High fructan barley lines produced by selective breeding may alter β-glucan and amylopectin molecular structure.
Six cross-bred barley lines developed by a breeding strategy with the target to enhance the fructan synthesis activity and reduce the fructan hydrolysis activity were analyzed together with their parental lines, and a reference line (Gustav) to determine whether the breeding strategy also affected the content and molecular structure of amylopectin and β-glucan. The highest fructan and β-glucan content achieved in the novel barley lines was 8.6 % and 12 %, respectively (12.3-fold and 3.2-fold higher than in Gustav). The lines with low fructan synthesis activity had higher starch content, smaller building blocks in amylopectin, and smaller structural units of β-glucans than the lines with high-fructan synthesis activity. Correlation analysis confirmed that low starch content was associated with high amylose, fructan, and β-glucan content, and larger building blocks in amylopectin.


Programmability in DDD pacing.
Safe and reliable DDD pacemakers with multiple programming capabilities have now been developed. Certain programmable parameters are basic, including mode, voltage (or current) output, pulse width, sensitivity and refractory periods in each chamber. Upper rate response as well as low rate settings and A-V delays are equally important. In certain models, the ability to program the blanking period has proven quite useful. The interrelationship between all these functions will assure the smooth overall performance of these sophisticated devices.


Overview of Zika infection, epidemiology, transmission and control measures.
The current Zika virus outbreak in the Americas and the proposed link to increases in microcephaly and neurological disorders have prompted the World Health Organization to declare a Public Health Emergency of International Concern on February 1, 2016. The virus is transmitted by Aedes mosquitoes and potentially by transfusion, perinatal and sexual transmission. The potential for spread into countries where Aedes mosquitoes are endemic is high. Previously, cases tended to be sporadic and associated with mild, non-specific symptoms. Prior outbreaks occurred in Yap Island in Micronesia in 2007, the first time Zika arose outside of Africa and Asia, and in French Polynesia in 2013. A birth data review has confirmed that the latter outbreak was followed by an increase in microcephaly cases. A coordinated international response is needed to address mosquito control; expedite development of diagnostic tests, vaccines and specific treatments for Zika; and address the proposed link to microcephaly and neurological diseases.


Banxia-Houpu decoction inhibits iron overload and chronic intermittent hypoxia-induced neuroinflammation in mice.
The Banxia-Houpu decoction (BHD), a renowned prescription documented in the Chinese medical book "The Synopsis of the Golden Chamber," has been proven to effectively mitigate inflammation within the central nervous system. Previous studies have demonstrated the efficacy of BHD in ameliorating symptoms in patients with obstructive sleep apnea (OSA). Nevertheless, the precise mechanisms and comprehensive effects of BHD on central system injury in OSA models have not been fully investigated. To investigate whether BHD could inhibit neuroinflammation to decrease iron-induced neurotoxic injury in CIH mice. C57BL/6N mice were divided into the Con, CIH, and BHD groups. Mice were exposed to CIH (21%-5% FiO2, 3 min/cycle, 8 h/d), and BHD was administered by gavage (3.51, 7.01, and 14.02 g/kg). The polarization of microglia, inflammatory factors, hepcidin, and brain iron levels were determined. The administration of BHD at a dosage of 7.01 g/kg demonstrated a significant reduction in neurobehavioral abnormalities, neuronal damage, and degeneration caused by CIH. BHD exhibited the ability to inhibit the transition of microglial polarization from M2 to M1 by upregulating CD163 expression and downregulating iNOS levels. Furthermore, BHD decreased pro-inflammatory factor levels and increased anti-inflammatory factor levels. Additionally, BHD was found to decrease hepcidin expression in astrocytes through the TLR4/MyD88/NF-κB signaling pathway. BHD reduced the total and neuronal iron levels by elevating FPN1 and reducing TfR1 levels. BHD exhibited positive effects on synapse and synaptic spine abnormalities, as well as an increase in the Bcl-2/Bax ratio, thereby mitigating neuronal damage induced by CIH. Based on these findings, BHD holds potential as a therapeutic intervention for neural damage injuries, which offers a theoretical foundation for the treatment of patients with OSA in clinical.


MPFL reconstruction and tibial tuberosity transposition in patients with patellar instability: May it troubleshots also trochlear dysplasia?
This study aimed to highlight short- and medium-term outcomes of combined medial patello-femoral ligament (MPFL) reconstruction and anterior tibial tuberosity (ATT) transposition surgery in patients with recurrent patellar instability and different degrees of trochlear dysplasia. Between January 2014 and May 2019, 25 patients with patellar instability underwent a surgical procedure combining the lowering/transposition of the ATT and the MPFL reconstruction. Each patient were preoperative assessed by Kujala score, International Knee Documentation Committee (IKDC), Tegner activity level scale. The assessment of instability predisposing factors was carried out with patellar height, tibial tuberosity-trochlear groove (TT-TG) distance, trochlear dysplasia, sulcus angle, patellar tilt and MPFL injuries. Functional outcomes were evaluated with Kujala, IKDC and Tegner scores at 3, 6 and 12 months after surgery. The average age of the patients was 20 years (range 13-43 years). Pre- operative Caton-Deschamps index was pathological in 10 (40%). Sulcus angle was elevated in 13 patients (52%) and TT-TG distance was irregular in 17 patients (68%). Trochlear dysplasia was present in 13 patients (9 type A, 3 type B, 1 type C according to Dejour's Classification). No re-dislocation occurred during the follow-up. There was a significant increase in the Kujala, IKDC and Lysholm scores after 3, 6 and 12 months, and the results were compared for the different follow-up times and patient's trochlear dysplasia degree. This prospective observational longitudinal study identified good clinical outcomes in patients who underwent MPFL reconstruction and ATT transposition for patellar instability. Finally, the different risk factors for patellar instability examined, particularly the presence of trochlear dysplasia, did not significantly influence the final functional results, which range from good to excellent without re-dislocation episodes.


Cis-monounsaturated fatty acids inhibit ferroptosis through downregulation of transferrin receptor 1.
Ferroptosis, a form of cell death mediated by lipid peroxidation, is implicated in various pathological processes. Although monounsaturated fatty acids (MUFAs) can inhibit ferroptotic lipid peroxidation, the underlying structural mechanism of this antagonistic effect remains poorly understood. We hypothesized that MUFAs with different structures (including chain length, conformation, and double bond position) may affect their regulatory effect on ferroptosis. In this study, 11 MUFAs with varying structures were screened to identify those with an inhibitory effect on ferroptosis. Results from 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide assays indicated that only exogenous MUFAs with cis-conformation and centered double bond could inhibit ferroptosis. Meanwhile, it was found that suppressing the expression of SCD1 and SCD5 genes could sensitize cells to ferroptosis indicating the protective role of endogenous MUFA against ferroptosis. Additionally, western blot analysis revealed that cis-MUFAs with centered double bond downregulated the protein levels of transferrin receptor 1. Flow cytometry confirmed that these MUFAs led to decreases in intracellular iron, reactive oxygen species, and lipid peroxides. It was also found that SCD1 inhibitor could enhance ferroptosis inducer-mediated tumor suppression both in vivo and in vitro. Overall, these findings shed light on the particular structural features of MUFAs that contribute to their ferroptosis-resistant properties and suggest the potential therapeutic relevance of natural MUFAs in a range of ferroptosis-related diseases.


High prevalence of storage mite sensitization in a general adult population.
Occupational and nonoccupational storage mite (SM) allergy has received considerable attention in recent years. The study aimed to evaluate both the prevalence and factors associated with sensitization to SMs in a general adult population from a warm and humid area where mites are the predominant allergens. An age-stratified random sample of 720 subjects was drawn from the population older than 18 years of A-Estrada (Galicia, Spain). From 697 eligible subjects, 469 (67%, median age 54 years, range 18-92 years, 44% males, 75% of cases from a rural environment) agreed to participate. Skin prick tests to SMs (Lepidoglyphus destructor and Tyrophagus putrescentiae), house dust mite (Dermatophagoides pteronyssinus), pollens, moulds and animal danders were performed in all cases. Wheals >or= 4 mm were considered positive. Epidemiological data were assessed by questionnaire. A design-based analysis was performed and all calculations were weighted to give unbiased estimates. Tyrophagus putrescentiae and L. destructor were the leading causes of allergic sensitization throughout all ages. SM sensitization was found in 104 cases (weighted value 24.4%, 95% CI 20.6-28.2). SM sensitization was inversely associated with age. Multivariate analysis showed that SM sensitization was not significantly associated with sex, smoking, educational level, farming profession, rural environment, indoor humidity, presence of pets, livestock or grain storage facilities near home. SMs (T. putrescentiae and L. destructor) are major aeroallergens in adults in the region studied, even in subjects without occupational exposure.


Normalization of regional cerebral blood flow in alcoholics during the first 7 weeks of abstinence.
Twenty-two institutionalized alcoholics were studied after 1, 3, 5 and 7 weeks of abstinence with measurements of the regional cerebral blood flow (rCBF), psychometric testing and clinical ratings. Twenty-two healthy volunteers served as age-matched controls. Mean rCBF was significantly reduced in the alcoholics at all measurements compared to the controls. The older alcoholics (median cut) showed a 9% increase of rCBF from the 1st to the 7th week (P less than 0.01). The mean rCBF in these alcoholics also increased more in the right than in the left hemisphere (P less than 0.05) during the investigation. The differences between the alcoholics and the controls were most pronounced in the right frontal lobe. The mean flow changes were correlated to improvement in clinical state. Right hemisphere and frontal lobe flow decreases were more accentuated in older alcoholics.


Osteitis of the radius following Bacillus Calmette-Guérin vaccination at birth: a case report.
The Bacillus Calmette-Guérin vaccine, which is used for the prevention of tuberculosis, is considered protective against the severe forms of childhood tuberculosis. However, some serious adverse reactions including osteitis of the long bones can occur. We report a case of an 18-month-old Sudanese girl who presented at the age of 3 months with swelling of her left forearm following Bacillus Calmette-Guérin vaccination administered at birth. Radiological and histological investigations confirmed tuberculous osteitis of the distal radius. She responded very well to antituberculous treatment with complete healing at follow-up visits. To the best of our knowledge this is the first case report of osteitis of the radius following Bacillus Calmette-Guérin vaccination described from Sudan. Bacillus Calmette-Guérin osteitis, although rare, should be considered a possible complication of the Bacillus Calmette-Guérin vaccination, and early diagnosis and treatment are essential.


