Increased exposure improves recruitment: early results of a program designed to attract medical students into surgical careers.
In recent years, general surgery and surgical subspecialty residency interests have remained somewhat static among medical students, casting some doubt on recruitment of the best students. A summer research program was designed to introduce interested medical students to surgical careers. In 2003, the division of cardiac surgery instituted an 8-week structured summer research experience for second-year medical students. Three students were competitively chosen from a pool of 20 to 30 interested applicants every year. They were taught basic operative suturing and knot-tying techniques. Students participated in large animal research projects, witnessed clinical operations, and developed individual clinical projects with an attending cardiac surgeon. The summer experience culminated with oral presentations to the cardiac surgery division, with many students producing manuscripts for publication or presentation at national meetings. From 2003 to 2012, 30 students participated in the program. Of 23 participants who had applied for residency, 12 (52.2%) matched into general surgery or a surgical subspecialty, including 3 into plastic surgery, 2 into cardiothoracic surgery, 1 into orthopedic surgery, and 1 into neurosurgery. These students produced 64 publications and presented at 51 national and regional meetings. These results suggest that an 8-week, structured program introducing students to cardiothoracic surgery can successfully attract students into surgical careers. The percentage (52%) of these students entering a surgical career compares favorably with national residency match results (16%) and graduating Johns Hopkins medical students (22%). Increased effort for early exposure to surgery may be a key factor in generating and securing surgical interest among medical students.


A new highly selective fluorescent sensor based on a novel fluorophore for cyanide and its applications in bioimaging.
A novel highly active fluorescence chemical sensor (TBI) for CN- was synthesized based on triphenylamine-benzothiazole as a new fluorophore, and was used for the first time as a fluorophore for detection of CN- . Fluorescence quantum yield of the probe clearly increased when using triphenylamine-benzothiazole as the group. The probe possessed good selectivity towards CN- and had anti-interference ability over common ions. After adding CN- , the UV-visible spectrum of TBI changed clearly and underwent a dramatic colour change from red to colourless, which could be observed clearly by the naked eye. The limit of detection for CN- was calculated to be 2.62 × 10-8 M, which was well below the WHO cut-off point of 1.9 μM. The novel probe displayed fast sensing of CN- . The detection mechanism was a nucleophilic addition reaction between CN- and a carbon atom -C = N- in indole salt. The π-conjugation and intramolecular charge transfer (ICT) transition in the TBI molecule were destroyed by this addition, which resulted in a change of fluorescence before and after the addition of CN- . The mechanism was verified using theoretical calculation, 1 H NMR titration, and mass spectra. In addition, the probe showed low cytotoxicity and could be used for biological imaging in HeLa cells.


Mechanical and thermal properties of γ-Mg2SiO4 under high temperature and high pressure conditions such as in mantle: A first principles study.
γ-Mg2SiO4 is an important mineral in mantle, and our knowledge on its mechanical and thermal properties is critical for many areas of geological sciences. In this work, the crystal structure of γ-Mg2SiO4 under high temperature and high pressure conditions is optimized by using the GOMASC method, and the total energy, thermal expansion coefficients, and elastic constants at different temperature and pressure conditions are obtained. On the basis of phonon spectrum, group velocity, phase velocity, Grüneisen parameter, and thermal conductivity are calculated for γ-Mg2SiO4 under high temperature and high pressure conditions. These calculated results can provide an important reference for geological research.


Saccharomyces cerevisiae Fermentation Product Did Not Attenuate Clinical Signs, but Psyllium Husk Has Protective Effects in a Murine Dextran Sulfate Sodium-Induced Colitis Model.
Yeast products and psyllium husk may provide relief from clinical signs of colitis due to their ability to promote gut integrity, modulate gut microbiota, or positively affect immune responses, which have been demonstrated in several species. The objective of this study was to investigate the effects of a Saccharomyces cerevisiae fermentation product (SCFP) and psyllium husk (PH) on cecal and fecal microbiota, colonic gene expression and histopathology, and mesenteric lymph node (MLN) immune cells in a dextran sulfate sodium (DSS)-induced colitis model. Male C57BL/6J mice (n = 54) were assigned to a control, 5% SCFP, or 5% PH diet. After 2 wk of diet adaptation, mice were provided distilled water or 3% (wt:vol) DSS for 5 d ad libitum. Body weight, food and water intakes, and disease activity index (DAI) were recorded daily during the treatment period. Fresh fecal samples were collected before and during treatment for microbial analyses. After treatment, mice were killed, followed by tissue collection. Tissues were stored in proper solutions until further analyses. Data were analyzed using the Mixed Models procedure of SAS 9.4 (SAS Institute). Consumption of SCFP increased (P < 0.05) species richness of the gut microbiota and relative abundance of Butyricicoccus in fecal and cecal samples compared with control or PH mice. PH mice had greater (P < 0.05) gene expression of claudin (Cldn) 2, Cldn3, Cldn8, and occludin(Ocln) compared with control mice. DAI, MLN immune cell populations, colonic histopathology, and colonic gene expression were not affected (P > 0.05) by SCFP in DSS mice. DSS mice consuming PH had lower (P < 0.05) DAI compared with control or SCFP mice. Results suggest that, despite the modest changes it had on cecal and fecal microbiota, SCFP did not attenuate clinical signs associated with DSS-induced colitis in mice, while PH showed protective effects.


Psychiatric symptoms and recent overdose among people who use heroin or other opioids: Results from a secondary analysis of an intervention study.
Drug overdose (OD) is the leading cause of accidental death in the United States and most of these deaths involve opioids. Despite research linking opioid abuse to mental illness, and evidence suggesting a large portion of opioid OD deaths are suicides, OD prevention strategies scarcely take into account mental health risk factors. We examined a sample of heroin or other opioid users enrolled in an intervention study to determine the prevalence of overdose, the prevalence of suicide attempts in overdose, and whether those with higher levels of psychiatric symptomatology would be more likely to experience a recent OD compared to other opioid users. By performing bivariate analyses and multivariate logistic regression models that controlled for poly drug use, criminal justice status, age, race, gender, and education, we evaluated the association of severe depression, severe anxiety, posttraumatic stress disorder (PTSD) and, psychosis and past three-month OD. Just over 12% (45/368) of recent opioid users reported a recent overdose. Four of these recent overdose victims reported that the overdose was a suicide attempt. Multiple logistic regression analysis revealed that severe depression (odds ratio 2.46; 95% CI: 1.24, 4.89), PTSD (odds ratio: 2.77; 95% CI: 1.37-5.60) and psychosis (odds ratio 2.39; 95% CI: 1.10-5.15) were significantly associated with elevated odds for OD. Findings suggest systematic mental health symptom screening and connection to mental health treatment for opioid users-especially those identified with OD-may be critical for OD prevention.


Immuno-enhancement effects of Platycodon grandiflorum extracts in splenocytes and a cyclophosphamide-induced immunosuppressed rat model.
Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats. For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen. PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage. Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.


Seasonal changes in activities of human neutrophils in vitro.
We present a retrospective analysis of previously collected blood samples to determine whether the immune response of neutrophils depends on the season i.e., short versus long days, in which blood samples were collected. The bactericidal activity and adhesive capacity of neutrophils, the production of reactive oxygen species (ROS), and CD11b/CD18 molecule expression level were investigated. The investigated neutrophils were divided into two groups based on the time of blood collection: the winter season with short days and the summer season with long days. We found seasonal variation in measurements of all the analyzed functional responses of neutrophils to stimuli. The strongest adhesion, as well as maximum values of ROS production, was presented by neutrophils isolated from the summer group. The highest bactericidal activity of neutrophils was also observed in blood donors from summer group. The magnitude of the immune functional activity of neutrophils varies with the season of the year and is decreased in winter.


Relation of N-glycosylation of apolipoprotein B-100 to cellular metabolism of low density lipoprotein.
We studied the functional role of N-linked sugar chains of apolipoprotein (apo) B-100 of low density lipoprotein (LDL) in cholesterol metabolism. The N-linked sugar chains of apo B-100 of LDL obtained from four homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and column chromatography. They consisted of one neutral (N) and two acidic (A1, A2) fractions. The ratio of apo B-100 acidic fractions (A1+A2) varied among 4 WHHL rabbits. Serial measurements of serum cholesterol levels showed that they decreased with aging in each of 4 WHHL rabbits. We investigated the relation of the ratio of acidic sugar chains of apo B-100 to the serum cholesterol levels. Reciprocals of the serum cholesterol levels were significantly correlated with the ratio of acidic sugar chains of apo B-100 (r = 0.901, P < 0.001). To elucidate the role of N-linked sugar chains of apo B-100, we investigated cellular uptake of LDL in normal rabbit skin fibroblasts. The amounts of association, degradation and cholesteryl esterification of LDL with a lower ratio of acidic sugar chains at 37 degrees C were greater than those of LDL with a higher ratio of acidic sugar chains. These results suggest that N-glycosylation of apo B-100 may be related with serum cholesterol levels and N-linked sugar chains of apo B-100 may play an important role in cellular metabolism of LDL.


Dominant and recessive alleles of the Drosophila easter gene are point mutations at conserved sites in the serine protease catalytic domain.
The easter gene, required for the development of all lateral and ventral pattern elements in the Drosophila embryo, appears to encode an extracellular serine protease. Dominant easter alleles increase the number of cells that give rise to lateral and ventral structures. We have found that nine dominant and four recessive mutations are caused by single amino acid substitutions at conserved sites in the putative serine protease catalytic domain. The activity of dominant products was assayed by injecting in vitro synthesized transcripts from the dominant alleles into young embryos. The results suggest that the dominant easter products cleave the normal substrate, but fail to respond to a spatially asymmetric regulator.


Hormone replacement therapy (HRT) in women after genital cancer.
Women treated for genital cancer are not only suffering from the disease itself, but are in most cases confronted with the side effects of the loss of ovarian function. Therefore, it is of utmost importance for the gynecologist, who cares for these patients, to strongly consider the benefits and drawbacks of hormone replacement therapy (HRT) in these women. Overall, it appears, that in women with vulva, vaginal, cervical, ovarian and tubal cancer individually adjusted HRT can be employed for the benefit and well-being of these patients considering psychosomatic, functional and organic aspects. Patients after endometrial cancer should be differentiated according to the stage of the disease. In all cases the individual minimal effective dose of HRT should be searched for.


