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But this week, during a videotaped speech to a conference on women's issues in Japan, Clinton staked out a strong view on paid family leave, a topic that could play a role in her 2016 campaign. Clinton was asked about family leave during a CNN-hosted town hall in June, and said it was a good idea but one that won't come to America anytime soon.
The United States is one of just four countries where employers are not required to grant new mothers any paid time off after giving birth. Republicans have resisted calls for offering maternity leave, as it would force company's to spend more on employee benefits.
I swear i've driven through a road in some town and there were heaps of those all down the street. Or you could just find a tree that blossoms, and do what Disco Bacon said and chain saw it down, and plant it at home. Small tsunamis, non-destructive and undetectable without specialized equipment, happen almost every day as a result of minor earthquakes and other events.
However, when tsunami waves become extremely large in height, they savagely attack coastlines, causing devastating property damage and loss of life. The amount of energy and water contained in a huge tsunami can cause extreme destruction when it strikes land. The initial wave of a huge tsunami is extremely tall; however, most damage is not sustained by this wave. Destruction is caused by two mechanisms: the smashing force of a wall of water traveling at high speed, and the destructive power of a large volume of water draining off the land and carrying all with it, even if the wave did not look large. Objects and buildings are destroyed by the sheer weight of the water, often reduced to skeletal foundations and exposed bedrock. Tsunami waves destroy boats, buildings, bridges, cars, trees, telephone lines, power lines - and just about anything else in their way. Especially along a high seismic area, known as the Ring of Fire, tsunamis may have dramatic consequences as they hit less developed countries. The buildings infrastructure in these poorer nations are not well built and cannot withstand the impact of the tsunami. One of the biggest and worst effects of a tsunami is the cost to human life because unfortunately escaping a tsunami is nearly impossible.
Buildings collapsing, electrocution, and explosions from gas, damaged tanks and floating debris are another cause of death.
Tsunami waves and the receding water are very destructive to structures in the run-up zone. Flooding and contamination of drinking water can cause disease to spread in the tsunami hit areas. Tsunamis not only destroy human life, but have a devastating effect on insects, animals, plants, and natural resources. The impact of a tsunami on the environment relates not only to the landscape and animal life, but also to the man-made aspects of the environment. Recycling and disposal of this waste in an environmentally sensitive manner where possible (crushing concrete, bricks, etc. Combined with the issue of waste is that of hazardous materials and toxic substances that can be inadvertently mixed up with ordinary debris. Last but not least, there may be radiation resulting from damage to nuclear plants, as it happened in Japan in March 2011. Loss of income in the local economy and future losses from the destruction of infrastructure will be a problem for some time to come. The total financial cost of the tsunami could be millions or even billions of dollars of damage to coastal structures and habitats. Victims of tsunami events often suffer psychological problems which can last for days, years or an entire lifetime. These people were suffering from grief and depression as their homes, businesses and loved ones were taken from them. Science, Technology and Medicine open access publisher.Publish, read and share novel research. Cardiovascular Lesions of Kawasaki Disease: From Genetic Study to Clinical ManagementHo-Chang Kuo1, 2 and Wei-Chiao Chang3, 4, 5[1] Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Taiwan[2] Chang Gung University College of Medicine, Kaohsiung, Taiwan[3] Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Taiwan[4] Cancer Center, Kaohsiung Medical University Hospital, Taiwan[5] School of Pharmacy, College of Pharmacy, Taipei Medical University,Taipei, Taiwan1.
Kuo HC, Liang CD, Wang CL, Yu HR, Hwang KP, Yang KD.Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease.
Huang WC, Huang LM, Chang IS, Chang LY, Chiang BL, Chen PJ, et al.Epidemiologic features of Kawasaki disease in Taiwan, 20032006Pediatrics. Park YW, Han JW, Park IS, Kim CH, Cha SH, Ma JS, et al.Kawasaki disease in Korea, 2003-2005. Instead, she focused on selling her book, Hard Choices, which focuses on her foreign policy opinions and diplomatic chops. Three states now buck the national trend and force employers to offer their employees time off. E-mail any and all tips to pcaldwell [at] motherjones [dot] com.Mother Jones is a nonprofit, and stories like this are made possible by readers like you.
