The distribution and asymmetry of mammalian cell surface saccharides utilizing ferritin-conjugated plant agglutinins as specific saccharide stains.
The preparation, properties, and some applications of ferritin conjugates of two plant agglutinins, concanavalin A and Ricinus communis agglutinin, are reported. These conjugates serve as specific electron-dense stains for cell- and membrane-bound saccharide residues of the alpha-D-mannopyranosyl and beta-D-galactopyranosyl configurations, respectively, and as examples of a wide range of ferritin-plant agglutinin conjugates useful as high resolution saccharide stains. By using a technique for preparing flattened membrane specimens, it was found with a variety of mammalian cell plasma membranes (lymphocyte, lymphoma, and myeloma and normal, spontaneously and virally transformed fibroblasts) that the ferritin conjugates were localized exclusively to the exterior face of the membrane, with essentially none found on the cytoplasmic face. On the exterior face the topographical distribution of ferritin conjugates appeared to be random. The asymmetrical distribution of saccharide residues to the outer membrane face can be explained by an "assembly line" process whereby new plasma membrane is made from intracellular precursor membranes. It also suggests that the saccharide-containing components of the plasma membrane do not rotate at any appreciable rate from one membrane surface to the other.


Preliminary studies on the characterization and distribution of Staphylococcus and Micrococcus species on animal skin.
A total of 221 strains of staphylococci and 98 strains of micrococci isolated from the skins of Eastern gray squirrels, Southern flying squirrels, raccoons, opossums, squirrel monkeys, swine, sheep, horses, cattle, and dogs were characterized in a preliminary attempt to resolve their natural relationships and distribution in nature. Staphylococci demonstrating the widest host range included Staphylococcus xylosus and unnamed Staphylococcus sp. 3. Unnamed Staphylococcus sp. 2 was isolated only from sheep, Staphylococcus sp. 4 only from opossums, Staphylococcus sp. 5 only from squirrel monkeys, and Staphylococcus sp. 6 only from swine. The predominant species isolated from human skin, including S. epidermidis, S. hominis, S. haemolyticus, and S. capitis, were either not isolated or only rarely isolated from animal skin. Micrococcus varians was the predominant Micrococcus species isolated from animal skin. M. luteus was only occasionally isolated. M. lylae, M. sedentarius, M. roseus, M. kristinae, and M. nishinomiyaensis, species occasionally isolated from human skin, were not isolated from animal skin.


Peripheral blood stem cell transplantation as an alternative to bone marrow transplantation: an overview.
Stem cells capable of restoring hematopoiesis following lethal bone marrow injury circulate in the blood of many animals, including humans. When collected through leukapheresis and reinfused following high-dose chemotherapy, stem cells offer a treatment option not currently open to some patients who are unable to undergo autologous bone marrow transplantation because of tumor involvement in the pelvis, prior pelvic radiation, or intolerance to general anesthesia. After stem cell infusion, hematologic and immunologic recovery are rapid in comparison to that after autologous bone marrow reinfusion; however, in some cases platelet engraftment is slower. There is some evidence that tumor contamination in the peripheral blood is much less than in the marrow. In any event, most relapses of malignant disease occur at the site of origin and represent treatment failure rather than growth of reinfused malignant cells. Prospective controlled trials are needed to evaluate stem cell in comparison to autologous bone marrow transplantation.


Biophotoelectrochemistry of Photosynthetic Proteins.
This chapter presents biophotoelectrochemical systems where one of nature's photosynthetic proteins, such as photosystem 1 (PS1), photosystem 2 (PS2), or bacterial reaction centers, are employed to create devices for technological applications. We use recent advances in biophotoelectrodes for energy conversion and sensing to illustrate the fundamental approaches in half-cell design and characterization. The aim is to guide electrochemists and photosynthetic researchers in the development of hybrid systems interfacing photosynthetic proteins with electrodes ranging from biosensors to biophotovoltaic cells. The first part gives an overview of the photosynthetic electron transfer chain with details on photosynthetic proteins and on the properties relevant for technological applications. The second part describes and critically discusses the main applications of biophotoelectrochemical cells based on photosynthetic proteins and exposes the respective requirement in electrode design. The following and final parts present the standard methodologies for the characterization of the biophotoelectrochemical half-cells with the main objectives of enhancing our mechanistic understanding of electron transfer, charge recombination, overpotential in photocurrent generation and protein degradation processes in devices, and thus open the perspectives for novel biophotoelectrochemical concepts and their rational optimization toward practical efficiencies.


A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis.
Renal fibrosis and tubular apoptosis are common mechanisms of progressive kidney disease. In vitro studies have implicated the c-Jun amino-terminal kinase (JNK) pathway in these processes. Both of the major JNK isoforms, JNK1 and JNK2, are expressed in the kidney, but their relative contribution to JNK signaling is unknown. This study investigated the role of JNK signaling in renal fibrosis and tubular apoptosis in the unilateral ureteral obstruction model using two different approaches: (1) Mice that were deficient in either JNK1 or JNK2 and (2) a specific inhibitor of all JNK isoforms, CC-401. Western blotting and immunostaining identified a marked increase in JNK signaling in the obstructed kidney, with substantial redundancy between JNK1 and JNK2 isoforms. Administration of CC-401 blocked JNK signaling in the rat obstructed kidney and significantly inhibited renal fibrosis in terms of interstitial myofibroblast accumulation and collagen IV deposition. This effect was attributed to suppression of gene transcription for the profibrotic molecules TGF-beta1 and connective tissue growth factor. CC-401 treatment also significantly reduced tubular apoptosis in the obstructed kidney. Genetic deletion of JNK1 or JNK2 did not protect mice from renal fibrosis in the unilateral ureteral obstruction model, but JNK1 deletion did result in a significant reduction in tubular cell apoptosis. In conclusion, this is the first study to demonstrate that JNK signaling plays a pathogenic role in renal fibrosis and tubular apoptosis. Furthermore, JNK1 plays a nonredundant role in tubular cell apoptosis. These studies identify the JNK pathway as a potential therapeutic target in progressive kidney disease.


Epichloe canadensis, a new interspecific epichloid hybrid symbiotic with Canada wildrye (Elymus canadensis).
Many Epichloë endophytes found in cool-season grasses are interspecific hybrids possessing much or all of the genomes of two or three progenitors. Here we characterize Epichloë canadensis sp. nov., a hybrid species inhabiting the grass species Elymus canadensis native to North America. Three distinct morphotypes were identified that were separated into two groups by molecular phylogenetic analysis. Sequence analysis of the translation elongation factor 1-α (tefA) and β-tubulin (tubB) genes revealed two copies in all isolates examined. Phylogenetic analyses indicated that allele 1 of each gene was derived from Epichloë amarillans and allele 2 from Epichloë elymi. This is the first documentation of an interspecific hybrid endophyte derived from parents of strictly North American origins. Alkaloid gene profiling using primers specific to genes in the peramine, loline, indole-diterpene and ergot alkaloid pathways may indicate chemotypic variation in the ergot alkaloid and loline pathways between the assigned morphotypes. All isolates have the gene enabling the production of peramine but lack genes in the indole-diterpene biosynthesis pathway. Morphology and phylogenetic evidence support the designation of isolates from El. canadensis as a new interspecific hybrid species.


Risk evaluation and mitigation strategies for older adults with persistent pain.
The U.S. Food and Drug Administration issued Risk Evaluation and Mitigation Strategies for certain analgesic agents, but all medicines for older adults warrant risk-reduction considerations. Although not all older adults have pain, a higher prevalence of persistent pain exists in this population. Nursing actions are needed to minimize the negative impact persistent pain, analgesic agents, or both have on physical, mental, and social functioning. Practices vary considerably, ranging from failing to use analgesic agents for older adults with considerable pain to exposing them to potentially life-threatening toxicities, overdoses, or drug interactions. Older adults tend to be more vulnerable to side effects and drug interactions due to differences in drug distribution, metabolism, and elimination; thus, vigilant assessment and monitoring is needed to mitigate risks whenever analgesic agents are used. This review delineates these vulnerabilities while informing clinicians of the strategies needed to promote safe, effective use of medications when treating pain in older adults.


[Interstitial pneumonia with Sjögren's syndrome: successful treatment with steroids and an immunosuppressant].
A 44-year-old woman was admitted to our hospital complaining of dyspnea. A chest X-ray film obtained on admission showed bilaterally shrunken lungs, and peripheral bundle-like and linear shadows. A chest CT scan revealed marked thickening of bronchovascular bundles and low lung volumes. Mild dryness of the mouth, and the results of a Rose-Bengal test, Schirmer test, and sialography led to the diagnosis of primary Sjögren's syndrome. Corticosteroid pulse therapy was followed by slight improvement. To determine the pathological diagnosis and to plan further therapy, video-assisted thoracoscopic lung biopsy was done. Examination of the biopsy specimen revealed alveolitis and infiltration of lymphocytes, which suggested active interstitial pneumonia. Therapy with corticosteroids and the immunosuppressant azathioprine was followed by marked improvement.


No evidence for involvement of endogenous opioid peptides in effects of clonidine on blood pressure, heart rate and plasma norepinephrine in anesthetized rats.
Endogenous opioid peptides have been implicated in the cardiovascular depressant actions of clonidine. The effects of clonidine have therefore been examined in anesthetized rats after pretreatment with naloxone, in morphine-dependent rats to determine if cross-tolerance operates and in hypophysectomized rats to determine whether circulating beta-endorphin may play a role. In normotensive and spontaneously hypertensive rats, naloxone (2 mg/kg i.v.) did not alter the blood pressure and heart rate response curves to successive doubling doses of clonidine (0.625-10 micrograms/kg i.v.). In normotensive and spontaneously hypertensive rats made morphine-dependent (3 X 75-mg morphine pellets s.c.), the cardiovascular responses to clonidine were not inhibited but rather enhanced with a greater maximal response of blood pressure and an increase in both the slope and the maximal response of the dose-heart rate response curve. Plasma clonidine levels were similar in normotensive and spontaneously hypertensive rats and corresponding morphine-dependent rats. In hypophysectomized rats, the effect of clonidine on blood pressure was also enhanced with an increase in the maximal response. The reduction in circulating norepinephrine concentrations produced by clonidine was similar in all groups. These results do not support a role for endogenous opioid peptides in the cardiovascular actions of clonidine but do suggest that factors in addition to a reduction in sympathetic nerve activity may be operating.


