[Circadian blood pressure characteristics in hospitalized unstable angina pectoris patients with hypertension].
Objective: To define the characteristic of circadian rhythm of blood pressure in unstable angina pectoris (UAP)patients with hypertension and its effects on the cardiovascular events. Methods: It was a prospective study.Based on coronary angiographic results, 742 consecutive hospitalized UAP patients with hypertension and 89 consecutive hospitalized hypertensive patients were recruited between September 2014 and December 2015 in this study. Clinical data and the results of 24-hour ambulatory blood pressure monitoring (ABPM) were analyzed. Results: The total prevalence of hypertension in UAP is about 77.1%(742/962) in our cohort. The decrease of night-time systolic and diastolic blood pressure in UAP patients complicated with hypertension was lower than that in hypertensive patients (P<0.05). The prevalence of dipper, non-dipper and reverse dipper pattern was 12.4%(92/742), 34.9%(259/742) and 52.7%(391/742) in UAP patients complicated with hypertension, 18.0%(16/89), 48.3%(43/89) and 33.7%(30/89) in hypertensive patients. Obviously, the abnormal circadian rhythm of blood pressure was more significant in UAP patients with hypertension than in hypertensive patients, characterized by higher reverse dipper pattern in UAP patients with hypertension compared to patients with hypertension(P=0.00), similar results were evidenced among the male and female patients and patients with various ages. Subgroup analysis showed that except similar results on the incidence of reverse dipper pattern in controlled blood pressure aged less than 45 years old, the incidence of reverse dipper pattern was all significantly higher in UAP patients complicating with hypertension than in hypertensive patients independent no matter blood pressure controlled or not (all P<0.05). After adjustment for sex, age, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other risk factors, binary logistic regression analysis showed that reverse dipper pattern was independently associated with UAP(OR=1.53, 95%CI 1.12-2.61). Conclusions: This finding suggests that UAP patients with hypertension often have abnormal circadian rhythm, characterized by higher reverse dipper circadian pattern. Elevated nocturnal blood pressure is independently related to UAP.


Visuomotor Functions in the Frontal Lobe.
This review surveys how vision becomes action through the frontal lobe. Signals from extrastriate areas create maps in frontal areas. These maps are shaped by visual features and shaded by goals, values, and experience, and they guide contingent activation of motor circuits to execute coordinated gaze, head, and limb movements. Frontal circuits also support the visual perception of learned objects, events, and actions. Other frontal circuits monitor consequences and exert executive control to improve the effectiveness of visually guided behavior.


[Pregabalin for the reduction of opiate withdrawal symptoms].
Pregabalin is a substance which modulates monoamine release in "hyper-excited" neurons. It binds potently to the α2-δ subunit of calcium channels. Pilotstudies on alcohol- and benzodiazepine dependent patients reported a reduction of withdrawal symptoms through Pregabalin. To our knowledge, no studies have been conducted so far assessing this effect in opiate dependent patients. We report the case of a 43-year-old patient with Pregabalin intake during opiate withdrawal. Multiple inpatient and outpatient detoxifications from maintenance replacement therapy with Buprenorphine in order to reach complete abstinence did not show success because of extended withdrawal symptoms and repeated drug intake. Finally he disrupted his heroine intake with a simultaneously self administration of 300 mg Pregabaline per day and was able to control the withdrawal symptoms. In this time we did control the Pregabalin level in serum and urine in our outpatient clinic. In the course the patient reported that he could treat further relapse with opiate or opioids with Pregabalin successful. This case shows first details for Pregabalin to relief withdrawal symptoms in opiate withdrawal.


The role of genes, intelligence, personality, and social engagement in cognitive performance in Klinefelter syndrome.
The determinants of cognitive deficits among individuals with Klinefelter syndrome (KS) are not well understood. This study was conducted to assess the impact of general intelligence, personality, and social engagement on cognitive performance among patients with KS and a group of controls matched for age and years of education. Sixty-nine patients with KS and 69 controls were assessed in terms of IQ, NEO personality inventory, the Autism Spectrum Quotient (AQ) scale, and measures of cognitive performance reflecting working memory and executive function. Patients with KS performed more poorly on memory and executive-function tasks. Patients with KS also exhibited greater neuroticism and less extraversion, openness, and conscientiousness than controls. Memory deficits among patients with KS were associated with lower intelligence, while diminished executive functioning was mediated by both lower intelligence and less social engagement. Our results suggest that among patients with KS, memory deficits are principally a function of lower general intelligence, while executive-function deficits are associated with both lower intelligence and poorer social skills. This suggests a potential influence of social engagement on executive cognitive functioning (and/or vice-versa) among individuals with KS, and perhaps those with other genetic disorders. Future longitudinal research would be important to further clarify this and other issues discussed in this research.


[Production of transgenic mice].
Transgenic mice are very useful for analyzing the functions of a gene either at the tissue level or at the whole body level. Here we describe the production of transgenic mice by the microinjection of DNA into the pronuclei of fertilized mouse eggs.


A circulating substance cross-reacting with antiimidazoline antibodies. Detection in serum in relation to essential hypertension.
It has been shown in various mammal species that clonidine, a well known centrally acting hypotensive agent, acts through the activation of imidazoline receptors (IRs) in the nucleus reticularis lateralis (NRL) of the brainstem. Specific binding sites sensitive to imidazolines and insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, other than catecholamines, should exist for these IRs. Such a ligand could play a role in the pathophysiology of human essential hypertension. Therefore, we developed two RIAs with polyclonal and monoclonal anticlonidine antibodies. These antibodies presented specificity spectra similar to that of the IRs: they bound imidazolines and not catecholamines at all. These RIAs were used to detect imidazoline-like immunoreactivity in the human serum. Immunoreactive substance was measured in 26 normotensive subjects' sera, and specificity of interaction between antibodies and sera was verified. None of the known endogenous substances tested so far were able to interact with the two antibodies. Immunoreactivity in 32 essential hypertensive patients' sera proved higher in approximately 30% of cases. Values of immunoreactivity positively correlated with the mean arterial pressure values. This study demonstrates the existence of an "imidazoline-like" immunoreactive substance in the human serum with high levels in some hypertensive patients.


Pathogenicity and virulence of Marburg virus.
Marburg virus (MARV) has been a major concern since 1967, with two major outbreaks occurring in 1998 and 2004. Infection from MARV results in severe hemorrhagic fever, causing organ dysfunction and death. Exposure to fruit bats in caves and mines, and human-to-human transmission had major roles in the amplification of MARV outbreaks in African countries. The high fatality rate of up to 90% demands the broad study of MARV diseases (MVD) that correspond with MARV infection. Since large outbreaks are rare for MARV, clinical investigations are often inadequate for providing the substantial data necessary to determine the treatment of MARV disease. Therefore, an overall review may contribute to minimizing the limitations associated with future medical research and improve the clinical management of MVD. In this review, we sought to analyze and amalgamate significant information regarding MARV disease epidemics, pathophysiology, and management approaches to provide a better understanding of this deadly virus and the associated infection.


The GTP-binding regulatory proteins, Gs and G(i), are altered in erythrocyte membranes of patients with ischemic heart disease resulting from coronary atherosclerosis.
Acute ischemic heart disease is associated with alterations in the cardiac adenylate cyclase system response, although the specificity and mechanism of these events are unknown. We studied the characteristics of inhibitory (G(i)) and stimulatory (Gs) GTP-binding regulatory proteins (G proteins) of adenylate cyclase in erythrocyte membranes of patients (n = 16) with nonacute ischemic heart disease resulting from coronary atherosclerosis. Gs was measured by reconstitution with the resolved catalytic unit of adenylate cyclase and by cholera toxin-catalyzed ADP-ribosylation of a 42-kD protein; G(i) was tested as a 41-kD substrate of pertussis toxin-catalyzed ADP-ribosylation. Gs activity was decreased by 27 +/- 2% in the cholate extract and by 25 +/- 3% in the supernatant of guanosine 5'-(gamma-thio)triphosphate-treated membranes. The amount of cholera toxin substrate was decreased by 33 +/- 3%, and the pertussis toxin substrate was increased by 27 +/- 5% compared with healthy subjects (n = 10). All changes in G-protein characteristics appear to be specific relative to other erythrocyte membrane proteins and hemoglobin. Those patients who have a decreased Gs possess approximately normal Gi, and those with increased G(i) showed no change in Gs. Patients with increased G(i) (normal Gs) exhibited more severe deterioration of their coronary arteries than did patients with decreased Gs (normal G(i)) (P < .05), but these two groups did not differ significantly in serum lipids, hormones, drug therapy, historical data, or baseline assessment (P < 0.05).


Inhibition of Autophagy Increases Proliferation Inhibition and Apoptosis Induced by the PI3K/mTOR Inhibitor NVP-BEZ235 in Breast Cancer Cells.
The phosphoinositide 3 kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway is a complicated intracellular pathway which leads to cell growth and tumor proliferation and plays a significant role in breast cancer. Multiple compounds targeting this pathway are being evaluated in clinical trials. NVP-BEZ235, a novel and orally available dual PI3K/mTOR inhibitor, showed great antitumor effect and provided a therapy strategy in breast cancer. In this study, we detect the effect of NVP-BEZ235 on cell viability, apoptosis, and autophagy in a breast cancer cell line. We also test the effect of NVP-BEZ235 on the expression of PI3K/AKT/mTOR pathway proteins p-AKT, p-mTOR, and p-70S6K. The results showed that the PI3K/AKT/mTOR proteins p-AKT, p-mTOR, and p-70S6K were obviously suppressed by NVP-BEZ235. NVP-BEZ235 inhibited cell proliferation and induced apoptosis and autophagy in breast cancer cells. In combination with autophagy inhibitors or autophagy gene knockdown, enhanced growth inhibition and apoptosis was induced by NVP-BEZ235 in MCF-7 cells. This study provides a novel treatment strategy that PI3K/AKT/mTOR pathway inhibitors in combination with autophagy inhibitors lead to further apoptosis in breast cancer cells.


