuga foetida L. collected in Guizhou Province, China. All of the compounds were identified by spectroscopic methods, as well as chemical methods. In the in vitro cytotoxicity evaluation of these compounds against 5 human cancer cell lines, cimigenol (8) exerted the most potent cytotoxic activity against SMMC-7721 (7.87 µM) and A-549 (12.16 µM), while cimiacerin B (9) also showed obvious cytotoxicity against the A-549 cell line, with an IC(50) value of 16.77 µM.


A case of association between hepatocellular carcinoma and porphyria variegata.
A correlation between acute intermittent porphyria or porphyria cutanea tarda and hepatocellular carcinoma (HCC) has been noted in several studies, but only one case of association between HCC and porphyria variegata has been reported. We therefore report another case of association between HCC and porphyria variegata. A 54-year-old nurse with familial porphyria variegata who developed an HCC was studied. The diagnosis of porphyria variegata was made in the course of a familial survey by means of measuring lymphocyte protoporphyrinogen oxidase activity, at a time when the patient had no symptoms. Eighteen years later the patient presented with a firm enlargement of the liver. Histologic examination showed a well-differentiated HCC. The diagnosis was confirmed by positive immunostaining for alpha-foetoprotein antibodies. Sixteen months after surgical resection of the HCC the patient was still alive.


Engineering Erg10 Thiolase from Saccharomyces cerevisiae as a Synthetic Toolkit for the Production of Branched-Chain Alcohols.
Thiolases catalyze the condensation of acyl-CoA thioesters through the Claisen condensation reaction. The best described enzymes usually yield linear condensation products. Using a combined computational/experimental approach, and guided by structural information, we have studied the potential of thiolases to synthesize branched compounds. We have identified a bulky residue located at the active site that blocks proper accommodation of substrates longer than acetyl-CoA. Amino acid replacements at such a position exert effects on the activity and product selectivity of the enzymes that are highly dependent on a protein scaffold. Among the set of five thiolases studied, Erg10 thiolase from Saccharomyces cerevisiae showed no acetyl-CoA/butyryl-CoA branched condensation activity, but variants at position F293 resulted the most active and selective biocatalysts for this reaction. This is the first time that a thiolase has been engineered to synthesize branched compounds. These novel enzymes enrich the toolbox of combinatorial (bio)chemistry, paving the way for manufacturing a variety of α-substituted synthons. As a proof of concept, we have engineered Clostridium's 1-butanol pathway to obtain 2-ethyl-1-butanol, an alcohol that is interesting as a branched model compound.


Dependence of magnetic domain-wall motion on a fast changing current.
A dependence of current-induced domain-wall motion in nanowires on the temporal shape of current pulses is observed. The results show that the motion of the wall is amplified for alterations of the current on a time scale smaller than the intrinsic time scale of the domain wall which is a few nanoseconds in permalloy. This effect arises from an additional force on the wall by the spin-transfer torque due to a fast changing current and improves the efficiency of domain-wall motion. The observations provide an understanding for the efficient domain-wall motion with nanosecond current pulses.


Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats.
The ability of progesterone to reduce the cerebral edema associated with traumatic brain damage first became apparent when we observed that males had significantly more edema than females after cortical contusion. In addition, edema was almost absent in pseudopregnant female rats, a condition in which progesterone levels are high relative to estrogen. Progesterone injections given after injury also reduced edema and were equally effective in both males and females. The present experiment was done to determine if the progesterone-induced reduction in edema could also prevent secondary neuronal degeneration and reduce the behavioral impairments that accompany contusion of the medial frontal cortex. Progesterone-treated rats were less impaired on a Morris water maze spatial navigation task than rats treated with the oil vehicle. Progesterone-treated rats also showed less neuronal degeneration 21 days after injury in the medial dorsal thalamic nucleus, a structure that has reciprocal connections with the contused area.


Assessment of pain, depression, and anxiety by visual analogue scale in Japanese women with rheumatoid arthritis.
Assessment of pain, depression, and anxiety by visual analogue scale in Japanese women with rheumatoid arthritis Visual analogue scales (VAS) of depression and anxiety were compared with standard full-length measures of these variables and with VAS of pain (VAS Pain). This was a good way to develop a practical methodology for the routine assessment of pain and affect in rheumatoid arthritis (RA) patients. The reliability of VAS Pain was studied by test-retest. The validity of VAS Pain in our sample was proved by correlations with the results of other tests. We also investigated the relationship between VAS Pain and C-reactive protein (CRP). In 145 female RA patients, VAS of depression and anxiety were significantly correlated with full-length measures of these variables, and accounted for the majority of the explained variance in VAS Pain, while the full-length standard measures contributed little more. In conclusion, VAS measurements of pain and affect were comprehensible, easily filled-out, and reliable in a sample of Japanese women with RA, and could capture some aspect of affective distress unique to RA patients.


The pharmacological properties of anisodamine.
Anisodamine is a naturally occurring atropine derivative that has been isolated, synthesized and characterized by scientists in the People's Republic of China. Like atropine and scopolamine, anisodamine is a non-specific cholinergic antagonist exhibiting the usual spectrum of pharmacological effects of this drug class. It appears to be less potent and less toxic than atropine and displays less CNS toxicity than scopolamine. Anisodamine has been shown to interact with and disrupt liposome structure which may reflect its effects on cellular membranes. Experimental evidence implicates anisodamine as an anti-oxidant that may protect against free radical-induced cellular damage. Its cardiovascular properties include depression of cardiac conduction and the ability to protect against arrhythmia induced by various agents. Anisodamine is a relatively weak alpha(1) adrenergic antagonist which may explain its vasodilating activity. Its anti-thrombotic activity may be a result of inhibition of thromboxane synthesis. The T(1/2) of anisodamine in humans is about 2-3 h. Numerous therapeutic uses of anisodamine have been proposed including treatment of septic shock, various circulatory disorders, organophosphorus (OP) poisoning, migraine, gastric ulcers, gastrointestinal colic, acute glomerular nephritis, eclampsia, respiratory diseases, rheumatoid arthritis, obstructive jaundice, opiate addiction, snake bite and radiation damage protection. The primary therapeutic use of anisodamine has been for the treatment of septic shock. Several mechanisms have been proposed to explain its beneficial effect though most mechanisms are based upon the assumption that anisodamine ultimately acts by an improvement of blood flow in the microcirculation. Preliminary studies suggest another important therapeutic use of anisodamine is for the treatment of OP poisoning. Additional research is needed to delineate further the clinical usefulness of anisodamine relative to other anti-muscarinic drugs such as atropine and scopolamine.


