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Impact of Early-Life Antibiotic Use on Gut Microbiota of Infants
Received Date: Sep 25, 2017 / Accepted Date: Oct 12, 2017 / Published Date: Oct 19, 2017
The human gut has a vast number of bacteria, which play a critical role in human health. At present, it is accepted that antibiotics have been one of the most common drugs in the world and early-life antibiotic use is associated with increased risk for several diseases. Antibiotic use during infancy will induce imbalances in gut microbiota, which is called dysbiosis. Therefore, more and more researches have been known about the impact of antibiotics on gut microbiota of infants. Here, we discuss some effects of antibiotics on gut microbiota and health of infants, including four types: structure of gut flora, metabolic capacity, diversity and stability of gut microbiota, risk of diseases. We also profile antibiotic resistance gene carried by gut microbiota and mechanism of intestinal drug-resistant bacteria. This article will also help provide recommendations for antibiotic use during infancy.
Keywords: Gut microbiota; Infants; Antibiotic resistance; Antibiotic resistance gene
Our microbiome, termed the second genome, comprises a vastly more significant number of cells and genes than those derived from the human gametes [1]. In healthy people gastrointestinal ecosystem, there are enormous and complicated bacteria, more than 10 trillion, called gut microbiota. Gut microbiota is often considered to be an important organ acquired by the human body, which is known as body's second brain [2]. It has been identified that our gut has nearly 9.88 million microbial genes [3]. Throughout the human lifetime, gut microbiota has a profound effect on all aspects of human health, such as protecting the host against pathogenic bacteria, promoting digestion and absorption of the host, drug metabolic and carcinogen, affecting the absorption and distribution of fat, regulating energy metabolism, regulating innate and adaptive immune systems and so on [4-10]. In a recent article, Vikram et al. reported that gut microbiota also promotes atherosclerosis [11]. And not only that, it has become evident that changes in the composition of the gut microbiota also have great physiological influence on people [12]. The type and number of gut microbiota are vulnerable to change by a variety of factors such as age, diet, antibacterial drugs and psychological pressure, causing imbalances in gut microbiota and diseases [refs]. Development of the intestinal microbiota in infants is characterized by rapid and large changes in microbial abundance, diversity, and composition [13,14]. Therefore, more and more attention has been given to the impacts of antibiotics on gut microbiota of infants. The gut of infants is sterile before they are born. At the time of birth, a variety of bacteria start breeding in infant gut. Originally, gut microbiota were mainly of Coliform, Enterococci and Clostridium. Five days later, Bifidobacteria occupied dominant positions. In neonates, the early development of the microbiota differs between antibiotic-treated and non-treated infants, but nothing is currently known about the long- term associations between lifetime antibiotic use and gut microbiota in infants. Furthermore, antibiotic resistance is of major public health concern globally and is expected to become an increasingly serious obstacle in the treatment of infections [15].
In this review, to better understand the impacts of early-life antibiotic use on gut microbiota and health of infants, we combine recent abroad pertinent literature. We describe the impacts of antibiotics from four aspects: (i) structure of gut flora, (ii) metabolic capacity, (iii) diversity and stability of gut microbiota, (iv) risk of diseases. We also discuss the potential effects of antibiotic resistance gene(s) carried by gut microbiota and investigate mechanism of intestinal drug resistant bacteria. This article aims to better understand effects of early-life antibiotic use on infants' gut microbiota and health take mechanism of intestinal drug-resistant bacteria into account and provide a reference for clinical treatment. Finally, the potential fields of further researches are prospected.
Antibiotic use disrupts structure of gut flora and metabolic capacity
In clinical treatment, antibiotics are a class of commonly used drugs. In recent years, experimental studies showed that antibiotics can destroy the structure of normal gut microbiota and change the functions [16,17]. In the study of Klemm and Dougan, they have found that antibiotics use led to remarkable changes in the structure of gut microbiota by phylogenetics analysis [18]. Antibiotics use during infancy is closely associated with the changes in the composition of gut microbiota which last for more than 6 months. To resolve the origin of gut microbiota and thoroughly research the possible impact of antibiotics use and other environmental factors on gut microbiota, a team of researchers from the Massachusetts General Hospital (MGH) and the Broad Institute selected a cohort of 43 U.S. infants and analyzed microbial development during the first 2 years of life systematically [19]. They identified multiple disturbances associated with antibiotic exposures, cesarean section, and formula feeding. What's more, experimental studies have proved that antibiotic exposures delayed microbiota maturation. Delayed microbiota maturation, as defined in healthy children, mirrors physiological disturbances in the host and occurs in mice exposed to antibiotics [20,21].
In a study at the University of Helsinki in Finland, Korpela et al. investigated 142 Finnish children aged 2-7 years (median age 5 years) who attended the same day-care centers at the time of the study to understand how the use of specific antibiotics can affect the intestinal microbiota in different ways [15]. The 16S rRNA sequencing data of the bacterial community obtained from the fecal samples showed that children's gut microbial community composition can clearly reflect the use of antibiotics and antibiotic use will slow down the development of microbial community [22,23]. Children who received macrolides, such as azithromycin and clarithromycin in early life had obvious changes in the gut microbiota composition and metabolic capacity. Specifically, the abundance of Actinobacteria, which included Bifidobacterium as the dominant genus, was reduced, whereas the abundances of the Gram-negative phyla Bacteroidetes and Proteobacteria were increased [24]. However, children who used penicillin didn't have such marked changes. Furthermore, the researchers found a positive correlation between overall lifetime antibiotic use and body mass index (BMI). The study results confirmed and extended previous results from mouse experiments and indicated that macrolide use may have detrimental effects on the developing microbiota of children, which may threaten the development of a healthy immune system and metabolism [20,25-27]. Generally speaking, the intestinal microflora can recover within 1 year after a macrolide course. However, if the child is repeatedly used in early life, the microbial community will not fully recover.
