Poly(l-alanine-co-l-lysine)-g-Trehalose as a Biomimetic Cryoprotectant for Stem Cells.
Poly(l-alanine-co-l-lysine)-graft-trehalose (PAKT) was synthesized as a natural antifreezing glycopolypeptide (AFGP)-mimicking cryoprotectant for cryopreservation of mesenchymal stem cells (MSCs). FTIR and circular dichroism spectra indicated that the content of the α-helical structure of PAK decreased after conjugation with trehalose. Two protocols were investigated in cryopreservation of MSCs to prove the significance of the intracellularly delivered PAKT. In protocol I, MSCs were cryopreserved at -196 °C for 7 days by a slow-cooling procedure in the presence of both PAKT and free trehalose. In protocol II, MSCs were preincubated at 37 °C in a PAKT solution, followed by cryopreservation at -196 °C in the presence of free trehalose for 7 days by the slow-cooling procedure. Polymer and trehalose concentrations were varied by 0.0-1.0 and 0.0-15.0 wt %, respectively. Cell recovery was significantly improved by protocol II with preincubation of the cells in the PAKT solution. The recovered cells from protocol II exhibited excellent proliferation and maintained multilineage potentials into osteogenic, chondrogenic, and adipogenic differentiation, similar to MSCs recovered from cryopreservation in the traditional 10% dimethyl sulfoxide system. Ice recrystallization inhibition (IRI) activity of the polymers/trehalose contributed to cell recovery; however, intracellularly delivered PEG-PAKT was the major contributor to the enhanced cell recovery in protocol II. Inhibitor studies suggested that macropinocytosis and caveolin-dependent endocytosis are the main mechanisms for the intracellular delivery of PEG-PAKT. 1H NMR and FTIR spectra suggested that the intracellular PEG-PAKTs interact with water and stabilize the cells during cryopreservation.


Equity and Performance Improvement: A Novel Toolkit That Makes Using an Equity Lens the Default.
Performance improvement methodologies do not currently include any structures that encourage analysis of how bias, inequity, or social determinants of health (SDOH) contribute to outcomes. The Montefiore Center for Performance Improvement developed a novel quality improvement (QI) toolkit that ingrains issues of diversity, equity, and inclusion (DEI) and SDOH into the Institute for Healthcare Improvement's tools. The toolkit prompts QI teams to evaluate DEI and SDOH at each step of the journey, including an updated charter and stratified baseline tool, a new fishbone diagram for the discovery phase with a tail to include DEI and SDOH, and additions in the Study and Act sessions of the Plan-Do-Study-Act worksheet to address these issues. After development and dissemination of this toolkit, the authors conducted a pre-post analysis of projects conducted by QI fellows in their institution. Prior to introducing the new toolkit, 22.9% of projects from 2016 to 2021 incorporated DEI/SDOH into any stage of the QI process. After implementing the amended tools, this increased to 88.9% in the 2022 fellowship. These results show that this simple approach can hardwire consideration of DEI and SDOH into improvement projects.


Feasibility, Image Quality and Clinical Evaluation of Contrast-Enhanced Breast MRI Performed in a Supine Position Compared to the Standard Prone Position.
To assess the feasibility, image quality and diagnostic value of contrast-enhanced breast magnetic resonance imaging (MRI) performed in a supine compared to a prone position. One hundred and fifty-one patients who had undergone a breast MRI in both the standard prone and supine position were evaluated retrospectively. Two 1.5 T MR scanners were used with the same image resolution, sequences and contrast medium in all examinations. The image quality and the number and dimensions of lesions were assessed by two expert radiologists in an independent and randomized fashion. Two different classification systems were used. Histopathology was the standard of reference. Two hundred and forty MRIs from 120 patients were compared. The analysis revealed 134 MRIs with monofocal (U), 68 with multifocal (M) and 38 with multicentric (C) lesions. There was no difference between the image quality and number of lesions in the prone and supine examinations. A significant difference in the lesion extension was observed between the prone and supine position. No significant differences emerged in the classification of the lesions detected in the prone compared to the supine position. It is possible to perform breast MRI in a supine position with the same image quality, resolution and diagnostic value as in a prone position. In the prone position, the lesion dimensions are overestimated with a higher wash-in peak than in the supine position.


Review of new hypertension guidelines.
The Eighth Joint National Committee (JNC 8) released its new guidelines on the management of adult hypertension in Dec 2013. The key departures from JNC 7 include target blood pressures and thresholds for initiation of elderly patients and in patients under age 60 with diabetes and kidney disease. In this review, we analyse the critical questions, basis of new recommendations, major deviations from JNC 7, the strengths and limitations of changes in previous management guidelines.


Towards comprehensive care in transition for young people with haemophilia.
In the last two decades, the transition from paediatric to adult care has received increasing attention. Health care professionals have become more aware of the unique needs of adolescents and young adults with chronic illnesses and efforts have been made to support youth through this challenging time of change. For patients with haemophilia and their families, there is little evidence regarding best practice for transition of care. We reviewed the transition literature and current guidelines for transition for patients with haemophilia. We advocate that comprehensive haemophilia care includes a conscientious approach to transition of care that should start in early adolescence and be developmentally sensitive. In considering the needs of patients and parents, we must engage both paediatric and adult health care providers to make the transfer smooth and ensure the best care possible during this time.


Microdeletions involving chromosomes 12 and 22 associated with syndromic Duane retraction syndrome.
Duane retraction syndrome (DRS) is the most common of the congenital cranial dysinnervation disorders (CCDDs). CCDDs can be monogenic or chromosomal in origin. Identification of the genetic cause(s) in patients and families with DRS facilitates definitive diagnosis and provides insights into these developmental errors. This study described a young girl with DRS on the left and several additional developmental abnormalities. Clinical examination including neuroimaging, sequencing of candidate genes associated with DRS, and array comparative genomic hybridization (array CGH) were performed. The proband had unilateral DRS type 3 on the left with somewhat low-set ears, mild motor delay with normal intelligence, and an asymmetric neck without a palpable right sternocleidomastoid muscle. Spine X-rays revealed a Klippel-Feil syndrome (KFS) and an MRI showed a webbed neck. She also had spina bifida at C8-T1 and a submucosal cleft palate. The parents of the proband were related with no other family member affected similarly. Sequencing of SALL4, CHN1, HOXA1, and TUBB3 did not show any mutation. Array CGH revealed de novo deletions of 21 Kb on chromosome 12q24.31 and 11 Kb on chromosome 22q13.31, each encompassing only one gene, ring finger protein 34, E3 ubiquitin protein ligase (RNF34) and peroxisome proliferator-activated receptor alpha (PPARA) respectively. This patient presents an unusual phenotype associated with a unique combination of two chromosomal microdeletions.


[Transcranial sonography for the diagnosis of Parkinson disease].
The detection of hyperechogenicity of the substantia nigra using trans cranial sonography can be predictive of the diagnosis of Parkinson Disease. To report an experience with transcranial sonography for the diagnosis of Parkinson disease. Material ana One hundred sixteen patients with movement disorders were subjected to a transcranial sonography to detect the presence of hyperechogenicity of the substantia nigra and basal ganglia. Afterwards, two physicians, unaware of the results oft he sonography, examined the patients and reached a clinical diagnosis. The concordance between ultrasound results and the clinical diagnosis was analyzed. In 64 patients, a clinical diagnosis of Parkinson disease was reached. Of these, 52 patients had substantia nigra hyperechogenicity and in 12, it was normal. On the other hand ultrasound was normal in 42 of 43 patients without a clinical diagnosis of Parkinson disease. Therefore the sensitivity and specificity of trans cranial ultrasound for the diagnosis of Parkinson disease was 81 and 97%, respectively. Transcranial sonography has a good sensitivity and specificity for the diagnosis of Parkinson disease.


Parafoveal telangiectasis and diabetic retinopathy.
Five patients with mild nonproliferative diabetic retinopathy had visual loss associated with parafoveal telangiectasis. Minimal macular edema with characteristic parafoveal plaques of subretinal pigment epithelial hyperplasia was seen in all patients. Fluorescein angiography revealed the presence of ectatic, dilated, leaking perifoveal capillaries. The occurrence of parafoveal telangiectasis in patients with diabetic retinopathy has, to our knowledge, not been previously described. One previous clinicopathologic report described the histologic appearance of parafoveal telangiectasis in a nondiabetic patient to be similar to that seen in diabetic patients. The association of parafoveal telangiectasis and diabetic retinopathy raises interesting speculations into the pathogenesis of the entity of parafoveal telangiectasis. In addition, the importance of obtaining fluorescein angiography prior to therapy of diabetic macular edema is emphasized.


Intracellular regulators of neuronal sprouting: II. Phosphorylation reactions in isolated growth cones.
Mechanisms potentially involved in the regulation of neurite growth were investigated. Since both the phosphatidylinositol (PI) pathway and protein kinase C have been implicated in transmembrane signal transduction, protein and lipid phosphorylation reactions were examined in intact growth cone particles (GCPs) isolated from fetal rat brain. Three major substrates of Ca2+-dependent phosphorylation were observed: proteins of 40 and 46 kDa and an acidic 80 kDa species separated in 2D PAGE (pp40, pp46, and pp80ac). The pp40 and pp80ac substrates had similar rates of 32P incorporation, whereas that of pp46 was more rapid. The importance of protein kinase C in growth cone function is indicated by the enhancement of phosphorylation of the 3 major substrates by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). An examination of the Ca2+-dependent 32P incorporation into pp40 and pp46 revealed serine to be the only amino acid phosphorylated under these conditions. A rapidly metabolized pool of phosphoinositides was observed in GCPs. This suggests the presence of the Pl pathway's enzymes in this fraction. Inositol trisphosphate (IP3) was found to stimulate the phosphorylation of pp40 and pp80ac, indicating a possible link between the activation of the PI pathway and protein phosphorylation. Our findings demonstrate the prominence of the PI pathway and of Ca2+-dependent protein phosphorylation in the growth cone and may suggest the involvement of these mechanisms in growth-factor signal transduction.