Oxidative stress in very low birth weight infants as measured by urinary 8-OHdG.
Very low birth weight (VLBW) infants can be subjected to oxidative stress in the course of intensive care. We measured 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative stress, and estimated the degree of oxidative stress in such infants. We also examined if the administered oxygen was related to oxidative stress. Urine samples of 50 Japanese VLBW infants [birth weights: 956.3+/-277.6g, and gestational ages: 28.0+/-2.6 weeks (mean +/- SD)] were collected on various postnatal days and 8-OHdG levels were determined using an ELISA kit. Sixteen term infants served as normal controls. As body weights at sampling increased, the average levels of urinary 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants under 1000g, 29.5+/-16.4 micromol/mol creatinine (n = 24); 1000-1500g, 23.8+/-14.9 (n = 12); over 1500g, 16.1+/-8.5 (n = 14); and control, 10.9+/-7.2 (n = 16). Significant differences were found between <1000g group and > or = 1500g group (p = 0.0030), <1000g group and control (p < 0.0001), and 1000-1500g group and control (p = 0.0108). Also as postconceptional age at sampling increased, the average levels of 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants before 252 days (36 weeks) of postconception: 27.4+/-15.5 micromol/mol creatinine (n = 34); after 252 days, 18.2+/-12.5 (n = 16). Differences between <252 days group and control (p < 0.0001), and <252 days group and > or = 252 days groups (p = 0.0253) were statistically significant. Among the three groups based on ambient oxygen concentration (21%, 22-29%, and > or = 30%) there was no significant difference (p = 0.417). The more premature the infants were, the more intense was the oxidative stress, hence, it is the prematurity rather than the administered oxygen which causes oxidative stress in VLBW infants. Drury et al. ["Urinary 8-hydroxydeoxyguanosine in infants and children" Free Radic. Res. 28 (1998) 423-4281 measured urinary 8-OHdG of 28 infants (24-40 weeks gestation) and found no gestation or birthweight related differences. This discrepancy seemed to be because of difference in birth weights and sampling period of the subjects.


Scanning electrochemical microscopy of DNA monolayers modified with Nile Blue.
Scanning electrochemical microscopy (SECM) is used to probe long-range charge transport (CT) through DNA monolayers containing the redox-active Nile Blue (NB) intercalator covalently affixed at a specific location in the DNA film. At substrate potentials negative of the formal potential of covalently attached NB, the electrocatalytic reduction of Fe(CN)6(3-) generated at the SECM tip is observed only when NB is located at the DNA/solution interface; for DNA films containing NB in close proximity to the DNA/electrode interface, the electrocatalytic effect is absent. This behavior is consistent with both rapid DNA-mediated CT between the NB intercalator and the gold electrode as well as a rate-limiting electron transfer between NB and the solution phase Fe(CN)6(3-). The DNA-mediated nature of the catalytic cycle is confirmed through sequence-specific and localized detection of attomoles of TATA-binding protein, a transcription factor that severely distorts DNA upon binding. Importantly, the strategy outlined here is general and allows for the local investigation of the surface characteristics of DNA monolayers both in the absence and in the presence of DNA binding proteins. These experiments highlight the utility of DNA-modified electrodes as versatile platforms for SECM detection schemes that take advantage of CT mediated by the DNA base pair stack.


Sulfometuron resistance as a genetic marker for yeast populations in wine fermentations.
Winemaking with selected yeasts requires simple and cheap techniques to monitor the yeast population dynamics. We obtained new sulfometuron (smr) resistant mutants, easy to detect by replica-plate assay, from selected wine yeasts. The mutations were dominant and were located at the ilv2 locus that encodes for acetolactate synthase enzyme. The mutants were genetically stable and maintained the killer phenotype of the parent yeast strain. They were genetically improved by elimination of recessive growth-retarding alleles followed by spore clone selection according to the must fermentation kinetics and the organoleptic quality of the wine. Some mutants were tested in industrial winemaking and were easily monitored during must fermentation using a simple plate assay. They accounted for more than 95% of the total yeasts in the must, and the resulting wine had as good a quality as those made with standard commercial wine yeasts.


Ventromedial Hypothalamus and the Generation of Aggression.
Aggression is a costly behavior, sometimes with severe consequences including death. Yet aggression is prevalent across animal species ranging from insects to humans, demonstrating its essential role in the survival of individuals and groups. The question of how the brain decides when to generate this costly behavior has intrigued neuroscientists for over a century and has led to the identification of relevant neural substrates. Various lesion and electric stimulation experiments have revealed that the hypothalamus, an ancient structure situated deep in the brain, is essential for expressing aggressive behaviors. More recently, studies using precise circuit manipulation tools have identified a small subnucleus in the medial hypothalamus, the ventrolateral part of the ventromedial hypothalamus (VMHvl), as a key structure for driving both aggression and aggression-seeking behaviors. Here, we provide an updated summary of the evidence that supports a role of the VMHvl in aggressive behaviors. We will consider our recent findings detailing the physiological response properties of populations of VMHvl cells during aggressive behaviors and provide new understanding regarding the role of the VMHvl embedded within the larger whole-brain circuit for social sensation and action.


Survival analysis without survival data: connecting length-biased and case-control data.
We show that relative mean survival parameters of a semiparametric log-linear model can be estimated using covariate data from an incident sample and a prevalent sample, even when there is no prospective follow-up to collect any survival data. Estimation is based on an induced semiparametric density ratio model for covariates from the two samples, and it shares the same structure as for a logistic regression model for case-control data. Likelihood inference coincides with well-established methods for case-control data. We show two further related results. First, estimation of interaction parameters in a survival model can be performed using covariate information only from a prevalent sample, analogous to a case-only analysis. Furthermore, propensity score and conditional exposure effect parameters on survival can be estimated using only covariate data collected from incident and prevalent samples.


A divergently transcribed open reading frame is located upstream of the Pseudomonas aeruginosa vfr gene, a homolog of Escherichia coli crp.
The Pseudomonas aeruginosa homolog of the Escherichia coli global transcriptional regulator CRP (or CAP) was recently identified and designated Vfr (S. E. H. West, A. K. Sample, and L. J. Runyen-Janecky, J. Bacteriol. 176:7532-7542, 1994). Nucleotide sequence analysis of the region 5' to vfr identified a 423-bp open reading frame (ORF), which was designated orfX. The deduced amino acid sequence of ORFX was 53% identical and 87% similar to a divergent ORF of unknown function located 5' to the E. coli crp gene. When orfX was expressed from a phage T7 promoter in E. coli, a protein with an apparent molecular mass of approximately 18 kDa was produced. We constructed a chromosomal deletion of the region containing the 5' end of orfX (orfX'), vfr, and the 3' end of trpC (trpC') in P. aeruginosa strains PAO1 and PA103. The cloned vfr gene restored Vfr-dependent production of exotoxin A and protease in the PA103 orfX'-vfr-trpC' deletion mutant, suggesting that ORFX is not required for Vfr production or activity. To determine whether transcription of orfX and vfr are controlled by the same mechanisms that control transcription of the region of the divergent ORF (dorf) and of crp, we compared the vfr-orfX and crp-dorf intergenic regions. Using S1 nuclease analysis, we determined that the distance between the orfX and vfr transcriptional start sites was 105 bp. Thus, the P. aeruginosa orfX and vfr promoters are arranged in a back-to-back orientation rather than the face-to-face orientation of the dorf and crp promoters. A CRP recognition site is associated with each promoter in the crp-dorf intergenic region; binding of the CRP-cyclic AMP complex to the stronger dorf CRP recognition site activates transcription from the dorf promoter and represses transcription from the crp promoter. The vfr-orfX intergenic region does not contain an obvious CRP recognition site. In addition, vfr was not required for transcription of orfX. Unlike the dorf and crp mRNAs, the 5' ends of the orfX and vfr mRNAs were not complementary. Thus, the orfX mRNA cannot hybridize to the 5' end of the vfr mRNA to inhibit vfr transcription, a mechanism that has been postulated to control crp transcription in E. coli.


