Immobilising effect of Ruta graveolens L. on human spermatozoa: coumarin compounds are involved

This study was designed to find out Ruta graveolens L. functional components, which have immobilisation effect on human spermatozoa for contraceptive use. A five‐step fractionation method was used to derive different components from rue aqueous extract by using hexane, chloroform, ethanol, acetone and ultrapure water. Gas chromatography–mass spectrophotometery (GC–MS) of all fractions and the aqueous extract were performed to determine the chemical components. The immobilisation assay and membrane integrity test were also performed with four different coumarins, which were found in GC–MS in a concentration of 10 μm . Hexane, chloroform, acetone and ethanol fractions could significantly decrease motility of sperms within the first and the second hours. Hexane fraction had also significant immediate effect. The aqueous fraction had no effect on sperm motility. Meanwhile, GC–MS revealed that aqueous extract and effective fractions had similar coumarin compounds. We performed the immobilisation assay on four different coumarins, which were found in GC–MS in a concentration of 10 μm . Reduction of sperm motility was only significant for xanthotoxin. In the sperm viability and membrane integrity tests, hexane and ethanolic fractions could impair sperm vitality significantly, in contrast to coumarins. These results indicated that a part of immobilising effect of rue could be due to its coumarins. The possible mechanism could be blocking of spermatozoa potassium channels.     

St Jude's Medical prosthesis in patients over 65

Between September 1979 and December 1982, 56 St Jude Medical valvular prostheses were implanted in 54 patients over 65 years of age. Surgery consisted in simple aortic valve replacement (35 cases), simple mitral valve replacement (12 cases), double aortic and mitral valve replacement (2 cases), valve replacement and coronary artery bypass surgery (3 cases), aortic valve replacement and replacement of the ascending aorta (1 case) and mitral valve replacement and tricuspid annuloplasty (1 case). The operative mortality (within 30 days of surgery) was 3.5% (2 cases). Patients were assessed by clinical examination, ECG, chest X-ray, echocardiogram and laboratory investigations on average 19 months after surgery. There were 3 late deaths (1 endocarditis, 1 cardiac failure and 1 subdural haematoma). No cases of significant haemolysis were observed. There were no cases of thrombosis of the valve or any deaths directly related to the valve. Four patients had cerebral embolism (4.9% per patient/year). None were fatal and only 1 patient had sequellae. Clinical improvement was very significant; 96% of the patients are now in the NYHA Classes I and II whilst 80% were in Class III or IV before surgery. The cardiothoracic ratio decreased significantly from 0.56 to 0.51 (p less than 0.01). The authors conclude that elderly patients may derive great benefits from valvular cardiac surgery and that age in itself is not a contraindication to this type of surgery. The St Jude Medical prosthesis is an excellent prosthesis but thromboembolism remains a major problem as with other mechanical prostheses. Anticoagulation for life is essential.     

Distinct neural ensemble response statistics are associated with recognition and discrimination of natural sound textures

The perception of sound textures, a class of natural sounds defined by statistical sound structure such as fire, wind, and rain, has been proposed to arise through the integration of time-averaged summary statistics. Where and how the auditory system might encode these summary statistics to create internal representations of these stationary sounds, however, is unknown. Here, using natural textures and synthetic variants with reduced statistics, we show that summary statistics modulate the correlations between frequency organized neuron ensembles in the awake rabbit inferior colliculus (IC). These neural ensemble correlation statistics capture high-order sound structure and allow for accurate neural decoding in a single trial recognition task with evidence accumulation times approaching 1 s. In contrast, the average activity across the neural ensemble (neural spectrum) provides a fast (tens of milliseconds) and salient signal that contributes primarily to texture discrimination. Intriguingly, perceptual studies in human listeners reveal analogous trends: the sound spectrum is integrated quickly and serves as a salient discrimination cue while high-order sound statistics are integrated slowly and contribute substantially more toward recognition. The findings suggest statistical sound cues such as the sound spectrum and correlation structure are represented by distinct response statistics in auditory midbrain ensembles, and that these neural response statistics may have dissociable roles and time scales for the recognition and discrimination of natural sounds.