The private practice nurse practitioner.
Nurse practitioners have endless possibilities for innovative practice. Deciding on provision of independent practice, suggestions for implementation and service, possible barriers, and solutions are discussed. Future directions for services are outlined.


Analysis of Microvasculature in Nonhuman Primate Macula With Acute Elevated Intraocular Pressure Using Optical Coherence Tomography Angiography.
To investigate responses of macular capillary vessel area density (VAD) of superficial and deep retinal vascular plexuses to elevations in intraocular pressure (IOP) in cynomolgus macaque monkeys using optical coherence tomography angiography (OCTA). In five general anesthetized male cynomolgus monkeys, the IOP was increased incrementally by 10 mmHg from baseline (10 mmHg) to 70 mmHg and then decreased back to 10 mmHg (recovery state). Structural OCT (30° × 30°) and OCTA (20° × 15°) centered on the macula were obtained at each IOP and 3, 15, and 30 minutes after recovery. En face images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were extracted, and VAD (%) compared with that at baseline was calculated. The VADs in the SVC and DVC at baseline and at 30 mmHg IOP were 34.96%, 34.15%, 35.38%, and 30.12%, respectively. The VAD plateaued until 30 mmHg; however, the VAD was affected more in the DVC than in the SVC (P = 0.008) at 30 mmHg. It showed a significant reduction at 40 mmHg (16.52% SVC, P = 0.006; 18.59% DVC, P = 0.012). In the recovery state, the SVC showed full retention of baseline VAD, but the DVC maintained VAD approximately 70% of that at baseline. Structural OCT showed hyperreflectivity in the nuclear layer, retinal swelling, and an undifferentiated ellipsoid zone from 50 mmHg. Despite physiological autoregulation, perifoveal microcirculation was affected at high IOP ≥ 40 mmHg, especially in the DVC, which explains the pathological mechanism of macular vulnerability in ischemic diseases.


Comparing calculated and experimental activity and dose values obtained from image-based quantification of 90Y SPECT/CT Data.
Selective internal radiation therapy (SIRT) is a treatment for various kinds of liver tumours by injecting 90Y bearing microspheres into the liver vessels. To perform meaningful post-treatment dosimetry, quantitative imaging is performed. This work uses a Monte-Carlo based reconstruction software with scatter and attenuation correction and collimator modelling that allows the quantification of 90Y bremsstrahlung SPECT/CT data. A dataset comprising 17 patients and measurements on a Jaszczak phantom, a NEMA IEC Body phantom and an anthropomorphic liver phantom are analysed and activities and dose values are acquired. These measured values are compared with applied activities and pre-treatment calculations, allowing to assess the quality of the SPECT reconstruction. A detailed uncertainty budget is presented, including uncertainties of the dose calibrator, the count rate, non-included interactions and other factors. The applied method is validated by finding measurements repeatable within the given uncertainty, and it is shown the influence of various parameters on the reconstruction process is negligible. Furthermore, activities and doses measured in the phantoms show good agreement with calculated values, if they are corrected for partial volume effects. The strict observation of metrological requirements and the creation of an uncertainty budget increase the reliability and traceability of this novel approach to 90Y dosimetry. It gives an example of successful voxel-based dosimetry based on quantitative 90Y SPECT/CT image data.


10-Valence-Electron C≡O and the 14-VE C≡Pt: Two Triple-Bonded Isoelectronic Families Differing by a dδ4 Ring.
10-VE A≡A' Diatomics, such as N≡N, C≡O, etc., have a strong σ2π4 triple bond plus a lone pair at each end. In our studies on 14-VE A≡B systems, such as C≡Pt, we find a similar bonding system plus a (5dδ)4 ring. Here, the A atom belongs to groups 13-17 and the B atom to groups 7-11. Also the BB' combinations, triatomics, such as PtCO or DsCO or uranyl, and longer chains, such as AuCN and [NC-Au-CN]-, are discussed. The δ ring directly contributes to nuclear quadrupole coupling constants, and DFT calculations using the BH and H or mPW1K functionals reproduce the experimental trends of the NQCC.


One year in review 2017: Behçet's syndrome.
A meta-analysis showed that methodological differences in prevalence studies such as a sample survey design or census design may be responsible for some of the variance in BS prevalence reported across countries, in addition to a true geographic variation. Efforts towards developing a data driven core set of outcome measures for clinical trials is continuing. Multimodal imaging using color fundus photography, fluorescein angiography, and optical coherence tomography is essential in visualising diagnostic features, detecting structural changes, and monitoring disease activity and response to treatment in Behçet's uveitis. Haemoptysis could also be due to bronchial artery enlargement in BS patients with pulmonary artery involvement and can be effectively treated with embolisation. Recent studies shed light on the link between immune system and thrombosis: fibrin clots seemed to be structurally different and plasmin resistant in BS. Newer genetic associations using immunochip were determined, but HLA-B51 is still the principal genetic link. Various studies on micro-RNA's, important molecules of immune regulation were published and discussed. Anti-TNF agents are still the key biologics for the treatment of various manifestations of BS. Two Phase III trials enrolling a small number of BS patients have shown the efficacy of adalimumab in the treatment of non-infectious, non-anterior uveitis. Interferon-alpha was found to induce long-lasting drug free remissions in a retrospective study. Small observational studies with non-TNF biologics such as ustekinumab, anakinra and canakinumab report beneficial results which await confirmation with further studies.


Synergistic pathogenicity of a phloem-limited begomovirus and tobamoviruses, despite negative interference.
In contrast to previous observations on phloem-limited geminiviruses supported in movement andaccumulation by RNA viruses such as cucumo- and tobamoviruses, tissue infiltration by Abutilon mosaic virus (AbMV) was enhanced by neither Tobacco mosaic virus nor Tomato mosaic virus (ToMV) in two different hosts, Nicotiana benthamiana and tomato. Both tobamoviruses exerted a negative effect on the DNA virus, resulting in a decrease in AbMV accumulation and significantly reduced infectivity in N. benthamiana. Despite these unexpected molecular observations, a striking synergistic enhancement in pathogenicity occurred with respectto stunting and necrosis. In situ hybridization revealed that this was not due to any alteration of tissue infiltration by AbMV, which also remained limited to the phloem in the mixed infections. Transgenically expressed ToMV 30K movement protein was not able to induce phloemescape of AbMV in tomato plants and did not lead to any obvious change in begomovirus symptomatology.


The TNF ligand superfamily and its relevance for human diseases.
The tumor necrosis factor (TNF) receptor superfamily comprises 10 different members of type I integral membrane glycoproteins with characteristic limited sequence homology for the extracellular cysteine-rich repeats. A parallel existing TNF ligand superfamily has been discovered by cloning of ligands for all of the TNF receptor superfamily members. These molecules are type II membrane glycoproteins, with the exception of LT-alpha, which is the only secreted protein of the family. TNF and CD95L also exist in biologically active shed soluble form. The TNF ligand superfamily presently contains nine different proteins. In addition, the NGFR p75 binds to a second family of proteins. These NGF-like dimeric soluble molecules are basic neurotrophic factors, and the five members are not related to the TNF superfamily ligands. The TNF-like ligands share some common biological activities, but other activities appear to be shared only by some ligands or are unique. The diverse biological effects mediated through the interaction of the members of the TNF receptor and ligand superfamilies have provided information on the regulation of cellular activation, including the involvement of T-cell-dependent immune responses as well as associations with human diseases.


Homologous recombination between transfected DNAs.
An extensive analysis of the fate and structure of polyomavirus-plasmid recombinant molecules transfected into Rat-1 cells has revealed that the DNA often becomes integrated within transformed cell DNA in a head-to-tail tandem arrangement. This occurs independently of the replicative capacity of the transforming DNA and is facilitated by the use of large quantities of DNA during transfection. These observations have led us to suggest that head-to-tail tandems are formed by homologous recombination between transfected DNAs either before or after integration within cellular DNA. To test this hypothesis, we have measured the transforming activity of pairs of mutant, nontransforming, recombinant plasmid DNAs that carry different lesions in the transforming gene of polyomavirus. The results show that, although the individual mutant DNAs are incapable of transformation, transfection with pairs of mutant DNAs leads to the formation of transformed cells at high frequency. Moreover, there is a direct relationship between the distance between the lesions in pairs of mutant DNAs and their transforming activity. Finally, analyses of the structures of integrated recombinant plasmid DNAs and the viral proteins within independent transformed cells prove that recombination occurs between the mutant genomes to generate a wild-type transforming gene.


Use of bevacizumab as a first-line treatment for metastatic breast cancer.
During clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca. A panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab. The subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training. This expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.


Integrity of nonviral fragments in recombinant Tomato bushy stunt virus and defective interfering RNA is influenced by silencing and the type of inserts.
Recombinant plant viruses have the propensity to remove foreign inserts during replication. This process is virus-specific and occurs in a host-dependent manner. In the present study, we investigated the integrity of foreign inserts in recombinant plant viruses using a model system consisting of Tomato bushy stunt virus (TBSV) and its defective interfering RNA (DI). These were tested in Nicotiana benthamiana plants that were either wild type or transgenic for the green fluorescent protein (GFP) gene. GFP-derived inserts were retained in the recombinant TBSV and DI population that were inoculated onto GFP-transgenic N. benthamiana plants in which silencing of the GFP transgene was initiated, but they were removed from the virus and DIs that were maintained on wild-type plants. A foreign insert derived from an endogenous N. benthamiana gene encoding the H subunit of the magnesium chelatase (NbChlH) was deleted, whereas the fragment of an RNA-dependent RNA polymerase gene (NbRdRP1m) was retained in the recombinant TBSV population. These results demonstrate that the recombination of TBSV to remove nonviral fragments is influenced by silencing and the type of inserts.


