Combination of genetic algorithm and partial least squares for cloud point prediction of nonionic surfactants from molecular structures.
Quantitative structure-property relationship (QSPR) analysis has been directed to a series of pure nonionic surfactants containing linear alkyl, cyclic alkyl, and alkey phenyl ethoxylates. Modeling of cloud point of these compounds as a function of the theoretically derived descriptors was established by multiple linear regression (MLR) and partial least squares (PLS) regression. In this study, a genetic algorithm (GA) was applied as a variable selection method in QSPR analysis. The results indicate that the GA is a very effective variable selection approach for QSPR analysis. The comparison of the two regression methods used showed that PLS has better prediction ability than MLR.


Seasonal changes in suicide in South Korea, 1991 to 2015.
Seasonality of suicidal behavior has been widely reported in many epidemiological studies with a well replicated suicide peak in spring followed by a trough in winter season. Research from some regions over the past few decades has shown a diminishing seasonal pattern of suicides and this introduced a new perspective on the suicide study. Data on all suicide deaths from the period 1991 to 2015 was extracted from the South Korean National Death Registration data set which was made available by Statistics Korea. Our findings confirmed a strong seasonal effect of suicides in South Korea throughout the study period and a marked diminishing pattern was observed since the period of 2006-2010. The rhythm of suicides kept changing across the time intervals with a spring peak followed by a second peak in late summer/autumn. The seasonality varied across age groups and the seasonal effect among the Korean elderly suicides was still found to be significant though a diminishing pattern was observed recently.


Changes of cell-surface thiols and intracellular signaling in human monocytic cell line THP-1 treated with diphenylcyclopropenone.
Changes of cell-surface thiols induced by chemical treatment may affect the conformations of membrane proteins and intracellular signaling mechanisms. In our previous study, we found that a non-toxic dose of diphenylcyclopropene (DPCP), which is a potent skin sensitizer, induced an increase of cell-surface thiols in cells of a human monocytic cell line, THP-1. Here, we examined the influence of DPCP on intracellular signaling. First, we confirmed that DPCP induced an increase of cell-surface thiols not only in THP-1 cells, but also in primary monocytes. The intracellular reduced-form glutathione/oxidized-form glutathione ratio (GSH/GSSG ratio) was not affected by DPCP treatment. By means of labeling with a membrane-impermeable thiol-reactive compound, Alexa Fluor 488 C5 maleimide (AFM), followed by two-dimensional gel electrophoresis and analysis by liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), we identified several proteins whose thiol contents were modified in response to DPCP. These proteins included cell membrane components, such as actin and β-tubulin, molecular chaperones, such as heat shock protein 27A and 70, and endoplasmic reticulum (ER) stress-inducible proteins. Next, we confirmed the expression in DPCP-treated cells of spliced XBP1, a known marker of ER stress. We also detected the phosphorylation of SAPK/JNK and p38 MAPK, which are downstream signaling molecules in the IRE1α-ASK1 pathway, which is activated by ER stress. These data suggested that increase of cell-surface thiols might be associated with activation of ER stress-mediated signaling.


Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects.
The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol.


Novel variant serotype of streptococcus suis isolated from piglets with meningitis.
Streptococcus suis is an emerging zoonotic pathogen causing severe infections in pigs and humans. In previous studies, 33 serotypes of S. suis have been identified using serum agglutination. Here, we describe a novel S. suis strain, CZ130302, isolated from an outbreak of acute piglet meningitis in eastern China. Strong pathogenicity of meningitis caused by strain CZ130302 was reproduced in the BALB/c mouse model. The strain showed a high fatality rate (8/10), higher than those for known virulent serotype 2 strains P1/7 (1/10) and 9801 (2/10). Cell adhesion assay results with bEnd.3 and HEp2 cells showed that CZ130302 was significantly close to P1/7 and 9801. Both the agglutination test and its complementary test showed that strain CZ130302 had no strong cross-reaction with the other 33 S. suis serotypes. The multiplex PCR assays revealed no specified bands for all four sets used to detect the other 33 serotypes. In addition, genetic analysis of the whole cps gene clusters of all serotypes was performed in this study. The results of comparative genomics showed that the cps gene cluster of CZ130302, which was not previously reported, showed no homology to the gene sequences of the other strains. Especially, the wzy, wzx, and acetyltransferase genes of strain CZ130302 are phylogenetically distinct from strains of the other 33 serotypes. Therefore, this study suggested that strain CZ130302 represents a novel variant serotype of S. suis (designated serotype Chz) which has a high potential to be virulent and associated with meningitis in animals.


Carotid body chemoreceptor activity in the new-born lamb.
1. Tidal volume, carotid artery oxygen tension (P(a,O2)) and blood pressure and chemoreceptor activity in the sinus nerve have been continuously measured and recorded in nine lambs anaesthetized with pentobarbitone sodium, and varying in age from some minutes after birth to 5 days after birth.2. Inhalation of 100% oxygen caused, after a delay of 3-4 sec, a rise in P(a,O2), a fall in minute ventilation (V) and chemoreceptor activity. The respiratory response was abolished after section of both sinus nerves.3. Inhalation of 10% oxygen in nitrogen caused a fall in carotid P(a,O2), a rise in respiration and in chemoreceptor activity. The respiratory response was abolished after both sinus nerves had been cut.4. Minute ventilation, carotid P(a,O2) and chemoreceptor activity increased on breathing 5% CO(2) in air. Section of both sinus nerves did not affect the maximum increase in ventilation but the lag of the respiratory response approximately doubled while respiration increased more slowly.5. From these results, it was calculated that the chemoreceptors had a latency of 0.25-0.5 sec and the time constant of the rate of change of chemoreceptor activity was 10-15 sec.6. The chemoreceptors responded to changes in P(a,O2) of +/-5-10 mm Hg.7. Comparison of these results with those reported in adult animals suggest that the peripheral chemoreceptors are fully mature at birth, that their response does not differ with the age of the lamb and that the carotid body chemoreceptors are concerned both in the mediation of the hypoxic drive to ventilation and in the respiratory response to inhaled CO(2).


Human Epidermal Growth Factor Receptor 2-Targeting [68Ga]Ga-ABY-025 PET/CT Predicts Early Metabolic Response in Metastatic Breast Cancer.
Imaging using the human epidermal growth factor receptor 2 (HER2)-binding tracer 68Ga-labeled ZHER2:2891-Cys-MMA-DOTA ([68Ga]Ga-ABY-025) was shown to reflect HER2 status determined by immunohistochemistry and in situ hybridization in metastatic breast cancer (MBC). This single-center open-label phase II study investigated how [68Ga]Ga-ABY-025 uptake corresponds to biopsy results and early treatment response in both primary breast cancer (PBC) planned for neoadjuvant chemotherapy and MBC. Methods: Forty patients with known positive HER2 status were included: 19 with PBC and 21 with MBC (median, 3 previous treatments). [68Ga]Ga-ABY-025 PET/CT, [18F]F-FDG PET/CT, and core-needle biopsies from targeted lesions were performed at baseline. [18F]F-FDG PET/CT was repeated after 2 cycles of therapy to calculate the directional change in tumor lesion glycolysis (Δ-TLG). The largest lesions (up to 5) were evaluated in all 3 scans per patient. SUVs from [68Ga]Ga-ABY-025 PET/CT were compared with the biopsied HER2 status and Δ-TLG by receiver operating characteristic analyses. Results: Trial biopsies were HER2-positive in 31 patients, HER2-negative in 6 patients, and borderline HER2-positive in 3 patients. The [68Ga]Ga-ABY-025 PET/CT cutoff SUVmax of 6.0 predicted a Δ-TLG lower than -25% with 86% sensitivity and 67% specificity in soft-tissue lesions (area under the curve, 0.74 [95% CI, 0.67-0.82]; P = 0.01). Compared with the HER2 status, this cutoff resulted in clinically relevant discordant findings in 12 of 40 patients. Metabolic response (Δ-TLG) was more pronounced in PBC (-71% [95% CI, -58% to -83%]; P < 0.0001) than in MBC (-27% [95% CI, -16% to -38%]; P < 0.0001), but [68Ga]Ga-ABY-025 SUVmax was similar in both with a mean SUVmax of 9.8 (95% CI, 6.3-13.3) and 13.9 (95% CI, 10.5-17.2), respectively (P = 0.10). In multivariate analysis, global Δ-TLG was positively associated with the number of previous treatments (P = 0.0004) and negatively associated with [68Ga]Ga-ABY-025 PET/CT SUVmax (P = 0.018) but not with HER2 status (P = 0.09). Conclusion: [68Ga]Ga-ABY-025 PET/CT predicted early metabolic response to HER2-targeted therapy in HER2-positive breast cancer. Metabolic response was attenuated in recurrent disease. [68Ga]Ga-ABY-025 PET/CT appears to provide an estimate of the HER2 expression required to induce tumor metabolic remission by targeted therapies and might be useful as an adjunct diagnostic tool.


Familial erythroleukaemia: a cytogenetic and haematological study.
Clinical and haematological details of 2 siblings with a familial myeloproliferative disorder (erythroleukaemia) are presented. Their father is presumed to have died from a similar disease. The 2 siblings showed similar but not identical chromosomal abnormalities detected initially in marrow and later in peripheral blood. Serial studies revealed the emergence of an increasingly diverse pattern of chromosomal changes coincident with the haematological and clinical progression of the disease. Other members of the family were screened for cytogenetic and haematological changes. The paternal sibship displayed an increased incidence of cancer.


