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Anaplasma phagocytophilum is a Gram-negative, obligate intracellular tick-transmitted bacterium that replicates in neutrophils. It causes tick-borne fever (TBF) in sheep and cattle, but also elicits febrile disease in humans as well as in other domestic animals such as dogs, horses, and cats. Although increasingly recognized in Europe, the first laboratory-confirmed case of TBF in cattle from Germany has been published only recently. We here present the unusual case of an intrauterine transmission of A. phagocytophilum in a calf from northern Germany. To our knowledge, this is the first report of such an event occurring under field conditions in cattle.
Keywords:Anaplasma phagocytophilum; Intrauterine infection; Tick-borne fever; Cattle; Germany
Anaplasma phagocytophilum is a Gram-negative, obligate intracellular tick-transmitted bacterium that replicates in neutrophils [1]. It was initially recognized as the causative agent of tick-borne fever (TBF) in sheep and cattle [2,3], but also causes febrile disease in dogs [4], horses [5], cats [6], and humans [1]. As a result of taxonomic changes in 2001, A. phagocytophilum comprises the former species Ehrlichia phagocytophila, E. equi, and the agent of human granulocytic ehrlichiosis [7]. However, this unification has been a matter of debate, because naturally circulating A. phagocytophilum strains are not equally infectious for different mammalian species [8,9]. The main vector of A. phagocytophilum in Europe is Ixodes ricinus[10]. Clinical symptoms in cattle include high fever, reduced milk yield, inappetence, cough, and abortion [10]. Leukopenia, thrombocytopenia, and anemia are typical laboratory findings [11]. The diagnosis is made from peripheral blood via microscopic detection of bacterial inclusions in granulocytes, so-called morulae, or by species-specific polymerase chain reaction (PCR) [12]. In contrast, the significance of serological tests is very limited, because they do not distinguish between recent or past infections [13]. Although increasingly recognized in Europe, the first laboratory-confirmed case of TBF in cattle from Germany has been published only recently [14]. We here report an unusual case of intrauterine transmission of A. phagocytophilum to a calf.
Case presentation
Clinical signs
In June 2011, a male Holstein-Friesian calf was obtained immediately after birth from a dairy farm in Lower-Saxony for inclusion in a study investigating the pathogenesis of alloantibody-induced bovine neonatal pancyotopenia (BNP) [15]. The dam was born in January 2007 and raised on the farm. She calved for the first time in 2009 and aborted in 2010 after her second mating. Thereafter, in September 2010 the cow was artificially inseminated. From May 2011 she was grazed on pasture. With the exception of an intramammary antibiotic treatment, the cow did not receive any systemic antimicrobials.
The animal experiments investigating BNP were approved by the Animal Welfare Committee of the Niedersächsisches Landesamt für Verbraucherschutz und Lebensmittelsicherheit, Oldenburg (reference number: 33.9-42502-04-09/1799). EDTA blood and serum samples were collected from the precolostral calf and its mother. The calf was then fed with colostrum that was known to induce BNP. Since its first day of life, the calf showed elevated rectal temperatures of at least 39.8°C. In contrast to the other animals from the same experimental group that developed BNP 3 to 4 days after birth, the calf already showed typical signs of BNP such as cutaneous hemorrhages, mucosal petechial hemorrhages, and melena from its second day of life onwards. Similarly, thrombocytopenia, leukopenia, and anemia developed rapidly (Table 1). At the age of 4 days, the calf was euthanized, because it stopped drinking and showed severe deterioration in its general condition and persistent recumbency. Because the dam was asymptomatic, she was not medicated.
Table 1. Rectal temperatures and blood cell counts of the calf and its mother
Laboratory test results
Results of blood counts and the course of the rectal temperature of the calf are shown in Table 1. In a Giemsa-stained smear of precolostral EDTA blood, morulae of A. phagocytophilum were detected in neutrophil granulocytes (Figure 1A). One day after birth, morulae were not only found in 60% of the 400 examined neutrophils, but also in 30% of the lymphocytes (Figure 1B) and in some monocytes. Blood smears remained positive for A. phagocytophilum until the calf was euthanized. Maternal blood smears were microscopically negative.
Figure 1. Morulae (arrow) of Anaplasma phagocytophilum in Giemsa-stained blood smears of the calf. Morulae in a neutrophil in a blood smear at 2 hours after birth. (A). Morulae in a lymphocyte in a blood smear at day 1 after birth (B). Magnification: 10 × 100.
The diagnosis was confirmed by amplification and sequencing of the 16S rRNA gene of A. phagocytophilum from blood samples taken on days 3 and 4 after birth as described previously [18,19]. The 16S rRNA gene sequence was identical to an A. phagocytophilum variant [GenBank: M73220] well-known mainly from ruminant infections. EDTA blood samples from the dam taken at parturition and 2 days postpartum contained the same 16S rRNA genotype. At day 19 postpartum, the dam was found to be negative for A. phagocytophilum DNA.
Serum samples from both animals were investigated by an indirect immunofluorescence test (IFT) (Focus Diagnostics, Cypress, CA, USA) using FITC-conjugated goat anti-bovine IgG (H + L) antibody (Dianova, Hamburg, Germany) as secondary antibody. Serum from the 2-day-old calf was negative for anti-A. phagocytophilum antibodies, whereas the cow had a titer of 1:256 (cut-off: 1:64) on days 2 and 19 post partum.
To determine whether both animals were infected by the same strain of A. phagocytophilum, the ankA gene as a further genotypic marker was amplified as described previously [20,21]. Unexpectedly, two ankA gene sequences belonging to two different clusters, I and IV [21] were amplified from the calf's blood at days 3 and 4 after birth. In contrast, the dam was infected with A. phagocytophilum carrying only the ankA gene variant of cluster I in blood samples taken at parturition and 2 days postpartum. The cluster I ankA sequences of both animals were 100% identical. To confirm that both animals were infected with the same A. phagocytophilum strain, multi locus sequence typing (Winter C, Huhn C, Wolfsperger T, Wüppenhorst N, von Loewenich FD: unpublished observations) was applied and revealed the same sequence type 140 in mother and calf. An overview of the A. phagocytophilum-specific test results is shown in Table 2. 16S rRNA and ankA gene sequences are available under the following accession numbers: [GenBank: KC776917 – KC776921].
Table 2. Summary of Anaplasma phagocytophilum-specific test results
Although TBF in cattle is known to cause abortion or stillbirth [10], to our knowledge a spontaneously occurring intrauterine infection of a bovine fetus with A. phagocytophilum has not been reported to date. In our case, evidence for an intrauterine infection comes from the fact that a significant proportion of neutrophils in the blood smear of the calf prepared 2 hours after birth were already infected. Furthermore, the calf was not tick-exposed during its short lifetime. It has been shown that oral transmission of A. phagocytophilum is inefficient in cattle [22], whereas it has been proven experimentally that intrauterine infection does occur [23]. That study showed absence of specific fetal antibodies in a calf delivered 17 days after the mother was experimentally infected and that the calf did not seroconvert until it was 26 days old [23]. The calf reported in the present case was likewise seronegative. Based on these circumstances, it seems most likely that it was infected in utero. It has been shown experimentally that adult cattle develop elevated antibody titers of > 1:320 at day 14 post infection and remain PCR-positive for A. phagocytophilum on average until day 22 [11]. Because the dam was PCR positive and showed an antibody titer of 1:256 at day 2 after parturition, we suggest that she had been infected 2 to 3 weeks earlier. As far as reported by the farmer the dam was clinically asymptomatic, but the symptoms that typically last for 1 week [11] might have gone unrecognized.
The molecular characterization of the A. phagocytophilum strain proved that mother and calf were infected with the same strain. However, two ankA gene variants were found reproducibly in the calf's blood. The possibility exists that the dam initially transmitted two strains that were not distinguishable apart from their ankA genes and that she had already cleared one of them at the time of delivery. It might also be that the bacterial burden of one of the strains had already fallen below the detection limit. Alternatively, intra-species recombination, as has been hypothesized earlier [21], could have taken place leading to the appearance of two ankA gene variants in the calf's blood.
A spontaneous bovine congenital infection with A. phagocytophilum is reported for the first time. Intrauterine infection of cattle has previously been produced experimentally, but this study confirms that this may also occur under field conditions.
Written informed consent was obtained from the owner for publication of this report.
BNP: Bovine neonatal pancytopenia; IFT: Indirect immunofluorescence test; PCR: Polymerase chain reaction; TBF: Tick-borne fever.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
TH and PH did the clinical investigation. TG, MG, and FvL performed the laboratory tests. TH, OD, MG, and FvL prepared the manuscript. All authors have read and approved its final version.
