The flow characteristics were studied by aligning the bars with t

The flow characteristics were studied by aligning the bars with the approach flow and conducting measurements at three different approach freestream velocities. Subsequently, the freestream velocity MLN4924 Ubiquitin inhibitor was kept constant and detailed measurements were conducted for four different bar inclinations relative to the approach flow. For each test condition, a high-resolution particle image velocimetry (PIV) technique was used to conduct detailed velocity measurements in streamwise-spanwise planes at middepth of flow. From these measurements, isocontours and profiles of the mean velocities, turbulence intensities, Reynolds shear stress, and production term in the transport equation for the turbulent kinetic energy were

obtained to study the flow characteristics around and downstream of the aligned and inclined bars. Flow characteristics near hydroelectric station trashracks are important for efficient turbine operation and reduction of fish entrainment.”
“Introduction The impressive results seen when giant and compressing lung bullae are

resected has inspired pneumonologists and thoracic surgeons to consider the possibility of applying a similar approach to the treatment of respiratory failure due to chronic obstructive pulmonary disease (COPD).\n\nState of the art The major problem with this surgical indication lies in our ability to understand fully the pathophysiology of lesions and thus identify which emphysematous patients will have a response most similar to that achieved in purely bullous disease.\n\nPerspectives At the present time

consideration should be given as to whether surgery is Buparlisib manufacturer the only means of reducing pulmonary distension. Indeed, as endoscopic alternatives develop could they reproduce its beneficial effects and what would be their place compared to the surgery?\n\nConclusions While waiting the development of these innovations, if the selection of the candidates is correct, the surgical treatment of lung hyperinflation can temporarily improve the quality of life of these patients by decreasing their dyspnea and increasing their exercise tolerance.”
“The use of vitamins including vitamin B-1, B-2 Bucladesine concentration and K-3 for the induction of systemic acquired resistance (SAR) to protect crops against plant pathogens has been evaluated previously. The use of vitamins is beneficial because it is cost effective and safe for the environment. The use of folate precursors, including ortho-aminobenzoic acid, to induce SAR against a soft-rot pathogen in tobacco has been reported previously.\n\nIn the present study, para-aminobenzoic acid (PABA, also referred to as vitamin B-x) was selected owing to its effect on the induction of SAR against Xanthomonas axonopodis pv. vesicatoria in pepper plants through greenhouse screening.\n\nDipping of pepper seedlings in a 1 mm PABA solution in field trials induced SAR against artificially infiltrated X. axonopodis pv.

In isolated rat pancreatic islets, similar to 80% of cells expres

In isolated rat pancreatic islets, similar to 80% of cells expressed both HAP1 and insulin. Expression of HAP1 in the INS-1 rat insulinoma cell line was also demonstrated by immunofluorescent staining. Western blotting further revealed that HAP1 in both the isolated rat pancreatic islets and the INS-1 cells also has

two isoforms, HAP1A and HAP1B, which are the same as those in the hypothalamus. These results demonstrated that HAP1 is selectively expressed in beta-cells of rat pancreatic islets, suggesting the involvement of HAP1 in the regulation of cellular trafficking ACY-738 inhibitor and secretion of insulin. (J Histochem Cytochem 58:255-263, 2010)”
“Prostate cancer (PCa) is the most commonly diagnosed type of cancer in men in western industrialized countries. As

a public health burden, the need for the invention of new cost-saving PCa immunotherapies is apparent. In this study, we present a DNA vaccine encoding for the prostate-specific antigen prostatic acid phosphatase (PAP) linked to the J-domain and the SV40 enhancer sequence. The PAP DNA vaccine induced a strong PAP-specific cellular immune response after electroporation MCC950 (EP)-based delivery in C57BL/6 mice. Splenocytes from mice immunized with PAP recognized the naturally processed PAP epitopes, indicating that vaccination with the PAP-J gene broke its self-tolerance against PAP. Remarkably, DNA vaccination with PAP-J inhibited tumor growth in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model that closely resembled human PCa. Therefore, this study highlights a novel cancer immunotherapy approach with the potential to control PCa in clinical settings. Received 30 September 2010; accepted 10 October 2011; published online 15 November 2011. doi:10.1038/mt.2011.241″
“(R)-[C-11]PK11195 is a tracer GSK923295 for activated microglia. The purpose of this study was to assess the validity of the simplified reference tissue model for analyzing (R)-[C-11]PK11195 studies in traumatic brain injury (TBI), where blood-brain barrier disruptions