Antibiotic exposures impair the diversity and stability of gut microbiota
The balance between gut microbiota and the host immune system ensures the host health and homeostasis [28]. Recent research of Bokulich et al. has demonstrated that antibiotic exposures, cesarean section and formula feeding will significantly diminish the diversity and stability of gut microbiota [19]. In collaboration with a team of Finnish researchers they have worked with for several years, the Massachusetts General Hospital team enrolled a group of 39 children in 3 years [29]. During the study period, they collected their fecal samples and found decreased microbial diversity and increased shortterm composition changes in the gut microbiota of antibiotic-treated children [30]. In this case, low-Bacteroides children were even more obvious. Whole-genome shotgun (WGS) sequencing analysis also showed that, in antibiotic-treated children, bacterial species were fewer and tended to be controlled by a single strain, which was very different from that of the children who had not been exposed to antibiotics. With the elapse of time, many samples analysis revealed that the gut microbiota of antibiotic-treated children could become less stable, particularly around the period of antibiotic therapy. It has been a fact that antibiotics intensified the dysbiosis [31].
Another, published in 2016 by Finnish researchers, reported that antibiotic use, and macrolide use in particular, was associated with a long-term reduction in microbial richness [15]. Antibiotic-treated children still did not reach the level of the control samples even 12- 24 months after the course. Some aspects of the microbiota, such as the abundance of Bifidobacterium and Bacteroides and macrolide resistance, normalized within 12 months after a macrolide course. However, the abundances of Collinsella and Lactobacillus remained reduced for up to 2 years after a macrolide course.
Infants, particularly those born prematurely, represent an interesting population because they received early and often extensive antibiotic therapy in the first months after birth [32]. Gibson et al. recently demonstrated that children who had been exposed to antibiotic therapy had a dramatical reduction in the diversity of their microbial population. Meropenem, ticarcillin-clavulanate and cefotaxime treatments were associated with decreased species richness; gentamicin and vancomycin had variable effects on species richness [33]. One of the key motivations of microbiome research is that the microbial population of early childhood is crucial to human health because the decreased diversity of gut microbiota will cause some allergies and autoimmune diseases [29].
Antibiotic use increases the risk of diseases
Some previous studies have shown that antibiotic exposure in children had been associated with increased risk of immune system diseases, such as inflammatory bowel disease, obesity, diabetes, asthma and allergies [34-37]. It is generally accepted that gut microbiota have close relationship to these disease [38]. Alterations in gut microbiota composition and bacterial metabolites have been increasingly recognized to affect host metabolism in metabolic diseases such as obesity and type 2 diabetes (DM2) [39]. Short-term antibiotics use can lead to long-term disorder of intestinal flora, which will result in the occurrence or aggravation of the diseases [40].
The researchers have investigated the associations between antibiotic use and childhood asthma, allergies, and body mass index changes [41]. Small intestine bacterial and coliform have a great influence on weight-regulating system and glucose homeostasis [42]. Another team discovered that macrolide use was positively relevant to asthma and overweight [15]. The possibility of suffering from asthma and overweight on children who had frequent macrolide use during the first 2 years of life increased significantly. In addition, the overweight children with asthma had unique microbiota. Odds ratio for the group that received 42 macrolide courses compared with the non-exposed was 6.11. Other results showed that macrolide use in childhood is associated with long-term distortions in the composition, function and antibiotic resistance of the intestinal microbiota.
Early exposure to antibiotics has been an important reason which causes childhood obesity [43]. Paolella and Vajro proposed three methods to cope with the impact caused by antibiotics: First, a more judicious use of antibiotics and for instance, the use of narrowerspectrum molecules for simple bacterial infections would surely be advantageous. Second, increase intake of ω-3 fatty acids. Finally, administration of prebiotics or probiotics is another possible strategy in this setting [44].
Gut microbiota carried antibiotic resistance gene
An increased incidence of antibiotic resistance genes observed in antibiotic-exposed children after treatment [29]. The presence of antibiotic resistance genes rose sharply and rapidly during antibiotic treatment and then declined swiftly after antibiotic therapy, whereas the antibiotic resistance genes still presented after antibiotic therapy discontinued for much longer periods of time. More interestingly, the researchers also observed that some children harboured antibiotic resistance genes as early as 2 months of age, before any antibiotic treatments. In recent report, researchers from Washington University School of Medicine (WUSM) demonstrated that gut microbiota in healthy American children also carried a large number of antibiotic resistance genes, likely to make harmful effects [32].
Nonetheless, to date, it has remained unclear where antibiotic resistance genes originated. Some previous studies have determined that some new-born infants harboured antibiotic resistance genes, potentially acquired from their mothers before their birth [45,46]. However, the reason for the increased abundance of antibiotic resistance genes is still unknown. Here are the possible explanations: (i) response to antibiotics passed on to the child from the environment (for example, mothers' breast milk), (ii) a response to a natural antibiotic molecule produced by other gut bacteria, (iii) pre-existing presence of the antibiotic resistance gene in the genomes of some early inhabitants of the gut [47], (iv) the spread of antibiotic resistance through natural populations due to widespread use of antibiotics [29]. Additional studies will be needed to find out the exact reasons for the early presence of antibiotic resistance genes in the gut microbiota of infants. Furthermore, it is particularly significant to understand the effects of childhood antibiotic exposure on the presence of antibiotic resistance genes.
Mechanism of intestinal drug resistant bacteria on infants
The incidence of antibiotics-resistant genes rises rapidly during antibiotic treatment then drop quickly after treatment was discontinued. But resistance genes encoded on small DNA molecules called mobile elements, one means by which resistance genes can be transmitted among bacteria, persisted much longer after antibiotic withdrawal [29]. After macrolide antibiotics treatment, in the infants' body, macrolide antibiotics drug resistance increased rapidly, namely, macrolide antibiotics promoted the production of antibiotic resistance. Based on the metagenomic analysis, one recent study discovered that macrolide resistance was high in the recently macrolide-exposed gut microbial, and bile-salt hydrolases were reduced [15]. Bile-salt metabolism (BSM) is an important function of intestinal microbes, which influences energy and metabolism of the host [48]. Frequent antibiotic intake will accelerate the production of antibiotic resistance in infants, particularly those born prematurely, because they received early and often extensive antibiotic therapy in the first months after birth [32].