This study was partly funded by the German Federal Institute for Agriculture and Nutrition (BLE), Bonn (grant 2810HS025 to OD). The article processing charge was funded by the German Research Foundation (DFG) and the Albert-Ludwigs-University Freiburg in the funding programme Open Access Publishing. The authors are grateful to Lesley Bell-Sakyi (The Tick Cell Biobank, The Pirbright Institute, Pirbright, United Kingdom) and Nicole Wüppenhorst (Institute of Medical Microbiology, University of Freiburg, Freiburg, Germany) for critical reading of the manuscript.
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Improvise, Adapt, and Overcome
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Wow, open space is costing a lot these days at the State Capitol complex ("Renovations Planned," June 17).
The state purchased the old Des Moines General Hospital in 2009 for $4.45 million. The annual expense to operate it costs $1 million. Now, the state will tear down the building at the cost of $2 million and the property will become open space. That's about $10 million the state will pay to have open space.
Who was behind this planning or lack of? That $10 million could have been applied to early childhood education as an investment in our future society and workforce by having well fed kids in safe environments and building healthy brains and bodies. Well, we certainly know where our priorities are by this spending fiasco.
As James W. Frick said, "Don't tell me where your priorities are. Show me where you spend your money and I'll tell you what they are."
- Kevin Pokorny, Des Moines


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What recession?
New creative interiors department defies recession
Luxury estate agent The Modern House, which specialises in selling modern homes by classic architects, is thumbing its nose at the credit crunch by launching an interiors department. The team of designers is happy to suggest a 'creative vision' for your modern home, or for a large-scale project. Astragal assumes the team's services will cost, if not a pretty penny, then a minimal and tasteful penny indeed.
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De Pere High School graduate Kathy McGurk stands in the area of the finish line Saturday, April 13, as officials get things set for this year's Boston Marathon, held two days later. McGurk ran the prestigious race for the first time and finished it before two bombs detonated near the finish line Monday afternoon. The first explosion occurred in front of the buildings to the near left in this photo.
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Kathy McGurk reached the finish line on Boylston Street in downtown Boston's Copley Square on fatigued legs but flush by what she had just accomplished.
"After dedicating so many months to training and imagining the moment for so long, the feeling was everything I ever dreamed," McGurk said. "Through absolute exhaustion, there is an overwhelming sense of happiness and pride."
Less than an hour later, after she had not only run her first Boston Marathon but completed the famous 26.2-mile race in a time of 3 hours, 36 minutes, 51 seconds, McGurk and so many others who were catching their breath ...


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The recently deceased Nelson Mandela distinguished himself through his charismatic leadership of South Africa and his inspirational compassion and forgiveness exhibited under exceedingly difficult conditions. The world, that now mourns his passing, knows him most affectionately as Madiba/Father (from his Xhosa clan name), the first black elected President of post apartheid South Africa (1994).
Based on Jordan Belfort's book charting his rise and fall, "The Wolf of Wall Street" recreates the wild ride through the 90s of this penny stock trader, soon multi-millionaire never bothered by ethics. Leonardo DiCaprio's tour-de-force performance drives the film from work at a Wall Street corporation to a shabby office to his own Stratton Oakmont Long Island firm.
The time: 1961; the setting: smoky, folky bar in New York City. The player: Llewyn Davis, a folk singer with a penchant toward being irresponsible, arrogant and needy. Think of the recent title character of "Francis Ha," and you have Llewyn Davis only 50 years ago and with a guitar.
First, the confessions: I never read Mary Poppins. I giggled over those penguins when the movie first came out in 1964. I admit I was delighted at the thought that a nanny could save the day; in fact, I would have given anything to have had a nanny save my day as a child.
When a film begins in its opening seconds with these words on the screen, "Some of this actually happened," humorous playfulness is on the way. And "American Hustle" does not disappoint with its stellar cast, often playing against type, and a delightfully mischievous approach to the con game.
The second films of three are often the weak links, but not "The Desolation of Smaug." Sure, exposition is chunked into the first 20 minutes just to fill in the plot and references to "The Lord of the Rings" are forced. The second of this series is uneven but exciting.
Late in the shrewd, revealing documentary "The Armstrong Lie," writer/director Alex Gibney says, "We wanted to believe the beautiful lie. I wanted to believe it, instead of the ugly truth." Count me in that group as well as someone, naïvely and foolishly, celebrating Armstrong's spectacular wins--both in cycling and against cancer--over his long career.
Rarely does one living person participate in major international events over two and a half decades. But that's exactly what Yehuda Avner experienced as speechwriter and assistant to five Israeli Prime Ministers beginning in 1958. Director, co/producer and writer Richard Trank's informative, well-researched documentary "The Prime Ministers: The Pioneers" presents Avner on camera, narrating his behind-the-scenes observations.
To celebrate its 50th anniversary, the National Theatre of Great Britain has prepared a film nummy smorgasbord. On the screen of the Tivoli Theatre, playing only on Sunday December 8 at noon, you can join in the celebration.
"Out of the Furnace" wants to be a blue collar, gritty film, and it succeeds. Set in Braddock, Pennsylvania (near Pittsburgh) in 2008, the future for the steel mill workers looks about as bleak as the sky and the town. Two brothers pursue different paths: Russell still employed at the mill, younger Rodney floundering, heading off to Iraq.
Near the end of the documentary "Design Is One: Lella & Massimo Vignelli," an expert observes that a good designer is the "intermediary between information and understanding," making the complex clear. As directors Roberto Guerra and Kathy Brew work through illustrative examples from the Vignellis' work, what that means becomes crystal clear.
Producers and directors Seth Kramer, Daniel A. Miller and Jeremy Newberger bring a welcome restraint to their documentary "Évocateur: The Morton Downey Jr. Show." Anyone familiar with Downey's nationally syndicated show from early 1988 to July 1989 remembers the loud, confrontational, trash-talking host who blew smoke in guests' faces while screaming at them.
If you have questions or need to contact KDHX, visit our answers portal at answers.kdhx.org.


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Gaming laptops are specifically designed for use with online games. Because of this, they have specialized parts and hardware that come installed. Some of the most important parts of a gaming laptop are the fans and the hard drives. The typical lifespan of a gaming laptop depends on a lot of factors. If you're thinking about buying a gaming laptop there are a few things that you can take into account to expand the lifespan of your gaming laptop.
Gaming laptops run really hot because they are constantly drawing power from the GPUs and CPUs. This heat causes the fans to run constantly on the unit. When any piece of hardware is running on a computer it will lower the lifespan. Although a broken fan or a failed hard drive is not enough to require a complete replacement of the computer, these are repairs that you will need to think about when purchasing a gaming laptop. Keeping the computer shutdown when it's not in use can dramatically increase the lifespan of your gaming laptop and will allow it to stay cool. Installing feet on the bottom of the computer so the vents on the bottom of the unit can run is another way to keep the computer cool. Typically, people start to see problems with their fans within 2-3 years.
The battery is another problem for gaming laptops because of the power usage across the unit. Batteries are drained quickly which leads to instability within the unit. A typical computer battery can last for as long as 5-6 years, while a gaming laptop's battery will probably have to be replaced within 2-3 years. The CPUs on a gaming laptop are much smaller, and generally less powerful, than the CPUs on a desktop computer. However, these CPUs are around more heat than a CPU on a desktop so they have a greater chance of burning up. Again, keeping your gaming laptop cool is the number one way to increase its lifespan.
With the introduction of new technology, RAM ports are beginning to expand their capacity. Do you remember when having 2-3 gigs of RAM was overkill? This was only a few years ago. Gaming laptops can go obsolete much faster than regular computers because of the RAM and processing power needed to run games. Buying a top of the line gaming computer may only increase the lifespan by a year or so. Upgrades can easily keep your gaming computer up to date, but expanding the GPU or the CPU can be hard since you are dealing with a laptop. Adding RAM and updating to a faster hard drive is relatively easy and can be done within an hour.
Buying a gaming laptop can be a great way to play games on the road or within your home. However, the typical lifespan of a gaming laptop does not usually exceed 2-3 years. Make sure that you know what you're buying before you make the investment. Ask questions about the ventilation, RAM capacities and available upgrades before you spend your money on a gaming laptop.


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DOL News Brief
February 23, 2012
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Talking Recovery in Richmond
Secretary Solis and Assistant Secretary of Labor for Employment and Training Jane Oates traveled last Friday to Richmond, Va., to discuss themes from President Obama's State of the Union address. The day began with a meeting at J. Sergeant Reynolds Community College with 35 African-American community, faith, education and business leaders. Solis highlighted the Labor
Department's commitment to training and skills development for those in minority and underserved communities, the importance of community colleges and the Summer Jobs+ program. Later, they visited Alstom Power, a manufacturing plant that uses clean, green energy technologies. They saw how the facility repairs power generation equipment in an energy efficient way, showcasing the resilience of American manufacturing during the economic recovery.