Importance of Experimental Environmental Conditions in Estimating Risks and Associated Uncertainty of Transgenic Fish Prior to Entry into Nature.
Salmonids show a high degree of phenotypic plasticity that can differ among genotypes, and this variation is one of the major factors contributing to uncertainty in extrapolating laboratory-based risk assessment data to nature. Many studies have examined the relative growth and survival of transgenic and non-transgenic salmonids, and the results have been highly variable due to genotype × environment interactions. The relative survival of fast- and slow-growing strains can reverse depending on the environment, but it is not clear which specific environmental characteristics are driving these responses. To address this question, two experiments were designed where environmental conditions were varied to investigate the contribution of rearing density, food amount, food type, habitat complexity, and risk of predation on relative growth and survival of fast-growing transgenic and slow-growing wild-type coho salmon. The first experiment altered density (high vs. low) and food amount (high vs. low). Density impacted the relative growth of the genotypes, where transgenic fish grew more than non-transgenic fish in low density streams, regardless of food level. Density also affected survival, with high density causing increased mortality for both genotypes, but the mortality of transgenic relative to non-transgenic fish was lower within the high-density streams, regardless of food level. The second experiment altered habitat complexity (simple vs. complex), food type (artificial vs. natural), amount of food (normal vs. satiation), and risk of predation (present vs. absent). Results from this experiment showed that genotype affected growth and survival, but genotype effects were modulated by one or more environmental factors. The effect of genotype on survival was influenced by all examined environmental factors, such that no predictable trend in relative survival of transgenic versus non-transgenic fry emerged. This was primarily due to variations in survival of non-transgenic fish under different environmental conditions (non-transgenic fry had highest survival in hatchery conditions, and lowest survival in complex conditions with natural food fed at a normal level with or without predators). Transgenic fry survival was only significantly influenced by predator presence. The effects of genotype on mass and length were significantly modulated by food type only. Transgenic fry were able to gain a large size advantage over non-transgenic fish when fed artificial food under all habitat types. These experiments support the observations of dynamic responses in growth and survival depending on the environment, and demonstrate the challenge of applying laboratory-based experiments to risk assessment in nature.


Oligodeoxynucleotides having a loop consisting of 3'-deoxy-4'-C-(2-hydroxyethyl)thymidines form stable hairpins.
Components that form stable hairpin loops are highly useful for the development of functional DNA and RNA molecules. We have designed and synthesized a sugar-modified thymidine analogue, 3'-deoxy-4'-C-(2-hydroxyethyl)thymidine (X), as a nucleosidic loop component stabilizing the hairpin structure. The ODNs I-1-4, 5'-d[CGAACG-X(n)-CGTTCG]-3' (I-1, n = 1; I-2, n = 2; I-3, n = 3; I-4, n = 4), forming the hairpin loop structures, of which the loop moiety consisted of the analogue X, and also the corresponding unmodified ODNs II-1-4, 5'-d[CGAACG-T(n)-CGTTCG]-3' (II-1, n = 1; II-2, n = 2;II-3, n = 3; II-4, n = 4), having a thymidine loop, were synthesized by the phosphoramidite method. The melting temperatures (T(m)) of the ODNs I-1-4 containing X in the loop moiety at 5 microM were 67.1, 68.1, 73.0, and 69.3 degrees C, respectively, and those of the control natural ODNs II-1-4 were 65.3, 67.0, 69.2, and 68.8 degrees C, respectively. Thus, the ODNs I-1-4 formed a more thermally stable hairpin than the corresponding unmodified ODNs II-1-4 having an equal number of loop residues. The hairpin structures of the modified ODNs I-1-4 and the unmodified ODNs II-1-4 were investigated by CD spectroscopy and molecular mechanics calculations. These results showed that the 4'-branched nucleoside X can stabilize hairpin structures when it is present in the loop moiety, probably due to the flexibility of the one-carbon-elongated 4'-branched structure.


Emergence of RAS mutations in patients with metastatic colorectal cancer receiving cetuximab-based treatment: a study protocol.
In the management of patients with RAS wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) therapies have demonstrated a clinical benefit, with longer survival. However, the correlation between the emergence of circulating RAS mutations and secondary resistance to anti-EGFR therapies requires further elucidation. In this study, we aim to examine evolutionary changes in RAS mutations through liquid biopsy in patients with mCRC during and after anti-EGFR therapy. A total of 120 patients diagnosed with RAS wild-type mCRC will be enrolled in this study. Patients will receive a cetuximab-based infusional 5-fluorouracil regimen as first-line treatment. Cetuximab-based treatment is expected to continue until disease progression, intolerable toxic effects, or withdrawal of consent. Blood samples from enrolled patients will be collected before and then every 3 months during cetuximab-based treatment and also at disease progression. These blood samples will be evaluated for RAS resistance mutations by using the MassARRAY platform. The primary endpoint is the percentage of RAS mutations detected in circulating DNA from patients during cetuximab treatment. The correlation between the tumor response and survival outcomes of these patients and the emergence of circulating RAS mutations will be further analyzed. Liquid biopsy is a powerful technology that can represent tumor heterogeneity in a relatively noninvasive manner. Because RAS mutations play a major role in resistance to anti-EGFR therapy for mCRC, examining evolutionary changes in these mutations during such treatment through liquid biopsy would be useful. After comprehensively analyzing the emergence of circulating RAS mutations and its clinical relevance in this study, our results should provide practical guidance on anti-EGFR therapy for mCRC. The date of trial registration ( NCT03401957 ) in this study was January 17, 2018.


Prostaglandin receptor EP4 expression by Th17 cells is associated with high disease activity in ankylosing spondylitis.
Th17 cells are involved in the pathogenesis of ankylosing spondylitis (AS). However, the mechanism underlying enhanced Th17 cell accumulation in AS remains unknown. The prostaglandin E2 receptor EP2/EP4 signaling pathway plays a critical role in the development of autoimmune Th17 cells. Interestingly, recent genome-wide association studies (GWAS) have identified five risk alleles for AS in PTGER4, the gene encoding for EP4. The aim of this study was to reveal a possible link between EP4 and disease activity in patients with AS. Th17 cells from patients with AS were analyzed for the transcriptional expression of prostaglandin receptor genes by quantitative RT-PCR. Th17 cells from patients with rheumatoid arthritis (RA) and from healthy individuals served as controls. EP4 receptor expression in Th17 cells was assessed ex vivo by flow cytometry and by western blot. Functional analysis using EP4-specific agonists was performed to reveal how EP4 regulates Th17 cells. EP4 is significantly overexpressed in Th17 cells from patients with AS compared to Th17 cells from healthy individuals or patients with RA or psoriatic arthritis (PsA). EP4 upregulation is unique to Th17 cells and is not found in other CD4+ T cell subsets. Specific activation of EP4 drives Th17 cell development and promotes EP4 expression in a positive feedback loop in AS but not in RA or PsA. Mechanistically, EP4 acts via upregulation of the interleukin-23 receptor (IL-23R), by suppressing the RORγt inhibitor FoxO1 and by enhancing STAT3 phosphorylation. Increased EP4 expression levels in Th17 cells from AS patients correlate with high disease activity as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 (r = 0.7591, p = 0.0016). EP4 is a potential marker of disease activity in patients with AS. Aberrant EP4 expression might contribute to pathogenic Th17 cell accumulation and represent a new target for the treatment of AS.


Genetic diversity in German draught horse breeds compared with a group of primitive, riding and wild horses by means of microsatellite DNA markers.
We compared the genetic diversity and distance among six German draught horse breeds to wild (Przewalski's Horse), primitive (Icelandic Horse, Sorraia Horse, Exmoor Pony) or riding horse breeds (Hanoverian Warmblood, Arabian) by means of genotypic information from 30 microsatellite loci. The draught horse breeds included the South German Coldblood, Rhenish German Draught Horse, Mecklenburg Coldblood, Saxon Thuringa Coldblood, Black Forest Horse and Schleswig Draught Horse. Despite large differences in population sizes, the average observed heterozygosity (H(o)) differed little among the heavy horse breeds (0.64-0.71), but was considerably lower than in the Hanoverian Warmblood or Icelandic Horse population. The mean number of alleles (N(A)) decreased more markedly with declining population sizes of German draught horse breeds (5.2-6.3) but did not reach the values of Hanoverian Warmblood (N(A) = 6.7). The coefficient of differentiation among the heavy horse breeds showed 11.6% of the diversity between the heavy horse breeds, as opposed to 21.2% between the other horse populations. The differentiation test revealed highly significant genetic differences among all draught horse breeds except the Mecklenburg and Saxon Thuringa Coldbloods. The Schleswig Draught Horse was the most distinct draught horse breed. In conclusion, the study demonstrated a clear distinction among the German draught horse breeds and even among breeds with a very short history of divergence like Rhenish German Draught Horse and its East German subpopulations Mecklenburg and Saxon Thuringa Coldblood.


Management and Reconstruction in the Breast Cancer Patient With a Fungating T4b Tumor.
A subset of women with locally advanced breast cancer presented with fungating tumor mass eroding and infiltrating the surrounding breast skin (T4b breast cancers). These patients often have chronic pain, large open wounds, frequent infections, malodorous drainage, social isolation, and general debilitation that present enormous therapeutic challenges. Because of the advanced nature of the disease, palliation, while minimizing recovery time and maximizing quality of life, is essential. From 2009 to 2014, a total of 12 consecutive patients underwent resection of fungating T4b breast tumors and subsequent chest wall reconstruction. Demographic, socioeconomic, and clinical data were collected retrospectively. Fifty percent of women had distant metastases at the time of reconstruction, and 17% of women presented to the emergency department in a hemodynamically unstable condition in either hemorrhagic shock or septic shock, necessitating delay of reconstruction for up to 1 week. Mean wound size for reconstruction was 473 cm(2). Reconstructive procedures included split-thickness skin grafting and thoracoepigastric advancement, latissimus dorsi, trapezius, and extended transverse and vertical rectus abdominis flaps. Postoperative survival ranged from 98 to 172 days (mean = 127 days), with 9 patients currently living. Seventy-five percent of patients had improved pain and reduced wound care needs after reconstruction. Postoperative reconstruction-specific complications occurred in 33% of cases, with 1 patient requiring a second operating room visit. Women with fungating T4b breast cancer tumors often present with metastatic disease and have significant need for pain and wound palliation. The reconstructive techniques performed are reliable, efficacious in palliating pain, and reducing wound care needs and have low complication rates.