are likely. Methods: Dynamic (R)-[C-11]PK11195 scans were acquired at 3 time points after TBI. Plasma input-derived binding potential (BPNDPI), volume of distribution (V-T) and K-1/k(2), and simplified reference tissue model-derived binding potential (BPNDSRTM) were obtained. Simulations were performed to assess the effect of varying K-1/k(2). Results: Early after TBI, an increase in V-T, but not in BPNDPI, was found. Early K-1/k(2) correlated with V-T and BPNDSRTM but not with BPNDPI. One and 6 mo after TBI, BPNDSRTM correlated with BPNDPI. Conclusion: Early after TBI, (R)-[C-11]PK11195 studies should be analyzed using plasma input models.”
“Flat epithelial atypia (FEA) of the breast have a tendency to calcify and, as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB).


“Background and ObjectivesAlloantibody formation again


“Background and Objectives\n\nAlloantibody formation against red blood cell (RBC) antigens is a common complication see more of transfusion therapy. However, the prevalence of RBC alloimmunization is hardly known in Black Africans. In Uganda, the practice is to transfuse ABO/D

compatible blood without screening for immune antibodies. The aim of this study was to determine the prevalence and specificities of RBC alloantibodies in transfused Ugandans.\n\nMaterials and Methods\n\nUsing a cross-sectional design, transfused patients at Mulago Hospital in Kampala, Uganda were investigated. Demographic characteristics and transfusion histories were recorded. EDTA blood samples were obtained from consenting patients and RBC alloimmunization was demonstrated using immunohaematological tests.\n\nResults\n\nA total of 214 transfused patients (mean age, 30 center dot 3 years; F/M ratio, 1 center dot 0) were investigated. Thirteen patients (6 center dot 1%) possessed RBC alloantibodies whose ALK signaling pathway specificities were six anti-E; three anti-S; one each of anti-D, -K and -Lea; and two samples were pan-reactive. Eleven (84 center dot 6%) of the alloimmunized patients had experienced up to 10 transfusion episodes. The number

of units of blood transfused and the transfusion episodes were significantly associated with the RBC alloimmunization rate (P = 0 center dot 01).\n\nConclusions\n\nThe prevalence of RBC alloimmunization in transfused Ugandans was 6 center dot 1% and was associated with the number of donor exposures. This immunization rate is similar to that observed in transfused Caucasians despite differences in RBC antigen distributions. Patients with malaria were less likely to develop RBC alloantibodies. Alloantibodies were mainly Pfizer Licensed Compound Library research buy against E and S antigens. We recommend the introduction of pretransfusion antibody tests in Uganda depending

on the recipient’s diagnosis.”
“The authors describe the factors that led Weill Cornell Medical College in Qatar (WCMC-Q) to establish the Center for Cultural Competence in Health Care from the ground up, and they explore challenges and successes in implementing cultural competence training. Qatar’s capital, Doha, is an extremely high-density multicultural setting. When WCMC-Q’s first class of medical students began their clinical clerkships at the affiliated teaching hospital Hamad Medical Corporation in 2006, the complicated nature of training in a multicultural and multilingual setting became apparent immediately. In response, initiatives to improve students’ cultural competence were undertaken.

