Rhein antagonizes P2X7 receptor in rat peritoneal macrophages.
P2X7 receptor plays important roles in inflammation and immunity, and thereby it serves as a potential therapeutic target for inflammatory diseases. Rhein, an anthraquinone derivative, exhibits significant anti-inflammatory and immunosuppressive activities in therapy. However, the underlying mechanisms are largely unclear. Here, we aimed to investigate the effects of rhein on P2X7 receptor-mediated responses in vitro. In HEK293 cells expressing rat P2X7 receptor, we first found that rhein concentration-dependently blocked ATP-induced cytosolic calcium concentration ([Ca(2+)]c) elevation and pore formation of the plasma membrane, two hallmarks of the P2X7 receptor activation. These two inhibitory effects of rhein were also observed in rat peritoneal macrophages. Furthermore, rhein counteracted macrophage phagocytosis attenuation and suppressed reactive oxygen species (ROS) production triggered by ATP/BzATP. Meanwhile, rhein reduced ATP/BzATP-induced IL-1β release in lipopolysaccharide-activated macrophages. Prolonged application of ATP caused macrophage apoptosis, while the presence of rhein suppressed this cell cytotoxicity. Such ATP/BzATP-induced cellular reactions were also inhibited by a well-known rat P2X7 receptor antagonist, brilliant blue G, in a similar way to rhein. Together, our results demonstrate that rhein inhibit ATP/BzATP-induced [Ca(2+)]c increase, pore formation, ROS production, phagocytosis attenuation, IL-1β release and cell apoptosis by antagonizing the P2X7 receptor in rat peritoneal macrophages.


Sequence and genomic organization of GBV-C: a novel member of the flaviviridae associated with human non-A-E hepatitis.
Recently, sequences from a novel virus, termed GB virus C (GBV-C), were identified in serum from several patients with cryptogenic hepatitis. In the present study, the nucleotide sequence of this virus has been extended to near-genome length. GBV-C encodes a putative single large polyprotein in which the structural proteins are positioned at the N-terminal end, with the non-structural proteins located at the C-terminal end. Amino acid sequence analysis of this large polyprotein reveals the presence of protease, helicase, and replicase motifs. Sequence alignments of the polyprotein followed by phylogenetic analyses suggest that GBV-C is a member of the Flaviviridae, most closely related to the recently described GB virus A.


Successful serial imaging of the mouse cerebral arteries using conventional 3-T magnetic resonance imaging.
Serial imaging studies can be useful in characterizing the pathologic and physiologic remodeling of cerebral arteries in various mouse models. We tested the feasibility of using a readily available, conventional 3-T magnetic resonance imaging (MRI) to serially image cerebrovascular remodeling in mice. We utilized a mouse model of intracranial aneurysm as a mouse model of the dynamic, pathologic remodeling of cerebral arteries. Aneurysms were induced by hypertension and a single elastase injection into the cerebrospinal fluid. For the mouse cerebrovascular imaging, we used a conventional 3-T MRI system and a 40-mm saddle coil. We used non-enhanced magnetic resonance angiography (MRA) to detect intracranial aneurysm formation and T2-weighted imaging to detect aneurysmal subarachnoid hemorrhage. A serial MRI was conducted every 2 to 3 days. MRI detection of aneurysm formation and subarachnoid hemorrhage was compared against the postmortem inspection of the brain that was perfused with dye. The imaging times for the MRA and T2-weighted imaging were 3.7±0.5 minutes and 4.8±0.0 minutes, respectively. All aneurysms and subarachnoid hemorrhages were correctly identified by two masked observers on MRI. This MRI-based serial imaging technique was useful in detecting intracranial aneurysm formation and subarachnoid hemorrhage in mice.


TGFβ inhibition and mesenchymal to epithelial transition initiation by Xenopus egg extract: first steps towards early reprogramming in fish somatic cell.
Xenopus egg extract is a powerful material to modify cultured cells fate and to induce cellular reprogramming in mammals. In this study, the response of goldfish fin cells to in vitro exposure to Xenopus egg extract, and subsequent culture, was studied using a cDNA microarray approach, gene ontology and KEGG pathways analyses, and qPCR validation. We observed that several actors of the TGFβ and Wnt/β-catenin signaling pathways, as well as some mesenchymal markers, were inhibited in treated cells, while several epithelial markers were upregulated. This was associated with morphological changes of the cells in culture, suggesting that egg extract drove cultured fin cells towards a mesenchymal-epithelial transition. This indicates that Xenopus egg extract treatment relieved some barriers of somatic reprogramming in fish cells. However, the lack of re-expression of pou2 and nanog pluripotency markers, the absence of DNA methylation remodeling of their promoter region, and the strong decrease in de novo lipid biosynthesis metabolism, indicate that reprogramming was only partial. The observed changes may render these treated cells more suitable for studies on in vivo reprogramming after somatic cell nuclear transfer.


Treatment of herpesvirus infections in HIV-infected individuals.
To discuss strategies available for the treatment of herpesvirus infections in individuals infected with HIV. Information was obtained from controlled and uncontrolled clinical trials, abstracts, conference proceedings, and review articles. Emphasis was placed on controlled investigations in subjects infected with HIV. Data from human studies were extracted by the author and evaluated according to the patient population studied, sample size, dosage regimen, and therapeutic response. Herpes group viruses are common opportunistic pathogens in HIV-infected individuals. Zoster, caused by varicella-zoster virus (VZV), is an early indication of the loss of cell-mediated immunity and HIV disease progression. Anorectal mucocutaneous disease is the most common manifestation caused by herpes simplex virus (HSV). Acyclovir is the drug of choice for treatment of both VZV and HSV infections. Cytomegalovirus (CMV) is the most common life-threatening viral infection in patients with AIDS; retinitis is the most frequent clinical manifestation. The response rate of CMV retinitis to initial treatment with either ganciclovir or foscarnet is equivalent, approximately 60-90 percent. Recent data suggest that the survival benefit may be greater with foscarnet. Advances in the development and application of antiviral drugs for herpes group viruses have made treatment and, in some cases, prevention of infections possible. Future efforts, aimed at earlier intervention and suppression of latent virus, may offer additional improvement in quality of life for the HIV-infected individual.


Reproductive responses following postpartum suppression of ovarian follicular development with a deslorelin implant during summer heat stress in lactating dairy cows.
The objective was to evaluate pregnancy rate to a timed artificial insemination (TAI) protocol in the autumn for cows treated with a non-degradable GnRH agonist implant (Deslorelin [DESL], 5mg) during the summer heat stress period compared with non-treated controls (CON). Cows were randomly assigned to receive or not a DESL implant within 1-4 days postpartum (dpp) twice weekly, from 25 June through 8 August 2001. All cows in DESL implant and CON treatments were injected with PGF(2alpha) 7 days after enrollment. Ultrasonography (US) monitored numbers of ovarian follicles and corpus luteum (CL) at approximately 10, 30, 35/36, 45/44, 56/55 and 66/63dpp, while DESL implants were in situ and concurrently CON, respectively. DESL implants were removed at two specific days, 28 August and 4 September. Cows had DESL implant in situ for a range of 28-67 days, depending on date of enrollment and implant removal. Within 61-100dpp, 31 days after implant removal, DESL implant and CON cows were initiated in a Presynch-Ovsynch and TAI protocol. Pregnancy was evaluated by US and palpation per rectum at 28 and 46 days after TAI, respectively. Plasma concentrations of progesterone were analyzed for sets of blood samples collected during the Presynch-Ovsynch and at TAI day followed 8 days later. Cows in the DESL-implant treatment had more (P<0.01) Class 1 (3-5mm) follicles, less (P<0.01) Class 2 (6-9mm), Class 3 (> or =10mm) follicles and CL compared with CON cows. Proportion of cows having initiated estrous cycles after calving was less (P<0.01) in the DESL-implant treatment (52.2%, 58/111) compared with CON (93.7%, 104/111) at the beginning of Ovsynch. Pregnancy rate to TAI was less (P<0.01) in the DESL implant (27.5%, 33/120) compared with CON (53.9%, 69/128). Pregnancy rate to TAI was less (P<0.01) in DESL-implanted cows that had initiated estrous cycles after calving (30.6%, 19/62) compared with CON (53.7%, 65/121) cows having initiated estrous cycles after calving. Furthermore, pregnancy rate was less (P<0.01) for cows having ovulations that had initiated estrous cycles after TAI in the DESL implant (39.1%, 18/46) compared with CON (62.1%, 54/87) treatments. Pregnancy losses from day 28 to day 46 of pregnancy did not differ between DESL implant (15.1%, 5/33) and CON (13.0%, 9/69) treatments. The DESL implant induced a delay in initiation of a new wave of follicular development during the postpartum-heat stressed period. The lesser pregnancy rate in the DESL-implant treatment group may be due to a pool of heat stress damaged follicles that were depleted in the control group with re-occurring follicle waves.


Serial MR observation of cortical laminar necrosis caused by brain infarction.
To examine the chronological changes characteristic of cortical laminar necrosis caused by brain infarction, 16 patients were repeatedly examined using T1-, T2-weighted spin-echo, T2*-weighted gradient echo, fluid attenuated inversion recovery (FLAIR) images, and contrast enhanced T1-weighted images at 1.0 or 1.5 T. High intensity cortical lesions were visible on the T1-weighted images from 2 weeks after ictus and became prominent at 1 to 3 months, then became less apparent, but occasionally remained at high intensity for 2 years. High intensity cortical lesions on FLAIR images became prominent from 1 month, and then became less prominent from 1 year, but occasionally remained at high intensity for 2 years. Subcortical lesions did not display high intensity on T1-weighted images at any stage. On FLAIR images, subcortical lesions initially showed slightly high intensity and then low intensity from 6 months due to encephalomalacia. Cortical lesions showed prominent contrast enhancement from 2 weeks to 3 months, but subcortical lesions were prominent from 2 weeks only up to 1 month. T2*-weighted images disclosed haemosiderin in 3 of 7 patients, but there was no correlation with cortical short T1 lesions. Cortical laminar necrosis showed characteristic chronological signal changes on T1-weighted images and FLAIR images. Cortical short T1 lesions were found not to be caused by haemorrhagic infarction.