Glomerular membrane attack complex is not a reliable marker of ongoing C5 activation in lupus nephritis.
Complement plays an important role in the pathogenesis of lupus nephritis (LN). With the emergence of therapeutic complement inhibition, there is a need to identify patients in whom complement-driven inflammation is a major cause of kidney injury in LN. Clinical and histopathological data were obtained retrospectively from 57 biopsies with class III, IV, and V LN. Biopsies were stained for complement components C9, C5b-9, C3c, and C3d and for the macrophage marker CD68. C9 and C5b-9 staining were highly correlated (r = 0.92 in the capillary wall). C5b-9 staining was detected in the mesangium and/or capillary wall of both active and chronic proliferative LN in all but one biopsy and in the capillary wall of class V LN in all biopsies. C5b-9 staining intensity in the tubular basement membrane correlated with markers of tubulointerstitial damage, and more intense capillary wall C5b-9 staining was significantly associated with nonresponse to conventional treatment. Glomerular C5b-9 staining intensity did not differ between active and chronic disease; in contrast, C3c and CD68 staining were associated with active disease. Evaluation of serial biopsies and comparison of staining in active and chronic LN demonstrated that C5b-9 staining persisted for months to years. These results suggest that C5b-9 staining is almost always present in LN, resolves slowly, and is not a reliable marker of ongoing glomerular C5 activation. This limits the utility of C5b-9 staining to identify patients who are most likely to benefit from C5 inhibition.


Relatives' perception of stressors and psychological outcomes - Results from a survey study.
To identify relevant stressors or resources of relatives of critically ill patients and explore their relationship with psychological outcomes. Prospective mixed-method study performed in 4 multidisciplinary ICUs of an urban academic hospital. Main relatives of consecutive patients with severe sepsis were questioned after 90days by structured interview. Quantitative data included demographic characteristics, ICU experience, Impact-of-Event Scale (posttraumatic stress) and Hospital Anxiety and Depression Scale (HADS); answers to open questions about stressors and resources were transcribed verbatim and analyzed by thematic analysis. 143/205 (70%) relatives participated. Satisfaction with communication and care was high. Experiencing a stressor predicted posttraumatic stress (p=0.014) and anxiety (p=0.019) after 90days. Most common stressors were feelings of helplessness and uncertainty. The perception of being overburdened in the ICU predicted posttraumatic stress, anxiety and depression (all p≤0.001); In addition, patient's death or survival with significant deterioration in quality of life compared to status before admission predicted depression (p=0.016). Our study confirmed a high prevalence of PICS-F among relatives of critically ill patients. Feeling overburdened and experiencing acute stressors may be related to negative psychological outcomes. In future, vulnerable relatives might be identified by a single-item screening tool on feeling overburdened.


A Case of Drug-Induced Severe Endocrinopathies: What Providers in the Emergency Department Need to Know.
The purpose of this article is to present a discussion of immune checkpoint inhibitors (ICIs) that are relatively new, yet growing, form of cancer therapy. Immune checkpoint inhibitors increase host immune response against neoplastic cells. Strengthened immunological response increases the potential for adverse events such as life-threatening endocrinopathies. The case of a 66-year-old man with metastatic melanoma treated with nivolumab and ipilimumab presented to the emergency department with marked hyperglycemia and elevated anion gap 19 days after receiving both agents is discussed. The patient received a diagnosis of immune-mediated diabetes requiring ongoing insulin even after discontinuation of ICIs. As treatment with this class of agents expands, emergency department providers will need to become familiar with the identification of their adverse reactions to provide the proper management of care.


Maternal and fetal factors in breech presentation.
The authors used ultrasound examination in an attempt to identify fetal and environmental differences between breech and vertex presentations. During a period of 13 months, 228 pregnancies with the fetus in breech position were found by routine ultrasound screening in the 33rd gestational week. Before delivery, 132 fetuses (58%) turned to vertex presentation and 96 (42%) remained in breech presentation. Fetal growth, posture, position, placental site, and amniotic fluid volume in the 33rd, 35th, and 38th gestational weeks were studied. In contrast to earlier proposed theories, no difference between the two groups (breech and vertex) was found regarding the frequency of extended fetal legs and cornual-fundal placental implantation. However, the neonates born in breech presentation had a shorter gestational age by ten days at delivery, and preterm delivery was more common. At birth, the breech neonates weighed 4.9% less than their vertex controls in relation to gestational age. In the breech group, there was an increased frequency of oligohydramnios, contracted pelvis, and uterine and fetal malformations. These conditions occurred only in 15% of the breech pregnancies; in the remaining 85%, no single cause of the breech presentation could be identified.


IS1491 from Pseudomonas alcaligenes NCIB 9867: characterization and distribution among Pseudomonas species.
A new insertion sequence, IS1491, has been cloned and sequenced. The 2489-bp IS1491 was isolated from a Pseudomonas alcaligenes NCIB 9867 (strain P25X) 4.8-kb PstI chromosomal fragment. IS1491 is flanked by an imperfect inverted repeat of 23 bp and carries two overlapping open reading frames, ORF1 and ORF2. Both ORF1 and ORF2 displayed homology to the IstA-like and IstB-like transposases encoded by the IS21 family of insertion sequences, which include two IS elements previously isolated from P. alcaligenes P25X, IS1474, and IS1475 (Yeo, C. C., and Poh, C. L. (1997). FEMS Microbiol. Lett. 149, 257-263). Transposition assays showed that IS1491 transposed at a frequency of approximately 1.4 x 10(-6). Transposition of IS1491 into the target pRK415 replicon was observed but when ORF2 was disrupted, a fusion between the donor and target replicons was detected. IS1491-like sequences were detected in total DNA of Pseudomonas putida NCIB 9869 (strain P35X), Pseudomonas aeruginosa, Pseudomonas stutzeri, Pseudomonas syringae, Pseudomonas mendocina, Comomonas acidovorans, and Comomonas testosteroni by hybridization with IS1491 DNA.


[Is obesity a real risk factor in cardiosurgical procedures?].
Obesity is generally presented to be a risk factor in surgical procedures including the cardiac ones. The aim of this work was to conduct a retrospective study comparing surgical results of the cardiosurgical procedures depending on each patient's body mass index data (BMI). All 4266 patients operated by our team during 1998-2002 have been included in the study. The patient subjects were allocated in 5 groups according to their individual BMIs. Preoperative, peroperative and postoperative data of all groups were compared. There were no significant differences in the preoperative and peroperative data between the groups. The postoperative results showed no statistical differences between the individual groups, indicating a trend towards better results in the groups with higher BMIs. On the contrary, the results of the group with the BMI of less than 20 kg/m2 were the worst, however they were also of no statistical significance. The restrospective study did not prove the obesity to be a risk factor in cardiosurgical procedures. On the contrary, it suggested the BMI of less than 20 kg/m2 to be a risk factor.


Modulation of H3.3 chromatin assembly by PML: A way to regulate epigenetic inheritance.
Although the promyelocytic leukemia (PML) protein is renowned for regulating a wide range of cellular processes and as an essential component of PML nuclear bodies (PML-NBs), the mechanisms through which it exerts its broad physiological impact are far from fully elucidated. Here, we review recent studies supporting an emerging view that PML's pleiotropic effects derive, at least partially, from its role in regulating histone H3.3 chromatin assembly, a critical epigenetic mechanism. These studies suggest that PML maintains heterochromatin organization by restraining H3.3 incorporation. Examination of PML's contribution to H3.3 chromatin assembly in the context of the cell cycle and PML-NB assembly suggests that PML represses heterochromatic H3.3 deposition during S phase and that transcription and SUMOylation regulate PML's recruitment to heterochromatin. Elucidating PML' s contributions to H3.3-mediated epigenetic regulation will provide insight into PML's expansive influence on cellular physiology and open new avenues for studying oncogenesis linked to PML malfunction.


Care transitions: a leverage point for safe and effective medication use in older adults--a mini-review.
Older adults often face challenges as they transition out of the acute care hospital, especially with regard to adhering to their medications. In this narrative review, we discuss medication adherence in older adults across the continuum of care, describing reasons for nonadherence, methods to assess adherence and tools to improve adherence, with particular focus on emerging techniques and technologies. Taking steps at care transitions to assess medications and foster adherence to the medication regimen can increase the safety of older adults following hospitalization.


Macrophages as a Cell-Based Therapy for Liver Disease.
Liver failure arising from acute and chronic liver disease is an unmet clinical need that urgently requires novel therapeutic options in addition to orthotopic liver transplantation. Cell therapies offer new strategies to recover liver function through the reconstitution of healthy parenchyma and resolution of tissue pathology. Macrophages are professional phagocytes that comprise a key part of the innate immune system providing an important defense mechanism against invading pathogens. Macrophages are an inherently diverse cell type with respect to ontogeny, tissue distribution, phenotype, and function. The ability of macrophages to afford innate immunity, efficiently scavenge apoptotic/necrotic cells, and modulate local tissue microenvironment makes them an attractive cell therapy candidate for various diseases. This review aims to outline the rationale and utility of macrophages to serve as a potential cell therapy for liver disease.