Screening.
Screening is the only practical approach for improving the management of hepatocellular carcinoma (HCC) patients, as early detection increases the application of curative treatments. A conference of experts from Japan, USA, and Europe (Barcelona 2005) advised surveillance every six months for patients with chronic liver disease at increased risk of HCC with abdominal US. Whether this approach benefits HCC patients in terms of survival is still uncertain, since available data are retrospective and biased by lead-time factors in the calculation of patient survival. Only one randomized controlled study in China showed the benefit of surveillance for HCC; however, in a population-based setting. Today, clinic-based, randomized studies are unfeasible for ethical reasons. In a cohort of 447 Italian patients with compensated cirrhosis, we compared the survival of HCC patients identified along three consecutive quinquennia of surveillance. HCC developed in 112 patients (3.4% per year) and was the prime cause of death. Forty-six patients (41%) had a single tumor with mean sizes of 3.7, 3.0, and 2.2 cm in the three quinquennia (first vs third, P = 0.0147; second vs third, P = 0.02) and 38(44%) underwent radical therapies. Mortality rates in HCC patients fell from 45% in the first quinquennium to 10% in the third (P = 0.0009), in parallel with a reduction in mortality of treated patients (34, 28, and 5%) (first vs third, P = 0.0024). Cirrhotic patients developing HCC during the last five years of surveillance survived longer than previously, as a consequence of improved management of the tumor and complications of cirrhosis. It remains controversial whether HCC screening is cost-effective, i.e. whether the cost of detection, confirmatory studies, and treatment are outbalanced by the number of life-years gained. In a retrospective study of Italian patients with cirrhosis, there was an incremental cost-efficacy ratio of surveillance vs no surveillance to be $USD 112 993 per liver-year saved. The cost of surveillance was increased by surgery applied to 15 patients with HCC detected during surveillance.


Effectiveness of speech therapy in adults with intellectual disabilities.
This study investigated the effect of speech therapy in a heterogeneous group of adults with intellectual disability. Thirty-six adults with mild and moderate intellectual disabilities (IQs 40-70; age 18-40 years) with reported poor speech intelligibility received tailored training in articulation and listening skills delivered in two 3-month periods. Pre- to post-changes in speech intelligibility and receptive vocabulary were assessed using standardized tasks. The results showed a positive effect of treatment on speech intelligibility and receptive vocabulary, irrespective of severity of intellectual disability, hearing loss and intellectual disability aetiology. Speech therapy for people with intellectual disability can be effective at adult age and hearing loss should not prevent treatment. Continued attention to speech can help augment verbal communication skills in this population.


Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.
Genome-wide association studies (GWAS) in ethnic/racial minority populations can help to fine-map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.3, associated with colon cancer risk (odds ratio 0.61 for the risk allele G, p = 2.4 × 10-8 ). The frequency of the G allele was 0.06 in African Americans, compared to <0.01 in Europeans, Asians and Amerindians in the 1000 Genomes project. In addition, a variant previously identified through fine-mapping in this GWAS in the region 19q13.1, rs7252505, was confirmed to be more strongly associated with CRC in the African American replication set than the variant originally reported in Europeans (rs10411210). The association between rs7252505 and CRC was of borderline significance (p = 0.05) in a Hispanic population GWAS with 1,611 CRC cases and 4,330 controls. With the three datasets combined, the odds ratio was 0.84 for the risk allele A (95% confidence interval 0.79-0.89, p = 3.7 × 10-8 ). This study further highlights the importance of conducting GWAS studies in diverse ancestry populations.


N-Methyl-2-pyrrolidone as a Reaction Medium for Gold(III)-Ion Reduction and Star-like Gold Nanostructure Formation.
The efficiency of a wet chemical route to synthesize gold nanostructures with tunable size and shape significantly depends on the applied solvent and the interaction of solvent molecules with other species such as gold ions. The ability of the organic solvent N-methyl-2-pyrrolidone (NMP) as a suitable medium for application in star-like gold nanostructure (AuNS) synthesis with a tunable morphology at ambient conditions has been investigated. The time-dependent analysis of the UV-vis absorption spectra of AuIIICl4 - in a pure NMP solution illustrates the role of NMP as simultaneous complexing and reducing agents. Kinetic studies indicate that AuIIICl4 - in NMP solution is reduced to AuICl2 -, with no need to use another reducing agent, any external energy sources, or solvent pretreatment. This is because AuI species stay stable in this solution unless poly(vinylpyrrolidone) (PVP) catalyzes their disproportionation. Morphological studies by transmission electron microscopy (TEM) specify the high-yield synthesis of AuNS with monocrystalline spikes in a concentrated NMP solution by PVP. This study illustrates that the presence of seeds, as another agent to catalyze the disproportionation of AuI species, makes it possible to synthesize AuNS in varying concentrations of PVP in this medium. The role of PVP concentration and the presence of seeds in the formation kinetics, morphology, and optical properties is systematically discussed. The results achieved through this study develop a straightforward and safe procedure for AuNS synthesis in high yield in a water-miscible organic polar solvent with tunable morphology and optical properties. Considering the high capability of NMP to dissolve various types of polymers and hydrophobic ligands, synthesizing AuNS in this solvent opens a window to a practical and easy way to fabricate gold-based nanomaterials with fascinating optical properties.


Time-resolved picosecond photocurrents in contacted carbon nanotubes.
We introduce coplanar stripline circuits to resolve the ultrafast photocurrent dynamics of freely suspended carbon nanotubes (CNTs) in the time domain. By applying an on-chip pump-probe laser spectroscopy, we demonstrate that CNTs, contacted by metal electrodes, exhibit a picosecond photocurrent response. We find a combination of an optically induced ultrafast displacement current, transport of photogenerated charge carriers at the Fermi velocity to the electrodes, and interband charge-carrier recombination processes to dominate the ultrafast photocurrent of the CNTs.


