Chronic administration of Dimebon does not ameliorate amyloid-β pathology in 5xFAD transgenic mice.
Dimebon has been tested as a potential modifier of Alzheimer's disease (AD), resulting in mixed clinical trial outcomes. Originally utilized as an antihistamine, Dimebon was later found to ameliorate AD symptoms in initial human trials. Although subsequent trials have reportedly failed to replicate these finding, there is a growing body of evidence that Dimebon might be neuroprotective in certain models of neurodegeneration. The precise mechanism by which Dimebon is thought to act in AD is unclear, though changes in receptor activity, mitochondria function, and autophagy activity have been proposed. It is thus necessary to test Dimebon in transgenic animal model systems to determine if and how the drug affects development and manifestation of pathology, and which pathogenic processes are altered. In the present study we treated mice harboring five familial mutations associated with hereditary AD (5xFAD line) with a chronic regime of Dimebon. The compound was not found to improve the general health or motor behavior of these mice, nor prevent accumulation of Aβ peptides in the brain. Modest changes in response to an anxiogenic task were, however, detected, suggesting Dimebon might improve behavioral abnormalities and cognition in disease in a mechanism independent of protecting against amyloidosis.


Diagnosis and control of rickettsial diseases.
Common isolation procedures on chick embryos and laboratory animals are not of great importance for routine diagnosis of rickettsioses. Detection of rickettsiae in skin lesions by immunofluorescence technique allows early diagnosis of Rocky Mountain spotted fever (RMSF). Broad spectrum of methods is at disposal for serological diagnosis of rickettsial diseases. Their choice is determined by laboratory equipment, professionality of laboratory staff, economy and simplicity of the given test. Though complement-fixation and microagglutination tests held their position and will certainly be used in future, the use of indirect immunofluorescence test is recommended for its sensitivity and simplicity. Latex agglutination test is valuable especially in the diagnosis of acute rickettsial infections. Recently introduced ELISA method is expected to fulfil the highest requirements as to sensitivity in differentiation of rickettsioses within the known classification groups. The efforts to obtain efficient antirickettsial vaccines have been limited to preparation of the vaccines against RMSF and Q fever. As to the latter, elaboration of chemovaccine and preparation of chloroform-methanol-treated phase I C. burnetii suspension of decreased reactogenity seem promising in field trials.


A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein.
ZEBRA is a site-specific DNA binding protein that functions as a transcriptional activator and as an origin binding protein. Both activities require that ZEBRA recognizes DNA motifs that are scattered along the viral genome. The mechanism by which ZEBRA discriminates between the origin of lytic replication and promoters of EBV early genes is not well understood. We explored the hypothesis that activation of replication requires stronger association between ZEBRA and DNA than does transcription. A ZEBRA mutant, Z(S173A), at a phosphorylation site and three point mutants in the DNA recognition domain of ZEBRA, namely Z(Y180E), Z(R187K) and Z(K188A), were similarly deficient at activating lytic DNA replication and expression of late gene expression but were competent to activate transcription of viral early lytic genes. These mutants all exhibited reduced capacity to interact with DNA as assessed by EMSA, ChIP and an in vivo biotinylated DNA pull-down assay. Over-expression of three virally encoded replication proteins, namely the primase (BSLF1), the single-stranded DNA-binding protein (BALF2) and the DNA polymerase processivity factor (BMRF1), partially rescued the replication defect in these mutants and enhanced ZEBRA's interaction with oriLyt. The findings demonstrate a functional role of replication proteins in stabilizing the association of ZEBRA with viral DNA. Enhanced binding of ZEBRA to oriLyt is crucial for lytic viral DNA replication.


Antiinsulin receptor antibodies in an insulin-dependent diabetic may arise as autoantiidiotypes.
An insulin-requiring diabetic patient with intermittent periods of increased insulin requirements and insulin resistance was studied. The patient was found to have high titers of antiinsulin antibodies; subfractionation of the patient's serum revealed several populations of antiinsulin antibodies with differing affinities and titers for insulin. The ability of one of the insulin antibody fractions to bind [125I]iodoinsulin was markedly inhibited by the patient's serum (insulin depleted) and by purified total immunoglobulin G from which antiinsulin antibodies and insulin were removed. These findings suggested an antiidiotypic antibody in the patient's immunoglobulin G fraction reacting specifically with the antiinsulin antibody subfraction. Finally, the patient's serum contained an antiinsulin receptor antibody, as demonstrated by the ability of serum to specifically immunoprecipitate covalently labeled soluble insulin receptors. In conclusion, these results suggest that this patient generated a widespread polyclonal response to insulin, with the development of several populations of antiinsulin antibodies. An antiidiotypic antibody to a specific insulin antibody subfraction was present in the patient's serum which we believe had structural similarity to the binding site of the insulin molecule, accounting for the reactivity of the antiidiotypic antibody with the insulin receptor.


[Estimating the burden of diseases due to high alcohol consumption in Korea].
This study estimated the burden of disease due to high alcohol consumption using DALY, a composite indicator recently developed by the Global Burden of Disease study group. The results were analyzed by age and sex. Firstly, high alcohol consumption-related diseases, and their relative risk (RR), were selected. Secondly, population attributable fractions (PAFs) were computed using formulae, including the relative risk (RR) and prevalence of exposure (Pe). Thirdly, the DALYs of high alcohol consumption-related diseases were estimated. Lastly, the attributable burdens of diseases due to high alcohol consumption wereconcluded as being the sum of the products that multiplied the DALYs of high alcohol consumption-related diseases by their population attributable fraction (PAF). The burden of high alcohol consumption in Korea was 2992.3 person years (PYs) per 100,000 persons in men, and 1426.6 in women. For men, the high alcohol consumption-induced diseases with the five biggest burdens were liver cirrhosis, hypertensive disease, liver cancer, cerebral infarction and intracerebral hemorrhage. For women, these were cerebral infarction, intracerebral hemorrhage, hypertensive disease, liver cirrhosis and liver cancer. This study highlighted the attributable fraction of diseases due to exposure to high alcohol consumption, by quantifying the results of exposure to risk factors. Therefore, it is now possible to assess interventions for risk factors in quantifiable terms in each population. Finally, measuring the risk factor burdens was expected to contribute to priority setting and effective resource allocation in public health policy.


Complete Genome Sequences of Two Astrovirus MLB1 Strains from Bhutanese Children with Diarrhea.
In addition to the eight genotypes of classic human astroviruses, seven new genotypes have been reported from two novel clades, MLB and VA. However, the epidemiology of these highly diverse astroviruses remains largely unknown. We report here the complete genome sequences of two MLB1 strains from Bhutanese children with diarrhea.


Bacterial cellulose nanocrystal as drug delivery system for overcoming the biological barrier of cyano-phycocyanin: a biomedical application of microbial product.
Phycocyanin, produced by Spirulina platensis, has been reported as an anti-inflammatory, anti-hyperalgesia, antioxidant, anti-tumor, and anti-cancer agent. However, the ingestion of phycocyanin in the body is often hindered by its instability against gastric pH conditions. The nano-drug delivery system has developed as a promising platform for efficient drug delivery and improvement as well as drug efficacy. Bacterial cellulose nanocrystal (BCNC) has it superiority as DDS due to its inherent properties such as nanoscale dimension, large surface area, - biocompatibility, and non-toxic. To improve its mechanical properties, BCNC was crosslinked with glutaraldehyde and was analyzed as a potential candidate for DDS. The Fourier transform infrared analysis of the BCNC suggested that hydrolysis did not alter the chemical composition. The index of crystallinity of the BCNC was 18.31% higher than that of the original BC, suggesting that crystalline BC has been successfully isolated. The BCNC particle also showed a needle-like morphology which is 25 ± 10 nm in diameter and a mean length of 626 ± 172 nm. Crosslinked BCNC also had larger pores than the original BCNC along with higher thermal stability. Optimum phycocyanin adsorption on crosslinked BCNC reached 65.3% in 3 h. The release study shows that the crosslinked BCNC can protect the phycocyanin retardation by gastric fluid until phycocyanin reaches the targeted sites. This study provides an alternative potential DDS derived from natural bioresources with less expenses and better properties to promote the application of BCNC as functional nanomaterials in biomedical science.


Prevalence and Predictors of Depression among Pregnant Women in Debretabor Town, Northwest Ethiopia.
Depression during pregnancy is a major health problem because it is prevalent and chronic, and its impact on birth outcome and child health is serious. Several psychosocial and obstetric factors have been identified as predictors. Evidence on the prevalence and predictors of antenatal depression is very limited in Ethiopia. This study aims to determine prevalence and associated factors with antenatal depression. Community based cross-sectional study was conducted among 527 pregnant women recruited in a cluster sampling method. Data were collected by face-to-face interviews on socio-demographic, obstetric, and psychosocial characteristics. Depression symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). The List of Threatening Experiences questionnaire (LTE-Q) and the Oslo Social Support Scale (OSS-3) were used to assess stressful events and social support, respectively. Data were entered into Epi-info and analyzed using SPSS-20. Descriptive and logistic regression analyses were carried out. The prevalence of antenatal depression was found to be 11.8%. Having debt (OR = 2.79, 95% CI = 1.33, 5.85), unplanned pregnancy (OR = 2.39, 95% CI = (1.20, 4.76), history of stillbirth (OR = 3.97, 95% CI = (1.67,9.41), history of abortion (OR = 2.57, 95% CI = 1.005, 6.61), being in the third trimester of pregnancy (OR = 1.70, 95% CI = 1.07,2.72), presence of a complication in the current pregnancy (OR = 3.29, 95% CI = 1.66,6.53), and previous history of depression (OR = 3.48, 95% CI = 1.71,7.06) were factors significantly associated with antenatal depression. The prevalence of antenatal depression was high, especially in the third trimester. Poverty, unmet reproductive health needs, and obstetric complications are the main determinants of antenatal depression. For early detection and appropriate intervention, screening for depression during the routine antenatal care should be promoted.