Tau pathology involves protein phosphatase 2A in parkinsonism-dementia of Guam.
Parkinsonism-dementia (PD) of Guam is a neurodegenerative disease with parkinsonism and early-onset Alzheimer-like dementia associated with neurofibrillary tangles composed of hyperphosphorylated microtubule-associated protein, tau. β-N-methylamino-l-alanine (BMAA) has been suspected of being involved in the etiology of PD, but the mechanism by which BMAA leads to tau hyperphosphorylation is not known. We found a decrease in protein phosphatase 2A (PP2A) activity associated with an increase in inhibitory phosphorylation of its catalytic subunit PP2Ac at Tyr(307) and abnormal hyperphosphorylation of tau in brains of patients who had Guam PD. To test the possible involvement of BMAA in the etiopathogenesis of PD, we studied the effect of this environmental neurotoxin on PP2A activity and tau hyperphosphorylation in mouse primary neuronal cultures and metabolically active rat brain slices. BMAA treatment significantly decreased PP2A activity, with a concomitant increase in tau kinase activity resulting in elevated tau hyperphosphorylation at PP2A favorable sites. Moreover, we found an increase in the phosphorylation of PP2Ac at Tyr(307) in BMAA-treated rat brains. Pretreatment with metabotropic glutamate receptor 5 (mGluR5) and Src antagonists blocked the BMAA-induced inhibition of PP2A and the abnormal hyperphosphorylation of tau, indicating the involvement of an Src-dependent PP2A pathway. Coimmunoprecipitation experiments showed that BMAA treatment dissociated PP2Ac from mGluR5, making it available for phosphorylation at Tyr(307). These findings suggest a scenario in which BMAA can lead to tau pathology by inhibiting PP2A through the activation of mGluR5, the consequent release of PP2Ac from the mGluR5-PP2A complex, and its phosphorylation at Tyr(307) by Src.


Analysis of a free-running synchronization artifact correction for MV-imaging with aSi:H flat panels.
Solid state flat panel electronic portal imaging devices (EPIDs) are widely used for megavolt (MV) photon imaging applications in radiotherapy. In addition to their original purpose in patient position verification, they are convenient to use in quality assurance and dosimetry to verify beam geometry and dose deposition or to perform linear accelerator (linac) calibration procedures. However, native image frames from amorphous silicon (aSi:H) detectors show a range of artifacts which have to be eliminated by proper correction algorithms. When a panel is operated in free-running frame acquisition mode, moving vertical stripes (periodic synchronization artifacts) are a disturbing feature in image frames. Especially for applications in volumetric intensity modulated arc therapy (VMAT) or motion tracking, the synchronization (sync) artifacts are the limiting factor for potential and accuracy since they become even worse at higher frame rates and at lower dose rates, i.e., linac pulse repetition frequencies (PRFs). The authors introduced a synchronization correction method which is based on a theoretical model describing the interferences of the panel's readout clocking with the linac's dose pulsing. Depending on the applied PRF, a certain number of dose pulses is captured per frame which is readout columnwise, sequentially. The interference of the PRF with the panel readout is responsible for the period and the different gray value levels of the sync stripes, which can be calculated analytically. Sync artifacts can then be eliminated multiplicatively in precorrected frames without additional information about radiation pulse timing. For the analysis, three aSi:H EPIDs of various types were investigated with 6 and 15 MV photon beams at varying PRFs of 25, 50, 100, 200, and 400 pulses per second. Applying the sync correction at panels with gadolinium oxysulfide scintillators improved single frame flood field image quality drastically [improvement of the signal-to-noise ratio (SNR) up to 66.1 dB for 6 MV and 66.0 dB for 15 MV]. Also for the EPID with a caesium iodide scintillator, the noise for the lower PRFs could be reduced (SNR at 6 MV of up to 56.3 dB and at 15 MV up to 46.7 dB). However, the simplistic readout interference model fails at higher PRFs, where image lag and ghosting effects due to trapped charges in the thin film transistor and scintillator postglowing require additional corrections. The presented free-running sync correction method improves SNR of single frames and enables imaging applications, like low-dose rate imaging at increased image frame rates (e.g., to track moving gold fiducials in the lung). Adaptive image guided radiotherapy protocols become even feasible in VMAT plans. Also simultaneous kilovolt and MV imaging applications can benefit from new possibilities of MV scatter removal in x-ray images.


Garlic exerts hepatoprotective effects during 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats.
The modifying effects of garlic (Allium sativum Linn.) on hepatic lipid peroxidation and antioxidant status during 4-nitroquinoline 1-oxide (4NQO)-induced oral carcinogenesis were investigated in male Wistar rats. Enhanced lipid peroxidation in the liver of tumour-bearing animals was accompanied by significant decreases in the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST) and reduced glutathione (GSH) levels. Administration of aqueous garlic extract significantly lowered lipid peroxidation and enhanced the levels of hepatic antioxidants and detoxifying enzymes. The results of the present study suggest that garlic exerts its hepatoprotective effects by influencing hepatic biotransformation enzymes and antioxidants.


Automaticity in speech perception: some speech/nonspeech comparisons.
Three experiments used sine-wave replicas of speech sounds to explore some differences between speech perception and general auditory perception. The experiments compared patterns of behavior in categorization and discrimination tasks for listeners reporting either speech or nonspeech percepts of sine-wave replicas of speech. We hypothesized that the perception of speech sounds is automatized, while the perception of less familiar sounds is not. The first experiment was designed to investigate the perception of relatively long initial consonant transitions using a synthetic /wa/-/ya/ sine-wave analog continuum. Speech listeners perceived the continuum categorically, but nonspeech listeners could not consistently categorize the items in the continuum. In the second experiment, both speech and nonspeech listeners could consistently categorize stimuli having final glides (an/ay/-/aw/ sine-wave replica continuum), but differences between speech and nonspeech listeners were found in the slopes of the identification functions, in reaction times, and in the effect of context. These differences are consistent with the hypothesis that speech perception is automatized. In the third experiment, nonspeech listeners' discrimination sensitivity was greater than speech listeners'. The observed pattern of results suggests that speech perception is accomplished by a fast, obligatory, and thus automatic perceptual mechanism.


Electronic Excitations in Nonpolar Solvents: Can the Polarizable Continuum Model Accurately Reproduce Solvent Effects?
In nonpolar solvents, both electrostatic and nonelectrostatic interactions play a role in tuning the electronic excitations of molecular solutes. This specificity makes the application of continuum solvation models a challenge. Here, we propose a strategy for the calculation of solvatochromic shifts on absorption spectra, using a coupling of the polarizable continuum model with a time-dependent density functional theory framework, which explicitly accounts for dispersion and repulsion, as well as for electrostatic effects. Our analysis makes a step further in the interpretation of the effects of nonpolar solvents and suggests new directions in their modeling using continuum formulations.


Preschool teachers' fidelity in implementing a comprehensive language-rich curriculum.
This study examined preschool teachers' fidelity to the language-focused curriculum (LFC; B. Bunce, 1995), a comprehensive classroom curriculum designed to improve at-risk children's language outcomes through targeted improvements to a classroom's activity contexts (e.g., dramatic play, art, storybook reading) and instructional processes (e.g., teacher use of open-ended questions, recasts, and expansions). Specific aims included to (a) examine program differentiation by determining how measures of activity contexts and instructional processes differentiated treatment and comparison teachers, (b) determine treatment teachers' adherence to both activity contexts and instructional processes over an entire academic year, and (c) determine treatment teachers' reported quality of program delivery and comfort with curriculum implementation. Fourteen preschool teachers were randomly assigned to implement the LFC or to maintain their prevailing curriculum. Fidelity was measured 3 times over an academic year using a curriculum fidelity checklist. LFC teachers exhibited fidelity to activity contexts more readily than to instructional processes. Teacher use of language-focused instructional processes was relatively low even after a year of LFC implementation. This study supports the need for speech-language pathologists to work closely with preschool educators to implement the activity contexts and instructional processes associated with high-quality preschool language-learning environments.


Partial Purification and Characterization of Polyphenol Oxidase Isozymes in Banana Bud.
Polyphenol oxidase was extracted from banana buds in the presences of Triton X-100, isoascorbate, and Polyclar AT, and two isozymes I and II have been separated and partially purified by chromatographies on Butyl Toyopearl 650 and DEAE-cellulose. I and II had different mobility in polyacrylamide gel electrophoresis with optimum pHs of 6.8 and 5.5, respectively. Both enzymes showed the apparent Km values of 0.5 mM for dopamine with substrate inhibitions at its higher concentrations. I and II were inhibited competitively by NaCI with the Ki values of 140 mM and 40 mM, respectively. I and II have a high heat stability, and 88 and 95% of the initial activities were retained after 1-hr incubation at 70°C, respectively.


A normal paediatric amylase range.
A normal paediatric range of plasma alpha-amylase activity was determined using the Phadebas blue starch method. The range for children over one year was 98--405 IU/l. Plasma amylase activity increased throughout infancy. Mature levels of activity were observed in some children by age 2 months and in most of them by 9 months.


Understanding bladder management on a palliative care unit: a grounded theory study.
Research regarding factors associated with nursing-initiated changes to bladder management at end-of-life is sparse. To explore the process of Palliative Care Unit (PCU) nurses' approach to bladder management changes. Nursing staff from one PCU in London, Canada were interviewed regarding bladder management care practices. A constructivist grounded theory was generated. Four interconnected themes emerged: humanity (compassionate support of patients); journey (making the most of a finite timeline); health condition (illness, functional decline); and context (orders, policies, supplies). These overlapping themes must be considered in light of ongoing changes which prompt recycling through the framework. While bladder management necessitates shared decision-making and individualised care, nurses' phronetic experience may serve to detect the presence of change and the need to consider other alternatives. End-of-life bladder management requires nurses to continually reconsider the significance of humanity, journey, health condition and context in light of ongoing changes.


Extending the search for folk personality constructs: the dimensionality of the personality-relevant proverb domain.
College students (95 men and 264 women) rated how well 211 familiar proverbs described their behavior and beliefs. A factor analysis of these data yielded 7 major dimensions; many of the factors were similar to recognized lexical personality factors. Big Five Conscientiousness and Neuroticism were each strongly associated with a single proverb dimension (interpreted as Restraint and Enjoys Life, respectively). Big Five Agreeableness, Extraversion, and Intellect/Imagination were all associated with several proverb dimensions. Agreeableness was most strongly associated with proverb dimensions representing Machiavellian behavior and strong Group Ties, and both Extraversion and Intellect showed particularly notable associations with an Achievement Striving dimension. The 2 remaining proverb dimensions, which represented a belief that Life is Fair and an attitude of Cynicism, could not be accounted for by the Big Five.