Polycyclic Aromatic Hydrocarbon Growth by Diradical Cycloaddition/Fragmentation.
The recent theoretical and experimental investigations on the growth of polycyclic aromatic hydrocarbons in pyrolytic environments highlight the possible role of the 1,4-cycloaddition/fragmentation (1,4-CAF) steps in the formation of PAH intermediates and consequently soot. The present theoretical study explores the possibility to generalize such mechanism to reactions involving various diradical compounds and stable multiring structures. The calculations were performed using the uB3LYP/6-311G(d,p) method and different composite methods, when possible, for more accurate energy estimates. First, the complex potential energy surface for the reactions between o-benzyne and naphthalene was investigated, including the 1,4-CAF mechanism to form anthracene and acetylene through the dibenzobicyclo[2.2.2]octatriene intermediate. Moreover, the products of the addition reactions to the α- and β-carbons and to the ring-junction atoms were determined. The energies for the optimized CAF structures, which constitute the most-favorable pathway from an energetic point of view, were calculated using CBS-QB3, G3(MP2)B3, and G3B3 methods and compared to the corresponding values for the o-benzyne + benzene reactions. Additional calculations were focused on the possible CAF reactions between o-benzyne and larger multiring structures, such as anthracene, phenanthrene, pyrene, and the four-ring PAHs. The results indicate how the energetics of such reactions is influenced by both the size of the PAH compound and the position of the carbon atoms involved. In the second part of the study, the energy barriers necessary to form multiring diradicals from the corresponding radical molecules were analyzed at a G3(MP2)B3 level of theory. Such calculations are preliminary for the subsequent study on the CAF reactions between the different diradical intermediates and benzene. While the size of the diradical does not affect significantly the energy barriers, the position of the diradical site is critical. The concerted Diels-Alder reactions between the naphthynes and naphthalene were also studied in order to further clarify the analogies between the reactions involving different diradicals. Based on these results, kinetic considerations were provided based on the comparison with the simpler o-benzyne + benzene system, although further higher-level calculations and master equation kinetic analyses will be required to derive the general kinetic rules.


An application study of membraneless-gas separation microfluidic paper-based analytical device for monitoring total ammonia in fish pond water using natural reagent.
The membraneless-gas separation microfluidic paper-based analytical device (ML-GS μPAD), consisting of donor, spacer, and acceptor layers, was developed to monitor total ammonia in fish pond water. The principle of the analysis involved the addition of sodium hydroxide solution to the sample zone in the donor layer containing ammonia/ammonium, and the produced ammonia gas diffuses through the spacer to the detection zone in the acceptor layer containing red rose extract to produce a color change from pink to blue corresponding to the ammonia/ammonium concentration. Under optimum conditions, the proposed method provided good linearity of ammonia in the range concentration of 0-100 mg L-1 (R2 = 0.9993) with LOD and LOQ of 2.25 and 7.51 mg L-1, respectively. This method was successfully applied to fish pond water samples without significant influence of interfering compounds with recoveries in the range of 103-110%, indicating good selectivity and accuracy of the proposed method.


Huntington's Disease: Calcium Dyshomeostasis and Pathology Models.
Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and mental impairment. At the molecular level, HD is caused by a mutation in the first exon of the gene encoding the huntingtin protein. The mutation results in an expanded polyglutamine tract at the N-terminus of the huntingtin protein, causing the neurodegenerative pathology. Calcium dyshomeostasis is believed to be one of the main causes of the disease, which underlies the great interest in the problem among experts in molecular physiology. Recent studies have focused on the development of animal and insect HD models, as well as patient-specific induced pluripotent stem cells (HD-iPSCs), to simulate the disease's progression. Despite a sesquicentennial history of HD studies, the issues of diagnosis and manifestation of the disease have remained topical. The present review addresses these issues.


Teriparatide for the Treatment of Medication-Related Osteonecrosis of the Jaw.
Medication-related osteonecrosis of the jaw (MRONJ) is a painful and intractable disease of the jaw that clinically presents as an area of ulceration with exposed necrotic bone. In severe cases, it can predispose to jaw fracture, skin fistula, or osteolysis extending beyond the region of the alveolar bone. No effective treatment has been established for this condition. Recently, teriparatide, a recombinant parathyroid hormone, and the only FDA-approved osteoanabolic drug for the treatment of glucocorticoid-induced osteoporosis, has been used for the treatment of MRONJ. We review the literature highlighting the effectiveness of teriparatide alone or as an adjunct in the treatment of MRONJ. Twenty publications met our selection criteria, comprising 54 patients with stage 2 or 3 MRONJ secondary to antiresorptive/antiangiogenic drugs. Trauma due to implant placement was the most common triggering factor for the development of MRONJ. Patients were treated with subcutaneous injections of 20-μg teriparatide for 3-12 months (5 1/2 months average). Symptomatic relief was achieved in almost all cases, with lesions healing completely in 49 of 54 patients. Based on our findings, teriparatide can play an important role in the treatment of MRONJ.


Finding communities in directed networks.
To identify communities in directed networks, we propose a generalized form of modularity in directed networks by presenting the quantity LinkRank, which can be considered as the PageRank of links. This generalization is consistent with the original modularity in undirected networks and the modularity optimization methods developed for undirected networks can be directly applied to directed networks by optimizing our modified modularity. Also, a model network, which can be used as a benchmark network in further community studies, is proposed to verify our method. Our method is supposed to find communities effectively in citation- or reference-based directed networks.


Management tools for Medicaid and State Children's Health Insurance Program (SCHIP).
Medicaid and the State Children's Health Insurance Program need analytic tools to manage their programs. Drawing upon extensive discussions with experts in states, this article describes the state of the art in tool use, making several observations: (1) Several states have linked Medicaid/State Children's Health Insurance Program administrative data to other data (eg, birth and death records) to measure access to care. (2) Several states use managed care encounter data to set payment rates. (3) The analysis of pharmacy claims data appears widespread. The article also describes "lessons learned" regarding building capacity and improving data to support the implementation of management tools.


Toxicity of Insecticides Targeting Rice Planthoppers to Adult and Immature Stages of Trichogramma chilonis (Hymenoptera: Trichogrammatidae).
Planthopper-targeting insecticides, pymetrozine, thiamethoxam, buprofezin, and nitenpyram, were tested under laboratory conditions for toxicity to adults and immatures of Trichogramma chilonis Ishii, using standard tests described by International Organization for Biological Control (IOBC). In the dry film residue test, all insecticides resulted in >90% mortality in T. chilonis adults and were ranked as moderately harmful. Persistent toxicity tests revealed that nitenpyram was short-lived and the other three insecticides were of slightly persistent toxicity to the wasp adults. Effects of the insecticides on egg, larval, and prepupal stages of T. chilonis were investigated with striped stem borer as host. At the three stages of T. chilonis (within the host egg), all the insecticides reduced parasitism rate, but nitenpyram and pymetrozine applied at egg stage, buprofezin and nitenpyram at larval stage, and buprofezin and thiamethoxam at prepupal stage of T. chilonis reduced parasitism by <30% in comparison with the control, and were thus ranked as harmless. Although insecticide treatment of the three immature stages of T. chilonis all reduced wasp emergence from host eggs, only thiamethoxam applied at larval stage and buprofezin at prepupal stage resulted in >30% reduction in emergence rate as compared with the control and were categorized as harmful. Immature duration of T. chilonis was only significantly extended by nitenpyram applied to egg stage than the control. Sex ratio of emerged wasps was not affected by the treatment to immature stages. The data are of significance for IPM programs incorporating inundative release of T. chilonis for control of lepidopteran rice pests where there is heavy co-occurrence of planthoppers.


Routes to complex dynamics in a ring of unidirectionally coupled systems.
We study the dynamics of a ring of unidirectionally coupled autonomous Duffing oscillators. Starting from a situation where the individual oscillator without coupling has only trivial equilibrium dynamics, the coupling induces complicated transitions to periodic, quasiperiodic, chaotic, and hyperchaotic behavior. We study these transitions in detail for small and large numbers of oscillators. Particular attention is paid to the role of unstable periodic solutions for the appearance of chaotic rotating waves, spatiotemporal structures, and the Eckhaus effect for a large number of oscillators. Our analytical and numerical results are confirmed by a simple experiment based on the electronic implementation of coupled Duffing oscillators.


Optically Induced Electron Transfer in Mixed-Valence States: A Model Study on Electronic Transitions, Relaxation Dynamics, and Transient Absorption Spectroscopy.
Quantum dynamical model calculations are performed on the optically induced electron transfer in a mixed-valence system interacting with different solvents. The simultaneously occurring processes of population transfer between electronic states and relaxation are studied in detail. Transient absorption traces, as recently recorded in our laboratory, are simulated, and the features of the spectra are related to the dynamics. The agreement with the experiment hints at the fact that the employed one-dimensional models catch the essentials of the photochemistry of the investigated systems and that they can be used for the interpretation of the transient absorption spectra. It is inferred that the ultrafast electron transfer processes take place on a sub-picosecond time scale and afterward relaxation occurs within several picoseconds.


Comparison of serum lipoprotein(a) levels in young and middle-aged patients presenting for the first time with ST-elevation myocardial infarction: a single-centre study.
Lipoprotein(a) [Lp(a) ] is associated with coronary artery disease due to its atherogenic and thrombogenic nature. In this study, we aimed to compare the level of Lp(a) in young and middle-aged patients with ST-elevation myocardial infarction (STEMI). This retrospective study included 287 patients aged 20-65 years who presented to the emergency department for the first time due to STEMI. The patients were divided into two groups: 20-45 years (young group, n = 111) and 46-65 years (middle-aged group, n = 176). The groups were compared in terms of demographic characteristics, co-morbidities and laboratory findings. In the young group, smoking (99, 89.2% vs 130, 73.9%; p = 0.001), family history of coronary artery disease (75, 67.6% vs 80, 45.5; p < 0.001), serum Lp(a) level [38.1 ± 27.9 (93 ± 68) vs 23.5 ± 23.2 mg/dl (57 ± 56 nmol/l); p < 0.001], triglyceride level [219.1 ± 231.9 (2.48 ± 2.62) vs 170.2 ± 105.6 mg/dl (1.92 ± 1.19 mmol/l); p = 0.018), ejection fraction (52.4 ± 6.1 vs 47.2 ± 7.7%; p = 0.004) and single-vessel disease (83, 74.8% vs 110, 62.5%; p = 0.031) were higher than in the middle-aged group. In multivariable logistic regression analyses, family history (OR: 2.073, 95% CI: 1.210-3.549; p = 0.008), low high-density lipoprotin cholesterol level (OR: 1.032, 95% CI: 1.003-1.062; p = 0.029) and Lp(a) elevation (OR: 1.981, 95% CI: 1.871-3.991; p < 0.001) were possible independent risk factors for STEMI in young patients. Lp(a) level was found to be a higher and a possible independent risk factor in young patients who presented with STEMI for the first time, compared to the middle-aged patient group. Lp(a) is a highly atherogenic molecule and it has been associated with stroke, heart failure, aortic stenosis, as well as coronary artery disease. Measurement of Lp(a) levels may be recommended in young patients with high cardiovascular risk.


