Effect of postinduction nutrient feed composition and use of lactose as inducer during production of thermostable xylanase in Escherichia coli glucose-limited fed-batch cultivations.
Escherichia coli is a microorganism routinely used in the production of heterologous proteins. The overexpression of a xylanase (Xyn 10 A Delta NC), which originated from the thermophile Rhodothermus marinus cloned under the control of the strong T7/lac promoter in a defined medium (mAT) using a substrate-limited feed strategy, was however shown to impose a significant metabolic burden on host cells. This resulted in a decreased cell growth rate and ultimately also a decreased target protein production. The investigation hence centers on the effect of some selected nutrient feed additives (amino acid [Cys] or TCA-intermediates [citrate, succinate, malate]) used to relieve the metabolic burden imposed during the feeding and postinduction phases of these glucose-limited fed-batch cultivations. The use of either succinic acid or malic acid as feed-additives resulted in an increase in production of approximately 40% of the heterologous thermostable xylanase. Furthermore, use of lactose as an alternative inducer of the T7/lac promoter was also proven to be a suitable strategy that significantly prolonged the heterologous protein production phase as compared with induction using isopropyl beta-D-thiogalactopyranoside (IPTG).


Could sexually transmissible infections be contributing to the increase in HIV infections among men who have sex with men in Australia?
To review existing data on sexually transmissible infections (STI) in men who have sex with men in Australia in order to determine the possible contribution of STI to diverging trends in HIV notifications in different states. We reviewed data from multiple sources, including routine national surveillance data, laboratory surveillance data, self-reported information on STI testing in men who have sex with men and ad hoc reports of STI prevalence. We found increasing rates of gonorrhoea and infectious syphilis notifications in urban men in Australia between 1997 and 2006, and increasing rates of chlamydia notifications in men aged 30-49 years. There was little difference in these trends by state. Differences in the population groups sampled meant we were unable to gain further information on trends in men who have sex with men from these studies. Data on STI testing showed an increase in anal STI testing between 2003 and 2006, which may have increased the number of diagnoses of chlamydia and gonorrhoea for men who have sex with men during this period. Over the past 10 years, there has been a substantial increase in diagnoses of gonorrhoea and infectious syphilis, and probably chlamydia, in men who have sex with men in Australia. However, it is unlikely that changes in the pattern of STI transmission are responsible for the recent divergence in HIV rates between Australian states because there is little evidence that trends in STI also differ by state.


New divergent dynamics in the isotropic to nematic phase transition of liquid crystals measured with 2D IR vibrational echo spectroscopy.
The isotropic phase of nematogenic liquid crystals has nanometer length scale domains with pseudonematic ordering. As the isotropic to nematic phase transition temperature (TNI) is approached from above, the orientational correlation length, ξ, of the pseudonematic domains grows as (T - T(*))(-1/2), where T(*) is 0.5-1 K below TNI. The orientational relaxation, which is a collective property of the pseudonematic domains, was measured with optical heterodyne detected-optical Kerr effect (OHD-OKE). The orientational relaxation obeys Landau-de Gennes theory, as has been shown previously. To examine the environmental evolution experienced by molecules in the pseudonematic domains, two-dimensional infrared (2D IR) vibrational echo experiments on the CN stretching mode of the non-perturbative vibrational probes 4-pentyl-4(')-selenocyanobiphenyl (5SeCB) and 4-pentyl-4(')-thiocyanobiphenyl (5SCB) in the nematogen 4-cyano-4(')-pentylbiphenyl (5CB) were performed. The 2D IR experiments measure spectral diffusion, which is caused by structural fluctuations that couple to the CN vibrational frequency. Temperature dependent studies were performed just above TNI, where the correlation length of pseudonematic domains is large and changing rapidly with temperature. These studies were compared to 2D IR experiments on 4-pentylbiphenyl (5B), a non-mesogenic liquid that is very similar in structure to 5CB. The time constants of spectral diffusion in 5CB and 5B are practically identical at temperatures ≥5 K above TNI. As the temperature is lowered, spectral diffusion in 5B slows gradually. However, the time constants for spectral diffusion in 5CB slow dramatically and diverge as T(*) is approached. This divergence has temperature dependence proportional to (T - T(*))(-1/2), precisely the same as seen for the correlation length of pseudonematic domains, but different from the observed orientational relaxation times, which are given by the Landau-de Gennes theory. The data and previous results show that spectral diffusion in 5CB has no contributions from orientational relaxation, and the structural dynamics responsible for the spectral diffusion are likely a result of density fluctuations. The results suggest that the correlation length of the density fluctuations is diverging with the same temperature dependence as the pseudonematic domain correlation length, ξ. The isotropic-nematic phase transition in liquid crystals is described in the context of the slowing of orientational relaxation associated with divergent growth of the orientational correlation length. The results presented here show that there is another divergent dynamical process, likely associated with density fluctuations.


Developmental Programming: Gestational Exposure to Excess Testosterone Alters Expression of Ovarian Matrix Metalloproteases and Their Target Proteins.
Prenatal testosterone (T)-treated sheep, similar to women with polycystic ovary syndrome (PCOS), manifests reproductive defects that include multifollicular ovarian phenotype. Women with PCOS manifest increased ovarian matrix metalloproteinases (MMPs) activity. We tested the hypothesis that gestational T excess in sheep would alter ovarian expression of MMPs, tissue inhibitors of MMP (TIMP) and their target proteins laminin B (LAMB), collagen, tumor necrosis factor alpha (TNF), and connexin 43 (GJA1) consistent with increased MMP activity and that these changes are developmentally regulated. The ovarian content of these proteins was quantified by immunohistochemistry in fetal day 90, 140, and adult (21 months of age) ovaries. Prenatal T excess lowered GJA1 protein content in stroma and granulosa cells of primary follicles from fetal day 90 ovaries and decreased stromal MMP9, TIMP1, and LAMB in fetal day 140 ovaries. In the adult, prenatal T-treatment (1) increased MMP9 in theca cells of large preantral follicles and stroma, TNF in granulosa cells of small and large preantral follicles and theca cells of large preantral and antral follicles, and GJA1 in stroma, theca cells of large preantral follicles, and granulosa cells of antral follicles and (2) reduced TIMP1 in stroma, theca cells of large preantral and antral follicles, LAMB in stroma and small prenatral follicles, and collagen content in stroma and around antral follicles. These findings suggest a net increase in MMP activity and its target proteins TNF and GJA1 in prenatal T-treated adult but not in fetal ovaries and their potential involvement in the development of multifollicular morphology.


Revision of monogeneans parasitising Lythrurus (Cypriniformes: Leuciscidae) in eastern U.S.A., with description of Dactylogyrus lythruri sp. n. and new records of Dactylogyrus crucis Rogers, 1967 (Monogenoidea: Dactylogyridae).
A revisionary study revealed two species of monogeneans, Dactylogyrus crucis Rogers, 1967 and Dactylogyrus lythruri sp. n., parasitising Lythrurus Jordan (formerly a subgenus of Notropis Rafinesque, 1818). New records and updated taxonomy of seven of 12 known minnows of the genus of Lythrurus are provided for D. crucis. A record of Dactylogyrus attenuatus Mizelle et Klucka, 1953 (syn. Dactylogyrus umbratilus [Kimpel, 1939], nomen nudum) on Lythrurus umbratilis (Girard) is referrable to D. crucis. Dactylogyrus lythruri is described from eight species of Lythrurus. It most closely resembles Dactylogyrus beckeri Cloutman, 1987, but is distinguished by having a smaller base of the male copulatory organ (MCO) and lacking a ventral enlargement of the distal end of the basal process. Previous reports of Dactylogyrus banghami Mizelle et Donahue, 1944 and Dactylogyrus cf. beckeri Cloutman, 1987 from Lythrurus atrapiculus (Snelson) and Lythrurus bellus (Hay) from Alabama, and Dactylogyrus confusus Mueller, 1938 from L. umbratilis in Illinois are herein relegated to D. lythruri. Four species of Lythrurus appeared not to be infected with Dactylogyrus.


On the relationships between resolution, dimensionless stability, pseudopotential well depth, acceptance, and transmission in mass filters.
The relationships between resolution, stability, pseudopotential well depth, acceptance aperture, and transmission for sinusoidal quadrupole mass filters are examined graphically and mathematically. Simple linear or power relationships are revealed. Comparison of these quantities plotted against resolving power show that the pseudopotential well depth correlates well with the mass filter transmission. Pseudopotential well depth is directly proportional to the product of dimensionless stability well depth and the AC voltage. This relationship extends to all quadrupoles regardless of operational zone because it is rooted in stability. Ion transmission and sensitivity scale directly with the pseudopotential well depth. Resolving power and pseudopotential well depth increase when operating in higher stability zones for all types of mass filters. Unfortunately, for fixed frequency sine wave mass filters, the increased resolving power and pseudopotential well depth are accompanied by a significant reduction of the mass range and increased in fringe field effects. For these reasons, sine mass filter operation in higher stability zones has been reported but not commercially produced. In contrast, for rectangular wave mass filter operation, there is no mass range limitation in any stability zone. The fringe field does not increase because the AC voltage is constant and does not change within a single stability zone or between them. A DC voltage is also unnecessary to access any zone. The high resolution and sensitivity of rectangular wave mass filters that can be gained by operation in higher stability zones without mass limit and limited fringe field restrictions suggest a bright and expansive future for this technology.


Comparison of Continuous and Interrupted Suturing Techniques in Ventricular Septal Defect Closure.
Our goal is to evaluate postoperative outcomes of continuous versus interrupted suturing techniques in ventricular septal defect (VSD) closure surgery. The study included 286 patients with isolated VSD who underwent VSD closure surgery between June 2010 and April 2017. VSD closure was performed by using the interrupted suturing technique in group 1 (n = 74, 25.9%) and the continuous suturing technique in group 2 (n = 212, 74.1%). The groups were compared in terms of mortality and rates of clinical morbidities such as infection and complete atrioventricular (AV) block. Early mortality occurred in 3 cases in group 1 (4.0%) and 5 cases in group 2 (2.3%). There was no late mortality in either group. One patient from both groups required extracorporeal membrane oxygenation (ECMO) at postoperative 48 hours. Five patients in group 1 (6.8%) and 11 patients in group 2 (5.2%) developed complete AV block postoperatively and received permanent pacemaker implants. Complication rates were similar between the patient groups operated on by using continuous and interrupted suturing techniques in our study, suggesting that neither technique is superior for VSD closure surgery.