Cognitive and neural mechanisms underlying false memories: misinformation, distortion or erroneous configuration?
Errors can affect our memory, yet even when there are gaps in our recollection of events, memory often serves us fairly well. Memory formation involves at least three different sub-processes, that are regulated by an underlying neural structure. From a cognitive neuropsychological perspective, a complex process of encoding, consolidating, and retrieval is involved in remembering an event, and it might be hindered by one's emotional state, physiological response to the event itself, and misinformation. As a result, it is very likely that one may struggle to remember specifics of what happened which can increase our susceptibility to the formation of false memories. This has major implications for everyday functioning, as in the case when you mistakenly remember you took your pills when you never did, or where errors have led to false accusations about trauma or abuse, and wrongful convictions of crimes. Memories sometimes contain biases and inaccuracies that prevent them from accurately recalling events. The review will provide an updated overview of current research advances on the cognitive and neural mechanisms underlying inaccurate, distorted, or false memories.


Pathology and immunohistochemical findings of west nile virus infection in psittaciformes.
West Nile virus (WNV) infection was diagnosed in 38 psittacine birds based on histology, immunohistochemistry, and reverse transcriptase polymerase chain reaction (RT-PCR). Rosellas (Platycercus spp, n = 13), conures (Enicognathus, Aratinga, and Nandayus spp, n = 6), and lorikeets (Trichoglossus spp, n = 6) represented the most commonly affected species. Clinical signs ranged from lethargy, ruffled feathers, anorexia, and weight loss in most birds to sudden death in others. Except for mild to moderate enlargement of liver and spleen, there were no significant gross lesions at necropsy. Histopathologic findings included lymphoplasmacytic and histiocytic hepatitis, interstitial nephritis, myocarditis, splenitis, enteritis, pancreatitis, and occasionally, encephalitis. Viral antigen was detected by immunohistochemistry in 34 of 35 hearts (97.1%), 29 of 32 pancreata (90.6%), 33 of 37 kidneys (89.2%), 31 of 35 intestines (88.6%), 27 of 33 gizzards (81.8%), 8 of 10 ovaries (80%), 27 of 34 spleens (79.4%), 30 of 38 livers (78.9%), 23 of 32 lungs (71.9%), 21 of 31 proventriculi (67.7%), 14 of 21 adrenals (66.7%), 10 of 16 testes (62.5%), 17 of 30 brains (56.7%), 15 of 27 skins (55.5%), 3 of 6 oviducts (50%), 15 of 34 skeletal muscles (44.1%), 11 of 27 crop or esophagus (40.7%), and 1 of 6 thymuses (16.7%). Kidney was positive for WNV by RT-PCR in all the cases tested. In conclusion, Psittaciformes are susceptible to West Nile virus infection, and WNV infections are often associated with nonspecific clinical signs and widespread viral distribution in this order of birds.


Histologic evaluation of response to implantation of polyvinilidine plates in dogs and rats.
The effect of implantation of polyvinilidine spinal plates was studied when placed on spinous processes of 11 mixed breed dogs and when placed within the thoracolumbar musculature of 12 male white rats. Specimens were also obtained from soft tissues adjacent to polyvinilidine plates 2 to 3 months after clinical surgery to repair spinal subluxations in three dogs. A similar pattern of dense, organized fibrous tissue interspersed with focal congregations of lymphocytes, plasma cells, and multinucleated giant cells was observed in the dog experiment, rat experiment, and in all clinical cases. Birefringent debris with polarization patterns identical to small slivers of polyvinilidine was associated with the observed reactions. It would appear that either a chemical or physical characteristic of the plates elicited this foreign body reaction. Grooving the inner surface of the plates, which is performed to increase the friction grip when applied to spinous processes, may make the surface texture of the plate more reactive or it may predispose the surface of the plate to minute fragmentation ("wear products").


PET/CT characterization of fibroosseous defects in children: 18F-FDG uptake can mimic metastatic disease.
The purpose of this study was to characterize the anatomic appearance and metabolic activity of nonossifying fibromas, fibrous cortical defects, and cortical desmoids on PET/CT images. Over a 14-month period, we identified eight nonossifying fibromas, four fibrous cortical defects, and two cortical desmoids in 330 children who underwent PET/CT for the evaluation of a known or suspected malignancy. CT, conventional radiography, MRI, or clinical follow-up was used to confirm the diagnoses of these fibroosseous lesions. Eleven of the 14 children underwent multiple PET/CT examinations; thus, 34 studies were included. The lesions showed variable metabolic activity as indicated by 18F-FDG uptake: 19 PET/CT examinations showed lesions with mild 18F-FDG uptake, eight showed moderate 18F-FDG uptake, and seven showed intense uptake. When PET reveals metabolically active osseous abnormalities in children who are at risk for bone metastases, benign fibroosseous lesions should be considered in the differential diagnosis before additional diagnostic procedures are undertaken. Benign fibroosseous lesions may be metabolically active and thus mimic metastatic osseous disease in children with underlying malignancies. Correlative CT or other anatomic imaging can confirm the benign nature of these lesions.


Estimating gene networks from gene expression data by combining Bayesian network model with promoter element detection.
We present a statistical method for estimating gene networks and detecting promoter elements simultaneously. When estimating a network from gene expression data alone, a common problem is that the number of microarrays is limited compared to the number of variables in the network model, making accurate estimation a difficult task. Our method overcomes this problem by integrating the microarray gene expression data and the DNA sequence information into a Bayesian network model. The basic idea of our method is that, if a parent gene is a transcription factor, its children may share a consensus motif in their promoter regions of the DNA sequences. Our method detects consensus motifs based on the structure of the estimated network, then re-estimates the network using the result of the motif detection. We continue this iteration until the network becomes stable. To show the effectiveness of our method, we conducted Monte Carlo simulations and applied our method to Saccharomyces cerevisiae data as a real application.


Secondary structure formation during RNA synthesis.
We observed the secondary structures that formed in an RNA molecule during its synthesis. Some of the secondary structures seen in nascent chains were observed to form, then to dissociate in favor of an alternative structure, and then to reform, as chain growth continued. The results show that secondary structures in an RNA molecule are in a state of dynamic equilibrium, and that the extension of a sequence by chain growth, or the reduction of a sequence by processing, may result in significant changes in the secondary structures that are present.


Two GPX-like proteins from Lycopersicon esculentum and Helianthus annuus are antioxidant enzymes with phospholipid hydroperoxide glutathione peroxidase and thioredoxin peroxidase activities.
This study investigated the enzymatic function of two putative plant GPXs, GPXle1 from Lycopersicon esculentum and GPXha2 from Helianthus annuus, which show sequence identities with the mammalian phospholipid hydroperoxide glutathione peroxidase (PHGPX). Both purified recombinant proteins expressed in Escherichia coli show PHGPX activity by reducing alkyl, fatty acid and phospholipid hydroperoxides but not hydrogen peroxide in the presence of glutathione. Interestingly, both recombinant GPXle1 and GPXha2 proteins also reduce alkyl, fatty acid and phospholipid hydroperoxides as well as hydrogen peroxide using thioredoxin as reducing substrate. Moreover, thioredoxin peroxidase (TPX) activities were found to be higher than PHGPX activities in terms of efficiency and substrate affinities, as revealed by their respective Vmax and Km values. We therefore conclude that these two plant GPX-like proteins are antioxidant enzymes showing PHGPX and TPX activities.


Chemosensory coding by neurons in the coeloconic sensilla of the Drosophila antenna.
Odor coding is based on the diverse sensitivities and response properties of olfactory receptor neurons (ORNs). In the Drosophila antenna, ORNs are housed in three major morphological types of sensilla. Although investigation of the Drosophila olfactory system has been expanding rapidly, the ORNs in one of these types, the coeloconic sensilla, have been essentially unexplored. We define four functional types of coeloconic sensilla through extracellular physiological recordings. Each type contains at least two neurons, with a total of at least seven distinct ORN classes that vary remarkably in their breadth of tuning. Analysis of 315 odorant-ORN combinations reveals how these neurons sample odor space via both excitation and inhibition. We identify a class of neurons that is narrowly tuned to small amines, and we find humidity detectors that define a cellular basis for hygroreception in Drosophila. The temporal dynamics of responses vary widely, enhancing the potential for complexity in the odor code. Molecular and genetic analysis shows that a broadly tuned ORN, antennal coeloconic 3B (ac3B), requires the odor receptor gene Or35a for its response in vivo. The activity of ac3B is not required for the response of the other ORN within that sensillum, ac3A. The functional analysis presented here, revealing a combination of highly specialized neurons and a broadly tuned ORN, along with the ancient origin of coeloconic sensilla, suggests that the specificities of these ORNs may reflect basic needs of an ancestral insect.


[Stability and distribution of oxytetracycline HCI during manufacture and storage of pig feed under field conditions].
The distribution of oxytetracycline hydrochloride in two batches of 4,000 kg of pig-rearing pellets (400 ppm) was studied. The stability of oxytetracycline in this feed was also determined. The concentration of oxytetracycline in the feed was determined by high pressure liquid chromatography. The premix contained more oxytetracycline (27 per cent) than the proportion stated. The results show that the first 1,000 kg of feed contained less (350 mg/kg) oxytetracycline than the other 7,000 kg (435 mg/kg). After producing 8,000 kg of feed with oxytetracycline, 4,000 kg of feed not containing oxytetracycline was produced. Still, this feed was found to contain 13 mg/kg of oxytetracycline. When the feed was stored for 150 days at a temperature of from 1 to 2 degrees C and again for 270 days at 20 to 25 degrees C, it contained 86.5 per cent of the oxytetracycline present after production of the feed.


