Study of precursors of ventricular tachycardia from data stored in the memory of a dual chamber implantable cardioverter defibrillator.
This study was performed to examine precursors of ventricular tachyarrhythmias in patients who experienced a sustained ventricular tachyarrhythmia and received appropriate therapy by ICD. From an overall consecutive population of 77 patients, 18 patients (1 woman, mean age 61.7 +/- 10.8 years) were selected for having experienced a sustained ventricular tachyarrhythmia and received at least one appropriate ICD therapy preceded by 20 minutes of internal information. The number of premature ventricular complexes (PVCs)/min for each of the 20 minutes preceding the onset of ventricular tachyarrhythmia, the shortest coupling intervals between PVC and normal sinus beat, and the presence of short-long-short (SLS) interval sequences were examined. Data were stratified according to underlying disease, left ventricular ejection fraction, rate of ventricular tachyarrhythmia, and antiarrhythmic therapy. One hundred twenty-eight episodes of spontaneous ventricular tachyarrhythmia were retrieved. Rapid ventricular tachyarrhythmia (>160 beats/min) were preceded by a significantly greater mean number (3.71 +/- 6.36)of PVCs than slower ventricular tachyarrhythmia (<or=160 beats/min) (0.63 +/- 0.88, P = 0.0004). The mean shortest PVC coupling interval was significantly shorter in patients with (588 +/- 99 ms) versus without (643 +/- 111 ms, P = 0.03)ischemic heart disease, before episodes of rapid(527 +/- 55 ms)versus slower (636 +/- 105 ms, P = 0.0001)ventricular tachyarrhythmia, and in the absence (538 +/- 80 ms)versus the presence(620 +/- 105 ms, P = 0.006)of amiodarone. SLS sequences preceded 29% of rapid ventricular tachyarrhythmic episodes, versus 8% of the slower ventricular tachyarrhythmia (P < 0.01). Significant differences were found in the characteristics of PVCs preceding ventricular tachyarrhythmic episodes in accordance to their rate and the underlying cardiomyopathy. Though insufficient in isolation, these findings may be helpful when combined with other observations to develop preventive algorithms, or to refine the programming of implantable devices.


Facilitating Colostrum Collection by Hospitalized Women in the Early Postpartum Period for Infant Trophic Feeding and Oral Immune Therapy.
Administration of colostrum for early trophic feedings and colostrum oral immune therapy for neonates in the NICU is essential to enhance gut maturation and lower risk of infections. However, it is often difficult for women to collect early colostrum because of its thick viscosity and low volume. Women may be unable to sit upright during pumping sessions because of postsurgical pain, acute or chronic illness, or birth complications and may need assistance. In this article, we describe specific techniques that providers can use to help women to collect colostrum when they are unable to accomplish collection on their own. Helping women collect and administer colostrum to their neonates in the NICU may engage and motivate them to continue to pump and provide breast milk for their hospitalized neonates.


Overgenerality memory style for past and future events and emotions related in bipolar disorder. What are the links with problem solving and interpersonal relationships?
This study investigated patients with Bipolar Disorder's abilities to generate specific past and future events in response to positive and negative cues words as well as emotional intensity related to these ones. The relationships between the number of generated specific events cognitive functioning, interpersonal problems and the ability to problem solving were investigated. Nineteen BD and nineteen healthy controls completed a French version of the AMT to evaluate the past and future events recall, in function of their valence, and emotions related. Furthermore, they completed the Optional Thinking Test, the Inventory of Interpersonal Problems and the neuropsychological measures. Compared to healthy controls, BD recollected (1) fewer specific past negative events and (2) fewer future specific positive and negative events furthermore, (3) they felt more emotional intensity related to future events. These results were explained in the light of theoretical models. Finally, specific past memories deficits in BD were linked with issues in problem solving but not with levels of distress arising from interpersonal problems. In view of AM functions in everyday life, all types of deficits should be taken into consideration, and AM remediation envisaged.


Cost-effectiveness of nucleic acid test screening of volunteer blood donations for hepatitis B, hepatitis C and human immunodeficiency virus in the United States.
The aim of this study was to examine the cost-effectiveness of adding nucleic acid testing (NAT) to serological (antibody and antigen) screening protocols for donated blood in the United States (US) with the purpose of reducing the risks of transfusion-transmission of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The costs, health consequences and cost-effectiveness of adding either minipool or individual-donor NAT to serological screening (SS) testing were estimated using a decision-analysis model. With the given modelling assumptions, adding minipool NAT would avoid an estimated 37, 128 and eight cases of HBV, HCV and HIV, respectively, and save approximately 53 additional years of life and 102 additional quality adjusted life years (QALYs) compared with SS, at a net cost of $154 million. SS + minipool NAT - p24 compared with SS alone resulted in an incremental cost-effectiveness ratio of $1.5 million per QALY gained (range in sensitivity analysis $1.0-2.1 million per QALY gained) in this US analysis. The cost effectiveness of adding NAT screening is outside the typical range for most healthcare interventions, but not for established blood safety measures.


Correlations among upper and lower tear menisci, noninvasive tear break-up time, and the Schirmer test.
To determine the relationships among tear meniscus parameters, noninvasive tear break-up time (NITBUT), and the Schirmer test. Experimental study. Thirty-six subjects were tested on one randomly selected eye. Real-time corneal optical coherence tomography (OCT) was used to image the upper and lower tear menisci during normal and delayed blinking followed by measurement of NITBUT and the Schirmer test. Digital images of the eye were taken for measuring the lid lengths to estimate tear volume in the menisci. Compared with normal blinking, significant increases of tear menisci occurred during delayed blinking (post hoc, P < .01). NITBUT was weakly but significantly correlated with the height (r = 0.36; P = .03) and area (r = 0.37; P = .03) of the lower tear meniscus during normal blinks. NITBUT was also correlated with the lower tear meniscus volume (r = 0.45; P < .05) and total tear meniscus volume (r = 0.43; P < .05) during normal blinking. The Schirmer test was not significantly related to any parameters of the tear menisci, volumes, or NITBUT; however, it was negatively correlated with the age of the subjects (r = -0.47; P = .004). The age was negatively correlated with the upper tear meniscus (r ranged from 0.36 to 0.37 for the radius, height, and area, P < .05) measured during delayed blinking. NITBUT appears correlated with the lower tear meniscus during normal blinking, and the Schirmer test appears not correlated with the noninvasively measured tear meniscus.


A phase II study of perioperative pembrolizumab plus mFOLFOX in patients with potentially resectable esophagus, gastroesophageal junction (GEJ), and stomach adenocarcinoma.
Perioperative chemotherapy/chemoradiation is standard in esophageal/gastric/gastroesophageal junction (GEJ) adenocarcinoma, immune checkpoint inhibitors (ICI) effect in setting of metastatic and postoperatively. This study is to assess ICI + chemotherapy perioperatively. Patients with locally advanced (T1N1-3M0 or T2-3NanyM0) potentially resectable esophageal/gastric/GEJ adenocarcinoma by PET/EUS/CT and staging-laparoscopy, were treated preoperative 4 cycles mFOLFOX6 (Oxaliplatin 85 mg/m2 /Leucovorin 400 mg/m2 /5-FU bolus 400 mg/m2 then infusion 2400 mg/m2 for 46 h q2weeks) and 3 cycles pembrolizumab (200 mg q3week). Those without distal disease post-neoadjuvant and eligible for resection underwent surgery. Postoperative treatment was initiated at 4-8 weeks with 4 cycles mFOLFOX and 12 cycles pembrolizumab. The primary objective is pathological response (ypRR with tumor regression score, TRS ≤2). The expression of ICI-related markers PD-L1 (CPS), CD8, and CD20 were analyzed before and after preoperative therapy. Thirty-seven patients completed the preoperative treatment. Twenty-nine patients had curative R0 resection. 6/29 (21%; 95% CI: 0.08-0.40) achieved ypCR with TRS 0 in resected patients. 26/29 (90%; 95% CI: 0.73-0.98) had ypRR with TRS ≤2. Twenty-six patients finished adjuvant therapy with a median 36.3-month follow-up. Three patients had recurrence/metastatic disease (at 9-, 10-, 22 months enrollment) with one dead at 23 months, and two are still alive at 28 and 36.5 months. The remaining (23/26) are free of disease with 3 years DFS of 88.5% and 3 years OS of 92.3%. There were no unexpected toxicities. Preoperative ICI + chemotherapy enhanced immune responses significantly with increasing expression of PD-L1 (CPS ≥10, p = 0.0078) and CD8 (>5%, p = 0.0059). The perioperative pembrolizumab and mFOLFOX combination in resectable esophageal/gastric/GEJ adenocarcinoma is very effective with 90% ypRR, 21% ypCR, and impressive long-time survival benefits.


A single GluN2 subunit residue controls NMDA receptor channel properties via intersubunit interaction.
NMDA receptors (NMDARs) are glutamate-gated ion channels that are present at most excitatory mammalian synapses. The four GluN2 subunits (GluN2A-D) contribute to four diheteromeric NMDAR subtypes that have divergent physiological and pathological roles. Channel properties that are fundamental to NMDAR function vary among subtypes. We investigated the amino acid residues responsible for variations in channel properties by creating and examining NMDARs containing mutant GluN2 subunits. We found that the NMDAR subtype specificity of three crucial channel properties, Mg(2+) block, selective permeability to Ca(2+) and single-channel conductance, were all controlled primarily by the residue at a single GluN2 site in the M3 transmembrane region. Mutant cycle analysis guided by molecular modeling revealed that a GluN2-GluN1 subunit interaction mediates the site's effects. We conclude that a single GluN2 subunit residue couples with the pore-forming loop of the GluN1 subunit to create naturally occurring variations in NMDAR properties that are critical to synaptic plasticity and learning.


