Lyme borreliosis in Portugal caused by Borrelia lusitaniae? Clinical report on the first patient with a positive skin isolate.
Borrelia lusitaniae was isolated from an Ixodes ricinus tick in Portugal in 1993 for the first time. Further, this borrelia genospecies has been found in ixodid ticks collected around the coasts of southern Portugal and North Africa. Its reservoir has not been defined yet. B. lusitaniae was isolated once until now from a patient with a long standing and expanding skin disorder. A 46-year-old Portuguese woman presented with a skin lesion on the left thigh which had evolved slowly over ten years. The patient reported limb paraesthesias, cramps, chronic headaches, and cardiac rhythm disturbances. History of tick bites was negative nor had the patient ever noticed a skin lesion comparable with erythema chronicum migrans. Skin biopsies were taken for histological evaluation, culture and DNA detection. Antibodies to borrelia were searched by indirect immunofluorescence assay and Western-blot. A bilateral carpal tunnel syndrome and local synovitis was diagnosed. Dermato-histology was normal, serology was negative. Spirochaetal organisms were cultured from a skin biopsy and identified as B. lusitaniae. The patient improved after a 2-week course of intravenous ceftriaxone; the skin lesions did not expand further. This culture confirmed skin infection by B. lusitaniae in a patient from Portugal suggests an additional human pathogen out of the B. burgdorferi sensu lato complex in Europe, particularly in Portugal.


The signaling pathways involved in metabolic regulation and stress responses of the yeast-like fungi Aureobasidium spp.
Aureobasidium spp. can use a wide range of substrates and are widely distributed in different environments, suggesting that they can sense and response to various extracellular signals and be adapted to different environments. It is true that their pullulan, lipid and liamocin biosynthesis and cell growth are regulated by the cAMP-PKA signaling pathway; Polymalate (PMA) and pullulan biosynthesis is controlled by the Ca2+ and TORC1 signaling pathways; the HOG1 signaling pathway determines high osmotic tolerance and high pullulan and liamocin biosynthesis; the Snf1/Mig1 pathway controls glucose repression on pullulan and liamocin biosynthesis; DHN-melanin biosynthesis and stress resistance are regulated by the CWI signaling pathway and TORC1 signaling pathway. In addition, the HSF1 pathway may control cell growth of some novel strains of A. melanogenum at 37 °C. However, the detailed molecular mechanisms of high temperature growth and thermotolerance of some novel strains of A. melanogenum and glucose derepression in A. melanogenum TN3-1 are still unclear.


Enantiomeric resolution of amino acid derivatives on chiral stationary phases by high-performance liquid chromatography.
Chiral stationary phases (CSPs) containing urethane-blocked alpha-arylglycines as chiral groups were synthesized and found to have good enantioselectivity for several N alpha-acylamino acid esters. Depending on the derivatization pattern of the amino acids, two different mechanisms of adsorption, generating opposite elution orders, could be observed. The best results were obtained utilizing amino acids as their N alpha-3,5-dinitrobenzoylamino acid esters. The high resolution makes this method suitable for racemization studies in peptide and protein chemistry, as was demonstrated in some examples. The mechanism of enantiomeric adsorption of N alpha-3,5-dinitrobenzoylamino acid esters on such CSPs could be elucidated by a new method based on energy calculations for the reversible diastereomeric complexes. The calculated structures of the adsorption complexes agreed well with the observed elution orders of the amino acid derivatives.


[Participation of hospital nephrology departments in outpatient dialysis care. Joint Statement of the »Deutsche Gesellschaft für Nephrologie (DGfN)«, »Verband leitender Klinikärzte in der Nephrologie (VLKN)«, »Verband Deutsche Nierenzentren (DN) e. V.« , »KfH Kuratorium für Dialyse und Nierentransplantation e. V.« and »PHV - Der Dialysepartner Patienten-Heimversorgung«].
The proposals by health care providers to impose drastic limits on chronic dialysis in hospitals to the extent that it can only be provided on loss-making terms, will jeopardize the cost efficiency of nephrological departments in hospitals and hence their continued existence. Such departments play a key role within the discipline, however, as the training of nephrologists is tied to them by further training regulations. The authors take the view that the proposals by health care providers are short-sighted with regard to the quality of care and the safeguarding of care in the future, and that they counteract the goals of quality assurance currently dominating the health policy agenda.


Influence of hamstring autograft diameter on graft failure rate in Chinese population after anterior cruciate ligament reconstruction.
There has been limited literature regarding the influence of hamstring autograft diameter on the outcome of anterior cruciate ligament (ACL) reconstruction in Asian population. This study was undertaken to investigate the failure rate after ACL reconstruction among Chinese patients treated with hamstring tendon autografts of different diameters. Our hypothesis was that an increase in hamstring tendon autograft diameter would reduce the risk of graft failure. A retrospective review of 394 consecutive patients who underwent ACL reconstruction using quadrupled semitendinous and gracillis autografts from 2009 to 2018 at our centre was performed. Logistic regression analysis was used to determine the relationship between graft failure rate and predictor variables, including hamstring graft diameter, gender and age. Hamstring graft diameter of 8.0 mm or more was found to be associated with significant reduction of risk in graft failure rate (P = 0.001, Relative Risk 0.19). No significant association was found between graft failure rate and gender or age. Hamstring graft diameter 8.0 mm or greater is associated with decreased graft failure rate and revision rate in our local Chinese population.


Hepatic microsomal p-nitroanisole O-demethylase. Effects of chlordecone or mirex induction in male and female rats.
The effects of chlordecone (CD) or mirex treatment on the hepatic microsomal monooxygenase system of male and female rats were investigated, and kinetic parameters (apparent Vmax and apparent Km) for p-nitroanisole O-demethylase were studied in detail. Both pesticides elevated the levels of cytochrome P-450 in a time- and dose-dependent manner. The maximum rate of p-nitroanisole metabolism in males was increased about 100 and 50% and the apparent Km was elevated about 40- and 18-fold by CD and mirex respectively. p-Nitroanisole metabolism in females was reduced slightly by treatment with either agent, and the apparent Km was increased about 14-fold by CD but was relatively unaffected by mirex treatment.


Trilobed flap reconstruction for distal nasal skin defects.
The bilobed flap is reliable for reconstruction of Mohs defects on the lower third of the nose. It uses skin from the proximal nose to reconstruct defects of the nasal tip and ala. The goal is to avoid alar rim displacement and asymmetry. The trilobed flap's design and execution leverage the strengths of the bilobed flap to allow application to a broader range of surgical nasal defect sizes and locations, particularly distal defects. To present our surgical execution and application of the trilobed flap for reconstruction of distal nasal Mohs surgery defects. Mohs surgery defects of the distal nose of 31 patients were reconstructed using a trilobed flap over a 3-year period. Pre- and postoperative photographs were independently and blindly evaluated and graded for alar symmetry and overall cosmesis. Median alar symmetry and overall cosmesis scores based on three reviewers were excellent. The trilobed flap offers a successful reconstructive option for Mohs defects of the distal nose that may not be optimally amenable to bilobed flap repair. Over 3 years, 31 trilobed flap repairs were performed with overall excellent outcomes.


Astrocytes Surviving Severe Stress Can Still Protect Neighboring Neurons from Proteotoxic Injury.
Astrocytes are one of the major cell types to combat cellular stress and protect neighboring neurons from injury. In order to fulfill this important role, astrocytes must sense and respond to toxic stimuli, perhaps including stimuli that are severely stressful and kill some of the astrocytes. The present study demonstrates that primary astrocytes that managed to survive severe proteotoxic stress were protected against subsequent challenges. These findings suggest that the phenomenon of preconditioning or tolerance can be extended from mild to severe stress for this cell type. Astrocytic stress adaptation lasted at least 96 h, the longest interval tested. Heat shock protein 70 (Hsp70) was raised in stressed astrocytes, but inhibition of neither Hsp70 nor Hsp32 activity abolished their resistance against a second proteotoxic challenge. Only inhibition of glutathione synthesis abolished astrocytic stress adaptation, consistent with our previous report. Primary neurons were plated upon previously stressed astrocytes, and the cocultures were then exposed to another proteotoxic challenge. Severely stressed astrocytes were still able to protect neighboring neurons against this injury, and the protection was unexpectedly independent of glutathione synthesis. Stressed astrocytes were even able to protect neurons after simultaneous application of proteasome and Hsp70 inhibitors, which otherwise elicited synergistic, severe loss of neurons when applied together. Astrocyte-induced neuroprotection against proteotoxicity was not elicited with astrocyte-conditioned media, suggesting that physical cell-to-cell contacts may be essential. These findings suggest that astrocytes may adapt to severe stress so that they can continue to protect neighboring cell types from profound injury.


Changes of cerebral tissue oxygen saturation at sleep transitions in adolescents.
In adults, cerebral oxy-([O₂Hb]) and deoxyhemoglobin concentrations ([HHb]) change characteristically at transitions of sleep stages. The aims were to assess these changes in adolescents and additionally to measure tissue oxygen saturation (StO₂) by near infrared spectroscopy (NIRS). Previously it was reported that in adults [O₂Hb] increased and [HHb] decreased at the transition from non-rapid eye movement sleep (NREMS) to REMS and wakefulness. Transitions to NREMS from REMS/wakefulness led to a decrease in [O₂Hb] and an increase in [HHb]. We measured [O₂Hb], [HHb] and tissue oxygenation (StO₂) with NIRS approximately above the left prefrontal cortex in 12 healthy adolescent males (aged 10-16 years). We found comparable signs and magnitudes of changes in [O₂Hb] and [HHb] as observed in adults. StO₂ increased at the transitions from NREMS to REMS and decreased from REMS to NREMS and at sleep onset (all p < 0.01, linear mixed effects model). Changes in oxygen metabolism during sleep transitions are similar in adolescents and adults. In addition, we show for the first time temporal changes of StO₂ at sleep transitions.