Isoproterenol administration during general anesthesia for the evaluation of children with ventricular preexcitation.
Rapid anterograde conduction in the setting of ventricular preexcitation is associated with an increased risk of sudden cardiac death. The effect of isoproterenol in this setting is unclear, particularly in younger anesthetized patients. The aim of this study was to determine the effect of isoproterenol on accessory-pathway conduction in children undergoing general anesthesia and its role in the risk-stratification process. The records of 151 pediatric patients with preexcitation undergoing electrophysiologic study under propofol anesthesia during a 5-year period were reviewed. Data included accessory-pathway effective refractory period, minimum 1:1 accessory pathway conduction with atrial pacing, and shortest preexcited R-R interval in atrial fibrillation. Measurements were repeated after administration of low-dose isoproterenol (mean, 0.013 μg/kg per min; range, 0.003 to 0.027). All accessory-pathway characteristics were significantly shortened with isoproterenol (P<0.001). Accessory-pathway effective refractory period increased modestly with age, both in the baseline state (r=0.172, P=0.04) and with isoproterenol (r=0.267, P<0.01) as did minimum 1:1 accessory pathway conduction with atrial pacing (r=0.178, P=0.034, and r=0.175, P<0.01, respectively). Accessory-pathway effective refractory period ≤250 ms was observed in only 5% of patients at baseline vs 25% after isoproterenol, and Shortest preexcited R-R interval in atrial fibrillation ≤250 ms was noted in 16% vs 41%. Tachycardia was induced in 48 of 151 patients before and in 102 of 151 after isoproterenol. In anesthetized children with ventricular preexcitation, accessory pathways display shorter conduction properties at younger ages and important adrenergic sensitivity at all ages. Use of low-dose isoproterenol resulted in a substantial increase in the number of patients who would otherwise meet typical criteria for ablation.


Experimental induction of rheumatoid factor and joint lesions in rabbits after intravenous injections of killed bacteria.
Rabbits receiving repeated intravenous injections of killed bacteria (Escherichia coli or Bacillus subtilis) developed IgM rheumatoid factor which reacted with autologous heat-aggregated IgG. In addition, 5/7 'Old English' and 7/8 'Sandy Lop' rabbits receiving killed E. coli developed rheumatoid-like synovial lesions. 'Old English' rabbits developed lesions of a more severe nature. Three of eight 'Sandy Lop' rabbits injected with killed B. subtilis had high levels of rheumatoid factor but only mild joint lesions.


Thresholds as a unifying theme in regulatory toxicology.
The scientific basis for the US Food and Drug Administration (FDA) threshold of regulation is discussed in relation to its toxicological testing recommendations for food contact substances and the existing methods it employs for exposure estimation. A case is made that the FDA's threshold of regulation is a natural extension of its toxicity testing regime. The genetic toxicity tests recommended in the exposure-based toxicological testing framework for food contact substances are examined regarding their ability to predict positively carcinogens of varying potency. In addition, the computational toxicology program MULTICASE v. 3.1 is also examined for its ability to predict positively carcinogens of varying potency. It is concluded that MULTICASE can provide equivalent results to genetic toxicity tests at the lowest dietary concentrations.


Inhibition of arsenazo III Ca transient with deuterium oxide in frog twitch fibers at a resting sarcomere length.
Arsenazo III calcium transients during twitches of frog skeletal muscle fibers were recorded in H2O Ringer (control) and deuterium oxide Ringer (test). In ten fibers, the amplitude of the test at a sarcomere length of 2.5 microns was reduced to 57% of the control and accompanied by extremely diminished tension responses. The latency was also increased to 158%.


[Genetic polymorphisms of drug metabolizing enzymes].
Multiple forms of CYP exist in humans. P450s comprise a superfamily of enzymes. These P450s play important roles in the oxidation of structurally diverse endobiotics and xenobiotic chemicals including anticancer drugs and carcinogens. The genes encoding most of the CYP1, CYP2, and CYP3 families show genetic polymorphism. In this article, we describe recent findings that these polymorphic enzymes can abolish or quantitatively or qualitatively alter drug metabolism in humans.


Uterine Fibroids: Assessing Unmet Needs from Bench to Bedside.
Uterine fibroids (leiomyomas) are noncancerous growths that can have deleterious effects on the health and quality of life for millions of women. Attempts to better understand the factors that influence prevalence and disparities associated with fibroids have been made; however, significant knowledge gaps continue to persist, which hinder care for individuals living with fibroids. The Society for Women's Health Research convened an interdisciplinary Uterine Fibroids Working Group to review the current state of knowledge about uterine fibroids and recommend areas in which to prioritize efforts to address research gaps and improve diagnosis, treatment, and access to care for patients with this chronic disease. Throughout a 2-day roundtable meeting, participants discussed updates on key literature, research, clinical practice, and public health data on uterine fibroids. Overarching themes and recommendations were identified and determined by consensus agreement of the participants at the conclusion of the meeting. Systematic studies of the etiology and pathology of uterine fibroids are needed to address important knowledge gaps and unmet clinical needs regarding the multifaceted management of fibroids and their effects on overall health and quality of life. The Working Group recommends addressing key deficits within the spheres of research, clinical care, and federal policy. Immediate needs include increasing research investment, improving fibroid assessment using pelvic imaging, implementing longitudinal study designs, addressing factors that contribute to disease disparities (especially among women of color), developing fertility-friendly treatment options, expanding awareness and education beyond gynecologic specialists, and advancing personalized patient care through shared decision-making approaches.


Homozygosity by descent for a rare mutation in the myophosphorylase gene is associated with variable phenotypes in a Druze family with McArdle disease.
We examined a large consanguineous Druze family with McArdle disease for mutations in the glycogen myophosphorylase (PYGM) gene. All affected subjects were autozygous for a single G to A transition that abolishes the 5' consensus splice site in the first nucleotide of intron 14. The G to A transition is a rare mutation, with only one previous report in a single white subject heterozygous for this mutation and another, more common, mutation at codon 49. The kindred in our study is the first family reported in which disease is caused by homozygosity for this rare mutation. This kindred was originally reported as the first familial case of McArdle disease in the Druze.


Development of an in vitro-based potency assay for anthrax vaccine.
The potency assay currently used to evaluate consistency of manufacture for the anthrax vaccine is contingent upon meeting specified parameters after statistical analysis of the percent survival and time to death of vaccinated guinea pigs after challenge with spores of a virulent strain of Bacillus anthracis. During the development of a new anthrax vaccine based upon recombinant protective antigen (rPA) adsorbed to aluminum hydroxide gel (Alhydrogel), we found that the serological response of female A/J mice, as measured by a quantitative anti-rPA IgG ELISA, may be an effective method to monitor a manufacturer's consistency for rPA-based vaccines. An advantage of the proposed in vitro-based potency assay is that it will not need stringent biosafety containment measures as required by the current guinea pig potency assay.


Functions of the osteocyte network in the regulation of bone mass.
Osteocytes establish an extensive intracellular and extracellular communication system via gap-junction-coupled cell processes and canaliculi throughout bone and the communication system is extended to osteoblasts on the bone surface. The osteocyte network is an ideal mechanosensory system and suitable for mechanotransduction. However, the overall function of the osteocyte network remains to be clarified, since bone resorption is enhanced by osteocyte apoptosis, which is followed by a process of secondary necrosis attributable to the lack of scavengers. The enhanced bone resorption is caused by the release of intracellular content, including immunostimulatory molecules that activate osteoclastogenesis through the canaliculi. Therefore, a mouse model is required in which the osteocyte network is disrupted but in which no bone resorption is induced, in order to evaluate the overall functions of the osteocyte network. One such model is the BCL2 transgenic mouse, in which the osteocyte network, including both intracellular and extracellular networks, is disrupted. Another model is the osteocyte-specific Gja1 knockout mouse, in which intercellular communication through gap junctions is impaired but the canalicular system is intact. Combining the findings from these mouse models with previous histological observations showing the inverse linkage between osteocyte density and bone formation, we conclude that the osteocyte network enhances bone resorption and inhibits bone formation under physiological conditions. Further, studies with BCL2 transgenic mice show that these osteocyte functions are augmented in the unloaded condition. In this condition, Rankl upregulation in osteoblasts and Sost upregulation in osteocytes are, at least in part, responsible for enhanced bone resorption and suppressed bone formation, respectively.


Mechanisms of viral hepatitis induced liver injury.
Among seven human hepatitis viruses (A to E, G and TT virus), hepatitis B (HBV) and C (HCV) viruses are able to persist in the host for years and principally contribute to the establishment of chronic hepatitis. During the course of persistent infection, continuous intrahepatic inflammation maintains a cycle of liver cell destruction and regeneration that often terminates in hepatocellular carcinoma (HCC). While the expression and retention of viral proteins in hepatocytes may influence the severity and progression of liver disease, the mechanisms of liver injury in viral hepatistis are defined to be due not to the direct cytopathic effects of viruses, but to the host immune response to viral proteins expressed by infected hepatocytes. In the process of liver injury, hepatocellular death (apoptosis) induced by the proapoptotic molecules of T cells activated following antigen recognition triggers a cascade of antigen nonspecific effector systems and causes necroinflammatory disease. Accordingly, the regulation of the immune response, e.g., via the cell death pathways, in chronically infected patients should prevent the development of HCC.


Flow cytometry and phytochemical analysis of a sunflower cell suspension culture in a 5-L bioreactor.
A cell suspension culture of sunflower (Helianthus annuus), a producer of immunologically active polysaccharides, was cultivated in a 5-L stirred tank bioreactor, operated in batch mode. After some changes in the internal bioreactor design a stable growth of Helianthus cells was achieved and the accumulated biomass reached 15.2 g/L (only approximately 5% lower compared to the accumulated biomass in shake-flasks). Flow cytometry used for measuring the cell cycle parameters of suspended Helianthus cells did not reveal significant differences between shake-flasks and bioreactor cultivation modes. For both cultivation methods significant enhancement of the percentage of S-phase cells was observed at the beginning of the cultivation process. Concerning the metabolite production the maximum in exopolysaccharides was reached at day 9 of the cultivation period (1.9 g/L), while the highest amounts of alpha-tocopherol were accumulated at the beginning of the cultivation process (day 2 of the cultivation). These finding were related to the respective stress levels caused by the inoculation procedure. The kinetic parameters of growth and polysaccharide production as well as the time course of carbon source utilization were monitored and discussed.