Risk factors for HIV infection among 15 to 25-year-old rural unmarried Yi adolescents in an ethnic minority region of China.
We aimed to analyze factors related to human immunodeficiency virus (HIV) infection among 15 to 25-year-old rural unmarried Yi adolescents in Liangshan Yi Autonomous Prefecture from 2011 to 2016, and to investigate the relationship among the HIV-related risk factors.Three sites (Butuo, Zhaojue, and Ganluo counties) with a Yi population were selected from 2011 to 2016 in Liangshan prefecture. We used questionnaires to investigate demographic and behavioral characteristics and performed HIV testing. Logistic regression analysis and multiple correspondence analysis (MCA) were used to analyze the data.A total of 6311 qualified rural unmarried Yi adolescents were involved in this study, with an HIV infection rate of 4.18% (264/6311). Logistic regression analysis indicated that males (OR = 1.56, 95% CI = 1.17-2.08), illiteracy (OR = 2.70, 95% CI = 1.79-4.08), primary school education or below (OR = 1.62, 95% CI = 1.12-2.36), history of out-migrating for work (OR = 1.58, 95% CI = 1.18-2.13), and injecting drug user (IDU) (OR = 6.42, 95% CI = 3.06-13.46) contributed to the risk of HIV infection. MCA revealed a strong interrelationship between the following risk factors and HIV infection: aged 23 to 25 years, IDU, history of out-migrating for work, and ever having sexual behaviors.HIV infection among 15 to 25-year-old rural unmarried Yi adolescents in Liangshan is a serious issue. MCA and logistic regression analysis can be used to assess the relationship between risk factors for HIV infection.


The teaching of clinical administration: opportunities and problems of role ambiguity.
The challenge of teaching clinical administration can felicitously be met by the ward director of the psychiatric inpatient ward. The theory of patient management centers around formation of an administrative alliance such that the patient becomes "coadministrator" of his treatment. The ward director must convey this and other basic principles; must deal with a variety of resistances to learning and practice of clinical administration; must function as supervisor while simultaneously administrating; and, finally, must orchestrate power and influence in relation to his role to achieve the most effective functioning of the ward team.


Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan. BMS-181339 Breast Cancer Study Group.
A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6-49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6-100) days to onset of and median duration of response was 125 (36-305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1-3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1-3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.


Transforming growth factor-alpha expression in in situ epidermal neoplasia.
Twenty cases of solar keratosis and 15 cases of Bowen's disease were investigated for the expression of transforming growth factor alpha (TGF-alpha) by an indirect immunoperoxidase technique using monoclonal antibody TGF-alpha AB-2 in formalin-fixed wax-embedded tissue. Twelve cases (60%) of solar keratosis and 13 cases (86%) of Bowen's disease showed marked overexpression of TGF-alpha in both membranous and cytoplasmic distributions. This suggests that overexpression of TGF-alpha may play an important role in the evolution of these two neoplastic conditions.


Esophageal dilation. Six-year experience in a small community hospital.
The results of this review indicate esophageal strictures can be effectively and safely managed by dilation in the community hospital setting.


Characterization of the interaction of metal-protoporphyrins photosensitizers with β- lactoglobulin.
We investigated the interaction of a series of metal-protoporphyrins (PPIXs) with bovine β- lactoglobulin (BLG) using a combination of optical spectroscopy and computational simulations. Unlike other studies, the simulations were not merely used to rationalize the experimental data but were employed to refine the experimental data itself. The study was carried out at two pH values, 5 and 9, where BLG is known to have different conformation dictated by the so-called Tanford transition which occurs near pH 7.5. The transition is postulated to regulate access to the interior binding cavity of the protein, thus the pH variation was used as a parameter to investigate whether PPIXs access the central cavity of BLG. The results of our study show that indeed binding increases significantly at alkaline pH, however, the increased affinity is not due to the accessibility of the central cavity. Instead, binding appears to be determined by the tendency of PPIXs to form large inhomogeneous aggregates at acidic pH which hinders interactions with proteins. The binding site determined through a combination of experimental and computational methods is located at the interface between two BLG monomers where the long α-helix segment of the protein face each other. This region is rich in positively charged Lys residues that interact with the propionic acid chains of the protoporphyrins. Establishing the modality of binding between protoporphyrins and BLG would have important consequences for the use of BLG:PPIX complexes in applications such as artificial photoreceptors, artificial metallo-enzymes, delivery of photosensitizers for phototherapy and even solar energy conversion.


Mercury exposure in young children living in New York City.
Residential exposure to vapor from current or previous cultural use of mercury could harm children living in rental (apartment) homes. That concern prompted the following agencies to conduct a study to assess pediatric mercury exposure in New York City communities by measuring urine mercury levels: New York City Department of Health and Mental Hygiene's (NYCDOHMH) Bureau of Environmental Surveillance and Policy, New York State Department of Health/Center for Environmental Health (NYSDOHCEH), Wadsworth Center's Biomonitoring Program/Trace Elements Laboratory (WC-TEL), and Centers for Disease Control and Prevention (CDC). A previous study indicated that people could obtain mercury for ritualistic use from botanicas located in Brooklyn, Manhattan, and the Bronx. Working closely with local community partners, we concentrated our recruiting efforts through health clinics located in potentially affected neighborhoods. We developed posters to advertise the study, conducted active outreach through local partners, and, as compensation for participation in the study, we offered a food gift certificate redeemable at a local grocer. We collected 460 urine specimens and analyzed them for total mercury. Overall, geometric mean urine total mercury was 0.31 microg mercury/l urine. One sample was 24 microg mercury/l urine, which exceeded the (20 microg mercury/l urine) NYSDOH Heavy Metal Registry reporting threshold for urine mercury exposure. Geometric mean urine mercury levels were uniformly low and did not differ by neighborhood or with any clinical significance by children's ethnicity. Few parents reported the presence of mercury at home, in a charm, or other item (e.g., skin-lightening creams and soaps), and we found no association between these potential sources of exposure and a child's urinary mercury levels. All pediatric mercury levels measured in this study were well below a level considered to be of medical concern. This study found neither self-reported nor measured evidence of significant mercury use or exposure among participating children. Because some participants were aware of the possibility that they could acquire and use mercury for cultural or ritualistic purposes, community education about the health hazards of mercury should continue.


Chlorination of bisphenol A in aqueous media: formation of chlorinated bisphenol A congeners and degradation to chlorinated phenolic compounds.
The chlorination of bisphenol A (BPA) in aqueous media was investigated in order to describe the degradation profile of this compound and the formation of chlorinated products. Aqueous solutions of BPA (approx. 1 mg/l) were chlorinated by sodium hypochlorite solution at room temperature and under weakly alkaline conditions. Chlorinated compounds were extracted with dichloromethane and determined by gas chromatography/mass spectrometry (GC/MS). BPA was consumed completely within 5 min of chlorination, when the initial chlorine concentration was 10.24 mg/l (molar ratio to BPA, 58.7). On the other hand, when the initial chlorine concentration was 1.03 mg/l (molar ratio, 6.56), 9.3% of BPA still remained after 60 min chlorination. Five chlorinated BPA congeners, 2-chlorobisphenol A (MCBPA), 2,6-dichlorobisphenol A (2,6-D2CBPA), 2,2'-dichlorobisphenol A (2,2'-D2CBPA), 2,2',6-trichlorobisphenol A (T3CBPA) and 2,2', 6,6'-tetrachlorobisphenol A (T4CBPA) were formed in the earlier stages of chlorination. Several chlorinated phenolic compounds, 2,4,6-trichlorophenol (T3CP), 2,6-dichloro-1,4-benzoquinone (D2CBQ), 2,6-dichloro-1,4-hydroquinone (D2CHQ), C9H10Cl2O2, C9H8Cl2O and C10H12Cl2O2, were also formed by further chlorination.


Repeated tender point injections of granisetron alleviate chronic myofascial pain--a randomized, controlled, double-blinded trial.
Serotonin (5-HT) mediates pain by peripheral 5-HT3-receptors. Results from a few studies indicate that intramuscular injections of 5-HT3-antagonists may reduce musculoskeletal pain. The aim of this study was to investigate if repeated intramuscular tender-point injections of the 5-HT3-antagonist granisetron alleviate pain in patients with myofascial temporomandibular disorders (M-TMD). This prospective, randomized, controlled, double blind, parallel-arm trial (RCT) was carried out during at two centers in Stockholm, Sweden. The randomization was performed by a researcher who did not participate in data collection with an internet-based application ( www.randomization.com ). 40 patients with a diagnose of M-TMD according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were randomized to receive repeated injections, one week apart, with either granisetron (GRA; 3 mg) or isotonic saline as control (CTR). The median weekly pain intensities decreased significantly at all follow-ups (1-, 2-, 6-months) in the GRA-group (Friedman test; P < 0.05), but not in the CTR-group (Friedman-test; P > 0.075). The numbers needed to treat (NNT) were 4 at the 1- and 6-month follow-ups, and 3.3 at the 2-month follow-up in favor of granisetron. Repeated intramuscular tender-point injections with granisetron provide a new pharmacological treatment possibility for myofascial pain patients with repeated intramuscular tender-point injections with the serotonin type 3 antagonist granisetron. It showed a clinically relevant pain reducing effect in the temporomandibular region, both in a short- and long-term aspect. European Clinical Trials Database 2005-006042-41 as well as at Clinical Trials NCT02230371 .


[Discrimination parameters for cellular polymorphism in dysplasias of the vaginal mucosa].
By using cytophometric methods, two populations of vaginal cells, normal and displasic, have been studied, evaluating the morphological differences existing between them.


Systemic and local factors and the maintenance of bone quality.
Bone formation, an essential process for the maintenance of bone mass and strength, depends on changes in osteoblast number or function. Bone formation is modified by systemic hormones such as parathyroid hormone, growth hormone, insulin and steroids, and by local factors that act in an antocrine or paracrine fashion on the osteoblast. Skeletal cells synthesize platelet-derived growth factors and fibroblast growth factors, agents which affect osteoblast cell replication. In addition, skeletal cells synthesize insulin-like growth factors and transforming growth factors beta, agents which also affect the differentiated function of the osteoblast. Systemic and local factors that modify bone formation are likely critical in the maintenance of normal bone.


