Cell-free translation of messenger RNAs from adult and fetal human muscle. Characterization of neosynthesized glycogen phosphorylase, phosphofructokinase and glucose phosphate isomerase.
Using a procedure of ethanol precipitation in concentrated guanidine . HCl solutions followed by chloroform/isoamylic alcohol extraction and washing in 3 M sodium acetate, we isolated high-molecular-weight cellular RNA from human fetal and adult skeletal muscle. About 500 micrograms RNA were obtained/g of fetal muscle and 50 micrograms RNA/g of adult muscle. Both RNA preparations were efficiently translated in a cell-free reticulocyte lysate system and directed synthesis of various polypeptides, one of them of Mr 200,000 probably corresponding to myosin heavy chains. Dodecylsulphate/polyacrylamide gel electrophoretic pattern of polypeptides neosynthesized using either fetal or adult RNA exhibited several differences. Three neosynthesized cytosolic muscle enzymes were purified from the translation mixtures using a micro-method of immunoaffinity chromatography; specificity of the neosynthesized polypeptides purified according to this procedure was checked by immunological competition with the corresponding unlabeled pure muscle enzymes. Successful cell-free translation of RNA from adult skeletal muscle and purification of neosynthesized human enzymes are reported for the first time. These methods, indispensable for further studies on human adult muscle gene expression, could also shed light on the mechanism of some inherited molecular diseases and tumoral or dystrophic processes.


A calibration-independent method for accurate complex permittivity determination of liquid materials.
This note presents a calibration-independent method for accurate complex permittivity determination of liquid materials. There are two main advantages of the proposed method over those in the literature, which require measurements of two cells with different lengths loaded by the same liquid material. First, it eliminates any inhomogeneity or impurity present in the second sample and decreases the uncertainty in sample thickness. Second, it removes the undesired impacts of measurement plane deterioration on measurements of liquid materials. For validation of the proposed method, we measure the complex permittivity of distilled water and compare its extracted permittivity with the theoretical datum obtained from the Debye equation.


Physiological Effects of Touching Wood.
This study aimed to clarify the physiological effects of touching wood with the palm, in comparison with touching other materials on brain activity and autonomic nervous activity. Eighteen female university students (mean age, 21.7 ± 1.6 years) participated in the study. As an indicator of brain activity, oxyhemoglobin (oxy-Hb) concentrations were measured in the left/right prefrontal cortex using near-infrared time-resolved spectroscopy. Heart rate variability (HRV) was used as an indicator of autonomic nervous activity. The high-frequency (HF) component of HRV, which reflected parasympathetic nervous activity, and the low-frequency (LF)/HF ratio, which reflected sympathetic nervous activity, were measured. Plates of uncoated white oak, marble, tile, and stainless steel were used as tactile stimuli. After sitting at rest with their eyes closed, participants touched the materials for 90 s. As a result, tactile stimulation with white oak significantly (1) decreased the oxy-Hb concentration in the left/right prefrontal cortex relative to marble, tile, and stainless steel and (2) increased ln(HF)-reflected parasympathetic nervous activity relative to marble and stainless steel. In conclusion, our study revealed that touching wood with the palm calms prefrontal cortex activity and induces parasympathetic nervous activity more than other materials, thereby inducing physiological relaxation.


Hookah Susceptibility and Transitions Over the First Year of College.
There has been a growth in popularity of hookah (or waterpipes) among American college students, despite the health risks. This study investigated factors that predict hookah susceptibility and whether hookah susceptibility predicts hookah initiation and continued use. The study established a cohort of 529 incoming college freshmen (51.6% female) who completed an online survey approximately 1 week before their arrival to a large U.S. university. Students were sent four follow-up surveys throughout the 2016-2017 academic year; 90.5% completed at least one follow-up survey. A total of 13.2% of the sample had used hookah at baseline and 9.9% initiated hookah use over the course of their freshman year. Among the nonusers who had no hookah susceptibility at baseline, 30.0% came to indicate some susceptibility. Multivariable logistic regression indicated that the personality construct conscientiousness was protective against becoming susceptible, whereas coming from a rural part of the state was a risk factor. Susceptibility predicted both continued use among the baseline ever-users and initiation among the baseline never-users. These findings highlight the role of susceptibility in the trajectory of hookah use among U.S. college students.


Phase-Specific and Lifetime Costs of Multiple Myeloma Among Older Adults in the US.
Health care costs associated with diagnosis and care among older adults with multiple myeloma (MM) are substantial, with cost of care and the factors involved differing across various phases of the disease care continuum, yet little is known about cost of care attributable to MM from a Medicare perspective. To estimate incremental phase-specific and lifetime costs and cost drivers among older adults with MM enrolled in fee-for-service Medicare. A retrospective cohort study was conducted using population-based registry data from the 2007-2015 Surveillance, Epidemiology, and End Results database linked with 2006-2016 Medicare administrative claims data. Data analysis included 4533 patients with newly diagnosed MM and 4533 matched noncancer Medicare beneficiaries from a 5% sample of Medicare to assess incremental MM lifetime and phase-specific costs (prediagnosis, initial care, continuing care, and terminal care) and factors associated with phase-specific incremental MM costs. The study was conducted from June 1, 2019, to April 30, 2021. Incremental MM costs were calculated for the disease lifetime and the following 4 phases of care: prediagnosis, initial, continuing care, and terminal. Of the 4533 patients with MM included in the study, 2374 were women (52.4%), 3418 (75.4%) were White, and mean (SD) age was 75.8 (6.8) years (2313 [51.0%] aged ≥75 years). The characteristics of the control group were similar; however, mean (SD) age was 74.2 (8.8) years (2839 [62.6%] aged ≤74 years). Mean adjusted incremental MM lifetime costs were $184 495 (95% CI, $183 099-$185 968). Mean per member per month phase-specific incremental MM costs were estimated to be $1244 (95% CI, $1216-$1272) for the prediagnosis phase, $11 181 (95% CI, $11 052-$11 309) for the initial phase, $5634 (95% CI, $5577-$5694) for the continuing care phase, and $6280 (95% CI, $6248-$6314) for the terminal phase. Although inpatient and outpatient costs were estimated as the major cost drivers for the prediagnosis (inpatient, 55.8%; outpatient, 40.2%), initial care (inpatient, 38.1%; outpatient, 35.5%), and terminal (inpatient, 33.0%; outpatient, 34.6%) care phases, prescription drugs (44.9%) were the largest cost drivers in the continuing care phase. The findings of this study suggest that there is substantial burden to Medicare associated with diagnosis and care among older adults with MM, and the cost of care and cost drivers vary across different phases of the cancer care continuum. The study findings might aid policy discussions regarding MM care and coverage and help further the development of alternative payment models for MM, accounting for differential costs across various phases of the disease continuum and their drivers.


Absence of a direct effect of recombinant interleukins and cultured peritoneal macrophages on early embryonic development in the mouse.
On the basis of their recent studies, several researchers have suggested that the infertility associated with mild endometriosis is due to the alteration of peritoneal fluid, resulting in impairment of the viability of gametes or embryos. Elevated numbers of macrophages and lymphocytes have been reported in the peritoneal fluid of patients with endometriosis. Interleukin-1 (IL-1) a major product of activated macrophages and Interleukin-2 (IL-2), a product of most activated T-cells, have been postulated to play a role in the infertility associated with this disease, possibly by acting as direct embryotoxic agents. We have examined the effect of purified recombinant IL-1 and IL-2, which are not species-specific, on in vitro development of mouse embryos. Both interleukins had no effect on development to the blastocyst stage or on early stages of implantation, as measured in vitro by attachment and outgrowth of blastocysts to fibronectin-coated dishes. Moreover, co-culture of mouse embryos with activated human peritoneal macrophages had no effect on embryogenesis. We conclude that neither IL-1, nor other products of human macrophages activated by lipopolysaccharide, nor IL-2 are directly toxic to early mouse embryonic development.


Glucocorticoid receptor transcriptional isoforms and resistance in multiple myeloma cells.
Although glucocorticoids play an important role in the treatment of multiple myeloma, some patients do not respond or develop resistance. The glucocorticoid receptor (GR), a single gene, mediates the effects of glucocorticoids. Using a model system of a multiple myeloma cell line sensitive to glucocorticoids and its early and late resistant variants, we have analyzed mutations in the GR gene, detected the presence of different transcriptional isoforms, quantified their levels of expression, and identified the promoters that regulate their expression. Levels of GR transcripts were comparable with the expression of total GR protein. Development of resistance correlates with an overall reduction in GR mRNA levels. This decrease in GR levels is neither due to mutation of the gene nor due to methylation. GRalpha is the predominant isoform in the sensitive cell line decreasing in expression in the early resistant cells and virtually undetectable in late resistant cells. GR-P is expressed at equivalent levels in both sensitive and early resistant cells, whereas in the late resistant cells, GR-P is the predominant isoform. GR-A is only expressed in the early resistant cell line. GRbeta is the least expressed isoform in all cell lines. Interestingly, the level of expression of exon 1-exon 2 RNA fragments remains similar in sensitive and resistant cell lines. Resistant cells became sensitive to glucocorticoids after GRalpha transfection. In conclusion, we show different patterns of expression of the GR isoforms and provide evidence that a decline in the expression of GRalpha may be associated with development of resistance.


Pancreatic Neuroendocrine Tumor Producing Insulin and Vasopressin.
The objective of the study is to report a rare case of pancreatic neuroendocrine tumor (pNET) producing insulin and vasopressin. We describe the clinical presentation and management of a metastatic pNET with refractory hypoglycemia and progressive severe hyponatremia. A 52-year-old patient had abdominal pain leading to the diagnosis of a tumor that was initially presumed to be splenic in origin. Investigations ultimately identified a pancreatic mass that on biopsy proved to be a pNET. Eventually, he developed extensive liver metastases, and with tumor progression, he manifested hypoglycemia and severe hyponatremia. He was managed with multiple therapies including somatostatin analogue, peptide-receptor-radionuclide-therapy (PRRT), diazoxide, and everolimus; none of these therapeutic modalities was successful in controlling functional and structural progression of the tumor. Ultimately, the pNET proved fatal and autopsy confirmed widely metastatic disease that stained strongly and diffusely for vasopressin, a feature not seen in the previous liver biopsy. This case illustrates the challenges of diagnosis and management of aggressive insulin-producing pNETs and highlights the potential concomitant ectopic production of vasopressin leading to refractory hyponatremia.


