Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolism of angiotensin II is required for its in vivo effect on dopamine release in the striatum of the rat

The effect of angiotensin (Ang) IV, an inhibitor of insulin‐regulated aminopeptidase (IRAP), on extracellular dopamine levels in the striatum of freely moving rats was examined using in vivo microdialysis. The Ang IV was administered locally in the striatum through the microdialysis probe. A concentration‐dependent (10–100 µm) increase in extracellular striatal dopamine was observed. The effect of Ang II (10–100 µm), which has only a weak affinity for IRAP, was similar to that observed for Ang IV. The effects of both peptides could not be blocked by the AT1 antagonist candesartan (10 nm and 1 µm) nor by the AT2 antagonist S‐(+)‐1‐([4‐(dimethylamino)‐3‐methylphenyl]methyl)‐5‐(diphenyl‐acetyl)‐4,5,6,7‐tetrahydro‐1H‐amidazo(4,5‐c) pyridine‐6‐carboxylic acid (1 µm), suggesting that the observed effects are both AT1 and AT2 independent. The effect of Ang II could be blocked by the aminopeptidase‐A inhibitor (S)‐3‐amino‐4‐mercaptobutylsulphonic acid as well as the aminopeptidase‐N inhibitor 2‐amino‐4‐methylsulphonylbutane thiol, indicating that the effect of Ang II is mediated via metabolism into Ang IV. Other IRAP inhibitors, such as Divalinal‐Ang IV and LVV‐haemorphin‐7, had similar effects on extracellular dopamine levels as compared with Ang IV. We propose a role for IRAP as mediator for the effects of Ang IV and related peptides on extracellular dopamine levels in the striatum of the rat.
Diabetes and Diabetic Retinopathy Management in East Africa: Knowledge, Attitudes, and Practices of Hospital Staff in Kenya

PurposeGood diabetes mellitus (DM) and diabetic retinopathy (DR) management depends largely on involved medical staff, prompting us to investigate knowledge, attitudes, and practices about DM and DR at a tertiary referral center in Kenya. DesignThe design for this study is exploratory qualitative using semistructured interviews. MethodsData from eye and diabetes clinic staff were collected until thematic saturation was reached, transcribed, and iteratively analyzed for relevant themes based on the constant comparative method. ResultsAmong 46 participants (mean age, 38 years; 54% females), most were physicians (n = 25, 54%), followed by nurses (n = 14, 30%) and clinical officers (n = 6, 13%). Diabetes mellitus and DR were seen as urgent health problems (n = 42, 91%), and regular ophthalmic screening of diabetic patients was universally recommended. Two thirds (n = 32, 70%) were unaware of DM and DR management guidelines at the hospital. Participants identified training of staff in diagnosing (n = 30, 65%), efficient detection and referral of diabetic patients (n = 24, 52%), and improved outreach services (n = 14, 30%) as most pressing areas of need. Communication among hospital departments was found to be suboptimal. Reported barriers to good DR management were lack of retinal laser treatment and costs. ConclusionsManagement outcomes for DM and DR may be improved by implementing integrated service provision, direct ophthalmological involvement in diabetic clinics, endorsement and effective distribution of guidelines, an increase in screening capacity, and the introduction of ongoing medical education covering DM and DR.
Electromagnetic Characterization of Thin Dielectric Materials From Amplitude-Only Measurements

A method is proposed for unique and accurate permittivity (<inline-formula> <tex-math notation="LaTeX">$\varepsilon _{r}$ </tex-math></inline-formula>) extraction of low-loss thin samples from reference-plane-invariant amplitude-only measurements without resorting to the information of explicit permittivity of a sample holder. Thanks to the amplitude-only measurements, it is possible to bypass the increased phase uncertainty of scattering parameters and retrieve unique <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{r}$ </tex-math></inline-formula>. An uncertainty analysis is followed to investigate improved accuracy attained by our method. Waveguide measurements at the <inline-formula> <tex-math notation="LaTeX">$X$ </tex-math></inline-formula>-band are next conducted to measure <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{r}$ </tex-math></inline-formula> of polyethylene and polyvinyl chloride samples with different lengths (the sample holder is a soda-lime glass) for validation of the method and for comparison its accuracy with other methods. From the comparison, we note that reference-plane-dependent methods necessitate precise knowledge of sample location for accurate <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{r}$ </tex-math></inline-formula> retrieval. Besides, it is observed that while compared reference-plane-invariant techniques either require that the sample holder does not move while positioning the sample over it or produce more than one solution for <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{r}$ </tex-math></inline-formula> measurement of low-loss dielectric samples, our method removes these two problems.
Nasal treatment with a microemulsion reduces allergen challenge-induced symptoms and signs of allergic rhinitis