Fibrosis, lipids, and calcium in human atherosclerotic plaque. In vitro differentiation from normal aortic walls by ultrasonic attenuation.
This study was designed to determine whether attenuation of ultrasound by the aortic wall is potentially useful in characterizing the atherosclerotic lesion. Measurements were made on fresh specimens taken from a human aorta at autopsy. Four hundred different sites, 4 mm in diameter each, corresponding to the dimension of the ultrasonic beam at the focal zone, were ultrasonically analyzed and histologically studied. Attenuation of ultrasound in each site was assessed by Fourier analysis of the echo produced by a specular reflector placed behind the specimen. Two parameters were measured over the range 7-11 MHz: the integrated attenuation index (per cm), and slope (per cm per MHz) of the best fit straight line relating attenuation and frequency. Histological examination--performed for each of the 400 sites where attenuation had been measured--identified four subsets (100 samples each): normal aortic walls, fibrous plaques, fibrofatty plaques, and calcified plaques. Results obtained from ultrasonic and histological analyses showed that the integrated attenuation index was lowest in normal walls (24 +/- 2.1, mean +/- SE) and progressively increased in fibrous (32 +/- 3.1), fibrofatty (82 +/- 6.5), and calcific (185 +/- 8.7) subsets (all intergroup differences were significant, except for the normal vs. fibrous comparison). The slope value was significantly lower in the fibrous than in the normal subsets: (10(-3)) 31.9 +/- 4.5 vs. (10(-3)) 99.5 +/- 9.1, respectively. Values of fibrofatty and calcific plaques overlapped: (10(-3)) 383 +/- 21 vs. (10(-3)) 320 +/- 23, respectively. Both were significantly different from normal and fibrous groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Intracranial haemorrhage from a meningioma in a patient receiving aspirin prophylaxis: a case report.
A case of acute subdural haematoma originating spontaneously from an angiomatous meningioma in a patient receiving prophylactic aspirin therapy is presented. To the best of our knowledge no comparable case and no discussion of possible complications of aspirin prophylaxis in patients with brain tumours have been published. Possible reasons and clinical significance of this complication are discussed. This observation questions the suitability of aspirin as prophylaxis for vascular disease in patients with meningiomas.


A xerographic method for the quantitative assessment of atherosclerotic lesions.
A new method has been developed for the quantitative assessment of atherosclerotic lesions, in which a conventional xerox machine is the sole equipment used. As an example, the aorta from a cholesterol-fed rabbit was removed in toto, opened longitudinally along its anterior margin, flattened in a transparent polypropylene bag and then xeroxed. The outlines of the atherosclerotic lesions were traced on translucent graph paper ruled into 1 mm squares. The squares within those outlines were counted and expressed as a percentage of the whole surface. This xerographic method is rapid and reproducible and is achieved without changing the magnification; it gives comparable or better results than other staining methods. As the aortic specimen is undamaged by fixation or staining, the specimen can be used for subsequent morphological or biochemical studies. Thus, the degree of surface involvement can be correlated with other morphological or biochemical changes in the same arterial samples.


Genome-wide association study revealed the genomic regions associated with skin pigmentation in an Ogye x White Leghorn F2 chicken population.
Skin color in chickens is an economically important trait that determines the first impression of a consumer toward a broiler and can ultimately affect consumer choice in the market. Therefore, identification of genomic regions associated with skin color is crucial for increasing the sales value of chickens. Although previous studies have attempted to reveal the genetic markers associated with the skin coloration in chickens, most were limited to investigations of candidate genes, such as melanin-related genes, and focused on case/control studies based on a single or small population. In this study, we performed a genome-wide association study (GWAS) on 770 F2 intercrosses produced by an experimental population of 2 chicken breeds, namely Ogye and White Leghorns, with different skin colors. The GWAS demonstrated that the L* value among the 3 skin color traits is highly heritable, and the genomic regions located on 2 chromosomes (20 and Z) were detected to harbor SNPs significantly associated with the skin color trait, accounting for most of the total genetic variance. Particular genomic regions spanning a ∼2.94 Mb region on GGA Z and a ∼3.58 Mb region on GGA 20 were significantly associated with skin color traits, and in these regions, certain candidate genes, including MTAP, FEM1C, GNAS, and EDN3, were found. Our findings could help elucidate the genetic mechanisms underlying chicken skin pigmentation. Furthermore, the candidate genes can be used to provide a valuable breeding strategy for the selection of specific chicken breeds with ideal skin coloration.


NanoBRET™ Live-Cell Kinase Selectivity Profiling Adapted for High-Throughput Screening.
Kinases represent one of the most therapeutically tractable targets for drug discovery in the twenty-first century. However, confirming engagement and achieving intracellular kinase selectivity for small-molecule kinase inhibitors can represent noteworthy challenges. The NanoBRETTM platform enables broad-spectrum live-cell kinase selectivity profiling in most laboratory settings, without advanced instrumentation or expertise. However, the prototype workflow for this selectivity profiling is currently limited to manual liquid handling and 96-well plates. Herein, we describe a scalable workflow with automation and acoustic dispensing, thus dramatically improving the throughput. Such adaptations enable profiling of larger compound sets against 192 full-length protein kinases in live cells, with statistical robustness supporting quantitative analysis.


Experimental evaluation of aerosol mitigation strategies in large open-plan dental clinics.
Aerosols are generated routinely during patient care in dentistry. Managing exposure risk requires understanding characteristics of aerosols created during procedures such as those performed using high-speed drills that operate at 200,000 revolutions per minute. A trained dentist performed drilling procedures on a manikin's incisors (teeth nos. 8 and 9) using a high-speed drill and high-volume evacuator. The authors used high-speed imaging to visualize the formation and transport of aerosol clouds and particle sampling to measure aerosol concentration and size distribution at several locations. The authors studied several aerosol mitigation strategies. Aerosols produced during high-speed drilling were erratic and yielded high concentrations that were at least an order of magnitude above baseline. High-speed imaging showed aerosols initially travelled at 1 m per second. Owing to erratic behavior of aerosols, supplemental suction was not effective at collecting all aerosols; however, barriers were effective. Barriers are the most effective mitigation strategy. Other methods studied have limitations and risks. To the authors' knowledge, this article presents the first characterization of aerosols generated during high-speed drilling by a dentist. With thorough preoperative planning and the use of this investigation's findings about effectiveness of mitigation strategies as a guide, dental offices may be able to return to prepandemic productivity.


Midwives and nurses awareness of patients' rights.
to determine the level of awareness of patients' rights among midwives and nurses working in the third and fourth largest cities in Turkey. cross-sectional descriptive survey conducted among participants working in university hospitals, state hospitals and village clinics. Questionnaires were distributed to 150 midwives and 350 nurses working in university hospitals (n = 200), state hospitals (n = 100) and village clinics (n = 100); 60% (n = 298) of the forms were returned. fifty-one per cent (n = 152) of midwives and nurses stated that they had not read any legislation related to patients' rights. Seventy-five per cent (n = 222) of respondents were aware of the legal arrangements. Only 34% (n = 74) of participants who knew of any legal basis for patients' rights said that legislation was in the form of a directive. No significant differences were observed in midwives' answers compared with nurses' answers. violation of patients' rights and health professionals' ignorance of appropriate practice means that there is an urgent need to reconsider how to approach this issue. It should be included in continuing education programmes at both graduate and postgraduate midwifery and nursing schools, and also demands more research.


A survey of protein nutrition in patients with inflammatory bowel disease--a rational basis for nutritional therapy.
The incidence of protein malnutrition was studied in 74 unselected patients with inflammatory bowel disease who were in the following categories: ileostomy (16), remission (15), elective surgery (12), acute attack (12), urgent surgery (10) and post-surgical complications (9). Compared with a control group, the patients in the urgent surgery group had low values for plasma albumin transferrin, pre-albumin and haemoglobin and these values were even lower in the patients who developed a major complication after surgery. There was no evidence of protein malnutrition in the ileostomy patients or in those in whom the disease was in remission. Nutritional therapy is strongly indicated in patients who are admitted to hospital with a severe attack of colitis and in whom urgent surgery is probable.


The Dung Beetle Compass.
What do a burly rower, a backstroke swimmer and a hard-working South African dung beetle all have in common? The answer is: they all benefit from moving along a straight path, and do so moving backwards. This, however, is where the similarity ends. While the rower has solved this navigational challenge by handing the task of steering to the coxswain, who faces the direction of travel, and the swimmer is guided down her lane by colourful ropes, the beetle puts its faith in the sky. From here, it utilises a larger repertoire of celestial compass cues than is known to be used by any other animal studied to date. A robust internal compass, designed to interpret directional information, has evolved under the selective pressure of shifting today's lunch efficiently out of reach of competitors, also drawn to the common buffet. While this is a goal that beetles might share with the hungry athletes, they reach it with drastically different brain powers; the brain of the beetle is several times smaller than a match head, containing fewer than a million neurons.


Influence of angiotensinogen M253T gene polymorphism and an angiotensin converting enzyme inhibitor on restenosis after percutaneous coronary intervention.
We studied the relation between renin-angiotensin system (RAS) related gene polymorphisms, such as angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M253T and angiotensin II type 1 receptor (AT1R) A1166C, and the effect of quinapril, an ACE inhibitor with high tissue-binding affinity, on preventing restenosis after percutaneous coronary intervention (PCI). A total of 253 patients successfully treated for coronary artery disease were randomly assigned to quinapril or control. Of the 215 patients who completed the follow-up, we determined gene polymorphisms in 204 patients with 241 lesions who provided blood samples for genotype determination. In the control, the ACE D homozygotes showed a smaller minimal lumen diameter (MLD) at follow-up (P=0.063). The other two genotypes of AGT and AT1R did not affect restenosis after PCI. According to quinapril treatment, the AGT T homozygotes significantly showed a beneficial effect of quinapril on MLD (P=0.013) and late lumen loss (P=0.013). The ACE I homozygotes also exhibited beneficial effects of quinapril on larger MLD (P=0.065). The AT1R genotype did not influence the quinapril effect. In conclusion, the AGT T homozygotes might benefit from effects of quinapril on preventing restenosis after PCI.