A viewpoint on drugs that prolong the QTc interval.
Insufficient evidence exists to suggest that prolongation of the QT interval corrected for heart rate (QTc) is necessarily beneficial. In all but life-threatening situations, QTc prolongation resulting from pharmacologic agents must be considered a risk. Because dose-response relations for torsades de pointes cannot be established and because prolongation of the QTc interval is thought to precede the development of torsades, it is reasonable to assume that the QTc prolongation itself constitutes the marker of risk. An assessment of the relation between the dose of a given drug and its effect on the QTc interval will aid in making the judgment that the potential benefit outweighs the risk. Ideally, a drug should demonstrate as wide a safety margin as possible, as reflected in a large separation between the ED50 value associated with therapeutic benefit and that associated with QTc prolongation.


Visible light induced photocatalytic reduction of Cr(VI) over polymer-sensitized TiO2 and its synergism with phenol oxidation.
In this study, both Cr(VI) reduction and phenol oxidation induced by polymer-sensitized TiO(2) were investigated under visible light. Study of the reaction mechanism indicated that poly(fluorene-co-thiophene) (PFT) acted as a semiconductor and was by itself able to reduce Cr(VI) under visible light irradiation. When coupled with TiO(2), PFT served not only as the electron donor for Cr(VI) reduction, but also as a sensitizer. Upon irradiation by visible light, electrons in the sensitizing PFT polymer are excited and are transferred to the conduction band of TiO(2). PFT-catalyzed reduction of Cr(VI) was significantly promoted by the presence of phenol, and synergism between Cr(VI) reduction and phenol degradation was demonstrated both by analysis of the FT-IR spectrum of PFT/TiO(2) and by measuring the effect of repeated use of PFT/TiO(2) on its photocatalytic efficiency. The results provide a cost-effective method to remove organic and inorganic pollutants simultaneously in the complex wastewater.


Evidence for excess familial clustering of Post Traumatic Stress Disorder in the US Veterans Genealogy resource.
A genealogy of the United States has been record-linked to National Veteran's Health Administration (VHA) patient data to allow non-identifiable analysis of familial clustering. This genealogy, including over 70 million individuals linked to over 1 million VHA patients, is the largest such combined resource reported. Analysis of familial clustering among VHA patients diagnosed with Post Traumatic Stress Disorder (PTSD) allowed a test of the hypothesis of an inherited contribution to PTSD. PTSD is associated strongly with military service and extended familial clustering data have not previously been presented. PTSD-affected VHA patients with genealogy data were identified by presence of an ICD diagnosis code in the VHA medical record in at least 2 different years. The Genealogical Index of Familiality (GIF) method was used to compare the average relatedness of VHA patients diagnosed with PTSD with their expected average relatedness, estimated from randomly selected sets of matched linked VHA patient controls. Relative risks for PTSD were estimated in first-, second-, and third-degree relatives of PTSD patients who were also VHA patients, using sex and age-matched rates for PTSD estimated from all linked VHA patients. Significant excess pairwise relatedness, and significantly elevated risk for PTSD in first-, second-, and third-degree relatives was observed; multiple high-risk extended PTSD pedigrees were identified. The analysis provides evidence for excess familial clustering of PTSD and identified high-risk PTSD pedigrees. These results support an inherited contribution to PTSD predisposition and identify a powerful resource of high-risk PTSD pedigrees for predisposition gene identification.


Modes of mononucleotide binding to ribonuclease T1.
The binding of the mononucleotide inhibitors 2'-GMP, 3'-GMP, and 5'-GMP to genetically engineered ribonuclease T1 has been investigated by conventional inhibition kinetics, fluorimetric titrations, molecular modeling, and fast relaxation techniques. The fluorimetric titrations in conjunction with molecular modeling revealed that apart from the already known primary binding site, three to four additional sites are present on the enzyme's surface. The association constants obtained from the fluorimetric titrations and the temperature jump experiments range between 3.1 x 10(6) M-1 and 4.3 x 10(6) M-1, indicating that the binding of the mononucleotides to the specific binding site of ribonuclease T1 is at least one order of magnitude tighter than has been anticipated so far. The kinetics of binding are nearly diffusion controlled with a kon determined for 2'-GMP and 3'-GMP, as (5.0 +/- 0.5 x 10(9) and 6.1 +/- 0.5 x 10(9) M-1, s-1 and koff as 1.2 +/- 0.2 x 10(3) and 2.0 +/- 0.3 x 10(3) s-1, respectively. Molecular modeling studies indicate that all three nucleotides are able to bind via their phosphate group to a positively charged array of surface amino acids including His27, His40, Lys41, and most probably Lys25 without obvious stereochemical hindrance. We propose that RNA wraps around RNase T1 in a similar fashion via phosphate binding when enzymatic hydrolysis occurs.


Monosodium glutamate derived tricolor fluorescent carbon nanoparticles for cell-imaging application.
Fluorescent carbon nanoparticle (FCN) is a new type of carbon-based materials. Because of its wide raw material sources, excellent optical properties and good biocompatibility, FCN is getting more and more attentions. However, its synthesis from resources at low cost under mild conditions is still a challenge. Here we report a novel and simple method derived from monosodium glutamate carbonization to make tricolor fluorescent carbon nanoparticles with an average size below 10nm, a high yield up to 35.2% based on the carbon content in the resource, a long life-time of 3.71ns, and a high fluorescence quantum yield up to 51.5% by using quinine sulfate as the standard substance. We discovered that the fluorescent stability of the FCNs was very excellent under UV irradiation for hours in aqueous solutions of pH ranged from 2.0 to 9.0. The cell viability tested under a pretty high concentration of FCNs indicated their safety for biological applications. Based on their high fluorescence quantum efficiency and the advantages mentioned above, these FCNs were then used for cell imaging and exhibited a perfect performance under 3 kinds of excitation bands (UV, blue, and green lights). Thus, they can be practically applied to immune labeling and imaging in vivo in the near future.


Endoscopic endonasal management of trigeminal schwannomas extending into the infratemporal fossa.
Extracranial trigeminal schwannomas extending into the infratemporal fossa are rare. The traditional surgical approaches to the infratemporal fossa are associated with complications, such as facial nerve dysfunction, hearing loss, dental malocclusion and cosmetic problems. We report eight patients (four males, four females, age range=31-62 years) who were treated between 2004 and 2009 for extracranial trigeminal schwannomas extending into the infratemporal fossa. Schwannomas were surgically removed using a purely endoscopic endonasal approach. The maximum diameters of the tumours ranged from 30 mm to 70 mm and all tumours were completely removed. There were no intraoperative or postoperative complications in this series. There were no recurrences during the follow-up period which ranged from 10 to 74 months (mean=30 months). The purely endoscopic endonasal approach may provide a minimally invasive and safe approach to remove extracranial trigeminal schwannomas extending into the infratemporal fossa. Radical resection was associated with an excellent long-term outcome in this series.


Neurophysiologic correlates of psychiatric disorders and potential applications in epilepsy.
There is increasing interest in psychiatric assessment using neurophysiologic tools such as electroencephalography (EEG), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). This is because these technologies have good temporal resolution, are relatively noninvasive, and (with the exception of MEG) are economical. Many different experimental paradigms and analysis techniques for the assessment of psychiatric patients involving these technologies are reviewed including conventional quantitative electroencephalography (QEEG), EEG cordance, low-resolution electromagnetic tomography (LORETA), frontal midline theta, midlatency auditory evoked potentials (P50, N100, P300), loudness dependency of the auditory evoked potential (LDAEP), mismatch negativity (MMN), contingent negative variation (CNV), and transcranial magnetic stimulation (TMS). Many of these neurophysiologic stimulus paradigms hold the promise of improving psychiatric patient care by improving diagnostic precision, predicting treatment response, and providing new phenotypes for genetic studies. Large cooperative multisite studies need to be designed to test and validate a few of these paradigms so that they might find use in routine clinical practice.


Isolation, crystallization and preliminary X-ray diffraction analysis of L-amino-acid oxidase from Vipera ammodytes ammodytes venom.
L-Amino-acid oxidase from the venom of Vipera ammodytes ammodytes, the most venomous snake in Europe, was isolated and crystallized using the sitting-drop vapour-diffusion method. The solution conditions under which the protein sample was monodisperse were optimized using dynamic light scattering prior to crystallization. The crystals belonged to space group C2, with unit-cell parameters a = 198.37, b = 96.38, c = 109.11 A, beta = 92.56 degrees . Initial diffraction data were collected to 2.6 A resolution. The calculated Matthews coefficient is approximately 2.6 A(3) Da(-1) assuming the presence of four molecules in the asymmetric unit.


Mortality of spontaneous intracerebral haemorrhage patients and high serum caspase-8 concentrations.
Apoptotic changes in brain samples have been found in haematoma areas of patients with spontaneous intracerebral haemorrhage (SIH) undergoing surgical haematoma evacuation. However, circulating caspase-8 concentrations in SIH patients have not been described. Thus, we carried out this study with the aim to explore whether there is an association of circulating caspase-8 concentrations and mortality in patients with SIH. We included patients with severe and supratentorial SIH. We established that the SIH was severe if Glasgow Coma Scale (GCS) was lower than 9. Intensive Care Units from 5 Spanish hospitals carried out the recruitment of patients of this observational and prospective study. We registered serum caspase-8 levels at moment of severe SIH diagnosis and 30-day mortality. Surviving (n = 41) in respect to non-surviving SIH patients (n = 38) showed lower serum caspase-8 levels (p < 0.001). The area under the curve to estimate 30-day mortality ability by serum caspase-8 levels was 0.75 (95% CI = 0.64-86; p < 0.001). Kaplan-Meier analysis found that patients with serum caspase-8 levels > 17.8 ng/mL showed higher death risk (Hazard ratio = 3.9; 95% CI = 1.99-7.63; p < 0.001). Multiple logistic regression analysis revealed the association of serum caspase-8 concentrations (controlling for intracerebral haemorrhage score, midline shift and early haematoma evacuation) with mortality at 30 days (Odds Ratio = 1.048; 95% CI = 1.018-1.079; p = 0.002). The association of serum caspase-8 concentrations with mortality of SIH patient mortality is the main of novel findings that have been revealed in our study.