Brief summary and Future prospects
Gut microbiota plays an important role in nutrient absorption, immune system development and metabolic homeostasis of the human body [49,50]. Antibiotics are among the many factors that influence the development of the microbiota and health [51].
In recent years, the research on gut microbiota of infants, particularly antibiotic-treated infants, has received more attention. Antibiotics use is detrimental to host health in the short and the long-term. In this review, to better understand the impacts of early-life antibiotic use on gut microbiota and health of infants, we showed: (i) antibiotics use leads to remarkable changes in the structure of gut microbiota and metabolic capacity, (ii) antibiotic exposures impair the diversity and stability of gut microbiota, (iii) antibiotic treatment increases the risk of diseases, such as inflammatory bowel disease (IBD), obesity, diabetes and asthma, as well as allergies, (iv) antibiotic resistance genes rise sharply and rapidly during antibiotic treatment and then declined swiftly after antibiotic therapy, whereas the antibiotic resistance genes still presented after antibiotic therapy discontinued for much longer periods of time. Meanwhile, we also investigate mechanism of intestinal drug resistant bacteria from some recent researches.
Because antibiotics are frequently used during the first critical years of gut microbiota development. Antibiotic use during childhood is prevalent in most parts of the world [52]. The average U.S. child receives about three courses of antibiotic by the age of 2 and 10 courses by the age of 10 [53]. Furthermore, the effectiveness of antibiotics has been weaken since they were introduced into modern medicine more than 70 years ago [54]. One important consequence of antibiotic usage is the spread of antibiotic resistance genes, which is a serious public health issue. Antibiotic resistance is of major public health concern globally and is expected to become an increasingly serious obstacle in the treatment. In an earlier review, it was shown that, on present trends, the annual global death toll from bacterial resistance would be more than ten million, a figure more significant than that die from cancer [55]. Furthermore, bacteria, viruses and other microbes will again evolve resistance [56]. It has been demonstrated that macrolide use promoted a marked increase in macrolide resistance of the microbiota [15]. And worse still, abuse and misuse of antibiotics make antibiotic resistance give birth to the 'super bacteria' [57,58]. In one study on Mycobacterium tuberculosis, the causative agent of tuberculosis, Warrier et al. [59] have discovered a novel bacterial drug resistance, antibiotic inactivation via N-methylation. Nevertheless, it is not clear whether this new drug resistance mechanism is widely present in bacteria, and how to inhibit bacterial drug resistance [58,59]. Currently, the UN General Assembly High-Level Meeting of Heads of State discussed sustainable access to effective antimicrobials in September, 2016. International scientists advocated awareness about lack of access to antibiotics and drug resistance [60].
Despite widespread use of antibiotics in children, the effects of antibiotic. With our growing appreciation of gut microbiota's role in human health and how to maintain healthy gut microbiota, it is particularly critical to understand the short-and long-term effects of antibiotic treatments on the gut microbiota. As we look to the future, additional studies will be needed to find out the effects of childhood antibiotic exposure on gut microbiota and health. Last but not least, little is currently known about mechanism of intestinal drug resistant bacteria in infants, but, it's certainly the case that antibiotic use will have a significant impact on gut microbiota of infants. Therefore, to better understand the health implications of early-life antibiotic use, mechanism of infant's intestinal drug resistant bacteria is another issue that requires further investigation and prompt attention.
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Citation: Hong YW, Si TS, Zhen YY, Xiu YW, Guo ZW (2017) Impact of Early-Life Antibiotic Use on Gut Microbiota of Infants. J Microb Biochem Technol 09:227-231. DOI: 10.4172/1948-5948.1000369
Copyright: © 2017 Hong YW, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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text: Lazaro, We should reach out to Natalie Cole, Gladys Knight, Chaka Khan, etc., to do just that. Grady Tate is an elder jazz master who could speak eloquently about these topics too. I've heard him do so at the Jazz Museum in Harlem's "Harlem Speaks" dialogue series. Quincy Jones would be perfect also. The star power of Marsalis, Redman, McBride and the big star wattage of Latifah was definitely a part of my reason for choosing them as an entry point. Their relative youth was also a factor for me. Yet more important, inside the critical community of jazz writers and programmers, is the range of ideological perspectives they represent. No one with ears to hear will deny Redman's or McBride's jazz chops. Yet both are more open than Wynton to experimentation with electronic instrumentation, playing fusion-influenced styles, and performing with MCs and others connected to hip hop. Joshua and Christian are both highly intelligent and can articulate their views well. Wynton ain't budging re: his stance on hip hop, and like him or not, he expresses his ideas well too. Latifah serves as a bridge between hip hop and jazz, and, I suspect, between the viewpoints of these three gents. So they'd cover a range of positions, speak with due respect and civility to one another and the audience, and then perform together. The effect could be dynamic: not only would Oprah's audience of millions hear high quality jazz among some of the best on their respective instruments, they'd see Latifah sing and swing with them, and, say, Lewis Nash on drums and Mulgrew Miller on piano. The dialogue wold move them from the role of "entertainer" and into the realm of public discourse. And the performance, if done well enough (w/that personnel, how could it be anything but?), will ascend to aesthetic heights rarely heard by Oprah's audience. This would be good for the music. We should surround and inundate Oprah with the request for her to have jazz on her show. It would certainly be fine if other talk show hosts like Jay Leno and David Letterman would feature jazz musicians, but since Oprah opened a dialogue about negative words and images in popular culture, her top-rated show would be a great place to begin a sea change in the recognition and appreciation of the intellectual brilliance and artistry of jazz musicians. Greg Thomas Host/Co-Producer www.JazzitUptv.com ---------------------------------------------------------------------- Message: 1 Date: Tue, 1 May 2007 08:36:32 -0400 From: "Lazaro Vega" <wblv.wblu.fm at gmail.com> Subject: Re: [JPL] An Open Letter to Oprah: A Jazz Alternative To: "Jazz Programmers Mailing List" <jazzproglist at jazzweek.com> Message-ID: <3862cff90705010536m6d3caee8v723b9aa2aeefa98f at mail.gmail.com> Content-Type: text/plain; charset=ISO-8859-1; format=flowed The star aspect is certainly her bag -- we're talking Harry Connick type star power. Greg's letter was wonderful; and Jae's ideas are right on, too. How easy/hard would it be convince Natalie Cole or Knight to "go to bat" for jazz with O?