The effects of a tsunami depend on the characteristics of the seismic event that generated the tsunami, the distance from its point of origin, its size (magnitude) and, at last, the configuration of the bathymetry (that is the depth of water in oceans) along the coast that the tsunami is approaching. They are very often too far away from land or they are too small to have any effect when they hit the shore. These tsunamis make landfall usually in the form of suddenly decreasing and then rapidly increasing water levels (not unlike a tidal bore) a combination of several large waves or bore-type waves. A small wave only 30 centimetres high in the deep ocean may grow into a monster wave 30m high as it sweeps over the shore. Most of the damage is caused by the huge mass of water behind the initial wave front, as the height of the sea keeps rising fast and floods powerfully into the coastal area.
Large objects such as ships and boulders can be carried several miles inland before the tsunami subsides.
Once the tsunami waves have knocked down infrastructure on the shore they may continue to travel for several miles inland, sweeping away more trees, buildings, cars and other man made equipment.
Whole areas and towns are a picture of destruction as the tsunami leaves at trail devastation and misery behind it. The tsunami of December 2004 that struck South East Asia and East Africa killed over 31,000 people in Sri Lanka only, leaving 23,000 injured. The areas close to the coast are flooded with sea water, damaging the infrastructure such as sewage and fresh water supplies for drinking.
Solid waste and disaster debris are the most critical environmental problem faced by a tsunami-hit country. Salination of water bodies such as rivers, wells, inland lakes, and groundwater aquifers can occur in most cases. Since radiation exists for a long time, it has the capacity to inflict damage upon anything exposed to it. There might also be appeals and donations from people who have seen pictures of the area in the media.
It is difficult to put an exact figure on the monetary cost but the cost may represent an important share of a nation’s GDP.
Survivors of the Sri Lankan tsunami of December 2004 were found to have PTSD (post traumatic stress disorder) when examined by the World Health Organization (WHO): 14% to 39% of these were children, 40% of adolescents and 20% of mothers of these adolescents were found to have PTSD 4 months after the tsunami.
IntroductionKawasaki disease (KD) is an acute febrile systemic vasculitis that was first described by Kawasaki et al. Evaluation of coronary artery aneurysms in Kawasaki disease by multislice computed tomographic coronary angiography.
ITPKC single nucleotide polymorphism associated with the Kawasaki disease in a Taiwanese population.PLoS ONE. CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children. A cult following soon arises around the mysterious assassin killing off criminals across the country, christening him "Kira"note (A Japanese Ranguage approximation of "killer"). When a small tsunami comes to the shoreline it is often seen as a strong and fast-moving tide. Generally tsunamis arrive, not as giant breaking waves, but as a forceful rapid increase in water levels that results in violent flooding. The effects can be further amplified where a bay, harbour, or lagoon funnels the waves as they move inland. It is the power behind the waves, the endless rushing water that causes devastation and loss of life. Under these conditions it is difficult for people to stay healthy and for diseases to be treated, so infections and illnesses can spread very quickly, causing more death.
Rapid clean-up of affected areas can result in inappropriate disposal methods, including air burning and open dumping, leading to secondary impacts on the environment. This also affects the soil fertility of agricultural lands, due to salination and debris contamination, which will affect yields in the medium and long term. Radiation is most dangerous to animals and humans causing destruction as molecules loose their electrons. Kawasaki, Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children). Clinton's past profile on domestic politics largely centered on her experience and wisdom on finding ways to offer universal health insurance—a topic that is mostly off the national radar thanks to Obamacare.