Effect of packaging atmospheres on storage quality characteristics of heavily marbled beef longissimus steaks.
The objective of this study was to investigate the effects of modified atmosphere packaging (MAP) systems on shelf-life and quality of beef steaks with high marbling. Four packaging types were used including 80% O2 MAP (80% O2+20% CO2), 50% O2 MAP (50% O2+30% CO2+20% N2), carbon monoxide MAP (0.4% CO+30% CO2+69.6% N2) and vacuum packaging (VP). Steaks were displayed under simulated retail conditions at 4°C for 12days. Purge loss, pH, color stability, oxidative stability and microbial counts were monitored. Aerobically packaged steaks exhibited a bright-red color at the first 4days. However, discoloration and oxidation became major factors limiting their shelf-life to 8days. Compared with aerobic packaging, anaerobic packaging extended shelf-life of heavily marbled beef steaks, due to better color stability, together with lower oxidation and microbial populations. Among all packaging methods, CO-MAP had the best preservation for steaks, with more red color than other packaging types.


The band 12 issue of norbornane: a study of higher shake-up states.
In line with a recent study of the electronic structure of the cage compound norbornane (J. Chem. Phys. 121 (2004), 10525; J. Phys. Chem. A 109 (2005), 4267), symmetry adapted cluster expansion configuration interaction (SAC-CI) general R calculations have been performed and compared with results obtained by the third order algebraic diagrammatic construction scheme [ADC(3)]. Comparison has been made with previously performed electron momentum spectroscopy (EMS) and ultraviolet photo-electron measurements. The region around ~25 eV (band 12), characterized by an elaborated band in the EMS spectrum which is missing in previous Green's function and ADC calculations, is investigated. This study is completed with outer-valence Green's function (OVGF) and SAC-CI/SD-R calculations, and results are obtained by employing (single and double) ionization extended second order ADC [ADC(2)-x]. Since ADC(3) only includes 2h-1p shake-up states, while SAC-CI general-R also includes higher order states, the agreement between both methods assures that the higher order shake-up states do not play an important role in the ionization spectrum of norbornane. While the band-12 issue of norbornane is therefore still open for further discussion, a tentative description in terms of ultrafast nuclear dynamical effects and autoionization processes has become more plausible.


Characterization of supercritical fluid extracts of St. John's wort (Hypericum perforatum L.) by HPLC-MS and GC-MS.
Supercritical fluid extracts (carbon dioxide without modifiers) of St. John's Wort (Hypericum perforatum L., Clusiaceae) were analyzed by GC-MS, HPLC-DAD and HPLC-DAD-MS. Besides the dominating phloroglucinols hyperforin (36.5 +/- 1.1%) and adhyperforin (4.6 +/- 0.1%), the extracts mainly contained alkanes (predominantly nonacosane), fatty acids and wax esters. The apolar components tended to accumulate in a waxy phase resting a top of the hyperforin-enriched phase. No components of higher polarity like naphthodianthrones were found. A set of hyperforin oxidation products was detected and tentatively assigned using HPLC-MS.


A sparse representation and dictionary learning based algorithm for image restoration in the presence of Rician noise.
Rician noise removal for Magnetic Resonance Imaging (MRI) is very important because the MRI has been widely used in various clinical applications and the associated Rician noise deteriorates the image quality and causes errors in interpreting the images. Great efforts have recently been devoted to develop the corresponding noise-removal algorithms, particularly the development based on the newly-established Total Variation (TV) theorem. However, all the TV-based algorithms depend mainly on the gradient information and have been shown to produce the so called "blocky" artifact, which also deteriorates the image quality and causes image interpretation errors. In order to avoid producing the artifact, this paper presents a new de-noising model based on sparse representation and dictionary learning. The Split Bregman Iteration strategy is employed to implement the model. Furthermore, an appropriate dictionary is designed by the use of the Kernel Singular Value Decomposition method, resulting in a new Rician noise removal algorithm. Compared with other de-noising algorithms, the presented new algorithm can achieve superior performance, in terms of quantitative measures of the Structural Similarity Index and Peak Signal to Noise Ratio, by a series of experiments using different images in the presence of Rician noise.


[Cooperative non-specific binding of the cyclic adenosine 3'--5'-monophosphate receptor protein (CRP) from Escherichia coli to double-stranded thymus and lambda pgal DNA].
Either free or combined with cAMP, CRP binds cooperatively to double-stranded thymus and lambda pgal DNA. The affinity of CRP for both DNAs in these non-specific interactions is increased by cAMP without noticeable change in the degree of cooperativity. Values of the intrinsic association constant, cooperativity parameter, and site size of DNA were determined from ultracentrifugal investigations under near-physiological ionic conditions.


Reliability and Validity of the Transcultural Self-Efficacy Tool Questionnaire (Greek Version).
This study aimed to investigate the psychometric characteristics of the Transcultural Self-Efficacy Tool (TSET). The translated questionnaire was distributed to 250 nurses and 150 student nurses. Internal consistency was determined and convergent validity was examined. The structure of the questionnaire was investigated using factor analysis. The internal consistency coefficient for all subscales was acceptable and more than .70. Cronbach's alpha was .91 for affective and self-awareness subscales and .85 for recognition and advocation. Six factors were revealed with eigenvalues of more than 1 and accounted for 60% of the total variance. The factorial composition of the TSET continues to be consistent with the underlying theoretical framework and the related literature. The Greek version of TSET was found to possess good reliability and validity.


Self-referential tags in the discourse of people with Alzheimer's disease.
In a study of the discourse of 100 people with Alzheimer's disease treated for 12 months with donepezil, we observed that, as a group, they used a form of tag, described here as a self-referential tag (SRT), 14 times more frequently than did caregivers. Patients use SRTs to check propositions dependent on episodic memory as in I haven't seen the doctor recently, have I? and to monitor information flow as in I told you that already, didn't I? Based on criteria developed for distinguishing checking from monitoring tags, we document the type and frequency of patients' SRT use in the ACADIE corpus and analyze these in relation to standard measures of cognitive function (Mini Mental State Exam and Alzheimer's Disease Assessment Scale-cognitive sub-scale) at baseline and 12 months. Patients using monitoring SRTs (N=31), with or without checking SRTs, show significantly better cognitive test scores at 12 months, than are seen in patients who never use tags (N=29), or who only use checking tags (N=40). SRT use may be an independent measure of potential treatment responsiveness.


A Cultural Memory of the Digital Age?
Considering digital cultural heritage as the digitalized assets from memory institutions and digital born art, this paper aims to build on its current normative definitions. This first notion addresses the subtle, yet complex relationship between technology and culture. In addition, we consider the criteria set for defining heritage in memory theorization. By doing so, we want to challenge the lack of uniform standards and approaches in dealing with digital cultural heritage and to give Aleida and Jan Assmann's Theory of Cultural Memory a normative dimension. Can there be a cultural memory of the digital age?


Robust and optimal use of information in stereo vision.
Differences between the left and right eye's views of the world carry information about three-dimensional scene structure and about the position of the eyes in the head. The contemporary Bayesian approach to perception implies that human performance in using this source of eye-position information can be analysed most usefully by comparison with the performance of a statistically optimal observer. Here we argue that the comparison observer should also be statistically robust, and we find that this requirement leads to qualitatively new behaviours. For example, when presented with a class of stereoscopic stimuli containing inconsistent information about eccentricity of gaze, estimates of this gaze parameter recorded from one robust ideal observer bifurcate at a critical value of stimulus inconsistency. We report an experiment in which human observers also show this phenomenon and we use the experimentally determined critical value to estimate the vertical acuity of the visual system. The Bayesian analysis also provides a highly reliable and biologically plausible algorithm that can recover eye positions even before the classic stereo-correspondence problem is solved, that is, before deciding which features in the left and right images are to be matched.


Two-dimensional proteome reference map of Vibrio tapetis, the aetiological agent of brown ring disease in clams.
Vibrio tapetis is the etiological agent of brown ring disease (BRD) in clams, one of the most threatening diseases affecting this commercially important bivalve. In this study we have constructed a proteome reference map of the V. tapetis type strain CECT 4600(T). Eighty-two proteins, consistently present in all 2D-gels, were identified by mass spectrometry or by de novo sequencing. The majority of the proteins identified (66%) belonged to four COG categories: 'Carbohydrate transport and metabolism', 'Post-translational modification, protein turnover and chaperones', 'Energy production', and 'Amino acid transport and metabolism'. Glyceraldehyde-3-phosphate dehydrogenase, enolase, fructose-bisphosphate aldolase, phosphoglycerate kinase. molecular chaperones Dnak and GroEL, alkyl hydroperoxide reductase, peptidyl-prolyl cis-trans isomerase B and factor Tu, were identified among the 20 most abundant proteins. A comparison of this reference map with that obtained for the V. tapetis strain GR0202RD, with different origin and pathophysiological characteristics, was performed. Under the culture conditions employed in this study, glucose degradation is one of the major pathways for energy production in Vibrio tapetis. In addition, the two strains studied, although with remarkable differences at genetic and pathophysiological levels, showed a high similarity under laboratory conditions. The results obtained here can be considered as a first step to gather valuable information on protein expression, related not only to diverse cellular functions and regulation but also to pathogenesis and bacterium-host interactions in the disease process.


Intracellular pH in unanesthetized dogs during panting.
Intracellular pH, arterial blood gases and several plasma enzymes were estimated in unanesthetized dogs during a 3-hour exposure to 30 degrees C/50% relative humidity, and 40 degrees C/50% relative humidity. No change occurred during mild heat stress, whereas during severe heat stress a profound respiratory alkalosis developed together with an increase in intracellular pH from 7.03 to 7.29. Most plasma enzymes increased by about 300% or more. In spite of extreme panting body temperature rose to 42.2 degrees C. Exposure to 40 degrees C/50% relative humidity with 4% CO2 in the climatic chamber inhibited the respiratory alkalosis and the increase of plasma enzymes. Though the panting frequency was lower the ventilatory heat dissipation was more efficient. Body temperature rose to only 39.8 degrees C. It is concluded that the intracellular buffering is not able to prevent marked changes of the intracellular pH during panting.


