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I wouldn't say High Heat Baseball 2002 was the worst baseball game ever released...I mean, who really needs base stealing or a two player option in a baseball game? Yes, High Heat Baseball 2002 is a bad baseball game. But 3DO has sent us an early look at High Heat Baseball 2003 for the Game Boy Advance...and while it's still missing a couple items, the game is definitely much better this time around.
- Exhibition, Playoff, Season, and Home Run Derby
- All MLB teams, players, and stadiums
- Link cable support for two players (two cartridges needed)
- Battery Save
- Only for Game Boy Advance
High Heat Baseball 2003, developed by the same team as last year's edition, is an extension of the engine created for last year's version on the Game Boy Advance, so the new edition will have a similar look in graphics and sound. What has been added to the game is a polygonal model for the batter, plastered on top of a 2D background. This is a technique that developers seem to be adopting for GBA game design, because it allows the developers to map thousands of different animations to a specific character without wasting cartridge space. It's a technique that made its GBA debut in Tony Hawk 2. The polygonal batter makes for smooth animation during his swing motion...but in our early look at the game it doesn't seem like this technique is used for much more than that. All batters have the same stance, swing and bunt animations, so it's a bit curious why the developer even bothered creating this engine...perhaps they're practicing the polygon technique for a future GBA project?
High Heat Baseball 2003 also features...ta-dah! base running! You can now lead off the bag and run for the next base during a pitch...even send your man on second home if the ball's deep enough. It's an important strategy to the game of baseball, so thank god Mobius added the feature for the second time around. And, unlike last year's game, two players can link up their system and challenge each other...but two cartridges are needed to take advantage of this feature. The only real element not addressed in this new version: fielders still cannot dive for the ball. Bummer.
Of course, the game will feature all of the players and MLB teams from the 2001 season, as well as basic renditions of all of the home team stadiums. The game will also have several gameplay modes, including exhibition, playoff, season play, as well as the much welcomed Home Run Derby. The cartridge will save statistics and seasons in progress on the internal battery...just like last year.
The game is set for release this April. Check out the first screenshots and video below.

domain: entertainment


Second Life is a free to play online immersive virtual world, much like a traditional MMORPG but without the dependency on conflict or objectives; here, the objective is simply to be! Hence, with over 1 million users, Second Life is a wonderful virtual universe that is completely created entirely by its users. Players can literally take on a second life; you create an avatar and set off to explore and discover yourself and the world! Servers for every imaginable time and place exist, from Victorian era London to fantastic realms, and each and every one is fully immersive and customizable. Get a life; a Second Life!
Second Life Key Features
Endless Possibilities From designing clothing and artwork to entire regions of cities and forests, every thing in the game can be made by players; what will your contribution be? Will you be an artist, a fashion designer, an architect? Customize your avatar, from eyes to feet to clothing, and be exactly who you want to be!
Vast Role-Play Options With special dedicated zones for everything from fantastic kingdoms to science fiction settings to 1920s Berlin, players can create characters in a vast number of worlds, throughout space, time, and imagination. Where will you settle?
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Unaccustomed Earth is a collection of 8 short stories by Jhumpa Lahiri, the last 3 of which form a novella. The stories are about ordinary people, their relationships & secrets. A widower in his 70s visits his daughter and her family but keeps a new relationship secret while his daughter has her own secrets. A sister notices her brother is an alcoholic & carries the guilt of being the first to introduce him to the substance. A couple attempt to have a romantic weekend away without their kids while attending a wedding but not everything goes to plan. A woman reminisces about an Uncle who was adopted into their lives when she was a girl & the impact he had on them. A woman stays with her partner for reasons unknown to her housemate who is attracted to her. And finally, the novella – Hema and Kaushik – three stories from different points of view about how their lives intertwined.
This is my first book by Jhumpa Lahiri & I cannot believe I haven’t read her all this time. I loved the stories, the layers in the relationships & the people, the things that are said & unsaid. I understood the pressures of Indian women in particular to be a certain way, to follow certain rules, or else be judged by Indian society no matter where in the world. Lahiri’s stories are set in the pre-internet days in the US & Europe but they pack a punch & are still relevant in this digital age. I especially loved the novella which is a journey of longing, life & death.
We are nuanced beings. We are not black and white. And that’s exactly why I love when authors write character-driven stories that bring out the imperfections in us all. Lahiri’s prose is simple, yet elegant. Her observations of humans & society, astute. I’m off to get her backlist. If you love short stories, grab this one!
|Fiction, Short Stories
|Random House India

domain: library


text:
Swiss Military HANOWASerie Colonel Automatik-HerrenuhrMechanische Armbanduhr mit automatischem Aufzug - Saphirglas - Gehäuse Edelstahl/RotgoldLederband braun - Swiss MadeListenpreis/UVP 698 €Abmessungen: Gehäuse-Ø 41 mm (ohne Kro
Soviet Military Operational Art: Colonel David M. Glantz
Military Memoir of Colonel John Birch: T. W. (Thomas William) Webb, John Webb
Soviet Military Intelligence in War: Colonel David M. Glantz
Military Dictionary: H. L. Scott, Colonel H. L. Scott
The Sociology of Military Science: Colonel (US Army Ret. Chris Paparone
They´re baaaaccck, Tracy sing-songed as she passed by where I was trying to study. I didn´t look up. ´´Who?´´ ´´Them.´´ She gestured with her chin. I finally looked up to see the small group of Marines coming into the restaurant where I worked part-time. I snorted and looked back down at my book. ´´I guess they can come in if they want to,´´ I said, turning a page. ´´This is a restaurant and they have to eat.´´ ´´And flirt with everything in a skirt.´´ She paused, looking over at me. ´´Aren´t you going over there? They are sitting down in your section.´´ Damn, she was right. I closed my book. So much for studying. I grabbed the menus and headed over to the table where the men sat, talking. As I approached, I took a moment to check them out. They were military judging by their short buzzed haircuts. There was a base nearby and a lot of the personnel came in for lunch or dinner with their families or friends. Between them and the locals, this place stayed pretty busy. ´´Good evening, gentlemen,´´ I said as I placed a menu in front of each man. They looked up, smiling and nodding in greeting. ´´What would you like to drink?´´ One of the men, a handsome blond with clear blue eyes, looked up at me. ´´You,´´ he answered, giving me a wink. The other men laughed at his joke. I gave him a smile. ´´You´re funny,´´ I answered. He leaned back in the... Happy ever after ending. No cliffhangers! 1. Language: English. Narrator: Theresa Stephens. Audio sample: http://samples.audible.de/bk/acx0/091292/bk_acx0_091292_sample.mp3. Digital audiobook in aax.
In Military and Mindful , Benefsheh Verell combines her knowledge of mindfulness practices with over twenty years in the Army as a Military Police and Information Operations officer to educate service members and their families about the mental, emotional, and physical benefits of yoga and meditation. Being a mom in the military is very difficult because there is always the underlying uncertainty of what the military will bring next. A mom in the military worries about deploying and how her kids will manage once she does. The feeling of guilt emerges for making career choices that take a mother away from her family. In Military and Mindful , mothers in the military learn how to balance their military career and motherhood without the feelings of guilt or stress. Unlike any other resource currently available for active-duty moms, Military and Mindful offers a template to unleashing one´s internal power. In addition to promoting a focused and positive mindset, Benefsheh Verell reveals how harnessing one´s internal power is essential to living a First-Class life.
History of the Fairfax:A Military Retirement Community Lieutenant General Frank Camm, Colonel John Schlight