Resistance to the tyrosine kinase inhibitor axitinib is associated with increased glucose metabolism in pancreatic adenocarcinoma.
Alterations in energy (glucose) metabolism are key events in the development and progression of cancer. In pancreatic adenocarcinoma (PDAC) cells, we investigated changes in glucose metabolism induced by resistance to the receptor tyrosine kinase inhibitor (RTKI) axitinib. Here, we show that human cell lines and mouse PDAC cell lines obtained from the spontaneous pancreatic cancer mouse model (Kras(G12D)Pdx1-cre) were sensitive to axitinib. The anti-proliferative effect was due to a G2/M block resulting in loss of 70-75% cell viability in the most sensitive PDAC cell line. However, a surviving sub-population showed a 2- to 3-fold increase in [C-14]deoxyglucose ([C-14]DG) uptake. This was sustained in axitinib-resistant cell lines, which were derived from parental PDAC. In addition to the axitinib-induced increase in [C-14]DG uptake, we observed a translocation of glucose transporter-1 (Glut-1) transporters from cytosolic pools to the cell surface membrane and a 2-fold increase in glycolysis rates measured by the extracellular acidification rate (ECAR). We demonstrated an axitinib-induced increase in phosphorylated Protein Kinase B (pAkt) and by blocking pAkt with a phosphatidylinositol-3 kinase (PI3K) inhibitor we reversed the Glut-1 translocation and restored sensitivity to axitinib treatment. Combination treatment with both axitinib and Akt inhibitor in parental pancreatic cell line resulted in a decrease in cell viability beyond that conferred by single therapy alone. Our study shows that PDAC resistance to axitinib results in increased glucose metabolism mediated by activated Akt. Combining axitinib and an Akt inhibitor may improve treatment in PDAC.


Controlling the orientation of spin-correlated radical pairs by covalent linkage to nanoporous anodic aluminum oxide membranes.
Ordered multi-spin assemblies are required for developing solid-state molecule-based spintronics. A linear donor-chromophore-acceptor (D-C-A) molecule was covalently attached inside the 150 nm diam. nanopores of an anodic aluminum oxide (AAO) membrane. Photoexcitation of D-C-A in a 343 mT magnetic field results in sub-nanosecond, two-step electron transfer to yield the spin-correlated radical ion pair (SCRP) (1)(D(+)˙-C-A(-)˙), which then undergoes radical pair intersystem crossing (RP-ISC) to yield (3)(D(+)˙-C-A(-)˙). RP-ISC results in S-T0 mixing to selectively populate the coherent superposition states |S'> and |T'>. Microwave-induced transitions between these states and the unpopulated |T(+1)> and |T(-1)> states result in spin-polarized time-resolved EPR (TREPR) spectra. The dependence of the electron spin polarization (ESP) phase of the TREPR spectra on the orientation of the AAO membrane pores relative to the externally applied magnetic field is used to determine the overall orientation of the SCRPs within the pores at room temperature.


[High-sensitivity C-reactive protein as a biomarker of risk in coronary artery disease].
Vascular inflammation plays a crucial role in the pathogenesis of atherosclerosis and mediates various stages of atherosclerotic plaque development, from lipid streak formation to the plaque rupture and destabilization that precedes the clinical syndromes of cardiovascular disease. Inflammatory biomarkers constitute valuable tools to study this process, enabling the effects of different therapeutic interventions to be assessed. Currently, C-reactive protein (CRP) determined by high-sensitivity methods (hs-CRP) is the most extensively studied biomarker. Data regarding hs-CRP and cardiovascular risk, though largely consistent, are of unclear clinical relevance. This article provides a comprehensive review of current knowledge concerning cardiovascular risk and hs-CRP, and concludes with an evidence-based analysis of the current role of hs-CRP in cardiovascular risk assessment.


Effect of changes in feeding schedule on the diurnal rhythms and daily activity levels of intestinal brush border enzymes and transport systems.
The activities of rat intestinal enzymes, sucrase, lactase, maltase, trehalase, gamma-glutamyltransferase, leucylnaphthylamide-hydrolyzing activity, and the transport system for glucose follow diurnal rhythms on ad libitum and restricted feeding regimes. In response to 6 days of restricted feeding, food available between 1400 and 1800 Eastern Standard Time, all rhythms shifted in time and the daily levels of activities were changed. Alkaline phosphatase activity followed a diurnal rhythm only in restricted fed animals. In restricted fed rats several activity patterns were observed, some with short periods of maximum activity, 3 h or less, and some with plateaus of maximum activity, 5-9 h long. In respect to the time of day of the synchronizer, sucrase peaked before feeding, glucose transport peaked during feeding, alkaline phosphatase peaked after feeding, and the other enzymes had higher levels of activity before, during and after feeding. The effect of restricted feeding on the daily activity levels were: a decrease in leucylnaphthylamide-hydrolyzing activity, no change in alkaline phosphatase, and increases in the others. These enzyme and transport systems exhibit a large amount of individual regulation or control as reflected by the lack of a uniform activity pattern and response to the synchronizer, and the variation in direction and magnitude of the adaptations to restricted feeding.


Lignocaine: its effects on wound healing.
In the light of clinical observations that local anaesthetic impairs wound healing, the effect of lignocaine at various concentrations, with and without adrenaline, on the tensile strength of skin wounds in rats 3, 5 and 7 days after operation was studied. Lignocaine had an adverse effect on wound healing at 5 and 7 days, perhaps due partly to the destructive effect of the intra- and subcutaneous injection, but certainly due also to the lignocaine itself. Adrenaline potentiated this effect. It was concluded that it is better to use dilute solutions of lignocaine, preferably without adrenaline, for local anaesthesia.


Analysis of the bovine viral diarrhea virus genome for possible cellular insertions.
Mucosal disease is the most severe disease resulting from bovine viral diarrhea virus (BVDV) infection in cattle. Two biotypes of BVDV may be isolated from animals with mucosal disease: cytopathic (cp) and noncytopathic (ncp). These "pairs" of cp/ncp viruses are often closely related and it has been suggested that the cp virus arises from a ncp virus by insertion of cellular RNA in the p125 region of the BVDV genome. We have used four pairs of cp/ncp BVDV isolated from cattle with mucosal disease, to examine the genomic sequence of the region of the genome coding for the nonstructural protein p125 (processed to p54/p80 in cp viruses) by PCR analysis and sequencing. We did not detect any cellular gene insertions in any of the four ncp viruses; however, we found a large duplication of the p80 gene and a ubiquitin gene insertion in three of the four cp isolates. Our results suggest that cellular RNA insertions in the p125 region may contribute significantly to the cytopathogenicity of BVDV. However, this does not appear to be the only mechanism of cytopathogenicity as we did not detect any insertions or duplications in one of the cp viruses. Comparison of the DNA sequence in the p80 region revealed greater homology within the "pairs" than to NADL, which lend further support to the hypothesis that a cp virus is originated from a ncp virus.


Correction: Immediate Effect of a Single Session of Whole Body Vibration on Spasticity in Children With Cerebral Palsy.
[This corrects the article on p. 273 in vol. 41, PMID: 28503461.].


[Exact description of non-glomerular and glomerular erythrocyte forms in pediatric hematuria].
We examined 70 urinary sediments of 35 children with non-glomerular hematuria (NGH) and 65 urinary sediments of 17 children with glomerular hematuria (GH) by phase-contrast microscopy at 1,000 X magnification. In each urinary sediment 200 erythrocytes were classified into 18 types of "non-glomerular erythrocytes" and 15 types of "glomerular erythrocytes". According to the percentage of greatly altered erythrocytes the urinary finding was termed isomorphic, mixed or dysmorphic. In 91% of the urinary sediments of patients with NGH the erythrocyte pattern was isomorphic, and in 91% of the urinary sediments of children with GH it was dysmorphic. 9 types of non-glomerular erythrocytes and 10 types of glomerular erythrocytes constituted 94.5% of all 26,809 erythrocytes examined. Torocytes (doughnut-like cells) can be considered characteristic for GH. This study demonstrates a high specificity of this method in discriminating NGH from GH. The exact morphological description of urinary erythrocytes allows the method to be reproducible. For future use examiners can concentrate on the 19 commonest erythrocyte types.


Tormentic acid inhibits hepatic stellate cells activation via blocking PI3K/Akt/mTOR and NF-κB signalling pathways.
The present study was to investigate the inhibitory effect and underlying mechanism of Tormentic acid (TA) on hepatic stellate cells (HSCs). HSC-T6 cells were stimulated with Platelet-derived growth factor-BB (PDGF-BB) and TA, and then cell proliferation, apoptosis, inflammatory factor, and collagen-related indicators were detected. In order to elucidate the potential mechanism, the PI3K/Akt/mTOR and NF-κB signalling pathways were also detected. The results showed that TA treatment markedly inhibited PDGF-BB-stimulated HSC-T6 cell activation, as evidenced by the inhibition of cell proliferation, migration and colony formation, as well as the decreased expression of TGF-β and α-SMA. TA treatment caused a significant increase in the activity of lactate dehydrogenase and significantly promoted cell apoptosis. TA treatment significantly reduced aspartate aminotransferase, alanine aminotransferase and total bilirubin activity. Importantly, TA inhibited the expression of collagen type I and III, alleviating the excessive deposition of extracellular matrix (ECM). Further experiments showed that TA administration significantly inhibited the phosphorylation of PI3K, Akt, FAK and mTOR and the protein expression of P70S6K, indicating the inhibition of the PI3K/Akt/mTOR pathway. Moreover, treatment with TA markedly decreased the phosphorylation of IκBα, NF-κB p65 and IKKα/β, thereby blocking the NF-κB signal transduction. In summary, this study demonstrates that TA significantly inhibits HSC activation and promotes cell apoptosis via the inhibition of the PI3K/Akt/mTOR and NF-κB signalling pathways. SIGNIFICANCE OF THE STUDY: Tormentic acid (TA) could inhibit HSC activation and alleviate collagen-based ECM deposition, suggesting that TA exerted anti-hepatic fibrosis. Further mechanism research revealed that the inhibition of TA on HSC activation might be through blocking the PI3K/Akt/mTOR and NF-κB signalling pathways. These findings provided a new cue to understand the protective effect of TA against liver fibrosis, which may provide a potential nature medicine for the treatment of liver fibrosis.