Prophylaxis of macular edema after cataract surgery in diabetic patients, topical Nepafenac versus intravitreal Ranibizumab.
To compare effect of topical Nepafenac versus intravitreal Ranibizumab on macular thickness after cataract surgery in diabetic patients with no preoperative macular edema. A prospective randomized controlled study recruited diabetic patients with visually significant cataract and no diabetic macular edema (DME). Patient underwent uncomplicated phacoemulsification with IOL implantation and were randomly assigned to receive post-operative topical Nepafenac, intra-operative intravitreal Ranibizumab, or no prophylactic treatment. Changes in subfoveal and perifoveal macular thickness were assessed by SD-OCT. The mean central macular thickness showed a significant increase in all study groups 1 week and 1 month postoperative when compared to baseline. At 3 months postoperative, there was a significant difference between Nepafenac and Control group (p = 0.017), Ranibizumab and Control groups (p = 0.009) with no significant difference between Nepafenac and Ranibizumab group (p = 0.545) regarding CMT. Comparable results could be detected as regarding peri-foveal macular thickness changes. Concerning BCVA, there was a significant difference between topical Nepafenac/control (p = 0.001) and intravitreal Ranibizumab/control (p = 0.004) at 1-week visit. No significant difference in BCVA was observed between Nepafenac and Ranibizumab group throughout the whole study period. In postoperative visits, cystoid macular edema occurred in three patients (7.9%) in Nepafenac group, one patient (2.7%) in Ranibizumab group, and seven patients (17.07%) in control group. Both postoperative topical Nepafenac and intra-operative intra-vitreal Ranibizumab are effective adjunctive to phacoemulsification in diabetic patients for prophylaxis of macular edema.


Simultaneous analysis of PhIP, 4'-OH-PhIP, and their precursors using UHPLC-MS/MS.
A novel method allowing simultaneous analysis of PhIP, 4'-OH-PhIP, and their precursors (phenylalanine, tyrosine, creatine, creatinine, glucose) has been developed as a robust kinetic study tool by using ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A direct hydrochloric acid (HCl) extraction was applied to achieve the simultaneous extraction of all seven analytes, with the mean recoveries ranging from 60% to 120% at two concentration levels. Then, an Atlantis dC18 column selected from four different chromatographic columns was ultimately used to separate these compounds within 15 min. The limits of detection range of allseven analytes were calculated as 0.14-325.00 μg L(-1). The intra- and interday precision of the proposed method were less than 15.4 and 19.9%, respectively. The proposed method was successfully applied to depict the kinetic profiles of PhIP, 4'-OH-PhIP, and their precursors in pork model, reducing the analysis time and cost in the kinetic study.


[Hyperspectral Band Selection Based on Spectral Clustering and Inter-Class Separability Factor].
With the development of remote sensing technology and imaging spectrometer, the resolution of hyperspectral remote sensing image has been continually improved, its vast amount of data not only improves the ability of the remote sensing detection but also brings great difficulties for analyzing and processing at the same time. Band selection of hyperspectral imagery can effectively reduce data redundancy and improve classification accuracy and efficiency. So how to select the optimum band combination from hundreds of bands of hyperspectral images is a key issue. In order to solve these problems, we use spectral clustering algorithm based on graph theory. Firstly, taking of the original hyperspectral image bands as data points to be clustered , mutual information between every two bands is calculated to generate the similarity matrix. Then according to the graph partition theory, spectral decomposition of the non-normalized Laplacian matrix generated by the similarity matrix is used to get the clusters, which the similarity between is small and the similarity within is large. In order to achieve the purpose of dimensionality reduction, the inter-class separability factor of feature types on each band is calculated, which is as the reference index to choose the representative bands in the clusters furthermore. Finally, the support vector machine and minimum distance classification methods are employed to classify the hyperspectral image after band selection. The method in this paper is different from the traditional unsupervised clustering method, we employ spectral clustering algorithm based on graph theory and compute the interclass separability factor based on a priori knowledge to select bands. Comparing with traditional adaptive band selection algorithm and band index based on automatically subspace divided algorithm, the two sets of experiments results show that the overall accuracy of SVM is about 94. 08% and 94. 24% and the overall accuracy of MDC is about 87. 98% and 89. 09%, when the band selection achieves a relatively optimal number of clusters using the method propoesd in this paper. It effectively remains spectral information and improves the classification accuracy.


Ostertagia nianqingtanggulaensis Kúng & Li, 1965 (Nematoda: Trichostrongyloidea) from sheep and goats at high altitudes in Nepal.
The trichostrongyloid nematode Ostertagia nianqingtanggulaensis Kúng & Li, 1965, previously recorded only from sheep in Tibet, is redescribed and is shown to be a common parasite of both sheep and goats at higher altitudes in the Himalayan foothills of western Nepal. Herbage examination indicated that infective larvae can overwinter on snow covered slopes. Use of tracer animals confirmed that migratory flocks are exposed to infection when grazing on alpine pastures during the summer months. In contrast, nearby non-migratory flocks kept at lower altitudes did not harbour O. nianqingtanggulaensis and tracer animals grazed with these flocks did not become infected with this species.


Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.
The effects of niflumic acid and flufenamic acid, two nonsteroidal anti-inflammatory agents known to block anion transport in red blood cells, on Ca2(+)-activated Cl- currents (ICl(Ca)) in Xenopus oocytes were examined. Both compounds reversibly inhibited ICl(Ca), elicited in response to depolarizing voltage steps, in a dose-dependent manner, with no effect on the shape of the current-voltage curve. The apparent inhibition constant for niflumic acid was 17 microM, whereas that for flufenamic acid was 28 microM. Niflumic acid also inhibited ICl(Ca) elicited by bath application of Ca2+ to oocytes permeabilized using the Ca2+ ionophore A23187, demonstrating that the inhibition of ICl(Ca) is due to a direct interaction with the Cl- channel, rather than by interference with Ca2+ entry through voltage-dependent Ca2+ channels. In addition to their use in the elimination of ICl(Ca) as a possible source of artifact when Xenopus oocytes are used as an expression system for exogenous ion channels and receptors, it is expected that these two compounds will find use as potent anion channel blockers.


Effects of different extremely low-frequency electromagnetic fields on osteoblasts.
It is well known that the extremely low-frequency electromagnetic field (EMF) can promote the healing of bone fractures, but its mechanism remains poorly understood. The purpose of this study was to examine the response of neonatal rat calvarial bone cells to the rectangular electromagnetic field (REMF), triangular electromagnetic field (TEMF), sinusoidal electromagnetic field (SEMF), and pulsed electromagnetic field (PEMF). The stimulatory effects of EMF were evaluated by the proliferation (methyltetrazolium colorimetric assay), differentiation (alkaline phosphatase (ALP) activity), and mineralization (area of mineralized nodules of the cells). REMF treatment of osteoblasts increased cellular proliferation and decreased ALP activity (p < 0.05). TEMF had an accelerative effect on the cellular mineralized nodules (p < 0.05). SEMF treatment of osteoblasts decreased the cellular proliferation, increased ALP activity, and suppressed mineralized nodules formation (p < 0.05). PEMF promoted the proliferation of osteoblasts, inhibited their differentiation, and increased the mineralized nodules formation (p < 0.05). Moreover, the effects of PEMF on osteoblasts were concerned with the extracellular calcium, P2 receptor on the membrane, and PLC pathway, but the response of osteoblasts on SEMF was only related to PLC pathway. The results suggested that the waveforms of EMF were the crucial parameters to induce the response of osteoblasts.


A patent review of the antimicrobial applications of lectins: Perspectives on therapy of infectious diseases.
Patents of lectins with antiviral, antibacterial and antifungal applications were searched and reviewed. Lectins are proteins that reversibly bind to specific carbohydrates and have the potential for therapy of infectious diseases as biopharmaceuticals, biomedical tools or in drug design. Given the rising concerns over drug resistance and epidemics, our patent review aims to add information, open horizons and indicate our view of the future perspectives about the antimicrobial applications of lectins. Patents with publications until December 2020 were retrieved from Espacenet using defined search terms and Boolean operators. The documents were used to identify the geographical and temporal distribution of the patents, characterize their lectins, and classify and summarize their antiviral, antibiotic and antifungal applications. Lectins are promising antiviral agents against viruses with epidemics and drug resistance concerns. Mannose-binding lectins were the most suggested antiviral agents since glycans with mannose residues are commonly involved in viral entry mechanisms. They were also immobilized onto surfaces to trap viral particles and inhibit their spread and replication. Many patents described the extraction, isolation, amino acid and nucleotide sequences, and expression vectors of lectins with antibiotic and/or antifungal activities in terms of MIC and IC50 for in vitro assays. The inventions also included lectins as biological tools in nanosensors for antibiotics susceptibility tests, drug-delivery systems for the treatment of resistant bacteria, diagnostics of viral diseases and as a vaccine adjuvant. Although research and development of new medicines is highly expensive, antimicrobial lectins may be worth investments given the emergence of epidemics and drug resistance. For this purpose, less invasive routes should be developed as alternatives to the parenteral administration of biologics. While anti-glycan neutralizing antibodies are difficult to develop due to the low immunogenicity of carbohydrates, lectins can be produced more easily and have a broad-spectrum activity. Protein engineering technologies may make the antimicrobial applications of lectins more successful.


