“EEG-fMRI is a non-invasive technique that allows the investigation of epileptogenic networks in patients with epilepsy. Lately, BOLD changes occurring before the spike were found in patients with generalized epilepsy. The study
of metabolic changes preceding spikes might improve our knowledge of spike generation. We tested this hypothesis in patients with idiopathic and symptomatic BKM120 ic50 focal epilepsy.\n\nEleven consecutive patients were recorded at 3 T: five with idiopathic focal and 6 with symptomatic focal epilepsy. Thirteen spike types were analyzed separately. Statistical analysis was performed using the timing of spikes as events, modeled with HRFs peaking between -9 s and +9 s around the spike. HRFs were calculated the most focal BOLD response. Eleven of the thirteen studies showed prespike BOLD responses. Prespike responses were more focal than postspike responses. Three studies Copanlisib showed early positive followed by later negative BOLD responses in the spike field. Three had early positive BOLD responses in the spike field, which
remained visible in the later maps. Three others had positive BOLD responses in the spike field, later propagating to surrounding areas. HRFs peaked between -5 and +6 s around the spike timing. No significant EEG changes could be identified prior to the spike.\n\nBOLD changes prior to the spike frequently occur in focal epilepsies. They are more focal than later BOLD changes and strongly related to the spike field. Early changes may result from increased neuronal activity in the spike field prior to the EEG spike and reflect an event more localized than the spike itself. (C) 2009 Elsevier Inc. All rights reserved.”
“Background An obesity epidemic is spreading worldwide. In addition to comorbidities, social and emotional problems contribute to
reduce the quality of life (QoL) of obese people. Considering the heterogeneity of outcomes from clinical and surgical approaches, it is recommended that severely obese patients participate in their treatment decisions. This study evaluated preferences of severely obese patients for obesity surgical treatment using the willingness selleck chemicals llc to pay (WTP) and to assess the impact of the presence of some clinical disorders, socioeconomic conditions and QoL on their decisions. Methods The selected patients were invited to answer the WTP questionnaire using two formats of contingent valuation questions: dichotomous choice (yes/no) and a bidding game. The answers were correlated with clinical features, QoL assessed by the SF-36 and the Moorehead-Ardelt Quality of Life Questionnaire II, Brazilian socioeconomic classification, and family and personal incomes. Results The group of patients who accepted the first bid was older and had higher frequency of sleep apnoea when compared to those who rejected the offer. A significant correlation between the bidding game value and family income was found (r=0.28; P<0.02).
falciparum and S. cerevisiae.
We found an abundance www.selleckchem.com/screening/apoptosis-library.html of epistatic interactions in the parasite and a much smaller number of such interactions in yeast. The genome of P. falciparum also harboured several epistatic interaction hotspots that putatively play a role in drug resistance mechanisms. The abundance of observed epistatic interactions might suggest a mechanism of compensation for the extremely limited repertoire of transcription factors. Interestingly, epistatic interaction hotspots were associated with elevated levels of linkage disequilibrium, an observation that suggests selection pressure acting on P. falciparum, potentially reflecting host-pathogen interactions or drug-induced selection.”
This paper investigates a general concept of reproducibility with regard to its application on experiments with homeopathic potencies.\n\nMethods: The experimental situation for distinguishing a homeopathic potency and its solvent is described in a formal way. This allows the application of the weak law of large numbers. Experimental arrangements are described in a formal way. This allows conclusions to be drawn about the possible existence SB273005 price of nonlocal influences on an experiment.\n\nConclusions: From a pragmatic as well as from a global point of view, a general concept of reproducibility supports decisions whether or not effects in experiments with homeopathic potencies do exist.”
“Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous disorder. All mendelian patterns of inheritance have been described. We identified a homozygous p.A335V mutation in the MED25 gene in an extended Costa Rican family
with autosomal recessively inherited Charcot-Marie-Tooth neuropathy linked to the CMT2B2 locus in chromosome 19q13.3. MED25, also known as ARC92 and ACID1, is a subunit of the human activator-recruited cofactor (ARC), a family of large transcriptional coactivator complexes related to the yeast Mediator. MED25 was identified by virtue of functional Entinostat does association with the activator domains of multiple cellular and viral transcriptional activators. Its exact physiological function in transcriptional regulation remains obscure. The CMT2B2-associated missense amino acid substitution p.A335V is located in a proline-rich region with high affinity for SH3 domains of the Abelson type. The mutation causes a decrease in binding specificity leading to the recognition of a broader range of SH3 domain proteins. Furthermore, Med25 is coordinately expressed with Pmp22 gene dosage and expression in transgenic mice and rats. These results suggest a potential role of this protein in the molecular etiology of CMT2B2 and suggest a potential, more general role of MED25 in gene dosage sensitive peripheral neuropathy pathogenesis.
