Heart Failure With Midrange Ejection Fraction: Prior Left Ventricular Ejection Fraction and Prognosis.
Aims: Evidence-based guidelines for heart failure management depend mainly on current left ventricular ejection fraction (LVEF). However, fewer studies have examined the impact of prior LVEF. Patients may enter the heart failure with midrange ejection fraction (HFmrEF) category when heart failure with preserved ejection fraction (HFpEF) deteriorates or heart failure with reduced ejection fraction (HFrEF) improves. In this study, we examined the association between change in LVEF and adverse outcomes. Methods: HFmrEF patients with at least two or more echocardiograms 3 months apart at the First Affiliated Hospital of Dalian Medical University between September 1, 2015 and November 30, 2019 were identified. According to the prior LVEF, the subjects were divided into improved group (prior LVEF < 40%), stable group (prior LVEF between 40 and 50%), and deteriorated group (prior LVEF ≥ 50%). The primary outcomes were cardiovascular death, all-cause mortality, hospitalization for worsening heart failure, and composite event of all-cause mortality or all-cause hospitalization. Results: A total of 1,168 HFmrEF patients (67.04% male, mean age 63.60 ± 12.18 years) were included. The percentages of improved, stable, and deteriorated group were 310 (26.54%), 334 (28.60%), and 524 (44.86%), respectively. After a period of follow-up, 208 patients (17.81%) died and 500 patients met the composite endpoint. The rates of all-cause mortality were 35 (11.29%), 55 (16.47%), and 118 (22.52%), and the composite outcome was 102 (32.90%), 145 (43.41%), and 253 (48.28%) for the improved, stable, and deteriorated groups, respectively. Cox regression analysis showed that the deterioration group had higher risk of cardiovascular death (HR: 1.707, 95% CI: 1.064-2.739, P = 0.027), all-cause death (HR 1.948, 95% CI 1.335-2.840, P = 0.001), and composite outcome (HR 1.379, 95% CI 1.096-1.736, P = 0.006) compared to the improvement group. The association still remained significant after fully adjusted for both all-cause mortality (HR = 1.899, 95% CI 1.247-2.893, P = 0.003) and composite outcome (HR: 1.324, 95% CI: 1.020-1.718, P = 0.035). Conclusion: HFmrEF patients are heterogeneous with three different subsets identified, each with different outcomes. Strategies for managing HFmrEF should include previously measured LVEF to allow stratification based on direction changes in LVEF to better optimize treatment.


Wnt/β-catenin signaling pathway is activated in the progress of mandibular condylar cartilage degeneration and subchondral bone loss induced by overloaded functional orthopedic force (OFOF).
To explore the role of Wnt/β-catenin signaling pathway in the pathogenesis and progression of temporomandibular joint osteoarthritis (TMJ OA) caused by overloaded force. We generated a rat model of forward mandibular extension device to induce TMJ OA by overloaded force. Condylar cartilage samples were collected at 2wk, 4wk, and 8wk after appliances were installed. Changes of the condylar cartilage and subchondral bone were evaluated by hematoxylin and eosin (HE), Safranin O and Fast Green staining (SO&FG), micro-CT, tartrate resistant acid phosphatase (TRAP) staining. The expression levels of β-catenin, COL-2, MMP3 and sclerostin (SOST) were detected by immunohistochemistry (IHC) and PCR. HE, SO&FG, micro-CT, OARSI and Mankin scores showed that the condyle cartilage layer was significantly thinner and proteoglycan loss in the overloded group. TRAP staining exhibited that the number of positive osteoclasts increased and OPG level decreased in the overload group. IHC, PCR showed that the expression of COL2 and SOST decreased, while MMP3 and β-catenin increased in the overload group. Wnt/β-catenin signaling pathway is activated in the progress of mandibular condylar cartilage degeneration and subchondral bone loss induced by overloaded functional orthopedic force (OFOF).


Women's priorities regarding physician behavior and their preference for a female physician.
Studies report that women have diverging preferences for physician gender. The present study explores some aspects of how women's preferences for physician gender are formed. Using data from a postal survey among Norwegian women, the association between preferences for physician gender and women's priorities regarding physician behavior is examined. Women who, in particular, value their physicians' democratic attitudes tend to prefer female physicians, in contrast to those who prefer a more dominating physician role. Surprisingly, women who especially emphasize the caring qualities of their physicians, do not have strong preferences for a female physician.


Isolation and characterization of the Legionella pneumophila outer membrane.
A whole cell lysate of Legionella pneumophila was fractionated into five membrane fractions by sucrose gradient centrifugation. Membranes were characterized by enzymatic, chemical, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Two forms of cytoplasmic membrane (CM-1, CM-2), a band of intermediate density (IM), and two forms of outer membrane (OM-1, OM-2) were detected. The CM-1 fraction was the purest form of cytoplasmic membrane, and fraction CM-2 was primarily cytoplasmic membrane associated with small amounts of peptidoglycan. The IM, CM-1, and CM-2 fractions were enriched in peptidoglycan, and the amount of carbohydrate and 2-keto-3-deoxyoctonic acid was not appreciably greater in outer membrane relative to cytoplasmic membrane. Phosphatidylethanolamine and phosphatidylcholine were found to be the major phospholipids in the membrane fractions. The major outer membrane proteins had molecular sizes of 29,000 and 33,000 daltons and were both modified by heating. The 29,000-dalton protein was tightly associated with the peptidoglycan and was equally distributed in the IM, OM-1, and OM-2.


Polychlorinated biphenyl residues in various fatty foods consumed in Guipúzcoa, the Basque Country (Spain).
Three congeners of polychlorinated biphenyls (PCBs)--the 2, 2', 3, 4, 4', 5'-, 2, 2', 4, 4', 5, 5'-hexachloro, and 2, 2', 3, 4, 4', 5, 5'-heptachlorobiphenyls--were determined in 18 samples of butter, 44 of fish (hake and anchovy) and 24 of egg, all of which came from markets in Guipúzcoa. The total content as Araclor 1260 was also determined. Quantitation was carried out by gas chromatography in a capillary column and electron capture detector. The total content in butter ranged from 20 to 60 ng/g (fat basis), in fish from 10 to 250 ng/g (edible part), and in eggs from 1 to 10 ng/g (edible part). None of these exceeded the tolerance limits established by the Canadian Government Guideline and USFDA.


Precore mutation of hepatitis B virus may contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis.
Studies focused on the correlation of mutations in the genome of Hepatitis B Virus (HBV) like Pre-S mutation, Basal Core promoter (BCP), Enhancer II (EnhII), especially Precore mutation, with the risk of hepatocellular carcinoma (HCC) have triggered stiff controversies. With an increasing number of studies in this field recently, we conducted this meta-analysis to appraise the correlations. We searched the commonly used databases both in English and Chinese till February 1(st), 2012. Meta-analysis was performed in fixed/random-effects models using STATA 10.0. Publication bias was examined through Egger's test and Begg's funnel plot. In total, 85 case-control studies were included involving 16745 HBV-infected patients, of whom 5781 had HCC. Statistically significant correlations were observed in Precore mutation G1896A (OR = 1.46, 95% confidence interval [CI] = 1.15-1.85, P(OR) = 0.002), G1899A (OR = 3.13, 95%CI = 2.38-4.13, P(OR)<0.001) and Pre-S mutation especially Pre-S1 deletion (OR = 2.94, 95%CI = 2.22 to 3.89) and Pre-S2 deletion (OR = 3.02, 95%CI = 2.03 to 4.50). Similar correlation existed between BCP double mutation A1762T/G1764A, T1753V, C1653T and HCC. In subgroup analysis, the Asians, genotype C or HBeAg positive patients with certain above mutations may be more susceptible to HCC. Besides, the mutations like G1896A and BCP double mutation may be associated with the progression of the liver diseases. Precore mutation G1896A, G1899A, deletions in Pre-S region as well as the other commonly seen mutations correlated with the increased risk of HCC, especially in Asians and may predict the progression of the liver disease.


The activation-induced deaminase functions in a postcleavage step of the somatic hypermutation process.
Activation of B cells by antigen fuels two distinct molecular modifications of immunoglobulin (Ig) genes. Class-switch recombination (CSR) replaces the Ig(mu) heavy chain constant region with a downstream constant region gene, thereby altering the effector function of the resulting antibodies. Somatic hypermutation (SHM) introduces point mutations into the variable regions of Ig genes, thereby changing the affinity of antibody for antigen. Mechanistic overlap between the two reactions has been suggested by the finding that both require the activation-induced cytidine deaminase (AID). It has been proposed that AID initiates both CSR and SHM by activating a common nuclease. Here we provide evidence that cells lacking AID, or expressing a dominant negative form of the protein, are still able to incur DNA lesions in SHM target sequences. The results indicate that an intact cytidine deaminase motif is required for AID function, and that AID acts downstream of the initial DNA lesions in SHM.


[A case of metastatic gastric cancer from breast cancer treated with proximal gastrectomy].
We report a case of a 72-year-old woman with breast cancer who developed significant stenosis due to gastric cardia metastasis. The patient had undergone radical mastectomy for breast cancer when she was 53 years old and had developed postoperative recurrent diseases in the sternum and lung when she was 62 years old. Nineteen years after mastectomy, computed tomography (CT) scans showed gastric cardia metastasis. As symptoms of cardiac stenosis gradually developed, we performed proximal gastrectomy. The specimen was histologically diagnosed as estrogen receptor( ER)-positive scirrhous carcinoma that had metastasized from the breast cancer. The patient resumed oral intake of food after surgery. Surgical treatment might be useful to improve the quality of life of patients with metastatic gastric tumor.


A survey of stakeholder perspectives on exoskeleton technology.
Exoskeleton technology has potential benefits for wheelchair users' health and mobility. However, there are practical barriers to their everyday use as a mobility device. To further understand potential exoskeleton use, and facilitate the development of new technologies, a study was undertaken to explore perspectives of wheelchair users and healthcare professionals on reasons for use of exoskeleton technology, and the importance of a variety of device characteristics. An online survey with quantitative and qualitative components was conducted with wheelchair users and healthcare professionals working directly with individuals with mobility impairments. Respondents rated whether they would use or recommend an exoskeleton for four potential reasons. Seventeen design features were rated and compared in terms of their importance. An exploratory factor analysis was conducted to categorize the 17 design features into meaningful groupings. Content analysis was used to identify themes for the open ended questions regarding reasons for use of an exoskeleton. 481 survey responses were analyzed, 354 from wheelchair users and 127 from healthcare professionals. The most highly rated reason for potential use or recommendation of an exoskeleton was health benefits. Of the design features, 4 had a median rating of very important: minimization of falls risk, comfort, putting on/taking off the device, and purchase cost. Factor analysis identified two main categories of design features: Functional Activities and Technology Characteristics. Qualitative findings indicated that health and physical benefits, use for activity and access reasons, and psychosocial benefits were important considerations in whether to use or recommend an exoskeleton. This study emphasizes the importance of developing future exoskeletons that are comfortable, affordable, minimize fall risk, and enable functional activities. Findings from this study can be utilized to inform the priorities for future development of this technology.