Traditional neurotherapeutics approach intended for direct nose to brain delivery.
Nasal delivery systems have a significant role in Persian traditional medicine. Most of them were utilized for central nervous system (CNS)-related disorders. In modern medicine, nasal drug delivery systems for brain delivery are highly regarded. Despite recent advances in drug delivery to the (CNS), delivery of therapeutics to the brain remains a major challenge because of the blood brain barrier (BBB). There are several mechanisms which regulate the drug transfer across the BBB. Local administration methods of therapeutic agents are often associated with adverse events, while the intranasal pathway has been suggested as a non-invasive alternative route to deliver drugs to the brain. This route can bypass the BBB and deliver drug molecules directly to the CNS. There are different nasal formulations have been addressed in Persian traditional pharmacopeias. The present review attempt to explore the famous and practical Qarabadin to find ancient nasal dosage forms. With an explore on traditional herbs in google scholar, scopus and science direct, we have found some original and review articles which have demonstrated our findings on the use of traditional herbs for CNS disorders. Four encyclopedia of multi-component formulations, including Qarabadin Salehi (1766), Qarabadin kabir (1781),Qarabadin Ghaderi (18th century), and Qarabadin Azam (1853), were searched for nasal formulations having CNS-related indications. Formulations were categorized based on dosage forms, and also, diseases which they were suggested for. While the names of illnesses were in ancient terminology of Traditional Medicine, they were translated to modern medical terminology by comparing their definitions, signs, and symptoms from two medical systems. Typical samples of each dosage form have been mentioned with details like amount of ingredients, scientific names of plants, and considerations pertaining to preparation or usage. Among all traditional nasal formulations, seven types were found that is used for sicknesses relating to CNS including Saoot, Nafookh, Atoos, Nashoogh, Shamoom, Lakhlakheh, and Bakhoor. The findings of this study reveal the physicochemical characteristics of each formulation, route of administration, and type of disease which they are suitable and also present some famous formulations.


Realization of Rapid Large-Size 3D Printing Based on Full-Color Powder-Based 3DP Technique.
The powder-based 3DP (3D printing) technique has developed rapidly in creative and customized industries on account of it's uniqueness, such as low energy consumption, cheap consumables, and non-existent exhaust emissions. Moreover, it could actualize full-color 3D printing. However, the printing time and size are both in need of upgrade using ready printers, especially for large-size 3D printing objects. Given the above issues, the effects of height and monolayer area on printing time were explored and the quantitative relationship was given in this paper conducted on the specimens with a certain gradient. On this basis, an XYX rotation method was proposed to minimize the printing time. The mechanical tests were conducted with three impregnation types as well as seven printing angles and combined with the characterization of surface structure based on the scanning electron microscope (SEM) digital images to explore the optimum parameters of cutting-bonding frame (CBF) applied to powder-based 3D printing. Then, four adhesives were compared in terms of the width of bonded gap and chromatic aberration. The results revealed that ColorBond impregnated specimens showed excellent mechanical properties which reached maximum when printed at 45° to Z axis, and α-cyanoacrylate is the most suitable adhesive to bond full-color powder-based models. Finally, an operation technological process was summarized to realize the rapid manufacturing of large-size full-color 3D printed objects.


Visible and Near-Infrared Emission from Lanthanoid β-Triketonate Assemblies Incorporating Cesium Cations.
The reaction of the β-triketonate ligands tris(4-methylbenzoyl)methanide and tribenzoylmethanide with the trivalent lanthanoids Eu3+, Er3+, and Yb3+ in the presence of Cs+ afforded polymeric structures where the repeating units are represented by bimetallic tetranuclear assemblies of formulation {[Ln(Cs)(β-triketonate)4]2}n. The only exception is the structure formed by the reaction of tris(4-methylbenzoyl)methanide, Yb3+, and Cs+, which yielded a polymeric assembly where the repeating units are mononuclear Yb3+ complexes bridged by Cs+ cations. Photophysical measurements on the obtained materials confirmed efficient sensitization from the ligand excited states to the 4f* excited states of the three lanthanoids. According to transient absorption data, Er3+ and Yb3+ are sensitized via energy transfer from the triplet state of the β-triketonate ligands. On the other hand, energy transfer to Eu3+ seems to occur via an alternative pathway, possibly directly via the singlet state or through ligand to metal charge transfer states. The emission measurements confirm efficient sensitization for all three lanthanoids and bright near-infrared emission for Er3+ and Yb3+, a characteristic that seems to be linked to the specific chemical structure of the β-triketonate ligands.


Hyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns.
Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/β-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/β-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification.


Definitions and terminology regarding child alignments, estrangement, and alienation: A survey of custody evaluators.
Parental alienation (PA) is a highly consequential family dynamic that causes harm to children and parents. While many mental health and legal professionals agree that PA is common and potentially very harmful to children, there is still the appearance that there is controversy and discord in the field. The purpose of this study was to test the extent of consensus in the field regarding the basic tenets of PA theory. Specifically, 11 key terms related to PA were identified through expert input and preliminary field-testing. An on-line survey was created specifically for the study to assess level of agreement with these key terms among custody evaluators. This profession was selected because of their high degree of training and experience with a variety of family conflict situations; 119 child custody evaluators selected as members of a professional custody evaluator listing (88% response rate) rated their endorsement of these 11 key definitions with response options including: strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree. Results revealed that roughly 80% of respondents agreed or strongly agreed with each of the 11 definitions. These results demonstrate a high degree of consensus and should guide future trainings of legal and mental health professionals to ensure a common language and understanding of this phenomenon.


Engineered Metal Oxide Nanoparticles as Fungicides for Plant Disease Control.
Metal oxide nanoparticles are considered to be good alternatives as fungicides for plant disease control. To date, numerous metal oxide nanoparticles have been produced and evaluated as promising antifungal agents. Consequently, a detailed and critical review on the use of mono-, bi-, and tri-metal oxide nanoparticles for controlling phytopathogenic fungi is presented. Among the studied metal oxide nanoparticles, mono-metal oxide nanoparticles-particularly ZnO nanoparticles, followed by CuO nanoparticles -are the most investigated for controlling phytopathogenic fungi. Limited studies have investigated the use of bi- and tri-metal oxide nanoparticles for controlling phytopathogenic fungi. Therefore, more studies on these nanoparticles are required. Most of the evaluations have been carried out under in vitro conditions. Thus, it is necessary to develop more detailed studies under in vivo conditions. Interestingly, biological synthesis of nanoparticles has been established as a good alternative to produce metal oxide nanoparticles for controlling phytopathogenic fungi. Although there have been great advances in the use of metal oxide nanoparticles as novel antifungal agents for sustainable agriculture, there are still areas that require further improvement.


Pinealectomy in agonadal infantile male rhesus monkeys (Macaca mulatta) does not interrupt initiation of the prepubertal hiatus in gonadotropin secretion.
The present study was undertaken to determine whether pineal hormones are responsible for initiation of the prepubertal hiatus in gonadotropin secretion that is observed between 2-3 months of age in the infantile male rhesus monkey. Six neonatally orchidectomized rhesus monkeys were pinealectomized at 4-6 weeks of age using a microneurosurgical technique. The time courses of circulating LH and FSH concentrations during the first 36 weeks of life in these animals were determined in weekly samples by RIA and compared to those observed in sham pinealectomized animals (n = 2) and in agonadal infantile males with an intact central nervous system (n = 3). The completeness of pinealectomy was verified by an absence of pineal rests in serial coronal sections of the brain. The absence of nocturnal elevations in circulating immunoreactive melatonin concentrations in pinealectomized monkeys was consistent with the foregoing histological findings. The developmental pattern of gonadotropin secretion in pinealectomized animals was unremarkable. Of particular interest in the context of the present question was the failure of pinealectomy to interrupt or to delay the decline in plasma LH and FSH concentrations that characteristically occurs in neonatally orchidectomized monkeys between 2-8 months of age. These findings suggest that, in the rhesus monkey, the pineal gland plays no major role in mediating the onset of the inhibition of LH and FSH secretion that occurs during transition from the infantile to the prepubertal phase of development and, therefore, is not responsible for initiating the protracted delay in the advent of puberty in this higher primate.


Transcriptomic and metabolite analyses provided a new sight of 1-MCP on organic acid metabolism in peach during storage.
In this study, "Xiahui 6" peaches were treated with 10 µL/L 1-methylcyclopropene (1-MCP) for 12 h and then stored at 20°C for 9 days; the regulation of 1-MCP on organic acids during storage was investigated through transcriptomic and metabolite analyses. Results showed that 1-MCP maintained higher gene expression of malate synthesis (PpPEPC1, PpPEPC2, and PpNAD-cytMDH) at the end of storage but extremely inhibited the gene expression of malate degradation (PpNADP-cytME) during storage, resulting that malate content in treated peaches was twice that of control group at day 7. Besides, the increasement of citrate synthesis and degradation-related genes (PpmitCS, PpcytACO, PpNAD-mitIDH, and PpNADP-cytIDH) at days 3 and 5 was postponed by 1-MCP treatment, accompanied by 0.5 times higher citrate content at day 7. Our results suggested that 1-MCP has inhibitory effects on both the synthesis and degradation of organic acids; however, the inhibitory effect of 1-MCP on organic acid degradation may be greater than that on organic acid synthesis. Practical Application: This study provides a theoretical basis for the application of 1-methylcyclopropene (1-MCP) in fruit preservation.


