text:
Just came back from a week's stay at Hotel Cheval. This is a small boutique hotel. Very charming. The way the rooms are built around the courtyard makes it feel as though you were in a small European town. In the courtyard are planters of small trees and flowers as well as plenty of little alcoves to sit in. There are two fireplaces with chairs around them. The fires are always lit in the evenings. A nice place to have a glass of wine or an after dinner drink.
Our room "Feathers" was nicely located just above one of the fireplaces with our windows , on two sides, facing the courtyard. The room was not big but not tight either.
The bed was very comfortable and the room very clean. The bathroom was a good size, with a shower for two and lots of space on the counter around the sink. Good toiletries .
There were two bathrobes to use as well as good quality towels in abundance. Also in the room there was an armoire, large enough to unpack all of your things. There was also a window seat with a small table. There was a coffee maker, wine glasses, ice bucket and everyday they left 2 bottles of water. The only thing I found the room was missing was a small refrigerator.
Breakfast on the weekends (Saturday & Sunday) was served in the Pony Room. It was buffet style and had something warm, either quiches, scrambled eggs and bacon, quesadilla's, etc. There was also fresh fruit, pastries, cereal and yogurt. Also bread to toast. Coffee and orange juice. It was very good and substantial. During the week they delivered to your door a bowl of fruit and either a muffin or pastry. I found this breakfast a little chintzy for the money you pay . For me that would be the only weak point for this hotel. They could use the Pony Room everyday and it would be a lot more comfortable for people to sit and have breakfast. The Pony Room was a bar in the late afternoon into the evening with entertainment.
There was ample parking, either on the hotel property or on the street. We slept with the window open and were woken up one evening by noise from the street cleaners. Otherwise the hotel was not noisy and everything shuts down at 10 pm. They lock the doors and you have to use a key to get in if you happen to be out later than that.
The staff were accommodating and helpful with requests for information or directions.
In all , it was a very pleasant stay and would recommend this charming little hotel to anyone and would certainly revisit it myself.
- Official Description (provided by the hotel):
- Hotel Cheval is Paso Robles' finest boutique, luxury hotel, located in the heart of downtown. Situated in California's prized Central Coast food and wine region, this sophisticated and intimate hotel offers well-traveled guests an experience unlike any other in the area. Hotel Cheval features exceptional, personalized service amidst thoughtfully designed and refined accommodations. ... more less
- Reservation Options:
- TripAdvisor is proud to partner with Travelocity, Expedia, Orbitz, Hotels.com and Hotwire so you can book your Hotel Cheval reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Cheval Hotel Paso Robles
- Boutique Hotel Cheval


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McDonald's restaurants becoming most preferred wedding venues in Hong Kong
18 July 2014 [12:23] -
More and more young couples in Hong Kong are turning to McDonald's fast-food restaurants to fit their shoestring wedding budgets. With prices starting as low as $350 per wedding, the place is pretty much a steal – the deal includes the venue, decorations, audio equipment, food, gifts and invitations. The dream wedding has only one drawback – years later, couples will have to tell their kids that they got married at McDonald's.
Surprisingly, not many couples are bothered by this. The demand for McDonald's weddings is growing in Hong Kong – the wedding party program that was started in three locations in 2011, has now been extended to 15 branches. And, believe it or not, it's not just about the money, there's a sentimental value associated with getting hitched at McDonald's.
"We started the program because many customers tell us that McDonald's is where they first started dating," a company spokesperson explained. "McDonald's is where their love stories grew. This connection is exactly why they want to hold their wedding parties and even anniversary parties at McDonald's – to relive sweet beginnings and bring their romantic story full circle."
Apart from weddings, engagement parties and bridal showers are also often held at these 15 branches."Our Wedding Party packages have just everything you need, including venue decoration, customized games and special gifts for bride & groom and your guests," McDonald's Hong Kong write on their website. "Everything will be taken care of by McDonald's. All you need to do is be there and enjoy the moment of your lifetime.
"The wedding program includes four packages to suit every budget – the most expensive one – the 'Love Forever Party' – costs HK$9,999 (US$1,290) and the cheapest one – the 'Happiness Party' – is HK$2,888 (US$372). The Love Forever package includes a decorated venue rental for two hours, wedding presents, a pair of McDonald's balloon wedding rings, a bridal bouquet, an apple pie cake display, a Crystal McDonald's house, an MC, invites, food worth HK $3,000 and seating for 50 guests.
The Happiness Party might not make couples too happy – they only get food worth HK $1,000, invites and seating for 20 guests along with basic party decorations. Still, I do think it's a steal compared to the average U.S. wedding, which costs a whopping US$30,000. The program is unique to McDonald's Hong Kong at the moment, but as more budget-conscious couples get wind of it, I have a feeling we will see McDonald's weddings all over the world.
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|By PR Newswire
Article Rating:
|February 13, 2013 03:45 PM EST
LUBBOCK, Texas, Feb. 13, 2013 /PRNewswire-USNewswire/ -- Among the select few physicians honored with the prestigious Patients' Choice Award this year is Dr. Michael Mendez.
(Photo: http://photos.prnewswire.com/prnh/20130213/DC59756)
In fact, of the nation's 870,000 active physicians and dentists, just five percent consistently received top scores from their patients on sites like Vitals (http://www.vitals.com), qualifying them for this honor in 2012.
Millions of patients go online each year to rate their doctors on various components of care, including accuracy of their diagnosis, the amount of time they spent with the doctor, and the doctor's bedside manner and follow-up care. Patients' Choice reviews these rankings and other quality measures to compile its yearly list of award winners.
Dr. Michael Mendez commented on the recognition: "I'm so honored to receive an award that's based on how my patients view the quality of care I provide. I strive each day to exceed my patients' expectations, and I'm grateful that they've recognized my efforts."
About Michael Mendez: a short profile by and about the honoree:
Our family medical clinic in Lubbock provides both inpatient and outpatient comprehensive medical services. Our staff is committed to excellence in providing compassionate, personalized health care through mutual trust, respect, quality, efficiency and service. We believe that working together we will improve the health of patients and the community we serve. We offer medical care for all ages with appointments or by walk-in. From the very young to geriatrics, we seek to care for you throughout your life.
For more information on this Patients' Choice Award winner, please visit Dr. Michael Mendez's profile on PatientsChoice.org.
Following the publication of Michael Mendez's selection for the Patient's Choice Award, American Registry seconded the honor and added Dr. Mendez to The Registry™ of Business Excellence. An exclusive recognition plaque has been designed to commemorate the honor. The doctor's custom wall plaque is shown here.
For more information on Dr. Michael Mendez, located in Lubbock, TX, please call 806-698-8088, or visit www.lubbockfamilymedicine.com.
This press release was written by American Registry, LLC with approval by and/or contributions from Dr. Mendez and was distributed by PR Newswire, a subsidiary of UBM plc.
Patients' Choice provides in-depth information on doctors in your area who have been recognized and awarded for outstanding patient care and expertise. The Patients' Choice Award is the honor roll of physicians who have received the highest ratings by their patients.
American Registry, LLC, recognizes excellence in top businesses and professionals. The Registry™ includes over 2 million significant business and professional recognitions. For more information, search The Registry at http://www.americanregistry.com.
Contact Info:
Dr. Michael Mendez
Phone: 806-698-8088
SOURCE American Registry
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text:
Innovative Health initiative is launched
One for the Girls: Innovative Health initiative is launched in Auckland
OneForTheGirls is a health initiative supported by the Auckland District Health Board to talk with teenage girls about the benefits of receiving the HPV (human papillomavirus) immunisation.