Methyl alpha-D-glucopyranoside enhances the enzymatic activity of recombinant beta-galactosidase inclusion bodies in the araBAD promoter system of Escherichia coli.
In this study, we utilized a catabolite repressor to improve the enzymatic activity of recombinant beta-galactosidase inclusion bodies (IBs) produced in Escherichia coli under the araBAD promoter system. Specifically, we employed methyl alpha-D: -glucopyranoside (alpha-MG) to lower the transcription rate of the beta-galactosidase structural gene. In deepwell microtiter plate and lab-scale fermentor culture systems, we demonstrated that the addition of alpha-MG after induction improved the specific beta-galactosidase production, even though beta-galactosidase was still produced as an IB. Particularly, the addition of 0.0025% alpha-MG led to the most significant increase in the specific activity of the beta-galactosidase. Interestingly, the beta-galactosidase IBs obtained in the presence of 0.0025% alpha-MG were more loosely packed, as determined by IB solubilization in guanidine hydrochloride solution. We propose that the reduced gene transcription rate was responsible for the increased specific beta-galactosidase activity and the loose packing that characterized the IBs produced in the presence of alpha-MG. This principle could be applied throughout the enzyme bioprocessing industry in order to enhance the activity of aggregate-prone enzymes within IBs.


SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies.
SYK and ZAP70 nonreceptor tyrosine kinases serve essential roles in initiating B-cell receptor (BCR) and T-cell receptor (TCR) signaling in B- and T-lymphocytes, respectively. Despite their structural and functional similarity, expression of SYK and ZAP70 is strictly separated during B- and T-lymphocyte development, the reason for which was not known. Aberrant co-expression of ZAP70 with SYK was first identified in B-cell chronic lymphocytic leukemia (CLL) and is considered a biomarker of aggressive disease and poor clinical outcomes. We recently found that aberrant ZAP70 co-expression not only functions as an oncogenic driver in CLL but also in various other B-cell malignancies, including acute lymphoblastic leukemia (B-ALL) and mantle cell lymphoma. Thereby, aberrantly expressed ZAP70 redirects SYK and BCR-downstream signaling from NFAT towards activation of the PI3K-pathway. In the sole presence of SYK, pathological BCR-signaling in autoreactive or premalignant cells induces NFAT-activation and NFAT-dependent anergy and negative selection. In contrast, negative selection of pathological B-cells is subverted when ZAP70 diverts SYK from activation of NFAT towards tonic PI3K-signaling, which promotes survival instead of cell death. We discuss here how both B-cell malignancies and autoimmune diseases frequently evolve to harness this mechanism, highlighting the importance of developmental separation of the two kinases as an essential safeguard.


2E-Decene-4,6-diyn-1-ol-acetate inhibits osteoclastogenesis through mitogen-activated protein kinase-c-Fos-NFATc1 signalling pathways.
An imbalance of osteoclasts and osteoblasts can result in a variety of bone-related diseases, including osteoporosis. Thus, decreasing the activity of osteoclastic bone resorption is the main therapeutic method for treating osteoporosis. 2E-Decene-4, 6-diyn-1-ol-acetate (DDA) is a natural bioactive compound with anti-inflammatory and anti-cancer properties. However, its effects on osteoclastogenesis are unknown. Murine bone marrow-derived macrophages (BMMs) or RAW264.7 cells were treated with DDA, followed by evaluation of cell viability, RANKL-induced osteoclast differentiation, and pit formation assay. Effects of DDA on RANKL-induced phosphorylation of MAPKs were assayed by western blot analysis. Expression of osteoclast-specific genes was examined with reverse transcription-PCR (RT-PCR) and western blot analysis. In this study, DDA significantly inhibited RANKL-induced osteoclast differentiation in RAW264.7 cells as well as in BMMs without cytotoxicity. DDA also strongly blocked the resorbing capacity of BMM on calcium phosphate-coated plates. DDA inhibited RANKL-induced phosphorylation of ERK, JNK and p38 MAPKs, as well as expression of c-Fos and NFATc1, which are essential transcription factors for osteoclastogenesis. In addition, DDA decreased expression levels of osteoclastogenesis-specific genes, including matrix metalloproteinase-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and receptor activator of NF-κB (RANK) in RANKL-induced RAW264.7 cells. Collectively, these findings indicated that DDA attenuates RANKL-induced osteoclast formation by suppressing the MAPKs-c-Fos-NFATc1 signalling pathway and osteoclast-specific genes. These results indicate that DDA may be a potential candidate for bone diseases associated with abnormal osteoclast formation and function.


Improved real-life adherence of 6-monthly denosumab injections due to positive feedback based on rapid 6-month BMD increase and good safety profile.
Almost 50 % of osteoporosis (OP) patients discontinue bisphosphonate (BP) therapy within 1-2 years after the start of their treatment. Denosumab's longer dosing interval with its administration every 6 months (Q6M) as a subcutaneous (sc) injection might result in a better real-life treatment adherence and persistence than weekly or monthly oral BP treatment regimen. The objectives of this open, investigator-initiated, prospective, observational, single-center study were to evaluate adherence with denosumab 60 mg sc every 6 months (Q6M) (Prolia(®)) injections in osteoporotic patients in a routine clinical care setting and to describe whether positive feedback to OP patients based on measured bone mineral density (BMD) increases and good safety profile have an impact on patients' real-life adherence. Results indicate that the rarity of adverse events and reduced dosage frequency together with the consistency of rapid and highly significant increases in BMD already after 6 months of denosumab therapy used as a positive reinforcement during doctor-patient interactions had a significant, positive impact on osteoporotic patient's adherence to continue with the 6-monthly sc denosumab injections.


Mechanical regulation of synapse formation and plasticity.
Dendritic spines are small protrusions arising from dendrites and constitute the major compartment of excitatory post-synapses. They change in number, shape, and size throughout life; these changes are thought to be associated with formation and reorganization of neuronal networks underlying learning and memory. As spines in the brain are surrounded by the microenvironment including neighboring cells and the extracellular matrix, their protrusion requires generation of force to push against these structures. In turn, neighboring cells receive force from protruding spines. Recent studies have identified BAR-domain proteins as being involved in membrane deformation to initiate spine formation. In addition, forces for dendritic filopodium extension and activity-induced spine expansion are generated through cooperation between actin polymerization and clutch coupling. On the other hand, force from expanding spines affects neurotransmitter release from presynaptic terminals. Here, we review recent advances in our understanding of the physical aspects of synapse formation and plasticity, mainly focusing on spine dynamics.


Micro-particles as interfering substances in colorimetric residual chlorine measurement.
Conventional methods using o-tolidine and N,N-diethyl-p-phenylenediamine as colorimetric reagents have been extensively applied worldwide in residual chlorine measurement for water quality and environmental management. Different types of interferences resulting in erroneous measurements while using colorimetry have been previously reported. In this study, we experimentally demonstrated micro-particles as interfering substances in selected inorganic (five metal oxidants) and organic (microalgae) particles. The results indicated erroneous measurements (viz. colour development) for three of the selected particles. These erroneous measurement levels were evaluated with reference to the chlorine concentration (in mg-Cl2/L, hereafter represented as mg/L) in relation to both representative colorimetric reagents in terms of the amount of particles and time variations. A novel viewpoint that filtration could be a possible solution to the erroneous measurement caused by such micro-particles was proposed.


[Comparison of the anticholinesterase action in vitro of tetanus toxin and parathion].
It is compared the true cholinesterase inhibition exerced in vitro either by the tetanus toxin and by "parathion". Rabbit's brain homogenates are used as source of the ChE. 4000 MLD of tetanus toxin show the same inhibitory effect than mg 1 of "parathion", during 30 min of incubation at 37 degrees C.


A simple ex vivo model for teaching Descemet membrane endothelial keratoplasty.
To describe a simple ex vivo porcine model for teaching Descemet Membrane Endothelial Keratoplasty (DMEK). Twenty freshly enucleated porcine eyes were used to create a pseudo-graft from the porcine lens capsule and implant it into an intact porcine globe using the standardized 'no-touch' technique of the Netherlands Institute for Innovative Ocular Surgery (NIIOS). The DMEK pseudo-graft could be inserted, centred, unfolded and appositioned in all cases. Practicing DMEK surgery under wetlab conditions was feasible by the described simple and low-cost model. This new tool may facilitate the adaptation of DMEK by cornea surgeons.


ELF1/PRR11/ARP2/3 promoted trophoblast cells proliferation and motility in early pregnancy.
Early pregnancy loss (EPL) is a common adverse pregnancy outcome with an incidence of approximately 10-30%. There are many factors that cause EPL, among which the lack of proliferation and invasive properties of trophoblast cells can lead to embryonic development. Therefore, in this study, the molecular biology of trophoblast cells was investigated. Placental villous tissues from EPL patients were collected to explore ELF1 and PRR11 gene expression. The proliferation and migration of trophoblast cells were assessed by MTT, crystalline violet staining, and traswell assays, respectively. Western blotting and RT-qPCR were performed to investigate the relationship between ELF1, PRR11, and ARP2/3. F-actin polymerization and FAK activation were evaluated by immunofluorescence and western blotting. Ultimately, ELF1/PRR11/ARP2/3 expression was verified in the EPL mice model RESULTS: ELF1 and PRR11 were lowly expressed in placental villous tissues from EPL. The overexpression of ELF1 and PRR11 promoted proliferation and migration of trophoblast cells. Moreover, while ELF1 bound to the PRR11 promoter and promoted transcriptional activation. Finally, ELF1/PRR11/ARP2/3 showed low expression in the placental tissue of EPL mice. Our study suggested that PRR11 promoted the motility of trophoblast cells by binding to the ARP2/3 complex to promote F-actin polymerization and FAK activation. In addition, ELF1 bound to the initiation site of PRR11 to promote its transcription. ELF1/PRR11/ARP2/3 may play an important role in EPL.