Chemical and biological investigations of beta-oligoarginines.
In view of the important role arginine plays in living organisms as the free amino acid and, especially, as a residue in peptides and proteins, the homologous beta-homoarginines are central in our investigations of beta-peptides (Fig. 1). The preparation of beta2-homoarginine derivatives suitably protected for solution- or solid-phase peptide syntheses is described with full experimental detail (9 and 12 in Scheme 1). The readily available Fmoc-beta3 hArg(Boc)2-OH is used for manual solid-phase synthesis of beta3-oligoarginines (on Rink amide or Rink amide AM resin) either by single amino acid coupling (Scheme 3) or, much better, by dimer-fragment coupling (Scheme 4). In this way, beta3-oligoarginine amides composed of 4, 6, 7, 8, and 10 residues, both with and without fluorescein labelling, were synthesized (Schemes 2-4), purified by preparative HPLC and identified by high-resolution mass spectrometry. The free amino acids (R)- and (S)-H-beta2 hArg-OH and (S)-H-beta3 hArg-OH were tested for their ability to function as substrates for NO synthase (iNOS); the beta3-oligoarginine amides (5, 6, and 7 residues) were tested for antibacterial (against six pathogens) and hemolytic (against rat and human erythrocytes) activities. All test results were negative: none of the free beta-homoarginines induced NO formation (Fig. 3), and there was no lysis of erythrocytes (concentrations up to 100 microM; Table 1), and no significant antibiotic activity (MIC > or = 64 microg/ml; Table 2). Cell-penetration studies with the fluorescence-labelled, peptidase-resistant beta3-oligoarginine amides were carried out with HeLa cells and human foreskin keratinocytes (HFKs). The results obtained with fluorescence microscopy are: i) the longer-chain beta-oligoarginine amides (8 and 10 residues; Figs. 4-6) enter the cells and end up in the nuclei, especially in the nucleoli, irrespective of temperature (37 degrees and 4 degrees with HFKs) or pretreatment with NaN3 (with HFKs), indicating a non-endocytotic and non-energy-dependent uptake mechanism; ii) the beta-tetraarginine derivative occupies the cell surface but does not enter the cells (with HeLa); iii) the cell-growth rate of the HFKs is not affected by a 1-microM concentration of the fluorescence-labelled beta-octaarginine amide (Fig. 7), i.e., there is no antiproliferative effect. In vivo experiments with mouse skin and the beta-octaarginine derivative show migration of the beta-peptide throughout the epidermis (Fig. 8). As a contribution to understanding the mechanism, we have also studied the behavior of fluorescence-labelled beta-octa- and beta-decaarginine amides (TFA salts) towards giant unilamellar vesicles (GUVs) built of neutral (POPC) or anionic (POPC/POPG mixtures) phospholipids: the beta-oligoarginine amides bind tightly to the surface of anionic GUVs but do not penetrate the lipid bilayer (Fig. 9) as they do with living cells. In contrast, a beta-heptapeptide FL-22, which had been used as a negative control sample for the cell-penetration experiments, entered the GUVs of negative surface charge. Thus, the mechanisms of cell and GUV-model penetration appear to be different. Finally, the possible applications and implications of the 'protein transduction' by beta-oligoarginines are discussed.


Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats.
The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO)] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg) and 400 LO (400 mg/kg) and its major component, citral (240 mg/kg), on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(P)H:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5'-diphospho (UDP) glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen.


Study protocol for a prospective randomised double-blind placebo-controlled clinical trial investigating a Better Outcome with Melatonin compared to Placebo Administered to normalize sleep-wake cycle and treat hypoactive ICU Delirium: the Basel BOMP-AID study.
Delirium is frequently observed in the intensive care unit (ICU) population, in particular. Until today, there is no evidence for any reliable pharmacological intervention to treat delirium. The Basel BOMP-AID (Better Outcome with Melatonin compared to Placebo Administered to normalize sleep-wake cycle and treat hypoactive ICU Delirium) randomised trial targets improvement of hypoactive delirium therapy in critically ill patients and will be conducted as a counterpart to the Basel ProDex Study (Study Protocol, BMJ Open, July 2017) on hyperactive and mixed delirium. The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin administered at night restores a normal circadian rhythm, and that restoration of a normal circadian rhythm will cure delirium. The Basel BOMP-AID study is an investigator-initiated, single-centre, randomised controlled clinical trial for the treatment of hypoactive delirium with the once daily oral administration of melatonin 4 mg versus placebo in 190 critically ill patients. The primary outcome measure is delirium duration in 8-hour shifts. Secondary outcome measures include delirium-free days and death at 28 days after study inclusion, number of ventilator days, length of ICU and hospital stay, and sleep quality. Patients will be followed after 3 and 12 months for activities of daily living and mortality assessment. Sample size was calculated to demonstrate superiority of melatonin compared with placebo regarding the duration of delirium. Results will be presented using an intention-to-treat approach. This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use; Good Clinical Practice (GCP) or ISO EN 14155 (as far as applicable), as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal. NCT03438526. Clinical Study Protocol Version 3, 10.03.2019.


Circulation of reassortant influenza A(H7N9) viruses in poultry and humans, Guangdong Province, China, 2013.
Influenza A(H7N9) virus emerged in eastern China in February 2013 and continues to circulate in this region, but its ecology is poorly understood. In April 2013, the Guangdong Provincial Center for Disease Control and Prevention (CDC) implemented environmental and human syndromic surveillance for the virus. Environmental samples from poultry markets in 21 city CDCs (n=8,942) and respiratory samples from persons with influenza-like illness or pneumonia (n=32,342) were tested; viruses isolated from 6 environmental samples and 16 patients were sequenced. Sequence analysis showed co-circulation of 4 influenza A(H7N9) virus strains that evolved by reassortment with avian influenza A(H9N2) viruses circulating in this region. In addition, an increase in human cases starting in late 2013 coincided with an increase in influenza A H7 virus isolates detected by environmental surveillance. Co-circulation of multiple avian influenza viruses that can infect humans highlights the need for increased surveillance of poultry and potential environmental sources.


Long-term results of multiple arterial bypass conduits.
Ongoing efforts to compare percutaneous coronary intervention with coronary bypass surgery for multivessel coronary disease mandate that surgeons reevaluate best practices for coronary surgery in order to maximize long-term outcomes. This review presents recent data for the long-term outcomes of multiple arterial grafting in terms of patient selection, conduit choice, and technical considerations. Multiple arterial grafting remains poorly utilized, with fewer than 10% of cases receiving more than one arterial graft. Bilateral internal thoracic artery grafting confers superior long-term survival and freedom from reoperation over single thoracic artery with saphenous vein. Use of a second internal thoracic artery graft is advantageous in diabetic patients despite higher risk of sternal wound complications. Routine use of skeletonized grafts and Y or T grafting to allow complete revascularization allows lower early complication rates and better long-term survival. Radial artery grafts confer superior long-term survival compared with saphenous vein grafts and should be considered in patients at high risk for sternal wound complications. Multiple arterial grafting confers superior long-term outcomes in comparison with single internal thoracic artery grafting and should be considered as the standard of care.


A ligand-based approach to identify quantitative structure-activity relationships for the androgen receptor.
We examined the three-dimensional quantitative structure-activity relationship (QSAR) of a group of endogenous and synthetic compounds for the androgen receptor (AR) using comparative molecular field analysis (CoMFA). The goal of these studies was to identify structural features necessary for high binding affinity and optimization of selective androgen receptor modulators (SARMs). A homology model of the AR was used as a scaffold to align six lead compounds that served as templates for alignment of the remaining 116 structures prior to CoMFA modeling. The conventional r(2) and cross-validated q(2) relating observed and predicted relative binding affinity (RBA) were 0.949 and 0.593, respectively. Comparison of predicted and observed RBA for a test set of 10 compounds resulted in an r(2) of 0.954, demonstrating the excellent predictive ability of the model. These integrated homology modeling and CoMFA studies identified critical amino acids for SARM interactions and provided QSAR data as the basis for mechanistic studies of AR structure, function, and design of optimized SARMs.


Synthesis of Pegylated Manganese Protoporphyrin as a Catalase Mimic and Its Therapeutic Application to Acetaminophen-Induced Acute Liver Failure.
Metalloporphyrin derivatives have been investigated for their therapeutic potential for oxidative stress-related diseases because of their scavenging of reactive oxygen species (ROS). Here, we describe the synthesis, physicochemical properties, and ROS-scavenging activities of one such derivative-polyethylene glycol (PEG)-conjugated manganese protoporphyrin (PEG-MnPP). Carboxyl groups of the protoporphyrin ring at the C6 and C7 positions were first conjugated with ethylenediamine to introduce amino groups into the protoporphyrin structure. The amino groups were then reacted with succinimidyl PEG, with an average molecular weight of 2000, to obtain pegylated protoporphyrin (PEG-PP). Manganese was chelated to the protoporphyrin ring by incubating PEG-PP and manganese acetate in methanol. Dynamic light scattering and fluorescent spectrometry analyses revealed that PEG-MnPP self-assembled into nanoparticles in aqueous media with an apparent diameter of 70 nm. PEG-MnPP effectively eliminated hydrogen peroxide from cell culture media and protected cultured mammalian cells from toxic insults induced by hydrogen peroxide exposure or by 6-hydroxydopamine treatment. Intravenous administration of PEG-MnPP to mice significantly suppressed acute liver failure that had been induced by acetaminophen overdose. These data warrant additional investigation to study the therapeutic potential of PEG-MnPP as a water-soluble metalloporphyrin-based catalase mimic for oxidative stress-associated diseases.


The fokI restriction-modification system. I. Organization and nucleotide sequences of the restriction and modification genes.
A DNA fragment that carried the genes coding for FokI endonuclease and methylase was cloned from the chromosomal DNA of Flavobacterium okeanokoites, and the coding regions were assigned to the nucleotide sequence by deletion analysis. The methylase gene was 1,941 base pairs (bp) long, corresponding to a protein of 647 amino acid residues (Mr = 75,622), and the endonuclease gene was 1,749 bp long, corresponding to a protein of 583 amino acid residues (Mr = 66,216). The assignment of the methylase gene was further confirmed by analysis of the N-terminal amino acid sequence. The endonuclease gene was downstream from the methylase gene in the same orientation, separated by 69 bp. The promoter site, which could be recognized by Escherichia coli RNA polymerase, was upstream from the methylase gene, and the sequences adhering to the ribosome-binding sequence were identified in front of the respective genes. Analysis of the gene products expressed in E. coli cells by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the molecular weights of both enzymes coincided well with the values estimated from the nucleotide sequences, and that the monomeric forms were catalytically active. No significant similarity was found between the sequences of the two enzymes. Sequence comparison with other related enzymes indicated that FokI methylase contained two copies of a segment of tetra-amino acids which is characteristic of adenine-specific methylase.