Theoretical and policy issues are discussed, along with proposals for future research in terms of industry structure, private governance, and sustainable value chains.”
“Background: Enzymes belonging to the same super family of proteins in general operate on variety of substrates and are inhibited by wide selection of inhibitors.
In this work our main objective was Quisinostat to expand the scope of studies that consider only the catalytic and binding pocket amino acids while analyzing enzyme specificity and instead, include a wider category which we have named the Interface Forming Residues (IFR). We were motivated to identify those amino acids with decreased accessibility to solvent after docking of different types of inhibitors to sub classes of serine proteases and then create a table (matrix) of all amino acid positions at the interface JQEZ5 as well as their respective occupancies. Our goal is to establish a platform for analysis of the relationship between IFR characteristics and binding properties/specificity for bi-molecular complexes.\n\nResults: We propose a novel method for describing binding properties and delineating serine proteases specificity by compiling an exhaustive table of interface forming residues (IFR) for serine proteases and their inhibitors. Currently,
the Protein Data Bank (PDB) does not contain all the data that our analysis would require. Therefore, an in silico approach was designed for building corresponding selleck compound complexes The IFRs are obtained by “rigid body docking” among 70 structurally aligned, sequence wise non-redundant, serine protease structures with 3
inhibitors: bovine pancreatic trypsin inhibitor (BPTI), ecotine and ovomucoid third domain inhibitor. The table (matrix) of all amino acid positions at the interface and their respective occupancy is created. We also developed a new computational protocol for predicting IFRs for those complexes which were not deciphered experimentally so far, achieving accuracy of at least 0.97.\n\nConclusions: The serine proteases interfaces prefer polar (including glycine) residues (with some exceptions). Charged residues were found to be uniquely prevalent at the interfaces between the “miscellaneous-virus” subfamily and the three inhibitors. This prompts speculation about how important this difference in IFR characteristics is for maintaining virulence of those organisms. Our work here provides a unique tool for both structure/function relationship analysis as well as a compilation of indicators detailing how the specificity of various serine proteases may have been achieved and/or could be altered. It also indicates that the interface forming residues which also determine specificity of serine protease subfamily can not be presented in a canonical way but rather as a matrix of alternative populations of amino acids occupying variety of IFR positions.
7 +/- 28.1) regions; additionally, the score of the Midwest was lower (p < 0.05) than the South region. In STEMI, the use of recanalization therapies was highest in the Southeast (75.4%, p = 0.001 compared to the
rest of the country), and lowest in the North-Northeast (52.5%, p < 0.001 compared to the rest of the country).\n\nConclusion: The use of demonstrably effective therapies in the treatment of acute coronary disease is much to be desired in the country, with important regional differences.”
“Polycrystalline silicon thin-film solar cells produced by continuous-wave diode-laser crystallization at the University of New South Wales were recently reported to have reached a conversion efficiency above 10%. One drawback A-769662 supplier of these cells, however, was that they exhibited efficiency degradation within several hours after the cell fabrication was completed. In this work we show that by applying laser firing to the rear point contacts of the solar cells, it is possible to stabilize and even to enhance the performance of these devices. Our investigation indicates that it is the poor quality of the Casein Kinase inhibitor contact between the aluminum and the silicon absorber that causes the cell degradation and offers an
elegant and industrial-compatible process to improve the cell performance. This is the first time that the laser firing process, initially developed for alloying an aluminum layer through a dielectric layer on crystalline silicon wafer solar cells, is being applied to polycrystalline silicon thin-film
solar cells. (C) 2013 Elsevier B.V. All rights reserved.”