Expression cloning of complementary DNA encoding three distinct isoforms of guinea pig Fc receptor for IgG1 and IgG2.
Three cDNA clones encoding the guinea pig Fc receptor for IgG1 and IgG2 (Fc gamma 1/gamma 2 R) have been isolated by an expression cloning strategy using mAb directed against the receptor. When transfected into COS-7 cells, these cDNA induced cell surface expression of the receptor that bound IgG1 and IgG2 antibodies complexed with the Ag. The ligand-binding affinities of these receptors were indistinguishable. Nucleotide sequencing has indicated that one of these clones, Fc gamma 1/gamma 2R-B1, is identical to the previously isolated cDNA clone homologous to the b2 isoform of human Fc gamma RIIB and that of murine Fc gamma RII, encoding a transmembrane glycoprotein containing two Ig-like extracellular domains. Two other clones, Fc gamma 1/gamma 2R-B2 and -B3, are identical to Fc gamma 1/gamma 2R-B1 except for an inframe insertion in the cytoplasmic region. The 48-nucleotide insertion found in Fc gamma 1/gamma 2R-B2 is identical to the first 48 nucleotides of the B3 insert that comprises 132 bp. Based on the size and homology of the inserted sequence, Fc gamma 1/gamma 2R-B2 and -B3 are identified as the homologues of the b1 isoform of human Fc gamma RIIB and that of murine Fc gamma RII, respectively. Reverse transcription and polymerase chain reaction of RNA revealed that macrophages and polymorphonuclear leukocytes expressed preferentially Fc gamma 1/gamma 2R-B1. On the other hand, B lymphocytes expressed all three forms, among which Fc gamma 1/gamma 2R-B2 and -B3 were selectively expressed in LPS-activated B lymphocytes that showed a dramatic increase in the levels of cell surface expression of Fc gamma 1/gamma 2R. These results suggest that the inserted sequences of Fc gamma 1/gamma 2R-B2 and -B3 are important to generate responses specific for B lymphocytes, which may include regulation of cell activation.


Comparative analysis reveals loss of the appetite-regulating peptide hormone ghrelin in falcons.
Ghrelin and leptin are key peripherally secreted appetite-regulating hormones in vertebrates. Here we consider the ghrelin gene (GHRL) of birds (class Aves), where it has been reported that ghrelin inhibits rather than augments feeding. Thirty-one bird species were compared, revealing that most species harbour a functional copy of GHRL and the coding region for its derived peptides ghrelin and obestatin. We provide evidence for loss of GHRL in saker and peregrine falcons, and this is likely to result from the insertion of an ERVK retrotransposon in intron 0. We hypothesise that the loss of anorexigenic ghrelin is a predatory adaptation that results in increased food-seeking behaviour and feeding in falcons.


Mandibular and dental abnormalities of two Pleistocene American lions (Panthera leo atrox) from Yukon Territory.
Fragmented mandibles of two Pleistocene lions (Panthera leo atrox) recovered from Yukon Territory possessed acquired pathological changes and congenital abnormalities, judging from the anatomy of contemporary and modern lions. One specimen showed evidence of chronic periodontitis, an extensive sclerosing osteomyelitis and congenital absence of left lower incisor teeth 1 and 2. The second showed long-standing loss of the left lower canine tooth with subsequent obliteration of the alveolus by lamellar and spicular bone and the congenital absence of two incisors in each half of the mandible. Both specimens had reduced incisive widths.


Effect of thioperamide on oxidative stress markers in middle cerebral artery occlusion model of focal cerebral ischemia in rats.
In view of the recent evidence for the involvement of histamine in cerebral ischemia, the present study evaluated the effect of thioperamide (THP), a selective histamine H3-receptor antagonist, on middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia in rats. The rats were subjected to 2 h of MCAO followed by 22 h reperfusion after which the grip strength, locomotor activity and spontaneous alternation performance were assessed. Animals were then killed and oxidative stress markers were estimated in the whole brain. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione (GSH) and antioxidant enzymes, such as glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD), was observed following MCAO, the last two being statistically insignificant. Pretreatment with THP (5.5 mg/kg i.p. and 11 mg/kg i.p.) significantly reversed the MCAO-induced increase in TBARS, but could not reverse the other parameters. Paradoxically, it further reduced the levels of GPx, GR and SOD. No significant changes were observed in the catalase levels and in the grip strength and spontaneous alternation behavior of rats. Locomotor activity was reduced slightly, but reversed on pretreatment with THP. The dual effect of THP on oxidative stress requires further investigation and raises doubts on its possible use in cerebral ischemia.


Imaging neuronal activity with genetically encoded calcium indicators.
Genetically encoded calcium indicators (GECIs), which are based on chimeric fluorescent proteins, can be used to monitor calcium transients in living cells and organisms. Because they are encoded by DNA, GECIs can be delivered to the intact brain noninvasively and targeted to defined populations of neurons and specific subcellular compartments for long-term, repeated measurements in vivo. GECIs have improved iteratively and are becoming useful for imaging neural activity in vivo. Here we summarize extrinsic and intrinsic factors that influence a GECI's performance and provides guidelines for selecting the appropriate GECI for a given application. We also review recent progress in GECI design, optimization, and standardized testing protocols.


Rapid identification of group B streptococci by counterimmunoelectrophoresis.
Beta-hemolytic streptococcal isolates have been examined by counterimmunoelectrophoresis (CIE) with group B antiserum to determine whether this techinque is of value in the rapid identification of group B strains. Ninety stock cultures and 100 clinical isolates of beta-hemolytic streptococci including representatives of groups A, D, C, G, and B were inoculated into Todd-Hewitt broth; after incubation at 37 C for 1, 2, 3, and 4 h, aliquots of the whole broth cultures were removed and tested by CIE. Antigen was not regularly detected in the 1-, 2-, and 3-h samples, but after 4 h all 126 group B streptococcal strains identified by the capillary precipitin reaction gave CIE precipitin bands with group B antiserum. None of the 58 non-group B strains gave precipitin reactions with this antiserum. Cerebrospinal fluid from an infant with group B streptococcal meningitis and peritoneal fluid from a patient with group B streptococcal peritonitis had free group B antigen detected by the CIE technique. CIE of broth cultures and direct body fluids appears to be a rapid and sensitive method for the identification of group B streptococcal strains.


Oxyresveratrol ameliorates allergic airway inflammation via attenuation of IL-4, IL-5, and IL-13 expression levels.
Oxyresveratrol is known to possess anti-inflammatory property. Current study investigates the immunosuppressive effect of oxyresveratrol by using mouse model of ovalbumin (OVA)-induced allergic airway inflammation. BALB/c mice were randomly divided into five groups having 8 mice in each group. Treatment with low dose (7 mg/kg) and high dose (15 mg/kg) of oxyresveratrol, and methylprednisolone (15 mg/kg; standard drug) was started 2 week after immunization of mice with ovalbumin and continued for 7d. Ovalbumin was also injected into pinna of right ear 24h before sacrificing the mice to evaluate delayed type hypersensitivity (DTH). H&E and PAS staining were used for histopathological evaluation of lungs. Reverse transcription polymerase chain reaction followed by gel electrophoresis were used for evaluation of mRNA expression levels of IL-4, IL-5, and IL-13. Oxyresveratrol significantly reduced total leucocyte count in both blood and bronchoalveolar lavage fluid (BALF). Treatment with oxyresveratrol normalized altered eosinophil and neutrophil counts in both blood and BALF. OVA-specific T-cell response was also significantly inhibited by oxyresveratrol. A significant attenuation of inflammatory cell infiltration and goblet cell hyperplasia was observed after treatment with oxyresveratrol. Data showed that oxyresveratrol significantly suppressed Th2 (T helper cells) type immune response which was obvious by the reduction in mRNA expression levels of IL-4, IL-5, and IL-13. Similarly, treatment with methylprednisolone also significantly reduced all the immunomodulatory and inflammatory parameters. Our study demonstrates that oxyresveratrol ameliorates allergic asthma. The anti-asthmatic activity might in part occur via the down regulation of IL-4, IL-5, and IL-13 expression levels.


Information needs of the dairy industry for health and nutrition management.
Current DHI records usage is demonstrated with lactation curves, peak milk production versus rolling average peak milk production, and linear score monitoring sensitivity. Suggestions for the future of DHI records include national congruity, reduction in DHI fees, increased use of electronic transfer of information, increased availability of records from all testing centers, decreased use of DHI supervisors, milk urea nitrogen testing, and tracking of metabolic diseases.


Assessment of the Aerosol Generation and Toxicity of Carbon Nanotubes.
Current interest in the pulmonary toxicity of carbon nanotubes (CNTs) has resulted in a need for an aerosol generation system that is capable of consistently producing a CNT aerosol at a desired concentration level. This two-part study was designed to: (1) assess the properties of a commercially-available aerosol generator when producing an aerosol from a purchased powder supply of double-walled carbon nanotubes (DWCNTs); and (2) assess the pulmonary sub-acute toxicity of DWCNTs in a murine model during a 5-day (4 h/day) whole-body exposure. The aerosol generator, consisting of a novel dustfeed mechanism and venturi ejector was determined to be capable of producing a DWCNT consistently over a 4 h exposure period at an average level of 10.8 mg/m³. The count median diameter was 121 nm with a geometric standard deviation of 2.04. The estimated deposited dose was 32 µg/mouse. The total number of cells in bronchoalveolar lavage (BAL) fluid was significantly (p < 0.01) increased in exposed mice compared to controls. Similarly, macrophages in BAL fluid were significantly elevated in exposed mice, but not neutrophils. All animals exposed to CNT and euthanized immediately after exposure had changes in the lung tissues showing acute inflammation and injury; however these pathological changes resolved two weeks after the exposure.