Launching on September 1, the OneForTheGirls website (www.oneforthegirls.org.nz) will offer girls a forum to discuss and discover important information surrounding cervical cancer and the HPV vaccine in a youth friendly environment.
The HPV Vaccination Programme, which aims to reduce HPV infection and the number of women in New Zealand who subsequently develop cervical cancer, is now available nationally for free for girls aged 17-18 from their primary healthcare provider. It is estimated that 4 in 5 people are exposed to the HPV virus in their lifetime.
Dr Nikki Turner, Director of the NZ Immunisation Advisory Centre says, "It's expected that with a successful immunisation programme, the incidence of HPV that leads to cervical cancer will decrease. Every year this may save 60 women from dying of cervical cancer. It is vital we provide accurate information so people can make an informed decision."
The OneForTheGirls campaign recognises the role technology plays in the way teenage girls communicate today. The innovative use of Facebook and Bebo applications is allowing the ADHB to talk with the girls in their own space.
As part of their commitment to this programme, the ADHB enlisted the help of AUT University communication students. The students have spearheaded a promotional campaign targeting young women and led the development of the OneForTheGirls website to ensure it is relevant and appealing to its audience.
Dr Denis Jury, ADHB Chief Planning and Funding Officer says, "This programme provides an opportunity for young women to be protected against the virus that causes most cervical cancers. It is an investment in protecting future generations."
OneForTheGirls will celebrate the launch of the HPV programme in style with a morning tea held for local high school girls and other invited guests. The Honourable Steve Chadwick, Associate Minister of Health along with Tee Twyford, NZGirl editor and Dr Nikki Turner will address the audience.


text:
Review August 2014 | Volume 122 | Issue 8
The Blood Exposome and Its Role in Discovering Causes of Disease
Stephen M. Rappaport,1 Dinesh K. Barupal,2 David Wishart,3 Paolo Vineis,4,5 and Augustin Scalbert2
Background: Since 2001, researchers have examined the human genome (G) mainly to discover causes of disease, despite evidence that G explains relatively little risk. We posit that unexplained disease risks are caused by the exposome (E; representing all exposures) and G × E interactions. Thus, etiologic research has been hampered by scientists' continuing reliance on low-tech methods to characterize E compared with high-tech omics for characterizing G.
Objectives: Because exposures are inherently chemical in nature and arise from both endogenous and exogenous sources, blood specimens can be used to characterize exposomes. To explore the "blood exposome" and its connection to disease, we sought human blood concentrations of many chemicals, along with their sources, evidence of chronic-disease risks, and numbers of metabolic pathways.
Methods: From the literature we obtained human blood concentrations of 1,561 small molecules and metals derived from foods, drugs, pollutants, and endogenous processes. We mapped chemical similarities after weighting by blood concentrations, disease-risk citations, and numbers of human metabolic pathways.
Results: Blood concentrations spanned 11 orders of magnitude and were indistinguishable for endogenous and food chemicals and drugs, whereas those of pollutants were 1,000 times lower. Chemical similarities mapped by disease risks were equally distributed by source categories, but those mapped by metabolic pathways were dominated by endogenous molecules and essential nutrients.
Conclusions: For studies of disease etiology, the complexity of human exposures motivates characterization of the blood exposome, which includes all biologically active chemicals. Because most small molecules in blood are not human metabolites, investigations of causal pathways should expand beyond the endogenous metabolome.
Citation: Rappaport SM, Barupal DK, Wishart D, Vineis P, Scalbert A. 2014. The blood exposome and its role in discovering causes of disease. Environ Health Perspect 122:769–774; http://dx.doi.org/10.1289/ehp.1308015
Address correspondence to S.M. Rappaport, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-7356 USA. Telephone: (510) 642-4355. E-mail: firstname.lastname@example.com
We thank V. Neveu for assistance in downloading data from the Human Metabolome Database and appreciate helpful discussions with M. Smith (University of California, Berkeley), C. Wild (International Agency for Research on Cancer), and P. Elliott and M. Chadeau-Hyam (Imperial College, London).
The work was undertaken during the tenure of a Senior Visiting Scientist Award (to S.M.R.) granted by the International Agency for Research on Cancer and a sabbatical award (to S.M.R.) from the Wellcome Trust, in the Department of Epidemiology and Public Health, Imperial College, London. Support for this work was also provided by grant P42ES04705 from the National Institute of Environmental Health Sciences (National Institutes of Health) and grant agreement 308610-FP7 European Commission (Project Exposomics) (to P.V.).
The authors declare they have no actual or potential competing financial interests.
Received: 16 December 2013
Accepted: 20 March 2014
Advance Publication: 21 March 2014
Final Publication: 1 August 2014
- Supplemental Material (5.5 MB) PDF
Worldwide mortality is dominated by noncommunicable diseases, particularly cardiovascular disease (29%), cancer (15%), and respiratory diseases (7%) (Lozano et al. 2012). These chronic diseases result from the combined effects of the human genome (G) and exposome (E; representing all exposures). (Although geneticists use the term "environment" to denote nongenetic factors, many scientists and the general public equate "environment" with "pollution," which represents only one class of exposures. We use the term "exposome" to encompass all exogenous and endogenous exposures.) But attribution of risks to G and E and their interaction (G × E) has been problematic because of disparities in characterizing genes and exposures (Rappaport and Smith 2010; Wild 2005). In fact, sequencing the human genome in 2001 permitted researchers to comprehensively explore G and its progeny (i.e., genome → transcriptome → proteome → metabolome) but did not promote detailed characterization of E, which in epidemiological and clinical research still relies on questionnaires, geographical information, and targeted surveys (Ezzati and Riboli 2013; Lim et al. 2012). In addition, the study of external and internal exposures (including endogenous chemicals) has focused on a limited number of molecules and metals that cannot compare with the resolution of genome-wide association studies (GWAS).
Interestingly, the variation in chronic-disease incidence explained by scores of GWAS has been so small that searches are under way for "missing heritability" (Goldstein 2009; Manolio et al. 2009) and "genetic dark matter" (Galvan et al. 2010; Martin and Chang 2012; Melhem and Devlin 2010). Even assuming that a host of rare alleles account for some unexplained phenotypic variation (Kraft and Hunter 2009), it is reasonable to posit that E and G × E are the primary causes of chronic diseases, as suggested by studies of families and twins (Hemminki et al. 2006; Lichtenstein et al. 2000), epigenetics (Gluckman et al. 2008, 2010; Smith and Meissner 2013), and gene-expression profiles that change with lifestyles and infections (Chen et al. 2012; Preininger et al. 2013). In fact, as shown in Figure 1, about half of the 50 million global deaths in 2010 were attributed to a small set of exposures, dominated by particulate air pollution (combined effects of ambient particles and household smoke), smoking (active and passive), and diet (Lim et al. 2012). This conundrum—where scientists use high-tech omics to detect small effects of G but rely upon low-tech methods to study potentially large effects of E and G × E—has produced a very uneven record of etiologic research.
Figure 1 – Risk factors for exposures that contribute to chronic-disease mortality. The chart was compiled from World Health Organization estimates of exposures affecting 50 million global deaths in 2010 (Lim et al. 2012). (Because some risk factors may be correlated, the indicated percentages are approximate.)