Therapeutic potential of bioactive compounds from Punica granatum extracts against aging and complicity of FOXO orthologue DAF-16 in Caenorhabditis elegans.
Some natural fruits have significant importance in improving health which provides many nutritional supplements essential to maintain proper metabolism with the age. In this study, phytochemical screening of extract (methanolic) of Punica granatum arils, outer and inner peels was confirmed by the respective spot tests. Quantification of phytochemical constituents revealed the plentiful of total phenols in the outer peels in comparison to inner peels and juice whereas total flavonoids and vitamin C are abundant in inner peel and juice, respectively. High-performance liquid chromatography, Gas chromatography along with mass spectrometry and Fourier-transform infrared spectroscopy analysis revealed the presence of compound 9, 17-octadecadienal, (Z) in the outer/inner peels. A compound N-hexadecanoic acid was also observed in the outer peels. Extracts from every section of the fruits were comprehensively evaluated for their antioxidant activity. Contrary to fruit aril juice, the extracts of outer and inner peels exhibited significant and dose-dependent in vitro antioxidant and radical-scavenging potentials. The supplementation of P. granatum extracts (PGEs) significantly enhanced the lifespan of C. elegans. The protective effect of PGEs was also observed against oxidative stress in C. elegans. Additionally, the involvement of FOXO orthologue DAF-16 dependent longevity was obtained with PGEs (outer peel and inner peel) fed TJ356 worms. Overall, the results indicate the vital role of PGEs especially the extracts of outer peels in life-saving mechanisms of C. elegans by virtue of their antioxidant asset and life-prolonging effects via daf-16 dependent Insulin signaling pathway. See also Figure 1(Fig. 1).


Impact of the Choosing Wisely® Campaign Recommendations for Hospitalized Children on Clinical Practice: Trends from 2008 to 2017.
The Choosing Wisely® Campaign (CWC) was launched in 2012. Five recommendations to reduce the use of "low-value" services in hospitalized children were published in 2013. The aim of this study was to estimate the frequency and trends of utilization of these services in tertiary children's hospitals five years before and after the publication of the recommendations. We conducted a retrospective, longitudinal analysis of hospitalizations to 36 children's hospitals from 2008 to 2017. The "low-value" services included (1) chest radiograph (CXR) for asthma, (2) CXR for bronchiolitis, (3) relievers for bronchiolitis, (4) systemic steroids for lower respiratory tract infection (LRTI), and (5) acid suppressor therapy for uncomplicated gastroesophageal reflux (GER). We estimated the annual percentages of the use of these services after risk adjustment, followed by an interrupted time series (ITS) analysis to compare trends before and after the publication of the recommendations. The absolute decreases in utilization were 36.6% in relievers and 31.5% in CXR for bronchiolitis, 24.1% in acid suppressors for GER, 20.8% in CXR for asthma, and 2.9% in steroids for LRTI. Trend analysis showed that one "low-value" service declined significantly immediately (use of CXR for asthma), and another decreased significantly over time (relievers for bronchiolitis) after the CWC. There was some decrease in the utilization of "low-value" services from 2008 to 2017. Limited changes in trends occurred after the publication of the recommendations. These findings suggest a limited impact of the CWC on clinical practice in these areas. Additional interventions are required for a more effective dissemination of the CWC recommendations for hospitalized children.


Protein Breakdown and Formation of Protease in Attached and Detached Cotyledons of Phaseolus vulgaris L.
In contrast to earlier reported results of similar experiments in peas, in which almost no increase in protease activity occurred in incubated detached cotyledons, we report here an increase in protease activity in both attached and detached bean cotyledons. Detached bean cotyledons showed continually increasing protease activity up to the 12th day, while that in attached cotyledons declined after 6 days. The free amino acid level in detached cotyledons reached a maximum at the 11th day; protease formation leveled off after 50% of the original seed protein was digested. These data suggest that high free amino acid levels may inhibit protease formation.The activity of partially purified protease in aqueous extracts was enhanced by 10 mm 2-mercaptoethanol or cysteine, indicating a sulfhydryl requirement for activation. Protease formation in detached cotyledons was inhibited 30% by 10 mug/ml cycloheximide and 50% by 100 mum abscisic acid. In contrast, alpha-amylase formation was inhibited 90% by 10 mug/ml cycloheximide and 95% by 20 mum abscisic acid. The cycloheximide data suggest that only a part of the protease, but all of the alpha-amylase, is synthesized de novo; the similar pattern of inhibition by abscisic acid emphasizes the concept that protease may exist in two forms.


High-pressure injection injuries to the upper extremity and the review of the literature.
High-pressure injection injuries of the hand are rare severe injuries. This study aimed to present a retrospective analysis of current and possible prognostic factors, treatment modalities and evaluation criteria. Ten patients who had high-pressure injection injury to their upper extremity between 2005-2018 were included in this study. All patients were evaluated for the compartment syndrome; if exists fasciotomy and wide debridement were performed. After the first debridement, the second debridement was considered within the first 24 hours. In this study, 10 patients (mean age: 30) were evaluated retrospectively. The injected materials were the animal vaccine, thinner, oil, diesel, water, plastic and paint. Preoperative and postoperative mean WBC levels were 14.73 K/µL and 9.62 K/µL, respectively. Preoperative and postoperative mean neutrophil levels were 11.4 K/µL and 6.49 K/µL, respectively. Early and serial debridement and compartment syndrome evaluation are required. Despite these cautions, amputation may occur. Material, injection force and the time elapsed are the main determinants in prognosis. Aggressive debridement is required in high-pressure injection injuries. However, the adequacy of debridement should be evaluated because it is mostly impossible to completely clean the tissue from diesel or thinner. According to the experience of 10 cases in our series, when clinical and macroscopic debridement adequacy was observed, a decrease in WBC and neutrophil levels was observed simultaneously. For this reason, WBC and neutrophil levels may be an indicator of the adequacy of debridement, although these injuries are very rare, larger series are needed for this interpretation.


Urethral catheter induced pseudoaneurysm of the bulbar artery.
Injuries of the urethra due to urethral catheter have been well recognised. We report a case of pseudoaneurysm of the artery to the bulb of the penis which formed due to necrosis of the arterial wall secondary to prolonged pressure due to a wrongly placed urethral catheter. The catheter was inflated in the bulbar urethra and left during surgery for 4 hours. The patient developed intermittent severe urethral bleeding. An angiogram of internal iliac artery showed a pseudo aneurysm involving the bulbar artery with arteriovenous communication. Super selective embolization of the feeding vessel was performed with cessation of the blood fl ow immediately. To our knowledge, pseudoaneurysm of the bulbar artery of penis has not previously been described.


Nanoscale electrodynamics of strongly correlated quantum materials.
Electronic, magnetic, and structural phase inhomogeneities are ubiquitous in strongly correlated quantum materials. The characteristic length scales of the phase inhomogeneities can range from atomic to mesoscopic, depending on their microscopic origins as well as various sample dependent factors. Therefore, progress with the understanding of correlated phenomena critically depends on the experimental techniques suitable to provide appropriate spatial resolution. This requirement is difficult to meet for some of the most informative methods in condensed matter physics, including infrared and optical spectroscopy. Yet, recent developments in near-field optics and imaging enabled a detailed characterization of the electromagnetic response with a spatial resolution down to 10 nm. Thus it is now feasible to exploit at the nanoscale well-established capabilities of optical methods for characterization of electronic processes and lattice dynamics in diverse classes of correlated quantum systems. This review offers a concise description of the state-of-the-art near-field techniques applied to prototypical correlated quantum materials. We also discuss complementary microscopic and spectroscopic methods which reveal important mesoscopic dynamics of quantum materials at different energy scales.


[Tumors of the oral cavity, oropharynx and salivary glands. Role of TC and MRI in neoplasm staging].
MRI and CT have an important role in the study of neoplasms of oropharynx, oral cavity and salivary glands. They play an invaluable role in the diagnosis and in the evaluation of the tumor growth. Moreover MRI allows multiplanar studies with the advantage of a more sensitive evaluation of the extension of the lesions.


Clinical course of a 66-year-old man with an acute ischaemic stroke in the setting of a COVID-19 infection.
A 66-year-old man was admitted to hospital with a right frontal cerebral infarct producing left-sided weakness and a deterioration in his speech pattern. The cerebral infarct was confirmed with CT imaging. The only evidence of respiratory symptoms on admission was a 2 L oxygen requirement, maintaining oxygen saturations between 88% and 92%. In a matter of hours this patient developed a greater oxygen requirement, alongside reduced levels of consciousness. A positive COVID-19 throat swab, in addition to bilateral pneumonia on chest X-ray and lymphopaenia in his blood tests, confirmed a diagnosis of COVID-19 pneumonia. A proactive decision was made involving the patients' family, ward and intensive care healthcare staff, to not escalate care above a ward-based ceiling of care. The patient died 5 days following admission under the palliative care provided by the medical team.


An empirical test for branch-specific positive selection.
The use of phylogenetic analysis to predict positive selection specific to human genes is complicated by the very close evolutionary relationship with our nearest extant primate relatives, chimpanzees. To assess the power and limitations inherent in use of maximum-likelihood (ML) analysis of codon substitution patterns in such recently diverged species, a series of simulations was performed to assess the impact of several parameters of the evolutionary model on prediction of human-specific positive selection, including branch length and d(N)/d(S) ratio. Parameters were varied across a range of values observed in alignments of 175 transcription factor (TF) genes that were sequenced in 12 primate species. The ML method largely lacks the power to detect positive selection that has occurred since the most recent common ancestor between humans and chimpanzees. An alternative null model was developed on the basis of gene-specific evaluation of the empirical distribution of ML results, using simulated neutrally evolving sequences. This empirical test provides greater sensitivity to detect lineage-specific positive selection in the context of recent evolutionary divergence.


Role and limitations of magnetic resonance imaging in the diagnostic work-up of patients with liver cancer.
The main objectives of liver imaging are detection and characterization of focal liver lesions. There is a wide range of imaging modalities available for the work-up of patients with liver cancer. In the current environment of cost containment, the most appropriate modality should be chosen to answer the clinical question. Contrast-enhanced computed tomography is currently the modality of choice for liver imaging for routine applications. Until recently magnetic resonance imaging was used only as a problem solving technique for lesions that were equivocal after contrast-enhanced computed tomography. However magnetic resonance with the use of tissue specific contrast agents, has already challenged the role of computed tomography portography in preoperative staging of liver cancer, and may soon completely replace this technique. It is also the primary modality for screening patients with cirrhosis for hepatocellular carcinoma. This review describes the role of magnetic resonance imaging, in the evaluation of patients with liver cancer, and outlines a rational approach for the diagnostic work-up of these patients.