Genome-wide ENU mutagenesis in combination with high density SNP analysis and exome sequencing provides rapid identification of novel mouse models of developmental disease.
Mice harbouring gene mutations that cause phenotypic abnormalities during organogenesis are invaluable tools for linking gene function to normal development and human disorders. To generate mouse models harbouring novel alleles that are involved in organogenesis we conducted a phenotype-driven, genome-wide mutagenesis screen in mice using the mutagen N-ethyl-N-nitrosourea (ENU). ENU was injected into male C57BL/6 mice and the mutations transmitted through the germ-line. ENU-induced mutations were bred to homozygosity and G3 embryos screened at embryonic day (E) 13.5 and E18.5 for abnormalities in limb and craniofacial structures, skin, blood, vasculature, lungs, gut, kidneys, ureters and gonads. From 52 pedigrees screened 15 were detected with anomalies in one or more of the structures/organs screened. Using single nucleotide polymorphism (SNP)-based linkage analysis in conjunction with candidate gene or next-generation sequencing (NGS) we identified novel recessive alleles for Fras1, Ift140 and Lig1. In this study we have generated mouse models in which the anomalies closely mimic those seen in human disorders. The association between novel mutant alleles and phenotypes will lead to a better understanding of gene function in normal development and establish how their dysfunction causes human anomalies and disease.


Transport of Drosophila fragile X mental retardation protein-containing ribonucleoprotein granules by kinesin-1 and cytoplasmic dynein.
Transport and translation of mRNA are tightly coupled to ensure strict temporal and spatial expression of nascent proteins. Fragile X mental retardation protein (FMRP) has been shown to be involved in translational regulation and is found in ribonucleoprotein (RNP) granules that travel along dendrites of neurons. In this study, GFP-tagged Drosophila homologue of FMRP (dFMR) was used to visualize RNP granule movement in Drosophila S2 cells. GFP-dFMR form granules that contain both endogenous dFMR and mRNA. Live fluorescence microscopy revealed that dFMR-containing RNP granules move bidirectionally in thin processes formed by S2 cells in the presence of cytochalasin D. Knocking down the heavy chains of either kinesin-1 (kinesin heavy chain) or cytoplasmic dynein (dynein heavy chain) by RNA interference blocks the movement of the dFMR granules. In contrast, knockdown of kinesin light chain (KLC), which is typically necessary for movement of membrane organelles by kinesin-1, had no effect on the dFMR granule translocation. In immunoprecipitation assays, dFMR associates with both kinesin heavy chain and dynein heavy chain, but not KLC. Based on these findings, we conclude that dFMR-containing RNP granules are moved by both kinesin-1 and cytoplasmic dynein and that KLC is not essential and is likely missing from RNP-transporting kinesin-1.


Local adaptation of sex induction in a facultative sexual crustacean: insights from QTL mapping and natural populations of Daphnia magna.
Dormancy is a common adaptation in invertebrates to survive harsh conditions. Triggered by environmental cues, populations produce resting eggs that allow them to survive temporally unsuitable conditions. Daphnia magna is a crustacean that reproduces by cyclical parthenogenesis, alternating between the production of asexual offspring and the sexual reproduction of diapausing eggs (ephippia). Prior to ephippia production, males (necessary to ensure ephippia fertilization) are produced parthenogenetically. Both the production of ephippia and the parthenogenetic production of males are induced by environmental factors. Here, we test the hypothesis that the induction of D. magna resting egg production shows a signature of local adaptation. We postulated that Daphnia from permanent ponds would produce fewer ephippia and males than Daphnia from intermittent ponds and that the frequency and season of habitat deterioration would correlate with the timing and amount of male and ephippia production. To test this, we quantified the production of males and ephippia in clonal D. magna populations in several different controlled environments. We found that the production of both ephippia and males varies strongly among populations in a way that suggests local adaptation. By performing quantitative trait locus mapping with parent clones from contrasting pond environments, we identified nonoverlapping genomic regions associated with male and ephippia production. As the traits are influenced by two different genomic regions, and both are necessary for successful resting egg production, we suggest that the genes for their induction co-evolve.


The rational design of Li-doped nitrogen adsorbents for natural gas purification.
Separation of nitrogen (N2) and methane (CH4) is one of the most challenging and energy-intensive processes in the natural gas industry, due to their close physico-chemical properties. The quest for an effective N2-selective adsorbent has long been the focus of research; however, the results have been sparse. In this work, a first-principle study has been used to construct and investigate Li-doped polycyclic aromatic hydrocarbons (PAHs) for N2 rejection in natural gas purification. We doped lithium on a series of linear/nonlinear PAHs consisting of two to six benzene rings. The adsorption affinity of the Li-doped organic molecular systems toward N2 and CH4 was evaluated by calculating the interaction energy using density functional theory. From the gas adsorption selectivities for different Li-doped PAHs, Li-doped phenanthrene and chrysene showed the highest N2 over CH4 equilibrium selectivities, with values of 119.7 and 80.8, respectively. It was found that the Li atom enabled the π bond of the aromatic substrate to interfere with the N2 lowest unoccupied molecular orbital, resulting in strong physisorption of N2. These results indicate the high potential of Li-doped phenanthrene and chrysene for N2 removal from natural gas.


Quantification of responses from proprioceptive neurons in the limbs of the crab, Cancer magister.
In the limbs of crustaceans, proprioception is monitored by chordotonal organs. One in particular, MC1, is arranged in a manner that is accessible for single unit recording of primary sensory neurons while simulating joint movement. The movement-sensitive cells are of two types, those sensitive to relaxation or to elongation of the chordotonal strand which corresponds to flexion or extension of the meropodite-carpopodite joint, respectively. A statistical method for the quantification of these movement-sensitive proprioceptive neuronal responses was implemented. This statistical index, eta(2), should allow neuronal responses recorded in different laboratories to be easily and quantitatively compared. In addition, an eta(2) value can be assigned to individual cells which represents a cell's consistency and degree to which the response is related to the stimulus. We found some cells to have a high eta(2) and to be consistent in their activity while other cells had a high degree of variability with low eta(2) values. J. Exp. Zool. 284:629-636, 1999.


Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer's disease.
Alzheimer's disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.


Olmesartan attenuates type 2 diabetes-associated liver injury: Cross-talk of AGE/RAGE/JNK, STAT3/SCOS3 and RAS signaling pathways.
Olmesartan (OLM), an angiotensin receptor blocker, was tested against diabetes/insulin resistance (IR) models associated with renal/cardiovascular complications. Methods: we tested its potential role against diabetes-induced hepatic hitches using an IR/type2 diabetic (IR/D) model induced by high fat/high fructose diet for 7 weeks + a single sub-diabetogenic dose of streptozotocin (35mg/kg; i.p). IR/D rats were orally treated with OLM (10 mg/kg), pioglitazone (PIO; 5 or 10 mg/kg) or their combinations for 4 consecutive weeks. OLM alone opposed the detrimental effects of IR/D; it significantly improved metabolic parameters, liver function, and abated hepatic oxidative stress, and inflammatory cytokine interleukin-6 (IL-6) and its upstream mediator nuclear factor kappa B. Consequently, OLM turned off the downstream cue p-Jak2/STAT3/SOCS3. Moreover, it suppressed the elevated AGE/RAGE/p-JNK pathway and increased the PPARγ/adiponectin cue to signify its anti-inflammatory and anti-oxidant capacity (GSH, MDA). Nevertheless, co-administration of OLM to PIO showed a synergistic improvement in all the aforementioned parameters in a dose dependent manner. Additionally, OLM with PIO10 provoked a surge in hepatic PPARγ and adiponectin (5 and 6 folds) with a sharp decrease of about 85% in the NF-κB/IL-6/p-STAT3/SCOS3 pathway. These effects were confirmed by the histopathological study. In conclusion, OLM and its combination with PIO enhanced insulin sensitivity and guarded against hepatic complications associated with type 2 diabetes probably via modulating various inter-related pathways; namely, metabolic alteration, renin-angiotensin system, inflammatory trajectories, as well as oxidative stress. This study manifests the potential synergistic effects of OLM as an adjuvant therapy to the conventional antidiabetic therapies.


Green tea selectively targets initial stages of intestinal carcinogenesis in the AOM-ApcMin mouse model.
One of the liabilities of the Apc(Min) mouse as a model for colon cancer is its lack of a robust tumor response in the large bowel. In our protocol, we treated the Apc(Min) mouse with azoxymethane, a colon-selective carcinogen. This protocol induced a 4-fold increase in the number of colon tumors. We utilized this protocol to investigate the possible mechanisms of inhibition of colorectal carcinogenesis by green tea. Mice received water or a 0.6% (w/v) solution of green tea as the only source of beverage. Green tea treatment commenced at the eighth week of age and lasted for either 4 or 8 weeks. Green tea significantly inhibited the formation of new adenomas, but was ineffective against larger tumors. Mechanistically, we investigated the effects of green tea on the expression of biomarkers involved in colon carcinogenesis. Western blotting analysis showed that green tea decreased the total levels of the early carcinogenesis biomarker beta-catenin and its downstream target cyclin D1. In contrast, the expression of COX-2 was not altered. Immunohistochemical analysis showed that green tea inhibited the formation of adenomas overexpressing beta-catenin and cyclin D1, but did not reduce the number of COX-2-expressing adenomas. Our results suggest that green tea specifically targets initial stages of colon carcinogenesis; the time of administration of green tea is pivotal for effective chemoprevention. Beverage levels of green tea do not inhibit the progress of any large adenomas or adenocarcinomas existing prior to the tea administration.


[Experimental studies of the "anticipation stress" syndrome].
Bioelectrical activity of the limbic structures (amygdala, dorsal and ventral hippocampus), the cortex and etologic responses during the formation of emotional stress of negative modality, were studied on Wistar rats under conditions of continuous many-hour neurotization. The presentation of stimuli according to a strict temporal shceme produced profound changes in the activity of the investigated cerebral structures and of the motor sphere. The established sequence in the involvement of the limbico-neocortical complex in the process of emotional stress with parallel use of the conditioned reflex to time, points to the participation of the hippocampus in the prediction of events (hippocampus leads to amygdala leads to cortex). Stages of biological reactions have been revealed, corresponding to the stages of Selye's adaptation syndrome. Stages of anxiety, adaptation and exhaustion proceeded with features characteristic of each group of animals ("inhibitory type", "steady type", "excitatory type", "overexcitatory type") and peculiar bioelectrical and etological responses.