One way to level the playing field would be to explore health impacts of E and G × E with exposome-wide association studies (EWAS) (Rappaport 2012) that obtain comprehensive, quantitative measurements of chemicals in human biospecimens (Holmes et al. 2008; Ritchie et al. 2010; Wang Z et al. 2011). This approach recognizes that meaningful exposures are mediated in the internal chemical environment (Rappaport and Smith 2010) by endogenous signaling molecules, exogenous chemicals, and reactive electrophiles (E-factors) that communicate with cells, tissues, and organs via mutations, posttranslational modifications, enzymes, transcription factors, and receptors (G-factors) (Brodsky and Medzhitov 2009; Liebler 2008; Menon and Manning 2013). Because blood transports chemicals to and from tissues and represents a reservoir of all endogenous and exogenous chemicals in the body at a given time (Nicholson et al. 2012b), the blood exposome offers a parsimonious but essentially unexplored means for interrogating biologically relevant exposures (Rappaport 2012).
Sources of data. To investigate the portion of the blood exposome represented by small molecules and metals, we obtained blood concentrations of 1,561 chemicals from samples of healthy human populations compiled by the Human Metabolome Database (HMDB; http://www.hmdb.ca) (Wishart et al. 2013) (1,451 chemicals) and the U.S. National Health and Nutrition Examination Survey (NHANES) [Centers for Disease Control and Prevention (CDC) 2009, 2012, 2013] (110 chemicals). Each molecule or metal was assigned one of the following four source categories: a) endogenous chemical (from intrinsic human metabolism; n = 1,223), b) food chemical (n = 195), c) pollutant (n = 94), or d) drug (n = 49). (The process for selecting chemicals is described in Supplemental Material, pp. 2–4.) To link individual chemicals with chronic-disease risks and systems biology, we retrieved additional data from the National Center for Biotechnology Information databases PubMed (http://www.ncbi.nlm.nih.gov/pubmed; citations on chronic-disease risk factors) and Biosystems (http://www.ncbi.nlm.nih.gov/biosystems/; data on human metabolic pathways). Although modest in size, these samples allowed us to explore the range of human blood concentrations, to test for differences in median levels across source categories and to map chemical similarities after weighting by blood concentration, disease-risk citations, and human metabolic pathways. Relevant data are given in Supplemental Material, Table S1.
HMDB entries were from metabolic studies in mostly Western populations, and included endogenous and food chemicals, drugs, and pollutants; NHANES included only nutrients and pollutants in U.S. populations. When a given chemical was present in both of these databases, we used NHANES concentrations. If the same chemical had been reported in more than one study or year, we used the geometric mean concentration. Numbers of individual subjects varied across chemicals. Drug concentrations were reported in clinical trials at therapeutic doses.
We used Chemical Abstract Service (CAS) registry number(s) as the query parameter to search PubMed along with medical subject headings (MeSH) annotations to retrieve the citations describing epidemiological studies. The search string was
(blood OR plasma OR serum) AND ("risk factors"[MeSH Terms] OR "relative risk*" OR "odds ratio*" OR "hazard ratio*") + CAS number + [EC/RN number]("journal article"[pt] NOT review[pt] NOT "meta analysis"[pt]) (hasabstract[text] AND "humans"[MeSH Terms]) english[lang] (neoplasms[mesh] OR diabetes[mesh] OR "cardiovascular diseases"[mesh] OR "Respiratory Tract Diseases"[mesh]).
For retrieval of pathway hits, PubChem identifiers for each compound were searched against the Biosystems database. Chemical similarity maps were generated using MetaMapp (http://metamapp.fiehnlab.ucdavis.edu/homePage).
Statistical analysis. Differences in median blood concentrations across source categories were evaluated with Kruskal-Wallis tests via SAS for Windows (v.9.3) (SAS Institute Inc., Cary, NC).
Blood concentrations. Cumulative distributions of blood concentrations are shown in Figure 2 for the four sources of chemicals. Concentrations ranged from 160 fM to 140 mM, a staggering 11 orders of magnitude. Within each category, concentrations covered a 107-fold range. Median blood levels of endogenous chemicals (0.94 μM), food chemicals (1.00 μM), and drugs (0.30 μM) were not significantly different (p = 0.246). In contrast, pollutant concentrations were 1,000 times lower (median, 2.4 × 10–4 μM, p < 0.0001), and only pollutants with blood levels above the median value overlapped with other distributions.
Figure 2 – Small molecules and metals in human blood. Each curve represents the cumulative distribution of chemical concentrations from a particular source category (pollutants, n = 94; drugs, n = 49; food chemicals, n = 195; endogenous chemicals, n = 1,223). Abbreviations: BDE 100, 2,2′,4,4′,6-pentabromodiphenyl ether; DDE, 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene; OCDD, 1,2,3,4,6,7,8,9-octachlorooxanthrene; PCB 170, 2,2′,3,3′,4,4′,5-heptachloro-1,1′-biphenyl.
Chemical-similarity maps. Endogenous and dietary molecules comprised > 100 chemical classes, particularly lipids, steroids, amino acids, fatty acids, and nucleotides (see Supplemental Material, Table S1). In addition to nutrients and vitamins, food chemicals included such bioactive molecules as aflatoxin B1 (a carcinogen from mold-infected grains and nuts), solanidine (a toxin from potatoes), sulforaphane (a DNA-protective agent from cruciferous vegetables), acetaldehyde (a mutagen from metabolism of alcohol), genistein (an endocrine-disrupting chemical from soy products) and trimethylamine-N-oxide (from metabolism of choline and carnitine; a suspected cause of atherosclerosis). Exogenous pollutants were primarily halogenated compounds—trihalomethanes, chlorinated pesticides, perfluorinated compounds, polychlorinated biphenyls (PCBs), brominated diphenyl ethers, and some chlorinated dioxins and furans—and metals, but also included a few volatile aromatic species (notably benzene) and metabolites of nicotine. This diversity is illustrated in Figure 3A, which maps the 1,561 chemicals by their structural similarities (Barupal et al. 2012), with symbol sizes indicating blood concentrations. Shown in Figure 3A, constellations of biochemical classes were populated largely by endogenous and food chemicals, whereas drugs clustered with aromatic compounds [between map locations AN (alkaloids) and BD (benzoic acids and phenols)] and pollutants were mainly at map peripheries [e.g., locations AH (organochlorine pesticides) and AX (PCBs)]. Metals and metalloids originated from foods (six most abundant: sodium, potassium, iron, calcium, phosphorus, and magnesium), pollution (six most abundant: silicon, strontium, nickel, lead, beryllium, and arsenic), and one drug (lithium).
Figure 3 – Chemical-similarity maps of small molecules and metals in human blood (Tanimoto coefficient ≥ 0.7; symbol color represents the source category).
(A) All chemicals (n = 1,561; symbol size reflects the blood/serum concentration). Map locations: AA, leucotrienes; AB, perfluorinated compounds; AC, alkylamines; AD, pteridines; AE, pyrimidine nucleotides; AF, aliphatic amino acids and derivatives; AG, sphingolipids; AH, organochlorine pesticides; AI, prenol lipids; AJ, sulfur compounds; AK, flavonoids; AL, pyrroles and indoles; AM, pyridines; AN, alkaloids; AO, benzoic acids and phenols; AP, eicosanoids; AQ, fatty acids and fatty amines; AR, steroids; AS, organic acids; AT, monosaccharides; AU, phosphates; AV, alcohols; AW, fatty acid esters and conjugates; AX, polychlorinated biphenyls; AY, simple aromatics; AZ, chlorinated dioxins and furans; BA, sulfates and nitrites/nitrates; BB, purine nucleotides; BC, aromatic amino acids and derivatives; BD, benzoic acids and phenols.