Conclusions. Intranasal microemulsion treatment can attenuate allergen challenge-induced nasal symptoms and plasma exudation in allergic rhinitis. We hypothesize that the mechanism of action involves modification of the allergen–mucosa interaction. The present observation suggests a novel principle for prevention in allergic rhinitis. Objective. To evaluate a specific microemulsion as a treatment for allergic rhinitis in an acute allergen challenge model. Patients and methods. Patients with allergic rhinitis were examined out of the pollen season. Treatment with a single dose of a specific microemulsion was given in a single-blind, placebo-controlled, and crossover design using a nasal pool device. Nasal allergen challenges were carried out and symptoms of allergic rhinitis were scored. Furthermore, nasal lavages were performed and levels of the plasma protein α2-macroglobulin were measured as an index of exudative inflammation. Results. The allergen challenges produced significant increases in nasal symptoms (p=0.007) and in nasal lavage fluid levels of α2-macroglobulin (p=0.008). The challenge-induced symptoms as well as the plasma exudation were attenuated by treatment with the microemulsion (p=0.016 and 0.012, respectively, compared with placebo).
Dysfunction of Pharyngeal Swallowing

Cineradiography of pharyngeal swallowing was performed in 854 patients (389 males and 465 females) with dysphagia and analyzed for pharyngeal function. Epiglottic dysmotility was registered in 206 patients (24%), defective closure of the laryngeal vestibule in 318 patients (37%), paresis in pharyngeal constrictors in 130 patients (15%), dysfunction of the cricopharyngeal muscle in 215 patients (25%), webs in 130 patients (15%), Zenker diverticula in 20 patients (2 %) and Killian-Jamie son diverticula in 16 patients (2%). The symptom dysphagia was more frequent among young women compared with young men. Over the age of 65 the relation was reversed. Pharyngeal dysfunction was more common among young men than young women and this was due to a high frequency of dysfunction of the laryngeal vestibule in young men. Epiglottic dysfunction and dysfunction of the laryngeal vestibule, pharyngeal paresis, cricopharyngeal incoordination and webs showed an increased frequency with age, while diverticula did not. Pharyngeal constrictor paresis was more common in men. Defective relaxation of the cricopharyngeal muscle and webs were more common among old women compared with old men.
Hip and knee implantations among patients with osteoarthritis and risk of cancer: A record‐linkage study from Denmark

A nationwide cohort study of hip and knee replacement patients in Denmark was undertaken to assess any carcinogenic potential of these implants. A cohort of 22,997 osteoarthritis patients who received hip replacements and of 4,771 osteoarthritis patients who received knee replacements during the period 1977 through 1989 were identified using the nationwide Danish Hospital Discharge Registry. These patients were followed for cancer occurrence through 1993, using the Danish Cancer Registry. There was no overall excess of cancer in either the hip implant cohort [standardized incidence ratio (SIR) = 0.94; 95% confidence interval (CI) = 0.91–0.98] or the knee implant cohort (SIR = 0.97; 95% CI = 0.89–1.06). The risk reduction in both groups of patients reflected for the most part reduced risks for cancers of the respiratory system and the digestive tract, particularly stomach cancer (SIR = 0.69; 95% CI = 0.50–0.81 for hip replacement patients; SIR = 0.46; 95% CI = 0.20–0.91 for knee replacement patients). Elevated risks were observed for melanoma of the skin in both groups of patients. There was no clear excess risk for lymphohematopoietic cancers or malignant neoplasms of the bone or connective tissue among implant patients in either implant group. Contrary to an earlier study in Sweden, we did not find an excess risk for kidney or prostate cancers. In summary, these nationwide results indicate no overall cancer hazard among hip and knee implant patients, but limited follow‐up warrants continued surveillance of individuals undergoing these increasingly common surgical procedures. Int. J. Cancer 81:719–722, 1999. © 1999 Wiley‐Liss, Inc.
THE FRANCHISE FACTOR IN THE DEFEAT OF THE IRISH PARLIAMENTARY PARTY, 1885–1918

