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Maya S. is currently a junior at SYA China. She comes to SYA from Choate Rosemary Hall (CT) and is a blogger for our Campus Reporter program. View more of Maya's work throughout her year abroad here.
Happy Chinese New Year!
It's the year of the Rooster! In China, the rooster is a sign of fidelity and punctuality, hence their significance as alarm clocks. At the end of January, I got to celebrate the New Year by eating plenty of dumplings, visiting local temple fairs, and watching CCTV's annual Spring Festival Gala. Though, the most exciting part of the New Year was definitely the fireworks.
I used to live in Chicago and would watch fireworks on the 4th of July but, I've realized that those were merely a murmur compared to the ones that exploded throughout Beijing. As soon as the clock struck midnight, the entire sky suddenly burst with bright, sparkling lights – in front of my window, in the far distance, in other buildings' reflections, and on the TV screen. From where I was standing, I counted 30 different locations where fireworks were being set off.
I learned that according to Chinese tradition, making a lot of noise during the New Year will drive away evil spirits. Hours later, when the noise finally died down, I certainly felt that Beijing would be free of any evil for a very long time.
Entering Tea Territory
After the New Year celebrations ended, everyone from SYA China headed to Yunnan. While there, the sky had been perfectly clear, and the sun was bright enough that I had to reapply sunscreen many times. After living in Beijing's frigid winter for so many months, I had forgotten how wonderful sunshine feels.
My favorite part of the Yunnan trip was living in rural villages. As an American high school student, accustomed to living in a fast-paced environment, I was very unfamiliar with the relaxed, simple culture of the villagers in Yunnan. This peaceful way of living, I soon learned, revolved mainly around tea. Essentially, growing tea is the villagers' occupation their entire lives. Every day, they tend to their thousands of tea shrubs, drink tea at every meal, and then sell their tea to larger markets in the city. The home I stayed in even had a nicely detailed, hand-embroidered portrait of a tea plant hung in the center of their wall.
The only way I can describe how people drink tea in China is "perpetually" because it never seems to end. No matter how much tea I drink, I am always served one more cup, thinking it's going to be the last one. I'm not complaining, though, the tea here is light, flavorful, and soothing. It was a pleasant surprise when my village host family gave me a bag of hand-picked tea leaves to take home with me.


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I'd like to say that I am a woman who loves women.
Women are fascinating and inspiring.
I think men are too, of course, but I've spent most of my life watching movies and shows by men, about men; reading books by men, for men; and listening to music written, produced, and sung by them.
Around the same time, I watched female characters, created by men, that all had the same characteristics: skinny, white, upset about a man, looking for a man, focused on a man, backstabbing a woman, competing with a woman for a man, etc.
I didn't act like these women. Of course, I didn't want to act like these women, so when
my guy friends said things like "you're not like other girls" or "you're just one of the guys," I took it as a compliment.
But it isn't a compliment, is it?
How could I love myself? How could I love women, when it's considered an insult to be one?
I was taught many things that even my alpha-female mother couldn't prevent:
1. Boys like the skinny girls now, but you'll have boobs before those skinny girls do.
2. Just kidding, boys like skinny girls with unrealistically-sized boobs for their body-types.
3. Did I mention you need to be skinny, but you also need to be able to eat a burger because men "like a woman that can eat"?
4. Boys don't like smart girls; they're intimidated.
5. Boys don't like athletic girls; they're intimated.
6. If a boy is mean to you, it's because he likes you.
7. Men are more sexual than women.
8. Sex doesn't mean the same thing for men.
9. Women are catty-backstabbers.
10. Show some cleavage.
11. Don't show cleavage; men can't handle that.
12. Seriously child, put those shoulders away, do you want to distract the boys from their studies?
13. Try being modest for once, you temptress.
14. Don't put out too early.
15. You're such a prude.
16. You don't want sex as much as a man does.
17. Don't let a man use you.
18. *Watches a million commercials where women are used as sex objects to sell cars, cheeseburgers, handbags, etc. You name it; we'll attach a half-naked woman's body to it and sell it.*
19. Well, what was she wearing?
20. Was she drinking?
21. You don't want to be like other women.
22. Women aren't funny
23. Women aren't interesting
24. If you're funny and interesting, you're just one of the guys.
This isn't an extensive list, but you get the point.
From my experience, there are all these expectations set on a woman's behavior: like we have to be this sexy-modest virgin that slays in the bedroom, who also doesn't get too drunk at parties while simultaneously maintaining her party girl image; hanging out with all male friends and no female friends because women are backstabbing b*tches.
That girl doesn't exist. And if she did, she would be miserable, and her guy friends would whine about being in the friend-zone.
I think we all go through a phase where we try to be that girl.
I know, I went through it.
I began to shrink my servings, then my body, and then my voice — all because somewhere along the line someone told me that's what men want; Someone told me that's what women should want.
So I tried to occupy less space, sit pretty, spend less time thinking about the world and more time thinking about makeup.
I struggled to laugh at stupid dude-jokes but, I'd think, "just laugh, men have precious egos, they won't like it if you're so sarcastic."
I'd buy anything that promised to make me skinnier; prettier.
I'd buy into the idea that this would make me happier.
I'd cry over crop tops that didn't expose a perfectly flat belly.
I'd try to be that girl.
A friend of mine once told me, "Women have to unlearn all the things that we were taught to find ourselves."
But it's hard to do that with friends that can't stop competing over who ate fewer calories.
Luckily, I found my women on the steps of Hillman Library, out on a smoke break.
Mary, who I was friends with in high school, Leah, Camille, Kelsi, and Cèlia.
They were uniquely beautiful people; unflinchingly stylish and effortlessly aware of their sexuality.
I still picture us gathered at our usual spot in the library talking politics, philosophy, and social justice over piles of books. We're all sleep deprived of studying or drinking; we're moving quickly from topic to topic: we're giving a run down on each of our research papers, then we're discussing places to travel, then half of us are napping with our heads on the table, and the other half is typing furiously in an Adderall-ridden trance.
We didn't talk about our weight, we never called other women sluts, we never called other women ugly—that's important. You are who you surround yourself with.
Of course, these women weren't perfect, but that's what made them so fascinating.
They taught me how to love myself and how to love other women; something I am forever grateful for.
Unfortunately, I'm still a hater…
If I see a woman that looks better than me at the gym, I hate her.
If I see a woman who looks damn good in a revealing outfit at the club, I hate her.
If my friends say another woman is so beautiful, I hate her.
I want to say things like "well, she's got a nice body but she's not very beautiful," "she's dressed a little slutty," or "she's ok, I guess."
I want to say these things, but I don't, because I know that my initial response is coached. I've been trained to view other women as competition for men's attention. I've been trained to think men's attention actually matters. So instead of trusting my not-so-instinctual instinct, I talk to myself.
"Haley, why are you thinking like that? She looks damn good, good for her for coming to the gym tonight to work off some stress. Praise girl, go lift, do your thing."
"Haley don't slut shame; you are the problem. She looks amazing, good for her. I support her decision to wear what she wants no matter what people will think."
"Yeah… she really is gorgeous."
I'm only a hater for a split-second, but it's a split-second long enough to remind me that I'm still un-learning.
Show Comments (40)

subset: commoncrawl


text:
In 2000, we set up a company in Germany, and started hiring Romanian and Moldovan IT engineers to work in Germany. In 2003, we established our first company in Moldova and currently we have two further companies in Moldova and also one in Japan.
The Moldova Work Recruiting Agency has now become a leading manpower agency with more than 25,000 jobs offered and 20,000 registered CVs. Our recruitment agency finds employment for Moldavan workers in construction, manufacturing, agriculture, cruise shipping, hotels, restaurants, and as au pairs, IT engineers, artists, drivers, doctors, nurses, and nannies in many countries in Europe, the Middle East, Japan and the U.S.A. The Moldovan Work Recruiting Agency is located in the center of Chisinau, the capital of the Republic of Moldova. We apply for an employment visa for our Moldovan workers and send them abroad. If you want the best Moldovan Recruitment Agency, just contact us!
Moldova Work is a professional, friendly, and reliable Moldovan staff agency. Every member of our recruitment agency staff is fluent in both spoken and written English; we can usually communicate most effectively in this "international" language.
We also have both Skype and Yahoo Messenger and we are always online during working hours, so you can ask any question, anytime. Please do not hesitate to contact us with any type of enquiry.
When our Moldova staffing agency begins a business relationship with your company for the first time, our staff can visit your company and explain our ways of doing business face to face. This way, you can get to know us that much better. If preferred, the Moldova Work Recruitment Agency can train its workers in languages, IT, and cultural issues in your own country.
The Moldova Work Recruitment Agency always tries to give accurate information about our job recruitment company, and never hides information from our customers and workers no matter what the consequences.
Our recruitment agency activity and our business methods always comply with internationally recognized regulations.


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When creating files in Windows, those files will have the DOS format. This creates annoying ^M characters at the end of lines, which can be seen in patches or diff files.
In order to localize them, use this command:
find . -not -type d -exec file "{}" ";" | grep CRLF
It will give an output like this for dos files:
./example.txt: ASCII text, with CRLF line terminators
Then open them in emacs, and launch that command:
M-x set-buffer-file-coding-system RET undecided-unix
M-x means escape and X. RET is return. Then save your file and you are done.