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'When their breath enters a room before they do': People share their nightmare roommate stories that will make you want to live alone forever
From poor hygiene to letting filthy dishes stack up and being late with rent, hell really is living with other people.So when one Reddit user asked if there were any 'red flags' for roommates, the web went wild with warning signs to look out for - and each had a horror story to tell.From the man whose mother cooked all his food and cleaned to the woman who turned out to be a heroin addict, these tales will make you yearn to live alone. From poor hygiene to letting filthy dishes stack up and being late with rent, people can ...
The five crucial things the most successful people do in the first hour of their day (and YOU should too!)
Did you know that how you choose to spend the first hour of your day can set you up for either glory or failure?According to experts, the most successful people in business do five things every single morning that sets them up for a productive day - and you should follow their lead. Lee Biggins, founder and managing director of CV-Library, said: 'When it comes to staying productive and setting yourself up for a successful day, it s important to make sure that you re energised and focused on what you want to accomplish.' Here, he shares five golden things ...
Are these the world's WORST mums and dads? Photos of people failing at raising their children will make you feel like parent of the year
There are thousands of books, guides and lectures about how best to raise your children.But these parents put anyone else's insecurity to shame with their wince-inducing mistakes and mishaps when it comes to bringing up their offspring.From going to the toilet with a daughter on their shoulders to taking a steamy selfie as their child looks on in the background - these hilariously tragic pictures are bound to shock. Spider-boy? This young boy was plastered to a door with gaffer tape - although he seemed perfectly happy about it One alarming photo showed a young boy with a bottle of ...
Why you should NEVER ask your partner how many lovers they've had (and why the number might mean nothing anyway)
It usually happens about two months in.You're snuggled up after a great sex session and the thought pops into your head, uninvited, and lingers: How many times have they done this before?The 'how many before me' question is undeniably interesting.You're curious about other areas of your partner's life, why wouldn't you be curious about their sexual past? The question 'how many before me' is undeniably tempting and usually happens around two months in But think twice before you actually ask this loaded question.What will you gain by knowing the answer? In my opinion, very little.Numbers mean nothing without knowing the ...
When signs go wrong: Hilarious photos capture the world's most ironic messages
Many will argue that there is no such thing as coincidence but these incredibly well timed photos make that hard to believe.Netizens have been sharing their most ironic photos online with the contradictory photos making it hard to believe that they weren't staged. From packaging that does anything but sell the product to buildings of which architects are sure to regret constructing there is a baffling amount of irony in these pictures. Netizens have been sharing their most infuriatingly ironic photos such as this one of a job that was not so well-done Pets have proven to be the kings ...
Is THIS Britain's poshest takeaway? FEMAIL tries Deliveroo's Michelin-starred restaurant meal service for the ultimate al desko lunch - with impressive results
Takeaways are synonymous with pizza, curry and Chinese - not exactly fine dining.But Deliveroo is hoping to change that impression by partnering with a Michelin-starred central London restaurant to deliver some of the capital's finest food direct to homes from this evening.The service has teamed up with Galvin at Windows in exclusive Park Lane - where Fred Sirieix from Channel 4's First Dates is general manager. But can high end food really retain its quality when it has been packed into delivery boxes, put in a bag on the back of a motorcycle, and whizzed through central London?FEMAIL's London-based food ...
Meet the great-grandmother with GUNS! Bikini clad 70-year-old shows off her muscles after training six days a week for bodybuilding competition... which she won
Many 70-year-olds may be spending their days in relaxing retirement, but not Mary Clayton.The great-grandmother from the Sunshine Coast gets to the gym at 4.30am six days a week to train for bodybuilding competitions. Her hard work has paid off too, as she won the over-60s section of the International Natural Body Building Australia Queensland Titles and is heading to the national titles this weekend. Great-grandmother with guns: Mary Clayton (above) is a 70-year-old bodybuilder First place: Ms Clayton won the over-60s title at the Queensland International Natural Bodybuilding competitionMs Clayton spent four months training for the competition, eating smaller ...
Goldsmith's wife breastfeeds her daughter while wearing a 3,700 Gucci gown at her sister's wedding
Jemima Jones had no compunction about feeding her three month- old daughter Eliza at her sister s wedding in Venice, ItalyBreastfeeding in public has long been a point of contention, with some mothers more relaxed about the practice than others.As my picture shows, the glamorous wife of millionaire financier Ben Goldsmith, health food caterer Jemima Jones, had no compunction about feeding her three month- old daughter Eliza at her sister s wedding in Venice, Italy.The former model, 29, nursed the tot while wearing a 3,780 Gucci pink floral maxi-dress on the steps of a public building.The photo was shared ...
'My mind plays tricks on me and says I m disgusting': Fit mum of twins with a six pack just nine months after giving birth shares clip to prove that she struggles with post-baby 'flaws'
Anna Strode, 32, shot to fame after showing off her incredible abs just nine months after giving birth to twin boys.The Melbourne-based mother wowed her 57,000 Instagram followers as she transformed her figure with simple 20 minute workouts that could be incorporated into daily life.But despite inspiring thousands of mothers, Ms Strode has shared a video to prove that even she struggles with body confidence... despite knowing she shouldn't. Proud mum: Anna Strode, 32, shot to fame after showing off her incredible abs just nine months after giving birth to twin boys Glowing: The Melbourne-based mother wowed her 57,000 Instagram ...