(B) Matching chemicals from (A) cited in studies of chronic-disease risks (n = 336; symbol size reflects the number of citations). Map locations: 1, selenium; 2, nitric oxide; 3, folic acid; 4, vitamin B12; 5, metformin; 6, cotinine; 7, lead; 8, bilirubin; 9, atorvastatin; 10, ascorbic acid; 11, thyroxine; 12, norepinephrine; 13, aspirin; 14, eicosapentaenoic acid; 15, magnesium; 16, calcium; 17, sodium; 18, uric acid; 19, creatinine; 20, ʟ-arginine; 21, homocysteine; 22, ʟ-methionine; 23, ʟ-valine; 24, β-carotene; 25, vitamin A; 26, vitamin D3; 27, cholesterol; 28, simvastatin; 29, aldosterone; 30, cortisol; 31, testosterone; 32, malondialdehyde; 33, ᴅ-glucose; 34, estradiol; 35, PCBs; 36, ethanol.
(C) Matching chemicals from (A) having human metabolic pathways (n = 658; symbol size reflects the number of pathways). Map locations: 1, adenosine triphosphate; 2, hydrogen peroxide; 3, adenosine diphosphate; 4, guanosine diphosphate; 5, guanosine triphosphate; 6, NADPH; 7, cyclic AMP; 8, adenosine monophosphate; 9, NADH; 10, NAD; 11, FAD; 12, manganese; 13, sodium; 14, calcium; 15, zinc; 16, magnesium; 17, potassium; 18, norepinephrine; 19, epinephrine; 20, ʟ‑phenylalanine; 21, ʟ‑tyrosine; 22, dopamine; 23, palmitic acid; 24, cholesterol; 25, ʟ‑glutamic acid; 26, adenine; 27, ʟ‑aspartic acid; 28, oxoglutaric acid; 29, pyruvic acid; 30, phosphate; 31, pyrophosphate; 32, formic acid; 33, uridine 5′-monophosphate; 34, uridine 5′-diphosphate; 35, ʟ‑arginine; 36, ʟ‑alanine; 37, ʟ‑cysteine; 38, ʟ‑serine; 39, arachodonic acid; 40, α-linolenic acid.
Because citations to risk factors summarize epidemiological and clinical evidence associating a chemical with disease phenotypes, we found PubMed citations for 960 searchable substances in our inventory (only chemicals with CAS registry numbers were searchable in PubMed), and obtained 19,656 citations matching 336 (35%) of these chemicals. (Numbers of matching citations are included in Supplemental Material, Table S1.) The distribution of citations per chemical was highly skewed, with a median value of 7.5 and a maximum of 4,499 (cholesterol). The large numbers of citations per chemical and positive skewness probably reflect publication bias in hypothesis-driven epidemiological studies and clinical trials. Median numbers of citations varied 2-fold across source categories (drugs, 10; endogenous, 6; food chemicals, 13; pollutants, 6; p = 0.041). When food chemicals were removed, median values for the other categories were not significantly different (p = 0.307). This indicates that a typical food chemical was about twice as likely to be cited as a chronic-disease-risk factor than a chemical from another category.
The chemical-similarity map for these 336 chemicals is shown in Figure 3B, where symbol size reflects the number of citations. This map shared prominent clustering patterns with Figure 3A, except that individual lipid molecules were largely absent (lipids tend to be reported as classes rather than discrete molecules in clinical and epidemiological studies) and most endogenous molecules with large blood concentrations had few PubMed citations. Several highly cited chemicals are familiar biomarkers of human diseases and causal exposures: for example, cholesterol (n = 4,449, cardiovascular disease), folic acid (n = 595, cancer and neural-tube defects), lead (n = 65, cardiovascular and neurological diseases), and cotinine (n = 78, smoking-related diseases), along with vitamins, hormones, and antioxidants. Aspirin was the most-cited drug (n = 515), followed by atorvastatin (n = 206).
Sequencing the human genome motivated mapping of G-centric molecular pathways at multiple levels and made metabolites with annotated pathways desirable targets for systems biology (Chen et al. 2012). In matching records retrieved from the Biosystems database for chemicals in our inventory, at least one human metabolic pathway had been reported for 658 of them (42%). (The numbers of pathways reported are included in Supplemental Material, Table S1.) Median numbers of pathways varied 6-fold across sources, with pollutants being significantly understudied (drugs, 4; endogenous, 6; food chemicals, 4; pollutants, 1; p < 0.0001). The chemical-similarity map of these 658 chemicals is shown in Figure 3C, with symbol size representing the number of pathways. The largest numbers of pathways corresponded to purine-nucleotide phosphates (maximum of 707 for adenosine triphosphate), amino acids and derivatives, fatty acids, and dietary metals. In contrast to prominent disease-risk citations that were distributed more or less evenly across source categories (Figure 3B), chemicals with many pathways were overwhelmingly endogenous molecules and essential nutrients (Figure 3C).
Because the sets of PubMed and Biosystems hits were not completely overlapping, we repeated the analysis of source categories for the 267 chemicals that had at least one disease-risk citation and at least one human metabolic pathway. Results from this subset of chemicals were essentially the same as for the complete data sets. Median numbers of PubMed hits varied 2.4-fold across source categories (drugs, 7; endogenous, 7; food chemicals, 17; pollutants, 9; p = 0.0261) but did not differ significantly when food chemicals were removed (p = 0.4135). In contrast, median numbers of human metabolic pathways varied 12-fold across source categories, and were much smaller for drugs and pollutants than for endogenous and food chemicals (drugs, 4; endogenous, 11.5; food chemicals, 12; pollutants, 1; p < 0.0001).
Discovering causes of disease. Data summarized in Figure 1 suggest that only about half of the current burden of chronic diseases can be attributed to known exposures and thus motivate more thorough scrutiny of the exposome to find unknown causes. This will be challenging because of the remarkable ranges of human exposures across sources and chemical classes that are displayed in Figures 2 and 3. Such extreme variation suggests that knowledge-driven studies are ill suited for discovering unknown causes of chronic diseases. There are simply too many diverse chemicals covering too great a concentration range to formulate reasonable hypotheses. We should narrow the list of chemical candidates by using EWAS to find discriminating exposures in biospecimens from diseased and healthy subjects (Holmes et al. 2008; Patel et al. 2010; Rappaport 2012; Ritchie et al. 2010; Wang Z et al. 2011), essentially following the same strategy as GWAS. Once identified, these chemicals can be targeted to investigate sources, causality, disease mechanisms, and interventions (Rappaport 2012). A good example of this two-stage strategy was provided by Hazen and coworkers, who linked risks of cardiovascular disease with blood concentrations of trimethylamine-N-oxide, a metabolite of choline and carnitine derived from microbial/human metabolism (Koeth et al. 2013; Tang et al. 2013; Wang Z et al. 2011).