Flow cytometric analysis of consecutive lymph node samples from patients with Hodgkin's disease: reproducible within one biopsy?
In Hodgkin's disease DNA aneuploidy is not a prognostic factor. However, the prognostic significance of DNA content in Hodgkin's disease may be missed by either intratumor DNA heterogeneity or DNA analysis of limited samples. For flow cytometry usually one section of 40-60 microns is used for the analysis. In breast cancer this proved to be insufficient. In Hodgkin's disease no data are available. Therefore, we examined if analysis of more sections does increase the yield of aneuploidy. Archival, formalin-fixed, parafin embedded tissues were used. From 13 patients four sections of 50 microns could be analysed for DNA content. In 12 of 13 patients the results were consistent in all four sections of one patient case; seven diploid, four aneuploid and one multiploid. In one case ploidy status changed: two sections were diploid and two were aneuploid. The DNA-index of the aneuploid samples ranged from 0.75 to 1.38 and varied from 0.02 to 0.14 within one case. The S-phase fraction remained constant within all evaluable cases (sd: 0.5-1.5%), except for one (sd: 4.7%). In conclusion, in Hodgkin's disease the ploidy status of the first section can be regarded to represent the whole tissue sample. Therefore, the absence of prognostic value of ploidy status is not explained by sampling errors in tissues analysed.


The adventitia, endothelium and atherosclerosis.
Despite many theories, the initiating circumstances for the development of atherosclerosis remain obscure. The development of animal models of atherosclerosis was based upon the different theories of the origins of atherosclerosis which suggested that it originates at the intimal surface of the vessel. A more recent model of atherosclerosis involves perivascular manipulation of the vessel by positioning of a hollow silastic collar around the artery. In this model, several of the features seen in early human atherosclerosis are generated within a period of 7 days. It is hypothesized that arterial wall hypoxia following occlusion of the vasa vasorum may be the initial lesion of atherosclerosis, and hence that in some cases atherosclerosis is a disease of the outer layers of the arterial wall.


Effects of sodium concentration and osmolality on water and electrolyte absorption form the intact human colon.
The influence of sodium concentration and osmolality on net water and monovalent electrolyte absorption from or secretion into the intact human colon was studied in healthy volunteers. WHEN ISOTONIC SOLUTIONS CONTAINING NACL AND/OR MANNITOL WERE INFUSED INTO THE COLON: (a) a direct linear relationship between luminal sodium concentration (in the range of 23-150 mEq/liter) and rate of net water, sodium, and chloride absorption was found. No water absorption was found when sodium concentration in the luminal fluid was below 20 mEq/liter; (b) water and sodium absorption from the isotonic test solutions was not enhanced by addition of 80-250 mg/100 ml of glucose; and (c) the rate of water and sodium absorption was decreased markedly when chloride was replaced by bicarbonate in the test solution. WHEN THE COLON WAS PERFUSED WITH HYPERTONIC TEST SOLUTIONS CONTAINING NACL AND MANNITOL OR UREA: (a) water was absorbed from hypertonic NaCl solutions against a lumen-to-blood osmotic gradient of 50 mOsm/kg; (b) when the osmolality of the mannitol solution was increased, water entered the colonic lumen at a more rapid rate. The relationship between the rate of water entering the colon and the osmolality of the test solution was a parabolic one; (c) sodium and chloride entered the colonic lumen at a rate that was lineraly related to that of water entrance when the lumen-to-blood osmotic gradient exceeded 150 mOsm/kg; (d) water flow into the colonic lumen was identical when equimolar urea or mannitol solutions were infused; (e) neither urea nor mannitol was absorbed in significant amounts from the hypertonic solutions; and (f) our results suggest that the equivalent pore radius of the human colon is smaller than the molecular radius of urea (2.3 A).


Esterolytic Properties of Leucine-Proteinase, the Leucine-Specific Serine Proteinase from Spinach (Spinacia oleracea L.) Leaves : A Steady-State and Pre-Steady-State Study.
Steady-state and pre-steady-state kinetics for the hydrolysis of p-nitrophenyl esters of N-alpha-carbobenzoxy(-l-)amino acids catalyzed by leucine-proteinase were determined between pH 5 and 10 (I = 0.1 molar) at 23 +/- 0.5 degrees C. For the substrates considered: (a) the acylation step is rate-limiting in catalysis; (b) the pH profiles of k(cat) and k(cat)/K(m) reflect the ionization of two groups with pK(a) values ranging between 6.5 and 6.9, and 8.1 and 8.3 (probably, the histidine residue involved in the catalytic triad and the N-terminus, respectively); and (c) values of K(m) are pH independent. Among the substrates examined, N-alpha-carbobenzoxy-l-leucine-p-nitrophenyl ester shows the most favorable catalytic parameters and allows to determine an enzyme concentration as low as 5 x 10(-10) molar at the optimum pH value (approximately 7.5).


Tumor necrosis factor-α-induced mononuclear cell death may contribute to polymorphonuclear cell predominance in the cerebrospinal fluid of patients with bacterial meningitis.
Bacterial meningitis is characterized by a marked predominance of polymorphonuclear leukocytes (PMNs: segmented granulocytes or neutrophils) in the cerebrospinal fluid (CSF), whereas aseptic meningitis is characterized by a predominance of mononuclear leukocytes (MNs: lymphocytes or monocytes). However, the pathophysiology of this predominance of PMNs in the CSF of patients with bacterial meningitis has never, to our knowledge, been clearly described. To investigate the predominant cell components of CSF from pediatric patients with bacterial meningitis, we investigated cell death in association with levels of tumor necrosis factor-alpha (TNF-α) in the CSF, using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and flow cytometry. The MTT assay of the CSF revealed that the PMNs had survived, while the MNs rapidly had undergone cell death. Although PMNs survived in CSF with high levels of TNF-α, PMN apoptosis was demonstrated with flow cytometry. The present study suggests that the pathophysiology of PMN predominance in the CSF of patients in the acute phase of bacterial meningitis is related to the rapid cell death of MNs and the survival of PMNs brought about by high levels of TNF-α.


Gallium Porphyrin and Gallium Nitrate Synergistically Inhibit Mycobacterial Species by Targeting Different Aspects of Iron/Heme Metabolism.
There is an urgent need for new effective and safe antibiotics active against pathogenic mycobacterial species. Gallium (Ga) nitrate (Ga(NO3)3) and Ga porphyrin (GaPP) have each been shown to inhibit the growth of a variety of mycobacterial species. The Ga(III) ion derived from Ga(NO3)3 has the potential to disrupt the mycobacterial Fe(III) uptake mechanisms and utilization, including replacing iron (Fe) in the active site of enzymes, resulting in the disruption of function. Similarly, noniron metalloporphyrins such as heme mimetics, which can be transported across the bacterial membrane via heme-uptake pathways, would potentially block the acquisition of iron-containing heme and bind to heme-utilizing proteins, making them nonfunctional. Given that they likely act on different aspects of mycobacterial Fe metabolism, the efficacy of combining Ga(NO3)3 and GaPP was studied in vitro against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium tuberculosis (M. tb). The combination was then assessed in vivo in a murine pulmonary infection model of M. abscessus. We observed that Ga(NO3)3 in combination with GaPP exhibited synergistic inhibitory activity against the growth of M. avium, M. tb, and M. abscessus, being most active against M. abscessus. Activity assays indicated that Ga(NO3)3 and GaPP inhibited both catalase and aconitase at high concentrations. However, the combination showed a synergistic effect on the aconitase activity of M. abscessus. The Ga(NO3)3/GaPP combination via intranasal administration showed significant antimicrobial activity in mice infected with M. abscessus. M. abscessus CFU from the lungs of the Ga(NO3)3/GaPP-treated mice was significantly less compared to that of nontreated or single Ga(III)-treated mice. These findings suggest that combinations of different Ga(III) compounds can synergistically target multiple iron/heme-utilizing mycobacterial enzymes. The results support the potential of combination Ga therapy for development against mycobacterial pathogens.


A 53-Year Bibliometric and Scientometric Analysis of Research in Culinary and Medicinal Mushrooms.
The research field of culinary and medicinal mushrooms has been well developed since the first relevant publication in 1966. However, to date, there has been no bibliometric analysis published specifically for this field. This study aimed to assess the most influential publications as well as the research trends and important drivers in the field of culinary and medicinal mushrooms. Scopus was used to identify relevant publications and the 1000 most-cited publications were identified and analyzed. Bradford's law of scattering shows one-third of the papers were published in 14 core journals, with a total of 102 papers published in International Journal of Medicinal Mushrooms. There is an insignificant negative correlation (Pearson's correlation coefficient, r = -0.355) between the journal impact factor and publication count. VOSviewer was used to generate a country network. China represents Asia's research center in this field, having contributed 20% of the 1000 most-cited publications. A term map was also created to visualize the co-occurrence of key terms in the domain. Different biological activities such as antioxidant and antitumor properties of mushrooms appeared to be a recurring topic in this field. Wasser (2003) showed the highest citation count (n = 1282), which is almost double the second most-cited publication (n = 611). There is a weak positive correlation (r = +0.237) between the years since publication and total citation count. In conclusion, this bibliometric study will assist researchers to comprehend the current status of the research on culinary and medicinal mushrooms, and to visualize the future impact of such an important field.


Bortezomib sensitizes non-small cell lung cancer to mesenchymal stromal cell-delivered inducible caspase-9-mediated cytotoxicity.
Delivery of suicide genes to solid tumors represents a promising tumor therapy strategy. However, slow or limited killing by suicide genes and ineffective targeting of the tumor has reduced effectiveness. We have adapted a suicide system based on an inducible caspase-9 (iC9) protein that is activated using a specific chemical inducer of dimerization (CID) for adenoviral-based delivery to lung tumors via mesenchymal stromal cells (MSCs). Four independent human non-small cell lung cancer (NSCLC) cell lines were transduced with adenovirus encoding iC9, and all underwent apoptosis when iC9 was activated by adding CID. However, there was a large variation in the percentage of cell killing induced by CID across the different lines. The least responsive cell lines were sensitized to apoptosis by combined inhibition of the proteasome using bortezomib. These results were extended to an in vivo model using human NSCLC xenografts. E1A-expressing MSCs replicated Ad.iC9 and delivered the virus to lung tumors in SCID mice. Treatment with CID resulted in some reduction of tumor growth, but addition of bortezomib led to greater reduction of tumor size. The enhanced apoptosis and anti-tumor effect of combining MSC-delivered Ad.iC9, CID and bortezomib appears to be due to increased stabilization of active caspase-3, as proteasomal inhibition increased the levels of cleaved caspase-9 and caspase-3. Knockdown of X-linked inhibitor of apoptosis protein (XIAP), a caspase inhibitor that targets active caspase-3 to the proteasome, also sensitized iC9-transduced cells to CID, suggesting that blocking the proteasome counteracts XIAP to permit apoptosis. Thus, MSC-based delivery of the iC9 suicide gene to human NSCLC effectively targets lung cancer cells for elimination. Combining this therapy with bortezomib, a drug that is otherwise inactive in this disease, further enhances the anti-tumor activity of this strategy.