Synthesis and Evaluation of Glycosyl Luciferins.
Measuring glycosidase activity is important to monitor any aberrations in carbohydrate hydrolase activity, but also for the screening of potential glycosidase inhibitors. To this end, synthetic substrates are needed which provide an enzyme-dependent read-out upon hydrolysis by the glycosidase. Herein, we present two new routes for the synthesis of caged luminescent carbohydrates, which can be used for determining glycosidase activity with a luminescent reporter molecule. The substrates were validated with glycosidase and revealed a clear linear range and enzyme-dependent signal upon the in situ generation of the luciferin moiety from the corresponding nitrile precursors. Besides, we showed that these compounds could directly be synthesized from unprotected glycosyl-α-fluorides in a two-step procedure with yields up to 75 %. The intermediate methyl imidate appeared a key intermediate which also reacted with d-cysteine to give the corresponding d-luciferin substrate rendering this a highly attractive method for synthesizing glycosyl luciferins in good yields.


How does financial burden influence the crash rate among taxi drivers? A self-reported questionnaire study in China.
Objective: Taxis play an important role in the transportation system of China, but they have a relatively high accident rate. The current study discusses the driver's financial burden in the Chinese context and explores its correlation with working conditions, risky driving behavior, and other characteristics of taxi drivers who are involved in accidents.Method: A total of 2,391 taxi drivers from 29 companies in four Chinese cities were interviewed and then asked to complete a questionnaire concerning their socio-demographic characteristics, working conditions, risky driving behavior, and accident frequency during the previous two years. Given the increase in the management fee (measured in CNY) charged by taxi companies, the drivers were divided into three groups: the "less than 150" group, the" 150 to 180" group and the "over 180" group, where were named Group 1, Group 2 and Group 3, respectively. Finally, the zero-inflated Poisson model was used to investigate the factors that contributed to the accident rate for each group.Result: The significant factors that lead to accidents differed significantly for drivers with different levels of financial burden. First, most of the factors were weakly correlated with the crash rate among Group 1 drivers. Second, many factors related to working conditions and risky driving behavior were significant for drivers in Groups 2 and 3, while working hours and off-duty days were significant only for drivers in Group 3. Third, working hours were negatively correlated with accident rates for drivers in Group 3, and the drivers who suffered from the heaviest financial burden were most affected by fatigue and sleep problems.Conclusion: Financial burden is the root cause behind the propensity of taxi drivers to be involved in accidents. Taxi companies should find ways to reduce drivers' expenses, and new technologies, such as taxi-calling or location and navigation based on mobile applications, should be introduced into the traditional taxi industry.


Treatment of adults with complications from previous hypospadias surgery.
Adults with complications from previous hypospadias surgery experience various problems, including urethral stricture, persistent hypospadias and urethrocutaneous fistula. Innate deficiencies of the corpus spongiosum and multiple failed operations makes further management challenging. We reviewed our prospective urethroplasty database of men who presented with complications of previous hypospadias surgery. Patients were included in study if they had greater than 6 months of followup. Our surgical management was defined as an initial success if there were no urethral complications. The overall success rate included men with the same result after additional treatment. A total of 50 men had followup greater than 6 months (median 89) and were included in study. These 50 patients presented with urethral stricture (36), urethrocutaneous fistula (12), persistent hypospadias (7), hair in the urethra (6) and severe penile chordee (7). Patients underwent a total of 74 urethroplasties, including stage 1 urethroplasty in 19, a penile skin flap in 11, stage 2 urethroplasty in 11, urethrocutaneous fistula closure in 9, permanent perineal urethrostomy in 6, excision and primary anastomosis in 6, a 1-stage buccal mucosa onlay in 4, tubularized plate urethroplasty in 3, combined techniques in 3 and chordee correction in 1. In 25 men (50%) treatment was initially successfully. Of the 25 men in whom surgery failed 18 underwent additional procedures, including 13 who were ultimately treated successfully for an overall 76% success rate (38 of 50). Managing problems from previous hypospadias surgery is difficult with a high initial failure rate. Additional procedures are commonly needed.


Human mitochondrial complex I assembly is mediated by NDUFAF1.
Complex I (NADH:ubiquinone oxidoreductase) is the largest multiprotein enzyme of the oxidative phosphorylation system. Its assembly in human cells is poorly understood and no proteins assisting this process have yet been described. A good candidate is NDUFAF1, the human homologue of Neurospora crassa complex I chaperone CIA30. Here, we demonstrate that NDUFAF1 is a mitochondrial protein that is involved in the complex I assembly process. Modulating the intramitochondrial amount of NDUFAF1 by knocking down its expression using RNA interference leads to a reduced amount and activity of complex I. NDUFAF1 is associated to two complexes of 600 and 700 kDa in size of which the relative distribution is altered in two complex I deficient patients. Analysis of NDUFAF1 expression in a conditional complex I assembly system shows that the 700 kDa complex may represent a key step in the complex I assembly process. Based on these data, we propose that NDUFAF1 is an important protein for the assembly/stability of complex I.


A simulation-based training program improves emergency department staff communication.
The objectives of this study were to evaluate the effectiveness of Project CLEAR!, a novel simulation-based training program designed to instill Crew Resource Management (CRM) as the communication standard and to create a service-focused environment in the emergency department (ED) by standardizing the patient encounter. A survey-based study compared physicians' and nurses' perceptions of the quality of communication before and after the training program. Surveys were developed to measure ED staff perceptions of the quality of communication between staff members and with patients. Pretraining and posttraining survey results were compared. After the training program, survey scores improved significantly on questions that asked participants to rate the overall communication between staff members and between staff and patients. A simulation-based training program focusing on CRM and standardizing the patient encounter improves communication in the ED, both between staff members and between staff members and patients.


Current status of 4-aminoquinoline resistance markers 18 years after cessation of chloroquine use for the treatment of uncomplicated falciparum malaria in the littoral coastline region of Cameroon.
The onset and rapid spread of chloroquine resistance and the introduction of amodiaquine for the treatment of uncomplicated malaria in Cameroon have influenced the proportion of Plasmodium falciparum sensitive and resistant alleles related to 4-aminoquinoline drugs. This study was undertaken to determine the prevalence of resistance markers to antimalarial 4-aminoquinolines in Douala in the Littoral Region, and Buea in the South West Region in June 2020. Dry blood spots were prepared from malaria microscopy positive cases and used for parasite DNA extraction by chelex-100 method. Plasmodium species identification was carried out by PCR amplification/agarose gel electrophoresis of 18srRNA. The Pfcrt and Pfmdr1 genes were amplified by PCR followed by restriction digestion. The prevalence of single nucleotide polymorphisms (SNPs) was compared between study sites and with previous studies carried out between 2003-2005 and 2009-2011 using the Chi square test. The results showed that Plasmodium falciparum was the dominant species occurring as mono-infections (84.6%). The wild type K76 allele of the Pfcrt gene was found in 74.9% of isolates while the wild N86, Y184 and D1246 alleles of the Pfmdr1 gene were found respectively in 87.2%, 89.6% and 100% of field isolates. The results showed a significant reduction in the mutant alleles compared to results obtained in 2003-2005 and 2009-2013. The KNYD haplotype was observed to be the most prevalent. The results indicated that there is a gradual erosion of the mutant Pfcrt and Pfmdr1 genotype and a gradual return to the sensitive P. falciparum genotype in Cameroon.


STEM: a software tool for large-scale proteomic data analyses.
We describe the software, STEM (STrategic Extractor for Mascot's results), which efficiently processes large-scale mass spectrometry-based proteomics data. V (View)-mode evaluates the Mascot peptide identification dataset, removes unreliable candidates and redundant assignments, and integrates the results with key information in the experiment. C (Comparison)-mode compares peptide coverage among multiple datasets and displays proteins commonly/specifically found therein, and processes data for quantitative studies that utilize conventional isotope tags or tags having a smaller mass difference. STEM significantly improves throughput of proteomics study.


Elastic constants of zero-temperature amorphous solids.
Elastic constants of zero-temperature amorphous solids are given as the difference between the Born term, which results from a hypothetical affine deformation of an amorphous solid, and a correction term, which originates from the fact that the deformation of an amorphous solid due to an applied stress is, at the microscopic level, nonaffine. Both terms are non-negative and thus it is a priori not obvious that the resulting elastic constants are non-negative. In particular, theories that approximate the correction term may spuriously predict negative elastic constants and thus an instability of an amorphous solid. Here we derive alternative expressions for elastic constants of zero-temperature amorphous solids that are explicitly non-negative. These expressions provide a useful blueprint for approximate theories for elastic constants and sound damping in zero-temperature amorphous solids.


Neuropeptide Y and cardiovascular regulation.
Neuropeptide Y is a vasoactive peptide and is widely distributed throughout the central and peripheral nervous systems. Neuropeptide Y is co-released with noradrenaline by perivascular nerve endings. At high concentrations, it has a direct vasoconstrictor effect. In addition, it enhances the vascular effect of various agonists, including noradrenaline and angiotensin II. Moreover, neuropeptide Y has an inhibitory effect on renin secretion. This peptide may have an important role in cardiovascular regulation.