domain: literature


With rain looming, Coughlin comfortably in Atlanta field ATLANTA (April 25) -- A pair of solid runs down Atlanta Dragway has earned reigning Pro Stock world champion Jeg Coughlin Jr. a safe mid-field spot in this weekend's POWERade Drag Racing...
With rain looming, Coughlin comfortably in Atlanta field
ATLANTA (April 25) -- A pair of solid runs down Atlanta Dragway has earned reigning Pro Stock world champion Jeg Coughlin Jr. a safe mid-field spot in this weekend's POWERade Drag Racing Series event. Coughlin opened with a 6.671 at 206.92 mph Friday afternoon before improving to a 6.668 at 206.67 mph in the slightly cooler evening to earn the No. 8 position in the provisional field.
"We're happy to be in the field but I don't think we scored the exact run we're looking for just yet with old yeller," Coughlin said, referring to his JEGS.com Chevrolet Cobalt. "We were in the left lane in Q2 and it doesn't appear to be as quick as the right, judging by the numbers everyone else posted. Even so, we still feel like we should have run quicker."
Coughlin and the other qualified drivers were relieved to have earned a spot in Day 1 as local weather forecaster paint a gloomy picture for the weekend.
"You do feel an added sense of urgency when you hear everyone talking about rain coming in," Coughlin said. "It would be a long night if you weren't in the show because there is always the possibility that we get rained out tomorrow.
"On the other hand, if it gets cloudy and the barometer starts going up, we could have the session of the weekend tomorrow morning. The bottom line, no matter what conditions we encounter, we need to be able to improve in relation to the other cars, even if we don't improve our position."
For the first time this year, Coughlin was joined in the pits and on the racetrack by his Victor Cagnazzi Racing teammate Dave Connolly, who signed Charter Communications and LifeLock as primary marketing partners.
"It's great to have Dave back with his new colors and new sponsors," Coughlin said. "It's the same team as last year and certainly it worked out well going to battle each week with that group over there sharing their data with us. Two cars are always better than one and now they're back for the long term, which is great."
-credit: team jegs


text:
Introduction to Cancer Biology
This course will cover the genetic basis of cancer, initiation and progression of cancer, signal transduction, tumor microenvironment, and metastasis. Additional topics will include cancer genomics, epithelial to mesenchymal transition, adhesion, angiogenesis, targeted therapies, and animal models. This course will also have a journal-club component, which will enable students to read and discuss scientific journal articles related to the course.
- Identify cancer biology terms and apply terms and information in textbook to case studies
- Discuss and present a scientific paper in detail, such as background information, experimental design, and findings

domain: biology


text:
Helen Miller's photographs and writing are published worldwide. Her award winning documentaries and short films have been made for television, cinema, galleries and festivals.
Helen studied at Canterbury College of Art, Liverpool School of Art, The Slade School of Art, University College London and the Banff School of Arts, Canada. She has a first class honours degree in Fine Art and MA in Fine Art Media. After lecturing at Falmouth College of Art, The Glasgow School of Art and The University of London she set up the partnership Underwood Miller of which she is Creative Director. She lives with her husband Sam Orlando Miller in London and Le Marche, Italy.
Clients include BBC, Channel 4, Conde Naste, IPC Media, Emap (Bauer), Independent on Sunday, The Donna Karan Company, Venice Estates, GA Design International, Lisa Sainsbury, Cocomaya and international private clients. Editorial publication includes The World of Interiors, AD France, AD America, Grand Designs, Vogue, Elle Decoration, The Telegraph, Times, Financial Times and Independent Newspapers.