Efficacy and safety of tyrosine kinase inhibitors alone or in combination with radiation therapy for metastatic renal cell carcinoma: A protocol for evidence-based systematic review and Bayesian network meta-analysis.
Given the lack of evidence for survival benefit in patients with metastatic renal cell carcinoma from the addition of radiation therapy to tyrosine kinase inhibitor therapy, this Bayesian network meta-analysis aimed to evaluate survival outcomes in patients receiving radiation therapy plus tyrosine kinase inhibitor therapy. The preferred reporting items for systematic reviews and meta-analyses reporting guidelines were followed to conduct this study. The electronic databases of PubMed, Cochrane Library, EMBASE, and Web of Science were searched from the inception to August 2021. All phase III clinical trials that reported the outcomes of tyrosine kinase inhibitor with radiation therapy compared with those of tyrosine kinase inhibitor or radiation therapy alone for patients with metastatic renal cell carcinoma were considered eligible for inclusion in this meta-analysis. Overall survival as the primary outcome of interest, and adverse events as secondary outcome of interest were recorded for meta-analysis. A Bayesian network meta-analysis is an appropriate statistical method to compare all treatment options by statistically simulating the estimated results of a comprehensive trial, and to compare treatments by common and associated comparators. In addition, Bayesian network meta-analysis can produce ranking probabilities of treatments, which may contribute to clinicians' clinical decision-making.


Effect of ultraviolet light on mengovirus: formation of uracil dimers, instability and degradation of capsid, and covalent linkage of protein to viral RNA.
UV irradiation of purified mengovirus resulted in a very rapid inactivation of the infectivity of the virions (D(37) [37% survival dose] = 700 ergs/mm(2)) which correlated in time with the formation of uracil dimers in the viral RNA. During the first 2 min of irradiation, an average of 1.7 uracil dimers were formed per PFU of virus inactivated. Hemagglutination activity of the virions began to decrease only after a lag period of about 5 min and at a much lower rate (D(37) = 84,000 ergs/mm(2)). This decrease coincided in time with the appearance of altered proteins in the capsid and a structural change in the capsid. Although 10- to 20-min irradiated virions appeared intact in the electron microscope and sedimented at 150S in sucrose density gradients, the RNA of the virions became accessible to RNase and extractable by low concentrations of sodium dodecyl sulfate, and the virions broke down upon equilibrium centrifugation in CsCl gradients. During longer periods of irradiation (30 to 60 min), a progressively greater proportion of the virions were converted to 14S protein particles and 80S ribonucleoprotein particles composed of intact viral RNA and about 30% of the capsid proteins, alpha, beta, and gamma. Empty capsids were not detectable at any time during 60 min of irradiation, by which time disruption of the virions was complete. Irradiation of complete virions also resulted in an increased sedimentation rate of the viral RNA and in the covalent linkage to the viral RNA of about 1% of the total capsid protein in the form of heterogeneous low-molecular-weight polypeptides. The two observations seem to be causally related, since irradiation of isolated viral RNA did not result in an increase in sedimentation rate of the RNA, even though uracil dimer formation in viral RNA occurred at about the same rate and to the same extent whether intact virions or viral RNA were irradiated.


MicroRNA-183 inhibits gastric cancer proliferation and invasion via directly targeting Bmi-1.
The aberrant expression of microRNA-183 (miRNA/miR-183) has been found to be involved in numerous tumor types. However, the role of miR-183 in gastric cancer pathology is unclear and requires investigation. In the present study, the miR-183 expression levels of gastric cancer cell lines and tissues obtained from gastric cancer patients were measured by reverse transcription quantitative polymerase chain reaction analysis. The effect of miR-183 on gastric cancer cell proliferation and invasion was evaluated using MTT, colony formation and Transwell assays. The target of miR-183 was identified and confirmed using a luciferase activity assay. The results revealed that miR-183 was significantly downregulated in gastric cancer cells compared with GES-1 normal gastric epithelial cells. In addition, miR-183 was reduced in gastric cancer tissues compared with adjacent normal tissues. The ectopic expression of miR-183 significantly inhibited gastric cancer cell proliferation, colony formation and invasion. Bmi-1 was also confirmed as a downstream target of miR-183 in the gastric cancer cells by western blot analysis and luciferase activity assays. In conclusion, miR-183 is downregulated in gastric cancer cells and tissues, and inhibits gastric cancer cell proliferation and invasion by targeting Bmi-1. Therefore, targeting miR-183 may be a potential therapeutic strategy in gastric cancer patients.


Marivirga lumbricoides sp. nov., a marine bacterium isolated from the South China Sea.
A novel, aerobic, heterotrophic, orange-pigmented, Gram-staining-negative, rod-shaped, gliding bacterial strain, designated JLT2000(T), was isolated from surface water of the South China Sea. The strain was oxidase- and catalase-positive. The major cellular fatty acids of strain JLT2000 T: were C12 : 0, iso-C15 : 1 G, iso-C15 : 0, iso-C17 : 0 3-OH, summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C18 : 0. MK-7 was the major respiratory quinone and the major polar lipids were phosphatidylcholine and phosphatidylethanolamine. The genomic DNA G+C content of strain JLT2000(T) was 37.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain JLT2000(T) formed a branch within the genus Marivirga, but was clearly separated from the two established species of this genus, Marivirga tractuosa and Marivirga sericea. The 16S rRNA gene sequence similarity of strain JLT2000(T) with the type strains of these two species was 95.8 % and 96.1 %, respectively. Strain JLT2000(T) had a shorter cell length and wider growth range in different temperatures and salinities than those of Marivirga tractuosa NBRC 15989(T) and Marivirga sericea NBRC 15983(T). In addition, strain JLT2000(T) could utilize more carbon sources and hydrolyse more polymers than Marivirga tractuosa NBRC 15989(T) and Marivirga sericea NBRC 15983(T). Based on this polyphasic analysis, strain JLT2000(T) represents a novel species of the genus Marivirga, for which the name Marivirga lumbricoides sp. nov. is proposed. The type strain is JLT2000(T) ( = JCM 18012(T) = CGMCC 1.10832(T)).


Molecular regulation of gene expression of catecholamine biosynthetic enzymes by stress: sympathetic ganglia versus adrenal medulla.
Stress induces tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) gene expression in sympathetic ganglia and adrenal medulla (AM). However, distinct molecular mechanisms appear to regulate these genes in these locations. The elevation of TH mRNA in response to single immobilization stress (IMO) in AM is robust, but transient, while the induction of TH and DBH mRNAs in sympathetic ganglia is slower and more long lasting. Injections of adrenocorticotropic hormone (ACTH) elicited induction of TH and DBH gene expression in rat sympathetic ganglia, but not in AM. The superior cervical (SCG) and stellate (StG) ganglia, but not AM, were found to express mRNA for the MC-2 receptor, the major ACTH responsive receptor in adrenal cortex. IMO led to increase in MC-2 receptor mRNA levels in SCG. Thus, ACTH, via the MC-2 receptor, may be directly involved in the stress-elicited regulation of norepinephrine biosynthesis in sympathetic ganglia. The signaling pathways triggered by IMO differed in these locations. In AM, IMO triggered activation of the MAP kinase, JNK, and induction of AP1 factors, Egr1 and phosphorylation of CREB. In contrast in the SCG, with IMO we did not observe changes in JNK and little binding to the AP1 motif of the TH promoter. However, there was an increase in CREB binding to the CRE site of the TH promoter. The results reveal differential mechanisms of regulation of catecholamine biosynthetic enzymes by stress in two components of the sympathoadrenal system and should provide basis for possible selective pharmacologic interventions.


Tear production in canine neonates--evaluation using a modified Schirmer tear test.
The ability of human newborns to produce tears has been a subject of controversy in the literature since the mid-20th century, and there has been considerable debate as to whether they are able to produce tears. Recently, it was established that total tear secretion (reflex + basal) in full-term infants is similar to those of adults whereas both reflex and basal tear production is reduced in premature babies. The objectives of this study were to assess whether newborn dogs have measurable aqueous tear production at the fourth week of life and to evaluate a modified Schirmer tear test (mSTT) as a useful method for measuring neonatal tear production in dogs. Thirty four-week-old healthy puppies from six litters were evaluated. A control group was composed of 10 normal adult dogs. The mSTT strips were obtained by cutting a 5 mm-wide strip in half (making two 2.5 mm-wide strips). The mSTT1 was performed in puppies and adult dogs. Values were compared using t-tests. In neonates, the average value for the mSTT1 was 13.6 ± 3.07 (range = 7-19 mm/min), which was significantly lower in neonates than in adult dogs (23.25 ± 3.5, range = 17-30 mm/min, P < 0.0001). Canine neonates do produce tears by the fourth week of life, which can be successfully measured with the mSTT. This report established for the first time that canine neonates have significantly reduced total (reflex + basal) tear secretion compared to adults.


Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation.
Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for the CFTR channel protein. The most common mutation in CF is F508del, which produces a misfolded protein with diminished channel activity. The development of small-molecule CFTR-modulator compounds offers an exciting and novel approach for pharmacological treatment of CF. The corrector lumacaftor helps rescue F508del-CFTR to the cell surface, and potentiator ivacaftor increases F508del-CFTR channel activity. The combination of lumacaftor-ivacaftor (Vertex Pharmaceuticals Incorporated) represents the first FDA-approved therapy for CF patients with two copies of the F508del mutation. Although this combination therapy is the first treatment to directly target the F508del-CFTR mutation, patients taking this drug displayed only modest improvements in lung function. This article summarizes recent data from clinical trials and research discoveries relating to the lumacaftor-ivacaftor treatment, and considers options for identifying future therapies that will be most efficacious for all CF patients.