Almost complete protection from [Met5]-enkephalin-Arg6-Gly7-Leu8 (Met-enk-RGL) hydrolysis in membrane preparations by the combination of amastatin, captopril and phosphoramidon.
The contents of [Met5]-enkephalin-Arg6-Gly7-Leu8 (met-enk-RGL) and its seven hydrolysis products-Y, YG, YGG, YGGF, YGGFM, YGGFMR, and YGGFMRG-were estimated after incubating met-enk-RGL with a membrane fraction from either guinea pig ileum or striatum for various times at 37 degrees C. After 15 min of incubation, met-enk-RGL was completely hydrolyzed in both the ileal and the striatal membrane preparations. The major hydrolysis products were YGGFMR, YGGF and Y, which indicates that dipeptidyl carboxypeptidase and aminopeptidase activities were mainly involved in the hydrolysis. Additionally, even when the ileal and the striatal preparations were incubated for 60 min in the presence of both captopril, a dipeptidyl carboxypeptidase inhibitor, and amastatin, an aminopeptidase inhibitor, 24% and 44% of enkephalin octapeptide, respectively, were hydrolyzed. The YGG fragment was the major hydrolysis product in both preparations. When the ileal and the striatal membrane fractions were incubated with met-enk-RGL in the presence of three peptidase inhibitors-captopril, amastatin, and phosphoramidon (an inhibitor of endopeptidase-24.11)-approximately 95% of the enkephalin octapeptide, remained intact in both cases. This shows that met-enk-RGL was almost exclusively hydrolyzed by three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I and phosphoramidon-sensitive endopeptidase-24.11, in both ileal and striatal membranes. We also reported the potencies of several opioids relative to that of met-enk-RGL in guinea pig ileum pretreated with the three peptidase inhibitors.


Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study.
Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = -3.60, P < 0.001), and a history of hypertension (t = -2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = -3.83, P < 0.001; VLF: t = -3.07, P = 0.002; LF: t = -2.79, P = 0.006) and a history of diabetes (SDANN index: t = -3.58, P < 0.001; VLF: t = -2.54, P = 0.012; LF: t = -2.87, P = 0.004) were independent factors for the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project (t = -2.38, P = 0.018) was related to the SDANN index. Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.


An operation for partial closure of an epiphysial plate in children, and its experimental basis.
In two cases of partial closure of epiphysial causing angular deformity, one of a finger and one of the lower end of a femur, the deformities were corrected by growth after resection of a small peripheral bone bridge and its replacement with a free transplant of fat. This procedure has a firm basis on experimental work. Thus, when part of a growth plate in the rabbit is destroyed but the formation of a bone bridge uniting epiphysis and metaphysis is prevented, the destroyed part is replaced by regeneration of cartilage from the adjacent parts of the plate. Moreover, it has been proved in rabbits that when a bone bridge is induced and later resected and replaced with fat, recurrence of the bridge can be prevented and subsequent growth may correct the deformity.


Is older maternal age a risk factor for preterm birth and fetal growth restriction? A systematic review.
To determine if there was an association between advancing maternal age and adverse pregnancy outcomes (preterm delivery and small-for-gestational-age births), a systematic review was conducted based on a comprehensive search of the literature from 1985 to 2002. Ten studies met the following inclusion criteria: (1) assessed risk factors for preterm birth by subtype (i.e., idiopathic preterm labor, preterm premature rupture of membranes) and small-for-gestational-age (SGA) birth (fetal growth restriction); (2) used acceptable definitions of these outcomes; (3) were published between January 1985 and December 2002; (4) were restricted to studies that have considered preterm birth due to idiopathic preterm labor or premature rupture of membranes or both; (5) were restricted to singleton live births; (6) were conducted in a developed country; and (7) were published in English. The majority of the studies reviewed found that older maternal age was associated with preterm birth. There is insufficient evidence to determine if older maternal age is an independent and direct risk factor for preterm birth and SGA birth, or a risk marker that exerts its influence on gestational age or birth weight or both through its association with age-dependent confounders. Future research is needed to quantify the independent and unconfounded impact of delayed childbearing on neonatal outcomes, as well as to identify the pathways involved.


Inhibition of the PI3K/AKT pathway reduces tumor necrosis factor-alpha production in the cellular response to wear particles in vitro.
Joint replacement is the most effective treatment for end-stage osteoarticular disease. However, macrophage-mediated aseptic loosening of joint prosthesis severely hampers the clinical effects of joint replacement. Until now, the mechanism by which macrophages regulate the secretion of inflammatory cytokines after particle stimulation is not clear. It is well known that the PI3K/AKT pathway participates in multiple cellular processes, including cell growth, survival, and inflammation. However, whether the PI3K/AKT pathway participates in the proinflammatory response of macrophages after particle stimulation and secondary aseptic loosening is still unknown. In this study, ceramic and titanium particles of different sizes were prepared to stimulate macrophages. LY294002, a specific inhibitor of PI3K, was pretreated prior to particle stimulation. The expression of tumor necrosis factor-alpha (TNF-α) and all the subunits of PI3K and AKT were detected by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot. The result showed that LY294002 could suppress the RNA and protein expression of TNF-α in RAW264.7 cells after stimulation of different particles. The subunits of PI3K (p110β and p85β), followed by activation of phosphor-AKT (Ser473), participated in the regulation of activating macrophages by wear particles, ultimately resulting in the secretion of TNF-α.


Prosthetic valve sparing aortic root replacement: an improved technique.
We describe a modified surgical technique to treat patients with a previous history of isolated aortic valve replacement who now require aortic root replacement for an aneurysmal or dissected aorta. This technique consists of replacing the aortic root with a Dacron conduit, leaving intact the previously implanted prosthesis, and re-implanting the coronary arteries in the Dacron graft. Our technique differs from other techniques in that we do not leave behind any aortic tissue remnant and also in that we use a felt strip to obliterate any gap between the old sewing ring and the newly implanted graft. In our opinion, this promotes better hemostasis. We demonstrate that this technique is safe, feasible, and results in acceptable outcomes.


Proteomic identification of ERP29 as a key chemoresistant factor activated by the aggregating p53 mutant Arg282Trp.
Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and a subset of p53 mutants may form amyloid-like aggregates that contribute to the gain of oncogenic functions (GOFs) and chemoresistance. Here we identify the pathways that may mediate the aggregation-associated GOF by using combined proteomic analysis and genome-wide recruitment profiling. Mass spectrometry revealed activation of unfolded protein response (UPR) pathway and upregulation of endoplasmic reticulum protein 29 (ERp29) in R282WTP53-expressing cells that were exposed to cisplatin stress. Chromatin immunoprecipitation sequencing identified a significant 'CCCASS' binding motif of Arg282Trp, which is present in the promoter region of ERP29 gene. The mutant p53 upregulated ERP29 mRNA and protein expression levels, whereas targeting ERP29 by specific small interfering RNAs suppressed the chemoresistant effect of Arg282Trp. The anti-aggregation peptide ReACp53 significantly decreased ERP29 expression and suppressed the chemoresistant effect. These findings highlight a role of ERP29 in the acquired chemoresistance of cancer cells expressing the aggregating p53 mutant Arg282Trp. Our results also suggest that ERP29-mediated GOF can be targeted by the anti-aggregation peptide ReACp53.


Immunomodulatory and Antibacterial Properties of the Chumash Medicinal Plant Trichostema lanatum.
Background: The woody shrub Trichostema lanatum Benth. (Lamiaceae) is native to Southern California and was reportedly used by the Chumash people as a disinfectant and for the treatment of rheumatism. Based on its traditional uses, this study investigated the antibacterial and immunomodulatory properties of extracts from T. lanatum.Methods: A methanolic extract of the leaves and stems of T. lanatum was tested for immunomodulatory activity by measuring the proliferation of murine macrophage cell cultures and the production of the pro-inflammatory cytokine TNF-α by the cells after treatment with T. lanatum. Antibacterial activity of the extract against a panel of six Gram-positive bacteria and two Gram-negative bacteria was evaluated using a disc-diffusion assay. Results: The T. lanatum extract inhibited the growth of Gram-positive bacteria, but not Gram-negative bacteria. Treatment of activated macrophage cell cultures with T. lanatum extract resulted in decreased proliferation of the activated macrophages and a decrease in the production of TNF-α. Conclusions: These results provide the first pharmacological support for the traditional use of T. lanatum by the Chumash people of Southern California as a disinfectant and treatment for rheumatism.


Dupilumab in Dermatology: Potential for Uses Beyond Atopic Dermatitis
Dupilumab inhibits the interleukin-4 receptor subunit α and is FDA approved for treatment of moderate-to-severe atopic dermatitis. It is a relatively new drug, and whether it is efficacious for other diseases in dermatology is an area of increasing interest. We searched the literature and ClinicalTrials.gov database for uses of dupilumab beyond atopic dermatitis in dermatology and for ongoing studies on new uses for dupilumab. Off-label reports identified described use of dupilumab for several different dermatologic conditions, including allergic contact dermatitis, hand dermatitis, chronic spontaneous urticaria, prurigo nodularis, and alopecia areata. Overall, there is limited but promising data for dupilumab use beyond atopic dermatitis in dermatology. The relatively safe adverse effect profile of dupilumab may make it an option for certain recalcitrant diseases in dermatology, but further studies will be needed to assess its efficacy and determine its best possible use. J Drugs Dermatol. 2019;18(10):1053-1055.