domain: artistic


text:
|Year : 2019 | Volume
| Issue : 4 | Page : 362-366
|Effect of ultrasonic root-end cavity preparation on dentinal microcrack formation: A micro-computed tomography study
Naina Sachdeva, Vineeta Nikhil, Padmanabh Jha
Department of Conservative Dentistry and Endodontics, Subharti Dental College and Hospital, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India
Click here for correspondence address and email
|Date of Submission||14-Feb-2019|
|Date of Decision||04-Jun-2019|
|Date of Acceptance||31-Jul-2019|
|Date of Web Publication||07-Nov-2019|
| Abstract|| |
Background: Root-end preparation during surgical endodontics may produce dentinal microcrack formation and/or propagation, leading to vertical root fractures.
Aim: This study aimed to evaluate and compare the microcrack formation and propagation during ultrasonic root-end cavity preparation, with diamond- and zirconium nitride-coated tips using micro-computed tomography (CT).
Methodology: Twenty-eight extracted, mature, free-of-defect, mandibular premolars were decoronated and micro-CT scanned for the presence of preexisting microcracks. Samples were prepared till F4, were obturated, and were re-scanned to determine an increase in the number of microcracks. After 3 mm of root-end resection, the samples were randomly divided for ultrasonic root-end preparation into Group 1 (n = 12): preparation was done with ProUltra Surg tip, Group 2 (n = 12): preparation was done with KiS tip, and Group 3 (n = 4): no preparation was done. The samples were rescanned, and data collected were analyzed using ANOVA and Student's t-test. The level of significance was set at 5%.
Results: Preexisting microcracks were observed in few samples. The mean percentage number increase of microcracks after root-end preparation in ProUltra Surg group was 1.25 and in KiS group, it was 0.5. The difference in mean percentage increase for the number of microcracks after root-end cavity preparation using ProUltra Surg tip and KiS tip was 0.75. However, this difference was not statistically significant (P = 0.34).
Conclusion: Both diamond- and zirconium nitride-coated ultrasonic tips resulted in more number of dentinal crack formation and propagation when preexisting cracks were present.
Keywords: KiS; micro-computed tomography; ProUltra Surg; root fracture; root-end cavity; ultrasonics
|How to cite this article:|
Sachdeva N, Nikhil V, Jha P. Effect of ultrasonic root-end cavity preparation on dentinal microcrack formation: A micro-computed tomography study. J Conserv Dent 2019;22:362-6
|How to cite this URL:|
Sachdeva N, Nikhil V, Jha P. Effect of ultrasonic root-end cavity preparation on dentinal microcrack formation: A micro-computed tomography study. J Conserv Dent [serial online] 2019 [cited 2022 Aug 16];22:362-6. Available from: https://www.jcd.org.in/text.asp?2019/22/4/362/270505
| Introduction|| |
Nonsurgical retreatment of root canal-failed cases might not always be possible because of natural, restorative, or iatrogenic obstructions. Surgical retreatment includes surgical debridement of pathological periradicular tissue, root-end resection, root-end cavity preparation, and filling to seal the root canal system effectively.
Conventionally, the root-end cavity was prepared with burs using a low-speed handpiece, but it carried some disadvantages such as preparation not being parallel to the canal, difficult access, and risk of perforation. The development of ultrasonic root-end preparation allowed deeper cavities that follow the original path of the root canal more closely and enhanced access. The more centered root-end preparation also lessens the risk of lateral perforation. To overcome the lesser cutting efficiency and longer preparation time of stainless steel root-end preparation tips, diamond- and zirconium nitride surface-coated tips were introduced.
The contact between the instrument and canal walls during preparation creates stress concentration in dentin and microcrack formation. From a clinical standpoint, these microcracks are important because they may further develop into vertical root fractures. A recent study has shown that root fracture is not an instant event but rather a gradual propagation of tiny, less pronounced craze lines in the tooth structure.
Diagnosing and locating crack lines are difficult in clinical trials even though cone-beam CT has improved the diagnosis., In the last years, micro-computed tomography (CT) has opened up new possibilities for endodontic research by allowing nondestructive, volumetric, quantitative, and qualitative assessments before and after endodontic procedures.
Thus, the present study evaluated and compared the crack formation during root-end cavity preparation with diamond- and zirconium nitride-coated root-end preparation tips using micro-CT.
| Methodology|| |
Twenty-eight atraumatically extracted, intact, mature, nonrestored, mandibular premolars, with single-root and single-straight canal (curvature <20°), free of external cracks and resorption, were selected and decoronated to a standardized root length of 17 mm. The roots were coated with a thin layer of polyethylene impression material and placed in acrylic resin as was described by Liu et al. The specimens were sent for micro-CT imaging (Phoenix v | tome | x m, Germany) to determine preexisting dentinal cracks. Micro-CT scans were captured at 75 kV and 400 μA. The long axis of the roots was adjusted to be perpendicular to the beam to provide scans in the same sagittal positions. Each root was rotated 360°, with a total scan time of approximately 2000 s. The distance from the X-ray source to the sample was 124 mm and to the detector was 812 mm. Typically, 1000 CT slices (pixel pitch 200 μ and voxel resolution 30.5 μ) were obtained per root.
A #10 K file (M-Access Dentsply Maillefer, Ballaigues, Switzerland) was inserted into the root canal until the tip of the file was just visible at the apical foramen, and the working length was established by deducting 0.5 mm from this length. The samples were prepared with ProTaper Universal (PTU) rotary files (Dentsply, Maillefer Ballaigues, Switzerland) up to F4 following the manufacturer's instructions. Between the use of each file, the canals were irrigated with 5 ml of 3% NaOCl (Amble Healthcare Private Limited, Delhi, India) and at last 3 ml of 17% ethylenediaminetetraacetic acid (Prevest Dentpro Limited, Jammu, Jammu and Kashmir, India) for 1 min followed by 5-ml distilled water. Thereafter, the samples were obturated with Gutta Percha and AH Plus ® sealer using single-cone technique. The roots were stored for 1 week at 37°C and 100% humidity to allow the sealer to set.
Root-end resection and root-end preparation
The apical 3 mm of each root was resected perpendicular to the long axis of the root using a straight flat bur (SF-12, Mani, Inc, Utsunomiya, Tochigi, Japan) in a high-speed handpiece with continuous water spray. All the samples were resent for micro-CT imaging for the determination of microcracks after root canal preparation and obturation.
Thereafter, the samples were randomly divided into:
- Group 1 (n = 12): Class-1 root-end cavities were prepared to the depth of 3 mm with ProUltra SURG tip #1 (Dentsply, Maillefer Ballaigues, Switzerland) at medium power setting (6) of ultrasonic device (Satelec P5 Newtron Acteon, France) as recommended by the manufacturer
- Group 2 (n = 12): Class-1 root-end cavities were prepared to the depth of 3 mm with a diamond-coated KIS tip #1 (Kavo Kerr Dental, France) at medium power setting (6) of ultrasonic device as recommended by the manufacturer
- Group 3 (n = 4): Control group – No preparation was done.
The root-end preparation of each group was performed under internal-water cooling, and the samples were sent for third micro-CT imaging to determine dentinal microcracks after root-end preparation.
Each sample was observed at 0.25-mm interval for apical 5 mm that created 20 slices per sample. Only apical 5 mm was evaluated because root-end preparation was done only in apical 3 mm, and an additional 2 mm was evaluated to observe if at all any effect was caused coronal to the prepared area.
If there were microcracks on the external surface of the root and/or on the internal root canal wall, the slice was accepted as having “crack,” and the number was noted. As the number of microcracks observed preoperatively was different in each sample, the percentage of microcracks was calculated to standardize the procedure, and the increase in percentage number of microcracks was evaluated. ANOVA and Student's t-test analysis were performed using Statistical Package for the Social Sciences 13.0 software (SPSS Inc., Chicago, IL, USA). The level of statistical significance was set at 5%.
| Results|| |
There were preexisting dentinal microcracks in few of the samples, and an increase in the number of dentinal microcracks was observed after root canal preparation and obturation and after root-end cavity preparation. However, this increase was statistically insignificant (P > 0.05) for both of the experimental groups [Table 1] and [Figure 1]. The control group did not show any increase in the number or propagation of microcracks. Samples with preexisting microcracks showed more number of microcrack formation and/or propagation after obturation and after root-end cavity preparation as compared to those which were free of microcracks. Both ProUltra SURG (1.25 ± 2.26) and KiS (0.5 ± 1.446) root-end preparation tips caused generation and/or propagation of microcracks; however, the difference was statistically insignificant (P = 0.34) [Table 2].
|Table 1: Comparison of mean of the percentage number of dentinal microcracks with confidence interval and P value observed at different stages with ProUltra Surg tip and KiS tip under micro-computed tomography imaging|
Click here to view
|Figure 1: Micro-computed tomography images (a) no dentinal microcrack, (b) preexisting dentinal microcrack, (c) microcracks after root canal obturation, (d) microcracks after root-end cavity preparation|
Click here to view
|Table 2: Mean percentage number of dentinal microcracks increased and standard deviation after the use of different tips for retrocavity preparation on observation under micro-computed tomography imaging|
Click here to view
| Discussion|| |
The purpose of root-end cavity preparation is to remove irritants from the root canal system inaccessible to the operator via a coronal entry.
A great concern to the clinician is the formation of microcracks or microfractures following root-end resection or root-end preparation. The root-end microcracks increase susceptibility to root fracture, the inability to seal the root-end preparation properly, and the possibility of the additional site of bacterial contamination. The development of microcracks and microfractures following sonic or ultrasonic root-end instrumentation is still controversial. Therefore, this study was conducted to evaluate the effect of root-end cavity preparation on the root dentin walls in terms of microcrack formation and propagation.
Standardization of the procedure was done to minimize the errors. Only freshly extracted, intact, noncarious, single-canal, same-length human mandibular premolars with single apical foramen were selected. Teeth with <20° curvatures were included as an increase in the degree of canal curvature may result in the generation of more dentinal cracks which may lead to a strong generation of stress at the point of maximum canal curvature. In a study by Çapar et al., it was observed that single-cone technique applied minimal pressure compared to the other filling techniques that create compaction forces on the root canal walls, leading to dentinal microcracks. Therefore, this technique was chosen as an obturating technique.