Induced theta oscillations mediate large-scale synchrony with mediotemporal areas during recollection in humans.
One functional aspect of theta oscillations that recent studies have begun to explore in humans is their role for the recollection of personal events. A specific role of theta for recollection but not for stimulus-familiarity would support links between cortical theta oscillations and hippocampal functioning, given that the hippocampus seems to be more critical for recollection than for stimulus-familiarity. During recollection, theta oscillations might mediate a dynamic link between hippocampal and neocortical areas, thereby allowing to recruit and bind distributed cortical representations. We recorded theta oscillations using whole-head magnetoencephalography while nine healthy subjects made recognition memory judgments on previously studied and unstudied pictures of faces. For each recognized face, subjects indicated whether they also recollected the background image in front of which that face was studied. Theta oscillations were higher in amplitude during recollection than during recognition in the absence of accurate memory for the background. These theta oscillations were induced in nature, meaning that they showed considerable phase variability from trial to trial. To nevertheless extract the field distribution of coherent theta oscillations from single trials, we calculated phase differences between sensor pairs at each time point of each single trial. This field information was used to localize the brain sources of synchronized theta-generators. The results suggest that recollection is associated with induced activity increase in a distributed synchronous theta network, including prefrontal, mediotemporal, and visual areas. These findings are compatible with the notion that theta oscillations are related to the binding of distributed cortical representations during recollection.


Separation of peroxidation products of diacyl-phosphatidylcholines by reversed-phase liquid chromatography-mass spectrometry.
Lipid peroxidation process has attracted much attention due to the growing evidence of its involvement in the pathogenesis of age-related diseases. The monitoring of the lipid peroxidation products in phospholipids, formed under oxidative stress conditions, may provide new markers for oxidative stress signaling and for disease states, giving new insights in the pathogenesis process. Reversed-phase liquid chromatographic method coupled to mass spectrometry was developed for the separation of oxidized glycero-phosphatidylcholine (GPC) peroxidation products formed by the Fenton reaction that mimic in vivo oxidative stress conditions. The LC-MS conditions were applied for the separation of peroxidation products of oleoyl- (POPC), lineloyl- (PLPC) and arachidonoyl-palmitoyl phosphatidylcholine (PAPC). The peroxidation products separated included products resulting from the insertion of oxygen atoms in the sn-2 chain (long-chain), and products with the sn-2 chain shortened resulting from cleavage of oxygen-centered radicals (short-chain). Among long-chain products were the keto, hydroxy, hydroperoxide and poly-hydroxy derivatives, while short-chain products included dicarboxylic acids, aldehydes and hydroxy-aldehydes. Separation of long-chain products formed in each phosphatidylcholine was observed, and the reconstructed ion chromatogram of each ion showed an increase in the number of peaks with the increase in the number of oxygen atoms inserted into the phospholipid. Separation of short-chain products took place according to the functional group present at the sn-2 moiety that allowed the elution of dicarboxylic acids distinct from aldehydes. Separation between isomeric structures that were present in short- and long-chain products was also achieved.


The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus causing the pandemic of severe pneumonia (Coronavirus Disease 2019, COVID-19). SARS-CoV-2 is highly pathogenic in human, having posed immeasurable public health challenges to the world. Innate immune response is critical for the host defense against viral infection and the dysregulation of the host innate immune responses probably aggravates SARS-CoV-2 infection, contributing to the high morbidity and lethality of COVID-19. It has been reported that some coronavirus proteins play an important role in modulating innate immunity of the host, but few studies have been conducted on SARS-CoV-2. In this study, we screened the viral proteins of SARS-CoV-2 and found that the viral ORF6, ORF8 and nucleocapsid proteins were potential inhibitors of type I interferon signaling pathway, a key component for antiviral response of host innate immune. All the three proteins showed strong inhibition on type I interferon (IFN-β) and NF-κB-responsive promoter, further examination revealed that these proteins were able to inhibit the interferon-stimulated response element (ISRE) after infection with Sendai virus, while only ORF6 and ORF8 proteins were able to inhibit the ISRE after treatment with interferon beta. These findings would be helpful for the further study of the detailed signaling pathway and unveil the key molecular player that may be targeted.


The Relationship between Ischemic Stroke Patients with and without Retroflex Tongue: A Retrospective Study.
Background. Patients suffering from stroke exhibit different levels of capability in retroflex tongues, in our clinical observation. This study aims to derive the association of tongue retroflexibility with the degree of severity for stroke patients. Methods. All ischemic stroke patients were collected from August 2010 to July 2013 in the Stroke Center, Changhua Christian Hospital, Taiwan. All participants underwent medical history collection and clinical examination, including tongue images captured by ATDS. Statistical analysis was performed to compare the differences of ischemic stroke patients with and without retroflex tongue. Result. Among the total of 308 cases collected, 123 patients cannot retroflex their tongues, that is, the non-RT group. The length of stay in the non-RT group, 32.0 ± 21.5, was longer than those of the RT counterparts, 25.9 ± 14.4 (p value: 0.007). The NIHSS on admission, 14.1 ± 7.8 versus 8.9 ± 5.2, was higher and the Barthel Index upon admission, 18.6 ± 20.7 and 35.0 ± 24.2, was lower for the non-RT patients than that of the RT counterparts. Also, the non-RT patients account for 60.2% and 75.6% for Barthel Index ≤ 17 and NIHSS ≥ 9, respectively. Conclusion. The stroke patients in non-RT group showed significantly poor prognosis and were more serious in the degree of severity and level of autonomy than RT group, indicating that the ability to maneuver tongue retroflex can serve as a simple, reliable, and noninvasive means for the prognosis of ischemic stroke patients.


A population-based study in synchronous versus metachronous metastatic esophagogastric adenocarcinoma.
Real-world data on treatment and outcomes in patients with synchronous metastatic disease compared with patients with metachronous metastatic disease in esophagogastric cancer have not been published before. The aim of our study was to explore treatment, overall survival (OS), and time to treatment fialure (TTF) in patients with synchronous and metachronous metastatic esophagogastric adenocarcinoma. Patients with synchronous metastatic disease (2015-2017) and patients with metachronous metastatic disease initially treated with curative intent for nonmetastatic disease (2015-2016) were selected from the Netherlands Cancer Registry. OS and TTF were assessed from metastatic diagnosis for patients with synchronous, early metachronous (⩽6 months) or late metachronous (>6 months) metastatic disease using Kaplan-Meier curves with two-sided log-rank test. Median OS was 4.2, 2.1, and 4.4 months in patients with synchronous, early metachronous, and late metachronous metastatic disease, respectively (p < 0.001). The proportion of patients receiving systemic treatment was 41.3%, 21.5%, and 32.5% for synchronous, early metachronous, and late metachronous metastatic disease, respectively (p = 0.001). Among patients receiving systemic treatment, median OS was 8.8, 4.5, and 9.1 months (p < 0.001) and median TTF was 6.1, 3.8, and 5.7 months (p < 0.001) in synchronous, early metachronous, and late metachronous metastatic disease, respectively. Patients with early metachronous metastatic disease have a worse survival compared with patients with synchronous or late metachronous metastatic disease. These patients less often receive systemic treatment, and even when treated, survival is worse compared with patients with synchronous or late metachronous metastatic disease, suggesting a more aggressive tumor behavior.


Efficacy and safety of tacrolimus in systemic lupus erythematosus patients with refractory thrombocytopenia: a retrospective study.
Objective We evaluated the efficacy and safety of tacrolimus in systemic lupus erythematosus patients with refractory thrombocytopenia. Methods We retrospectively reviewed the data for 20 systemic lupus erythematosus patients with refractory thrombocytopenia and treated with tacrolimus during the period January 2013 to January 2015. In addition to glucocorticoids, all patients were treated with tacrolimus, 1 mg taken twice daily. The clinical effect of tacrolimus treatment in patients was evaluated by analysis of platelet counts at baseline and after one, three and six months of tacrolimus treatment. Levels of anti-double-stranded DNA antibodies and complement C3, C4 were determined individually. Results After one month of tacrolimus treatment, three patients (15%) did not respond, three patients (15%) achieved a complete response and the other 14 patients (75%) achieved a partial response. After three months of tacrolimus treatment, the platelet counts of all patients were significantly improved. A partial response was seen in 14 patients (75%) and the complete response rate increased to 25% (five patients). After six months, all patients attained partial response or complete response without relapse, and the rate of complete response increased to 75%. Compared to pretreatment, anti-double-stranded DNA antibody levels and the disease activity index score were markedly decreased after tacrolimus treatment. The levels of serum C3 and C4 were increased significantly ( P < 0.05). Conclusions Our survey revealed that a six-month course of tacrolimus is a safe and effective treatment for systemic lupus erythematosus patients with refractory thrombocytopenia.


Subcortical interactions between somatosensory stimuli of different modalities and their temporal profile.
Interactions between inputs of different sensory modality occur along the sensory pathway, including the thalamus. However, the temporal profile of such interaction has not been fully studied. In eight patients who had been implanted an intrathalamic electrode for deep brain stimulation as symptomatic treatment of tremor, we investigated the interactions between mechanical taps and electrical nerve stimuli. Somatosensory evoked potentials (SEPs) were recorded from Erb's point, cervical spinal cord, nucleus ventrointermedialis of the thalamus, and parietal cortex. A handheld electronic reflex hammer was used to deliver a mechanical tap to the skin overlying the first dorsal interosseous muscle and to trigger an ipsilateral digital median nerve electrical stimulus time-locked to the mechanical tap with a variable delay of 0 to 50 ms. There were significant time-dependent interactions between the two sensory volleys at the subcortical level. Thalamic SEPs were decreased in amplitude at interstimulus intervals (ISIs) from 10 to 40 ms with maximum effect at 20 ms (-42.8 +/- 10.5%; P < 0.001). A similar decrease was also seen in the number and frequency of the high-frequency components of thalamic SEPs (-25 +/- 4%). A smaller reduction (-18.1 +/- 5.8%; P < 0.001) was present in upper cervical response at ISI = 20 ms. There were no changes in peripheral responses. Cortical SEPs were almost completely absent in some subjects at ISIs from 20 to 50 ms. There were no changes in SEP latencies. Our results indicate that significant time-dependent interactions between sensory volleys occur at the subcortical level. These observations provide further insight into the physiological mechanisms underlying afferent gating between sensory volleys of different modality.