Cytochemical localization of catalase activity in yeast peroxisomes.
Diaminobenzidine oxidation product occurred in peroxisomes and in the intracristate spaces of mitochondria. The reaction was inhibited only in peroxisomes when 3-amino-1,2,4-triazole was present, but cyanide and azide inhibited deposition in both kinds of organelles.


[Preliminary results of DERMATEL: prospective randomized study comparing synchronous and asynchronous modalities of teledermatology].
There is considerable variability in the results of studies that evaluate diagnostic reliability in teledermatology. There are only two studies that compare the synchronous and asynchronous modalities of teleconsult in the same sample. We present the results of the pilot project DERMATEL, a study of diagnostic concordance that aims to increase the evidence of these aspects. One-hundred-fifty.nine patients referred by the general practitioner in the first consult were randomized (algorithm 3:2:1) in three arms: asyncronous teledermatology (store-and-forward or SAF), synchronous teldermatology (real-time or VTC), and conventional consult (CC). We used high-quality, fixed digital images in all cases. The patients on the VTC teledermatology arm were also evaluated by videoconference. Finally all patients attended a face-to-face consult, considered the gold standard of patient care. A second dermatologist evaluated the diagnostic and management concordance between the teleconsults and the face-to-face consults. One-hundred.forty-seven patients completed the study as follows: 74 in the SAF teledermatology arm, 47 in the VTC teledermatology arm and 26 in the conventional consult (control group). The teledermatological (SAF and VTC) and face-to-face evaluations were identical in 100 of 121 patients (82.6%). The errors were mild in 14 cases (11.6%) and severe in 7 (5.8%). The diagnostic concordance was very high (kappa=0,813). The errors grouped by diseases were as follows: 6/54 (11%) for tumors, 10/30 (33.3%) for inflammatory conditions, 1/20 (5%) for infectious diseases, 3/12 (25%) for alopecia/acne and 1/5 (20%) for others. There were 15 errors in the SAF teledermatology arm (20.3%) and 6 in the VTC teledermatology arm (12.8%); these differences were not statistically significant (chi2 1.12; p=0.288). The reliability of dermatological teleconsult is very high, especially for tumoral or infectious diseases. The synchronous interaction with audio requires more resources, is difficult to coordinate and its diagnostic efficacy is not superior to SAF teledermatology.


A block cipher algorithm identification scheme based on hybrid k-nearest neighbor and random forest algorithm.
Cryptographic algorithm identification, which refers to analyzing and identifying the encryption algorithm used in cryptographic system, is of great significance to cryptanalysis. In order to improve the accuracy of identification work, this article proposes a new ensemble learning-based model named hybrid k-nearest neighbor and random forest (HKNNRF), and constructs a block cipher algorithm identification scheme. In the ciphertext-only scenario, we use NIST randomness test methods to extract ciphertext features, and carry out binary-classification and five-classification experiments on the block cipher algorithms using proposed scheme. Experiments show that when the ciphertext size and other experimental conditions are the same, compared with the baselines, the HKNNRF model has higher classification accuracy. Specifically, the average binary-classification identification accuracy of HKNNRF is 69.5%, which is 13%, 12.5%, and 10% higher than the single-layer support vector machine (SVM), k-nearest neighbor (KNN), and random forest (RF) respectively. The five-classification identification accuracy can reach 34%, which is higher than the 21% accuracy of KNN, the 22% accuracy of RF and the 23% accuracy of SVM respectively under the same experimental conditions.


Pediatric Critical Care Nurses' Practices Related to Sedation and Analgesia.
Pediatric intensive care unit (PICU) nurses may consider additional factors beyond validated tools when managing pain and sedation of children. However, these other factors and related beliefs, practices, and decision-making for analgesia and sedation have not been well described. This study describes nurses' beliefs, practices, and decision-making related to sedation and analgesia for mechanically ventilated children on a PICU and a pediatric cardiovascular ICU at a tertiary academic children's medical center in the United States. A 35-item web-based survey tool was developed to more fully identify nurses' pain, sedation, comfort, and analgesia beliefs, decisions, planning, and procedures for children who were mechanically ventilated in the ICU. It was distributed to 102 nurses in the PICU, pediatric cardiovascular ICU, and pediatric critical care float pool. Twenty-six nurses (25%) responded; a majority worked the night shift and had 5 years or less of ICU experience. While participants believed intubated pediatric patients required moderate to deep sedation, approximately only half reported patients were adequately sedated. They reported that they were more likely to manage pain and sedation using specific behaviors and changes in vital signs than scores on a standardized scale. Nurses also reported routinely incorporating nonpharmacologic comfort measures. Premedication was more common for invasive procedures than for routine nursing care. Pediatric ICU nurses in this study considered factors beyond standardized scales when evaluating and managing pain and sedation of ventilated children. Nurses prioritized children's specific behaviors, vital signs, and their own nursing judgment above standardized scales. Research is needed to describe nurses' practices beyond this small study and to define and validate additional assessment parameters to incorporate into decision-making to improve management and care outcomes.


An AI-based intervention for improving undergraduate STEM learning.
We present results from a small-scale randomized controlled trial that evaluates the impact of just-in-time interventions on the academic outcomes of N = 65 undergraduate students in a STEM course. Intervention messaging content was based on machine learning forecasting models of data collected from 537 students in the same course over the preceding 3 years. Trial results show that the intervention produced a statistically significant increase in the proportion of students that achieved a passing grade. The outcomes point to the potential and promise of just-in-time interventions for STEM learning and the need for larger fully-powered randomized controlled trials.


Esophageal carcinoma with pseudohyperparathyroidism and hypercorticism.
An unusual case of bihormonal activity by squamous cell carcinoma of the esophagus is presented. It is a rare presentation of esophagus carcinoma because of the following reasons: 1. Synthesis of cortisteroids by esophageal carcinoma. 2. Pseudohyperparathyroidism caused by the same tumor. 3. Presentation of hypokalemic alkalosis as the initial manifestation and lack of specific gastrointestinal symptomatology of esophageal carcinoma.


Effectiveness of subarachnoid drug infusion for pediatric tumor-related pain.
Although the effectiveness of subarachnoid continuous drug infusion has been established in cancer pain management, its clinical use in children is rare. A 14-year-old girl with neurofibromatosis type I complained of right leg pain stemming from a growing tumor on her right buttock. Continuous and breakthrough right leg pain were unbearable, even at high doses of systemic opioids that caused severe constipation and deep sedation. Subsequent continuous infusion of bupivacaine and morphine through a subarachnoid catheter effectively relieved the girl's pain. The corresponding decrease in systemic opioid also improved her activities of daily living. The patient eventually died of cachexia due to the rapidly growing buttock lesion that was pathologically confirmed post-mortem as a malignant peripheral nerve sheath tumor. Subarachnoid continuous drug infusion may be very useful in controlling severe pain with few side-effects, even in the field of pediatric palliative care.


Subjective and Performance-Based Cognition and Their Associations with Head Injury History in Older Former National Football League Players.
Investigate the association between self-reported subjective and performance-based cognition among older (50-70 years) former professional American football players, as well as the relationship of cognitive measures with concussion history and years of football participation, as a proxy for repetitive head impact exposure. Among older former National Football League (NFL) players ( N = 172; mean age = 60.69 ± 5.64), associations of subjective (Patient Reported Outcome Measurement Information System Cognitive Function-Short Form) and performance-based cognitive measures (Brief Test of Adult Cognition by Telephone [BTACT] Executive Function and Episodic Memory indices) were assessed via univariable and multivariable regression models, with a priori covariates of depression and race. A similar univariate and multivariable regression approach assessed associations between concussion history and years of football participation with subjective and performance-based cognitive measures. In a sample subset ( n = 114), stability of subjective cognitive rating was assessed via partial correlation. Subjective ratings of cognition were significantly associated with performance-based assessment, with moderate effect sizes (episodic memory ηp2 = 0.12; executive function ηp2 = 0.178). These associations were weakened, but remained significant ( P s < 0.05), with the inclusion of covariates. Greater concussion history was associated with lower subjective cognitive function ( ηp2 = 0.114, P < 0.001), but not performance-based cognition. The strength of association between concussion history and subjective cognition was substantially weakened with inclusion of covariates ( ηp2 = 0.057). Years of participation were not associated with measures of subjective or objective cognition ( P s > 0.05). These findings reinforce the importance of comprehensive evaluation reflecting both subjective and objective measures of cognition, as well as the consideration of patient-specific factors, as part of a comprehensive neurobehavioral and health assessment of older former contact sport athletes.


Complete covalent structure of nisin Q, new natural nisin variant, containing post-translationally modified amino acids.
The third member of the nisin variant, nisin Q, produced by Lactococcus lactis 61-14, is a ribosomally-synthesized antimicrobial peptide, the so-called lantibiotic containing post-translationally modified amino acids such as lanthionine and dehydroalanine. Here, we determined the complete covalent structure of nisin Q, consisting of 34 amino acids, by two-dimensional (1)H nuclear magnetic resonance (NMR) spectroscopy. Sequential assignment of nisin Q containing the unusual amino acids was performed by total correlation spectroscopy (TOCSY) and nuclear Overhauser enhancement spectroscopy (NOESY). The observed long range nuclear Overhauser effect (NOE) in nisin Q indicated assignment of all five sets of lanthionines that intramolecularly bridge residues 3-7, 8-11, 13-19, 23-26, and 25-28. Consequently, the covalent structure of nisin Q was determined to hold the same thioether linkage formation as the other two nisins, but to harbor the four amino acid substitutions, in contrast with nisin A.