Meet the wives who tell their friends EVERYTHING about their sex lives... and their mortified husbands who wish they'd just shut up
For most of us, there are certain things which are always best left undisclosed. Your annual income, for one. Not to mention your feelings about your mother-in-law.And, of course, the true state of your sex life. What goes on between the sheets should stay there. Shouldn t it? Not according to a new breed of unabashed middle-class women who thrive on divulging the most intimate details of their sex lives- not only with their friends but, in some cases, even with their mothers.And these are no loud-mouthed ladettes. Rather, they re wives and mothers holding down responsible jobs, who pride ...
That's a very fashionable feline! Tiny kitten that was saved from Hurricane Matthew is adopted, as pictures of it wearing a warm SWEATER made from a sock took the internet by storm
In times of need, people are always willing to go above and beyond - even for the smaller, fluffier members of our families. After being rescued from Hurricane Matthew in Raleigh, North Carolina, one little kitten was lucky enough to meet some wonderful animal lovers who not only saved him life, but turned him into an online sensation. The cat was brought in from the storm to Petsmart's Banfield Pet Hospital after being found, and to help warm up the adorable baby, the staff fashioned him a teeny tiny sweater made out of a sock. Sweet sweater: A kitten rescued ...
The student who was PAID to party: Woman, 21, reveals how a clothing brand flew her to the US to spend her summer socialising with the super rich
A student was given the best summer job after a clothing company flew her the US to wear their clothes and party on yachts.Ella Crockett, who's in her third year at Newcastle University, won the job as an ambassador for fashion brand Jack Wills.She was shipped out to Nantucket Island on the east coast of the USA and told to promote the label among super rich kids. Ella Crockett, pictured with a friend, chronicled her summer of partying in Nantucket on her social media She was flown out to America and paid to be a clothes horse and party on ...
'I could barely breathe because of the smell': Model who wore a raw MEAT dress tells how it decomposed on her body during a photoshoot
A top model who wore a dress made of raw meat for a magazine photoshoot has admitted that it started to smell disgusting after a few hours under the hot studio lights.Yulia Kaunova, from Russia, wore the unusual dress for a shoot for the Maxim international men's magazine in Russia's second city of St Petersburg.Designer Natalya Fadeeva sewed slices of raw beef together on Ms Kaunova's body in the studio dressing room to ensure the garment was as fresh as possible. Russian model Yulia Kaunova posted a picture of her raw meat dress for a shoot for the Maxim international ...
It's Meccano Mickey! Kate makes friends with a ROBOT as she visits a workshop project in Rotterdam before jetting home to William
She may have been without her beloved husband Prince William during her trip to the Netherlands but it seems that the Duchess of Cambridge had no trouble making friends in Rotterdam this afternoon - even if they were made of plastic. Kate, 34, was pictured shaking hands with a robot constructed form Meccano in Rotterdam where she went to learn about Bouwkeet, the social Makerspace of Bospolder-Tussendijken.The Duchess was performing her first solo engagement abroad today but seemed to have no trouble in getting acquainted with both the people of Holland and their robot friends. The Duchess met with youngsters ...
Queen M xima of the Netherlands dons a 2,000 Givenchy dress in her native Buenos Aires - as her husband makes friends with Kate on the other side of the world
Her husband may have been more than 10,000km away making friends with the British royals.But Queen M xima didn't seem fazed at missing out on the fun as she attended a series of solo engagements in Buenos Aires on Tuesday.The stylish royal, who is married to King Willem-Alexander, looked in her element in the Argentinian capital - which is also her birthplace - as she threw on an eye-popping green leopard print dress. Queen M xima was all smiles as she attended a series of engagements in Buneos Aires on Tuesday. The Dutch royal opted for a 2,000 Givenchy dress ...
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Roomi is looking for experienced Android engineers to join our engineering team in SF and NYC to help build the Roomi Android app.
You must have made significant contributions to a popular (1000+ reviews) Android app.
- 1-3 years of experience building Android apps – Someone who has developed beautiful, useful apps that are live in the Google Play store. An engineer who's comfortable handling plenty of responsibility and can see a project to completion with minimal help and intervention.
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About Roomiapp
Roomi is re-inventing the roommate search by prioritizing the person as much as the place and price. Our free, mobile app simplifies the roommate search with straightforward tools. Instantly post and find rooms. Make meaningful connections based on shared values, common interests, and compatible lifestyles. Roomi is there for you before, during and after the move, helping you feel at home as part of our dynamic, co-living community. By helping people live better together, Roomi is changing the world, one shared home at a time.


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ORL-5FA Aligning Lamination Device After dispensing Optical Resin is a 1-by-1 system device which aligns and laminate such as LCD and the touch sensor after the optical elasticity resin is dispensed at high accuracy such as.
Accuracy of lamination±1μm
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|A highly accurate alignment is possible according to the combination of special lens, digital CCD camera and the picture processing
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|55mm×41mm - 110mm×83mm
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|60 seconds with the 3.5 inch panel as specified
|Accuracy of lamination


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Diamond plates are available in various plate sizes (from credit card to bench plate size) and grades of grit. A coarser grit is used to remove larger amounts of metal more rapidly, such as when forming an edge or restoring a damaged edge. A finer grit is used to remove the scratches of larger grits and to refine an edge. There are two-sided plates with each side coated with a different grit.[14]
I would say they are worth the money. Go for it. I took a blunted Pampered Chef kitchen knife from completely dull to razor sharp in about an hour (of bumbling and repairing mistakes LOL) heavy grinding. If you have a severely damaged blade, grab one of those cheesey two sided stones from Harbor Freight to do your heavy grinding. From there these stones will work very well.