Further studies on antigen variation in Staphylococcus aureus.
The plating of successive Staphylococcus aureus subcultures of daily transfers proved that discontinuous variation resembling a genetic mutation and selective outgrowth of the variant are responsible for antigen variation. Every subculture of S. aureus, when repeatedly transferred, contained a mixture of cells with original antigen 17 (or 13) and final antigen 1 (or 3) that are relevant for research, serological diagnosis, and epidemiological study of staphylococcal diseases.


Detection of serotype-specific antibodies to the four dengue viruses using an immune complex binding (ICB) ELISA.
Dengue virus (DENV) infections are preferentially diagnosed by detection of specific IgM antibodies, DENV NS1 antigen assays or by amplification of viral RNA in serum samples of the patients. The type-specific immunity to the four worldwide circulating DENV serotypes can be determined by neutralization assays. An alternative to the complicated neutralization assays would be helpful to study the serotype-specific immune response in people in DENV hyperendemic areas but also in subjects upon DENV vaccination. In consecutive samples of patients with DENV-1- 4 infection type-specific antibodies were detected using an immune complex binding (ICB) ELISA. During incubation of serum samples and enzyme- labeled recombinant envelope domain III (EDIII) antigens immune complexes (ICs) are formed, which are simultaneously bound to a solid phase coated with an Fc-receptor (CD32). After a single washing procedure the bound labeled ICs can be determined. To further improve type-specific reactions high concentrations of competing heterologous unlabeled ED III proteins were added to the labeled antigens. Follow-up serum samples of 64 patients with RT-PCR confirmed primary DENV-1, -2, -3 or -4 infections were tested against four enzyme-labeled recombinant DENV EDIII antigens. Antibodies to the EDIII antigens were found in 55 patients (sensitivity 86%). A complete agreement between the serotype detected by PCR in early samples and the serotype-specific antibody in later samples was found. Type-specific anti-EDIII antibodies were first detected 9-20 days after onset of the disease. In 21% of the samples collected from people in Vietnam secondary infections with antibodies to two serotypes could be identified. The data obtained with the ICB-ELISA show that after primary DENV infection the corresponding type-specific antibodies are detected in almost all samples collected at least two weeks after onset of the disease. The method will be of value to determine the distribution of the various type-specific anti-DENV antibodies in DENV endemic areas.


Diffuse alveolar hemorrhage as a life threatening manifestation of newly diagnosed granulomatosis with polyangiitis following COVID-19 infection - a case report.
A case report of a patient with newly diagnosed granulomatosis with polyangiitis (GPA) after undergoing COVID-19 (Coronavirus Disease 2019) is discussed. GPA is one of the ANCA-associated vasculitis, which is characterized by the presence of autoantibodies against cytoplasmic enzymes neutrophils (Anti Neutrophil Cytoplasmatic Antibodies). It is a vasculitis that mainly affects small blood vessels, leading to damage to the kidneys, lungs, and upper respiratory tract, including the paranasal sinuses and orbits. This disease can result in an acute life-threatening condition. Such complications include diffuse alveolar hemorrhage (DAH), a condition characterized by blood leakage from the pulmonary vessels into the alveoli, often leading to acute vital signs and even respiratory failure. DAH can have many causes - autoimmune diseases including vasculitides as well as non-immunological causes. Early and adequate comprehensive therapy including immunosuppressive treatment (cyclophosphamide/rituximab and glucocorticoids) can be life-saving.


The assessment of health policy changes using the time-reversed crossover design.
The time-reversed crossover design is a quasi-experimental design which can be applied to evaluate the impact of a change in health policy on a large population. This design makes use of separate sampling and analysis strategies to improve the validity of conclusions drawn from such an evaluation. The properties of the time-reversed crossover design are presented including the use of stratification on outcome in the sampling stage, which is intended to improve external validity. It is demonstrated that, although this feature of the design introduces internal validity threats due to regression toward the mean in extreme-outcome strata, these effects can be measured and eliminated from the test of significance of treatment effects. Methods for within- and across-stratum estimation and hypothesis-testing are presented which are similar to those which have been developed for the traditional two-period crossover design widely used in clinical trials. The procedures are illustrated using data derived from a study conducted by the United Mine Workers of America Health and Retirement Funds to measure the impact of cost-sharing on health care utilization among members of its health plan.


Cleaning Strategies of Synthesized Bioactive Coatings by PEO on Ti-6Al-4V Alloys of Organic Contaminations.
The effect of various cleaning methods on coating morphology and their effectiveness in removing organic contaminants has been studied in this research. Bioactive coatings containing titanium oxides and hydroxyapatite (HAP) were obtained through plasma electrolytic oxidation in aqueous electrolytes and molten salts. The cleaning procedure for the coated surface was performed using autoclave (A), ultraviolet light (UV), radio frequency (RF), air plasma (P), and UV-ozone cleaner (O). The samples were characterized using scanning electron microscopy (SEM) with an EDS detector, X-ray photoelectron spectroscopy (XPS), X-ray phase analysis (XRD), and contact angle (CA) measurements. The conducted studies revealed that the samples obtained from molten salt exhibited a finer crystalline structure morphology (275 nm) compared to those obtained from aqueous electrolytes (350 nm). After applying surface cleaning methods, the carbon content decreased from 5.21 at.% to 0.11 at.% (XPS), which directly corresponds to a reduction in organic contaminations and a decrease in the contact angle as follows: A > UV > P > O. This holds true for both coatings obtained in molten salt (25.3° > 19.5° > 10.5° > 7.5°) and coatings obtained in aqueous electrolytes (35.2° > 28.3° > 26.1° > 16.6°). The most effective and moderate cleaning method is ozone treatment.


The experience of beauty derived from sorrow.
We studied the neural mechanisms that are engaged during the experience of beauty derived from sorrow and from joy, two experiences that share a common denominator (beauty) but are linked to opposite emotional valences. Twenty subjects viewed and rerated, in a functional magnetic resonance imaging scanner, 120 images which each had classified into the following four categories: beautiful and sad; beautiful and joyful; neutral; ugly. The medial orbito-frontal cortex (mOFC) was active during the experience of both types of beauty. Otherwise, the two experiences engaged different parts of the brain: joyful beauty engaged areas linked to positive emotions while sorrowful beauty engaged areas linked to negative experiences. Separate regions of the cerebellum were engaged during experience of the two conditions. A functional connectivity analysis indicated that the activity within the mOFC was modulated by the supplementary motor area/middle cingulate cortex, known to be engaged during empathetic experiences provoked by other peoples' sadness. Hum Brain Mapp 38:4185-4200, 2017. © 2017 Wiley Periodicals, Inc.


Crimean Congo hemorrhagic fever: requires vigilance and not panic.
Crimean Congo hemorrhagic fever (CCHF) has been in the news with reports of its outbreak in India from Gujarat. CCHF is caused by a virus which is a member of the Nairovirus genus of the family Bunyaviridae. All of these viruses are transmitted by either ixodid or argasid ticks. Humans get this infection after a bite of an infected tick or from one infected human to another by contact with infectious blood or body fluids. Workers in livestock and agriculture industry, slaughterhouses, and veterinary practice are most prone to this infection. In severe cases after 3-6 days of the onset of symptoms hemorrhagic manifestations occur. IgG and IgM antibodies may be detected in serum by ELISA from about the sixth day of the illness. The mainstay of treatment in CCHF is supportive. Management of DIC, sepsis, shock and MODS should be undertaken. The antiviral drug Ribavirin has shown benefits. Benefits of treatment with ribavirin outweigh the fatal risks, and ribavirin may therefore be recommended. People at risk should use effective personal protective measures against tick bites. Acaricide treatment of livestock in CCHF virus endemic areas is effective in reducing the population of infected ticks.


A meta-QTL analysis highlights genomic hotspots associated with phosphorus use efficiency in rice (Oryza sativa L.).
Phosphorus use efficiency (PUE) is a complex trait, governed by many minor quantitative trait loci (QTLs) with small effects. Advances in molecular marker technology have led to the identification of QTLs underlying PUE. However, their practical use in breeding programs remains challenging due to the unstable effects in different genetic backgrounds and environments, interaction with soil status, and linkage drag. Here, we compiled PUE QTL information from 16 independent studies. A total of 192 QTLs were subjected to meta-QTL (MQTL) analysis and were projected into a high-density SNP consensus map. A total of 60 MQTLs, with significantly reduced number of initial QTLs and confidence intervals (CI), were identified across the rice genome. Candidate gene (CG) mining was carried out for the 38 MQTLs supported by multiple QTLs from at least two independent studies. Genes related to amino and organic acid transport and auxin response were found to be abundant in the MQTLs linked to PUE. CGs were cross validated using a root transcriptome database (RiceXPro) and haplotype analysis. This led to the identification of the eight CGs (OsARF8, OsSPX-MFS3, OsRING141, OsMIOX, HsfC2b, OsFER2, OsWRKY64, and OsYUCCA11) modulating PUE. Potential donors for superior PUE CG haplotypes were identified through haplotype analysis. The distribution of superior haplotypes varied among subspecies being mostly found in indica but were largely scarce in japonica. Our study offers an insight on the complex genetic networks that modulate PUE in rice. The MQTLs, CGs, and superior CG haplotypes identified in our study are useful in the combination of beneficial alleles for PUE in rice.


Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. We sought to determine the factors that selectively define GIP- vs. GLP-1-expressing cells. We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. EMSA was performed to assess the binding of these transcription factors to the GIP promoter. Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. Promoter truncation analysis revealed a major loss of promoter activity when the sequence between -184 to -145 bp was deleted. EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP.


Clinical Practice Guidelines for Endoscope Reprocessing.
Gastrointestinal endoscopy is effective and safe for the screening, diagnosis, and treatment of gastrointestinal disease. However, issues regarding endoscope-transmitted infections are emerging. Many countries have established and continuously revise guidelines for endoscope reprocessing in order to prevent infections. While there are common processes used in endoscope reprocessing, differences exist among these guidelines. It is important that the reprocessing of gastrointestinal endoscopes be carried out in accordance with the recommendations for each step of the process.