Histochemical in situ identification of bovine embryonic blood cells reveals differences to the adult haematopoietic system and suggests a close relationship between haematopoietic stem cells and primordial germ cells.
Cryostat sections of bovine embryos of exactly known age (obtained from artificial insemination), ranging from 32 to 60 days post-insemination, were treated with a wide range of antibodies directed against cell surface antigens or lineage-specific factors in order to demonstrate different types of fetal blood cells and their precursors. An antibody specific to bovine c-kit (bk-1) stained not only presumptive haematopoietic stem cells in the dorsal aorta and the embryonic liver, but also a subpopulation of putative primordial germ cells in the gonadal anlage, the latter being further characterised by a positive labelling with the lectins STA, WFA and WGA and a histochemical reaction for alkaline phosphatase. The antibody against CD 45, commonly regarded as a pan-leukocyte marker, reacted in the bovine embryo with different types of blood cells, as well as with presumptive vasculogenetic cells and a subpopulation of putative primordial germ cells. CD 61 immunoreaction proved to be a useful tool for demonstrating megakaryocytopoiesis in the embryonic liver, in addition to the lumen of blood vessels and the mesonephros. Staining with BM-2 was restricted to a single population of medium-sized, round to oval cells, forming small groups within the parenchymal strands of the liver. Characterised furthermore by a U-shaped nucleus, this BM-2-positive cell type apparently represents a developmental stage in the granulopoietic lineage. B-lymphocytopoiesis in the bovine liver was detected with antibodies directed against WC-4 and IgM, but not until day 58 post-insemination. Using antibodies to CD 14, no positive results could be obtained in embryonic tissues, although anti-CD 14-positive macrophages were easily recognised in lymph nodes of adult bovines. The antibody against CD 68, however, identified two populations of primitive macrophages in our samples. One population was located in parenchymal strands of the embryonic liver, probably acting as nursing cells for haematopoietic foci, and the other was observed intravasally in the sinusoids of the liver, most probably representing primitive Kupffer cells.


Distribution of P2Y6 and P2Y12 receptor: their colocalization with calbindin, calretinin and nitric oxide synthase in the guinea pig enteric nervous system.
The distribution of P2Y(6) and P2Y(12) receptor-immunoreactive (ir) neurons and fibers and their coexistence with calbindin, calretinin and nitric oxide synthase (NOS) has been investigated with single and double labeling immunostaining methods. The results showed that 30-36% of the ganglion cells in the myenteric plexus are strongly P2Y(6) receptor-ir neurons; they are distributed widely in the myenteric plexus of stomach, jejunum, ileum and colon, but not in the submucosal plexus, with a typical morphology of multipolar neurons with a long axon-like process. About 42-46% of ganglion cells in both the myenteric and submucosal plexuses show P2Y(12) receptor-ir. About 28-35% of P2Y(6) receptor-ir neurons were found to coexist with NOS and 41-47% of them coexist with calretinin, but there was no coexistence of P2Y(6) receptor-ir with calbindin. In contrast, all P2Y(12) receptor-ir neurons were immunopositive for calbindin, although occasionally P2Y(12) receptor-ir neurons without calbindin immunoreactivity were found, while none of the P2Y(12) receptor-ir neurons were found to coexist with calretinin or NOS in the gastrointestinal system of guinea pig. The P2Y(12) receptor-ir neurons coexpressing calbindin-ir in the small intestine are Dogiel type II/AH, intrinsic primary afferent neurons.


Citrobacter freundii bacteraemia presenting as typhoid fever.
Citrobacter infections usually arise opportunistically in immunocompromised persons. We report the case of a young man in whom Citrobacter freundii caused a primary invasive illness similar to typhoid fever.


Treatment Switch to Dolutegravir With 2 Nucleoside Reverse-Transcriptase Inhibitors (NRTI) in Comparison to Continuation With Protease Inhibitor/Ritonavir Among Patients With Human Immunodeficiency Virus at Risk for Prior NRTI Resistance: A Cohort Analysis of Real-World Data.
Switching antiretroviral regimens when human immunodeficiency virus (HIV) viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse-transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared with remaining on a boosted protease inhibitor (protease inhibitor/ritonavir [PI/r]) regimen in people with HIV (PWH) with prior documented virologic failure and/or exposure to mono/dual NRTIs. We used the Quebec HIV Cohort including 10 219 PWH whose data were collected at 4 sites in Montreal, Canada. We included all PWH with documented virologic failure or exposure to mono/dual NRTI therapy who were virologically suppressed on a PI/r-based regimen for at least 6 months on or after January 1, 2014 (n = 532). A marginal structural Cox model analysis was used to estimate the effect of the switch to dolutegravir on virologic outcome compared with remaining on PI/r. The outcome was defined as 2 consecutive viral loads (VLs) >50 copies/mL or 1 VL >50 copies/mL if it occurred at the last VL available. Among 532 eligible participants, 216 (40.6%) had their regimen switched to dolutegravir with 2 NRTIs, whereas 316 (59.4%) remained on the PI/r with 2 NRTIs. The weighted hazard ratio for the effect of dolutegravir switch on virologic failure compared with patients whose regimen remained on PI/r was 0.57 (95% confidence interval, 0.21-1.52). We did not find evidence of an increased risk for virologic failure after switching to dolutegravir from PI/r among patients with previous virologic failure or prior exposure to mono/dual NRTI.


Partial cytological diploidization of neoautotetraploid meiosis by induced cross-over rate reduction.
Polyploids, which arise from whole-genome duplication events, have contributed to genome evolution throughout eukaryotes. Among plants, novel features of neopolyploids include traits that can be evolutionarily or agriculturally beneficial, such as increased abiotic stress tolerance. Thus, in addition to being interesting from an evolutionary perspective, genome duplication is also increasingly recognized as a promising crop improvement tool. However, newly formed (neo)polyploids commonly suffer from fertility problems, which have been attributed to abnormal associations among the multiple homologous chromosome copies during meiosis (multivalents). Here, we test the long-standing hypothesis that reducing meiotic cross-over number may be sufficient to limit multivalent formation, favoring diploid-like bivalent associations (cytological diploidization). To do so, we developed Arabidopsis thaliana lines with low cross-over rates by combining mutations for HEI10 and TAF4b. Double mutants showed a reduction of ~33% in cross-over numbers in diploids without compromising meiotic stability. Neopolyploids derived from the double mutant show a cross-over rate reduction of about 40% relative to wild-type neotetraploids, and groups of four homologs indeed formed fewer multivalents and more bivalents. However, we also show that the reduction in multivalents comes with the cost of a slightly increased frequency of univalents and that it does not rescue neopolyploid fertility. Thus, while our results do show that reducing cross-over rates can reduce multivalent frequency in neopolyploids, they also emphasize that there are additional factors affecting both meiotic stability and neopolyploid fertility that will need to be considered in solving the neopolyploid fertility challenge.


Evolving kernel extreme learning machine for medical diagnosis via a disperse foraging sine cosine algorithm.
Kernel extreme learning machine (KELM) has been widely used in the fields of classification and identification since it was proposed. As the parameters in the KELM model have a crucial impact on performance, they must be optimized before the model can be applied in practical areas. In this study, to improve optimization performance, a new parameter optimization strategy is proposed, based on a disperse foraging sine cosine algorithm (DFSCA), which is utilized to force some portions of search agents to explore other potential regions. Meanwhile, DFSCA is integrated into KELM to establish a new machine learning model named DFSCA-KELM. Firstly, using the CEC2017 benchmark suite, the exploration and exploitation capabilities of DFSCA were demonstrated. Secondly, evaluation of the model DFSCA-KELM on six medical datasets extracted from the UCI machine learning repository for medical diagnosis proved the effectiveness of the proposed model. At last, the model DFSCA-KELM was applied to solve two real medical cases, and the results indicate that DFSCA-KELM can also deal with practical medical problems effectively. Taken together, these results show that the proposed technique can be regarded as a promising tool for medical diagnosis.


The role of helper lipids in the intracellular disposition and transfection efficiency of niosome formulations for gene delivery to retinal pigment epithelial cells.
In this work, we carried out a comparative study of four different niosome formulations based on the same cationic lipid and non-ionic tensoactive. The niosomes prepared by oil-in-water emulsion technique (o/w) only differed in the helper lipid composition: squalene, cholesterol, squalane or no helper lipid. Niosomes and nioplexes elaborated upon the addition of pCMS-EGFP reporter plasmid were characterized in terms of size, zeta potential and polydispersity index. The capacity of the niosomes to condense, release and protect the DNA against enzymatic degradation was evaluated by agarose gel electrophoresis. In vitro experiments were carried out to evaluate transfection efficiency and cell viability in retinal pigment epithelial cells. Moreover, uptake and intracellular trafficking studies were performed to further understand the role of the helper lipids in the transfection process. Interestingly, among all tested formulations, niosomes elaborated with squalene as helper lipid were the most efficient transfecting cells. Such transfection efficiency could be attributed to their higher cellular uptake and the particular entry pathways used, where macropinocytosis pathway and lysosomal release played an important role. Therefore, these results suggest that helper lipid composition is a crucial step to be considered in the design of niosome formulation for retinal gene delivery applications since clearly modulates the cellular uptake, internalization mechanism and consequently, the final transfection efficiency.


The effect of the combined system of hydrodynamic cavitation, ozone, and hydrogen peroxide on chlorophyll a and organic substances removal in the raw water.
Increased levels of nutrients and algae can cause drinking water problems in communities. Harmful algal blooms affect humans, fish, marine mammals, birds, and other animals. In the present study, we investigated the use of a combined system [Hydrodynamic Cavitation, Ozone (O3), and Hydrogen Peroxide (H2O2)] on the removal of Chlorophyll a and Organic substances in the raw water was investigated. The Effect of different operating conditions such as pH, cavitation time, pressure, distance, flow rate, ozone dose, and hydrogen peroxide concentration was studied. Utilizing the Taguchi design method, experiments were planned and optimized. The combined system treatment yielded a maximum reduction in Chlorophyll a and Total Organic Carbon (TOC) at an optimum condition of pH 5, cavitation pressure 5 bar, flow rate of 1 m3/h, a distance of 25 cm from the orifice plate, O3 3 g/h and 2 g/l of H2O2 concentrations. The most efficient factor in the degradation of TOC and Chlorophyll a, was cavitation pressure based on the percentage contributions of each parameter (38.64 percent and 35.05 percent, respectively). H2O2 was found to have the most negligible impact on degradation efficiency (4.24 percent and 4.11 percent, respectively).


Trans-ACPD inhibits cAMP formation via a pertussis toxin-sensitive G-protein.
In primary cultured striatal neurons we found that (+-)-trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) could inhibit forskolin-induced cAMP formation in a dose-dependent manner (EC50 156 +/- 38 microM, n = 5, maximal inhibition 37.8 +/- 1.2, n = 37). The trans-ACPD-induced inhibition was totally abolished in neurons preincubated with Bordetella pertussis toxin (1 microgram/ml), demonstrating the involvement of a G-protein. This is the first report in intact neurons of a glutamate metabotropic receptor negatively coupled to cAMP formation.