A comparison study of two methods of peanut agglutinin staining with S100 immunostaining in 29 cases of histiocytosis X (Langerhans' cell histiocytosis)
Staining with peanut agglutinin (PNA) and with polyclonal antibody to S100 protein have both been recommended as aids in the diagnosis of histiocytosis X (Langerhans' cell histiocytosis). Although a large body of literature attests to the utility of S100 staining in this condition, the few published studies that involve PNA staining have employed varying methods of radically different results. We studied formaldehyde solution-fixed, paraffin-embedded tissue from 29 cases of histiocytosis X by using standard avidin-biotin immunostaining for S100 protein, as well as two published methods of PNA staining. All cases stained positively for S100 protein. By utilizing prior trypsinization and a three-step procedure, all cases also stained with PNA. With a two-step PNA-staining procedure, however, 9 cases failed to stain with PNA, and 3 cases showed a diffuse staining pattern that was not considered characteristic of Langerhans' and histiocytosis X cells. We concluded that both the S100 and the three-step PNA procedures are sensitive methods for the diagnosis of histiocytosis X.


Predictors of communication quality: the patient, provider, and nurse call center triad.
The purpose of this study was to examine characteristics of communication quality in a managed care context in which a nurse call center was used as the patient point of entry to the health system. The study sought to determine the level of communication quality among patients, health care providers, and nurses in the call center. Having measured the timeliness, accuracy, usefulness, and quantity of communication variables, a reasonable picture of communication quality emerged. The study explored patient differences in their perception of communication quality due to socioeconomic status, needs, experience, age, and various other factors. Likewise, providers who differ in training, specialty, and experience should have different perceptions and expectations of communication through nurse call center interaction.


Understanding the Microstructure Formation of Polymer Films by Spontaneous Solution Spreading Coating with a High-Throughput Engineering Platform.
An important step of the great achievement of organic solar cells in power conversion efficiency is the development of low-band gap polymer donors, PBDB-T derivatives, which present interesting aggregation effects dominating the device performance. The aggregation of polymers can be manipulated by a series of variables from a materials design and processing conditions perspective; however, optimization of film quality is a time- and energy-consuming work. Here, we introduce a robot-based high-throughput platform (HTP) that is offering automated film preparation and optical spectroscopy thin-film characterization in combination with an analysis algorithm. PM6 films are prepared by the so-called spontaneous film spreading (SFS) process, where a polymer solution is coated on a water surface. Automated acquisition of UV/Vis and photoluminescence (PL) spectra and automated extraction of morphological features is coupled to Gaussian Process Regression to exploit available experimental evidence for morphology optimization but also for hypothesis formulation and testing with respect to the underlying physical principles. The integrated spectral modeling workflow yields quantitative microstructure information by distinguishing amorphous from ordered phases and assesses the extension of amorphous versus the ordered domains. This research provides an easy to use methodology to analyze the exciton coherence length in conjugated semiconductors and will allow to optimize exciton splitting in thin film organic semiconductor layers as a function of processing.


Abnormal vascular tone in infants and children with lung hypoplasia: Findings from cardiac catheterization and the response to chronic therapy.
We describe four cases of chronic pulmonary hypertension in infants and children with chronic lung disease and pulmonary hypoplasia due to severe congenital diaphragmatic hernia (CDH) or congenital cystic adenomatoid malformation (CCAM). We report data from cardiac catheterization under various conditions: baseline respiratory support and room air, hyperoxic and inhaled nitric oxide challenge. We further report cardiac catheterization measures after chronic pulmonary vasodilator therapy with sildenafil alone or a combination of sildenafil and inhaled nitric oxide (three patients). Case series. Tertiary academic center. Infants and children ages 0-11 yrs with CDH (n = 3) or CCAM (n = 1) with evidence of chronic pulmonary hypertension by echocardiogram and cor pulmonale (n = 3). Catheterization and pulmonary vasodilator therapy. Pulmonary vascular resistance, pulmonary arterial pressure, and changes in these measures were assessed. A 20% change in pulmonary vascular resistance was considered a clinically significant response. Ten catheterizations were performed in four patients. All patients had elevated pulmonary vascular resistance and pulmonary arterial pressures at initial catheterizations and significant vasodilation during inhaled nitric oxide. Chronic lung disease following pulmonary hypoplasia from CDH and CCAM is associated with abnormal pulmonary vascular tone in infants and children with evidence of chronic pulmonary hypertension. Chronic pulmonary vasodilator therapy may improve pulmonary vascular function and enhance lung growth in infants and children who are treated during their period of potential for rapid lung growth.


Novel genetic variants in microRNA genes and familial breast cancer.
MicroRNA (miRNA) plays an important role in tumorigenesis, but whether miRNA is a cancer predisposition factor or not is still unknown. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk. To test this hypothesis, we screened genetic variants in 17 selected miRNA genes, which are predicted to regulate key breast cancer genes, in 42 patients with familial breast cancer. Seven novel genetic variants were observed in 7 primary or precursor miRNA genes. Among them, 1 rare variant in the precursor of miR-30c-1 and 1 rare variant in the primary precursor of miR-17 were only observed in noncarriers of BRCA1/2 mutations. In functional assays, these 2 variants resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR-30c-1 and miR-17. In the target in vitro assay, we observed that miR-17 could bind to the 3'UTR of BRCA1 mRNAs, which is predicted to be a target for miR-17. Our findings suggest that functional genetic variants in miRNA genes can potentially alter the regulation of key breast cancer genes. Whether they confer genetic susceptibility to breast cancer remains to be determined.


metabCombiner: Paired Untargeted LC-HRMS Metabolomics Feature Matching and Concatenation of Disparately Acquired Data Sets.
LC-HRMS experiments detect thousands of compounds, with only a small fraction of them identified in most studies. Traditional data processing pipelines contain an alignment step to assemble the measurements of overlapping features across samples into a unified table. However, data sets acquired under nonidentical conditions are not amenable to this process, mostly due to significant alterations in chromatographic retention times. Alignment of features between disparately acquired LC-MS metabolomics data could aid collaborative compound identification efforts and enable meta-analyses of expanded data sets. Here, we describe metabCombiner, a new computational pipeline for matching known and unknown features in a pair of untargeted LC-MS data sets and concatenating their abundances into a combined table of intersecting feature measurements. metabCombiner groups features by mass-to-charge (m/z) values to generate a search space of possible feature pair alignments, fits a spline through a set of selected retention time ordered pairs, and ranks alignments by m/z, mapped retention time, and relative abundance similarity. We evaluated this workflow on a pair of plasma metabolomics data sets acquired with different gradient elution methods, achieving a mean absolute retention time prediction error of roughly 0.06 min and a weighted per-compound matching accuracy of approximately 90%. We further demonstrate the utility of this method by comprehensively mapping features in urine and muscle metabolomics data sets acquired from different laboratories. metabCombiner has the potential to bridge the gap between otherwise incompatible metabolomics data sets and is available as an R package at https://github.com/hhabra/metabCombiner and Bioconductor.


A proposal for the study of cementless short-stem hip prostheses.
With the recent evolution of hip arthroplasty, new models of short stems have emerged. So far, we do not have a clear strategy to analyze their outcomes, since there is confusion around the definition of short stem and there is no consensus for their classification. The purpose of this study was to review the current state of the art of cementless short stems considering the main design characteristics; it provides a definition of short stem and proposes a classification, grouping them into families by means of a nomenclature that describes them accurately. We conducted a search in the PubMed and Scopus databases and consulted various implant manufacturers, foundations devoted to research on joint arthroplasty, organizations of independent experts on medical device analysis, and national arthroplasty registries. The stems studied were classified according to a new nomenclature system. We identified 44 different models that share 84 design variables and may be grouped into three types and 16 generic families. The stems were manufactured by 20 different companies. Short stems are those occupying the neck, metaphysis and the proximal aspect of the limit between the metaphysis and diaphysis, regardless of the geometric type of endosteum present. A wide variety of models was identified, with multiple design variables. In order to classify them, it was necessary to design a whole new nomenclature capable of describing them in an unequivocal, unique and distinctive way.


The Relation between Neonatal Intensive Care Units and Postpartum Post-Traumatic Stress Disorder after Cesarean Section.
The experience of a neonate hospitalized in the NICU is an understandably traumatic experience for parents, especially for the mothers of neonates. This mental distress resulting from preterm birth and/or NICU hospitalization can be understood as post-traumatic symptomatology, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 version). The aim of this study is to investigate the impact of the admission of a neonate to the NICU (forany reason) on the development of postpartum PTSD in a sample of women after cesarean section. A total of 469 women who gave birth with cesarean section from July 2019 to June 2020 participated in this study out of the original sample of 490 women who consented to participate. Data were obtained from the researcher's socio-demographic questionnaire and the post-traumatic stress checklist (PCL-5) from the Diagnostic and Statistical Manual of Mental Disorders DCM-5 version. In total,11.7% of the sample experienced postpartum PTSD. There is a strong relationship between the inclusion of a neonate to the NICU due to perinatal stress, breathing difficulties, infections, and IUGR with postpartum PTSD (37.7%) in relation to the perinatal stress Criterion A (fear for the life of the neonate), the first criterion of postpartum PTSD. Additional measures must be taken for mothers of children who have been admitted to the neonatal intensive care unit with psychological support interventions and a reassessment of their mental state.


Electron cooling in decaying low-pressure plasmas.
A simple analytical fluid dynamic model is developed for evaporative electron cooling in a low-pressure decaying plasma and compared to a two-dimensional simulation and experimental data for the particular case of argon. Measured electron temperature and density developments are fully reproduced by the ab initio model and the simulation. Further, it is shown that in the late afterglow thermalization of electrons occurs by coupling to the ion fluid via Coulomb collisions at sufficiently high electron densities and not by coupling to the neutral background.


