Enumeration 1-Genericity in the Local Enumeration Degrees.

We discuss a notion of forcing that characterizes enumeration 1-genericity, and we investigate the immunity, lowness, and quasiminimality properties of enumeration 1-generic sets and their degrees. We construct an enumeration operator Δ such that, for any A, the set ΔA is enumeration 1-generic and has the same jump complexity as A. We deduce from this and other recent results from the literature that not only does every degree a bound an enumeration 1-generic degree b such that a'=b', but also that, if a is nonzero, then we can find such b satisfying 0e<b<a. We conclude by proving the existence of both a nonzero low and a properly Σ02 nonsplittable enumeration 1-generic degree, hence proving that the class of 1-generic degrees is properly subsumed by the class of enumeration 1-generic degrees

Chitosan-Genipin Microspheres for the Controlled Release of Drugs: Clarithromycin, Tramadol and Heparin

The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1–10 μm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 ºC for 5 h and with 5 mM genipin at 50 ºC for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 ºC, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs

Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

Predictive coding of visual motion in both monocular and binocular human visual processing

Neural processing of sensory input in the brain takes time, and for that reason our awareness of visual events lags behind their actual occurrence. One way the brain might compensate to minimize the impact of the resulting delays is through extrapolation. Extrapolation mechanisms have been argued to underlie perceptual illusions in which moving and static stimuli are mislocalised relative to one another (such as the flash-lag and related effects). However, where in the visual hierarchy such extrapolation processes take place remains unknown. Here, we address this question by identifying monocular and binocular contributions to the flash-grab illusion. In this illusion, a brief target is flashed on a moving background that reverses direction. As a result, the perceived position of the target is shifted in the direction of the reversal. We show that the illusion is attenuated, but not eliminated, when the motion reversal and the target are presented dichoptically to separate eyes. This reveals extrapolation mechanisms at both monocular and binocular processing stages contribute to the illusion. We interpret the results in a hierarchical predictive coding framework, and argue that prediction errors in this framework manifest directly as perceptual illusions

Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins

The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin⋅biotin bond. Implications for the molecular mechanism of unbinding of HA⋅hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA⋅hyaladherin complexes and HA-rich extracellular matrices

High Dengue Case Capture Rate in Four Years of a Cohort Study in Nicaragua Compared to National Surveillance Data

Dengue is a major public health problem in tropical and subtropical regions; however, under-reporting of cases to national surveillance systems hinders accurate knowledge of disease burden and costs. Laboratory-confirmed dengue cases identified through the Nicaraguan Pediatric Dengue Cohort Study (PDCS) were compared to those reported from other health facilities in Managua to the National Epidemiologic Surveillance (NES) program of the Nicaraguan Ministry of Health. Compared to reporting among similar pediatric populations in Managua, the PDCS identified 14 to 28 (average 21.3) times more dengue cases each year per 100,000 persons than were reported to the NES. Applying these annual expansion factors to national-level data, we estimate that the incidence of confirmed pediatric dengue throughout Nicaragua ranged from 300 to 1000 cases per 100,000 persons. We have estimated a much higher incidence of dengue than reported by the Ministry of Health. A country-specific expansion factor for dengue that allows for a more accurate estimate of incidence may aid governments and other institutions calculating disease burden, costs, resource needs for prevention and treatment, and the economic benefits of drug and vaccine development

Barriers to following dietary recommendations in Type 2 diabetes

Aims  To evaluate barriers to following dietary recommendations in patients with Type 2 diabetes. Methods  We conducted focus groups and surveys in urban and suburban VA and academic medical centres. For the written survey, a self-administered questionnaire was mailed to a random sample of 446 patients with diabetes. For the focus groups, six groups of patients with diabetes (three urban, three suburban) were conducted, with 6–12 participants in each group. The focus groups explored barriers across various types of diabetes self-management; we extracted all comments relevant to barriers that limited patients’ ability to follow a recommended diet. Results  The written survey measured the burden of diabetes therapies (on a seven-point rating scale). Moderate diet was seen as a greater burden than oral agents (median 1 vs. 0, P  = 0.001), but less of a burden than insulin (median 1 vs. 4, P  < 0.001). A strict diet aimed at weight loss was rated as being similarly burdensome to insulin (median 4 vs. 4, P  = NS). Despite this, self-reported adherence was much higher for both pills and insulin than it was for a moderate diet. In the focus groups, the most commonly identified barrier was the cost (14/14 reviews), followed by small portion sizes (13/14 reviews), support and family issues (13/14 reviews), and quality of life and lifestyle issues (12/14 reviews). Patients in the urban site, who were predominantly African-American, noted greater difficulties communicating with their provider about diet and social circumstances, and also that the rigid schedule of a diabetes diet was problematic. Conclusions  Barriers to adherence to dietary therapies are numerous, but some, such as cost, and in the urban setting, communication with providers, are potentially remediable. Interventions aimed at improving patients’ ability to modify their diet need to specifically address these areas. Furthermore, treatment guidelines need to consider patients’ preferences and barriers when setting goals for treatment. Diabet. Med. (2004)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73213/1/j.1464-5491.2004.01342.x.pd

Refractory Hypertension and Isosexual Pseudoprecocious Puberty Associated with Renin-Secreting Ovarian Steroid Cell Tumor in a Girl

Steroid cell tumor, not otherwise specified (NOS), are rare ovarian tumor, in addition, it is more rare in children. The majority of these tumors produce several steroid hormones, particularly testosterone. Estrogen also secreted by steroid cell tumor, NOS, but it is uncommon. Furthermore, hypertension is an infrequent sign in steroid cell tumor, NOS. An 8.5-yr-old girl with hypertension and frequent vaginal spotting visited at our clinic. On laboratory evaluation, secondary hypertension due to an elevated plasma renin level and isosexual pseudoprecocious puberty was diagnosed. Right solid ovarian mass was detected in radiologic tests. She underwent a right ooporectomy and it revealed renin and progesterone receptor positive steroid cell tumor, NOS. After operation, her blood pressure returned to normal level and vaginal bleeding disappeared. Even though this case is very rare, when hypertension coincides with virilization or feminization, a renin-secreting ovarian steroid cell tumor, NOS, should be considered