“AIM The aim of this study was to compare executive function in children with left- and right-sided unilateral cerebral palsy (CP) and typically developing children.\n\nMETHOD There was a cross-sectional cohort of 46 children with unilateral CP (24 right-side, 22 left-side; 25 males, 21 females; mean age 11y 1mo, SD 2y 5mo) and 20 typically developing children (nine males, 11 females; mean age 10y 10mo, SD 2y 4mo). Four cognitive domains of executive function were assessed: attentional control, cognitive flexibility, goal setting, and information processing. check details Subtests from the Delis-Kaplan Executive Function System, the Test of Everyday Attention for Children, the Rey-Osterrieth Complex figure, and the Wechsler Intelligence Scale for Children – Fourth Edition were utilized. Between-group differences (right unilateral CP, left unilateral CP, and typically developing children) were examined using analyses of covariance.\n\nRESULTS Children with CP performed significantly more poorly than typically developing children on all executive function measures (aggregate executive function: F(1,63)=31.16; p<0.001; eta(2)=0.33). There were no significant differences between children with left and right unilateral CP, except in the case of inhibition/switching total errors, with children with left unilateral CP making fewer errors than children with right unilateral CP(F(1,39)=4.14; p=0.049; eta(2)=0.
This case is very rare, because most cases of pancreatic metastasis from lung cancer
have already widespread disease at the time of diagnosis. This case illustrates that pancreatic metastasis from U0126 datasheet pulmonary adenocarcinoma should be borne in mind, even if the pancreatic tumor is a solitary lesion without additional organ metastasis.”
“Objective: This study was conducted to explore the association between sexual orientations and poly-cystic ovary syndrome (PCOS)-related parameters. Materials and methods: A cross-sectional study with participants recruited from the regular outpatient clinic at the Department of Obstetrics and Gynecology at Taipei Medical University Hospital, Taipei, Taiwan between July 2012 and December 2013 was carried GSK3326595 out. A total of 97 women met the criterion of having been diagnosed with PCOS. Among these 97 women, 89 were heterosexuals and eight were self-identified as lesbians. At the same time, 78 women without PCOS were enrolled to serve as the control group. Participants were given a standard questionnaire and had blood withdrawn for biochemical analysis of androgen parameters-including total testosterone, androstenedione, sex hormone binding globulin, free androgen
index, 17 beta-estradiol (E2), luteinizing hormone, and follicular-stimulating hormone. The biochemical data were measured to compare the PCOS clinical parameters PXD101 present in people of different sexual orientations (lesbians and heterosexuals). Results: The women with PCOS, regardless of sexual orientation, had higher percentages and serum levels of hyperandrogenism-related clinical parameters than the women without PCOS [acne (87.5% and 60.7% vs. 23.1%), p smaller than 0.001]; hirsutism (62.5% and 57.3% vs. 15.4%, p smaller than = 0.001)]; and biochemical parameters (total
T. p smaller than 0.05 or p smaller than 0.001, and luteinizing hormone/follicular-stimulating hormone ratio, p smaller than = 0.001). The sexual orientation of women with PCOS affected their body mass index (BMI), because lesbians with PCOS possessed higher BMI than heterosexual women with PCOS (26.5 +/- 1.9 vs. 22.5 +/- 0.55; p smaller than 0.05). However, hyperandrogenism-related clinical and biochemical parameters were not significantly different statistically between women with PCOS but of different sexual orientations. Conclusion: Our preliminary data showed that sexual orientation influenced the BMI of women with PCOS, but did not affect hyperandrogenism-related clinical or biochemical characteristics. This observation requires further confirmation. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.”
“Rationale: The nonspecific clinical presentation of pulmonary embolism (PE) frequently leads to delay in its diagnosis.
9, P = 0.001) and HS-RDEB (r = 0.73, P = 0.001) and decreased for DM-EBS (r = -0.62, P = 0.01), with positive but nonsignificant correlations for the other types.\n\nThe BEBS score
appears valid and reproducible, gives appropriate scores for different subtypes, and reflects changes with age.”