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- Home
- About Us
About Us
Capsule Supplies is a family-run business that has been providing healthful options in empty pill capsules since 2002. Our mission is to provide the highest quality empty gel capsules at prices that in most cases meet or beat the competition's. Our facility is FDA-registered and in compliance with Good Manufacturing Practice (GMP).
Capsule Supplies was founded to provide cleaner options for your capsule needs. Therefore, when we say a product does not contain any toxic or potentially toxic ingredients, rest assured that we mean it. This cannot be said by other capsule companies. In fact, because the FDA does not require labeling certain additives, such as sodium lauryl sulfate, other capsule companies may not even know that the capsules they are selling contain these potential toxins. Capsule Supplies guarantees that we disclose ALL ingredients to empower healthier choices. Whether you need empty pill capsules or a capsule filling machine, you can find it right here.
A portion of our profits is donated to local no-kill animal shelters and the Wounded Warrior Project.
Contact information:
Call us at 888-515-7094


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Schmidt: slow down on infrastructure money
(WJBK) - Gov. Rick Snyder presented the concept in his State of the State last night to raise new revenues to repair the state's sagging and aging infrastructure - but not the details on how to raise the money and, as far as state senator Wayne Schmidt is concerned, there is no rush to flesh out those details.
The governor got everyone's attention with his line about needing to find revenue from "fees, taxes, grants, and bonds," but that was it. To which the former chair of the House Transportation Committee asserts the state has "coasted for a long time" but "there's no question. We have to see what Washington is going to do first."
His reference, of course, is to statements from the president-elect that the new Trump administration will offer its own version of infrastructure restructuring and until and unless that is revealed, Senator Schmidt concludes, "I'm not sure how the legislature feels," and he favors doing nothing on the Snyder administration blueprint now. "I don't believe so. It's certainly not what I want to do."
He reports the state needs to gauge the spending of the $600 million being spent on the roads. "What is the impact of that?" he wants to find out and is willing to wait "two years" to reach that conclusion.
The state could take the lead on this reform but he's in no mood to do that either. "That's a pretty fair conclusion."
Meanwhile back in Macomb County, home of the infamous Fraser sinkhole, Rep. Pete Lucida sees no need for any state revenue right now suggesting the money should come from the local governments.
"We need to budget at local government as much as we can first," he argues while suggesting there is not enough state revenue to fix all these infrastructure challenges that may pop-up around the state.
The locals have complained they don't have the revenue either.
Sen. Coleman Young, II thinks the governor should go for it. "If he's serious and he wants to be a leader, he needs to raise the revenue. I don't think he has a choice. Just do it and let the chips fall where they may."
Gov. Snyder has said earlier that it is unrealistic to begin this program at $4 billion a year as his infrastructure commission suggests. "We have a road map and we should begin to go down that road," he believes but the dollar amount and funding sources remain to be divulged.