Transcription terminator-like element within a Saccharomyces cerevisiae promoter region.
We analyzed a cloned fragment of the yeast URA3 promoter region that contains a sequence of DNA capable of functioning as a highly efficient transcription terminator. BAL 31 deletions have shown the signal for the transcription termination activity is less than or equal to 110 base pairs and resides between bases 45 and 155 upstream of the URA3 primary ATG codon at base 227. In our in vivo assay system, the DNA fragment is able to terminate transcripts very efficiently in either orientation. The terminated transcripts bind to oligodeoxythymidylate cellulose columns and promote the synthesis of full-length cDNAs, suggesting that the transcripts are polyadenylated. The 110-base-pair region contains no sequence resembling terminator consensus sequences described by Zaret and Sherman (K.S. Zaret and F. Sherman, Cell, 28:563-573, 1982) or Henikoff and Cohen (S. Henikoff and E.H. Cohen, Mol. Cell. Biol., 4:1515-1520, 1984). We discuss the possible physiological relevance of this sequence to bona fide termination of transcription and to URA3 regulation in Saccharomyces cerevisiae.


Electroconvulsive therapy for psychosis in a patient with epilepsy related to hypothalamic hamartoma.
Psychosis is more common in people with temporal lobe epilepsy than it is in the general population. Treatment can be difficult in these patients because of the complex interactions between antipsychotic and antiepileptic drugs. Some antipsychotic drugs also decrease the seizure threshold. We report the case of a 49-year-old man with a hypothalamic hamartoma, with a history of both gelastic and temporal lobe seizures. The patient was rendered seizure-free after three neurosurgical procedures but developed a drug-resistant paranoid psychosis. He was treated with electroconvulsive therapy (ECT). After two weeks with six stimulations that resulted in seizures, the psychiatric phenomena disappeared completely. There was no relapse of either the psychiatric symptoms or the seizures during the 42 months of follow-up. This case report suggests that ECT might be safe for psychosis in patients with a history of seizures that have previously been successfully treated with neurosurgery, although caution should be exercised in drawing general conclusions from a single case report.


Effect of repeated collection on semen characteristics of alpacas.
Semen characteristics of alpacas were studied after repeated collections. Twelve adult males were divided into three groups of four each for semen collection once, twice, or three times every other day. The duration of copulation; volume of ejaculate; pH; motility; sperm concentration (number of sperm/milliliter semen); total number of sperm per ejaculate; and percentages of live, normal, and abnormal spermatozoa were analyzed by regression analysis. Semen color and consistency were analyzed by the chi-square test. Between the first, second, and third ejaculations, there were differences (p < 0.05) in sperm concentration; percentages of normal spermatozoa and abnormal spermatozoa; sperm with abnormal heads and abnormal tails; and consistency (viscous, viscous, and semi-viscous). There were no differences (p > 0.05) in ejaculated volume, percentage of live spermatozoa, pH, percentage of cytoplasmic droplets, and duration of copulation. Some males from which semen was collected on the three-mating schedule ejaculated only seminal plasma during the second and third copulation starting on Day 10 of the study. There were differences between males (p < 0.05) for most of the characteristics studied. In sum, frequency of mating affected some semen characteristics that may be important determinants of the fertility of male alpacas.


Long-term results of retropubic permanent 125iodine implantation of the prostate for clinically localized prostatic cancer.
The historical series of retropubic prostate radioactive source implantation from the Memorial Sloan-Kettering Cancer Center has served as the framework for the current transperineal implant approaches used in the treatment of localized prostatic cancer. We report the final assessment of the 15-year outcome. Between March 1970 and December 1987, 1,078 patients with biopsy proved adenocarcinoma of the prostate were treated at our cancer center with permanent implantation of 125iodine via a retropubic approach. In addition, all patients underwent bilateral pelvic lymphadenectomy before implantation. The clinical stages of disease were B1 in 234 patients (22%), B2 in 472 (44%), B3 in 145 (14%) and C in 227 (20%). Of the patients 733 (68%) had pathologically negative lymph nodes, whereas 345 (32%) had positive lymph nodes at lymph node dissection. Median followup was 11 years. Multivariate analysis identified nodal involvement, high grade disease, clinical stage B3/C and implant doses less than 140 Gy, as independent predictors of local relapse. Independent predictors of distant metastases included nodal involvement, stage B3/C disease and poorly differentiated histological status. The local recurrence-free survival rates for patients with negative nodes at 5, 10 and 15 years were 69, 44 and 24%, respectively. The distant metastases-free survival rates at 5, 10 and 15 years for patients with negative lymph nodes were 59, 36 and 21%, respectively. 125Iodine implantation of the prostate via the retropubic approach was associated with a greater than expected incidence of local relapse at 15 years. Technical limitations of the retropubic technique resulting in suboptimal distribution of the isotope within the prostate are believed to be the explanation for the inferior local control outcome. Although long-term results are not yet available, the 5-year results of the computer optimized transperineal prostate implantation suggest that improved implant techniques will translate into a greater likelihood of tumor control.


Effect of Buccal Implant Inclination on Stresses Around Two-Implant-Retained Overdentures with Resilient Stud Attachments.
This study aimed to evaluate the effect of buccal implant inclination on stresses around two-implant-retained overdentures with resilient stud attachments. Four acrylic models representing a mandibular edentulous ridge were constructed. For each model, two implants were placed at canine areas. Models were classified into four types according to the degree of buccal implant inclination: Group I (GI, 0 degrees), Group II (GII, 10 degrees), Group III (GIII, 20 degrees), and Group IV (GIV, 30 degrees). Overdentures were connected to the implants with Locator attachments. Regular light-retention inserts were used for all groups, and extended range inserts were also used for GIV (GIVext), making a fifth comparison group. Four strain gauges were bonded at the buccal, lingual, mesial, and distal surfaces of each implant to monitor the stresses during bilateral and unilateral load application. Tensile stresses were recorded at distal and lingual gauges, and compressive stresses were recorded at mesial and buccal gauges for all groups. GIV recorded the highest stresses, followed by GIII, GII, GIVext, and GI. Distal position recorded the highest stresses, followed by lingual, mesial, and buccal. Nonloading side was associated with significantly higher stresses than loading side. The peri-implant stresses increase as the buccal implant inclination increases when resilient stud attachments are used for implant overdentures. Therefore, it is recommended to insert the implants parallel to each other to decrease peri-implant stresses. However, when buccal inclination is inevitable due to anatomical limitations, it should be limited to 10 degrees for standard nylon inserts, or extended range inserts are recommended.


Risk factors for the progression of cystic fibrosis lung disease throughout childhood.
Previous studies of risk factors for progression of lung disease in cystic fibrosis (CF) have suffered from limitations that preclude a comprehensive understanding of the determinants of CF lung disease throughout childhood. The epidemiologic component of the 27-year Wisconsin Randomized Clinical Trial of CF Neonatal Screening Project (WI RCT) afforded us a unique opportunity to evaluate the significance of potential intrinsic and extrinsic risk factors for lung disease in children with CF. Describe the most important intrinsic and extrinsic risk factors for progression of lung disease in children with CF. Variables hypothesized at the onset of the WI RCT study to be determinants of the progression of lung disease and potential risk factors previously identified in the WI RCT study were assessed with multivariable generalized estimating equation models for repeated measures of chest radiograph scores and pulmonary function tests in the WI RCT cohort. Combining all patients in the WI RCT, 132 subjects were observed for a mean of 16 years and contributed 1,579 chest radiographs, and 1,792 pulmonary function tests. The significant determinants of lung disease include genotype, poor growth, hospitalizations, meconium ileus, and infection with mucoid Pseudomonas aeruginosa. The previously described negative effect of female sex was not seen. Modifiable extrinsic risk factors are the major determinants of progression of lung disease in children with CF. Better interventions to prevent or treat these risk factors may lead to improvements in lung health for children with CF.


Comparative study of multireference perturbative theories for ground and excited states.
Three recently developed multireference perturbation theories (PTs)-generalized Van Vleck PT (GVVPT), state-specific multireference PT (SS-MRPT), and multiconfiguration PT (MCPT)-are briefly reviewed and compared numerically on representative examples, at the second order of approximations. We compute the dissociation potential curve of the LiH molecule and the BeH(2) system at various geometries, both in the ground and in the first excited singlet state. Furthermore, the ethylene twisting process is studied. Both Møller-Plesset (MP) and Epstein-Nesbet partition are used for MCPT and SS-MRPT, while GVVPT uses MP partitioning. An important thrust in our comparative study is to ascertain the degree of interplay of dynamical and nondynamical correlation for both ground and excited states. The same basis set and the same set of orbitals are used in all calculations to keep artifactual differences away when comparing the results. Nonparallelity error is used as a measure of the performance of the respective theories. Significant differences among the three methods appear when an intruder state is present. Additionally, difficulties arise (a) in MCPT when the choice of a pivot determinant becomes problematic, and (b) in SS-MRPT when there are small coefficients of the model function and there is implicit division by these coefficients, which generates a potential instability of the solutions. Ways to alleviate these latter shortcomings are suggested.


The "Interdisciplinary Orofacial Examination Protocol for Children and Adolescents": a resource for the interdisciplinary assessment of the stomatognatic system.
The Interdisciplinary Orofacial Examination Protocol for Children and Adolescents (Protocolo de exploración interdisciplinaria orofacial para niños y adolescents, Barcelona, 2008) is very useful in providing a fast, initial, expedient detection of possible morphological and functional disorders, and to guide the patient toward the appropriate professionals. With this tool it is possible to detect the risk factors which can negatively affect morphological and functional harmony and guide patients toward the necessary treatment as early as possible. This Protocol, developed by 4 orthodontists, 1 ENT and 3 speech language therapists, also contributes to the unification of concepts and nomenclature used by distinct specialists, thus making professional understanding easier and more dynamic.