Discontinuous sets of knee extensions induce higher cardiovascular responses in comparison to continuous ones.
The strength training can promote significant cardiovascular responses during its performance and it is interesting to devise strategies to reduce them, without compromising the strength production. To compare the acute cardiovascular responses of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR) and double product (DP) during the unilateral knee extension (four series of 8 maximum repetitions) performed continuously or discontinuously. Both protocols involved a 2-minute interval between the series and the discontinuous protocol had an extra interval of 2 seconds between the 4th and the 5th repetitions. Eight healthy men trained in muscular strength (aged 26+/- 6 years) participated in the data collection and were randomly divided in two non-consecutive days. The cardiovascular responses were measured by photoplethysmography (Finapres, Ohmeda, Louisville, CO, USA) at rest, at the end of each series and 2 minutes after the performance of each protocol. The discontinuous series showed significantly higher values when compared to the protocol of the continuous series for: SAP (mmHg) at the 2nd (173.1+/- 5.4 vs 152.0+/- 4.0; p=0.001), 3rd (188.9+/- 8.6 vs 162.4+/- 6.0; p=0.000) and 4th series (193.1+/- 8.1 vs 161.6+/- 5.9; p=0.000); DAP (mmHg) at the 3rd (103.8+/- 4.1 vs 86.1+/- 3.3; p=0.000) and 4th series (104.1+/- 2.7 vs 83.4+/- 3.3; p=0.000); DP (mmHg.bpm) at the 2nd (17,907.5+/- 1,350.7 vs 14,541.9+/- 1,848.0; p=0.03), 3rd (19,687.3+/- 1,444.3 vs 15,612.1+/- 1,180.3; p=0.008) and 4th series (21,271.0+/- 1,794.2 vs 15,992.0+/- 1,093.4; p=0.001). The discontinuous protocol promoted higher increase in pressure responses when compared to the continuous one. However, due to the characteristics of the study design, further studies are necessary to support these findings.


[The relationship between regional levels of mortality of ischemic heart disease and social economic factors in the Russian Federation].
The study was carried out to evaluate input of particular indices considered by Rosstat into indices of mortality of ischemic heart disease in three age groups at regions of the Russian Federation in 2003-2013. The data base of the Institute of demographic studies of the Russian Economic School was used as the source of data concerning mortality of ischemic heart disease and myocardium infarction. The panel data analysis was applied to form panel of 800 observations (on every variable) i.e. on 80 subjects of the Russian Federation in 2003-2012. The base «United inter-sectoral informational statistical system" was used as source of factorial indices. It is established that the most significant impact on mortality of ischemic heart disease, including of myocardium infarction, is render such stress factors as alcohol abuse and urban residence at that this dependence only increases with age. The number of physicians and per capita level of gross value added demonstrate negative correlation with mortality of ischemic heart disease in all age groups both in males andfemales. The level of consumption of carbohydrates (grams per day) correlates positively with mortality of ischemic heart disease and negatively with mortality of myocardium infarction in all groups. The application of non-typical techniques of mathematical statistics is necessary for more accurate evaluation of factors effecting level of mortality of ischemic heart disease. From methodological point of view, the most proper is carrying out of prospective cohort studies.


Current Status of the Utilization of Powered Wheelchair in Preschool Children with Locomotive Disability in Japan.
[Purpose] This study aimed to elucidate the actual state of powered wheelchair (PWC) prescription for preschool children with disabilities in Japan, and also to determine the approximate number of preschool children with disabilities who would potentially benefit from PWC use. [Subjects and Methods] A total of 318 facilities providing rehabilitation for disabled children in Japan were enrolled in the study. A questionnaire about PWC use for preschoolers was mailed to the facilities. Each study items were analyzed employing the Fisher's exact test. [Results] Of the 318 facilities, consent to participate in this study was obtained from 108 (return rate: 34.0%). After PWC provision, many facilities reported improvement in quality of life indices for preschool children with disabilities. It was revealed that there were 6 preschool children from 2 to 6 years of age with disabilities who might acquire a means of independent locomotion through PWC provision and thereby experience improved quality of life. [Conclusion] There was no negative comment from the facilities studied about the prescription and provision of PWC for preschool children with disabilities.


Proliferative Brenner tumor or ovarian metastases? A case report.
A case of low-grade superficial transitional papillomas of the urinary bladder and concomitant bilateral ovarian tumors with close similarities to the rare proliferative Brenner tumor is reported. Due to lack of benign Brenner elements, metastases from the bladder tumors were suggested. Death was apparently related to the effect of chemotherapy, and metastases were never confirmed. In review of the case, the authors found that the morphologic appearances and biological behavior of the ovarian tumors were more consistent with a proliferative Brenner tumor than with metastases. It is pointed out that a proliferative Brenner tumor should not be excluded in the absence of benign Brenner elements when other features are characteristic. Bilateral proliferating Brenner tumors are probably not reported previously. Histogenetic implications of a combined proliferative complex of bladder papillomas and Brenner tumor are briefly discussed.


Transcatheter arterial embolic therapies for hepatocellular carcinoma: a literature review.
Palliative therapies for hepatocellular carcinoma (HCC) include transcatheter arterial embolic therapies, radiation therapy and systemic chemotherapies such as sorafenib. Conventional transcatheter arterial chemoembolization (cTACE) is the golden standard for the treatment of intermediate-stage HCC, and involves the administration of chemotherapuetic drugs, with or without lipiodol, by means of a catheter directly to the feeding artery of the targeted tumor followed by administration of embolic agents, while the concept of drug-eluting bead TACE (DEB-TACE) builds on the rationale for cTACE. DEB-TACE has been demonstrated to substantially improve the pharmacokinetic profile of TACE, providing levels of consistency and repeatability in patients that are not available with cTACE. On the other hand, the technique of radioembolization therapy for HCC involves the delivery of high-dose radiation via the hepatic artery. In the present review, we summarize the current status of these transcatheter arterial embolic therapies in HCC.


Effects of an alfalfa protein hydrolysate on the gene expression and activity of enzymes of the tricarboxylic acid (TCA) cycle and nitrogen metabolism in Zea mays L.
The effects through which an alfalfa protein hydrolysate (EM) possessing gibberellin- and auxin-like activity may promote plant nitrogen (N) nutrition have been investigated in Zea mays L. Treatment with 0.01 or 0.1 mg L(-1) EM for 48 h resulted in enhanced plant growth and leaf sugar accumulation. Concomitantly, the level of nitrates decreased, whereas total N percentage was unchanged. The activity of a number of enzymes involved in carbon (C) metabolism (malate dehydrogenase, MDH; isocitrate dehydrogenase, IDH; citrate synthase, CS) and N reduction and assimilation (nitrate reductase, NR; nitrite reductase, NiR; glutamine synthetase, GS; glutamate synthase, GOGAT; aspartate aminotransferase, AspAT) was significantly induced by EM supply to plants, and the transcription pattern of MDH, IDH, CS, and NR strongly correlated with data of enzyme activity. The transcript accumulation of asparagine synthetase (AS) was also induced by EM in the roots. The results suggest that EM might promote nitrogen assimilation in plants through a coordinate regulation of C and N metabolic pathways and open the way for further research on protein hydrolysates as a valid tool to improve N use efficiency and, as a consequence, to reduce the intensive use of inorganic N fertilizers in agriculture.


Hymenoptera venoms used to produce allergen extracts.
To review the methods and materials used for collection, purification, commercial production, and clinical application of Hymenoptera venoms. Most of the sources for this review are the experience and expertise of the authors. Published reports and review articles on Hymenoptera venom collection and production were identified through database searches (PubMed). Studies describing the methods for Hymenoptera venom collection and production were selected for review. Meticulous methods for identification and collection of the insects are required. Collection and purification of the venoms from the insects are based on validated methods and result in a commercial extract that is standardized for the major allergenic proteins required for accurate diagnosis and safe and effective treatment of patients allergic to insect sting. The steps required for mixing, purifying, testing, and standardizing the products are described. Hymenoptera venom extracts were developed using many new methods for the collection, purification, and commercial production of the unique materials required for this product. Clinical applications for diagnosis and treatment are affected by the integrity and stability of the allergens after processing and purification.


Spectral function of the one-dimensional Hubbard model away from half filling.
We calculate the photoemission spectral function of the one-dimensional Hubbard model away from half filling using the dynamical density-matrix renormalization group method. An approach for calculating momentum-dependent quantities in finite open chains is presented. Comparison with exact Bethe ansatz results demonstrates the unprecedented accuracy of our method. Our results show that the photoemission spectrum of the quasi-one-dimensional conductor TTF-TCNQ provides evidence for spin-charge separation on the scale of the conduction bandwidth.


Differential item functioning analysis of the Vanderbilt Expertise Test for cars.
The Vanderbilt Expertise Test for cars (VETcar) is a test of visual learning for contemporary car models. We used item response theory to assess the VETcar and in particular used differential item functioning (DIF) analysis to ask if the test functions the same way in laboratory versus online settings and for different groups based on age and gender. An exploratory factor analysis found evidence of multidimensionality in the VETcar, although a single dimension was deemed sufficient to capture the recognition ability measured by the test. We selected a unidimensional three-parameter logistic item response model to examine item characteristics and subject abilities. The VETcar had satisfactory internal consistency. A substantial number of items showed DIF at a medium effect size for test setting and for age group, whereas gender DIF was negligible. Because online subjects were on average older than those tested in the lab, we focused on the age groups to conduct a multigroup item response theory analysis. This revealed that most items on the test favored the younger group. DIF could be more the rule than the exception when measuring performance with familiar object categories, therefore posing a challenge for the measurement of either domain-general visual abilities or category-specific knowledge.


How Old Do You Think I Am? Speech-Language Predictors of Perceived Age and Communicative Competence.
Purpose Spoken language serves as a primary means of social interaction, but speech and language skills change with age, a potential source of age-related stereotyping. The goals of this study were to examine how accurately age could be estimated from language samples, to determine which speech and language cues were most informative, and to assess the impact of perceived age on judgments of the speakers' communication skills. Method We analyzed narratives from 84 speakers aged 30-89 years to identify age-related differences and compared these differences to factors affecting perceptions of age and communicative competence. Three groups of raters estimated the speakers' ages and judged the quality of their communication: 44 listeners listened to audio-recorded narratives, 51 readers read transcripts of the narratives, and 24 voice raters listened to 10-s samples of speech extracted from one of the narratives. Results Older speakers spoke more slowly but showed minimal linguistic differences compared to younger speakers. Speakers' ages were estimated quite accurately, even from 10-s samples. Estimates were largely based on cues available in the acoustic signal-speech rate and vocal characteristics-so listeners were more accurate than readers. However, an overreliance on these cues also contributed to overestimates of speakers' ages. Communication ratings were not strongly related to perceived age but were influenced by various aspects of speech and language. In particular, speakers who produced longer narratives and spoke more quickly were judged to be better communicators. Conclusion Speakers tend to be judged on relatively superficial aspects of spoken language, in part because age-related change is most evident at these levels. Implications of these findings for age-related theories of stereotyping and speech-language intervention are discussed.