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The era of big government has returned with a vengeance, in the form of the largest federal work force in modern history.
The Obama administration says the government will grow to 2.15 million employees this year, topping 2 million for the first time since President Clinton declared that "the era of big government is over" and joined forces with a Republican-led Congress in the 1990s to pare back the federal work force.
febrero 02, 2010
Largest-ever federal payroll to hit 2.15 million
Publicadas por ✡Talmid✡ a la/s 8:31 p. m.
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|Publication number
|Publication type
|Application number
|Publication date
|Sep 17, 2002
|Filing date
|Apr 18, 2000
|Priority date
|Apr 18, 2000
|Fee status
|Also published as
|Publication number
|John Thomas Parry, Gary Robert Viviano, James Edward Gantz, Jr.
|Original Assignee
|Pacesetter, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (13), Referenced by (12), Classifications (4), Legal Events (5)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention generally relates to an implantable cardiac stimulation device. The present invention more particularly relates to such a device which includes a system for and implements a method of automatically conducting a non-invasive programmed stimulation (NIPS) procedure for inducing a tachyarrhythmia of a heart to permit the performance of electrophysiological studies.
Frequently, a clinician must perform electrophysiological studies in patients having implanted permanent pacemakers or cardioverters/defibrillators to determine accurately the patient's pathological condition, cardiovascular characteristics and other information needed in order to prescribe a particular therapeutic treatment for the patient. Such studies often require the inducement of a tachyarrhythmia of the heart such as ventricular tachycardia.
Originally, these studies were invasive because they required the surgical insertion of instruments such as temporary intracardiac pacing catheters into the patient. Thus, these studies were accompanied by some risk and preferably were performed in hospitals. Therefore, these studies were not only expensive, but also time consuming and caused patient anxiety.
In order to avoid medical risks to the patient and hospitalization, non-invasive programmed stimulation (NIPS) procedures have been developed to permit the electrophysiological studies to be performed in a physician's office during routine follow-up visits.
These procedures utilize the implanted cardiac stimulation device and an external programmer. By virtue of the presence of a permanent pacing/defibrillation lead associated with the implanted cardiac stimulation device, the need for placement of a temporary intracardiac pacing catheter is eliminated. Typically, NIPS procedures consist generally of the application of premature electrical pulses at precise intervals to the myocardium of the patient's heart by the implanted cardiac stimulation device and its associated lead or leads. The implanted device applies the stimulation pulses under commands from the external programmer which is manually controlled by the clinician. Prior to the procedure, the clinician manually defines the intervals between the successive stimulation pulses on the programmer. After the implanted device applies the succession of stimulation pulses to the heart, the clinician then, on the programmer, manually observes results such as tachyarrhythmia induction or lack of capture by the stimulation pulses. Thereafter, the clinician alters the stimulation pulse intervals and causes the programmer to initiate another application of the successive stimulation pulses to the patient's heart by the implanted cardiac stimulation device. As a result, NIPS studies, as currently constituted, are tedious to administer, consume considerable time, and lead to considerable cost to the electrophysiology laboratory.
The present invention provides a system and method for use in an implantable cardiac stimulation device that automatically induces a tachyarrhythmia of a heart to permit the performance of an electrophysiological test of the heart. In accordance with the present invention, the system and method permits the implantable cardiac stimulation device to perform a NIPS procedure automatically once initial parameters are established in the device by an external programmer under control of a clinician.
In accordance with the present invention, a NIPS protocol is stored in a memory within the implantable cardiac stimulation device. A processor accesses the NIPS protocol stored in the memory to control a pulse generator that repeatedly delivers groups of pacing pulses to a chamber of the heart. The pacing pulses are separated in time by pacing or interpulse intervals to overdrive pace the patient's heart. After each group of pacing pulses is delivered to the heart, the processor varies the pacing intervals according to the NIPS protocol prior to reinitiating the delivery of the next group of stimulation pulses. The processor terminates the delivery of the stimulation pulses if it detects the tachyarrhythmia of the heart after a group of stimulation pulses have been delivered to the heart.
In accordance with a further aspect of the present invention, the processor, in accordance with the NIPS protocol, determines capture of the heart by each delivered stimulation pulse and terminates the delivery of the stimulation pulses to the heart by the pulse generator when a predetermined number of successive pacing pulses fail to capture the heart. In accordance with a still further aspect of the present invention, the processor requires a minimum pacing interval to determine capture of the heart by a stimulation pulse. In accordance with the NIPS protocol, the processor terminates the delivery of the stimulation pulses to the heart when a pacing interval falls below the minimum pacing interval.
In accordance with still further aspects of the present invention, each group of stimulation pulses includes a first set of pulses employed to capture the heart at an overdrive pacing rate and a second set of pulses to induce the tachyarrhythmia. The processor, in accordance with the NIPS protocol, varies the pacing intervals of the second set of pacing pulses between the application of the groups of stimulation pulses.
In accordance with still further particular aspects of the present invention, the second set of pacing pulses includes a last pulse and a second to the last pulse and the processor decrements the pacing interval between the last pulse and the second to the last pulse responsive to the last pulse capturing the heart in accordance with the NIPS protocol. Further, the second set of pacing pulses further includes a third to the last pulse. The processor, in accordance with the NIPS protocol, decrements the pacing interval between the second to the last pulse and the third to the last pulse and resets the pacing interval between the last pulse and the second to the last pulse to an initial interval responsive to the last pulse failing to capture the heart.
The application of the successive groups of pacing pulses is automatically continued with intergroup pacing interval adjustment until the tachyarrhythmia is detected by the processor. The procedure may further be terminated if manually terminated by the clinician, if a predetermined number of pacing pulses fail to capture the heart, or if a pacing interval falls below the minimum interval required by the processor to determine capture of the heart.
Further features and advantages of the present invention may be readily understood by reference to the following description taken in conjunction with the accompanying drawings, in which:
FIG. 1 is a functional block diagram of a dual-chamber implanted stimulation device illustrating the basic elements of a stimulation device which can provide cardioversion, defibrillation, and pacing stimulation, which device embodies and may utilize the present invention to advantage;
FIG. 2 shows one group of stimulation pulses which may be used for performing a NIPS procedure in accordance with the preferred embodiment of the present invention; and
FIG. 3 shows a flow chart describing an overview of the operation of the device of FIG. 1 in accordance with the preferred embodiment of the present invention.
The following description is of the best mode presently contemplated for practicing the invention. This description is not to be taken in a limiting sense but is made merely for the purpose of describing the general principles of the invention. The scope of the invention should be ascertained with reference to the issued claims. In the description of the invention that follows, like numerals or reference designators will be used to refer to like parts or elements throughout.
In FIG. 1, a simplified block diagram is shown of a dual-chamber implantable stimulation device 10 embodying the present invention and which is capable of treating both fast and slow arrhythmias with stimulation therapy, including cardioversion, defibrillation, and pacing stimulation. While a dual-chamber device is shown, this is for illustration purposes only, and one of skill in the art could readily eliminate or disable the appropriate circuitry to provide a single-chamber stimulation device capable of treating one chamber with cardioversion, defibrillation and pacing stimulation.
To provide atrial chamber pacing stimulation and sensing, the stimulation device 10 is shown in electrical communication with a patient's heart 12 by way of an implantable atrial lead 20 having an atrial tip electrode 22 and an atrial ring electrode 24 which typically is implanted in the patient's atrial appendage.
The stimulation device 10 is also shown in electrical communication with the patient's heart 12 by way of an implantable ventricular lead 30 having, in this embodiment, a ventricular tip electrode 32, a ventricular ring electrode 34, a right ventricular (RV) coil electrode 36, and an SVC coil electrode 38. Typically, the ventricular lead 30 is transvenously inserted into the heart 12 so as to place the RV coil electrode 36 in the right ventricular apex, and the SVC coil electrode 38 in the superior vena cava. Accordingly, the ventricular lead 30 is capable of receiving cardiac signals, and delivering stimulation in the form of pacing and shock therapy to the right ventricle.
While only two leads are shown in FIG. 1, it is to be understood that additional stimulation leads (with one or more pacing, sensing and/or shocking electrodes) may be used in order to efficiently and effectively provide pacing stimulation to the left side of the heart or atrial cardioversion and/or defibrillation. For example, a lead designed for placement in the coronary sinus region could be implanted to deliver left atrial pacing, atrial shocking therapy, and/or for left ventricular pacing stimulation.
The housing 40 (shown schematically) for the stimulation device 10 includes a connector (not shown) having an atrial tip terminal 42 and an atrial ring terminal 44, which are adapted for connection to the atrial tip electrode 22 and the atrial ring electrode 24, respectively. The housing 40 further includes a ventricular tip terminal 52, a ventricular ring terminal 54, a ventricular shocking terminal 56, and an SVC shocking terminal 58, which are adapted for connection to the ventricular tip electrode 32, the ventricular ring electrode 34, the RV coil electrode 36, and the SVC coil electrode 38, respectively. The housing 40 (often referred to as the "can", "case" or "case electrode") may be programmably selected to act as the return electrode, or anode, alone or in combination with one of the coil electrodes, 36 and 38. For convenience, the names of the electrodes are shown next to the terminals.