This article examines Irish nationalist attitudes towards electoral reform between 1885 and 1918. It argues that before 1917 mainstream Irish nationalist opinion attached little importance to the franchise, being instead more concerned about the consequences for home rule if the number of Irish parliamentary seats was reduced through redistribution. However, the introduction of wartime legislation to reform the franchise and registration system repoliticized electoral reform in nationalist Ireland. While the Irish parliamentary party vociferously protested at the coalition government's belated attempt to redistribute Irish constituencies, its critics (a coalition of heterodox nationalists, socialists, and suffragettes) accused it of deliberately conspiring to exclude Ireland from the ‘fourth’ reform bill because the young men and women it would enfranchise intended to vote for Sinn Fein. This article argues that the concerns of the Irish party regarding redistribution were genuine and legitimate, while the conspiracy theory was essentially a propaganda device. None the less, the theory gained widespread attention because its underlying assumption about the voting behaviour of the new electorate was shared not only by its exponents, but by sections of the press, the British administration in Ireland, and the Irish party itself. Indeed, so convinced was the party that the cleavage in Ireland was as much generational as ideological that ultimately the franchise was a factor in its defeat at the 1918 general election.
Development of a calibrated automated thrombography based thrombin generation test in mouse plasma

Summary. Background: Mouse models have become increasingly important in thrombosis research. However, only a limited number of assays are available for assessment of the coagulation system in mouse plasma. Objectives: To quantify tissue factor‐initiated thrombin generation in murine platelet‐rich and platelet‐free plasma and to develop a test for measurement of resistance to activated protein C (APC) in mouse plasma. Methods: Thrombin generation was monitored with calibrated automated thrombography (CAT) using a low‐affinity fluorogenic substrate for thrombin. Results: To overcome the higher activity of coagulation inhibitors in mouse plasma as compared with human plasma, the reaction temperature was lowered to 33 °C and the assay was carried out at a 2‐fold higher final plasma dilution (1:3) than commonly used for CAT in human plasma. This increased the endogenous thrombin potential (ETP) 4‐ to 5‐fold and enabled reliable measurement of thrombin generation in both platelet‐free and platelet‐rich mouse plasma. For the APC resistance measurement, the reaction conditions were further optimized with respect to tissue factor, phospholipid, APC and CaCl2 concentrations. The test was validated using plasma of mice with different genetic background with respect to the factor V Leiden mutation (FV Leiden). Mice homozygous for FV Leiden had higher APC sensitivity ratios (mean 5.46; 95% CI 4.88–6.03) than heterozygous FV Leiden mice (mean 4.21; 95% CI 3.53–4.89) and than wild‐type mice (mean 2.71; 95%CI 2.15–3.27). Conclusions: We have established reaction conditions for measurement of thrombin generation and APC resistance in mouse plasma. This assay enables evaluation of the coagulation system and the function of the protein C system in mouse models.
Cardiovascular , Pulmonary , and Renal Pathology Fibroblast Growth Factor-2 Promotes in Vitro Mitral Valve Interstitial Cell Repair through Transforming Growth Factor-/ Smad Signaling

Transforming growth factor (TGF)and fibroblast growth factor (FGF)-2 both promote repair in valve interstitial cell (VIC) injury models; however, the relationship between TGFand FGF-2 in wound repair are not well understood. VIC confluent monolayers were wounded by mechanical injury and incubated separately or in combination with FGF-2, neutralizing antibody to FGF-2, neutralizing antibody to TGF, and betaglycan antibody for 24 hours after wounding. Phosphorylated Smad2/3 (pSmad2/3) was localized at the wound edge (WE) and at the monolayer away from the WE. Down-regulation of pSmad2/3 protein expression via small-interfering RNA transfection was performed. The extent of wound closure was monitored for up to 96 hours. FGF-2 incubation resulted in a significant increase in nuclear pSmad2/3 staining at the WE. Neutralizing antibody to TGFalone or with FGF-2 present resulted in a similar significant decrease in pSmad2/3. Neutralizing antibody to FGF-2 alone or with FGF-2 present showed a similar significant decrease in pSmad2/3; however, significantly more staining was observed than treatment with neutralizing antibody to TGF. Incubation with betaglycan antibody inhibited FGF-2–mediated pSmad2/3 signaling. Wound closure corresponded with pSmad2/3 staining at the WE. Downregulation of pSmad2/3 via small-interfering RNA transfection significantly reduced the extent to which FGF-2 promoted wound closure. Fibroblast growth factor-2 promotes in vitro VIC wound repair, at least in part, through the TGF/Smad2/3 signaling pathway. (Am J Pathol 2011, 178:119–127; DOI: 10.1016/j.ajpath.2010.11.038)
Glycosylation enhances functional stability of the chemotactic cytokine CCL2.