His actions soon attract the attention of the international police community (who have grave concerns about the vigilante killings) and the world's greatest detective, an enigma known only as "L".L becomes determined to solve the mystery of Kira and his impossible killing method, employing increasingly aggressive and risky strategies to get what he wants.
When the giant breaking waves of a tsunami batter the shoreline, they can destroy everything in their path. Land animals are killed by drowning and sea animals are killed by pollution if dangerous chemicals are washed away into the sea, thus poisoning the marine life. The damage caused by radiation to the DNA structure determines birth defects, cancers even death. Currently, it is the leading cause of acquired heart disease in children in developed countries; however, its etiology remains unknown.
If she wants to run for president again, anchoring her campaign on getting the US in line with the international consensus of letting workers take a bit of paid time off to take care of newborns or a sick loved one seems like a no-brainer. It features original songs written by famed Broadway composer Frank Wildhorn (of Bonnie and Clyde and Dracula the Musical fame), along with lyrics by Wildhorn's longtime lyricist Jack Murphy and a book by Ivan Menchell.


In Japan, Korea, and Taiwan, the incidence ranges from 69 to 218 cases per 100,000 children less than 5 years of age.
A TV drama premiered in Japan on July 5, 2015, with an all-new cast.This series has a set of character sheets and an extensive set of Headscratcher pages.
Cooper, al, Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource. Molkara, et al.Transforming growth factor-beta signaling pathway in patients with Kawasaki disease. In fact, we at TVTropes have NINE different Death Note Abridged pages (click for the index). Simasathien, et al.The effect of BCG vaccine at birth on the development of atopy or allergic disease in young children.
Accidental Truth: In the manga, when the killings started, various tabloids put forward the Crackpot Theory that L was Kira, so it was harder for the SPK to seriously put this theory forward when it became true. Huang, et al.Polymorphisms of transforming growth factor-beta signaling pathway and Kawasaki disease in the Taiwanese population. Accomplice by Inaction: This is an audience reaction to Ryuk, and while he didn't force Light to kill criminals he did start the plot by dropping the book in the human world. The most serious complication of KD is the development of coronary artery lesions (CAL), including myocardial infarction, coronary artery fistula formation, [14] coronary artery dilatation, and coronary artery aneurysm.
Vetter, et al.Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease.
Thus, KD patients with coronary artery ectasia or dilatation that disappears within the first 8 weeks after disease onset are defined as having transient ectasia or dilatation (transient CAL).
Light also pulls this a few times, most notably, and with the worst sense of timing, at the end. Rem in particular is much more beautiful than her manga counterpart (she now has longer hair, wears a white dress, and no longer sports an eye patch). Adaptation Dye-Job: Misa has black hair in the live-action movies, while Naomi Misora goes from having black hair to brown hair. Then there's Matt, whose hair came out dark greenish brown in the anime, green in some trading card art, was never established in the manga, was blue in the official game, and is bright red in most fanart. This increase of eosinophils after IVIG treatment is inversely correlated with IVIG treatment failure in KD. Mello's eyes were pitch black in the manga (to match L and Near), but changed to blue for the anime.
The mafia boss Rod Ross has light skin in the manga and anime, but is dark-skinned in the DS game.
An increase in eosinophils and IL-5 levels after IVIG treatment is inversely correlated with CAL formation. The "Shinigami Eyes" in the manga cause the user's eyes to become gold, with red pupils and light yellow sclerae.
In the live-action version, the irises simply change to gold, while the anime depiction has the irises glow a bright red. In the Korean production of the stage musical, L (as played by Kim Junsu) sports light brown hair as opposed to black. Adaptation Expansion: The series is based on a short story about a schoolboy who finds a Death Note and mistakes it for a diary.
As a result, he accidentally kills his friends, until Ryuk helpfully gives him the "Death Eraser", which grants him the power to bring people back from the dead. Somewhere along the road to adapting it into a full series, the schoolboy became a mega genius with a god complex, the boring Film Noirish detective became a freakish mega genius with a sweet tooth, and the Deus ex Machina ending was replaced with plans by the bucketload, and the rest is history. Adaptation-Induced Plot Hole: The anime omits several scenes from the manga which, while usually not problematic, have lead to plotholes. In the manga, it's explained that SPK member Ill Ratt is a spy for Mello, which is how the mafia learned the SPK's names and were able to kill them.