The stimulation device 10 further includes a programmable microcontroller 60 which controls the various modes of stimulation therapy including a non-invasive programmed stimulation (NIPS) procedure in accordance with the present invention. As is well known in the art, the microcontroller 60 includes a microprocessor, or equivalent control circuitry, designed specifically for controlling the delivery of stimulation therapy and may further include RAM or ROM memory, logic and timing circuitry, state machine circuitry, and I/O circuitry. Typically, the microcontroller 60 includes the ability to process or monitor input signals (data) as controlled by a program code stored in a designated block of memory. The details of the design and operation of the microcontroller 60 are not critical to the present invention. Rather, any suitable microcontroller 60 may be used that carries out the functions described herein. The use of microprocessor-based control circuits for performing timing and data analysis functions is well known in the art. Representative types of control circuitry that may be used for embodying the invention include the microprocessor-based control system of U.S. Pat. No. 4,940,052 (Mann et al.), the state-machine of U.S. Pat. No. 4,712,555 (Sholder) and U.S. Pat. No. 4,944,298 (Sholder). For a more detailed description of the various timing intervals used within the stimulation device and their interrelationship, see U.S. Pat. No. 4,788,980 (Mann et al.). The '052, '555, '298 and '980 patents are incorporated herein by reference. As shown in FIG. 1, an atrial pulse generator 70 and a ventricular pulse generator 72 generate pacing stimulation pulses for delivery by the atrial lead 20 and the ventricular lead 30, respectively, via a switch bank 74. The pulse generators, 70 and 72, are controlled by the microcontroller 60 via appropriate control signals, 76 and 78, respectively, to trigger or inhibit the stimulation pulses. The microcontroller 60 further includes timing circuitry that controls the operation of the stimulation device timing of such stimulation pulses (e.g., pacing rate and atrio-ventricular (AV) delay), as well as keeping track of the timing of any refractory periods, PVARP intervals, noise detection windows, evoked response windows, alert intervals, marker channel timing, etc., that is well known in the art.
The switch bank 74 includes a plurality of switches for switchably connecting the desired electrodes to the appropriate I/O circuits, thereby providing complete electrode programmability. Accordingly, the switch bank 74, in response to a control signal 80 from the microcontroller 60, determines the polarity of the stimulation pulses (e.g., unipolar or bipolar) by selectively closing the appropriate combination of switches (not shown) as is known in the art. An atrial sense amplifier 82 and a ventricular sense amplifier 84 are also coupled to the atrial and ventricular leads 20 and 30, respectively, through the switch bank 74 for detecting the presence of cardiac activity. The switch bank 74 determines the "sensing polarity" of the cardiac signal by selectively closing the appropriate switches, as is also known in the art. In this way, the clinician may program the sensing polarity independent of the stimulation polarity.
Each sense amplifier, 82 and 84, preferably employs a low power, precision amplifier with programmable gain and/or automatic gain control, bandpass filtering, and a threshold detection circuit, known in the art, to selectively sense the cardiac signal of interest. The automatic gain control enables the device 10 to deal effectively with the difficult problem of sensing the low frequency, low amplitude signal characteristics of ventricular fibrillation.
The outputs of the atrial and ventricular sense amplifiers, 82 and 84, are connected to the microcontroller 60 which, in turn, inhibit the atrial and ventricular pulse generators, 70 and 72, respectively, in a demand fashion whenever cardiac activity is sensed in the respective chambers.
For arrhythmia detection, the device 10 utilizes the atrial and ventricular sense amplifiers, 82 and 84, to sense cardiac signals to determine whether a rhythm is physiologic or pathologic. As used herein "sensing" is reserved for the noting of an electrical depolarization, and "detection" is the processing of these sensed depolarization signals and noting the presence of an arrhythmia. The timing intervals between sensed events (e.g., the P-P and R-R intervals) are then classified by the microcontroller 60 by comparing them to a predefined rate zone limit (i.e., bradycardia, normal, low rate VT, high rate VT, and fibrillation rate zones) and various other characteristics (e.g., sudden onset, stability, physiologic sensors, and morphology, etc.) in order to determine the type of remedial therapy that is needed (e.g., bradycardia pacing, anti-tachycardia pacing, cardioversion shocks or defibrillation shocks, also known as "tiered therapy"). In accordance with the present invention, the microcontroller 60 may employ a high rate classification to determine if a tachyarrhythmia is present for terminating the NIPS procedure when the tachyarrhythmia has been induced by the NIPS procedure.
Cardiac signals are also applied to the inputs of an analog to digital (A/D) data acquisition system 90. The data acquisition system 90 is configured to sense or acquire intracardiac electrogram signals, convert the raw analog data into a digital signal, and store the digital signals for later processing and/or telemetric transmission to an external device 102. The data acquisition system 90 is coupled to the atrial and ventricular leads, 20 and 30, through the switch bank 74 to sample cardiac signals across any pair of desired electrodes.
The data acquisition system is preferably coupled to the microcontroller, or other detection circuitry, for detecting an evoked response from the heart 12 in response to an applied stimulus, thereby aiding in the detection of "capture". As will be seen hereinafter, capture detection is especially desirable in implementing a NIPS procedure. Capture occurs when an electrical stimulus applied to the heart is of sufficient energy and applied at an appropriate time in a cardiac cycle to depolarize the cardiac tissue, thereby causing the heart muscle to contract. The microcontroller 60 detects a depolarization signal during a window following a stimulation pulse, the presence of which indicates that capture has occurred. The microcontroller 60 may enable capture detection by starting a capture detection window when a ventricular stimulation pulse is issued using the timing circuitry within the microcontroller 60, and enabling the data acquisition system 90 via control signal 92 to sample the cardiac signal that falls in the capture detection window and, based on the amplitude, determines if capture has occurred. As is known in the art, this form of capture detection requires a minimum interpulse interval to sustain the window detection. Further, capture detection is preferably performed on a beat-by-beat basis during a NIPS procedure.
The implementation of capture detection circuitry and algorithms are well known. See for example, U.S. Pat. No. 4,729,376 (Decote, Jr.); U.S. Pat. No. 4,708,142 (Decote, Jr.); U.S. Pat. No. 4,686,988 (Sholder); U.S. Pat. No. 4,969,467 (Callaghan et al.); and U.S. Pat. No. 5,350,410 (Mann et al.), which patents are hereby incorporated herein by reference. The type of capture detection system used is not critical in the implementation of the present invention.
The microcontroller 60 is further coupled to a memory 94 by a suitable data/address bus 96, wherein the programmable operating parameters used by the microcontroller 60 are stored and modified, as required, in order to customize the operation of the stimulation device 10 to suit the needs of a particular patient. Such operating parameters define, for example, pacing pulse amplitude, pulse duration, electrode polarity, rate, sensitivity, automatic features, arrhythmia detection criteria, and the amplitude, waveshape and vector of each shocking pulse to be delivered to the patient's heart 28 within each respective tier of therapy. The memory 94 preferably also stores a NIPS protocol from which the microcontroller automatically controls the NIPS procedure.
The operating parameters of the implantable device 10, the NIPS protocol, and the NIPS initializing parameters or values may be non-invasively programmed into the memory 94 through a telemetry circuit 100 in telemetric communication with an external device 102, such as a programmer, transtelephonic transceiver, or a diagnostic system analyzer. The telemetry circuit 100 is activated by a control signal 106 from the microcontroller 60. The telemetry circuit 100 also allows intracardiac electrograms, status information relating to the operation of the device 10 (as contained in the microcontroller 60 or memory 94) to be sent to the external device 102 through the established communication link 104.
The stimulation device 10 further includes a physiologic sensor 110. Such sensors are commonly called "rate-responsive" sensors. The physiological sensor 110 is used to detect and generate a raw signal representing the activity of the patient, to which the microcontroller 60 responds by adjusting the rate and AV Delay at which the atrial and ventricular pulse generators, 70 and 72, generate stimulation pulses. The type of sensor used is not critical to the present invention and is shown only for completeness.
The stimulation device additionally includes a battery 114 which provides operating power to all of the circuits show in FIG. 1. For the stimulation device 10, which employs shocking therapy, the battery must be capable of operating at low current drains for long periods of time and then be capable of providing high-current pulses (for capacitor charging) when the patient requires a shock pulse. The battery 114 must also have a predictable discharge characteristic so that elective replacement time can be detected. Accordingly, the device 10 may employ lithium/silver vanadium oxide batteries, as is common in many such device to date.
The stimulation device 10 further includes a magnet detection circuitry (not shown), coupled to the microcontroller 60. It is the purpose of the magnet detection circuitry to detect when a magnet is placed over the stimulation device 10, which magnet may be used by a clinician to perform various test functions of the stimulation device 10 and/or to signal the microcontroller 60 that an external programmer 102 is in place to receive or transmit data, including NIPS procedure initializing parameters to the microcontroller 60 through the telemetry circuits 100 or instructions to initiate or terminate a NIPS procedure.
As further shown in FIG. 1, the device includes an impedance measuring circuit 120 which is enabled by the microcontroller 60 by a control signal 122. The known uses for an impedance measuring circuit 120 include, but are not limited to, lead impedance surveillance during the acute and chronic phases for proper lead positioning or dislodgment; detecting operable electrodes and automatically switching to an operable pair if dislodgment occurs; measuring respiration or minute ventilation; measuring thoracic impedance for determining shock threshold; detecting when the device has been implanted; measuring stroke volume; and detecting the opening of the valves, etc. The impedance measuring circuit 120 is advantageously coupled to the switch bank 74 so that any desired electrode (including the RV and SVC coil electrodes, 36 and 38) may be used. The impedance measuring circuit 120 is shown only for completeness.
An important function of the device 10 is to function as an implantable cardioverter/defibrillator (ICD) device. That is, it is capable of detecting the occurrence of an arrhythmia, and automatically applying an appropriate electrical shock therapy to the heart aimed at terminating the detected arrhythmia. To this end, the microcontroller 60 further controls a shocking 130 by way of a control signal 132. The shocking circuit 130 generates shocking pulses of low (up to 0.5 Joules), moderate (0.5-10 Joules), or high energy (11 to 40 Joules), as controlled by the microcontroller 60. Such shocking pulses are applied to the patient's heart through at least two shocking electrodes, and as shown in this embodiment, using the RV and SVC coil electrodes, 36 and 38, respectively. In alternative embodiments, the housing 40 may act as an active electrode in combination with the RV electrode 36 alone, or as part of a split electrical vector using the SVC coil electrode 38 (i.e., using the RV electrode as common).
Cardioversion shocks are generally considered to be of low to moderate energy level (so as to minimize pain felt by the patient), and/or synchronized with an R-wave and/or pertaining to the treatment of tachycardia. Defibrillation shocks are generally of moderate to high energy level (i.e., corresponding to thresholds in the range of 5-40 Joules), delivered asynchronously (since R-waves may be too disorganized), and pertaining exclusively to the treatment of fibrillation. Accordingly, the microcontroller 60 is capable of controlling the synchronous or asynchronous delivery of the shocking pulses.