Molecular mechanisms of therapeutic hypothermia on neurological function in a swine model of cardiopulmonary resuscitation.
To explore the molecular mechanisms by which mild hypothermia following resuscitation improves neurological function in a porcine model of cardiac arrest. Thirty-three inbred Chinese Wuzhishan (WZS) minipigs were used. After 8 min of untreated ventricular fibrillation (VF), the surviving animals (n=29) were randomly divided into two groups including serum group (n=16) and molecular group (n=13). Serum group animals were used to measure porcine-specific tumour necrosis factor-alpha (TNF-α), interleukin (IL-6, IL-10), matrix metalloproteinase (MMP9), Aquaporin-4 (AQP4), tissue inhibitor to metalloproteinase-1 (TIMP1), neuron-specific enolase (NSE) and S100B at 0.5 h, 6 h, 12 h, 24 h and 72h recovery by enzyme-linked immunosorbent assay (ELISA). Molecular group animals were used to measure cerebral cortex messenger RNA (mRNA) and protein expression of nuclear factor-κB (NF-κB), MMP9 and AQP4 by real-time (RT) quantitative polymerase chain reaction (PCR) and Western blotting at 24 h and 72 h recovery. Animals were further divided into either normothermia or hypothermia groups. Hypothermia (33°C) was maintained for 12 h using an endovascular cooling device. Swine neurologic deficit scores (NDS) were used to evaluate neurological function at 24-h and 72-h recovery. Twenty-nine of the 33 (87.9%) animals were successfully resuscitated. The hypothermia group exhibited higher survival rates at 24 h (75%) and 72 h (62.5%) compared to the normothermia group (37.5% and 25%, respectively). Hypothermia markedly inhibited expression of NF-κB, TNF-α, MMP9 and NSE, and promoted expression of TIMP1 (P<0.01). The mean NDS at 24-h and 72-h recovery was 112.5 and 61, respectively, in the hypothermic group, and 230 and 207.5, respectively, in the normothermia group. Brain protection induced by hypothermia involves inhibition of inflammatory and brain edema pathways.


Familial dysautonomia.
Familial dysautonomia (FD) is a neurodevelopmental genetic disorder within the larger classification of hereditary sensory and autonomic neuropathies, each caused by a different genetic error. The FD gene has been identified as IKBKAP. Mutations result in tissue-specific expression of mutant IkappaB kinase-associated protein (IKAP). The genetic error probably affects development, as well as maintenance, of neurons because there is neuropathological and clinical progression. Pathological alterations consist of decreased unmyelinated and small-fiber neurons. Clinical features reflect widespread involvement of sensory and autonomic neurons. Sensory loss includes impaired pain and temperature appreciation. Autonomic features include dysphagia, vomiting crises, blood pressure lability, and sudomotor dysfunction. Central dysfunction includes emotional lability and ataxia. With supportive treatment, prognosis has improved greatly. About 40% of patients are over age 20 years. The cause of death is usually pulmonary failure, unexplained sudden deaths, or renal failure. With the discovery of the genetic defect, definitive treatments are anticipated.


Continuing antiplatelet therapy before cardiac surgery with cardiopulmonary bypass: a meta-analysis on the need for reexploration and major outcomes.
To determine major adverse outcomes, including the risk of mediastinal reexploration, death, stroke and myocardial infarction, associated with continuing antiplatelet therapy in patients undergoing surgery with cardiopulmonary bypass. A meta-analysis of parallel randomized, controlled trials published in English. A university-based electronic search. Patients undergoing surgery with cardiopulmonary bypass (CPB). Continuing antiplatelet therapy versus stopping antiplatelet therapy before the surgery. A search was conducted in PubMed, EMBASE, MEDLINE(R), and the Cochrane Central Register of Controlled Trials. Twelve studies were retained for analysis. Continuing antiplatelet drugs for CPB increases the rate of reexploration by a standardized mean difference (SMD) 0.22, 95% confidence interval (CI) 0.06, 0.39; I-square 0%; p value 0.01; classical fail-safe number 5. The number needed to harm (NNTH) is 87 (95% CI 390, 44). There was no statistical difference for death at 30 days and 1 year, myocardial infarction at 30 days, and stroke at 30 days. Continuing antiplatelet drugs increases blood loss, SMD 0.27 (95% CI 0.09, 0.45), I-square 73.1%; p = 0.003. Continuing antiplatelet therapy for patients undergoing surgery with CPB is associated with a low risk for reexploration.


Simultaneous Living Donor Kidney Transplant and Laparoscopic Native Nephrectomy: An Approach to Kidney Transplant Candidates with Suspected Renal-Cell Carcinoma.
Introduction: Kidney transplant candidates are occasionally found during the pre-transplant evaluation to have a suspicious mass in a native kidney. Further work-up and management of such a mass may delay transplantation for several months, which may create logistic barriers to transplant, particularly if there are timing constraints of the donor. In this study, we report our experience with simultaneous living donor kidney transplant and laparoscopic native nephrectomy, where the indication for nephrectomy was a suspicious lesion. Methods: We performed a retrospective review of patients who underwent simultaneous kidney transplant and native nephrectomy using prospectively collected data. We analyzed relevant patient characteristics, surgical details, pathologic results, and long-term follow-up. Results: We identified 16 patients who underwent simultaneous living donor kidney transplantation and laparoscopic native nephrectomy at our institution between 2013 and 2018. Ten (62.5%) patients were found to have renal-cell carcinoma (RCC) on the final pathology. No patients had recurrent RCC, at a median follow-up of 4 years. Conclusion: For patients who are planning to undergo a living donor kidney transplant and are found to have a small mass that is suspicious for RCC, a simultaneous living donor kidney transplant and laparoscopic native nephrectomy is a possible approach in selected patients.


Recanalization of obstructed Tenckhoff peritoneal dialysis catheter: wire/stylet manipulation combined with endoluminal electrocauterization.
We report the results of fluoroscopically guided wire/stylet manipulation combined with endoluminal electrocauterization in seven patients with obstructed Tenckhoff peritoneal dialysis catheters. In preparation for clinical application, electrocauterization was performed using a stone basket to recanalize surgically removed Tenckhoff catheters obstructed with omental fat ingrowing through the side holes. All ingrowing omental fat was removed easily by electrocauterization with the rotating movement of a stone basket. The technique was then applied in vivo in seven cases with ingrowing omental fat and malpositioned catheter; six (86%) were successfully recanalized. Among those six cases with initial success, four maintained good catheter function with durable patency (mean 261.3 days). No significant complication was noted.


Defining the Active Fraction of Daptomycin against Methicillin-Resistant Staphylococcus aureus (MRSA) Using a Pharmacokinetic and Pharmacodynamic Approach.
Our objective was to study the pharmacodynamics of daptomycin in the presence of varying concentrations of human serum (HS) in vitro to quantify the fraction of daptomycin that is 'active'. Time kill experiments were performed with daptomycin (0 to 256 mg/L) against two MRSA strains at log-phase growth, in the presence of HS (0%, 10%, 30%, 50%, 70%) combined with Mueller-Hinton broth. Daptomycin ≥ 2 mg/L achieved 99.9% kill within 8 h at all HS concentrations; early killing activity was slightly attenuated at higher HS concentrations. After 1 h, bacterial reduction of USA300 upon exposure to daptomycin 4 mg/L ranged from -3.1 to -0.5 log10CFU/mL in the presence of 0% to 70% HS, respectively. Bactericidal activity was achieved against both strains at daptomycin ≥ 4 mg/L for all fractions of HS exposure. A mechanism-based mathematical model (MBM) was developed to estimate the active daptomycin fraction at each %HS, comprising 3 bacterial subpopulations differing in daptomycin susceptibility. Time-kill data were fit with this MBM with excellent precision (r2 >0.95). The active fraction of daptomycin was estimated to range from 34.6% to 25.2% at HS fractions of 10% to 70%, respectively. Despite the reported low unbound fraction of daptomycin, the impact of protein binding on the activity of daptomycin was modest. The active fraction approach can be utilized to design in vitro experiments and to optimize therapeutic regimens of daptomycin in humans.


Capturing ultrafast photoinduced local structural distortions of BiFeO3.
The interaction of light with materials is an intensively studied research forefront, in which the coupling of radiation energy to selective degrees of freedom offers contact-free tuning of functionalities on ultrafast time scales. Capturing the fundamental processes and understanding the mechanism of photoinduced structural rearrangement are essential to applications such as photo-active actuators and efficient photovoltaic devices. Using ultrafast x-ray absorption spectroscopy aided by density functional theory calculations, we reveal the local structural arrangement around the transition metal atom in a unit cell of the photoferroelectric archetype BiFeO3 film. The out-of-plane elongation of the unit cell is accompanied by the in-plane shrinkage with minimal change of interaxial lattice angles upon photoexcitation. This anisotropic elastic deformation of the unit cell is driven by localized electric field as a result of photoinduced charge separation, in contrast to a global lattice constant increase and lattice angle variations as a result of heating. The finding of a photoinduced elastic unit cell deformation elucidates a microscopic picture of photocarrier-mediated non-equilibrium processes in polar materials.


The Taxonomy Dictionary: a resource for correct spelling of taxa.
This article describes 'The Taxonomy Dictionary', a resource that can enhance the spelling engine of a text editor such as Word, so that it can correctly spell every taxon described and listed in the largest taxonomy databases. It contains around 1.4 million unique words, and once installed an incorrectly spelled taxon will be marked by the spelling engine and it will suggest possible correct spellings. Installation instructions for Firefox, LibreOffice and Microsoft Word can be found on the GitHub repository. The software is licensed with a GPL3 licence.