Dentinal microcracks can be diagnosed in vitro utilizing microscopes, dyes, and/or transillumination. However, all these methods result in the destruction of samples. In the present study, samples were micro-CT scanned as this is a nondestructive, three-dimensional technique that provides quantitative as well as qualitative assessments.
Instead of the number of microcracks, the percentage number of microcracks was calculated to standardize the procedure. The micro-CT imaging revealed preexisting microcracks in some of the samples. This is in accordance with the studies of Barreto et al., Singh et al., and Arias et al. These preexisting dentinal microcracks may be attributed to noniatrogenic factors such as age changes, the effect of functional stresses such as occlusal interference or parafunctional stresses, any excessive force on teeth during extraction, or environmental changes on dentin such as dehydration.
It has been reported that instrumentation of root canals alone weakens the roots. In the present study, there was a mean percentage increase in the number of dentinal cracks in the experimental group from preoperative (21.29 ± 49.41) to after root canal preparation and obturation (22.66 ± 53.55). It is in accordance with the studies by Jain et al., Karataş et al., and Harandi et al. who concluded that there is an increase in the initiation of dentinal cracks after cleaning and shaping. Shemesh et al. attributed it to nickel-titanium (NiTi) rotary kinematics. However, in the present study, this increase was found to be statistically insignificant (P > 0.05), which is in accordance with the study done by Beling et al. On the other hand, Onnink et al. found a statistically significant difference between prepared and unprepared teeth in terms of crack formation, which may be because the authors used lateral compaction technique for obturation, whereas in the present study, the single-cone obturation technique was used which results in less stress on the root canal wall, thereby resulting in lesser crack formation. Jamleh et al. concluded that the incidence of microcracks after PTU instrumentation can be attributed to many factors. First, the continuous motion of the PTU system will have a greater threading effect. The use of a PTU instrument with taper up to 9% may also have contributed to the higher incidence of microcracks observed. Bier et al. found that when NiTi rotary instruments with a taper of 0.06 or more are used, dentinal defects result.
In the present study, root-end cavity preparation was done using two different ultrasonic tips: ProUltra SURG and KiS tip. The micro-CT imaging revealed that both the groups showed increase in the percentage of cracks when compared to the preoperative and the postobturation groups, but this increase was statistically insignificant (P > 0.05). In addition, samples with preexisting cracks showed more development of microcracks after root-end cavity preparation than those which do not have.
Recent studies by Saunders et al. and Layton et al. demonstrated the presence of root-end cracks in extracted teeth after ultrasonic preparation. There were significantly more root ends with cracks after ultrasonic root-end preparation than after root-end resection only. In root ends that had any cracks, significantly more canal cracks per root occurred when the ultrasonic tip was used on the high-frequency setting for root-end preparation than when the ultrasonic tip was used on the low-power setting. In the present study, medium-frequency power setting was used for root-end preparation as per manufacturer's guidelines on the freshly extracted teeth, which could be the reason for significantly less number of microcracks.
On comparing both the groups, there was more increase in the mean percentage of microcrack formation in ProUltra SURG group than KiS group, but the difference among both the groups was statistically insignificant (P > 0.05). ProUltra SURG tip is a zirconium nitride-coated tip, whereas KiS is a diamond-coated tip. Diamond-coated tips have better cutting efficiency than zirconium nitride-coated tips, which may be the reason for lesser number of crack formation or propagation in KiS tips. Gunes and Aydinbelge also concluded in their study that diamond-coated root-end tips are more efficient in removing dentin and thus minimizing dentinal fractures. Ishikawa et al. and Taschieri et al. reported no insignificant difference among zirconium nitride-coated and diamond-coated ultrasonic root-end tip groups in the number of microcracks in their in vitro studies. Along the similar lines, Gondim et al. reported that no significant differences in chipping and cracking area were detected in treatments with diamond-coated, stainless steel, and zirconium nitride-coated tips, but stainless steel root-end tips showed a greater number of teeth with cracking and a larger chipping area, probably due to the longer preparation time needed. Both the KiS and ProUltra SURG tips are very efficient and provide good vision and have excellent cutting efficiency.
| Conclusion|| |
Preexisting dentinal microcracks result in more number of microcrack formation/propagation after root-end cavity preparation. Root-end cavity preparation with both diamond-coated and zirconium nitride-coated ultrasonic tips caused insignificant increase in dentinal microcracks. However, further in vivo and in vitro studies with more number of samples and in curved roots should be carried out to extrapolate the results clinically.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Karataş E, Gündüz HA, Kırıcı DÖ, Arslan H, Topçu MÇ, Yeter KY. Dentinal crack formation during root canal preparations by the twisted file adaptive, ProTaper next, ProTaper universal, and WaveOne instruments. J Endod 2015;41:261-4.
Harandi A, Mirzaeerad S, Mehrabani M, Mahmoudi E, Bijani A. Incidence of dentinal crack after root canal preparation by ProTaper universal, Neolix and SafeSider systems. Iran Endod J 2017;12:432-8.
Shemesh H, Bier CA, Wu MK, Tanomaru-Filho M, Wesselink PR. The effects of canal preparation and filling on the incidence of dentinal defects. Int Endod J 2009;42:208-13.
Onnink PA, Davis RD, Wayman BE. An in vitro
comparison of incomplete root fractures associated with three obturation techniques. J Endod 1994;20:32-7.
Jamleh A, Komabayashi T, Ebihara A, Nassar M, Watanabe S, Yoshioka T, et al.
Root surface strain during canal shaping and its influence on apical microcrack development: A preliminary investigation. Int Endod J 2015;48:1103-11.
Bier CA, Shemesh H, Tanomaru-Filho M, Wesselink PR, Wu MK. The ability of different nickel-titanium rotary instruments to induce dentinal damage during canal preparation. J Endod 2009;35:236-8.
Saunders WP, Saunders EM, Gutmann JL. Ultrasonic root-end preparation, part 2. Microleakage of EBA root-end fillings. Int Endod J 1994;27:325-9.
Layton CA, Marshall JG, Morgan LA, Baumgartner JC. Evaluation of cracks associated with ultrasonic root-end preparation. J Endod 1996;22:157-60.
Gunes B, Aydinbelge HA. Effects of ultrasonic root-end cavity preparation with different surgical-tips and at different power-settings on glucose-leakage of root-end filling material. J Conserv Dent 2014;17:476-80.
] [Full text]
Ishikawa H, Sawada N, Kobayashi C, Suda H. Evaluation of root-end cavity preparation using ultrasonic retrotips. Int Endod J 2003;36:586-90.
Taschieri S, Del Fabbro M, Testori T, Francetti L, Weinstein R. Endodontic surgery with ultrasonic retrotips: One-year follow-up. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:380-7.
Gondim E Jr., Gomes BP, Ferraz CC, Teixeira FB, Souza-Filho FJ. Effect of sonic and ultrasonic retrograde cavity preparation on the integrity of root apices of freshly extracted human teeth: Scanning electron microscopy analysis. J Endod 2002;28:646-50.
Dr. Naina Sachdeva
Subharti Dental College and Hospital, Swami Vivekanand Subharti University, NH-58, Delhi-Haridwar Bypass Road, Meerut - 250 005, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]
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Vail Valley Voices: What life quality do we want?
Eagle County voters will face a handful of ballot issues on our mail-in ballot in November. Be sure to register for a mail ballot – you will only be sent a ballot if you voted by mail in the past or are on the mail-ballot list. The ballot is full of a variety of local, county and state issues.
Consider what you want your community to look like as you consider the various issues. Let’s accept the general premise that no one likes tax increases, especially in an uncertain economy.
But before you knee-jerk react by voting no down the line, it’s time to quit the political posturing on both sides and candidly talk about what we expect from local government and what we want our community to look like.
I’d suggest we model our community after our world-class resorts. Frankly, there isn’t any help coming from the state. And we’ll have less help from the state moving forward.
That results in local ballot issues to raise our mill levies or sales taxes to support our local entities and local community to create a world-class community to match our resorts.
Vail Resorts continues (rightly) to invest in their products, from new lifts to new restaurants to new marketing infrastructure. We, as a community, should follow this example of leadership and invest in our community by supporting the school district and fire protection district mill levies.
You can argue that, much like private industry, that government can cut expenses to fix the problem. That’s well and fine, except they have done this to a large extent already.
Staff levels, both in the administrative offices and the classroom, have been cut drastically the past few years. Services and infrastructure including busses and computers have been delayed. Merit pay has been in place since before it was popular. In fact, other districts are looking to Eagle County as a case study of how to implement this model. Look closely and you’ll see our school district already models private industry.
Strong public schools are an investment not only in our children, but in our local economy.
Eagle County’s recent Economic Development Plan spotlighted learning and education as a pillar of our economic growth. Can you afford to invest less than $8 per month in your community ($92 a year on a $500,000 home)? Better yet, can you afford not to?
The ballot language requires this money to be spent in the classroom, on teachers, support staff and on the cuts that have already taken place over the past three years – and it is worded to protect taxpayers, as it is capped to only replace lost state funding.
It’s a question of community, and a strong public school system is essential to a strong community.
Similarly, the Eagle River Fire Protection District has a mill levy on the ballot to support their operations and to continue to provide world-class service to the community equal to our world-class resorts. This essential service begs the question of what we want from our municipal services – low taxes or world-class services?
We are home to world-class resorts. I’d like to have a world-class community to match it. Don’t punish our local entities due to the irresponsible behavior from Washington or due to partisan politics. Consider what type of community you’d like to live in and vote “yes” to support our schools and fire district when you vote this fall.
Chris Romer, of Eagle-Vail, is speaking here as a private citizen, as the Vail Valley Partnership where he works does not take stances on candidates or ballot issues.