A Scalable Chemical Approach for the Synthesis of a Highly Tolerant and Efficient Oil Absorbent.
In the past, bio-inspired extreme water repellent property has been strategically embedded on commercially available sponges for developing selective oil absorbents. However, most of the reported materials lack physical and chemical durability, limiting their applicability at practically harsh settings. Herein, a stable dispersion of polymeric nanocomplexes was exploited to achieve a chemically reactive coating on the highly compressible melamine foam. A superhydrophobic melamine foam (SMF) was achieved after post-covalent modification of the reactive coating through 1,4-conjugate addition reaction at ambient conditions. The durability of the embedded extreme water repellent property in the as-modified melamine foam has been elaborately demonstrated through exposing it to severe physical manipulations, chemically harsh aqueous media including pH 1, pH 12, surfactant contaminated water, river water, seawater and prolonged UV irradiation. Thus, the highly tolerant SMF was utilized as an efficient oil absorbent wherein oils of varying densities could be selectively recovered from an oil/water interface with high (e.g., 137 g g-1 for chloroform and 83 g g-1 for diesel) oil absorption capacity. Moreover, the selective oil absorption capacity of the as-synthesized material remained unaffected at practically relevant severe chemical and physical settings, and the extreme water repellency of the material remained unaltered even after repetitive (at least 50 cycles) use for oil/water separation.


Spatial patterns of increased spinal cord membrane-bound protein kinase C and their relation to increases in 14C-2-deoxyglucose metabolic activity in rats with painful peripheral mononeuropathy.
1. Three-dimensional spatial patterns of changes in membrane-bound protein kinase C (PKC) were examined in the lumbar spinal cords (L1-L5) of rats with an experimental painful peripheral mononeuropathy. Painful peripheral mononeuropathy was produced by loosely ligating the rat's common sciatic nerve, resulting in chronic constrictive nerve injury (CCI). Changes in spinal cord membrane-bound PKC distribution were assayed by employing an established quantitative [3H]-phorbol-12,13-dibutyrate ([3H]PDBu) autoradiographic assay, which includes spinal cord sectioning, incubation of spinal cord sections with [3H]PDBu, production of autoradiographs, and computer-assisted image processing. 2. Sciatic nerve ligation induced demonstrable thermal hyperalgesia in response to radiant heat stimulation and spontaneous pain-related behaviors (such as lifting of the nerve-ligated hind paw) in CCI rats 3, 7, and 10 days after unilateral sciatic nerve ligation. 3. Consistent with behavioral changes, CCI rats examined 3 or 10 days after sciatic nerve ligation displayed a three-dimensional pattern of increased membrane-bound PKC in the lumbar spinal cord (L1-L5) strikingly different from that of sham-operated rats: in the dorsoventral dimension, reliable increases in membrane-bound PKC occurred mainly within spinal cord laminae I-IV and V-VI in CCI rats; in the ipsilateral-contralateral dimension, changes in membrane-bound PKC were seen on both sides of the spinal cord in CCI rats with reliably higher levels of membrane-bound PKC on the side ipsilateral than on the side contralateral to sciatic nerve ligation; in the rostrocaudal dimension, increases in membrane-bound PKC in the spinal cord dorsal horns of CCI rats extended from spinal segments L2-L5. 4. Both three-dimensional increases in spinal cord membrane-bound PKC and nociceptive behaviors (thermal hyperalgesia and spontaneous pain behaviors) in CCI rats were reliably reduced after three daily intrathecal treatments with 80 nmol GM1 ganglioside (a glycosphingolipid shown to prevent PKC translocation/activation), the first of which was given 1 h after sciatic nerve ligation. This reduction was seen 24 h but not 7 days after the last GM1 ganglioside treatment. 5. This three-dimensional increase in membrane-bound PKC in the spinal cord dorsal horn of CCI rats displayed high correlations with thermal hyperalgesia and with spontaneous pain-related behaviors in CCI rats observed both 3 and 10 days after sciatic nerve ligation. Similar correlations were observed between decreases in levels of membrane-bound PKC in the spinal cord dorsal horn and the attenuation of nociceptive behaviors in CCI rats after three daily intrathecal treatments with GM1 ganglioside.(ABSTRACT TRUNCATED AT 400 WORDS)


Indoor radon exposure and excess of lung cancer mortality: the case of Mexico-an ecological study.
Radon is a radioactive gas that can migrate from soils and rocks and accumulate in indoor areas such as dwellings and buildings. Many studies have shown a strong association between the exposure to radon, and its decay products, and lung cancer (LC), particularly in miners. In Mexico, according to published surveys, there is evidence of radon exposure in large groups of the population, nevertheless, only few attention has been paid to its association as a risk factor for LC. The aim of this ecological study is to evaluate the excess risk of lung cancer mortality in Mexico due to indoor radon exposure. Mean radon levels per state of the Country were obtained from different publications and lung cancer mortality was obtained from the National Institute of Statistics, Geography and Informatics for the period 2001-2013. A model proposed by the International Commission on Radiological Protection to estimate the annual excess risk of LC mortality (per 105 inhabitants) per dose unit of radon was used. The average indoor radon concentrations found rank from 51 to 1863 Bq m-3, the higher average dose exposure found was 3.13 mSv year-1 in the north of the country (Chihuahua) and the mortality excess of LC cases found in the country was 10 ± 1.5 (range 1-235 deaths) per 105 inhabitants. The highest values were found mainly in the Northern part of the country, where numerous uranium deposits are found, followed by Mexico City, the most crowded and most air polluted area in the country. A positive correlation (r = 0.98 p < 0.0001) was found between the excess of LC cases and the dose of radon exposure. Although the excess risk of LC mortality associated with indoor radon found in this study was relatively low, further studies are needed in order to accurately establish its magnitude in the country.


Isolated pericardial agenesis revealed by bradycardia and heart MRI in a healthy 5-year-old child.
We present a five-year-old boy with an unremarkable medical history who was incidentally found to have bradycardia and electrocardiographic signs of right axial deviation. Initial echocardiogram showed left displacement of the cardiac apex with slight enlargement of the right ventricle, while frontal chest radiograph showed a lucent area between the aorta and pulmonary artery. Cardiac magnetic resonance imaging finally revealed a partial left pericardial agenesis and abnormal displacement of the heart into the left hemithorax.


Analysis of risk factors associated with antibiotic-resistant Escherichia coli.
Antimicrobial-resistant bacteria represent a major threat to human and animal health. We compared equine fecal samples (n=264) from 138 horses from hospital and nonhospital (livery stable and riding school) premises in North West England to determine the prevalence of Escherichia coli, Salmonella, and Campylobacter and rates of antimicrobial-resistant E. coli strains. Campylobacter jejuni was detected only in hospitalized horses (1.1%), and no Salmonella was identified. Data analysis of the horses' management and veterinary treatments (Tx) identified risk factors associated with shedding of antimicrobial-resistant E. coli. The hospital was the major source of resistant and multi-drug-resistant (MDR) E. coli. Moreover, shedding of antimicrobial-resistant E. coli was associated significantly with hospitalization for a gastrointestinal problem (odds ratio [OR]:±95% confidence intervals=8.50:1.79-40.32), receipt of oral antimicrobial Tx (OR=3.52:1.11-11.10), multiple antimicrobial Tx in hospital (OR/Tx=1.05:1.01-1.09), or geldings (OR=4.62:1.23-17.46). Interestingly, intravenous antimicrobial Tx was negatively associated with shedding of antimicrobial-resistant E. coli (OR=0.18:0.04-0.76). MDR E. coli was associated with hospitalization, antimicrobial Tx in hospital (OR/Tx=3.65:1.54-8.68), and increased age (OR/year=1.11:1.03-1.19). Thus, equine hospitals in this geographic location appear to be an important source of antimicrobial-resistant and MDR E. coli strains, but unlikely reservoirs of Salmonella or Campylobacter. Thus, it is important to moderate antimicrobial Tx given to hospitalized horses to lessen exposure and fecal shedding of resistant pathogens.


Tailoring Physical Properties of Dual-Network Acrylamide Hydrogel Composites by Engineering Molecular Structures of the Cross-linked Network.
We demonstrate the impact of engineering molecular structures of poly(acrylamide) (PAAm) and poly(N-isopropylacrylamide) (PNIPAm) hydrogel composites on several physical properties. The network structure was systematically varied by (i) the type and the concentration of difunctional cross-linkers and (ii) the type of native or chemically modified natural polymers, including sodium alginate, methacrylate/dopamine-incorporated porcine skin gelatin and fish skin gelatin, and thiol-incorporated lignosulfonate, which are attractive biopolymers generated in pulp and food industries because of their abundance, rich chemical functionalities, and environmental friendliness. First, we added cross-linking agents of varying lengths at different concentrations to assess how the cross-linking agent modulates the mechanical properties of acrylamide-based composites with alginate. After chemically modifying gelatins from fish or porcine skin with methacrylate and/or dopamine, the acrylamide-based composites were fabricated with the chemically modified gelatins and thiolated lignosulfonate to assess the stress-strain behavior. Furthermore, swelling ratios were measured with respect to temperature change. The mechanical properties were systematically modulated by the changes in the molecular structure, that is, the length of the chemical unit between two end alkene groups in the difunctional cross-linker and the types of the additive natural polymers. Overall, PAAm hydrogel composites exhibit a significant, negative correlation between toughness and the volume fraction of the swollen state and between strain at fracture and the volume fraction of the swollen state. In contrast, PNIPAm hydrogel composites showed positive, but only moderate correlations, which is attributed to the difference in the network polymer structure.