Just to prove that we're not merely sharpening geeks, here's an interesting side note. The word whet pops up in some unexpected places. A small species of owl is called the saw-whet owl because the sound it makes reminded people of the sound made when sharpening a saw with a file. And the phrase "to whet your appetite" comes from the idea of your hunger growing sharper at the thought of food.
This coarse grit whetstone is great for prepping old and dull knives that need to be sharpened with a fine grit stone. One of my good knives edge looked like someone had tried to chop barbed wire. After ten minutes on each side of the stone, the edge was smooth and free of imperfections. After it hit the knife with the fine grit stone, I was cutting onions and apples like hot butter! I would soak this stone for 12-24 hours before using. It sucks water like a sponge. The surface needs to be damp when you sharpen.
Removing the burr is fairly simple. You'll need a leather strop or block (this sort of thing), which is designed to catch the metal fibres from the knife. You could do it with a fibrous tea towel or some newspaper if you like, but I'd suggest going with leather to begin with. The motion is fairly similar to sharpening. Draw the knife over the leather, going away from the edge at roughly the same angle as when you sharpened.
Table mounted device – Typically the manual powered table mounted sharpener looks virtually identical to the electric powered sharpener with a slot for each stage. Where they differ is that each slot in the manual powered sharpener has only one groove and you pull the blade through this groove toward you to sharpen the blade. Once the blade is sufficiently sharp you place it in the honing groove to refine the edge and pull it toward you again several times. If there is a third, cleaning, stage you repeat the process for that stage as well.
The composition of the stone affects the sharpness of the blade (a finer grain, usually, though not always, produces sharper blades), as does the composition of the blade (some metals take and keep an edge better than others). For example, Western kitchen knives are usually made of softer steel and take an edge angle of 20–22°, while East Asian kitchen knives are traditionally of harder steel and take an edge angle of 15–18°. The Western-style kitchen knives are generally in the range of 52–58 on the Rockwell scale, which denotes the relative hardness of a material.
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The unique three stone system features a 6" medium Arkansas, 6" fine Arkansas and 6" coarse synthetic stone mounted on a molded plastic triangle with handles on the end for easy stone selection. The sturdy molded plastic base has non-skid rubber feet for safety, a V-shaped trough to catch oil drippings and easy-to- read stone identification markings.
All stones require either water or oil as a lubricant to sharpen the knife. We prefer water stones because they're easier to use, less messy and don't have the possibility to go rancid like oil does. If you choose a water stone, all you have to do is either add water to the stone before placing the knife on the surface, or soak the stone in water for 10 minutes before use. You'll want to read the instruction for the stone you purchase to find out how to use it properly.
You want sharpening stones that will be useful for the majority of your edges now, and that will remain useful as you expand both your tools and your sharpening toolkit in the future. Ending up with duplicate stones or ones that are no longer useful as you gain new knives or tools is a waste of money. The goal is to start with something that will stay with you as your needs develop.
You might not need to spend hundreds of pounds to get the best knife sharpener, but you do need to know what you're doing. Warner gave me a crash course in the technique. As a newbie to this method, it took a while to get used to (especially since Warner handed me a knife that had never previously been sharpened) but after half an hour's practice and a little encouragement, I got the hang of it. Here's what I learned...
Again, burr formation is critical to success and if you are using a 1,000 grit stone on a dull knife, you may be there for a while but it will form. If you are grinding on one side for more than 3-4 minutes, flip the knife and work the opposite side, always feeling for a burr with your thumb on the opposite side to which you are working on. Remember, the fatigued metal is being forced down the blade towards the edge of the edge by your actions and the abrasive properties of the stone.
Since 1814, knives bearing the Wusthof name and the Trident logo have been crafted in the world's "Cutlery Capital" of Solingen, Germany. Today, in a state-of-the-art facility, that tradition of quality is ensured as old-world craftsmanship meets twenty first century production methods. Knives are amongst the most important kitchen implements and should therefore always be kept sharp. Yet even the sharpest blades will go blunt at some point! When this happens, the blade will need to be sharpened again quickly. Professional chefs swear by using a whetstone for sharpening. This particularly gentle and effective way of sharpening is becoming increasingly popular with knife connoisseurs and yet there is always the issue of achieving the correct angle. After all, when sharpening on a whetstone, the knife must always be held at precisely the right angle to the stone, otherwise you will get an uneven cutting edge. The new slider from Wusthof ensures this can no longer happen and is also exceptionally easy to handle. The knife is simply placed on the wedge-shaped slider with its structured silicone surface and then pulled gentle over the whetstone. The pre-set 14° angle ensures that the knife always maintains a consistent angle - from the tip to the end of the blade. The soft silicone surface prevents the blade from getting scratched. The underneath of the slider has two ceramic strips on the bottom to ensure it glides smoothly over the whetstone. The ergonomic shape of this practical sharpening aid fits nicely in the hand and will be much appreciated for its ease of use. Even for those without any experience, this new product is just the thing for effortless sharpening using a whetstone.
The little white pieces don't seem to damage my stones, though I am careful to apply the bulk of my pressure to the blade edge. They ride back and forth just fine. There is a little bit of an art to finding the right movements so the jig doesn't fall off the side of your stone but you can still use most of the stone. It's sort of angled down and away from the top corner to the opposite bottom corner
The most important aspect of a sharpening stone is the grit. If you have knives that have taken a beating and are either nicked up or really dull, you'll need a courser stone to get it back into shape. And in order to put an exceptionally sharp edge on an already sharp knife, you'll need a finer grit stone. If your knives are already in pretty good shape and just need a touch up, buying just a finer grit stone might be enough, but don't think you can get away without a courser stone for knives that need more TLC. It is possible to buy a combination, or two-sided sharpening stone.