This is not explained in the anime, but in the Relight 2 special, the mafia are cut, and Light blackmails the president to send their names to Kiyomi Takada. From our previous reports, we found that the T-helper (Th) type 2 immune response was elevated in the acute stage of KD, including eosinophils, [29] IL-4, IL-5, [35] and eotaxin. In this version, Light's meetings with her and Teru Mikami are moved to earlier than occurred in the anime, and they kill the SPK.
The eosinophil changes were correlated to changes of IL-5 levels but not to eosinophil cationic protein (ECP) levels, suggesting a Th2 immune reaction in KD.
However, while fixing one plothole, said special creates another: as the mafia are cut, Soichiro making the trade for Shinigami Eyes and his subsequent death is omitted in the process, leaving plotholes regarding Soichiro's absence as well as how Light was able to acquire Mello's true name.
Matt does not appear in any live-action adaptation, because Mello doesn't appear in the films, and in the drama he is merely a split-personality of Near. Since Matt was Mello's Satellite Character in the manga and anime, there was no reason for him to appear in the live-actions. EV patients also had elevated eosinophil levels after IVIG therapy, but not as high as that of the KD patients after IVIG treatment. That role is given to some blonde woman named Cathy Campbell, only known from a postcard in Raye's wallet.
Clinical phenotype and presentation of Kawasaki diseaseAs shown in Figures 1–8, the clinical characteristics of KD patients include fever lasting longer than 5 days, diffuse mucosal inflammation, bilateral non-purulent conjunctivitis, dysmorphic skin rashes, indurative angioedema over the hands and feet, and cervical lymphadenopathy. In fact, Naomi Misora doesn't really exist; instead, Shoko Himura Halle Lidner takes on some of her characteristics. In addition to the diagnostic criteria, there is a broad range of non-specific clinical features, including irritability, uveitis, aseptic meningitis, cough, vomiting, diarrhea, abdominal pain, gallbladder hydrops, urethritis, arthralgia, arthritis, hypoalbuminemia, [5] liver function impairment, and heart failure. Diagnosis of Kawasaki diseaseTo date, there is no specific diagnostic laboratory test for KD. All along, he plays on a reactionary tendency in public opinion — people don't like crime, people don't like criminals, and so if someone's killing off the worst ones, who's really going to disapprove? In Japan, at least 5 of 6 criteria (fever and 5 other clinical criteria) should be fulfilled for a diagnosis of KD. Then he pushes the envelope, making his brand of vigilante justice more and more mainstream.
However, patients with 4 of the principal clinical features can be diagnosed when coronary aneurysm or dilatation is identified.
However, according to the American Heart Association (AHA) criteria, [15] fever lasting more than 5 days is essential for the diagnosis of KD.Some patients who do not fulfill the criteria have been diagnosed with “incomplete” or “atypical” KD, a diagnosis often based on echocardiographic identification of CAL.
The term “incomplete” may be preferable to “atypical” because these patients have insufficient criteria instead of atypical presentation. Even if patients exhibit 4 or fewer signs of the clinical criteria for KD, physicians should consider the redness or crust formation at the BCG inoculation site as a possible indicator of KD. The incidence of CAL in patients exhibiting 4 principal symptoms of KD is slightly higher than that in patients with 5 to 6 principal symptoms.
Patients with at least 4 principal symptoms require the same treatment as patients with complete (typical) presentation of KD, and those with 3 or fewer principal symptoms should be treated similarly when they meet the supplementary criteria. The AHA criteria (2004), which incorporate suggestions for laboratory tests and early echocardiography, are helpful for diagnosing incomplete KD.