Clinical Features of Craniopharyngioma With Tumoral Hemorrhage: A Retrospective Case-Controlled Study.
Craniopharyngioma (CP) with tumoral hemorrhage is a very rare syndrome presenting with various manifestation and unfavorable outcomes. The current retrospective study was performed to summarize the clinical features of CP with tumoral hemorrhage. In this study, 185 patients with pathological diagnosis of CP (18 patients with hemorrhage) were enrolled. Clinical characteristics, radiological and surgical treatments, and post-operative complications were analyzed. In addition, the correlations between sexual hormones and tumor volume were explored. Drowsiness, acute syndrome, and pituitary deficiency were more frequent in patients with hemorrhage patients. Prothrombin time (PT) were higher in patients with hemorrhage. Luteinizing hormone (LH) and testosterone (T) were lower in male patients with hemorrhage. Post-operative electrolyte disturbances, hypothalamic syndrome, and death appeared more frequently in the hemorrhage group. Moreover, prolactin (PRL) and cortisol 8AM were found to be correlated with the volume of the tumor and the hematoma, respectively. The current study presented the clinical features of CP apoplexy from the aspects of clinical characteristics, radiography, surgical treatment, and post-operative complications. Patients with CP apoplexy could benefit from the proper processing of peritumoral hemorrhage and post-operative monitoring of the electrolyte.


Tides of change: improving glucometrics in a large multihospital health care system.
This study explores the relationship between education for inpatient diabetes providers and the utilization of insulin order sets, inpatient glucometrics, and length of stay in a large health care system. The study included patients with and without the diagnosis of diabetes. An education campaign included provider-directed diabetes education administered via online learning modules and in-person presentations by trained individuals. Relationships among provider-attended diabetes education, order set usage, and inpatient glucometrics (hypo- and hyperglycemia) were analyzed, as well as length of stay. Insulin use knowledge scores for all providers averaged 52%, and improved significantly to 93% (P < .001) by the end of the education intervention period. Likewise utilization of electronic basal-bolus order sets increased from a baseline of 20% for patients receiving insulin to 86% within 6 weeks (P < .01) of introduction of order sets. During the study, the incidence of hypoglycemia and hyperglycemia declined from 1.47% to 1.27% and from 23.21% to 17.80%, respectively. However, these improvements were not sustained beyond the completion of the education campaign. Education of diabetes health care providers was provided in a large, multihospital system through the use of online learning modules. Adoption of standardized insulin order sets was associated with an improvement in glucometrics. This educational and quality initiative resulted in overall improvements in insulin knowledge, adherence to recommended order sets, inpatient glucometrics, and patient length of stay. These improvements were not sustained, reinforcing the need for repeated educational interventions for those involved in providing inpatient diabetes care.


[Rapid identification of Oncomelania hupensis snail habitat in the Poyang Lake region by Geographic Information System (GIS) and Remote Sensing (RS)].
To identify Oncomelania hupensis snail habitats and areas with high transmission potential by GIS/RS. Marshland areas near high endemic villages of schistosomiasis in the Poyang Lake region were selected. Corresponding map was digitized and (Landsat 5 TM) image was corrected according to the digital map. The image in dry seasons was calculated by both normalized difference vegetation index (NDVI) and tasseled cap model. Result showed that snails spots were distributed in class 6, 7 and 8. Farther analysis of both NDVI and tasseled cap model showed that the snail habitats were mainly distributed in the areas where NDVI value was more than 110, and in tasseled cap wetness value between -10 to 3 with correction rate 94.93%. First step was to use unsupervised classification to define the class 6, 7 and 8 snail habitat environment. Second step was to extract the value by NDVI model, and to define a healthy vegetation as snail suspicious habitat when NDVI value was more than 110. Then the third step was to use tasseled cap wetness model to define the areas as snail habitats which value was between -10 to 3.


Multiple inhibition of platelet activation by aurintricarboxylic acid prevents vascular stenosis after endothelial injury in hamster carotid artery.
Activated platelets are instrumental in restenosis due to their role in thrombus formation. Aurintricarboxylic acid (ATA) has been reported to prevent platelet activation by inhibiting von Willebrand factor binding to platelet glycoprotein (GP)Ib. We investigated the effects of ATA in vitro and in vivo in hamsters. ATA inhibited the in vitro platelet aggregation induced by ADP, botrocetin and thrombin, but not by collagen. The IC50 values during the ex vivo platelet aggregation by ADP, botrocetin and thrombin were 8.2 +/- 1.8 microM, 0.9 +/- 0.4 microg/ml and 2.4 +/- 0.8 unit/ml, respectively. The platelet retention time to collagen-coated beads of hamster blood samples was inhibited by ATA (0.1, 0.3 and 1.0 mg/kg per hour) in a dose-dependent manner. Continuous administration of ATA (0, 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg per h) via an infusion pump produced dose-dependent antithrombotic effects: the time to occlude the carotid artery after vascular injury with a modified catheter was prolonged. Only when infused at doses of 3.0 and 10.0 mg/kg per hour, bleeding times were significantly prolonged. The continuous treatment with ATA (1.0 mg/kg per h) using a 2ML1 Alzet infusion pump for 2 weeks, resulted in a decrease in neointimal area by 22.2 +/- 6.8% when measured 2 weeks after injury induction. DNA synthesis using DDT1MF2 hamster SMCs was decreased by ATA in a dose-dependent manner. ATA reduced the number of platelets adhering on the injured area, as detected by electron microscopy. These results indicated that treatment with ATA inhibited platelet adhesion but also SMC proliferation. These observations may explain the effect of ATA on neointima formation.


A potential bioactive hard-stock fat replacer comprised of a molecular gel.
Short-chain ceramides, such as N-acetoyl-d-erythro-sphingosine (C2), have a remarkable ability to structure edible oils, such as canola oil, into self-standing organogels without any added saturated or trans fats. These short-chain ceramides are ubiquitously found in foods ranging from eggs to soybeans. As the ceramide fatty acid chain length increases, there is an increase in the melting temperature of the organogel and a decrease in the elastic modulus. Gelation ability is lost at 2 wt% when the fatty acid chain length increases to six carbons; however, organogels form at 5 wt% up to 18 carbons. Short-chain ceramides, C2, decrease cell viability of colon, prostate, ovarian, and leukemia cell lines, while ceramides with long-chain fatty acids, C18, do not affect the viability of these cancer cell lines. This suggests that a bioactive spreadable fat, with no trans or added saturated fat, with the potential to alter the viability of cancer cell growth, is possible.


Isokinetic performance of hip muscles after revision total hip arthroplasty via previous anterolateral approach.
We investigated the isokinetic performance of hip muscles and clinical outcomes after revision total hip arthroplasty (THA) via same anterolateral approach used in primary surgery. Thirty patients who had undergone previous THA via an anterolateral approach underwent both acetabular and femoral component revision after aseptic loosening. The Harris Hip Score (HHS) was evaluated during a minimum 2-year follow-up. The isokinetic muscle strength of the operated and nonoperated hips was assessed 1 year after surgery. The HHS improved from 49.0 to 77.4. Operated and nonoperated hips exhibited similar isokinetic performance during all measurements (flexion, extension, and abduction) (p>0.05). This prospective study showed that the anterolateral approach preserves abductor strength after revision THA in aseptic cases with acceptable functional and clinical results. The main clinical relevance of this study is that the same anterolateral approach used in previous primary THA is also safe and viable for revision THA.


Phase II Study of Docetaxel, Cisplatin, and 5-Fluorouracil Chemoradiotherapy for Unresectable Esophageal Cancer.
We performed a phase II study of triple-drug combination chemoradiotherapy (DCF-R therapy), in which docetaxel was added to the standard chemoradiotherapy (cisplatin [CDDP]/5-fluorouracil [5-FU]) for unresectable advanced esophageal cancer. Sixty-one patients with unresectable advanced esophageal cancer underwent the following DCF-R therapy: intravenous infusion of l60 mg/m2 docetaxel and 60 mg/m2 of CDDP (day 1), and 600 mg/m2 of 5-FU (days 1-5); 2 courses administered within a 4-week interval. Radiotherapy comprised 60 Gy in total. Response rates were 85.2% for the main lesion, 80.7% for metastasized lymph nodes, and 67.6% for distant organ metastases. Common adverse effects were leukopenia, anemia, and nausea, in 98.4%, 62.3%, and 60.7% of patients, respectively. Treatment completion rate was 90.2% and no treatment-associated deaths occurred. Median survival time was 406 days and 1-, 2-, and 5-year survival rates were 58.6%, 39.1%, and 22.8%, respectively. DCF-R therapy for unresectable advanced esophageal cancer demonstrated a high antitumor effect with sufficient safety.


Preferred seat orientation of senior high-school students.
The height of the front of the seat is the primary determinant of appropriate seat size in the school setting. In the present study, this dimension was fixed at 445 mm and, using a brief adjustment period, students adjusted the angle of the seat to their preferred rear seat height (PRSH) under three fixed and one adjustable desk height conditions and for one desk height, under two time conditions. PRSH was significantly greater at an 800 mm desk height (454+/-14 mm) compared to 735 mm (447+/-15 mm) and 720 mm (444+/-16 mm). When desk height as well as rear seat height were adjustable, PRSH was 446+/-15 mm and preferred desk height 751+/-25 mm. Taller students or those with larger popliteal heights selected lower PRSHs at all desk heights, with PRSH more strongly related to popliteal height (r = -0.54 to -0.59) than stature (r = -0.44 to -0.50). No differences were found in PRSH between short (<5 min) and long (30 min) adjustment periods for the 735 mm desk height. The nearly horizontal seat positions found in this study were between those recommended by other authors.


Perianal and Perineal Spindle Cell Variant of Embryonal Rhabdomyosarcoma in an Infant.
We present a case of a perianal and perianal spindle cell variant of embryonal rhabdomyosarcoma (RMS). A 3-month-old male child presented with a firm mass in the perianal region. The mass measured 5 cm × 3 cm × 2 cm was surgically removed. Biopsy was performed; it showed embryonal RMS. Immunohistochemical (IHC) stains were performed using vimentin, myogenin, spinal muscular atrophy, and muscle-specific actin, which all showed positive results. The histological examination and IHC stains were consistent with a spindle cell variant of embryonal RMS.