In vivo treatment with antibody against IGF-1 receptor suppresses growth of human rhabdomyosarcoma and down-regulates p34cdc2.
In a previous study, we have shown that insulin-like growth factor type 2 (IGF-2) functions as an autocrine growth factor in human rhabdomyosarcoma (RMS) cell lines. In addition, we demonstrated that the inhibition of binding of IGF-2 to the IGF-1 receptor, mediated by suramin, blocked the growth of RMS cells in vitro. We now report that, in vivo, a specific IGF-1 receptor blocking antibody (alpha IR-3), but not suramin, suppresses RMS tumor growth. Both progression of tumor growth in tumor-bearing animals and formation of newly established tumors were suppressed by treatment with alpha IR-3. Histological analysis of tumors from treated animals did not reveal necrotic lesions, implying that the treatments had no cytotoxic effect. The decrease in tumor growth was associated with a decrease of p34cdc2, a cellular protein involved in cell cycle regulation, suggesting that treatment resulted in the arrest of cellular proliferation. We speculate, therefore, that agents which block the IGF signaling pathway may find application in treatment of RMS.


Genetic determinants of uterine fibroid size in the multiethnic NIEHS uterine fibroid study.
We conducted a follow-up association study across extended candidate chromosomal regions for uterine leiomyoma (UL), or fibroids, to search for loci influencing the size of UL in 916 premenopausal North American women participants to the NIEHS uterine fibroid study. Proportional odds models with adjustments for confounders were fitted to evaluate the association of a final set of 2,484 single nucleotide polymorphisms (SNPs) with the size of uterine fibroids measured by transabdominal and transvaginal ultrasounds. SNP association with UL size was tested in a case-only design comparing three categories of tumor size (small, medium and large tumors) and in a design that included UL-free controls as the lowest category of a four-level ordinal outcome to account for misclassifications due to small, undetected tumors. In the case-only design, rs2285789 in SORCS2 (sortilin-related VPS10 domain containing receptor 2) was the sole variant that remained significant after correction for multiple testing (Bonferroni-adjusted P=0.037). Several other SNPs, namely those located in MYT1L, TMCC1 and BRCA1, reached promising associations. In the design that included the controls, several genes of potential relevance to UL pathogenesis were associated (Bonferroni-unadjusted P < 0.01) with tumor size, particularly LIFR-AS1 (leukemia inhibitory factor receptor alpha-antisense RNA 1), which showed the strongest association (Bonferroni-unadjusted P=0.0006) among the genes with regulated expression in UL. In conclusion, SORCS2, a known GWAS candidate for circulating IGF-I and IGFBP-3, may act through IGF-I signaling to affect the size of fibroids. Through down-regulation of LIFR, LIFR-AS1 may mediate the inhibitory action of LIF (leukemia inhibitory factor), a cytokine involved in embryonic uterine development. Replication analyses are needed to substantiate our reported associations of SORCS2 and LIFR-AS1 with the size of fibroids.


Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer.
Peritoneal recurrence is a major cause of death in advanced gastric cancer. Although many kinds of chemotherapy intended to prevent peritoneal recurrence of gastric cancer have been evaluated, few have been successful. Few studies have assessed the clinical significance of continuous hyperthermic peritoneal perfusion in peritoneal recurrence. From 1992 to 1999, a total of 124 patients with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis underwent potentially curative gastrectomy and were enrolled in this study. Prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) was performed in 45 patients younger than 65 years old and without comorbidity who gave informed consent. Seventy-nine patients who did not meet the inclusion criteria represented the control group. After reconstruction of the alimentary tract, P-CHPP was carried out for 40 minutes with 150 mg cisplatin, 15 mg mitomycin C, and 150 mg etoposide in 5 to 6 L physiologic saline maintained at 42 degrees C to 43 degrees C. The surgical results, recurrent pattern, and postoperative morbidity were assessed by univariate and multivariate analysis. When compared with patients not undergoing P-CHPP, patients treated by P-CHPP had higher incidences of respiratory failure (73% vs 19%; P <.0001) and renal failure (7% vs 0%; P <.03). Neither 5-year survival (49% vs 56%) nor the patterns of recurrence (peritoneal, hematogenous, and lymphatic) were affected by P-CHPP. P-CHPP by our methods had no efficacy as prophylactic treatment for peritoneal recurrence induced by gastric cancer. New therapeutic strategies, such as chemosensitivity assessment, are necessary to obtain good therapeutic results with CHPP.


Application of Bifacial Semitransparent CuInSe2 Absorber to the Bottom Cell in Bifacial Semitransparent Perovskite/CuInSe2 Tandem Solar Cell for Albedo Environment.
Although various types of bifacial solar cells exist, few studies have been conducted on bifacial semitransparent CuInSe2 solar cells (BS-CISe SCs) despite the attractive potential in power generation from both sides in an albedo environment. The optimized BS-CISe SCs with 300 and 800 nm-thick absorber via a streamlined single-stage co-evaporation process exhibit a power conversion efficiency (PCE) of 6.32% and 10.6%, respectively. When double-sided total 2.0 sun illumination is assumed in an albedo environment, the bifacial power generation densities (BPGD) of them increases to 9.41% and 13.9%. Four-terminal bifacial semitransparent tandem solar cells (4T-BST SCs) are fabricated to increase the BPGD by mechanically stacking a BS-perovskite (PVK) top cell on top of a BS-CISe bottom cell with the 300 and 800 nm-thick absorber layers. When summed up, the best top and bottom cell PCEs of the 4T-BST SC with 300 and 800 nm-thick BS-CISe SC are 18.8% and 21.1%, respectively. However, the practical BPGD values of the 4T-BST SC under total 2 sun illumination are interestingly 23.4% and 24.4%, respectively. This is because the BS-CISe bottom cell's thickness affects how much rear-side illumination is transmitted to the BS-PVK top cell, increasing its current density and BPGD.


Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma.
Objective: MicroRNAs (miRNAs) have been explored in malignancies. We investigated the functions of clustered miRNAs hsa-miR-221/222-3p in hepatocellular carcinoma (HCC). Methods: Human miRNA tissue atlas website was determined expression levels in liver tissue. Four databases, TarBase, miRTarBase, miRecords and miRPathDB, were found experimentally validated target genes of clustered miRNAs. TargetScanHuman was predicted target genes. The STRING website was depicted protein-protein interaction (PPI) networks. The OncoLnc website analyzed prognostic values for hsa-miR-221/222-3p and their target genes. The MCODE plugin calculated modules of PPI networks. Receiver operating characteristic (ROC) curves were predicted 1, 3, and 5 years prognostic values. Results: Expression of clustered miRNAs was high in liver tissues. A total of 1577 target genes were identified. Enrichment analysis showed that target genes were enriched mainly in cancer, Wnt signaling and ErbB signaling pathways. Two modules were calculated using PPI networks. Has-miR-221-3p was not associated with prognosis (P = 0.401). Has-miR-222-3p and target genes ESR1, TMED7, CBFB, ETS2, UBE2J1 and UBE2N of the clustered miRNAs were associated with HCC survival (all P < 0.05). Has-miR-222-3p, CBFB, and UBE2N showed good performance of ROC in prognosis prediction at 1, 3, and 5 years (all area under curves > 0.600). Conclusion: Has-miR-222-3p and target genes, especially CBFB, UBE2N, may serve as prognostic predictors for HCC.