I found this super slow motion youtube video of recoil. [ame="http://www.youtube.com/watch?v=XXZUMGRxPM4"]Firearm cycling slow motion / ciclo das armas camera lenta - YouTube[/ame] Does the barrel start to rise before the bullet leaves? I've heard it said that slower loads shoot higher from a handgun because they are in the barrel longer. Do you think that is actually true (or if true, is it true for that reason?). How much does follow through affect accuracy? These are the sorts of questions of interest to me when I look at this video Oh, also, anyone know of video like this with a Gen 4 Glock so we can see exactly what is going on with the brass to the head ejection pattern Do you think Glock has such video? The must have, I'd think. Good news is my Gen 4 Glock 17 hasn't brassed me in the head as much recently. Problem seems to have virtually fixed itself. And finally, what the heck really is a double-tap??? Because I don't see anyway two bullets are coming out for one recoil Wanna kill these ads? We can help!


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text:
My potager vegetables
Lettuce Semi-cos Freckles (green with dark spots) and Little Leprechaun (red leaves with green and red heart); Little Gem Intred (reddish-purple); butterhead Marvel of Four Seasons Courgettes Yellowy-orange Atena Polka’, light green Clarion and dark green Nero di Milano Runner beans Celebration (salmon pink flowers), Desiree (white flowers) and St George (red and white flowers)
I’m hoping Santa might leave me some seeds and plants to create a potager. Not a huge one like Villandry or Versailles has, but just big enough tofitin my back garden – 2 x 4m (6% x 13ft) would be fine. The definition of a potager is a kitchen garden, but I think the modern understanding of a potager is a garden in which you can grow fruit, flowers and vegetables alongside each other. Ifit’s colourful and attractive, even better.
Mini and patio vegetable varieties are perfect for a potager, together with some spotted and
bronze-leafed lettuces, different-coloured dwarf beans and red, yellow, orange and white chard. I’d also add red, white and yellow beetroot to the list. Some climbing beans have pink and red flowers as well as white, and the red and white blooms of runner bean Painted Lady are as colourful as sweet peas. Broad
Garden designs bristol Photo Gallery

domain: agronomy


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In This Section
Turn Your Passion Into a Profession with Practical Training and Experience
Here you’ll take a hands-on approach to learning, using state-of-the-art tools in a nurturing environment that supports your passions. You’ll acquire valuable experience in real-world settings, like Philadelphia’s world-class medical centers, rehabilitation centers, and geriatric care facilities. And you’ll benefit from expert guidance in the intellectual, cultural, and ethical nuances required to secure positions that are financially and personally rewarding.
Our students focus on improving patients’ lives, and our graduates translate that enthusiasm into rewarding careers as physical therapists, occupational therapists, physician assistants, and professionals in exercise science and wellness management.
College NewsView All
USciences Serves in Honor of Martin Luther King Jr. Day
January 21, 2020
In recognition of Martin Luther King Jr. Day of Service, more than 270 USciences students joined faculty and staff volunteering at a variety of service activities on January 20, 2020.
Students Get Hands-On Experience in New Pediatric Occupational Therapy Lab
January 13, 2020
This fall, USciences' Department of Occupational Therapy opened the first pediatric occupational therapy laboratory on campus.
USciences Awarded $4.9 Million in Research Grants in 2019
December 19, 2019
USciences faculty researchers and students were supported by $4.9 million in grant funding awarded to the University in 2019. The additional dollars support ongoing investigations in each of the University's three colleges as well as student involvement in those projects.
W.W. Smith Charitable Trust Representatives Meet USciences Scholarship Recipients
December 19, 2019
W.W. Smith Charitable Trust provides funding for undergraduate students scholarships amounting to $71,000 in aid to support 17 undergraduate students.
For DrOT Alumna, USciences Provided an Accelerated Program and a Fulfilling Campus Experience
December 03, 2019
Pooja Patel DrOT'17 found that USciences offered an accelerated degree program and a well-rounded education.
University of the Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495

domain: news


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In Spain we approach the end of the first week of quarantine to try to curb the spread of the coronavirus. As we should already know, one of the most important measures to achieve this is to wash your hands thoroughly.
As usual, Google has given us a good morning with a doodle that today serves a tribute to Ignaz Philipp Semmelweisthe first doctor that stressed the importance of proper hand-washing.
They have also created a poster that you can print
Semmelweis was a doctor in the NINETEENTH century, and he was known as “the savior of mothers.”after discovering that this small gesture managed to reduce fever puerperal (inflammatory involvement, localized or widespread, that occurs after birth as a result of the changes and injuries).
Unfortunately, many of the companions of Semmelweis initially saw their ideas with skepticism, and it took several decades until their hygiene recommendations were validated by the scientific community.
For this reason, Google has decided that it will be the own Semmelweis who teach us how to wash correctly hands in this doodle. Below you can see all the procedure that you must follow:
In fact, Google is following the steps of the procedure recommended by the World Health Organization (WHO). In addition to each one of the steps to follow, we indicate the optimal duration of each of them.
In addition, Google has also created a poster (in this link we can find the highest quality) we can print or have it saved on our mobile devices to never forget the procedure to follow when washing your hands.
it was originally published in

domain: medical


On the world market arrives new model of Jeep. This is the 2017 Jeep Renegade, first car by Fiat Chrysler cars. The new model will be more comfortable and luxurious than its predecessor. This SUV will be a recognized by the smaller size. It will delight lovers of mid-size SUVs. In it will be built a modern technological achievements, which are used in autoproduction.
2017 Jeep Renegade: Interior and Exterior
Wheelbase of this model will amount to 2.5 mm. In the cabin will be housed two rows of seats. He will be able to comfortably accommodate 5 adults. Exterior of this model will be characterized by various innovations. The 2017 Jeep Renegade will have a seven-slot chromed grill, big round headlights and angulaer edges around him. You will access the 2017 Renegade and four equipment option namely Latitude, Trailhawk, Sport, and Limited. The standard vertical grid of the car will come with seven holes and the headlights redesigned to have a look round. The front bumper will be modified and encoders automobile strong look.
In the car will be a touch screen. For this additional feature, customers will have to pay extra money. The screen size will be 6.5 inches. On it will be read out vital functions of the car. Colors in the cab of this model will be available in various colors. These are for example: gray, classic black, brown and sand moderate.
2017 Jeep Renegade: Engine and Performance
Chassis of the new model is prepared and developed by the company Fiat. However, engineers have added certain substances in order to meet the standards of chassis of Jeep. As for the engine of the new car, it is mentioned two solutions. The first is a turbocharged 1.4 liter four cylinder engine. It will be mated to 6 speed shifter physical and will have 160 HP. Second variant is 2.4 liter gasoline engine, which would be matched on 9 speed automatic transmission system. This engine will create energy of 184 horse power. The 2017 Jeep Renegade will be compiled for the city and off road driving.
2017 Jeep Renegade: Date of Release and Price
As for placement on the world market, we expect it to be at the end of 2016 or early 2017. The price of this model is not yet known. The company did not want to comment anything about it. It is speculated that the basic model would cost around 18 500 dollars. More advanced trims of 2017 Jeep Renegade, as Trailhawk, would cost around 26 000 dollars.
Company officials expect that this model will achieved great popularity. To travellers will provide great comfort and pleasure when traveling. This model is the right choice for fans of mid-size SUV, as we have already mentioned.


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Tumor Suppressor Genes from tissue cancer to check mutations
please i need a specific PCR kit (ready to use) for Tumor Suppressor Genes from tissue cancer to check breast cancer mutations:
1-KIT FOR PCR BRACA 1
2-KIT FOR PCR BRACA 2
3-KIT FOR PCR PTEN
4- KIT FOR PCR CHEACK 2
5- KIT FOR PCR P53
if any one can help..........
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This summer brought more than just blistering heat; cities across the country felt the pressure of devastating ransomware attacks. More than 40 municipalities, including 22 in the state of Texas, were the victims of cyberattacks. Major cities like Baltimore and Albany, as well as smaller towns like Lake City, Florida, were attacked by cybercriminals holding data and systems hostage with ransomware.
Exploiting big business is nothing new. The Old West was full of train robbers looking to make off with payroll and other valuables. But these modern-day criminals have come a long way since the James-Younger Gang and Butch Cassidy. Today, cybercriminals are targeting small-town America in the hopes that these cash-strapped government organizations have lax security measures and the inability to rebuild infrastructure after an attack. Lake City, Florida, for example, paid nearly $460,000 in bitcoin, assuming that it would be less expensive than reconstructing its systems.
The rate of ransomware attacks on public-sector targets this year is outpacing last year and not showing any indication of slowing down. Many of these cash-strapped governments are looking for new ways to protect themselves from cybercriminals. Getting a handle on cybersecurity issues begins with information. Identifying vulnerabilities allows local governments to direct resources toward weak links. For municipalities that outsource payroll and credit card processing, conducting due diligence on the third-party provider’s security protocols is often overlooked. Local agencies must also conduct an audit of their internal security controls, including penetration testing of cyberdefense systems. Many are even looking to state governments to assist in cybersecurity audits on the local level. Washington state, for example, funds testing of local agencies’ systems that includes various performance and cybersecurity audits.
For many local governments, the gravity of having a solid cybersecurity plan in place isn’t recognized until after a breach occurs. Governments need to increase awareness throughout the agency and get in front of issues that have historically received little attention. Phishing and ransomware attacks typically go unnoticed by IT teams and system administrators, so agencies need awareness training to keep staff up-to-date on the latest exploits and reduce the number of potential threats.
High-profile attacks on municipalities underscore the urgency of leveraging information and technology to defeat cybercrime. Yet keeping cybersecurity at the forefront of priorities is a challenge for small governments. LanYap Networks can help. Just give us a call!
Still searching? Use our Search Page to find what you are looking for.