Hypoxia-Induced Pro-Protein Therapy Assisted by a Self-Catalyzed Nanozymogen.
The success of intracellular protein therapy demands efficient delivery and selective protein activity in diseased cells. Therefore, a cascaded nanozymogen consisting of a hypoxia-activatable pro-protein, a hypoxia-inducing protein, and a hypoxia-strengthened intracellular protein delivery nanovehicle was developed. RPAB, an enzymatically inactive pro-protein of RNase, reversibly caged with hypoxia-cleavable azobenzene, was delivered with glucose oxidase (GOx) using hypoxia-responsive nanocomplexes (NCs) consisting of azobenzene-cross-linked oligoethylenimine (AOEI) and hyaluronic acid (HA). Upon NC-mediated delivery into cancer cells, GOx catalyzed glucose decomposition and aggravated tumoral hypoxia, which drove the recovery of RPAB back to the hydrolytically active RNase and expedited the degradation of AOEI to release more protein cargoes. Thus, the catalytic reaction of the nanozymogen was self-accelerated and self-cycled, ultimately leading to a cooperative anti-cancer effect between GOx-mediated starvation therapy and RNase-mediated pro-apoptotic therapy.


Tailored antireflux surgery.
With increasing age, the functional condition of the lower esophageal sphincter is getting weaker. Recent progress in peri-operative intensive care and the development of laparoscopic technique makes antireflux surgery a safe choice of GERD treatment in the elderly. This work evaluated the long-term results of tailored antireflux surgery in a group of elderly (more than 60 years old) patients. Five hundred and eighty one patients underwent antireflux surgery in our department from 1999 to 2005. Seventy of them (12.0%) were older than 60 years. Exclusion criteria of surgery were ASA IV classification and high grade esophageal dysmotility. Toupet's wrap was offered to patients with esophageal dysmotility or esophageal sphincter pressure higher than 15 mm Hg (16 cases). The rest were offered Nissen-Rossetti's complete wrap (54 cases). There was zero mortality and no further significant dysphagia. Pathological gastro-esophageal reflux after the surgery was detected in 6 patients (8.6%), which was a higher proportion than in the group of patients under 60 years. Good results of antireflux surgery with zero mortality and low morbidity can be achieved even in the elderly (more frequent use of incomplete Toupet's wrap).


Age-related changes in the effects of 5-hydroxytryptamine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis.
The trigeminal subnucleus caudalis (Vc) is the critical brainstem relay site of orofacial nociceptive processing to higher brain centers. The descending serotonergic pathway from the brainstem exerts inhibitory or facilitatory effects on nociceptive transmission in the spinal dorsal horn and the Vc, and SG neurons of the Vc exhibit hyperpolarization, no response or depolarization in response to 5-hydroxytryptamine (5-HT) application. In this study, we examined age-related changes in the effects of 5-HT on SG neurons of the Vc using immature, peripubertal and adult male mice and gramicidin-perforated patch recordings under the current-clamp mode. In the three age groups, hyperpolarization was the major response in SG neurons exhibiting membrane potential changes in response to 5-HT application. The proportion of the SG neurons responding to 5-HT by hyperpolarization was significantly higher in the immature (20/27) than in the adult mice (10/26; P<0.05). The proportion of SG neurons showing no response to 5-HT was significantly higher in the peripubertal (11/21) and the adult mice (13/26) compared with the immature mice (5/27). The amplitude of 5-HT-induced hyperpolarization significantly decreased with increasing postnatal age (correlation coefficient=-0.43, P<0.05). The mean amplitude of 5-HT-induced hyperpolarization was significantly higher in the immature mice (-9.7±1.1 mV, n=20) than in the peripubertal (-5.3±1.0 mV, n=10) and the adult mice (-5.4±0.9 mV, n=10; both P<0.05). These results suggest that the descending serotonergic modulatory influence over the orofacial nociceptive processing in the Vc may change during postnatal development and postnatal age of three weeks is a critical period for changes in 5-HT-induced hyperpolarizing effects in mice.


Rodent models of sleep apnea.
Rodent models of sleep apnea have long been used to provide novel insight into the generation and predisposition to apneas as well as to characterize the impact of sleep apnea on cardiovascular, metabolic, and psychological health in humans. Given the significant body of work utilizing rodent models in the field of sleep apnea, the aims of this review are three-fold: first, to review the use of rodents as natural models of sleep apnea; second, to provide an overview of the experimental interventions employed in rodents to simulate sleep apnea; third, to discuss the refinement of rodent models to further our understanding of breathing abnormalities that occur during sleep. Given mounting evidence that sleep apnea impairs cognitive function, reduces quality of life, and exacerbates the course of multiple chronic diseases, rodent models will remain a high priority as a tool to interrogate both the pathophysiology and sequelae of breathing related abnormalities during sleep and to improve approaches to diagnosis and therapy.


Determinants of item nonresponse in a large national sex survey.
The study aim was to describe patterns of item nonresponse in a sex survey and identify factors associated with high nonresponse. A random sample of 4548 respondents to the National Survey of Sexual Attitudes and Lifestyles in Britain, 1990-1991 was assessed. Both respondent-wise and variable-wise patterns of incomplete response are described in terms of distinctive characteristics of nonrespondents and questions with a high nonresponse rate. Logistic regression was used to model the determinants of extreme nonresponse. For at least 90% of respondents, the item nonresponse was ignorable for most practical purposes and recall difficulties were indicated as its main cause, while the sensitivity of the questions had a large effect mainly among those in the top 5% of the overall nonresponse distribution. The latter were also distinguishable in terms of refusals to answer some face-to-face questions. Several overlapping indicators of poor educational and social background were associated with elevated overall nonresponse, particularly among the top 5% of the distribution. Thus recall accuracy rather than sensitivity of some sex survey questions was the key difficulty for a majority of the respondents whose overall nonresponse was satisfactorily low. The sensitivity of the topic had a large effect on item nonresponse only for a small group of participants.


Observational Aranesp Survey to Investigate the Q3W Schedule (OASIS): a prospective observational study of treatment of chemotherapy-induced anaemia with every 3 weeks darbepoetin alfa.
This prospective observational study examined the adherence to published European guidelines on erythropoiesis-stimulating agents (ESAs) and the pattern of use and effect of darbepoetin alfa (DA) 500 microg once every 3 weeks (Q3W) for the treatment of chemotherapy-induced anaemia (CIA). A total of 293 patients were included (263 solid tumour, 30 haematologic malignancy). Their mean age was 63 years, 51% were male, 57% had platinum-based chemotherapy. DA was started at a haemoglobin (Hb) level between 9 and 11 g/dL in 82% of patients. In an analysis correcting for transfusions, 55% of patients achieved > or =2 g/dL increase in Hb, and a Hb level of >11 g/dL was reached in 81%. Transfusion rate was 27%. Most patients (70%) were treated in a Q3W chemotherapy, and planned synchronisation of chemotherapy and Q3W DA could be maintained in 76%. Adherence to European guidelines for DA treatment was good, and Q3W DA treatment was in synchronisation with Q3W chemotherapy in the majority of the patients, thereby reproducing the findings of a recent phase III study.


Implementing and Evaluating SBIRT for Alcohol Use at a Level 1 Trauma Center: A Behavioral Medicine Approach.
To facilitate the early identification and treatment of alcohol misuse among trauma patients, the American College of Surgeons (ACS) requires ACS-accredited level 1 trauma centers to have an active alcohol screening and brief intervention program. The development, implementation, and evaluation of a screening, brief intervention, and referral to treatment as a new institutional standard of care for alcohol misuse at a level 1 trauma center is described. The Division of Behavioral Medicine, a health psychology-based service, was nominated to manage this initiative as a result of clinical training and expertise in assessment, evidence-based psychological interventions, and case management. Trauma patients with elevated blood alcohol concentrations were screened at the time of admission and several months post-hospitalization. Clinical data suggest that screening for alcohol misuse can help identify patients at risk for, and struggling with, alcohol use disorders, encourage positive changes in alcohol consumption patterns, and increase access to treatment. Recommendations for enhancing the effectiveness of this process, associated challenges and limitations, and considerations for future clinical and research endeavors are discussed.


High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model.
To investigate potential dietary risk factors of Alzheimer's disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-beta (Abeta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.


Bretylium tosylate binds preferentially to muscarinic receptors labelled with [3H]oxotremorine M (SH or 'high affinity' receptors) in rat heart and brain cortex.
Bretylium tosylate is an antiarrhythmic agent. In guinea pig atria it showed the properties of a competitive muscarinic (cholinergic) antagonist and could distinguish between two muscarinic receptor classes or states in cardiac membranes. We decided to further investigate its binding properties at muscarinic cholinergic receptors of the rat heart and brain (cortex), keeping in mind the recently discovered heterogeneity of muscarinic receptor protein. Bretylium tosylate recognized two receptor classes or states in the heart with Ki values of 0.9 and 11 microM. All cardiac membrane receptors showed a homogeneous (11 microM) Ki value for the drug in the presence of GTP in the incubation medium, or after in vivo pretreatment with islet activating protein (IAP). Bretylium tosylate was able (but only at a high concentration, 1 mM) to slow the dissociation kinetics of the tracer, which suggests that it also bound to an allosteric site on the muscarinic receptor, or that it affected the receptor environment. In the brain cortex, as in the heart, bretylium tosylate displayed a high affinity for receptors labelled with the agonist [3H]oxotremorine M (Ki value: 0.8 microM for the SH-or cardiac-type high-affinity receptors), and a 8- to 10-fold lower affinity for cortex M and L receptors. These data suggest that the antagonist bretylium tosylate had binding properties in rat cardiac membranes analogous to those of the partial agonist pilocarpine and that it interacted with a single type of receptor.


Electric switching of visible and infrared transmission using liquid crystals co-doped with plasmonic gold nanorods and dichroic dyes.
Smart windows and many other applications require synchronous or alternating facile electric switching of transmitted light intensity in visible and near infrared spectral ranges, but most electrochromic devices suffer from slow, nonuniform switching, high power consumption and limited options for designing spectral characteristics. Here we develop a guest-host mesostructured composite with rod-like dye molecules and plasmonic nanorods spontaneously aligned either parallel or orthogonally to the director of the liquid crystal host. This composite material enables fast, low-voltage electric switching of electromagnetic radiation in visible and infrared ranges, which can be customized depending on the needs of applications, like climate-dependent optimal solar gain control in smart windows.