[Results of combined therapy for malignant tumors of the nasal cavity and accessory nasal sinus depending on the fractionation of preoperative radiotherapy].
Data on the treatment of 215 patients with locally advanced malignancies of the nasal cavity and accessory nasal sinus are presented. All patients received preoperative radiotherapy using different fractionation schemes under a total target dose (TTD) of 32-40 Gy. Surgery was carried out two weeks later. Whenever radicality of surgery was in doubt, postoperative gamma therapy included exposure to 2 Gy 5 times a week (TTD--30-40 Gy) (n=121). Group I (n-57) received radiation at standard fractionated dosage. In group II (n=66), fractionation, tentatively considered "dynamic" was used while, in group III, fractionation was dynamic in actual fact. In group IV (n=10), superfractionation (1+1 Gy) was employed in group V (n=6),--gamma-neutron therapy. Patients in group VI (n=51) were operated on as scheduled and received 5 Gy, twice a week (TTD--20 Gy). According to 5-year follow-up, the best results were obtained with the use of larger doses of preoperative radiation (groups II, III, VI). Postoperative radiotherapy proved ineffective and it would be useless unless ablative procedures were definitely faulty during surgery.


[Expression of H19 long non-coding RNA and ZEB1 in the trophoblast of women with spontaneous abortion].
To investigate the expression of H19 long non-coding RNA (lncRNA) and zinc finger E-box-binding protein 1 (ZEB1) in the trophoblast of women with spontaneous abortion. Methods: A total of 20 women underwent miscarriage were enrolled as a miscarriage group, while 20 women underwent artificial abortion were enrolled as a control group. Reverse transcriptional fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of H19 lncRNA and miR-200, and Western blot was used to detect the expression of ZEB1. Results: Compared to the control group, a tendency of decreased H19 was detected in the miscarriage group, with no significant difference (1.28±0.08 vs 1.66±0.21, P=0.091). There was no significant difference in miR-200 between the 2 groups (0.75±0.35 vs 0.58±0.33, P=0.0.533). The expression of ZEB1 was significantly decreased in the miscarriage group compared to that in the control group (0.22±0.03 vs 0.41±0.04, P=0.0003). The expression of H19 lncRNA and ZEB1 was positively correlated (r=0.529, P=0.0005), and the correlation between H19 lncRNA and miR-200 had no statistical significance (r=0.0293, P=0.858). The correlation between miR-200 and ZEB1 also had no statistical significance (r=-0.132, P=0.416). Conclusion: Down-regulation of ZEB1 in the trophoblast might be related to miscarriage. H19 lncRNA may regulate the expression of ZEB1.


Evaluation of nutritional risk screening-2002 and subjective global assessment for general surgery patients: a prospective study.
To investigate the reliability of nutritional risk screening (NRS-2002) and Subjective Global Assessment (SGA) tools to predict the length of hospital stay, complications and mortality, and to compare these tools in predicting outcomes of surgical patients. The prospective study was conducted at the Surgery Department of Numune Training and Research Hospital, Adana, Turkey, from March 30 to September 30, 2010. The patients were divided into 3 groups. Group 1 included patients requiring major surgical operations for gastrointestinal malignancy; Group 2 and 3 included patients undergoing moderate surgery and minor surgical operations respectively. Discrimination characteristics of the scoring systems were evaluated using receiver operating characteristic curves. Nutritional risk at admission was found to be increased in 132 (22.5%) patients by NRS-2002, and 90 (15.3%) by SGA. The sensitivity and specificity of NRS-2002 for complications were 53.3% and 96.6% respectively. The SGA values were 55% and 98.5% respectively. NRS-2002 and SGA at admission had a reliable power of discrimination (AUC > 0.8) for mortality and to predict complications in major gastrointestinal surgical patients. SGA and NRS-2002 methods had positive predictive power in estimating the mortality risk in general surgical patient population. Both scoring tools were also positive in estimating post-operative complication risk in major surgical patients.


SpaceOAR to improve dosimetric outcomes for monotherapy high-dose-rate prostate implantation in a patient with ulcerative colitis.
High-dose-rate (HDR) brachytherapy is an attractive option for patients receiving definitive radiation therapy for prostate cancer with decreased overall dose to the pelvis. However, ulcerative colitis increases rectal toxicity risk and may be a contraindication. A synthetic hydrogel, SpaceOAR (Augmentix Inc., Waltham, MA, USA), can facilitate the use of HDR brachytherapy for patients where rectal toxicity is a limiting factor. SpaceOAR gel (13.19 cc) was utilized in a monotherapy HDR prostate treatment with Ir-192 under transrectal ultrasound guidance, with the intention of decreasing rectal dose. SpaceOAR gel was inserted transperineally into the patient 18 days prior to the procedure. The HDR brachytherapy procedure was tolerated without incident. All planning constraints were met, and the following dosimetry was achieved: Prostate - V100% = 97.3%, V150% = 35%, V200% = 14.5%; Urethra - V118% = 0%; Rectum - D2 cc = 51.6%, V75% = 0 cc. The rectum-catheter spacing was on average between 6-8 mm. Average spacing for our 10 most recent patients without SpaceOAR was 3 mm. SpaceOAR did not hinder or distort ultrasound imaging or increase treatment time. SpaceOAR successfully increases catheter-rectal wall spacing and decreases rectal dose due to improved planning capabilities, while decreasing the likelihood of rectal perforation. One application of this tool is presented to mitigate potential toxicities associated with ulcerative colitis. At five months, one week, and one day follow-up, the patient reported no bowel issues following HDR brachytherapy.


The long-term cost of childhood conduct problems: Finnish Nationwide 1981 Birth Cohort Study.
Commonly recognized childhood conduct problems often lead to costly problems in adulthood. This study aimed to evaluate the long-term cumulative cost of childhood conduct problems until the age of 30. The costs included inpatient care, nervous system medicine purchases, and criminal offences. The study used population-based nationwide 1981 birth cohort data. Families and teachers assessed the conduct problems of the eight-year-olds based on Rutter questionnaires. We grouped 5,011 children into low-level of conduct problems (52%), intermediate-level of conduct problems (37%), and high-level of conduct problems (11%) groups, based on combined conduct symptoms scores. The analysis included the cohort data with the Care Register for Health Care, the Drug Prescription Register, and the Finnish Police Register. The cost valuation of service use applied national unit costs in 2016 prices. We used Wilcoxon rank-sum test to test the differences between groups and gender. During 1989-2011, average cumulative costs of the high-level (€44,348, p < .001) and the intermediate-level (€19,405, p < .001) of conduct problems groups were higher than the low-level of conduct problems group's (€10,547) costs. In all three groups, the boys' costs were higher than girls' costs. The costs associated with conduct problems in childhood are substantial, showing a clear need for cost-effective interventions. Implementation decisions of interventions benefit from long-term cost-effectiveness modelling studies. Costing studies, like this, provide cost and cost offset information for modelling studies.


Comparison of Databases for Complex Evidence Syntheses on Education for the Health Professions.
Increased requests for assistance with literature searches on educational topics within the health professions motivated two health science librarians to analyze search function and results in eleven bibliographic databases on questions representing three allied health instructional target populations (patient, caregiver, and future health professionals). Results overlap and relevance were estimated and useful functions and subject headings were examined, as evidence for future search and database recommendations. This research confirmed the authors' hypothesis that PubMed and CINAHL overlapped significantly yet yielded sufficient unique citations to recommend searching both, plus at least one education-specific database. For the six questions researched, psychology and sports medicine databases were less productive.


Sixteen additional enhancers associated with the chicken Sox2 locus outside the central 50-kb region.
The transcription factor Sox2 plays a central role in the regulation of neuro-sensory development, and many other developmental processes. To gain an in depth understanding of the Sox2 gene regulation, we previously investigated the Sox2-proximal 50-kb region of the chicken genome to determine enhancers based on functional assays using chicken embryo electroporation. We identified 11 enhancers with specificity for neuro-sensory tissues. In this study, we extended the analysis of Sox2 locus-associated enhancers to a 200-kb region and identified 16 additional enhancers with functions in neuro-sensory development. These enhancers roughly correspond to a fraction of the sequence blocks that are highly conserved between chicken and mammalian genomes. The neural enhancers were activated in sequence, thereby creating a complex pattern of functional overlaps in the developing central nervous system (CNS). The variations in the specificities of the sensory enhancers also reflected the intermediate steps of sensory tissue development. This study provides an example where a single transcription factor gene has numerous regulatory elements that allow it to fulfill many functional roles in different biological contexts.


Bone formation in tricalcium phosphate-filled periodontal intrabony lesions. Histological observations in humans.
The capacity of a tricalcium phosphate (TCP) ceramic to promote bone formation after grafting in intrabony defects was studied in humans. Five biopsies were collected from 4 patients during reentry surgery 16 to 40 months after implantation. They were processed without demineralization for histological examination. In the less mature samples, the grafted material was surrounded by a highly fibrous, highly cellular, and poorly vascularized connective tissue. Howship's lacuna-like cavities were clearly visible at the surface of the material. They contained resorbing mononuclear phagocytes. At a more mature stage, TCP granules were embedded in an acellular fibrous material which underwent mineralization from the medullary spaces towards the granules. The bone formed was subsequently remodeled. The implanted material itself was progressively modified. It first acquired the staining appearance of bone. After its structure became loose and vacuolated, it was invaded by cells and vessels. The present data indicate that TCP has osteogenic potential and is subject to degradation. Unlike in experimental wounds, these processes are of long duration in human defects.