Optimally, EWAS would employ untargeted methods to compare blood exposomes between cases and controls nested in cohort studies. Although untargeted high-resolution mass spectrometry (MS) can detect > 30,000 features of small molecules in human serum (Ivanisevic et al. 2013), use of untargeted platforms in our laboratories cannot reliably measure blood concentrations less than approximately 0.1 μM in 50 μL of serum. Given the extraordinary dynamic range of small molecules and metals (Figure 2), untargeted analyses may miss about 90% of pollutants and 30% of endogenous and food chemicals, including hormones (e.g., estradiol, testosterone), carcinogens (e.g., aflatoxin B1, benzene), and endocrine disruptors [e.g., genistein, PCBs, DDE (1,1-bis-(4-chlorophenyl)-2,2-dichloroethene)].Thus, although increased sensitivity can be anticipated with untargeted MS, EWAS currently require a combination of untargeted (Holmes et al. 2008; Ritchie et al. 2010; Wang Z et al. 2011) and semitargeted (Patel et al. 2010) methods to quantify exposures. In addition, as for the Human Genome Project (National Human Genome Research Institute 2013), different laboratories could address specific parts of the exposome in a complementary and collaborative way.
Magnitudes of exposures. Ranges of blood concentrations varied greatly within and between sources of exposure as shown in Figure 2. Although we had anticipated that endogenous and food chemicals would have similar blood levels, we were surprised to observe the near-perfect overlap of concentrations of these chemicals with those of drugs. Such similar cumulative distributions suggest that blood concentrations of endogenous human metabolites and food chemicals are in the therapeutic range of pharmacologic agents. We were also somewhat surprised to observe that blood concentrations of pollutants were 1,000 times lower than those of chemicals from other categories. Such disparate blood levels across exposure sources awaken arguments by Ames and colleagues that natural toxins and protective chemicals are consumed in much greater quantities than synthetic chemicals and, therefore, should be considered when assessing disease risks (Ames 1983; Ames et al. 1987, 1990a, 1990b). This further emphasizes the importance of EWAS for interrogating all chemicals that can cause chronic diseases.
Epidemiology and systems biology. Weighting chemicals by blood concentrations (Figure 3A), epidemiological (risk factor) citations (Figure 3B), or human metabolic pathways (Figure 3C) altered the appearances of chemical-similarity maps. Epidemiological citations downgraded the importance of endogenous molecules while upgrading pollutants and drugs, but weighting by numbers of metabolic pathways had the opposite effect. These markedly different maps were unanticipated because it is generally thought that epidemiology and systems biology work hand in glove to elucidate causes and mechanisms of disease (Nicholson et al. 2012b).
Epidemiologists are interested in causes of disease, including genetic factors (G) and exposures (E) related to metabolism, diet, pollution, infections, lifestyles, and behaviors. When they have used blood concentrations to quantify chemical exposures from G, E, and G × E, epidemiologists have successfully linked chronic diseases to targeted endogenous and exogenous chemicals (Figures 1 and 3B). We assumed that chemicals that had been repeatedly associated with chronic diseases (Figure 3B) would be logical candidates for exploration of metabolic pathways. However, because only 29% of the chemicals in our database with three or more PubMed risk-factor citations also had a Biosystems hit (i.e., 189/658), this was apparently not the case.
Systems biologists focus on metabolic pathways that are under homeostatic control and, therefore, presume a G-centric hierarchy that culminates in the endogenous metabolome (Nicholson et al. 2012b). From the systems-biology perspective, the most meaningful metabolites are those that participate in many pathways (Loscalzo et al. 2007), and Figure 3C points to products of energy metabolism and essential nutrients as filling that role. If such molecules can be linked to disease, then their concentrations can promote early diagnosis and treatment even if causal E and G × E factors are unknown. For example, high concentrations of branched-chain amino acids (leucine, isoleucine, and valine) predict incipient diabetes and offer avenues for treatment (Newgard 2012; Wang TJ et al. 2011). However, the poor track record of GWAS in explaining the variation of chronic diseases suggests that systems biologists who look only at endogenous metabolites (i.e., molecules produced under human genomic control) will miss opportunities to discover causal pathways. Indeed, of the 41,000 small molecules currently thought to populate the human body (Wishart et al. 2013), only 2,626 (6.4%) (Recon X 2013) are products of endogenous human metabolism.
The microbiome. When considering G and G × E effects, it is important to remember that 90% of the approximately 1014 cells in the human body actually reside in the gut microbiota (Savage 1977). This superorganism contributes ~ 500,000 microbial protein-coding genes (Qin et al. 2010) compared with a human complement of ~ 20,000 protein-coding genes. Thus, human biospecimens contain a plethora of bioactive molecules generated from microbial metabolism (Nicholson et al. 2012a) in addition to chemicals introduced by the diet, drugs, infectious organisms, pollution, and lifestyle factors (Nicholson and Wilson 2003; Rappaport and Smith 2010). Chemicals produced by the microbiota control development and maintenance of the human immune system as well as important cell-signaling processes (Nicholson et al. 2012a) and appear to be intimately involved in development of chronic diseases (Blumberg and Powrie 2012; Haiser and Turnbaugh 2012). Although research involving microbial contributions to the human exposome is in its infancy, it should expand dramatically as the important roles played by the microbiota are recognized in disease etiology (Koeth et al. 2013; Ridaura et al. 2013; Tang et al. 2013; Wang Z et al. 2011).
Internal and external measures of exposure. To discover unknown exposures that cause disease, we advocate data-driven EWAS that profile chemicals in blood from disease cases and controls (Rappaport 2012). Internal measures of exposure, such as the blood exposome, offer advantages for EWAS because they represent all sources of chemicals, including those generated inside the body, and blood specimens are often archived in prospective cohort studies (Rappaport and Smith 2010). As EWAS discover new disease associations, knowledge-driven studies will be needed to curate exposure sources and quantify exposure–response relationships—thereby strengthening causal inferences—and to suggest interventions (Rappaport 2012). To the extent that important exposures originate outside the body, this follow-up will involve exposure scientists, industrial hygienists, food scientists, and analytical chemists who measure chemicals in air, water, and food, as well as biologists who evaluate mechanisms of action (Lioy and Rappaport 2011; Rappaport 2011; Scalbert et al. 2014; Wild 2012). Thus, the process of identifying causal exposures can require measurements of chemicals both inside and outside the body across a diverse scientific milieu.
Limitations. Because we relied on publically accessible data, our findings and their interpretation are conditioned by the chemicals compiled by the HMDB and NHANES and by publications and metabolic pathways curated through the National Center for Biotechnology Information. Most of the 1,561 chemicals we investigated in human blood were derived from foods and endogenous processes because these are major foci of the HMDB. Most of the pollutants in our database were reported by NHANES. Yet, we exclued a roughly equal number of other pollutants in NHANES because they were not detected in most blood samples (CDC 2009, 2012, 2013). If nondetects from NHANES had been included, the shift toward lower blood concentrations of pollutants relative to chemicals from other sources would have been even greater. We also recognize that some of our data could be biased. For example, using PubMed citations to assess disease associations of particular exposures can introduce biases related to prior publications and to research priorities for different diseases, numbers of investigators, journals, and so on. As noted previously, the Biosystems database of human metabolic pathways reflects apparent biases favoring chemicals that are involved in many pathways regardless of disease associations. Finally, we were unable to investigate possible effects of chemical interactions on disease risks. Despite these limitations, the vast diversity and concentration ranges of blood chemicals should be apparent, as should differences in median blood concentrations observed across source categories (Figures 2 and 3).
The extreme complexity and dynamic range of the blood exposome (Figures 2 and 3) should motivate data-driven studies to discover unknown causes of chronic diseases, regardless of their exogenous and endogenous origins (Rappaport 2012). Candidate exposures can be identified by EWAS that compare omic profiles in blood from diseased and healthy subjects.
The apparent disconnect between chemical-specific disease risks (Figure 3B) and human metabolic pathways (Figure 3C) indicates that systems biologists are only marginally engaged in elucidating causal disease pathways. We promote a more global approach to systems biology (Nicholson and Wilson 2003) that expands beyond the endogenous metabolome to the blood exposome, illustrated here by a large sample of circulating small molecules and inorganic species.