Patients with fever for 5 days or more (with 2 or 3 principal clinical features for KD) without other causes should undergo laboratory testing, and if there is evidence of systemic inflammation, an echocardiogram should be obtained even if the patient does not fully meet the clinical criteria for KD. Likewise, infants 6 months or younger with fever for 7 days or more without other causes should undergo laboratory testing, and if evidence of systemic inflammation is found, an echocardiogram should be obtained even if the infant fulfills no clinical criteria for KD. After Light dies, everything he worked for becomes meaningless and he sees the monster he became. Alas, Poor Villain: Even though the villains go into He Who Fights Monsters territory, and cross the Moral Event Horizon, their tragic downfalls and deaths still feel like this trope. There are several risk factors for developing coronary arteritis, such as low serum albumin, age younger than 1 year, and long duration of the fever before treatment. Young patients with low albumin run a very high risk for CAL and IVIG treatment resistance. The way he calls out to Takada and Misa, asking what he should do now that he's lost and going to die, is pretty heartwrenching. Also, when he's running away, he sees a younger version of himself (before he became Kira). The worst prognosis occurs in children with so-called “giant aneurysms of the coronary arteries” (those with a maximal diameter of >8 mm), as thrombosis is promoted both by sluggish blood flow within the massively dilated vascular space and by the frequent development of stenotic lesions later. Also in the manga, where he becomes insanely desperate for Ryuk's help after being shot by Matsuda and abandoned by Mikami, but Ryuk plays with his desperation before writing his name in his Death Note. AspirinAspirin has been used in the treatment of KD for many years, even before the usage of IVIG.
Horrified, Light lies bloody on the ground, all allies having died or abandoned him, knowing that his death is coming. Although aspirin has important anti-inflammatory (high dose) and anti-platelet (low dose) effects, it does not appear to reduce the frequency of CAL formation.
As his heart gives out, Light repeats over and over how he doesn't want to die, like a helpless child. Practices regarding the duration of high-dose aspirin administration vary across countries and centers, many of which reduce the aspirin dose when the patient is afebrile.
For children who develop CAL, low-dose aspirin (or other anti-platelet agents) is continued indefinitely until the inflammatory markers return to the normal range and the echocardiogram does not display abnormalities.
This review reiterates the recommendation that exposing children to high-dose aspirin therapy in the acute phase of KD is unnecessary because available data show no appreciable benefit to IVIG therapy response, CAL formation, or fever duration.
The patients were divided into Group 1, receiving high-dose aspirin (N = 274), and Group 2, without high-dose aspirin (N = 335).
These results provide evidence that high-dose aspirin in the acute phase of KD does not affect the treatment results (CAL and IVIG resistance rate) or inflammatory condition.
High-dose aspirin treatment in the acute phase of KD appears unnecessary, and further randomized controlled trials are needed.However, Reye syndrome is a risk in children who receive salicylates while they are experiencing active infection with varicella or influenza and has been reported in patients receiving high-dose aspirin for a prolonged period after KD.
All Love Is Unrequited: Played 100% straight with Sayu, Misa and Light, and later with Kiyomi Takada and Light.
Dipyridamole has been widely used to treat patients with a coronary aneurysm resulting from KD.
All There in the Manual: In the manga, you have no idea what happens to Misa Amane unless you read the supplementary book, "How To Read".


G6PD deficiency, an X-linked disorder, is the most common enzymatic disorder of red blood cells in humans. Towards the end of the series, Aizawa gets this feeling when he drives Light to Takada's hotel. While affected patients are usually asymptomatic, some have episodic anemia, while a few have chronic hemolysis. Alternate Character Reading: The kanji for Light's name is "tsuki", meaning "Moon", but his parents opted for it to be read as "Light" instead. The likelihood of developing hemolysis and the severity of disease are determined by the magnitude of the enzyme deficiency, which in turn is determined by the biochemical characteristics of the G6PD variant.