We compare the clinical phenotypes of these patients with those o

We compare the clinical phenotypes of these patients with those of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43 years. ECD followed (n=12) or was diagnosed simultaneously selleck chemicals llc with (n=11) but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon alpha-2a treatment in only 50% of patients (8 of 16). We found the BRAF(V600E)

mutation in 11 (69%) of 16 LCH lesions and in 9 (82%) of 11 ECD lesions. Eight patients had mutations in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAF(V600E) mutation.”
“The purpose is to develop a new image toggle tool with automatic density normalization (ADN) and automatic alignment (AA) for comparing serial digital mammograms (DMGs). We developed an ADN and AA process to compare the images of serial DMGs. In image density normalization, a linear interpolation was applied by taking two points of high- and low-brightness areas. The alignment was calculated by determining

the point of the greatest correlation while shifting the alignment between the current and prior images. These processes were performed on a PC with a 3.20-GHz 5-Fluoracil Xeon processor and 8 GB of main memory. We selected 12 suspected breast cancer patients who had undergone screening DMGs in the past. Automatic processing was retrospectively performed on these images. Two radiologists subjectively Selleckchem AZD9291 evaluated them. The process of the developed algorithm took approximately 1 s per image. In our preliminary experience, two images could not be aligned approximately. When they were aligned, image toggling allowed detection of differences between examinations easily. We developed a new tool to facilitate comparative reading of DMGs on a mammography viewing

system. Using this tool for toggling comparisons might improve the interpretation efficiency of serial DMGs.”
“The aim of this study was to develop new hydrophilic polyesters for tissue engineering applications. In our approach, poly(benzyloxymethyl glycolide-co-epsilon-caprolactone)s (pBHMG-CLs) were synthesized through melt copolymerization of E-caprolactone (CL) and benzyl-protected hydroxymethyl glycolide (BHMG). Deprotection of the polymers yielded copolymers with pendant hydroxyl groups, poly(hydroxymethylglycolide-co-epsilon-caprolactone) (pHMG-CL). The synthesized polymers were characterized by GPC, NMR, and DSC techniques. The resulting copolymers consisting of up to 10% of HMG monomer were semicrystalline with a melting temperature above body temperature.

The first patient with a previously unknown pituitary adenoma had

The first patient with a previously unknown pituitary adenoma had a leuprolide injection for prostate gland downsizing prior to brachytherapy. The second patient with a known pituitary microadenoma had a biochemical recurrence

and was treated with leuprolide and radiation therapy. The first patient developed symptoms of apoplexy click here a few hours after the leuprolide injection. He underwent a transsphenoidal resection of the sellar mass with complete neurologic recovery. The second patient did not have any adverse events after leuprolide with follow-up MRI scans showing no growth of the microadenomas. The presence of a pituitary tumor is not a contraindication for leuprolide therapy. While patients with a macroadenoma should have surgery first, those with a microadenoma may be considered for leuprolide therapy after careful evaluation by a multidisciplinary team.”
“We report an autopsy case of a coronary aneurysm with massive adventitial inflammation post-percutaneous coronary intervention with sirolimus-eluting stent (SES) insertion in

the left circumflex (LCX) coronary artery for ischemic heart disease 3 years prior to death. The internal elastic membrane Kinase Inhibitor Library high throughput was disrupted opposite the site of the eccentric LCX plaque due to injury during stenting, and the adventitia showed massive inflammatory cell infiltration, mainly consisting of eosinophils. The LCX showed aneurysmal dilatation with inflammatory cell infiltration. Inappropriate SES implantation attracted chronic inflammation. Chronic inflammation can lead to the development

of coronary artery aneurysms.”
“Objectives: Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on caries risk and experimental dental caries. Methods: Experimental dental caries was induced in rat maxillary molars which were inoculated orally with Streptococcus mutans MT8148 and maintained on a cariogenic Tipifarnib mw diet (diet 2000) and high sucrose water during the experimental period. CS-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (day 0) and for 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. Maxillary molars were harvested on day 31. Results: The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rate, concentration of S. mutans in the stimulated saliva and caries activity score did not significantly differ between 0 and 30 days after the start of CS exposure. Histological examination of the caries-affected area on maxillary molars 30 days after CS exposure showed expansion compared to control rats.