Mechanism of entomotoxicity of the plant lectin from Hippeastrum hybrid (Amaryllis) in Spodoptera littoralis larvae.
Plant lectins have received a lot of attention because of their insecticidal properties. When orally administered in artificial diet or in transgenic plants, lectins provoke a wide range of detrimental effects, including alteration of the digestive enzyme machinery, fecundity drop, reduced feeding, changes in oviposition behavior, growth and development inhibition and mortality. Although many studies reported the entomotoxicity of lectins, only a few of them investigated the mode of action by which lectins exert toxicity. In the present paper we have studied for the first time the insecticidal potential of the plant lectin from Hippeastrum hybrid (Amaryllis) (HHA) bulbs against the larvae of the cotton leafworm (Spodoptera littoralis). Bioassays on neonate larvae showed that this mannose-specific lectin affected larval growth, causing a development retardation and larval weight decrease. Using primary cell cultures from S. littoralis midguts and confocal microscopy we have elucidated FITC-HHA binding and internalization mechanisms. We found that HHA did not exert a toxic effect on S. littoralis midgut cells, but HHA interaction with the brush border of midgut cells interfered with normal nutrient absorption in the S. littoralis midgut, thereby affecting normal larval growth in vivo. This study thus confirms the potential of mannose-specific lectins as pest control agents and sheds light on the mechanism underlying lectin entomotoxicity.


Multiple origins of two Ochrosia (Apocynaceae) species endemic to the Bonin (Ogasawara) Islands.
The genus, Ochrosia, is widely distributed from the West Indian Ocean throughout tropical Asia to the Middle Southern Pacific region. Ochrosia comprises many island-endemic species, suggesting that long-distance dispersal and isolation after migration are key factors for clarifying the diversification process. However, the phylogeny and biogeography of endemic Ochrosia species have not been evaluated well due to the difficulty of adequate sampling from the entire distribution range of the genus. In this study, we focused on two Ochrosia species endemic to the Bonin (Ogasawara) Islands in the northwest Pacific. The Bonin Islands are of volcanic origins and consist of two islands groups, the Ogasawara and Volcano Islands groups, approximately 300 km apart. Ochrosia nakaiana is endemic to the Ogasawara Islands group, whereas O. hexandra is endemic to the Volcano Islands group. To elucidate the phylogenetic positions of these two endemic Ochrosia species, we conducted molecular phylogenetic studies with dating and biogeographic analyses including other Ochrosia species. The phylogenetic trees showed that the two endemic species had distinct origins; O. nakaiana was closely related to O. oppositifolia and O. iwasakiana, whereas O. hexandra was related to O. mariannensis. Based on the chloroplast DNA phylogeny, the genus, Ochrosia, divided into two major lineages 36.6 million years ago. Further, the two endemic species of the Bonin Islands were independently derived approximately 1-2 million years ago. Ochrosia nakaiana originated from the Southeast Asia, New Caledonia, or other Pacific Islands, while O. hexandra derived from O. mariannensis in Micronesia. We demonstrated different origins of the two endemic Ochrosia species on the Bonin Islands. This study provided an excellent example of the complex origins and speciation of flora in the oceanic islands.


Synthesis and antiallergic activity of N-[4-(4-diphenylmethyl-1-piperazinyl)butyl]-1,4-dihydro-4-oxopyridine-3 - carboxamides.
A new series of oxopyridinecarboxamide derivatives 3a--g and 5a were synthesized and evaluated for their antiallergic activity. 1,4-Dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxamides 3a and 5a exhibited potent antiallergic activity (inhibitory rates of 80.7 and 88.3%, respectively, at 20 mg/kg, p.o.) in the rat passive cutaneous anaphylaxis (PCA) test and also exhibited much more potent in vitro inhibitory activity than caffeic acid against the enzyme 5-lipoxygenase (5-LO). Their in vitro antihistamine activity, however, was weaker than that of ketotifen. Compounds 3a and 5a are viewed as promising candidates for antiallergic agents.


Biotrauma and Ventilator-Induced Lung Injury: Clinical Implications.
The pathophysiological mechanisms by which mechanical ventilation can contribute to lung injury, termed "ventilator-induced lung injury" (VILI), is increasingly well understood. "Biotrauma" describes the release of mediators by injurious ventilatory strategies, which can lead to lung and distal organ injury. Insights from preclinical models demonstrating that traditional high tidal volumes drove the inflammatory response helped lead to clinical trials demonstrating lower mortality in patients who underwent ventilation with a lower-tidal-volume strategy. Other approaches that minimize VILI, such as higher positive end-expiratory pressure, prone positioning, and neuromuscular blockade have each been demonstrated to decrease indices of activation of the inflammatory response. This review examines the evolution of our understanding of the mechanisms underlying VILI, particularly regarding biotrauma. We will assess evidence that ventilatory and other "adjunctive" strategies that decrease biotrauma offer great potential to minimize the adverse consequences of VILI and to improve the outcomes of patients with respiratory failure.


Relevance of functional neuroimaging studies for understanding migraine mechanisms.
Advances in imaging have provided further insights into the complex migraine pathophysiology. Functional neuroimaging by means of PET and functional MRI studies have addressed crucial migraine-related issues, improving our understanding of the circuitry that may be involved in the generation, maintenance and recurrence of pain symptoms in migraine. In the last few years, a growing body of imaging literature has also explored pathophysiology of associated migraine symptoms. Of great interest will be the use of advanced imaging techniques to elucidate neural correlates of migraine prodromal, in order to identify clinical subgroups of migrainous subjects. However, the interpretation of the biological significance of these various functional changes could remain incomplete without a combination of expanding genomic information about neurochemical pathways and genetic polymorphisms linked to specific migraine subtypes. Hopefully, a more detailed picture of the migraine neurobiology will emerge from future neuroimaging studies, which may eventually lead to better and more rational treatments.


In vivo metabolism study of (R)-bambuterol in humans using ultra high performance liquid chromatography with tandem mass spectrometry.
(R)-Bambuterol, a selective β2-adrenoceptor agonist, has been approved as a new drug for the treatment of asthma and chronic obstructive pulmonary disease by the China Food and Drug Administration and is currently under phase I clinical trials. In this study, a combined method based on ultra high performance liquid chromatography with triple quadrupole mass spectrometry and ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was employed for the identification of the major metabolites of (R)-bambuterol in human plasma and urine after an oral dose of 10 mg. The metabolites were separated by gradient elution program and different sample preparation methods were compared. Totally, 12 metabolites of (R)-bambuterol were identified, including four metabolites in plasma and all 12 metabolites in urine. Among these, four metabolites are reported for the first time. The possible metabolic pathways of (R)-bambuterol were subsequently proposed. The results indicated that (R)-bambuterol was metabolized via hydrolysis, demethylation, oxygenation, glucuronidation, and sulfation pathways in vivo. This study revealed that this combined method was accurate and sensitive to identify the possible metabolites and to better understand the metabolism of (R)-bambuterol in vivo.


Preferential translation of vesicular stomatitis virus mRNAs is conferred by transcription from the viral genome.
Host protein synthesis is inhibited in cells infected with vesicular stomatitis virus (VSV). It has been proposed that viral mRNAs are subjected to the same inhibition but are predominantly translated because of their abundance. To compare translation efficiencies of viral and host mRNAs during infection, we used an enhanced green fluorescent protein (EGFP) reporter expressed from a recombinant virus or from the host nucleus in stably transfected cells. Translation efficiency of host-derived EGFP mRNA was reduced more than threefold at eight hours postinfection, while viral-derived mRNA was translated around sevenfold more efficiently than host-derived EGFP mRNA in VSV-infected cells. To test whether mRNAs transcribed in the cytoplasm are resistant to shutoff of translation during VSV infection, HeLa cells were infected with a recombinant simian virus 5 (rSV5) that expressed GFP. Cells were then superinfected with VSV or mock superinfected. GFP mRNA transcribed by rSV5 was not resistant to translation inhibition during superinfection with VSV, indicating that transcription in the cytoplasm is not sufficient for preventing translation inhibition. To determine if cis-acting sequences in untranslated regions (UTRs) were involved in preferential translation of VSV mRNAs, we constructed EGFP reporters with VSV or control UTRs and measured the translation efficiency in mock-infected and VSV-infected cells. The presence of VSV UTRs did not affect mRNA translation efficiency in mock- or VSV-infected cells, indicating that VSV mRNAs do not contain cis-acting sequences that influence translation. However, we found that when EGFP mRNAs transcribed by VSV or by the host were translated in vitro, VSV-derived EGFP mRNA was translated 22 times more efficiently than host-derived EGFP mRNA. This indicated that VSV mRNAs do contain cis-acting structural elements (that are not sequence based), which enhance translation efficiency of viral mRNAs.


Statistical methods for microarray assays.
The paper shortly reviews statistical methods used in the area of DNA microarray studies. All stages of the experiment are taken into account: planning, data collection, data preprocessing, analysis and validation. Among the methods of data analysis, the algorithms for estimating differential expression, multivariate approaches, clustering methods, as well as classification and discrimination are reviewed. The need is stressed for routine statistical data processing protocols and for the search of links of microarray data analysis with quantitative genetic models.


The ambiguous pulmonary venoatrial junction: a new perspective.
The pulmonary venoatrial junction (PVAJ) has recently received attention due to the widespread use of catheter ablation for atrial fibrillation. However, the literature lacks a consensus in the definition of the PVAJ. We aim to review the inconsistent definitions for the PVAJ and related implications in imaging and catheter ablation for atrial fibrillation. The PVAJ as described by embryology, gross anatomy, histology and imaging is ambiguous, leading to disparities in its definition. Because of differing definitions of the PVAJ, there is a broad range in the prevalence of anatomic variations, including (1) percentage of common pulmonary veins (10-79% on the left), (2) supernumerary pulmonary veins (10-42%) and (3) ostial diameter and shape. We postulate several reasons for this broad range in the described prevalence of anatomic variation of the PV as follows: (1) different definitions of the PVAJ, (2) different vantage points, (3) different imaging modalities, and (4) different prevalence of anatomic variants among different study populations. The ambiguous PVAJ with its gradual transition from the left atrium to the pulmonary veins defies precise definition even though it plays an important role in the management of atrial fibrillation. Physicians should be aware of variability in the language used to describe the PVAJ and resultant discrepancy in reported anatomical information.