Diagnostic accuracy for coronary artery disease of multislice CT scanners in comparison to conventional coronary angiography: an integrative literature review.
To examine the quality of cardiac imaging done by multislice computed tomography (MSCT) and its ability to correctly identify significantly occluded segments of coronary arteries compared with quantitative coronary angiography. Databases searched were CINAHL, MEDLINE, EBSCO, Academic Search Premier, and Web of Science and Health Source: Nursing/Academic edition. Keywords used were "Computed Tomography,""Coronar* Angiogra*," and "Coronary Artery Disease." Studies from peer-reviewed journals published from 2002 to 2008 that compared quantitative coronary angiography to MSCT were evaluated. Additional sources were identified from review of reference lists from articles found in the electronic search. MSCT was best employed to screen for the absence of disease in patients who were in sinus rhythm, who had no previous bypass grafts or stents placed, had a low risk of calcifications, and who were not obese. Both 40- and 64-slice technology demonstrated the highest accuracy in screening for the absence of disease on a vessel-based analysis. Those who have multiple risk factors and are asymptomatic should still be screened via catheterization. More studies are needed to determine the effectiveness of newer 64-slice technology as a tool to positively identify CAD.


Cell-specific coupling of the cloned human 5-HT1F receptor to multiple signal transduction pathways.
We recently described the cloning of a fifth member of the 5-hydroxytryptamine (5-HT)1 (serotonin1) receptor class that inhibits adenylyl cyclase, namely the human 5-HT1F receptor (Adham et al. 1993a). In the present study we have examined in greater detail the functional coupling of the 5-HT1F receptor in two different cell lines, NIH-3T3 and LM(tk-) fibroblasts (receptor densities of 1.7 and 4.4 pmol/mg protein, respectively). The maximal inhibitory response elicited by 5-HT was significantly greater in NIH-3T3 as compared to LM(tk-) cells, whereas the EC50 values were comparable. To investigate the relationship between receptor occupancy and inhibition of cAMP accumulation mediated by 5-HT1F receptors in NIH-3T3 cells (and hence the degree of receptor reserve), we used the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The half-maximal response required only about 10% receptor occupancy, consistent with a receptor reserve of 90% (88 +/- 2.1%, n = 4) for 5-HT-induced inhibition of FSCA. Despite the presence of such a high degree of receptor reserve, a range of intrinsic activities was displayed by structurally diverse classes of compounds. For example, sumatriptan and lysergol were as efficacious as 5-HT itself and thus acted as full agonists, whereas metergoline and 1-NP behaved as partial agonists and as shown previously (Adham et al. 1993a), methiothepin was a silent antagonist (Kb = 438 nM). We have also investigated activation of additional signal transduction pathways by the 5-HT1F receptor and found that the responses differ in the two cell lines with respect to stimulation of phospholipase C. For example, in NIH-3T3 cells no elevation of inositol phosphates (IP) of [Ca2+]i was observed even at very high agonist concentrations (100 microM). In contrast, in LM(tk-) cells concentrations of 5-HT as low as 10 nM induced stimulation of IP and a rapid increase of [Ca2+]i. The 5-HT1F receptor failed to alter arachidonic acid release in either cell line. The maximal increase in IP accumulation in LM(tk-) cells was modest, averaging about 100% above basal. The increases of IP and [Ca2+]i required 5-HT concentrations less than one order of magnitude greater than those inhibiting FSCA (EC50 = 17, 55 and 8 nM, respectively), and both responses were blocked by 100 microM methiothepin. All three responses (cAMP, IP, and [Ca2+]i) were sensitive to pertussis toxin pre-treatment, suggesting the involvement of Gi/Go protein(s) in these signal transduction pathways.(ABSTRACT TRUNCATED AT 400 WORDS)


Can whole-body MRI replace CT in management of metastatic testicular cancer? A prospective, non-inferiority study.
Concerns of imaging-related radiation exposure in young patients with high survival rates have increased the use of magnetic resonance imaging (MRI) in testicular cancer (TC) stage I. However, computed tomography (CT) is still preferred for metastatic TC. The purpose of this study was to compare whole-body MRI incl. diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) with contrast-enhanced, thoracoabdominal CT in metastatic TC. A prospective, non-inferiority study of 84 consecutive patients (median age 33 years) with newly diagnosed metastatic TC (February 2018-January 2021). Patients had both MRI and CT before and after treatment. Anonymised images were reviewed by experienced radiologists. Lesion malignancy was evaluated on a Likert scale (1 benign-4 malignant). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated on patient and lesion level. The primary outcome was demonstrating non-inferiority regarding sensitivity of MRI compared to CT. The non-inferiority margin was set at 5%. ROC curves and interobserver agreement were calculated. On patient level, MRI had 98% sensitivity and 75% specificity compared to CT. On lesion level within each modality, MRI had 99% sensitivity and 78% specificity, whereas CT had 98% sensitivity and 88% specificity. MRI sensitivity was non-inferior to CT (difference 0.57% (95% CI - 1.4-2.5%)). The interobserver agreement was substantial between CT and MRI. MRI with DWIBS was non-inferior to contrast-enhanced CT in detecting metastatic TC disease. www. gov NCT03436901, finished July 1st 2021.


Quantification, prediction, and the online impact of sentence truth-value: Evidence from event-related potentials.
Do negative quantifiers like "few" reduce people's ability to rapidly evaluate incoming language with respect to world knowledge? Previous research has addressed this question by examining whether online measures of quantifier comprehension match the "final" interpretation reflected in verification judgments. However, these studies confounded quantifier valence with its impact on the unfolding expectations for upcoming words, yielding mixed results. In the current event-related potentials study, participants read negative and positive quantifier sentences matched on cloze probability and on truth-value (e.g., "Most/Few gardeners plant their flowers during the spring/winter for best results"). Regardless of whether participants explicitly verified the sentences or not, true-positive quantifier sentences elicited reduced N400s compared with false-positive quantifier sentences, reflecting the facilitated semantic retrieval of words that render a sentence true. No such facilitation was seen in negative quantifier sentences. However, mixed-effects model analyses (with cloze value and truth-value as continuous predictors) revealed that decreasing cloze values were associated with an interaction pattern between truth-value and quantifier, whereas increasing cloze values were associated with more similar truth-value effects regardless of quantifier. Quantifier sentences are thus understood neither always in 2 sequential stages, nor always in a partial-incremental fashion, nor always in a maximally incremental fashion. Instead, and in accordance with prediction-based views of sentence comprehension, quantifier sentence comprehension depends on incorporation of quantifier meaning into an online, knowledge-based prediction for upcoming words. Fully incremental quantifier interpretation occurs when quantifiers are incorporated into sufficiently strong online predictions for upcoming words.


Fibroblast growth factor 17 and bone morphogenetic protein 15 enhance cumulus expansion and improve quality of in vitro-produced embryos in cattle.
Bone morphogenetic protein 15 (BMP15) and members of the fibroblast growth factor (FGF) family are expressed by the oocyte and are involved in the control of cumulus cell function. We tested the hypothesis that FGF17, alone or combined with BMP15 in the maturation medium, enhances cumulus expansion, meiosis progression, embryonic development, and expression of mRNA encoding key genes regulating expansion (prostaglandin-endoperoxide synthase 2 [PTGS2], hyaluronan synthase 2 [HAS2], tumor necrosis factor-stimulated gene 6 [TNFAIP6], and pentraxin 3 [PTX3]) and markers of oocyte developmental competence (phosphofructokinase [PFKP], gremlin [GREM1], versican [VCAN], and the genomic progesterone receptor [nPR]) in cumulus cells. Fibroblast growth factor 17 and BMP15 increased the percentage of fully expanded cumulus-oocyte complexes (COCs), but there was no additive effect when both were combined. Neither FGF17 nor BMP15 altered the percentage of oocytes reaching meiosis II at the end of COC culture or cleavage and blastocyst rates after IVF. However, embryo quality, as assessed by the number of cells in the inner cell mass, was improved by the combination of FGF17 with BMP15. Fibroblast growth factor 17 alone did not alter gene expression in cumulus cells at the end of IVM, whereas BMP15 increased PTGS2 and PTX3 mRNA levels. The combination of FGF17 and BMP15 increased nPR mRNA abundance in cumulus cells but did not change the expression of other markers of developmental competence. This study provides novel evidence that FGF17 enhances cumulus expansion in bovine COCs submitted to IVM and that the supplementation of the IVM medium with FGF17 and BMP15 may improve embryo quality.


Contribution to the echinococcosis control programme in China by NIPD-CTDR.
As a zoonotic parasitosis caused by the parasitism of Echinococcus larvae, echinococcosis imposes serious disease and economic burdens on human beings and society, and is thus a global public health issue. Its complex life history, wide distribution, the combined influence of various epidemic factors, coupled with the unique natural environment, customs, and religious beliefs in endemic areas, pose a huge challenge to the national echinococcosis control programme in China. Accurate early detection and confirmation of diagnosis of echinococcosis, the use of effective drugs, real-time surveillance of the infection status of populations and various hosts, controlling the source of infection, and blocking the route of transmission are of enormous significance for control. In this paper, the work by NIPD-CTDR on the prevention and control of echinococcosis in China is reviewed, with a view to providing reference for the further promotion of the national echinococcosis control programme.


Single-laboratory validation of a saponification method for the determination of four polycyclic aromatic hydrocarbons in edible oils by HPLC-fluorescence detection.
An analytical method is reported for the determination of four polycyclic aromatic hydrocarbons (benzo[a]pyrene (BaP), benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF) and chrysene (CHR)) in edible oils (sesame, maize, sunflower and olive oil) by high-performance liquid chromatography. Sample preparation is based on three steps including saponification, liquid-liquid partitioning and, finally, clean-up by solid phase extraction on 2 g of silica. Guidance on single-laboratory validation of the proposed analysis method was taken from the second edition of the Eurachem guide on method validation. The lower level of the working range of the method was determined by the limits of quantification of the individual analytes, and the upper level was equal to 5.0 µg kg(-1). The limits of detection and quantification of the four PAHs ranged from 0.06 to 0.12 µg kg(-1) and from 0.13 to 0.24 µg kg(-1). Recoveries of more than 84.8% were achieved for all four PAHs at two concentration levels (2.5 and 5.0 µg kg(-1)), and expanded relative measurement uncertainties were below 20%. The performance of the validated method was in all aspects compliant with provisions set in European Union legislation for the performance of analytical methods employed in the official control of food. The applicability of the method to routine samples was evaluated based on a limited number of commercial edible oil samples.