Changes in pancreatic and intestinal enzyme activities following chenodeoxycholic acid feeding.
The effect of CDCA feeding on pancreatic and intestinal enzymes was studied. Mice were fed 0.5% w/w chenodeoxycholic acid in a normal diet. Pancreatic lipase concentration was significantly increased after 3 days on the CDCA diet, while amylase and trypsin concentrations were significantly higher at 23 days when compared with the controls. At 70 days there was a significant increase in the concentrations of amylase, trypsin, and lipase. Protein concentrations paralleled the rise in enzyme levels. Amylase and lipase, when measured as specific activities, were still higher than the controls at 70 days. Intestinal amylase levels did not change during the experiments, but intestinal alpha-glucosidase activity increased significantly in the CDCA-treated animals. The results are discussed in terms of their similarity with those reported to occur after feeding soybean trypsin inhibitor.


Body Fat Patterning, Hepatic Fat and Pancreatic Volume of Non-Obese Asian Indians with Type 2 Diabetes in North India: A Case-Control Study.
To evaluate body fat patterning and phenotype including hepatic fat and pancreatic volume of non-obese (BMI: < 25 kg/m2) Asian Indians with type 2 diabetes residing in North India. Non-obese patients with type 2 diabetes (n = 93) and non-obese, normo-glycemic subjects (n = 40) were recruited. BMI, waist & hip circumferences, skinfold thickness at 8 sites, body fat, lean mass and detailed abdominal fat evaluation [total abdominal fat, total subcutaneous fat (superficial, deep, anterior, and posterior), total intra-abdominal fat (intra-peritoneal, retroperitoneal)], liver span, grades of fatty liver and pancreatic volume were compared. Waist circumference, subscapular skinfolds and total truncal fat (on DEXA) were higher whereas calf, total peripheral skinfolds and total leg fat (on DEXA) lower in patients. Specifically, the following volumes were higher in cases as compared to controls; total abdominal fat (19.4%), total intra-abdominal fat (49.7%), intra-peritoneal fat (47.7%), retroperitoneal fat (70.7%), pancreatic volume (26.6%), pancreatic volume index (21.3%) and liver span (10.8%). In cases, significant positive correlations were observed for pancreatic volume with BMI, waist and hip circumferences, W-HR, subscapular, abdominal and total truncal skinfolds, truncal, total subcutaneous, total intra-abdominal, intra-peritoneal, retroperitoneal fat depots, liver span and fatty liver. In non-obese Asian Indians with type 2 diabetes, subcutaneous and intra-abdominal obesity, including fatty liver, and pancreatic volume were higher and peripheral subcutaneous adiposity was lower than BMI matched non-diabetic subjects. Importantly, increased pancreatic volume in patients was highly correlated with multiple measures of abdominal obesity and liver fat.


Halopenitus malekzadehii sp. nov., an extremely halophilic archaeon isolated from a salt lake.
Strain CC65(T), a novel extremely halophilic archaeon, was isolated from a brine sample of a salt lake in Iran. The novel strain was light yellow-pigmented, non-motile, pleomorphic and required at least 1.7 M NaCl and 0.02 M MgCl₂ for growth. Optimal growth was achieved at 3.5 M NaCl and 0.4 M MgCl₂. The optimum pH and temperature for growth were pH 7.5 and 40 °C, respectively, while it was able to grow over a pH and a temperature range of pH 6.5-9.0 and 30-50 °C, respectively. Analysis of 16S rRNA gene sequence revealed that strain CC65(T) clustered with the sole member of the genus Halopenitus, Halopenitus persicus DC30(T) with a sequence similarity of 98.0%. The polar lipid profile of strain CC65(T) consisted of phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester. An unidentified glycolipid and two minor phospholipids were also observed. The only quinone present was MK-8(II-H₂). The DNA G+C content of strain CC65(T) was 63.8 mol%. On the basis of the biochemical and physiological characteristics, as well as DNA-DNA hybridization (44% with Halopenitus persicus IBRC 10041(T)), strain CC65(T) is classified as a novel species of the genus Halopenitus, for which the name Halopenitus malekzadehii sp. nov. is proposed. The type strain is CC65(T) ( = IBRC-M 10418(T) =KCTC 4045(T)).


An unusual case of interstitial lung disease in a patient with cardiopulmonary syndrome as the initial presentation of Erdheim-Chester disease.
Erdheim-Chester disease (ECD) is a very rare disorder with only approximately 600 cases reported in the literature. ECD has been recently reclassified as a histiocytic dendritic cell neoplasm. The clinical spectrum ranges from asymptomatic tissue accumulation of histiocytes to invasive tissue infiltration, which can cause fulminant multisystem failure. It typically presents with bone pain and constitutional symptoms. Extraosseous manifestations are not uncommon. ECD-associated interstitial lung disease has been described in 20%-35% of patients. Diagnosis is primarily by tissue biopsy and immunohistochemistry showing xanthogranulomas composed of foamy histiocytes that stain positive for CD68, CD14 and CD163 and negative for CD1á and langerin. We report a case of ECD in a young man with cardiopulmonary involvement who presented with haemoptysis and dyspnoea.


Cadmium and children: exposure and health effects.
Cadmium exposure and accumulation in the body start at young age. Exposure routes in children are mainly via food, environmental tobacco smoke and house dust. Excretion from the body is limited. Cadmium accumulation in the kidney is responsible for effects such as nephrotoxicity and osteoporosis which are observed at adult age. Cadmium exposure through inhalation is also associated with lung cancer in adulthood. Although transfer to the neonate through the placenta and through breast milk is limited, teratogenic and developmental effects were observed in experimental animals. The database on human studies involving children is limited, yet effects on motoric and perceptual behaviour in children have been associated with elevated in utero cadmium exposure. In school age children urinary cadmium levels were associated with immune suppressive effects. More studies are needed to confirm these results. Experimental data in vitro and in animals refer to effects of cadmium on the hypothalamus-pituitary axis at different levels. This may lead to disorders of the endocrine and/or immune system. Cadmium exposure at early age should be limited as much as possible to prevent direct effects on children and to prevent accumulation of cadmium which may have serious health effects only becoming manifest at older age.


An Example-Based Brain MRI Simulation Framework.
The simulation of magnetic resonance (MR) images plays an important role in the validation of image analysis algorithms such as image segmentation, due to lack of sufficient ground truth in real MR images. Previous work on MRI simulation has focused on explicitly modeling the MR image formation process. However, because of the overwhelming complexity of MR acquisition these simulations must involve simplifications and approximations that can result in visually unrealistic simulated images. In this work, we describe an example-based simulation framework, which uses an "atlas" consisting of an MR image and its anatomical models derived from the hard segmentation. The relationships between the MR image intensities and its anatomical models are learned using a patch-based regression that implicitly models the physics of the MR image formation. Given the anatomical models of a new brain, a new MR image can be simulated using the learned regression. This approach has been extended to also simulate intensity inhomogeneity artifacts based on the statistical model of training data. Results show that the example based MRI simulation method is capable of simulating different image contrasts and is robust to different choices of atlas. The simulated images resemble real MR images more than simulations produced by a physics-based model.


Charge Density Waves and the Hidden Nesting of Purple Bronze K_{0.9}Mo_{6}O_{17}.
We introduce the first multiorbital effective tight-binding model to describe the effect of electron-electron interactions in this system. Upon fixing all the effective hopping parameters in the normal state against an ab initio band structure, and with only the overall scale of the interactions as the sole adjustable parameter, we find that a self-consistent Hartree-Fock solution reproduces extremely well the experimental behavior of the charge density wave (CDW) order parameter in the full range 0<T<T_{c}, as well as the precise reciprocal space locations of the partial gap opening and Fermi arc development. The interaction strengths extracted from fitting to the experimental CDW gap are consistent with those derived from an independent Stoner-type analysis.


Self-assembled nanostructures of fully hydrated monoelaidin-elaidic acid and monoelaidin-oleic acid systems.
In recent years, there has been a surge of interest in exploring the effect of trans-fatty acids (TFAs) on biological membrane properties. The research studies are motivated by an increasing body of evidence suggesting that the consumption of TFAs increases the risk of developing negative health effects such as coronary heart disease and cancer. The ultimate goal of studying the lipid-fatty acid interactions at the molecular level is to predict the biological role of fatty acids in cells. In this regard, it is interesting to elucidate the effect of loading TFAs and their counterpart cis-fatty acids (CFAs) on the physical properties of lipid model membranes. Here, the present study focuses on discussing the following: (1) the effect of mixing monoelaidin (ME, TFA-containing lipid) with its counterpart monoolein (MO, CFA-containing lipid) on modulating the fully hydrated self-assembled structure, and (2) the influence of solubilizing oleic acid (OA) and its trans counterpart elaidic acid (EA) on the fully hydrated ME system. The ME model membrane was selected due to its sensitivity to variations in lipid composition and temperature. Synchrotron small-angle X-ray scattering (SAXS) was applied for studying the temperature-dependent structural behavior of the fully hydrated ME/MO-based system prepared with an equal ME/MO weight ratio and also for characterizing the fully hydrated OA- and EA-loaded ME systems. Wide-angle X-ray (WAXS) experiments were also performed for characterizing the formed crystalline lamellar phases at ambient temperatures. The results demonstrate the significant influence of the partial replacement of ME by MO on the phase behavior. The addition of MO induces the lamellar-nonlamellar phase transitions at ambient temperatures and promotes the formation of the inverted type hexagonal (H(2)) phase above 72 °C. The fully hydrated ME/EA and ME/OA systems with their rich polymorphism exhibit an interesting temperature-dependent complex behavior. The experimental findings show that the temperature-induced phase transitions are dictated by the solubilized fatty acid concentration and its configuration. Both EA and OA have a significant impact on the fully hydrated ME system. Similar to previous published studies, OA induces a significantly stronger mean negative membrane curvature as compared to EA. The two phase diagrams are discussed in terms of water-lipid and lipid-fatty acid interactions, membrane bending, and lipid packing concepts. A newly observed interesting epitaxial relationship for the lamellar-hexagonal phase transition in the EA-loaded ME system is illustrated and discussed in detail.