“The interaction of the periodontal pathogen. Porphyromonas gingivalis, with oral streptococci such as Streptococcus gordonii precedes colonization of the subgingival pocket and represents a target for limiting P. gingivalis colonization of the oral cavity. Previous selleck screening library studies showed that a synthetic peptide (designated BAR) derived from the antigen I/II protein of S. gordonii was a potent competitive inhibitor of P. gingivalis adherence to S. gordonii and subsequent biofilm formation. Here we show that despite its inhibitory activity, BAR is rapidly degraded by intact P. gingivalis cells in vitro. However, in the presence of soluble Mfa protein, the P. gingivalis receptor for Metabolism inhibitor BAR, the peptide is protected from proteolytic degradation suggesting that the affinity of BAR for Mfa is higher than for P. gingivalis proteases.
The rate of BAR degradation was reduced when the P. gingivalis lysine-specific gingipain was inhibited using the specific protease inhibitor, z-FKcK, or when the gene encoding the Lys-gingipain was inactivated. In addition. substituting D-Lys for L-Lys residues in BAR prevented degradation of the peptide when www.selleckchem.com/products/oicr-9429.html incubated with the Lys-gingipain and increased its specific adherence inhibitory activity in a S. gordonii-P. gingivalis dual species biofilm model. These results suggest that Lys-gingipain accounts in large part for P. gingivalis-mediated degradation of BAR and that more effective peptide inhibitors of P. gingivalis adherence to streptococci can be produced by introducing modifications that limit the susceptibility of BAR to the Lys-gingipain and other P. gingivalis associated proteases.
(C) 2010 Elsevier Inc. All rights reserved.”
“The present study was designed to examine whether endogenous neurogenesis and neovascularization occur in the neocortex of the ischemic rat brain after unilateral middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were divided into six groups (n = 29): one control group (n = 4) and five groups composed of animals sacrificed at increasing times post-MCAO (2 days and 1, 2, 4, and 8 weeks; n = 5 per group). To determine the presence of neurogenesis and neovascularization in the ischemic brain, nestin, Tuj1, NeuN, GFAP, Tie2, RECA, and 5-bromo-2′-deoxyuridine (BrdU) were analyzed immunohistochemically. In addition, nestin, GFAP, and Tie2 expression was determined by Western blotting. Triple-labeling of nestin, BrdU, and laminin was performed to visualize the interaction between endogenous neurogenesis and neovascularization.
On the other hand, immunohistochemistry, Masson’s trichrome staining and silver impregnation demonstrated APP and DKK-3 proteins in fifth GW fetal liver in which intralobular bile ducts and hepatic plates had not completely developed. DKK-3 and AFP mRNAs were upregulated on the seventh day (7D) after 80% hepatectomy. In the liver tissue, DKK-3 and AFP proteins were detected in mesenchymal cells in the periportal area and parenchyma, respectively. These data for DKK-3 expression in adult livers
suggest the possible presence of adult HSLCs in the periportal area. The pattern of histological staining suggested that 7D liver was in the process of regeneration, showing a character similar to the fifth AZD7762 research buy GW fetal liver. It is speculated that DKK-3 is upregulated in immature and developing livers, and has possible involvement in hepatic differentiation and liver regeneration.”
“A group of 72 patients with 111 asymptomatic carotid stenoses (ACS), mean age 65.42 +/- 9.21, and a group Vactosertib order of 36 patients with 58 symptomatic carotid stenoses (SCS), mean
age 67.63 +/- 8.79, were analyzed prospectively during a 3-year follow-up period. All patients underwent color duplex scan sonography (CDS), carotid arteriography, computed tomography (CT) scan, and neurological examination. The aim of the study was to analyze the correlation between echo plaque morphology (degree and plaque quality), local hemodynamic plaque characteristics, ischemic CT findings, and onset of new neurological events and deaths. The results analysis showed significantly more ACS in the group of 30-49% stenosis (p < 0.001), but significantly more SCS in the group of 70-89% (p < 0.0001) and >= 90% stenosis (p < 0.05). Fibrous plaque was more frequent in the ACS group (p < 0.001), while ulcerated and mixed plaques were more frequent in the SCS group (both p < 0.0001). In the SCS group, a significantly higher frequency of increased peak systolic and end diastolic velocities was noted at the beginning and end of the study (both p < 0.01),
as well as for contralateral common (CCA) or internal carotid artery (ICA) occlusion ( p < 0.05 QNZ cell line and p < 0.01, respectively), but reduced carotid blood flow volume (p < 0.05) only at the end of the study. In the ACS group, the best correlation with new neurological events and deaths was shown with positive CT findings, peak systolic flow velocity over 210 cm/sec, end diastolic flow velocity over 110 cm/sec, plaque stenosis >= 70%, plaque ulceration, mixed plaque (all p < 0.0001); stenosis >= 50% (p < 0.001); and reduced carotid blood flow volume (p < 0.05).”