"A Better Life"
More than 600 people gathered last Thursday at the Department of Labor auditorium for two screenings of the film "A Better Life" a story about a father who wants to provide a better future for his son. The first event was tailored for students, while the second featured community leaders and advocates in the D.C. metro area. Film director Chris Weitz, Occupational Safety and Health Administration investigator Diana Cortez, Wage and Hour Division investigator Lucia Garcia and DOL senior counselor Irasema Garza served as panelists for a discussion about the film, which was moderated by Secretary Solis. "This film touches upon many issues important to the Latino community from work safety to immigration and I'm glad we could have an open discussion here today," Solis said.
DepSec Visits Minneapolis
Deputy Secretary of Labor Seth Harris visited the Twin Cities area on Tuesday. He gave a talk to a job club symposium hosted by the department's Center for Faith-based and Neighborhood Partnerships. In the afternoon, he toured the Brooklyn Park campus of Hennepin Technical College to see firsthand how community colleges are partnering with local employers and nonprofit organizations to better train American workers to succeed in a skills-based economy. "Jobs Clubs have a critical role to play in helping job seekers regain their footing and transition back into the workforce. They leverage the power of neighbors and communities," Harris said. "Hennepin Tech is showing that the president's plan to invest in community colleges is the right decision. Community colleges around the country are preparing workers for in-demand jobs and creating pipelines for companies that are growing and hiring for the present and the future."
Solis Hosts UBB Team
After 20 months of work with more than 100,000 hours logged, the Upper Big Branch Mine accident investigation team was greeted by Secretary Solis in Washington last week. Solis hosted leader Norman Page and the other members of the team that relocated to Beckley, W.Va., for more than a year and a half to complete the most extensive accident investigation in the history of the Mine Safety and Health Administration. Solis was joined by Assistant Secretary of Labor for Mine Safety and Health Joe Main to thank the team for their hard work, persistence and diligence throughout the investigation, which concluded in December.
Secretary Delivers 2012 Latino State of the Union
Secretary Solis was honored to deliver the keynote address at the Mexican American Legal Defense and Educational Fund's 2012 Latino State of the Union. The event, hosted at the Newseum last Thursday, was kicked off with remarks by Solis and capped off with an all star panel which included MALDEF President Tom Saenz and other top Latino community advocates. The discussion, which took place in front of about 100 people and broadcasted online to thousands more, focused on civil rights, law and public policy. Solis set the tone, speaking largely about the state of Latinos in almost every sector of our society. "This is indeed a "make-or-break" moment for the Latino community," she said. "Latinos in the middle class and all those trying to get into the middle class need our help more than ever."
Main Gets First-Hand Look at New Coal Mining Technology
Assistant Secretary of Labor for Mine Safety and Health Joseph Main recently visited three coal mines to catch up on the latest mining technology put in place by Consol Energy and Alpha Natural Resources. Last Friday, Main traveled to Emerald Mine in western Pennsylvania for a demonstration of a new rock dust method called foam dusting currently in development by Strata Mine Services and DSI Underground Systems. Three days later, Main and members of his staff headed to northern West Virginia, where officials of Robinson Run No. 95 Mine showcased a wireless voice and text communication system that enables mine personnel at the surface to connect with workers hundreds of feet underground. The final leg of the tour occurred in Greene County, Pa., at the Bailey Mine. Along with Consol's Lou Barletta and Todd Moore, Main traveled underground to observe mine haulage equipment outfitted with a proximity detection system. Such systems provide audible and visual warnings and stop mobile machines before a pinning or crushing accident occurs. "These kinds of trips are invaluable opportunities to understand how the mining industry is progressing and what we need to focus our attention on to improve miner safety and health," said Main.
Job Clubs Shine in Valley of the Sun
Jay Williams, director of the Office of Recovery for Auto Communities and Workers, joined the Center for Faith-based and Neighborhood Partnerships at North Phoenix Baptist Church yesterday for another job club symposium. Williams discussed the important role the manufacturing sector plays in our economy to create new jobs and highlighted President Obama's "insourcing" proposals from his recent State of the Union address for bringing good-paying manufacturing jobs back to the United States. The event also featured two informative panels about the success of Phoenix area job clubs in serving the long-term unemployed.
Borzi Joins Discussion on New Ideas for Retirement Saving
Current retirement models may not do enough to help workers be financially secure in their post-career lives. This was the premise of the "Re-imagining Pensions," conference hosted on Capitol Hill this week by the Pension Rights Center; The Urban Institute; and Covington and Burling. Assistant Secretary for the Employee Benefits Security Administration Phyllis Borzi participated in a morning panel, responding with questions to presenters who offered their ideas for re-working current retirement models. Borzi agreed that there is a need to help a greater number of workers save more for retirement and pointed out that any changes to the current system would need to address a number of potential concerns before being implemented.
Upcoming Deadlines & Events
Open Funding Opportunities
Event Spotlight: EBSA Women and Retirement Forum
The department's Employee Benefits Security Administration will hold a free women's retirement savings forum on Saturday, Feb. 25, from 12:30 3:30 p.m. EST at Bunker Hill Community College, lecture hall C202. Held in coordination with the Center for Retirement Research at Boston College, "Women and Retirement: What Every Woman Should Know Before It's Too Late" will be open to the public and the media.
EBSA Women and Retirement: What Every Woman Should Know Before it's Too Late
EBSA Health Benefits Laws Compliance Assistance Seminar
EBSA Voluntary Fiduciary Correction Program and Abandoned Plan Program Workshop
ETA H-2B Final Rule Webinar
MSHA Spring Thaw Workshop
OFCCP The 16 Equal Employment Opportunity and Affirmative Action Obligations
OFCCP Building Partnerships for the Community
OFCCP Building Veteran Partnerships
OFCCP Collaboration Event
OFCCP Community Based Organizations Roundtable Collaboration
OFCCP Community Based Organization Focused Event- Hispanic Community
OFCCP Community Outreach and Education Event
OFCCP Compliance Assistance Seminar
OFCCP Compliance Assistance/Technical Assistance Seminar
OFCCP Compliance Assistance Seminar - Construction
OFCCP Compliance Assistance Seminar - New and/or Small Contractors
OFCCP Development of Written Affirmative Action Programs
OFCCP National Origin Discrimination
OFCCP The OFCCP Internet Applicant Recordkeeping Rule
OFCCP Operation Home Work Veterans EXPO
OFCCP Policy Group for Trades Women Issues Meeting
OFCCP Preparing for an OFCCP Evaluation (Service and Supply)
OFCCP So You've Been Scheduled
OFCCP Supply and Service AAP/Educational Seminar
OFCCP Supply and Service AAP Seminar for Small and New Contractors
OFCCP VEVRAA/Disability Regulations
OFCCP Women in the Construction Trades Compliance Assistance Seminar
OFCCP Workplace Accommodations
OLMS Compliance Seminar
OSEC Job Clubs & Career Ministries On the Front Lines of Getting Americans Back to Work
OSHA 7th Annual Central Alabama Construction Safety Conference and Expo
OWCP Town Hall Meetings to Assist Nuclear Weapons Workers
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CC2C Bus Tour: Highlighting American Innovation
Secretary Solis joined Dr. Jill Biden, wife of Vice President Joe Biden, on a whirlwind bus tour this week to highlight innovative ways that community colleges are partnering with businesses to train students for jobs in high growth industries. The tour began Wednesday at Columbus State Community College where Solis and Dr. Biden learned about a number of programs including LogisticsArt,
which works with 16 central Ohio
International Scene
APEC Working Group Promotes Inclusive Economies
The Bureau of International Labor Affairs participated in the annual Human Resources Development Working Group meeting of the Asia-Pacific Economic Cooperation in Moscow, Russia. During the Feb. 5-10 meeting, Chris Watson of ILAB outlined best practices for countries that seek to bring more people into the formal economy by enhancing protections through the social safety net.Watson also distributed a questionnaire designed to generate dialogue among the participating countries on the need for an inclusive approach that ensures that people with disabilities are integrated into the 21st century workforce. Participants included representatives of 17 Asia-Pacific countries. The working group's next general meeting is scheduled to take place in Indonesia in 2013.
Around DOL
Agreement with Louisiana to Reduce Misclassification of Employees
Nancy J. Leppink, deputy administrator of the Wage and Hour Division, and Louisiana Workforce Commission Executive Director Curt Eysink entered into a memorandum of understanding on Thursday regarding the improper classification of employees as independent contractors. This partnership is the 13th of its kind for the Department of Labor. "This memorandum of understanding helps us send a message: We're standing united to end the practice of misclassifying employees," said Leppink.