Negative effects of Rhabdias bufonis (Nematoda) on the growth and survival of toads (Bufo bufo).
The growth and survival of juvenile toads, Bufo bufo, infected with a common lung nematode, Rhabdias bufonis, were studied. Toads were raised from tadpoles in the laboratory and infected 2 months after metamorphosis. Individual toads were exposed to doses of 10, 40, 80 or 160 larvae, which enabled examination of the hypothesis that parasite-induced mortality is affected by worm numbers. Growth of infected toads began to diverge from that of uninfected controls at 6 weeks post infection (WPI) and by 12 WPI the most heavily infected toads were approximately half the mass of controls. No controls died throughout the experiment; however, mortality of infected toads was strongly affected by parasite density. A mechanism for mortality is suggested by the significant negative relationship between parasite density and dietary intake. This parasite-induced anorexia was detected at 3 WPI and persisted up to 9 WPI. Patterns of reduced host growth, survival and dietary intake provide experimental evidence of the negative consequences of parasitic infection in a natural parasite-host system which may also be present under natural conditions.


The effects of prolactin on pulmonary maturation in the fetal rabbit.
The effect of ovine prolactin administration on the fetal rabbit pulmonary pressure volume relationship was determined. Using pentobarbital anesthesia, on Day 24 of gestation, a midline incision on the maternal abdomen was made to expose the bicornuate uterus. Fetal rabbits in one horn of the uterus were injected intramuscularly with a dose of 1.0 mg (0.05 ml) of prolactin solution. Similarly, fetuses in the opposite horn were administered an equivalent volume of control vehicle. On Day 26 of gestation, no significant enhancement of lung maturation, as judged from the pressure volume relationship, was found to result from prolactin administration. These results suggest that prolactin does not initiate the secretion of surface active material into the alveolar lumen of the fetal lung in sufficient amounts to induce physiologic maturation of the rabbit fetal lung.


Plasmon-Enhanced Surface-Enhanced Raman Scattering Mapping Concentrated on a Single Bead for Ultrasensitive and Multiplexed Immunoassay.
A single microbead (MB)-concentrated surface-enhanced Raman scattering (SERS) mapping strategy is proposed for ultrasensitive and multiplexed immunoassay with high precision. In this design, the SERS tags are specifically immobilized on the surface of a plasmonic gold nanoparticle (GNP) layer-coated single MB via target protein-mediated immune coupling. By this means, even ultralow target dosage can bring highly concentrated SERS tags on the confined small zone around the single MB, and the target-induced SERS signals are largely enhanced by the plasmonic layer, endowing the proposed strategy with ultrahigh sensitivity to quantify subpicogram per milliliter levels of proteins. Moreover, the per-pixel averaged SERS intensity is adopted for target quantitation through mapping the SERS signals around the MB's surface, achieving greatly improved reproducibility compared with traditional single-point measurement. Benefiting from the intrinsic merits of SERS mapping, this elegant strategy also enables multiplexed immunoassay on a single MB.


Counterion displacement in the molecular evolution of the rhodopsin family.
The counterion, a negatively charged amino acid residue that stabilizes a positive charge on the retinylidene chromophore, is essential for rhodopsin to receive visible light. The counterion in vertebrate rhodopsins, Glu113 in the third transmembrane helix, has an additional role as an intramolecular switch to activate G protein efficiently. Here we show on the basis of mutational analyses that Glu181 in the second extracellular loop acts as the counterion in invertebrate rhodopsins. Like invertebrate rhodopsins, UV-absorbing parapinopsin has a Glu181 counterion in its G protein-activating state. Its G protein activation efficiency is similar to that of the invertebrate rhodopsins, but significantly lower than that of bovine rhodopsin, with which it shares greater sequence identity. Thus an ancestral vertebrate rhodopsin probably acquired the Glu113 counterion, followed by structural optimization for efficient G protein activation during molecular evolution.


Redox and spectral properties of flavodoxin from Anabaena 7120.
We report here on the spectrophotometric and electrochemical properties of the flavodoxin from Anabaena 7120 and compare these properties with those of flavodoxins that have been studied previously. Molar absorption coefficients have been determined for all three oxidation states of this protein, at various wavelengths. For oxidized flavodoxin, molar absorption coefficients for the absorption maxima at 464 and 373 nm were 9200 and 8500 M-1 cm-1, respectively. Reduction by the first electron produced a neutral blue semiquinone which exhibited an absorption maximum at 575 nm. The molar absorption coefficients at 575 nm were 200 M-1 cm-1 for the oxidized form, 5100 M-1 cm-1 for the semiquinone form, and 250 M-1 cm-1 for the hydroquinone form. Redox potentials have been determined, in the pH range of 6.0 to 8.5, for both electron transfers. At pH 7.0, the midpoint potential values for the first and second electron transfers were -0.196 and -0.425 V, respectively. We determined that the first electron transfer is pH dependent and that a proton transfer accompanies this one electron transfer. It was also determined that the second electron transfer is pH independent in the pH range of 6.0 to 8.5.


Urinary nicotine metabolite excretion and lung cancer risk in a female cohort.
A nested lung cancer case-control study was carried out using 397 12 h urine samples originally collected from a cohort of over 26,000 women aged 40-64 at entry who were then followed for up to 15 years. The urine samples from active smokers were first identified using a simple qualitative method and their total nicotine metabolites/creatinine ratios then determined by automated colorimetric methods. The results obtained demonstrated the capacity of nicotine metabolite estimations in a single 12 h sample of urine to predict the subsequent risk of lung cancer. The risk of lung cancer among the biochemically proven active smokers during this period was 7.8 times that of the non-smokers, suggesting that the dose-response relationship between smoking and lung cancer is no less step in women than in men. The smoking-related risk of adenocarcinoma was less than that of other lung carcinomas. It is suggested that this biochemical epidemiology approach to exploring the relationship between smoking and lung cancer could profitably be applied to the study of other smoking-related diseases.


Prevalence of obstructive sleep apnoea following head and neck cancer treatment: a cross-sectional study.
The obstructive sleep apnoea-hypopnoea syndrome (OSAHS) is a sleep-related breathing disorder characterised by repetitive pharyngeal collapse. OSAHS is associated with a reduced quality of life. A high OSAHS prevalence has been reported in patients treated for head and neck cancer (HNC). The aim of the present study was to identify the prevalence of OSAHS within a Dutch population of patients treated for HNC. Consecutive HNC patients with a follow-up of 6 months to 5 years after treatment of an oral or oropharynx carcinoma were eligible for inclusion. Two questionnaires were used to assess the presence of OSAHS-related complaints. Subsequently, polysomnography was used in patients with OSAHS-related complaints to confirm the diagnosis of OSAHS. Four out of 33 included patients were diagnosed with OSAHS, yielding a prevalence of 12%. Since recognition and treatment of OSAHS might play an important role in improving quality of life of HNC patients, we suggest screening all patients with an oral or oropharynx carcinoma for the presence of OSAHS-related complaints prior to and following HNC treatment.


Airway hyperresponsiveness to adenosine induced by lipopolysaccharide in Brown Norway rats.
We have explored the effects of bacterial endotoxin (lipopolysaccharide; LPS) on the response of the airways of Brown Norway (BN) rats to adenosine. Comparisons have been drawn with the effects on responses to methacholine and 5-hydroxytryptamine. In vehicle-challenged animals, adenosine, given i.v. was only a weak bronchoconstrictor. In contrast, 1 h following intratracheal administration of LPS, 0.3 mg kg-1, bronchoconstrictor responses to adenosine were markedly and selectively enhanced. At this time point, there were no significant changes in leukocyte numbers, eosinophil peroxidase and myeloperoxidase activities or protein concentrations in bronchoalveolar lavage (BAL) fluid. Twenty-four hours after challenge, the sensitivity of the airways to both adenosine and methacholine was reduced relative to the earlier time point and there were substantial increases in each marker of inflammation in BAL fluid. The bronchoconstrictor response to adenosine was blocked selectively by methysergide, disodium cromoglycate and the broad-spectrum adenosine receptor antagonist, 8-SPT, but not by DPCPX or ZM 243185, selective antagonists for the A1 and A2A receptors, respectively. Thus, the response to adenosine augmented following LPS is mast cell mediated and involves a receptor which can be blocked by 8-SPT but not by selective A1 or A2A receptor antagonists. It thus bears similarity to the augmented response to adenosine induced by allergen challenge in actively sensitized BN rats. Exposure to LPS could be a factor along with allergen in determining the increased sensitivity of the airways of asthmatics to adenosine.


Three-dimensional simultaneous brain mapping of T1, T2, T2∗ and magnetic susceptibility with MR Multitasking.
To develop a new technique that enables simultaneous quantification of whole-brain T1 , T2 , T2∗ , as well as susceptibility and synthesis of six contrast-weighted images in a single 9.1-minute scan. The technique uses hybrid T2 -prepared inversion-recovery pulse modules and multi-echo gradient-echo readouts to collect k-space data with various T1, T2, and T2∗ weightings. The underlying image is represented as a six-dimensional low-rank tensor consisting of three spatial dimensions and three temporal dimensions corresponding to T1 recovery, T2 decay, and multi-echo behaviors, respectively. Multiparametric maps were fitted from reconstructed image series. The proposed method was validated on phantoms and healthy volunteers, by comparing quantitative measurements against corresponding reference methods. The feasibility of generating six contrast-weighted images was also examined. High quality, co-registered T1 , T2 , and T2∗ susceptibility maps were generated that closely resembled the reference maps. Phantom measurements showed substantial consistency (R2 > 0.98) with the reference measurements. Despite the significant differences of T1 (p < .001), T2 (p = .002), and T2∗ (p = 0.008) between our method and the references for in vivo studies, excellent agreement was achieved with all intraclass correlation coefficients greater than 0.75. No significant difference was found for susceptibility (p = .900). The framework is also capable of synthesizing six contrast-weighted images. The MR Multitasking-based 3D brain mapping of T1 , T2 , T2∗ , and susceptibility agrees well with the reference and is a promising technique for multicontrast and quantitative imaging.