Impact of yttria stabilization on Tb3+ intra-shell luminescence efficiency in zirconium dioxide nanopowders.
This paper reports the observation of Tb(3+) 4f-4f emission gain in ZrO2 nanocrystals stabilized by Y2O3 as the amount of stabilizer increases from 0% to 10% mol. The nanocrystals were obtained via microwave solvothermal technology. The photoluminescence properties of as-grown samples are investigated. The possibility of biological applications of the material is tested on living organisms (mice). The result indicates the potential use of the studied material as a luminescent nanomarker.


The effect of expanded mental health benefits on treatment initiation and specialist utilization.
To measure the effects of a mental health benefit design change on treatment initiation for psychiatric disorders of employees of a large U.S.-based company. Mental health treatment administrative claims data plus eligibility information provided by the company for the years 1995-1998. We measure the effect of a change in mental health benefits consisting of three major elements: a company-wide effort to destigmatize mental illness; reduced copayments for mental health treatment; and an effort to increase access to specialty mental health providers. We identified the subsample of employees that were continuously enrolled in the company's health plan over the period 1995-1998, were between the ages of 18 and 65, and were actively employed. Our results suggest that the combined effect of destigmatization and reduced copayments led to an 18 percent increase (p<.01) in the probability of initiating mental health treatment. The results suggest that the effort to increase access to specialty providers was effective, but only for nonphysician providers: initiation at nonphysician mental health providers increased nearly 90 percent (p<.01) relative to nonspecialty providers, while use of psychiatrists declined by nearly 40 percent (p<.01). Our results suggest that the benefit change increased initiation for mental health treatment overall and encouraged the use of nonphysician specialty mental health providers.


Teratoid Wilms' tumor, an important variant of nephroblastoma.
The teratoid histologic variant of Wilms' tumor is rare, with only 15 prior reported cases. We review these and report an additional case in which a cytogenetic abnormality was identified that has not previously been reported in a teratoid Wilms' tumor. A medline search revealed 15 previously reported cases of the teratoid variant of Wilms' tumor. We summarized the characteristics of these cases with attention to radiologic appearance, stage, laterality, histology, response to chemotherapy and outcomes. Characteristic radiologic features suggesting teratoid Wilms' tumor were calcific densities and stippling, or areas of attenuation indicating adipose tissue. The majority of teratoid Wilms' tumor patients had a high tumor stage at presentation (50% stage III or greater). The incidence of bilateral tumors was 38%. Chemotherapy was administered in nine cases and in only one (11%) was there a cytoreductive response. Four deaths (25%) occurred amongst these patients. Teratoid Wilms' tumors appear to present with a high stage, increased incidence of bilaterality and have a high mortality rate. Treatment strategies should focus on total surgical extirpation, including metastatic sites when feasible, due to this entity's limited response to chemotherapy.


Probing heat and oxidation induced conformational changes of molecular chaperone artemin by excitation-emission fluorescence spectroscopy.
Artemin is a potent molecular chaperone, which protects Artemia embryos undergoing encystment against extreme environmental stresses. In the present work, we have examined the structural changes of artemin from A. urmiana upon exposure to oxidant and heat, by using CD measurements as well as excitation-emission fluorescence spectroscopy as a powerful tool for monitoring the conformational transitions and molecular interactions in proteins. We have also provided here the first document on reporting the three dimensional fluorescence spectra of a protein using ANS. Totally, the fluorescence results indicated that the microenvironments of tyrosine and tryptophan residues and the hydrophobic pockets as well as the polypeptide backbone or secondary structure of the chaperone were influenced in responses to heat and H2O2 in different degrees. Moreover, the native state of artemin did not induce a considerable exposure of the internal non-polar groups to the solvent. Besides, the excitation-emission spectra of heated artemin by ANS revealed new emission peaks at 430-450 nm when it was excited at 330 nm, which suggests probable exposure of new binding sites for hydrophobic or electrostatic interactions of the protein with ANS. The protein also showed a greater conformational sensitivity to the temperature fluctuations compared to oxidation. Here, we presented some evidence in support of the relation between artemin and its stress dependent activation in vitro and in vivo. This study can expect that the EEM fluorescence spectroscopy could provide a promising tool to study conformational transitions of proteins.


YC-1 potentiates cAMP-induced CREB activation and nitric oxide production in alveolar macrophages.
Alveolar macrophages play significant roles in the pathogenesis of several inflammatory lung diseases. Increases in exhaled nitric oxide (NO) are well documented to reflect disease severity in the airway. In this study, we investigated the effect of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a known activator of soluble guanylyl cyclase, on prostaglandin (PG)E₁ (a stable PGE₂ analogue) and forskolin (a adenylate cyclase activator) induced NO production and inducible NO synthase (iNOS) expression in rat alveolar macrophages (NR8383). YC-1 did not directly cause NO production or iNOS expression, but drastically potentiated PGE₁- or forskolin-induced NO production and iNOS expression in NR8383 alveolar macrophages. Combination treatment with YC-1 and PGE₁ significantly increased phosphorylation of the cAMP response element-binding protein (CREB), but not nuclear factor (NF)-κB activation. The combined effect on NO production, iNOS expression, and CREB phosphorylation was reversed by a protein kinase (PK)A inhibitor (H89), suggesting that the potentiating functions were mediated through a cAMP/PKA signaling pathway. Consistent with this, cAMP analogues, but not the cGMP analogue, caused NO release, iNOS expression, and CREB activation. YC-1 treatment induced an increase in PGE₁-induced cAMP formation, which occurred through the inhibition of cAMP-specific phosphodiesterase (PDE) activity. Furthermore, the combination of rolipram (an inhibitor of PDE4), but not milronone (an inhibitor of PDE3), and PGE₁ also triggered NO production and iNOS expression. In summary, YC-1 potentiates PGE₁-induced NO production and iNOS expression in alveolar macrophages through inhibition of cAMP PDE activity and activation of the cAMP/PKA/CREB signaling pathway.


Near Full-Length Genomic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF107_01B) Identified Among Men Who Have Sex with Men in Heilongjiang Province of China.
We reported a novel human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) among four epidemiologically unlinked patients through men having sex with men in Heilongjiang Province, China. It was named CRF107_01B (this is temporary as we have not received the CRF number from HIV databases). A near full-length genome phylogenetic tree showed that CRF107_01B was generated by two CRF01_AE segments that was described as cluster 5 lineage of CRF01_AE (CRF01-5) inserted into the B (Western origin) backbone. The emergence of CRF107_01B increased the complexity of HIV-1.


Adsorption, desorption and activities of acid phosphatase on various colloidal particles from an Ultisol.
Adsorption, desorption and activity of acid phosphatase on various soil colloidal particles and pure clay minerals were studied. Higher adsorption amounts and low percentage of desorption of acid phosphatase were found on fine soil clays (<0.2 microm). Electrostatic force and ligand exchange are the major driving forces that are involved in the adsorption of enzymes on soil clays. More enzyme molecules were adsorbed on soil clays in the presence of organic components. However, enzymes on organic clays were more easily released. One-third of the enzyme on goethite was adsorbed via ligand exchange process. Some other interactions, such as van der Waals force, hydrophobic force and hydrogen bonding may be more important in the adsorption of enzyme on kaolinite and the enzyme in this system cannot be easily removed. Coarse clays (0.2-2 microm) and inorganic soil clays had higher affinities for enzyme molecules than fine clays and organic clays, respectively. The activity of enzyme bound on soil clays was inhibited and the thermal stability was increased in the presence of organic matter. Data obtained in this study are helpful for a better understanding of the interactions of enzymes with inorganic and organic constituents in soil and associated environments.


Marginal zone lymphomas.
In the World Health Organization classification of tumors of hematopoietic and lymphoid tissues, the group of marginal zone lymphomas comprises three different entities, namely the extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, the nodal marginal zone B-cell, and the splenic marginal zone B-cell lymphoma (with or without circulating villous lymphocytes). This article addresses each of the marginal zone lymphomas.


Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management.
Organ and stem cell transplantation has been one of the greatest advances in modern medicine, and is the primary treatment modality for many end-stage diseases. As our population ages, so do the transplant recipients, and with that comes many new challenges. Respiratory viruses have been a large contributor to the mortality and morbidity of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Respiratory viruses are generally a long-term complication of transplantation and primarily acquired in the community. With the emergence of molecular methods, newer respiratory viruses are being detected. Respiratory viruses appear to cause severe disease in the older transplant population. Influenza vaccine remains the mainstay of prevention in transplant recipients, although immunogenicity of current vaccines is suboptimal. Limited therapies are available for other respiratory viruses. The next decade will likely bring newer antivirals and vaccines to the forefront. Our goal is to provide the most up to date knowledge of respiratory viral infections in our aging transplant population.


Use of Colchicine for Pericardial Inflammation: Risks and Toxicities-A Cautionary Tale.
Colchicine is commonly used as part of the treatment of acute and recurrent pericarditis. Neuromyopathy is a well-known, but probably underreported, side effect of colchicine. Here we present a unique case of a 56-year-old woman with recurrent episodes of colchicine-induced neuromyopathy over many years. (Level of Difficulty: Beginner.).


Synthesis of gamma-glutamylcysteine as a major low-molecular-weight thiol in lactic acid bacteria Leuconostoc spp.
Some members of lactic acid bacteria are known to synthesize glutathione (GSH) or to import it from growth medium, whereas others are not. Analysis of the genome sequences of several Leuconostoc spp. indicate the presence of the gene gshA that encodes gamma-glutamylcysteine synthetase, but not the gene gshB encoding glutathione synthetase. We report here that, in cells of Leuconostoc kimchii and Leuconostoc mesenteroides, gamma-glutamylcysteine (gamma-GC) is present in large amount, whereas GSH is not detectable. The level of gamma-GC was higher at the stationary phase than at the exponential phase. Expression of the gshA gene in Leuconostoc spp. analyzed by S1 mapping showed the increased mRNA level upon hydrogen peroxide treatment. From high-resolution S1 mapping, the transcriptional start site was mapped and the putative promoter elements were suggested. This work suggests that gamma-GC has a significant role in Leuconostoc spp. as the major low-molecular-weight thiol.


Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity.
Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.


Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options.
Studies reviewed show that lentiviral gene therapy directed either at inhibiting the synthesis of brain acetaldehyde generated from ethanol or at degrading brain acetaldehyde fully prevent ethanol intake by rats bred for their high alcohol preference. However, after animals have chronically consumed alcohol, the above gene therapy did not inhibit alcohol intake, indicating that in the chronic ethanol intake condition brain acetaldehyde is no longer the compound that generates the continued alcohol reinforcement. Oxidative stress and neuroinflammation generated by chronic ethanol intake are strongly associated with the perpetuation of alcohol consumption and alcohol relapse "binge drinking". Mesenchymal stem cells, referred to as guardians of inflammation, release anti-inflammatory cytokines and antioxidant products. The intravenous delivery of human mesenchymal stem cells or the intranasal administration of mesenchymal stem cell-generated exosomes reverses both (i) alcohol-induced neuro-inflammation and (ii) oxidative stress, and greatly (iii) inhibits (80-90%) chronic alcohol intake and relapse binge-drinking. The therapeutic effect of mesenchymal stem cells is mediated by increased levels of the brain GLT-1 glutamate transporter, indicating that glutamate signaling is pivotal for alcohol relapse. Human mesenchymal stem cells and the products released by these cells may have translational value in the treatment of alcohol-use disorders.


Erythropoietin Inhibits the Increase of Pulmonary Labile Zinc and the Expression of Inflammatory Mediators Following Subarachnoid Hemorrhage in Rats.
Aneurysmal subarachnoid hemorrhage (SAH) is a common condition with relatively poor clinical outcome. Pulmonary complication after SAH is an important contributor to poor outcome. Previous studies have shown that labile zinc and inflammatory mediators participate in many pathophysiological processes. The present study investigated the effects of SAH on the levels of labile zinc and certain proinflammatory factors in rat lung and determined the effect of erythropoietin (EPO) on the pulmonary labile zinc and the inflammatory factor after SAH in rats. Experiment 1 aimed to investigate the time course of increase of pulmonary labile zinc, wet/dry weight ratio, and the expression of inflammatory mediators after SAH. In Experiment 2, we chose the maximum time point which lung injury was maximally severity and assessed the effect of EPO on regulation of the pulmonary labile zinc, inflammatory reaction, and wet/dry weight ratio after SAH. SAH caused a gradual increase of pulmonary labile zinc as demonstrated by fluorescence staining with Zinpyr-4. The levels of TNF-α and IL-8 and the lung wet/dry weight ratios were higher in the SAH groups compared to the control group and peaked on 3 days following SAH (p < 0.05). EPO significantly reduced the pulmonary labile zinc, the inflammatory mediators, and the lung wet/dry weight ratio compared with SAH group (p < 0.05). EPO can protect lung from SAH-induced injury by attenuating pulmonary inflammation and labile zinc accumulation in vivo.


Microbial fuel cells and their electrified biofilms.
Bioelectrochemical systems (BES) represent a wide range of different biofilm-based bioreactors that includes microbial fuel cells (MFCs), microbial electrolysis cells (MECs) and microbial desalination cells (MDCs). The first described bioelectrical bioreactor is the Microbial Fuel Cell and with the exception of MDCs, it is the only type of BES that actually produces harvestable amounts of electricity, rather than requiring an electrical input to function. For these reasons, this review article, with previously unpublished supporting data, focusses primarily on MFCs. Of relevance is the architecture of these bioreactors, the type of membrane they employ (if any) for separating the chambers along with the size, as well as the geometry and material composition of the electrodes which support biofilms. Finally, the structure, properties and growth rate of the microbial biofilms colonising anodic electrodes, are of critical importance for rendering these devices, functional living 'engines' for a wide range of applications.


Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value.
Antimitochondrial antibodies (AMA) are the serologic cornerstone in the diagnosis of primary biliary cirrhosis (PBC), even if they are not detectable in a proportion of patients, notwithstanding the most sensitive and sophisticated technologies used. To fill in the serologic gap in AMA-negative PBC, there is sound evidence to consider antinuclear antibody (ANA) patterns, such as anti-multiple nuclear dots and anti-membranous/rim-like, as PBC-specific surrogate hallmarks of the disease, and their detection can be considered virtually diagnostic. Furthermore, particular ANA specificities, such as anti-gp210, anti-p62, anticentromere antibodies, and anti-dsDNA, may provide additional diagnostic and prognostic information.


EBV-positive, HHV8-negative large B-cell lymphoma with an unusual germinotropic growth pattern in an immunocompetent patient.
Clinicopathologic and cytogenetic findings of an unusual EBV+ve, HHV8-ve germinotropic lymphoma, with a nongerminal center immunophenotype occurring in an immunocompetent individual, are presented. A comprehensive literature search revealed a single report of three similar cases. These may represent a unique subset of EBV-positive large B-cell lymphomas in immunocompetent individuals.


Cosmetic and functional considerations in ptosis surgery. The elusive "perfect" result.
Correction of ptosis to achieve a fair or even good result is usually possible, but the "perfect" result is often elusive. Many factors play a part in diagnosis and repair of the ptotic lid, and these factors may enhance or inhibit the achievement of the best result. The correct operation must be selected for each type of ptosis with the realization that the best obtainable result may necessarily fall short of the elusive "perfect" result.


Complete genome sequence of the thermophilic Thermus sp. CCB_US3_UF1 from a hot spring in Malaysia.
Thermus sp. strain CCB_US3_UF1 is a thermophilic bacterium of the genus Thermus, a member of the family Thermaceae. Members of the genus Thermus have been widely used as a biological model for structural biology studies and to understand the mechanism of microbial adaptation under thermal environments. Here, we present the complete genome sequence of Thermus sp. CCB_US3_UF1 isolated from a hot spring in Malaysia, which is the fifth member of the genus Thermus with a completely sequenced and publicly available genome (Genbank date of release: December 2, 2011). Thermus sp. CCB_US3_UF1 has the third largest genome within the genus. The complete genome comprises of a chromosome of 2.26 Mb and a plasmid of 19.7 kb. The genome contains 2279 protein-coding and 54 RNA genes. In addition, its genome revealed potential pathways for the synthesis of secondary metabolites (isoprenoid) and pigments (carotenoid).


[New European medical flight safety guidelines. Their significance for the ophthalmologists].
In 1996 the new European Flight Crew Medical Requirements were finalized. The ophthalmological changes compared to the existing German standards range from the organization of evaluations to the necessary frequency of examinations. They also cover different examination techniques and different criteria for fitness. The changes in the requirements for ophthalmological fitness primarily affect ametropia, anisometropia, color vision and phoria. Knowledge of the European requirements is very important to advise pilots and any patient interested in becoming a pilot.


Effects of decapitation-stress on the phosphorylation of cortical membrane proteins.
The endogenous phosphorylation of membrane-bound proteins was studied in preparations from the cerebral cortex of rats sacrificed by immersion in liquid nitrogen or by decapitation. Compared to quick-frozen rats, samples from decapitated animals demonstrated a two-fold increase in 32P-phosphate incorporation into specific protein bands with apparent molecular weights of 56K, and 52K (designated E1 and E2) and a decreased incorporation into a phosphoprotein of 47K (designated F). The phosphorylation of two proteins (78K and 34K) in membranes from decapitated rats was found to be highly stimulated by exogenously added cyclic AMP. On the other hand, the phosphorylation of specific protein bands in preparations from quick frozen rats was minimally affected by addition of cyclic AMP. The results indicate that conditions which lead to increases in cyclic AMP levels in the brain in situ induce specific changes in phosphorylative activity, and these can be detected by assaying isolated membrane fragments in vitro.


La/LaF3 co-modified MIL-53(Cr) as an efficient adsorbent for the removal of tetracycline.
Chromium based metal-organic framework (MIL-53(Cr)) has enormous potential in the removal of organic contaminants from aqueous solutions due to its outstanding water stability, whereas its poor adsorption capacity limits the application. In this study, La/LaF3-MIL-53(Cr) was successfully synthesized by taking the advantages of La doping and LaF3 encapsulation with one-step hydrothermal method. Diverse analysis tools were utilized to verify that La not only existed in the framework, but also was loaded in the pores in the form of LaF3. The adsorption experiment results demonstrated that 0.3-La/LaF3-MIL-53(Cr) exhibited significantly improved adsorption capacity by four times compared with the pristine MIL-53(Cr) material. XPS and FTIR revealed that the affinity of La to tetracycline was significantly stronger than that of Cr and the excellent dispersion of LaF3 in the material may also be the cause of the increase in adsorption capacity. This study described a simple method to combine two different forms of modification and the modified material was potential for tetracycline adsorption.


2,6-Dichloro-1,4-benzoquinone formation from chlorination of substituted aromatic antioxidants and its control by pre-ozonation in drinking water treatment plant.
Halobenzoquinones are frequently detected as disinfection by-products in drinking water. Among identified halobenzoquinones, 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) is particularly toxic and is frequently detected in drinking water. Synthetic aromatic antioxidants discharged to source water may increase the risk of 2,6-DCBQ formation, as many studies suggest that aromatic compounds are the most likely precursors to 2,6-DCBQ. Herein, we investigated the formation of 2,6-DCBQ from chlorination of three model aromatic antioxidants, including 3-tert-butyl-4-hydroxyanisole (BHA), 2,6-di-tert-butyl-4-methylphenol (BHT) and bis(4-tert-butylphenyl)amine (BBPA). Only BBPA produced 2,6-DCBQ under chlorination, while chlorination of BHA and BHT formed α, β-unsaturated C4-dicarbonyl ring-opening products and phenolic compounds. Based on mass balance and intermediate transformation analysis, mechanisms for the formation of 2,6-DCBQ from BBPA chlorination involved hydrolysis, tert-butyl group cleavage, chlorine substitution, desamination and oxidation. Mitigating aromatic compounds will be an efficient method for 2,6-DCBQ control, such as pre-ozonation, because the intermediates involved in 2,6-DCBQ formation were aromatic compounds. Real water samples from two drinking water treatment plants (DWTPs), one with pre-ozonation (DWTP 2) and the other without pre-ozonation (DWTP1), were analyzed. The two DWTPs were built along the Yangtse river in Nanjing city. Raw water parameters from the two DWTPs, including dissolved organic carbon (DOC), UV absorbance at 254 nm (UV254) and NH3-N, indicated the water quality between these sources was similar. Pre-ozonation in DWTP 2 vanished 2,6-DCBQ in raw water. Concentrations of 2,6-DCBQ in finished water from DWTP 1 (5.69 ng/L) was higher than concentrations generated from DWTP 2 (1.31 ng/L). These results demonstrate that pre-ozonation, granular activated carbon (GAC) and quartz sand treatments at DWTP 2 remove more 2,6-DCBQ precursors than the conventional quartz sand and GAC treatments in DWTP 1. These results suggest the pre-ozonation, GAC and quartz sand treatments can help minimize concentrations of 2,6-DCBQ generated in DWTPs.