Ontogenetic distribution of 5-HT2C, 5-HT5A, and 5-HT7 receptors in the rat hippocampus.
It is known that serotonin exerts its different nociceptive and motor functions by interacting with distinct receptors subtypes, which could be either G-protein coupled or ionotropic. Previous reports demonstrated the early activation of serotonin receptor transcripts during rat development, suggesting a potential role of the serotoninergic system during ontogeny. In this study we have compared the cellular distribution of three serotonin receptor subtypes: 5-HT2C, 5-HT5A, and 5-HT7. Immunocytochemical methods were used in slices of rat hippocampus obtained during the postnatal development. 5-HT2c immunoreactivity was strong at all developmental stages in the CA1 region, whereas differences were observed between P0 and P5 in the CA3 region. The 5-HT5A receptor immunosignal in CA1 and CA3 was strong at P0, decreased at P11, and then increased in the adult. The immunoreactivity to 5-HT7 receptors was high in all regions at P0 and then decreased progressively during postnatal development; the signal was stronger for 5-HT2c than for 5-HT5A and 5-HT7 receptors. Changes in the expression level of each receptor may result in differences in functional and pharmacological properties of the cells expressing them as well as in the hippocampal neuronal network. The distribution of the three serotonin receptor subtypes studied varied during the ontogeny, which supports their potential role during development and will help to understand their mechanisms.


Mentored postdoctoral training in Zimbabwe: A report on a successful collaborative effort.
Low-and-middle-income countries (LMICs) have high disease burdens, necessitating increased research. However, LMIC research output constitutes only 2% of global total. To increase output, researchers must be capacitated. The University of Zimbabwe (UZ) and the University at Buffalo (UB), developed and implemented the AIDS International Research Training Program (AITRP), in 2008, that focused on graduate scholars. The subsequent HIV Research Training Program (HRTP), begun in 2016, and piloted post-doctoral training to enhance research productivity at UZ. This report discusses the collaboration. As of 2016, prospective candidates applied by submitting letters of intent, research proposals, curriculum vitae and biographical sketches. The scholars research training included hypothesis and project development, completion of grant applications, research project budgets, research presentations to diverse audiences and the application of advanced statistics to research data. The first cohort of five postdoctoral scholars were trained at UZ and UB, between 2016 and 2019. Through the formalized postdoctoral training approach, scholars identified areas of focus. In 2017, one of the scholars obtained a National Institutes of Health (NIH) Emerging Global Leader Award and is now a highly-rated researcher based in South Africa. A second scholar made NIH D43 and K43 grant applications, while the remaining three are academicians and early researchers at UZ. Although research output in Africa and many LMICs is low, it can be built through cooperation similar to the UZ-UB HRTP. This manuscript reports on an effort aimed at building individual and institutional research capacity in Zimbabwe. This can serve as a model for building other similar training programs.


Epigenetics for anthropologists: An introduction to methods.
The study of epigenetics, or chemical modifications to the genome that may alter gene expression, is a growing area of interest for social scientists. Anthropologists and human biologists are interested in epigenetics specifically, as it provides a potential link between the environment and the genome, as well as a new layer of complexity for the study of human biological variation. In pace with the rapid increase in interest in epigenetic research, the range of methods has greatly expanded over the past decade. The primary objective of this article is to provide an overview of the current methods for assaying DNA methylation, the most commonly studied epigenetic modification. We will address considerations for all steps required to plan and conduct an analysis of DNA methylation, from appropriate sample collection, to the most commonly used methods for laboratory analyses of locus-specific and genome-wide approaches, and recommendations for statistical analyses. Key challenges in the study of DNA methylation are also discussed, including tissue specificity, the stability of measures, timing of sample collection, statistical considerations, batch effects, and challenges related to analysis and interpretation of data. Our hope is that this review serves as a primer for anthropologists and human biologists interested in incorporating epigenetic data into their research programs.


Modified frailty index predicts complications and death after non-bariatric gastrectomies.
The modified frailty index (mFI) has been shown to predict mortality and morbidity after major operations. The aim of the present study was to assess the mFI as a preoperative predictor of short-term postoperative complications and 30-day mortality in patients undergoing gastrectomy for non-bariatric diseases. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried for patients who underwent total or partial gastrectomy from 2005 to 2011. A mFI was calculated based on 11 variables as previously described. The population divided into the following four categories based on the mFI score: the non-frail (mFI 0), the low frail (mFI 1), the intermediate frail (mFI 2) and frail (mFI ≥3). Thirty-day mortality and postoperative complications were evaluated. Overall, 5,711 patients underwent a gastrectomy for non-bariatric diseases. Higher mFI score was associated with higher rates of mortality (from 1.2% in the non-frail group to 10.7% in frail group, P<0.001), overall morbidity (26.7% vs. 51.1%, P<0.001), postoperative Clavien IV complication (6% vs. 24.6%, P<0.001), serious complications (19.3% vs. 42.6%, P<0.001), sepsis-related complications (8.4% vs. 16.4%, P<0.001), cardiopulmonary complications (5% vs. 20.7%, P<0.001) and failure to rescue (5.7% vs. 21.8%, P<0.001). Higher mFI score in patients undergoing non-bariatric gastrectomy, is associated with a stepwise greater risk of postoperative morbidity and mortality. MFI Score can be easily calculated preoperatively, from the patient's history, and it can be used as an exceptionally useful criterion for treatment planning.


[Ventral spinal cord compression on the C1-C2 levels with injury of the craniocervical junction].
While CII vertebral dent fracture, neurological complications occur due to its 4 mm shift. The direct approach application (transoral--while the dent fracture or anterolateral--while hagman fracture occurrence) makes possible to achieve an adequate decompression of spinal cord and the vertebral channel reconstruction. Rigid occipitocervical spondilodesis achievement is guaranteed by the metallic loop application and the vertebral arches fixation. While conservative treatment of such a fracture the bones fragments reposition due to the sceletal pulling conduction constitutes the preliminary stage of external immobilization (SOMI or Halo) application.


Male sexual dysfunction and quality of life in schizophrenia.
To describe the prevalence and clinical correlates of sexual dysfunction in a sample of adult male outpatients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol, focusing on associations between sexual dysfunction and patient-perceived quality of life. Sexual dysfunction was assessed in 139 outpatients with DSM-IV schizophrenia who were receiving olanzapine, risperidone, quetiapine, or haloperidol, but no other medications associated with sexual side effects. Structured assessments were made of psychiatric symptoms, quality of life, and relationships. Sexual dysfunction occurred in 45.3% of patients. Patients with and without sexual dysfunction did not significantly differ with respect to severity of psychiatric symptoms. However, as compared with patients without sexual dysfunction, patients with sexual dysfunction reported significantly lower ratings on global quality of life (t = 2.4, df = 136, p = .02) and the level of enjoyment in their life (t = 2.5, df = 136, p = .01). Patients with sexual dysfunction were significantly less likely than those without sexual dysfunction to report having a romantic partner (17.5% vs. 43.4%; chi(2) = 10.7, df = 1, p = .001), though they were not significantly less likely to report difficulty making friends (27.0% vs. 32.9%; chi(2) = 0.57, df = 1, p = .45). Among patients with romantic partners, those with sexual dysfunction reported significantly poorer quality of their relationships (t = 2.3, df = 42, p = .02) and were less likely to talk to their partner about their illness (t = 2.0, df = 42, p = .047). Sexual dysfunction is common in men with schizophrenia who are treated with olanzapine, risperidone, quetiapine, or haloperidol and is associated with diminished quality of life, decreased occurrence of romantic relationships, and reduced intimacy when relationships are established. High prevalence and substantial interference with quality of life combine to make sexual dysfunction an important area for clinical assessment and appropriate intervention in the community management of schizophrenia.


Comparison between braced and non-braced Legg-Calvé-Perthes-disease patients: a radiological outcome study.
Twenty-three hips of 23 Legg-Calvé-Perthes-disease (LCPD) patients treated with abduction orthosis and 28 hips of 25 non-braced LCPD patients were evaluated radiologically retrospectively. The mean age of the brace group was 6.82 years and the mean follow-up was 12.30 years. The mean age and mean follow-up were 7.03 and 17.85 years for non-braced patients, respectively. The hips were evaluated according to lateral pillar classification. There were eight Herring A, 15 Herring B and five Herring C hips in the non-braced patients group; and there were five Herring A, 11 Herring-B and seven Herring C hips in the brace group. The groups were similar in terms of mean age, mean follow-up, sex distribution and lateral pillar grade. Patients' end results were evaluated according to Stulberg classification. All Herring A patients healed with Stulberg class 1 or 2, either braced or non-braced. Fifty-three percent of non-braced hips and 65% of the hips treated with brace healed with satisfactory radiological outcome. There were no significant differences between the groups in terms of end result. The overall results of this study suggest that Herring's lateral pillar classification is a useful system for the prediction of the long-term outcome of the disease and that there was no significant difference between the braced and non-braced patients in terms of radiological end result.


Pregnancy exposure to phthalates and DNA methylation in male placenta - An epigenome-wide association study.
Exposure to phthalates during pregnancy may alter DNA methylation in the placenta, a crucial organ for the growth and development of the fetus. We studied associations between urinary concentrations of phthalate biomarkers during pregnancy and placental DNA methylation. We measured concentrations of 11 phthalate metabolites in maternal spot urine samples collected between 22 and 29 gestational weeks in 202 pregnant women. We analyzed DNA methylation levels in placental tissue (fetal side) collected at delivery. We first investigated changes in global DNA methylation of repetitive elements Alu and LINE-1. We then performed an adjusted epigenome-wide association study using IlluminaHM450 BeadChips and identified differentially methylated regions (DMRs) associated with phthalate exposure. Monobenzyl phthalate concentration was inversely associated with placental methylation of Alu repeats. Moreover, all phthalate biomarkers except for monocarboxy-iso-octyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were associated with at least one DMR. All but three DMRs showed increased DNA methylation with increased phthalate exposure. The largest identified DMR (22 CpGs) was positively associated with monocarboxy-iso-nonyl phthalate and encompassed heat shock proteins (HSPA1A, HSPA1L). The remaining DMRs encompassed transcription factors and nucleotide exchange factors, among other genes. This is the first description of genome-wide modifications of placental DNA methylation in association with pregnancy exposure to phthalates. Our results suggest epigenetic mechanisms by which exposure to these compounds could affect fetal development. Of interest, four identified DMRs had been previously associated with maternal smoking, which may suggest particular sensitivity of these genomic regions to the effect of environmental contaminants.