Perhaps the most compelling reason for embracing the blood exposome is the potential to discover all chemicals that cause disease and then to intervene in order to modify exposures and the concomitant burden of disease (Christiani 2011). The current inventory of small molecules and metals associated with chronic diseases consists of about 300 chemicals that have been targeted repeatedly in epidemiological and clinical studies (Figure 3B). With recognition of their health significance, these chemicals have been routinely monitored for clinical interventions (e.g., cholesterol, folic acid, vitamins) and as regulated pollutants (e.g., lead, arsenic, benzene, PCBs). Yet, further scrutiny of these recognized health hazards adds little to our understanding of disease causation. If we expect to reduce the burden of chronic diseases, it is time to find the undiscovered health-impairing and health-promoting chemicals to which humans are exposed (Figure 1), not only small molecules and metals but also proteins and foreign DNA and RNA.
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[deleted post]C7 is best among C7,C6-01 and C5-03.
Agent 47, 09 Mar 2011Which Nokia is cheaper; C6-01 or C7? Plz Reply....c6-01 is cheaper than c7
Hi frndz,, i just bot d phone yest.. its amazin.. earphones r not dat gud which come in the box.. so i just purchased sony deep bass earphones for 1k.. 3.5mm jack.. sounds like heaven seriously.. battery back up is really gud.. n everything is perfect.. but only thing is while on a phone call m facing difficulties,, numbers r getting dailed automatically in the middle of conversation theres is some kinda static while on phone call.. and its really hard to talk while sleepin on.. i think sensor is doing somethin here on its own while on a phone call.. plz help me out wat to do if some one knows it??//?///?
the major prob of this phone is hanging and can't open after the battery finish.i bought this phone last year december.during this 5 months i faced lot of problems and send it for repair.anybody can help me?i wan 2 sell this phone for secondhand
[deleted post]No Doubt C7 is bttr amoung them
Hey guys I would like to buy C601 is this phne support skpe,gtalk,n fring for using net work c7 or c601 beter plz reply me
billi, 31 May 2011pls let me know is it worth buying this phone? I want to know the overall performance? Good or bad? i am using this phone from past 1 month.
it is not so good not so bad. Though the screen is 3.2" but the width is less than others phones.
Battery backup is average. Clear balck display is amazing, touch sensitivity is very good, but music is no loud, i have seen some movies on it, contrast is not so good on comparision to others, however the colours look awesome on standby screen.
i am using LG Android 2.2 also, direct comaprison B/W 2 OS it would say Symbion is far far behind.
My score 6 out of 10.
for Android 8.5/10.
i have just bought d phone......pretty decent considering d price.......but not a good battery life......having problem with GPS connection.........ovi maps do not connect through GPS......Can anybody help me with Signed\Unsigned apps.????.......how to run d unsigned apps?????
i am in love with c6-01,
previously i used htc, the nokia c6-00.
but believe me u will love this c6-01.
its amazing.
4 of my friends bought it after seeing me use it
Good Phone. Perfect Pictures and Crystal Video quality. Amazing display (Clear Black Display). Poor and Poor Battery Life
this phone is very nice but just one issue; mobile office is not coming with licence version and one need to search for crack file on the net.
Anonymous, 29 May 2011so u need tips on how to prolong ur bat3, correct?i want to know is that normal or i have a problem in my battery
pilipino, 31 May 2011I'm also starting to have problem w/ c6's touch sensitivity I don't know why.. It was ok at th... moreput ur hand set in water?> after putting then put in warm water ,,, then keep it for sometym in sunlight,, after this u will free with ur problm?
ABS, 31 May 2011hii i am going to buy dis phone 2morrow is the phone is perfectly ok with battery life or any ... moreI want to nokia
pls let me know is it worth buying this phone? I want to know the overall performance? Good or bad?
Ohms, 09 May 2011Warlock Thanks for your enlightenment towards symbian. actually I believe what makes c7 to b ... moreyes your product is fantastic and i will like to buy nokia c6-01 review


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A signaling protein released during rheumatoid arthritis dramatically reduced Alzheimer's disease pathology and reversed the memory impairment of mice bred to develop symptoms of the neurodegenerative disease, a new study by the University of South Florida reports. Researchers found that the protein, GM-CSF, likely stimulates the body's natural scavenger cells to attack and remove Alzheimer's amyloid deposits in the brain.
The study appears online today in the Journal of Alzheimer's Disease.
People with rheumatoid arthritis, a chronic disease leading to inflammation of joints and surrounding tissue, are less likely than those without arthritis to develop Alzheimer's. While it was commonly assumed that non-steroidal anti-inflammatory drugs may help prevent onset and progression of Alzheimer's disease, recent NSAID clinical trials proved unsuccessful for patients with Alzheimer's.
The USF researchers are among the first to look at what effect innate immunity gone awry in rheumatoid arthritis may play in protecting against Alzheimer's disease.
"Our findings provide a compelling explanation for why rheumatoid arthritis is a negative risk factor for Alzheimer's disease," said principal investigator Huntington Potter, PhD, professor of molecular medicine at the USF Health Byrd Alzheimer's Institute and director of the Florida Alzheimer's Disease Research Center.
"Moreover, the recombinant human form of GM-CSF (Leukine®) is already approved by the FDA and has been used for years to treat certain cancer patients who need to generate more immune cells," Dr. Potter said. "Our study, along with the drug's track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer's disease."
The researchers analyzed three rheumatoid arthritis growth factors in mouse models and identified the signaling protein GM-CSF as the most promising for potential protective benefit against Alzheimer's disease. Then, they peripherally injected GM-CSF into two groups of mice – those genetically altered to develop memory problems mimicking Alzheimer's disease and normal, aged mice. Behavioral tests confirmed the Alzheimer's mice were exhibiting signs of memory impairment at age 12 months. Another two control groups of mice – the Alzheimer's mice and normal mice – were administered saline (placebo).
After the 10th day of injections, all the mice began a series of behavioral testing. At the end of the 20-day study, the cognitively impaired mice treated with GM-CSF performed substantially better on tests measuring their working memory and learning. In fact, their memories were similar to normal aged mice without dementia. Even the normal mice treated with GM-CSF performed slightly better than their untreated peers. The Alzheimer's mice administered saline continued to do poorly on the tests.
"We were pretty amazed that the treatment completely reversed cognitive impairment in 20 days," said Tim Boyd, PhD, who, together with Steven Bennett, PhD, is a study lead author.
In addition, the brains of GM-CSF-treated Alzheimer's mice showed more than a 50-percent decrease in beta amyloid, a substance forming the sticky clumps of plaques that are a hallmark of Alzheimer's disease. This reduction in Alzheimer's plaques and associated restoration of memory was accompanied by more immune cells known as microglia in the brain. Microglia are like the body's natural garbage collection cells that rush to damaged or inflamed areas to get rid of toxic substances.
The researchers suggest that GM-CSF boosted during the immune system overdrive of rheumatoid arthritis helps harness the beneficial properties of inflammation in the brain. The protein may do this by recruiting more microglia from the peripheral blood into the brain to remove Alzheimer's plaques, Dr. Potter said. An apparent increase in neural cell connections in the brains of the GM-CSF-treated mice may also help explain GM-CSF's association with improving memory decline in Alzheimer's disease, the researchers said.