Transient paraplegia after neurolytic splanchnic block in a patient with metastatic colon carcinoma.
We present a patient with metastatic colon carcinoma who developed paraplegia following a neurolytic splanchnic block. A 41-year old man with metastatic adenocarcinoma of the colon received a splanchnic neurolytic block using alcohol because of severe abdominal pain. Bilateral motor weakness and a sensorial deficit in both legs developed after the procedure. Diffusion magnetic resonance imaging revealed spinal cord ischemia between T8 and L1. The motor and sensorial deficits were almost completely resolved at the end of the third month. We think that anterior spinal artery syndrome due to reversible spasms of the lumbar radicular arteries using alcohol have resulted in transient paraplegia. The retrograde spread of alcohol to neural structures may have also contributed.


Exploration of Chick Embryo and Chorioallantoic Membrane on Imaging Navigated Platforms for Anticancer Pharmaceutical Evaluations.
Conforming to the current replace-reduce-refine 3Rs' guidelines in animal experiments, a series of explorative efforts have been made to set up operable biomedical imaging-guided platforms for qualitative and quantitative evaluations on pharmacological effects of tumor vascular-disrupting agents (VDAs), based on the chick embryos (CEs) with its chorioallantoic membrane (CAM), in this overview. The techniques and platforms have been hierarchically elaborated, from macroscopic to microscopic and from overall to specific aspects. A protocol of LED lamplight associated with a new deep-learning algorithm was consolidated to screen out weak CEs by using the CAM vasculature imaging. 3D magnetic resonance imaging (MRI) and laser speckle contrast imaging (LSCI) to monitor the evolution of CE and vascular changes in CAM are introduced. A LSCI-CAM platform for studying the effects of VDAs on normal and cancerous vasculature of CAM and possible molecular mechanisms has been demonstrated. Finally, practical challenges and future perspectives are highlighted. The aim of this article is to help peers in biomedical research to familiarize with the CAM platform and to optimize imaging protocols for the evaluation of vasoactive pharmaceuticals, especially anticancer vascular targeted therapy.


[Practical Aspects of the Use of Oral Anticoagulant Rivaroxaban for the Prevention of Adverse Outcomes After Acute Coronary Syndrome].
This review examines the reasons for long-term use of anticoagulants after an acute coronary syndrome, the study analysis the results of ATLAS ACS 2-TIMI 51 and with the main features of the use of rivaroxaban for the prevention of adverse outcomes in patients of this category that are important from a practical point of view.


Clinical features of patients with esophageal and second primary cancers.
The prevalence of esophageal cancer (EC) with second primary cancers (SPC) is increasing worldwide. This study was aimed to understand the clinical features of EC patients with SPC in the Taiwanese population. Clinical and laboratory data for 180 EC patients with or without SPC were collected between January 2009 and December 2013. Information on treatment approaches, location of SPCs and ABO blood type were also collected and stratified. The most common SPC in EC patients was hypopharyngeal cancer, followed by laryngeal cancer and hepatocellular carcinoma in our study. Malignancies of colon, prostate and lung were also found. There was a significant higher portion of blood type A in the EC patients with SPC compared with those without (42.4% vs 19.5%, P=0.006). The frequency and SPC site distribution and blood type A should be considered in clinical evaluation of EC patients with a high risk of developing SPC in the Taiwanese population.


Plexiform Schwannoma of Brachial Plexus in Axilla: A Rare Case Report.
The most common tumours in the brachial plexus are benign schwannomas, followed by neurofibromas and malignancies, originating from the peripheral nerve sheath. The clinical manifestations of brachial plexus tumours are variable according to their location, extension, neurological elements involved and pathology. Brachial plexus tumours are rare in the upper extremity, and axillary schwannoma is uncommon. This case reports a 59-year-old woman with a tumour in her left axilla for two years, gradually enlarging with numbness in her left little finger. Microsurgical interfascicular dissection operation was performed to remove the tumour. Νumbness disappeared after the procedure, and no tumour recurrence was observed during the 30-month follow-up. To the best of our knowledge, plexiform schwannoma of the brachial plexus in the axilla has not been reported so far. In this article, such a case is reported, where this tumour was diagnosed by the histopathological examination and confirmed with immunohistochemistry.


Postanesthesia care of the biliary lithotripsy patient.
Alabama Lithotripsy Services is a consortium of Baptist Medical Centers in Birmingham, Montclair, and Princeton, Druid City Regional Medical Center in Tuscaloosa, and Huntsville Hospital in Huntsville, AL. This consortium is the first of two mobile lithotripsy services currently involved in the Food and Drug Administration investigational study using the Medstone (Medstone International, Inc, Irvine, CA) STS Lithotripter in the treatment of biliary gallstones. This procedure is a safe and effective alternative to abdominal surgery. Postanesthesia nurses need to know the population and criteria for selecting patients, how the lithotripter operates, postanesthesia care, possible complications, advantages, and disadvantages, as well as the future consideration of biliary lithotripsy using the Medstone STS Biliary Lithotripter.


Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder.
Humans with lesions to the orbital/medial prefrontal cortex and interconnected areas display impulsive aggressive behavior. To examine further the relationship between impulsive aggression and orbital/medial prefrontal dysfunction, we measured the behavioral performance of psychiatric patients with a disorder characterized by impulsive aggression, Intermittent Explosive Disorder (IED). Presently, no evidence exists for a localized brain lesion in IED subjects. However, on the basis of the location of brain lesions that produce acquired impulsive aggression, we hypothesized that IED subjects would exhibit test performance similar to patients with lesions to the orbital/medial prefrontal cortex. Subjects with IED and controls were administered three tests sensitive to lesions of the orbital/medial prefrontal circuit: the Iowa Gambling Task, facial emotion recognition, and odor identification, and two control tests of working memory. On the gambling task, IED subjects continued to make disadvantageous decisions throughout the 100 trials, whereas controls learned to avoid disadvantageous decisions. On the facial recognition test, IED subjects were impaired at recognizing "anger," "disgust," and "surprise," and they were biased to label neutral faces with "disgust" and "fear." On odor identification, IED subjects were mildly anosmic and were impaired relative to controls. However, on the working memory control tests, both groups performed similarly. Across tests, the performance of IED subjects resembles the performance of patients with orbital/medial prefrontal lesions in previous studies. These results extend the link between dysfunction of the orbital/medial prefrontal circuit and impulsive aggressive behavior.


Critical appraisal tools used in systematic reviews of in vitro cell culture studies: A methodological study.
Systematic reviews (SRs) of preclinical studies are marked with poor methodological quality. In vitro studies lack assessment tools to improve the quality of preclinical research. This methodological study aimed to identify, collect, and analyze SRs based on cell culture studies to highlight the current appraisal tools utilized to support the development of a validated critical appraisal tool for cell culture in vitro research. SRs, scoping reviews, and meta-analyses that included cell culture studies and used any type of critical appraisal tool were included. Electronic search, study selection, data collection and methodological quality (MQ) assessment tool were realized. Further, statistical analyses regarding possible associations and correlations between MQ and collected data were performed. After the screening process, 82 studies remained for subsequent analysis. A total of 32 different appraisal tools were identified. Approximately 60% of studies adopted pre-structured tools not designed for cell culture studies. The most frequent instruments were SYRCLE (n = 14), OHAT (n = 9), Cochrane Collaboration's tool (n = 7), GRADE (n = 6), CONSORT (n = 5), and ToxRTool (n = 5). The studies were divided into subgroups to perform statistical analyses. A significant association (OR = 5.00, 95% CI = 1.54-16.20, p = 0.008) was found between low MQ and chronic degenerative disorders as topic of SR. Several challenges in collecting information from the included studies led to some modifications related to the previously registered protocol. These results may serve as a basis for further development of a critical appraisal tool for cell culture studies capable of capturing all the essential factors related to preclinical research, therefore enhancing the practice of evidence-based.


Strong transmission and reflection of edge modes in bounded photonic graphene.
The propagation of linear and nonlinear edge modes in bounded photonic honeycomb lattices formed by an array of rapidly varying helical waveguides is studied. These edge modes are found to exhibit strong transmission (reflection) around sharp corners when the dispersion relation is topologically nontrivial (trivial). An asymptotic theory is developed that establishes the presence (absence) of typical edge states, including, in particular, armchair and zigzag edge states in the topologically nontrivial (trivial) case. In the presence of topological protection, nonlinear edge solitons can persist over very long distances.


[3 + 3] Cycloaddition of Azides with in Situ Formed Azaoxyallyl Cations To Synthesize 1,2,3,4-Tetrazines.
A formal [3 + 3] cycloaddition reaction between azides and in situ formed azaoxyallyl cations has been realized. This reaction provided an efficient and practical pathway to synthesize 1,2,3,4-tetrazines in good yields under mild conditions. Biologically active molecules could also be well compatible, highlighting the potential value of this reaction.


AAV-mediated gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization.
Adeno-associated viral (AAV) vectors have been used to express several different proteins in the eye. The purpose of this study was to determine whether AAV-mediated intraocular gene transfer of pigment epithelium-derived factor (PEDF) inhibits the development of choroidal neovascularization (CNV) in a murine model. C57BL/6 mice were given intravitreous or subretinal injections of a PEDF expression construct packaged in an AAV vector (AAV-chicken beta-actin promoter-exon 1-intron 1[CBA]-PEDF) or control vector (AAV-CBA-green fluorescent protein[GFP]). After 4 or 6 weeks, the Bruch's membrane was ruptured by laser photocoagulation at three sites in each eye. After 14 days, the area of CNV at each rupture site was measured by image analysis. Intraocular levels of PEDF were measured by enzyme-linked immunosorbent assay. Four to six weeks after intraocular injection of AAV-CBA-PEDF, levels of PEDF in whole-eye homogenates were 6 to 70 ng. The average area of CNV at sites of the Bruch's membrane rupture showed no significant difference in eyes injected with AAV-CBA-PEDF compared with uninjected eyes. In contrast, 4 to 6 weeks after intraocular injection of 1.5 x 10(9) or 2.0 x 10(10) particles of AAV-CBA-PEDF, the area of CNV at the Bruch's membrane rupture sites had significantly decreased compared with CNV area at rupture sites in eyes injected with AAV-CBA-GFP. These data suggest that intraocular expression of PEDF or other antiangiogenic proteins with AAV vectors may provide a new treatment approach for ocular neovascularization.