FIG. 2 illustrates a group 140 of stimulation or pacing pulses forming a pulse train which are provided to the right ventricle of the heart by the pulse generator 72 to implement a NIPS procedure in accordance with this preferred embodiment of the present invention. The group 140 of pulses includes a first set 142 of pulses and a second set 144 of pulses. Each pulse of the first set is referred to as an S1 pulse and may range in number from, for example, 3-20, the number of S1 pulses being a programmable parameter. Immediately successive S1 pulses have a programmable interpulse interval (S1—S1) on the order to 300-400 milliseconds to provide overdrive pacing of the heart. Each S1 pulse also preferably has a programmable amplitude and pulse width of, for example, 4.5 volts (v) and 0.5 milliseconds, respectively, to assure capture of the heart by each S1 pulse. It is the purpose of the first set 142 of pulses to overdrive capture the heart.
The second set 144 of pulses, commonly referred to as the extra pulses, includes pulse S2, pulse S3, and pulse S4. The number of extra pulses may also be a programmable parameter and vary from that described herein. Each of the S2, S3, and S4 pulses also preferably has a programmable amplitude and pulse width of, for example, 4.5 V and 0.5 milliseconds, respectively. The last S1 pulse and the extra pulses are separated in time by interpulse intervals S1-S2, S2-S3, and S3-S4 which are progressively decreasing. The extra pulse interpulse intervals may be initially set by the programmer 102 and may be 280 milliseconds, 260 milliseconds, and 240 milliseconds, respectively. The intended purpose of the extra pulses is to place the last extra pulse, pulse S4, in accordance with this embodiment, in an overdriven cardiac cycle of the heart where the stimulated heart tissue is only partially refractory for inducing the tachyarrhythmia.
To place the pulse S4 as described above, the microcontroller 60 in accordance with this preferred embodiment and the stored NIPS protocol, adjusts or varies the interpulse intervals S2-S3, and S3-S4 in a prescribed manner after each group 140 of pulses is delivered to the heart. After each adjustment of the interpulse intervals, the pulse train is reinitiated and delivered to the heart. The foregoing process continues until the tachyarrhythmia is induced.
A prescribed manner in which the microcontroller 60 may vary the interpulse intervals and hence control the performance of the NIPS protocol of this embodiment is particularly illustrated in FIG. 3. In this flow chart, the various algorithmic steps are summarized in individual "blocks". Such blocks describe specific actions or decisions that are carried out as the algorithm proceeds. Where a microcontroller (or equivalent) is employed, the flow charts presented herein provide the basis for a "control program" that may be used by such a microcontroller (or equivalent) to effectuate the desired control of the stimulation device. Those skilled in the art may readily write such a control program based on the flow charts and other descriptions presented herein.
The process of FIG. 3 initiates at an activity step 150 wherein initializing parameters are provided to the microcontroller 60 or memory 94 via the telemetry circuit 100. It is, of course, assumed that the NIPS protocol to be implemented has already been stored in the memory 94 in the same manner. The initializing parameters may be, for example, the initial S1-S1, S1-S2, S2-S3, and S3-S4 intervals, the amplitude and durations of the stimulation pulses, the time between successive pulse trains, and the interval by which each coupling interval will be decremented as called for by the protocol. Also, at this time, any normal automatic capture back-up pulse function is suspended while capture verification is enabled on a beat-to-beat basis.
After the initial parameters have been established, the process proceeds to activity step 152 wherein the microcontroller 60 causes the pulse generator 72 to deliver the first pulse train or first group of stimulation pulses as illustrated in FIG. 2 to the heart. After the first pulse train has been applied, the microcontroller next, in decision block 154 determines if the tachyarrhythmia has been induced. If the tachyarrhythmia is detected by the microcontroller, the process returns. However, if not, the process then advances to decision block 156. In decision block 156, the microcontroller determines if pulse S4 captured the heart. If pulse S4 captured the heart, the processor advances to activity step 158 to decrement the S3-S4 interpulse interval, by, for example, 10 milliseconds. If pulse S4 failed to capture the heart as determined in decision block 156, the process advances to activity blocks 160 and 162 in that order to decrement the S2-S3 interpulse interval and to reset the S3-S4 interval, if previously decremented, to its initial value. The process is now ready to reinitiate another pulse train with the adjusted intervals unless a termination condition exists to be described subsequently. Absence such a condition, the process will continue to adjust the interpulse intervals as described above after each pulse train. The pulse trains are reinitiated by the microcontroller until the tachyarrhythmia is detected in decision block 154.
After either activity block 158 are activity block 162 is completed, the microcontroller determines if a condition exists to terminate the NIPS procedure. The first such condition is illustrated by decision block 164 wherein the microcontroller determines if there has been a capture failure. More particularly, in accordance with this embodiment, such a capture failure is a condition wherein a predetermined number of consecutive stimulation pulses have failed to capture the heart. A predetermined number of successive stimulation pulses failing to capture the heart may be, for example, two consecutive pulses. As previously mentioned, capture is preferably verified after each stimulation pulse. If capture fails it is noted by the microcontroller. In decision block 164, the microcontroller performs an analysis of the notations. If the notations indicate that two consecutive stimulation pulses failed to capture the heart, the process immediately returns.
The next termination condition is illustrated by decision block 166. Here, the microcontroller determines if the NIPS procedure has been manually terminated by the clinician initiating a command to terminate the procedure from the external programmer 102. Such a command is received through the telemetry circuit 100 of the device 10. If a termination command is given, it will be noted by the microcontroller upon receipt and will be acted upon when the process reaches decision block 166. If such a notation of termination is present when the process reaches decision block 166, the microcontroller will terminate the NIPS procedure by immediately returning.
Lastly, the final termination condition is illustrated by decision block 168. Here, the microcontroller determines if any one of the interpulse intervals has been decremented to such as extent as to be shorter than the minimum interval required to support a beat-by-beat capture determination. If an interpulse interval is too short, the process immediately returns. If no pulse intervals is too short, the process reverts to activity block 152 to initiate the delivery of the next pulse train.
From the foregoing, it may be seen that the present invention provides a new and improved procedure for inducing a tachyarrhythmia of the heart to support an electrophysiological study. The procedure, such as a NIPS procedure, may be used to induce either a ventricular or atrial tachyarrhythmia. Since the procedure is truly automated, the tachyarrhythmia may be induced in less time, with less anxiety to the patient, and with reduced clinical cost.
While the invention has been described by means of specific embodiments and applications thereof, it is understood that numerous modifications and variations could be made thereto by those skilled in the art without departing from the spirit and scope of the invention. It is therefore to be understood that within the scope of the claims, the invention may be practiced otherwise than as specifically described herein.
|Cited Patent
|Filing date
|Publication date
|Mar 19, 1981
|Jun 28, 1983
|Telectronics Pty. Ltd.
|Two pulse tachycardia control pacer
|Oct 19, 1984
|Aug 18, 1987
|Sholder Jason A
|Pacemaker system and method for measuring and monitoring cardiac activity and for determining and maintaining capture
|May 28, 1985
|Nov 24, 1987
|Cordis Corporation
|Automatic cardiac capture threshold determination system and method
|Mar 27, 1985
|Dec 15, 1987
|Siemens-Elema Ab
|Physiologically responsive pacemaker and method of adjusting the pacing interval thereof
|May 28, 1985
|Mar 8, 1988
|Cordis Corporation
|Cardiac pacer and method providing means for periodically determining capture threshold and adjusting pulse output level accordingly
|Jul 18, 1986
|Dec 6, 1988
|Siemens-Pacesetter, Inc.
|Pacemaker having PVC response and PMT terminating features
|Jan 25, 1989
|Jul 10, 1990
|Siemens-Pacesetter, Inc.
|Microprocessor controlled rate-responsive pacemaker having automatic rate response threshold adjustment
|May 23, 1989
|Jul 31, 1990
|Siemens-Pacesetter, Inc.
|Atrial rate based programmable pacemaker with automatic mode switching means
|Aug 7, 1989
|Nov 13, 1990
|Telectronics N.V.
|Pacemaker with improved automatic output regulation
|Nov 23, 1992
|Sep 27, 1994
|Siemens Pacesetter, Inc.
|Autocapture system for implantable pulse generator
|Jan 16, 1996
|Aug 5, 1997
|Medtronic, Inc.
|Method and apparatus for induction of fibrillation
|Jan 27, 1998
|May 4, 1999
|Vitutsom Medical B.U.
|System for inducing tachycardia utilizing near field T-wave sensing
|Dec 11, 1997
|Jul 20, 1999
|Pacesetter, Inc.
|Automatic capture detection during non-invasive programmed stimulation of a patient's heart
|Citing Patent
|Filing date
|Publication date
|Apr 16, 2002
|Sep 28, 2004
|Cardiac Pacemakers, Inc.
|Method and apparatus for safely disabling runaway pacing protection in a cardiac rhythm management device
|May 18, 2007
|Apr 3, 2012
|Imperception, Inc.
|Shock timing technology
|Jul 31, 2008
|Jan 22, 2013
|Medtronic, Inc.
|Extravascular arrhythmia induction
|Aug 21, 2007
|Mar 19, 2013
|Imperception, Inc.
|Defibrillation shock strength determination technology
|Jul 31, 2008
|Oct 15, 2013
|Medtronic, Inc.
|Extravascular arrhythmia induction
|Apr 3, 2012
|Sep 9, 2014
|Imperception, Inc.
|Shock timing technology
|Apr 16, 2002
|Oct 16, 2003
|Cardiac Pacemakers, Inc.
|Method and apparatus for safely disabling runaway pacing protection in a cardiac rhythm management device
|May 18, 2007
|Feb 7, 2008
|Charles Swerdlow
|Shock timing technology
|Aug 21, 2007
|Feb 28, 2008
|Swerdlow Charles D
|Defibrillation shock strength determination technology
|Jul 31, 2008
|Feb 4, 2010
|Medtronic, Inc.
|Extravascular arrhythmia induction
|Jul 31, 2008
|Feb 4, 2010
|Medtronic, Inc.
|Extravascular arrhythmia induction
|Jul 22, 2009
|Feb 4, 2010
|Medtronic, Inc.
|Extravascular arrhythmia induction
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|Apr 18, 2000
Owner name: PACESETTER, INC., CALIFORNIA
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|Mar 17, 2006
|Fee payment
Year of fee payment: 4
|Mar 17, 2010
|Fee payment
Year of fee payment: 8
|Mar 21, 2014
|Fee payment
Year of fee payment: 12
|Mar 21, 2014
|Surcharge for late payment
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Resident Scholars and Artists Lecture Series: Amara Solari
Resident Scholars and Artists Lecture Series
Amara Solari
Associate Professor of Art History and Anthropology
"Contagious Stench" of Idolatry: The Rhetoric of Disease and Sacrilegious Acts in Colonial New Spain
In the historical theater of colonial New Spain, Spanish colonists frequently cited the catastrophic population decline of the indigenous population due to epidemic disease and the enduring presence of pre-Columbian religiosity as among the colony's most distressing social problems. In this talk, I analyze both visual and textual sources to argue that early modern models for disease and its infectious nature, specifically disease's status as both a biological and social contagion, informed period understandings of idolatry. By the turn of the seventeenth century, the rhetorical tropes used to discuss and describe disease and idolatry had become nearly identical. Moreover, in the Yucatán Peninsula, the conceptual conflation of illnesses of the body and of the soul led to the deployment of strategies for combating corporeal disease as a means to alleviate the threat of idolatry's infiltration into recently Christianized Maya pueblos.
Light lunch at 11:45 a.m. Presentation starts promptly at 12:00 p.m.