Effect of putative efflux pump inhibitors and inducers on the antimicrobial susceptibility of Campylobacter jejuni and Campylobacter coli.
The CmeABC efflux pump plays an important role in the antimicrobial resistance of Campylobacter jejuni and Campylobacter coli. The aim of this investigation was to study the effect of putative efflux pump inhibitors, phenyl-arginine-beta-naphthylamide (PAbetaN) and 1-(1-naphthylmethyl)-piperazine (NMP), as well as the effect of putative efflux pump inducers, sodium salicylate and sodium deoxycholate, on the MIC levels of erythromycin, ciprofloxacin, kanamycin, tetracycline and rifampicin for C. jejuni and C. coli. Our results indicated that susceptibility to erythromycin and rifampicin increased, respectively, 8- to 32- and 8- to 64-fold in the presence of PAbetaN and to a lesser extent in the presence of NMP. Salicylate produced a 2- to 4-fold increase in ciprofloxacin MIC values, whereas little effect was observed in the presence of deoxycholate.


Coronavirus infection and ABO blood grouping: Correlation or coincidence?
Association between the ABO blood group and patient outcomes in COVID-19 patients is still unexplored. A known association may help to understand possible risks in advance to the management of such COVID-19 patients. The present study was designed to test such association if there is any, between the ABO blood group and the severity of COVID-19 patients. The present hospital-based observational study was conducted at a COVID-19 dedicated tertiary care hospital in North India over a period of six months during the first wave of the pandemic in the country. Five hundred consecutive patients, who tested positive for COVID-19 using RT-PCR on oropharyngeal/nasopharyngeal swabs, admitted to the hospital were included in the study. ABO and Rhesus (Rh) blood grouping was done on leftover hematology blood samples using gel column agglutination technology. Required clinical details of patients including age, gender, clinical symptoms, comorbidities, outcomes, etc., were obtained from the patient's case sheets. The most common blood group was 'B' (42.8%) followed by 'O' (23.4%), and 'A' (22.4%) while the least common was 'AB' (11.4%). Rh positive was seen in 96.2% while 3.8% were negative. Baseline characteristics were comparable including length of hospital stay, duration of symptoms, and associated comorbid illnesses. The need for intensive care unit (ICU) admissions (P = 0.05) and intubations (P = 0.20) was similar across all four blood groups. Differences in the severity of COVID-19 disease and mortalities among the groups were non-significant. There was no observed association found between the ABO blood group and COVID-19 infection requiring hospitalization, ICU admission, intubation, and outcomes. However, there was a higher proportion of breathlessness and the presence of at least one comorbidity in blood group O as compared to others.


Differentiation of Serratia marcescens and Serratia liquefaciens by tests for lipase and phospholipase production.
The production of lipase and phospolipase by certain members of the Enterobacteriaceae was examined by thin-layer chromatography of resting-cell suspensions incubated with triolein or lecithin. Most strains of Serratia marcescens produced both enzymes while most strains of Serratia liquefaciens exhibited strong lipase but only a minor phospholipase activity. Enterobacter spp. (25 strains), Klebsiella pneumoniae (20 strains), Escherichia coli (15 strains), Citrobacter freundii (7 strains) and Proteus spp. (20 strains) lacked both types of enzymic activity except for the following: three strains of Enterobacter cloacae, two of Proteus mirabilis and three of Proteus vulgaris possessed slight lipase activity; about one-half of the Enterobacter aerogenes and Enterobacter hafniae strains examined produced slight phospholipase activity. It is suggested that tests for lipase and phospholipase should be used in conjunction with those for DNAase production and sugar fermentation for the differentiation of S. marcescens and S. liquefaciens.


[Monoclonal antibodies to flavivirus antigens induced by a vaccinal strain of yellow fever].
Monoclonal antibodies (MABs) YEL-2 induced by the vaccine FNS Dakar yellow fever (YF) virus were characterized for their capacity to enter into serological reactions and to react with heterologous flaviviruses. YEL-2 MABs belong to the IgG2a class of immunoglobulins, possess the antihemagglutination properties, are active in indirect IF test but do not activate complement and have no neutralizing properties. The inability to enter into CFT in the presence of antihemagglutinating properties suggests that YEL-2 MABs are directed for the structural E glycoprotein. YEL-2 MABs reacted similarly with the vaccine 17D strain and the FNS Dakar strain by which they had been induced. In addition to YF virus, YEL-2 MABs reacted with Tyuleniy, Rosio, Ilhéus, Uganda S, Karshi, and Sokuluk viruses, the reaction with Tyuleniy virus reaching the same titer as with the homologous virus but was of one-way nature. No reaction of YEL-2 MABs was observed with the viruses of the tick-borne encephalitis complex, Japanese encephalitis, West Nile, Dengue 2 and 4 viruses. These results specify the antigenic classification of flaviviruses.


A novel isoform of cytoplasmic actin that binds poly-L-proline.
An actin-like protein was purified to apparent homogeneity from chick-embryo homogenates and chick-embryo fibroblasts by the use of poly-L-proline-agarose affinity chromatography; we therefore refer to this protein as PBP (poly-L-proline-binding protein). PBP binds to deoxyribonuclease-agarose, co-migrates with known actin standards on SDS/polyacrylamide-gel electrophoresis, and has an amino acid composition similar to that of actin. Linear peptide maps after digestion with Staphylococcus aureus proteinase reveal its apparent homology with gamma-actin; however, isoelectric-focusing experiments show that PBP is clearly more acidic than any of the three major isoforms of actin. PBP polymerizes in the presence of ATP to form fibrillar structures resembling actin paracrystalline aggregates. In chick-embryo fibroblasts, immunofluorescence with antibodies to PBP shows that its distribution is cytoplasmic: perinuclear staining of the cytoplasm, generalized cytoplasmic staining and peripheral fibrillar structures are evident. In contrast, antibodies specific for the (alpha, gamma)-actins reveal the typical stress fibre structures characteristic of fibroblastic cells. PBP appears to constitute a novel isoform of cellular actin, distinct from the known actin isoforms in terms of its lower isoelectric point, its ability to bind poly-L-proline and its distinct subcellular localization.


A Trusted Lightweight Communication Strategy for Flying Named Data Networking.
Flying Ad hoc Network (FANET) is a new resource-constrained breed and instantiation of Mobile Ad hoc Network (MANET) employing Unmanned Aerial Vehicles (UAVs) as communicating nodes. These latter follow a predefined path called 'mission' to provide a wide range of applications/services. Without loss of generality, the services and applications offered by the FANET are based on data/content delivery in various forms such as, but not limited to, pictures, video, status, warnings, and so on. Therefore, a content-centric communication mechanism such as Information Centric Networking (ICN) is essential for FANET. ICN addresses the problems of classical TCP/IP-based Internet. To this end, Content-centric networking (CCN), and Named Data Networking (NDN) are two of the most famous and widely-adapted implementations of ICN due to their intrinsic security mechanism and Interest/Data-based communication. To ensure data security, a signature on the contents is appended to each response/data packet in transit. However, trusted communication is of paramount importance and currently lacks in NDN-driven communication. To fill the gaps, in this paper, we propose a novel trust-aware Monitor-based communication architecture for Flying Named Data Networking (FNDN). We first select the monitors based on their trust and stability, which then become responsible for the interest packets dissemination to avoid broadcast storm problem. Once the interest reaches data producer, the data comes back to the requester through the shortest and most trusted path (which is also the same path through which the interest packet arrived at the producer). Simultaneously, the intermediate UAVs choose whether to check the data authenticity or not, following their subjective belief on its producer's behavior and thus-forth reducing the computation complexity and delay. Simulation results show that our proposal can sustain the vanilla NDN security levels exceeding the 80% dishonesty detection ratio while reducing the generated end-to-end delay to less than 1 s in the worst case and reducing the average consumed energy by more than two times.


Nomogram incorporating Epstein-Barr virus DNA and a novel immune-nutritional marker for survival prediction in nasopharyngeal carcinoma.
Since Immune response, nutritional status and Epstein-Barr Virus (EBV) DNA status have been confirmed to be relevant to the prognosis of patients with nasopharyngeal carcinoma (NPC), we believe that the combination of these factors is of great value for improving the predictive ability. LA (lymphocytes × albumin), a novel indicator, had not been studied yet in NPC. We combined it with EBV DNA and used nomograms to increase the accuracy of prognosis. A total of 688 NPC patients were retrospectively reviewed and further divided into training and validation cohort randomly. Kaplan-Meier analyses were used to to distinguish the different survival outcomes. Multivariate Cox analyses were used to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Calibration curves, concordance indexes (C-indexes) and decision curve analyses (DCA) were used to evaluate the nomograms' predictive value. Patients with low LA and positive EBV DNA correlated with poorer 5-year PFS and OS (all P < 0.005). In multivariate Cox analyses, LA and EBV DNA were both confirmed to be independent prognostic factors for PFS and OS (all P < 0.05). Prognostic nomograms incorporating LA and EBV DNA achieved ideal C-indexes of 0.69 (95% CI: 0.65-0.73) and 0.77 (95% CI: 0.71-0.82) in the prediction of PFS and OS. Otherwise, the calibration curves and DCA curves also revealed that our nomograms had pleasant predictive power. LA is a novel and powerful biomarker for predicting clinical outcomes in NPC. Our nomograms based on LA and EBV DNA can predict individual prognosis more accurately and effectively.


Activity of mersacidin, a novel peptide, compared with that of vancomycin, teicoplanin, and daptomycin.
Mersacidin, a new peptide antibiotic, was four- to eightfold less active (MIC for 90% of isolates, 8 micrograms/ml) than vancomycin, teicoplanin, or daptomycin against Staphylococcus aureus. Coagulase-negative staphylococci were inhibited by 8 micrograms/ml, and the MICs of mersacidin for hemolytic streptococci and Streptococcus pneumoniae were 4 to 8 micrograms/ml. The mersacidin MICs for anaerobic organisms were as follows: Clostridium perfringens, 4 micrograms/ml; Propionibacterium acnes, 8 micrograms/ml; peptococci, 1 microgram/ml; and peptostreptococci, 8 micrograms/ml. Mersacidin had no activity against members of the family Enterobacteriaceae, Neisseria and Haemophilus species, or Pseudomonas aeruginosa. The size of the inoculum, the pH of the assay (5.5 to 7.5), the type of medium, and the anaerobic conditions had minimal effects on the MICs and MBCs of mersacidin. Overall, mersacidin proved less active than available glycopeptides and peptolides.