[Unsuspected danger of a medicinal preparation].
Inhaled foreign bodies are commonly reported in childhood but less so among adults. We report the case of a patient who inhaled a medicinal preparation containing meprobamate and quinine sulfate. The consequence of this was caustic damage to the airways. A 64-year-old woman came to the emergency room because of dyspnea, oropharyngeal pain and sialorrhea. She reported that she had inhaled a capsule containing meprobamate and quinine sulfate the previous day. Flexible bronchoscopy showed evidence of caustic damage to the larynx and lower airways. The patient was treated by fasting, corticoids and intravenous broad-spectrum antibiotics. All the lesions recovered and she was discharged from the hospital 15 days after the event. Inhalation of drugs mostly leads to airway obstruction. Risk of harm is influenced by neurological status, the motility of the digestive system and the properties of the drug. To the best of our knowledge, this is the first time that caustic airway disease has been described following inhalation of a medicinal preparation containing meprobamate and quinine. It highlights the need to be familiar with the chemical properties of medications when prescribing them to patients who are at risk of aspiration.


Monoclonal S-100 immunocytochemistry of pigmented naevi with tactile-like corpuscles.
We examined 12 cases of pigmented naevi with tactile-like corpuscles by immunohistochemistry using polyclonal and monoclonal antibodies against S-100 protein. Naevus cells, the tactile-like corpuscles, and the attached lamellae and fibroblastic cells gave a strong reaction with S-100 protein and the beta-subunit antibodies. The same cells gave only a weak reaction with the alpha-subunit antibody with the exception of about 4 per cent of corpuscles and 1-1.5 per cent of naevus cells, whether pigmented or not, which gave a strong reaction with this antibody. These results suggest that the non-pigmented naevus cells and the constituent cells of the corpuscles are closely related and the latter might derive from the former by organoid differentiation.


Long-term rhythm control of drug-refractory atrial fibrillation with "hybrid therapy" incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation.
We evaluated the long-term efficacy, safety, and applicability of a "hybrid" therapy strategy for rhythm control in atrial fibrillation (AF), incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation. One hundred thirteen patients (paroxysmal AF [n = 70], persistent/permanent AF [n = 43]) with refractory symptomatic AF were treated with this strategy and followed for 1 to 81 months (mean 30 +/- 23). All-cause mortality, AF recurrences, and progression to permanent AF were monitored and recorded by implanted device data logs. There was no procedural mortality. Rhythm control was achieved in 90% of all patients at 3 and 5 years, with comparable efficacy in subpopulations with paroxysmal (98%), persistent, or permanent AF (87%, p >2). Overall survival was 84% at 3 years and 80% at 5 years, and was higher in patients with paroxysmal AF than in patients with persistent or permanent AF (86% vs 67% at 4 years, p <0.001). Patients with persistent or permanent AF had a greater need for cardioversion (p <0.004) and right atrial ablation (p <0.04) than patients with paroxysmal AF to achieve comparable rhythm control. A hybrid therapy strategy can provide safe and effective long-term rhythm control in patients with drug-refractory AF, and can be implemented in subpopulations presenting with paroxysmal, persistent, or permanent AF.


Improvement in glycemia after glucose or insulin overload in leptin-infused rats is associated with insulin-related activation of hepatic glucose metabolism.
Insulin regulates glucose homeostasis through direct effects on the liver, among other organs, with leptin modulating insulin's hepatic actions. Since central leptin may modify insulin signaling in the liver, we hypothesized that leptin infusion activates hepatic glycogen synthesis following peripheral administration of a bolus of glucose or insulin, thus regulating glycemia. Oral glucose and intraperitoneal insulin tolerance tests were performed in control, intracerebroventricular leptin-treated and pair-fed rats during 14 days. An improvement in glycemia and an increase in hepatic free glucose and glycogen concentrations after glucose or insulin overload were observed in leptin-treated rats. In order to analyze whether the liver was involved in these changes, we studied activation of insulin signaling by Western blotting and multiplex bead immunoassay after leptin infusion. Our studies revealed an increase in phosphorylation of insulin receptor substrate-1 and Akt in leptin-treated rats. Examination of parameters related to glucose uptake and metabolism in the liver revealed an augment in glucose transporter 2 and a decrease in phosphoenolpyruvate carboxylase protein levels in this group. These results indicate that central leptin increases hepatic insulin signaling, associated with increased glycogen concentrations after glucose or insulin overload, leading to an improvement in glycemia.


A randomized study comparing propranolol and diltiazem in the treatment of unstable angina.
One hundred consecutive patients hospitalized in the coronary care unit for unstable angina, excluding patients with Prinzmetal's variant angina, were randomized within 24 hours of admission to treatment with diltiazem (50 patients) or propranolol (50 patients). Also excluded were patients with previous coronary artery bypass surgery and those receiving a beta-receptor blocking agent at the time of hospital admission. Left ventricular function and the extent of coronary artery disease were similar in the two groups. During the hospital stay, the number of chest pain episodes decreased from a mean (+/- SD) of 0.75 +/- 0.1 per patient per day to 0.26 +/- 0.07 (p less than 0.05) with diltiazem and 0.29 +/- 0.1 (p less than 0.05) with propranolol therapy. The circadian distribution of chest pain episodes was affected similarly. After 1 month, 14 of the patients treated with diltiazem were symptom-free compared with 13 treated with propranolol. At a mean follow-up time of 5.1 months (range 1 to 15), death had occurred in two patients in each group and myocardial infarction in five diltiazem- and four propranolol-treated patients (difference not significant). Coronary artery bypass surgery had been performed in 21 diltiazem- and 19 propranolol-treated patients (difference not significant). Only 15 patients were symptom-free, 9 treated with diltiazem and 6 with propranolol. This similar result observed with the two forms of treatment suggests that coronary artery spasm may not be the main factor involved in unstable angina when Prinzmetal's variant angina is excluded. It also suggests that diltiazem can be used as an alternative to the usual treatment with beta-receptor blocking drugs.


Amino acid content in astroglial primary cultures from different brain regions during cultivation.
Free amino acids in astroglial primary cultures obtained from newborn rat cerebral cortex, striatum and hippocampus were analyzed and compared during cultivation. Glutamate and taurine exhibited the highest concentrations. Aspartate and glutamate showed the highest values after 1 and 3 weeks of cultivation with lower values after 2 weeks in culture, while taurine, beta-alanine/hypotaurine and phosphoethanolamine showed the highest value after 2 weeks in culture. The non-neuroactive amino acids and gamma-aminobutyric acid were present at a low level and the former showed the lowest concentration at 2 weeks of cultivation. Astrocytes from the different regions did generally not differ with respect to amino acid content. We conclude that the morphological and biochemical maturation of glia in culture is accompanied with marked quantitative changes in amino acid pattern.


Embolism bubble adhesion force in excised perfused microvessels.
The mechanics of gas embolism bubble adhesion to the vessel wall is poorly understood. New strategies to treat gas embolism may result from an understanding of adhesion forces, including the molecular determinants of bubble adhesion. The authors conducted experiments to measure the adhesion force of bubbles contacting the vessel wall. Microbubbles were injected into excised arterioles. Bubbles resided for 5, 10, 20, or 30 min with the endothelium intact or damaged and with a physiologic salt solution, physiologic salt solution with 5% bovine serum albumin, or rat serum as the perfusate. Inflow pressure was raised until the bubble dislodged. The differential pressure across the microbubble, deltaP, was recorded at the moment of bubble movement. Bubble diameter, D, and length, L, were determined by videomicroscopy. The adhesion force per unit surface area of a bubble contacting the vessel wall, K = deltaPD/4 L, was calculated for each experiment. K at 10 min contact time (physiologic salt solution, 141 +/- 29; serum, 153 +/- 57 dyne/cm2) was higher than at 5 min (physiologic salt solution, 56 +/- 22; serum, 71 +/- 29 dyne/cm2), 20 min (physiologic salt solution, 46 +/- 29) and 30 min (physiologic salt solution, 14 +/- 5) (P < 0.05). Endothelium removal reduced K at 10 min (physiologic salt solution, 68 +/- 46; serum, 60 +/- 14 dyne/cm2) (P < 0.05). K was higher with 5% bovine serum albumin present at 10 min (349 +/- 149, P < 0.05), correlating with in vivo estimates. The adhesion force developed between a microbubble and the vessel wall depends on multiple factors, including bubble residence time, presence of the endothelium, and perfusion solution.


In vitro inhibition of recombinant ligand-gated ion channels by high concentrations of milnacipran.
Tricyclic antidepressants are known to inhibit various ligand-gated ion-channel (LGIC) receptors, and some of their clinical features may be associated with this activity. The effects of milnacipran, a selective inhibitor of the reuptake of serotonin and noradrenaline, on LGIC receptors have not yet been investigated on such ion-channel receptors. To determine the in vitro effect of milnacipran on four recombinant LGIC receptors, nicotinic acetylcholine, N-methyl-D-aspartate, gamma-amino butyric acid (GABA) and 5-hydroxytryptamine3A receptors. Receptors were expressed in Xenopus oocytes and LGIC activity measured using a two-voltage clamp technique. There was no interaction at the GABA receptor. The results at the other LGIC receptors showed that they could be inhibited by high concentrations of milnacipran. At high concentrations, milnacipran can inhibit certain LGICs. It is, however, unlikely that these interactions have any clinical consequence under normal therapeutic conditions, since the concentrations required are considerably higher than those achieved in plasma of treated patients.


Study of the low-temperature plasma treatment effect on the structure, physical and chemical surface characteristics of 40X13 steel.
The article examines the influence of a new unparalleled method of low-temperature plasma treatment at 300 Pa pressure on the structure, properties and corrosion resistance of 40X13 steel. Experiments proved that increase in corrosion resistance is achieved by means of innhibition of oxygen depolarization, changes in its limiting stages and, as a consequence, decreased formation rates of oxides and hydroxides of iron and chromium.


Treatment of cystic epithelial downgrowth with intralesional administration of mitomycin C.
To report a case of postoperative cystic epithelial downgrowth treated with needle aspiration and intralesional administration of mitomycin C. Case report. A 60-year-old woman with a history of right cataract surgery 7 years ago presented with decreased vision of 1/60. The reduced vision was diagnosed secondary to a large acquired cystic epithelial downgrowth on the surface of the iris occluding the pupil. The cystic epithelial downgrowth was treated with aspiration and intralesional administration of mitomycin C solution. There was no evidence of recurrence on follow-up 1 year after the procedure. Treatment of acquired cystic epithelial downgrowth with needle aspiration and intralesional administration of mitomycin C resulted in a satisfactory outcome without undertaking more extensive and invasive surgical treatments.