What makes a sound natural, and what are the neural codes that support recognition and discrimination of real-world natural sounds? Although it is known that the early auditory system decomposes sounds along fundamental acoustic dimensions such as intensity and frequency, the higher-level neural computations that mediate natural sound recognition are poorly understood. This general lack of understanding is in part attributed to the structural complexity of natural sounds, which is difficult to study with traditional auditory test stimuli, such as tones, noise, or modulated sequences. Such stimuli can reveal details of the neural representation for relatively low-level acoustic cues, yet they don’t capture the rich and diverse statistical structure of natural sounds. Thus, they cannot reveal many of the computations associated with higher-level sound properties that facilitate auditory tasks such as natural sound recognition or discrimination. A class of stationary natural sounds termed textures, such as the random sounds emanating from a running stream, a crowded restaurant, or a chorus of birds, have been proposed as alternative natural stimuli which allow for manipulating high-level acoustic structure (1). Texture sounds are composed of spatially and temporally distributed acoustic elements that are collectively perceived as a single source and are defined by their statistical features. Identification of these natural sounds has been proposed to be mediated through the integration of time-averaged summary statistics, which account for high-level structures such as the sparsity and time-frequency correlation structure found in many natural sounds (1–3). Using a generative model of the auditory system to measure summary statistics from natural texture sounds, it is possible to synthesize highly realistic synthetic auditory textures (1). This suggests that high-order statistical cues are perceptually salient and that the brain might extract these statistical features to build internal representations of sounds.Although neural activity throughout the auditory pathway is sensitive to a variety of statistical cues such as the sound contrast, modulation power spectrum, and correlation structure (4–12), how sound summary statistics contribute toward basic auditory tasks such as recognition and discrimination of sounds is poorly understood. Furthermore, it is unclear where along the auditory pathway summary statistics are represented and how they are reflected in neural activity. The inferior colliculus (IC) is one candidate midlevel structure for representing such summary statistics. As the principal midbrain auditory nucleus, the IC receives highly convergent brainstem inputs with varied sound selectivities. Neurons in the IC are selective over most of the perceptually relevant range of sound modulations and neural activity is strongly driven by multiple high-order sound statistics (4–7, 10). In previous work, we showed the correlation statistics of natural sounds are highly informative about stimulus identity and they appear to be represented in the correlation statistics of auditory midbrain neuron ensembles (4). Correlations between neurons have also been proposed as mechanisms for pitch identification (13) and sound localization (14). This broadly supports the hypotheses that high-order sound statistics are reflected in the response statistics of neural ensembles and that these neural response statistics could potentially subserve basic auditory tasks.Here using natural and synthetic texture sounds, we test the hypothesis that statistical structure in natural texture sounds modulates the response statistics of neural ensembles in the IC of unanesthetized rabbits, and that distinct neural response statistics have the potential to contribute toward sound recognition and discrimination behaviors. By comparing the performance of neural decoders with human texture perception, we find that place rate representation of sounds (neural spectrum) accumulates evidence about the sounds on relatively fast time scales (tens of milliseconds) exhibiting decoding trends that mirror those seen for human texture discrimination. High-order statistical sound cues, by comparison, are reflected in the correlation statistics of neural ensembles, which require substantially longer evidence accumulation times (>500 ms) and follow trends that mirror those measured for human texture recognition. Collectively, the findings suggest that spectrum cues and accompanying place rate representation (neural spectrum) may contribute surprisingly little toward the recognition of auditory textures. Instead, high-order statistical sound structure is reflected in the distributed patterns of correlated activity across IC neural ensembles and such neural response structure has the potential to contribute toward the recognition of natural auditory textures.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

Performance of existing diagnosis/classification criteria for Behcet's disease in Iranian patients: analysis of 5666 patients and 2406 controls

Aim: To analyse the performance of existing diagnosis/classification criteria for Behcet's disease (BD) in Iranian patients. There are 13 sets: Curth (1946), Hewitt (1969), Mason and Barnes (1969), Hewitt revised (1971), Japan (1972), Hubault and Hamza (1974), O'Duffy (1974), Cheng and Zhang (1980), Dilsen (1986), Japan revised (1988), International (1990), Iran (1993), Classification Tree (1993), and Dilsen revised criteria (2000). Methods: All patients from the Behcet's Disease Registry (5666) and control patients (2406) entered the study. Sensitivity, specificity and accuracy were calculated. Results: The most sensitive was Curth criteria with (99.7%), followed by Classification Tree (97.3%), Zhang (93.5%), Iran (91.4%), Japan revised (86.4%), Japan (85.3%), Dilsen (83.7%), Hubault and Hamza (81.6%), Dilsen revised (81.2%), International criteria (79.8%), Hewitt (73.8%), O'Duffy (70.7%), and Masson and Barnes (65.7%). The most specific was Masson and Barnes (99.6%), followed by the International criteria (98.3%), Dilsen revised (98.2%), O'Duffy (97.6%), Japan (97.1%), Japan revised (97%), Classification Tree (96.7%), Hewitt (95.8%), Iran (95.8%), Zhang (92.4%), Dilsen (91.4%), Hubault (90.8%), and Curth (78.6%). The most accurate criteria was Classification Tree (97.1%), followed by Curth (93.4%), Zhang (93.1%), Iran (92.7%), Japan revised (89.6%), Japan (88.8%), Dilsen revised (86.2%), Dilsen (86%), International criteria (85.3%), Hubault (84.3%), Hewitt (80.4%), O'Duffy (78.8%), and Mason and Barnes (75.8%). Discussion: Among the existing criteria, the best to classify Iranian patients is the Classification Tree. The second most accurate is Curth criteria. The difference is statistically significant. Further, Curth criteria is not optimized, having very high sensitivity and low specificity.     

Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD.     