“The aim of this study was to compare insulin responsevness to acute glucose infusion in cows of Holstein Friesian (HF) and Busa breeds during the peripartal period. Eight cows per each group (HF and Busa), were chosen.
The recombination activities of the BPDs and partials were enhanced with the existence of Fe impurity. The SFs near the surface region showed obvious dark contrast in EBIC, which was different from that observed in the clean samples. The X partial kept moving with sustained electron-beam irradiation whereas this partial in selleck chemicals llc the clean samples stopped motion when it was connected
to the sample surface. The dark contrast of the SFs and the peculiar motion behavior of the X partial are discussed with the CL results. (C) 2014 The Japan Society of Applied Physics”
“Introduction The efficacy and safety of contraceptives have been questioned for decades; however, whether a relationship exists between hormonal contraceptives and gestational diabetes (GDM) is undetermined The aim of this study was to investigate whether maternal risk for GDM was influenced by type of contraceptive method DZNeP cost used before pregnancy. Methods Data collected in 2007 and 2008 by the Missouri Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed to determine if type of contraception before pregnancy influenced maternal risk for GDM. We used a logistic regression model
to determine the adjusted odds for GDM given exposure to hormonal forms of contraception. Results Of the 2,741 women who completed the 2007-2008 PRAMS survey, 8.3% were diagnosed with gestational diabetes, and 17.9% of the respondents had used hormonal contraceptive methods. Women who used hormonal methods of birth control had higher odds for gestational diabetes (adjusted odds ratio [AOR] = 1.43; 95% confidence click here interval [CI], 1.32-1.55) than did women who used no contraception. A protective
effect was also observed for women who had used barrier methods of contraception (AOR = 0.79; 95% CI, 0.72-0.86). Conclusion Findings suggest there may be a relationship between type of contraceptive method and GDM. More research is needed to verify contraception as a potential risk factor for GDM.”
“Spasmodic dysphonia (SD) remains one of the most difficult of laryngeal pathologies to treat. With limited role for speech therapy, various surgical modalities have been tried with various success rates. The objective of the study is to report the results of vocal outcome after thyroarytenoid myoneurectomy in patients of adductor spasmodic dysphonia (ASD). 15 patients of ASD were selected. GRBAS, and voice handicap index (VHI) were used for perceptual evaluation of voice. Thyroarytenoid myoneurectomy was performed by vaporizing the muscular layer of the vocal fold with CO2 laser, at an intensity of 6 W with 1.2 mm diameter in scanner mode. Voice analysis was repeated at 12, 24 and 48 months follow-up. Preoperative GRBAS scores and VHI score of all the patients were poor. At 12 months 12/15 (80 %) patients having strain score of 0. There was marked improvement in VHI scores at 6 months. 10/15 (67 %) patients have been followed up for 24 months. 5/10 (50 %) patients have strain (S) value of 0.
conclude that the radiolucent feature of the PEEK cage, which produces the image finding PEEK double lucency, aids in the Napabucasin determination of fusion. (DOI: 10.3171/2011.11.SPINE1141)”
“This study documented diversity and dynamics of foliage macro-invertebrates sampled from edges and centers of wheat-weeds agro-ecosystem of district Faisalabad (30 degrees 31.5 N and 73 degrees 74 E; 184.41 m l). A total of 4,228 foliage of macro-invertebrates belonging to phylum Arthropoda (92.41%) and Mollusca (7.59%) were recorded. Diptera (27.65%), Hemiptera (27.58%), Coleoptera (18.21%) and Hymenoptera (7.36%) were dominant while Orthoptera, Neuroptera, Lepidoptera and Araneae collectively formed (11.62%) arthropods. Mollusca constituted only of pulmonate gastropods (7.59%). The overall diversity was (H’ = 3.36), that varied seasonally at statistically significantly level. Maximum
diversity was recorded in autumn (H’ = 3.57), that was followed by spring (H’ = 3.23) and winter (H’ = 3.09). In contrary TPX-0005 price to the general findings, Diversity of macro-invertebrate populations in the center (H’= 3.363) was significantly higher than the edges (H’= 3.299) of the fields (p = smaller than 0.001). Moreover the richness (S= 58), diversity (H’= 3.23) and evenness (E= 0.79) was recorded higher on wheatcompared to the richness (S= 61), diversity (H’= 3.16) and evenness (E = 0.77) on weeds in wheat-weeds agro-ecosystem.”