A description of the ICU liaison nurse role in Argentina.
Recognising and responding to clinical deterioration in hospital patients has been promoted by many western countries to improve patient safety. In non-western and developing countries it is likely to be even more important to focus on strategies of patient safety. This paper reflects the services provided by Intensive Care Unit Liaison Nurses (ICULN) in the first year of their work, July 2010-June 2011, in an Argentinean hospital. This practice audit aimed to describe the ICULN patient care activities performed for patients discharged from the ICU and ward patients with complex care needs, and to identify education activities carried with ward nursing staff caring for these patients. Experienced critical care nurses, with strong communication and education skills were appointed as ICULNs. They were asked to assess ward patients transferred from ICU once per shift and ward patients as requested by staff. They had to provide patient complex care if necessary and education to ward nurses caring for these patients. A total of 387 patients were followed by ICULNs. The median age of patients was 49 (IQR 26) years (range 15-89). A total of 369 (95.3%) of the patients were discharged from ICU and 18 (4.7%) were ward patients who required complex care. The most frequent conditions patients had were surgery, neurologic conditions, trauma and sepsis. Thirty four (9.2%) of 369 patients who were initially in ICU, were readmitted during the same hospitalisation. During the study period ICULNs performed 5973 patient care and 1709 staff education activities. ICULNs provide advanced assessment and surveillance of ICU discharged and complex ward patients, and facilitate ICU-ward transition assisting and educating ward staff. Further evaluation is necessary to better describe the role in Argentina and the effect of ICULN service on patient outcomes and on staff.


Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: a mediator between peripheral infection and neurodegeneration?
Parkinson disease (PD), a chronic neurodegenerative disease, has been proposed to be a multifactorial disorder resulting from a combination of environmental mechanisms (chemical, infectious, and traumatic), aging, and genetic deficits. Microglial activation is important in the pathogenesis of PD. We investigated dopaminergic (DA) neurotoxicity and the underlying mechanisms of formyl-methionyl-leucyl-phenylalanine (fMLP), a bacteria-derived peptide, in relation to PD. We measured DA neurotoxicity using a DA uptake assay and immunocytochemical staining (ICC) in primary mesencephalic cultures from rodents. Microglial activation was observed via ICC, flow cytometry, and superoxide measurement. fMLP can cause selective DA neuronal loss at concentrations as low as 10(-13) M. Further, fMLP (10(-13) M) led to a significant reduction in DA uptake capacity in neuron/glia (N/G) cultures, but not in microglia-depleted cultures, indicating an indispensable role of microglia in fMLP-induced neurotoxicity. Using ICC of a specific microglial marker, OX42, we observed morphologic changes in activated microglia after fMLP treatment. Microglial activation after fMLP treatment was confirmed by flow cytometry analysis of major histocompatibility antigen class II expression on a microglia HAPI cell line. Mechanistic studies revealed that fMLP (10(-13) M)-induced increase in the production of extracellular superoxide from microglia is critical in mediating fMLP-elicited neurotoxicity. Pharmacologic inhibition of NADPH oxidase (PHOX) with diphenylene-iodonium or apocynin abolished the DA neurotoxicity of fMLP. N/G cultures from PHOX-deficient (gp91PHOX-/ -) mice were also insensitive to fMLP-induced DA neurotoxicity. fMLP (10(-13) M) induces DA neurotoxicity through activation of microglial PHOX and subsequent production of superoxide, suggesting a role of fMLP in the central nervous system inflammatory process.


Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration.
Diazoxide (DIAZ) has been shown to be neuroprotective in animal models of different brain pathologies. However, the direct protective effect of DIAZ in different in vivo models of retinal degeneration has not yet been shown. Therefore, the aim of the present study was to investigate the neuroprotective role of this compound in two rodent model systems: monosodium-glutamate (MSG)- and chronic bilateral carotid artery occlusion (BCAO)-induced retinal degeneration. Rats were subjected either to s.c. MSG treatment on postnatal days 1, 5 and 9, or to BCAO at 2 months of age, followed by intravitreal DIAZ treatment. Histological examination was carried out 14 or 21 days after treatments, respectively. MSG treatment destroyed almost the entire inner retina, with the inner nuclear and ganglion cell layers being fused. DIAZ treatment significantly ameliorated the MSG-induced retinal degeneration. BCAO led to a severe degeneration of all retinal layers, and DIAZ proved to be protective also in this model. Our results may have clinical implications in reducing glutamate-induced excitotoxicity or ischemic retinal degeneration in ophthalmic diseases.


Size-dependent cannibalism in noctuid caterpillars.
The effects of relative body size and conspecific density on cannibalism in the caterpillar Litoprosopus futilis were examined in simple container experiment. The results of the experiments and field observations indicate that the opportunity to consume live conspecific is afforded only when there is a physical advantage of large size.


Congo red dye diversely affects organisms of different trophic levels: a comparative study with microalgae, cladocerans, and zebrafish embryos.
Global consumption of synthetic dyes is roughly 7 × 105 tons per year, of which the textile industry expends about two-thirds. Consumption of synthetic dyes produces large volumes of wastewater discharged into aquatic ecosystems. Colored effluents produce toxic effects in the hydrobionts, reduce light penetration, and alter the photosynthetic activity, causing oxygen depletion, among other effects. Some dyes, such as Congo red (CR), are elaborated with benzidine, a known carcinogenic compound. Information regarding dye toxicity in aquatic ecosystems is scarce; therefore, our study was aimed at evaluating the toxicity of CR on a battery of bioassays: the microalga Pseudokirchneriella subcapitata, the cladocerans Daphnia magna and Ceriodaphnia rigaudi, and the zebrafish Danio rerio. P. subcapitata was the most sensitive species to CR (IC50, 3.11 mg L-1); in exposed individuals, population growth was inhibited, but photosynthetic pigments and macromolecule concentrations were stimulated. D. magna was tolerant to high dye concentrations, the determined LC50 (322.9 mg L-1) is not an environmentally relevant value, but for C. rigaudi, LC50 was significantly lower (62.92 mg L-1). In zebrafish embryos, exposure to CR produced yolk sac edema, skeletal deformities, and stopped larvae hatching; lack of heart beating was the only observed lethal effect. CR affected organisms of different trophic levels diversely. Particularly, the effects observed in microalgae confirm the vulnerability of primary producers to dye-polluted wastewaters, because dyes produced toxic effects and interfered with photosynthesis. Different cladoceran species displayed different acute effects; thus, species sensitivity must also be considered when toxicity of dyes is assessed. Inhibition of fish larvae hatching is a significant effect not previously reported that warns about the toxicity of dyes in fish population dynamics. Synthetic azo colorants should be considered as emerging pollutants because they are discharged into the aquatic environment and are not currently included in the environmental regulation of several countries.


Object tracking in motion-blind flies.
Different visual features of an object, such as its position and direction of motion, are important elements for animal orientation, but the neural circuits extracting them are generally not well understood. We analyzed this problem in Drosophila, focusing on two well-studied behaviors known as optomotor response and fixation response. In the neural circuit controlling the optomotor response, columnar T4 and T5 cells are thought to be crucial. We found that blocking T4 and T5 cells resulted in a complete loss of the optomotor response. Nevertheless, these flies were still able to fixate a black bar, although at a reduced performance level. Further analysis revealed that flies in which T4 and T5 cells were blocked possess an intact position circuit that is implemented in parallel to the motion circuit; the optomotor response is exclusively controlled by the motion circuit, whereas the fixation response is supported by both the position and the motion circuit.


Compartment syndrome in a patient monitored with an automated blood pressure cuff.
Noninvasive blood pressure monitoring may be hazardous in patients with seizures or movement disorders. We report on a patient with hyperactivity and tremor in whom a compartment syndrome was apparently induced by an automated blood pressure cuff. As the patient moved, the device seems to have continued to cycle in an attempt to obtain a stable baseline reading. Pressure tubing to the self-inflating bladder on such devices should be disconnected between readings in situations where frequent, easy observation is not possible.


[The oxymeter, a new device for the continuous transcutaneous measurement of the arterial oxygen partial pressure].
The transcutaneous measurement of the arterial pO2 is a practicable method for routine clinical use. The covering, calibration and fixation of the electrode are simple. In normal circulatory states the correlation between arterial and transcutaneous pO2 is high. The stability of the electrode permits its use even for long term monitoring. Recalibration is necessary at intervals of 12 h. Orientating blood gas analysis for control is nevertheless essential. After a measuring period of 5--6 h a blistering under the electrode is possible. The placement of the electrode has to be changed after 4 h. The continuous measurement opens new possibilities for the therapy, diagnosis and trend analysis.


Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.
Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1-0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.


Newer modalities of ultrasound imaging and treatment of the prostate.
Gray-scale ultrasound is widely used for assessing BPH and for obtaining prostate biopsies. However, it has limited value for evaluating cancer in the prostate. To improve ultrasound as an imaging modality of the prostate, many new technologies, such as color and power Doppler, 3-dimensional ultrasound of the prostate, and contrast-enhanced ultrasound have been developed. In addition, treatment modalities using ultrasound for the treatment of BPH have been developed. This review presents the recent developments in ultrasound of the prostate.


The effects of metoclopramide on postoperative ileus. A randomized double-blind study.
Metoclopramide or placebo was administered postoperatively in a randomized, double-blind fashion to 115 patients undergoing laparotomy. The effect of metoclopramide on postoperative adynamic ileus (PAI) was evaluated. The patients were stratified into two groups: Group A--those with laparotomy without a gastrointestinal anastomosis or ostomy procedure, and group B--those with laparotomy undergoing an anastomosis or ostomy procedure. Metoclopramide reduced nausea and emesis postoperatively. However, the only significant effect on postoperative adynamic ileus was an earlier return to tolerance of solid foods in the patients in Group A.