Last resort for renal transplant recipients, 'restored kidneys' from living donors/patients.
Because of the grave shortage of deceased kidney allografts in Japan, we have embarked on a new source of organs, 'Restored kidneys' from living patients. From January 1991 through September 2006, 42 kidneys (eight benign pathology, eight small renal cancers, eight ureteral cancers, six aneurysms, eight severe nephrotic syndrome from four patients and four ureteral stenosis) were obtained from 38 patients/donors after extensive discussion of treatment modalities and risks. All patients/donors agreed to undergo total nephrectomy. The lesions were removed/repaired ex vivo on the back table, then transplanted. All recipients were notified of all possible risks including donor disease recurrence. One, 5 and 10-year patient survival rates of restored transplant patients were 92.9%, 79.3% and 63.8%, respectively. One, 5 and 10-year graft survival rates of restored kidney transplant patients were 78.6%, 51.8% and 42.7%, respectively. There were no recurrences of small renal cell carcinomas. There was one recurrence of ureteral cancer in the transplanted kidney 15 months after operation. In countries where deceased donors are scarce, such as Japan, the restored kidneys can be a last resort for renal allografts.


Downregulation of neurodevelopmental gene expression in iPSC-derived cerebral organoids upon infection by human cytomegalovirus.
Human cytomegalovirus (HCMV) is a betaherpesvirus that can cause severe birth defects including vision and hearing loss, microcephaly, and seizures. Currently, no approved treatment options exist for in utero infections. Here, we aimed to determine the impact of HCMV infection on the transcriptome of developing neurons in an organoid model system. Cell populations isolated from organoids based on a marker for infection and transcriptomes were defined. We uncovered downregulation in key cortical, neurodevelopmental, and functional gene pathways which occurred regardless of the degree of infection. To test the contributions of specific HCMV immediate early proteins known to disrupt neural differentiation, we infected NPCs using a recombinant virus harboring a destabilization domain. Despite suppressing their expression, HCMV-mediated transcriptional downregulation still occurred. Together, our studies have revealed that HCMV infection causes a profound downregulation of neurodevelopmental genes and suggest a role for other viral factors in this process.


Prostheses and orthoses in the collections of the Auschwitz-Birkenau State Museum.
The authors described 424 orthopaedic appliances left by the prisoners of the Nazi Concentration Camp in Oświęcim. A collection of prostheses and orthoses, which is currently a part of the Auschwitz-Birkenau State Museum's exhibition, is extraordinary as it illustrates the fate of innocent, crippled people, who were incarcerated and murdered. Another point of value of the collection is its technical aspect, as it provides a clear picture of construction of prostheses and orthoses at the beginning of the 20th century.


Comparative study of fibronectin gene expression in tissues from hypertrophic scars and diabetic foot ulcers.
To explore the expression characteristic of fibronectin gene in hypertrophic scars and diabetic ulcer tissues. The biopsies from normal skins, hypertrophic scars and diabetic foot ulcers were taken. The technique of quantitative polymerase chain reaction (PCR) was used to evaluate the gene expression of fibronectin in the above biopsies. Fibronectin gene expression was enhanced in hypertophic scars and decreased in diabetic foot ulcers compared with that in normal skins. Quantitative comparison showed about 2-fold increase of fibronectin mRNA level in hypertrophic scars and about 3-fold decrease of fibronectin mRNA level in diabetic ulcers as compared with that in normal skins. Fibronectin gene expression is influenced by the tissue environment. Different expression and synthesis of fibronectin may cause different outcomes in wound healing.


Cortical blindness, a rare complication of pre-eclampsia.
This is a case report of a previously undiagnosed pregnant teenager who presented to the emergency department with cortical blindness. She was found to be pre-eclamptic with the HELLP syndrome. She underwent immediate cesarean section, with delivery of a viable 32-week-old infant. Computed tomography and magnetic resonance imaging studies revealed abnormalities in the occipital lobes and a possible subarachnoid hemorrhage. Her vision improved immediately after the cesarean section, and returned to normal in a few days.


Switching by Lepsiella vinosa (Gastropoda) in South Australian mangroves.
In South Australian mangroves Lepsiella vinosa feeds on two species of barnacles, Balanus amphitrite and Elminius modestus, and only attacks other types of prey if no barnacles are available. Laboratory experiments indicate that L. vinosa can be trained to either species and switches in terms of Murdoch's (1969) model.The distribution of barnacles is heterogeneous and distinct prey patches are found in the mangroves. In high density patches, that is over 25 B. amphitrite per metre length of pneumatophore, L. vinosa concentrated its attacks on B. amphitrite irrespective of the relative abundance of the two species. In moderate density patches, that is less than 25 B. amphitrite per metre length of pneumatophore, L. vinosa fed on the two species as expected on the basis of relative abundance. There was, however, also an association between changes in the absolute density of B. amphitrite and the proportion it formed in the diet.Prey selection in the moderate density patches was not random and was influenced by previous feeding history. L. vinosa which fed on the more abundant species, E. modestus, selected this species at a higher rate than expected in subsequent surveys. This result suggests that "ingestive conditioning" took place in the field, and provides some support for the switching hypothesis.Field cage experiments indicate that L. vinosa shows switching provided that the density of the preferred prey was not too high. L. vinosa had a weak preference for B. amphitrite over E. modestus, c was calculated to be 1.26, when equal numbers of each species were present. The preference appears to be consistent between individual L. vinosa as few individuals fed predominantly on only one prey species.The switching response in L. vinosa was asymmetrical with regard to the two prey species. L. vinosa switched to B. amphitrite when it was more abundant irrespective of prior training. L. vinosa trained to E. modestus, or unfed, prior to the experiment switched to E. modestus when it was more abundant, but, those trained to B. amphitrite did not. L. vinosa also showed asymmetry in its feeding rate. Those trained to E. modestus, or unfed, attacked prey at the average rate observed in the field irrespective of the prey presented. L. vinosa trained to B. amphitrite showed a marked reduction in feeding rate when B. amphitrite was less abundant.Absolute density as well as the relative density of the two prey species influenced prey selection. Higher predation on B. amphitrite was found, despite a fixed relative abundance of one B. amphitrite to five E. modestus, when the barnacle density was increased from 11.2 to 56 per metre of pneumatophore.


Primary nasoplasty in unilateral and bilateral cleft nasal deformity.
A six-step nasoplasty for the primary correction of the unilateral and bilateral cleft nasal deformity is presented. A review of the evolution of primary nasal reconstruction and preliminary results of the method are described and illustrated.


[Repair of articular cartilage defect with a large area: an experimental study].
To compare and evaluate potentialities and biological characteristics of grafts of chondrocytes cultured on fascia, periosteum and articular cartilage in repairing large defects of articular cartilage. The large defects of articular cartilage were repaired with grafts of freeze-stored and fresh chondrocytes cultured on fascia, periosteum and articular cartilage, which were evaluated by a number of observation methods. The fresh and freeze-stored fascial chondrocytes were superior to free grafts of chondrocytes in potentiality of formation of new cartilaginous tissue, structure and metabolism of newly formed tissue. Relatively good results were also obtained similarly by using fresh autografts of periosteum and cartilage. Chondrocytes can be cultured normally on fascia, which can be regarded as an ideal carrier of chondrocytes.


In vivo [31P]NMR studies on the influence of age on rat brain hypoxia.
In this paper the response of cerebral phosphate metabolism to mild hypoxia in young, medium and old rats has been studied via in-vivo [31P]nuclear magnetic resonance (NMR). It was found that the young adults (5-6 months) were more sensitive to this mild stress than either the mature adult (11-12 months) or senescent (23-24 months) rats even though the depth of hypoxia (paO2 = 45-55 mm Hg) was equal for all age groups. They displayed an earlier onset of acidosis, a greater fall in PCr and larger rise in Pi. This response is presumably an attempt to maintain adequate adenosine triphosphate (ATP) levels via anaerobic glycolysis. In contrast, mature adults and senescent adults appear to be able to maintain ATP levels by increasing mitochondrial rates. Acidosis is less severe as are drops in PCr and rises in Pi. Recovery is less complete for the young rats: Pi levels remain high while PCr and pHi levels stay low after normoxia has been reinstigated. All metabolite levels in the mature and senescent adults return to within 10% of control levels. All the data were analyzed and differences were found to be statistically significant. This study reveals that, contrary to popular belief, mature and old rats respond more favorably to reduced O2 than younger individuals. This is due to a more severe anaerobic acidosis in the latter age group. Speculations to explain this disparity are based on the fact that previous in-vitro studies involve systems that are totally or partially disconnected from the organism will not account for important feedback control present in an in-vivo system as studied here.


Methane yield from switchgrass and reed canarygrass grown in Eastern Canada.
Methane yields from silage made from switchgrass- and reed canarygrass-seeded plots with two N application rates and three harvest dates were assessed in Eastern Canada. The average specific methane yield from reed canarygrass-seeded plots (0.187 NL CH4 g VS(-1)) was less than from switchgrass-seeded plots (0.212 NL CH4 g VS(-1)). Switchgrass did not establish well and made up only a small proportion of the DM yield. As a consequence, the average methane yield per hectare from reed canarygrass-seeded plots (1.37 GL CH4 ha(-1)) was significantly greater than switchgrass-seeded plots (0.91 GL CH4 ha(-1)). Increased N fertilization reduced specific methane yields but increased methane yield per hectare, primarily because of increased DM yield. Delaying harvest resulted in decreased methane yields per hectare and specific methane yields, particularly for reed canarygrass. Further long-term research could help identify important factors influencing methane yields from crops during a complete stand life cycle.


Enriched prostaglandin E-9 ketoreductase activity in outer medullary cells of the rabbit kidney.
PGE2 metabolism was examined in rabbit renal slices and cell suspensions from the outer medulla, enriched (TALH) and depleted (OMC) for the thick ascending limb of Henle's loop. Metabolism was negligible in intact cells, either OMC or TALH fractions. However, in OMC and TALH homogenates, transformation of PGE2 to PGF2 alpha by NADPH-dependent prostaglandin E-9 ketoreductase (PGE-9KR) was observed at a PGE2 concentration of 4 X 10(-9) M. This activity was not reversible and was enriched ten-fold in the TALH with 41% of PGE2 transformed to PGF2 alpha after 30 min incubation. PGF2 alpha formation from PGE2 could not be detected in homogenates of cortex, medulla or papilla. PGE-9KR activity, particularly in the thick ascending limb, may be a source of PGF2 alpha in urine.