[The role of Wacława Moszyński in the development of the Polish School of Machine and Mechanism Theory].
The end of the 19th and the first half of the 20th centuries saw the emergence and intensive development of many disciplines in the technical sciences, and the laying of a groundwork for those disciplines in their current form. In Poland, a country deprived of independent statehood until 1918, this was additionally a period when native research centres and scientific schools came into being, and when Polish-language specialist literatures emerged as well. Many of the eminent personages whose activities contributed to those trends have already been described in biographical notes and articles. There are still, however, not enough studies dealing with the substance of their scientific and professional achievements. One of the personages in question was Wacława Moszyński, professor of the Warsaw Technical University, a pioneer of machine construction and mechanism theory, author of the first academic textbook in the field to be published in Poland. The current article discusses Moszyński's contribution to the development of mechanism and machine theory. The first part of the article gives an outline of the history of the discipline until 1945, presents the context of the after-war activities of the author, and evaluates his influence on the development of machine and mechanism theory in Poland; it also carries a short biography of Moszyński. The rest of the article is devoted to Moszyński's scientific achievements, and describes his approach to matters of structure, kinematics and dynamics, with special focus on those of his formulations and solution to problems that appear particularly innovative and original. The article also points out those proposals by Moszyński which made him a precursor of other disciplines, such as vibroacoustics, biomechanics and ergonomics. The paper also presents the role of Moszyński's work as a foundation for the development of the Warsaw research-and-teching centre in the field. The achievements and methods of the Warsaw school combined with the those of other centres in Poland, which based on the earlier Lwów tradition, thus leading to very significant research and educational accomplishments.


Dynamics of coupled mode solitons in bursting neural networks.
Using an electrically coupled chain of Hindmarsh-Rose neural models, we analytically derived the nonlinearly coupled complex Ginzburg-Landau equations. This is realized by superimposing the lower and upper cutoff modes of wave propagation and by employing the multiple scale expansions in the semidiscrete approximation. We explore the modified Hirota method to analytically obtain the bright-bright pulse soliton solutions of our nonlinearly coupled equations. With these bright solitons as initial conditions of our numerical scheme, and knowing that electrical signals are the basis of information transfer in the nervous system, it is found that prior to collisions at the boundaries of the network, neural information is purely conveyed by bisolitons at lower cutoff mode. After collision, the bisolitons are completely annihilated and neural information is now relayed by the upper cutoff mode via the propagation of plane waves. It is also shown that the linear gain of the system is inextricably linked to the complex physiological mechanisms of ion mobility, since the speeds and spatial profiles of the coupled nerve impulses vary with the gain. A linear stability analysis performed on the coupled system mainly confirms the instability of plane waves in the neural network, with a glaring example of the transition of weak plane waves into a dark soliton and then static kinks. Numerical simulations have confirmed the annihilation phenomenon subsequent to collision in neural systems. They equally showed that the symmetry breaking of the pulse solution of the system leaves in the network static internal modes, sometime referred to as Goldstone modes.


T-Cell Prolymphocytic Leukemia: An Overview of Current and Future Approaches.
T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell hematologic neoplasm with a very poor prognosis and limited treatment options to date. Single-agent alemtuzumab remains the first line of therapy for the treatment-naive and relapsed/refractory patients. Prospective clinical trials are difficult to conduct given that these patients have a short life expectancy after the initial diagnosis. As a result, researchers are implementing the use of targeted therapies in vitro and ex vivo followed by in vivo trials on a small subset of patients which are reviewed here. Newer approaches in the treatment of T-PLL are developing based on recognizing the cytogenetic phenotype of each patient and targeting the identified defective genes that are usually involved in the cell cycle regulation such as protooncogenes, tumor suppressors, and deoxyribonucleic acid (DNA) repair genes. These could potentially redirect the management in the near future and improve the overall survival (OS) and the progression-free survival (PFS) for these patients.


[Detection of Weissella spp. in milk samples of two dairy cows with clinical mastitis. A case report].
This case report describes the isolation and differentiation of Weissella (W.) spp. from the milk of two cows (A and B) with clinical mastitis (milk changes, asymmetry of the udder and increased somatic cell counts). Quarter milk samples obtained from two dairy cows of different farms had been submitted to the diagnostic laboratory of the Clinic for Ruminants in Vienna for bacteriological examination. Alpha-hemolytic catalase-negative gram-positive cocci in pure culture on Columbia blood agar were isolated and could not be assigned to a Lancefield group. The isolates were biochemically characterized as Leuconostoc spp. (API® 20 Strep, bioMérieux). A control examination of cow B within 7 weeks confirmed these findings. 16S rDNA sequencing indicated W. paramesenteroides (cow A) and W. cibaria (cow B). The analysis by pulsed-field gel electrophoresis (PFGE) showed identical SmaI/ApaI profiles for both W. cibaria isolates (cow B), which differed from the W. paramesenteroides fingerprint of cow A (67% similarity). This study indicates a possible relationship between the detection of Weissella spp. and the occurrence of bovine intramammary infections.


Transferrin receptor expression in reactive and neoplastic lesions of lymphnodes.
Transferrin, the major iron binding protein in human plasma transports iron to various tissues. The first step in cellular iron uptake is binding of transferrin complex to the cell surface membrane by specific molecule known as transferrin receptors. Transferrin receptors are found in limited sites in normal tissues, in contrast, the receptors are widely distributed in majority of carcinomas and sarcomas. Presence of increased transferrin receptors implies a stage of moderate or less differentiation corresponding to elevated proliferative activity and therefore, has a prognostic value. Demonstration of transferrin receptors and its distribution pattern within a tumour as well as its quantitative determination can provide data helpful for, both, an additional understanding of tumour biology and as an approach for planning therapy. In present study, we analysed 60 cases, 30 each of reactive lymphadenitis and lymphomas for transferrin receptors using immunohistochemical technique (DAKO, Code-K0673). Grade II and Grade III intensity was recorded in the germinal centers and the histiocytes in sinus histocytosis indicating the proliferating cells and activated histocytes. Most of the low grade non-Hodgkin lymphomas (83.66%) showed weak (Grade I) positivity for transferrin receptors. Intermediate grade lymphomas showed moderate (Grade II) to high intensity (Grade III) for transferrin receptors (57.14% and 42.85%) respectively. Seventy five percent of high grade lymphomas showed strong (Grade III) positivity. All the 9 cases of Hodgkin lymphoma (100%) showed grade III positivity. Proportion of the cells within a tumour expressing transferrin receptors in high density are therefore likely to represent the growth fraction of the tumour.


Reasons given by college students for drinking: a discriminant analysis investigation.
Based on self-reported levels of alcohol consumption, 473 college students (295 female and 178 male) were placed into at-risk or not-at-risk groups. Using reasons given for drinking as the independent variables, discriminant analysis procedures were conducted separately on the males and females to determine if a function could be found which would discriminate between the groups. For the female group, 11 of 22 reasons defined a discriminant function which accounted for 36% of the variance between the groups (p < .001). This function was also able to correctly classify 71% of the holdout sample. For the males, five of the 22 reasons defined a discriminant function which accounted for 36% of the variance between the groups (p < .001). This function was able to correctly classify 69% of the holdout sample.


Copper(I) Complexes of a Flexible Bis-phospholane Ligand: Route to Paddle-Wheel- and Box-Type Macrocycles.
Two bis-phospholane copper(I) metallamacrocycles were selectively synthesized starting from the same two building blocks, namely, ligand 1 and [Cu(NCCH3)4]BF4. Reaction conditions (ligand:metal (L:M) ratio and dilution) can be tuned to obtain either a paddle-wheel- (2, L:M = 3:2) or box-type complex (3, L:M = 8:4). Their structures were unequivocally determined by X-ray crystallography. The solution 31P{1H} NMR spectrum of complex 2 consists of a broad signal, as is common for such complexes, whereas complex 3 shows splitting of the 31P{1H} NMR signal into a pseudoquartet due to 63,65Cu-31P coupling, a rare occurrence exhibited only by highly symmetrical copper(I) phosphine complexes.


Detecting RNA-protein interactions by photocross-linking using RNA molecules containing uridine analogs.
Various cross-linking techniques form covalent attachments between proteins and RNAs. Straight ultraviolet (UV) cross-linking using short-wavelength UV light is inherently very inefficient. Therefore, it is often desirable to increase the efficiency of cross-linking. The uridine analogs 4-thiouridine and halogenated uridine (5-bromouridine or 5-iodouridine) are much more photoreactive than uridine. Accordingly, RNAs substituted with these bases are quite effective for cross-linking applications. This protocol describes the detection of RNA-protein interactions by photocross-linking using RNA molecules containing 4-thiouridine, but identical procedures apply to using 5-bromouridine or 5-iodouridine. Fully substituted RNAs are useful in determining whether any proteins interact with the RNA of interest. However, it may be preferable to use site-specifically substituted RNA if one has foreknowledge of critical regions in the RNA of interest. For any cross-linking application using substituted RNA, it is essential to remember that the uridine analogs are activated at a wavelength >304 nm (312 nm) than is used for short-wavelength (254 nm) cross-linking.