A Comparative Study on the Uptake and Toxicity of Nickel Added in the Form of Different Salts to Maize Seedlings.
In soil ecotoxicological studies, a toxic metal is usually added in the form of either an inorganic or organic salt with relatively high solubility. Nitrate, chloride, acetate, or sulfate are commonly considered as valid options for that aim. However, recent studies have shown that different salts of the same metal at the same cationic concentration may exhibit different toxicities to plants and soil organisms. This information should be considered when selecting data to use for developing toxicological criteria for soil environment. A comparative study was carried out to evaluate the toxicity of five nickel (Ni) salts: NiCl₂, NiSO₄, Ni(II)-citrate, Ni(CH₃COO)₂, and Ni(II)-EDTA (ethylenediaminetetraacetate), on maize seedlings. The plant metrics used were plant height, shoot and root biomass, leaf soluble sugars and starch, and the Ni contents of the shoots and roots. The results indicated that when Ni was added to the soil, toxicity varied with the selected anionic partner with the following toxicity ranking NiSO₄ < Ni(CH₃COO)₂ < Ni(II)-citrate < NiCl₂ < Ni(II)-EDTA. Taking the plant-height metric as an example, the effective concentrations for 50% inhibition (EC50) were 3148 mg·kg(-1) for NiSO₄, 1315 mg·kg(-1) for NiCl₂, and 89 mg·kg(-1) for Ni(II)-EDTA. Compared with the Ni in the other salts, that in Ni(II)-EDTA was taken up the most efficiently by the maize roots and, thus, resulted in the greatest toxic effects on the plants. Nickel generally reduced leaf soluble sugars, which indicated an effect on plant carbohydrate metabolism. The outcome of the study demonstrates that different salts of the same metal have quite different ecotoxicities. Therefore, the anionic counterpart of a potentially toxic metal cation must be taken into account in the development of ecotoxicological criteria for evaluating the soil environment, and a preferred approach of leaching soil to reduce the anionic partner should also be considered.


Purkinje-like cells in the cochlear nucleus of the Common Tree Shrew (Tupaia glis) identified by calbindin immunohistochemistry.
The dorsal cochlear nucleus (DCN) of Tree Shrews (Tupaia glis; n=2) was examined by calbindin (CB) immunohistochemistry for the presence of Purkinje-like cells (PLCs), detected previously in only four different mammals. We found up to eight CB-immunoreactive PLCs in the left and right DCN, and a few axons, likely of PLC origin, that appeared to leave the DCN. These findings suggest that PLCs may have a wider distribution through mammalian species, and may represent more than just misrouted cells.


Using chromatographic and spectroscopic parameters to characterize preference and kinetics in the adsorption of humic and fulvic acid to goethite.
Humic substances (HS) are very heterogeneous, and preferential adsorption of certain components takes place during their interaction with minerals. Our results indicated that for fulvic acid (FA) the relatively large (3.6-18.2 kDa) particles were preferred in the adsorption to goethite, whereas for humic acid (HA) the intermediate sized (3.6-12.0 kDa) fractions were preferred. Correlations between molar mass (Mw) and specific UV absorption values (SUVA) with ratios of UV light absorbance (E2/E3, E4/E6) were observed. The adsorption did not change the relation between E2/E3 and Mw, E4/E6 and SUVA. The E2/E3 and E4/E6 can probably be used as indicators of molar mass and aromaticity of HS in studying the preferential adsorption. The adsorption of HA and FA to goethite was fast and reached a steady state in about 6 h. The intermediate sized HA particles (3.6-12.0 kDa) were adsorbed quickly, and part of them was subsequently replaced by somewhat larger particles (>50 kDa). For FA, preferential adsorption of relative large particles (3.6-18.2 kDa) took place quickly, and there was a limited substitution by particles with higher aromaticity. Without specifying the property especially the molar mass range of HS under study, confusion can arise from researches using different HS materials.


Special Considerations in Patients with Cranial Neurostimulatory Implants.
Over the past 50 years, incredible progress has been made with implantable devices. Management can become complex, as unique issues arise with interaction of these devices with other devices and technologies. The cochlear implant (CI) is the most commonly implanted device in the head and neck. Because of its internal magnet, CIs can interfere with MRI, causing imaging artifacts, pain, and device complications. Other implants demonstrate similar issues with imaging and co-implantation. This article provides an overview of special considerations regarding neurostimulation devices within the head and neck. We focus on interactions between implantable devices and other technologies or devices.


Localization factor: a new parameter for the quantitative characterization of surface structure with atomic force microscopy (AFM).
In this work we present the possible application of a new parameter called localization factor for the quantitative characterization of surface structures with atomic force microscopy (AFM). For this purpose contact mode AFM images were taken from technologically different polycrystalline gold thin films and were evaluated according to the following parameters: surface roughness (R(a), R(RMS)), roughness factor (f(r)) and localization factor. The localization factor was compared with the other surface parameters. We demonstrate that this new parameter can be used to identically characterize these gold thin film surfaces with contact mode AFM in the 1-1000 μm(2) scan range. The mathematical background and possible application fields of the localization factor are also discussed in our paper.


[Establishment and characterization of human inflammatory breast carcinoma neoplasm transplantation in nude mice].
To establish and characterize human inflammatory breast cancer xenograft in nude mice. Animal studies, Northern and Western blot, zymograms and immunohistochemistry were used in our studies. Human transplantable inflammatory carcinoma were established in nude mice. This xenograft as its human counterpart exhibited striking erythema of the overlying skin, lympho-vascular invasion and other similar biological characteristics. It also exhibited lung metastasis 4-6 weeks after growth. This xenograft was ER, PR, Her-2/neu negative and p53, EGFR positive. Comparative studies of inflammatory breast cancer xenograft with non-inflammatory xenograft indicated 10-20 fold overexpression of E-cadherin and MUC1. This human inflammatory breast carcinoma xenograft will provide an excellent animal model to allow us to further dissect out both the upstream regulatory machinery and downstream effector molecules responsible for the inflammatory carcinoma phenotype.


Availability of zinc from germinated, fermented and autoclaved black-gram (Phaseolus mungo) in rats.
The availability of zinc in the autoclaved black-gram diet was better as compared to germinated, fermented and raw black-gram diets and this may be due to more destruction of phytate.


Giant melanoma: novel problem, same approach.
Thick melanomas are relatively common; however, melanomas greater than 10 cm in size are rarely encountered. Though the size may seem daunting, the work up and principles of wide surgical excision remain the same. Sentinel lymph node biopsy should also be considered in patients with no clinical evidence of metastatic disease.


Emergency medicine and palliative care.
The emergency department cares for seriously ill patients across the trajectory of illness from diagnosis to death or cure. Emergency departments participate in critical illness trajectories that include initiation of life-sustaining therapies as well as caring for patients and families in their final moments of life. Emergency clinicians are uniquely poised to identify critical palliative care interventions to be used when patients and families are most in need with respect to symptom management, decisions regarding intervention and procedures to sustain life and participate in critically important decisions regarding withdrawing and withholding nonbeneficial life-sustaining therapies.


Investigation on biomass steam gasification in a dual fluidized bed reactor with the granular kinetic theory.
The dual fluidized bed (DFB) reactor is promising to convert biomass into high-quality syngas efficiently. In this work, a three-dimensional model is built based on the granular kinetic theory to predict the biomass steam gasification in dual fluidized bed reactors. The model is firstly validated against a series of experimental results. Then, the effects of some essential operation parameters including the biomass flow rate (Fb), the steam to fuel ratio (Rsf) and the gasification temperature (Tg) on the biomass steam gasification properties in a DFB reactor are comprehensively analyzed with the orthogonal method. In the concerned ranges of the operation parameters, the cold gas efficiency is found to be the most sensitive to Fb and least sensitive to Tg. The optimal cold gas efficiency of the DFB gasifier is 82.9% when Fb, Rsf and Tg are 15 kg/h, 1.5 and 900 °C, respectively, and the H2 mole fraction is 46.62%.


An Athlete With Bicuspid Aortic Valve Regurgitation and Left Ventricular Dilatation: A Clinical Conundrum.
The physiologic cardiac adaptations caused by intensive exercise and the pathophysiologic changes caused by significant regurgitant valvular lesions can be challenging to differentiate. We describe the clinical course of an asymptomatic 31-year-old elite triathlete with a moderately regurgitant bicuspid aortic valve and severe left ventricular and aortic dilatation. (Level of Difficulty: Intermediate.).


Effect of transplant education on nurses' attitudes toward organ donation and plans to work with transplant patients.
Despite the increase in rates of solid organ transplantation in the past 2 decades, nurses are inconsistently educated regarding issues of organ donation and posttransplant care. To characterize the attitudes of registered nurses before and after a graduate-level elective on issues in transplantation. Pre-experimental, pretest and posttest interventional study. 30 graduate students, who are registered nurses, who enrolled in a transplant elective at a university in the Southeastern United States. Investigator-designed survey tool consisting of 18 questions delivered in an electronic format. Statistically significant results were seen in nurses' attitudes toward encouraging others to become organ donors (P = .04), preparation to discuss transplantation with others (P< .001), advocacy to discuss transplantation among colleagues (P = .003), confidence in working with transplant patients (P = .005), confidence in speaking to communities about organ donation (P = .001), and plans to encourage others to get involved in transplantation (P = .03). These results support the need for providing focused education on transplantation issues to registered nurses, particularly in the academic setting.


[Functional treatment of crush fracture of the distal femur--case histories].
Functional treatment of crush fractures of distal femur in 2 patients is described. Quadriceps-plasty has been performed in both cases due to the muscle adhesion to bony fragments. Osteosynthesis was contraindicated by the nature of the fracture. Functional treatment resulted in good function and efficient gait in both patients.


Comparison of Repair Index in Cigarette and Waterpipe Smokers: A Bio-Monitoring Assessment Using Human Exfoliated Buccal Mucosa Cells.
Repair index (RI) using DNA changes reveals the activity of carcinogenesis. Cigarette and waterpipe smoking are important contributors to oral cavity malignancy. The RI in cigarette and waterpipe smokers has not been compared so far. The aim of this study was to compare the RI in cigarette and waterpipe smokers using the human exfoliated buccal mucosa cells. The exfoliated buccal mucosa cells of 60 cigarette and waterpipe smokers and 20 nonsmokers were evaluated in a case-control study. The number of micronuclei (MN), broken egg (BE), karyorrhexis (KR), and karyolysis (KL) were counted in 1000 cells from randomly selected fields. The RI = (KL + KR)/(MN + BE) was calculated and compared between subjects and controls. Data were analyzed by one-way analysis of variance (ANOVA), Tukey's Honest Significant Difference (HSD), and Spearman's correlation coefficient test at P < 0.05 probability level. The difference of MN (P < 0.0001), BE (P < 0.0001), KR (P < 0.0001), and KL (P < 0.0001) count was significant between cigarette smokers, waterpipe smokers, and nonsmokers. The RI was significantly different between groups (P = 0.007). The RI was significantly higher in cigarette smokers compared to waterpipe smokers (P = 0.04) and nonsmokers (P = 0.009). The RI was significantly higher in cigarette smokers compared to waterpipe smokers. The finding suggests that due to higher interrupted cellular hemostasis, the risk of carcinoma in waterpipe smokers can be greater than that in cigarette smokers.