Cross-modal recognition of familiar and unfamiliar objects by the monkey: the effects of ablation of polysensory neocortex or of the amygdaloid complex.
Nine rhesus monkeys were trained to a standard level of cross-modal recognition (CMR) in the directions vision to touch and touch to vision. Their level of performance remained essentially unchanged with unfamiliar objects. Five then received bilateral removals of frontal, temporal and parietal polysensory cortex in one stage or successively, and 4 underwent removal of the amygdaloid complex in one stage. All animals were retrained to criterion with familiar objects and then again tested with unfamiliar objects. Postoperatively, the monkeys with extensive neocortical removals were unimpaired or slightly impaired with familiar objects, and slightly impaired (in only one direction) with unfamiliar objects. The animals with amygdaloid ablations showed a different pattern of change: with familiar objects they were unimpaired (if removals were less extensive), or were severely but transiently impaired (if the removals of the amygdala were more extensive and/or other structures were involved); with unfamiliar objects they were unimpaired, tending to improve. The neocortical polysensory areas may be necessary for generating new visual representations during learning--a performance required only for the CMR of unfamiliar objects.


The morphology of proximal tibiofibular joint (PTFJ) predicts incident radiographic osteoarthritis: data from Osteoarthritis Initiative.
To determine whether the morphology of proximal tibiofibular joint (PTFJ) is associated with increased risk of incident radiographic osteoarthritis (iROA) over 4 years in the OA Initiative (OAI) study. A nested matched case-control study design was used to select participants from OAI study. Case knees were defined as those with iROA. Control knees were matched one-to-one by sex, age and radiographic status with case knees. T2-weighted MR images were assessed at P0 (the visit when incident ROA was found on radiograph), P1 (1 year prior to P0) and at OAI baseline. The contacting area of PTFJ (S) and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ) and coronal plane (posterior stress-bolstering area, Sυ) were assessed, respectively. 354 case knees and 354 matched control knees were included, with a mean age of 60 and a mean body mass index (BMI) of 28 kg/m2. Baseline PTFJ morphological parameters (S, Sτ and Sυ) were significantly associated with iROA over 4 years, and these associations remained unchanged after adjustment for BMI, number of knee bending activities, self-reported knee injury and surgery. S, Sτ and Sυ were also significantly associated with iROA at P1 and P0. In subgroup analysed, S, Sτ and Sυ were associated with risks of incident joint space narrowing in the medial, but not the lateral tibiofemoral compartment. Greater contacting area, load-bearing area and posterior stress-bolstering area of PTFJ were associated with increased risks of iROA, largely in the medial tibiofemoral compartment.


Fatalities in Oil and Gas Extraction Database, an Industry-Specific Worker Fatality Surveillance System - United States, 2014-2019.
The U.S. oil and gas extraction (OGE) industry faces unique safety and health hazards and historically elevated fatality rates. The lack of existing surveillance data and occupational safety and health research called for increased efforts to better understand factors contributing to worker fatalities in the OGE industry. This report describes the creation of the Fatalities in Oil and Gas Extraction (FOG) database, presents initial findings from the first 6 years of data collection (2014-2019), highlights ways that FOG data have been used, and describes the benefits and challenges of maintaining the surveillance system. 2014-2019. In 2013, the National Institute for Occupational Safety and Health (NIOSH) created the FOG database, a surveillance system comprising an industry-specific worker fatality database. NIOSH researchers worked with OGE partners to establish inclusion criteria for the database and develop unique database variables to elucidate industry-specific factors related to each fatality (e.g., phase of operation, worker activity, and working alone). FOG cases are identified through various sources, such as Occupational Safety and Health Administration (OSHA) reports, media reports, and notifications from professional contacts. NIOSH researchers compile source documents; OGE-specific database variables are coded by multiple researchers to ensure accuracy. Data collection ceased in 2019 because grant funding ended. During 2014-2019, a total of 470 OGE worker fatalities were identified in the FOG database. A majority of these fatalities (69.4%) were identified from OSHA reports and Google Alerts (44.7% and 24.7%, respectively). Unique database variables created to characterize fatalities in the OGE industry (i.e., phase of operation, worker activity, working alone, and working unobserved) were identified in approximately 85% of OGE worker fatality cases. The most frequent fatal events were vehicle incidents (26.8%), contact injuries (21.7%), and explosions (14.5%). The event type was unknown among 5.7% of worker fatalities. Approximately three fourths of fatalities identified through the FOG database were among contractors. Approximately 20% of cases included workers who were working alone. The FOG database is a resource for identifying safety and health trends and emerging issues among OGE workers (e.g., exposure to hydrocarbon gases and vapors and fatalities resulting from cardiac events) that might not be available in other surveillance systems. The FOG database also helps researchers better identify groups of workers that are at increased risk for injury in an already high-risk industry. Challenges exist when maintaining an industry-specific surveillance system, including labor-intensive data collection, the need for researchers with substantial knowledge of the industry, delays in access to timely data, and missing source file data. Continued surveillance of worker fatalities in the OGE industry is recommended to help identify new safety and health hazards and guide research and prevention activities. Industry, academic institutions, and government can use findings from the FOG database to identify factors contributing to fatal injuries in OGE and develop interventions to improve worker safety and health. The findings in this report also can be used by other industries with high fatality rates to support the development of worker fatality surveillance systems.


Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes.
Stimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achieve this, 3T3-L1 adipocytes were exposed to 0.75 mM palmitate for 24 h, to induce insulin resistance, before treatment with 10 μM isoorientin or the comparative controls such as CL-316,243 (10 μM), pioglitazone (10 μM) and compound C (1 μM) for 4 h. Relevant bioassays and Western blot analysis were conducted on these insulin resistant cells. Our results showed that palmitate exposure could induce insulin resistance and mitochondrial dysfunction as measured by reduction in glucose uptake and impaired mitochondrial bioenergetics parameters. However, treatment with isoorientin reversed these effects by improving glucose uptake, blocking lipid accumulation, and modulating the process of mitochondrial respiration. Mechanistically, isoorientin could mediate lipid metabolism by activating 5' AMP-activated protein kinase (AMPK), while also effectively modulating the expression of genes involved in fat browning such as peroxisome proliferator-activated receptor gamma (PPAR)γ/α and uncoupling protein 1 (UCP1). In conclusion, isoorientin impacts insulin resistance in vitro by improving glucose uptake and mitochondrial function, consistent to modulating the expression of genes involved in energy metabolism and fat browning.


Microwave-assisted synthesis of highly luminescent CdSeTe@ZnS-SiO2 quantum dots and their application in the detection of Cu(II).
Highly luminescent and low toxic glutathione-capped CdSeTe@ZnS-SiO(2) quantum dots were successfully synthesized via a promising microwave strategy, and then applied in the detection of Cu(2+).


Intergenerational Patterns of Smoking and Nicotine Dependence Among US Adolescents.
We examined associations between parental and adolescent smoking and nicotine dependence in the United States. We used data from the 2004 to 2012 National Survey on Drug Use and Health, which ascertained smoking behaviors of 1 parent and 1 adolescent aged 12 to 17 years in 35 000 dyads. We estimated associations between parental and adolescent smoking behaviors, adjusted for covariates. Parental current dependence was strongly associated with adolescents' lifetime smoking (adjusted odds ratio [AOR] = 2.96; 95% confidence interval [CI] = 2.47, 3.55), whereas parental current nondependent smoking (AOR = 2.26; 95% CI = 1.92, 2.67) and former smoking (AOR = 1.51; 95% CI = 1.31, 1.75) were less strongly associated. Only parental nicotine dependence was associated with adolescent nicotine dependence (AOR = 1.66; 95% CI = 1.00, 2.74). Associations between parental and adolescent smoking did not differ by race/ethnicity. Parents' education, marital status, and parenting and adolescents' mental health, beliefs about smoking, perception of schoolmates' smoking, and other substance use predicted adolescent smoking and dependence. Reducing parental smoking would reduce adolescent smoking. Prevention efforts should encourage parental smoking cessation, improve parenting, address adolescent mental health, and reinforce adolescents' negative beliefs about smoking.


The role of ATF-2 in oncogenesis.
Activating Transcription Factor-2 is a sequence-specific DNA-binding protein that belongs to the bZIP family of proteins and plays diverse roles in the mammalian cells. In response to stress stimuli, it activates a variety of gene targets including cyclin A, cyclin D and c-jun, which are involved in oncogenesis in various tissue types. ATF-2 expression has been correlated with maintenance of a cancer cell phenotype. However, other studies demonstrate an antiproliferative or apoptotic role for ATF-2. In this review, we summarize the signaling pathways that activate ATF-2, as well as its downstream targets. We examine the role of ATF-2 in carcinogenesis with respect to other bZIP proteins, using data from studies in human cancer cell lines, human tumours and mouse models, and we propose a potential model for its function in carcinogenesis, as well as a theoretical basis for its utility in anticancer drug design.


Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels.
Volume-regulated anion channels (VRACs) are hexamers of LRRC8 proteins that are crucial for cell volume regulation. N termini (NTs) of the obligatory LRRC8A subunit modulate VRACs activation and ion selectivity, but the underlying mechanisms remain poorly understood. Here, we report a 2.8-Å cryo-electron microscopy structure of human LRRC8A that displays well-resolved NTs. Amino-terminal halves of NTs fold back into the pore and constrict the permeation path, thereby determining ion selectivity together with an extracellular selectivity filter with which it works in series. They also interact with pore-surrounding helices and support their compact arrangement. The C-terminal halves of NTs interact with intracellular loops that are crucial for channel activation. Molecular dynamics simulations indicate that low ionic strength increases NT mobility and expands the radial distance between pore-surrounding helices. Our work suggests an unusual pore architecture with two selectivity filters in series and a mechanism for VRAC activation by cell swelling.