A SEA lion pup has been captured after hiding under a San Diego police car for four hours in the middle of a road.
Police Sergeant Jack Knish said officers got a call about 4am (local time) yesterday that the pup was crossing a street in the Ocean Beach area.
Sgt Knish says an officer parked his car in the middle of the road and went to investigate. That's when the sea lion came out from under another car and scuttled under the patrol car.
SeaWorld experts retrieved the growling pup at about 8am.
Rescuer Kevin Robinson grabbed it by the tail and put it in a net.
Mr Robinson said the pup, who was less than a year old, was dehydrated but uninjured.
He said the pup weighs about 11kg - less than half what it should weigh.
Mr Robinson says it will be released within two months.
Read more at The San Diego Union-Tribune
Originally published asSea lion pulled from under police car


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Regulatory Mechanisms of Estrogen on Vascular AgeingView this Special Issue
Research Article | Open Access
Ho-Sun Lee, Sangseob Leem, Bermseok Oh, Taesung Park, "Effect of Interaction between Early Menarche and Genetic Polymorphisms on Triglyceride", Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 9148920, 9 pages, 2019. https://doi.org/10.1155/2019/9148920
Effect of Interaction between Early Menarche and Genetic Polymorphisms on Triglyceride
Early menarche has been associated with increased risk of metabolic syndrome. Therefore, investigating the association of each component of metabolic syndrome with age at menarche, and interactions between them, might lead to a better understanding of metabolic syndrome pathogenesis. In this study, we evaluated age at menarche for risk of metabolic syndrome and associations with its components. As a result, the risk of MetS incidence was significantly increased only at ≤12 years of age at menarche (OR = 1.91, ). Women with early menarche (≤12 years) had significantly higher levels of triglycerides (β coefficient = 37.83, ). In addition, hypertriglyceridemia was significantly increased at early menarche with 1.99 (95% CI: 1.16–3.41, ). With GWAS-based pathway analysis, we found the type 2 diabetes mellitus, stress-activated protein kinase signaling, and Jun amino-terminal kinase cascade pathways (all nominal , all FDR < 0.05) to be significantly involved with early menarche on triglyceride levels. These findings may help us understand the role of early menarche on triglyceride and interaction between gene and early menarche on triglyceride for the development of metabolic syndrome.
Menarche, defined as the first menstrual period in a woman’s life, is a marker of female puberty and the onset of ovarian and other endocrine functions related to reproductive capacity. Age of menarche has declined over the last several decades through improvement of socioeconomic conditions or exposure to environmental chemicals and received a great deal of attention as having important health implications . Age at menarche (AAM) can be a risk factor for disease, and there were several studies on the interaction between AAM and genetic factors especially for breast cancer susceptibility [2–4]. Early menarche is often defined as menarche before the age of 12 years (≤11 years old), but some investigators base definition on menarche at ≤12 years . A number of studies have reported associations between early menarche onset and intermediate quantitative traits such as increased blood glucose levels , impaired glucose tolerance , and insulin resistance , further supporting a link between early pubertal development and an adverse metabolic profile. Others have reported adverse metabolic consequences (e.g., diabetes) arising from early sexual maturation [9, 10]. One possible mechanism for this association is a direct link between puberty timing and glucose regulation, supported by the insulin-sensitizing agent metformin delay of menarche in girls with precocious puberty . It is conceivable that part of the association between menarche onset and type 2 diabetes risk is explained by increased adiposity [9, 10]. However, these data are not consistent, and the relationship between AAM and metabolic components remains poorly understood. Metabolic syndrome (MetS) is considered a worldwide epidemic. In general, the International Diabetes Federation estimates that one-quarter of the world’s adult population has MetS . Higher socioeconomic status, sedentary lifestyle, and high body mass index (BMI) significantly associate with MetS. Data from the National Health and Nutrition Examination Survey (NHANES, 1999–2006) reported that nearly 34% of all U.S. adults, and 50% of those aged 60 years or older, were estimated to have MetS . The prevalence of MetS in Korea has also been steadily increasing in recent years, from 24.9%, in 1998, to 31.3%, in 2007; this prevalence is relatively high compared to those of other Asian countries . MetS is characterized by the clustering of five pathological traits, including large waist circumference, hypertriglyceridemia, low-density lipoprotein (LDL) cholesterol level, hypertension, and hyperglycemia. However, mechanisms and differences, correlated with the relative risk of susceptibility to MetS, remain poorly characterized.
To date, genome-wide association studies (GWAS) have identified several susceptibility regions and genes for MetS and its component phenotypes [14, 15]. Since the first report from a GWA study of obesity, an increasing number of genetic factors have been shown to associate with several traits of obesity and MetS. Despite the success of recent GWAS, the identified variants explain only a small proportion of the heritability of most complex diseases . Heritability estimates of MetS range from approximately 10 to 30%  among individuals; therefore, implicated genes may interact synergistically with environmental factors, in the pathogenesis of MetS.
Here, we investigated the role of AAM on MetS components for MetS risk. Specifically, we examined the association between AAM and levels of individual component of MetS such as triglyceride (TG). Furthermore, we evaluated GWAS-identified genetic variants for interaction effects with MetS components using a pathway-based analysis and characterized the role of AAM in the pathogenesis of MetS.
2.1. Study Design and Participants
This study, an ongoing prospective investigation, is a population-based cohort included in the Korean Genome and Epidemiology Study (KoGES) . Originally, 5018 woman participants, aged 40 to 69 years, were recruited from the Korean rural (Ansung) and urban (Ansan) communities at baseline, as part of the Korean Association Resource Project (KARE). From 2007 to 2008, the samples were scrutinized for quality control purposes, and 3493 participants remained. We excluded those with reported AAM of ≤10 years () or ≥19 years () or missing (), probably due to recall error or the presence of a comorbid pathological condition. Finally, information was available from 3180 women for the study of AAM.
These cohorts included a standardized health interview, using well-established questions, to determine the demographic and socioeconomic characteristics of all subjects, including menstruation history. AAM was defined as the age of the first menstrual period. Women reported their AAM in single years and were classified for this study as having an AAM of ≤12, 13, 14, 15, 16, or ≥17 years . Comprehensive health examinations, including evaluation of anthropometric indexes, measurement of blood pressure, questionnaire-based interviews, and collection of biospecimens for assays (e.g., C-reactive protein), were conducted biennially by health professionals who were trained with a standardized protocol. Women who smoked regularly during the previous 12 months were classified as current smokers. Levels of physical activity were semiquantitatively assessed using a questionnaire previously validated against objective methods  and were coded as inactive, moderately inactive, moderately active, and active. Educational attainment was categorized into three groups: less than 7 years (elementary school graduates), 7–9 years (middle school graduates), and more than 10 years (high school graduates). Monthly household income was also categorized into three groups: less than $1000 USD (in 2014), $1000–2000, and ≥$2000 . In addition, we performed the additional analysis for oxidative stress-related exposure with OBS score and inflammatory marker with C-reactive protein (CRP) at each AAM [22, 23]. Written informed consent was obtained from all participants at the KoGES. This study was approved by the Institutional Review Board of Seoul National University.
2.2. Definition of the Metabolic Syndrome and Its Components
We used the definition of MetS proposed by the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines . As detailed in our study, participants having three or more of the following criteria were defined as having MetS, except for the determination of central obesity. Waist circumference cut-off values were used based on guidelines from the Korean Society for the Study of Obesity : (1) central obesity, given as waist high circumference (≥85 cm); (2) high concentration of serum triglycerides (≥150 mg/dl); (3) low concentrations of serum HDL cholesterol (<50 mg/dl); (4) hypertension (systolic/diastolic pressure ≥ 130/85 mmHg) or antihypertensive medication; and (5) high concentrations of fasting glucose (≥100 mg/dl) or antidiabetic medication.
The data used for GWAS was obtained from KoGES, which was conducted by the Korean National Institute of Health. DNA samples were isolated from the peripheral blood of all participants and genotyped, using the Affymetrix Genome-Wide Human SNP array 5.0 (Affymetrix Inc., Rockville, MD, USA). Quality control procedures were adopted, such as missing genotype frequency > 0.5% and minor allele frequency (MAF) ≤ 0.05. After sample and genotype quality controls, 344,396 SNPs for 3180 individuals were available in the KARE database [26, 27]. The KARE data used to support the findings of this study are restricted by the Institutional Review Board of the Korean National Institute of Health, who can contact at National Biobank of Korea (http://koreabiobank.re.kr, 82–1661-9070).