Secreted from a source, they spread through the tissue to form gr

Secreted from a source, they spread through the tissue to form gradients by which they ERK inhibitors high throughput screening affect the differentiation of precursor cells in a concentration-dependent manner. In this context, the antagonistic roles of the morphogens of the Wnt family and Sonic hedgehog (Shh) in the specification of cell types along the dorso-ventral axis of the neural tube have been studied in detail. However, more recently, morphogens have been demonstrated to act well beyond the early stages of nervous system development, as additional roles of morphogen gradients in vertebrate

neural circuit formation have been identified. Both Wnt and Shh affect neural circuit formation at several stages by their influence on neurite extension, axon pathfinding and synapse formation. In this review, we will summarize the mechanisms of morphogen function during PI3K inhibitor axon guidance in the vertebrate nervous system.”
“To investigate the consequences of differences in drill-guide angle and tibial tunnel diameter on the amount

of tibial anatomical anterior cruciate ligament (ACL) footprint coverage and the risk of overhang of the tibial tunnel aperture over the edges of the native tibial ACL footprint.\n\nTwenty fresh-frozen adult human knee specimens with a median age of 46 years were used for this study. Digital templates mimicking the ellipsoid aperture of tibial tunnels with a different drill-guide angle and a different diameter were designed. The centres of these templates selleck chemicals were positioned over the geometric centre of the tibial ACL footprint. The amount of tibial ACL footprint coverage and overhang was calculated. Risk factors for overhang were

determined. Footprint coverage and the risk of overhang were also compared between a lateral tibial tunnel and a classic antero-medial tibial tunnel.\n\nA larger tibial tunnel diameter and a smaller drill-guide angle both will create significant more footprint coverage and overhang. In 45 % of the knees, an overhang was created with a 10-mm diameter tibial tunnel with drill-guide angle 45A degrees. Furthermore, a lateral tibial tunnel was found not to be at increased risk of overhang.\n\nA larger tibial tunnel diameter and a smaller drill-guide angle both will increase the amount of footprint coverage. Inversely, larger tibial tunnel diameters and smaller drill-guide angles will increase the risk of overhang of the tibial tunnel aperture over the edges of the native tibial ACL footprint. A lateral tibial tunnel does not increase the risk of overhang.”
“Objective In one district of Orissa state, we used the World Health Organization’s Workforce Indicators of Staffing Need (WISN) method to calculate the number of health workers required to achieve the maternal and child health ‘service guarantees’ of India’s National Rural Health Mission (NRHM). We measured the difference between this ideal number and current staffing levels.

The degree of Co/Fe interdiffusion is primarily chemically driven

The degree of Co/Fe interdiffusion is primarily chemically driven, and the approximate 20% Fe substitution for Co is thermodynamically stable. (C) 2011 American Institute of Physics. [doi:10.1063/1.3634063]“
“The electromagnetic exposure of cell phone users depends on several parameters. One of the most dominant of these is the distance between the cell phone and the head DMH1 concentration tissue. The pinna can be regarded as a spacer between the top of the phone

and the head tissue. The size of this spacer has not yet been systematically studied. The objective of this article is to investigate the variations of distance as a function of age of the exposed person, and the mechanical force on the pinna and how it affects the peak spatial specific absorption rate (psSAR). The distances were measured for adults and children (6-8 years of age) while applying a well-defined force on the pinna using a custom-developed measurement device. The average distances of the pinnae to the heads and their standard deviations showed no major differences between the

two age groups: 10.5 +/- 2.0 mm for children (6-8 years) and 9.5 +/- 2.0 mm for adults. The pinnae of our anatomical high-resolution head models of one adult and two children were transformed according to the measurement results. The numerical exposure analysis showed that the reduced distance due to the pinna compression can increase the maximum 10 g psSAR by approximately 2 dB for adults and children, if the exposure HSP990 in vitro maximum is associated with the upper part of the phone. Bioelectromagnetics 31:406-412, 2010. (C) 2010 Wiley-Liss, Inc.”
“Purpose: Relative costs and utilization-related outcomes of a fluticasone propionate 250 mu g + salmeterol 50 mu g combination (FSC), tiotropium bromide, and ipratropium as initial maintenance therapy in COPD have not been compared in a commercially-insured population.\n\nMethods: This retrospective, observational cohort study used health care claims data from January 2004 to June 2009 from a large administrative database for patients aged >= 40 years with COPD. Time-to-first COPD-related health care event beginning 30 days following therapy initiation

with FSC (n = 16,684), ipratropium alone or in fixed dose combination with albuterol (n = 14,449), or tiotropium (n = 12,659) was estimated using Cox AZD4547 in vivo proportional hazard models that controlled for differences in patient demographic characteristics, health care utilization, and comorbidities at baseline. Mean adjusted costs and numbers of COPD-related health care encounters and prescription medication fills were compared among patients with 12 months of follow-up (FSC, n = 12,595; ipratropium, n = 10,617; tiotropium, n = 9126).\n\nResults: With FSC as the reference, risk for a COPD-related hospitalization and/or emergency department visit was significantly higher for ipratropium (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.50-1.