[Parental aptitude to prevent child sexual abuse after a participatory education intervention].
To evaluate the aptitude of parents regarding the educational impact of equity education for children to prevent child sexual abuse using participatory strategies. Quasi-experimental design. Ninety-two parents with children in preschool were included in the study. The parents were given a course using participatory educational strategies for one hour daily over a period of 20 days. Prior to the course, a group of experts in child education and sexology prepared a questionnaire with 20 sentences. A Wilcoxon test was used to compare intergroup differences We found statistically significant differences in the parents' responses before and after the educational intervention, with a median (range) of 10(2-12)/18(6-20), p<0.01. A significant change in aptitude was noted when parents attended classes using a participatory strategy to learn about the impact of educational equity for the prevention of child sexual abuse. Thus, it is imperative to continue evaluating different educational strategies.


Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response.
The metabolic activation of clopidogrel is a two-step process. It has been suggested that paraoxonase-1 (PON1) is a rate-limiting enzyme in the conversion of 2-oxo- clopidogrel to an active thiol metabolite. Conflicting results have been reported in regard to (1) the association of a common polymorphism of PON1 (Q192R) with reduced rates of coronary stent thrombosis in patients taking clopidogrel and (2) its effects on platelet inhibition in patient populations of European descent. Blood samples from 151 subjects of mixed racial background with established coronary artery disease and who received clopidogrel were analyzed. Platelet aggregation was determined with light transmittance aggregometry and VerifyNow(®) P2Y12 assay. Genotyping for cytochrome P450 2C19 (CYP2C19)*2 and *3 and PON1 (Q192R) polymorphisms was performed. Carriers of CYP2C19*2 alleles exhibited lower levels of platelet inhibition and higher on-treatment platelet aggregation than noncarriers. There was no significant difference in platelet aggregation among PON1 Q192R genotypes. Homozygous carriers of the wild-type variant of PON1 (QQ192) had similar on-treatment platelet reactivity to carriers of increased-function variant alleles during maintenance clopidogrel dosing, as well as after administration of a clopidogrel 600 mg loading dose. CYP2C19*2 allele is associated with impaired platelet inhibition by clopidogrel and high on-treatment platelet aggregation. PON1 (Q192R) polymorphism does not appear to be a significant determinant of clopidogrel response.


Genetic, functional and sequence analysis of the xylR and xylS regulatory genes of the TOL plasmid pWW0.
Mutant derivatives of a plasmid, pCF20, which carries the XhoI-D fragment of the TOL plasmid pWW0 have been isolated using Tn5 transposon mutagenesis. Insertion mutations of the xylR and xylS regulatory genes of the catabolic pathway have been isolated and characterized and their ability to induce catechol 2,3-oxygenase activity determined. Analysis of the insertion mutants and also segments of the XhoI-D fragment cloned into plasmid pUC8 in maxicells has identified a 68 kDa polypeptide product encoded by the xylR gene. No clear candidate for the xylS polypeptide was observed. The nucleotide sequence of the xylS region, the intergenic region and part of the xylR region has been determined and open reading frames (ORFs) assigned for both genes. The ORF designated xylS appears capable of encoding a polypeptide of approximately 37 kDa.


Analysis of Response Evaluation Criteria in Solid Tumors reduction ratio of primary chemotherapy in unresectable advanced or recurrent colorectal cancer.
Response Evaluation Criteria in Solid Tumors (RECIST) is used to assess the objective response of solid tumors to treatment. However, it remains unclear to what extent the response rate assessed by RECIST reflects a reduction of tumor size in multiple organs in patients with unresectable advanced or recurrent colorectal cancer (CRC) with multiple organ metastases. It is also unclear whether the management of liver metastases with systemic chemotherapy in CRC patients with multiple organ metastases improves their prognosis, although surgical resection has been shown to be the most effective treatment approach to CRC cases with liver metastases. A total of 38 CRC patients who underwent systemic chemotherapy in Kyushu Medical Center Hospital between January 2013 and April 2016 were examined. The patients had measurable lesions in multiple organs, including the liver, and did not undergo curative surgery for metastatic lesions after initiation of chemotherapy. The association between the total reduction ratio (TRR) of all lesions and liver lesion reduction ratio (LRR) was retrospectively analyzed. A total of 18 patients (47%) had H3 liver metastases, and the median liver lesion occupancy rate in the sum of the measured lesions with RECIST was 76%. TRR and LRR were strongly correlated, regardless of the volume of the liver metastases. Although a TRR of >30% was significantly associated with improved overall survival (OS), this improvement was not observed in patients with H3 liver metastases. TRR was correlated with LRR and was associated with a better OS. CRC patients with both multiple organ and H3 liver metastases exhibited poor survival, even with a high reduction ratio by chemotherapy.


How old do you feel? The role of age discrimination and biological aging in subjective age.
Subjective age, or how young or old individuals experience themselves to be relative to their chronological age, is a crucial construct in gerontology. Subjective age is a significant predictor of important health outcomes, but little is known about the criteria by which individuals' subjectively evaluate their age. To identify psychosocial and biomedical factors linked to the subjective evaluation of age, this study examined whether perceived age discrimination and markers of biological aging are associated with subjective age. Participants were 4776 adults (Mage = 68) from the 2008 and 2010 waves of the Health and Retirement Study (HRS) who completed measures of subjective age, age discrimination, demographic variables, self-rated health and depression, and had physical health measures, including peak expiratory flow, grip strength, waist circumference, systolic and diastolic blood pressure. Telomere length was available for a subset of participants in the 2008 wave (n = 2214). Regression analysis indicated that perceived age discrimination, lower peak expiratory flow, lower grip strength, and higher waist circumference were associated with an older subjective age, controlling for sociodemographic factors, self-rated health, and depression. In contrast, blood pressure and telomere length were not related to subjective age. These findings are consistent with the hypothesis that how old a person feels depends in part on psychosocial and biomedical factors, including the experiences of ageism and perceptible indices of fitness and biological age.


[Field trials of a number of IBR vaccines in dairy cattle].
Vaccination of ninety-six cows which showed titres of less than or equal to 1:2 on inoculation, using vaccines containing attenuated live IBR virus (Tracherine, Resbo. IBR PI3, Respacine 3) elicited a moderate serological response. Inoculation of these vaccines in 192 cows showing titres of greater than or equal to 1:3 on vaccination did not result in a significant increase in titre. Inactivated IBR vaccines (Iffavax and Ibeair H) induced a satisfactory serological response in 140 cows, regardless of the IBR virus titres of the animals on inoculation. Within five months after vaccination, four animals vaccinated with Ibeair H were found to be only moderately immune against intranasal infection using virulent IBR virus. The present authors prefer the use of vaccines containing attenuated live virus.


Reproductive health knowledge and use of contraceptives among adolescent mothers in a sub-urban community in Oyo State, Nigeria.
This survey explored the reproductive health knowledge and use of contraceptives among 316 young mothers in Ogbere, a sub-urban community in Oyo State, Nigeria. A cluster sampling technique was used to recruit the respondents and data were collected from them through face-to-face interviews using questionnaires. The ages of the respondents ranged from 17-20 with a mean of 18.9. The majority (76.9%) of the respondents were married and had primary school education (72.8%). Fivepercent had lost a pregnancy due to abortion, miscarriage or still birth. Forty-three percent had fair, 34.5% poor, and 22.5% good knowledge of contraceptives; 53% did not know any of the routes for HIV transmission. A large majority (70%) had never used any contraceptives, 29% had done so. Eighty percent of those who had ever used any contraceptive were using one at the time of the survey. The most popular contraceptives used were condoms (44.4%) and pills (16.1%). Interventions to improve the economic status and promote use of contraceptives are recommended for this population.


Differential influence of diabetes mellitus on increased jeopardized myocardium after initial angioplasty or bypass surgery: bypass angioplasty revascularization investigation.
Data are absent that compare midterm angiographic outcome between patients with and without diabetes after initial percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG). Importantly, diabetes mellitus may differentially influence long-term survival after PTCA or CABG. Patients with multivessel coronary disease who were previously enrolled in the Bypass Angiopathy Revascularization Investigation to compare initial PTCA versus CABG (n=1829) and who had a reduction in jeopardized myocardium after initial revascularization and at least 1 angiogram during 5-year follow-up were analyzed (n=897). This included 369 CABG-treated patients (16% with diabetes) and 528 PTCA-treated patients (18% with diabetes). The influence of diabetes on angiographic increase in percentage of jeopardized myocardium after initial revascularization with either PTCA or CABG was investigated. Among PTCA patients, the mean percentage increase in total jeopardized myocardium was significantly greater in those with diabetes than in those without at 1-year protocol-directed angiography (42% versus 24%, P=0.05) and on the first clinically performed (unscheduled) angiogram within 30 months (63% versus 50%, P=0.01) but not at 5-year protocol-directed angiography (34% versus 26%, P=0.33). This excess midterm risk associated with diabetes persisted after statistical adjustment. In contrast, among CABG patients, diabetes was not associated with percentage increase in jeopardized myocardium at any angiographic follow-up interval. Presence of diabetes differentially influences worsening of jeopardized myocardium after initial PTCA compared with CABG. This differential effect occurs irrespective of whether follow-up angiography is undertaken for clinical or nonclinical purposes.