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This was a perfect day to be in Prescott!! The class seemed to soak up the new information about coloring faces and hair like a sponge. Eveyone has increased the size of their marker stash by about 300%. I am hoping everyone finds the time to practice, especially shadows and highlights!!!
The next class is scheduled for May 21st and we will be advancing our coloring to maximize the Copic Marker blending and shading features. I will be introducing the class to the Copic AirBrush System!! Stay tuned for more information. I will be taking the Advanced Copic Certification Class this Monday in Phoenix. I am so excited to actualy be meeting Debbie Olsen in person!


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Brian Hansel
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I have owned gun dogs that are good at reminding me of a rule you always obey in upland hunting -- once you start out on a hunt you better not stop. That dog is not going to stop until it hits paydirt so if you do it is your own fault if the bird flushes wild. The Minnesota Vikings started building a Super Bowl team the year Childress arrived. Zygi and Mark Wilf were going to finally bring an NFL championship to Minnesota no matter what it cost. They went from 8-8 to 10-6 to 12-4 and then they lost their focus.
Boys' Hockey Little Falls 21, Wadena-Deer Creek 0 Girls' Hockey Detroit Lakes 7, Long Prairie-Grey Eagle/Wadena-Deer Creek 3 Boys' Basketball Long Prairie 52, Wadena-Deer Creek 37 Jordan Reed (WDC) 13 points, 11 rebounds Pine River-Backus 60, Verndale 58 Zach Meidinger (V) 26 points Girls' Basketball Wadena-Deer Creek 46, Staples-Motley 37 Courtney Volkmann (WDC) 14 points, Rachel Craig (WDC) 13 points Bertha-Hewitt 50, Verndale 42 Lizzy Yungbauer (V) 12 points
Boys' Hockey Eveleth-Gilbert 4, Wadena-Deer Creek 1 Wrestling Wadena-Deer Creek Invitational Team Results: Badger-Greenbush-Middle River (BGM) 222.5, Wadena-Deer Creek (WDC) 191, Perham (Per) 172, Thief River Falls (TRF) 147.5, Pequot Lakes Pine River Backus (PLB) 143.5, Bertha-Hewitt-Verndale (BHV) 111.5, Long Prairie-Grey Eagle (LPG) 63, Unattached 42 Individual Results First: 119- Mitch Steffens (WDC), 125- Kasey Horn (BHV) Second: 103- Sam Waln (WDC), 140- Jared Wegscheid (WDC), 145- Jacob Wegscheid (WDC), 189- Isaac Lustila (WDC)
Supper was not quite on the table for some area residents Nov. 24 when the power failed for 1,784 Todd-Wadena Electric customers. Todd-Wadena buys electrical power from Minnesota Power and when a piece of equipment at a sub-station in Verndale failed, the resulting outage left customers in Wadena, Verndale and Aldrich in the dark. According to a report which Todd-Wadena line superintendent Mark Christianson received from Minnesota Power, a transformer and bus locked out for safety reasons. A lockout prevents further trouble but it also forces crews to respond.
The potential is there for Norman Gallant's Wadena-Deer Creek Wolverines to claim a Section 6A wrestling title this season if the cards fall just right. Coming off an 8-9 season, the Wolverines are widely regarded as a serious challenger to Border West's claim on the section crown. The Buccaneers have another powerhouse of their own so a team trip to St. Paul in March could come down to a showdown in February. Keeping everyone healthy will be the key for WDC according to Gallant. "Our biggest issue is going to be health," Gallant said.
Sarah Beckstrom iced a pair of goals as the St. Louis Park Orioles crushed Long Prairie-Grey Eagle/Wadena-Deer Creek 8-1 Saturday in the second round of the Pequot Lakes Invitational. The Orioles erupted for six of their eight goals in the first period. George Behl's Blue Devils broke up the shutout in the third period when Katelyn Barthel pushed the puck into the net at the 16:32 mark. The Class AA Orioles out-shot the Blue Devils 39-9. The loss dropped the Blue Devils to 1-3. St.
Colin Turchin returns for a Bertha-Hewitt-Verndale wrestling club that had several grapplers shine individually last season. The big heavyweight is ranked sixth by the Guillotine in Class A after putting together a season that saw him win 32 of 43 matches and qualify for state with a runner-up finish in the Section 6A meet. The Raiders will be looking for new talent to take the places of Jake Braaten and Amos Schmidt. Both standouts joined Turchin at state. Braaten ended his prep career with a 144-62 record. His section victory and trip to St. Paul produced a 30-4 record.
The Wadena-Deer Creek Wolverines have brought a contagious condition with them from the fall volleyball season -- winning. First-year girls' basketball head coach Keith Ferris saw his Wadena-Deer Creek Wolverines rally from a 30-21 deficit Tuesday night to defeat traditional opening night foe Pierz 61-49 on the Elementary hardcourt. Coming off an unbelievable 33-0 volleyball season that made them the darlings and the champions of the Class AA state tournament, the Wolverines rode the double figure scoring of Emily Miron, Avery Jackson and Courtney Volkmann in beating Pierz.
A pheasant rooster standing on a yard in town, a Hungarian partridge on our front step, four big turkeys under a bird feeder and a wolf sleeping on West Battle Lake. These are four of the stories that imparted from relatives over the Thanksgiving Holiday Weekend just past. What the heck is going on? Last Monday the area tasted a good dusting of snow followed by some horribly cold temperatures.
Girls' Basketball Wadena-Deer Creek 74, Sebeka 64 WDC: Caitlin Volkmann 22 points, 6 three-point field goals Avery Jackson 16 points Courtney Volkmann 10 points Emily Miron 11 rebounds, 4 blocks Sebeka: Alicia Boe 18 points Katianne Brockpahler 14 points Jessica Lillquist 13 points Katie Huttunen 12 points


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Washington, D.C. – J-Lab Partners with CUNY to Create E-Guide: "Law for Media Startups," a new resource for entrepreneurs launching news ventures and educators teaching students how to do it, was published today by CUNY's Tow-Knight Center for Entrepreneurial Journalism.
Tag Archives | publications
In New Orleans, public radio, local startups, and more are teaming up for the news
In New Orleans' topsy-turvy world of journalism — where alliances shift, talent is raided, and a newspaper war is blossoming — WWNO public radio has, for the past year, steered a determined course. Informed by research and bolstered by a sense of opportunity, it is erecting, piece by piece, the components for an all-news format,
Public Media Join Non-Profit Startups to Collaborate, Fill Local News Gap
Public broadcasters have always done partnerships, but in the last year these and other public-media outlets have begun piecing together the infrastructure for local-news reports that will offer more than cutaways in "Morning Edition" and "All Things Considered." As a result, they are airing more investigative and enterprise journalism than ever before.
In New Jersey, a university teams up with local news organizations to collaborate for impact
Montclair State's Center for Cooperative Media is betting there are returns on getting newspapers, broadcasters, bloggers, and wire services all in the same building. The germ of the idea came at a 2011 meeting in Newark.
In St. Louis, two news organizations are navigating the tricky path to a merger
If all goes as hoped, in coming months St. Louis Public Radio (SLPR) and the St. Louis Beacon will formally merge their two newsrooms. It will be the first time a public radio station with a staff of journalists has combined its operations with another daily-news producing outlet.
With a coming void in Oregon's news ecosystem, public broadcasting's trying to build a new kind of state wire
Can Oregon Public Broadcasting (OPB), working with local newspapers, TV and radio stations, and bloggers, make a substantial state news report in the face of cutbacks elsewhere? In March 2013, OPB hired a former Associated Press reporter to undertake this ambitious vision.
Public Broadcasters Beefing up Local News, Taking on New Roles in their Media Ecosystems
July 8, 2013For immediate release Contact: Jan firstname.lastname@example.com Washington, D.C. – Unfettered by competitive pressures and fortified by their trusted brand, public broadcasters in many states and cities are finding new ways to engage in more local news – especially more investigative and enterprise journalism – than ever before, according to a new J-Lab
News Collaboration Project Yields 146 Partners, Revenue Models Still a Nut to be Cracked
For immediate releaseMarch 4, 2015 Contact: Jan email@example.com Washington, D.C. – A J-Lab pilot project that called for eight newspapers and one public radio station to network with local blogs delivered nine different models of collaboration, five success stories and roadmaps for rethinking local news, according to the project's findings. In "Networked Journalism: What Works,"
Online News Startups Need More Data to Convert Users into Supporters
For Immediate Release May 30, 2012 Contact: Jan Schaffer, email@example.com Erin Polgreen, firstname.lastname@example.com Washington, D.C. – The rise of social media tools has empowered online news startups to distribute their content, market their sites and monitor users. However, most small news sites say they cannot lasso data to track whether they are turning users into supporters
Enterprise Reporting Awards a "Home Run"
For immediate releaseDec. 15, 2011 Contact: Jan firstname.lastname@example.com Washington, D.C. – Fourteen media partnerships awarded $5,000 apiece a year ago to produce a single enterprise-journalism project ended up producing hundreds of pieces of content and far exceeded expectations in terms of impact. The $70,000 awarded to the winners of the Philadelphia Enterprise Reporting Awards