Methods: Parents of children with ADHD beginning treatment wi

\n\nMethods: Parents of children with ADHD beginning treatment with LDX voluntarily completed surveys through an automated telephone system or the Internet before and 6 weeks after LDX treatment

initiation. Prescribing physicians received individual reports of the responses for each survey completed by their patients’ parents. All patients whose parents completed both baseline and 6 week surveys were included in the analyses. Subgroup analyses were conducted for those previously treated with medications to treat ADHD, including mixed amphetamine salts-extended drug discovery release.\n\nResults: LDX treatment was associated with a significant decrease in ADHD symptom interference with school activities, family interactions, homework, and social interactions (P<.01; N=11,576). Parents rated satisfaction with LDX as significantly higher than with their child’s previous treatment (P<.01). On average, global improvement, tolerability, convenience, and satisfaction with LDX were all highly rated.\n\nConclusion:

CYT387 in vivo Patients treated with LDX showed significant symptom improvement and parents reported significantly greater satisfaction than with prior treatment. CNS Spectr. 2010;15(4):248-256.”
“Dietary guidelines based on 5 food groups was used as a main nutrition education tool until 1996 when food based dietary guidelines (FBDGs) were promoted after 2 years of formulation and development. These

FBDGs for the general population were designed to promote desirable and culturally acceptable eating behavior. The nine qualitative guidelines of Thai FBDGs include: 1. eat a variety of foods from each of the five food groups and maintain proper weight, 2. eat adequate rice, or alternate carbohydrate, 3. eat plenty of vegetables and fruits regularly, 4. eat fish, lean meats, eggs, legumes and pulses regularly, SNX-5422 5. drink sufficient amount of milk every day, 6. take moderate amounts of fat, 7. avoid excessive intake of sweet and salty foods, 8. eat clean and uncontaminated foods, and 9. avoid or reduce consumption of alcoholic beverages. In 1998, the quantitative part of Thai FBDGs or food guide model was established as “Nutrition Flag” after rigorous test for understanding and acceptability among consumers. Promotion and dissemination of the Thai FBDGs have been carried out at national and community levels through basic health, agricultural and educational services and training activities, as well as periodic campaigning via multiple communication channels and media. Recently in 2009, the FBDGs for infant and preschool children were introduced to replace the previous infant and young child feeding guidelines. There has been no formal evaluation on the impact of promotion of the Thai FBDGs but some periodic testing of knowledge and practices have shown positive results.

1% in patients with AFL Conclusion AFL was prevalent among pa

1% in patients with AFL.\n\nConclusion AFL was prevalent among patients with CB. Therefore, GPs should test pulmonary function in CB patients to ensure that the appropriate therapy is administered.”
“Viscoelasticity and strain-induced birefringence under oscillatory AL3818 shear flow of cellulose/1-buthyl-3-methyl-imidazolium

chloride (BmimCl) solutions were measured at various temperatures covering a wide frequency zone from the terminal flow to the glassy zone for dilute (2 wt %) and semiconcentrated solution (10 wt %) to clarify the dynamical segment size of the cellulose chain. The estimated dynamical segment size, M-S, obtained from viscoelasticity is much smaller than that from flow birefringence. M-S estimated from dynamic birefringence was 2300