Alleviation of apoptosis of bone marrow-derived mesenchymal stem cells in the acute injured kidney by heme oxygenase-1 gene modification.
Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is beneficial for the treatment of acute kidney injury (AKI), but the poor survival of BMSCs limits the repair effect. The oxidative stress in the AKI microenvironment is regarded as the main reason. Considering the potent anti-oxidant ability of heme oxygenase-1 (HO-1), HO-1 overexpression in BMSCs can be expected to improve the survival of BMSCs and correspondingly enhance the AKI repair effect. Here, BMSCs are transfected with pLV-HO-1/eGFP and pLV-eGFP by the lentivirus vector to get HO-1-BMSCs and eGFP-BMSCs, respectively. Ischemia/reperfusion-AKI kidney homogenate supernatant (KHS) is prepared for treating BMSCs, eGFP-BMSCs and HO-1-BMSCs. AKI-KHS results in a high inhibitory rate of BMSCs growth and a high proportion of TUNEL positive BMSCs, while HO-1 overexpression inverses this phenomenon and re-establishes the antioxidant and oxidant balance in HO-1-BMSCs. Phosphorylations of p53 and p38 mitogen-activated protein kinases (p38 MAPK) in HO-1-BMSCs decrease. Lower levels of monocyte chemotactic protein 1, tumor necrosis factor-α and interleukin 1β are also observed in supernatant of HO-1-BMSCs. The in vivo study shows that HO-1 overexpression sharply decreases the apoptosis of BMSCs in the injured kidney, and correspondingly the renal function of the AKI rats improves significantly. In conclusion, BMSCs with HO-1 overexpression suggests a better survival in the I/R-AKI microenvironment and a better kidney repair effect. The anti-oxidant effect via the inactivations of the downstream p53 and p38MAPK in BMSCs and the anti-inflammation could be the mechanisms. It provides a novel approach for the cell-based AKI-therapy.


IFITM3 promotes NiV envelope protein-mediated entry into MDCK cells and interacts with the fusion subunit of the F protein.
IFITM proteins are a host restriction factor with broad-spectrum antiviral activity, but the role in the paramyxovirus entry remains unclear. Nipah virus (NiV) is a zoonotic virus of the paramyxoviridae with extremely high lethality. Here, we assessed the role of IFITM3 on NiV G and F glycoprotein-mediated virus entry. Using NiV pseudovirus bearing NiV G and F proteins to infect IFITM3-induced MDCK cells, we found that overexpression of IFITM3 promotes NiV G and F proteins-mediated virus entry. Mechanistically, the subcellular distribution showed that F protein completely co-localized with IFITM3, but G protein does not. Immunoprecipitation further indicated that IFITM3 strongly captures F protein rather than G protein. F protein truncation found that the F1 subunit completely co-localized and captures with IFITM3, but not the F2 subunit. Furthermore, IFITM3 strongly binds to F1 truncations containing fusion peptide (FP), and F1 strongly captures IFITM3 truncation with the intramembrane domain (IMD). Together, the results suggest that IFITM3 can promote NiV G and F proteins-mediated virus entry into MDCK cells, and IFITM3 directly interacts with the F1 subunit of NiV F protein dependent on the former's IMD and the latter's FP, which may occur after incorporation of fusion peptides into the cell membrane following virus fusion activation.


Resistant and multi-resistant Gram-positive severe infections: the GISIG working methodology.
Five thematic working groups composed of Italian infectious disease experts and a group coordinator, supported by a scientific secretary, identified controversial issues in the field of severe healthcare-associated infections caused by multidrug-resistant organisms. The five group coordinators received training courses on data sources and electronic databases, literature search strategies, the scientific revision methods of quality assessment, and the construction of an evidence matrix. The working plan identified the following step: definition of the controversial issues and identification of documents for a systematic literature review. A specific methodology to classify the selected evidence was used that required the evaluation of the quality of review documents and statement documents and evaluation of the quality of original research. An original method to assess review documents and statement documents was proposed. A matrix model to extract and evaluate the evidence from original studies was designed using the CONSORT method to evaluate randomized clinical trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies, cohorts, and retrospective studies. A modified GRADE working group method was applied for grading quality of evidence and strength of recommendations. The working groups reviewed the available studies and formulated recommendations to be voted on at the national consensus conference held in Rome in June 2009.


Some neurochemical studies on auditory regions of mouse brain.
The mouse brain auditory pathway has been dissected into five regions: geniculate bodies, posterior colliculi, superior olives, cochlear nuclei, and cochleas. The following analyses were made in these regions and in the auditory cortex: protein, glutamate, gamma-aminobutyrate, taurine, choline acetyltransferase, and glutamate decarboxylase. Taurine levels (nmol . mg of protein-) were highest in cortex (93) and geniculate bodies (60) and lowest in the cochlear nuclei (27) and cochleas (29). Concentrations of gamma-aminobutyrate (same units) were highest in the geniculate bodies (28), low in the superior olives and cochlear nuclei (9 to 10), and undetectable in the cochleas. The distribution of glutamate decarboxylase activity reflected that of gamma-aminobutyrate. The activities of choline acetyltransferase (nmol . of acetylcholine synthesized . h . -1 mg of protein-1) were highest in the superior olives (60) and low in the cochleas (3). These results are interpreted as biocyemical support for previous physiological and pharmacological identification of the olivo-cochlear bundle as cholinergic and the cochlear-nucleus neurones as non-cholinergic. The results also provide further evidence for a role of GABA in the posterior colliculi, but not in the cochleas.


Variation in Candida spp. distribution and antifungal resistance rates among bloodstream infection isolates by patient age: report from the SENTRY Antimicrobial Surveillance Program (2008-2009).
The variation in Candida spp. causing bloodstream infection (BSI) and the frequency of resistance to fluconazole by patient age have been previously described. However, similar data have been shown for neither the echinocandins nor the newer triazoles. We analyzed the 24-h reference MIC data from the SENTRY Antimicrobial Surveillance Program to compare the antifungal resistance profiles and species distribution of Candida BSI isolates according to patient age. MIC results were obtained for anidulafungin, caspofungin, micafungin, fluconazole, posaconazole, and voriconazole, and recently revised Clinical and Laboratory Standards Institute breakpoints were applied. A total of 1239 Candida BSI isolates were obtained from 79 medical centers in 2008 to 2009: 50.0%, 17.4%, 17.4%, 9.8%, and 1.8% were Candida albicans (Ca), Candida glabrata (Cg), Candida parapsilosis (Cp), Candida tropicalis (Ct), and Candida krusei (Ck), respectively. Ca was most common in the 60- to 79-year age group (52.3%) and least common in the 80- to 99-year age group (46.7%), whereas Cg was most common in the 80- to 99-year age group (28.6%) and least common in the 0- to 19-year age group (2.0%). Cp and Ct were most common in the 0- to 19-year age group (28.5% and 12.9%, respectively), and Ck was most common among the patients in the 20- to 39-year age group (3.5%). No resistance to echinocandins was detected among isolates of Ca, Cp, and Ct from all age groups. Likewise, no resistance to posaconazole or voriconazole was observed in isolates of Ca, Cp, or Ck from all age groups. Resistance to both azoles and echinocandins was most prominent among isolates of Cg with the highest resistance rates to echinocandins (16.7%), fluconazole (16.7%), posaconazole (5.0%), and voriconazole (11.1%) among isolates from the 20- to 39-year age group. Both species distribution and antifungal resistance patterns vary markedly with patient age. Cg BSI isolates may show lower susceptibility rates to both azoles and echinocandins with the highest rates of resistance detected in 20- to 59-year-old patients.


Stereotactic body radiation therapy and thermal ablation for treatment of NSCLC: A systematic literature review and meta-analysis.
Stereotactic body radiation therapy (SBRT) is the standard of care for inoperable early stage non-small cell lung cancer (NSCLC). Use of image guided thermal ablation (IGTA; including microwave ablation [MWA] and radiofrequency ablation [RFA]) has increased in NSCLC, however there are no studies comparing all three. To compare the efficacy of IGTA (including MWA and RFA) and SBRT for the treatment of NSCLC. Published literature databases were systematically searched for studies assessing MWA, RFA, or SBRT. Local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were assessed with single-arm pooled analyses and meta-regressions in NSCLC patients and a stage IA subgroup. Study quality was assessed with a modified methodological index for non-randomized studies (MINORS) tool. Forty IGTA study-arms (2,691 patients) and 215 SBRT study-arms (54,789 patients) were identified. LTP was lowest after SBRT at one and two years in single-arm pooled analyses (4% and 9% vs. 11% and 18%) and at one year in meta-regressions when compared to IGTA (OR = 0.2, 95%CI = 0.07-0.63). MWA patients had the highest DFS of all treatments in single-arm pooled analyses. In meta-regressions at two and three-years, DFS was significantly lower for RFA compared to MWA (OR = 0.26, 95%CI = 0.12-0.58; OR = 0.33, 95%CI = 0.16-0.66, respectively). OS was similar across modalities, timepoints, and analyses. Older age, male patients, larger tumors, retrospective studies, and non-Asian study region were also predictors of worse clinical outcomes. In high-quality studies (MINORS score ≥ 7), MWA patients had better clinical outcomes than the overall analysis. Stage IA MWA patients had lower LTP, higher OS, and generally lower DFS, compared to the main analysis of all NSCLC patients. NSCLC patients had comparable outcomes after SBRT and MWA, which were better than those with RFA.


Epithelial expression of interleukin-37b in inflammatory bowel disease.
Interleukin (IL)-37 is a member of the IL-1 cytokine family. We investigated IL-37b expression in the inflamed mucosa of inflammatory bowel disease (IBD) patients. Furthermore, we analysed IL-37b expression in human colonic epithelial cells. The human colonic epithelial cell line T84 and human colonic subepithelial myofibroblasts (SEMFs) were used. IL-37b expression in the IBD mucosa was evaluated by immunohistochemistry. IL-37b mRNA and protein expression were determined by real time-polymerase chain reaction (PCR) and Western blotting, respectively. IL-37b was not detected in the normal colonic mucosa. In the inflamed mucosa of IBD patients, epithelial IL-37b expression was increased markedly. In ulcerative colitis (UC) and Crohn's disease (CD) patients, IL-37b expression was enhanced in the affected mucosa. In the intestinal epithelial cell line T84, the expression of IL-37b mRNA and protein was enhanced by tumour necrosis factor (TNF)-α. This IL-37b induction by TNF-α was mediated by nuclear factor (NF)-κB and activator protein (AP)-1 activation. Furthermore, IL-37b inhibited TNF-α-induced interferon-γ-inducible protein (IP)-10 expression significantly in human colonic SEMFs. Epithelial IL-37b expression was increased in IBD patients, especially UC patients. IL-37b may be involved in the pathophysiology of IBD as an anti-inflammatory cytokine and an inhibitor of both innate and acquired immune responses.