The protective role of hydrogen-rich saline in experimental liver injury in mice.
Reactive oxygen species (ROS) are considered to play a prominent causative role in the development of various hepatic disorders. Antioxidants have been effectively demonstrated to protect against hepatic damage. Hydrogen (H(2)), a new antioxidant, was reported to selectively reduce the strongest oxidants, such as hydroxyl radicals (·OH) and peroxynitrite (ONOO(-)), without disturbing metabolic oxidation-reduction reactions or disrupting ROS involved in cell signaling. In place of H(2) gas, hydrogen-rich saline (HS) may be more suitable for clinical application. We herein aim to verify its protective effects in experimental models of liver injury. H(2) concentration in vivo was detected by hydrogen microelectrode for the first time. Liver damage, ROS accumulation, cytokine levels, and apoptotic protein expression were, respectively, evaluated after GalN/LPS, CCl(4), and DEN challenge. Simultaneously, CCl(4)-induced hepatic cirrhosis and DEN-induced hepatocyte proliferation were measured. HS significantly increased hydrogen concentration in liver and kidney tissues. As a result, acute liver injury, hepatic cirrhosis, and hepatocyte proliferation were reduced through the quenching of detrimental ROS. Activity of pro-apoptotic players, such as JNK and caspase-3, were also inhibited. HS could protect against liver injury and also inhibit the processes leading to liver cirrhosis and hepatocyte compensatory proliferation.


Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10.
IL (interleukin)-22 is an IL-10-related cytokine; its main biological activity known thus far is the induction of acute phase reactants in liver and pancreas. IL-22 signals through a receptor that is composed of two chains from the class II cytokine receptor family: IL-22R (also called ZcytoR11/CRF2-9) and IL-10Rbeta (CRF2-4), which is also involved in IL-10 signaling. In this report, we analyzed the signal transduction pathways activated in response to IL-22 in a rat hepatoma cell line, H4IIE. We found that IL-22 induces activation of JAK1 and Tyk2 but not JAK2, as well as phosphorylation of STAT1, STAT3, and STAT5 on tyrosine residues, extending the similarities between IL-22 and IL-10. However our results unraveled some differences between IL-22 and IL-10 signaling. Using antibodies specific for the phosphorylated form of MEK1/2, ERK1/2, p90RSK, JNK, and p38 kinase, we showed that IL-22 activates the three major MAPK pathways. IL-22 also induced serine phosphorylation of STAT3 on Ser(727). This effect, which is not shared with IL-10, was only marginally affected by MEK1/2 inhibitors, indicating that other pathways might be involved. Finally, by overexpressing a STAT3 S727A mutant, we showed that serine phosphorylation is required to achieve maximum transactivation of a STAT responsive promoter upon IL-22 stimulation.


High intra-abdominal pressure increases plasma catecholamine concentrations during pneumoperitoneum for laparoscopic procedures.
Laparoscopic procedures are associated with several complications, such as hemodynamic, respiratory, and endocrine complications. In our previous clinical study, plasma epinephrine and norepinephrine concentrations remained unchanged after the insertion of a Veress needle, but increased significantly immediately after insufflation with carbon dioxide into the peritoneum. The mechanisms for this increase are unknown. To investigate whether gas insufflation during pneumoperitoneum affects plasma catecholamine concentrations during laparoscopic procedures. Experimental study in pigs. The plasma concentrations of epinephrine and norepinephrine were measured in the pigs before and after pneumoperitoneum. The mean arterial pressure, heart rate, cardiac output, and arterial blood gas levels were measured, and the systemic vascular resistance was calculated. Air, nitrous oxide, or carbon dioxide were insufflated in turn into the peritoneal cavity of supine pigs. Thereafter, carbon dioxide was insufflated into the peritoneal cavity while the pig was in the left lateral decubitus position, and then in the right lateral decubitus position. Measures were performed before pneumoperitoneum and at the intra-abdominal pressures of 10 mm Hg and 20 mm Hg. One hour of resting time was allowed between each procedure. As compared with baseline values, the plasma concentrations of epinephrine and norepinephrine remained unchanged at 10 mm Hg but increased significantly at 20 mm Hg regardless of the gas used for the pneumoperitoneum (P<.05). The type of gas and differences in the position of the animals had no effect on the plasma epinephrine and norepinephrine concentrations. Excessive intra-abdominal pressure, but not the type of gas or body position, increases plasma catecholamine concentrations during the insufflation of gas into the abdominal cavity. Therefore, excessive insufflation of the pneumoperitoneum should be avoided.


Health-care reform and chiropractic in the 1990s.
The organization and finance of health care in the United States are likely to change dramatically during the 1990s. During the first half of the decade, pro-competition strategies, which characterized the 1980s, are likely to continue. However, by the end of the decade, the country will probably adopt some form of national health care. After briefly discussing both possibilities, this paper investigates their likely impact on the future practice of chiropractic in the United States, and concludes with some policy recommendations.


Dopaminergic modulation of motor coordinaton in Parkinson's disease.
We applied the idea of synergies and the framework of the uncontrolled manifold hypothesis to explore the effects of dopamine replacement therapy on finger interaction and coordination in patients with early-stage Parkinson's disease (PD). Eight patients performed single-finger and multi-finger force production tasks with both the dominant and non-dominant hand before (off-drug) and after (on-drug) taking their dopaminergic medications. Synergy indices were defined as co-varied adjustments of commands to fingers that stabilized the total force produced by the hand. PD patients showed significantly lower maximal finger forces off-drug compared to the on-drug condition, while indices of finger individuation (enslaving) were unchanged. The synergy indices were weaker during steady-state force production off-drug compared to on-drug. Anticipatory adjustments of synergies prior to the quick force pulse initiation were delayed and reduced off-drug as compared to the on-drug condition. These drug effects were observed in both the symptomatic and asymptomatic hands of the patients whose symptoms were limited to one side of the body. The study demonstrates dopaminergic modulation of motor coordination in PD and supports that the analysis of different components of multi-finger synergies offers a set of indices sensitive to the effects of dopamine replacement therapy in early-stage PD. The results suggest an important role of the basal ganglia in synergy formation and in feed-forward synergy adjustments. Future studies using these methods may yield more objective, quantitative biomarker(s) of motor coordination impairments in PD, and better understanding of subcortical involvement in the neural control of natural actions.


New reagents for detecting free radicals and oxidative stress.
Free radicals and oxidative stress play important roles in the deterioration of materials, and free radicals are important intermediates in many biological processes. The ability to detect these reactive species is a key step on the road to their understanding and ultimate control. This short review highlights recent progress in the development of reagents for the detection of free radicals and reactive oxygen species with broad application to materials science as well as biology.


Water uptake by roots: effects of water deficit.
The variable hydraulic conductivity of roots (Lp(r)) is explained in terms of a composite transport model. It is shown how the complex, composite anatomical structure of roots results in a composite transport of both water and solutes. In the model, the parallel apoplastic and cell-to-cell (symplastic and transcellular) pathways play an important role as well as the different tissues and structures arranged in series within the root cylinder (epidermis, exodermis, cortex, endodermis, stelar parenchyma). The roles of Casparian bands and suberin lamellae in the root's endo- and exodermis are discussed. Depending on the developmental state of these apoplastic barriers, the overall hydraulic resistance of roots is either more evenly distributed across the root cylinder (young unstressed roots) or is concentrated in certain layers (exo- and endodermis in older stressed roots). The reason for the variability of root Lp(r), is that hydraulic forces cause a dominating apoplastic flow of water around protoplasts, even in the endodermis and exodermis. In the absence of transpiration, water flow is osmotic in nature which causes a high resistance as water passes across many membranes on its passage across the root cylinder. The model allows for a high capability of roots to take up water in the presence of high rates of transpiration (high demands for water from the shoot). By contrast, the hydraulic conductance is low, when transpiration is switched off. Overall, this results in a non-linear relationship between water flow and forces (gradients of hydrostatic and osmotic pressure) which is otherwise hard to explain. The model allows for special root characteristics such as a high hydraulic conductivity (water permeability) in the presence of a low permeability of nutrient ions once taken up into the stele by active processes. Low root reflection coefficients are in line with the idea of some apoplastic bypasses for water within the root cylinder. According to the composite transport model, the switch from the hydraulic to the osmotic mode is purely physical. In the presence of heavily suberized roots, the apoplastic component of water flow may be too small. Under these conditions, a regulation of radial water flow by water channels dominates. Since water channels are under metabolic control, this component represents an 'active' element of regulation. Composite transport allows for an optimization of the water balance of the shoot in addition to the well-known phenomena involved in the regulation of water flow (gas exchange) across stomata. The model is employed to explain the responses of plants to water deficit and other stresses. During water deficit, the cohesion-tension mechanism of the ascent of sap in the xylem plays an important role. Results are summarized which prove the validity of the coehesion/tension theory. Effects of the stress hormone abscisic acid (ABA) are presented. They show that there is an apoplastic component of the flow of ABA in the root which contributes to the ABA signal in the xylem. On the other hand, (+)-cis-trans-ABA specifically affects both the cell level (water channel activity) and water flow driven by gradients in osmotic pressure at the root level which is in agreement with the composite transport model. Hydraulic water flow in the presence of gradients in hydrostatic pressure remains unchanged. The results agree with the composite transport model and resemble earlier findings of high salinity obtained for the cell (Lp) and root (Lp(r)) level. They are in line with known effects of nutrient deprivation on root Lp(r )and the diurnal rhythm of root Lp(r )recently found in roots of LOTUS.


Fanconi anemia proteins stabilize replication forks.
Fanconi anemia (FA) is a recessive genetic disorder characterized by hypersensitivity to crosslinking agents that has been attributed to defects in DNA repair and/or replication. FANCD2 and the FA core complex bind to chromatin during DNA replication; however, the role of FA proteins during replication is unknown. Using Xenopus cell-free extracts, we show that FANCL depletion results in defective DNA replication restart following treatment with camptothecin, a drug that results in DSBs during DNA replication. This defect is more pronounced following treatment with mitomycin C, presumably because of an additional role of the FA pathway in DNA crosslink repair. Moreover, we show that chromatin binding of FA core complex proteins during DNA replication follows origin assembly and origin firing and is dependent on the binding of RPA to ssDNA while FANCD2 additionally requires ATR, consistent with FA proteins acting at replication forks. Together, our data suggest that FA proteins play a role in replication restart at collapsed replication forks.