If you don't have a problem with the water-lubrication system in your working environment, Waterstones is the most common and affordable models to obtain. They are available in various abrasive grit grade from coarse to extra fine mesh. They generally made by Aluminum Oxide, which provides faster cutting. The downside of the Waterstone, they wear down more quickly as the impact of the old abrasive materials that break the stone itself. It is why Waterstone requires frequent flattening to keep it evenly. It is recommended you have one of diamond stones to help you for regular flattening become easier.
However, due to limited natural deposits and extensive quarrying over the centuries, true, high quality, Japanese water stones are now few and far between and are very expensive. Thus, various companies are now producing synthetic Japanese Water Stones which generally have a more consistent composition and grit size than natural stones as well as often begin somewhat harder and thus, lasting a bit longer; not to mention being cheaper to purchase.
Cost – While you can get a perfectly serviceable sharpening stick or stone sharpener for short money and some very high-quality tabletop manual 2 and 3-stage sharpeners for less than $50, high-quality mechanical systems will often run you $200 or even more. While that's not so much money it's likely to impact the quality of your life it is a lot to pay to keep a decent edge on your knives. While how much you ultimately pay for a sharpener is entirely up to you, you may want to consider your commitment to cooking and how often you are actually liable to use the device. If this is your first sharpener you might also want to consider learning how to sharpen a blade using a classic stick or stone sharpener first, before deciding if moving up to a mechanical sharpener is the right thing for you.
A single stone of 120 grit and a combination stone of 1000 and 3000 grits come along with a stone holder all for a price of less than many other individual stones. The stones are 6 7/8" long and 2 1/8" wide. A flattening stone of some kind would be needed, but with economical options available in those, the overall price of this kit would still be low. This entry level set is a good budget minded option.
Method 1: Use an Electric Sharpener. Quality electric sharpeners are an option, but I strongly discourage their use. First off, they remove a tremendous amount of material from your edge. Sharpen your knife a dozen times, and you've lost a good half-centimeter of width, throwing it off balance, and rendering any blade with a bolster (i.e. most high-end forged blades) useless. Secondly, even the best models provide only an adequate edge. If you don't mind replacing your knives every few years and are happy with the edge they give you, they'll do the trick. But a much better choice is to...
As you see in the pictures, it is always very important to keep same angle of about 10' to 15', which is about two coins height between the blade and the whetstone. Gently push the point you want to sharpen with your first, second and third fingers. While keeping the angle and pushing the point with your fingers, stroke the blade until it reaches the other edge of the whetstone. Then pull the blade back until it reaches the edge of the whetstone. This back and forth is counted as one stroke. Repeat it for about five strokes until you can see or feel some small burrs (edge curvatures). Then move the position of your fingers to where you have not sharpened yet, and repeat this five strokes of sharpening processed from the tip to the base of the blade.
Unfortunately, the arrays of modern whetstone can be bewildering to the inexperienced sharpeners that so often times many of them end up with a crap or wrong decision on stone type for their utensils. The most difficult to determine is whether the whetstone is fake or fabricated with low quality of materials. To avoid this you can only go for the reliable brand of a whetstone.
Diamond sharpening stones are becoming really popular because of their ability to cut fast. We tend not to recommend diamond sharpening stones/plates because a lot of damage can be done very quickly. Also diamonds are pretty sharp and at arato level they leave deep scratches in the blade that need to be polished out quite aggressively. Diamond stones can be used with and without lubricant.
In summary: Peter Nowlan is a professional knife sharpener based in Halifax (Canada) and he recommends the KnifePlanet Sharpening Stone Set, a beginners and intermediate kit that includes 4 sharpening grits: 400/1000, 3000/8000, a bamboo base and the KnifePlanet Flattening Stone. The Japanese Naniwa 3-stone combination is also a great (and more expensive) choice, ideal for professionals and more advanced sharpeners: the Naniwa stones are slightly bigger compared to KnifePlanet's. In both cases, a coarse, medium and fine grit combination is very effective to sharpen and refine the edge:
Prior to using any kind of sharpening stone, it is advised that individuals soak the sharpening stone in light machine oil or household oil for at least 12 hours before being used. Before being used, it is advisable to wipe the surface of the sharpening stone to get rid of grime, grit or dirt that may have accumulated overtime during the time of storage.
This is a good size stone and has the two different grits needed for knife sharpening. No instructions were included, but there are many websites with written and video instructions, so this is not an issue for most people. A fair amount of dust is generated during the sharpening process, so protect the work surface and wash the knife after sharpening is completed.
This package includes a bamboo base to hold the stone, a premium quality whetstone (#1000 / #6000), a simple instruction manual, a knife sharpening angle guide and a detailed eBook that will help the beginners to learn the basic and advanced tips about effective knife sharpening.This special stone has versatile uses. You can use it to sharp scissors, kitchen knives, hunting knives and pocket knives too.
The double sided 400 and 1000-grit Water Stone Sharpening Block by Whetstone enables you to safely and easily sharpen and polish your kitchen cutlery, hunting or pocket knives, blades and razors. You can even use it for your gardening tools! This stone only requires water, no oil needed! Made with durable green silicon carbide, this honing tool will last for years to come.
The DuoSharp Plus stones are nicely sized at 8" long by 2 5/8" wide and have two grits on each stone to maximize value. The Plus in the name refers to an area of continuous grit in the otherwise interrupted grit surface of the stone. This area is for sharpening edges with fine points that might be difficult on the interrupted surface. A coarse/fine DuoSharp Plus stone is a good single stone to start a sharpening toolkit.
I bet those Vikings, relatives of mine no doubt, never had it so good. They never had surated blades to sharpen or needed to wear cool things around their necks to woo the women (they just grabbed them by the hair I guess). I love my stone. So useful and beautiful. I always have spit to wet it with, and I always have a way to sharpen my tool. Wazoo makes high quality products. I give them the highest rating I have. Dudes!