News You Can Use
WB: 'African-American Women in the Military: Past and Present'
The Women's Bureau and The Black Archives of Mid-America will present "African-American Women in the Military: Past and Present," featuring an intergenerational panel of African-American women veterans on March 10 from 8:30 to 11:30 a.m. CDT at The Black Archives of Mid-America, 1722 E. 17th Terrace, Kansas City, Mo. 64108. Attendees are asked to pre-register for the free event. This event kicks off a year-long focus on women veterans being developed by the Women's Bureau, which will highlight their current employment opportunities and reintegration into the civilian workforce. To RSVP, send an email to Olivia Schuckman at email@example.com.
More Time Allotted to Comment on Caregiver Proposal
The comment period on a proposed rule to extend wage protections to workers who provide in-home care services has been extended by 14 days. Originally set to conclude on Feb. 27, the comment period has been extended to March 12. The rule proposed by the department's Wage and Hour Division would extend the Fair Labor Standards Act's minimum wage and overtime pay requirements to nearly 2 million workers who are currently exempt because they are classified as "companions." If enacted, the proposal would clarify that companionship services are those directly related to the fellowship and protection of a care recipient.
Webinars and Public Briefing on H-2B Final Rule
The department has scheduled three webinars and one public briefing to educate stakeholders, program users and other interested members of the public on changes to the H-2B program made by a final rule and applying for temporary labor certifications under the new regulations. The rule will be effective on April 23. Each webinar is limited to 200 participants. The department encourages organizations or other groups of participants to access the webinars together from a single, centralized location to maximize attendance.
DOL Working for You
Job Corps Grad Scores American Idol Success
Tyler Morgan overcame tough, sometimes homeless teen years to proudly graduate from Oregon's Tongue Point Job Corps with a culinary certificate. So winning an audition to perform on American Idol at the same time was for him icing on the cake! Morgan, one of 7,000 local contestants who auditioned for the show's judges, continued in the competition with his singing of an original up tempo song. The 18-year-old cannot comment on his eventual fate since the show's final outcome has yet to be broadcast. Morgan, however, did say he is now "back in the real world," prepared to put his education to good use as a chef while not giving up his dream of becoming a recording artist. Job Corps "gave me foundational skills and taught me how to stay calm," he said.
OWCP Examiners Win Benefits for California Widow
Thanks to the persistence of claims examiners in the Office of Workers' Compensation Programs' Long Beach District Office, a California widow now has all of the benefits to which she's entitled. OWCP examiner Benjamin Guillermo reviewed more than 20 years of payments to Rosa Marie Tovar, whose husband, Alfredo, died on the job in 1986. After discovering that Mrs. Tovar's insurance carrier had neglected to apply annual cost-of-living adjustments to her benefits, Guillermo and colleague Michele Pappagianis worked for months to secure more than $200,000 in back-owed benefits and interest. Mrs. Tovar said that the payment will help her make student loan payments for her children, Alfredo and Esmeralda. Marco Adame, district director of OWCP's Long Beach office, called Guillermo and Pappagianis' effort "a great example of how our day-to-day work can make a huge positive impact on injured workers and their families."
DOL in Action
$32 Million Returned to Tribune Employee Stock Ownership Plan
The Employee Benefits Security Administration has announced that Tribune Co., GreatBanc Trust Co. and various insurance carriers have completed funding of a global settlement in the amount of $32 million to be allocated among the Tribune Employee Stock Ownership Plan's participants, and to pay for legal and administrative expenses. The settlement is with, among others, the department and the plaintiffs in a private class action lawsuit, and resolves the department's claims of violations of the Employee Retirement Income Security Act. "The settlement ensures that the Tribune Employee Stock Ownership Plan's participants and beneficiaries will be able to receive the benefits that are rightfully theirs," said Secretary Solis. "I am pleased that participants' hard earned retirement savings have been returned."
Improving the Quality of Workforce Data
This week, Secretary Solis announced the availability of $12 million for grants through the Workforce Data Quality Initiative, which will enable states to build or expand longitudinal databases that link workforce and education data to improve understanding about the performance of workforce development programs. "The grants awarded through this initiative will result in high-quality, long term data that will provide consumers, practitioners and policymakers with comprehensive information about the relationship between education and workforce development programs," she said.
List Industries Cited for Repeat and Serious Violations
The Occupational Safety and Health Administration has proposed $56,000 in penalties against List Industries Inc. after an inspection of its Deerfield Beach, Fla., manufacturing plant found amputation hazards that previously had been cited during OSHA inspections in 2007 and 2009.
Jeffboat Cited After Worker Fatality at Barge Manufacturing Facility
Jeffboat LLC has been cited by the Occupational Safety and Health Administration for nine safety including one willful violations at its Jeffersonville, Ind., facility after a worker was fatally crushed when he became trapped between a malfunctioning transfer car and a barge. Proposed fines total $119,000.
Lawsuits Filed Against Farmer, Contractors in South Florida
The Labor Department is suing farm labor contractors and a South Florida grower over alleged violations of the Fair Labor Standards Act and the Migrant and Seasonal Agricultural Worker Protection Act that occurred during the 2011 green beans harvest in Miami-Dade County. The department is asking that Fisteac Farm Labor Inc., Joseph Fisteac, Ledford Farms and Troy Ledford pay workers three years of back wages and an equal amount of liquidated damages.
Employees Exposed to Electrical Hazards in San Antonio
Fresh From Texas has been cited by the Occupational Safety and Health Administration with eight serious violations for exposing workers to numerous electrical hazards at the company's facility in San Antonio, including failing to ensure that workers were provided with adequate working space around electrical equipment, to ensure that the working space was not used for storage and not properly covering electrical equipment such as condenser units. Proposed penalties total $40,500.
New York Union President Sentenced for Embezzlement
Guy Masocco, former president of Steelworkers Local 897 in Cheektowaga, N.Y., was sentenced to 10 months of home confinement and three years of probation, and ordered to pay $31,701 in restitution after pleading guilty in August 2011 to embezzling from his union. An Office of Labor-Management Standards investigation found that, from December 2004 to November 2009, Masocco used his union credit card for personal expenses and submitted false claims to the union for reimbursement of wages he said he lost while conducting union business.
2 Workers Suffer Finger Amputations in Mount Enterprise, Texas
Mount Enterprise, Texas-based J.P. Spivey Supply has been cited by the Occupational Safety and Health Administration for one willful and 13 serious safety and health violations after two workers had fingers amputated from coming into contact with a moving saw blade while cutting material. Proposed penalties total $57,200.
Defunct Company Ordered to Restore $661K to Retirement Plan
Compass Capital Partners Ltd. and owner Harris M. DeWese have been ordered to restore $661,206 to the defunct West Chester, Pa., company's retirement plan under a summary judgment obtained by the department. An investigation by the Employee Benefits Security Administration found that DeWese withdrew funds from the plan eight times from October 2006 to October 2007 and deposited them in his personal account and a Compass Capital Partners bank account. "These actions show a flagrant breach of fiduciary responsibility," said Phyllis C. Borzi, assistant secretary of labor for employee benefits security.
2 Florida Companies Cited After Explosion at Gas Station
Coomes Oil & Supply Inc. and Florida Rock & Tank Lines Inc. have been cited by the
Occupational Safety and Health Administration for safety hazards after an employee of the latter company was burned in an explosion at the 5th Wheel gasoline station in St. Augustine, Fla. Proposed penalties to both companies total $77,000.
Companies Cited After Complaint Filed on Behalf of Foreign Students
After responding to a complaint on behalf of foreign students hired under the U.S. Department of State's J-1 visa program, the Occupational Safety and Health Administration has issued citations totaling nearly $290,000. Exel Inc., which manages a Palmyra, Pa., facility for the Hershey Co., was issued nine citations for record keeping violations, and one for failure to develop and implement an effective hearing conservation program. SHS Group LP, a temporary staffing provider at the facility, was issued one citation for its failure to provide training on lockout/tagout of energy sources to employees.
Trinidad Drilling Cited for Exposing Workers to Fall, Electrical Hazards
Trinidad Drilling has been cited by the Occupational Safety and Health Administration for exposing workers to falls and electrical hazards at the company's worksite at Well No. 1H, Phantom Wolfcamp, northwest of Barstow, Texas. Proposed penalties total $79,805.
Precision Drilling Cited for Exposing Workers to Safety Hazards
Precision Drilling Co. L.P. has been cited by the Occupational Safety and Health Administration with serious and repeat safety violations following an inspection of the company's work site northeast of Pecos, Texas. The serious violations are failing to ensure portable fire extinguishers were kept in their designated places and to remove or repair damaged electrical cords. Proposed penalties total $69,300.
Assistance for Minnesota Workers Impacted by Flooding
A $477,065 National Emergency Grant will provide continued temporary employment for eligible dislocated workers assisting with cleanup and recovery efforts made necessary by the severe storms and floods that hit southeastern Minnesota in 2010.