Improving Usability of the Pediatric Code Cart by Combining Lean and Human Factors Principles.
Cardiac arrests are common in hospitalized children. Well-organized code carts are needed during these events to help staff efficiently find supplies and medications for the patient. This study aimed to improve the efficiency and utilization of the code cart at a major academic pediatric medical center. This quality improvement project used a phased approach to redesign the code cart. A multidisciplinary team used Lean and Human Factors principles to improve the efficiency and intuitiveness of the redesigned cart. Nurses and respiratory therapists participated in simulations asking for certain supplies with the original and redesigned code cart and filled out surveys for feedback on each code cart. Facilitators measured retrieval times during each simulation. We performed 10 simulations with the original code cart and 13 with the redesigned code cart. Staff could find intraosseous access equipment more quickly (23.9 versus 46.4 seconds; P = 0.003). In addition, staff reported they were less likely to open the wrong drawer or grab the wrong equipment and that the redesigned code cart was overall more well organized than the original code cart. Finally, the redesigned code cart reduced the cost by over 800 dollars per full cart restock. Revising the code cart using Lean and Human Factors improves efficiency and usability and can contribute to cost savings.


The variations of mercury in sediment profiles from a historically mercury-contaminated reservoir, Guizhou province, China.
Baihua Reservoir in Guizhou Province, China, experienced serious Hg contamination from Guizhou Organic Chemical Plant (GOCP) between 1971 and 1997. However, the biogeochemical cycling of Hg in this reservoir is not well studied. Sediment cores were collected in fall 2002, spring 2003 and in spring and fall 2004. THg and MeHg concentrations in all sediment profiles ranged from 0.26 to 38.9 mg/kg and from 0.5 to 27.5 microg/kg (d.w.), respectively. The distribution of THg in sediment cores was characterized by a few peaks, which may correspond to the Hg-containing wastewater discharge history of the GOCP. The average THg concentrations in sediments cores decreased from upstream to downstream due to the deposition of particulate Hg, which is the major form of Hg in water. THg and MeHg concentrations in pore water varied from 6.1 to 5860 ng/L and from 0.3 to 15.4 ng/L, respectively, which were significantly higher than levels in the overlying water column. Average diffusive flux from sediment to water is 1642 and 36 ng/m2/day for THg and MeHg. The spatial distribution of THg in pore water from upstream to downstream showed the same trend as the sediment, but MeHg in pore water did not show a declining pattern with distance from the GOCP. These results suggested that sediments experienced serious contamination of Hg, and the contaminated sediment is an important Hg contamination source to the overlying water.


Single CuO/Cu2O/Cu Microwire Covered by a Nanowire Network as a Gas Sensor for the Detection of Battery Hazards.
In this study, a strategy to prepare CuO/Cu2O/Cu microwires that are fully covered by a nanowire (NW) network using a simple thermal-oxidation process is developed. The CuO/Cu2O/Cu microwires are fixed on Au/Cr pads with Cu microparticles. After thermal annealing at 425 °C, these CuO/Cu2O/Cu microwires are used as room-temperature 2-propanol sensors. These sensors show different dominating gas responses with operating temperatures, e.g., higher sensitivity to ethanol at 175 °C, higher sensitivity to 2-propanol at room temperature and 225 °C, and higher sensitivity to hydrogen gas at ∼300 °C. In this context, we propose the sensing mechanism of this three-in-one sensor based on CuO/Cu2O/Cu. X-ray diffraction (XRD) studies reveal that the annealing time during oxidation affects the chemical appearance of the sensor, while the intensity of reflections proves that for samples oxidized at 425 °C for 1 h the dominating phase is Cu2O, whereas upon further increasing the annealing duration up to 5 h, the CuO phase becomes dominant. The crystal structures of the Cu2O-shell/Cu-core and the CuO NW networks on the surface were confirmed with a transmission electron microscope (TEM), high-resolution TEM (HRTEM), and selected area electron diffraction (SAED), where (HR)TEM micrographs reveal the monoclinic CuO phase. Density functional theory (DFT) calculations bring valuable inputs to the interactions of the different gas molecules with the most stable top surface of CuO, revealing strong binding, electronic band-gap changes, and charge transfer due to the gas molecule interactions with the top surface. This research shows the importance of the nonplanar CuO/Cu2O layered heterostructure as a bright nanomaterial for the detection of various gases, controlled by the working temperature, and the insight presented here will be of significant value in the fabrication of new p-type sensing devices through simple nanotechnology.


Dual-promoter lentiviral system allows inducible expression of noxious proteins in macrophages.
In-depth studies of innate immunity require efficient genetic manipulation of macrophages, which is especially difficult in primary macrophages. We have developed a lentiviral system for inducible gene expression both in macrophage cell lines and in primary macrophages. A transgenic mouse strain C3H.TgN(SRA-rtTA) that expresses reverse tetracycline transactivator (rtTA) under the control of macrophage-specific promoter, a modified human Scavenger Receptor A (SRA) promoter was generated. For gene delivery, we constructed a dual-promoter lentiviral vector, in which expression of a "gene-of-interest" is driven by a doxycycline-inducible promoter and the expression of a selectable surface marker is driven by an independent constitutive promoter UBC. This vector is used for transduction of bone marrow-derived macrophage precursors. The transduced cells can be enriched to 95-99% purity using marker-specific monoclonal antibodies, expanded and differentiated into mature macrophages or myeloid dendritic cells. We also successfully used this approach for inducible protein expression in hard to transfect macrophage cell lines. Because many proteins, which are expressed by activated or infected macrophages, possess cytotoxic, anti-proliferative or pro-apoptotic activities, generation of stable macrophage cell lines that constitutively express those proteins is impossible. Our method will be especially useful to study immunity-related macrophage proteins in their physiological context during macrophage activation or infection.


Evoked potential latency change with age suggests differential aging of primary somatosensory cortex.
The latencies of the first two cortical peaks in the somatosensory evoked potential were examined in subjects of various ages. Recent work on specialization of primary sensory cortex in primates implicates the cortical site of origin of the second cortical peak, P25, in the selective sensory losses of old age. The latency of the P25 peak changed significantly with age. The latency of the preceeding N20 peak, also of cortical origin but originating from a different site, showed no significant age-related change. Sex differences were present in both N20 and P25 latencies but were independent of the age effect in the latter. Our results provide electrophysiological evidence for differential aging of anatomically separate areas of somatosensory cortex.


[Amplification methods of DNA from paraffin-embedded tissues of oral leukoplakia].
To set up a feasible method for detection of objective genes from paraffin-embedded tissues of oral leukoplakia (OLK). Twenty-five pieces of formalin-fixed, paraffin-embedded tissues of OSCC were selected and ATM gene was detected respectively by 3 methods: the microdissection-nested PCR method, proteinase K-PCR method and conventional phenol-chloroform-PCR method. The positivity rates were compared statistically. The positivity rates of these 3 methods were 84%, 52% and 64% respectively. Significant difference was found in positivity rate between the microdissection-nested PCR method and the proteinase K-PCR method (P = 0.032). The microdissection-nested PCR method merits recommendation because it is more efficient, easy to perform and has the advantage of less sample amount.


Outcomes and bleb-related complications of trabeculectomy.
To determine rates of success and complications of trabeculectomy surgery. Case series. Consecutive patients undergoing trabeculectomy by 2 surgeons between May 2000 and October 2008. By using the Wilmer Institute's billing database, we identified all patients at least 12 years of age coded as having undergone trabeculectomy between May 2000 and October 2008 by 1 of 2 glaucoma surgeons and whose surgery was not combined with another operation. From the chart, we abstracted demographic information on the patients and clinical characteristics of the eyes. The Kaplan-Meier product-limit method and Cox proportional hazard models were used to look at success rates and characteristics associated with inadequate intraocular pressure (IOP) reduction. Complications were tabulated. (1) Success rate of trabeculectomy, as determined by the achievement of each of 4 different IOP goals, with or without IOP-lowering medications; and (2) incidence of surgical complications. During the study period, 797 eyes of 634 persons underwent trabeculectomy without concurrent surgery. The success rates 4 years after surgery, with or without the use of IOP-lowering eye drops, were 70%, 72%, 60%, and 44%, for achievement of target IOP, ≤18 mmHg and ≥20% IOP reduction, ≤15 mmHg and ≥25% reduction, and ≤12 mmHg and ≥30% reduction, respectively. Increased chance of success was associated with European-derived race; use of mitomycin C (MMC); higher concentrations of MMC, when used; and higher preoperative IOP. Age and previous intraocular surgery were not associated with surgical success. Complications included worsening lens opacity in 242 of 443 phakic eyes (55%), loss of ≥3 lines of acuity (Snellen) in 161 eyes (21%), surgery for bleb-related problems in 70 eyes (8.8%), and infection occurring >6 weeks after surgery in 27 eyes (3.4%). A total of 101 eyes of 94 patients had at least 1 subsequent operation for inadequate IOP control. Trabeculectomy surgery performed by 2 experienced glaucoma specialists achieved target IOP at 4 years in 70% of those operated and was associated with progressive cataract and small risks of bleb-related complications. These results are comparable to those reported in smaller series.


Understanding systematic reviews and meta-analysis.
This review covers the basic principles of systematic reviews and meta-analyses. The problems associated with traditional narrative reviews are discussed, as is the role of systematic reviews in limiting bias associated with the assembly, critical appraisal, and synthesis of studies addressing specific clinical questions. Important issues that need to be considered when appraising a systematic review or meta-analysis are outlined, and some of the terms used in the reporting of systematic reviews and meta-analyses--such as odds ratio, relative risk, confidence interval, and the forest plot--are introduced.