corresponding to 14 repeating glucose residues from 2-10 wt %, showing weak concentration dependence. This value is comparable to the reported value of Kuhn segment size, M-K. This relationship, M-S approximate to M-K, holding even at dilute solution, is in contrast with the large difference (M-S approximate to 5M(K)) for polystyrene in dilute solution, indicating that the chain rigidity affects the relationship between M-S and M-K.”
“Purpose: GW786034 mouse We present a case of a 4-year-old child who was incidentally found to have a suprasellar arachnoid cyst (SAC) after initial CT imaging at 6 weeks of age but who demonstrated no anomalies. This is only the sixth case

of intracranial de novo ACs documented in the English literature and only the second case of SAC to arise de novo. Methods: Case review after an SAC was found on an MRI scan at 4 years of age which had not been present on a previous CT of the head. Results: Apparent de novo SAC formation in a healthy 4-year-old female without a history of intracranial infection, surgery or trauma. Conclusion: The pathophysiology leading to the formation of the cyst might well be congenital, although there is some question as to how early Endocrinology & Hormones inhibitor in development the cysts are formed as our child was a 32-week GA preemie with an initial scan at 38 weeks GA. With the use of fast MRI scans instead of CT scans and the continued neuro-imaging of premature infants, we can take a better look at the anatomy and better determine the timing of development of the SAC. Copyright (C) 2013 S. Karger AG, Basel”
“Dioleoylphosphatidylcholine and other phosphatidylcholines containing different fatty acid moieties were found to increase the ability of nonesterified fatty acids (NEFA) to sustain continuous intraerythrocytic growth of Plasmodium falciparum in the presence of specific proteins. Other phospholipids, including phosphatidylethanolamine, phosphatidylserine, and phosphatidic acid, were beneficial to parasite growth. Different combinations and concentrations of NEFA tested in the presence of phospholipids and bovine albumin had variable effects on parasite growth.

We experimentally and theoretically investigated the piezoelectri

We experimentally and theoretically investigated the piezoelectric potential drop in the ZnO NR-based NG due to the piezoelectric potential screening effect. A simple thermal annealing treatment was applied to the pristine ZnO NRs in air atmosphere to stabilize the output performance

of the NG even in the presence of UV light. The piezoelectric output voltage from the surface-passivated NG was approximately 25 times higher than that from the NG with no passivation under UV light illumination.”
“Kanamycin (KM) and amikacin (AK) are the key aminoglycoside drugs against tuberculosis (TB) and resistance to them severely affects the options for treatment. Many explanations have been proposed for drug resistance to these drugs but still some mechanisms are unknown. Proteins are the functional moiety of the cell and manifest in most of the biological processes; so, these learn more are potential foci for the development of new therapeutics, diagnostics and vaccine. We examined the KM and AK resistant isolates of Mycobacterium tuberculosis using proteomic analysis comprising of two dimensional gel electrophoresis (2DGE), matrix assisted laser desorption ionization time-of-flight/time-of

flight (MALDI-TOF/TOF) and bioinformatic tools like BLASTP, InterProScan, KEGG motif scan and molecular docking. Proteins intensities of twelve spots were found to be consistently increased in KM and AK resistant isolates and these were identified as Rv3867, Rv1932, Rv3418c, Rv1876, Rv2031c, Rv0155, Rv0643c, Staurosporine nmr Rv3224, Rv0952, and Rv0440. Among these, Rv3867 and Rv3224 were identified as proteins with unknown function. All the proteins identified were cellular proteins. Molecular docking shows the proper interaction check details of both drugs with these molecules. Also, Rv1876 and Rv3224 were found to be probably involved in iron regulation/metabolism indicating the role of iron in imparting resistance to second line drugs. Biological significance The study that was carried out shows that two dimensional electrophoresis along with mass spectrometry is still

the best approach for proteomic analysis. To the best of our knowledge it is the first ever report on proteomic analysis of M. tuberculosis isolates resistant to second line drugs (kanamycin and amikacin). The major finding implicates that the genes/proteins involved in iron metabolism and the two hypothetical proteins (Rv3867 and Rv3224) might be playing some crucial role in contributing resistance to second line drugs. Further exploitation in this direction may lead to the development of newer therapeutics against tuberculosis. (C) 2013 Elsevier B.V. All rights reserved.”
“The development of carriers to sustain drugs at stomach surface is an attractive strategy to increase drug bioavailability locally and systematically.