Behavioral alterations produced by chronic naloxone injections.
Repeated blockade of the endorphin receptors eventually induces symptoms resembling an opiate abstinence syndrome, despite the complete absence of opiate narcotics. Rats were injected with 0.6 mg/kg naloxone or with injection vehicle alone twice a day for six days. They were observed twice a day for four subsequent days. Body shakes, head shakes, scratches and total symptoms were significantly elevated in the naloxone treated group over controls. Symptoms were completely reversed by a small dose of morphine but not by naloxone. In a second experiment, rats were injected for ten days with the same dosage of naloxone. The abstinence-like syndrome began after six days of naloxone and continued for several days after cessation of injections. Total symptoms, body shakes, scratches and aggression were significantly elevated over controls and were reversed by morphine but not by naloxone.


Impact, mechanisms, and novel chemotherapy strategies for overcoming resistance to anthracyclines and taxanes in metastatic breast cancer.
Despite advances in treatment of patients with metastatic breast cancer (MBC), prognosis remains poor and median survival is 2-3 years. Resistance to antineoplastics mediated by many factors, potentially including overexpression of drug efflux proteins or altered beta-tubulin isotype expression limits the effectiveness of MBC chemotherapy. Capecitabine, approved for anthracycline- and taxane-resistant MBC, has produced modest responses, highlighting the need for more effective treatments for MBC resistant to multiple chemotherapeutic agents. Agents with potential to reverse drug resistance have not proven effective. Albumin-bound paclitaxel is a formulation that may enhance delivery to tumor tissues. Conversely, ixabepilone, an epothilone analog, has been reported to have lower susceptibility to at least some mechanisms of tumor resistance and clinical activity in resistant/refractory MBC. The topoisomerase-I inhibitor irinotecan also has low cross-resistance with other antineoplastics, and has shown some activity against refractory MBC. Development of new agents and identification of genetic biomarkers in translational studies promise to improve management of patients with resistant/refractory breast cancer.


Scanning electron microscopic studies of ileal epithelial cells in suckling rats.
The ileal epithelial cells containing the tubulo-vacuolar systems and supranuclear vacuoles in suckling rats were investigated with scanning electron microscopy, using specimens treated with osmium-thiocarbohydrazide-osmium staining methods, and critical point drying and cracking. The cracked surface of the apical cytoplasm is seen as irregular and small hollows and pores of the anastomosing and branching tubulo-vacuolar system. The cracked surface of the supranuclear vacuoles shows the ellipsoidal structures. Numerous pores of various size and irregular shape are present on the apical inner surface of the supranuclear vacuole. These pores are clearly the openings from the tubulo-vacuolar system to the supranuclear vacuole. Some small pores are visible on the inner lateral surface of the supranuclear vacuole, especially near the nucleus. They are probably the pathways of the absorbed materials from the supranuclear vacuole into the lateral cytoplasm. Usually, the inclusions of the supranuclear vacuole reveal the globes or coarse and sponge-like networks.


Author Correction: The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT).
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


The evidence for the antiatherogenicity of high density lipoprotein in man.
It has long been recognized that patients with clinical coronary heart disease (CHD) have, on average, higher concentrations of plasma very low density and low density lipoproteins than do healthy subjects. The same studies clearly demonstrated that coronary victims tend also to have low plasma concentrations of high density lipoprotein (HDL). It is only recently, however, that the possible significance of this second observation has been examined. Direct evidence for an inverse relationship between HDL cholesterol concentration and the prevalence of clinical CHD, independent of other plasma lipoproteins, has been provided by the Honolulu Heart and Cooperative Lipoprotein Phenotyping Studies. The Tromsø Heart and Framingham Studies subsequently demonstrated that this relationship precedes the clinical manifestation of coronary disease. More recently, angiographic studies have confirmed that the severity of existing coronary atherosclerosis is inversely related to HDL cholesterol concentration. Other investigations have shown that coronary victims also have low mean concentrations of apolipoproteins AI and AII (the major protein components of HDL), although the reduction of apoAI concentration may be less marked that that of HDL cholesterol, and preliminary findings from Tromsø have suggested that apolipoprotein AI may be less powerful that HDL cholesterol as a predictor of CHD. Such observations have supported the porposal that HDL may exert a protective effect against coronary atherosclerosis. Final comfirmation (or otherwise) of this hypothesis, however, must await the results of carefully controlled animal experiments and of regression studies in patients with angiogrphically defined atherosclerosis.


Urinary tract infection and indwelling urinary catheters: prospective study in gynecological surgery with antibiotic prophylaxis.
Urinary tract infections are the most common cause of hospital-acquired infections, and the use of indwelling urinary catheters is a predisposing factor for their development. The aims of this study were to estimate the frequency of pre and postoperative bacteriuria, identify the microorganisms involved, count the colony-forming units, determine the antibiotic sensitivity profile and compare the results from pre and postoperative urinalyses among women undergoing gynecological surgery with implantation of a urinary catheter. Non-controlled prospective observational single-cohort epidemiological study carried out at a university hospital. Urine samples were collected before and 24 hours after catheterization for urinalysis, culturing and antibiotic sensitivity testing. Pre and postoperative urinalyses were compared using Wilcoxon and McNemar non-parametric tests. Fifty-one women participated in the study. Escherichia coligrew in six preoperative samples (11.8%) and Klebsiella pneumoniae in one (1.9%), but bacterial growth did not occur in any postoperative sample. Urinalysis showed lower number of pus cells in the postoperative urine samples (P < 0.05). There were no differences in red blood cell counts or in the nitrite and leukocyte esterase tests, between the samples. Bacteriuria was found in 13.7% of the preoperative samples. Gram-negative bacteria sensitive to most antibiotics were identified. In the postoperative samples, no bacterial growth was observed. Urinalysis only showed significant reduction of leukocyturia in the postoperative period.


Estimation of regression quantiles in complex surveys with data missing at random: An application to birthweight determinants.
The estimation of population parameters using complex survey data requires careful statistical modelling to account for the design features. This is further complicated by unit and item nonresponse for which a number of methods have been developed in order to reduce estimation bias. In this paper, we address some issues that arise when the target of the inference (i.e. the analysis model or model of interest) is the conditional quantile of a continuous outcome. Survey design variables are duly included in the analysis and a bootstrap variance estimation approach is proposed. Missing data are multiply imputed by means of chained equations. In particular, imputation of continuous variables is based on their empirical distribution, conditional on all other variables in the analysis. This method preserves the distributional relationships in the data, including conditional skewness and kurtosis, and successfully handles bounded outcomes. Our motivating study concerns the analysis of birthweight determinants in a large UK-based cohort of children. A novel finding on the parental conflict theory is reported. R code implementing these procedures is provided.


Mechanisms and Regulation of Neuronal GABAB Receptor-Dependent Signaling.
γ-Aminobutyric acid B receptors (GABABRs) are broadly expressed throughout the central nervous system where they play an important role in regulating neuronal excitability and synaptic transmission. GABABRs are G protein-coupled receptors that mediate slow and sustained inhibitory actions via modulation of several downstream effector enzymes and ion channels. GABABRs are obligate heterodimers that associate with diverse arrays of proteins to form modular complexes that carry out distinct physiological functions. GABABR-dependent signaling is fine-tuned and regulated through a multitude of mechanisms that are relevant to physiological and pathophysiological states. This review summarizes the current knowledge on GABABR signal transduction and discusses key factors that influence the strength and sensitivity of GABABR-dependent signaling in neurons.


Association between endometrial senescent cells and immune cells in women with repeated implantation failure.
The aim of this study was to compare women with recurrent implantation failure (RIF) and control group in terms of the associations between p16-positive senescent cells and certain types of immune cells in human endometrium during the mid-luteal phase METHODS: Immunohistochemical staining was performed in 116 endometrial biopsies taken from 57 women presenting RIF, and control group of 59 women who became pregnant after the first intracytoplasmic sperm injection. Endometrial tissue sections were stained immunohistochemically for p16 (Senescent cells), CD4 (T-helpers), CD8 (T-killers), CD14 (Monocytes), CD68 (Macrophages), CD56 (Natural killers), and CD79α (B-cells). The percentage of positively stained cells for each marker was calculated by HALO image analysis software. The quantity and the relationship between senescent cells and immune cells were assessed and compared between the two groups. The correlation coefficient was highest between senescent cells and CD4+ cells and was lowest between senescent cells and CD14+ cells in RIF women, similarly to the control group. However, most of the observed correlations among senescent and immune cells weaken notably or disappear in the RIF group. When comparing senescent cell-to-immune cell quantitative ratios, only p16+/CD4+ cell ratio was significantly higher in RIF women as compared with patients from the control group. Our study indicates that the quantity of senescent cells in human endometrium during the mid-luteal phase has the strongest association with the amount of T helpers. Moreover, the specificity of this association might have an important impact on the occurrence of RIF.


Implementation of a computer-assisted monitoring system for the detection of adverse drug reactions in gastroenterology.
To investigate the effectiveness of a computer monitoring system that detects adverse drug reactions (ADRs) by laboratory signals in gastroenterology. A prospective, 6-month, pharmaco-epidemiological survey was carried out on a gastroenterological ward at the University Hospital Erlangen-Nuremberg. Two methods were used to identify ADRs. (i) All charts were reviewed daily by physicians and clinical pharmacists. (ii) A computer monitoring system generated a daily list of automatic laboratory signals and alerts of ADRs, including patient data and dates of events. One hundred and nine ADRs were detected in 474 admissions (377 patients). The computer monitoring system generated 4454 automatic laboratory signals from 39 819 laboratory parameters tested, and issued 2328 alerts, 914 (39%) of which were associated with ADRs; 574 (25%) were associated with ADR-positive admissions. Of all the alerts generated, signals of hepatotoxicity (1255), followed by coagulation disorders (407) and haematological toxicity (207), were prevalent. Correspondingly, the prevailing ADRs were concerned with the metabolic and hepato-gastrointestinal system (61). The sensitivity was 91%: 69 of 76 ADR-positive patients were indicated by an alert. The specificity of alerts was increased from 23% to 76% after implementation of an automatic laboratory signal trend monitoring algorithm. This study shows that a computer monitoring system is a useful tool for the systematic and automated detection of ADRs in gastroenterological patients.