Notch/Hes signaling and miR-9 engage in complex feedback interactions controlling neural progenitor cell proliferation and differentiation.
Canonical Notch signaling has diverse functions during nervous system development and is critical for neural progenitor self-renewal, timing of differentiation and specification of various cell fates. A key feature of Notch-mediated self-renewal is its fluctuating activity within the neural progenitor cell population and the oscillatory expression pattern of the Notch effector Hes1 and its target genes. A negative feedback loop between Hes1 and neurogenic microRNA miR-9 was found to be part of this oscillatory clock. In a recent study we discovered that miR-9 expression is further modulated by direct binding of the Notch intracellular domain/RBPj transcriptional complex to the miR-9_2 promoter. In turn, miR-9 not only targets Hes1 but also Notch2 to attenuate Notch signaling and promote neuronal differentiation. Here, we discuss how the two interwoven feedback loops may provide an additional fail-save mechanism to control proliferation and differentiation within the neural progenitor cell population. Furthermore, we explore potential implications of miR-9-mediated regulation of Notch/Hes1 signaling with regard to neural progenitor homeostasis, patterning, timing of differentiation and tumor formation.


Dynamic conformational changes of extracellular S5-P linkers in the hERG channel.
The hERG channel has an unusually long 'S5-P linker' (residues 571-613) that lines the outer mouth of the pore. Previously, we have shown that residues along this S5-P linker are critical for the fast-inactivation process and K(+) selectivity of the hERG channel. Here we used several approaches to probe the structure of this S5-P linker and its interactions with other domains of the hERG channel. Circular dichroism and NMR analysis of a synthetic hERG S5-P linker peptide suggested that this linker is quite dynamic: its central region (positions 583-593) can be unstructured or helical, depending on whether it is immersed in an aqueous phase or in contact with a hydrophobic environment. Cysteine introduced into positions 583-597 of the S5-P linker can form intersubunit disulphide bonds, and at least four of them (at 584, 585, 588 and 589) can form disulphide bonds with counterparts from neighbouring subunits. We propose that the four S5-P linkers in a hERG channel can engage in dynamic conformational changes during channel gating, and interactions between S5-P linkers from neighbouring subunits contribute importantly to channel inactivation.


Efficacy of thyroid blockade on thyroid radioiodine uptake in 123I-mIBG imaging.
Although iodinated radiopharmaceuticals usually contain a small quantity of unbound iodine, it is difficult to establish the degree to which thyroid activity on scintigraphic images reflects uptake of free radioiodine. The objective of the present study was to examine the effectiveness of thyroid blockade in subjects undergoing (123)I-meta-iodobenzylguanidine (mIBG) imaging and to estimate the relative contribution of bound and unbound radioiodine to imaging findings. All subjects were participants in prospective trials of (123)I-mIBG cardiac imaging in which pretreatment with thyroid blockade was optional unless locally required. In a pilot project, 15 subjects (6 blocked) had thyroid uptake measured at 4 h using a probe system. Fifteen-minute (early) and 4-h (late) anterior planar chest images that included the thyroid region were visually scored for thyroid uptake (scale of 0-4) in another group of 152 subjects (98 blocked). Quantitative analysis based on thyroid regions of interest was performed on anterior planar images from a further sample of 669 subjects (442 blocked). For all 3 investigations, quantitative comparisons of thyroid uptake were made between the blocked and nonblocked subjects. There was no statistical difference between probe uptake of the 6 blocked and 9 nonblocked subjects. However, in the second series, mean visual score on the late images was significantly lower for blocked than nonblocked subjects (P < 0.001). In the region-of-interest analyses, net thyroid counts were significantly higher on the late images of nonblocked subjects (P < 0.0001), and compared with early images, 87% of subjects who received blockade showed decreased or unchanged counts whereas 75% of nonblocked subjects had increased net thyroid activity. In nonblocked subjects, an estimated 79% of thyroid counts on late images could be attributed to unbound (123)I. On the basis of 3 different methods for assessing thyroid uptake of (123)I, use of thyroid blockade pretreatment in (123)I-mIBG imaging prevents increase of thyroid activity over time because of uptake of unbound (123)I. In most subjects, there is a low level of (123)I-mIBG thyroid activity that probably represents specific uptake in sympathetic nerve terminals.


Continuous time-resolved estimated synthetic 4D-CTs for dose reconstruction of lung tumor treatments at a 0.35 T MR-linac.
Objective.To experimentally validate a method to create continuous time-resolved estimated synthetic 4D-computed tomography datasets (tresCTs) based on orthogonal cine MRI data for lung cancer treatments at a magnetic resonance imaging (MRI) guided linear accelerator (MR-linac).Approach.A breathing porcine lung phantom was scanned at a CT scanner and 0.35 T MR-linac. Orthogonal cine MRI series (sagittal/coronal orientation) at 7.3 Hz, intersecting tumor-mimicking gelatin nodules, were deformably registered to mid-exhale 3D-CT and 3D-MRI datasets. The time-resolved deformation vector fields were extrapolated to 3D and applied to a reference synthetic 3D-CT image (sCTref), while accounting for breathing phase-dependent lung density variations, to create 82 s long tresCTs at 3.65 Hz. Ten tresCTs were created for ten tracked nodules with different motion patterns in two lungs. For each dataset, a treatment plan was created on the mid-exhale phase of a measured ground truth (GT) respiratory-correlated 4D-CT dataset with the tracked nodule as gross tumor volume (GTV). Each plan was recalculated on the GT 4D-CT, randomly sampled tresCT, and static sCTrefimages. Dose distributions for corresponding breathing phases were compared in gamma (2%/2 mm) and dose-volume histogram (DVH) parameter analyses.Main results.The mean gamma pass rate between all tresCT and GT 4D-CT dose distributions was 98.6%. The mean absolute relative deviations of the tresCT with respect to GT DVH parameters were 1.9%, 1.0%, and 1.4% for the GTVD98%,D50%, andD2%, respectively, 1.0% for the remaining nodulesD50%, and 1.5% for the lungV20Gy. The gamma pass rate for the tresCTs was significantly larger (p< 0.01), and the GTVD50%deviations with respect to the GT were significantly smaller (p< 0.01) than for the sCTref.Significance.The results suggest that tresCTs could be valuable for time-resolved reconstruction and intrafractional accumulation of the dose to the GTV for lung cancer patients treated at MR-linacs in the future.


Ipsilateral jugular to distal subclavian vein transposition to relieve central venous hypertension in rescue vascular access surgery: a surgical report of 3 cases.
Central venous thrombosis may often arise following central venous cannulation for temporary haemodialysis access. Venous thrombosis may be clinically asymptomatic due to the presence of collateral circulation. However, if an arteriovenous (AV) fistula is prepared below the obstructed venous segment, then symptoms may occur. Central venous hypertension interferes with dialysis, compromises limb function and threatens its safety. Percutaneous treatment is mostly used. However, in some cases endovascular treatment may not be as easy and long term patency uncertain.We report our experience on 3 patients on chronic hemodialysis treatment presenting with a patent AV fistula and ipsilateral subclavian vein chronic fibrotic obstruction. They were treated by ipsilateral internal jugular to distal subclavian vein transposition. Two separate surgical incisions were performed to expose the subclavian vein distally to the occlusion and the jugular vein that was distally ligated and transposed. There was no mortality nor significant postoperative complications. Resolution of hypertensive symptoms was achieved within 3-4 weeks in all patients. The AV fistula was used for dialysis treatment starting from the first postoperative day. At follow-up (mean 13 months), there was no recurrence of upper limb venous hypertension.In patients with subclavian occlusion and ipsilateral low flow, patent AV fistula, jugular to distal subclavian vein transposition may prove useful in cases when percutaneous angioplasty is technically not feasible or long term patency is not expected.


Perceptions of Unprofessional Social Media Behavior Among Emergency Medicine Physicians.
Use of social media (SM) by physicians has exposed issues of privacy and professionalism. While guidelines have been created for SM use, details regarding specific SM behaviors that could lead to disciplinary action presently do not exist. To compare State Medical Board (SMB) directors' perceptions of investigation for specific SM behaviors with those of emergency medicine (EM) physicians. A multicenter anonymous survey was administered to physicians at 3 academic EM residency programs. Surveys consisted of case vignettes, asking, "If the SMB were informed of the content, how likely would they be to initiate an investigation, possibly leading to disciplinary action?" (1, very unlikely, to 4, very likely). Results were compared to published probabilities using exact binomial testing. Of 205 eligible physicians, 119 (58%) completed the survey. Compared to SMB directors, EM physicians indicated similar probabilities of investigation for themes involving identifying patient images, inappropriate communication, and discriminatory speech. Participants indicated lower probabilities of investigation for themes including derogatory speech (32%, 95% confidence interval [CI] 24-41 versus 46%, P < .05); alcohol intoxication (41%, 95% CI 32-51 versus 73%, P < .05); and holding alcohol without intoxication (7%, 95% CI 3-13 versus 40%, P < .05). There were no significant associations with position, hospital site, years since medical school, or prior SM professionalism training. Physicians reported a lower likelihood of investigation for themes that intersect with social identity, compared to SMB directors, particularly for images of alcohol and derogatory speech.


Perioperative and rehabilitation outcome after lower-limb amputation in elderly Chinese patients in Hong Kong.
Major amputation of the lower limb is considered the last resort when limb salvage is impossible. The aim of this study is to determine the morbidity, mortality, and rehabilitation outcome of patients that underwent a lower-limb amputation. A retrospective cohort study was conducted among 100 elderly patients who underwent a total of 120 lower-limb amputations in a regional hospital in Hong Kong from 1996 to 2001. The mean age of the amputees was 77.9 years; 58 were female. 95% of the amputations were performed because of infection with or without vascular compromise; 55 transfemoral and 60 transtibial amputations contributed 96% of the case mix. Some 43% of patients experienced early complications and 12% required re-amputation. The early (30-day) mortality rate was 15%. Only 55% of the amputees survived after 4 years. A 44% return-home rate was achieved. However, only 11% of the amputees could walk without help from other people. Although prostheses were issued to 42% of the survivors, compliance was only 53%; 24% of the survivors lost their remaining leg within 2 years. The outcome of major lower-extremity amputation remains poor. Efforts should be made to retain these limbs. When it is proven impossible, one should strive to preserve the knee joint whenever feasible.


Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics.
Opioids, and more specifically μ-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest. It has been shown that allosteric modulators play key roles in influencing receptor function such as its tolerance to a ligand and affect downstream pathways. There has been a high variance of chemical structures that provide allosteric modulation at a given receptor, but recent studies and reviews tend to focus on the altered cellular mechanisms instead of providing a more rigorous description of the allosteric ligand's structure-function relationship. In this review, we aim to explore recent developments in the structural motifs that potentiate orthosteric binding and their influences on cellular pathways in an effort to present novel approaches to opioid therapeutic design.


Maternal mortality in health institutions with emergency obstetric care facilities in Enugu State, Nigeria.
In order to assess the current level of maternal mortality in health institutions with comprehensive emergency obstetric care in Enugu State, South Eastern Nigeria, a retrospective analysis of maternal deaths for the years 1999-2003 was carried out to establish the maternal mortality ratios in the eligible health institutions. Each maternal death was studied in detail to establish the socio-demographic characteristics of the women who died; their referral sources, type of delay (if any), medical causes of death and their preventability. In-depth interviews of the service providers were carried out to throw more light on the maternal mortality situation in the state. Five out of seven eligible health institutions were studied. Within the 5-year period (1999-2003), there were 141 maternal deaths and 18,257 live births giving a maternal mortality ratio of 772 maternal deaths per 100,000. The folders of 89 out of the 141 women who died were retrieved. Of these 89 maternal deaths, 51.7% of them were unemployed, 52.4% were referred from private hospitals; type 3 delay was the commonest type of delay encountered in the care of the women. Referral delay was the main cause of delay accounting for 46.4% of all cases of type 3 delay. The leading causes of maternal deaths among the women were obstetric haemorrhage (19.1%), sepsis (18.0%), prolonged obstructed labour/ruptured uterus (16.9%) and pre-eclampsia/eclampsia (16.9%). The in-depth interviews corroborated the high maternal mortality ratio recorded and the type 3 delays in tackling obstetric emergencies. It also showed some discrepancies between reality and the health providers' perception of the magnitude of maternal mortality situation in the state. It was concluded that in health institutions in Enugu State with comprehensive emergency obstetric care facilities, the maternal mortality ratio remains high due to type 3 delays. Most of the referrals come from private hospitals, hence the need to retrain the private practitioners in emergency obstetric care.


Differential effects of oxygen on human dermal fibroblasts: acute versus chronic hypoxia.
The observation that many chronic wounds are ischemic has spurred a series of studies evaluating the response of cells exposed to hypoxia. To date, these studies have shown largely beneficial effects from hypoxia, such as increased cellular replication and procollagen synthesis. These findings are counter-intuitive from a clinical standpoint because cellular growth and synthetic function are known to be retarded in chronic ischemic wounds. We have established an in vitro system in which human dermal fibroblasts grown chronically at 5 +/- 3 mm Hg will proliferate at a rate three times slower than those fibroblasts grown under standard culture conditions (namely an oxygen partial pressure of 150 mm Hg). No phenotypic changes are noted in chronically hypoxic cells, and the growth-retarding effects are reversible when the cells are returned to standard oxygen conditions. Competitive reverse transcription-polymerase chain reaction showed that acute exposure to hypoxia (up to 1 week) results in a 6.3-fold increase in the relative expression of transforming growth factor-beta1 messenger RNA, whereas chronic exposure to hypoxia leads to a 3.1-fold decrease in this message. Collagen production measured at both the mRNA and protein level is also decreased in the setting of chronic hypoxia. We propose that this system may be the most appropriate setting for studying the role of oxygen on dermal fibroblasts in ischemic, nonhealing wounds.


Back to Basics: Social Determinants of Health.
Social determinants of health (SDOH) are the conditions that people are born into and live under that affect their health. Nurses are responsible for addressing these determinants when possible. Perioperative nurses encounter the effects of SDOH when patients express concern about surgery scheduling times, transportation, child care, and other support-related issues during the perioperative period. Some SDOH are related to social identity (eg, race, ethnicity, sexual orientation) as a result of the oppression and discrimination that some groups experience. Perioperative nurses can establish trust with their patients by identifying their needs and partnering with community-based organizations to address some of those needs (eg, transportation, legal assistance), which may help relieve stress for their patients and promote better postsurgical outcomes. Although health care workers can assist individual patients to address the effects of SDOH on their health and life, policy change is needed to ensure long-term benefits.


Astragalus polysaccharides attenuates TNF-α-induced insulin resistance via suppression of miR-721 and activation of PPAR-γ and PI3K/AKT in 3T3-L1 adipocytes.
Insulin resistance is associated with obesity and type 2 diabetes. The aim of this study was to explore the mechanism of how Astragalus Polysaccharides (APS) improves insulin resistance in 3T3-L1 adipocytes. A cell culture model of insulin resistance was established in mature 3T3-L1 adipocytes by treating them with TNF-α, high glucose and insulin. Glucose uptake levels were detected in each group. To determine the mechanism by which APS improves insulin resistance in 3T3-L1 adipocytes, qRT-PCR was used to detect the expression of miR-721, and Western blots were used to detect the expression or activity of PPAR-γ, PAKT, PI3K, AKT, and GLUT4. Immunostaining was used to detect the expression of GLUT4. We successfully madea model of insulin resistance in mature 3T3-L1 adipocytes. APS increased glucose uptake levels in insulin-resistant adipocytes in a dose- and time-dependent manner, and also increased insulin sensitivity. APS suppressed miR-721 with its target gene PPAR-γ in a dose-dependent manner. miR-721 or PPAR inhibitor T0070907 inhibited the expressions of PPAR-γ, pAKT, and GLUT4 and also reduced glucose accumulation. APS attenuated these miR-721- and PPAR-γ-induced changes. APS increased insulin sensitivity by attenuating the effects of miR-721. The PI3K inhibitor wortmannin reduced the APS-increased pAKT, glucose uptake, and GLUT4 levels, and also reduced those levels in the presence of insulin with or without APS. Taken together, our findings suggest that APS promotes glucose uptake and increases insulin sensitivity in 3T3-L1 adipocytes and may involve the miR-721-PPAR-γ-PI3K/AKT-GLUT4 signaling pathway. These might be new therapeutic targets for treating insulin resistance in obesity and diabetes.


[Total hip arthroplasty for non-functional bony ankylosed hip in young and middle-aged patients].
To explore the effectiveness of total hip arthroplasty (THA) for non-functional bony ankylosed hip in young and middle-aged patients. Between January 2010 and March 2013, 14 cases (19 hips) of non-functional bony ankylosed hip were treated by THA. There were 9 males and 5 females, aged 37.5 years on average (range, 23- 58 years). The left hip was involved in 6 cases, the right hip in 3 cases, and bilateral hips in 5 cases. The causes were tuberculosis in 2 patients, ankylosing spondylitis in 5 patients, traumatic arthritis in 5 patients, osteoarthritis in 1 patient, and suppurative infection in 1 patient. The disease duration was 7-18 years with an average of 8.9 years. Flexion stiffness was observed in 10 hips, flexion abduction stiffness in 6 hips, and flexion adduction shortening stiffness in 3 hips. Only 5 patients could walk with a crutch before operation. Harris hip score was 24.368 ± 7.625. The average operation time was 63.4 minutes (range, 50-90 minutes). The average intraoperative blood loss was 196.8 mL (range, 100-400 mL). Patients obtained primary healing of incision; no complication of neurovascular injury, fracture, joint dislocation, or infection occurred. All patients were followed up 2.2 years on average (range, 1 year to 4 years and 3 months). The Harris score was 86.837 ± 7.742 at last follow- up, showing significant difference when compared with preoperative score (t = -41.956, P = 0.000). The results were excellent in 5 hips, good in 11 hips, fair in 2 hips, and poor in 1 hip, with an excellent and good rate of 84.2%. All patients could basically take care of themselves; 2 patients could walk with crutch, and the other patients could walk without crutch. X-ray films showed that prosthesis was in good position; no shifting, loosening, or sinking was found. Heterotopic ossification occurred in 2 hips. THA is an effective surgical approach to treat non-functional bony ankylosed hip in young and middle- aged patients.


Ten tips to encourage student interaction with screen-capture type vodcasts.
Video podcasts (vodcasts) are gaining popularity in medical education, but they can be a passive learning modality if students do not actively engage with the content. Of the two categories of vodcast software, screen-capture (mp4 output) and Flash™ (HTML5/Flash output), screen-capture has greater potential to result in passive learning because students cannot physically interact with the content. However, screen-capture offers several advantages for the producer (often faculty) and the consumer (students). As such, this type of software is popular with medical school faculty. To encourage active learning, ten tips are presented with specific strategies that faculty can use with screen-capture type vodcasts. Many of the tips also apply to Flash-type vodcasts. By incorporating these strategies, faculty with limited technical abilities can create engaging vodcasts that stimulate active learning.


A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus.
A novel human protein serine/threonine phosphatase, PP5, and a structurally related phosphatase in Saccharomyces cerevisiae, PPT1, have been identified from their cDNA and gene respectively. Their predicted molecular mass is 58 kDa and they comprise a C-terminal phosphatase catalytic domain and an N-terminal domain, which has four repeats of 34 amino acids, three of which are tandemly arranged. The phosphatase domain possesses all the invariant motifs of the PP1/PP2A/PP2B gene family, but is not closely related to any other known member (< or = 40% identity). Thus PP5 and PPT1 comprise a new subfamily. The repeats in the N-terminal domain are similar to the tetratricopeptide repeat (TPR) motifs which have been found in several proteins that are required for mitosis, transcription and RNA splicing. Bacterially expressed PP5 is able to dephosphorylate serine residues in proteins and is more sensitive than PP1 to the tumour promoter okadaic acid. A 2.3 kb mRNA encoding PP5 is present in all human tissues examined. Investigation of the intracellular distribution of PP5 by immunofluorescence, using two different antibodies raised against the TPR and phosphatase domains, localizes PP5 predominantly to the nucleus. This suggests that, like other nuclear TPR-containing proteins, it may play a role in the regulation of RNA biogenesis and/or mitosis.