Transgenerational sublethal effects of abamectin and pyridaben on demographic traits of Phytonemus pallidus (Banks) (Acari: Tarsonemidae)

In addition to determining the lethal effects, identifying sublethal effects of a pesticide is crucial to understanding the total impact a pesticide may have on a pest population. We determined the sublethal effects the two pesticides, abamectin and pyridaben, have on the cyclamen mite, Phytonemus pallidus (Banks) (Acari: Tarsonemidae)—a major pest of strawberry. Demographic traits of the P. pallidus progeny (F1 generation) produced by parents (F0 generation) treated with a low lethal concentration (LC₁₅) of abamectin and pyridaben were assessed using the age-stage, two-sex life table theory. The total longevity of the F1 generation (males = 10.78 days; female = 14.35 days) was the shortest in the progeny of the abamectin treated parents, differing significantly from the progeny of mites treated with pyridaben (males = 11.50 days, females = 15.63 days), and the control population (males = 13.50 days, females = 17.81 days). The intrinsic rates of increase (r) and the finite rates of increase (λ) of the progeny of abamectin (r = 0.0854 day⁻¹, λ = 1.0891 day⁻¹) and pyridaben (r = 0.0951 day⁻¹, λ = 1.0997 day⁻¹) treated parents were significantly lower than in the control mites (r = 0.1455 day⁻¹, λ = 1.1567 day⁻¹). The lowest fecundity (5.35 eggs/female), occurred in F1 female offspring of parents treated with LC₁₅ concentrations of abamectin, which was significantly lower than in the pyridaben (6.11 eggs/female) and control treatments (11.45 eggs/female). Transgenerational sublethal effects of abamectin and pyridaben in P. pallidus can be effectively used to for optimizing IPM programs against this pest on strawberries.

     

Quantifying the atomic-level mechanics of single long physisorbed molecular chains

Individual in situ polymerized fluorene chains 10–100 nm long linked by C–C bonds are pulled vertically from an Au(111) substrate by the tip of a low-temperature atomic force microscope. The conformation of the selected chains is imaged before and after manipulation using scanning tunneling microscopy. The measured force gradient shows strong and periodic variations that correspond to the step-by-step detachment of individual fluorene repeat units. These variations persist at constant intensity until the entire polymer is completely removed from the surface. Calculations based on an extended Frenkel–Kontorova model reproduce the periodicity and magnitude of these features and allow us to relate them to the detachment force and desorption energy of the repeat units. The adsorbed part of the polymer slides easily along the surface during the pulling process, leading to only small oscillations as a result of the high stiffness of the fluorenes and of their length mismatch with respect to the substrate surface structure. A significant lateral force also is caused by the sequential detachment of individual units. The gained insight into the molecule–surface interactions during sliding and pulling should aid the design of mechanoresponsive nanosystems and devices.Ever since the invention of the atomic force microscope (AFM) (1) and the first imaging applications, force spectroscopy has been applied to study the mechanical behavior of polymers (2); more complex chain-like biomolecules, e.g., DNA complementary strands (3); and proteins, subject to controlled extension (2) or applied force (4), mostly in solution and at room temperature. Reactive groups are chemically inserted at the ends and/or along each molecule to firmly bind some of them to suitably functionalized tips and sample surfaces. Irreversible jumps in curves of force vs. vertical separation may be associated in this way with the rupture of bonds or the unfolding of coiled subunits. If reproducible, the lowest peak in the histogram of the forces attained just before each jump is attributed to such an event in a single molecular chain or complementary pair. In the case of homogeneous polymers or protein segments, simulations based on two-state rate theory combined with a standard model of polymer nonlinear elasticity can reproduce such events, whereas reversible plateaus or continuous rises in the force may be associated with fast binding–rebinding processes or with large thermal fluctuations (2). Attention thus has focused on conformational changes strongly influenced by pulling speed or imposed force jumps (4) and also by external stimuli, e.g., optical excitation of inserted chromophores (5) or specific reactants or enzymes (6). Furthermore, mechanical forces recently were discovered by chemists as a unique stimulus to induce specific chemical reactions. In this so-called mechanochemistry, sonication typically is applied to polymer systems and is believed to result in a strong force acting on the weakest link in the chain, where the reaction takes place (7, 8). Regardless of the direct or indirect exposure to force, it is clear that the mechanics of polymer chains constrained in their surrounding environment is of utmost importance for a variety of biophysical and chemical processes as well as self-healing materials applications (9, 10).A few pulling studies have been conducted on polyelectrolytes unspecifically adsorbed on self-assembled monolayers via tunable electrostatic interactions (11), including DNA (12). They merely revealed noisy force plateaus, interpreted as continuous partial desorption of single chains, terminated by a drop to zero upon complete detachment from the surface. Despite the undisputed merit of these studies, little is known about the mechanical behavior of single molecular chains pulled off a surface, both defined and characterized on the atomic scale, in the absence of significant thermal fluctuations and drifts. Measurements at low temperature reduce the diffusion of adsorbates and provide an opportunity to determine the energetic landscape of specific molecules interacting with a surface under controlled conditions. As demonstrated here, the sliding and detachment mechanisms of individual polymer repeat units can then be inferred from the analysis of pulling experiments. A detailed interpretation of our results, based on a modified Frenkel–Kontorova (FK) model (13), also is presented.