Summit Equipment & Supply Cited with 24 Safety Violations
Summit Equipment & Supply has been cited by the Occupational Safety and Health Administration with 24 safety violations for failing to provide adequate guards on machinery and train workers in proper safety procedures at its Akron, Ohio, facility, among other hazards. OSHA opened the investigation on Aug. 25, 2011, after receiving a complaint alleging unsafe working conditions. Proposed fines total $56,400.
Basic Grain Products Cited After Worker Injured by Conveyor Belt
Grants Announced to Train Workers in High-Skill, High-Demand Jobs
Traveling through Cincinnati, Ohio, to promote a Community College to Career bus tour, Secretary Solis announced more than $183 million in grants to provide education, training and job placement assistance for American workers in high-growth industries such as advanced manufacturing, energy, health care and information technology through the second round of the H-1B Technical Skills Training Grant Competition. The grants, funded through fees paid by employers to bring foreign workers into the United States under the H-1B program, are intended to prepare American workers for these jobs and to help businesses reduce their need to use the H-1B program.
Georgia Air Products Manufacturer Cited for Safety, Health Violations
The Occupational Safety and Health Administration has proposed $53,300 in penalties against air distribution products manufacturer Price Industries Inc. after identifying 13 safety and health violations at the company's Suwanee, Ga., plant. OSHA's October inspection was initiated in response to a complaint.
Milk Specialties Cited with Willful, Other Violations After Fire at Facility
Milk Specialties Co. has been cited by the Occupational Safety and Health Administration with three safety violations, including one willful violation for combustible dust hazards. OSHA opened an inspection following a report of a fire resulting from a dust explosion in a machine at the company's Fond du Lac, Wis., facility. Proposed fines total $72,000.
Jones General Contracting Cited with Trenching Violations
Louisiana's Department of Children and Family Services Violates FMLA
Louisiana's Department of Children and Family Services in Baton Rouge, La., has agreed to pay a former employee $36,599 following an investigation by the Wage and Hour Division that found violations of the Family and Medical Leave Act when the employee was terminated after missing work due to a serious health condition.
Amy Food Cited for Exposing Workers to Possible Amputations
Amy Food Inc. has been cited by the Occupational Safety and Health Administration with one willful, four serious and three other-than-serious citations for exposing workers to possible amputation hazards at the company's Houston facility. OSHA initiated a safety inspection following a complaint alleging that several employees had suffered near amputation incidents while operating machinery. Proposed penalties total $77,100.
Wisconsin Grain Co-op Cited for Failing to Protect Workers from Falls
Landmark Services Cooperative, a Wisconsin grain cooperative, has been cited by the Occupational Safety and Health Administration with one willful safety violation for failing to protect workers from falls while they were loading grain products into rail cars at the co-op's Evansville facility. Proposed fines total $70,000.
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National Toxicology Program (NTP) Division
The National Institute of Environmental Health Sciences (NIEHS) is home to the National Toxicology Program , a Health and Human Services interagency program dedicated to testing and evaluating substances in our environment.
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Director, NIEHS & NTP
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John R. Bucher, Ph.D.
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Director, National Toxicology Program Division
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As Director of NIEHS, Linda Birnbaum, Ph.D. also serves as the Director of the NTP. John Bucher, Ph.D., serves as NTP Associate Director and Director of the NTP Division, which is housed at NIEHS. Bucher provides daily oversight and guidance to the Program.
The NTP is comprised of three core agencies:
- National Institute of Environmental Health Sciences, National Institutes of Health
- National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention
- National Center for Toxicological Research (NCTR) , Food and Drug Administration
The National Toxicology Program Division oversees and carries out the activities of the NTP.
The Division is responsible for carrying out the goals of NTP including:
- Providing toxicological evaluations on substances of public health concern
- Developing and validating improved toxicology methods (more sensitive, specific, and rapid)
- Developing approaches and generating data to strengthen the science base for risk assessments
- Communicating results with all stakeholders
The National Toxicology Program Division is comprised of four branches and the NTP Laboratory, as well as the five offices in the Division Office.
- Branches/Laboratories:
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Recent Stories about NTP Activities
- Kidney toxicity screening tool developed by grantee and NTP team - September 2015
- NTP panel agrees flame retardant mixture exhibits carcinogenic activity - August 2015
- Tox21 tools promoted at UC Davis meeting - July 2015
- NTP completes chemical spill studies, finds water advisory level protective - July 2015
- New data tools top the agenda at NTP board meeting - July 2015
- Expert panel identifies research needs on high folic acid intake - June 2015
- NTP hosts regional meeting to highlight juvenile toxicology - April 2015
- NTP trainees get practical support before SOT - April 2015
- New method will reduce animal use in pertussis vaccine testing - April 2015
- Toxicology and public health merge at SOT conference in San Diego - April 2015
- NTP presents SAN trimer results at Toms River public meeting - March 2015


text:
Diets enriched with sphingolipids may improve blood lipid profiles. Studies in animals have shown reductions in cholesterol absorption and alterations in blood lipids after treatment with sphingomyelin (SM). However, minimal information exists on effect of SM on cholesterol absorption and metabolism in humans. The objective was to assess the effect of SM consumption on serum lipid concentrations and cholesterol metabolism in healthy humans.
Ten healthy adult males and females completed a randomized crossover study. Subjects consumed controlled diets with or without 1 g/day SM for 14 days separated by at least 4 week washout period. Serum lipid profile and markers of cholesterol metabolism including cholesterol absorption and synthesis were analyzed.
Serum triglycerides, total, LDL- and VLDL- cholesterol were not affected while HDL cholesterol concentrations were increased (p = 0.043) by SM diet consumption. No change in cholesterol absorption and cholesterol fractional synthesis rate was observed with supplementation of SM compared to control. Intraluminal cholesterol solubilization was also not affected by consumption of SM enriched diet.
In humans, 1 g/day of dietary SM does not alter the blood lipid profile except for an increased HDL-cholesterol concentration and has no effect on cholesterol absorption, synthesis and intraluminal solubilization compared to control.
Trial registration
Keywords:Sphingomyelin; Cholesterol absorption; Fractional synthetic rate; Bile; Human
Sphingolipids are key components of cell membranes which regulate several functions of the cell [1]. Sphingomyelin (SM), a major part of sphingolipid, is localized to the plasma membrane and lysosomal and golgi membranes [2]. SM is present in considerable quantities in the Western diet [3]. The per capita consumption of SM in the United States is estimated to be 300–400 mg/d; milk (dairy products) and eggs provide 220 mg/d of SM [4,5].
Sphingomyelin plays an important role in cell membrane formation and plasma lipoprotein metabolism including cholesterol efflux, cholesterol absorption, synthesis, and conversion to bile acids, cholesterol esters and other metabolites [5]. ABCG1 mediates the efflux of SM and cholesterol from cell membranes depending on their level and distribution in the membrane [6,7]. Metabolic regulation of SM and cholesterol appear to be inter-coordinated [8,9]. SM has a strong affinity with cholesterol and correlates with the quantity of cholesterol in cell membranes [5,8,10]. As SM binds to cholesterol, it could bind to luminal cholesterol and inhibit absorption directly.
SM may be relatively resistant to solubilization into bile salt micelles or form cholesterol-SM bilayers [11]. SM enriched micelles have been shown to markedly reduce cholesterol solubility compared to phospholipid (PL) enriched micelles [12]. Hence, SM and the ratio of cholesterol to SM have the potential to markedly alter cholesterol trafficking and homeostasis in cells, including enterocytes [4,9]. In addition to affecting sterol balance across cells, SM could affect cholesterol absorption from the lumen of the gut. Indeed, SM has been demonstrated to reduce cholesterol absorption in mice and reduce cholesterol uptake by CaCo2 cells [2,4]. Consumption of SM affects plasma and tissue levels of cholesterol and reduces cholesterol absorption in intestines of rats and mice [13-16]. In mice, diet enriched with 0.1% SM reduced cholesterol absorption by 20.48% [17]. This dose is near the range possible for enrichment of human diets that would allow assessment of the effects of dietary SM on cholesterol absorption and synthesis. Co-administration of cholesterol and SM leads to inhibition of absorption of both lipids in rats [13]. At 1:1 molar ratios (SM/Cholesterol), cholesterol absorption is reduced from 68 to 9% while at ratios of 0.5:1.0, absorption is reduced to 25% [13]. Since the average diet contains 300–400 mg/day of sphingolipid (an amount comparable to dietary cholesterol and accounting for 0.01-0.02% of the diet by weight), it appears very likely that, even without any dietary manipulation, sphingolipids impact cholesterol absorption.