Hypoxia-Related Radiomics and Immunotherapy Response: A Multicohort Study of Non-Small Cell Lung Cancer.
Immunotherapy yields survival benefit for some advanced stage non-small cell lung cancer (NSCLC) patients. Because highly predictive biomarkers of immunotherapy response are an unmet clinical need, we used pretreatment radiomics and clinical data to train and validate a parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy. Three cohorts of NSCLC patients treated with immunotherapy were analyzed: training (n = 180), validation 1 (n = 90), and validation 2 (n = 62). The most informative clinical and radiomic features were subjected to decision tree analysis, which stratified patients into risk groups of low, moderate, high, and very high risk of death after initiation of immunotherapy. All statistical tests were 2-sided. The very high-risk group was associated with extremely poor overall survival (OS) in validation cohorts 1 (hazard ratio [HR] = 5.35, 95% confidence interval [CI] = 2.14 to 13.36; 1-year OS = 11.1%, 95% CI = 1.9% to 29.8%; 3-year OS = 0%) and 2 (HR = 13.81, 95% CI = 2.58 to 73.93; 1-year OS = 47.6%, 95% CI = 18.2% to 72.4%; 3-year OS = 0%) when compared with the low-risk group (HR = 1.00) in validation cohorts 1 (1-year OS = 85.0%, 95% CI = 60.4% to 94.9%; 3-year OS = 38.9%, 95% CI = 17.1% to 60.3%) and 2 (1-year OS = 80.2%, 95% CI = 40.3% to 94.8%; 3-year OS = 40.1%, 95% CI = 1.3% to 83.5%). The most informative radiomic feature, gray-level co-occurrence matrix (GLCM) inverse difference, was positively associated with hypoxia-related carbonic anhydrase 9 using gene-expression profiling and immunohistochemistry. Utilizing standard-of-care imaging and clinical data, we identified and validated a novel parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy. Based on this model, clinicians can identify patients who are unlikely to respond to immunotherapy.


Synthesis and characterization of nitrogen-rich macrocyclic ligands and an investigation of their coordination chemistry with lanthanum(III).
Derivatives of the ligand 1,4,7,10-tetraazacyclododecane (cyclen) containing pendant N-heterocyclic donors were prepared. The heterocycles pyridine, pyridazine, pyrimidine, and pyrazine were conjugated to cyclen to give 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L(py)), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyd)), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyr)), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L(pz)), respectively. The coordination chemistry of these ligands was explored using the La(3+) ion. Accordingly, complexes of the general formula [La(L)(OTf)](OTf)2, where OTf = trifluoromethanesulfonate and L = L(py) (1), L(pyd) (2), L(pyr) (3), and L(pz) (4), were synthesized and characterized by NMR spectroscopy. Crystal structures of 1 and 2 were also determined by X-ray diffraction studies, which revealed 9-coordinate capped, twisted square-antiprismatic coordination geometries for the central La(3+) ion. The conformational dynamics of 1-4 in solution were investigated by variable-temperature NMR spectroscopy. Dynamic line-shape and Eyring analyses enabled the determination of the activation parameters for the interconversion of enantiomeric forms of the complexes. Unexpectedly, the different pendant N-heterocycles of 1-4 give rise to varying values for the enthalpies and entropies of activation for this process. Density functional theory calculations were carried out to investigate the mechanism of this enantiomeric interconversion. Computed activation parameters were consistent with those experimentally determined for 1 but differed somewhat from those of 2-4.


Laparoscopic endoscopic cooperative surgery as a minimally invasive treatment for gastric submucosal tumor.
Laparoscopic wedge resection is a useful procedure for treating patients with submucosal tumor (SMT) including gastrointestinal stromal tumor (GIST) of the stomach. However, resection of intragastric-type SMTs can be problematic due to the difficulty in accurately judging the location of endoluminal tumor growth, and often excessive amounts of healthy mucosa are removed; thus, full-thickness local excision using laparoscopic and endoscopic cooperative surgery (LECS) is a promising procedure for these cases. Our experience with LECS has confirmed this procedure to be a safe, feasible, and minimally invasive treatment method for gastric GISTs less than 5 cm in diameter, with outcomes similar to conventional laparoscopic wedge resection. The important advantage of LECS is the reduction in the resected area of the gastric wall compared to that in conventional laparoscopic wedge resection using a linear stapler. Early gastric cancer fits the criteria for endoscopic resection; however, if performing endoscopic submucosal dissection is difficult, the LECS procedure might be a good alternative. In the future, LECS is also likely to be indicated for duodenal tumors, as well as gastric tumors. Furthermore, developments in endoscopic and laparoscopic technology have generated various modified LECS techniques, leading to even less invasive surgery.


Lateralization of auditory rhythm length in temporal lobe lesions.
In the visual modality, short rhythmic stimuli have been proven to be better processed (sequentially) by the left hemisphere, while longer rhythms appear to be better (holistically) processed by the right hemisphere. This study was set up to see if the same holds in the auditory modality. The rhythm task as originally designed by Seashore was computerized and is part of the Fepsy Neuropsychological battery. This task was performed by 85 patients with intractable temporal lobe epilepsy (left TLE = 32; right TLE = 53) enrolled in the Dutch Collaborative Epilepsy Surgery Program. They performed the task before and 6 months after surgery. The task consists of 30 pairs of rhythmic patterns in 3 series of 10 items. The series contains patterns of 5, 6, or 7 notes. The purpose is to indicate whether the two patterns are the same or different. Reaction times are also measured. If the hypothesis is true, the short-item sequence will be better processed by patients with right temporal lobe epilepsy (nonimpaired left temporal lobe), the longer sequence will be better processed by the left temporal epilepsy group (nonimpaired right temporal lobe). No overall laterality effect on rhythm perception could be found and no difference was found between both test moments. IQ did not correlate with rhythm performance. However, there was an interaction effect of laterality and rhythm length on performance and reaction time. This effect can be explained by the increase after the operation of the score of the left focus group and a decrease in the right focus group on the longer rhythms. This effect was somewhat less strong in the reaction times: a clear tendency for faster reaction times after surgery in the left and longer reaction times in the right focus group. The effect could not be explained for by the difference in extent of resection in either temporal lobe. This study showed that memory for and discrimination of auditory rhythm is dependent on which hemisphere is used in processing. The effect could be demonstrated for the right hemisphere, which uses a holistic processing of stimuli, which outperforms the left in rhythms consisting of a long sequence. In left temporal resections an improvement occurs on the longer rhythms and in right temporal resections the performance on the longest rhythms decreases.


The staging of lymphoedema and accompanying symptoms.
Community nurses are recognized as potentially having a much greater role to play in identifying, referring and helping in the long-term management of lymphoedema. This will require knowledge of all stages of the diagnostic and treatment process. In this article, the author discusses staging, or the assessment of the severity of the disease. Staging can be useful not only in deciding the best course of treatment for the individual, but also in measuring the progress of treatment.


Making the transition from technologist to manager.
To prepare for the transition to management, technical personnel must (1) develop their administrative, communication, and interpersonal skills; (2) learn to delegate, and (3) learn management principles and concepts. This last activity can be accomplished through in-house management training programs, on-the-job training, or formal management degree programs. These activities will help increase the chances for success among technical personnel making the transition into management in a clinical or industrial setting.


[Intrauterine pregnancy complicated by coexisting ectopic pregnancy].
Authors have presented the case of coexisting 11 week intrauterine and ectopic pregnancies in the 25 years old woman, which had earlier been operated on the left ovary dermoid cyst. That operation could be regarded as an ectopic pregnancy risk factor, but the suspicion of an ectopic pregnancy has been suggested only by physical examination, and sonography and laparoscopy were most important in final diagnosis. Ectopic pregnancy has been removed by laparotomy according to the progression of the disease. The case has drawn the attention to the necessity of thorough diagnosis in pregnant women particularly in those ones with lower abdominal pain in early pregnancy and with unfavorable gynaecological and obstetric past, for example appendages operation such as in our case. It was also been emphasized, that the complex diagnosing of patients with already recognized ectopic pregnancy should be proceeded. Sonography, especially the one equipped with the endovaginal probe, plays the most important part in diagnosing. In some questionable cases laparoscopy, along with diagnostical significance, also makes the surgical treatment possible.


Primary subcutaneous hydatid cyst with palisading granulomatous reaction.
Palisading granulomatous reactions are prominent microscopic characteristics that are seen in many diseases. Isolated subcutaneous cystic echinococcosis is rarely documented. Palisading granuloma as a host immune reaction to Echinococcus granulosus in an isolated primary subcutaneous hydatid cyst has been reported only once before. In this report, we are describing a 53-year-old male who developed a slowly growing subcutaneous thigh mass. Light microscopy confirmed the presence of hydatid cyst. Further radiological workup for liver and lung has not shown any visceral hydatid focus.


[Percutaneous coronary intervention effectiveness in acute coronary syndromes in patients over 80 years old--follow-up study].
Atherosclerosis is a chronic and progressive inflammatory process that causes the most advanced changes in elderly people. In 2006 we published the results of the analysis of acute coronary syndromes in patients after 80 years of age. Conducted the study have decided to extend the observation of distant patients. THE AIM of this study was to assess the effectiveness of remote monitoring percutaneous coronary intervention (PCI) performed in patients with acute coronary syndrome after 80 years of age and to demonstrate the potential benefits of the treatment on the basis of well-being and quality of life of studied patients. The study included 15 women and 16 men aged from 80 to 92 years, which in 2005 because of acute coronary syndrome (ACS) PCI was performed with stenting of coronary vessels. The 31-person group of patients after percutaneous coro-: nary intervention to the end of the observation period 24 patients survived, while seven died. A comparison group of patients living with the deceased showed a number of differences, both clinical as well as the biochemical parameters evaluated. Women accounted for up to 72% among the deceased patients. Moreover, increased posthospitalization mortality in patients with ST elevation myocardial infarction was documented. The majority of patients during the observation period was in class II according to the criteria of the Canadian Society of Cardiology. Analysis of the obtained results in the observation of distant percutaneous balloon therapy with stenting of coronary vessels in patients after 80 years of age showed a majority of respondents declared by the benefit of the treatment administered in the form of improved well-being and quality of life. The analysis of deaths during follow-up period showed the increased mortality during posthospitalization period in patients with ST elevation myocardial infarction and documented the predominance of patients with diabetes and other co-morbidities, especially in women.


Crystallization and preliminary X-ray diffraction analysis of mouse galectin-4 N-terminal carbohydrate recognition domain in complex with lactose.
Galectin-4 is thought to play a role in the process of tumour conversion of cells of the alimentary tract and the breast tissue; however, its exact function remains unknown. With the aim of elucidating the structural basis of mouse galectin-4 (mGal-4) binding specificity, we have undertaken X-ray analysis of the N-terminal domain, CRD1, of mGal-4 in complex with lactose (the basic building block of known galectin-4 carbohydrate ligands). Crystals of CRD1 in complex with lactose were obtained using vapour-diffusion techniques. The crystals belong to tetragonal space group P42(1)2 with unit-cell parameters a = 91.1, b = 91.16, c = 57.10 A and preliminary X-ray diffraction data were collected to 3.2 A resolution. An optimized crystallization procedure and cryocooling protocol allowed us to extend resolution to 2.1 A. Structure refinement is currently under way; the initial electron-density maps clearly show non-protein electron density in the vicinity of the carbohydrate binding site, indicating the presence of one lactose molecule. The structure will help to improve understanding of the binding specificity and function of the potential colon cancer marker galectin-4.