Two distinct superconducting states controlled by orientations of local wrinkles in LiFeAs.
For iron-based superconductors, the phase diagrams under pressure or strain exhibit emergent phenomena between unconventional superconductivity and other electronic orders, varying in different systems. As a stoichiometric superconductor, LiFeAs has no structure phase transitions or entangled electronic states, which manifests an ideal platform to explore the pressure or strain effect on unconventional superconductivity. Here, we observe two types of superconducting states controlled by orientations of local wrinkles on the surface of LiFeAs. Using scanning tunneling microscopy/spectroscopy, we find type-I wrinkles enlarge the superconducting gaps and enhance the transition temperature, whereas type-II wrinkles significantly suppress the superconducting gaps. The vortices on wrinkles show a C2 symmetry, indicating the strain effects on the wrinkles. By statistics, we find that the two types of wrinkles are categorized by their orientations. Our results demonstrate that the local strain effect with different directions can tune the superconducting order parameter of LiFeAs very differently, suggesting that the band shifting induced by directional pressure may play an important role in iron-based superconductivity.


Respiratory viruses in pediatric emergency department patients and their family members.
Respiratory viral infections account for a substantial fraction of pediatric emergency department (ED) visits. We examined the epidemiological patterns of seven common respiratory viruses in children presenting to EDs with influenza-like illness (ILI). Additionally, we examined the co-occurrence of viral infections in the accompanying adults and risk factors associated with the acquisition of these viruses. Nasopharyngeal swab were collected from children seeking medical care for ILI and their accompanying adults (Total N = 1315). Study sites included New York Presbyterian, Bellevue, and Tisch hospitals in New York City. PCR using a respiratory viral panel was conducted, and data on symptoms and medical history were collected. Respiratory viruses were detected in 399 children (62.25%) and 118 (17.5%) accompanying adults. The most frequent pathogen detected was human rhinovirus (HRV) (28.81%). Co-infection rates were 14.79% in children and 8.47% in adults. Respiratory syncytial virus (RSV) and parainfluenza infections occurred more often in younger children. Influenza and HRV occurred more often in older children. Influenza and coronavirus were mostly isolated in winter and spring, RSV in fall and winter and HRV in fall and spring. Children with HRV were more likely to have history of asthma. Adults with the same virus as their child often accompanied ≤ 2-year-old-positive children and were more likely to be symptomatic compared to adults with different viruses. Respiratory viruses, while presenting the same suite of symptoms, possess distinct seasonal cycles and affect individuals differently based on a number of identifiable factors, including age and history of asthma.


The prognosis and management of cervical cancer associated with pregnancy.
We sought to evaluate the prognosis of patients with stage IB cervical cancer related to pregnancy. We reviewed 53 patients from the University of Michigan diagnosed with cervical cancer related to pregnancy between 1960-1989. Patients with stage IB disease were compared with a control group less than 46 years old to determine whether pregnancy influenced survival. The mean age of the patients was 30.5 years (range 22-45). The number of patients treated by 5-year periods decreased from a high of 17 during 1965-1969 to a low of three during 1985-1989. The following cell types and stages were treated: squamous cell stages IA (four), IB (35), and IIB (six); adenocarcinoma stages IB (five) and IIB (two); and small-cell stage IIB (one). The 35 patients with stage IB disease had a cumulative 5-year survival of 83%. Positive lymph nodes were present in eight of 24 patients. There was no significant difference in 5-year survival according to the time of therapy (P = .45): Ten second-trimester patients had 90% survival, five third-trimester patients had 75% survival, and 20 postpartum patients had 75% survival. Eighteen of 21 patients treated by radical hysterectomy survived: three of four treated at term, five of five treated in the second trimester, and ten of 12 treated postpartum. Seven of 12 patients treated by radiation therapy survived: one of one treated at term, five of six treated in the second trimester, and one of five treated postpartum. When we compared these patients with 170 nonpregnant women less than 46 years old with stage IB squamous cell cancer, pregnancy did not adversely influence survival (P = .13). The number of patients diagnosed with invasive cervical cancer related to pregnancy has decreased. Survival is not altered by pregnancy for stage IB disease.


The dose response of several benzimidazole anthelmintics against resistant strains of Haemonchus contortus and Trichostrongylus colubriformis selected with thiabendazole.
Dose response lines for eight benzimidazole anthelmintics and thiophanate were determined, using standardised strains of thiabendazole selected and resistant Haemonchus contortus and Trichostrongylus colubriformis. Against H contortus, thiophanate, thiabendazole, parbendazole and oxibendazole were inactive. Mebendazole was inactive at dose rates of 6.26 and 12.5 mg/kg, although significant activity occurred at 25 mg/kg. Fenbendazole, cambendazole, oxfendazole and albendazole demonstrated significant activity at dose rates equal to or greater than the recommended therapeutic level. Thiophanate was inactive against resistant T colubriformis. The remaining compounds only showed significant activity when used at dose rates in excess of the recommended therapeutic level. These results show that a side resistance exists among the benzimidazole anthelmintics and suggests that changes in dose response lines could be expected to occur if resistant strains are selected with benzimidazoles other than thiabendazole.


Congenital supravalvular aortic stenosis in a kitten.
A three-month-old, male intact Norwegian forest cat without any clinical signs was referred to the cardiology service of the author's teaching hospital for evaluation of a cardiac murmur. The murmur was systolic with an intensity of 4 out of 6 with the point of maximal intensity at the left heart base. Echocardiography revealed a moderate mitral valve regurgitation and a moderate dynamic left ventricular outflow tract obstruction both resulting from systolic anterior motion of the mitral valve (SAM). Moreover, left ventricular concentric hypertrophy was noted. Oral atenolol therapy was initiated. Recheck examination 3.5 months later revealed unchanged murmur characteristics in the still asymptomatic kitten. Echocardiography showed no SAM, but there was a severe fixed aortic stenosis apparent caused by a discrete supravalvular lesion, 4 mm distal to the valve, with an hourglass morphology. Supravalvular aortic stenosis is a rare congenital anomaly in cats, which has not been reported antemortem yet.


Introgression of chromosome 1P from Agropyron cristatum reduces leaf size and plant height to improve the plant architecture of common wheat.
Introducing Agropyron cristatum chromosome 1P into common wheat can significantly reduce the plant height and leaf size, which can improve the plant architecture of common wheat. A new direction in crop breeding is the improvement of plant architecture for dense plantings to obtain higher yields. Wild relatives carry an abundant genetic variation that can increase the diversity of genes for crop genetic improvement. In this study, the A. cristatum 1P addition line, 1PS and 1PL telosomic addition lines were obtained by backcrossing the addition/substitution line II-3-1 (2n = 20'' W + 1P" + 2P") with the commercial recurrent parent cv. Jimai 22. Four continuous years of agronomic trait investigation in the genetic populations suggested that the introduction of A. cristatum chromosome 1P into wheat can significantly improve wheat plant architecture by reducing the plant height, leaf length and leaf width. A. cristatum chromosome arm 1PS reduced the plant height and leaf length of wheat, whereas introducing A. cristatum chromosome arm 1PL reduced the plant height, leaf length and leaf width. Altogether, our results demonstrated that A. cristatum chromosome 1P carries the dominant genes for small leaves and a dwarf habit for the enhancement of plant architecture in wheat. This study highlights wild relative donors as new gene resources for improving wheat plant architecture for dense planting.


Characterization of the human myocardial proteome in dilated cardiomyopathy by label-free quantitative shotgun proteomics of heart biopsies.
Proteomic profiling of heart tissue might help to discover the molecular events related to or even causing cardiovascular diseases in human. However, this material is rare and only available from biopsies taken for diagnostics, e.g., assessment of inflammatory events or virus persistence. Within this chapter, we describe a workflow for the quantitative proteome analysis of heart biopsies. Starting with 1-2 mg of tissue material, crude protein extracts were prepared, digested with LysC and trypsin, and then analyzed by LC-ESI-tandem mass spectrometry. Due to the low technical variance, the method can be used for label-free quantitation of disease-specific alterations in the human heart. Methods discussed include homogenization of biopsy tissue, sample preparation, proteolytic digestion, as well as data analysis for label-free quantitation.


Flash-induced photophosphorylation in Rhodospirillum rubrum chromatophores. I. The relationship between cytochrome c-420 content and photophosphorylation.
The content of cytochrome c-420 in Rhodospirillum rubrum chromatophores prepared by grinding with alumina is 5--10% of that in whole cells, and 20--40% in chromatophores by 'French' pressing. Flash-induced phosphorylation of various chromatophores which varied in cytochrome content from 7 to 40% is proportional to the cytochrome content. Extrapolating the cytochrome c-420 content to that observed in whole cells, a ratio ATP/P+X- near 1 is calculated. At low flash intensity the phosphorylation per flash is proportional to flash energy. Photophosphorylation in flashes given after a time of several minutes is only slightly dependent on the number of flashes. If the flashes are spaced from 0.1 to 10 s, relative phosphorylation in the first flash is about 70% and in the second 90+ of that observed in the following flashes. Proton binding is not affected by the cytochrome c-420 content and a ratio of H+/P+x- of 2.3 was found. These results can be explained by a working hypothesis in which charge separation occurring at one reaction centre and the resulting electron transport mediated amongst others by c-420, results in the injection of two protons into an ATPase, this in contrast to a chemiosmotic mechanism, where the protons are released in the chromatophore inner space.


[Construction of recombinant fowlpox virus expressing E0 gene of classical swine fever virus shimen strain and the animal immunity experiment].
The CSFV E0 gene was amplified from the plasmid pMD18-T-E0 by PCR and cloned into the FPV-P11 and FPV-pSY. The identified recombinant DNA was transfected into chicken embryo fibroblasts (CEF) to package Fowlpox virus. E0 gene was confirmed to be integrated into the genome of recombinant Fowlpox virus by PCR, and Western blot was employed for detection of E0 expression in the chicken embryo fibroblasts infected with recombinant Fowlpox virus . The results of ELISA showed that systemic immune response to CSFV could be induced effectively after the mice were immunized three times with recombinant Fowlpox virus through celiac route, the titer of antibody was 1 : 4096. The protection experiment showed that 75% of piglets immunized three times with recombinant Fowlpox virus were survived, indicating that the recombinant Fowlpox virus was effective. This paper lays foundation for the study of CSFV live vector vaccine.