Reduction of LDL cholesterol and elevation of HDL cholesterol by SM consumption in rats and mice makes SM a potential "functional food" [5]. However, Ohlsson et al. found no significant changes in plasma lipid profile after consumption of SM by humans, [18,19]. These studies were free living studies and not well controlled with the background diet during the study. Earlier study [18] was a parallel designed study and the latter one [19] analysed the postprandial lipids with single dose SM administration. Both these studies tested a milk drink -like formulation containing sphingolipids (975 mg) including SM (700 mg), glucoceramides (180 mg) and gangiosides (95 mg). Hence, there is a need of a study with well controlled background diet and cross design to determine the effect of SM when consumed alone on lipid metabolism. There are no such studies with humans to report the effect of SM consumption on cholesterol kinetics including cholesterol absorption and synthesis. The aim of the current study was to analyze the effect of dietary SM supplementation on serum lipids, cholesterol absorption and synthesis and its effects on the intraluminal cholesterol solubilization process under a well controlled situation in humans.
Ten subjects (5 males and 5 females) of age 32.7 ± 4.1 y; height 170 ± 11 cm; body weight 66.2 ± 9.5 kg and BMI 23 ± 2 kg/m2 (Mean ± SD) completed the controlled randomized cross over study. No adverse events were reported during the study. No significant changes in body weights were observed throughout the study.
Total, LDL- and VLDL-cholesterol in serum were not altered by SM consumption compared with control diet phase (Table 1). Triglyceride concentrations also were unaffected by dietary SM. In contrast, HDL-cholesterol concentrations increased (p = 0.043) with SM supplementation compared to control phase. There was no significant change in cholesterol absorption (Figure 1) or cholesterol FSR (Figure 2) after consumption of diet with SM compared to diet without SM.
Table 1. Effect of SM and control diets on serum lipid profile
Figure 1. Effect of SM consumption on cholesterol absorption. Cholesterol absorption of each subject after consuming a diet with or without SM is expressed as pool/pool. On day 16 of each phase, subjects received oral and intravenous doses of stable isotope labeled cholesterol and blood was collected at baseline and at 24, 48, 72, and 96 hours. Cholesterol absorption was measured using the dual isotope method as described in methods.
Figure 2. Effect of SM consumption on cholesterol FSR. Cholesterol FSR of each subject after consuming a diet with or without SM is expressed as pool/day. On Day 19 of each phase, after an overnight fast, baseline blood was drawn and deuterated water was administered. On day 20, blood was obtained at the same time as isotope administration on Day 19 for measurement of FSR as described in the methods.
Luminal bile acid concentrations were similar after a liquid meal in subjects fed either diet (Figure 3). The amount of micellar (solubilized) cholesterol was similar between the subjects fed SM or control (AUC: 34.2 ± 8.0 vs 39.2 ± 5.6, respectively) (Figure 4). As total cholesterol was also similar, solubilization of cholesterol was the same in subjects fed either diet (Figure 5).
Figure 3. Effect of SM consumption on luminal bile acid concentrations. Concentrations of bile acids in the lumen after consumption of a diet with and without SM have been measured and expressed as milli molar concentrations. Open and closed circles represent bile acid concentrations after a SM diet and control diet respectively. Data are presented as means ± SEM.
Figure 4. Effect of SM consumption on luminal total and subphase cholesterol concentrations. Concentrations of total and subphase cholesterol are shown in panel A and B respectively. Cholesterol content was measured in total luminal content and the aqueous subphase which contains the solubilized cholesterol after ingesting a standardized meal. Open and closed circles represent cholesterol concentrations after a SM diet and control diet respectively. Data are presented as means ± SEM.
Figure 5. Effect of SM consumption on ratio of luminal subphase cholesterol concentrations. Ratios between the total and subphase cholesterol after ingesting a standard meal measured and expressed as percentages. Open and closed circles represent ratios of luminal subphase cholesterol concentrations after a SM diet and control diet respectively. Data are presented as means ± SEM.
The results of the current study indicate that in humans, dietary SM supplementation of 1 g/day for a diet containing 240 mg cholesterol/day does not affect cholesterol absorption, synthesis or serum lipids except for an effect of raising serum HDL-cholesterol. Current study represents the first definitive study to measure the lipid profile, cholesterol absorption and synthesis in humans under well controlled background diets. Studies in humans, to date, on the effect of SM on cholesterol metabolism or absorption have been limited despite its potential effect demonstrated in rodents and cell culture. Although there has been a human trial with administration of SM enriched formulated drink, study had been conducted under free living conditions without robust control on background diet [18].
Effect of dietary sphingolipids on plasma lipids was examined by Ohlsson et al. [18] in a parallel design of 48 healthy adults who consumed a sphingolipid enriched milk drink containing 975 mg sphingolipid with 700 mg as SM daily for 4 weeks. Consumption of sphingolipids in this amount had no effect on plasma lipids. Previous studies on effect of sphingolipids on postprandial lipid concentrations showed no change in plasma lipid profile. Although our study was only 2 weeks in duration and was 1 g SM/day with a cross over design, we found similar results with the exception of increased HDL-cholesterol with SM dietary enrichment.
Findings from studies with various animal models [13-17] have shown reductions in plasma total and LDL cholesterol along with reduction in intestinal cholesterol absorption. SM supplemented diet (0.5%) for 45 days reduced the hepatic lipids and plasma non HDL cholesterol levels in Zucker fatty rats [16]. Hyperlipidemic APOE*3 Leiden mice consuming a Western diet supplemented with 0.2 and 0.4% sphingolipids for 3 weeks had reduced plasma cholesterol and triglycerides, whereas, lower supplementations (0.1%) had no effect on plasma lipids. When higher levels were fed (1%), cholesterol absorption was reduced by 50% in this animal model leading to a 57 and 58% reduction in plasma total cholesterol and triglycerides respectively [15]. In male Sprague Dawley rats, cholesterol absorption was 19.5% after SM treatment compared to 37.6% in control animals [20].
Rodent studies have also suggested that the ratio between SM and cholesterol may also be a significant determinant for the inhibitory effect of SM on cholesterol absorption. Cholesterol absorption was reduced by different range of molar ratios of SM and cholesterol between 0.5 and 2.6 in rats [13]. Intestinal cholesterol absorption was 17, 9 and 25% when rats treated with SM and cholesterol at 2.6:1, 1:1 and 0.5:1.0 ratio respectively, compared to 68% when treated with cholesterol alone without SM [13]. However, our study used SM to cholesterol molar ratio of 1.0:0.3 which is closer to one of the molar ratios used in the animal study [13] but we found no significant change in either cholesterol absorption or synthesis.
It is disappointing that the previous findings in animal and cell culture studies could not be replicated in humans because of the potential that SM might be used as a functional food. There may be several reasons for these species/experimental condition differences in our findings. SM is not rapidly hydrolysed in intestine in rodents. SMase, which is responsible for digesting SM, is present in very low quantities in pancreatic juice and bile from liver of rats [21]. SMase is an alkaline enzyme that is active at pH 9 and hence is inactive in gastric and duodenal lumen. Hydrolysis of SM in the upper small intestinal lumen is very deliberate, ineffective and incomplete which might be responsible for the inhibitory effect of cholesterol absorption by SM in animal models [22]. In contrast, in humans the hydrolysis of SM is faster and more efficient than rodents as SMase is secreted into the bile [23]. Recently it has been demonstrated that humans can digest and absorb most of the SM consumed in normal diets [24]. It has also been reported that enzymes responsible for digestion of SM including intestinal alkaline SMase and ceramidase are well expressed in humans [25,26]. Unlike animals, SMase is expressed both in the intestine as well as in liver [21,23,27] in humans. However, the digestion of sphingolipid by these enzymes remains poorly defined. The effects of these enzymes may be affected not only by the presence of other lipids but also the ratio between bile salt and SM as well as bile salt and ceramide [28,29].
Although it has been reported that SM could bind to luminal cholesterol and resist solubilization into bile salt micelles [11,12], we found no changes in the concentrations of luminal bile acids and cholesterol in humans in the current study. These findings suggest that the inhibitory effects of SM on cholesterol absorption in rodents is likely different than the effects in humans. Although this is the first definitive study of the effect of SM on cholesterol metabolism and absorption in humans, there were some limitations of current study: 1. The presence of multiple enzymes in the human gut including SMase were not analysed which may explain why we did not see the effects of SM in humans found in rodents. 2. Our sample size was small but given the minimal changes observed a larger sample would likely have shown similar results. 3. There may have been confounding problems with solubilizing SM with olive oil as this may not truly represent how SM might be present in the matrix of a high SM diet; however, this was only practicable way to ensure added SM in the diet. 4. The dose of SM may not have been sufficient to observe changes in cholesterol absorption/metabolism given the proposed higher efficiency of SMase in humans vs. rodents.