Inborn Errors of Immunity Associated With Type 2 Inflammation in the USIDNET Registry.
Monogenic conditions that disrupt proper development and/or function of the immune system are termed inborn errors of immunity (IEIs), also known as primary immunodeficiencies. Patients with IEIs often suffer from other manifestations in addition to infection, and allergic inflammation is an increasingly recognized feature of these conditions. We performed a retrospective analysis of IEIs presenting with allergic inflammation as reported in the USIDNET registry. Our inclusion criteria comprised of patients with a reported monogenic cause for IEI where reported lab eosinophil and/or IgE values were available for the patient prior to them receiving potentially curative therapy. Patients were excluded if we were unable to determine the defective gene underlying their IEI. Patients were classified as having eosinophilia or elevated IgE when their record included at least 1 eosinophil count or IgE value that was greater than the age stratified upper limit of normal. We compared the proportion of patients with eosinophilia or elevated IgE with the proportion of samples in a reference population that fall above the upper limit of normal (2.5%). The query submitted to the USIDNET registry identified 1409 patients meeting inclusion criteria with a monogenic cause for their IEI diagnosis, of which 975 had eosinophil counts and 645 had IgE levels obtained prior to transplantation or gene therapy that were available for analysis. Overall, 18.8% (183/975) of the patients evaluated from the USIDNET registry had eosinophilia and 20.9% (135/645) had an elevated IgE. IEIs caused by defects in 32 genes were found to be significantly associated with eosinophilia and/or an elevated IgE level, spanning 7 of the 10 IEI categories according to the International Union of Immunological Societies classification. Type 2 inflammation manifesting as eosinophilia or elevated IgE is found in a broad range of IEIs in the USIDNET registry. Our findings suggest that allergic immune dysregulation may be more widespread in IEIs than previously reported.


Focal weakness following herpes zoster.
Three patients presented with focal weakness of an arm which followed segmental herpes zoster affecting the same limb. Neurophysiological investigations suggest that the site of the lesion lay at the root, plexus, or peripheral nerve level. This reflects the various ways in which the virus may affect the peripheral nervous system.


Calibrating skinfold calipers.
While athletes are routinely assessed for changes in subcutaneous adipose tissue with skinfold calipers, absolute dynamic calibration of caliper jaw compression is currently not possible. The first part of this study describes how dynamic compression of foam rubber blocks can be used to monitor the relative calibration of a single pair of calipers as springs fatigue, or to alert an investigator to variations in measurement values between different calipers. The second part of the study, carried out on 10 female athletes, demonstrated that the significant differences established by the foam block method of calibration also translated into a significant difference for the sum of seven subcutaneous skinfolds. Foam blocks can be used as a simple, inexpensive method to establish a calibration range and can also be used to recheck calipers periodically, depending upon their use.


Bioactive fractions containing methyl eugenol-derived sex pheromonal components in haemolymph of the male fruit fly Bactrocera dorsalis (Diptera: Tephritidae).
Sex pheromonal components of the tephritid fruit fly Bactrocera dorsalis (Hendel), 2-allyl-4,5-dimethoxyphenol and (E)-coniferyl alcohol, are biosynthesized from a highly potent male attractant, methyl eugenol, then sequestered and stored in the rectal gland prior to their release during courtship at dusk. These sex pheromonal components have been detected in the haemolymph and crop organ. Hence, attempts were made to separate and identify the haemolymph fractions which contained the sex pheromonal components. Identification of these bioactive fractions in methyl eugenol-fed male flies using gel filtration column chromatography and biodetection using live male flies showed two fractions as highly attractive to conspecific males. These fractions show a significant increase in protein absorbance in the elution profile of haemolymph from methyl eugenol-fed males compared with that from methyl eugenol-deprived males. The molecular mass of these bioactive fractions as determined by using gel filtration was in the peptide range of 3.3 to 5.5 kDa. Subsequent gas chromatography-mass spectrometry analyses further confirmed the presence of the pheromonal components in the bioactive fractions. The presence of these methyl eugenol-derived sex pheromonal components in specific haemolymph fractions suggests the involvement of a sex pheromone binding complex.


Some properties of 3-phosphoglycerate phosphatase from developing rice grain.
Some properties of 3-P-glycerate phosphatase from developing caryopsis of rice (Oryza sativa L., variety IR26) were studied. The enzyme was found to be soluble and not bound to starch, and concentrated mainly in the pericarp-aleurone layer; its maximum activity was at 12 to 14 days after flowering. Contents of 3-P-glycerate and chlorophyll were highest in the grain at 7 to 8 days after flowering when starch synthesis was at a maximum. The enzyme was purified about 100-fold by precipitation with 50 to 80% ammonium sulfate, followed by chromatography through Sephadex G-200 and CM-Sephadex C-50. The pH optimum was from 5.7 to 6 and no cation was required for activity. The purified preparation had an apparent Km of 2.85 mm and was inhibited by Cu(2+), Hg(2+), Zn(2+), Fe(3+), molybdate, and F(-). The enzyme also exhibited high activity toward UTP, ATP, and p-nitrophenyl phosphate; moderate activity toward other phosphates; but no activity toward phytate. A molecular weight of about 23,000 was obtained for the 3-P-glycerate peak during gel filtration on Sephadex G-200, which corresponded to a value of 26,000 for the major protein fraction by thin layer gel filtration on Sephadex G-150. Zymograms of the whole extract and semipurified preparations showed two phosphatase bands with 3-P-glycerate as substrate.


The potassium--titanyl phosphate laser for treatment of turbinate dysfunction.
Patients with nasal turbinate dysfunction most often are seen by the physician with such symptoms as watery nasal secretions, nasal obstruction, congestion, facial pressure, or pain. There will often have been multiple attempts to manage the problem medically and symptomatically with antihistamines, decongestants, antibiotics, nasal cromolyn, and topical or systemic steroid therapy. Some patients will have undergone numerous attempts at surgical therapy, most often with cryosurgery or cauterization. The cause of the symptoms of turbinate dysfunction for most of these patients is either vasomotor rhinitis, allergic rhinitis, or polypoid hypertrophic turbinates. A visible-wavelength laser with a wavelength of 532 nm, the potassium-titanyl phosphate laser has been used with nasal endoscopes to perform laser photocoagulation of the nasal turbinates. A description of the technique and early results have been previously reported. This article reports good long-term results with the technique.


Salt effect on microscopic structure and stability of colloidal complex obtained from neutral/polyelectrolyte block copolymer and oppositely charged surfactant.
The salt effect on complex formation of poly(acrylamide)-block-poly(acrylic acid) (PAM-b-PAA) and dodecyltrimethylammonium bromide (DTAB) at different NaBr concentrations, C(NaBr), was investigated by laser light scattering (LLS) and small angle neutron scattering (SANS). LLS and SANS clearly indicates that the aqueous solution of PAM-b-PAA and DTAB associate into colloidal complexes. For low surfactant-to-polymer charge ratio Z lower than the critical value Z(C), the colloidal complexes are single DTAB micelles dressed by a few PAM-b-PAA. Above Z(C), the colloidal complexes form a core-shell microstructure. The complex formation in the PAM-b-PAA/DTAB is enhanced by addition of salt: Z(C) decreases with increasing C(NaBr). This is considered to similar to the cmc behavior for the pure surfactant system. The core of the complex consists of densely packed surfactant micelles (DTA(+)), and PAA block chains bind to these micelles, displace their counteranions (Br-) and bridge them. The corona of the complex is constituted from the PAM. Since the interaction between polyelectrolyte and oppositely charged surfactant is primarily electrostatic in nature, the core radius and the intermicellar distance of the DTA(+) micelles inside the core depend on C(NaBr). The addition of salt screens the electrostatic attraction between oppositely charged PAA block and DTAB, which weakens the interaction. With increasing C(NaBr), therefore, the core of the colloidal complex is considered to swell, which leads to the increases in the core radius R(C) and the intermicellar distance of the DTA(+) micelles inside the core. The aggregation number expressed in terms of DTA(+) micelles per complex is also evaluated using the analogy with the homopolyelectrolyte/surfactant system.


Comparison of Health-Related Quality of Life in Outpatients with Chagas and Matched Non-Chagas Chronic Heart Failure in Colombia: A Cross-Sectional Analysis.
Chagas disease represents an important cause of heart failure (HF) and affects health-related quality of life (HRQoL). The study aimed to evaluate and compare the HRQoL of patients with chagasic HF and matched non-Chagas controls to identify factors associated with HRQoL. A cross-sectional study with pair-matched controls was conducted in Colombia. From October 2018 to December 2019, a total of 84 HF patients were screened for study subjects. Four were excluded, resulting in 80 patients for the analysis, among whom 40 patients with Chagas were enrolled as cases and 40 gender- and age-matched non-Chagas patients as controls. The Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) were used to measure HRQoL. Demographic, clinical, and laboratory data were obtained from each subject. Health-related quality of life scores were significantly worse among the Chagas group than among the non-Chagas group in the KCCQ domains of physical functioning and symptoms and in the MLWHFQ scale. In the multivariate analysis, the variables associated with lower HRQoL scores were living alone, obesity, having less than 12 years of education, and an increase in left ventricular diameters in the systole and diastole. Health-related quality of life in patients with chronic HF is impaired across all domains. Chagas patients showed worse HRQoL scores than non-Chagas patients. Six variables, some potentially modifiable, were independently associated with worse HRQoL.


Effect of pH on Orthophosphate Uptake by Corn Roots.
Orthophosphate (Pi) influx in washed corn roots was studied with experimental conditions allowing a distinction of pH effects on Pi ionization in the medium and on the transport system itself. There appeared to be no relationship between the pH dependencies of membrane potential, H(+) secretion, and (32)Pi influx. The Pi uptake versus pH curves were compared to the calculated ones describing the concentrations of the different ionized Pi forms in the medium and in the cell walls; the latter were obtained using the theoretical model described by Sentenac and Grignon (1981) Plant Physiol 68: 415-419). The conclusion was that the transported form is H(2)PO(4) (-) and the concentration sensed by the transport system is the local one. The ionic compositions of experimental media were manipulated to ensure constant pH and various H(2)PO(4) (-) concentrations, or constant H(2)PO(4) (-) concentration and various pH values in the walls. The kinetic analysis of the results in the micromolar range showed that the transport system has an intrinsic sensitivity to pH, and is switched from a low activity state at pH > 6 to a high activity one at pH < 4 (pH in the walls). This change could be triggered by the protonation of a group with pK 5.5.


Outcomes of congenital heart disease: a review.
One million Americans are affected by congenital heart disease (CHD) (American Heart Association [AHA], 2003). As survival has improved, evidence has accumulated that CHD touches many aspects of the lives of those affected. Children and adults report difficulties with physical growth and/or stature. Gross motor abnormalities are common in both groups, and significantly reduced exercise tolerance is reported in adults with CHD, including those with minor defects. Behavioral and psychiatric abnormalities are reported in adolescents and young adults, including a significant incidence of depression and anxiety disorders. The data are conflicting regarding quality of life (QOL) in children and adults with CHD. More research is needed examining outcomes, particularly outcomes of those diagnosed, managed, and repaired using modern technology.