Symptomatic patients with P369S-R408Q mutations: familial Mediterranean fever or mixed auto-inflammatory syndrome?
A 51-year-old South African female of Ashkenazi Jewish descent was admitted with acute pleuritic chest pain, shortness of breath, fatigue and fever. She experienced vague abdominal and calf pains for 30 years. Her monozygotic twin was investigated independently for recurrent abdominal pain. Despite initially responding to antibiotics, treating suspected pneumonia, she developed recurrent fevers and pleuritic chest pain. After thorough investigation without significant findings, she re-attended days after discharge with similar symptoms. Familial Mediterranean fever (FMF) was suggested as she met diagnostic criteria and responded to colchicine, though FMF normally presents before 20 years old. Genetic testing showed no pathogenic mutations but heterozygous P369S and R408Q mutations. The significance of these mutations remains unclear, as they are found in asymptomatic patients, suggesting incomplete penetrance. She remains well, with full symptom resolution, but mixed auto-inflammatory syndrome may be a more appropriate diagnosis in symptomatic patients with both P369S and R408Q mutations.


The maturational process of gonadotropin-releasing hormone neurons in the male rat: a role for the adrenal gland in the increase in secretory function.
The aim of this study was to define the maturational process of the LHRH neuron in the male rat and the role of the adrenal and testis. Maturing (7-week-old) and adult (12-week-old) male rats were adrenalectomized (ADX), castrated (TX), or ADX and TX; controls were sham operated. Two weeks later, LHRH release from explants of the median eminence area (MEA), MEA LHRH content, and serum testosterone (T) were determined. MEA were incubated for 5 min with 150 microM copper and then for 15 min with 10 microM prostaglandin E2 (Cu/PGE2). LHRH release in response to Cu/PGE2 increased 3-fold between 7 and 9 weeks of age [from 10.4 +/- 1.8 to 29.2 +/- 2.1 pg/15 min.MEA (mean +/- SE)], and there was no further increase thereafter. ADX, TX, or ADX plus TX of 7-week-old rats prevented the increase in Cu/PGE2-stimulated release. In contrast, ADX of 12-week-old rats did not alter LHRH release, whereas TX or ADX plus TX drastically reduced it (75%). The MEA content increased gradually between 7 and 14 weeks of age (from 2.0 +/- 0.2 to 3.0 +/- 0.3 ng). ADX of either 7- or 12-week-old rats did not alter LHRH content, whereas TX or ADX plus TX reduced it to 1.3 ng in both age groups. Serum T increased 6.7-fold between 7 and 9 weeks of age (from 1.06 +/- 0.42 to 6.70 +/- 0.57 ng/ml), and there was no further increase thereafter. ADX of 7-week-old rats did not alter serum T, whereas ADX of 12-week-old rats reduced serum T to 0.62 +/- 0.15 ng/ml. Serum T was undetectable in TX or ADX plus TX rats of both age groups. In summary, maturation of the male reproductive system is associated with a moderate increase in LHRH content of the median eminence and marked increases in the secretory function of the LHRH neuron and in serum T; the testis is essential for these maturational increases. In addition to the testis, the adrenal is necessary for the maturational increase in the secretory function of the LHRH neuron, but not for the increase in LHRH content or that in serum T. It is proposed that dissociable mechanisms regulate LHRH secretion and content in the maturing male, and that T and a substance of adrenal origin (steroid?) are required for the maturational increase in secretory function of the LHRH neuron.


Glucocorticoid-Induced Leucine Zipper Protects the Retina From Light-Induced Retinal Degeneration by Inducing Bcl-xL in Rats.
The aim of the present study was to investigate the neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ) in a light-induced retinal degeneration model and to explore the underlying mechanisms. Intravitreal injection of recombinant GILZ-overexpressing lentivirus (OE-GILZ-rLV) and short hairpin RNA targeting GILZ recombinant lentivirus (shRNA-GILZ-rLV) was performed to up- and downregulate retinal GILZ, respectively. Three days after stable transduction, rats were exposed to continuous bright light (5000 lux) for 2 days. Retinal function was assessed by full-field electroretinography (ERG), and the retinal structure was examined for photoreceptor survival and death in rats kept under a 12-hour light:2-hour dark cycle following light exposure. The expression levels of retinal Bcl-xL, caspase-9, and caspase-3 were examined by Western blotting or real-time PCR at 1, 3, 5, and 7 days after light exposure. Exposure to bright light downregulated retinal GILZ in parallel with the downregulation of Bcl-xL and the upregulation of active caspase-3. Overexpression of retinal GILZ attenuated the decrease of Bcl-xL and the activation of caspase-9 and caspase-3 at 1, 3, 5, and 7 days after bright light exposure, respectively. GILZ silencing aggravated the downregulation of Bcl-xL induced by bright light exposure. Bright light exposure reduced the amplitude of ERG, increased the number of apoptotic photoreceptor cells, and decreased retinal thickness; and GILZ overexpression could attenuate all these effects. Overexpression of GILZ by OE-GILZ-rLV transduction protected the retina from light-induced cellular damage by activating antiapoptotic pathways.


A novel phenol-bound pectic polysaccharide from Decalepis hamiltonii with multi-step ulcer preventive activity.
To investigate H(+), K(+)-ATPase inhibition, anti-H pylori, antioxidant, and the in vivo antiulcer potential of a pectic polysaccharide from Swallow root (Decalepis hamiltonii; SRPP). SRPP, with known sugar composition [rhamnose: arabinose: xylose: galactose in the ratio of 16:50:2:32 (w/w), with 141 mg/g of uronic acid] was examined for anti-ulcer potency in vivo against swim/ethanol stress-induction in animal models. Ulcer index, antioxidant/antioxidant enzymes, H(+), K(+)-ATPase and gastric mucin levels were determined to assess the anti-ulcer potency. Anti-H pylori activity was also determined by viable colony count and electron microscopic studies. SRPP, containing phenolics at 0.12 g GAE/g, prevented stress-induced gastric ulcers in animal models by 80%-85%. Down regulation of gastric mucin 2-3 fold, antioxidant/antioxidant enzymes and upregulation of 3 fold of H(+), K(+)-ATPase in ulcerous animals were normalized upon treatment with SRPP. Histopathological analysis revealed protection to the disrupted gastric mucosal layer and epithelial glands. SRPP also inhibited H(+), K(+)-ATPase in vitro, at an IC(50) of 77 microg/mL as opposed to that of 19.3 microg/mL of Lansoprazole and H pylori growth at Minimum Inhibitory Concentration (MIC) of 150 microg/mL. In addition, free radical scavenging (IC(50)-40 microg/mL) and reducing power (3200 U/g) activities were also observed. SRPP, with defined sugar composition and phenolics, exhibited multi-potent free radical scavenging, antioxidant, anti-H pylori, inhibition of H(+), K(+)-ATPase and gastric mucosal protective activities. In addition, SRPP is non-toxic as opposed to other known anti-ulcer drugs, and therefore may be employed as a potential alternative for ulcer management.


Oncological control after radical prostatectomy in men with clinical T3 prostate cancer: a single-centre experience.
To determine the effectiveness of cancer control afforded by radical prostatectomy (RP) in patients with clinical stage T3 prostate cancer. We retrospectively reviewed data for patients treated by RP for clinical stage T3 prostate cancer between 1995 and 2005. The following case characteristics were analysed: patient age, clinical presentation, preoperative prostate-specific antigen (PSA) level, Gleason score, tumour stage (2002 Tumour-Node-Metastasis), surgical procedure, pathological data, margin and lymph node status, and recurrence. Biochemical recurrence was defined as an increase in PSA level of >0.2 ng/mL after surgery. Kaplan-Meier survival curves were generated, and prognostic factors were evaluated. Overall, 100 patients were included; only 79% of them had pT3 disease based on the pathological specimen. The median follow-up after RP was 69 months. The RP was open in 77 and laparoscopic in 23, with no significant difference between these approaches (P = 0.38). The 5-year PSA-free survival after surgery was 45%, and 5-year cancer-specific survival was 90%. On univariable analysis, Gleason score >7 (P = 0.01), pathological stage (pT2-T3a vs T3b) (P < 0.001), positive lymph node (P < 0.001), and positive margin (P < 0.001) were associated with recurrence. On multivariable analysis, lymph node, margin status and Gleason score were also significant (P < 0.05). RP can be recommended as an alternative primary treatment that results in acceptable cancer control for clinical stage T3 prostate cancer in selected cases. However, the patient should be warned that surgery alone might not be sufficient to control the cancer, and that adjuvant therapy might be needed during the course of the disease.


Demonstration of optically-assisted reconfigurable average of two 20-Gbaud 4-phase-encoded data channels using nonlinear wave mixing.
Networks can play a key role in high-speed and reconfigurable arithmetic computing. However, two performance bottlenecks may arise when: (i) relying solely on electronics to handle computation for multiple data channels at high data rates, and (ii) the data streams input to a processing node (PN) are transmitted as phase-encoded signals over an optical network. We experimentally demonstrate the operation of optically-assisted reconfigurable average of two 4-phase-encoded data channels at 10- and 20-Gbaud rates. Our input signals are two streams of 2-bit numbers representing a binary floating-point format, and the operation results in 7-phase-encoded output signals represented by 3-bit numbers. The average operation is achieved in three stages: (1) phase encoding and division-using an optical modulator to encode the data streams; (2) summation-using a highly nonlinear fiber (HNLF); and (3) multicast-using a periodically poled lithium niobate (PPLN) waveguide to multicast back the result into the original signal wavelengths. The experimental results validate the concept, and the measured penalties indicate that: (i) the error vector magnitudes (EVMs) of optical signals increase at each stage and reach ∼18-21% for the final multicast results, and (ii) compared to the inputs, the optical signal-to-noise ratio (OSNR) penalty of output is ∼6.7 dB for the 10-Gbaud rate and ∼6.9 dB for the 20-Gbaud rate at a bit error rate (BER) of 3.8e-3.