The role of cellular cooperation in thromboplastin synthesis.
Increasing evidence [1, 2, 3] demonstrates the clinical importance of monocyte thromboplastin synthesis in the pathogenesis of thrombosis and disseminated intravascular coagulation. Among the first to describe this was the group of the late F Josso [4, 5]. In addition, monocytes and macrophages appear to contribute to fibrin deposition in inflammatory lesions [6, 7]. Several procoagulant substances have been reported to appear in monocyte cultures. Among these, thromboplastin is the most potent and probably also the most important and well studied. Based as it is on our own work, this brief review will deal only with thromboplastin. It is a phospholipid-protein complex, consisting in human material of one species of protein (apoprotein III) mol. wt. approximately 52,000 surrounded by phospholipids [8] in an optimal molecular ratio of apoprotein:phospholipids of approximately 1:80 [9]. Apoprotein III is an integral membrane glycoprotein which apparently is located mainly on the outside of the plasma membrane. The molecular weight has recently been confirmed in our laboratory by Western blotting, using a monoclonal antibody to apoprotein III developed here (Johnsen, unpublished).


House dust mite sublingual immunotherapy in allergic rhinitis.
Allergen immunotherapy has been shown to be effective in treatment of allergic rhinitis (AR). Sublingual immunotherapy (SLIT) is generally recommended for treating seasonal AR in adults and children; however, questions remain in regard to AR treatment in relation to house dust mite (HDM). Due to heterogeneous formulations, different outcome reporting systems, and the lack of a standardized dose, HDM SLITs have not been standardized in published studies. Nevertheless, studies continuously report positive effects of HDM SLIT in AR, and HDM SLIT remains a treatment option for patients with HDM-induced allergic asthma that frequently co-exists with AR. Therefore, it is likely that HDM SLIT usage will increase. This review will focus on HDM SLIT in AR exclusively.


Effect of Thermal Cycling on the Flexural Strength and Hardness of New-Generation Denture Base Materials.
To evaluate the flexural strength and Vickers microhardness of different CAD-CAM denture base materials. Sixty rectangular specimens (64 × 10 × 3.3 ± 0.2 mm) were fabricated from 3 different denture base materials (G-CAM, Graphene-reinforced polymethylmethacrylate, GC), Ivotion Base (Prepolymerized polymethylmethacrylate, IV), and Denturetec (3D-printed resin, DT) either by using additive (DT) or subtractive manufacturing (IV and GC). Specimens of each group were divided into 2 subgroups (thermal cycled or nonthermal cycled, n = 10/group). Nonthermal cycled specimens were stored in distilled water at 37°C for 24 hours and subjected to 3-point flexural strength test with a universal testing machine. Thermal cycled specimens were initially evaluated for Vickers microhardness and subjected to thermal cycling (10,000 cycles at 5-55°C). Vickers microhardness values were remeasured, and the specimens were subjected to 3-point flexural strength test. Data were analyzed by using 2-way analysis of variance and Bonferroni-corrected Tukey honestly significant difference tests (α = 0.05). Material type and condition significantly affected flexural strength (p ≤ 0.004), whereas their interaction was nonsignificant (p = 0.778). Overall flexural strength of the materials in decreasing order was GC, IV, and DT (p < 0.001), regardless of the condition. Material had a higher effect on flexural strength (ηp2 = 0.731) than thermal cycling (ηp2 = 0.142). The effect of the interaction between the material type and thermal cycling on Vickers microhardness was significant (p < 0.001). GC had the highest microhardness before and after thermal cycling (p < 0.001). IV had higher microhardness than DT before thermal cycling (p < 0.001). However, DT and IV showed similar microhardness after thermal cycling (p = 0.665). Thermal cycling decreased the microhardness of GC and IV (p ≤ 0.022), whereas its effect on DT's microhardness was nonsignificant (p = 0.538). Material type had the highest effect on microhardness (ηp2 = 0.864) followed by the interaction between the main factors (ηp2 = 0.258). Graphene-reinforced polymethylmethacrylate had the highest flexural strength and Vickers microhardness values, regardless of thermal cycling. Thermal cycling reduced the flexural strength of all resins. Thermal cycling reduced the microhardness of milled polymethylmethacrylate, but not that of 3D-printed resin.


A role for Grb2 in apoptosis?
Src homology type 2 (SH2) and type 3 (SH3) domains appear to have an important role in signal transduction pathways initiated by tyrosine kinases. SH2 domains allow proteins with signalling functions to interact with tyrosine kinases and tyrosine-phosphorylated proteins at the plasma membrane, whereas SH3 domains allow a distinct type of interaction through binding to proline-rich sequences. The adaptor protein Grb2 consists of one SH2 domain and two SH3 domains and connects tyrosine kinase receptors to activation of the Ras pathway. Its closely related counterpart, Grb3-3, thought to arise by alternative splicing of Grb2 transcripts, lacks a functional SH2 domain but retains functional SH3 domains. We recently presented evidence that Grb3-3 might deliver specific signals causing cells to undergo apoptosis. This review will document the mechanism of Grb3-3 function and discuss its putative involvement in several pathologies. It also further strengthens the notion that cells may use alternative splicing as a means to drive either a proliferative or a suicidal program.


A radiopaque polymer hydrogel used as a fiducial marker in gynecologic-cancer patients receiving brachytherapy.
We assessed a novel Food and Drug Administration-approved hydrogel, synthesized as absorbable iodinated particles, in gynecologic-cancer patients undergoing computed tomography (CT) or magnetic resonance (MR) based brachytherapy after external beam radiation. Nineteen patients underwent CT-guided (n = 13) or MR-guided (n = 6) brachytherapy for gynecologic cancers. Seventy-seven hydrogel injections were placed. The hydrogel material was injected into gross residual disease and/or key anatomic landmarks in amounts ranging from 0.1 to 0.4 mL. The visibility of the tracer was scored on CT and on MR images using a 5-point scoring scale. A Cohen's kappa statistic was calculated to assess interobserver agreement. To assess the unadjusted effects of baseline parameters on hydrogel visibility, we modeled visibility using a linear mixed-effect model. Injections were without complication. The kappa statistic was 0.77 (95% confidence interval [CI], 0.68-0.87). The volume of hydrogel injected was significantly associated with visibility on both CT (p = 0.032) and magnetic resonance imaging (p = 0.016). We analyzed visibility by location, controlling for amount. A 0.1-cc increase in volume injected was associated with increases of 0.54 (95% CI = 0.05-1.03) in the CT visibility score and 0.83 (95% CI = 0.17-1.49) in the MR visibility score. Injection of 0.4 cc or more was required for unequivocal visibility on CT or MR. No statistically significant correlation was found between tumor type, tumor location, or anatomical location of injection and visibility on either CT or magnetic resonance imaging. In this first report of an injectable radiopaque hydrogel, targets were visualized to assist with three-dimensional-based brachytherapy in gynecologic malignancies. This marker has potential for several applications, is easy to inject and visualize, and caused no acute complications.


Visfatin Amplifies Cardiac Inflammation and Aggravates Cardiac Injury via the NF-κB p65 Signaling Pathway in LPS-Treated Mice.
Visfatin is an adipocytokine that has been demonstrated to be involved in cardiovascular diseases. This study aims at determining the role of visfatin in sepsis-induced cardiac injury and identify its possible mechanisms. Dynamic changes in visfatin expression in mice with lipopolysaccharide- (LPS-) induced septicemia were measured. Additionally, mice were pretreated with visfatin and further administered LPS to observe the effects of visfatin on cardiac injury. Finally, septic mice were also pretreated with JSH-23 to investigate whether visfatin regulates cardiac injury via the NF-κB p65 pathway. Visfatin expression levels in both the heart and serum were increased in LPS-treated mice and peaked at 6 hours, and visfatin was derived from cardiac macrophages. In septic mice, pretreatment with visfatin reduced the survival rate, worsened cardiac dysfunction, and increased the expression of cardiac injury markers, including creatine kinase myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Treatment with visfatin also increased the infiltration of CD3+ cells and F4/80+ cells, amplified the cardiac inflammatory response, and elevated myocardial cell apoptosis. Treatment with JSH-23 reversed the effects of visfatin in septic mice. This study showed that visfatin amplifies the cardiac inflammatory response and aggravates cardiac injury through the p65 signaling pathway. Visfatin may be a clinical target for preventing cardiac injury in sepsis.


Adsorption of microcystin-LR on mesoporous carbons and its potential use in drinking water source.
Microcystin-LR (MC-LR) is a common toxin derived from cyanobacterial blooms an effective, rapid and non-toxic method needs to be developed for its removal from drinking water treatment plants (DWTP). For an adsorption-based method, mesoporous carbon can be a promising supplemental adsorbent. The effect of mesoporous carbon (MC1, MC2, and MC3) properties and water quality parameters on the adsorption of MC-LR were investigated and the results were analyzed by kinetic, isotherm, thermodynamic, Derjaguin-Landau-Verwey-Overbeek (DLVO), and intraparticle diffusion models. MC1 was the most appropriate type for the removal of MC-LR with a maximum adsorption capacity of 35,670.49 μg/g. Adsorption of MC-LR is a spontaneous reaction dominated by van der Waals interactions. Pore sizes of 8.5-14 nm enhance the pore diffusion of MC-LR from the surface to the mesopores of MC1. The adsorption capacity was not sensitive to changes in the pH (3.2-8.0) and the existence of organic matter (2-5 mg/L). Furthermore, the final concentration of MC-LR was below the WHO guideline level after a 10-min reaction with 20 mg/L of MC1 in the Nak-Dong River, a drinking water source. The MC-LR adsorption mainly competed with humic substances (500-1000 g/mole); however, they did not have a great effect on adsorption.