Conservative treatment of acute colonic diverticulitis: are antibiotics always mandatory?
Most patients admitted for acute colonic diverticulitis (AD) are managed conservatively and receive antibiotics, although it is uncertain whether all patients with AD benefit from this treatment. The aim of this study was to evaluate the influence of antibiotic treatment on outcome in the conservative management of patients with mild AD. A retrospective audit of 311 patients (64% F, mean age 60 years) hospitalized for AD was carried out. All patients were initially treated conservatively with observation and restriction of oral intake. Patients receiving antibiotics (n=118) were compared with patients treated with observation and restriction of oral intake only (n=193). Mean follow-up time (FU) was 30 months. Inflammation in patients treated with antibiotics was more pronounced (laboratory parameters (C-reactive protein, white blood cell count) were higher (p<0.01), fever was more common (p<0.01) and CT grading of inflammation was classified as severe in a higher proportion (p<0.01)) compared with patients treated without antibiotics. When initially treated with antibiotics, 3 patients (3%) failed to respond to treatment and had to undergo surgery. There were 7 (4%) failures in patients initially treated without antibiotics, and antibiotics were then added. During FU, 29% of patients treated with antibiotics had further events (recurrent AD and/or subsequent surgery) compared with 28% (NS) among those treated without antibiotics. In a multivariate analysis, the risk of a further event was not influenced by antibiotic treatment (OR 1.03, CI 95% 0.61-1.74). Our results indicate that antibiotics are not mandatory in mild AD. Treatment without antibiotics appears to be safe and seems not to change the rate of further events. These results warrant further randomized prospective studies.


[Biomolecular prognostic factors in colorectal cancer].
There is general agreement that staging of colorectal neoplasms based on classic anatomopathological parameters does not allow accurate selection of patients at higher risk of an adverse outcome. For this reason, identification of new prognostic factors is desirable. Such factors should be easily determined and expressed at an early stage of carcinogenesis. Moreover, it would be useful to identify factors predictive of response to radiotherapy and chemotherapy. Various molecules are involved in the carcinogenetic pathway and metastasis formation. The aim of this review is to analyse whether any of them are currently useful in clinical practice and which of them warrant further study. At present, apart from CEA, whose prognostic value has been known for some time, we do not have sufficient data to definitively incorporate any of the other biomarkers in clinical practice. The most promising factors would appear to be loss of heterozigosity of chromosome 18q21 (DCC) and microsatellite instability. However, other molecules warrant further in-depth study. In particular, growth factor receptors may play a role not only as prognostic factors but also in view of their therapeutic potential.


Elite Youth Sports-From Best Pediatric Science Practice To Sports Practice-2016.
In my 2015 editorial, I selected two research publications with a focus on an applied sports sciences perspective. This year I have chosen to focus on two publications from a methodological viewpoint, highlighting the importance of laboratory procedures and extraction of data through a systematic review respectively. The first publication by Leites and colleagues (J Appl Physiol) addresses questions in relation to thermoregulation and carbohydrate metabolism in young people. This topic is difficult to conduct due to additional ethical and safety concerns due to exercising in the heat. Nonetheless, there are important basic science questions to be answered. Using a range of measurement techniques including rectal thermometry, 13C-enriched carbohydrate isotopes and procedures to standardize the heat stress equally between a group of men and boys, this project demonstrates an exemplary range of experimental skills. In my second selected paper by Lesinski et al., (Brit J Sports Med), both a systematic review and a meta-analyses were conducted to investigate the dose-response relationships of resistance training on physical performance in youth athletes. As the requirement for more evidence based practice is demanded, the move away from a narrative review to a more methodological and rigorous approach is to be encouraged. It is, in my opinion, a skill that we should be encouraging all our early career pediatric researchers to learn from the outset, the outcome of which can only make our discipline stronger.


[Vasculitic polyneuropathy as a complication in chronic polyarthritis].
Polyneuropathy due to vasculitis in connection with rheumatoid arthritis is a rare complication of the disease. Special investigations can help us to distinguish between a peripheral sensory-neuropathy with a good prognosis, the neuropathy of the autonomous nervous system and the severe form of mononeuritis multiplex. The bad prognosis of this form is due to the diffuse vasculitis of internal organs. We describe 5 patients with rheumatoid arthritis and different forms of vasculitis. The differential diagnosis, therapy and prognosis are described in detail.


Effect of electron-phonon scattering on shot noise in nanoscale junctions.
We investigate the effect of electron-phonon inelastic scattering on shot noise in nanoscale junctions in the regime of quasiballistic transport. We predict that when the local thermal energy of the junction is larger than its lowest vibrational mode energy eV(c), the inelastic contribution to shot noise (conductance) increases (decreases) with bias as V (sqrt[V]). The corresponding Fano factor thus increases as sqrt[V]. We also show that the inelastic contribution to the Fano factor saturates with increasing thermal current exchanged between the junction and the bulk electrodes to a value which, for V >> V(c), is independent of bias. These predictions can be readily tested experimentally.


Comprehensive Wet-Bench and Bioinformatics Workflow for Complex Microbiota Using Oxford Nanopore Technologies.
The advent of high-throughput sequencing techniques has recently provided an astonishing insight into the composition and function of the human microbiome. Next-generation sequencing (NGS) has become the gold standard for advanced microbiome analysis; however, 3rd generation real-time sequencing, such as Oxford Nanopore Technologies (ONT), enables rapid sequencing from several kilobases to >2 Mb with high resolution. Despite the wide availability and the enormous potential for clinical and translational applications, ONT is poorly standardized in terms of sampling and storage conditions, DNA extraction, library creation, and bioinformatic classification. Here, we present a comprehensive analysis pipeline with sampling, storage, DNA extraction, library preparation, and bioinformatic evaluation for complex microbiomes sequenced with ONT. Our findings from buccal and rectal swabs and DNA extraction experiments indicate that methods that were approved for NGS microbiome analysis cannot be simply adapted to ONT. We recommend using swabs and DNA extractions protocols with extended washing steps. Both 16S rRNA and metagenomic sequencing achieved reliable and reproducible results. Our benchmarking experiments reveal thresholds for analysis parameters that achieved excellent precision, recall, and area under the precision recall values and is superior to existing classifiers (Kraken2, Kaiju, and MetaMaps). Hence, our workflow provides an experimental and bioinformatic pipeline to perform a highly accurate analysis of complex microbial structures from buccal and rectal swabs. IMPORTANCE Advanced microbiome analysis relies on sequencing of short DNA fragments from microorganisms like bacteria, fungi, and viruses. More recently, long fragment DNA sequencing of 3rd generation sequencing has gained increasing importance and can be rapidly conducted within a few hours due to its potential real-time sequencing. However, the analysis and correct identification of the microbiome relies on a multitude of factors, such as the method of sampling, DNA extraction, sequencing, and bioinformatic analysis. Scientists have used different protocols in the past that do not allow us to compare results across different studies and research fields. Here, we provide a comprehensive workflow from DNA extraction, sequencing, and bioinformatic workflow that allows rapid and accurate analysis of human buccal and rectal swabs with reproducible protocols. This workflow can be readily applied by many scientists from various research fields that aim to use long-fragment microbiome sequencing.


Investigation on the Structure of a LiB3O5-Li2Mo3O10 High-Temperature Solution for Understanding the Li2Mo3O10 Flux Behavior.
LiB3O5 is the most widely used nonlinear optical crystal. Li2Mo3O10 (a nominal composition) is a typical flux used to produce large-sized and high-quality LiB3O5 crystals. The structure of the LiB3O5-Li2Mo3O10 high-temperature solution is essential to understanding the flux behavior of Li2Mo3O10 but still remains unclear. In this work, high-temperature Raman spectroscopy combined with density functional theory (DFT) was applied to study the LiB3O5-Li2Mo3O10 solution structure. Raman spectra of a LiB3O5-Li4Mo5O17-Li2Mo4O13 polycrystalline mixture were recorded at different temperatures until the mixture melted completely. The solution structure was deduced from the spectral changes and verified by DFT calculations. When the mixture began to melt, its molybdate component first changed into the Li2Mo3O10 melt; meanwhile, the complicated molybdate groups existing in the crystalline state transformed into Mo3O102- groups, which are formed by three corner-sharing MoO3Ø-/MoO2Ø2 (Ø = bridging oxygen atom) tetrahedra. When LiB3O5 dissolved in the Li2Mo3O10 melt, the crystal structure collapsed into polymeric chains of [B3O4Ø2-]n. Its basic structural unit, the B3O4Ø2- ring, coordinated with the Mo3O102- group to form a MoO3·B3O4Ø2- complex and a Mo2O72- group. On the basis of the LiB3O5-Li2Mo3O10 solution structure, we discuss the LiB3O5 crystal growth mechanism and the compositional dependence of the solution viscosity.


Regulation of breathing and autonomic outflows by chemoreceptors.
Lung ventilation fluctuates widely with behavior but arterial PCO2 remains stable. Under normal conditions, the chemoreflexes contribute to PaCO2 stability by producing small corrective cardiorespiratory adjustments mediated by lower brainstem circuits. Carotid body (CB) information reaches the respiratory pattern generator (RPG) via nucleus solitarius (NTS) glutamatergic neurons which also target rostral ventrolateral medulla (RVLM) presympathetic neurons thereby raising sympathetic nerve activity (SNA). Chemoreceptors also regulate presympathetic neurons and cardiovagal preganglionic neurons indirectly via inputs from the RPG. Secondary effects of chemoreceptors on the autonomic outflows result from changes in lung stretch afferent and baroreceptor activity. Central respiratory chemosensitivity is caused by direct effects of acid on neurons and indirect effects of CO2 via astrocytes. Central respiratory chemoreceptors are not definitively identified but the retrotrapezoid nucleus (RTN) is a particularly strong candidate. The absence of RTN likely causes severe central apneas in congenital central hypoventilation syndrome. Like other stressors, intense chemosensory stimuli produce arousal and activate circuits that are wake- or attention-promoting. Such pathways (e.g., locus coeruleus, raphe, and orexin system) modulate the chemoreflexes in a state-dependent manner and their activation by strong chemosensory stimuli intensifies these reflexes. In essential hypertension, obstructive sleep apnea and congestive heart failure, chronically elevated CB afferent activity contributes to raising SNA but breathing is unchanged or becomes periodic (severe CHF). Extreme CNS hypoxia produces a stereotyped cardiorespiratory response (gasping, increased SNA). The effects of these various pathologies on brainstem cardiorespiratory networks are discussed, special consideration being given to the interactions between central and peripheral chemoreflexes.