High-level expression of human thyroid-stimulating hormone in Chinese hamster ovary cells by co-transfection of dicistronic expression vectors followed by a dual-marker amplification strategy.
The utilization of dicistronic mRNA expression vectors, containing the gene of interest upstream of an amplifiable marker gene, has shown success in rapidly, efficiently and reproducibly obtaining stable cell lines that express high levels of the protein of interest. For this reason, human thyroid-stimulating hormone (hTSH), a heterodimeric glycoprotein composed of non-covalently linked alpha- and beta-subunits, was expressed in Chinese hamster ovary (CHO) cells using a system based on dicistronic expression vectors. These contained the genes of interest and the amplifiable gene markers dihydrofolate reductase (DHFR) and adenosine deaminase (ADA), separated by an internal ribosome entry site isolated from the encephalomyocarditis virus. After the cells (CHO-DHFR-) had been co-transfected with the expression vectors and submitted to gene amplification in culture medium containing stepwise increments of methotrexate, it was possible to isolate clones that presented a secretion level of up to 7.2+/-1.3 microg/10(6) cells per day, the highest ever reported for the expression of this glycoprotein hormone. A second treatment, involving the utilization of deoxycoformycin, directed to amplify the ADA marker gene, provided a clone with an additional 2-3-fold increase in hTSH secretion, reaching a secretion level of 17.8+/-7.6 microg/10(6) cells per day. Cell culture and hTSH production in a hollow-fibre bioreactor were set up in order to carry out a preliminary physico-chemical, immunological and biological characterization of this hormone in comparison with pituitary-extracted hTSH (from the National Institute of Diabetes and Digestive and Kidney Diseases) and the only recombinant hTSH now available (Thyrogen). The availability of recombinant hTSH is very important in the diagnosis and therapy of thyroid carcinoma, via stimulation of radioiodine uptake.


Glomerular filtration rate and albuminuria predict mortality independently from coronary artery calcified plaque in the Diabetes Heart Study.
Risk stratification in individuals with type 2 diabetes (T2D) remains an important priority in the management of associated morbidity and mortality, including from cardiovascular disease (CVD). The current investigation examined whether estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) were independent predictors of CVD-mortality in European Americans (EAs) with T2D after accounting for subclinical CVD. The family-based Diabetes Heart Study (DHS) cohort (n=1,220) had baseline measures of serum creatinine, eGFR, UACR and coronary artery calcified plaque (CAC) assessed by non-contrast computed tomography scan. Cox proportional hazards regression was performed to determine risk for all-cause mortality and CVD-mortality associated with indices of kidney disease after accounting for traditional CVD risk factors and CAC as a measure of subclinical CVD. Participants were followed for 8.2±2.6 years (mean±SD) during which time 247 (20.9%) were deceased, 107 (9.1%) from CVD. Univariate analyses revealed positive associations between serum creatinine (HR:1.56; 95% CI:1.37-1.80; p<0.0001) and UACR (1.59; 1.43-1.77; p>0.0001) and negative associations between serum albumin (0.74; 0.65-0.84; p<0.0001) and eGFR (0.66; 0.58-0.76; p<0.0001) with all-cause mortality. Associations remained significant after adjustment for traditional CVD risk factors, as well as for CAC. Similar trends were noted when predicting risk for CVD-mortality. The DHS reveals that kidney function and albuminuria are independent risk factors for all-cause mortality and CVD-mortality in EAs with T2D, even after accounting for CAC.


Genotypic and Phenotypic Diversity of Kluyveromyces marxianus Isolates Obtained from the Elaboration Process of Two Traditional Mexican Alcoholic Beverages Derived from Agave: Pulque and Henequen (Agave fourcroydes) Mezcal.
Seven Kluyveromyces marxianus isolates from the elaboration process of pulque and henequen mezcal were characterized. The isolates were identified based on the sequences of the D1/D2 domain of the 26S rRNA gene and the internal transcribed spacer (ITS-5.8S) region. Genetic differences were found between pulque and henequen mezcal isolates and within henequen mezcal isolates, as shown by different branching patterns in the ITS-5.8S phylogenetic tree and (GTG)5 microsatellite profiles, suggesting that the substrate and process selective conditions may give rise to different K. marxianus populations. All the isolates fermented and assimilated inulin and lactose and some henequen isolates could also assimilate xylose and cellobiose. Henequen isolates were more thermotolerant than pulque ones, which, in contrast, presented more tolerance to the cell wall-disturbing agent calcofluor white (CFW), suggesting that they had different cell wall structures. Additionally, depending on their origin, the isolates presented different maximum specific growth rate (µmax) patterns at different temperatures. Concerning tolerance to stress factors relevant for lignocellulosic hydrolysates fermentation, their tolerance limits were lower at 42 than 30 °C, except for glucose and furfural. Pulque isolates were less tolerant to ethanol, NaCl, and Cd. Finally, all the isolates could produce ethanol by simultaneous saccharification and fermentation (SSF) of a corncob hydrolysate under laboratory conditions at 42 °C.


Treadmill training post stroke: are there any secondary benefits? A pilot study.
To explore the secondary benefits of treadmill training for people in the chronic stage of recovery from stroke. Modified random assignment, matched-pair control group design with repeated measures. Outpatient stroke centre. Twenty individuals post first stroke who acknowledged walking slower than pre stroke. Participants matched by side of hemiparesis and motor impairment. Twelve 20-minute sessions of walking on a treadmill or weekly phone call. Depression (Beck Depression Index), mobility and social participation (Stroke Impact Scale 3.0 subscales) were assessed initially, at the end of 12 treatments (four weeks) and six weeks later. No significant difference was found between groups for any dependent measure. The ANOVA to investigate main effects in each group found no significant findings in the control group; however in the treatment group significant improvements over time for depression (P = 0.005, P < 0.001), mobility (P = 0.008) and social participation (P = 0.004) were demonstrated. A task-specific intervention designed to improve gait speed may potentially provide secondary benefits by positively impacting depression, mobility and social participation for people post stroke.


Unified method to integrate and blend several, potentially related, sources of information for genetic evaluation.
A condition to predict unbiased estimated breeding values by best linear unbiased prediction is to use simultaneously all available data. However, this condition is not often fully met. For example, in dairy cattle, internal (i.e. local) populations lead to evaluations based only on internal records while widely used foreign sires have been selected using internally unavailable external records. In such cases, internal genetic evaluations may be less accurate and biased. Because external records are unavailable, methods were developed to combine external information that summarizes these records, i.e. external estimated breeding values and associated reliabilities, with internal records to improve accuracy of internal genetic evaluations. Two issues of these methods concern double-counting of contributions due to relationships and due to records. These issues could be worse if external information came from several evaluations, at least partially based on the same records, and combined into a single internal evaluation. Based on a Bayesian approach, the aim of this research was to develop a unified method to integrate and blend simultaneously several sources of information into an internal genetic evaluation by avoiding double-counting of contributions due to relationships and due to records. This research resulted in equations that integrate and blend simultaneously several sources of information and avoid double-counting of contributions due to relationships and due to records. The performance of the developed equations was evaluated using simulated and real datasets. The results showed that the developed equations integrated and blended several sources of information well into a genetic evaluation. The developed equations also avoided double-counting of contributions due to relationships and due to records. Furthermore, because all available external sources of information were correctly propagated, relatives of external animals benefited from the integrated information and, therefore, more reliable estimated breeding values were obtained. The proposed unified method integrated and blended several sources of information well into a genetic evaluation by avoiding double-counting of contributions due to relationships and due to records. The unified method can also be extended to other types of situations such as single-step genomic or multi-trait evaluations, combining information across different traits.


ST segment elevation caused by ostial right coronary artery obstruction in infective endocarditis: a case report.
Acute coronary syndrome (ACS) is a rare, but serious complication of infective endocarditis, and diagnosis can be challenging given clinical overlap with other syndromes. A rare cause of ACS in infective endocarditis is mechanical obstruction of the coronary artery. We present the case of a patient with infective endocarditis who developed ST segment myocardial infarction due to occlusion of the right coronary artery ostium by a vegetation. A 53-year-old female with no prior history of coronary artery disease was transferred to our tertiary care facility for evaluation and treatment of suspected myopericarditis. After transfer she developed inferior ST segment elevations on ECG along with fever and positive blood cultures for methicillin susceptible Staphylococcus aureus (MSSA). A transesophageal echocardiogram revealed a vegetation on the aortic valve that intermittently prolapsed into the right coronary ostium. She decompensated from a hemorrhagic brain infarct and subsequently transferred to the intensive care unit. She underwent surgical aortic valve debridement without prior cardiac catheterization given the danger of septic coronary embolization. After a prolonged hospital course with multiple complications, she was able to discharge home, with no neurologic deficits on follow-up. ACS presents a diagnostic and therapeutic challenge in the setting of infective endocarditis. Careful attention to the history, physical exam and testing can help differentiate infective endocarditis from other conditions sharing similar symptoms. Traditional atherosclerotic ACS management may cause great harm when treating patients with infective endocarditis. The presence of a multidisciplinary endocarditis team is ideal to provide the best clinical outcomes for this population.


Attentional bias as trait: correlations with novelty seeking.
Pseudoneglect is traditionally viewed as reflecting right hemisphere specialization for processing spatial information, which brings about relatively greater activation of the right hemisphere and orienting towards the contralateral space. Such interpretation implies that the leftward attentional bias is a population trait. Animal studies, however, suggest that orienting bias is a trait of the individual and individual differences in the direction and magnitude of this orienting bias reflect individual differences in asymmetry in dopaminergic brain systems, which are also reflected in other behavioral differences. The present study was designed to test the hypothesis that healthy individuals show consistent attentional bias, the direction and magnitude of which varies among individuals and is associated with the degree of novelty seeking, a temperament trait associated with dopamine asymmetry. Forty-nine right-handed participants performed the greyscales task on two separate occasions and completed the Tridimensional Personality Questionnaire. Although on average some degree of leftward attentional bias was observed on both occasions, both the direction and the magnitude of the bias differed greatly, with some individuals showing a strong leftward bias whereas others showed a strong rightward bias. A highly significant correlation was found between degree and magnitude of this bias on the two testing sessions, supporting the hypothesis that it may reflect an individual trait. As predicted, higher scores on novelty seeking were associated with rightward attentional bias, suggesting that this bias may reflect asymmetries in dopaminergic circuits in healthy individuals.