Efficient, high-performance semantic segmentation using multi-scale feature extraction.
The success of deep learning in recent years has arguably been driven by the availability of large datasets for training powerful predictive algorithms. In medical applications however, the sensitive nature of the data limits the collection and exchange of large-scale datasets. Privacy-preserving and collaborative learning systems can enable the successful application of machine learning in medicine. However, collaborative protocols such as federated learning require the frequent transfer of parameter updates over a network. To enable the deployment of such protocols to a wide range of systems with varying computational performance, efficient deep learning architectures for resource-constrained environments are required. Here we present MoNet, a small, highly optimized neural-network-based segmentation algorithm leveraging efficient multi-scale image features. MoNet is a shallow, U-Net-like architecture based on repeated, dilated convolutions with decreasing dilation rates. We apply and test our architecture on the challenging clinical tasks of pancreatic segmentation in computed tomography (CT) images as well as brain tumor segmentation in magnetic resonance imaging (MRI) data. We assess our model's segmentation performance and demonstrate that it provides performance on par with compared architectures while providing superior out-of-sample generalization performance, outperforming larger architectures on an independent validation set, while utilizing significantly fewer parameters. We furthermore confirm the suitability of our architecture for federated learning applications by demonstrating a substantial reduction in serialized model storage requirement as a surrogate for network data transfer. Finally, we evaluate MoNet's inference latency on the central processing unit (CPU) to determine its utility in environments without access to graphics processing units. Our implementation is publicly available as free and open-source software.


The O-methyltransferase PMT2 mediates methylation of pinosylvin in Scots pine.
Heartwood extractives are important determinants of the natural durability of pine heartwood. The most important phenolic compounds affecting durability are the stilbenes pinosylvin and its monomethylether, which in addition have important functions as phytoalexins in active defense. A substantial portion of the synthesized pinosylvin is 3-methoxylated but the O-methyltransferase responsible for this modification has not been correctly identified. We studied the expression of the stilbene pathway during heartwood development as well as in response to wounding of xylem and UV-C treatment of needles. We isolated and enzymatically characterized a novel O-methyltransferase, PMT2. The methylated product was verified as pinosylvin monomethylether using ultra performance liquid chromatography-tandem mass spectrometry and high performance liquid chromatography analyses. The PMT2 enzyme was highly specific for stilbenes as substrate, in contrast to caffeoyl-CoA O-methyltransferase (CCoAOMT) and PMT1 that were multifunctional. Expression profile and multifunctional activity of CCoAOMT suggest that it might have additional roles outside lignin biosynthesis. PMT1 is not involved in the stilbene pathway and its biological function remains an open question. We isolated a new specific O-methyltransferase responsible for 3-methoxylation of pinosylvin. Expression of PMT2 closely follows stilbene biosynthesis during developmental and stress induction. We propose that PMT2 is responsible for pinosylvin methylation in Scots pine (Pinus sylvestris), instead of the previously characterized methyltransferase, PMT1.


The spectral distribution of firefly light. II.
The in vivo peak emission wavelengths of bioluminescence are reported for 15 species of American fireflies. A spectrophotometric study of the dorsal light organs of 155 specimens of the Jamaican firefly Pyrophorus plagiophthalamus showed three distinct color distributions with peak emission wavelengths at 550.1 +/- 1.5 mmicro, 556.8 +/- 1.4 mmicro, and 562.4 +/- 1.0 mmicro. Similar spectral measurements of 35 ventral light organs of the same insects gave peak emission wavelengths ranging from 547 through 594 mmicro. This is a wider distribution than the total range of all 34 species of firefly studied to date. There was no obvious correlation between the colors of the ventral and dorsal light organs. It appears that P. plagiophthalamus is a special case in which the luciferase enzyme is not only different among members of the same species, but it may be different for the dorsal and ventral light organs in a single individual. A minimum of six different luciferase molecules for P. plagiophthalamus ventral light organs is proposed. The statistical precision in making these spectrophotometric measurements is discussed.


Effects of propofol on lactate accumulation and oedema formation in focal cerebral ischaemia in hyperglycaemic rats.
In cerebral ischaemia, hyperglycaemia brings about severe lactate accumulation and neuronal damage when compared with normoglycaemia. Propofol has been known to suppress glucose metabolism in the brain and possess neuroprotective properties in cerebral ischaemia. Therefore, in this study we examined if propofol could attenuate lactate accumulation and neuronal damage in cerebral ischaemia under hyperglycaemic conditions. Ten male wistar rats were divided into two experimental groups: low-dose (approximately 12 mg kg(-1) h(-1)) and high-dose (approximately 60 mg kg(-1) h(-1)) propofol groups (n=5 for each). Following injection of 2 g kg(-1) glucose intraperitoneally, the middle cerebral artery was occluded for 1 h, and then reperfused for the following 2 h. Lactate accumulation and oedema formation were estimated consecutively using nuclear magnetic resonance (NMR) techniques. Lactate accumulation and oedema formation increased continuously during ischaemia and reperfusion in the low-dose propofol group, which was attenuated in the high-dose propofol group. Lactate/NAA (N-acetylaspartate) ratio (as an index of lactate accumulation) 60 and 120 min after reperfusion were 2.67 and 3.26 in low-dose group and 0.30 and 0.10 in high-dose group. For NMR images the number of pixels with a low average diffusion coefficient (an index of the oedema formation), 60 and 120 min after reperfusion were 250.0 and 317.8 in low-dose group, and 16.0 and 12.4 in high-dose group. High-dose propofol attenuated lactate accumulation and oedema formation in cerebral ischaemia in hyperglycaemic rats.


[The effect of breach presentation on the development of the hips].
Authors examined, using sonographic methods in 100 children with breech-presentation, which of the intrauterine postures means a major danger in the development of hip dysplasia. It was found that acetabular alterations, requiring therapy or not, develop more frequently in groups in which the hips were in total flexion, the knees in semiflexion and the lower extremities in major external rotation. Based on their results they state that not the simple breech position is the greatest danger in the development of dysplasia and dislocation in babies born with breech presentation.


Impaction allografting and the Kerboull acetabular reinforcement device: 35 hips followed for 3-7 years.
The incidence of acetabular loosening with segmental and cavitatory bone loss increases as the number of total hips implanted increases. Revision hip arthroplasty using impacted bone graft and an acetabular reinforcement device is one solution to this problem. Clinically and radiographically, we assessed 35 hips in 33 patients who had undergone revision hip arthroplasty using impaction grafting and the Kerboull acetabular reinforcement device. Mean follow-up was 5 (3-7) years. The mean Mayo score preoperatively was 30, which improved to a mean score of 85. Good to excellent clinical results were seen in 25 patients. The 8 individuals scoring below 80 had significantly more co-morbid conditions than the others. No acetabular reconstruction required re-revision. Aseptic loosening occurred in 6 patients. Graft resorption occurred in 5 cases, resulting in inferior hook fracture of the Kerboull device. This was noted at a mean of 13 months after surgery. Further follow-up showed this to be non-progressive, with incorporation of the remaining graft to the host bone. These patients all had good to excellent Mayo hip scores. Early results of revision acetabular surgery using impaction grafting and the Kerboull shell in patients with severe osteolysis have shown good functional outcome. However, 6 of 35 patients had radiographic evidence of aseptic loosening without progression for 4 years. Long-term follow-up is required to ensure that this loosening does not result in failure.


2023 Expert Consensus of the Taiwan Society of Cardiology on the Diagnosis and Treatment of Cardiac Amyloidosis.
Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.


Traditional and electronic informed consent for biobanking: a survey of U.S. biobanks.
Biobanks face unique challenges obtaining consent from biospecimen contributors. Electronic consent (e-consent) presents one option for streamlining the biobank consent process, and improving contributor understanding of consent information. An e-mail survey was conducted to establish the extent of current biobank e-consent and interest in future use of e-consent. A total of 235 biobanks were surveyed and 65 (28%) responded with a fully completed survey. Few of these 65 biobanks (8%) reported using e-consent; however, the majority (75%) were interested in e-consent. Many (48%) biobanks were in discussions with institutional stakeholders about using e-consent in the future. Anticipated benefits of e-consent included improved efficiency and increased enrollment. Perceived barriers to e-consent adoption included lack of funding, issues with human subjects approval, and factors affecting user uptake (e.g., computer literacy). Biobanks using e-consent reported cost, technology issues, and difficulty training staff as barriers to e-consent adoption. Traditional consenting methods (e.g., face-to-face, phone, and mail) continued to be used at biobanks reporting use of e-consent. The survey results suggest strong interest in e-consent among U.S. biobanks, and a need to consider a range of implementation issues, including user preferences and receptivity; institutional and technical support; integration with clinical data networks; electronic signature capture; and what type of e-consent to implement. Biobanks will need evidence-based guidance for purposes of addressing these issues, so that e-consent processes enhance efficiency, as well as contributor receptivity, understanding, and trust.


Synthesis and optical properties of pyrrolo[3,2-b]pyrrole-2,5(1H,4H)-dione (iDPP)-based molecules.
We describe the synthesis and photophysical properties of a series of derivatives of pyrrolo[3,2-b]pyrrole-2,5(1H,4H)-dione-3,6-diyl (iDPP) linked to two oligothiophenes of variable length (nT). The iso-DPP-oligothiophenes (iDPPnTs) differ from the common pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione-3,6-diyl-oligothiophene analogues (DPPnTs) by a different orientation of the two lactam rings in the bicyclic iDPP unit compared to DPP. In contrast to the highly fluorescent DPPnTs, the new isomeric iDPPnTs exhibit only very weak fluorescence. We demonstrate with the help of quantum-chemical calculations that this can be attributed to a different symmetry of the lowest excited state in iDPPnT (A in C2 symmetry) compared to DPPnTs (B) and the corresponding loss in oscillator strength of the lowest energy transition. Upon extending the oligothiophene moiety in the iDPPnTs molecules, the charge transfer character of the lowest A excited state becomes more pronounced. This tends to preclude high fluorescence quantum yields even in extended iDPPnTs systems.