The current study included only healthy subjects. More studies may be needed to determine whether SM affects cholesterol absorption and plasma lipids in hyperlipidemic subjects. The dose of SM supplementation used in the current study was 1 g/day and was well tolerated as observed in a previous human study in humans consuming 975 mg per day of sphingolipid or 4 weeks [18]. To determine an inhibitory effect on cholesterol absorption and reduction in plasma lipids, the dose could be increased provided that the increased dose does not cause any deleterious effects. Unfortunately, the cost of such supplementation may make additional supplement prohibitive and identifying foods with high SM content might be a more practicable approach.
In conclusion, consumption of 1 g/day of SM added to the diet in humans does not affect cholesterol absorption, synthesis and blood lipid profile except an increase in HDL. Hence, further studies are needed to investigate the safety and efficacy of SM consumption with optimal higher doses.
Subjects and Methods
Human subjects
Healthy adult males and females (n = 10), ages 18–45, were recruited by advertisement. Subjects were screened for cardiovascular, pulmonary, renal, gastrointestinal, hepatobiliary disease or soy allergy and excluded if any exclusionary conditions were found. Subjects with diabetes mellitus and plasma total and LDL cholesterol exceeding 200 mg/dl and 120 mg/dl, respectively, were excluded. Only subjects with Apo A-IV 1/1 and Apo E 3/3 genotypes were enrolled to minimize the effects of variability in cholesterol absorption related to differing genotypes. Women were non-pregnant and were on no oral or implantable contraceptive or took the same contraceptive throughout all sessions of the study.
Study design and procedures
Once screened and signatures in informed consent forms were obtained, subjects supplied a 3 day diet diary. Based upon caloric intake from the diet diary, the total calories to maintain steady weight were estimated and diet menus prepared on a 3 day rotating schedule. Diets were designed to contain 240 mg cholesterol/day with 30% calories as fat (15% monosaturated) with a P/S ratio of 0.5. Subjects were randomized to diets with or without added 1 g SM, provided as milk SM (Avanti Polar Lipids, Inc. Alabaster AL), dissolved in corn oil and added to the diet at a dose of 1 g/day (Table 2).
Table 2. Composition of the background diets
On Day 0, after an overnight fast, subjects visited the General Clinical Research Center (GCRC) at Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, had a physical examination and had blood drawn for serum total, HDL and LDL cholesterol and triglyceride measurement. Thereafter, subjects visited the GCRC every third day to pick up prepared diets which were frozen after preparation. Subjects were weighed weekly to ensure maintenance of basal weight.
After two weeks on the diet (Day 14), study subjects were seen after a 16 hours fast at the GCRC. Urine samples were obtained for pregnancy testing on women of childbearing age. Topical anesthesia was applied to the nose and throat, and sedation was used with intravenous midazolam if subjects wished. A nasoduodenal tube was placed with fluoroscopic guidance with the tube tip at the ligament of Treitz. Subjects ingested a meal consisting of olive oil, egg and egg white, sucrose, vanilla extract and 0.15 M NaCl in 240 ml water [30,31]. Duodenal drainage (15 ml - 20 ml) was collected by siphonage in 15-minute intervals for 1 hour and then 30-minute intervals during the second hour. Aliquots were saved and stored at -70°C for each time period until analysis [32].
On day 16, subjects received oral and intravenous doses of stable isotope labeled cholesterol and blood was collected at baseline and at 24, 48, 72, and 96 hours for measurement of cholesterol absorption using the dual isotope method. On Day 19, cholesterol fractional synthesis rate (FSR) was assessed. After an overnight fast, baseline blood was drawn for RBC cholesterol isotopic ratio and for serum total, HDL, and LDL cholesterol and triglycerides. Subjects were given oral deuterated water and the next day (Day 20), blood was obtained at the same time as isotope administration on Day 19.
After completing the baseline studies, subjects participated in the alternative arm of the study with a washout period of at least 4 week between studies. Thereafter, the same sequence of events was performed as described for the first phase of the study. This study was approved by the Institutional Review Board of CCHMC and the Scientific Advisory Committee of the GCRC.
Laboratory analyses
Serum lipid profile analysis
Serum total and HDL cholesterol and triglyceride concentrations were measured enzymatically by Quest Diagnostics Nichols Institute, a certified Center for Disease Control Lipid Research Clinic.
Cholesterol absorption measurement
Free cholesterol was extracted from RBC according to established methods [33]. 13C cholesterol enrichments in RBC lipid extracts were determined using an on-line gas chromatography/combustion/isotope ratio mass spectrometry approach (Agilent 6890 N chromatograph interfaced with a Finnigan Delta V Pulse isotope ratio mass spectrometer (Bremen, Germany)). Isotope abundance, expressed in delta (d) per mil (‰), was calculated using CO2 as a reference gas and further corrected against the international reference standard, Pee Dee Belemnite limestone. The measurement of free-cholesterol deuterium enrichment was performed using online gas chromatography/pyrolysis/isotope ratio mass spectrometry and expressed relative to standard mean ocean water and a series of standards of known enrichment. Isotope abundance, expressed in d ‰, was calculated using H2 as reference gas. The average 13C and D7 enrichments of 48 and 72 hours RBC free cholesterol relative to baseline samples were used to calculate the cholesterol absorption coefficient using the ratio of orally ingested 13C cholesterol to intravenously administered D7 cholesterol as described by Bosner et al. [34] and by us [35].
Cholesterol FSR determination
Cholesterol synthesis rates were assessed after 24 hours of deuterium water administration using the deuterium incorporation approach [36] as previously described [35]. This method measures cholesterol synthesis as the rate of deuterium incorporation from body water into RBC membrane free cholesterol over a 24 hours period. Deuterium enrichment was measured in both RBC free cholesterol and plasma water as described above. Enrichments were expressed relative to standard mean ocean water using a calibration curve of working standards [36].
Intraluminal cholesterol solubilization
Duodenal aspirates of 0.5 ml aliquots were saved to represent total luminal contents and 12–15 ml separated into the oil, subphase (aqeous) and pelleted phases by ultracentrifugation at 39,000 rpm for 60 min in a SW40 rotor (Beckman Coulter, Inc., Fullerton, CA) at 37 degrees C as described earlier [32]. Cholesterol was measured in the total and subphase intraluminal contents by gas liquid chromatography; the ratio of subphase to total cholesterol was considered solubilized cholesterol. Bile acid concentrations were measured in the subphase using enzymatic assays (Trinity Biotech, Bray, Ireland).
Apolipoprotein genotypes
DNA from peripheral blood was isolated according to instructions provided in the High Pure PCR Template Preparation Kit (Boehringer Mannheim, Indianapolis, IN). ApoE and ApoA-IV genotypes were determined as described earlier [37,38].
Statistical analysis
Results were expressed as mean ± SEM obtained from ANOVA using the root mean square error to estimate the pooled standard error. End point variables were tested for statistical significance by paired t-test with p < 0.05. All statistical measures were analyzed using Statistical Package for the Social Sciences version 10.0.
SM: Sphingomyelin; GCRC: General clinical research center; CCHMC: Cincinnati children's hospital medical Center; FSR: Fractional synthesis rate.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
JEH, LAW and PJ designed research; DDB and JEH coordinated and completed the trial and collected all the data; VRR performed the laboratory analysis, compiled data and performed the statistical analysis; VRR and PJ wrote the final draft and had primary responsibility for the final conduct. All authors read and approved the final manuscript.
We thank Dr. Scott Harding Adjunct professor, Department of Human Nutritional Sciences, University of Manitoba and Khatima khalloufi, Richardson Centre for Functional Foods and Nutraceuticals for their help with the analytical part of the study and Suzanne Summer and the staff of the Body Composition Core of the General Clinical Research Center for their help with dietary management for the study. Supported in part by the National Institutes of Health DK068463 and by an Institutional Clinical and Translational Science Award, NIH/NCRR Grant Number 5UL1RR026314-03.
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text:
I found something satisfying,
Pleasing to my taste,
As I offered some to others,
I found that not all felt the same.
I looked for things more tasty,
Something a bit more pleasing,
Dreaming of the perfect stew,
With the most irresistable of seasonings.
Only the most liked go into this brew,
Full of things that amaze me,
But my desire is to amaze you.
Everytime I gave a taste,
Some enjoyed it, some disliked it,
If it is not perfect, it can't be done,
I'm not a psychic,
I can't please everyone.
I'm naked, covered in blood,
My hands caked in mud.
Through my window shines,
the fullness of the moon,
I opened a cabinet to put away my spoon,
Thinking I should try something else,
Then I saw new ingredients,
It just appeared on my shelf,
Needless to say I added it,
I could make something good,
It never occured to me,
It might not be healthy,
Or even if I should.
I looked at what I was creating,
It looked vile,
Like a dead monkey,
And a mutant dog that are mating,
Swimming in the after birth,
Of a week old still born child.
It rose out of the pot,
Untill we were at eye level,
I looked to my left,
Where I was getting these ingredients?