24-hour blood pressure monitoring in patients with anterior ischemic optic neuropathy.
To define parameters of ambulatory diurnal blood pressure in patients who had experienced anterior ischemic optic neuropathy (AION) in a case-controlled study. Twenty-four patients with AION and 24 control subjects who were matched for age, gender, medical diagnoses, and medications underwent ambulatory automated blood pressure monitoring for 24 hours. The overall diurnal pattern of blood pressure appeared to be normal in all subjects, showing lower blood pressures at night than during the day, an overnight nadir, and an ascending blood pressure curve in the morning to reach daytime levels. Also, patients with AION did not differ from control subjects with respect to the nighttime diastolic nadir or daytime peak systolic blood pressure. However, during the daytime, patients with AION had lower mean systolic and diastolic blood pressures than did matched control subjects. The widest difference between their blood pressure curves occurred after awakening in the morning, when patients with AION had a less steep and more irregular rise of blood pressure. Patients who had signs of vertebrobasilar insufficiency in addition to AION had lower mean diastolic blood pressure during both daytime and nighttime and a lower minimum daytime diastolic blood pressure. On ambulatory measurements of diurnal blood pressure, patients with AION consistently had a lower mean blood pressure than did control subjects and a lag in the usual rise in blood pressure in the morning to meet increasing daytime demands for perfusion. Chronic hypoperfusion of small end-arterial vessels that supply the optic nerve head may predispose to AION, and may be caused by relative hypotension owing to overtreated hypertension or to abnormal vascular autoregulation. Internists should be asked to monitor blood pressure carefully when treating hypertensive patients who are at risk for AION, to avoid hypotension, especially on awakening in the morning.


Transportation of pediatric femur fractures to a tertiary care center: a retrospective review.
Pediatric femur fractures are common injuries presenting to tertiary care trauma centers. Transportation of these patients occurs most commonly via ambulance or flight. The purpose of this study is to evaluate whether mode of transportation affects time to surgery or hospital stay for pediatric patients with femur fractures. Utilizing a trauma registry we queried pediatric femur fractures between January 2001 and December 2009. Patient age, gender, mechanism of injury, month of injury, type of fracture, transportation, county of origin, time to operating room (TTOR), hospital length of stay (HLOS), and treatment received were identified and compared. In total, 519 femur fractures were identified, 257 (49.5%) of which were isolated injuries. Flight transportation was utilized in 13.6 % (35 of 257) of these isolated fractures. Mean TTOR for flight patients was 29 hours, HLOS 3.2 days. For ambulance transportation mean TTOR was 41 hours, HLOS 3.2 days. Neither variable was statistically different between transportation groups (TTOR p > 0.50; HLOS p > 0.95). No statistical difference was seen in HLOS (p > 0.47) and TTOR (p > 0.71) for patients originating further distances from the hospital. Transportation method and distance from the hospital did not affect the TTOR and HLOS for isolated pediatric femur fractures. The use of air transportation for this group of patients, many of whom are injured by relatively low energy mechanisms, may be excessively costly and does not accelerate treatment.


Iodido-bis-(morpholine-4-carbodi-thio-ato-κ(2) S,S')(1,10-phenanthroline-κ(2) N,N')bis-muth(III).
The title compound, [Bi(C4H8NOS2)2I(C12H8N2)], is monomeric, with the Bi(III) atom chelated by the two S atoms of two morpholine-4-carbodi-thio-ate ligands and the two N atoms of a 1,10-phenanthroline ligand. An iodide ligand completes the coordination sphere, with the seven-coordinate Bi(III) atom adopting a highly distorted monocapped octa-hedral geometry.


Mortality from Influenza A/H1N1 in a tertiary care teaching institution in North India.
The recent influenza A/H1N1 pandemic has caused considerable morbidity and some mortality and is therefore a severe threat to certain individuals. Up to 31 January 2010, there had been 1,229 confirmed deaths from Influenza A/H1N1 in India. This study was a retrospective analysis of deaths caused by RT-PCR-confirmed cases of Influenza A/H1N1 in a tertiary care institution in North India from September 2009 until January 2010. Among 125 patients admitted to the Influenza A/H1N1 ward of the hospital, a total of 16 deaths had occurred in patients who were positive for Influenza A/H1N1. Two deaths were in the paediatric age group. Most patients who died had some predisposing illness, such as pregnancy, underlying chronic respiratory illness, diabetes, obesity, etc. In the present study, deaths from Influenza A/H1N1, as with seasonal influenza, appeared to occur primarily in individuals with underlying illness. In India, such individuals may be considered first for preventive strategies, including vaccination.


[Transcranial magnetic stimulation (TMS), inhibition processes and attention deficit/hyperactivity disorder (ADHD) - an overview].
Motor system excitability can be tested by transcranial magnetic stimulation CFMS). In this article, an overview of recent methodological developments and research findings related to attention deficit/hyperactivity disorder (ADHD) is provided. Different TMS parameters that reflect the function of interneurons in the motor cortex may represent neurophysiological markers of inhibition in ADHD, particularly the so-called intracortical inhibition. In children with a high level of hyperactivity and impulsivity, intracortical inhibition was comparably low at rest as shortly before the execution of a movement. TMS-evoked potentials can also be measured in the EEG so that investigating processes of excitability is not restricted to motor areas in future studies. The effects of methylphenidate on motor system excitability may be interpreted in the sense of a 'fine-tuning' with these mainly dopaminergic effects also depending on genetic parameters (DAT1 transporter). A differentiated view on the organization of motor control can be achieved by a combined analysis of TMS parameters and event-related potentials. Applying this bimodal approach, strong evidence for a deviant implementation of motor control in children with ADHD and probably compensatory mechanisms (with involvement of the prefrontal cortex) was obtained. These findings, which contribute to a better understanding of hyperactivity/impulsivity, inhibitory processes and motor control in ADHD as well as the mechanisms of medication, underline the relevance of TMS as a neurophysiological method in ADHD research.


[Platelets haemostatic in patients with multiple myeloma].
Multiple myeloma (MM) is a type of disseminated cancer which derive plasma cells that are immune system cells in bone marrow and produce monoclonal protein. It represents approximately 1% of all cancers, but recent statistics indicate both increasing incidence and earlier age of onset. Haemostatic disorders are an important clinical problem in patients with MM. The most common disturbances symptoms are bleeding and deep-vein thrombosis can due to platelet dysfunction, inhibition of fibrin and increased clearance of coagulation factors connected with monoclonal protein presence. The aim of study is a presentation of disturbances haemostatic in patients with MM, which make up important clinical and diagnostic problems.


Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect.
Surfactant protein A (SP-A) plays a role in host defense and inflammation in the lung. In the present study, we investigated the hypothesis that SP-A is involved in bleomycin-induced pulmonary fibrosis. We studied the effects of human SP-A on bleomycin-induced cytokine production and mRNA expression in THP-1 macrophage-like cells and obtained the following results. 1) Bleomycin-treated THP-1 cells increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, and IL-1beta production in dose- and time-dependent patterns, as we have observed with SP-A. TNF-alpha levels were unaffected by treatment with cytosine arabinoside. 2) The combined bleomycin-SP-A effect on cytokine production is additive by RNase protection assay and synergistic by enzyme-linked immunosorbent assay. 3) Although the bleomycin effect on cytokine production was not significantly affected by the presence of surfactant lipid, the additive and synergistic effect of SP-A-bleomycin on cytokine production was significantly reduced. We speculate that the elevated cytokine levels resulting from the bleomycin-SP-A synergism are responsible for bleomycin-induced pulmonary fibrosis and that surfactant lipids can help ameliorate pulmonary complications observed during bleomycin chemotherapy.


Treating persistent pain after breast cancer: practice gaps and future directions.
This paper discusses the growing problem of persisting pain after successful treatment of breast cancer and presents recommendations for improving pain-related outcomes for this group. We discuss the dominant treatment approach for persisting pain post-breast cancer treatment and draw contrasts with contemporary treatment approaches to persistent pain in non-cancer-related populations. We discuss modern application of the biopsychosocial model of pain and the notion of variable sensitivity within the pain system, moment by moment and over time. We present the implications of increasing sensitivity over time for treatment selection and implementation. By drawing on transformative changes in treatment approaches to persistent non-cancer-related pain, we describe the potentially powerful role that an intervention called pain science education, which is now recommended in clinical guidelines for musculoskeletal pain, may play in improving pain and disability outcomes after successful breast cancer treatment. Finally, we present several research recommendations that centre around adaptation of the content and delivery models of contemporary pain science education, to the post-breast cancer context.


Structure and activity of insect cytokine GBP which stimulates the EGF receptor.
Growth-blocking peptide (GBP) is an insect cytokine that possesses diverse biological activities such as larval growth regulation, cell proliferation, and stimulation of immune cells. GBP is a 25-amino acid peptide with one disulfide bond. It has been revealed that the tertiary structure of GBP consists of an N- and C-terminal disordered region and a well-structured core. Although there is only a slight similarity between the primary structures of GBP and EGF and the molecular weight of GBP is about half that of EGF, GBP directly binds and activates the EGF receptor of human keratinocyte cells. Furthermore, the tertiary structure of the well-defined region of GBP is similar to that of the C-terminal domain of EGF. This review will focus on the tertiary structure of GBP and its activities, as compared with those of EGF.


Wolbachia infection at least partially rescues the fertility and ovary defects of several new Drosophila melanogaster bag of marbles protein-coding mutants.
The D. melanogaster protein coding gene bag of marbles ( bam ) plays a key role in early male and female reproduction by forming complexes with partner proteins to promote differentiation in gametogenesis. Like another germline gene, Sex lethal , bam genetically interacts with the endosymbiont Wolbachia , as Wolbachia rescues the reduced fertility of a bam hypomorphic mutant. Here, we explored the specificity of the bam-Wolbachia interaction by generating 22 new bam mutants, with ten mutants displaying fertility defects. Nine of these mutants trend towards rescue by the w Mel Wolbachia variant, with eight statistically significant at the fertility and/or cytological level. In some cases, fertility was increased a striking 20-fold. There is no specificity between the rescue and the known binding regions of bam , suggesting w Mel does not interact with one singular bam partner to rescue the reproductive phenotype. We further tested if w Mel interacts with bam in a non-specific way, by increasing bam transcript levels or acting upstream in germline stem cells. A fertility assessment of a bam RNAi knockdown mutant reveals that w Mel rescue is specific to functionally mutant bam alleles and we find no obvious evidence of w Mel interaction with germline stem cells in bam mutants. Reproduction in the Drosophila melanogaster fruit fly is dependent on the bag of marbles ( bam ) gene, which acts early in the process of generating eggs and sperm. Mutations to this gene negatively impact the fertility of the fly, causing it to be sterile or have fewer progeny. Interestingly, we find that the bacteria Wolbachia , which resides within reproductive cells across a wide range of insects, partially restores the fertility and ovary phenotype of several bam mutants of which the resultant Bam protein is altered from wildtype. The protein function of Bam is further suggested to be important by the lack of rescue for a fly that has a fertility defect due to low expression of a non-mutated bam gene. Previous work makes similar conclusions about Wolbachia with another reproductive gene, Sex lethal ( Sxl ), highlighting the potential for rescue of fertility mutants to occur in a similar way across different genes. An understanding of the ways in which Wolbachia can affect host reproduction provides us with context with which to frame Wolbachia 's impact on host genes, such as bam and Sxl, and consider the evolutionary implications of Wolbachia 's infection in D. melanogaster fruit flies.