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Those lucky lads over at CHUD have been sent a brand-spanking new Watchmen featurette. And unlike some previous glimpses at the movie, this one shows the team actually shooting scenes. Not to mention setting a bloke on fire for a big prison stunt. Don't try this at home, kids. Well, unless you're a trained stuntman slathered in special gel.
Source: ( CHUD )


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Welcome to Tao of Dolly!
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text: NRL Rule Changes - scrums and dropouts Tue 21 May, 2013, 4:25pmNRL.com Tweet Email Print The rule changes come into effect in round 15. Credit: NRL Photos Copyright: NRL Photos Fans can expect to see even more action in Telstra Premiership matches with the NRL today announcing new guidelines that will reduce time-wasting.The introduction of a maximum time limit for the forming of scrums follows recommendations from the NRL Competition Committee, with statistics showing that an average of eight minutes per match was being lost packing scrums.The Committee also found that the 40-second time limit for drop-outs was excessive with the limit to be reduced to 30 seconds. Under the new scrum guidelines for the Telstra Premiership and Holden Cup:Both competing teams must be properly bound and be ready to pack into the scrum 30 seconds after the head referee has blown his whistle to indicate that play is to restart with a scrum; After the expiration of 30 seconds, and in the event that only one side is bound and ready to pack into the scrum, they will be awarded a penalty (not a differential) at the centre where the scrum was to have packed; In the event that no side is bound and ready to pack into the scrum, the side with the loose head and feed will receive the penalty (not a differential); If, in the opinion of the referee, the restart is being delayed due to the circumstances of the game the referee may call time off. While Match Officials will begin to instruct players as to the new guidelines starting this week, penalties in matches for breaches will start being awarded from Round 15."This is a great example of the Competition Committee identifying an issue in the game and acting quickly to address it," NRL General Manager of Football Operations, Mr Nathan McGuirk, said today."Due to the fact these changes are to be introduced a third of the way through a season, we believe that a period of adjustment for players and officials to this amendment is required, which is why penalties will not be enforced until the start of Round 15."We hope this period will allow the players and officials to familiarise themselves with the changes." Tweet Email Print Send to a friend: Your Name: Your Email: Friend's Name: Friend's Email: Close Submit loading image needs to go here


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Stereoview : Man Holding Stereo Plate Camera Ca.1904
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Stereoview. Albumin prints. Original,not a copy. Underwood & Underwood Publisher. Titled "(38) A sudden terrific volcanic explosion-smoke,steam and stones thrown from the crater of Asama-yama, Japan." The man on the left is holding a 5x7 inch stereo plate camera. You can see the two brass lenses in the front. Excellent contrast and sharpness. No reserve.


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Your Thoughts: "Muppets Most Wanted" Theatrical Film
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Rep. Paula Hawks (D-9/Hartford) held a campaign town hall here in Aberdeen yesterday evening. I'll summarize her comments in a moment, but first, I'd like to address why I like Paula and why we need more good teachers like her to run for office.
Good teachers are great conversationalists. Sure, good teachers can make good speeches (Paula showed us that at McGovern Day). Good teachers can stand in front of a crowd and speak intelligently on their fields of expertise without notes, as Paula did at the beginning of her program last night. But good teachers shine when they step away from their prepared comments and let their students lead the conversation, when they trade places with their audience and become the listeners. Good teachers listen closely, respond fearlessly, and tie ideas together on the fly to help their students see a bigger picture.
Paula listened intently to every question last night. She picked out and reiterated key points raised to show that she understood what her constituents were saying. She responded with detailed, policy-oriented answers that showed she was ready for any question. Our current Congresswoman, with her ten years of experience in elected office, has yet to project such professional confidence. Yet Paula, with her ten years of teaching experience, has no problem conveying her knowledge, her openness, and her readiness to do the job of representing South Dakota in Congress.
* * *
Now, let's turn to what Rep. Hawks talked about with Brown County voters.
Agriculture, COOL, and CRP
Rep. Hawks noted that South Dakota lacks a seat on the House Agriculture Committee for the first time in sixty years. She cannot fathom Rep. Kristi Noem's decision to abandon House Ag in favor of House Ways and Means. Rep. Hawks said agriculture is too important to South Dakota not to have our lone Congressperson on House Ag, and upon election, Hawks says she will demand a seat on that committee.
Hawks cited two vital agriculture issues where we need change. She is appalled at Congress's repeal of Country of Origin Labeling (COOL). As a mom, she wants to know where the food she feeds her kids comes from. She acknowledged that Rep. Noem gave COOL some support, but Hawks promises to lead a fight to restore COOL. She acknowledged the ag-industrial Farm Bureau's position that COOL might trigger tariffs and boycotts from other countries, but she waved the "America First" flag here and said other countries should not dictate policy for South Dakota and the United States.
Hawks also said agriculture and tourism, two of South Dakota's biggest economic sectors, depend on strengthening the Conservation Reserve Program. Hawks said 150,000 CRP acres will expire soon and will likely be plowed into cropland. That's a lot of habitat for the pheasants, ducks, and deer that visitors spend a lot of money in our state to come hunt. And of 727 applications to place over 42,000 acres of South Dakota land back into CRP, the feds only offered to accept two applications for 101 acres. Agriculture depends on conservation, and hunt-tourism depends on habitat. We need more CRP acres.
Energy: "Fossil Fuels Are on the Way Out"
Hawks said South Dakota has an opportunity to be an even bigger leader in renewable fuels. She noted we already have helped lead the nation into ethanol, which she wants to see expand to cellulosic ethanol. Now we need to take the lead in the wind and solar energy that we could abundantly produce. Hawks said she understands that South Dakota's electric cooperatives have invested in new coal-fired power generation and don't want to lose out on a return on that investment, but, echoing her Senate candidate counterpart Jay Williams, Hawks said last night, "fossil fuels are on the way out" and renewables are on the way in. We can either be reactive and play catch-up, or we can be proactive and position ourselves to lead the country in renewable energy production and jobs. Rep. Hawks prefers the latter.
Rep. Noem's HEALTH Act
Rep. Noem has been seeking election-year headlines by pushing her Indian Health Service reform bill, known as the HEALTTH Act. Rep. Hawks acknowledged that the bill has some good elements, like reforming administrative practices at IHS. However, Hawks said the bill includes no funding and thus is an empty shell. It is also an amendment to the Affordable Care Act. Placing this reform in a law that Noem has voted to repeal 63 times puts it on shaky ground in any Congress controlled by Noem's party. Hawks said the bill privatizes IHS services in ways that won't work as well in South Dakota as elsewhere. The bill also takes too much of a top-down, one-size-fits-all approach and does not provide for enough collaboration with tribes to ensure adaptation of the reforms to specific needs in specific communities. Building collaboration with the tribes isn't easy, said Hawks, and it takes more than showing up the day before the election.
Rep. Hawks notes that an easy step for improving health care for tribal members and thousands of other South Dakotans would be to expand Medicaid under the Affordable Care Act. Hawks invited Noem to join a bipartisan effort to persuade Republican legislators, but Noem shurgged Medicaid expansion off as strictly a state issue.
Guns, Pheasants, Obama, and Six-Shooters
Queried on gun policy, Rep. Hawks says she loves hunting pheasants but can't bring herself to shoot Bambi. She said that President Obama hasn't taken away our guns and she doesn't foresee or support any confiscation of firearms.
That said, Hawks wholeheartedly supports the President's "No Fly, No Buy" proposal. If an individual is too dangerous to step on an airplane, that individual is too dangerous to buy a gun. Hunter Hawks also said a 30-round clip has no use in hunting. She proposed six rounds as a reasonable limit for magazines. Fellow hunters in the audience backed her up by noting that the federal duck stamp purchasers are restricted to three rounds in the chamber, while deer hunters can only load five rounds. (Again, as Jay Williams suggested last month in Aberdeen, if you can't hit a bird with three shots, you're a poor marksman who maybe ought to go practice some more before you march around the countryside with a loaded weapon.) Hawks also said there's no need for military-style firearms to be in the hands of untrained civilians.
Mental Health Stigma
When an audience member turned the guns discussion to mental health, Rep. Hawks made a remarkable segue to a broader issue about the stigma we place on seeking treatment for mental illness. People talk openly about fighting cancer and their treatments for other physical maladies; Hawks said we should be able to talk about treatment for mental illness as openly, without fear of criticism or shaming. No legislation will fix that stigma, but Hawks showed she can take a moral position that can encourage shifts in attitudes for the public good.
Partisan Politics and Inside Baseball
Turning from policy to politics, Rep. Hawks asserted that Republicans will take a hit this year for nominating Trump and for their Obama-obstructionism. She said that the Democrats have a good shot at taking over the Senate and will "make great strides" in the House. Trump will drive more voters away, and Hawks thinks that will help her campaign. Hawks said her campaign's poll numbers "have been very good" and Noem is getting "a little nervous." Hawks said her campaign had received confirmations of three debates, at Dakotafest, on SDPB, and on KELO, but that now "complications" have arisen with Dakotafest, where Noem is now slated to appear with her Republican Senate colleagues in a panel discussion.
Noem may also be nervous about Republican support for Hawks. Last night, Hawks said Republicans have given her campaign moral and financial support and have told her they are ready for a change. When Republicans are ready for change, you know things must be tough.
Living in D.C., Serving South Dakota
Rep. Hawks said that in her first conversation with Senator Tim Johnson, our last Democratic Senator asked her right away, "What are you going to do with your kids?" Hawks said she would bring them to live with her in Washington, D.C., so she could be a full-time Congresswoman and a full-time mom. "Good answer," said Johnson, who did the same with his kids. Hawks says she talked to Johnson's son Brendan, and he said he wouldn't have had his upbringing, with his dad, in D.C., any other way.
Hawks said that when she went to Pierre to represent District 9 in the State House, she was urged to get a "burner" phone to list for constituent contact. Hawks said she rejected that advice and gave out her personal cell phone number. She said she wants all constituents, including Republicans, to be able to reach her as easily as possible.
Hawks continues reaching constituents today in Sioux Falls and next week in Spearfish, Custer, and Rapid City.