Comparing the Impact of Online Ratings and Report Cards on Patient Choice of Cardiac Surgeon: Large Observational Study.
Patients may use two information sources about a health care provider's quality: online physician reviews, which are written by patients to reflect their subjective experience, and report cards, which are based on objective health outcomes. The aim of this study was to examine the impact of online ratings on patient choice of cardiac surgeon compared to that of report cards. We obtained ratings from a leading physician review platform, Vitals; report card scores from Pennsylvania Cardiac Surgery Reports; and information about patients' choices of surgeons from inpatient records on coronary artery bypass graft (CABG) surgeries done in Pennsylvania from 2008 to 2017. We scraped all reviews posted on Vitals for surgeons who performed CABG surgeries in Pennsylvania during our study period. We linked the average overall rating and the most recent report card score at the time of a patient's surgery to the patient's record based on the surgeon's name, focusing on fee-for-service patients to avoid impacts of insurance networks on patient choices. We used random coefficient logit models with surgeon fixed effects to examine the impact of receiving a high online rating and a high report card score on patient choice of surgeon for CABG surgeries. We found that a high online rating had positive and significant effects on patient utility, with limited variation in preferences across individuals, while the impact of a high report card score on patient choice was trivial and insignificant. About 70.13% of patients considered no information on Vitals better than a low rating; the corresponding figure was 26.66% for report card scores. The findings were robust to alternative choice set definitions and were not explained by surgeon attrition, referral effect, or admission status. Our results also show that the interaction effect of rating information and a time trend was positive and significant for online ratings, but small and insignificant for report cards. A patient's choice of surgeon is affected by both types of rating information; however, over the past decade, online ratings have become more influential, while the effect of report cards has remained trivial. Our findings call for information provision strategies that incorporate the advantages of both online ratings and report cards.


Parameter estimation and interval type-2 fuzzy sliding mode control of a z-axis MEMS gyroscope.
This paper reports a hybrid intelligent controller for application in single axis MEMS vibratory gyroscopes. First, unknown parameters of a micro gyroscope including unknown time varying angular velocity are estimated online via normalized continuous time least mean squares algorithm. Then, an additional interval type-2 fuzzy sliding mode control is incorporated in order to match the resonant frequencies and to compensate for undesired mechanical couplings. The main advantage of this control strategy is its robustness to parameters uncertainty, external disturbance and measurement noise. Consistent estimation of parameters is guaranteed and stability of the closed-loop system is proved via the Lyapunov stability theorem. Finally, numerical simulation is done in order to validate the effectiveness of the proposed method, both for a constant and time-varying angular rate.


Remnant liver function during surgery for extensive hepatic resection.
True functional reserve of remnant liver should be determined at the same condition that contemplated hepatectomy has been performed, and this condition can be achieved before resection by temporary clamping of the inflow vessels of hepatic lobes to be removed. Using indocyanine green (ICG), the remnant liver function (RLF) was evaluated whether or not the method can be a useful indicator for or against hepatomy. In the study of healthy dogs, the RLF proved to be a reliable indicator to prospect hepatic failure which may occur after extensive resection of the liver. Then, the method was employed in nine patients who underwent 40 to 70 per cent hepatectomy. The results indicated that the RLF with ICG during surgery, if performed under stable hemodynamics, is a beneficial tool to decide the resectability in equivocal cases.


Subacute toxicity of antimicrobial peptide S-thanatin in ICR mice.
Antibiotics are commonly used for infectious diseases and saved a lot of lives since its discovery, but the emergence of drug-resistant microorganism has brought a tremendous challenge to clinical therapy at present. Antimicrobial peptides, which are of broad antimicrobial spectrum and rare resistance development in pathogens, are expected to replace conventional antibiotics. S-thanatin, a novel antimicrobial peptide with 21 amino acid residues, was proved of significant benefit on therapy of pathogens infection. To evaluate the security of S-thanatin, its subacute toxicity was examined in ICR mice by continually intravenous injection with 125, 50, 20 mg/kg (1/4, 1/10, 1/25 LD(50)) or saline with equal volume for two weeks. Results demonstrated that neither significant difference of serum chemistry and hematology, nor pathological changes were changed in major organs caused by S-thanatin between groups. In conclusion, S-thanatin appears to be a safe antimicrobial peptide for further preclinical trials.


Discriminating between sleep and exercise-induced fatigue using computer vision and behavioral genetics.
Following prolonged swimming, Caenorhabditis elegans cycle between active swimming bouts and inactive quiescent bouts. Swimming is exercise for C. elegans and here we suggest that inactive bouts are a recovery state akin to fatigue. It is known that cGMP-dependent kinase (PKG) activity plays a conserved role in sleep, rest, and arousal. Using C. elegans EGL-4 PKG, we first validate a novel learning-based computer vision approach to automatically analyze C. elegans locomotory behavior and an edge detection program that is able to distinguish between activity and inactivity during swimming for long periods of time. We find that C. elegans EGL-4 PKG function impacts timing of exercise-induced quiescent (EIQ) bout onset, fractional quiescence, bout number, and bout duration, suggesting that previously described pathways are engaged during EIQ bouts. However, EIQ bouts are likely not sleep as animals are feeding during the majority of EIQ bouts. We find that genetic perturbation of neurons required for other C. elegans sleep states also does not alter EIQ dynamics. Additionally, we find that EIQ onset is sensitive to age and DAF-16 FOXO function. In summary, we have validated behavioral analysis software that enables a quantitative and detailed assessment of swimming behavior, including EIQ. We found novel EIQ defects in aged animals and animals with mutations in a gene involved in stress tolerance. We anticipate that further use of this software will facilitate the analysis of genes and pathways critical for fatigue and other C. elegans behaviors.


In vivo tumor surveillance by NK cells requires TYK2 but not TYK2 kinase activity.
Tyrosine kinase 2 (TYK2) is a Janus kinase (JAK) that is crucially involved in inflammation, carcinogenesis and defense against infection. The cytotoxic activity of natural killer (NK) cells in TYK2-deficient (Tyk2-/-) mice is severely reduced, although the underlying mechanisms are largely unknown. Using Tyk2-/- mice and mice expressing a kinase-inactive version of TYK2 (Tyk2K923E ), we show that NK cell function is partly independent of the enzymatic activity of TYK2. Tyk2-/- and Tyk2K923E NK cells develop normally in the bone marrow, but the maturation of splenic Tyk2-/- NK cells (and to a lesser extent of Tyk2K923E NK cells) is impaired. In contrast, the production of interferon γ (IFNγ) in response to interleukin 12 (IL-12) or to stimulation through NK cell-activating receptors strictly depends on the presence of enzymatically active TYK2. The cytotoxic activity of Tyk2K923E NK cells against a range of target cells in vitro is higher than that of Tyk2-/- NK cells. Consistently, Tyk2K923E mice control the growth of NK cell-targeted tumors significantly better than TYK2-deficient mice, showing the physiological relevance of the finding. Inhibitors of TYK2's kinase activity are being developed for the treatment of inflammatory diseases and cancers, but their effects on tumor immune surveillance have not been investigated. Our finding that TYK2 has kinase-independent functions in vivo suggests that such inhibitors will leave NK cell mediated tumor surveillance largely intact and that they will be suitable for use in cancer therapy.


Paraoxonase and arylesterase activities in adults with vitamin B12 deficiency.
The purpose of this study was to investigate paraoxonase (PON) and arylesterase (ARES) enzyme activity in adults with vitamin B12 deficiency, and specific changes in the activities of these enzymes following vitamin B12 treatment. A total of 46 patients with vitamin B12 deficiency (aged 18-82 years) and 45 healthy volunteer controls (aged 19-64 years) participated in this study. Venous blood samples were collected, and serum vitamin B12, homocysteine (HCY), methylmalonic acid, PON1, and ARES levels were measured. Paired comparison showed that pre- and post-treatment values for PON and ARES were similar between patients and controls (both P > 0.05). There was no statistically significant relationship between patients' pre-/post-treatment PON or HCY levels and serum vitamin B12 levels, compared with those of the control group (P > 0.05). The results of the present study do not support the hypothesis that the antioxidant enzymes PON and ARES have an underlying role in vitamin B12 deficiency and related hyperhomocysteinemia. Our findings suggest that PON and ARES do not play a role in the systemic effects of vitamin B12 deficiency.


Agents that increase cellular cAMP inhibit production of interleukin-2, but not its activity.
Proliferation of lectin-treated mouse thymocytes induced by the tumor promoter, 12-0-tetradecanoyl-13-acetate, is markedly inhibited by cAMP analogues, prostaglandin E and methylisobutylxanthine. Proliferation induced by interleukin-2 is resistant to inhibition by these compounds. The tumor promoter induces interleukin-2 production in a subpopulation of lectin-treated thymocytes, and production of this lymphokine is inhibited by agents that increase cellular cAMP.


Barrier wound protection decreases surgical site infection in open elective colorectal surgery: a randomized clinical trial.
Surgical site infection following colorectal surgery is a frequent and costly problem. Barrier protection at the time of this form of surgery has been used with varying results. The aim of this randomized study was to examine the efficacy of barrier retractional wound protection in the prevention of surgical site infections in open, elective colorectal surgery. One hundred thirty consecutive patients undergoing open elective colorectal resectional surgery were randomly assigned to have either barrier retractional wound protection or standard wound retraction. Patients were then followed up for a minimum of 30 days postoperatively. The primary end point was surgical site infection as defined by the Centers for Disease Control and Prevention. The secondary end point was performance of the wound protector as assessed by operating surgeons. There was a significant reduction in the incidence of incisional surgical site infections when the wound protector was used: 3 of 64 (4.7%) vs 15 of 66 (22.7%); P = .004. Most surgical site infections were diagnosed after discharge from the hospital (78%), and there was no difference in the rates of reoperation, readmission, or formal wound drainage between the 2 groups. Surgeons found the wound protector to be helpful with retraction during surgery, with 88% (7/8) adopting it as part of their standard setup. In this study the use of barrier wound protection in elective open colorectal resectional surgery resulted in a clinically significant reduction in incisional surgical site infections. Barrier wound protection of this nature should be considered routine in this type of surgery.


Engineering NLR immune receptors for broad-spectrum disease resistance.
Two recent reports by Maekawa et al. and Narusaka et al. demonstrated the transfer of a nucleotide-binding domain and leucine-rich repeat (NLR) family of immune receptors into evolutionarily diverged plants without causing adverse fitness consequences. The applications of NLRs in engineering durable and broad-spectrum resistance in plants are highlighted here.