A review of applications of operational research in healthcare coordination in disaster management.
Many disasters that have happened in the last decades, including the latest COVID-19 pandemic, have caused a shortage of healthcare resources and change in healthcare operations. Given these impacts, the Operational Research (OR) community has applied various approaches to improve the emergency medical responses. Coordination of healthcare facilities is one of the emergency medical response strategies to ensure the continued provision of medical services during disasters. Although the existing literature reviews of OR approaches have included the perspective of healthcare management, they focused mostly on the application of OR in disaster operations and logistics management. The importance of coordination in healthcare systems during disasters is well recognised in the literature, but to the best of our knowledge there has been no review of the published research in this area. This study provides a focused literature review of the OR contributions in the coordination in healthcare systems during disasters. Definitions of the terms in use in this field are provided. An overall descriptive statistics of the reviewed articles is given, followed by the review of the presented research problems, disaster types, and developed methodologies. The main characteristics of models for the coordination in the healthcare system are described. Measures of coordination effectiveness that denote healthcare resilience are discussed. Based on our findings, we suggest future research directions in the context of existing models extension, and application and development of other methodologies with the aim to provide a solid basis for OR research in the healthcare disaster management.


Role of GABAergic system in the comorbidity of pain and depression.
Patients with chronic pain often suffer with depressive symptoms, and these two conditions can be aggravated by each other over time, leading to an increase in symptom intensity and duration. The comorbidity of pain and depression poses a significant challenge to human health and quality of life, as it is often difficult to diagnose early and treat effectively. Therefore, exploring the molecular mechanisms underlying the comorbidity of chronic pain and depression is crucial to identifying new therapeutic targets for treatment. However, understanding the pathogenesis of comorbidity requires examining interactions among multiple factors, which calls for an integrative perspective. While several studies have explored the role of the GABAergic system in pain and depression, fewer have examined its interactions with other systems involved in their comorbidity. Here, we review the evidence that the role of GABAergic system in the comorbidity of chronic pain and depression, as well as the interactions between the GABAergic system and other secondary systems involved in pain and depression comorbidity, providing a comprehensive understanding of their intricate interplay.


The impact of adolescent social isolation on dopamine D2 and cannabinoid CB1 receptors in the adult rat prefrontal cortex.
Adolescent experiences of social deprivation result in profound and enduring perturbations in adult behavior, including impaired sensorimotor gating. The behavioral deficits induced by adolescent social isolation in rats can be ameliorated by antipsychotic drugs blocking dopamine D2 receptors in the prefrontal cortex (PFC) or by chronic administration of a cannabinoid CB1 receptor antagonist. The patterning and abundance of D2 receptors in the PFC evolves concurrently with CB1 receptors through the period of adolescence. This evidence suggests that mature expression and/or surface distribution of D2 and CB1 receptors may be influenced by the adolescent social environment. We tested this hypothesis using electron microscopic immunolabeling to compare the distribution of CB1 and D2 receptors in the PFC of adult male Sprague-Dawley rats that were isolated or socially reared throughout the adolescent transition period. Prepulse inhibition (PPI) of acoustic startle was assessed as a measure of sensorimotor gating. Social isolation reduced PPI and selectively decreased dendritic D2 immunogold labeling in the PFC. However, the decrease was only evident in dendrites that were not contacted by axon terminals containing CB1. There was no apparent change in the expression of CB1 or D2 receptors in presynaptic terminals. The D2 deficit therefore may be tempered by local CB1-mediated retrograde signaling. This suggests a biological mechanism whereby the adolescent social environment can persistently influence cortical dopaminergic activity and resultant behavior.


Lupeol supplementation improves blood pressure and lipid metabolism parameters in stroke-prone spontaneously hypertensive rats.
Supplementation with lupeol (0.67 g·kg(-1)) of the AIN-93M-based diet fed for 7 weeks to stroke-prone spontaneously hypertensive rats caused significantly decreased blood pressure as compared with a control group. Urinary 8-hydroxy-2'-deoxyguanosine was significantly lower in the lupeol group. Finally, lupeol suppressed the hepatic mRNA expression levels of the genes involved in triglyceride and cholesterol synthesis.


Brugada Syndrome: More than a Monogenic Channelopathy.
Brugada syndrome (BrS) is an inherited cardiac channelopathy first diagnosed in 1992 but still considered a challenging disease in terms of diagnosis, arrhythmia risk prediction, pathophysiology and management. Despite about 20% of individuals carrying pathogenic variants in the SCN5A gene, the identification of a polygenic origin for BrS and the potential role of common genetic variants provide the basis for applying polygenic risk scores for individual risk prediction. The pathophysiological mechanisms are still unclear, and the initial thinking of this syndrome as a primary electrical disease is evolving towards a partly structural disease. This review focuses on the main scientific advancements in the identification of biomarkers for diagnosis, risk stratification, pathophysiology and therapy of BrS. A comprehensive model that integrates clinical and genetic factors, comorbidities, age and gender, and perhaps environmental influences may provide the opportunity to enhance patients' quality of life and improve the therapeutic approach.


Use of adrenaline to manage suspected anaphylaxis following COVID-19 vaccination: An Australian retrospective cohort study.
The rate of anaphylaxis following COVID-19 vaccinations is estimated to be 2-11 cases per million doses administered. However, adrenaline is occasionally used in individuals who are later diagnosed with immunisation stress-related responses, as their initial presenting signs and symptoms can appear similar to that of anaphylaxis. This study aims to describe the clinical profile of individuals who had received adrenaline following a COVID-19 vaccine and their subsequent revaccination outcomes. We examined notifications of cases who had received adrenaline following a COVID-19 vaccine in New South Wales, Australia. The cases were classified into Brighton Collaboration Case Definition (BCCD) for anaphylaxis, their clinical presentation, management and subsequent revaccination outcomes were compared. From 22 February 2021 to 30 September 2021, there were 222 cases where adrenaline was administered. Of these, 32 (14 %) fulfilled Level 1 BCCD, 59 (27%) Level 2, 2 (1%) Level 3, 97 (44%) Level 4 and 32 (14 %) Level 5. The most commonly reported symptoms were sensation of throat closure (n = 116, 52%), difficulty breathing (n = 82, 37%) and nausea (n = 55, 25 %). Of the 176 (79%) individuals who proceeded to further vaccination, 89 (51%) received the same vaccine formulation and only 14 (8%) experienced another allergic adverse event with 9 (5%) receiving adrenaline. Less than one in five individuals who received adrenaline met Level 1 BCCD criteria for anaphylaxis. Many reactions that were treated with adrenaline had little to no diagnostic certainty of anaphylaxis and in such cases repeat vaccination had a high likelihood of being tolerated. Increased awareness and education on objective signs and symptoms of anaphylaxis is required to ensure appropriate use of adrenaline.


High-pressure synthesis of seven lanthanum hydrides with a significant variability of hydrogen content.
The lanthanum-hydrogen system has attracted significant attention following the report of superconductivity in LaH10 at near-ambient temperatures and high pressures. Phases other than LaH10 are suspected to be synthesized based on both powder X-ray diffraction and resistivity data, although they have not yet been identified. Here, we present the results of our single-crystal X-ray diffraction studies on this system, supported by density functional theory calculations, which reveal an unexpected chemical and structural diversity of lanthanum hydrides synthesized in the range of 50 to 180 GPa. Seven lanthanum hydrides were produced, LaH3, LaH~4, LaH4+δ, La4H23, LaH6+δ, LaH9+δ, and LaH10+δ, and the atomic coordinates of lanthanum in their structures determined. The regularities in rare-earth element hydrides unveiled here provide clues to guide the search for other synthesizable hydrides and candidate high-temperature superconductors. The hydrogen content variability in lanthanum hydrides and the samples' phase heterogeneity underline the challenges related to assessing potentially superconducting phases and the nature of electronic transitions in high-pressure hydrides.


A Community Health Worker Model to Support Hereditary Cancer Risk Assessment and Genetic Testing.
To evaluate the effects of a community health worker-supported hereditary cancer risk-assessment and genetic testing program in a safety-net hospital serving more than 70% medically underserved patients. This community health worker pilot program began in January 2020 at women's health clinics by administering original National Comprehensive Cancer Network (NCCN)-based questionnaires. Patients meeting high-risk criteria were offered video-based genetic education and testing, notified of results using telehealth, and offered indicated counseling. We compared the rate of genetic counseling and testing in the first 18 months of the pilot program with that in the prior 18 months. In the first 18 months of the pilot program, 940 patients were screened through the community health worker program: 196 were identified as high-risk, 103 patients were tested, and pathogenic variants were identified in 10 (9.7%), two of whom had a personal cancer history. In addition, 73 patients were tested per usual practice by a certified genetic counselor: pathogenic variants were identified in 16 (21.9%), 11 (68.8%) of whom had a personal cancer history. In the 18 months before the program, 68 patients underwent genetic testing with a certified genetic counselor, pathogenic variants were identified in 16 (23.5%), 13 (81.3%) of whom had a personal cancer history. The community health worker program led to a significant increase in testing among unaffected patients based on family history alone (odds ratio [OR] 7.0; 95% CI 3.7-13.2; P <.001), paralleled by a respective significant increase in the identification of pathogenic variants (OR 4.33; 95% CI 1.0-18.9; P =.051). This pilot program demonstrates the feasibility of a community health worker-supported program, using self-administered questionnaires and telehealth-based genetic services in a primarily medically underserved population. This program improved the detection of unaffected high-risk patients based on family history, increasing the volume of tests performed for this indication. Programs of this type may improve family history-based hereditary cancer testing in medically underserved patients, further enabling cancer-prevention strategies.


A comparison of confounder selection and adjustment methods for estimating causal effects using large healthcare databases.
Confounding adjustment is required to estimate the effect of an exposure on an outcome in observational studies. However, variable selection and unmeasured confounding are particularly challenging when analyzing large healthcare data. Machine learning methods may help address these challenges. The objective was to evaluate the capacity of such methods to select confounders and reduce unmeasured confounding bias. A simulation study with known true effects was conducted. Completely synthetic and partially synthetic data incorporating real large healthcare data were generated. We compared Bayesian adjustment for confounding (BAC), generalized Bayesian causal effect estimation (GBCEE), Group Lasso and Doubly robust estimation, high-dimensional propensity score (hdPS), and scalable collaborative targeted maximum likelihood algorithms. For the hdPS, two adjustment approaches targeting the effect in the whole population were considered: Full matching and inverse probability weighting. In scenarios without hidden confounders, most methods were essentially unbiased. The bias and variance of the hdPS varied considerably according to the number of variables selected by the algorithm. In scenarios with hidden confounders, substantial bias reduction was achieved by using machine-learning methods to identify proxies as compared to adjusting only by observed confounders. hdPS and Group Lasso performed poorly in the partially synthetic simulation. BAC, GBCEE, and scalable collaborative-targeted maximum likelihood algorithms performed particularly well. Machine learning can help to identify measured confounders in large healthcare databases. They can also capitalize on proxies of unmeasured confounders to substantially reduce residual confounding bias.