Reliability of heart rate responses to non-steady-state activities of daily living in men with spinal cord injuries.
The reliability of heart rate responses to non-steady-state tasks among 37 men with spinal cord injuries (lesion level: C4/5-L5) was examined with a simple heart rate recording device (Sport Tester PE3000). Three identical trials of 6 different transfers and an 8-cm curb ascent were performed on one day (Trial 1 and 2; n = 37) and one week later (Trial 3; n = 12). Pearson's r and intraclass correlations for the highest and the mean heart rate provoked during Trial 1 and 2 ranged from 0.73 to 0.97 for the transfers and from 0.92 to 0.97 for the curb ascent. Correlations were somewhat lower for Trial 1 versus Trial 3. A paired t-test revealed lower heart rate responses to Trial 2 and 3, suggesting a moderate learning effect and/or a reduction in psychological stress. It was concluded that heart rate responses to non-steady-state tasks, as recorded by a Sport Tester PE3000, are reproducible in men with spinal cord injuries.


Metastatic non-seminomatous germ cell tumour and dermatomyositis.
Twenty to thirty percent of cases of dermatomyositis in adults are associated with malignancy. We report a case in which dermatomyositis heralded the development of a testicular germ cell tumour. Germ cell testicular tumours are treatable and our case emphasizes the importance of measuring blood levels of beta-human chorionic gonadotrophin and alpha-fetoprotein and examination of the testes in young males with indications of possible malignancy.


Prevalence and characterization of class 1 and class 2 integrons in Escherichia coli isolated from meat and meat products of Norwegian origin.
The aim of the study was to investigate the prevalence of integrons and to characterize inserted gene cassettes in Escherichia coli isolated from meat and meat products of Norwegian origin. The strains investigated (n = 241 resistant out of 944 investigated) were collected within the frame of the Norwegian monitoring programme for antimicrobial resistance in bacteria from feed, food and animals (NORM-VET) during the years 2000-2003. PCR and DNA sequencing were used for detection of the integrase genes and gene cassettes within the integrons. Integrons were detected in 43 (18%) of the 241 resistant isolates. Class 1 integrons were detected in 29 (12%) strains and class 2 integrons were detected in 14 (6%) strains. Ten different gene cassettes were detected: dfrA1, dfr2a, dfrA12, aadA1, aadA2, catB2, oxa-30, sat, sat1 and orfF. The dfrA1 + aadA1 combination was the most prevalent cassette combination, detected in 12 of 29 class 1 integrons. Twelve (of 14) class 2 integrons contained a cassette area consistent with that on Tn7, the remaining two contained the cassettes sat + sat1 + aadA1. Nearly one-third of the class 1 integrons (9 of 29) lacked the sul1 gene. Ten gene cassettes (one dfr2a, two catB2 and seven aadA1) were expressed at levels below breakpoint values normally used to classify strains as resistant. Integrons of class 1 or 2 were present in approximately 18% of the resistant E. coli strains investigated. Certain cassette combinations in class 1 integrons seem to be more widespread than others, like the dfrA1 + aadA1. Low-level expression of antimicrobial resistance, caused by the expression of certain gene cassettes in some integrons represents an obstacle in classifying strains as susceptible or resistant.


Beta-blockade as an alternative to cardioplegic arrest during cardiopulmonary bypass.
As an alternative to cardioplegic arrest, cardiac surgical conditions have been produced using beta-blocker-induced minimal myocardial contraction (MMC) during cardiopulmonary bypass. The technique of MMC involves the use of high-dose intravenous esmolol to suppress myocardial chronotropy and inotropy sufficiently to produce cardiac surgical conditions. The purpose of this study was to compare conventional crystalloid cardioplegic arrest with MMC in terms of ischemia avoidance, myocardial edema formation, and cardiac function. Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to crystalloid cardioplegic arrest for 2 hours. Surgical conditions were produced in the other 6 dogs for 2 hours using intravenous esmolol without aortic clamping or cardioplegia. Arterial and coronary sinus lactate concentrations were determined as a gauge of myocardial ischemia. Myocardial water content was determined using microgravimetry and preload recruitable stroke work was determined using sonomicrometry and micromanometry. Significant lactate washout was demonstrated after cardioplegic arrest but not after MMC. Myocardial water content was significantly less during and after MMC compared with cardioplegic arrest (p < 0.05). Preload recruitable stroke work was decreased compared with baseline values in both groups (p < 0.05). In contrast to a previous study that involved 1 hour of MMC, in this study, ventricular function was decreased to the same extent as with cardioplegic arrest after 2 hours of MMC. This was attributed to the accumulation of ASL-8123, the primary metabolite of esmolol, which possesses beta-antagonist properties. Although postbypass ventricular function is similar in both groups, MMC appears to be superior in terms of ischemia avoidance and myocardial edema formation.


The Morphological Analysis of Cells in the Bronchoscopic Brushing and TBNA of Patients with Lung Adenocarcinoma.
Biopsy, brushing, and transbronchial needle aspiration (TBNA) are the most common methods for diagnosis of lung adenocarcinoma and are taken during the same diagnostic bronchoscopic procedure. However, it is not clear what the morphological diagnostic criteria of cytology by brushing or TBNA are. A retrospective analysis was performed on 136 patients who underwent video bronchoscopy examination for diagnostic purposes. All the subjects were performed brushing or TBNA and confirmed as lung adenocarcinoma by biopsy or postoperative pathology. An additional 140 randomly selected patients with benign lung diseases were included in the study and used as a control group. The benign cells usually confused with adenocarcinoma cells were ciliated columnar cells, mucous columnar cells, ciliated cuboid cells, and reactive ciliated cells, respectively. The number of cases diagnosed as adenocarcinoma cells, carcinoma cells, suspicious cancer cells, and atypical proliferative cells by cytology was 101, 11, 20, and 4, respectively. The main basis for the interpretation of adenocarcinoma cells is the enlargement of individual nucleus, the arrangements of multistage papillary, and the general enlargement of nuclei, while the main clue for the interpretation of suspicious cancer cells and dysplasia cells comes from escape cells. The results suggested that the degree of nuclear enlargement, multiple papillary arrangement, and escape cells or escape trend cells are important clues for the interpretation of lung adenocarcinoma cells, while the atypical proliferative cells were similar to escape cells or escape trend cells, which were essentially benign cells beside the cancer.