Cochlearols A and B, polycyclic meroterpenoids from the fungus Ganoderma cochlear that have renoprotective activities.
(+)- and (-)-cochlearols A (1) and B (2), two meroterpenoids with novel polycyclic skeletons, were isolated from the fruiting bodies of the fungus Ganoderma cochlear. Their structures and stereochemistry were determined by using spectroscopic, computational and single-crystal X-ray diffraction methods. Cochlearol A is a new normeroterpenoid containing a naturally unusual dioxaspiro[4.5]decane motif. Biological studies showed that (-)-2 is a strong inhibitor of p-Smads, exhibiting renoprotective activities in TGF-β1 induced rat renal proximal tubular cells.


ECMO support for right main bronchial disruption in multiple trauma patient with brain injury--a case report and literature review.
Extracorporeal membrane oxygenation (ECMO) may offer life-saving treatment in severe pulmonary contusion or acute respiratory distress syndrome when conventional treatments have failed. However, because of the bleeding risk of systemic anticoagulation, ECMO should be performed only as a last resort in multiple trauma victims. Here, we report ECMO as a bridge for right main bronchus reconstruction and recovery of traumatic wet lung in a 31-year-old male multi-trauma patient with right main bronchial disruption, bilateral pulmonary contusion, cerebral contusion and long bone fracture. The patient was discharged without any obvious complication. ECMO support in a traumatic brain injured patient with severe hypoxemia caused by lung contusion and/or tracheal bronchus disruption is not an absolute contraindication.


Excess-entropy-based anomalies for a waterlike fluid.
Many thermodynamic and dynamic properties of water display unusual behavior at low enough temperatures. In a recent study, Yan et al. [Phys. Rev. Lett. 95, 130604 (2005)] identified a spherically symmetric two-scale potential that displays many of the same anomalous properties as water. More specifically, for select parametrizations of the potential, one finds that the regions where isothermal compression anomalously (i) decreases the fluid's structural order, (ii) increases its translational self-diffusivity, and (iii) increases its entropy form nested domes in the temperature-density plane. These property relationships are similar to those found for more realistic models of water. In this work, the authors provide evidence that suggests that the anomalous regions specified above can all be linked through knowledge of the excess entropy. Specifically, the authors show how entropy scaling relationships developed by Rosenfeld [Phys. Rev. A 15, 2545 (1977)] can be used to describe the region of diffusivity anomalies and to predict the state conditions for which anomalous viscosity and thermal conductivity behavior might be found.


Three-part head-splitting proximal humerus fracture through a unicameral bone cyst.
Unicameral bone cysts are rare in adults and are most often found incidentally on radiographs. However, they can persist from the adolescent period and may be present in locations that predispose to or exacerbate fractures.This article describes a case of a healthy 40-year-old woman who sustained a proximal humerus trauma that involved a large unicameral bone cyst, resulting in a 3-part head-splitting fracture. The epiphyseal location of the cyst contributed to the severity and extent of the fracture that resulted from a simple fall. Given the age of the patient, open reduction and internal fixation with a locking plate and lag screws was performed. The patient chose open reduction and internal fixation to preserve a hemiarthroplasty procedure in case of future revision. Successful humeral head reconstruction was achieved, and the patient fully recovered. One year postoperatively, the patient underwent arthroscopic debridement to alleviate subjective stiffness and decreased range of motion.Multipart head-splitting fractures require complex repair strategies. The gold standard for the treatment of these injuries is hemiarthroplasty. However, the decision process is difficult in a young patient given the average survival of autoplastic prostheses and the added difficulty of later revision. The current case demonstrates the complexity of decision making resulting from a rare injury in a young, healthy patient and shows that open reduction and internal fixation can provide acceptable reconstruction in such situations.


Perceiving the language of films.
Children appear to be familiar with the language of film makers or at least to perceive and remember films less well when the rules of this cinematic language are broken. In this experiment a simple action sequence filmed from a static viewpoint was made up into two films of four shots. One film was edited according to the rules of directional continuity specified by Hollywood cinema, that is the four shots were presented so as to preserve the subject's direction of movement across cuts. The other film was edited disregarding these rules. Apart from this difference both films were identical. Children aged seven, nine, and thirteen years watched either of these films and reconstructed the action using pictures representing the four shots. The children who saw the conventional version were better able to reconstruct what they had seen than those who saw the unconventional version.


Unexpected significance of a minor reaction pathway in daytime formation of biogenic highly oxygenated organic compounds.
Secondary organic aerosol (SOA), formed by oxidation of volatile organic compounds, substantially influence air quality and climate. Highly oxygenated organic molecules (HOMs), particularly those formed from biogenic monoterpenes, contribute a large fraction of SOA. During daytime, hydroxyl radicals initiate monoterpene oxidation, mainly by hydroxyl addition to monoterpene double bonds. Naturally, related HOM formation mechanisms should be induced by that reaction route, too. However, for α-pinene, the most abundant atmospheric monoterpene, we find a previously unidentified competitive pathway under atmospherically relevant conditions: HOM formation is predominately induced via hydrogen abstraction by hydroxyl radicals, a generally minor reaction pathway. We show by observations and theoretical calculations that hydrogen abstraction followed by formation and rearrangement of alkoxy radicals is a prerequisite for fast daytime HOM formation. Our analysis provides an accurate mechanism and yield, demonstrating that minor reaction pathways can become major, here for SOA formation and growth and related impacts on air quality and climate.


Space-time properties of Gram-Schmidt vectors in classical Hamiltonian evolution.
Not all tangent space directions play equivalent roles in the local chaotic motions of classical Hamiltonian many-body systems. These directions are numerically represented by basis sets of mutually orthogonal Gram-Schmidt vectors, whose statistical properties may depend on the chosen phase space-time domain of a trajectory. We examine the degree of stability and localization of Gram-Schmidt vector sets simulated with trajectories of a model three-atom Lennard-Jones cluster. Distributions of finite-time Lyapunov exponent and inverse participation ratio spectra formed from short-time histories reveal that ergodicity begins to emerge on different time scales for trajectories spanning different phase-space regions, in a narrow range of total energy and history length. Over a range of history lengths, the most localized directions were typically the most unstable and corresponded to atomic configurations near potential landscape saddles.


Advances in the diagnosis and early management of gestational trophoblastic disease.
Gestational trophoblastic disease describes a group of rare pregnancy related disorders that span a spectrum of premalignant and malignant conditions. Hydatidiform mole (also termed molar pregnancy) is the most common form of this disease. Hydatidiform mole describes an abnormal conceptus containing two copies of the paternal genome, which is classified as partial when the maternal genome is present or complete when the maternal genome is absent. Hydatidiform mole typically presents in the first trimester with irregular vaginal bleeding and can be suspected on ultrasound but confirmation requires histopathological evaluation of the products of conception. Most molar pregnancies resolve without treatment after uterine evacuation, but occasionally the disease persists and develops into gestational trophoblastic neoplasia. Close monitoring of women after molar pregnancy, with regular measurement of human chorionic gonadotrophin concentrations, allows for early detection of malignancy. Given the rarity of the disease, clinical management and treatment is best provided in specialist centres where very high cure rates are achievable. This review looks at advances in the diagnosis and early management of gestational trophoblastic disease and highlights updates to disease classification and clinical guidelines. Use of molecular genotyping for improved diagnostic accuracy and risk stratification is reviewed and future biomarkers for the earlier detection of malignancy are considered.


Ablative CO2 lasers for skin tightening: traditional versus fractional.
With patients more resistant to invasive treatments and those that result in significant downtime, there has been a rise in using lasers to improve skin laxity and induce tissue tightening as an alternative to surgery. Traditional and fractional ablative resurfacing induces skin tightening through precise dermal heating and a wound-healing effect. The purpose of this review was to discuss the mechanism of action of using ablative lasers to induce skin tightening and compare traditional versus fractional technologies. A review of the literature was performed. The authors discuss traditional and fractional ablative lasers for achieving skin tightening. Neocollagenesis and dermal remodeling seen after ablative resurfacing contributes to the clinical improvement seen in tissue tightening. Fractional photothermolysis may enhance tissue tightening effects of ablative lasers because of its ability to ablate deeper into the reticular dermis without significant risk for scarring.


[Calcified thrombosis of the inferior vena cava in children].
A new case of calcified thrombus in the Inferior Vena Cava is described, and added to the 19 previously reported cases in literature. The etiology of these calcified thrombi is unknown, but a precise diagnostic an therapeutic approach is now well established. On plain X-ray of the abdomen, the right paravertebral bullet-shaped calcification is diagnostic. No further investigations are necessary, except in the neonatal period, when the thrombus is incompletely calcified, suggesting neuroblastoma or adrenal hemorrhage. Definitive diagnosis, in that case, can be made by abdominal ultrasonography. In the current state of our knowledge, the clinical tolerance of this anomaly is excellent. No specific treatment appears to be necessary.


Functional mapping and Ca2+ regulation of nicotinic acetylcholine receptor channels in rat hippocampal CA1 neurons.
Diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including fast-desensitizing alpha7-containing receptors thought to be Ca2+-permeable, are expressed in the CNS, where they appear to regulate cognitive processing and synaptic plasticity. To understand the physiological role of nAChRs in regulating neuronal excitability, it is important to know the distribution of functional receptors along the surface of neurons, whether they can increase [Ca2+]i, and/or are regulated by Ca2+. We mapped the distribution of receptors on the membrane of rat hippocampal CA1 stratum radiatum interneurons and pyramidal cells in acute slices by recording nAChR-mediated currents elicited by local UV laser-based photolysis of caged carbachol in patch-clamped neurons. The local application (approximately 7 microm patches) allowed mapping of functional nAChRs along the soma and dendritic tree, whereas the fast uncaging minimized the effects of desensitization of alpha7-containing nAChRs and allowed us to measure the kinetics of responses. The alpha7-containing nAChRs were the predominant subtype on interneurons, and were located primarily at perisomatic sites (<70 microm from the soma; in contrast to the more uniform distribution of glutamate receptors); no currents were detectable on pyramidal neurons. The activation of nAChRs increased [Ca2+]i, indicating that these native receptors in acute slices are significantly Ca2+-permeable, consistent with previous observations made with recombinant receptors. In addition, they exhibited strong desensitization, the rate of recovery from which was controlled by [Ca2+]i. Our results demonstrate the strategic location and Ca2+ regulation of alpha7-containing nAChRs, which may contribute to understanding their involvement in hippocampal plasticity.