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I painted these for my son's nursery. It makes me feel very nostalgic to look at these and think about him being a little peanut swaddled in a blanket underneath this nursery art. Today I bought the ingredients for Joseph's chocolate chip pancake birthday breakfast. . .because he's turning five! In the upper corners you can see some finishing touches that Joseph added when he was two:-)
I post these today so that a friend can check them out:-)


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I have anxiously awaited the arrival of my Pumpkin Spice Meal Replacement Shakes. Sweet, spicey, and most of all healthy. Nikki and I enjoyed our morning exercise jumpstarted after our morning grape flavored Spark. Upon our return we quickly mixed the powder and 8 ounces of cool water and enjoyed our creamy creation of 22 grams of protein.
I have a new favorite flavor for my morning meal. Pumpkin Spice has replaced my Chocolate Mocha for my morning commute to work.
Our Advocare journey has been a blessing energy to exercise, supplements to enhance and meal replacement shakes when needed that are wonderful.
Questions are comments please post I'll give honest answers and reviews. Want more information to order your Pumpkin Spice today go to www.advocare.com/141014530


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Our previous studies have shown that exercise caused changes in the tissue activities of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase in spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. To determine whether the changes observed were due to changes in mRNA levels of the enzymes, levels of tissue mRNA were determined by quantitative RNase protection assay. Comparisons of tissue enzyme activities and mRNA levels in sedentary and exercised animals showed that, in some cases (e.g., glutathione peroxidase in SH and WKY myocardium), parallel changes in enzyme activity and mRNA levels occurred, whereas in other cases (e.g., catalase in SH and WKY liver), nonparallel changes were found. Exercise of hypertensive rats altered antioxidant enzyme mRNA levels to those seen in normotensive animals in some, but not all, cases. The results suggest that transcriptional control over changes in exercise-related antioxidant enzyme activities is operative in some cases, although in other cases posttranscriptional regulatory mechanisms may exist.
- glutathione peroxidase
- catalase
- Cu/Sn superoxide dismutase
- mRNA
- spontaneously hypertensive rat
chronic hypertension is known to cause a variety of changes in myocardium, including the increased production of reactive oxygen species (ROS) (1, 28), which have been implicated in the pathway leading to coronary heart disease (8, 29). One method of treatment of hypertension is a regular aerobic exercise program, and it has been shown that exercising individuals have both diminished hypertension and a lower rate of coronary heart disease compared with sedentary hypertensive individuals (9). However, exercise for hypertensive subjects is not without risk because it can increase aerobic metabolism, leading to an elevation in the levels of tissue ROS, and ROS elevation resulting from hypertension and exercise can cause cell damage by modification of molecules, including DNA, membrane lipids, and proteins (23, 24).
To protect against this increase in ROS due to hypertension or exercise, a possible tissue response is an increase in the activity of a group of enzymes generally referred to as antioxidant enzymes, which protect the cells from ROS-generated damage (11, 21). However, exercise has been shown to alter antioxidant enzyme tissue activities in a variety of different ways depending on the type of exercise program used, the amount of exercise, and the existence of a resting period between the exercise regimen and the tissue collection. Some examples of such variation in the response of the specific tissue enzyme activities to exercise are seen from studies on superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in rat liver and myocardium, in which increases, decreases, and unaltered tissue activities for each of these enzymes have been reported using different exercise regimens and resting periods (10, 13, 14, 26). Such variable responses to exercise have also been observed in other species, including humans, in whom it has been shown that different exercise training programs can lead to different antioxidant enzyme tissue activity changes and different levels of postexercise oxidative stress (2, 19).
Previous studies in our laboratory have examined the long-term effects of exercise on tissue antioxidant enzyme-specific activities in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats (13). It was found that exercise training did not cause a significant change in the total SOD activity in the myocardium but did cause decreases in total SOD activity in the liver and decreases in catalase and GPX activities in both the myocardium and liver (13). To determine whether the regulation of these activities is under transcriptional and/or posttranscriptional controls, in the present studies the mRNA levels for the antioxidant enzymes Cu/Zn SOD, catalase, and GPX were determined in myocardium and liver and compared with changes in the tissue-specific activities of these enzymes. Our studies show that both transcriptional and posttranscriptional regulation may occur in particular cases but that transcriptional regulation appears to be the predominant mechanism.
WKY (normotensive) male rats were obtained from Charles River Laboratories (Wilmington, MA), and the SH (genetically hypertensive) male rats were obtained from Harlan Sprague Dawley (Indianapolis, IN) at an age of 11–12 wk. Tri reagent and high-salt precipitation solution were obtained from Molecular Research Center (Cincinnati, OH). The Maxiscript in vitro transcription kit, the RNase protection assay (RPA) II kit, and pTRI-β-actin-125-rat (a linearized plasmid containing partial sequence of rat β-actin cDNA) were bought from Ambion (Austin, TX). The restriction enzymes Sal I,EcoR I, and Pst I were purchased from New England Biolabs (Beverly, MA). The T4 DNA ligase, restriction enzymesBgl II and Sma I, pGEM marker, and lambda marker were purchased from Promega Biotech (Madison, WI). Proteinase K, T4 DNA polymerase, 50- and 25-bp DNA ladders, and 2-deoxynucleotide 5′-triphosphates were obtained from GIBCO BRL (Gaithersburg, MD). Radiochemicals ([α-32P]CTP and [α-32P]dATP) were purchased from Dupont-NEN (Boston, MA). Plasmids containing the cDNAs used to synthesize the probes were generously provided by Dr. Y.-S. Ho (LK440-cGPX, glutathione peroxidase), Dr. T. Hashimoto (pRCA38-cCAT, catalase), and Dr. L. B. Clerch (a pGEM-blue plasmid containing the 5′Pst I fragment of the rat Cu/Zn SOD sequence).
Animal care, exercise program, and tissue preparation.
The experiments involving rats were approved by and were in conformity with the guidelines of the Ohio University Institutional Animal Care and Use Committee. The exercise program used was the same as one used previously that caused a significant change in the specific activities of the antioxidant enzymes (13). In summary, the rats were exercised 5 out of 7 days/wk as follows: 15-min duration, 10 m/min (belt speed), 0° (incline) for week 1; 30 min, 10 m/min, 0° forweek 2; 30 min, 10 m/min, 5° for week 3; 30 min, 20 m/min, 5° for week 4; 45 min, 20 m/min, 5° for week 5; and 60 min, 20 m/min, 5° for weeks 6–10. Rats in the control (sedentary) group were removed from their cages once a day for 5 days/wk and placed on the stationary treadmill for 15 min to account for handling stress. After a 1-wk detraining sedentary period, the systolic blood pressures of the rats were determined by the tail-cuff technique, and the body weights were measured. The animals were euthanized by CO2-induced asphyxiation, and the outer wall of the left ventricle, remainder of the heart, liver, and quadriceps femoris were immediately removed and washed with cold phosphate buffer to remove erythrocytes (13). The tissues were cut into ∼100- to 300-mg portions and stored separately at −80°C in 1.5-ml centrifuge tubes.
Preparation of tissue extract and SOD enzyme assay.
Homogenates of the tissues were prepared in 1.0 ml of phosphate buffer per 100 mg of tissue by using a Powergen 125 homogenizer as described previously (3, 13). The samples were spun at maximum speed at 4°C in a Marathon microcentrifuge, and the supernatant was used. The protein concentrations of the supernatants were determined by use of the Bio-Rad Bradford protein assay kit. SOD activity was measured by the cytochrome c reduction procedure by using 3- to 200-μl aliquots of homogenate supernatant in a final assay volume of 3.0 ml (3). The assays were performed on samples without cyanide to measure total SOD activity and on samples after preincubation with 1 mmol/l sodium cyanide for 2 h at 37°C to measure Mn SOD activity so that Cu/Zn SOD activity was obtained by the difference between these values. A unit of enzyme activity is the amount of enzyme that gave 50% inhibition of the control rate of cytochrome c reduction.
Preparation of total RNA from tissues.
With the use of liver and the outer wall of the left ventricle, total RNA was isolated using the Tri reagent kit following the general method recommended by the manufacturer. Tissue was homogenized using a Powergen 125 homogenizer at room temperature, with eight 1-s bursts used for liver and 12 1-s bursts for myocardium. Typical yields of total RNA were found to be ∼0.7 μg/mg for the myocardium and 3 μg/mg for the liver. Denaturing 1% agarose gels containing 19% formaldehyde were run on the RNA preparations to check the integrity of the RNA by the presence of the 18S and 28S rRNA bands (22), and any sample that did not have clear unsmeared rRNA bands was discarded. Tissue samples stored at −80°C were used within 6 mo of harvesting but were stable for up to 12 mo of storage. RNA content of samples was determined by absorbance at 260 nm (22).
Preparation of mRNA probes for the antioxidant enzymes.
Standard procedures were used for minipreparations and large-scale plasmid preparations (22). Plasmids containing cDNA inserts of GPX, catalase, and Cu/Zn SOD were linearized with the use of Sal I,Bgl II, and Sma I before transcription (18).
For transcription, the Ambion MAXIscript in vitro transcription kit was used with [α-32P]CTP as the radiolabeled nucleotide. Transcription of the commercial linearized plasmid containing partial rat β-actin cDNA sequence was performed according to the MAXIscript protocol, and, by using T7 RNA polymerase, a 190-base full-length probe was obtained that contained 126 bases complementary to the rat β-actin mRNA sequence. T7 RNA polymerase was used for transcription of the catalase and GPX cDNAs, and SP6 RNA polymerase was used for transcription of the Cu/Zn SOD cDNA. Labeled RNA probes were purified on an 8 M urea-acrylamide gel, and the eluted probes were used within 3 days of preparation.
Preparation of 32P-labeled DNA standard ladders.
Both 25- and 50-bp DNA ladders for gel electrophoresis calibration were prepared using the standard protocol of the GIBCO BRL kit with dATP as the 32P-labeled deoxyribonucleotide. Ladder preparations were used within 2 wk of their preparation.
RPA and gel analysis.
For quantitative analysis of mRNA levels by RPA (17), the recommended procedures of the RPA II kit were followed using 10-μg samples of total RNA. The optimized amounts of each probe were previously determined to be 1 × 105 cpm catalase and 1 × 105 cpm β-actin, 2 × 104 cpm Cu/Zn SOD and 6 × 104 cpm β-actin, 8 × 104cpm GPX and 8 × 104 cpm β-actin in the myocardium, and 1 × 105 cpm GPX and 1 × 105 cpm β-actin in the liver (18). After electrophoresis of triplicate samples and appropriate control samples, the gels were mounted onto filter paper and dried and exposed to Fuji RX Medical X-ray Film at −80°C for up to 2 days using an intensifying screen. Developed films were then scanned using a Bio-Rad GS-670 densitometer and the ratio of antioxidant mRNA probe to β-actin probe intensity was calculated. Figure 1 A shows a typical autoradiograph of Cu/Zn-SOD mRNA analysis from myocardium, and Fig. 1 B shows a typical autoradiograph of catalase mRNA analysis from liver.
Statistical methods.
The mean values (±SD) for the ratios of the antioxidant mRNA probe to the β-actin mRNA probe were obtained from four separate animals with triplicate RPA analyses of each preparation. Minitab 12.22 was used for one-way ANOVA of the data to determine whether significant differences between the mean data existed at the 95% confidence level (P< 0.05).
Effects of exercise and hypertension on systolic blood pressures.
There was no significant change in blood pressure due to exercise for WKY rats (116 ± 10 and 118 ± 12 Torr, respectively, for sedentary and exercised animals), but there was a significant increase for the SH rats (185 ± 3 and 202 ± 10 Torr, respectively, for sedentary and exercised animals). The small but significant increase in blood pressure in the SH rats is in agreement with earlier observations of this phenomenon (13, 27) and may reflect an anticipatory response to exercise by SH animals in the exercised group (5, 15).
Determination of Mn SOD and Cu/Zn SOD activities.
The previous work in our laboratory (13) measured only total SOD activity; to compare separate Cu/Zn and Mn SOD activities with their mRNA levels, it was necessary to determine individual Cu/Zn SOD and Mn SOD activities. Table 1 shows results of analyses of the Cu/Zn SOD and Mn SOD tissue-specific activities in myocardium and liver. There are no significant changes in the myocardium for both SOD enzyme activities, and, whereas liver also showed no significant changes in Mn SOD activity, significant changes were found in liver Cu/Zn SOD activities. Because there were significant changes in Cu/Zn SOD activity, the Cu/Zn SOD mRNA levels were determined along with catalase and GPX mRNA levels for comparison with changes seen in tissue-specific enzyme activities.
RPA analysis on tissue antioxidant mRNA levels.
Table 2 shows the levels of the antioxidant enzyme mRNA expressed in myocardium and liver relative to β-actin mRNA levels obtained by the scanning of RPA autoradiographs. In myocardium, there are several significant changes in the mRNA levels of the three antioxidant enzymes due to exercise and hypertension. In some cases, no significant changes in myocardial mRNA levels were found, namely for Cu/Zn SOD between WKY sedentary and WKY exercised rats and for GPX between the WKY exercised and SH exercised rats. The liver mRNA levels showed significant changes in comparison with the WKY sedentary control in all cases except for Cu/Zn SOD in the sedentary SH rats. The mRNA levels for Cu/Zn SOD and GPX showed decreases due to exercise, whereas catalase mRNA levels increased as a result of exercise and hypertension.
As shown in Table 2, exercise in either WKY or SH rats, or hypertension alone in some cases, caused significant changes in antioxidant enzyme mRNA expression. These changes often, but not always, paralleled the changes seen in antioxidant enzyme tissue-specific activities (Fig.2). Examples of parallelism between changes in enzyme activity and mRNA levels include the changes in GPX enzyme activity and mRNA levels that decrease in the myocardium and liver of both WKY and SH rats as a result of exercise. Of the five cases of nonparallelism seen in Fig. 2, four of these involved catalase, with one showing a decrease in the mRNA level and an increase in the enzyme activity and the other three showing increases in mRNA levels and decreases in enzyme activity. Independently of exercise, hypertension was also found to affect myocardial mRNA levels; the Cu/Zn SOD and GPX mRNA levels were higher in SH than in WKY rats, and the enzyme activities of GPX and catalase also increased. Thus, although not all of the antioxidant enzymes showed elevated expression as a result of hypertension, the general trend was an increase in antioxidant enzyme expression as a result of hypertension.
If exercise training were to provide a beneficial effect to tissues in terms of protection against oxidative damage directly through alteration of antioxidant enzyme expression, a relationship in exercise might exist between increases in antioxidant enzyme expression and decreases in tissue oxidative damage. In fact, this simple relationship does not appear to exist, given that in the myocardium of exercised WKY rats, increases in lipid peroxidation (13) are associated with decreases in antioxidant enzyme expression, whereas in liver of the same animals, both lipid peroxidation and antioxidant enzyme expression levels are decreased. These results therefore do not provide clear evidence for a beneficial effect of exercise in which elevations of antioxidant enzyme expression would decrease tissue oxidative damage, and it seems likely that other factors must be involved in mitigating levels of tissue oxidative damage during exercise.
Of particular interest is the comparison of mRNA levels in exercised SH rats to those in WKY rats to examine whether exercise in SH rats changed expression levels to normotensive levels. Although not all mRNA levels were changed in this fashion, our results show that exercise was partially effective in this regard by decreasing myocardial mRNA levels for Cu/Zn SOD and GPX to values that were even lower than those in the sedentary animals. For the catalase mRNA level in myocardium, exercise caused an increase in the mRNA level toward the WKY level, but the attained level of mRNA in the myocardium of the SH exercised rats was actually higher than that in the WKY animals. These results indicate that exercise in SH rats does not have the same effect on antioxidant enzyme expression as treatment of SH rats with antihypertensive drugs, in which it was found that, with three different drugs, enzyme expression was altered to normotensive levels (18). Because exercise (13), unlike antihypertensive drug treatment (3), does not return SH rat blood pressure to the normotensive level, it is possible that the differences in antioxidant enzyme expression seen as a result of exercise and antihypertensive drug treatment relate to the different effects of these treatments on blood pressure.
Parallel changes for mRNA levels and tissue-specific activities that are strongly suggestive of exercise- and/or hypertension-induced transcriptional control were seen in all sedentary-vs.-exercised comparisons for GPX. Other parallel changes also suggestive of transcriptional control were seen for sedentary-vs.-exercise comparisons for myocardial catalase and liver Cu/Zn SOD of WKY rats and the normotensive-vs.-hypertensive comparison for liver catalase in sedentary animals. The changes in antioxidant enzyme tissue-specific activities that do not correspond to changes in their mRNA levels (e.g., catalase in the myocardium for both SH rats and catalase in the liver for the exercised WKY and SH rats) could be due to in vivo posttranscriptional regulation, given that previous work has shown increases in antioxidant mRNA levels due to binding of stabilizing proteins (6, 7) and increases in antioxidant enzyme activity without a corresponding increase in enzyme protein (4, 12). However, such changes could also be the result of the in vitro instability of mRNA, although there are several cases (namely, for catalase in liver of exercised WKY and SH rats and in myocardium of exercised SH animals) in which mRNA levels were elevated in comparison to enzyme activity levels.
Our results differ in some instances from those reported in two previous studies on the effects of exercise on rat antioxidant enzyme mRNA levels (10, 26). One of these differences is in the results for Cu/Zn SOD mRNA levels, as our studies showed either a decrease or no change with exercise whereas both the previous studies showed increases with exercise. Additionally, for catalase, we found a decrease in the mRNA levels in the normotensive rats and an increase in the hypertensive rats due to exercise, whereas the previous study found an increase in catalase mRNA levels due to exercise (26). A third difference is that GPX mRNA levels in our study were found to be decreased in both myocardium and liver as a result of exercise, whereas one of the earlier studies (26) reported an increase in the GPX mRNA level in the myocardium due to exercise, and the other study (10) found no change in the GPX mRNA level in the myocardium and a significant decrease in the liver.
These differences may be related to different experimental factors in the studies, which include the type of rats used, the duration of resting period allowed after the last exercise training period, the myocardial tissue analyzed, and the method of mRNA quantitation used. The two previous studies used either male Fischer 344 or female Sprague-Dawley rats, whereas our studies used male WKY and SH rats, and it is possible that there may be genetic differences in how the different animals respond to exercise. With the shorter term (not more than 24 h) resting periods used in the previous studies, there may be short-term changes in antioxidant enzyme expression that are different from the longer term changes that were detected by our experimental protocol in which a 7-day resting period was used. Another possible reason for differences in results is that our studies used the outer wall of the left ventricle, rather than mixed myocardium, and it is known that the left ventricle undergoes changes that are different from those in other regions of the heart (16, 25). A final possible reason for the differences in the data is that our study used the RPA for mRNA analysis, whereas both previous studies used Northern blot hybridization, a technique that is far less specific and sensitive than RPA (17, 20).
In conclusion, our results show that exercise or hypertension caused changes in antioxidant enzyme mRNA levels in the myocardium and the liver that may or may not parallel changes in the tissue-specific enzyme activities. Exercise of hypertensive rats did not return mRNA levels to those seen in normotensive animals in all cases, although GPX and Cu/Zn SOD levels in myocardium were moved much closer to normotensive levels. Those cases in which the changes in mRNA levels paralleled the changes in the enzyme activities are strongly suggestive of transcriptional regulation of the antioxidant enzymes, and in those cases in which there was not a parallel change in mRNA levels and enzyme activities, it would seem probable that there is posttranscriptional regulation of the antioxidant enzymes by one or more different mechanisms.
We thank Dr. L. B. Clerch (Georgetown University, Washington, DC), Dr. T. Hashimoto (Shinshu University School of Medicine, Matsumoto, Japan), and Dr. Y.-S. Ho (Wayne State University, MI) for generously providing the cDNA clones used in these studies.
Address for reprint requests and other correspondence: P. Johnson, Dept. of Chemistry and Biochemistry, Clippinger Laboratories, Ohio Univ., Athens, OH 45701 (E-mail:johnsonp{at}ohio.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
- Copyright © 2000 the American Physiological Society