Sulfate-Induced Stomata Closure Requires the Canonical ABA Signal Transduction Machinery.
Phytohormone abscisic acid (ABA) is the canonical trigger for stomatal closure upon abiotic stresses like drought. Soil-drying is known to facilitate root-to-shoot transport of sulfate. Remarkably, sulfate and sulfide-a downstream product of sulfate assimilation-have been independently shown to promote stomatal closure. For induction of stomatal closure, sulfate must be incorporated into cysteine, which triggers ABA biosynthesis by transcriptional activation of NCED3. Here, we apply reverse genetics to unravel if the canonical ABA signal transduction machinery is required for sulfate-induced stomata closure, and if cysteine biosynthesis is also mandatory for the induction of stomatal closure by the gasotransmitter sulfide. We provide genetic evidence for the importance of reactive oxygen species (ROS) production by the plasma membrane-localized NADPH oxidases, RBOHD, and RBOHF, during the sulfate-induced stomatal closure. In agreement with the established role of ROS as the second messenger of ABA-signaling, the SnRK2-type kinase OST1 and the protein phosphatase ABI1 are essential for sulfate-induced stomata closure. Finally, we show that sulfide fails to close stomata in a cysteine-biosynthesis depleted mutant. Our data support the hypothesis that the two mobile signals, sulfate and sulfide, induce stomatal closure by stimulating cysteine synthesis to trigger ABA production.


Modulation of the antioxidant defence as a factor in apoptosis.
This review focuses on evidence that oxidative stress during apoptosis is controlled, at least in part, by modulating cellular antioxidant defences. Evidence is presented from studies of apoptosis induced by glucocorticoids, HIV-1 infection and tumour necrosis factor-alpha. Glucocorticoid treatment of murine lymphocyte cell lines leads to the down-regulation of primary antioxidant defence enzymes, including catalase, superoxide dismutases, thioredoxin and DT-diaphorase. Following HIV-1 infection, disturbances in glutathione metabolism are seen, and decreased antioxidant enzyme activities have been reported for HIV-1-infected cell lines. The viral protein Tat may mediate these effects. Cellular resistance to apoptosis induced by tumour necrosis factor-alpha is modulated by the expression of manganese superoxide dismutase or Bcl-2. The loss of antioxidant defences is predicted to lead to oxidative stress, which could contribute to the mechanism of apoptosis through an effect on redox-sensitive transcription factors, calcium homeostasis or cysteine proteases.


Combination of Xpert MTB/RIF and TBAg/PHA Ratio for Prompt Diagnosis of Active Tuberculosis: A Two-Center Prospective Cohort Study.
The prompt diagnosis of active tuberculosis (ATB) is still a challenge in clinical practice, especially in TB-endemic countries. We prospectively enrolled consecutive patients with suspected pulmonary TB from two tertiary hospitals. Acid-fast staining (AFS), Xpert MTB/RIF (Xpert), Mycobacterium tuberculosis culture, and T-SPOT.TB were simultaneously performed. 226 ATB and 348 non-TB patients were diagnosed in Tongji hospital (test cohort), and 86 ATB and 110 non-TB patients were diagnosed in Guangzhou Chest Hospital (validation cohort). Using ATB as patient group and non-TB as control group, for diagnosis of ATB in Tongji Hospital, the sensitivity of AFS was 17.70% (95% CI: 13.08-23.44%). The sensitivity of Xpert and culture were 53.54% (95% CI: 46.81-60.14%) and 46.46% (95% CI: 39.86-53.19%), respectively. The sensitivity of T-SPOT.TB was 81.42% (95% CI: 75.60-86.14%), but the specificity was 71.55% (95% CI: 66.60-76.04%). Calculation of the ratio of TB-specific antigen to phytohaemagglutinin (TBAg/PHA) of T-SPOT.TB assay increased the specificity but with a loss of sensitivity. Combination of Xpert and culture slightly increased the sensitivity compared to using these methods separately. Combination of Xpert and TBAg/PHA ratio (defined as Xpert positive or TBAg/PHA ≥ 0.2) increased diagnostic accuracy, and the sensitivity and specificity of combination of them were 85.84% (95% CI: 80.45-89.98%) and 95.98% (95% CI: 93.36-97.59%), respectively. The diagnostic model was also established based on combination of Xpert and TBAg/PHA ratio. The area under the curve of the diagnostic model was 0.952 (95% CI: 0.932-0.973) for diagnosis of ATB, with a sensitivity of 88.05% (95% CI: 83.10-91.98%) and a specificity of 96.26% (95% CI: 93.70-98.00%) when a cutoff value of 0.44 was used in Wuhan cohort. The performance of combination of Xpert and TBAg/PHA ratio was similar in Guangzhou Chest Hospital. Our data suggest that combination of Xpert and TBAg/PHA ratio may be a good algorithm for prompt diagnosis of ATB in high endemic areas.


Novel mutations in the folliculin gene associated with spontaneous pneumothorax.
Spontaneous pneumothorax is mostly sporadic but may also occur in families with genetic disorders, such as Birt-Hogg-Dubé syndrome, which is caused by mutations in the folliculin (FLCN) gene. The aim of the present study was to investigate the presence and type of mutation in a Swiss pedigree and in a sporadic case. Clinical examination, lung function tests and high-resolution computed tomography were performed. All coding exons and flanking intronic regions of FLCN were amplified by PCR and directly sequenced. The amount of FLCN transcripts was determined by quantitative real-time RT-PCR. Two novel mutations in FLCN were identified. Three investigated family members with a history of at least one spontaneous pneumothorax were heterozygous for a single nucleotide substitution (c.779G>A) that leads to a premature stop codon (p.W260X). Quantitative real-time RT-PCR revealed a reduction of FLCN transcripts from the patient compared with an unaffected family member. DNA from the sporadic case carried a heterozygous missense mutation (c.394G>A). Lung function of this patient was normal and computed tomography showed similar bilateral cysts, as observed in the two members of the unrelated Swiss family. Mutations in the folliculin gene are associated with cystic lung lesions in an otherwise morphological normal lung and predispose to spontaneous pneumothorax.


Nanofluidic bubble pump using surface tension directed gas injection.
A new concept for liquid manipulation has been developed and implemented in surface-micromachined fluid channels. It is based on the surface tension directed injection of a gas into the liquid flow through micrometer-sized holes in the microchannel wall. The injected gas is directed to an exhaust by a cross-sectional asymmetry of the microchannel and thereby moves minute liquid volumes. Successful pumping experiments were performed with single stroke volumes of tens of picoliters at frequencies around 1 Hz. The minimum actuation pressure is 0.6 bar for a 2-microm channel height, in accordance with theoretical predictions.