Partial carbon dioxide rebreathing: a reliable technique for noninvasive measurement of nonshunted pulmonary capillary blood flow.
To determine the validity and clinical utility of the partial CO2 rebreathing technique for measurement of nonshunted pulmonary capillary blood flow and cardiac output. Prospective, controlled animal laboratory investigation and clinical trial. Animal research facility and intensive care unit of a university hospital. Fifteen adult sheep, weighting 58 to 78 kg. Mechanically ventilated patients with different underlying diseases (n = 12) and with adult respiratory distress syndrome (ARDS) (n = 8). CO2 elimination rate (VCO2) was measured breath-by-breath with a system developed for the study and also by gas collection (validation procedure in patients with different underlying diseases). Partial CO2 rebreathing maneuvers, cardiac output by thermodilution, and blood gas analysis were performed in sheep with lung atelectasis and in patients with ARDS. The degree of correlation between VCO2 measured with the system developed and gas collection was very good (r2 = .95, p < .0001), and bias and precision calculations (1 +/- 9 mL/min) showed close agreement between methods. The overall degree of correlation between partial CO2 rebreathing measurements and cardiac output was moderate (r2 = .54, p < .0001), the noninvasive method tending to underestimate cardiac output, as shown by bias and precision calculations (-1.69 +/- 1.90 L/min). In contrast, the overall degree of correlation between partial CO2 rebreathing measurements and nonshunted pulmonary capillary blood flow was good (r2 = .73, p < .0001). Bias and precision calculations (0.25 +/- 0.83 L/min) showed a tendency for the partial CO2 rebreathing technique to slightly overestimate pulmonary capillary blood flow. Variance differences between partial CO2 rebreathing measurements and cardiac output could be mostly explained by intrapulmonary right-to-left shunt fraction (r2 = .51, p < .0001). Our results support the use of the system developed for breath-by-breath VCO2 measurements. The lack of agreement between partial CO2 rebreathing measurements and cardiac output was mostly explained by intrapulmonary right-to-left shunt, suggesting that this technique may not be appropriate for monitoring cardiac output in patients with increased venous admixture. In contrast, our results demonstrate that the partial CO2 rebreathing technique is reliable for measurement of the effective nonshunted pulmonary capillary blood flow. This technique may prove useful to guide ventilatory therapy adjustments in an attempt to optimize nonshunted pulmonary capillary blood flow.


Electrophysiological Measures of Visual Working Memory in Social Anxiety.
Socially anxious individuals are very sensitive to threatening information in the environment, so visual working memory (VWM) is of great significance for them. However, the influence of social anxiety on VWM is unclear. In the present study, we aimed to investigate the VWM in individuals with social anxiety using electrophysiological techniques. Event-related potentials (ERPs) of high socially anxious (HSA) individuals and low socially anxious (LSA) individuals were recorded during a change-detection task with two memory conditions (two and four items). Electrophysiological results indicated that compared with the LSA individuals, the HSA individuals had significantly more active contralateral delay activity (CDA) in condition of memorizing four items. However, there was no significant difference between the HSA and LSA groups in response accuracy in the conditions memorizing two and four items. From the electrophysiological results, individuals with high social anxiety could maintain more information in VWM. However, maybe anxiety consumes the available cognitive resources to compensate for the supposed to be impaired effective performance, so that individuals with high social anxiety perform the same as individuals with low social anxiety in terms of behavioral outcomes.


Mechanisms for phase distortion in a traveling wave tube.
We present a view of the physics of phase distortion in a traveling wave tube (TWT) based on unique insights afforded by the MUSE models of a TWT [IEEE Trans. Plasma Sci. 30, 1063 (2002)]]. The conclusion, supported by analytic theory and simulations, is that prior to gain compression phase distortion is due to harmonic frequencies in the electron beam and the resulting "intermodulation" frequency at the fundamental, and not the often cited "slowing down of electrons in the electron beam." We draw these conclusions based on MUSE simulations that allow explicit control of electron beam frequency content, an analytic solution to the S-MUSE model [IEEE Trans. Plasma Sci. 30, 1063 (2002)]] that reveals that phase distortion is due to the fact that the fundamental frequency is an intermodulation product of itself, and large signal LATTE [IEEE Trans. Plasma Sci. 30, 1063 (2002)]] simulations that are modified to remove the effect of the slowing down of electrons in the electron beam. As applications of the theory we compare S-MUSE simulations to an amplitude phase model using the analytic phase transfer curve, we study dependence of phase distortion on circuit dispersion and electron beam parameters at the second harmonic with large signal LATTE simulations for narrow and wide band TWT designs, and we consider the phase distortion theory in the context of TWT linearization.


A new method to quantify male pelvic floor displacement from 2D transperineal ultrasound images.
To develop a method to quantify displacement of pelvic structures during contraction of the pelvic floor muscles from transperineal ultrasound images in men and investigate the reliability of the method between days. Ten healthy male volunteers (aged 28-41 years) attended 2 separate data collection sessions. Ultrasound images were recorded during voluntary pelvic floor muscle contractions in cine-loop (video) format with the transducer aligned in the midsagittal plane on the perineum. Five anatomic points were defined to represent contraction from striated urethral sphincter (SUS), levator ani (LA), and bulbocavernosus (BC) muscles. Displacement of each point was calculated between the relaxed and contracted-state images. Intraclass correlation coefficient (ICC) values were calculated from displacement data to assess reliability of the method between days. Displacements of the 5 anatomic points closely matched predictions based on anatomic considerations of the male pelvic musculature. ICC values for displacement data calculated from 1, 2, and 3 repetitions ranged between 0.82 and 0.95 for ICC (2,1), 0.85 and 0.97 for ICC (2,2), and 0.86 and 0.97 for ICC (2,3), respectively. The new method reliably calculates displacements of points previously validated for women (ano-rectal junction and bladder base) in addition to new measures of muscle actions (SUS and BC) specific to men. Future use might include assessment of clinical populations to understand how these displacements relate to symptoms of incontinence.


Linking cascading effects of fish predation and zooplankton grazing to reduced cyanobacterial biomass and toxin levels following biomanipulation.
Eutrophication has been one of the largest environmental problems in aquatic ecosystems during the past decades, leading to dense, and often toxic, cyanobacterial blooms. In a way to counteract these problems many lakes have been subject to restoration through biomanipulation. Here we combine 13 years of monitoring data with experimental assessment of grazing efficiency of a naturally occurring zooplankton community and a, from a human perspective, desired community of large Daphnia to assess the effects of an altered trophic cascade associated with biomanipulation. Lake monitoring data show that the relative proportion of Daphnia spp. grazers in June has increased following years of biomanipulation and that this increase coincides with a drop in cyanobacterial biomass and lowered microcystin concentrations compared to before the biomanipulation. In June, the proportion of Daphnia spp. (on a biomass basis) went from around 3% in 2005 (the first year of biomanipulation) up to around 58% in 2012. During months when the proportion of Daphnia spp. remained unchanged (July and August) no effect on lower trophic levels was observed. Our field grazing experiment revealed that Daphnia were more efficient in controlling the standing biomass of cyanobacteria, as grazing by the natural zooplankton community never even compensated for the algal growth during the experiment and sometimes even promoted cyanobacterial growth. Furthermore, although the total cyanobacterial toxin levels remained unaffected by both grazer communities in the experimental study, the Daphnia dominated community promoted the transfer of toxins to the extracellular, dissolved phase, likely through feeding on cyanobacteria. Our results show that biomanipulation by fish removal is a useful tool for lake management, leading to a top-down mediated trophic cascade, through alterations in the grazer community, to reduced cyanobacterial biomass and lowered cyanobacterial toxin levels. This improved water quality enhances both the ecological and societal value of lakes as units for ecosystem services.


Successful pregnancy in a patient with systemic lupus erythematosus, renal transplantation and chronic renal failure. A case report.
Systemic lupus erythematosus with renal involvement is associated with excessive pregnancy wastage as well as substantial maternal risk. The same may be said of borderline renal function after renal transplantation. We treated a patient who had both problems and who carried a pregnancy to term successfully.


Management of the Cirrhotic Patient Before Liver Transplantation: The Role of the Referring Gastroenterologist.
The referral of a patient with cirrhosis to a liver transplant center for evaluation is usually made by a local gastroenterologist. The role of the referring gastroenterologist begins with early identification and modification of high-risk behaviors, which may delay listing a patient for liver transplantation. The local gastroenterologist must also fully appreciate what constitutes a timely referral of a patient to a liver transplant center and the consequences of late referral. Although patients experience the inevitable deterioration of their liver function, which in turn advances their priority on the liver transplant waiting list, the referring gastroenterologist must also anticipate medical complications of cirrhosis, and should initiate appropriate surveillance and prophylaxis programs to detect and prevent these complications. Finally, the referring gastroenterologist constitutes a vital link of information between the patient and the transplant center. Adherence to these guidelines will increase the probability that a patient with chronic liver failure will undergo successful liver transplantation and will decrease post-transplant morbidity.


Contextual interference effects with two tasks.
The present study was intended to test whether the standard contextual interference effect would be observed when only two patterns were practiced in blocked or random schedules of multisegment movement tasks rather than three patterns which is the norm. In line with the basic effect, Blocked learners' performance was closer to ideal during acquisition, but Random learners had smaller errors at 24-hr. retention. In addition, random learners had better recall of the details of the patterns they had practiced. Learners' predictions of retention performance did not match the group differences actually observed.


[Adjuvanticity of vitamin A in advanced irradiated cervical cancer (author's transl)].
For treatment of patients with inoperable cervical cancer (FIGO III) a randomized trial has been initiated. Patients were randomized to receive either conventional irradiation therapy together with vitamin A palmitate (1.5 mill. IU/day; total dose 30 mill. IU), applied orally, or irradiation alone. 42 patients have been included in this study. Patients were monitored by several immunological tests. Delayed cutaneous hypersensitivity reaction to a battery of recall antigens did not reveal any changes, neither within nor between the treatment groups. A challenge reaction to DNCB could be evoked after treatment in 50% of the patients in both treatment groups. No significant changes of immunoglobulin levels have been observed after termination of therapy in each treatment group. When lymphocyte reactivity to PHA (maximum response during therapy) was compared within the groups, it was found, that 66% of the patients who received an irradiation combined with vitamin A palmitate, showed an increase in their blastogenic response, while in irradiated patients without vitamin A palmitate a response was only in 33%. This difference being statistically significant in comparison to pretreatment values. From immunological data it can be concluded that vitamin A has an effect on functional response of T-cells. Concerning the clinical outcome, after an observation period of 12 months relapse rates were lower in the vitamin A group, but not significantly reduced. Therefore further follow up is warranted.


Cancer pain can be relieved.
In Pakistan, 70% of cancer patients with daily pain were found to be suffering severe pain. Cancer pain could be largely prevented by such inexpensive drugs as acetylsalicylic acid, codeine, and oral morphine.


Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects.
Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs) is widespread among human immunodeficiency virus-infected patients. This article reviews the clinical pharmacokinetic and pharmacodynamic interactions between NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic compounds that may induce and/or inhibit drug metabolizing enzymes and drug transporters. Although the weight of evidence for the effects of certain NHPs varies and many studies of these products lack scientific rigor, it has been observed that St. John's wort clearly induces cytochrome P450 3A4 and P-glycoprotein and reduces protease inhibitor and nonnucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure. Limited clinical research suggests that intake of garlic and vitamin C results in reductions in ARV concentrations. The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase ARV concentrations, but by clinically unimportant amounts. Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly affecting lopinavir concentrations. Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained.


Neuromuscular blocking effect of fluoxetine and its interaction with rocuronium.
As selective serotonin reuptake inhibitors have an inhibitory effect on nicotinic acetylcholine receptors, they may affect the neuromuscular transmission and interact with neuromuscular blockers. This study was designed to observe the effect of fluoxetine on neuromuscular transmission and its interaction with rocuronium using the rat phrenic nerve hemidiaphragm and rabbit head drop methods. Rat phrenic nerve hemidiaphragms were mounted and stimulated using a train of four pulses (TOF). The effect of fluoxetine was studied on both indirectly and directly stimulated basal twitch responses by plotting cumulative dose response curves (DRCs). DRCs of rocuronium were obtained in the absence, and presence of 5 μm and 20 μm fluoxetine to study its interaction. ED5 , ED50 and ED95 values of rocuronium DRCs in absence and presence of fluoxetine were calculated. Fluoxetine significantly inhibited twitch responses in both indirect and directly stimulated preparations. Fluoxetine (20 μm) caused an increase in the potency of rocuronium such that the ED50 and ED95 values of rocuronium DRCs were significantly decreased. Partially inhibited twitch responses by fluoxetine (100 μm) were not reversed by neostigmine (3.3 μm) or 3,4 diaminopyridine (0.25 μm). Rabbits were given fluoxetine 0.25 mg kg(-1) and 1 mg kg(-1) orally for 15 days, and on 15th day, rocuronium infusion was given, and time for head drop was recorded. The time of head drop was significantly reduced in fluoxetine pretreated as compared to control group. Fluoxetine blocks the neuromuscular transmission and increases the potency of rocuronium-induced neuromuscular block.


Adolescent idiopathic scoliosis.
Adolescent idiopathic scoliosis, a lateral curvature of the spine, is an insidious disorder that usually occurs in previously well children. The onset is generally during the growth spurt of the early teens. While a potentially disabling disease entity, serious deformity can be averted through early detection and proper management. The nurse can be instrumental in this procedure by learning the necessary examination techniques and conscientiously screening all susceptible patients entering the health care setting.


Diagnosis of Posterior Urethral Valves in an Infant Using Point-of-Care Ultrasound.
This case describes a 7-week-old male infant presenting with vomiting and decreased urine output. Initial point-of-care ultrasound (POCUS) demonstrated a normal pylorus; however, assessment of bladder volume revealed the problem. The bladder was distended with a thickened, trabeculated wall and there was bilateral hydroureter, consistent with bladder outlet obstruction. Renal POCUS revealed bilateral hydronephrosis and perinephric fluid collections consistent with calyceal rupture. A voiding cystourethrogram confirmed the diagnosis of posterior urethral valves which were eventually ablated by urology. To our knowledge, this is the first case report of POCUS leading to a diagnosis of posterior urethral valves in an infant. This case highlights how POCUS can expedite evaluation of decreased urine output.


Two Cases of Autoimmune Syndrome Induced by Adjuvants (ASIA): A Multifaceted Condition Calling for a Multidisciplinary Approach.
Silicone implants have been used for cosmetic enhancement and reconstructive purposes for over 60 years. Despite assiduous efforts to ensure safety, there is continuous evidence that they are not as biologically inert as previously postulated. We present two cases of autoimmune syndrome induced by adjuvants (ASIA) in Hispanic women. The first patient developed biopsy-proven immune-mediated necrotizing myopathy that was successfully treated with the combination of silicone explantation along with immunosuppressive therapy. Findings after implant removal demonstrated rupture and leakage of silicone from gluteal implants. The second patient developed autoimmune hemolytic anemia in the setting of a ruptured silicone breast implant. Similarly, the patient was treated with corticosteroids followed by breast implant removal with complete resolution of symptoms. The successful treatment of these patients was achieved by collaboration between rheumatology and plastic surgery, which emphasizes the need for a multidisciplinary approach in the diagnosis and management of patients with ASIA.


Ruthenium-catalyzed synthesis of functionalized 1,3-dienes.
Functionalized 1,3-diene derivatives have been prepared by regioselective allylation of various nucleophiles with 1,3-dienic carbonates in the presence of a (N,O-carboxylate) allylruthenium precatalyst.


Markers of human papillomavirus infection and their correlation with cervical dysplasia in human immunodeficiency virus-positive women.
Human papillomavirus (HPV) genotypes and HPV DNA load were analysed in cervical smears from 76 human immunodeficiency virus (HIV)-positive and 54 HIV-negative women. The prevalence of genotypes was similar for all women, with the exception of HPV62, which was over-represented in HIV-positive samples. HIV-positive women showed a higher prevalence of multiple genotypes that correlated neither with CD4(+) T-cell counts nor with cervical dysplasia. No significant differences were observed in terms of total or single-type HPV DNA load. The HPV DNA load in both HIV-positive and HIV-negative women was significantly higher in squamous intra-epithelial lesions than in negative Pap smears.


Agenda Setting and Evidence in Maternal Health: Connecting Research and Policy in Timor-Leste.
The evidence-based policy (EBP) movement has received significant attention in the scientific literature; however, there is still very little empirical research to provide insight into how policy decisions are made and how evidence is used. The lack of research on this topic in low- and middle-income countries is of particular note. We examine the maternity waiting home policy in Timor-Leste to understand the role of context, policy characteristics, individual actors, and how evidence is used to influence the policy agenda. The research tracked the maternity waiting home policy from 2005 to 2009 and is based on in-depth interviews with 31 senior policy-makers, department managers, non-government organization representatives, and United Nations advisors. It is also informed by direct observation, attendance at meetings and workshops, and analysis of policy documents. The findings from this ethnographic case study demonstrate that although the post-conflict context opened up space for new policy ideas senior Ministry of Health officials rather than donors had the most power in setting the policy agenda. Maternity waiting homes were appealing because they were a visible, non-controversial, and logical solution to the problem of accessing maternal health services. Evidence was used in a variety of ways, from supporting pre-determined agendas to informing new policy directions. In the pursuit of EBP, we conclude that the power of research to inform policy lies in its timeliness and relevance, and is facilitated by the connection between researchers and policy-makers.


Acquisition of syngeneic I-A determinants by T cells proliferating in response to poly (Glu60Ala30Tyr10).
The T cell proliferative response in mice to the synthetic polymer GAT is under Ir gene control, mapping to the I-A subregion of the H-2 major histocompatibility complex (MHC). Antigen-dependent proliferation in vitro of in vivo GAT-primed lymph node cells can be inhibited by a monoclonal antibody to Ia-17, an I-A public determinant. Using this antibody for direct immunofluorescent analysis, T cells in GAT-stimulated proliferative culture are identified that express syngeneic I-A during culture. This expression is strictly antigen dependent, requires restimulation in vitro, and requires the presence of I-A-positive adherent antigen-presenting cells. T cells bearing I-A can be enriched by a simple affinity procedure, and I-A-positive cells separated on a FACS are shown to retain antigen-specific reactivity. The acquisition of I-A determinants by T cells under these culture conditions is not nonspecific. The Ia determinants borne by T cell blasts appear to be dictated by the I subregion to which the relevant Ir gene maps, and which codes for the Ia molecule involved in presentation of the antigen. Thus, (B6A)F1 (H-2b X H-2a)F1 LNC express I-Ak antigens when proliferating to GAT but not when stimulated by GLPhe, the response to which is under I-E subregion control. The relation of Ir gene function to Ia-restricted antigen presentation and self-Ia recognition is discussed.


Lipolysis-stimulated lipoprotein receptor: a novel membrane protein of tricellular tight junctions.
Tricellular tight junctions (tTJs) are specialized structural variants of tight junctions that restrict the free diffusion of solutes at the extracellular space of tricellular contacts. Their presence at cell corners, situated in the angles between three adjacent epithelial cells, was identified early by electron microscopy, but despite their potential importance, tTJs have been generally ignored in epithelial cell biology. Tricellulin was the first molecular component of tTJs shown to be involved in their formation and in epithelial barrier function. However, the precise molecular organization and function of tTJs are still largely unknown. Recently, we identified the lipolysis-stimulated lipoprotein receptor (LSR) as a tTJ-associated membrane protein. LSR recruits tricellulin to tTJs, suggesting that the LSR-tricellulin system plays a key role in tTJ formation. In this paper, we summarize the identification and characterization of LSR as a molecular component of tTJs.


Improvement and validation of a high-performance liquid chromatography in tandem mass spectrometry method for monitoring of omeprazole in plasma.
Omeprazole (OME) is a proton pump inhibitor with a 58% bioavailability after a single oral dose. It is subject to marked interindividual variations and significant drug-drug interactions. The authors developed a simple and rapid method based on liquid chromatography in tandem with mass spectrometry with solid phase extraction and isotope-labeled internal standard to monitor plasma levels of OME in pharmacokinetics and drug-drug interaction studies. OME and its internal standard (OME-D3) were eluted with a Zorbax Extend C-18 rapid resolution column (4.6 × 50 mm, 3.5 μm) at 25°C, under isocratic conditions through a mobile phase consisting of 1 mM ammonium acetate, pH 8.5 (55%), and acetonitrile (45%). The flow rate was 0.8 mL/min, and the chromatogram run time was 1.2 minutes. OME was detected and quantified by liquid chromatography in tandem with mass spectrometry with positive electrospray ionization, which operates in multiple-reaction monitoring mode. The method was linear in the range of 1.5-2000 ng/mL for OME. The validation assays for accuracy and precision, matrix effect, extraction recovery, and stability of the samples for OME did not deviate more than 20% for the lower limit of quantification and no more than 15% for other quality controls. These findings are consistent with the requirements of regulatory agencies. The method enables rapid quantification of OME concentrations and can be used in pharmacokinetic and drug-drug interaction studies.