2.4. Statistical Analysis
For demographics and characteristics of subjects, data were presented as means and standard deviations for continuous variables, or a percentage (%), for categorical variables (Table 1). Differences among subjects in different groups were detected using the Kruskal-Wallis test, for continuous variables, and the chi-square test, for categorical variables.
Values are expressed as means ± SDs (standard deviations) or number (%). BMI: body mass index; OBS: oxidative balance score; CRP: C-reactive protein; a104 KRW: equivalent with 1000 US dollar in 2014. b value was examined by the Kruskal-Wallis test or chi-square test.
At first, logistic regression analyses were performed to determine the odds ratios (ORs) of MetS (Figure 1), and its five components, depending on each year of menarche, with 16 years of age as a reference group (Figure 2). Logistic regression models were adjusted for age, area, income, education, and CRP levels. Next, we evaluated beta coefficients for each year of menarche, using linear regression analyses for individual components of MetS, with 16 years of age as a reference group (Table 2). This reference group was chosen because it covers the median of AAM (median age = 16.0) .
SBP: systolic blood pressure; DBP: diastolic blood pressure; FI: fasting insulin; FG: fasting glucose; WC: waist circumference; TG: triglyceride; HDL: high-density lipoprotein. aAge at menarche as a dummy variable (≤12 years: 0, >12 years: 1), .
To test the interactions between SNPs and AAM, we performed interaction tests for identifying genetic variants associated with MetS and its characteristic components. In addition, we performed the joint test of the main and interaction effects with one degree of freedom (df). We then used the following equation: where is the MetS component for individual and = (=1) of MetS for a binary trait. We then used the Wald test statistic to report the results of the joint () test, with two dfs and the gene-risk factor () with one df, referring to their respective null hypotheses of the joint effects ( = 0 and = 0) and of the interaction effect ( = 0), respectively.
The critical values for accessing the significance of interaction were calculated by Bonferroni correction () or the false discovery rate (FDR), with a value less than 0.05. Quantile-quantile (QQ) plots of the values for the joint test and interaction analysis suggested a moderate inflation of the genome-wide analysis only for TG. The inflation factors were 1.32 and 1.24 for interaction and joint effects, respectively, for TG in KARE dataset (Supplemental Figure S2). There were no genomic inflations for other components ( < 1.05). Therefore, for genomic controls of TG, the inverse normal transformed TG was used as a response, adjusting for age, area, income, education, and CRP levels for KARE. All analyses were performed using the R software version 2.11.1 (http://www.r-project.org/). Data management, descriptive statistics for the covariates and outcome variates, and the regression analyses were conducted using the Stats R package.
2.5. Pathway-Based Analysis
Pathway-based approaches using GWAS data are now used routinely to study complex diseases . To analyze pathways interacting AAM with TG genetic polymorphism, we used the improved gene set enrichment analysis (GSEA) . This approach has the advantage that genetic variant associations, mapping to any genes, provide insight into biological functions, signal pathways, and mechanisms of disease.
In our study, 344,396 SNPs were mapped to genes within 20 kb boundaries. Pathways consisting of <20 or >200 genes were excluded from further analysis, to reduce the multiple testing issue and avoid testing overly narrow or broad functional categories [22, 27]. A false discovery rate (FDR) was used for multiple testing correction, with values < 0.05 considered significant. Improved GSEA approaches use a comprehensive pathway and gene set database from SNP data. Pathway-related information is obtained from the KEGG (Kyoto Encyclopedia of Genes and Genomes pathway database), BioCarta, and GO (gene ontology) databases .
3.1. Characteristics of Participants
A total of 3180 women (mean age: 56.07 years; SD: 8.88 years) were included in this study. Demographic characteristics of the women are presented in Table 1, which shows the baseline characteristics of the study population stratified by AAM. The mean age of menarche was 15.83 (SD of 1.89) years. Because of the small group numbers for each subject having earlier ages of menarche, we combined subjects aged 11 and 12 years of menarche. At baseline, women with earlier menarche were slightly younger, had higher BMI and higher alcohol consumption, and more frequently lived in urban areas (Table 1). The individuals with early menarche were more likely higher educated and had higher monthly incomes. However, we observed no association of OBS scores as an oxidative stress-related exposure and CRP levels as an inflammation marker with AAM. All women with early menarche had never regularly smoked.
3.2. Risks of Metabolic Syndrome and Its Association with Triglyceride by Age at Menarche
Figure 1 shows the ORs of MetS by each year of AAM (from 12 to 17 years). Compared with the reference group (age at 16 years), the risk of incident MetS was significantly increased only at ≤12 years of AAM with 1.91 (95% CI, 1.03–3.55, ), after adjustment for area, age, income, education, and CRP levels. We also investigated ORs between AAM and five individual components of MetS. Only hypertriglyceridemia was significantly increased at ≤12 years of AAM with 1.99 (95% CI, 1.16–3.41, , Figure 2). However, other phenotypes did not significantly associate with AAM (Supplemental Figure S1).
We then examined the association between AAM and each component of MetS, separately. Linear regression analysis (Table 2) showed that women with earlier AAM had higher waist circumference and TG, compared with those with average AAM, after adjusting for the same covariates (). The corresponding regression coefficients of waist circumference and TG were 3.54 (95% CI = 1.53–5.55, ) and 37.83 (95% CI = 16.00–59.66, ), respectively. From these results (Figure 2 and Table 2), early menarche (12 years and before) is associated with increased risk of MetS, and this association appeared to be mediated mainly by increased TG of MetS.
3.3. Interaction between Genotypes and Age at Menarche on Triglyceride
As we considered that AAM was a modulator for the development of MetS, we conducted the joint analysis of the main SNP effect and its interaction effect with AAM interaction on MetS, and its individual traits, for all 352,228 SNPs. A list of SNPs associated with AAM-TG interactions, at , by joint test, is provided in Table 3. The strongest statistical evidence for SNP × AAM joint interaction was an SNP of rs6589566, located on the chromosome 11, in zinc finger protein 1 (ZPR1) (). We found that main genetic effects of SNPs located chromosomes 11 and 8 were the primary contributors to these joint associations. Specifically, we identified SNP rs1501675, located within an intronic region of ARHGEF28, as the most significant SNP, with for AAM-to-TG. Other interesting SNPs were located near (±2 kb) or within the loci LOC10537172, SCG2, TTT4, and LOC107986425 (all nominal values < 5 × 10−4).
Based on these findings, we tested pathway level-based interaction between AAM and genetic variation, according to SNPs with significant values for enriched biological processes, in TG. When mapping SNPs were limited to 20 kb regions flanking a gene, three pathways, type 2 diabetes mellitus, stress-activated protein kinase (SAPK) signaling pathway, and Jun amino-terminal kinases (JNK) cascade, were significantly enriched, with association signals and FDR < 0.05 (Table 4).
In this study, we observed that early menarche (at or before 12 years of age) was associated with high prevalences of MetS; however, later AAM showed no significant association. In particular, this trend appeared to be mediated by increased TG, with earliest menarche ages associated with increased TG, in our study population. A number of studies have previously investigated the association between menarcheal age and MetS with elevated blood glucose or BMI or TG [30–32]. Recently, two studies have examined the association between AAM and risk of MetS in the Korean population. One study, of 1464 Korean women, showed that the relative risk of MetS was 3.84 (96% CI: 1.52–9.70) for menarche at age <12 years in premenopausal women (from the KNHANES database) from 2007 to 2009, along with higher blood pressure . Won et al. also recently reported that 12,336 participants with early menarche (age < 12 years) were at increased risk of MetS (OR = 1.35, 95% CI: 1.03–2.12), with higher prevalence of hypertension and diabetes in KNHANES from 2010 to 2013 .
Puberty is the transition to adulthood that culminates in the production of mature gametes and the initiation of reproductive activity. The process begins within the central nervous system, where gonadotropin-releasing hormone (GnRH) neurons are activated to release the neurohormone, stimulating pituitary gonadotropic hormone secretions that in turn direct gonadal steroid hormone production. Therefore, a younger AAM is associated with higher cumulative exposure to ovarian hormones . Estrogen increases TG by promoting synthesis of TG in the liver and secreting TG into the circulation as very-low-density lipoprotein (VLDL) particles . TG levels correlatively increase during pregnancy with estrogen-induced stimulated secretion of hepatic TG-rich lipoprotein . However, the etiology of MetS, with regard to its association with TG, has yet to be unraveled completely with consideration of AAM.