Electrochemical sensing platform for naphthol isomers based on in situ growth of ZIF-8 on reduced graphene oxide by a reaction-diffusion technique.
Enhancing the dispersibility and conductivity is an effective solution to develop the application zeolitic imidazole frameworks (ZIF) in the electrochemical field. This work thus employs a novel reaction-diffusion framework (RDF) technique for the in situ growth of ZIF-8 crystals on graphene oxide (GO@ZIF-8) matrixes. In detail, the outer electrolyte of 2-methyl imidazole naturally diffuses into the inner agar gel matrix containing Zn2+ cations and GO nanosheets. The long reaction-diffusion makes the growth of ZIF-8 crystals controllable in a vertical gradient. After thermal treatment, the title product of ZIF-8 in situ grown on reduced graphene oxide (rGO@ZIF-8) is obtained and thus exhibits good dispersibility, high conductivity, large surface area, and more catalytic sites. The glassy carbon electrode (GCE) was modified by casting the rGO@ZIF-8 suspension. The obtained rGO@ZIF-8/GCE displays excellent catalytic activity toward naphthol (NAP) isomers. Under the optimal conditions, the amperometric currents of 1-NAP and 2-NAP demonstrate the good linear relationship in wide ranges of 0.05-12 μM and 0.02-15 μM, respectively. Their limits of detection are as low as 15 and 17 nM, respectively. The fabricated modified electrode exhibits excellent selectivity, stability, and reproducibility. The sensor is also utilized to detect NAP molecules in real water samples and indicates good accuracy and reliability.


Physician-patient-companion communication and decision-making: a systematic review of triadic medical consultations.
To systematically review quantitative and qualitative studies exploring physician-adult patient-adult companion (triadic) communication and/or decision-making within all medical encounters. Studies were identified via database searches and reference lists. One author assessed eligibility of studies, verified by two co-authors. Data were extracted by one author and cross-checked for accuracy. Two authors assessed the quality of included articles using standardized criteria. Of the 8409 titles identified, 52 studies were included. Summary statements and tables were developed for each of five identified themes. Results indicated companions regularly attended consultations, were frequently perceived as helpful, and assumed a variety of roles. However, their involvement often raised challenges. Patients with increased need were more often accompanied. Some companion behaviours were felt to be more helpful (e.g. informational support) and less helpful (e.g. dominating/demanding behaviours), and preferences for involvement varied widely. Triadic communication in medical encounters can be helpful but challenging. Based on analysis of included studies, preliminary strategies for health professionals are proposed. Preliminary strategies for health professionals include (i) encourage/involve companions, (ii) highlight helpful companion behaviours, (iii) clarify and agree upon role preferences of patient/companions. Future studies should develop and evaluate specific strategies for optimizing triadic consultations.


Flipping riboswitches.
Riboswitches are common cis-acting regulatory elements in bacteria. They are made of nascent RNA that changes its conformation in response to direct binding of cognate metabolites. The publication of five high-resolution crystal structures provides a comprehensive view of how riboswitches sense their ligands and points to new challenges in this emerging field.


Male White-shouldered Fairywrens (Malurus alboscapulatus) elevate androgens greater when courting females than during territorial challenges.
Androgens like testosterone mediate suites of physical and behavioral traits across vertebrates, and circulation varies considerably across and within taxa. However, an understanding of the causal factors of variation in circulating testosterone has proven difficult despite decades of research. According to the challenge hypothesis, agonistic interactions between males immediately prior to the breeding season produce the highest levels of testosterone measured during this period. While many studies have provided support for this hypothesis, most species do not respond to male-male competition by elevating testosterone. As a result, a recent revision of the hypothesis ('challenge hypothesis 2.0') places male-female interactions as the primary cause of rapid elevations in testosterone circulation in male vertebrates. Here, we offer a test of both iterations of the challenge hypothesis in a tropical bird species. We first illustrate that male White-shouldered Fairywrens (Malurus alboscapulatus) differ by subspecies in plasma androgen concentrations. Then we use a social network approach to find that males of the subspecies with higher androgens are characterized by greater social interaction scores, including more time aggregating to perform sexual displays. Next, we use a controlled experiment to test whether males respond to simulated territorial intrusion and/or courtship competition contexts by elevating androgens. We found that males elevated androgens during territorial intrusions relative to flushed controls, however, males sampled during courtship competitions had greater plasma androgens both relative to controls and males sampled while defending territories. Ultimately, our results are consistent with challenge hypothesis 2.0, as sexual interactions with extra-pair females were associated with greater elevation of androgens than territorial disputes.


Sirtuin 1 Expression in Canine Mammary Tumors: A Pilot Study.
Sirtuin 1 (SIRT1) is a protein involved in aging, cell protection, and energy metabolism in mammals. Recently, SIRT1 has been intensively studied in medical oncology, but the role of SIRT1 is still controversial, as it has been proposed as both an oncogene and a tumor suppressor. The aim of this study is to investigate the expression of SIRT1 by immunohistochemistry in canine mammary tissues, and by Western blot and immunofluorescence analysis in different canine mammary cell lines. Our results showed a decrease in SIRT1 expression from normal mammary gland tissue, and from benign and well-differentiated malignant tumors (G1) to less differentiated ones (G2-G3). Furthermore, a shift in the subcellular localization of SIRT1 from the nucleus to the cytoplasm was observed in less differentiated malignant tumors. However, further studies are needed to investigate the subcellular localization of SIRT1 in canine cancer cells and the role it may play in oncogenesis in animals.


Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes.
Insufficient regeneration of central nervous system (CNS) axons contributes to persisting neurological dysfunction after spinal cord injury (SCI). Peripheral nerve grafts (PNGs) support regeneration by thousands of injured intraspinal axons and help them bypass some of the extracellular barriers that form after SCI. However this number represents but a small portion of the total number of axons that are injured. Here we tested if rhythmic sensory stimulation during cycling exercise would boost the intrinsic regenerative state of neurons to enhance axon regeneration into PNGs after a lower thoracic (T12) spinal transection of adult rats. Using True Blue retrograde tracing, we show that 4 weeks of cycling improves regeneration into a PNG from lumbar interneurons but not by primary sensory neurons. The majority of neurons that regenerate their axon are within 5 mm of the lesion and their number increased 70% with exercise. Importantly propriospinal neurons in more distant regions (5-20 mm from the lesion) that routinely exhibit very limited regeneration responded to exercise by increasing the number of regenerating neurons by 900%. There was no exercise-associated increase in regeneration from sensory neurons. Analyses using fluorescent in situ hybridization showed that this increase in regenerative response is associated with changes in levels of mRNAs encoding the regeneration associated genes (RAGs) GAP43, β-actin and Neuritin. While propriospinal neurons showed increased mRNA levels in response to SCI alone and then to grafting and exercise, sensory neurons did not respond to SCI, but there was a response to the presence of a PNG. Thus, exercise is a non-invasive approach to modulate gene expression in injured neurons leading to an increase in regeneration. This sets the stage for future studies to test whether exercise will promote axon outgrowth beyond the PNG and reconnection with spinal cord neurons, thereby demonstrating a potential clinical application of this combined therapeutic intervention.


Management of lymphocysts after radical gynecologic surgery.
Pelvic lymphocysts developed in 3 of 124 patients undergoing radical surgery for cervical cancer. All were managed by percutaneous aspiration under local anesthesia in an outpatient setting. Sclerosis was required in one patient. This management plan is superior to laparotomy in being less morbid and equally effective.


Intestinal-Type Adenocarcinoma: Classification, Immunophenotype, Molecular Features and Differential Diagnosis.
Intestinal-type adenocarcinoma is the second most frequent sinonasal adenocarcinoma. High incidence of these tumors is seen among workers with occupational wood dust exposure, particularly of hardwood dusts. Intestinal-type adenocarcinoma has striking histomorphologic and immunophenotypic similarities with colorectal adenocarcinomas, but on the level of molecular pathologic mechanisms these tumors have their own specific features different from gastrointestinal tumors. This article provides an update on current histopathologic classification of intestinal-type adenocarcinomas, their immunophenotypic properties, recent advances in molecular pathologic features and differential diagnostic considerations.


Gliogenesis during embryonic development in the rat.
With the aid of thymidine-H3 autoradiography gliogenesis in the rat brain was seen to start during embryonic stages, which might continue into the postnatal stages of development. Gliogenesis followed a caudo-rostral gradient closely following neurogenesis. Ependymogenesis was found to occur in parallel with gliogenesis.


Influence of high natural field temperature during grain filling stage on the morphological structure and physicochemical properties of rice (Oryza sativa L.) starch.
This study investigated the effects of natural high temperature in the field during grain filling stage on the morphological structure and physicochemical properties of rice starch. High natural field temperature during rice grain filling stage resulted in poor processing and appearance quality, higher gelatinization properties including gelatinization temperature, gelatinization enthalpy, swelling power, and water solubility due to the reduction of amylose content. High temperature decreased the setback and trough viscosities, and increased breakdown, implying that the pasting properties were slightly better. High temperature did not change the starch crystalline type, while it significantly affected relative crystallinity, as well as pitting and unevenness on the surface of the starch granules with lower granule size. The above results imply that high temperature can degrade cooking and eating quality, and increase pasting properties of starch slightly.


Antibiotic resistance genes (ARGs) and their associated environmental factors in the Yangtze Estuary, China: From inlet to outlet.
The occurrence of antibiotic resistance genes (ARGs) and their associated environmental factors in estuaries are poorly understood. In this study, we comprehensively analyzed ARGs in both water and sediments from inlet to outlet of the Yangtze Estuary, China. The relative abundances of ARGs were higher in the turbidity maximum zone (TMZ) than other sites, implying that suspended particulate matter (SPM) was the major reservoir for ARGs in water. ARGs showed an increasing trend from inlet to outlet in sediments. Positively correlation between intI1 and sul1 in both water and sediments indicated that sul1 may be regulated by intI1. Correlation analysis and redundancy analysis showed that the spatial variations of estuarine ARGs were positively correlated with sample properties (e.g., temperature, SPM, pH) and chemical pollutants (e.g., heavy metals and antibiotic residues), among which chemical pollutants were the major drivers for the ARG distribution in both water and sediments.