Evaluation of heliox in children hospitalized with acute severe asthma. A randomized crossover trial.
To determine whether breathing a blend of 70% helium:30% oxygen (heliox) would improve pulmonary function, decrease clinical score, and improve the sensation of dyspnea in children hospitalized with acute severe asthma. Prospective, randomized, double-blind, crossover study. The inpatient pediatric service of a military, tertiary care, teaching hospital. Children 5 to 18 years who required hospital admission for treatment of acute asthma. All patients received 5 mg of nebulized albuterol every 1 to 4 h, with a dose given within 30 min of the start of the study, and IV administered methylprednisolone. Patients breathed heliox and a 30% oxygen-enriched air mixture for 15 min each in random order. Clinical score, dyspnea score, oxygen saturation, heart rate, and respiratory rate, followed by FVC, FEV1, peak expiratory flow rate (PEFR), and, mean midexpiratory flow rate (FEF25-75) were obtained at study entry, 15 min after breathing the first gas mixture (heliox or air per randomization), 15 min after breathing the second mixture, and again 15 min after stopping the second gas mixture (study end values). Eleven children were enrolled, and all completed the study. There were no significant differences between study entry and study end spirometric values. Using the paired t test, we found no significant differences between mean values (SD) of FEV1 and FVC obtained while breathing heliox vs air; FEV1-heliox, 53% (18%) of the predicted value; FEV1-air, 52% (16%) of the predicted value (p = 0.36); FVC-heliox, 69% (22%) of the predicted value; and FVC-air, 70% (21%) of the predicted value (p = 0.50). The differences in values for PEFSR and FEF25-75 while breathing heliox vs air were small but did reach statistical significance in favor of heliox: PEFR-heliox, 56% (20%) of the predicted value; PEFR-air, 50% (16%) of the predicted value (p = 0.04); FEF25-75-heliox, 32% (13%) of the predicted value; and FEF25-75-heliox, 29% (11%) of the predicted value (p = 0.006). Heliox had no effect on either clinical or dyspnea scores. The short-term inhalation of heliox did not benefit this group of children hospitalized with acute, severe asthma.


Comparison of prefrontal cortex sucrose seeking ensembles engaged in multiple seeking sessions: Context is key.
Encoding of memories, including those associated with prior drug or reward, is thought to take place within distinct populations of neurons, termed ensembles. Neuronal ensembles for drug- and reward-seeking have been identified in regions of the medial prefrontal cortex, but much of our understanding of these ensembles is based on experiments that take place in a single reward-associated environment and measure ensemble encoding over short durations of time. In contrast, reward seeking behavior is evident across different reward-associated environments and persists over time. Using TetTag mice and Fos immunohistochemistry, we examined the relationship between persistent sucrose-seeking and ensemble encoding in mice that undergo seeking sessions in the same or different sucrose self-administration contexts 2 weeks apart. We found that prelimbic (PrL) and anterior cingulate cortex ensembles tagged in the first seeking session were highly sensitive to the context in which a second seeking session took place: reactivation of these ensembles was reduced in the same context but elevated in a distinct sucrose self-administration context. Correlational analyses revealed that ensemble reactivation in the PrL was proportional to the persistence of sucrose seeking behavior across sessions in differing ways in female mice. In the same context, reactivation was proportional to the persistence of non-reinforced operant responses, whereas in a distinct context, reactivation was proportional to the persistence of non-reinforced head entries into the sucrose receptacle. This study underlines the importance of the medial prefrontal cortex importance in maintaining a reward-seeking ensemble over time and identifies context-dependent changes in behavioral correlates of ensemble reactivation.


Transcriptome and Proteomics Analysis of Wheat Seedling Roots Reveals That Increasing NH4 +/NO3 - Ratio Induced Root Lignification and Reduced Nitrogen Utilization.
Wheat growth and nitrogen (N) uptake gradually decrease in response to high NH4 +/NO3 - ratio. However, the mechanisms underlying the response of wheat seedling roots to changes in NH4 +/NO3 - ratio remain unclear. In this study, we investigated wheat growth, transcriptome, and proteome profiles of roots in response to increasing NH4 +/NO3 - ratios (N a : 100/0; N r1: 75/25, N r2: 50/50, N r3: 25/75, and N n : 0/100). High NH4 +/NO3 - ratio significantly reduced leaf relative chlorophyll content, Fv/Fm, and ΦII values. Both total root length and specific root length decreased with increasing NH4 +/NO3 - ratios. Moreover, the rise in NH4 +/NO3 - ratio significantly promoted O2 - production. Furthermore, transcriptome sequencing and tandem mass tag-based quantitative proteome analyses identified 14,376 differentially expressed genes (DEGs) and 1,819 differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that glutathione metabolism and phenylpropanoid biosynthesis were the main two shared enriched pathways across ratio comparisons. Upregulated DEGs and DEPs involving glutathione S-transferases may contribute to the prevention of oxidative stress. An increment in the NH4 +/NO3 - ratio induced the expression of genes and proteins involved in lignin biosynthesis, which increased root lignin content. Additionally, phylogenetic tree analysis showed that both A0A3B6NPP6 and A0A3B6LM09 belong to the cinnamyl-alcohol dehydrogenase subfamily. Fifteen downregulated DEGs were identified as high-affinity nitrate transporters or nitrate transporters. Upregulated TraesCS3D02G344800 and TraesCS3A02G350800 were involved in ammonium transport. Downregulated A0A3B6Q9B3 is involved in nitrate transport, whereas A0A3B6PQS3 is a ferredoxin-nitrite reductase. This may explain why an increase in the NH4 +/NO3 - ratio significantly reduced root NO3 --N content but increased NH4 +-N content. Overall, these results demonstrated that increasing the NH4 +/NO3 - ratio at the seedling stage induced the accumulation of reactive oxygen species, which in turn enhanced root glutathione metabolism and lignification, thereby resulting in increased root oxidative tolerance at the cost of reducing nitrate transport and utilization, which reduced leaf photosynthetic capacity and, ultimately, plant biomass accumulation.


Dermoscopic feature analysis of different skin lesions in Langerhans cell histiocytosis.
Dermoscopy was used to investigate skin lesions in 15 children with Langerhans cell histiocytosis (LCH). Purplish-red globules or patches could be seen in different rashes under dermoscopy, and histopathology showed extravasation of red blood cells. The dermoscopy findings closely correlated with the histopathology results. Purplish-red globules or patches could be useful as important dermoscopy features for the differential diagnosis of LCH.


Patterns of inflammatory immune responses in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine: clustering analysis in Korea.
Sepsis is characterized by heterogeneous immune responses that may evolve during the course of illness. This study identified inflammatory immune responses in septic patients receiving vitamin C, hydrocortisone, and thiamine. This was a single-center, post-hoc analysis of 95 patients with septic shock who received the vitamin C protocol. Blood samples were drawn on days 1-2, 3-4, and 6-8 after shock onset. Group-based multi-trajectory modeling was used to identify immune trajectory groups. The median age was 78 years (interquartile range, 70-84 years), and 56% were male. Clustering analysis identified group 1 (n=41), which was characterized by lower interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels, and these levels remained stationary or mildly increased until day 7. Conversely, group 2 (n=54) expressed initially higher IL-6, TNF-α, and IL-10 levels that decreased rapidly by day 4. There was a nonsignificant increase in lymphocyte count and a decrease in C-reactive protein level until day 7 in group 2. The intensive care unit mortality rate was significantly lower in group 2 (39.0% vs. 18.5%, P=0.03). Group 2 also had a significantly higher decrease in the mean (standard deviation) vasopressor dose (norepinephrine equivalent: -0.09±0.16 μg/kg/min vs. -0.23±0.31 μg/kg/min, P<0.001) and Sequential Organ Failure Assessment score (0±5 vs. -4±3, P=0.002) between days 1 and 4. There may be different subphenotypes in septic patients receiving the vitamin C protocol.


Literacy, comprehension, and informed consent in clinical research.
Institutional review boards (IRBs) and informed consent have recently come under increasing scrutiny. The provision of appropriate and understandable information and its comprehension are key elements of the informed consent process. This article examines how literacy and other factors might impact on comprehension of the information provided. Better understanding of these issues and how to best address them are crucial to allowing clinical research subjects to participate as well-informed and willing partners in scientific inquiry.


Novel and Specific MRI Features Indicate the Clinical Features of Patients With Rare Hepatic Tumor Epithelioid Hemangioendothelioma.
To investigate the MRI features and clinical significance of hepatic epithelioid hemangioendothelioma (HEHE). Clinical records and MRI findings were retrospectively evaluated in nine HEHE patients from May 2010 to January 2020. There were 121 lesions in nine patients with a predominantly peripheral distribution. Five lesions (4.13%) in two patients (22.22%) had evidence of capsular retraction, and three patients had lung metastasis (33.33%). Dynamic contrast-enhanced MRI showed progressive enhancement, mainly in two ways: ring enhancement with hypovascularity in four patients (44.44%) and ring enhancement with hypervascularity in five patients (55.56%). Imaging demonstrated a multilayer ring appearance, which was typically observed on T2-weighted imaging (T2WI). The most common appearance consisted of two layers of varying signal, with some images displaying up to four layers. There were significant differences in the size of lesions between different layers of multilayer ring appearance (p < 0.001). All lesions exhibited a two-layer appearance on diffusion-weighted imaging (DWI), with hyperintensity at the periphery and a slightly high signal at the center (except for those with a single layer on T2WI). The "vascular penetration sign" was observed in most lesions, and the blood vessels of 112 lesions (92.56%) were portal vein branches, and five (4.13%) were hepatic vein branches. Pulmonary metastasis was found in three patients with the "vascular penetration sign" of hepatic vein branches. The multilayer ring appearance on T2WI, the "vascular penetration sign", and the two enhancement patterns may be of great significance in the diagnosis and treatment of HEHE. The "vascular penetration sign" of hepatic vein branches may indicate extrahepatic metastasis.