Thermodynamic analysis of porphyrin binding to Momordica charantia (bitter gourd) lectin.
Owing to the use of porphyrins in photodynamic therapy for the treatment of malignant tumors, and the preferential interaction of lectins with tumor cells, studies on lectin-porphyrin interaction are of significant interest. In this study, the interaction of several free-base and metalloporphyrins with Momordica charantia (bitter gourd) lectin (MCL) was investigated by absorption spectroscopy. Difference absorption spectra revealed that significant changes occur in the Soret band region of the porphyrins on binding to MCL. These changes were monitored to obtain association constants (Ka) and stoichiometry of binding. The tetrameric MCL binds four porphyrin molecules, and the stoichiometry was unaffected by the presence of the specific sugar, lactose. In addition, the agglutination activity of MCL was unaffected by the presence of the porphyrins used in this study, clearly indicating that porphyrin and carbohydrate ligands bind at different sites. Both cationic and anionic porphyrins bind to the lectin with comparable affinity (Ka =10(3)-10(5) m(-1)). The thermodynamic parameters associated with the interaction of several porphyrins, obtained from the temperature dependence of the Ka values, were found to be in the range: DeltaH degrees = -98.1 to -54.4 kJ.mol(-1) and DeltaS degrees =-243.9 to -90.8 J.mol(-1).K(-1). These results indicate that porphyrin binding to MCL is governed by enthalpic forces and that the contribution from binding entropy is negative. Enthalpy-entropy compensation was observed in the interaction of different porphyrins with MCL, underscoring the role of water structure in the overall binding process. Analysis of CD spectra of MCL indicates that this protein contains about 13%alpha-helix, 36%beta-sheet, 21%beta-turn, and the rest unordered structures. Binding of porphyrins does not significantly alter the secondary and tertiary structures of MCL.


Two regions of cadherin cytoplasmic domains are involved in suppressing motility of a mammary carcinoma cell line.
E-cadherin has been termed an "invasion suppressor," yet the mechanism of this suppression is not known. In contrast, several reports indicate N-cadherin does not suppress but, rather, promotes cell motility and invasion. Here, by characterizing a series of chimeric cadherins we defined a previously uncharacterized region consisting of the transmembrane domain and an adjacent portion of the cytoplasmic segment that is responsible for the difference in ability of E- and N-cadherin to suppress movement of mammary carcinoma cells, as quantified from time-lapse video recordings. A mutation in this region enabled N-cadherin to suppress motility, indicating that both E- and N-cadherin can suppress, but the activity of N-cadherin is latent, presumably repressed by binding of a specific inhibitor. To define regions common to E- and N-cadherin that are required for suppression, we analyzed a series of deletion mutants. We found that suppression of movement requires E-cadherin amino acids 699-710. Strikingly, beta-catenin binding is not sufficient for and p120ctn is not involved in suppression of these mammary carcinoma cells. Furthermore, the comparable region of N-cadherin can substitute for this required region in E-cadherin and is required for suppression by the mutant form of N-cadherin that is capable of suppressing. Variations in expression of factors that bind to the two regions we have identified may explain previously observed differences in response of tumor cells to cadherins.


Causes and treatment outcomes of third, fourth and sixth cranial nerve palsy.
To evaluate the causes and the treatment outcomes of third, fourth and sixth cranial nerve palsy Medical records of 157 cases with extra-ocular muscle palsy from third, fourth or sixth cranial nerve palsy between January 1995 and December 2009 were reviewed. Demographic data, age, causes of extra-ocular muscle palsy and treatment outcomes were record and analyzed. The patients who were followed-up less than 6 months, myasthenia gravis and extra-ocular muscles fibrosis were excluded from the present study. One hundred and fifty-seven cases from 600 cases were included in the present study. The most common cranial nerve palsy was the sixth cranial nerve with 63 cases (40.1%). Of 157 cases, the causes were trauma 41 cases (26.1%), microvascular occlusion cause 34 cases (21.7%) and congenital cause 21 cases (13.4%). Cranial nerve palsy patients from microvascular occlusion cause spontaneously improved 25 of 34 cases (73.50%) in 6 months. All patients (21 cases)from congenital cranial nerve palsy had extra-ocular muscle surgery and 17 patients (80.9%) were successful. Sixth cranial nerve palsy was the most common cranial nerve palsy. Most patients with cranial nerve palsy from vascular cause spontaneously improved in 6 months. Congenital cranial nerve palsy patients need extra-ocular muscle surgery and most cases were successful


The population biology of parasite-induced changes in host behavior.
The ability of parasites to change the behavior of infected hosts has been documented and reviewed by a number of different authors (Holmes and Bethel, 1972; Moore, 1984a). This review attempts to quantify the population dynamic consequences of this behavior by developing simple mathematical models for the most frequently recorded of such parasite life cycles. Although changes in the behavior of infected hosts do occur for pathogens with direct life cycles, they are most commonly recorded in the intermediate hosts of parasites with complex life cycles. All the changes in host behavior serve to increase rates of transmission of the parasites between hosts. In the simplest case the changes in behavior increase rates of contact between infected and susceptible conspecific hosts, whereas in the more complex cases fairly sophisticated manipulations of the host's behavioral repertory are achieved. Three topics are dealt with in some detail: (1) the behavior of the insect vectors of such diseases as malaria and trypanosomiasis; (2) the intermediate hosts of helminths whose behavior is affected in such a way as to make them more susceptible to predation by the definitive host in the life cycle; and (3) the behavior and fecundity of molluscs infected with asexually reproducing parasitic flatworms. In each case an expression is derived for R0, the basic reproductive rate of the parasite when first introduced into the population. This is used to determine the threshold numbers of definitive and intermediate hosts needed to maintain a population of the pathogen. In all cases, parasite-induced changes in host behavior tend to increase R0 and reduce the threshold number of hosts required to sustain the infection. The population dynamics of the interaction between parasites and their hosts are then explored using phase plane analyses. This suggests that both the parasite and intermediate host populations may show oscillatory patterns of abundance. When the density of the latter is low, parasite-induced changes in host behavior increase this tendency to oscillate. When intermediate host population densities are high, parasite population density is determined principally by interactions between the parasites and their definitive hosts, and changes in the behavior of intermediate hosts are less important in determining parasite density. Analysis of these models also suggests that both asexual reproduction of the parasite within a host and parasite-induced reduction in host fecundity may be stabilizing mechanisms when they occur in the intermediate hosts of parasite species with indirect life cycles.(ABSTRACT TRUNCATED AT 400 WORDS)


Superlubric-pinned transition of a two-dimensional solid dusty plasma under a periodic triangular substrate.
The superlubric-pinned transition in the depinning dynamics of a two-dimensional (2D) solid dusty plasma modulated by 2D triangular periodic substrates is investigated using Langevin dynamical simulations. When the lattice structure of the 2D solid dusty plasma perfectly matches the triangular substrate, two distinctive pinned and moving ordered states are observed as the external uniform driving force gradually increases from zero. When there is a mismatch between the lattice structure and the triangular substrate, however, on shallow substrates, it is discovered that all of the particles can slide freely on the substrate even when the applied driving force is tiny. This is a typical example of superlubricity, which is caused by the competition between the substrate-particle and particle-particle interactions. If the substrate depth increases further, as the driving force increases from zero, there are three dynamical states consisting of the pinned state, the disordered plastic flow state, and the moving ordered state. In an underdense system, where there are fewer particles than potential well minima, it is found that the occurrence of the three different dynamical states is controlled by the depth of the substrate, which is quantitatively characterized using the average mobility.


Enantioselective Addition of a 2-Alkoxycarbonyl-1,3-dithiane to Imines Catalyzed by a Bis(guanidino)iminophosphorane Organosuperbase.
A chiral bis(guanidino)iminophosphorane catalyzes enantioselective addition reactions of a 1,3-dithiane derivative as a pronucleophile. The chiral uncharged organosuperbase facilitates the addition of benzyloxycarbonyl-1,3-dithiane to aromatic N-Boc-protected imines to provide optically active α-amino-1,3-dithiane derivatives, which are valuable versatile building blocks in organic synthesis.


The future of chiropractic: a psychosocial view.
As the total health-care delivery system in the United States has come under increasing public scrutiny, the role of chiropractic has become of interest. An overview of chiropractic, with an analysis of its social functions and a projection of its future indicates that chiropractic is more congruent with the values of its lower-middle-class clientele than is orthodox medicine. Chiropractors function adquately to legitimize their patients' entrance into the "sick role" and to provide an alternative channel to therapy. The marginal role of the chiropractor in the health-care system, as compared to that of the physician, is stable and functional for the chiropractors thenselves, as well as for their patients. Chiropractic likewise serves the physician, both as a boundary-defining mechanism and as a means of disengagement from troublesome patients. For these reasons, we believe that the role of chiropractic within the health-care system will remain stable in the future.


Identification of Potential Abnormal Methylation-Modified Genes in Coronary Artery Ectasia.
Coronary artery ectasia (CAE) is an easily recognized abnormality of coronary artery anatomy and morphology. However, its pathogenesis remains unclear. This study aimed to identify abnormal methylation-modified genes in patients with CAE, which could provide a research basis for CAE. Peripheral venous blood samples from patients with CAE were collected for RNA sequencing to identify differentially expressed genes (DEGs), followed by functional enrichment. Then, the DNA methylation profile of CAE was downloaded from GSE87016 (HumanMethylation450 BeadChip data, involving 11 cases and 12 normal controls) to identify differentially methylated genes (DMGs). Finally, after taking interaction genes between DEGs and DMGs, abnormal methylation-modified genes were identified, followed by protein-protein interaction analysis and expression validation using reverse transcriptase polymerase chain reaction. A total of 152 DEGs and 4318 DMGs were obtained from RNA sequencing and the GSE87016 dataset, respectively. After taking interaction genes, 9 down-regulated DEGs due to hypermethylation and 11 up-regulated DEGs due to hypomethylation were identified in CAE. A total of 10 core abnormal methylation-modified genes were identified, including six down-regulated DEGs due to hypermethylation (netrin G1, ADAM metallopeptidase domain 12, immunoglobulin superfamily member 10, sarcoglycan dela, Dickkopf WNT signaling pathway inhibitor 3, and GATA binding protein 6), and four up-regulated DEGs due to hypomethylation (adrenomedullin, ubiquitin specific peptidase 18, lymphocyte antigen 6 family member E, and MX dynamin-like GTPase 1). Some signaling pathways were identified in patients with CAE, including cell adhesion molecule, O-glycan biosynthesis, and the renin-angiotensin system. Abnormal methylation-modified DEGs involved in signaling pathways may be involved in CAE development.