Comparison of clinical imaging and pathological findings of various brain lesions including cerebrovascular diseases and other systemic diseases.
Looking back at the cases of brain cutting conducted in Sumitomo Hospital over the past 32 years, cases where clinical brain imaging could be compared with pathological findings other than degenerative diseases are examined and carefully selected, and instructive examples of them are presented. Although there are some limitations, the comparison between clinical brain imaging and pathological finding is significant to the final diagnosis and understanding of the pathogenesis of brain lesions.


Muscle sympathetic activity in resting and exercising humans with and without heart failure.
The sympathetic nervous system is critical for coordinating the cardiovascular response to various types of physical exercise. In a number of disease states, including human heart failure with reduced ejection fraction (HFrEF), this regulation can be disturbed and adversely affect outcome. The purpose of this review is to describe sympathetic activity at rest and during exercise in both healthy humans and those with HFrEF and outline factors, which influence these responses. We focus predominately on studies that report direct measurements of efferent sympathetic nerve traffic to skeletal muscle (muscle sympathetic nerve activity; MSNA) using intraneural microneurographic recordings. Differences in MSNA discharge between subjects with and without HFrEF both at rest and during exercise and the influence of exercise training on the sympathetic response to exercise will be discussed. In contrast to healthy controls, MSNA increases during mild to moderate dynamic exercise in the presence of HFrEF. This increase may contribute to the exercise intolerance characteristic of HFrEF by limiting muscle blood flow and may be attenuated by exercise training. Future investigations are needed to clarify the neural afferent mechanisms that contribute to efferent sympathetic activation at rest and during exercise in HFrEF.


Inheritance and Allelic Relationship Among Downy Mildew Resistance Genes in Pearl Millet.
Pearl millet downy mildew (DM), caused by Sclerospora graminicola, is of serious economic concern to pearl millet farmers in the major crop-growing areas of the world. To study the inheritance and allelic relationship among genes governing resistance to this disease, three DM-resistant pearl millet lines (834B, IP 18294-P1, and IP 18298-P1) and one susceptible line (81B) were selected on the basis of disease reaction under greenhouse conditions against two isolates of S. graminicola (Sg 526-1 and Sg 542-1). Three resistant parents were crossed with the susceptible parent to generate F1, F2, and backcross BC1P1 (susceptible parent × F1) and BC1P2 (resistant parent × F1) generations for inheritance study. To carry out a test for allelism, the three resistant parents were crossed with each other to generate F1 and F2 generations. The different generations of these crosses were screened for disease reaction against two isolates (Sg 526-1 and Sg 542-1) by artificial inoculation under greenhouse conditions. The segregation pattern of resistance in the F2 and corresponding backcross generations revealed that resistance to DM is controlled by a single dominant gene in 834B and IP 18294-P1 and by two dominant genes in IP 18298-P1. A test for allelism inferred that a single dominant gene for resistance in 834B is nonallelic to that which governs resistance in IP 18294-1, whereas one of the two dominant genes for DM resistance in IP 18298-P1 against the test isolates is allelic to the gene for DM resistance in 834B and a second gene is allelic to the resistance gene present in IP 18294-P1.


Experimental autoimmune damage to rat male accessory glands. I. Transfer of autoimmune response by spleen cells.
Spleen cells obtained 30 days after the first immunization of rats isoimmunized with an extract of male accessory glands (MAG) were capable of adoptively transferring specific cell-mediated immunity to normal syngenic recipients. Humoral and cell-mediated immune responses were investigated in donor and in the recipient rats that were killed 7 days after intravenous (IV) injection of the cells. In recipient rats the cell-mediated immunity showed multiple ways of expression and in some cases this was exemplified by a sharp increase in regard to the donor's response. Furthermore, a widespread reactivity in the spleen, lymph nodes, and thymus cells was detected. On the contrary, no circulating antibodies to MAG antigens were demonstrated after the spleen cell transfer. Cell separation studies showed that a nylon wool-nonadherent cell was responsible for the transfer of the cell-mediated immune response. This was abrogated by depletion of T lymphocytes and treatment with antirat thymocytes serum and complement. The mechanism of transfer and development of the cell-mediated immunity in recipient rats is discussed.


[Exercise-induced left bundle-branch block in patients with coronary artery disease versus patients with normal coronary arteries].
Exercise-induced left bundle-branch block does not always denote the presence of underlying coronary artery disease. The aim of this study was to analyze the clinical characteristics and evolution of patients with rate-dependent left bundle-branch block. 9,318 consecutive exercise stress studies were reviewed. The clinical characteristics and evolution (mean follow-up: 6.9 years) of 20 patients with exercise-induced left bundle-branch block in which coronary angiography had been performed were analyzed. Eight out of 20 patients had normal coronary arteries (group A) and 12 had coronary artery disease (group B). Peak O2 consumption, peak myocardial O2 consumption, and heart rate when block appeared (132 20 vs. 95.4 23 beats/min; p = 0.002) were significantly higher in group A. Seven of the 8 patients with normal coronary arteries had chest pain coinciding with the first beat of left bundle-branch block. There were no deaths during follow-up in group A, but permanent left bundle-branch block appeared in 5 patients of this group who experienced disappearance of exercise-related pain. There were 3 deaths in group B and 2 patients had acute myocardial infarction during follow-up. One patient in each group developed atrioventricular block and required pacemaker implantation. In contrast with patients with left bundle-branch block and coronary artery disease, the prognosis of patients with painful left bundle-branch block and normal coronary arteries is good. However, the development of permanent left bundle-branch block is frequent. Atrioventricular block, although rare, may occur.


Room-Temperature Macroscopic Coherence of Two Electron-Hole Plasmas in a Microcavity.
Macroscopic coherence of Bose condensates is a fundamental and practical phenomenon in many-body systems, such as the long-range correlation of exciton-polariton condensates with a dipole density typically below the exciton Mott-transition limit. Here we extend the macroscopic coherence of electron-hole-photon interacting systems to a new region in the phase diagram-the high-density plasma region, where long-range correlation is generally assumed to be broken due to the rapid dephasing. Nonetheless, a cooperative state of electron-hole plasma does emerge through the sharing of the superfluorescence field in an optical microcavity. In addition to the in situ coherence of e-h plasma, a long-range correlation is formed between two 8-μm-spaced plasma ensembles even at room temperature. Quantized and self-modulated correlation modes are generated for e-h ensembles in the plasma region. By controlling the distance between the two ensembles, multiple coupling regimes are revealed, from strong correlation to perturbative phase correlation and finally to an incoherent classical case, which has potential implications for tunable and high-temperature-compatible quantum devices.


Cross-leg free flap for limb salvage in the setting of radiation.
Limb salvage in an irradiated patient with limited recipient vessels leaves few options for reconstruction. Cross-leg free flaps have been used to reconstruct defects that would otherwise lead to amputation in patients with no ipsilateral recipient vessels. We present the first documented case of a cross-leg free flap for limb salvage in a radiated bed after infection and tumour resection.


Mercury Contamination from Dental Amalgam.
Mercury in dental amalgam is a hidden source of global mercury pollution, resulting from the illegal diversion of dental mercury into the artisanal and small-scale gold mining sector, to crematoria emissions from the deceased and sewage sludge that is sold to farmers. These significant mercury sources result in air, water, and food contamination that consequently have a negative impact on human health. The aim of the present study was to investigate and report on all of the various pathways mercury in dental amalgam can enter the environment. The present study searched the electronic data bases of PubMed and Google Scholar. Peer reviewed journals and references of studies included for full-text review were examined for potentially relevant studies. Articles published between 2000 to 2018 were searched and specifically screened for articles that referenced "Dental Amalgam," and the following key words in various combinations: "Minamata Convention on Mercury Treaty," "Sewage Sludge," "Cremation," and "Artisanal and Small-Scale Gold Mining." Data were included on the most populous countries of China, India, the United States, Brazil, and the European Union collectively. We also included data on cremation statistics and current global trends, looking at populations where cremation is a common practice, such as Japan and India. Dental amalgam represents a significant, but understudied area of global mercury pollution that includes cremation, sewage sludge, burial, and small-scale gold mining. Mercury used in products and processes, including dental amalgams, is a global pollutant. Even after the last mercury dental amalgam is placed, its toxic legacy will continue for decades, because of its pervasive bioaccumulation in the environment. Government regulatory agencies should make it mandatory to utilize available technologies, not only in developing countries, but also in developed countries, to reduce mercury contamination. The authors declare no competing financial interests.


Cushing's disease: pituitary imaging.
Fourteen patients with adrenocorticotropic hormone (ACTH)-dependent hypercortisolism underwent pituitary scanning with computed axial tomography (CT) and magnetic resonance imaging (MRI). Computed tomography revealed pituitary macroadenomas in two patients, pituitary hyperplasia in one and a suspicion of pituitary microadenoma in one. Thirteen patients underwent MRI. One with a macroadenoma diagnosed on CT did not undergo MRI. The MRI revealed a pituitary macroadenoma in one, microadenoma in three and hyperplasia in two cases. Magnetic resonance imaging following gadolinium diethylene triamine penta acetic acid (gd-DTPA) enhancement revealed four more pituitary microadenomas. All patients who had pituitary adenomas (micro and macro) and hyperplasia underwent trans-sphenoidal pituitary surgery. One of the two patients, who had an enlarged pituitary on imaging but no demonstrable adenoma, was found to have a microadenoma at surgery. Patients with ACTH-dependent hypercortisolism should undergo MRI of the pituitary gland to identify/localize corticotroph pituitary adenomas. The study should include gd-DTPA enhancement in cases where the scan is normal.


Mother rabbits and their offspring: timing is everything.
Mother rabbits nurse once every 24 hr for ca. 3 min. The contribution of pup stimulation to the regulation of this process was investigated by: reducing litter size to one pup, covering all the mother's nipples, or taping the mouths of an eight-pup litter. Time inside the nest box with the young significantly increased under all these conditions. Yet, eight pups sucking on a single nipple allowed a normal time in the nest box. Bringing the litter to the mother earlier than usual promoted maternal behavior expression twice in 24 hr; the proportion of responsive females and the time at which they responded depended on the size of the litter suckled. These findings indicate that: (a) suckling determines the time inside the nest box and prevents mothers from responding to further pup stimulation for a variable time; (b) pup exposure promotes maternal behavior, even "out of phase" with circadian rhythmicity.