The USF Health Byrd Alzheimer's Institute plans to begin a pilot clinical trial later this year investigating GM-CSF (Leukine) in patients with mild or moderate Alzheimer's disease.
Journal article (online): "GM-CSF up-regulated in Rheumatoid Arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice;" Tim D. Boyd, PhD; Steven P. Bennett, PhD; Takashi Mori, DVM, PhD; Nikolas Governatori, BS; Melissa Runfeldt, BS; Michelle Norden; Jaya Padmanabhan, PhD; Peter Neame, PhD; Inge Wefes, PhD; Juan Sanchez-Ramos, PhD, MD; Gary W. Arendash, PhD, Huntington Potter, PhD; Journal of Alzheimer's Disease; Vol. 21:2 (August 23, 2010).
About USF Health
USF Health (www.health.usf.edu) is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida's colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, the University of South Florida is one of the nation's top 63 public research universities and one of only 25 public research universities nationwide with very high research activity that is designated as community-engaged by the Carnegie Foundation for the Advancement of Teaching.
About the Journal of Alzheimer's Disease
The Journal of Alzheimer's Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 3.83 according to Thomson Reuters' Journal Citation Reports (2010). The Journal is published by IOS Press (http://www.iospress.nl).
Anne DeLotto Baier | EurekAlert!
Further information:
Further reports about: > Alzheimer > Disease > Leukine > Potter > USF > anti-inflammatory drug > cognitive impairment > health services > immune cell > mouse model > rheumatoid arthritis > signaling protein > toxic substance
A Map of the Cell's Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and "charge-density-waves" in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology
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All posts in Sport News
Australia Scored Record 263 Runs in T20
Pallekele, Australia and Sri Lanka played the first T20I match at Pallekele international cricket ground in which Australia beat Sri Lanka by 85 runs and lead the series by 1-0. In this T20I series, two matches are going to play …
Sarfaraz 21st Position up in One Day ICC Ranking
Dubai, International Cricket Council has issued the new ranking for the players in the ODI format of cricket. Pakistani wicket keeper batsman, Sarfaraz Ahmed has shown
Pakistan won 5th ODI against England 2016
Pakistan defeated England in the 5th and last ODI match of the series by 4 wickets but the hosts has won the ODI series
Pakistan Vs England T20 Pakistani Squad
The 13 member squad of Pakistan for the sole T20 match against England has been announced by the National Selection Committee. 7th September 2016 is the date for
Shahid Afridi Become Second Best All Rounder in T20
Shahid Afridi is the leading all rounder of Pakistan and he became the second best all rounder across the world in the T20 format of
Waseem Criticizes Bad Performance of Pakistan Cricket Team
Waseem Akram is the ex captain and leading swing bowler of Pakistan cricket team and she criticized over the bad performance of Pakistan cricket team.
Sarfaraz Ahmed First Century as Pakistani Wicket Keeper in Lords
London, Sarfaraz Ahmed is the leading wicket keeper batsman of Pakistan cricket team and he became the first wicket keeper batsman of Pakistan, who made century in the
Pakistan Team at Top in ICC Test Rank
Dubai, ICC has announced the new test ranking in which Pakistan reached at the first position in the test ranking and India is trailing at the
Rio Olympics Closing Ceremony 2016
The 31st Olympic Games are ended and the Olympic torch was put out in the colorful closing ceremony. During the ceremony, the beautiful firework was done
Pakistan Won First ODI Against Ire
Dublin, Pakistan is playing the one day international series against Ireland, which comprised of only two one day international matches and it is before the start of the


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Today didn't go as well as I would've expected it to be...
The horror.....
2 comments:
- Andre said...
so what actually made you left the mall earlier than you expected??is it because that cute guy ;p???
anyway, had the same problem, I just returned landed in amsterdam, my mobile went off, my atm got no cash init, can't use my credit card cause I need pincode to use it (never need a pin in Jakarta, but strange enough need it here, and seumur2 gak pernah tau)...Negotiate with the train officer to let me travel first and pay tomorrow, 30 minutes begging and she allowed me to take the train in the end ;p
- June 18, 2009 at 1:21 AM
- Nadia Juliana said...
Nooooo :p I met this guy when I was heading home :)
This guy was sooo metrosexual though, kind of a big turn down, since he's way more fashionable than I am hahahahah
Aww that's an interesting experience since you're not in your own country and having to 'ask' the train officer for a "free ride!" :p
Thanks for commenting :) :) :) I'll talk to you soon on MSN :D
- June 18, 2009 at 12:26 PM


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Explore Get Hut, Tiki and more!
Explore related topics
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#PinMyDreamBackyard My husband would be in grill heaven
Freshome.com Gabriela Simona- this would help with being landlocked with limited airline service!
Google Image Result for http://st.houzz.com/simages/19273_0_8-3865-tropical-living-room.jpg
Should I have my husband build this??
Perfect outdoor space just off the studio
☮ American Hippie Bohéme Boho Lifestyle ☮ Outdoor Swing Chairs
Pictures of Herringbone arbor and privacy screen from Atlanta Decking and Fence Company.
I want this


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This is Us: Celebration Service
One day each year we forego our usual Sunday plan. We celebrate new life, both earthly and spiritual. We get loud. (This includes whistles, wild cheers and our awesome Woo girls.) We pray and sing and eat and play together and enjoy this beautiful church family.
Pulpit Rock, you make us proud.
Remember a couple months ago when we spent a Sunday morning recognizing, honoring and praying for our law enforcement officers? We shared how, as a church, we are called to seek the welfare and flourishing of our city. Well. Be encouraged, church. One of the officers there that day recently sent us a letter we thought you should read…
The Avett Brothers and the Heart of Pulpit Rock
A recent concert at Red Rocks inspired Thomas to reflect on our tone at Pulpit Rock and how it shapes the way we talk about our opponents, ourselves and issues.
The Mess in "Us"
Being a part of an "us" is messy and awkward and painful. But that doesn't mean it's not worth it. We are seen and known loved despite our messy "us-ness.".
Surprised by Freedom
It takes years to recover from the subtle damage that spiritual control has on faith. That's why it's so incredible to me—even shocking—when I hear our leaders say from the pulpit that it's OK if we don't agree on certain tenets that are not primary to our faith.
We pray to see Colorado Springs flourish.
At Pulpit Rock, we are called to seek the welfare and flourishing of our city. We recently recognized seventeen men and women who are peacemakers in our city. It was a powerful time for the body of Christ at Pulpit Rock to stand in support of the law enforcement community in Colorado Springs.
Skip the Drive-Thru
Any person who has texted behind the wheel, stalked Instagram like a coveting neighbor, chased that first high, lied/cheated/stolen "just a little," drunk dialed, etc. etc. knows you shouldn't, but you do it anyway. This happened to me a mere few days ago.
The Joy of the Journey
I've been reading and thinking a lot about joy lately. Am I happier than I was a month ago? Probably not. But ever so slightly, I am learning to embrace the joy of the mission; the joy of the journey.
Every Thought Captive
Sometimes my thoughts take me captive instead of the other way around. I'm exhausted at my own bondage, and I am grateful at the true freedom that Jesus offers. But here's the bizarre thing: I don't always want to be rescued.
Questions On Joy
We asked you to send us your questions about joy. And many of you did. Thomas addressed some in his sermon, but let's continue the conversation here.