Travel Burden as a Measure of Healthcare Access and the Impact of Telehealth within the Veterans Health Administration.
Travel is a major barrier to healthcare access for Veteran Affairs (VA) patients, and disproportionately affects rural Veterans (approximately one quarter of Veterans). The CHOICE/MISSION acts' intent is to increase timeliness of care and decrease travel, although not clearly demonstrated. The impact on outcomes remains unclear. Increased community care increases VA costs and increases care fragmentation. Retaining Veterans within the VA is a high priority, and reduction of travel burdens will help achieve this goal. Sleep medicine is presented as a use case to quantify travel related barriers. The Observed and Excess Travel Distances are proposed as two measures of healthcare access, allowing for quantification of healthcare delivery related to travel burden. A telehealth initiative that reduced travel burden is presented. Retrospective, observational, utilizing administrative data. VA patients with sleep related care between 2017 and 2021. In-person encounters: Office visits and polysomnograms; telehealth encounters: virtual visits and home sleep apnea tests (HSAT). Observed distance: distance between Veteran's home and treating VA facility. Excess distance: difference between where Veteran received care and nearest VA facility offering the service of interest. Avoided distance: distance between Veteran's home and nearest VA facility offering in-person equivalent of telehealth service. In-person encounters peaked between 2018 and 2019, and have down trended since, while telehealth encounters have increased. During the 5-year period, Veterans traveled an excess 14.1 million miles, while 10.9 million miles of travel were avoided due to telehealth encounters, and 48.4 million miles were avoided due to HSAT devices. Veterans often experience a substantial travel burden when seeking medical care. Observed and excess travel distances are valuable measures to quantify this major healthcare access barrier. These measures allow for assessment of novel healthcare approaches to improve Veteran healthcare access and identify specific regions that may benefit from additional resources.


Erythroid side scatter: A parameter that improves diagnostic accuracy of flow cytometry myelodysplastic syndrome scoring.
Flow cytometry immunophenotyping (FCM) is a benchmark test for integrated diagnosis of myelodysplastic syndromes (MDS). Our department's FCM-MDS-score follows international guidelines and additionally includes the maturing erythroid (mEry) side scatter (SSC)/lymphocyte SSC ratio (mErySSCr), often increased in MDS patients. A recent exploratory computational flow analysis study highlighted mErySSC as the top feature for separating MDS from non-MDS. Thus, we sought to systematically evaluate the diagnostic accuracy of mErySSCr in conventional diagnostic FCM as used currently in-house. Historical MDS (n = 93), chronic myelomonocytic leukemia (CMML; n = 27) and non-neoplastic cytopenia (n = 57) cohorts were created. Differences between these cohorts and LG-MDS entities were mapped and the mErySSCr cut-off was refined. Prospective bone marrows (n = 213) received for marrow failure work-up were used to determine the sensitivity and specificity of mErySSCr, both as a sole parameter and as a component of the MDS-score. Low-grade (LG)-MDS mErySSCr differed more prominently from controls (p = <0.0001) than high-grade (HG)-MDS (p = 0.024). CMML and controls had a similar mErySSCr. As sole parameter, mErySSCr specificity was 91.1% (n = 112 non-MDS diagnoses) and sensitivity was 36% for LG-MDS (n = 36) and 25% for new HG-MDS diagnoses (n = 16). The specificity of the MDS-score was similar if mErySSCr was omitted (81.3% with and 82.1% without). The MDS-score sensitivity for new HG-MDS diagnoses and CMML (n = 17) was 100%, and was not affected by mErySSCr. The score sensitivity for LG-MDS however, dropped from 86.1% to 72.2% when mErySSCr was excluded. mErySSCr increases the diagnostic accuracy of flow-based MDS scoring in our setting, particularly for LG-MDS.


A multi-disciplinary approach to the management of fungal osteomyelitis: current concepts in post-traumatic lower extremity reconstruction: a case report.
Limb salvage in fungal osteomyelitis of the post-traumatic lower extremity represents a difficult clinical problem requiring aggressive management. We report lower extremity salvage by radical bony debridement, free tissue transfer, distraction osteogenesis with bone-docking, and a novel antifungal regimen in a clinical setting of infection with Scedosporium inflatum, historically requiring amputation in 100% of cases. We treated Scedosporium inflatum osteomyelitis of the tibia and calcaneus with radical debridement of infected bone, free partial medial rectus abdominis muscle flap coverage, transport distraction osteogenesis, and combination voriconazole/terbinafine chemotherapy, a novel antifungal regimen. We achieved successful control of the infection, limb salvage, and an excellent functional outcome through aggressive debridement of infected bone and soft tissue, elimination of dead space within the bony defect, the robust perfusion provided by the free flap, the hypervascular state induced by distraction osteogenesis, and the synergism of the novel antifungal regimen.


Training in critical care echocardiography.
Echocardiography is useful for the diagnosis and management of hemodynamic failure in the intensive care unit so that competence in some elements of echocardiography is a core skill of the critical care specialist. An important issue is how to provide training to intensivists so that they are competent in the field. This article will review issues related to training in critical care echocardiography.


Temporal requirements of associative short-term potentiation in CA1 neurons of rat hippocampus.
Temporal separation and juxtaposition of stimulations for the induction of associative short-term potentiation in the rat hippocampus were examined. A series of stimulations of stratum radiatum during brief tetanic stimulations of stratum oriens resulted in a short-term potentiation (of about 3 min duration) of stratum radiatum-induced CA1 population excitatory postsynaptic potential. Potentiation was evident when the stratum radiatum stimulus preceded the onset of the conditioning tetanus by no more than 50 ms, or followed by no more than 80 ms. These parameters closely resemble those found for associative long-term potentiation, suggesting the possibility of shared mechanisms for the induction of these two forms of potentiation.


Adipokines and metabolic syndrome risk factors in women with previous gestational diabetes mellitus.
Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for metabolic syndrome and CVD. The aim of the study was to evaluate the relationships between levels of cytokines, components of metabolic syndrome and cardiovascular risk markers in women with previous gestational diabetes. Women (n = 41) with gestational diabetes background (cases) and 21 healthy women (controls) in the postpartum period were enrolled. Demographic and clinical data, lipid and carbohydrate metabolism and uric acid and adipokine levels (TNF-α, IL-6, leptin and adiponectin) were compared and their relationships analysed. Metabolic syndrome prevalence was calculated by WHO and NCEP-ATPIII definitions. There were significant differences between cases and controls: body mass index (kg/m(2) ) 27.4 ± 5.6 vs 23.9 ± 3.6 (p = 0.013), waist circumference (cm) 85.2 ± 12.9 vs 77.5 ± 9.0 (p = 0.017), metabolic syndrome (WHO definition) 14.6% vs 0% (p = 0.012), metabolic syndrome (NCEP-ATPIII definition) 22% vs 0% (p = 0.002), low HDL 36.6% vs 9.5% (p = 0.024), fasting glucose (mmol/L) 5.4 ± 0.6 vs 4.9 ± 0.2 (p < 0.001), glucose 120' oral glucose tolerance test (mmol/L) 5.8 ± 1.7vs 4.7 ± 0.8 (p = 0.007), fasting insulin (μU/mL) 13.4 ± 8.1 vs 8.4 ± 4.3 (p = 0.004), HOMA index 3.3 ± 2.3 vs 1.8 ± 1.0 (p = 0.002), HbA(1c) (%) 5.4 ± 0.2 vs 5.2 ± 0.2 (p = 0.021), uric acid (mg/dL) 4.1 ± 1 vs 3.5 ± 0.6 (p = 0.009), leptin (ng/mL) 32 025.5 ± 19 917.3 vs 20 258.9 ± 16 359.9 (p = 0.023), respectively. Women with previous gestational diabetes have central adiposity, atherogenic lipid profile, carbohydrate intolerance and adverse adipokine profile, all of which are risk factors for the future development of metabolic disease and CVD.


Effect of Tailored Antiplatelet Therapy to Reduce Recurrent Stent Thrombosis and Cardiac Death After a First Episode of Stent Thrombosis.
The recurrence rate of coronary stent thrombosis (ST) is high. Patients with ST often demonstrate high on-treatment platelet reactivity (HPR). It is suggested that patients at high risk of atherothrombotic events, that is patients with ST, could benefit from tailored antiplatelet therapy (APT). This study evaluated whether tailored APT, based on platelet function testing, reduced the rate of cardiac death and/or recurrent ST at 1 year after ST, compared with a historical cohort of patients with ST without tailored APT. Patients with definite ST visited our ST outpatient clinic for platelet function testing and tailored APT. These patients were evenly matched to a historical cohort of patients with ST treated with aspirin and clopidogrel, which was the standard of care at that time. The primary end point was a composite of cardiac death and/or recurrent definite ST after 1 year. In total, 113 patients who visited the outpatient clinic were included. HPR was observed in 46%, 6.7%, and 0% of the patients on clopidogrel, prasugrel, and ticagrelor, respectively. After tailored APT, 93% of the patients with HPR demonstrated normal platelet reactivity. The primary end point was observed in 4 patients who had visited the outpatient clinic and in 23 patients of the historical cohort. The odds ratio of tailored APT on the primary end point was 0.26 (95% confidence interval 0.11 to 0.64, p = 0.003), independent from the possible confounders prior myocardial infarction and stent type. In conclusion, the outpatient ST clinic was associated with lower HPR rates in patients with ST after tailored APT. Patients who visited the ST outpatient clinic had a lower risk for cardiac death and/or recurrent ST compared with a historical cohort of patients with ST without tailored APT. Regarding the high HPR rate in patients with ST on clopidogrel, these patients might benefit in particular from the strategy of tailored APT.