Evaluation of the salivary flow of patients undergoing conventional radiotherapy for head and neck cancer.
The purpose of this cross-sectional, quantitative study was to evaluate the salivary flow of 20 patients undergoing conventional 2-dimensional radiotherapy in the head and neck region. Unstimulated salivary flow was measured with the spitting technique. In addition, xerostomia was evaluated through the Eisbruch grading system and the Xerostomia Inventory (XI). The patients were evaluated 3 times: D0, before the first radiotherapy session; D17, after the 17th radiotherapy session; and D35, after the last radiotherapy session. Most of the patients in the present study were men (70%). The larynx was the most frequent site of cancer in this sample (45%). The most prevalent oral alteration during radiotherapy was odynophagia (75%). The analysis of subjective symptoms of xerostomia revealed no statistically significant differences (P = 0.059). However, statistically significant differences in the XI were found, with scores increasing from D0 to D17 and D35 (P = 0.004). With regard to the objective symptoms of xerostomia, most patients started treatment in grade 1 and remained in the same category at the end of radiation. There was a slight increase in salivary volume during treatment, an atypical finding that can probably be explained by the use of low-level laser, which was applied to prevent oral mucositis in all of the patients. The mean total radiation dose (65 Gy) received by the patients in the present sample did not appear to influence the XI values or salivary volume. The data reinforced the subjective nature of xerostomia, which is not always related to hyposalivation.


Treatment of invasive Enterobacter cloacae burn wound sepsis with topical nitrofurazone.
Nine patients with invasive Enterobacter cloacae burn wound sepsis were identified in a series of 400 admissions to our Burn Center. In vitro antibacterial testing of topical agents revealed sensitivity to nitrofurazone cream. Treatment of this series of patients with nitrofurazone resulted in an overall 66% survival compared with an 86% mortality reported in the literature. We recommend that topical antibacterial sensitivity testing be routinely performed in the microbiology laboratory for isolates from burn patients, and that nitrofurazone cream be included among the agents tested for effectiveness.


Sex pili as immunogens.
Groups of chickens were vaccinated intravenously with live cultures of Escherichia coli K12 possessing transfer factors F, I, A2 or no transfer factor (Tra-minus) and their immunity challenged by injecting them intravenously with an F-plus strain of Salmonella heidelberg or an F-plus or I-plus strain of Salmonella typhimurium. Compared with the Tra-minus strain, vaccination with the F-plus, but not the I-plus or A2-plus, K12 strain significantly reduced the mortality rate caused by the F-plus salmonella strains; vaccination with the I-plus or A2-plus, but not the F-plus, K12 strain significantly reduced the mortality rate caused by the I-plus salmonella strain.


The defining characteristics of support. Results of a research project.
Support is a central concept in nursing practice; not only for psychiatric nurses, but for all nurses. Yet, the ambiguity about the definition of support is troubling. More importantly, nurses are "doing things" to and for patients, but are these interventions truly supportive? What kinds of support do our patients want and need? As nursing advances towards a scientific basis for practice, we must be clear about the what and why of our actions (Sebastian, 1990). As nurses become more outcome oriented, we must know what patients value in their treatment. This study is an initial attempt to clarify for psychiatric nurses the concept of support; may it be the first of many.


Distinct actions by Paenibacillus sp. strain E18 α-L-arabinofuranosidases and xylanase in xylan degradation.
We cloned a Paenibacillus sp. strain E18 5.3-kb xylanolytic gene cluster that contains three open reading frames encoding two family 43 α-L-arabinofuranosidases (Abf43A and Abf43B) and one family 10 xylanase (XynBE18). The deduced amino acid sequences of Abf43A and Abf43B were at most 68% and 63% identical to those of two putative family 43 proteins from Clostridium sp. strain DL-VIII (EHI98634.1 and EHI98635.1), respectively, but were only 11% identical to each other. Recombinant Abf43A and Abf43B had similar activities at 45°C and pH 6.0 but varied in thermostabilities and substrate specificities. Abf43B was active against only 4-nitrophenyl α-L-arabinofuranoside, whereas Abf43A acted on 4-nitrophenyl α-L-arabinofuranoside, wheat arabinoxylan, 4-nitrophenyl α-D-xylopyranoside, and sugar beet arabinan. The sequential and combined effects on xylan degradation by XynBE18, Abf43A, and Abf43B were characterized. For beechwood, birchwood, and oat spelt xylans as the substrates, synergistic effects were found when XynBE18 and Abf43A or Abf43B were incubated together and when the substrates were first incubated with Abf43A or Abf43B and then with XynBE18. Further high-performance liquid chromatography (HPLC) analysis showed that the amounts of xylobiose and xylose increased sharply in the aforementioned reactions. For water-soluble wheat arabinoxylan as the substrate, Abf43A not only released arabinose but also had a synergistic effect with XynBE18. Synergy may arise as the result of removal of arabinose residues from xylans by α-L-arabinofuranosidases, which eliminates steric hindrance caused by the arabinose side chains and which allows xylanases to then degrade the xylan backbone, producing short xylooligosaccharides.


Current diagnostic role of CT in evaluating internal hernia.
Transmesenteric hernia is frequently encountered in practice, and because of the high risk of strangulation, even small internal hernias are dangerous. Knowledge of the characteristic imaging features and the mechanism of internal hernia can lead to early detection and correct diagnosis, both of which can save the patient's life. This article describes common CT findings of internal hernia with emphasis on various postoperative transmesenteric hernias as well as other common internal hernias.


Effect of number and position of intraocular lens haptics on anterior capsule contraction: a randomized, prospective trial.
The present study aimed to evaluate the degree of anterior capsule contraction (capsulorhexis contraction) with three different single-piece, hydrophilic acrylic intraocular lenses (IOLs). Patients were prospectively randomized to be implanted with one of three types of IOLs during cataract surgery: the Ophtec Precizon (IOL A), the Lucid Korea Microflex (IOL B), and the Carl Zeiss Asphina (IOL C). One week, 2 weeks, and 6 months after surgery, the area of the anterior capsule opening was measured using digital retro-illumination images after dilation of the pupil. The data were then evaluated using POCOman software. The study included 236 eyes of 202 patients. The area of the anterior capsule opening reduced by 3.53 ± 3.31 mm (17.06% ± 15.99%) between 1 week and 2 months post-operatively in the IOL A group, by 0.62 ± 1.32 mm (2.87% ± 6.03%) in the IOL B group, and by 1.09 ± 1.53 mm (4.72% ± 6.10%) in the IOL C group. The IOL B group showed minimal anterior capsule contraction 2 months after surgery (p < 0.001). IOLs with a four-plate haptic design (IOL B) showed more anterior capsular stability than those with a two-loop plate haptic (IOL A) or two-plate haptic (IOL C) design. The number and position of haptics in a capsular bag may affect anterior capsule contraction. We assume that supporting the zonules evenly may play a role in anterior capsular stability. Current Controlled Trials ISRCTN76566080 , Retrospectively registered (Date of registration: 14 Feb 2018).


Atypical thyroiditis in Huelva, Spain.
To report an epidemic of atypical thyroiditis that occurred in southwestern Europe during 1995. We present the clinical, laboratory, morphologic, and histologic features of 672 cases of thyroiditis and describe the results of treatment. During 1995, atypical thyroiditis was diagnosed in 672 of 725 patients with thyroid disorders encountered at our medical center in Huelva, Spain. Of these patients, 98% were women with normal ovarian function. The clinical findings were acute or subacute manifestation of diffuse nodular enlargement of the thyroid and spontaneous, severe pain on deglutition and palpation of the gland. Initial hematology and serum biochemistry studies, free triiodothyronine, free thyroxine, thyrotropin, and thyroid-stimulating immunoglobulins were in the normal range, but after the second week, the thyrotropin level began to increase. Thyroid antibodies (thyroglobulin and thyroid peroxidase) increased up to 300 times the high-normal level. Ultrasonography exhibited diffuse nodular enlargement of the thyroid gland, with irregular hypoechoic, normal, and hyperechoic zones. Fine-needle aspiration biopsy showed abundant lymphocytic infiltration. The best treatment results were obtained with the combination of levothyroxine and deflazacort. Because the epidemic appeared after a severe drought of 5-year duration (1991 to 1995) and affected women with normal ovarian function, our etiopathogenetic hypothesis was that an estrogen-like chemical substance polluted the area swamps. The high concentration of the pollutant was attributable to diminished water levels (8% of their capacity at the end of the drought period), and this situation may have affected the population through tap water used for human consumption. We describe an atypical autoimmune thyroiditis that affected primarily women of reproductive age, after a severe drought. The main features were a very painful, diffuse nodular enlargement of the thyroid gland, substantially increased thyroid antibodies, good response to levothyroxine and deflazacort combination treatment, and a benign evolution to chronic thyroiditis. Pollutants from various sources should be considered when atypical thyroiditis occurs in any community.


Adaptation and Validation of a Serious Game for Motor Learning Training in Children with Cerebral Palsy.
Objective: Children with cerebral palsy (CP) present motor learning disorders and somatosensory dysfunction. Although many protocols use videogames in children with CP, few apply or examine motor learning principles. This study aims at (1) implementing therapist-user-designer collaboration in adapting a videogame to the principles of motor learning and the characteristics of users with CP, and (2) piloting the effectiveness of these adaptations by analyzing the achievement of motor learning parameters (learning rate acquisition, retention, and transfer to motor and somatosensory function). Materials and Methods: Periodical interprofessional meetings conducted to the adaptation of a videogame, requiring the control of a joystick for traveling through a maze, to motor learning principles. In a pilot validation, effects in unilateral upper limb function, gross manual dexterity, and somatosensory thresholds were assessed before and after 10-week training in 13 children with CP. Results: After 10-week training with the adapted serious game, children showed learning rates above 90% and improvement in motor learning parameters along the sessions. Manual dexterity and pronation-supination of the dominant hand improved after training. No significant effects were found on somatosensory thresholds. Conclusion: Serious games are useful as motor learning tools for improving motor function in children with PC. Cooperative work among professionals and users is advisable for designing efficient videogames according to rehabilitation best practices.