[Devic's optic neuromyelitis. Follow-up of the evolution of the medullary lesions using magnetic resonance].
The nosology of Devic's optic neuromyelitis (NMOD) is controversial. Although classically considered to be a variety of multiple sclerosis, there are a number of differentiating characteristics which would permit classification as a separate condition. The evolution of changes in the medulla, as shown by magnetic resonance, is described in a patient with recurrent episodes of myelitis and optic neuritis. In successive exacerbations widening of the medulla was seen, with the appearance of areas of cavitation which later gave rise to atrophy of the medulla. During an 18 year follow-up period the symptoms were only of visual and medullary pathology, on magnetic resonance no other lesions were found in other parts of the central nervous system. The condition corresponded to Devic's optic neuromyelitis (NMOD). Whether it is a variant type of multiple sclerosis or a distinct entity, NMOD shows differentiating characteristics.


[Chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar affect diversity of gut microbiota in rat model of malignant ascites induced by Walker-256 cells].
This study aims to explore the effects of chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar on the diversity of gut microbiota in the rat model of malignant ascites, identify the key differential microbial taxa, and reveal the biological mechanism of water-expelling effect of the two chemical ingredient groups. The rat model of malignant ascites induced by Walker-256 cells was established, and phenolphthalein was used as the positive drug. The rats were orally administrated with corresponding agents for consecutive 7 days. On day 6, fresh feces samples were collected from the rats, and 16 S rDNA high-throughput sequencing and GC-MS were employed to determine the composition of gut microbiota and the content of short-chain fatty acids, respectively. On day 7, serum and intestinal tissue samples were collected for the determination of related indicators. Compared with the control group, the model group showed decreased feces volume and urine volume(P<0.01), increased volume of ascites and levels of Na~+, K~+, and Cl~- in urine(P<0.01), down-regulated mRNA and protein levels of intestinal AQP8(P<0.01), lowered abundance of beneficial Lactobacillus(P<0.01) while risen abundance of potential pathogenic Lachnospiraceae and Anaeroplasma(P<0.01), and reduced content of short-chain fatty acids(P<0.01). Compared with the model group, administration with chemical ingredient groups B and C alleviated all the above indicators(P<0.01). In conclusion, chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar could alleviate the disordered gut microbiota in rats with malignant ascites to expel water through increasing the abundance of beneficial Lactobacillus and reducing the abundance of harmful Lachnospiraceae and Anaeroplasma. This study can provide a reference for the reasonable clinical application of Kansui Radix stir-fried with vinegar.


Infusion chemotherapy with cisplatinum and fluorouracil in the treatment of locally-advanced and metastatic gallbladder cancer.
Gallbladder cancer (GBC) has a poor prognosis. Chemotherapy is traditionally considered to be ineffective. The goal of the current study was to evaluate the efficacy of infusional 5-fluorouracil (5-FU) and cisplatinum (CDDP) in patients with inoperable GBC. A total of 65 patients with inoperable GBC received palliative chemotherapy with CDDP and 5-FU. All the patients had clinically measurable disease as well as adequate bone marrow, hepatic, and renal function. Response was assessed after three cycles of chemotherapy. A total of 19 patients had locally advanced unresectable cancer and 46 patients had metastatic cancer. There were 39 females and 26 males, with a median age of 50 years. A total of 212 chemotherapy cycles were administered to the patients. Response evaluation after three cycles of chemotherapy revealed complete response in five patients [7.69%; 95% confidence interval (95% CI): 2.87-16.22], partial response in 17 patients (26.15%; 95% CI: 16.57-37.81), stabilization of disease in 9 patients (13.85%; 95% CI: 6.96-23.88), and progression in 21 patients (32.30%; 95% CI: 21.80-44.35). At 6 months 44.6% patients were alive and 18.5% patients were alive at 12 months. The median overall survival was 5.7 months and the median time to disease progression was 3.1 months. This chemotherapy combination was well tolerated. There were no chemotherapy-related deaths. Infusion chemotherapy with CDDP and 5-FU appears to have a fair amount of activity in patients of inoperable GBC, with acceptable toxicity. Tumor shrinkage following treatment with this regimen enabled surgical resection in two patients. We believe that this promising combination must be tested against gemcitabine-based combinations in patients with inoperable GBC.


Drugs as reinforcers--collaborative opportunities in epidemiology and behavioral pharmacology: comment on Alessi, Roll, Reilly, and Johanson (2002).
Despite reliance on a relatively small sample, the study by S. M. Alessi, J. M. Roll, M. P. Reilly, and C.-E. Johanson (2002) yielded remarkably consistent results, indicating that drug preference can be switched using conditioning procedures. However, because the study included only adults with limited drug involvement, the findings need to be interpreted taking the nature of the sample into account. This limitation points to opportunities for collaboration between experimental and epidemiologic researchers. Specifically, nesting experimental studies within longitudinal epidemiologic studies would reduce the potential for bias in sample selection while providing experimental data that are usually not available in observational epidemiologic research.


[Treatment of prolactinoma with a new dopamine agonist].
Eleven patients (6 men, 5 women, mean age 42 [25-65] years) with prolactinomas were treated for 4-16 months with a new dopamine agonist (CV 205-502), at a daily dose of between 0.075 and 0.45 mg. All patients had previously undergone surgery and/or been treated with bromocriptine or lisuride, but had not tolerated this therapy well, and/or had not shown sufficient suppression of serum prolactin levels. Baseline prolactin levels were between 149 and 4120 ng/ml. During treatment, levels fell significantly in all patients, to between 2.0 and 683 ng/ml, and to within the reference range in five patients. In seven patients, the adenoma size decreased by 10 to greater than 50%. Adverse reactions were less frequent and less marked than with the prior therapy. The new dopamine agonist is an alternative treatment for prolactinomas where other therapies have been unsuccessful.


N-Acetylcysteine inhibit the translocation of mixed lineage kinase-3 from cytosol to plasma membrane during transient brain ischemia in rat hippocampus.
Mixed lineage kinase-3 (MLK3) is a recently described member of the MLK subfamily of Ser/Thr protein kinases that interacts with mitogen-activated protein kinase (MAPK) pathways. In this study, we investigated the translocation of MLK3 during transient cerebral ischemia in rat hippocampus. Transient brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. Our data show that MLK3 can translocate from cytosolic fraction to the membrane fraction during ischemia and the increased MLK3 in the membrane fraction bind to postsynaptic density protein 95 (PSD-95). The antioxidant N-acetylcysteine (NAC) could inhibit the translocation of MLK3 from cytosolic fraction to the membrane fraction and decrease the interactions of MLK3 and PSD-95 in the membrane fraction. Consequently, these results indicate that reactive oxygen species (ROS) was closely associated with MLK3 translocation induced by transient global ischemia in rat hippocampus.