'Decipio': examining Virchow in the context of modern 'democracy'.
More than 100 years ago Rudolf Virchow advocated for enhanced democracy and socioeconomic reforms in order that the state could empower people to achieve better health. With reference to these now famous assertions this article traces the promises and pit-falls of democracy from ancient Greece to neo-liberal economies, to ascertain if the democratic state is indeed the ideal mechanism for promoting public health. In the end we conclude that contemporary western political systems are not rooted in the interest of the people, but are rather deceptive forces of branding designed to promote underlining agendas. This 'decipractic' (decipo = to deceive) system of politics demands a vigilant analysis and response from those in the health and academic communities to ensure that governments can be a mechanism for positive change in the public's interest.


Risk Factors for Opisthorchis Viverrini Infection: A Systematic Review.
Opisthorchis viverrini (O. viverrini) infection is the primary cause of cholangiocarcinoma (CCA) and a major public health challenge along the Mekong River in Thailand, Vietnam, Laos PDR, Cambodia, China and Myanmar. This systematic review appraised the risk factors for O. viverrini infection. Literature searches were conducted using Medical Subject Headings (MeSH) and keywords, without date or language restriction, in PubMed, EMBASE, Global Health, and Thai Journals Online. References from relevant papers also were reviewed to expand the scope of the search. The inclusion criteria were human subjects. The primary outcome was O. viverrini infection. The exclusion criteria were in vitro, animal, genetic research, and systematic reviews. All included studies were summarized and reported as follows: study design, age, sample size, setting, data collection and fecal examination methods, adjusted odds ratio and 95% confidence interval, significant risk factors, and other findings. The search results show that across all databases 1,098 records were identified. Twenty-four articles were included in the systematic review, consisting of cross-sectional studies (79.2%), cohort studies (12.5%), and case-control studies (8.3%). The majority of study settings were in Thailand (75%). The People's Democratic Republic of Laos (Lao PDR) accounted for the second greatest number of studies (20.8%), and 4.2% of the studies originated in Vietnam. Key findings included demographic, environmental, geographic, health behavior, treatment with praziquantel, and a history of O. viverrini infection that was significantly associated with O. viverrini infection. Health professionals should investigate the potential risk factors for the disease and should seek and develop innovative methods for prevention and control of O. viverrini infection in these countries.


Essential tremor impairs the ability to suppress involuntary action impulses.
Essential tremor (ET) is a movement disorder characterized primarily by action tremor which affects the regulation of movements. Disruptions in cerebello-thalamocortical networks could interfere with cognitive control over actions in ET, for example, the ability to suppress a strong automatic impulse over a more appropriate action (conflict control). The current study investigated whether ET impacts conflict control proficiency. Forty-one ET patients and 29 age-matched healthy controls (HCs) performed a conflict control task (Simon task). Participants were instructed to give a left or right response to a spatially lateralized arrow (direction of the arrow). When the action signaled by the spatial location and direction of the arrow were non-corresponding (induced conflict), the inappropriate action impulse required suppression. Overall, ET patients responded slower and less accurately compared to HCs. ET patients were especially less accurate on non-corresponding conflict (Nc) versus corresponding (Cs) trials. A focused analysis on fast impulsive response rates (based on the accuracy rate at the fastest reaction times on Nc trials) showed that ET patients made more fast errors compared to HCs. Results suggest impaired conflict control in ET compared to HCs. The increased impulsive errors seen in the ET population may be a symptom of deficiencies in the cerebello-thalamocortical networks, or, be caused by indirect effects on the cortico-striatal pathways. Future studies into the functional networks impacted by ET (cortico-striatal and cerebello-thalamocortical pathways) could advance our understanding of inhibitory control in general and the cognitive deficits in ET.


A novel biological sources consistency evaluation method reveals high level of biodiversity within wild natural medicine: A case study of Amynthas earthworms as "Guang Dilong".
For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.


Nonintubated needlescopic video-assisted thoracic surgery for management of peripheral lung nodules.
Video-assisted thoracic operations are usually performed with 5-mm or 10-mm instruments under general anesthesia with single-lung ventilation. Management of peripheral lung nodules by a needlescopic video-assisted thoracoscopic operation, without endotracheal intubation, has rarely been attempted. We evaluated the feasibility and safety of this minimally invasive technique in managing peripheral lung nodules. From August 2009 through March 2011, 46 patients with peripheral lung nodules were treated using 3-mm needlescopic video-assisted thoracoscopic operations for wedge resection with epidural anesthesia and sedation, without endotracheal intubation. A definitive diagnosis was obtained in all 46. Extension of the 3-mm incisions was required in 8 patients because of primary lung cancer requiring a lobectomy in 3, pleural adhesions in 3, and difficulty in identifying or resecting the nodule in 2. Two patients required conversion to intubated single-lung ventilation because of dense adhesions between the lungs and the diaphragm. Operations lasted a mean of 69.2 ± 46.8 minutes. Postoperative side effects occurred in 4 patients, including sore throat, headache, and vomiting requiring medication. Operative complications developed in 1 patient who had air leaks for more than 3 days postoperatively. The mean postoperative chest tube drainage and hospital stay were 1.1 days and 2.7 days, respectively. Postoperative neuralgia was noted in 12 patients (26%). Most patients (74%) were very satisfied or satisfied with the resulting scars. Nonintubated needlescopic video-assisted thoracoscopic operations are technically feasible and safe and may be a less invasive alternative in the management of selected patients with peripheral pulmonary nodules.


Differential expression of Dusp1 and immediate early response genes in the hippocampus of rats, subjected to forced swim test.
The forced swim test (FST) is widely used to screen for potential antidepressant drugs and treatments. Despite this, the nature of stillness during FST and whether it resembles "depressive-like behavior" are widely debated issues. Furthermore, despite being widely used as a behavioral assay, the effects of the FST on the brain transcriptome are rarely investigated. Therefore, in this study we have investigated changes in the transcriptome of the rat hippocampus 20 min and 24 h after FST exposure. RNA-Seq is performed on the hippocampus tissues of rats 20 min and 24 h after an FST. Differentially expressed genes (DEGs) were identified using limma and used to construct gene interaction networks. Fourteen differentially expressed genes (DEGs) were identified only in the 20-m group. No DEGs were identified 24 h after the FST. These genes were used for Gene Ontology term enrichment and gene-network construction. Based on the constructed gene-interaction networks, we identified a group of DEGs (Dusp1, Fos, Klf2, Ccn1, and Zfp36) that appeared significant based on multiple methods of downstream analysis. Dusp1 appears especially important, as its role in the pathogenesis of depression has been demonstrated both in various animal models of depression and in patients with depressive disorders.


Indicators of the Lipid Peroxidation-Antioxidant Protection System as Important Metabolic Markers of Reproductive Potential in Men.
We analyze results of recent studies demonstrating unfavorable state of the reproductive health in the male population that manifested not only in spermatogenesis deterioration, but also in oxidative stress (both systemic and in seminal fluid). The data on the effect of ROS and components of the antioxidant defense system on gamete quality in men with infertility associated with obesity and diabetes mellitus are presented. Some features of oxidative stress in men of reproductive age of various ethnic groups are shown. Evaluation of the parameters of oxidative stress provides new insight into the molecular mechanisms of functional activity of the semen and may become a promising direction for the development of new methodological recommendations for personalized diagnosis, prevention, and correction of reproductive disorders in men.


Which is responsible for cardiac autonomic dysfunction in non-diabetic patients with metabolic syndrome: Prediabetes or the syndrome itself?
Cardiac autonomic dysfunction (CAD) is associated with both prediabetes and metabolic syndrome (MS). Heart rate variability (HRV) and heart rate turbulence (HRT) are reliable 24-h Holter-ECG findings of cardiac autonomic function. This study aimed to investigate the relation between MS and its components and CAD using HRV and HRT. The study included 80 non-diabetic patients with MS and 70 control subjects. All study population and the patients with MS were further analyzed for each diagnostic component of MS to investigate which criteria impaired HRV and HRT. HRV and HRT parameters were disturbed in patients in the MS group. While impairment in HRV and HRT was significantly related to the presence of the fasting plasma glucose (FPG) criterion, there were no differences between groups in terms of the other 4 MS criteria. Moreover, FPG level was significantly correlated with SDNN (r=-0.352, p<0.001), SDNN index (r=-0.423, p<0.001), SDANN (r=-0.301, p<0.001), RMSSD (r=-0.237, p<0.001), pNN50 (r=-0.237, p<0.001), turbulence onset (TO) (r=0.365, p<0.001) and turbulence slope (TS) (r=-0.365, p<0.001). Among the MS diagnostic criteria, only FPG level was an independent determinant of all HRV and HRT parameters. This study confirms the relation between MS and CAD. Increased FPG alone appears to be responsible for the mentioned findings among the 5 diagnostic criteria. Accordingly, CAD may be the result of prediabetes, not MS in patients with MS.


Morphologic criteria for the diagnosis of prostatic adenocarcinoma in needle biopsy specimens. A study of 250 consecutive cases in a routine surgical pathology practice.
The diagnosis of prostate adenocarcinoma in needle core biopsy specimens is based on multiple diagnostic criteria and supportive features, most of which have been defined mainly from observations in transurethral resection and prostatectomy specimens. There is little information on the frequency with which diagnostic and supportive features of prostate cancer occur within benign glands. The few reports dealing with diagnostic criteria of cancer in needle biopsies have been largely confined to analysis of selected cases that posed particular diagnostic difficulty. To analyze the frequency with which numerous diagnostic or supportive features of prostate cancer occur in an unselected, consecutively performed series of 18-gauge prostate needle biopsy specimens. Two hundred fifty consecutive 18-gauge prostate needle biopsy specimens (150 malignant and 100 benign) were evaluated, using hematoxylin-eosin-stained histologic sections. The frequency of the histologic features in malignant and benign glands was as follows: prominent nucleoli (94% and 25% of malignant and benign specimens, respectively), marginated nucleoli (88% and 7%), multiple nucleoli (64% and 0%), blue-tinged mucinous secretions (52% and 0%), intraluminal crystalloids (40.6% and 1%), intraluminal amorphous eosinophilic material (86.7% and 2%), collagenous micronodules (2% and 0%), glomerulations (15.3% and 0%), perineural invasion (22% and 0%), retraction clefting (38.6% and 7%), and invasion of fat (0.7% and 0%). Since not all diagnostic or supportive features of cancer are evident in any single case of cancer, particularly in needle biopsy specimens in which sampling is limited, awareness of these data would be helpful in the assessment of small foci of atypical glands being considered for cancer.