HLA antigens, phytohemagglutinin stimulation, and corticosteroid response.
Although it is clear that the major histocompatibility complex is associated with lymphocyte glucocorticoid sensitivity in mice, there has been less evidence for a similar relationship in man. We have typed 158 individuals for: (1) 13 A locus and 16 B locus antigens, (2) degree of stimulation of their purified lymphocytes by phytohemagglutinin A (PHA), and (3) degree of inhibition of the PHA stimulation by prednisolone and prednisolone-21-hemisuccinate. In contrasts of individuals with a particular antigen (homozygous or heterozygous) with all remaining individuals, HLA-B7 was found to be associated with an enhancing effect on the log stimulation by PHA while other antigens of these series did not have significant associations. In similar contrasts, A10 was associated with a decrease in sensitivity to glucocorticoid inhibition of PHA stimulation as measured by the log I50 of the suppression of PHA stimulation. Other antigens of these series were not found to have significant associations with the glucocorticoid sensitivity of lymphocytes in this assay.


The decrease in prolidase activity in myeloproliferative neoplasms.
The development of bone marrow fibrosis is a severe complication in hematological diseases. The progress of bone marrow myelofibrosis is evaluated by a trephine examination and may be characterized by the biochemical markers of collagen turnover determination. Investigation of serum prolidase activity and biochemical markers of collagen metabolism in order to establish its role in the development of bone marrow fibrosis. The group of 37 patients with myeloproliferative neoplasms (MPN) before treatment, consisted of 16 patients with chronic myeloid leukemia (CML), 7 with primary myelofibrosis (PMF), 8 with essential thrombocythopenia (ET), and 6 with polycythemia vera (PV). It was found that the plasma activity of prolidase (Pro) was reduced to almost half together with the serum level of osteocalcin (BGL), and hydroxyproline (H-PRO) in the serum and urine of patients with MPN in comparison to the control group. In the MPN group of patients, the levels of N-terminal procollagen III peptide (PIIINP), type I procollagen (PICP) and the C-terminal telopeptide of type I collagen (ICTP) were significantly higher. The alteration of collagen turnover markers in the MPN patient group (the elevation of synthesis and inhibition of collagen catabolism rate) has suggested that a diminished prolidase activity may contribute to such alteration of collagen metabolism and should be consider a biomarker of MPN progress.


Chopstick-Like Structure for the Free Transfer of Microdroplets in Robot Chemistry Laboratory.
As we all know, chopsticks can hold food, so can we use this method to carry Newtonian fluids such as droplets? This paper studies the process of this transfer and uses this method to realize the manipulation of open microfluidics by robots. To realize this transfer operation, we first analyzed the force of droplets in this chopstick-like structure and found that the bidirectional movement of droplets in this structure can be achieved by changing the structural parameters. Afterward, the whole process of the transfer of droplets using the chopstick-like structure was analyzed, and the parameter requirements for realizing this transfer were determined. The research in this paper provides a theoretical basis for the controllable manipulation of droplets which can be widely used in unmanned laboratories.


Combined branch retinal artery and central retinal vein obstruction.
We observed seven patients with the unusual combination of a central retinal vein obstruction in conjunction with a simultaneous branch retinal artery obstruction. The patients presented with sectoral retinal whitening, as well as diffuse peripapillary and superficial retinal hemorrhages. In five of the seven patients, the retinal hemorrhages appeared most florid in the territory of the obstructed arteriole, resulting initially in the consideration that these cases represented a combined branch retinal artery and branch retinal vein obstruction. In all cases, however, the presence of dilated, tortuous veins with diffuse retinal hemorrhages, in addition to generalized delay in arteriovenous transit on fluorescein angiography, localized the venous blockage to the central retinal vein. No intra-arterial retinal emboli were visualized. Initially, five of the seven patients suffered markedly diminished visual function; although visual acuity returned to near normal in all but two patients. In the two patients with non-resolving, markedly impaired visual acuity, neovascularization of the iris complicated the clinical course. Both of these patients were treated with panretinal photocoagulation, with resolution of the iris neovascularization. These seven patients highlight another variation of combined arterial and venous retinal vascular disease.


Thirty years of socialistic health care: dentistry in Hungary.
The present status of dentistry in Hungary can be understood better through the country's political and economic history. Circumstances led to the development of a primarily socialistic form of health care. However, the mere existence of the private practice of dentistry in the system attests to the incomplete success of socialism in providing for the dental health needs of its citizens. As Americans confront national health issues, an examination of other modes of health care delivery is important to minimize mistakes and optimize benefits.


A physiologically based pharmacokinetic (PBPK) model to describe organ distribution of 68Ga-DOTATATE in patients without neuroendocrine tumors.
Physiologically based pharmacokinetic (PBPK) models combine drug-specific information with prior knowledge on the physiology and biology at the organism level. Whole-body PBPK models contain an explicit representation of the organs and tissue and are a tool to predict pharmacokinetic behavior of drugs. The aim of this study was to develop a PBPK model to describe organ distribution of 68Ga-DOTATATE in a population of patients without detectable neuroendocrine tumors (NETs). Clinical 68Ga-DOTATATE PET/CT data from 41 patients without any detectable somatostatin receptor (SSTR) overexpressing tumors were included. Scans were performed at 45 min (range 30-60 min) after intravenous bolus injection of 68Ga-DOTATATE. Organ (spleen, liver, thyroid) and blood activity levels were derived from PET scans, and corresponding DOTATATE concentrations were calculated. A whole-body PBPK model was developed, including an internalization reaction, receptor recycling, enzymatic reaction for intracellular degradation and renal clearance. SSTR2 expression was added for several organs. Input parameters were fixed or estimated using a built-in Monte Carlo algorithm for parameter identification. 68Ga-DOTATATE was administered with a median peptide amount of 12.3 µg (range 8.05-16.9 µg) labeled with 92.7 MBq (range 43.4-129.9 MBq). SSTR2 amounts for spleen, liver and thyroid were estimated at 4.40, 7.80 and 0.0108 nmol, respectively. Variability in observed organ concentrations was best described by variability in SSTR2 expression and differences in administered peptide amounts. To conclude, biodistribution of 68Ga-DOTATATE was described with a whole-body PBPK model, where tissue distribution was mainly determined by variability in SSTR2 organ expression and differences in administered peptide amounts.


[Lung topography and function in thoracic deformity].
In kyphoscoliosis, a rotation of the convex-sided lung around a vertical axis, can be observed. In comparison of "pure" scoliotics with kyphoscoliotics, the degree of kyphosis seems to counteract the rotating effect of scoliosis. This effect is possibly related to the duration of the deformity, insofar as, rotation increases primarily due to scoliosis and then tends to disappear with age-related development of accompanying kyphosis. The clinical relevancy and the kyphosis-dependent changes lf lung function, are discussed.


Nanoparticles as Versatile Tools for Mechanotransduction in Tissues and Organoids.
Organoids are 3D multicellular constructs that rely on self-organized cell differentiation, patterning and morphogenesis to recapitulate key features of the form and function of tissues and organs of interest. Dynamic changes in these systems are orchestrated by biochemical and mechanical microenvironments, which can be engineered and manipulated to probe their role in developmental and disease mechanisms. In particular, the in vitro investigation of mechanical cues has been the focus of recent research, where mechanical manipulations imparting local as well as large-scale mechanical stresses aim to mimic in vivo tissue deformations which occur through proliferation, folding, invagination, and elongation. However, current in vitro approaches largely impose homogeneous mechanical changes via a host matrix and lack the required positional and directional specificity to mimic the diversity of in vivo scenarios. Thus, while organoids exhibit limited aspects of in vivo morphogenetic events, how local forces are coordinated to enable large-scale changes in tissue architecture remains a difficult question to address using current techniques. Nanoparticles, through their efficient internalization by cells and dispersion through extracellular matrices, have the ability to provide local or global, as well as passive or active modulation of mechanical stresses on organoids and tissues. In this review, we explore how nanoparticles can be used to manipulate matrix and tissue mechanics, and highlight their potential as tools for fate regulation through mechanotransduction in multicellular model systems.


T1 correlates age: A short-TE MR relaxometry study in vivo on human cortical bone free water at 1.5T.
Large pores of human cortical bone (>30μm) are filled with fluids, essentially consisting of water, suggesting that cortical bone free water can be considered as a reliable surrogate measure of cortical bone porosity and hence quality. Signal from such pores can be reliably captured using Short Echo Time (STE) pulse sequence with echo-time in the range of 1-1.5msec (which should be judiciously selected correspond to T2(⁎) value of free water molecules). Furthermore, it is well-known that cortical bone T1-relaxivity is a function of its geometry, suggesting that cortical bone free water increases with age. In this work, we quantified cortical bone free water longitudinal relaxation time (T1) by a Dual-TR technique using STE pulse sequence. In the sequel, we investigated relationship between STE-derived cortical bone free water T1-values and age in a group of healthy volunteers (thirty subjects covering the age range of 20-70years) at 1.5T. Preliminary results showed that cortical bone free water T1 highly correlates with age (r(2)=0.73, p<0.0001), representing cortical bone free water T1 as a reliable indicator of cortical bone porosity and age-related deterioration. It can be concluded that STE-MRI can be utilized as proper alternative in quantifying cortical bone porosity parameters in-vivo, with the advantages of widespread clinical availability and being cost-effective.


Causality and double-negative metamaterials.
The causality of waves propagating in a double-negative (DNG) metamaterial (epsilon (r)<0 and mu(r)<0) has been investigated both analytically and numerically. By considering the one-dimensional electromagnetic problem of a pulsed current sheet radiating into a DNG medium, it is shown that causality is maintained in the presence of a negative index of refraction only if the DNG medium is dispersive. A Drude model DNG medium is used in this study. Spectrograms of the wave phenomena in the dispersive DNG medium show that the higher frequency components, which create the leading edge of the electromagnetic signals and see a double positive (DPS) medium (epsilon (r)>0 and mu(r)>0), arrive causally before the negative index effects germinate completely. Comparisons with approximate analytical results demonstrate the presence of the negative index of refraction properties in the continuous wave portion of the signals. This dynamic pulse reshaping between the positive and negative index of refraction wave components causes an apparent delay in the realization of the negative index of refraction properties. Pulse broadening of the signal tails is associated with both dispersion and a larger negative index of refraction seen by the associated wave components.


Decreased responsiveness of GH3 cells to the dopaminergic inhibition of prolactin.
The inhibitory regulation of PRL secretion by dopamine (DA) or the dopaminergic agonists bromergocryptine (CB-154) and apomorphine was studied in cultured GH3 cells, an established rat anterior pituitary cell line which produces both PRL and GH. The basal release of PRL from GH3 cells was unaffected when incubated for 6 h with DA concentrations as high as 10(-4) M. The inability of DA to suppress PRL secretion could not be explained by the catabolism of DA or the presence of unknown inhibitors (e.g. estradiol) in the fetal calf serum present in the incubation media. Apomorphine and CB-154 were only partially effective in suppressing PRL release at high concentrations of 10(-4) and 10(-5) M, respectively. Various concentrations of the dopaminergic antagonist d-butaclamol did not reverse the inhibitory action of 10(-5) M CB-154, while equal concentrations (10(-5) M) of both d- and l-butaclamol significantly suppressed PRL release. The greatly lowered responsiveness of GH3 cells to dopaminergic inhibition of PRL is suggestive of some impairment of DA receptors. This hypothesis is supported by radioligand binding studies in which high affinity dopaminergic binding sites are absent in the same cell line used in this study.