Mac-1 negative NK cells constitute the predominant subset in the livers of mice transvenously injected with tumor cells.
We evaluated age-related differences in hepatic natural killer (NK) cell phenotypes in juvenile (2-week-old) and adult (8-week-old) C57BL/6(B6) mice, and determined NK cell cytotoxicity and apoptosis in tumor inoculated mice. Juvenile mice had a preponderance of Mac-1(-) NK cells that exhibited significantly higher cytotoxicity levels. The Mac-1(-) NK cell population was the predominant subset in the liver of mice inoculated with the CMT-93 mouse rectum carcinoma cell line, which paralleled a dramatic decrease in the numbers of Mac-1(+) NK cells. The decrease in Mac-1(+) NK cells was driven by an apoptotic pathway.


Comparative evaluation of gliadins from four extraction protocols using advanced analytical techniques.
Gliadin, a major component of gluten, is known to trigger celiac disease; therefore, its extraction is important to study its properties as well as its presence in gluten-free products. Four gliadin extraction procedures Osborne (1924), Weiss (1993), Wallace (1989) and DuPont (2005), were investigated on six wheat cultivars using advanced analytical techniques such as dynamic light scattering (DLS), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Higher zeta potential of extracted gliadin was observed in DuPont (23.53-27), followed by Weiss (16.17-20.80), Osborne (16.17-20.13), and Wallace (14.60-19.47). Particle Z-average size (15.74-184.83 nm) was found to have an inverse relationship with the Polydispersity index (0.17-184.83). The surface morphological structure of TEM studies revealed the compact globular particle arrangement of gliadin, besides rod-shaped arrangement, was also found in DuPont and Wallace extracted gliadin. XRD pattern of gliadin exposed the crystalline domain at 44.1°, 37.8°, and 10.4° diffraction peaks. The d-spacing obtained from XRD and TEM-SAED analysis supports the presence of crystalline domains in gliadin apart from the amorphous domain. The insight obtained from this work will provide a better understanding of morphology and other properties of the same protein extracted with different extraction procedures.


Participation of Patients From Racial and Ethnic Minority Groups in Phase 1 Early Cancer Drug Development Trials in the US, 2000-2018.
Despite federal initiatives encouraging the enrollment of individuals from racial and ethnic minority groups in US clinical trials, no studies to date have specifically examined demographic disparities among participants in phase 1 drug development trials for patients with metastatic cancer. To assess trends in the enrollment of patients from racial and ethnic minority groups in US phase 1 therapeutic drug trials for metastatic cancer from 2000 to 2018. In this cross-sectional study, ClinicalTrials.gov was queried in July 2021 to identify completed phase 1 drug trials for metastatic cancer in the US from January 1, 2000, to December 31, 2018, with published results, yielding 221 phase 1 trials with 8309 participants aged 18 years or older with metastatic solid tumors. Proportions of each racial and ethnic group of trial participants were compared with that from the North American Association of Central Cancer Registries' Cancer in North America (CiNA) database. Statistical analysis was performed from July 12, 2021, to March 15, 2022. For each racial and ethnic group, the difference between trial and CiNA proportions was examined using a 2-sample test for equality of proportions with continuity correction. The 8309 phase 1 trial participants (4198 men [50.5%]; median age, 59 years) included 23 American Indian or Alaska Native participants (0.3%), 371 Asian or Pacific Islander participants (4.5%), 514 Black participants (6.2%), 401 of 5076 Hispanic or Latinx participants (7.9%), and 7154 White participants (86.1%). Industry funded 165 of the 221 trials (74.7%). White patients were overrepresented overall compared with the corresponding CiNA cohort (7154 of 8309 [86.1%] vs 4 113 096 of 4 891 486 [84.1%]; difference, 2.0 percentage points; P < .001). There was an increase in overrepresentation of White patients from 2000 to 2011 (trials, 2780 of 3245 [85.7%]; CiNA, 2 378 019 of 2 800 711 [84.9%]; difference, 0.8 percentage points; P = .23) to 2012-2018 (trials, 4374 of 5063 [86.4%]; CiNA, 1 735 077 of 2 090 775 [82.9%]; difference, 3.5 percentage points; P < .001) and corresponding worsening representation of American Indian or Alaska Native patients (2000-2011: trials, 10 of 3245 [0.3%]; CiNA, 10 905 of 2 800 711 [0.4%]; difference, -0.08 percentage points; 2012-2018: trials, 13 of 5063 [0.3%]; CiNA, 9484 of 2 090 775 [0.5%]; difference, -0.20 percentage points), Asian or Pacific Islander patients (2000-2011: trials, 121 of 3245 [3.7%]; CiNA, 75 033 of 2 800 711 [2.7%]; difference, 1.1 percentage points; 2012-2018: trials, 151 of 5063 [3.0%]; CiNA 70 535 of 2 090 775 [3.4%]; difference, -0.75 percentage points), Black patients (2000-2011: trials, 244 of 3245 [7.5%]; CiNA, 322 701 of 2 800 711 [11.5%]; difference, -4.0 percentage points; 2012-2018: trials, 270 of 5063 [5.3%]; CiNA, 255 625 of 2 090 775 [12.2%]; difference, -6.9 percentage points), and Hispanic or Latinx patients (2000-2011: trials, 161 of 1792 [9.0%]; CiNA, 169 297 of 2 800 711 [6.0%]; difference, 3.0 percentage points; 2012-2018: trials, 240 of 3295 [7.3%]; CiNA, 156 118 of 2 090 775 [7.5%]; difference, -0.2 percentage points). Similar disparities were observed when comparing industry-funded and academic center-sponsored trials. In this cross-sectional study of participants in phase 1 clinical trials of drugs for metastatic cancer, worsening disparities were observed over time in the accrual of patients from racial and ethnic minority groups. These findings may represent widening inequalities in access to trial sites and worsening systemic biases. More efforts are needed to diversify phase 1 cancer drug trials to improve equity in access to new treatments and to ensure that safety and efficacy findings from early drug trials are generalizable across populations.


Relation of adenomatous hyperplasia of the gastric mucosa to carcinogenesis.
Experimental studies of stomach carcinogenesis were carried out in two series of Wistar rats (66 and 174 animals). In both series submucosal foci of adenomatous hyperplasia were observed either without atypia, or with atypia at different, gradually increasing degrees. The number of these focal lesions in the submucosa (87 in the first series) was smaller than that of focal dysplastic changes with varying grades of atypia within the mucosa. On the basis of different degrees of atypia observed in these adenomatous hyperplasias, we have to assume that a phase shifting occurs in those areas that show lower grades or absence of atypia. In the framework of carcinogenesis this kind of adenomatous hyperplasia is interpreted as an incomplete or incompletely persisting carcinogenesis. In analogy to our experimental findings we found identical lesions in three human cases where different grades of atypia were observed distant from the primary stomach cancer. These results are discussed with reference to the animal experiments and to the literature.


Unification venoplasty during two versus one venous reconstruction: Computational fluid dynamics study.
Two versus 1 venous reconstruction is sometimes required for Hepato-Biliary-Pancreatic and Transplantation surgery. V-shape venoplasty is considered to be useful knack of unification method during 2 versus 1 venous reconstruction in clinical practice. The usefulness of V-shape unification venoplasty was proven by the present computational fluid dynamics study.


Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry.
Psychotropic drugs are frequently prescribed 'off-label' to children and adolescents and carry the risk of serious adverse drug reactions (sADR). We examined the frequency of sADRs of psychotropic drugs in pediatric inpatients and explored their potential preventability through following the recommendations of a web-based pediatric drug information system (PDIS). The potential socio-economic impacts of using this online system is also addressed. Routine clinical data from all inpatients treated in a child and adolescent psychiatry department between January 2017 and December 2018 were retrospectively examined for the occurrence of sADRs as defined by the European Medicines Agency. The preventability of the sADRs was assessed based on the information of the PDIS. Furthermore, the expected prolongation of the hospital stay due to sADRs was calculated as well as the associated treatment costs. The study was supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. In total, 1036 patients were screened of whom 658 (63.5%) received psychopharmacological treatment. In 53 (8.1%) of these patients 54 sADRs were documented, of which 37 sADRs were identified as potentially preventable through PDIS. Mitigating sADR through PDIS would likely have prevented prolonged hospital stays and conferred considerable savings for health insurance companies. PDIS provides systematic and evidence-based information about pediatric psychopharmacotherapy and helps to prevent prescribing errors. Therefore, PDIS is a useful tool to increase drug therapy safety in child and adolescent psychiatry. Further prospective studies are needed to confirm the results.


Gender-specific associations between activities of daily living disability and depressive symptoms among older adults in China: Evidence from the China Health and Retirement Longitudinal Study.
To evaluate the associations between BADL/IADL disability and depressive symptoms from the perspective of gender among older adults in China. This cross-sectional study used the data from the second wave of the China Health and Retirement Longitudinal Study (CHARLS). The sample included 3463 older adults aged 60 years and older across China. Multivariable logistic regression models were conducted. Among 3463 older adults, 1240 (35.8%) were classified as depressed, the prevalence of BADL and IADL disabilities were 756 (21.8%) and 1194 (34.5%), respectively. After controlling for covariates, BADL/IADL disability was significantly associated with an increased risk of depression prevalence both in men and women among older adults. Compared with IADL independent, IADL disability was about two times more likely to develop depressive symptoms in men (OR = 2.165, 95% CI = 1.661-2.822), which was much higher than that in women (OR = 1.748, 95% CI = 1.415-2.160). In contrast, the odds of being depressed for women with BADL disability (OR = 1.824, 95% CI = 1.447-2.299) were much higher than the odds for men with BADL disability (OR = 1.791, 95% CI = 1.348-2.379). Older adults with BADL/IADL disability were more likely to have depressive symptoms both for men and women. However, the associations between depressive symptoms and BADL/IADL disability were different in gender. Our results suggest that differential institutional care service and appropriate strategies for improvement in mental health are required.