An investigation of two-way text messaging use with deaf students at the secondary level.
Deaf and hard-of-hearing students are often delayed in developing their independent living skills because of parental restrictions on activities outside the home due to worries about their child's inability to communicate, their whereabouts, and their general safety. Recent accounts of the use of two-way text messagers suggests that, like electronic mail, distance communication problems that have long plagued deaf people may be ameliorated--by the use of such technology (M. R. Power & D. Power, 2004; S. S. Rhone & Cox News Service, 2002). This project was designed as an initial foray into investigating the use of two-way text messaging technology as a way of increasing the independence of deaf adolescents and reducing their parents' anxiety about their safety and responsibility. All the deaf and hard-of-hearing students in the deaf and hard-of-hearing programs at two urban high schools (ages 13-19), the staff of the deaf departments at these two schools, and the parents/guardians of the students participated in this study. Preuse surveys, postuse surveys, and monthly statistics on the number of times each pager was used enabled us to chart how often the participants used the technology. The data were used to identify concerns that parents have about student independence and safety, the extent to which deaf students engage in independent activities, and expectations surrounding how two-way text messaging use might increase independence and literacy skills. The data collected on this project to date confirm that two-way text messaging technology is indeed useful for deaf adolescents and helps alleviate some of the concerns that have kept them from developing independence as quickly or readily as their hearing peers. The potential policy implications for this research are discussed.


Future possibilities for the treatment of septic shock with herbal components.
The treatment of septic shock remains challenging even with the armamentarium of modern antibiotics and intensive care technologies. Reliance on antibiotics and other methods targeting modulation of the systemic inflammatory response such as steroids, hemofiltration, and cytokine antagonists has not led to reliable successful treatment for inflammation and infection-related shock. In part, this is attributable to the continuous evolution of antibacterial drug resistance. Herbal medicine has been used in treating infections and shock, worldwide, for thousands of years. The active components contained in these naturally occurring products usually have one or more of the following properties: (1) direct attack or suppression on bacterial pathogens, (2) modulation of the host's immune system resulting in suppression of inflammation and overproduction of inflammatory mediators, and (3) neutralization of toxic free-radicals. In vitro and in vivo animal and human clinical studies of herbal medicines' effectiveness in the treatment of septic shock are needed. Their pharmacological mechanisms need to be elucidated at molecular level to investigate and improve targeted therapy using heretofore unexplored uses for traditional herbal remedies. Herein, we discuss historical examples of herbal remedies used to fight infection. In addition, we discuss the use of herbal and traditional medicines as potential adjuncts in the ongoing battle against septic shock and systemic infections.


Plasma and erythrocyte essential fatty acids during total parenteral nutrition in infants: effects of a cutaneous supply.
In order to prevent essential fatty acid (EFA) deficiency induced by fat-free total parenteral nutrition (TPN), 10 infants on TPN were rubbed three times daily for 20 days using oenethera oil (80% EFA). Total EFA amount provided cutaneously was 1900 mg/kg/d. Plasma and red blood cells phospholipids were determined on days 1 and 20 in these 10 treated and six untreated infants on TPN and compared with those of normal control infants. On day 1, plasma nonessential FA including 20:3 n-9(p less than 0.01) were increased in both TPN groups while 18:2 n-6 and 18:3 n-3 (p less than 0.001 and p less than 0.01) were decreased. On the 20th day, EFA deficiency had worsened with a decrease in plasma level of 20:4 n-6 (p less than 0.02) and a higher than normal triene/tetraene ratio : 3.4 +/- 1.1 and 2.3 +/- 0.6 vs 0.1 +/- 0.1 (p less than 0.02). As for red blood cells phospholipids, 16:0 was increased and 18:2 n-6 and 20:3 n-6 were decreased (p less than 0.05) on day 1. On day 20, these FA were more abnormal while 20:3 n-9 became significantly increased (p less than 0.05). No difference was observed between the TPN groups at any time. These results show that cutaneous application of large amounts of EFA-rich oil is unable to prevent or cure TPN induced EFA deficiency.


[Laparoscopic cholecystectomy: 3 years of experience at a university hospital].
We analyse the first 174 patients treated with laparoscopic cholecystectomy (LC) and their follow-up results. Average age was 57 years. Intraoperative cholangiography was not done in anyone. Conversion rate into other forms of intervention was 6.3%. The rate of common bile duct injury has been null. Total morbidity was 6.3%. Two cases of pulmonary embolism and two biliary leakages stand out in the postoperative morbidity. There was no death. After a follow-up period of up to 36 months, only 1 case of residual choledocholithiasis was registered, and it was cured with endoscopy. In this series morbid-mortality figures are low. LC is a safe procedure in the treatment of cholelithiasis, even in older patients.


Murine monoclonal anti-idiotype antibody as a potential network antigen for human carcinoembryonic antigen.
Carcinomas of the gastrointestinal tract are not curable by standard therapies. Thus, new therapeutic approaches for this disease are needed. This study proposes the use of anti-Id mAb as Ag substitutes to induce anti-tumor immunity in gastrointestinal cancer patients. Recently, we have generated and characterized one monoclonal anti-Id antibody, designated 3H1 (Ab2), which mimics biologically and antigenically a distinct and specific epitope of the 180,000 m.w. carcinoembryonic antigen (CEA) primarily expressed in high density by human pancreatic and colonic tumor cells. This epitope is unique to CEA and not present on other CEA-related lower m.w. members of the Ag family also found on normal tissues. The antigenic determinant as defined by the mAb 8019 (Ab1) against which the Ab2, 3H1 was raised, is absent on normal adult tissues by immunoperoxidase staining and haematopoietic cells including granulocytes by flow cytometry analysis. Anti-Id (Ab2) 3H1 induced CEA-specific antibodies in mice and rabbits. The immune sera from both mice and rabbits competed with Ab1 for binding to the colon carcinoma cell line LS174T and inhibited the binding of radioiodinated Ab1 to Ab2. This indicates that anti-anti-Id (Ab3) in mice and rabbits share idiotopes with Ab1 (8019). Furthermore, monoclonal Ab3 that bind to CEA have been generated from mice immunized with 3H1. The Ab3 (both polyclonal as well as monoclonal) immunoprecipitated the same 180,000 m.w. CEA as Ab1 (8019) by Western blotting analysis and showed almost identical immuno-staining patterns as Ab1 on colonic adenocarcinoma tissue sections from several patients. Collectively these data suggest that Ab2 3H1 could potentially be used clinically as a network Ag for immunotherapy of patients with CEA positive tumors.


Ionic liquid salt bridge in dilute aqueous solutions.
A new type of salt bridge composed of a hydrophobic room-temperature ionic liquid, recently proposed (T. Kakiuchi and T. Yoshimatsu, Bull. Chem. Soc. Jpn., 2006, 79, 1017), has been shown to be satisfactorily usable in dilute aqueous solutions of submillimolar range. A stable phase-boundary potential has been demonstrated between an ionic liquid, 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C(8)mim+][C(1)C(1)N-), and an aqueous KCl solution of submillimolar level, which is lower than the solubility of [C(8)mim+][C(1)C(1)N-] in water, 1.6 mmol dm(-3) at 25 degrees C. The phase-boundary potential between [C(8)mim+][C(1)C(1)N-] and water is maintained constant over more than four orders of magnitude change in the concentration of an aqueous electrolyte solution. The ionic-liquid salt bridge is a superior alternative to salt bridges based on equitransferent electrolytes in practical applications, particularly, the potentiometry of samples of low ionic strengths, such as potentiometric pH measurements of rainwater.


Stigmatization, discrimination, and mental health: the impact of multiple identity status.
The authors present the empirical characteristics of the Experience of Discrimination Scale (EDS) using baseline data from the Center for Mental Health Services-funded, multisite Consumer Operated Services Project. Specific hypotheses focused on the influence of multiple identity status on reports of discrimination. Data indicated that discrimination caused by mental disability was associated with level of psychiatric symptoms and perceived social rejection as a result of mental illness, whereas discrimination for other reasons was associated with broader quality of life and social interaction indicators. The clinical and policy implications of findings are discussed.


Spatial generalization and aggregation of massive movement data.
Movement data (trajectories of moving agents) are hard to visualize: numerous intersections and overlapping between trajectories make the display heavily cluttered and illegible. It is necessary to use appropriate data abstraction methods. We suggest a method for spatial generalization and aggregation of movement data, which transforms trajectories into aggregate flows between areas. It is assumed that no predefined areas are given. We have devised a special method for partitioning the underlying territory into appropriate areas. The method is based on extracting significant points from the trajectories. The resulting abstraction conveys essential characteristics of the movement. The degree of abstraction can be controlled through the parameters of the method. We introduce local and global numeric measures of the quality of the generalization, and suggest an approach to improve the quality in selected parts of the territory where this is deemed necessary. The suggested method can be used in interactive visual exploration of movement data and for creating legible flow maps for presentation purposes.


Can caffeine antagonize alcohol-induced performance decrements in humans?
Design aspects and results of experiments that investigated the effects of caffeine on alcohol-induced performance decrements in humans are discussed. Simple conclusions concerning those outcomes are unwarranted because they seem to depend on the tasks used and the dosages of both drugs, with both antagonism and potentiation of alcohol-induced effects having been reported. Results indicate that legally intoxicated individuals cannot antagonize alcohol-induced, driving-related decrements with caffeine prior to driving an automobile, thought to be the major behavior for which caffeine is used in attempts to antagonize alcohol-induced decrements. We offer suggestions for research concerning subjects' habitual use or nonuse of caffeine and typical alcohol consumption levels, the interval between alcohol and caffeine ingestion, and the effects of caffeine and alcohol alone on performance tasks. We also suggest that statistical analyses should allow for a differentiation of results in which caffeine partially offsets an alcohol-induced decrement from more positive results in which caffeine returns functioning to its normal level.