Detection of selenium-containing biological constituents by high-performance liquid chromatography-plasma source mass spectrometry.
Mass spectrometry with inductively coupled argon plasma excitation (ICP-MS) was used as a multi-element specific detection method for HPLC for the speciation of selenium (Se) in biological samples. Se-containing biological constituents were separated on a size-exclusion column and were detected Se-specifically at m/z 78 and 82 for natural abundance 78Se and 82Se, respectively. Se peaks not identical with known authentic samples were detected. Diets with different Se contents induced changes in the distributions Se-containing constituents more in urine, kidney and liver samples than in plasma and red blood cells samples. The results indicate that HPLC-ICP-MS is a specific and sensitive means for the speciation of Se-containing biological constituents.


Thermal energetics and behaviour of a small, insectivorous marsupial in response to the interacting risks of starvation and predation.
Central to understanding animal ecology is how prey cope with the interacting risks of starvation and predation. This trade-off is modulated by the energy requirements of prey, yet relatively few studies have incorporated physiological mechanisms for energy savings when considering the behavioural response of prey to predation risk. In our study, we aimed to determine individual variation in behaviour, resting metabolism, body temperature and response to 24-h starvation within a captive population of fat-tailed dunnarts (Sminthopsis crassicaudata; 15-g insectivorous marsupials), and then, using semi-outdoor enclosures, test whether foraging effort and thermal energetics are adjusted in response to manipulation of ground cover, which for small mammals can simulate predation risk. We found that, under the low cover (high predation risk) treatment, dunnarts consumed less food and employed a greater daily reduction in body temperature between their active and rest phase. This result supports the hypothesis that rest-phase thermoregulatory energy savings are employed, even when food is available, if predation risk is perceived to increase the cost of foraging. Individuals exhibited correlated variation along two orthogonal axes incorporating the measured behavioural and metabolic variables, but these differences were not correlated with responses to starvation and predation risk. Our experiment demonstrates that flexibility in daily energy requirements provided by heterothermy can have important consequences for how small mammals respond to both starvation and predation risks. Such challenges are amplified in degraded habitat with introduced predators, making the capacity for heterothermy an even more important mechanism for survival.


Functional Age Predicted by Electronic Short Physical Performance Battery Can Detect Frailty Status in Older Adults.
The importance of evaluating frailty status of older adults in clinical practice has been gaining attention with cumulative evidence showing its relevance in clinical outcomes and decision-making. We aimed to develop and validate whether the functional age predicted by an electronic continuous short physical performance battery (eSPPB) could predict frailty status. We reviewed medical records of outpatients (N=834) of Asan Medical Center, aged 51-95 years. We used the eSPPB data of 717 patients as a development cohort, and that of 117 patients, who also underwent comprehensive geriatric assessments, as a validation cohort. Frailty index was calculated by counting deficits of 45 geriatric items including comorbidities, daily functions, mobility, mood, and cognition. For functional age, we used balance score (0-4), gait speed (m/s), and stand-up time (s) measured 5 times in the chair rise test. From the development cohort, we established a functional age using the formula (83.61 - 1.98*[balance score] - 5.21*[gait speed] + 0.23*[stand-up time]), by multivariate linear regression analysis with chronological age as a dependent variable (R2 = 0.233). In the validation cohort, the functional age positively correlated with frailty index (p < 0.001). C-statistics classifying frailty (defined as frailty index ≥0.25) was higher (p < 0.001) with functional age (0.912) than that with chronological age (0.637). A cut-off functional age of ≥77.2 years maximized Youden's J when screening for frailty, with sensitivity of 94.4% and specificity of 80.8%. A newly developed functional age predictor using eSPPB parameters can predict the frailty status as defined by the deficit accumulation method and may serve as a physical biomarker of human aging.


Dextrocardia, aortopulmonary window with transposition of the great arteries, case report.
Transposition of the great arteries (D-TGA) in combination with aortopulmonary window (APW) is a very rare entity and carries high morbidity and mortality. Only few cases have been reported with this association. We report the first case of D-TGA and APW with mirror image dextrocardia which was repaired successfully.


Complete Atrioventricular Block After Kidney Transplantation in a Patient With Fabry Disease Receiving Enzyme Replacement Therapy: A Case Report.
Fabry disease (FD) is a rare X-linked lysosomal storage disorder that results from the deficient activity of the lysosomal enzyme α-galactosidase A (α-Gal A) enzyme. Kidney transplantation is an option for treating end-stage renal disease in patients with FD. However, only a few cases of kidney transplantation have been reported involving patients with FD and end-stage renal disease and cardiomyopathy after enzyme replacement therapy. A 53-year-old man who underwent peritoneal dialysis was referred to our department because his brother was diagnosed with FD. The diagnosis of FD was also confirmed in our patient on account of the reduced leukocyte α-Gal A enzyme activity and mutation in the α-galactosidase A gene (p.Arg301Gln). Though our patient had end-stage renal disease, he received enzyme replacement therapy with 1 mg/kg agalsidase-β every 2 weeks (Fabrazyme; Genzyme Co, Mass, USA) owing to markedly diffuse cardiac hypertrophy. Six years later, he underwent successful deceased-donor kidney transplantation. The post-transplantation course was uneventful, 4 months after transplantation. However, though he showed T-cell-mediated rejection on kidney biopsy, lamellar lysosomal inclusions were not present in vascular endothelial cells. After several months, a permanent pacemaker was inserted owing to a complete atrioventricular block; the patient died of sepsis and candidemia 1 year later. Deceased-donor kidney transplantation was successfully performed in an FD patient with sustained enzyme replacement therapy. However, owing to high cardiac morbidity and infection risks even after enzyme replacement therapy, close monitoring of these risks is essential for increasing patient survival after kidney transplantation.


Sulfonylurea for improving neurological features in neonatal diabetes: A systematic review and meta-analyses.
In monogenic diabetes due to KCNJ11 and ABCC8 mutations that impair KATP- channel function, sulfonylureas improve long-term glycemic control. Although KATP channels are extensively expressed in the brain, the effect of sulfonylureas on neurological function has varied widely. We evaluated published evidence about potential effects of sulfonylureas on neurological features, especially epilepsy, cognition, motor function and muscular tone, visuo-motor integration, and attention deficits in children and adults with KCNJ11 and ABCC8-related neonatal-onset diabetes mellitus. We conducted a systematic review and meta-analyses of the literature (PROSPERO, CRD42021254782), including individual-patient data, according to PRISMA, using RevMan software. We also graded the level of evidence. We selected 34 of 776 publications. The evaluation of global neurological function before and after sulfonylurea (glibenclamide) treatment in 114 patients yielded a risk difference (RD) of 58% (95%CI, 43%-74%; I2 = 54%) overall and 73% (95%CI, 32%-113%; I2 = 0%) in the subgroup younger than 4 years; the level of evidence was moderate and high, respectively. EEG studies of epilepsy showed a RD of 56% (95%CI, 23%-89%; I2 = 34%) in patients with KCNJ11 mutations, with a high quality of evidence. For hypotonia and motor function, the RDs were 90% (95%CI, 69%-111%; I2 = 0%) and 73% (95%CI, 35%-111%; I2 = 0%), respectively, with a high level of evidence. Glibenclamide significantly improved neurological abnormalities in patients with neonatal-onset diabetes due to KCNJ11 or ABCC8 mutations. Hypotonia was the symptom that responded best. Earlier treatment initiation was associated with greater benefits.


Nutrient restriction induces failure of reproductive function and molecular changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.
People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ≥ 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor α, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function.


Effect of Sleep State and Position on Obstructive Respiratory Events Distribution in Adolescent Children.
This study aimed to examine the effect of sleep state (rapid eye movement [REM] versus non-rapid eye movement [NREM]) and position (supine versus non-supine position) on obstructive respiratory events distribution in adolescent population (ages 12 to 18 y). This was a retrospective study that included 150 subjects between the ages of 12 to 18 y with an apnea-hypopnea index (AHI) > 1/h. Subjects using REM sleep-suppressant medications and subjects with history of genetic anomalies or craniofacial syndromes were excluded. The median age was 14 y with interquartile range (IQR) of 13 to 16 y, 56% of patients were males and the median body mass index (BMI) z-score was 2.35 (IQR: 1.71-2.59) with 77.3% of patients fulfilling obesity criteria. Respiratory obstructive events were more common in REM sleep. The median REM obstructive AHI (OAHI) was 8.9 events per hour (IQR: 2.74-22.8), whereas the median NREM OAHI was 3.2 events per hour (IQR: 1.44-8.29; p < 0.001). African American adolescents had more REM obstructive events with median REM OAHI of 13.2 events per hour (IQR: 4.88-30.6), which was significantly higher than median REM OAHI of 4.94 (IQR: 2.05-11.36; p = 0.004) in white adolescents. Obstructive events were more common in supine position with higher median supine OAHI of 6.55 (IQR: 4-17.73) when compared to median non-supine OAHI of 2.94 (IQR: 1-6.54; p < 0.001). This study shows that sleep related obstructive respiratory events in the adolescents (12 to 18 y of age) occur predominantly in REM sleep and in supine position.


Biotransformation of sophoricoside in Fructus sophorae by the fungus Schizophyllum commune.
Biotransformation of sophoricoside in Fructus sophorae was performed with Schizophyllum commune. Sophoricoside was firstly metabolized to 4',5,7-trihydroxyisoflavone (2), and then to 4',7-dihydroxy-5-methoxyisoflavone (3) and 5,7-dihydroxy-4'-methoxyisoflavone (4) as determined by NMR and MS analyzes. The content of compound (2) was increased by more than 30-fold, and compound (3) is a new product that showed good cytotoxic activity with an IC(50) of 12.1 nmol/ml against MCF-7 cells.