However, due to limited natural deposits and extensive quarrying over the centuries, true, high quality, Japanese water stones are now few and far between and are very expensive. Thus, various companies are now producing synthetic Japanese Water Stones which generally have a more consistent composition and grit size than natural stones as well as often begin somewhat harder and thus, lasting a bit longer; not to mention being cheaper to purchase.
Everten is Australia's leading online kitchenware retailer. A passionate Australian family business, we pride ourselves on having the best range available, stocking over 10000 products from the world's leading brands matched with the best service. As the very first online kitchenware retailer to become a Google Trusted Store in Australia, you know that you can trust us to deliver quality kitchenware at unbeatable prices with full product warranties to your door for just a flat rate of $8.90 anywhere in Australia. Read more about us


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Diamond Back
Diamond Back's sound is as prolific as Dream Theater with the punch of Tool. The songs vary from long epic adventures to hard-hitting shorter bites. In general, it's heavy.
In a music industry filled with much hype but little delivery comes a band that just doesn't care. Diamond Back, out of Ottawa, Ontario, is a hard rock band that focuses on writing good music, rather than trying to impress a very cliquey group of scenesters. The band has been perfecting their craft waiting for the right day to come storming out.
The lineup consists of Greg McLaughlin, on lead vocals and guitar, Derek Feltmate on guitar, Fahim Rahman on bass and Liam McLaughlin on drums.
Diamond Back's main songwriter, Greg McLaughlin, lists Daniel John, John Mayer, Maynard James Keenan, Phil Collins and Stevie Ray Vaughan as his influences. The sound of the band has been compared to Metallica, Rush, Tool and Godsmack.
Written By: Greg McLaughlin
I begin to remember what it feels like
Breathing for the very first time
It's not like it matters, but when the wave hits
I'm reminded how I'm still alive
But slowly I fade into the tide
Dragged in by the sirens calling my name
"Come in deeper"
I'm sinking faster than before
Not like death, it hurts a bit more.
I drag my feet into the water
Lifeless, breathless and mindless, I know who's there
I'm underneath the tide
Dragged in by your voice, it's calling my name
"Come in closer"
I'm sinking faster than before
Not like death, it hurts a bit more.
I can't let go of this
The irresistable way you taste
I'm drowning faster than before
Not like death, this hurts too much more.
I'm drowning faster than before
Not like death, I can't let go.
White Stains
Written By: Greg McLaughlin
Verse 1:
I can't
get these
thoughts from my mind.
I burn
for this love
and thinkin about...
you want this.
Oh, the things that you say...
Are turned around instead.
The magick (perversions) of your (my) ways,
the white stains in my head.
Verse 2:
I want
to give up
my lust for you.
I try
to confess
my gift for you.
You want this.
Hey lady
won't you understand
how much I need this moment?
White stains on my hands.
Your picture,
burned inside my head.
I see the liquid dripping
from your mouth instead.
Verse 3:
I'm a man
for my sins.
You feel my eyes upon you.
I burn
like mine eyes
and thinkin' about...
you want this.
Must I come undone?
Written By: Greg McLaughlin
Alone, individual,
in my neverending
loss for words.
I scrape my hands against the cold stone;
I cry out to be heard.
I wish that I could be tall enough to see above the wall
I wish that I could be strong enough to break down the wall
Alone, individual,
in my neverending
loss for words.
I scrape my hands against the cold stone;
I cry out to be heard.
Beneath the dead rock and mortar;
I cry out to be heard
I wish that I could be tall enough to see above the wall
I wish that I could be strong enough to break down the wall
Tracks to be released to radio include Submission, Mortar and White Stains, as part of the White Stains EP
Set List
Skriptorium (7:30)
White Stains (6:00)
Mortar (6:30)
Submission (4:30)
Tommy (5:00)
Cyrus (10:30)
American Morning (8:00)
Sober (remake of Tool) (5:00)


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Diocese page | Bishops list | Sources list | Location list | Source essay | Map | Bibliography | Diocesan history/Analysis | Links | CCED History | Jurisdiction list |
Lichfield and Coventry Diocese Links
Record Offices holding important deposits of archives relating to the diocese
- Lichfield Record Office, The Friary, Lichfield. WS13 6QG.
- email: firstname.lastname@example.com
- website:
Websites of the modern diocese and cathedral
- Diocese of Lichfield
- http://www.lichfield.anglican.org/
- Lichfield Cathedral
- http://www.lichfield-cathedral.org/
Websites of relevant local historical and genealogical societies
Useful resources for further research on this region


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Dredging for a new pier at Inverie on the west coast of Scotland began at the end of July.
Pierse Construction will build the £6.5M pier in a sheet pile cofferdam.The firm said this would reduce the contract from 90 weeks to 60.
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Endonovo Therapeutics Inc
Company Snapshot: Endonovo Therapeutics Inc
Company Overview
Endonovo Therapeutics, Inc. is an innovative biotechnology company developing bioelectronic devices and therapies for regenerative medicine. Endonovo's Immunotronics™ platform is a non-invasive, non-implantable bioelectronic device for treating/preventing vital organ failure through the reduction of inflammation, cell death and the promotion of regeneration. Endonovo's Cytotronics™ platform provides for a method of expanding and manipulating cells using simulated microgravity and Time-Varying Electromagnetic Fields (TVEMF) for tissue engineering and cell therapies. The Company's initial concentration is on the treatment of acute and chronic inflammatory conditions of the liver using its proprietary Immunotronics™ platform.
Client News
- Jan 11 2019 Endonovo Therapeutics Issues Shareholder Letter and Update
- Jan 3 2019 Endonovo Therapeutics Enters into $10 million Common Stock Purchase Agreement with Azure Capital
- Dec 18 2018 Endonovo Therapeutics Announces Receipt of Notice of Allowance from the United States Patent and Trademark Office
- Dec 13 2018 Endonovo Expands SofPulse Commercialization
- Dec 3 2018 Endonovo Therapeutics Announces Strategic Relationship with US Authentic Trading Company


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