The human chemokine CCL2 gene was expressed in the yeast P.pastoris and gave rise to a mixture of differently glycosylated recombinant proteins. In comparison to non-glycosylated E.coli-derived CCL2, glycosylated yeast CCL2L was 4-20 times less active in a chemotactic assay in vitro. However, CCL2L could maintain full activity upon prolonged incubation at 37 degrees C, whereas the non-glycosylated chemokine readily lost activity. It could be hypothesized that glycosylation is a mechanism used by the organism to modulate CCL2 stability. The partial loss of specific activity due to glycosylation is balanced by the advantage of prolonging the effectiveness of chemokine. Thus, differential glycosylation allows one to obtain highly effective short-lived CCL2 or less-effective long-lived CCL2 and may thus represent a novel mechanism of adaptation to pathological versus physiological conditions.
Altered ventricular repolarization during hypoglycaemia in patients with diabetes

There is circumstantial evidence implicating hypoglycaemia in the sudden overnight death of young patients with insulin‐dependent (Type 1) diabetes mellitus (IDDM), the mechanism of which is unknown. We have investigated the effects of hypoglycaemia on the electrocardiogram in 15 patients with diabetes (8 with IDDM and 7 with NIDDM) using a high resolution computer‐based system. Patients were randomized to either 2 h of euglycaemia or hypoglycaemia (at around 3 mmol l−1 ) during the afternoon, using hyperinsulinaemic glucose clamps, the two visits separated by a period of at least 4 weeks. Corrected QT interval (QTc), plasma potassium, and adrenaline were measured at baseline and at 0, 60, and 120 min. The degree of QTc lengthening (from baseline) during clamped hypoglycaemia was greater compared to the euglycaemic control period in patients with IDDM (median{range} at 60 min, 156{8 to 258 } vs 6{−3 to 28} ms, p <0.02) and NIDDM (120 min, 128{16 to 166} vs 4{ −3 to 169} ms, p <0.05). The fall in plasma potassium was greater during clamped hypoglycaemia compared to euglycaemia in those with NIDDM ( p <0.03) but not with those with IDDM ( p >0.06). The rise in plasma adrenaline was greater during clamped hypoglycaemia in both groups (IDDM p <0.02, NIDDM p <0.02) and there was a strong relationship between the rise in adrenaline and increase in QTc ( r = 0.73, p <0.0001). These data demonstrate alteration of ventricular repolarization with lengthening of the QT interval during hypoglycaemia and suggest a possible mechanism by which hypoglycaemia could cause ventricular arrhythmias. © 1997 by John Wiley & Sons, Ltd.
Effects of Sleep on Word Pair Memory in Children – Separating Item and Source Memory Aspects

Word paired-associate learning is a well-established task to demonstrate sleep-dependent memory consolidation in adults as well as children. Sleep has also been proposed to benefit episodic features of memory, i.e., a memory for an event (item) bound into the spatiotemporal context it has been experienced in (source). We aimed to explore if sleep enhances word pair memory in children by strengthening the episodic features of the memory, in particular. Sixty-one children (8–12 years) studied two lists of word pairs with 1 h in between. Retrieval testing comprised cued recall of the target word of each word pair (item memory) and recalling in which list the word pair had appeared in (source memory). Retrieval was tested either after 1 h (short retention interval) or after 11 h, with this long retention interval covering either nocturnal sleep or daytime wakefulness. Compared with the wake interval, sleep enhanced separate recall of both word pairs and the lists per se, while recall of the combination of the word pair and the list it had appeared in remained unaffected by sleep. An additional comparison with adult controls (n = 37) suggested that item-source bound memory (combined recall of word pair and list) is generally diminished in children. Our results argue against the view that the sleep-induced enhancement in paired-associate learning in children is a consequence of sleep specifically enhancing the episodic features of the memory representation. On the contrary, sleep in children might strengthen item and source representations in isolation, while leaving the episodic memory representations (item-source binding) unaffected.
Clinical evaluation of five portable tonometers.