Pharmacokinetics of ceftriaxone in Green sea turtles (Chelonia mydas) following intravenous and intramuscular administration at two dosages.
Green sea turtles are widely distributed in tropical and subtropical waters. Adult green sea turtles face many threats, primarily from humans, including injuries from boat propellers, being caught in fishing nets, pollution, poaching, and infectious diseases. To the best of our knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for green sea turtles. Therefore, the present study aimed to describe the pharmacokinetic characteristics of ceftriaxone (CEF) in green sea turtles, Chelonia mydas, following single intravenous and intramuscular administrations at two dosages of 10 and 25 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 96 hr. The plasma concentrations of CEF were measured by liquid chromatography tandem mass spectrometry. The concentrations of CEF in the plasma were quantified up to 24 and 48 hr after i.v. and i.m. administrations at dosages of 10 and 25 mg/kg b.w., respectively. The Cmax values of CEF were 15.43 ± 3.71 μg/ml and 43.48 ± 4.29 μg/ml at dosages of 10 and 25 mg/kg, respectively. The AUClast values increased in a dose-dependent fashion. The half-life values were 2.89 ± 0.41 hr and 5.96 ± 0.26 hr at dosages of 10 and 25 mg/kg b.w, respectively. The absolute i.m. bioavailability was 67% and 108%, and the binding percentage of CEF to plasma protein was ranged from 20% to 29% with an average of 24.6%. Based on the pharmacokinetic data, susceptibility break-point and PK-PD index (T > MIC, 0.2 μg/ml), i.m. administration of CEF at a dosage of 10 mg/kg b.w. might be appropriate for initiating treatment of susceptible bacterial infections in green sea turtles.


Intravitreal dexamethasone implant as an option for anti-inflammatory therapy of tuberculosis uveitis.
Tuberculosis-associated uveitis remains a diagnostic and therapeutic challenge. After diagnosis of tuberculosis and initiation of anti-tuberculosis therapy for tuberculosis uveitis, the clinical responses are favorable. However, at 4-6 weeks of the therapy, there commonly occurs paradoxical deterioration due to an increase in inflammation which is often accompanied by cystoid macular edema. Thus, adjuvant administration of anti-inflammatory regimen should be considered. For this purpose, systemic and periocular steroids, systemic and intravitreal immunosuppressive agents have been tested. Nevertheless, there is no report in the literature about intravitreal dexamethasone slow-release implants for the treatment of this inflammatory condition. Case presentation. We presented a tuberculosis uveitis case whose ocular inflammation is partially modified by systemic and periocular steroid injections and then well controlled by the intravitreal dexamethasone implant. Intravitreal dexamethasone implant injection seems to be a safe and potent option for the treatment of macular edema secondary to tuberculosis uveitis.


[Interpretation of contemporary positioning of traditional Chinese medicine injections and analysis of key problems].
According to the current situations and development of (TCMIs), the author of the article reveals the scientific connotation of TCMIs in theory, preparations and clinic application, and points out that TCMIs are an innovative and breakthrough of conventional dosage forms of traditional Chinese medicines, the combination of traditional theory and modern technology as well as a type of modern dosage form with the characteristics of traditional Chinese medicines, which conforms to the principle of including the essence and excluding the wastes for traditional Chinese medicine preparations, meets the demands for quick-acting of traditional Chinese medicines and guides one of the development orientation of traditional Chinese medicines. In the meantime, an analysis was also made on key issues, such as adverse reactions of TCMIs, modern clinical application, special drug delivery route and diversity of components and ingredients.


Impacts of offshore oil spill accidents on island bird communities: A test run study around Orkney and Svalbard archipelagos.
The sea area around the Orkney archipelago, Scotland is subjected to substantial maritime shipping activities. By contract, the Svalbard archipelago, Norway currently has a rather low marine traffic profile. Future projections, however, indicate that the Trans-Arctic route might change the whole transportation picture and Svalbard may be at the centre of maritime activities. Both archipelagos have sensitive environmental resources at sea and inland, including bird communities. There are, for instance, 13 Red Listed species present in Orkney and 2 in Svalbard. In this regard, it is important to address oil spill risks along existing and projected shipping routes. Hypothetical spills were simulated in twelve scenarios for both the Orkney and Svalbard archipelagos with the OpenDrift open-source software. The results indicate risks to seabird communities. For Orkney, the spills resulted in the most extensive contamination of the sea and land environments in autumn. For Svalbard, autumn spills on the contrary presented the lowest risk to seabirds. Based on the simulations, we recommend increased caution for shipping activities in the problematic seasons, improved local readiness for ship accidents and sufficient pre-incident planning.


A single buffer that universally serves both restriction digestion and loading.
Restriction digestion is routinely performed in a buffer compatible with the restriction enzyme used. To load the samples on agarose gels for electrophoresis it is then necessary to add a loading buffer. A 10X loading buffer is often used, and consists of a dye to track the electrophoresis and a dense solution so that the digestion mixture sinks into the well. We describe a new buffer, which acts as a universal digestion buffer as well as a loading buffer. This avoids double handling of samples, which wastes both time and consumables. Importantly, the efficiency of digestion was found not to be significantly decreased in this new buffer.


Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin.
Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.


Copidosoma floridanum (Hymenoptera: Encyrtidae) Rapidly Alters Production of Soldier Embryos in Response to Competition.
Most social insects are free living and produce castes that develop in response to extrinsic environmental cues. Caste-forming polyembryonic insects, in contrast, are all endoparasitoids that form social groups inside the bodies of host insects. The best studied polyembryonic wasp is Copidosoma floridanum (Ashmead), which produces ∼3,000 clonal offspring that develop into two castes named reproductive and soldier larvae. Caste determination in this species is mediated by whether or not embryos inherit primary germ cells (PGCs). Prior results showed that C. floridanum increases the proportion of female soldier larvae it produces per host in response to other parasitoids like Microplitis demolitor. Here we show that caste ratio shifts occur through increased formation of embryos lacking PGCs. Our results further indicated that increased soldier production was a specific response to multiparasitism elicited by the chorion of M. demolitor eggs.


Genetic variants in SERPINA4 and SERPINA5, but not BCL2 and SIK3 are associated with acute kidney injury in critically ill patients with septic shock.
Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. Recently the first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, using a prospective cohort of critically ill patients with sepsis/septic shock, in Finland. This is a prospective, observational multicenter study. Of 2567 patients without chronic kidney disease and with genetic samples included in the Finnish Acute Kidney Injury (FINNAKI) study, 837 patients had sepsis and 627 patients had septic shock. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, considering stages 2 and 3 affected (severe AKI), stage 0 unaffected, and stage 1 indecisive. Genotyping was done using iPLEXTM Assay (Agena Bioscience). The genotyped SNPs were rs8094315 and rs12457893 in the intron of the BCL2 gene, rs2093266 in the SERPINA4 gene, rs1955656 in the SERPINA5 gene and rs625145 in the SIK3 gene. Association analyses were performed using logistic regression with PLINK software. We found no significant associations between the SNPs and severe AKI in patients with sepsis/septic shock, even after adjustment for confounders. Among patients with septic shock (252 with severe AKI and 226 without AKI (149 with KDIGO stage 1 excluded)), the SNPs rs2093266 and rs1955656 were significantly (odds ratio 0.63, p = 0.04276) associated with stage 2-3 AKI after adjusting for clinical and demographic variables. The SNPs rs2093266 in the SERPINA4 and rs1955656 in the SERPINA5 were associated with the development of severe AKI (KDIGO stage 2-3) in critically ill patients with septic shock. For the other SNPs, we did not confirm the previously reported associations.


Entanglement distribution using a biphoton frequency comb compatible with DWDM technology.
We demonstrate a distribution of frequency-multiplexed polarization-entangled photon pairs over 16 frequency channels using demultiplexers for the signal and idler photons with a frequency spacing of 25 GHz, which is compatible with dense wavelength division multiplexing (DWDM) technology. Unlike conventional frequency-multiplexed photon-pair distribution by a broadband spontaneous parametric down-conversion (SPDC) process, we use photon pairs produced as a biphoton frequency comb by SPDC inside a cavity where one of the paired photons is confined. Owing to the free spectral range of 12.5 GHz and the finesse of over 10 of the cavity, the generated photons having a narrow linewidth in one channel are separated well from those in the other channels, which minimizes channel cross-talk in advance. The observed fidelities of the photon pairs range from 81 % to 96 % in the 16 channels. The results show the usefulness of the polarization-entangled biphoton frequency comb for frequency-multiplexed entanglement distribution via a DWDM system.


Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis.
This study aimed to evaluate the impact of baseline left ventricular (LV) systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation (TAVI). Survival of patients undergoing TAVI was also compared with that of a population undergoing surgical aortic valve replacement. One hundred forty-seven consecutive patients (mean age=80±7 years) undergoing TAVI in 2 centers were included. Mean follow-up period was 9.1±5.1 months. At baseline, 34% of patients had impaired LV ejection fraction (LVEF) (<50%) and 66% had normal LVEF (≥50%). Procedural success was similar in these 2 groups (94% vs 97%, P=.41). All patients achieved improvement in transvalvular hemodynamics. At follow-up, patients with a baseline LVEF<50% showed marked LV reverse remodeling, with improvement of LVEF (from 37%±8% to 51%±11%). Early and late mortality rates were not different between the 2 groups, despite a higher rate of combined major adverse cardiovascular events (MACEs) in patients with a baseline LVEF<50%. The predictors of cumulative MACEs were baseline LVEF (HR=0.97, 95% CI=0.94-0.99) and preoperative frailty (HR=4.20, 95% CI=2.00-8.84). In addition, long-term survival of patients with impaired or normal LVEF was comparable with that of a matched population who underwent surgical aortic valve replacement. TAVI resulted in significant improvement in LV function and survival benefit in high-risk patients with severe aortic stenosis, regardless of baseline LVEF. Patients with a baseline LVEF<50% were at higher risk of combined MACEs.