Model of the haemodynamic reactions to intermittent coronary sinus occlusion.
Coronary sinus pressure data have been obtained from anaesthetized dogs during pressure controlled intermittent coronary sinus occlusion. It is the main aim of this paper to provide a mathematical procedure for modelling the typical time course of sinus pressure after temporary obstruction of the sinus. The model is produced by fitting a parameterized function to the systolic and diastolic pressures in order to represent mathematically the shape of the curves. The parameters characterize the rise in coronary sinus pressure following occlusion, and are used to calculate 'derived quantities' which mimic the physician's visual assessment of trace recordings and their clinical implications in certain forms of coronary sinus pressure reaction. This procedure should be thought of as a kind of pattern recognition which reflects the changing state of the myocardium. The mathematical results are shown to bear a close resemblance to the clinical effects of coronary sinus occlusion.


Implication of protein kinase C alpha in PAF-stimulated phospholipase D activation in Chinese hamster ovary (CHO) cells expressing PAF receptor.
Protein kinase C (PKC) isozyme(s) involved in regulation of platelet-activating factor (PAF)-induced phospholipase D (PLD) activation was investigated in CHO cells stably expressing cloned guinea-pig PAF receptor (WT-H cells). Three PKC isozymes, alpha, epsilon, and zeta, were identified by Western blotting, which displayed different kinetics of translocation from cytosol to membrane upon PAF stimulation. Cytosolic PKC alpha was rapidly translocated to membrane in response to PAF within 30 s and then returned to cytosol by 10 min. This kinetics was well correlated with PAF-induced transient PLD activation. Pretreatment of the cells with 100 nM 4 beta-phorbol 12-myristate 13-acetate (PMA) for 2 h resulted in down-regulation of PKC alpha, leaving PKC epsilon and zeta unchanged. Under the same conditions, PAF and PMA-mediated PLD activation were markedly reduced. These data suggest that PKC alpha is involved in the regulation of PAF-stimulated PLD activation in WT-H cells.


Composting of swine manure spiked with sulfadiazine, chlortetracycline and ciprofloxacin.
The fate of chlortetracycline (CTC), sulfadiazine (SDZ) and ciprofloxacin (CIP) during composting of swine manure and their effect on composting process were investigated. Swine manure was spiked with antibiotics, mixed with saw dust (1:1 on DW basis) and composted for 56 d. Antibiotics were spiked to a final concentration of 50 mg/kg CTC+10 mg/kg SDZ+10 mg/kg CIP (High-level) or 5 mg/kg CTC+1 mg/kg SDZ+1 mg/kg CIP (Low-level), and a control without antibiotics. Antibiotics at high concentrations delayed the initial decomposition that also affected the nitrogen mineralization. CTC and SDZ were completely removed from the composting mass within 21 and 3d, respectively; whereas, 17-31% of the spiked CIP remained in the composting mass. Therefore, composting could effectively remove the CTC and SDZ spiked even at high concentrations, but the removal of ciprofloxacin (belonging to fluoroquinolone) needs to be improved, indicating this antibiotic may get into the ecosystem through land application of livestock compost.


The neuroradiographic diagnosis of lumbar herniated nucleus pulposus: I. A comparison of computed tomography (CT), myelography, CT-myelography, discography, and CT-discography.
The accuracy of five imaging modalities for the diagnosis of lumbar herniated nucleus pulposus (HNP) is compared prospectively in 124 patients, all of whom underwent surgical exploration. All tests were read independently of each other and the level of confidence in each diagnosis was recorded. The results are based on negative (106) as well as positive (125) findings at the 231 disc sites (level and side) explored. Computed tomography-discography (disco-CT) was the most accurate test (87%) compared to 77% for CT-myelography (myelo-CT), 74% for CT, 70% for myelography, 64% for disc injection pain, and 58% for discography. The false positive rate was lower for disco-CT (19%) than for myelo-CT (24%), CT (24%), and myelography (30%). The false negative rate was also lower for disco-CT (8%) than for myelo-CT (22%), CT (29%), and myelography (30%). Disco-CT was the most accurate test (94%) in patients who had prior disc surgery compared with 81% for myelo-CT, 80% for CT, and 74% for myelography. Disco-CT was also the most accurate test for patients with foraminal HNP (91% compared with 71% for CT, 65% for myelo-CT, and 58% for myelography). Disc injection reproduced the patient's clinical pain pattern in only 36% of herniated discs. This test has high specificity (89%), but low sensitivity (43%). The risks from myelography followed by discography within a 72-hour period are similar to those reported for myelography alone. Disco-CT is the most accurate of these tests (P less than 0.05) for the diagnosis of lumbar HNP.(ABSTRACT TRUNCATED AT 250 WORDS)


Correlation analysis of the in-clinic and telephone batteries from the AREDS cognitive function ancillary study. AREDS Report No. 15.
To determine whether the AREDS Telephone Battery can be substituted for the In-Clinic Cognitive Function Battery to assess cognitive function, so that participants could still provide follow-up information without having to come to the clinic. Correlation analysis was performed on scores of the following in-clinic and telephone administrations: 1) Modified Mini-Mental State Examination (3MS), conducted in person vs. Telephone Interview Cognitive Status (TICS-M); 2) Wechsler Memory Scale-III (WMS-III), Logical Memory I and II; 3) Digits Backwards (a sub-test of the WMS-R); 4) Verbal Fluency; and 5) Letter Fluency (F,A,S). A total of 1,738 AREDS participants completed an In-Clinic Battery and a Telephone Battery within twelve months. Significant positive correlations were found for all tests, ranging from rho = 0.89 between the 3MS and TICS-M scores (95% CI; 0.88 - 0.90), to rho = 0.71 for Letter Fluency (95% CI; 0.68 - 0.74). The linear relationships between the In-Clinic Battery and Telephone Battery scores support the hypothesis that the Telephone Battery is an appropriate substitute for participants who are unable to complete an in-clinic assessment of cognitive function.


Fitting data to model: structural equation modeling diagnosis using two scatter plots.
This article introduces two simple scatter plots for model diagnosis in structural equation modeling. One plot contrasts a residual-based M-distance of the structural model with the M-distance for the factor score. It contains information on outliers, good leverage observations, bad leverage observations, and normal cases. The other plot contrasts the residual-based M-distance with the quantile of a chi distribution. It allows the researcher to visually identify clusters of potential outliers. The article further studies the effect of the potential outliers on the overall model evaluation when they are removed according to the order of the clusters exhibited in the plot. Suggestions are provided on determining the outlier status of outstanding cases in real data analysis. Recommendations are also made on the choice of robust methods and maximum likelihood following outlier removal.


Comparative analysis of microorganism adhesion on coated, partially coated, and uncoated orthodontic archwires: A prospective clinical study.
This study aimed to compare the microorganism adhesion on coated, partially coated, and uncoated orthodontic archwires after clinical use. The correlation between surface roughness (SR) and bacterial colonization was also evaluated. A total of 48 archwire segments (0.016 × 0.022-in) were equally divided into 4 groups: nickel-titanium coated, nickel-titanium partially coated, uncoated stainless steel, and uncoated nickel-titanium. The archwires were randomly inserted in a split-mouth study design. After 4 weeks of clinical use, the total number of microorganisms adhering to the archwire was quantified and transformed into colony-forming units. SR was evaluated using a profilometer. A one-way and two-way ANOVA, post-hoc Tukey test, paired-samples t test, and Pearson correlation coefficient were used for statistical analysis. All the archwires presented microorganism adhesion, with the nickel-titanium-coated group demonstrating the highest value (P < 0.001). A statistically significant increase in SR was observed after clinical use for all groups (P < 0.05). No correlation between SR and bacterial adhesion was detected. Microorganism adhesion occurred on all of the archwires tested, especially on the esthetic fully coated. Because SR was not correlated with microorganism adhesion, future studies should evaluate the effect of surface free energy and superficial chemical changes on in-vivo microorganism adhesion.


Assessment of hearing loss induced by tympanic membrane perforations under blast environment.
This study provides an approach to estimating tympanic membrane perforation-induced hearing loss (HL) using a human middle ear model. Sixty-one cases of tympanic membrane perforation originating from fireworks were reported from the Ear-Nose-Throat Department. The otoscope, audiometry data and diagnosis records were organized, and gender, age, etiology, perforation size and diseased ear side were classified as independent variables. A multinomial regression model was used to analyze the potential effects of the variables on HL. Meanwhile, a human middle ear model was implemented to calculate the ensued HL resulting from different perforation areas and sites. In addition, linear regression models were used to establish functions between perforation size and HL. The audiometry data indicate that HL at high frequencies (f > 2 kHz) is much more profound than that at the speech frequency band (f < 1 kHz). Compared with mild HL (<15 dB), mediate HL (15-30 dB) was correlated with the perforation area (p < 0.05, 95% CI), while severe HL (>30 dB) was affected by both perforation size and age (p < 0.05, 95% CI). However, other factors, including gender and diseased ear side, do not show a statistically significant effect on HL. Furthermore, the Kruskal-Wallis test result reveals that HL at frequencies of 0.25 kHz ≤ f ≤ 8 kHz is strongly associated with the perforation size (p < 0.05, 95% CI). It is conclusive that HL is positively proportional to the perforation size. However, HL is not correlated with the perforation site for small perforation areas of < 10% (p > 0.05, 95% CI).


Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients.
Virologic outcome among 104 lamivudine (3TC)-experienced individuals infected with human immunodeficiency virus type 1 who switched to a didanosine (ddI)-containing triple- or quadruple-drug regimen was compared with those who continued receiving a 3TC-containing regimen. A significantly increased independent risk of virologic failure was associated with continuing a 3TC-containing regimen. In addition, most patients for whom the ddI-containing regimen failed lost the M184V/I mutation. These results show that ddI continues to provide activity against viruses with the M184V/I mutation and suggest that the presence of the M184V/I mutation should not preclude the use of ddI in nucleoside-experienced patients.