“We describe a new mechanism by which CTG tract expansion affects myotonic dystrophy (DM1). Changes to the levels of a panel of RNAs involved in muscle development and function that are downregulated in DM1 are due to aberrant localization of the transcription factor SHARP (SMART/HDAC1-associated
repressor protein). Mislocalization of SHARP in DM1 is consistent with increased CRM1-mediated export of SHARP to the cytoplasm. A direct link between CTG repeat expression and SHARP mislocalization is demonstrated as expression of expanded CTG repeats in normal cells recapitulates cytoplasmic SHARP localization. These results demonstrate a role for the inactivation of SHARP transcription in DM1 biology.”
“Background: Prior studies examining the relation between diabetes mellitus (DM) and prostate cancer risk have reported controversial selleck screening library findings. We examined this association by conducting a detailed meta-analysis of the peer-reviewed literature. Methods: A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to November, 2012 was performed. Methodological quality assessment of the trials was based on the Newcastle-Ottawa Scaleq and the meta-analysis was performed using STATA 12.0. Dose-response regression was conducted with SPSS 19.0. Results: We included 29 studies in the meta-analysis (13 case-control studies, 16 cohort studies), and found an inverse association between DM and prostate cancer (relative risk (RR) 0.84, 95% confidence interval (CI), 0.78-0.91).
We showed that UCP1 turnover is very different in iBAT and inguinal WAT (ingWAT); the former showed minimal changes in protein content, whereas the latter showed major changes. Similarly, in iBAT both mtDNA content and the expression of mitochondrial proteins were stable and expressed at similar levels during reversible transitions from 29 degrees INCB28060 datasheet C to 4 degrees C, whereas ingWAT revealed dynamic changes. Further analysis
showed that in iBAT, the expression patterns for UCP1 and other mitochondrial proteins resembled each other, whereas in ingWAT, UCP1 varied similar to 100-fold during the transition from cold to warmth, and no other mitochondrial proteins matched UCP1. In turn, quantitative analysis of thermogenic capacity determined by estimating the proportion of UCP1 to respiratory complex components showed no significant differences between brown and brite adipocytes, suggesting similar thermogenic potentiality. Ourresults indicate that dynamics
ofbrownadipocytes turnover during reversible transition from warm buy XMU-MP-1 to cold may determine the thermogenic capacity of an individual in a changing temperature environment.”
“Managed bees are used to transfer pollen from male to female flowers in kiwifruit, but the contribution of wild insects has been long overlooked. We approached such contribution with multiple criteria (pollinator abundance, foraging behavior, pollinating efficiency, and response to weather conditions) in the absence of imported colonies.
An abundant and rich community of pollinators (57 % were non-Apis insects) visited kiwifruit flowers and assured a fruit set and size not different from those obtained by optimal hand pollination. Honeybees were more abundant and visited more flowers per time but bumblebees were Selleckchem MI-503 more efficient on a per-visit basis. Other taxa are expected to contribute less because of their lower numbers (hoverflies, wild bees, butterflies, beetles) or their passive behavior (non-syrphid flies). Visitation patterns of pollinators were complementary. Our results highlight the important contribution of wild insects to the pollination of kiwifruit.”
“We report the design and synthesis of a series of novel DGAT1 inhibitors in the benzimidazole class with a pyridyl-oxy-cyclohexanecarboxylic acid moiety. In particular, compound 11A is a potent DGAT1 inhibitor with excellent selectivity against ACAT1. Compound 11A significantly reduces triglyceride excursion in lipid tolerance tests (LTT) in both mice and dogs at low plasma exposure. An in vivo study in mice with des-fluoro analogue 10A indicates that this series of compounds appears to distribute in intestine preferentially over plasma. The propensity to target intestine over plasma could be advantageous in reducing potential side effects since lower circulating levels of drug are required for efficacy.