BACKGROUND Intraocular pressure (IOP) measurements obtained with five commercially available portable tonometers (Keeler Pulsair 2000, Tomey Pro-Ton, Tono-Pen XL, Perkins, and Shiotz) were compared to IOPs measured with a Goldmann tonometer in order to predict whether instrument accuracy justified substitution of a portable instrument for the Goldmann in all or specific circumstances. METHODS A total of 31 patients (59 eyes) were assessed. The order of techniques was random except that in each case Goldmann tonometry was performed first and Shiotz tonometry was performed last. Examiners were masked to all other IOP measurements. Correlation and regression analyses were used to predict Goldmann IOP from the other portable tonometer readings. In addition, the difference in pressure readings was compared to mean pressure readings. RESULTS Comparisons of means, correlations, regression equations, and box plots of difference scores were performed to determine which techniques were more accurate. The results varied slightly depending on the method used. All IOPs obtained with portable tonometers showed significant correlation and regression equations compared to the Goldmann IOPs. The correlation ranged from (r = 0.75) for the Keeler Pulsair to (r = 0.66) for the Schiotz. Three tonometers (Tono-Pen, Schiotz, and the Pro-Ton) showed a small significant underestimation of the Goldmann IOPs. CONCLUSIONS All portable tonometers were able to accurately predict Goldmann IOPs. While three of the tonometers were found to underestimate Goldmann IOP on average, these results can be corrected by either adding the underestimation or by using the best fitting regression equation.
Activated CD4+ CD25+ T cells suppress antigen‐specific CD4+ and CD8+ T cells but induce a suppressive phenotype only in CD4+ T cells

CD4+ CD25+ regulatory T cells are increasingly recognized as central players in the regulation of immune responses. In vitro studies have mostly employed allogeneic or polyclonal responses to monitor suppression. Little is known about the ability of CD4+ CD25+ regulatory T cells to suppress antigen‐specific immune responses in humans. It has been previously shown that CD4+ CD25+ regulatory T cells anergize CD4+ T cells and turn them into suppressor T cells. In the present study we demonstrate for the first time in humans that CD4+ CD25+ T cells are able to inhibit the proliferation and cytokine production of antigen specific CD4+ and CD8+ T cells. This suppression only occurs when CD4+ CD25+ T cells are preactivated. Furthermore, we could demonstrate that CD4+ T‐cell clones stop secreting interferon‐γ (IFN‐γ), start to produce interleukin‐10 and transforming growth factor‐β after coculture with preactivated CD4+ CD25+ T cells and become suppressive themselves. Surprisingly preactivated CD4+ CD25+ T cells affect CD8+ T cells differently, leading to reduced proliferation and reduced production of IFN‐γ. This effect is sustained and cannot be reverted by exogenous interleukin‐2. Yet CD8+ T cells, unlike CD4+ T cells do not start to produce immunoregulatory cytokines and do not become suppressive after coculture with CD4+ CD25+ T cells.
Reliability of isometric trunk moment measurements in healthy persons over 50 years of age.

OBJECTIVE To determine the short- and long-term test-retest reliability of maximum isometric trunk moment measurements in healthy volunteers over 50 years of age, to compare these results with those from volunteers younger than 50 years, and to test whether volunteers' anticipatory emotional state affects the precision of these measurements. METHODS Forty-two older persons (21 females; age range 50-90 years) and 44 younger persons (19 females; age range 18-49 years) performed maximum isometric trunk extensions, flexions, and rotations using dynamometers (DAVID, Fi, David Health Solutions Ltd, Helsinki, Finland). They repeated the tests after 1-2 days (short-term) and at 6 weeks (long-term). Retest-reliability was evaluated for age- and gender-specific subgroups, with assessment of intraclass correlation coefficient (ICC2,1) , standard error of measurement, smallest real difference, and smallest real difference, in percent. RESULTS For the elderly group, smallest real difference, in percent values varied up to 33% and were similar to those obtained from young volunteers. Precision of the trunk rotation tests was lower than that of trunk flexion or extension. Retest agreement exceeded 0.75 (ICC2,1) for all tests, with no relevant differences observed between gender- and age-specific subgroups. Neither participants' motivation nor their anticipatory emotions correlated with the individual coefficients of variation of the trunk muscle moment measurements. CONCLUSION Isometric maximum trunk extension and flexion moment measurements taken from healthy persons > 50 years old are as reliable as those from persons < 50 years old, and can be expected to enable an acceptable level of detection of expected changes in muscle strength parameters as a result of planned exercise interventions.