Influence of catchment vegetation on mercury accumulation in lake sediments from a long-term perspective.
Organic matter (OM) cycling has a large impact on the cycling of mercury (Hg) in the environment. Hence, it is important to have a thorough understanding on how changes in, e.g., catchment vegetation - through its effect on OM cycling - affect the behavior of Hg. To test whether shifts in vegetation had an effect on Hg-transport to lakes we investigated a sediment record from Herrenwieser See (Southern Germany). This lake has a well-defined Holocene vegetation history: at ~8700years BP Corylus avellana (hazel) was replaced by Quercus robur (oak), which was replaced by Abies alba (fir) and Fagus sylvatica (beech) ~5700years BP). We were particularly interested in testing if coniferous vegetation leads to a larger export of Hg to aquatic systems than deciduous vegetation. When hazel was replaced by oak, reduced soil erosion and increased transport of DOM-bound mercury from the catchment resulted in increases in both Hg-concentrations and accumulation rates (61ngg(-1) and 5.5ngcm(-2)yr.(-)(1) to 118ngg(-1) and 8.5ngcm(-2)yr.(-)(1)). However, even if Hg-concentrations increased also in association with the introduction of fir and beech (173ngg(-1)), as a result of higher Hg:C, there was no increase in Hg-accumulation rates (7.6ngcm(-2)yr.(-)(1)), because of a decreased input of OM. At around 2500years BP Hg-accumulation rates and Hg-concentration indicated an additional input of Hg to the sediment (316ngg(-1) and 10.3ngcm(-2)yr.(-)(1)), which might be due to increased human activities in the area, e.g., forest burning or mining. Our results contrast those of several paired-catchment studies that suggest a higher release of Hg from coniferous than deciduous forest, and there is a need for studies with a long-term perspective to increase our understanding of the effects of slow and gradual processes on mercury cycling.


Nickela-electrocatalyzed C-H Alkoxylation with Secondary Alcohols: Oxidation-Induced Reductive Elimination at Nickel(III).
Nickela-electrooxidative C-H alkoxylations with challenging secondary alcohols were accomplished in a fully dehydrogenative fashion, thereby avoiding stoichiometric chemical oxidants, with H2 as the only stoichiometric byproduct. The nickela-electrocatalyzed oxygenation proved viable with various (hetero)arenes, including naturally occurring secondary alcohols, without racemization. Detailed mechanistic investigation, including DFT calculations and cyclovoltammetric studies of a well-defined C-H activated nickel(III) intermediate, suggest an oxidation-induced reductive elimination at nickel(III).


Spirostanol saponins and esculin from Rusci rhizoma reduce the thrombin-induced hyperpermeability of endothelial cells.
Rusci rhizoma extracts are traditionally used against chronic venous disorders (CVD). To determine the effect of its secondary plant metabolites on the endothelium, phenolic compounds and saponins from Butcher's broom were isolated from a methanolic extract, and their activity on the thrombin-induced hyperpermeability of human microvascular endothelial cells (HMEC-1) was investigated in vitro. In addition to the six known spirostanol saponins deglucoruscin (5), 22-O-methyl-deglucoruscoside (6), deglucoruscoside (7), ruscin (8), ruscogenin-1-O-(α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranoside (9) and 1-O-sulpho-ruscogenin (10), three new spirostanol derivatives were isolated and identified: 3'-O-acetyl-4'-O-sulphodeglucoruscin (1), 4'-O-(2-hydroxy-3-methylpentanoyl)-deglucoruscin (2) and 4'-O-acetyl-deglucoruscin (3). Furthermore, the coumarin esculin (4), which is also prominently present in other medicinal plants used in the treatment of CVD, was isolated for the first time from Rusci rhizoma. Five of the isolated steroid derivatives (2, 5, 8, 9 and 10) and esculin (4) were tested for their ability to reduce the thrombin-induced hyperpermeability of endothelial cells in vitro, and the results were compared to those of the aglycone neoruscogenin (11). The latter compound showed a slight but concentration-dependent reduction in hyperpermeability to 71.8% at 100μM. The highest activities were observed for the spirostanol saponins 5 and 8 and for esculin (4) at 10μM, and these compounds resulted in a reduction of the thrombin-induced hyperpermeability to 41.9%, 42.6% and 53.3%, respectively. For 2, 5 and 8, the highest concentration tested (100μM) resulted in a drastic increase of the thrombin effect. The effect of esculin observed at a concentration of 10μM was diminished at 100μM. These in vitro data provide insight into the pharmacological mechanism by which the genuine spirostanol saponins and esculin can contribute to the efficacy of Butcher's broom against chronic venous disorders.


Adrenergic control of motor activity: effects of PNMT inhibition upon open field behavior in the rat.
Two inhibitors of brain PNMT were given to rats in doses which caused equivalent reductions in enzyme activity. Each drug produced similar and dose-related decreases in ambulation, rearing and defecation during open field behavioral testing. Central adrenergic (epinephrine containing) system may be necessary for normal open field behavior. This may reflect an interaction with other monoamines, particularly dopamine.


One-stage posterior surgery combined with anti-Brucella therapy in the management of lumbosacral brucellosis spondylitis: a retrospective study.
This study aimed to assess the clinical efficacy of one-stage posterior surgery combined with anti-Brucella therapy in the treatment of lumbosacral brucellosis spondylitis (LBS). From June 2010 to June 2020, the clinical and radiographic data of patients with LBS treated by one-stage posterior surgery combined with anti-Brucella therapy were retrospectively analyzed. The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and Oswestry Disability Index scores (ODI) were used to evaluate the clinical outcomes. Frankel's classification system was employed to access the initial and final neurologic function. Fusion of the bone grafting was classified by Bridwell's grading system. A total of 55 patients were included in this study with a mean postoperative follow-up time of 2.6 ± 0.8 years (range, 2 to 5). There were 40 males and 15 females with a mean age of 39.8 ± 14.7 years (range, 27 to 57). The Brucella agglutination test was ≥ 1:160 in all patients, but the blood culture was positive in 43 patients (78.1%). A statistical difference was observed in ESR, CRP, VAS, ODI, and JOA between preoperative and final follow-up (P < 0.05). Neurological function was significantly improved in 20 patients with preoperative neurological dysfunction after surgery. According to Bridwell's grading system, the fusion of bone grafting in 48 cases (87.2%) was defined as grade I, and grade II in 7 cases (12.7%). None of the infestation recurrences was observed. One-stage posterior surgery combined with anti-Brucella therapy was a practical method in the treatment of LBS with severe neurological compression and spinal sagittal imbalance.


Validation and comparative studies of four sulfonamide immunoassays based on the same generic polyclonal antibody.
Four different immunoassays based on the same generic polyclonal antibody were validated by high performance liquid chromatography, respectively. They also were compared with each other in terms of sensitivity, precision, and accuracy for the quantification or screening of sulfonamide residues in food samples. Correlation studies showed that there was a good correlation between the immunoassays and liquid chromatography data. The conventional plate assay has better precision and the plate-enhanced chemiluminescent assay has higher sensitivity. These two methods all could be used as quantification methods for large numbers of samples and complements of the conventional analytical methods in laboratory. The flow-through strip assay has higher sensitivity and the dip-stick strip assay was less affected by matrix effect. These two methods all could be used as valuable tools for the rapid on-site screening of sulfonamide residues in animal-derived food samples.


Identification of S-1,2,2-trichlorovinyl-N-acetylcysteine as a urinary metabolite of tetrachloroethylene: bioactivation through glutathione conjugation as a possible explanation of its nephrocarcinogenicity.
The elimination and metabolism of [14-C]-tetrachloroethylene (Tetra) was studied in female rats and mice after the oral administration of 800 mg/kg [14-C]-Tetra. Elimination of unchanged Tetra was the main pathway of elimination in both species and amounted to 91.2% of the dose in rats and 85.1% in mice. [14-C]-Carbon dioxide (CO2) was found to be a trace metabolite of [14-C]-Tetra. Only a small part of the applied dose was transformed to urinary (rats = 2.3%, mice = 7.1%) and fecal (rats = 2.0%, mice = 0.5%) metabolites. The urinary metabolites were separated and quantified by high performance liquid chromatography (HPLC) and identified by gas liquid chromatography/mass spectrometry (GC/MS). The following metabolites could be identified: oxalic acid (8.0% of urinary radioactivity in rats, 2.9% in mice), dichloroacetic acid (5.1%, 4.4%), trichloroacetic acid (54.0%, 57.8%), N-trichloroacetyl-aminoethanol (5.4%, 5.7%), trichloroethanol, free and conjugated (8.7%, 8.0%), S-1,2,2-trichlorovinyl-N-acetylcysteine (N-acetyl TCVC) (1.6%, 0.5%), and another conjugate of trichloroacetic acid (1.8%, 1.3%). The structures of the identified metabolites indicate two different pathways operative in Tetra biotransformation: cytochrome P-450-mediated epoxidation forming reactive metabolites in the liver and conjugation of Tetra with glutathione (GSH) catalyzed by glutathione transferase(s). The formation of reactive intermediates by renal processing of the glutathione conjugates may provide a molecular mechanism for the nephrotoxicity and nephrocarcinogenicity of Tetra in male rats.


Effects of Micronutrients or Conditional Amino Acids on COVID-19-Related Outcomes: An Evidence Analysis Center Scoping Review.
Recent narrative reviews have described the potential efficacy of providing individuals infected with coronavirus disease 2019 (COVID-19) with additional micronutrients to reduce disease severity. Although there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19-related health outcomes. A literature search of the MEDLINE database and hand search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and 8 studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, and the other 4 studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous ascorbic acid, intramuscular cholecalciferol, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In 6 of the 8 included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared with sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists must rely on clinical expertise and indirect evidence to guide medical nutrition therapy for patients infected with COVID-19.


Man, or Machine? Artificial Intelligence Language Systems in Plastic Surgery.
Artificial intelligence (AI) language models are computer programs trained to understand and generate human-like text. The latest AI language models available to the public have impressive language generation capability with immediate applications in both academia and private practice. Plastic surgeons can immediately leverage this technology to more efficiently allocate valuable human capital to higher-yield tasks. This can ultimately translate to higher patient volume, higher research output, and improved patient communication. Commercially available models offer business solutions that should not be ignored by plastic surgeons hoping to establish, optimize, or grow their practices. In this paper, the authors review the current state of AI language systems, discuss potential applications, and explore the risks and limitations of this technology.