Several studies have also demonstrated the importance of environmental triggers (including endogenous and exogenous exposure to hormone) in the development of chronic disease. Therefore, assay of gene-environmental interactions helps to understand the etiology of disease. Although several GWA studies have investigated AAM and breast cancer risk [4, 37], few GWA studies have focused on AAM and MetS with its components. Therefore, we conducted pathway analysis for investigating interaction of genetic variants and TG using GSEA. We found that T2 diabetes mellitus, stress-activated protein kinase, and JNK cascade pathways were associated with AAM on TG levels.
During puberty, there are proinflammatory and prooxidative changes and relative insulin resistance, which also play a role in the development of T2D [38, 39]. Early puberty may be causally related to lower insulin sensitivity and inflammatory changes . Reductions of insulin sensitivity and compensatory hyperinsulinemia are physiological during puberty, and this partly reflects the effects of increased growth hormone and IGF-1. Recent study reported that GnRH signaling may regulate T2D using pathway enrichment analysis . However, it was reported that obesity drives metabolic risk in the prepubertal population rather than premature adrenarche . More detailed mechanisms of the synergistic effects of early menarche and TG require further investigation.
SAPK/JNK are members of the MAPK family and are activated by a variety of environmental stresses, inflammatory cytokines, and growth factors. GnRH can activate the JNK/SAPK, p38, and ERK5 cascades in different cell models with varying kinetics . In addition, JNKs may be a central mediator of impaired glucose metabolism and insulin resistance . JNKs are also activated in obesity in numerous metabolically important cells and tissues such as adipose tissue, macrophages, the liver, skeletal muscle, and regions of the brain and pituitary. Recent studies have clearly established the important roles JNK signaling fulfils in macrophages, the liver, and cells of the anterior pituitary. Macrophage TG accumulation upregulates PON2 expression via the MEK/JNK/c-Jun pathway, and these effects could be related, at least in part, to cellular TG-induced ROS formation . Collectively, these studies place JNKs as important mediator of disruptions to metabolic homeostasis. In addition, 2-methoxyestradio activated SAPK/JNK in endothelial cells in a concentration-dependent manner . Although several studies shed light on the associations of stress-related pathway and TG, assessing interaction of AAM is still challenging.
Our study provides some interesting results on the interplay between AAM and the genome for TG; however, some limitations need to be considered. One of them is the relatively small sample size of women with early menarche, which may provide a lack of statistical power, limiting the magnitude of interaction effects. In addition, another weakness could be the cross-sectional design of the study, with self-reported medical histories and recalled AAM. Even though AAM can be recalled by women with moderate accuracy, the use of self-reported menarcheal age may lead to some degree of recall bias , and recall can be influenced by the individual’s current health condition . Since TG might be associated with other chronic diseases such as cardiovascular disease or hyperlipidemia , we tried to investigate the association between TG and other chronic diseases such as hyperlipidemia and coronary artery disease (CAD) in the study participants. Based on self-reported data to chronic diseases, we could not investigate the association between TG and other chronic diseases such as hyperlipidemia and CAD due to this small sample size lack of information. Considering confounding factors on TG, we could not investigate the effect of lipid-lowering drug and estrogen use on TG due to the small size. Due to lack of relevant information, the confounding factors mentioned above are excluded from our analysis, which may limit the strength of our findings.
This is a first attempt of a genome-wide gene-AAM interaction study on MetS components in Korean women. We identified that type 2 diabetes mellitus, the SAPK signaling pathway, and JNK cascade were associated with TG including the genetic interaction with AAM. These findings may help us understand the role of AAM on the development of MetS and gene-environment interactions that confer MetS susceptibility.
GWAS dataset and epidemiological data for KARE project are third party data and are available under the approval of the data access committee of the National Biobank of Korea, who can be contacted at email@example.com.
Conflicts of Interest
The authors declare that there is no conflict of interest regarding the publication of this paper.
This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) grant (2013M3A9C4078158) and by grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant numbers HI16C2037, HI15C2165 and HI16C2048).
Supplemental Figure S1. Risk of components of MetS in each age of menarche. ORs are adjusted by area, age, income, education, and C-reactive protein levels. Reference category is menarche at 16 years of age. Size of rectangle represents number of samples. A: high blood pressure; B: high fasting glucose; C: abdominal obesity; D: low HDL cholesterol. Supplemental Figure S2. Quantile-quantile plot of observed values vs. expected values (on a −log10 scale) for joint and interaction analyses of SNP and age at menarche on TG. A: interaction test; B: joint test; C: interaction test by reverse normal distribution; D: joint test by reverse normal distribution. (Supplementary Materials)
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Copyright © 2019 Ho-Sun Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Here's the latest from John Bird, Program Coordinator for Aboriginal Justice and Right Relations with the United Church of Canada.
Sent to all on the national Living Into Right Relations email list. Please
circulate widely wherever Sun-owned newspapers are distributed.
Here is a reply by Professor John Milloy of Trent University to
a column on Attawapiskat Chief Theresa Spence by Peter Worthington that appeared
in The Peterborough Examiner, and I imagine all or most of the Sun Media
Thanks to John Milloy for writing it, and to Jean Koning for
bringing it to our attention.
Aboriginal Justice and Right Relations
3250 Bloor St. W., Suite 300, Toronto, ON M8X 2Y4
or 800-268-3781, Ext. 4045
the Jan. 31, 2013 e-edition of The Peterborough Examiner:
"Spence gets attention but that's all" ( Column, Jan. 28) -
Worthington's column is simply grotesque: from its cruel comment on Bobby Sands
- "it was a self-liquidating problem" - to its abysmal ignorance of the history
and the current state of First Nations affairs.
For example, we have 600
or so chiefs because those chiefs were created by the Indian Act passed by the
government of our founding Prime Minister, Sir John A., and forced on
communities ever after. Yes, those tribes Mr. Worthington denigrates are
nations. The British Imperial government declared that in the Proclamation of
1763, which became part of our new constitution in 1982. Clearly, according to
Mr. Worthington, who as far as I know does not have a law degree, a series of
Supreme Court justices, who have confirmed that idea, have got it wrong.
And, as former Prime Minister Paul Martin pointed out recently, First
Nations asked for help managing their funds and the Kelowna Accord provided for
a special auditor general for First Nations. Prime Minister Harper refused to
help, has refused to make that appointment. Is it not blaming the victim to
complain about Chief Spence's accounting given that fact and the fact that the
Department of Indian Affairs, in providing a third rate education (currently the
subject of an inquiry by the Human Rights Commission in Ottawa) to communities,
has not equipped First Nations governments to cope with such responsibilities.
Finally, may I remind The Examiner and its readers that one of the leading
educational programs the department conducted from 1883 to 1996, in service to
Worthington's much vaunted integration, was residential schools and that their
deplorable legacy of cultural destruction and personal dysfunction caused the
Prime Minister to stand in Parliament and deliver an historic apology, if only
to escape the pain of the financial penalties of thousands of court cases
launched by abused exstudents.
I am not surprised by Mr. Worthington's
baseless opinion; he is who he is. I am disappointed that The Examiner,
published just down the road from Trent's Department of Indigenous Studies,
where the facts of the situation can be had, did not care to ask for a more
informed column. I think that would have served the interests of your readers
more than the ideological diatribe of Mr. Worthington you decided (or were
told?) you had to print.
PROF. JOHN S. MILLOY Department of Canadian
Studies Trent University
P.S. - And while it
irks me to do anything to promote the writings of people for the Sun media
group, here is a url for Peter Worthington's original column:
in case you think it doesn't matter what the Sun publishes, here's what its own
website says about its reach. It's probably a pretty safe bet that Worthington's
column appeared in at least one Sun-Media-owned newspaper near you. No wonder
Canadians are confused about Aboriginal issues:
"Sun Media Corporation, a
subsidiary of Quebecor Media Inc., is Canada's largest newspaper publisher,
based on the circulation of paid and free newspapers, publishing over 15.1
million copies each week.
With 36 paid-circulation daily newspapers and
6 free dailies in 9 of the 10 largest urban markets in Canada, each with its own
dedicated website, and almost 200 community newspapers, shopping guides and
other specialty publications, Sun Media Corporation's English and French
language newspapers and websites make it a leading provider of local news and
Sun Media Corporation includes the activities of Osprey
Media and Canoe.ca, an integrated enterprise offering e-commerce, information
and communication services that operates a network of Internet portals that
attracts over 10.5 million unique visitors per month in Canada, including 5.7
million in Québec."