Chiral dinuclear Ln(iii) complexes derived from S- and R-2-(6-methoxy-2-naphthyl)propionate. Optical and magnetic properties.
The reaction of LnCl3·6H2O with (S)-(+)-2-(6-methoxy-2-naphthyl)propionic acid (S-HL), best known as naproxen, and 1,10-phenanthroline (phen) in EtOH allows the isolation of dinuclear chiral compounds S-1-4 of the formula [Ln2(S-L)6(phen)2]·3DMF·H2O [Ln(iii) = Eu (1), Gd (2), Tb (3) and Dy (4)]. The use of the R-enantiomeric species of the HL ligand led to complexes R-1-4 with the formula [Ln2(R-L)6(phen)2]·3DMF·H2O. Compounds R- andS-1, 3 and 4 show strong sensitized metal-centred luminescence in the visible region. Moreover, Dy(iii) complexes R- andS-4 display field-induced single-molecule magnet (SMM) behaviour. For chiral and emissive compounds circularly polarized luminescence (CPL) measurements have also been performed.


Unilateral Absence of the Latissimus Dorsi: A Report of a Rare Case.
The latissimus dorsi is the largest muscle in the human body, located in the lower posterior thorax, and it contributes to motion in the upper extremity and provides assistance in respiration. This case report describes a rare occurrence of a unilateral absence of the latissimus dorsi accompanied by contralateral scoliosis in a 73-year-old female cadaver. The absence of the muscle along with the absence of the thoracodorsal nerve and branches of the subscapular and axillary arteries was identified during a standard dissection course. The implications of this rare case extend to an array of surgical interventions, including head, neck, breast, and torso reconstructive applications. It is important to investigate potential anomalies of the latissimus dorsi, while planning or performing free flap transfers. The report also highlights the importance of understanding this variation for educational and research purposes.


Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage.
Sphingosine-1-phosphate (S1P) lyase irreversibly cleaves S1P, thereby catalysing the ultimate step of sphingolipid degradation. We show here that embryonic fibroblasts from S1P lyase-deficient mice (Sgpl1-/--MEFs), in which S1P and sphingosine accumulate, have features of Niemann-Pick disease type C (NPC) cells. In the presence of serum, overall cholesterol content was elevated in Sgpl1-/--MEFs, due to upregulation of the LDL receptor and enhanced cholesterol uptake. Despite this, activation of sterol regulatory element-binding protein-2 was increased in Sgpl1-/--MEFs, indicating a local lack of cholesterol at the ER. Indeed, free cholesterol was retained in NPC1-containing vesicles, which is a hallmark of NPC. Furthermore, upregulation of amyloid precursor protein in Sgpl1-/--MEFs was mimicked by an NPC1 inhibitor in Sgpl1+/+-MEFs and reduced by overexpression of NPC1. Lysosomal pH was not altered by S1P lyase deficiency, similar to NPC. Interestingly, lysosomal Ca2+ content and bafilomycin A1-induced [Ca2+]i increases were enhanced in Sgpl1-/--MEFs, contrary to NPC. These results show that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis.


Seesawing end-tidal carbon dioxide: portent of critical carbon dioxide embolism in retroperitoneoscopy.
An abrupt increase in end-tidal CO2 (EtCO2; from 35 to 58 mm Hg) followed by a sudden fall (to 18 mm Hg) was noted during retroperitoneoscopic adrenalectomy under general anaesthesia in a 23-year-old patient with adrenal hyperplasia. This was accompanied by hypotension (systolic blood pressure of 60 mm Hg), desaturation (88% SpO2) and ST depression (3.5 mm). The patient was resuscitated with fluids and vasopressor drugs and about 4 mL of air was aspirated through the central venous catheter, confirming the diagnosis of an intraoperative gas embolism. Later, a rent in the adrenal vein extending into the inferior vena cava was discovered and sutured. The blood pressure, EtCO2, ST segment and pulse oximetry returned to normal after 15 min. This case demonstrates that gas embolism may transpire during retroperitoneoscopic adrenalectomy and an acute rise followed by a sharp fall in EtCO2 should alert the anaesthesiologist to this rare but potentially fatal complication.


Stabilization provided by neighboring strands is critical for the mechanical stability of proteins.
Single-molecule force spectroscopy studies and steered molecular dynamics simulations have revealed that protein topology and pulling geometry play important roles in determining the mechanical stability of proteins. Most studies have focused on local interactions that are associated with the force-bearing beta-strands. Interactions mediated by neighboring strands are often overlooked. Here we use Top7 and barstar as model systems to illustrate the critical importance of the stabilization effect provided by neighboring beta-strands on the mechanical stability. Using single-molecule atomic force microscopy, we showed that Top7 and barstar, which have similar topology in their force-bearing region, exhibit vastly different mechanical-stability characteristics. Top7 is mechanically stable and unfolds at approximately 150 pN, whereas barstar is mechanically labile and unfolds largely below 50 pN. Steered molecular dynamics simulations revealed that stretching force peels one force-bearing strand away from barstar to trigger unfolding, whereas Top7 unfolds via a substructure-sliding mechanism. This previously overlooked stabilization effect from neighboring beta-strands is likely to be a general mechanism in protein mechanics and can serve as a guideline for the de novo design of proteins with significant mechanical stability and novel protein topology.


The effect of same-day pregnancy testing on the incidence of luteal phase pregnancy.
To assess the impact of same-day pregnancy testing on the incidence of luteal phase pregnancy (pregnancy in which conception occurs before sterilization). Retrospectively, all patients (N = 1006) undergoing laparoscopic tubal ligations at the Regional Medical Center, Memphis, from May 1990 through December 1991 were reviewed for sterilization failures. Negative urine pregnancy tests were documented on all scheduled patients at their preoperative examination. After the first 401 sterilizations, same-day pregnancy testing with enzyme-linked immunosorbent assay (ELISA) pregnancy tests was instituted. We reviewed the records of all presumed sterilization failures as well as all patients with a positive pregnancy test on the day of surgery. Last menstrual period, ultrasound records, and date of delivery were analyzed to determine time of conception. Seven luteal phase pregnancies were discovered among the first 401 sterilization cases (17 per 1000). No luteal phase pregnancies occurred in the next 605 sterilizations after institution of same-day pregnancy testing. Eight patients' sterilizations were canceled because of a positive pregnancy test on the morning of surgery. If these patients had not been eliminated, the incidence of luteal phase pregnancies in this second group would have been 13 per 1000 sterilization procedures. Same-day pregnancy testing with an ELISA-type pregnancy test is a rapid, inexpensive, and effective means of reducing the incidence of luteal phase pregnancy.


[Botulinum Toxin in the Musculoskeletal System].
Over the last 20 years, botulinum toxin has proven to be an effective agent in the orthopaedic treatment of musculoskeletal diseases. The author presents a detailed summary of the data on the use of botulinum toxin in different indications. New indications and dosages will be developed in the coming years. As some of the newer indications for botulinum toxin are off-label, its pharmacokinetics must be carefully considered and the indication must be strictly based on current study data. Physicians using this drug should attend special professional courses.


An Efficient Technique for the Long-term Preservation of SMILE Lenticules Using Desiccation.
To evaluate a desiccation protocol for the long-term preservation of human small incision lenticule extraction (SMILE) lenticules and to study their integration in an in vivo rabbit model. Lenticules were retrieved after SMILE procedures in patients, then desiccated according to a novel protocol. Histologic and electron microscopic analyses were performed. Six rabbit eyes received grafts with an inlay technique, which consisted of inserting a desiccated lenticule into a stromal pocket. Rabbits were killed at different times between 6 and 24 weeks. Rabbit corneas were analyzed using optical coherence tomography, histology, and DAPI staining. Microscopic analysis of desiccated lenticules showed a preserved stromal architecture after rehydration. A decellularization of the lenticules after desiccation was observed without any chemical treatment. All rabbit corneas remained clear after grafting human lenticules and no rejection occurred. Optical coherence tomography showed regular lenticular implantation and no decrease in lenticule thickness. Histologic analysis showed no inflammatory infiltration around lenticules and no nuclear material inside lenticules after 6 months. A favorable integration of desiccated human SMILE lenticules in rabbit corneas was observed. The refractive issue of lenticular implantation must be investigated next. Clinical trials are needed to evaluate the use of desiccated SMILE lenticules to treat hyperopia or keratoconus in humans. [J Refract Surg. 2023;39(7):491-498.].


[Dehydrogenase denaturation by guanidine hydrochloride measured by fluorescence (author's transl)].
Denaturation and subsequent renaturation of the enzymes Lactate, Glucose-6-phosphate, Glutamate and Alcohol dehydrogenases, by means of fluorescence spectra and the variation of enzyme activity in each conformational state, have been studied. The denaturating agent has been Guanidine chloride in a range of concentration from 0.5 to 6 M. Special behaviour has been observed in each enzyme in the presence of the denaturating agent. The action of this agent is compared with that of urea. The renaturation percentages obtained are relatively low. Interaction between the denaturating agent and the aminoacids producing the fluorescence of the enzymes is observed.


[Intermittent claudication and critical limb ischemia : from diagnosis to management].
In case of atheromatous disease, the practitioner should be part of a multidisciplinary decision due to the associated comorbities. The angiologic assessment is of paramount importance in the diagnosis of peripheral artery disease even when the diagnosis seems clear. Unfortunately the patient is very often straightforward sent to radiological investigations who are faster. In all stages of peripheral artery disease, the medical treatment should be tried first except in case of critical limb ischemia where an invasive approach must be performed for revascularisation. In case of lifestyle-limiting symptoms and only after failure of medical treatment a revascularisation strategy is then indicated.