[2,2'-Bis(di-phenyl-phosphan-yl)-1,1'-binaphthyl-κ2 P,P']di-chlorido-platinum(II) acetonitrile trisolvate.
The crystal structure (150 K) of the racemic title compound, [PtCl2(C44H32P2)]·3CH3CN, has been determined. The asymmetric unit comprises a single mol-ecule of the title compound co-crystallized with three aceto-nitrile solvent mol-ecules. Four mol-ecules are observed in the unit cell, with R and S enanti-omers present in a 2:2 ratio. Evidence of intra-molecular π-stacking is observed with no discernable inter-molecular inter-actions.


Increase of plasma renin activity after subcutaneous application of compound 48/80 in the rat.
Subcutaneous (s.c.) administration of compound 48/80 (3.0 mg/kg) to conscious rats produced a time-dependent long-lasting increase of plasma renin activity (PRA). A dose-related increase of the hematocrit was also observed after injection of compound 48/80. The onset of the hematocrit increase preceded that of PRA increase. Pretreatment with a dose of more than 20 mg/kg of histamine H1-receptor antagonists such as tripelennamine or diphenhydramine prior to the injection of compound 48/80 (3.0 mg/kg s.c.) attenuated or abolished the effects of compound 48/80 on PRA, hematocrit and plasma extravasation. Pretreatment with cimetidine (histamine H2-receptor antagonist, 40 mg/kg i.p.) had no effect on these plasma variables. The increase of PRA caused by s.c. administration of compound 48/80 was not affected by the pretreatment with propranolol (beta-adrenoceptor antagonist, 10 mg/kg i.p.), which completely inhibited the isoproterenol (0.5 mg/kg s.c.)-induced PRA increase. Administration of compound 48/80 did not induce a significant PRA increase in the nephrectomized rats although the increase of hematocrit following s.c. administration of compound 48/80 persisted despite the absence of kidneys. S.c. administration of compound 48/80 (3.0 mg/kg) led to a significant decrease of histamine content at the site of injection and to a significant increase in plasma histamine concentration without affecting arterial blood pressure. The present data suggest that s.c. administration of compound 48/80 stimulates the release of histamine from cutaneous mast cells, which cause an increase in vascular permeability to plasma protein via the stimulation of histamine H1-receptors, then leads to hypovolemia. The resulting hypovolemia may directly stimulate the juxtraglomerular cells of the kidney to release renin.


A dynamic temperature difference control recording system in shallow lake mesocosm.
The effects of climate change on shallow lakes were studied via control experiments, such as a mesocosm study. Accurate control, monitoring and recording of temperature difference are crucial for the ongoing simulation of warming mesocosm. In this article, we provide a method that can adjust automatically and allow real-time monitoring and recording of water temperature. This system is composed of three main parts: the temperature sensor DS18B20, which measures and outputs the digital temperature value; a C8051F320 microcontroller, which acquires, analyses and stores the temperature data and performs control upon start and shutdown of external heating elements; and external heating devices perform heating until the target temperature difference is achieved.•This system can maintain a certain temperature difference under gradually changing external environmental conditions.•This system can achieve real-time online monitoring of water temperature.•This system has an excellent ability to resist disturbance.


Hypothalamic melanocortin system regulates sympathetic nerve activity in brown adipose tissue.
To clarify the neuronal mechanism of the hypothalamic melanocortin system in regulating energy metabolism, we investigated the effects of centrally administered alpha-melanocyte-stimulating hormone (alpha-MSH) and agouti-related protein (AGRP), an agonist and an antagonist for the melanocortin 4 receptor (MC4-R), respectively, on the activity of sympathetic nerves innervating brown adipose tissue (BAT) and on BAT temperature. A bolus infusion of alpha-MSH (1 nmol) into the third cerebral ventricle (i3vt) significantly increased sympathetic nerve activity and elevated BAT temperature (P<0.05). The i3vt infusion of AGRP (1 nmol) gradually suppressed BAT sympathetic nerve activity and was accompanied by a significant reduction in BAT temperature (P<0.05). In conclusion, the hypothalamic melanocortin system may regulate peripheral energy expenditure, as well as thermogenesis, through its influence on BAT sympathetic nerve activity.


Refractive index spectral dependence, Raman spectra, and transmission spectra of high-purity 72Ge, 73Ge, 74Ge, 76Ge, and natGe single crystals.
The results of the precise measurement of the refractive index of stable germanium isotopes Ge72, Ge73, Ge74, and Ge76 single crystals with high enrichment and a germanium single-crystal Genat of natural isotopic composition with the Fourier-transform interference refractometry method from 1.94 to 20 μm with 0.1 cm-1 resolution and accuracy of 2×10-5 to 1×10-4 are shown. The content of 72 impurities measured by the mass spectrometric method was below 10-5-10-6 wt. %. Oxygen and carbon concentrations measured by IR spectroscopy in all crystals are within 5×1015 cm-3. All germanium crystals have a hole conductivity with specific electric resistivity of 45-50 Ohm×cm. The coefficients of the generalized Cauchy dispersion function approximating the experimental refractive index values all over the measuring range are given. The transmission and Raman spectra are also given.


Interventions in leaks and obstructions of the interatrial baffle late after Mustard and Senning correction for transposition of the great arteries.
The objective of this study was to describe the institutional experience with interventional treatment of atrial sequelae late after atrial correction for transposition of the great arteries (TGA). A retrospective observational study identified 13 long-term survivors of atrial correction for TGA (median age, 20.5 years; range, 13.8-33.0) with atrial inflow obstruction and/or interatrial defects. Balloon-expandable stents were used for relief of atrial inflow obstructions and interatrial defects closed with devices. Feasibility, periprocedural complications, residual or new obstructions or leaks at follow-up were investigated. Fourteen successful procedures were performed in 12 patients; one procedure failed. Five stents were placed for obstruction of the superior caval vein, three for obstruction of the inferior caval vein, and one for obstruction of the pulmonary venous return. Five septal occluders were implanted. Localization of the interatrial defects required atypical implantation techniques and resulted in atypical device positions. No complications occurred with stent or device implantation. There were no residual shunts through or around the septal occluders. None of the patients had new implant-related obstruction or leakage during a median follow-up of 21 months (range, 6-45). Stent implantation for obstruction of the pulmonary or systemic venous return in patients after atrial redirection for TGA is safe and effective. Follow-up suggests excellent maintenance of patency. Interatrial defects can be closed with septal occluders despite atypical defect positions in these patients. Combined use of both devices in adjacent positions is feasible. These interventions help to avoid high-risk surgery.


Modeling microbial cross-feeding at intermediate scale portrays community dynamics and species coexistence.
Social interaction between microbes can be described at many levels of details: from the biochemistry of cell-cell interactions to the ecological dynamics of populations. Choosing an appropriate level to model microbial communities without losing generality remains a challenge. Here we show that modeling cross-feeding interactions at an intermediate level between genome-scale metabolic models of individual species and consumer-resource models of ecosystems is suitable to experimental data. We applied our modeling framework to three published examples of multi-strain Escherichia coli communities with increasing complexity: uni-, bi-, and multi-directional cross-feeding of either substitutable metabolic byproducts or essential nutrients. The intermediate-scale model accurately fit empirical data and quantified metabolic exchange rates that are hard to measure experimentally, even for a complex community of 14 amino acid auxotrophies. By studying the conditions of species coexistence, the ecological outcomes of cross-feeding interactions, and each community's robustness to perturbations, we extracted new quantitative insights from these three published experimental datasets. Our analysis provides a foundation to quantify cross-feeding interactions from experimental data, and highlights the importance of metabolic exchanges in the dynamics and stability of microbial communities.


A hybrid strategy with bioresorbable vascular scaffolds and drug eluting stents for treating complex coronary lesions.
Due to the inherent limitations of current generation BVSs, complex coronary artery disease often contains BVS unsuitable segments. Our aim was to assess the feasibility of a hybrid approach using bioresorbable vascular scaffolds (BVSs) and drug-eluting stents (DESs) for the treatment of complex coronary artery lesions not suitable for a scaffolding only approach. A retrospective multicenter cohort analysis was performed on patients with complex de novo or in-stent restenosis lesions treated with a hybrid BVS (Absorb BVS, Abbott Vascular, Santa Clara, CA) and DES strategy. The primary endpoint was target lesion failure (TLF) defined as a composite of cardiac death, target-vessel myocardial infarction (MI) and target lesion revascularization (TLR). A total of 98 patients (105 lesions) were treated with the hybrid strategy. Isolated long lesions in which either proximal or distal reference vessel diameters were not suitable for BVS were an indication in 36.2% (n=38) of cases. In contrast, 28% (n=29) of lesions treated with the hybrid strategy were bifurcations in which the side branch was predominantly treated with DES (n=28). DES bailout after BVS implantation was an indication in 21.9% (n=23 lesions). The rates of type B2/C and long lesions (>28mm) were 95.2% and 74.3% respectively. The mean total BVS and DES lengths implanted were 37.5±24.1mm and 25.0±14.7mm respectively. The rate of TLF in the overall cohort of patients (median follow-up 405days [interquartile range 189-658]) was 11.4% at 1-year. This was primarily driven by TLR (9.5%), with rates of cardiac death and target vessel MI of 2.1% and 1.4% respectively. No cases of definite or probable BVS/DES thrombosis occurred. In conclusion, the use of a hybrid BVS/DES strategy was feasible and associated with acceptable outcomes at 1-year, considering the length and complexity of lesions treated. Further, larger studies with longer follow-up are needed to confirm our findings.


[Handling modern imaging procedures in a high-tech operating room].
Operating rooms are the central unit in the hospital network in trauma centers. In this area, high costs but also high revenues are generated. Modern operating theater concepts as an integrated model have been offered by different companies since the early 2000s. Our hypothesis is that integrative concepts for operating rooms, in addition to improved operating room ergonomics, have the potential for measurable time and cost savings. In our clinic, an integrated operating room concept (I-Suite, Stryker, Duisburg) was implemented after analysis of the problems. In addition to the ceiling-mounted arrangement, the system includes an endoscopy unit, a navigation system, and a voice control system. In the first 6 months (9/2005 to 2/2006), 112 procedures were performed in the integrated operating room: 34 total knee arthroplasties, 12 endoscopic spine surgeries, and 66 inpatient arthroscopic procedures (28 shoulder and 38 knee reconstructions). The analysis showed a daily saving of 22-45 min, corresponding to 15-30% of the daily changeover times, calculated to account for potential savings in the internal cost allocation of 225-450 EUR. A commercial operating room concept was evaluated in a pilot phase in terms of hard data, including time and cost factors. Besides the described effects further savings might be achieved through the effective use of voice control and the benefit of the sterile handle on the navigation camera, since waiting times for an additional nurse are minimized. The time of the procedure of intraoperative imaging is also reduced due to the ceiling-mounted concept, as the C-arm can be moved freely in the operating theater without hindering cables. By these measures and ensuing improved efficiency, the initial high costs for the implementation of the system may be cushioned over time.