11C-5-hydroxytryptophan positron emission tomography after radiofrequency ablation of neuroendocrine tumor liver metastases.
The aim was to assess the feasibility of (11)C-5-hydroxy-tryptophan positron emission tomography ((11)C-5-HTP-PET) in the follow-up after radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumors (NETs). Contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasound (CEUS) are commonly used to evaluate the liver after RFA of NETs. In general, (11)C-5-HTP-PET is more sensitive in the visualization of NETs, but no studies have investigated its role after RFA. Six consecutive patients with liver metastases from NETs were subjected to RFA treatment. All patients underwent baseline imaging before RFA and on two occasions (1-2 and 6-11 months) after RFA. The imaging consisted of (11)C-5-HTP-PET, CEUS and CECT on all three occasions. Thirty RFA areas were evaluated, and residual tumors (RTs) were depicted in eight areas (22%). (11)C-5-HTP-PET depicted RTs after RFA with maximum sensitivity (100%) and specificity (100%), using radiological follow-up as the gold standard. (11)C-5-HTP-PET detected five out of eight RTs earlier than CECT or CEUS. In general, the sensitivity of (11)C-5-HTP-PET exceeded that of CECT and CEUS for early visualization of NET liver metastases. (11)C-5-HTP-PET can be used in the follow-up after RFA for the purpose of detecting RT, and it provides additional information to CEUS and CECT by detecting new lesions.


Admission standard electrocardiogram for early risk stratification in patients with unstable coronary artery disease not eligible for acute revascularization therapy: a TRIM substudy. ThRombin Inhibition in Myocardial Infarction.
The purpose of this study was to determine the prognostic capacity of a single electrocardiogram (ECG) obtained early after admission to the hospital in patients suspected of non-Q-wave myocardial infarction and unstable angina pectoris. Six hundred twenty-nine patients from the TRIM study were included. The patients were divided into subgroups on the basis of ST-segment changes in the inclusion ECG. Death, acute myocardial infarction, or refractory angina (despite treatment) were registered during a follow-up period of 30 days. Patients with ST depression had a significantly higher event rate compared with patients with other ECG changes or with normal ECG results. The difference in event rates between patients with ST depression and patients without ST depression regarding the composite of death and acute myocardial infarction was highly significant (P =.0008). A significant association between the magnitude of the ST-segment depression (in millimeters) and the risk of cardiac events was also demonstrated. Multivariate analysis proved ST depression early after admission to be an independent predictor of high risk. In patients with unstable coronary artery disease, ST-segment depression at admission is a strong predictor of early (30 days) cardiac events and the extent of ST depression carries important prognostic information as well.


Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy.
Metabolic cardiomyopathy is an emerging cause of heart failure in patients with obesity, insulin resistance, and diabetes. It is characterized by impaired myocardial metabolic flexibility, intramyocardial triglyceride accumulation, and lipotoxic damage in association with structural and functional alterations of the heart, unrelated to hypertension, coronary artery disease, and other cardiovascular diseases. Oxidative stress plays an important role in the development and progression of metabolic cardiomyopathy. Mitochondria are the most significant sources of reactive oxygen species (ROS) in cardiomyocytes. Disturbances in myocardial substrate metabolism induce mitochondrial adaptation and dysfunction, manifested as a mismatch between mitochondrial fatty acid oxidation and the electron transport chain (ETC) activity, which facilitates ROS production within the ETC components. In addition, non-ETC sources of mitochondrial ROS, such as β-oxidation of fatty acids, may also produce a considerable quantity of ROS in metabolic cardiomyopathy. Augmented ROS production in cardiomyocytes can induce a variety of effects, including the programming of myocardial energy substrate metabolism, modulation of metabolic inflammation, redox modification of ion channels and transporters, and cardiomyocyte apoptosis, ultimately leading to the structural and functional alterations of the heart. Based on the above mechanistic views, the present review summarizes the current understanding of the mechanisms underlying metabolic cardiomyopathy, focusing on the role of oxidative stress.


Evaluation of the APTIMA Combo 2 Assay using self-administered vaginal swabs for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae.
We report on the performance of the APTIMA Combo 2 assay for the detection of chlamydial infection and gonorrhea using self-administered vaginal specimens in specimen transport medium and specimen kept dry. The results are compared with the results using the Amplicor assay and the BD ProbeTec assay™.


DNA sequence comparison of the regulatory signals at the 5' end of the mouse and chick alpha 2 type I collagen genes.
We have isolated a DNA segment that contains the presumptive transcriptional and translational control signals located at the 5' end of the mouse alpha 2(I) collagen gene. The DNA sequence of the first exon of this gene and of 400 base pairs preceding the start of transcription was compared with an analogous sequence in the chick alpha 2(I) collagen gene. The most striking similarity is a block of 68 nucleotides surrounding the translation initiation site which is perfectly conserved except for four contiguous nucleotides in the middle of the conserved sequence. These four nonconserved bases lie between the arms of a perfect inverted repeat with nine nucleotides in each arm. The very high degree of sequence conservation of this segment suggests that both the inverted repeat and the rest of the perfectly conserved sequence have a regulatory role, possibly in translation. The segment preceding the transcription start shows blocks of similarities interspersed with dissimilar sequences. The conserved sequences include the TATA box, CAT box, a G/C rich sequence around -110, a segment that contains almost exclusively pyrimidines on one strand and is sensitive to endonuclease S1 in both promoters, and several other segments that extend to 350 base pairs preceding the start of transcription. Although the distances between these regions of similarity and the TATA box are not the same in the two promoters, we believe the conserved sequences play a role in the transcriptional activation of this gene.


Genital vitiligo in children: Factors associated with generalized, non-segmental vitiligo.
It remains uncertain as to whether genital vitiligo of childhood is segmental or a forme fruste of non-segmental disease. This type of vitiligo is sometimes termed figure-of-eight disease due to female predominance and perineal and perianal hypopigmentation or depigmentation around two orifices, the anal and vaginal introitus. The objective of this series was to categorize the features of genital-limited vitiligo of childhood including comorbidities, family history, and long-term course. IRB-approved retrospective chart review of vitiligo cases. Eight cases of vitiligo that began in childhood in the genital area were identified, including clinical course and comorbidities. Involvement of the contiguous skin, including inner thighs, buttocks, and scrotum, was noted in all males. In females, only 1 patient had other sites of vitiligo, which was a solitary lesion on the chest. Therapeutic response to topical corticosteroids for perianal skin was seen in five of six children and topical calcineurin inhibitors with or without calcipotriene in four out of four patients. Segmental disease limited to the genitalia was more common in females than males, suggesting that perhaps intervention and work-up for comorbid autoimmune diseases may be required for males with genital-limited vitiligo at onset, but may be deferred in females and added if observation of spread is noted. Differentiation from lichen sclerosus et atrophicus may require biopsy.


Pro-apoptotic Bax molecules densely populate the edges of membrane pores.
How the pro-apoptotic Bax protein permeabilizes the mitochondrial outer membrane is not fully understood. Previously, using cryo-electron microscopy (cryo-EM), we showed that activated Bax forms large, growing pores. Whether formed in liposomes or in mitochondrial outer membranes, Bax-induced pores exhibit the same morphology, with negative curvature flanking the edges and with no visible protein structure protruding from the membranes. Here we used cryo-EM to show that gold-labeled Bax molecules, after activation by Bid, became localized strictly at pore edges. This argues that Bax acts at short range to deform the membrane. Also, Bax molecules populated the walls of both small and large pores at the same density, implying that Bax is continuously recruited to the pores as they widen. Moreover, because all Bax molecules became oligomerized after membrane insertion, we infer that Bax oligomers are present at pore edges. We suggest that oligomerization may promote pore enlargement.


Impact of mental disorders on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study.
It is unclear whether mental disorders are an independent risk factor for atrial fibrillation (AF) in patients with diabetes. We aimed to investigate whether patients with diabetes who have mental disorders have an increased risk for AF. Using the Korea National Health Insurance Service database, we enrolled 2,512,690 patients diagnosed with diabetes without AF between 2009 and 2012. We assessed five mental disorders: depression, insomnia, anxiety, bipolar disorder, and schizophrenia. Newly diagnosed AF was identified during the follow-up period, and multivariate Cox regression analysis was performed. Among the 2,512,690 patients (mean age 57.2 ± 12.3 years; 60.1% men), 828,929 (33.0%) had mental disorders. Among the five mental disorders, anxiety (68.1%) was the most common, followed by insomnia (40.0%). During a median follow-up duration of 7.1 years, new-onset AF was diagnosed in 79,525 patients (4.66 per 1,000 person-years). Patients with diabetes who had mental disorders showed a higher risk for AF (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.17-1.21; p-value < 0.001). Depression, insomnia, and anxiety were significantly associated with higher risk for AF (adjusted HR [95% CI]: 1.15 [1.12-1.17], 1.15 [1.13-1.18], and 1.19 [1.67-1.21], respectively; all p-values < 0.001), whereas bipolar disorder and schizophrenia were not. Mental disorders, especially depression, insomnia, and anxiety, were associated with an increased risk for AF in patients with diabetes. Greater awareness with a prompt diagnosis of AF should be considered for patients with both DM and mental disorders.


Experimental study on malfunction of pacemakers due to exposure to different external magnetic fields.
Cardiac pacemaker malfunction due to exposure to magnetic fields may cause serious problems in some work environments for workers having cardiac pacemakers. The aim of this study was to find the magnetic field interference thresholds for several commonly used pacemaker models. We investigated 16 pacemakers from three different manufacturers with the frequency range of 2 to 1,000 Hz, using sinusoidal, pulse, ramp, and square waveforms. The magnetic fields were produced by a computer-controlled Helmholtz coil system. Pacemaker malfunction occurred in six of 16 pacemakers. Interaction developed almost immediately after high-intensity magnetic field exposure started. With each waveform, at least two pacemakers exhibited interference. In most exposure settings, there was no interference at magnetic field levels below the international occupational safety limits. Nevertheless, some frequencies using ramp or square waveforms interfered with pacemakers even at levels below public exposure limits. The occurrence of interference depended greatly on the waveform, frequency, magnetic field intensity, and the sensing configuration of the pacemaker. Unipolar configurations were more susceptible for interference than the bipolar ones. In addition, magnetic fields perpendicular to the pacemaker loops were more likely to cause interference than parallel fields. There is a need for further investigations on pacemaker interference caused by different external magnetic fields to ensure safe working environment to workers with a pacemaker.