Thyroid Hormone Induces DNA Demethylation in Xenopus Tadpole Brain.
Thyroid hormone (T3) plays pivotal roles in vertebrate development, acting via nuclear T3 receptors (TRs) that regulate gene transcription by promoting post-translational modifications to histones. Methylation of cytosine residues in deoxyribonucleic acid (DNA) also modulates gene transcription, and our recent finding of predominant DNA demethylation in the brain of Xenopus tadpoles at metamorphosis, a T3-dependent developmental process, caused us to hypothesize that T3 induces these changes in vivo. Treatment of premetamorphic tadpoles with T3 for 24 or 48 hours increased immunoreactivity in several brain regions for the DNA demethylation intermediates 5-hydroxymethylcytosine (5-hmC) and 5-carboxylcytosine, and the methylcytosine dioxygenase ten-eleven translocation 3 (TET3). Thyroid hormone treatment induced locus-specific DNA demethylation in proximity to known T3 response elements within the DNA methyltransferase 3a and Krüppel-like factor 9 genes, analyzed by 5-hmC immunoprecipitation and methylation sensitive restriction enzyme digest. Chromatin-immunoprecipitation (ChIP) assay showed that T3 induced TET3 recruitment to these loci. Furthermore, the messenger ribonucleic acid for several genes encoding DNA demethylation enzymes were induced by T3 in a time-dependent manner in tadpole brain. A TR ChIP-sequencing experiment identified putative TR binding sites at several of these genes, and we provide multiple lines of evidence to support that tet2 contains a bona fide T3 response element. Our findings show that T3 can promote DNA demethylation in developing tadpole brain, in part by promoting TET3 recruitment to discrete genomic regions, and by inducing genes that encode DNA demethylation enzymes.


Role of platelet activating factor in development of thrombocytopenia and neutropenia in dogs with endotoxemia.
To determine the role of platelet activating factor (PAF) in lipopolysaccharide (LPS)-induced thrombocytopenia and neutropenia in dogs. 42 dogs. Blood samples were obtained from dogs given LPS (40 microg/kg of body weight; n = 16), PAF (1 microg/kg; 6), PAF (5 microg/kg/h for 90 minutes; 4), or physiologic saline (0.9% NaCl) solution (0.1 ml/kg/h for 90 minutes; 3) IV to monitor changes in blood cell counts, using automated counters and blood smears stained with Giemsa. Blood samples were also obtained from dogs given LPS (40 microg/kg) that had (n = 5) or had not (6) been treated beforehand with TCV-309, a potent PAF antagonist. Concentration of PAF in blood was determined by use of 125I-radioimmunoassay in dogs given LPS at 1 mg/kg (n = 3) and 40 microg/kg (9). Thrombocytopenia and neutropenia were found in all dogs except those given saline solution. The LPS-induced thrombocytopenia was significantly suppressed by prior treatment with TCV-309. The PAF concentrations increased markedly 1 hour after injection of 1 mg/kg of LPS and increased slightly but significantly 10 minutes after injection of 40 microg/kg of LPS. PAF plays an important role in the development of LPS-induced thrombocytopenia and neutropenia in dogs. Control of PAF production, PAF-induced effects, or both may be important in the treatment of dogs with gram-negative bacterial infections and associated thrombocytopenia and neutropenia.


[In-vivo Confocal Microscopy for the Diagnosis of Mucous Membrane Pemphigoid].
An early diagnosis is crucial for the outcome of mucous membrane pemphigoid (MMP). The sensitivity of the so-called diagnostic gold standard, direct and indirect immune fluorescence (DIF/IIF) ranges from 30 to 80 %, and is thus lower than desirable. Moreover, conjunctival biopsy, mandatory in most cases, entails the risks of exacerbation. The purpose of this study is to establish the contribution of non-invasive in vivo confocal microscopy to the recognition of MMP. We examined the conjunctiva of ten patients and ten control subjects with the confocal microscope Heidelberg Retina Tomograph II/Rostock Cornea Module and checked for differences in qualitative and quantitative structure of the connective tissue. Pemphigoid patients showed an increase and/or aggregation of reticular connective tissue with hyperreflective strands in the substantia propria, as well as an increased subepithelial fibrosis compared to controls. The basal membrane zone was thicker and more hyperreflective than in the healthy subjects. In-vivo confocal microscopy may serve as a useful additional diagnostic method in the detection of MMP.


Total synthesis of gambierol: subunit coupling and completion.
The preceding manuscript detailed our synthesis of the gambierol A-C and F-H ring precursors. Reported herein is a description of the coupling of the two precursors and the conversion of the coupled material into gambierol. Coupling of the subunits involved ester formation, enol ether RCM, and mixed thioketal formation and reduction. By employing this strategy we were able to bring highly advanced subunits into the coupling and, as a result, we were able to minimize the number of post-coupling transformations required to complete gambierol. At the completion of the synthesis, we generated 7.5 mg (1.5 % overall yield) of (-)-gambierol in 44 steps (longest linear sequence).


Natural occurrence of Fusarium mycotoxins in field samples from the 1992 Wisconsin corn crop.
Analysis of 98 moldy corn samples collected in Wisconsin between November 1992 and January 1993 for Fusarium toxins by various immunochemical assays revealed overall average mycotoxin concentrations of 305.6, 237.7, and 904.3 ng/g for type A trichothecenes (TCTCs), deoxynivalenol (DON)-related type B TCTCs (total DON), and zearalenone (ZE), respectively. A small portion (5.1%) of the samples was found to be contaminated with high levels ( > 1 microgram/g) of type A TCTCs and total DON during the whole survey. Over 40% of the samples had 100 to 1,000 ng of total DON per g, while 17% of the samples had the same levels of type A TCTCs. The analytical data were consistent with those from mycological examinations for the samples in which various toxic Fusarium spp., including F. sporotrichioides, F. poae, and F. graminearum, were found. The samples received in November 1992 had relatively low concentrations of toxin; the average levels of type A TCTCs and total DON were 9.9 and 79 ng/g, respectively. The toxin concentrations became progressively higher in the samples received in December. The average levels for the type A TCTCs and total DON increased to 920 and 335 ng/g, respectively. However, the levels of ZE were higher in the samples collected earlier. The average levels for samples collected in November and late December were 1,195 and 242 ng/g, respectively. Analysis of selected samples by high-performance liquid chromatography monitoring with an enzyme-linked immunosorbent assay revealed that T-2 toxin, HT-2 toxin, diacetoxyscirpenol, neosolaniol, and T-2 tetraol (T-2-4ol) were common in these samples. Statistical analysis revealed a weak correlation between the levels of total type A TCTCs and total DON in the samples (r = 0.18, P = 0.09), but a strong correlation between the levels of ZE and total type B TCTCs (r = 0.75, P < 0.0001) was found. The mycotoxin levels of total type A TCTCs, total DON-related type B TCTCs, and ZE in the cobs (5.2, 3.9, and 21 micrograms/g, respectively) were considerably higher than those in the kernels (1.0, 0.5, and 0.5 microgram/g, respectively). The type A toxin levels increased from a range of 14 to 35 ng/g to a range of 110 to 538 ng/g after the moldy corn samples were held at 5 degrees C for 8 days in the laboratory.


Longitudinal association between self-rated health and timed gait among older persons.
We evaluated the longitudinal association between self-rated health (SRH) and timed gait, an indicator of lower extremity dysfunction, in a community-based sample of older persons. Participants (N = 754) were evaluated at 18-month intervals for 72 months. SRH was categorized as Excellent/Very Good/Good and Fair/Poor. Participants were asked to walk a 10-foot course "as fast as it feels safe and comfortable," turn around, and walk back, with timed gait defined as normal (≤10 s) or slow (>10 s). Generalized multinomial logit models, adjusted for demographic features, biomedical and psychosocial factors, and activities of daily living, evaluated the association between SRH and the likelihood of 6 possible transitions (from normal or slow timed gait to normal timed gait, slow timed gait, or death) over time. We also ran a repeated measures linear mixed model with change in timed gait as the outcome. Compared with participants reporting Excellent/Very Good/Good SRH, those reporting Fair/Poor SRH were more likely to transition from normal to slow timed gait or to death. SRH was not associated with transitions from slow timed gait to normal timed gait or to death. In addition, time to complete the gait task increased (i.e., slowed) over time among participants reporting Fair/Poor SRH compared with those reporting Excellent/Very Good/Good SRH. Among older persons, SRH is associated with the development of lower extremity dysfunction but not with recovery from lower extremity dysfunction. This relationship may indicate an intermediate step in the pathway from SRH to mortality.


Adherence to guidelines regarding total hip replacement for fractured neck of femur.
Introduction In 2011 the National Institute for Health and Care Excellence (NICE) published guidelines suggesting that clinicians offer total hip replacement (THR) to patients with displaced intracapsular hip fractures who could walk independently outside with no aids or one stick, who are not cognitively impaired and are ASA (American Society of Anesthesiologists) grade ≤2. They also stated that best practice is operating within 36 hours of presentation. This audit aimed to determine whether Scarborough Hospital was following these guidelines and compared the results with the national average. Methods Two years of data (January 2012 - December 2013) were collected retrospectively from Scarborough Hospital's hip fracture database on all patients presenting with an intracapsular hip fracture. Data were analysed to determine whether patients who had a THR fulfilled NICE criteria. Furthermore, patients with hemiarthroplasties who were eligible for THRs were identified. Finally, the time to surgery was calculated to examine whether patients receiving THRs waited longer than patients receiving hemiarthroplasties. Results In 2012, 48.6% of all eligible patients received a THR while in 2013 the figure was 55.9%. These percentages are much higher than the national average. However, 36 (53.7%) of the 67 patients who received a THR did not fulfil all the NICE criteria, mainly owing to high ASA grade. The mean time from presentation to theatre for THR was 8 hours and 37 minutes longer for THR patients than for hemiarthroplasty in 2012. This difference was reduced to 2 hours and 12 minutes in 2013. Conclusions Small general hospitals can meet and even exceed the standards regarding treatment strategies for hip factures. However, there is still room for improvement. Departmental training may be useful in achieving this aim. The anaesthetic team should be involved at the earliest opportunity, to help optimise patients preoperatively and determine whether patients listed for THR with higher ASA grades are suitable for this surgery.