Venom resistance in the hedgehog, Erinaceus europaeus: purification and identification of macroglobulin inhibitors as plasma antihemorrhagic factors.
Hedgehog (Erinaceus europaeus) plasma contains factor(s) which neutralize the hemorrhagic activity of European viper (Vipera berus) venom. These antihemorrhagic factor(s) were purified by gel filtration on Sephacryl S-200 and chromatography on Cibacron Blue Sepharose. The macroglobulin fraction obtained was characterized for proteinase inhibiting activity, molecular weight and purity by polyacrylamide gel electrophoresis and immunological cross-reactivity and was found to contain the three macroglobulin proteinase inhibitors--alpha 2-macroglobulin, alpha 2-beta-macroglobulin and beta-macroglobulin. The purified macroglobulins were totally able to neutralize Vipera berus venom hemorrhagic activity, but no distinction between them in this respect was possible.


An anatomic and biomechanic study of the wrist extensor retinaculum septa and tendon compartments.
The anatomy of the extensor retinaculum of the wrist has been described previously; the purpose of this study was to describe the specific anatomy of the septal attachments on the radius and to investigate the mechanical strength of each septal attachment on the radius and each of the 6 compartments of the extensor retinaculum. Thirty-four wrists from 24 fresh-frozen and 10 embalmed cadavers were used. First, anatomic measurements of the individual extensor retinaculum septums were performed with calipers and a 3-dimensional digitizer. Next each extensor retinaculum septum was excised as a bone-retinaculum-bone autograft and was tested in tension to failure with a materials testing machine. Finally the 6 extensor retinaculum compartments were tested to failure. Septum 1/2 had the largest radial surface area and septum 3/4 had the smallest. Septum 1/2 also was found to have the highest failure strength at 51.3 +/- 15.3 N. In compartment testing, compartments 1 and 2 had the highest overall resistance to failure and compartment 5 had the lowest. Compartment 6, which was thought to be the weakest because of clinically observed subluxation of the extensor carpi ulnaris tendon, had stronger failure data than expected. This study offers detailed analysis of the extensor retinaculum compartments and 3-dimensional anatomy of the septal attachments. Clinically this study lends insight to the strength of bone-retinaculum-bone autografts and the etiology of extensor carpi ulnaris subluxation.


Anti-inflammatory activity of four Bolivian Baccharis species (Compositae).
Hexanic, dichloromethanic, ethanolic and aqueous extracts from Baccharis obtusifolia HBK, Baccharis latifolia (R. et P.) Pers., Baccharis pentlandii D.C. and Baccharis subulata Wedd., plants used in the traditional medicine of South America have been studied for their in vitro anti-inflammatory activity in cellular systems. Calcium ionophore A23187-stimulated mouse peritoneal macrophages were validated as a source of cyclooxygenase-1 (COX-1) (prostaglandin E2, PGE2) and 5-lipoxygenase (5-LOX) (leukotriene C4, LTC4), and mouse peritoneal macrophages stimulated with Escherichia coli lipopolysaccharide (LPS) were used for testing cyclooxygenase-2 (COX-2) (PGE2), nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) activity. Most of the extracts tested were active in all assays.


Data of a fluorescent imaging-based analysis of anti-cancer drug effects on three-dimensional cultures of breast cancer cells.
Three-dimensional (3D) cell culture is a powerful tool to study cell growth under 3D condition. To perform a simple test for anti-cancer drugs in 3D culture, visualization of non-proliferated cells is required. We propose a fluorescent imaging-based assay to analyze cancer cell proliferation in 3D culture. We used a pulse-labeling technique with a photoconvertible fluorescent protein Kaede to identify non-proliferated cells. This assay allows us to observe change in cell proliferation in 3D culture by simple imaging. Using this assay, we obtained the data of the effects of anti-cancer drugs, 5-fluorouracil and PD0332991 in a breast cancer cell line, MCF-7.


Discrete nonlinear reduction model for horizontal cell response in the carp retina.
In this paper we present a new model for the spatial behavior of the external horizontal cells in the carp retina which elucidates more precisely the mechanisms of their intercellular connections. The area and intensity effects of a brief light stimulus on the L-type response were recorded and analysed. We discovered clear nonlinearities in the behavior of the response which could not be explained by the simple summative model presently accepted. Proposed here is a new model, the spatial reduction mechanism, which explains the experimental evidences including these nonlinearities. We also present the results of a computer simulation using our new model in parallel with the actual results obtained experimentally. The physiological implications of these findings are discussed.


HeLa nuclear protein recognizing DNA termini and translocating on DNA forming a regular DNA-multimeric protein complex.
Employing an exonuclease III protection assay we detected a protein in crude HeLa nuclear extracts binding, with apparent sequence specificity, to molecular ends of adenovirus type 2 (Ad2) DNA. This protein, designated nuclear factor IV (NFIV), was purified to homogeneity and was shown to be a hetero-dimer of 72,000 and 84,000 Mr. Binding to terminal Ad2 sequences was strongly enhanced by the presence of either of the sequence-specific DNA-binding proteins nuclear factor I and nuclear factor III. These proteins appeared to function as blockades for translocation of NFIV on DNA, thus producing apparent sequence specificity. In the absence of such a blockade, NFIV moved freely, without energy input, on any double-stranded DNA forming a regular DNA-multimeric protein complex as shown by methidiumpropyl EDTA footprinting and electron microscopy. Binding is completely dependent upon the presence of molecular ends. Evidence was obtained for a two-step mechanism in which termini are recognized by NFIV and used as a starting point for subsequent translocation. The possible functions of the protein in adenovirus DNA replication and in cellular processes requiring DNA termini are discussed.


Interleukin (IL)-17 promotes macrophages to produce IL-8, IL-6 and tumour necrosis factor-alpha in aplastic anaemia.
Aplastic anaemia (AA) is thought to be an autoimmune-mediated disease with active destruction of haematopoietic cells through a T helper type 1 (Th1) cell response. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies indicate that IL-17 might be an essential effector cytokine in the T-cell mediated autoimmune process. It can drive the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6 and IL-8 by a variety of cells. The present study investigated the genetic and protein expression of IL-17 in patients with AA. The effect of IL-17 on IL-6 and IL-8 production by macrophages was also studied. AA patients showed an elevated expression of IL17A mRNA in bone marrow mononuclear cells and peripheral blood mononuclear cells. Higher IL-17 in bone marrow and peripheral blood plasma was also observed in AA patients compared with normal controls. IL-17 induced the production of IL-6 and IL-8 by macrophages both from patients with AA and normal controls. IL-17 stimulation also resulted in the production of TNF-alpha. These results suggested that elevated expression of IL-17 and IL-17-induced IL-6, IL-8 and TNF-alpha may be involved in the mechanisms of AA.


Aerosol and droplet generation in upper and lower GI endoscopy: whole procedure and event-based analysis.
Aerosol-generating procedures have become an important healthcare issue during the coronavirus disease 2019 (COVID-19) pandemic because the severe acute respiratory syndrome coronavirus 2 virus can be transmitted through aerosols. We aimed to characterize aerosol and droplet generation in GI endoscopy, where there is little evidence. This prospective observational study included 36 patients undergoing routine peroral gastroscopy (POG), 11 undergoing transnasal endoscopy (TNE), and 48 undergoing lower GI (LGI) endoscopy. Particle counters took measurements near the appropriate orifice (2 models were used with diameter ranges of .3-25 μm and 20-3000 μm). Quantitative analysis was performed by recording specific events and subtracting background particles. POG produced 1.96 times the level of background particles (P < .001) and TNE produced 2.00 times (P < .001), but a direct comparison showed POG produced 2.00 times more particles than TNE. LGI procedures produced significant particle counts (P < .001) with 2.4 times greater production per procedure than POG but only .63 times production per minute. Events that were significant relative to the room background particle count were POG, with throat spray (150.0 times, P < .001), esophageal extubation (37.5 times, P < .001), and coughing or gagging (25.8 times, P < .01); TNE, with nasal spray (40.1 times, P < .001), nasal extubation (32.0 times, P < .01), and coughing or gagging (20.0, P < .01); and LGI procedures, with rectal intubation (9.9 times, P < .05), rectal extubation (27.2 times, P < .01), application of abdominal pressure (9.6 times, P < .05), and rectal insufflation or retroflexion (7.7 times, P < .01). These all produced particle counts larger than or comparable with volitional cough. GI endoscopy performed through the mouth, nose, or rectum generates significant quantities of aerosols and droplets. Because the infectivity of procedures is not established, we therefore suggest adequate personal protective equipment is used for all GI endoscopy where there is a high population prevalence of COVID-19. Avoiding throat and nasal spray would significantly reduce particles generated from upper GI procedures.


The effects of monobromobimane on neuronal cell death in the hippocampus after transient global cerebral ischemia in rats.
Calcium accumulation and free radical formation in the mitochondria are suggested to result in opening of the mitochondrial permeability transition pore that may be an initial step in neuronal cell death. The purpose of the present study was to determine whether monobromobimane (MBM) was a possible protective agent against neuronal cell death after transient global ischemia and the swelling of isolated hippocampal mitochondria. Infusion of MBM (1 or 3 microg) to cerebral ventricles 30 min before ischemia attenuated the expression of TUNEL-labeled cells and neuronal cell death in the hippocampal CA1 region at 72 h of reperfusion dose-dependently. Treatment with MBM inhibited an increase in caspase-3-like activity at 48 h of reperfusion in the hippocampus. MBM (30-300 microM) also inhibited an enhanced swelling rate induced by Ca2+ and phenylarsineoxide in the isolated hippocampal mitochondria. These results suggest that in vivo treatment with MBM may protect against neuronal cell death through inhibition of the mitochondrial swelling and caspase-3-dependent apoptotic pathway.