The valva portalis renalis in the duck (Anas platyrhynchos).
The morphology of the valva portalis renalis of the duck was investigated, using histological, SEM and TEM techniques. The wall thickness of the vena iliaca externa, the vena portalis renalis caudalis, the vena iliaca communis and the vena renalis caudalis was morphometrically evaluated. The blood pressure in these veins was measured using a three-way H2O manometer. The valva portalis renalis was composed primarily of epithelioid cells and lined with endothelium. Throughout the entire valva there was a dense complex of nerve structures made up of fibers and fiber bundles which also extended beneath the endothelium of the valva and around the subendothelial epithelioid cells. The wall thicknesses of the veins supplying the renal portal system (vena iliaca externa and vena portalis renalis caudalis) were greater than those of the vessels collecting the renal refluent venous blood (vena iliaca communis and vena renalis caudalis). In addition, the blood pressure values taken in the vena iliaca externa and the vena portalis renalis caudalis were much higher than those in the vena iliaca communis and the vena renalis caudalis. The above observations suggest that the renal portal system works at higher blood pressure levels than the general venous system and that the valva portalis renalis regulates its aperture in order to maintain a constant blood pressure and a continuous blood flow in the renal portal system vessels, hence avoiding damage to the renal parenchyma caused by pressure overloads.


Adrenal Rest Tumor of the Liver Preoperatively Diagnosed as Hepatocellular Carcinoma.
Hepatic adrenal rest tumors are rare and show similar findings to hepatocellular carcinoma (HCC). It is difficult to distinguish an adrenal rest tumor from HCC due to radiological similarity. We report a case of an adrenal rest tumor in the liver that mimicked HCC radiologically. A 67-year-old female was referred to our hospital due to the finding of a hepatic mass. Enhanced computed tomography revealed a 17 mm well-defined tumor that was enhanced in the arterial phase and washed out in the portal and delayed phase in the posterosuperior subsegment of the right hepatic lobe, and HCC was suspected. We performed a subsegmental resection of the liver. Microscopic findings showed that the tumor was composed of pale cells, and tumor cells were aligned in alveolar or fascicular arrangements in a similar manner to features of adrenocortical tissue. Immunohistochemically, the tumor expressed synaptophysin and CD56. The final histopathologic diagnosis in this case was an adrenal rest tumor of the liver. An adrenal rest tumor is similar to HCC in radiological findings. This hepatic tumor should be added to the list of radiological differential diagnoses of hypervascular hepatic tumors.


Probing the interior of neutron stars with gravitational waves.
We show here how the internal structure of a neutron star can be inferred from its gravitational wave spectrum. Under the premise that the frequencies and damping rates of a few w-mode oscillations are found, we apply an inversion scheme to determine its mass, radius, and density distribution. In addition, an accurate equation of state of nuclear matter can also be determined.


NF-κB-Interacting Long Noncoding RNA Regulates HIV-1 Replication and Latency by Repressing NF-κB Signaling.
NF-κB-interacting long noncoding RNA (NKILA) was recently identified as a negative regulator of NF-κB signaling and plays an important role in the development of various cancers. It is well known that NF-κB-mediated activation of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-driven gene expression is required for HIV-1 transcription and reactivation of latency. However, whether NKILA plays essential roles in HIV-1 replication and latency is unclear. Here, by ectopic expression and silencing experiments, we demonstrate that NKILA potently inhibits HIV-1 replication in an NF-κB-dependent manner by suppressing HIV-1 LTR promoter activity. Moreover, NKILA showed broad-spectrum inhibition on the replication of HIV-1 clones with different coreceptor tropisms as well as on LTR activity of various HIV-1 clinical subtypes. Chromatin immunoprecipitation (ChIP) assays revealed that NKILA expression abolishes the recruitment of p65 to the duplicated κB binding sites in the HIV-1 LTR. NKILA mutants disrupting NF-κB inhibition also lost the ability to inhibit HIV-1 replication. Notably, HIV-1 infection or reactivation significantly downregulated NKILA expression in T cells in order to facilitate viral replication. Downregulated NKILA was mainly due to reduced acetylation of histone K27 on the promoter of NKILA by HIV-1 infection, which blocks NKILA expression. Knockdown of NKILA promoted the reactivation of latent HIV-1 upon phorbol myristate acetate (PMA) stimulation, while ectopic NKILA suppressed the reactivation in a well-established clinical model of withdrawal of azidothymidine (AZT) in vitro These findings improve our understanding of the functional suppression of HIV-1 replication and latency by NKILA through NF-κB signaling.IMPORTANCE The NF-κB pathway plays key roles in HIV-1 replication and reactivation of HIV-1 latency. A regulator inhibiting NF-κB activation may be a promising therapeutic strategy against HIV-1. Recently, NF-κB-interacting long noncoding RNA (NKILA) was identified to suppress the development of different human cancers by inhibiting IκB kinase (IKK)-induced IκB phosphorylation and NF-κB pathway activation, whereas the relationship between NKILA and HIV-1 replication is still unknown. Here, our results show that NKILA inhibits HIV-1 replication and reactivation by suppressing HIV-1 long terminal repeat (LTR)-driven transcription initiation. Moreover, NKILA inhibited the replication of HIV-1 clones with different coreceptor tropisms. This project may reveal a target for the development of novel anti-HIV drugs.


Growth hormones. 1. Polymorphism (minireview).
Pituitary growth hormone (GH) is not a single molecular species, but a whole set of similar molecules, the individual specific characteristics of which constitute the polymorphism of this hormone. The present paper deals mainly with various forms of human GH, called "variants", and touches on this polymorphism in other species as well. The 22 K variant (MW = 22,000 daltons) is the predominant form of GH to which all other variants are compared as to chemical structure and biological effect. These variants are classified into two large groups: 1) mass variants, the molecular weight of which is modified in comparison with that of 22 K; these can be subdivided into aggregated and non-aggregated forms, and 2) charge variants with modified electrophoretic mobility. Outside this classification are entities which are not yet well known; these include bioinactive GH, correctly detected by RIA but deprived of biological activity or, on the contrary, strongly bioactive GH lacking immunoreactivity and consequently difficult to study. Another outsider is the SV-hGH-2 variant encoded from a gene different from the hGH-N gene normally coding for the other variants. In this case, the product could be considered a true isohormone of 22 K and no longer a variant. The pituitary expression of this gene has never been evidenced to date, but according to recent data, it could be expressed at the placental level and be implicated in human placental growth hormone (hPGH) synthesis. hPGH is a newly-found GH in pregnant women which takes over pituitary GH from the 25th week onwards. After the GH molecules are released by the pituitary in the blood stream, they are partially taken up and carried by binding proteins. The physiological role of this phenomenon could be the setting up of a GH reservoir and a GH sparing process since the metabolic clearance rate of the complex GH-binding protein is slower than that of free GH, thus increasing the biological half-life of the hormone.


Antimicrobial Effects of a Lipophilic Fraction and Kaurenoic Acid Isolated from the Root Bark Extracts of Annona senegalensis.
Root bark preparation of Annona senegalensis Pers. (Annonaceae) is used in Nigerian ethnomedicine for treatment of infectious diseases. Extraction of the A. senegalensis powdered root bark with methanol-methylene chloride (1 : 1) mixture yielded the methanol-methylene extract (MME) which was fractionated to obtain the ethyl acetate fraction (EF). The EF on further fractionation gave two active subfractions, F1 and F2. The F1 yielded a lipophilic oily liquid while F2 on purification, precipitated white crystalline compound, AS2. F1 was analyzed using GC-MS, while AS2 was characterized by proton NMR and X-ray crystallography. Antibacterial and antifungal studies were performed using agar-well-diffusion method with 0.5 McFarland standard and MICs calculated. GC-MS gave 6 major constituents: kaur-16-en-19-oic acid; 1-dodecanol; 1-naphthalenemethanol; 6,6-dimethyl-bicyclo[3.1.1]hept-2-ene-2-ethanol; 3,3-dimethyl-2-(3-methylbuta-1,3-dienyl)cyclohexane-1-methanol; 3-hydroxyandrostan-17-carboxylic acid. AS2 was found to be kaur-16-en-19-oic acid. The MICs of EF, F1, and AS2 against B. subtilis were 180, 60, and 30 μg/mL, respectively. AS2 exhibited activity against S. aureus with an MIC of 150 μg/mL, while F1 was active against P. aeruginosa with an MIC of 40 μg/mL. However, the extracts and AS2 exhibited no effects against Candida albicans and Aspergillus niger. Therefore, kaurenoic acid and the lipophilic fraction from A. senegalensis root bark exhibited potent antibacterial activity.


Alcohol consumption and work performance.
This study examines the work performance of 136 males, including both self-reports and reports of workplace collaterals. Comparisons are made on several dimensions of work performance and different levels of alcohol consumption. Different levels of drinking are not associated with scales of self-reported work performance, but relatively heavy drinkers are less frequently absent and late to work than their lighter drinking counterparts. Collateral reports of work performance, however, indicate that heavier drinkers are more likely to score lower on self-direction at work, conflict avoidance at work and interpersonal relations at work. The relationship of alcohol consumption to the technical aspects of work performance is less clear. There is, however, an overall negative relationship between alcohol consumption and technical aspects of work performance as indicated by workplace collateral reports. The implications for the design of workplace intervention programs are considered.


DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway.
Peritoneal metastasis is a major cause of death in patients with advanced gastric carcinoma. DJ-1 is now considered to play an important role in the metastasis of various malignancies. However, it remains largely unclear whether DJ-1 is involved in the development of peritoneal metastasis by gastric carcinoma. In the present study, we showed that the expression of DJ-1 was significantly upregulated in gastric cancer specimens with peritoneal metastasis compared to those without peritoneal metastasis. Knockdown of DJ-1 expression significantly inhibited invasion and migration, in vitro and the in vivo peritoneal metastatic abilities of SGC7901 gastric cancer cells. Moreover, knockdown of DJ-1 also diminished the expression of matrix metallopeptidase (MMP)-2 and MMP-9. All of these effects were reversed by restoration of DJ-1 expression. Following investigation of the pathway through which DJ-1 regulates cell invasion and migration, DJ-1 was found to cause phosphorylation of Akt in SGC7901 gastric cancer cells. Inhibition of the Akt pathway in SGC7901 cells mimicked the effects of DJ-1 knockdown on cell migration, invasion, MMP-2 and MMP-9 expression, and abolished the effects of DJ-1 in promoting SGC7901 cell invasion and migration. Taken together, the present study revealed that DJ-1 plays an important role in the development of peritoneal carcinomatosis from gastric carcinoma, at least partially through activation of the Akt pathway and consequent upregulation of MMP-2 and MMP-9 expression. Thus, DJ-1 may be a potential therapeutic target for peritoneal carcinomatosis of gastric carcinoma.