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Eva Macias-Moreton
More ideas from Eva
Oh lord there's a thing called FURNITURE SMUT? I've been blind TOT
"Let others wage wars; you, happy Austria, marry." Headcanon with uro-boros about Austria totally creeping on everyone else's kids. (by thesouschef)
oh my god. I am so weirdly attracted to this<<<Russia would put flowers in his beard
Attack on Titan and Princess Mononoke. Bertolt Hoover x Annie Leonhardt. I love this ship.
Levi attack on titan a choice with no regrets ova 2
Actually I went to Niagara Falls last year and learned that several decades ago a lady did this and took her cat with her XD
*That awkward moment when you don't know what it means*
Fun Stuff,Feminism,Canada,Hetalia,Artsy,Face,Lol,Funny
empress allura


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Ric Flair Reportedly In Hospital With Serious Medical Issue
Professional wrestling icon Ric Flair is reportedly in the hospital dealing with a "serious medical issue."
Professional wrestling icon Ric Flair is reportedly in the hospital dealing with a "serious medical issue."
WWE Hall of Famer George "The Animal" Steele passed away on Friday at the age of 79.
Longtime professional wrestler Jimmy "Superfly" Snuka passed away on Sunday. He was 73 years old.
Tonight during "Monday Night Raw" at The Smoothie King Center in New Orleans, an exciting announcement is expected to be made about "Wrestlemania XXXIV" coming to New Orleans in 2018.
WWE Live returns this January to the Cajundome in Lafayette this Sunday, January 8, 2017.
A total of 53 former wrestlers have sued World Wrestling Entertainment, claiming the WWE is responsible for head injuries suffered during matches that became more severe in later years.
Wrestling legend Jerry "The King" Lawler and fiancé, Lauryn McBride, are facing domestic assault charges after being arrested early this morning.
Former WWE star Chyna was found dead yesterday at a home in Los Angeles. Police are investigating it as a possible overdose.
"Survivor Series" is being held at Phillips Arena and is reportedly one of several targets for an ISIS-related attack.
WWE Hall of Fame wrestler Jimmy "Superfly" Snuka was arrested yesterday and charged with murdering his girlfriend Nancy Argentino back in 1983.


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|Story Views
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LAW AND ORDER: President Trump stood up for our law enforcement officers and pushed back against the rising tide of crime with three key Executive Orders.
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A LAW ENFORCEMENT LEADER: Jeff Sessions is an Attorney General Americans can trust to restore public safety to communities across the country.
HONORING AND LISTENING: President Trump has shown his commitment to law enforcement officers, thanking them for their service and discussing how to reverse rising crime.
FOLLOWING THROUGH: President Trump gave his commitment to the American people during the election that he would address public safety and lawlessness.
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text:
This is the Paxos Filesystem Server application
Spice Stellar Mi-508 smartphone was launched in August 2014. The phone comes with a 5.00-inch touchscreen display with a resolution of 480 pixels by 854 pixels.
The Spice Stellar Mi-508 is powered by 1.3GHz dual-core it comes with 512MB of RAM. The phone packs 4GB of internal storage that can be expanded up to 32GB via a microSD card. As far as the cameras are concerned, the Spice Stellar Mi-508 packs a 8-megapixel primary camera on the rear and a 2-megapixel front shooter for selfies.
The Spice Stellar Mi-508 runs Android 4.4 and is powered by a 2000mAh removable battery.
The Spice Stellar Mi-508 is a dual SIM (GSM and GSM) smartphone that accepts Regular and Regular. Connectivity options include Wi-Fi, GPS, Bluetooth and FM. Sensors on the phone include Proximity sensor and Accelerometer.
How to download Paxos FS Demo 3 form Spice Stellar Mi-508?
- Check the Android version to verify compatibility of Paxos FS Demo 3 with Spice Stellar Mi-508.
Find Android version: go to "Settings" - "About the phone" - "Android version". Make sure Paxos FS Demo 3 is compatible with Spice Stellar Mi-508.
- Click the download button to download Paxos FS Demo 3 in Spice Stellar Mi-508.
- Once the download and installation are complete, find Paxos FS Demo 3 in your home screen and tap the icon to open it.
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ASHSANPEDRO REYESpaxosfsEX


text:
Lyrics Depot is your source of lyrics to Monster by Rollins Band. Please check back for more Rollins Band lyrics.
Monster Lyrics
Artist: Rollins Band
Album: Get Some Go Again
I'm a monster
Walking these streets
Crawling these walls
Whatever it takes to get to you
It all starts and ends with you
Sometimes you hurt me but it's true
Don't want to love you but I do
I'm a monster
You touch me deep inside
Monster, monster from you I cannot hide
I'm a monster
No need to fear me
Crawl into my cave with me
Don't let this time go wasted
And I'm burning
Burning hard, burning real
Doing anything to feel
Something's gonna break before I'm done
Doing damage sounds like fun
Let's go out, let's go get some
Rollins Band Lyrics
Rollins Band Get Some Go Again Lyrics
More Rollins Band Music Lyrics:
Rollins Band - Alien Blueprint Lyrics
Rollins Band - Change It Up Lyrics
Rollins Band - Down And Away Lyrics
Rollins Band - Followed Around Lyrics
Rollins Band - Obscene Lyrics
Rollins Band - Spilling Over The Side Lyrics
Rollins Band - Turned Inside Out Lyrics
Rollins Band - Your Number Is One Lyrics


text: "There is nothing simpler in life than sandwiches and pies" thought Ryan Handel as he dreamed of the concept of @simplethingsrestaurant. Today simplethings reminds us to enjoy each moment - which is easy to do when you're biting into one of their delicious peach pies. 📍Los Angeles, CA #chownow #chownowla


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Transgender People
Usually, if you are male, you don't think about it much. It feels normal. And, for most girls, it feels very natural to be female. But that's not true for everyone. Transgender people who are male feel they should be female, and transgender girls feel they should be male.
People who are transgender feel like they're living inside a body that's all wrong for them. They often say they feel "trapped in someone else's body."
What Does It Mean to Be Transgender?
When you think of yourself as male or female, it's called gender identity. Everyone has a gender identity — the inborn sense of ourselves as being male or female.
Most people's gender identity matches their anatomy. But people who are transgender feel different from their physical appearances.
What society expects of us as men, women, boys, and girls also affects what we feel about ourselves. Every culture has "rules" about what is expected for men and what is expected for women. These expectations can include things like hairstyles, clothing, and jobs — and how people should act or behave.
Society doesn't have to state these "rules." Everyone knows them because we see them all over. So most of us grow up believing men should act a certain way and women should act a certain way without thinking about it much. Transgender people, though, have a very different sense of themselves.
Some transgender people know they feel "different" from the time they're young kids. Others start sensing it around puberty or even later. When people who are transgender become aware that they feel mismatched with their bodies, they may feel confused and emotionally conflicted.
Some people decide to physically change their bodies — through surgery or taking hormones — to match the gender they feel they really are. Physically becoming the opposite gender can be a long, complicated, and expensive process.
Not everyone decides to get surgery or hormones, though. Some transgender people are most comfortable keeping their physical anatomy but dressing as the opposite gender. Some aren't completely sure what they want yet, but may start by asking to be called a new name and use the pronouns that go with that name (such as "Amanda" instead of "Anthony" and "she" instead of "he").
Once transgender people start living their lives as the opposite gender, many issues may come up — like how to fill out forms that require checking "female" or "male," and even which public bathrooms to use.
As with any group, not all transgender people want or think the same things. It all depends on what that particular person needs to feel most comfortable in both body and mind.
Transgender Health
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Cherish Being Transsexual
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