Deficits in Lower Limb Muscle Reflex Contraction Latency and Peak Force Are Associated With Impairments in Postural Control and Gross Motor Skills of Children With Developmental Coordination Disorder: A Cross-Sectional Study.
This cross-sectional, exploratory study aimed to compare neuromuscular performance, balance and motor skills proficiencies of typically developing children and those with developmental coordination disorder (DCD) and to determine associations of these neuromuscular factors with balance and motor skills performances in children with DCD.One hundred thirty children with DCD and 117 typically developing children participated in the study. Medial hamstring and gastrocnemius muscle activation onset latencies in response to an unexpected posterior-to-anterior trunk perturbation were assessed by electromyography and accelerometer. Hamstring and gastrocnemius muscle peak force and time to peak force were quantified by dynamometer, and balance and motor skills performances were evaluated with the Movement Assessment Battery for Children (MABC).Independent t tests revealed that children with DCD had longer hamstring and gastrocnemius muscle activation onset latencies (P < 0.001) and lower isometric peak forces (P < 0.001), but not times to peak forces (P > 0.025), than the controls. Multiple regression analysis accounting for basic demographics showed that gastrocnemius peak force was independently associated with the MABC balance subscore and ball skills subscore, accounting for 5.7% (P = 0.003) and 8.5% (P = 0.001) of the variance, respectively. Gastrocnemius muscle activation onset latency also explained 11.4% (P < 0.001) of the variance in the MABC ball skills subscore.Children with DCD had delayed leg muscle activation onset times and lower isometric peak forces. Gastrocnemius peak force was associated with balance and ball skills performances, whereas timing of gastrocnemius muscle activation was a determinant of ball skill performance in the DCD population.


Evidence for a Functional O-Linked N-Acetylglucosamine (O-GlcNAc) System in the Thermophilic Bacterium Thermobaculum terrenum.
Post-translational modification of proteins is a ubiquitous mechanism of signal transduction in all kingdoms of life. One such modification is addition of O-linked N-acetylglucosamine to serine or threonine residues, known as O-GlcNAcylation. This unusual type of glycosylation is thought to be restricted to nucleocytoplasmic proteins of eukaryotes and is mediated by a pair of O-GlcNAc-transferase and O-GlcNAc hydrolase enzymes operating on a large number of substrate proteins. Protein O-GlcNAcylation is responsive to glucose and flux through the hexosamine biosynthetic pathway. Thus, a close relationship is thought to exist between the level of O-GlcNAc proteins within and the general metabolic state of the cell. Although isolated apparent orthologues of these enzymes are present in bacterial genomes, their biological functions remain largely unexplored. It is possible that understanding the function of these proteins will allow development of reductionist models to uncover the principles of O-GlcNAc signaling. Here, we identify orthologues of both O-GlcNAc cycling enzymes in the genome of the thermophilic eubacterium Thermobaculum terrenum. The O-GlcNAcase and O-GlcNAc-transferase are co-expressed and, like their mammalian orthologues, localize to the cytoplasm. The O-GlcNAcase orthologue possesses activity against O-GlcNAc proteins and model substrates. We describe crystal structures of both enzymes, including an O-GlcNAcase·peptide complex, showing conservation of active sites with the human orthologues. Although in vitro activity of the O-GlcNAc-transferase could not be detected, treatment of T. terrenum with an O-GlcNAc-transferase inhibitor led to inhibition of growth. T. terrenum may be the first example of a bacterium possessing a functional O-GlcNAc system.


[Pharyngeal branchial cyst: description of one clinical case].
Brachial cysts are abnormalities in the development of the branchial apparatus, being the more common ones those of the second arch. Cysts localized in the pharyngeal wall (Bailey's type IV) are extremely rare; therefore its differential diagnosis should include all benign and malignant lesions that can be found in the pharyngeal wall. Treatment is the total excision of the cyst through per oral or external cervical approach in order to avoid recurrences.


Increased tumor-specific CD8+ T cell induction by dendritic cells matured with a clinical grade TLR-agonist in combination with IFN-gamma.
The limited response rate of cancer patients treated with dendritic cell (DC)-based vaccines indicates that vast improvements remain necessary. In many murine tumour models it has been demonstrated that the use of innate triggers (e.g. TLR triggers) in the maturation of DC results in higher efficacy. However, as few of these innate triggers are generated clinical grade, there remains a great necessity to fill the gap between fundamental mouse studies and a clinical trial in humans. In the present study we used a TLR2/4-agonist (FMKp which is available clinical grade) in combination with IFN-gamma (FIcocktail) in the maturation of elutriated monocyte-derived DC and compared it with the most used DC in current clinical trials (TNF-alpha/PGE-2, i.e. TP-cocktail). In addition to the assessment of CD4+ T cell polarizing capacity, we compared the quantity and intrinsic quality of induced CD8+ T cells of 2 different DC maturation protocols with all cells from the same donor. Besides differences in the cytokine profile, which could be coupled to increased Th1 and Th17 polarization, we demonstrate in this study that FMKp/IFN-gamma matured DC are twice as effective in inducing cytotoxic T cells against known tumor antigens. Both DCs induced phenotypically equivalent effector memory CD8+ T cells that did not show a significant difference in their intrinsic capacity to kill tumor cells. These findings point to the therapeutic applicability of FI-DC as superior inducers of functional antigen-specific T cells. Their increased chemokine secretion is suggestive of a mechanism by which these DC may compensate for the limited migration observed for all ex vivo cultured DC when applied in patients.


Dietary Antioxidants: Potential Anticancer Agents.
There are several extrinsic and intrinsic factors involving reactive oxygen species that play critical roles in tumor development and progression by inducing DNA mutations, genomic instability, and aberrant pro-tumorigenic signaling. There are various essential micronutrients including minerals and vitamins in the diet, which play pivotal roles in maintaining and reinforcing antioxidant performance, affecting the complex network of genes (nutrigenomic approach) and encoding proteins for carcinogenesis. A lot of these antioxidant agents are available as dietary supplements and are predominant worldwide. However, the best antioxidant micronutrient (or a combination of micronutrients) for reducing cancer risks is unknown. The purpose of this review is to survey the literature on modern biological theories of cancer and the roles of dietary antioxidants in cancer. The roles and functions of antioxidant micronutrients, such as vitamin C (ascorbate), vitamin E (alpha-tocopherol), selenium, and vitamin A, provided through diet for the prevention of cancer are discussed in the present work.


Measurement of ultrafast phenomena in the femtosecond time domain.
Considerable progress has taken place in the generation and application of ultrashort optical pulses. The methods and techniques for extending time-resolved measurements into the femtosecond (10(-15) second) time domain are described, and recent applications and fertile areas for investigation with femtosecond pulses are discussed.