That is when I saw the devil,
The laughing, smiling devil.
The cooking pot was my mind,
The satistfying thing was truth,
The stew was cultivation in time,
Evil and deceptions,
Had let this monster loose.
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Last Updated: July 9, 2014
Office Still Lags Outside Energy, Tech Markets
CHICAGO��If you see the office employment rates increasing in individual markets, you�ll see an increase in absorption� as well as greater investor appeal, Sperry Van Ness� Albert Lindeman tells GlobeSt.com.
You can now be notified via email if this story is updated by clicking on the "Follow this Story" link. You must be a registered member to take advantage of this "members only" benefit.
One of the best interviews ever on GlobeSt because there are lots of real facts and figures about multiple markets that are useful for readers!!!


text:
On Barbaro: The Horse That You Hold Dear
By: Jonathan David Morris
Most people don't care about thoroughbred horse racing.
Three Saturdays each spring, countless Americans gather 'round to watch a bunch of horses they've never ridden or even seen up close in person compete in the Triple Crown races. We curl our toes and clench our lips. Our hearts beat quickly. And for an annual total of roughly six minutes, most of us do seem to care.
But most of us don't really care about thoroughbred horse racing. We just think we care about thoroughbred horse racing.
What we really care about is Triple Crown racing. Which, as we all know, is the only racing that counts.
When a horse by the name of Barbaro won this year's Kentucky Derby in decisive, almost arrogant fashion a couple of weeks ago, all the familiar "Will this be the year?" Triple Crown talk started up full force again. No horse since Affirmed in '78 (or was it Yastrzemski in '67.?) has worn the proverbial three-pronged headpiece, and every year America gets behind whichever horse seems like he could.
Had Barbaro simply tried and failed like so many others, his story would be. well, like so many others. He would be this year's version of last year's "whichever horse almost won it last year." On May 20th, however, his story took a much different turn.
The stage was set at Pimlico Race Course for the 131st running of the Preakness Stakes. With a buzz in the air and the race about to begin, Barbaro broke through his gate a moment too early, and had to be re-corralled.
A minute later, the race finally-officially-got underway. And the planets, it seemed, prepared to align.
Within seconds, however, Barbaro stumbled, and fractured his right hind leg.
In an instant, his run at Triple Crown history was over. His racing career itself was over. And like any horse with a leg injury, his life was suddenly in jeopardy.
I have to be honest. After watching Barbaro's fate unfold at the Preakness, I was somewhat depressed the rest of the evening. I've been following all the updates on his condition since it happened, and I was relieved to learn he did well in surgery. At one point the night of the Preakness, I actually found myself praying for this horse to survive his injuries. I know I'm not the only one who did this. Countless Americans have vowed to keep Barbaro in their prayers.
All this sympathy is good, in my opinion. I'm glad that it's happening. But when you stop and think about it, it's really pretty weird.
I mean, here we are, praying to the same God credited with creating the universe-and for what? A horse most of us have never ridden or even seen up close in person? Why would we do this?
And more importantly: If most of us don't really care about horse racing, what gives us the right-when it comes to Barbaro-to honestly, truthfully care?
It would be easy to cast off these feelings as collective guilt here. Human beings routinely force horses to run around in circles for no real reason. Deep down, most of us probably realize this is bizarre. But I think what it really comes down to is the same question I find myself asking every time I watch horse racing, which is: "Do the horses enjoy it?" Obviously, that question is impossible to answer. But if you looked at Barbaro's face when he broke through the gate too early, it really looked like he cared about winning. He probably didn't, but after breaking his leg-and shattering the dream-a minute later, all that mattered was he looked like he did.
In that moment, Barbaro wasn't a horse anymore. He was a boxer trying to beat the ten count. And he was more than that. He was anyone who ever wanted something so badly that they totally screwed things up.
Am I blowing this way the hell out of proportion? Absolutely. But that's the whole point. The Triple Crown, itself, is blown out of proportion. Sports are blown out of proportion. So are most things we hear on the news. There's a reason for this. And in case you haven't noticed, it's because life is pointless. Not that we're necessarily here for no reason-that's not what I'm saying. But who among us hasn't felt useless at some point? Who hasn't opened their eyes in the morning and said to themselves, "Again?"
People fear change, but they hate the inevitable. That's why we root for things that aren't supposed to happen. Sometimes this means rooting for a Triple Crown horse. Other times, it means rooting against Barry Bonds making homerun history.
Barbaro surviving is another thing we root for. After all, it's against the odds. Most horses who suffer his injuries are euthanized right on the track.
All things considered, horse racing exists for the sake of gamblers. But all things considered, all of us gamble everyday when we get out of bed. We bet on our lives having some kind of meaning. We look ourselves in the mirror, and look like we care if we win. In the end, most of us can identify more with all those nameless, faceless horses who get euthanized. We toil in anonymity. And we die largely underreported deaths.
This doesn't mean we shouldn't care about Barbaro. Quite the opposite. I think we should. It just means that caring about Barbaro means caring about more than Barbaro. In a way, it means caring enough to keep caring-whatever the odds are.
So feel better, Barbaro. And hey: Get well soon.
Jonathan David Morris is a Staff Writer for The New Media Alliance. The New Media Alliance is a non-profit (501c3) national coalition of writers, journalists and grass-roots media outlets.
Columns by this author can be read regularly on TheRealityCheck.org.


text:
TV review
Review: The Walking Dead – Season 4, Episode 5
There are several moments in this fifth episode of the season when the events being depicted on-screen are torturously tense. From the gruesome, tone-setting teaser through to the surprise conclusion, this episode stands up as one of the finest episodes of The Walking Dead so far
By Alex Straker | Notebook | Monday, 18 November 2013 at 6:47 pm
Breathless Review: Series 1 , Episode 5
The comedy of manners that is Breathless becomes more of a tragedy this week, as events cause everyone's mask to slip, even that of top man Mr Powell (Jack Davenport).
By Lina Talbot | Arts | Friday, 8 November 2013 at 6:40 pm
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7 Accessories That Every Woman Should Have in Her Wardrobe
Certain accessories should make it into every woman's closet in order to provide a foundation for throwing an outfit together at the last minute. Since accessories can make or break an outfit, it is important to keep a few essential items in the closet to help you pull off the perfect look each and every time that you go out the door.
1. A Classic Trench Coat
Offering a timeless look that transcends generations, the classic trench is a must have for any woman's closet. This is a good alternative when a coat is needed, but a heavier, winter style is too much. The trench is a coat that offers a distinctive appearance that goes well with many different styles of outfits including casual and business casual. In fact, putting a trench coat on completely hides whatever it is that you are wearing underneath, so it's a great tool for camouflage when you want to hide a rumpled or stained outfit.
2. Black Pumps with Heels
A pair of black shoes can be worn with almost any type of outfit from casual to work to evening wear. In fact, you can pack up a pair of black pumps in an oversized bag and take them with you on a casual outing for which you are wearing flats and switch your shoes for dinner wear. Closed toes with those black pumps offer a classic look that is perfect whether you are wearing a dress or jeans.
3. Ballet Flats
Comfortable and stylish , ballet flats can be worn with almost every type of outfit including those in which you are wearing shorts, pants, skirts, jeans or a dress. One of the most endearing aspects concerning ballet flats is that they are definitely girly in appearance. They are easy to slip on and easy to take off, making them the perfect "quick change" footwear.
4. An Oversized but Classy Bag or Satchel
Every woman can use an oversized bag or satchel for so many different occasions from overnight trips to full-day adventures to shopping outings to so much more. A neutral-colored bag allows you to pair it with a greater number of outfits. Oversized bags can be stylish, while holding lots of daily essentials. They are terrific for days or nights when you want to carry an extra pair of footwear, a wrap, or a quick change of clothes.
5. Dangling Earrings
Dangling earrings can easily be paired up as stylish accents for an endless array of fashionable outfits. Choose silver or grey tone earrings for the best opportunity to match your dangling earrings attractively. They add a touch of dazzle that instantly brightens up any outfit.
6. A Cashmere Wrap
Cashmere offers a touch of luxury. Combining a neutral-colored cashmere wrap with a pair of slacks or a skirt creates an elegant outfit that can be worn with confidence to a luncheon, bridal shower, business meeting, or casual outing. The wrap can also be carried in an oversized bag for those moments when it isn't needed.
7. The Black Dress
From a funeral service to a gallery showing to an evening gala, the little black dress makes its appearance in numerous places, all the while looking perfectly appropriate. The black dress truly is a staple that should find its way into every woman's wardrobe. Slip on the black dress and a pair of matching shoes, and you have an outfit that can be worn during the day or evening, depending on the accessories that you select to wear with it.
Post contributed by Christine Harding, on behalf of Wish.co.uk