The World Health Organization has classified the different G6PD variants according to the magnitude of the enzyme deficiency and the severity of hemolysis. Class II variants also have severe enzyme deficiency, but are usually only intermittently associated with hemolysis. Class III variants have moderate enzyme deficiency (10–60% of normal), with intermittent hemolysis usually associated with infection or drugs.
Class V variants have increased enzyme activity, and classes IV and V are of no clinical significance. The incidence of hemolysis development in a patient with G6PD deficiency after taking aspirin is dosage-related. However, just few studies [56] have suggested that aspirin can be safely administered in therapeutic doses to G6PD-deficient subjects without nonspherocytic hemolytic anemia. Mello has a Hair-Trigger Temper and is Sour Outside, Sad Inside, Misa is over-dependent on the affection of Light, and Light himself has immense delusions of grandeur and is arrogant to the point where he could be a candidate for medical narcissism. Anti-platelet therapy is most commonly used to prevent thrombotic events for adults with atherosclerotic vascular disease, children with certain types of congenital heart disease, stroke, and KD.
In relinquishing the Death Note, he loses all memory of ever being Kira and turns genuinely upstanding and moral; apart from, you know, not mass murdering criminals, he also refuses to manipulate Misa, in contrast to his Kira self where his manipulation defined their relationship. Intravenous immunoglobulin (IVIG or IVGG)responsivenessThe efficacy of IVIG administered in the acute phase of KD for reducing the incidence of coronary artery abnormalities is well established. Antagonist in Mourning: In the anime, Light goes so far as to hallucinate his rival, L, sitting next to him and talking to him. Treatment of KD before day 5 of illness appears no more likely to prevent cardiac sequelae than treatment on days 5–9.
IVIG resistance (or IVIG unresponsiveness, initial IVIG treatment failure)The incidence of IVIG resistance varies from 9.4% to 23% between centers (but it can be as high as 38%, as reported in one US cohort).
Methylprednisolone pulse therapyAt present, the usefulness of steroids in the initial treatment of KD is not well established.
IVMP suppresses cytokine levels faster, and subsequently, the outcomes are similar to those of IVIG-responsive patients who receive a second dose of IVIG. The first dose of IVIG is well established, while IVMP or additional IVIG for IVIG-resistant KD patients requires further investigation.
IVMP (N = 13) and additional IVIG treatment (N = 14) were not significantly different in terms of preventing the development of coronary artery aneurysm. There were no convulsions, gastrointestinal symptoms, infections, malignant arrhythmias, or sudden death in any subject.
The early administration of TNF- receptor antagonists in KD may provide effective adjunctive therapy. Infliximab, which binds the pro-inflammatory cytokine TNF-, has been evaluated in several studies and shown to have a significant effect in KD patients with IVIG resistance. StatinsChronic vascular inflammation and endothelial dysfunction persists in KD patients with CAL, even long after the acute stage. Low-dose aspirin can be prescribed until CAL normalizes, but it does not have an effect on inflammation or endothelial dysfunction. Lipid abnormalities in the acute phase of KD, with decreased triglycerides and high-density lipoprotein cholesterol (HDL-C) levels have been reported in previous studies. Chronic vascular inflammation is also significantly improved, as is endothelial dysfunction, with no adverse effects. However, long-term and randomized control trials are needed before further conclusions can be drawn.
However, the association between dyslipidemia and atherosclerosis in KD patients is not certain. Other treatmentsAcute KD can lead to the development of large coronary artery aneurysms that may persist for years. Further trials are needed to clarify the optimal dose, safety, and timing of CyA treatment.
This indicates the possible treatment role of plasma exchange (PE) for KD with IVIG resistance. PE is considered safe and effective in the prevention of CAL in KD that is refractory to IVIG therapy. PE can be performed at an early stage, as soon as fractional increases in inflammatory markers are found after the first or second dosage of IVIG therapy. Genetic association study in Kawasaki diseaseThe higher incidence of KD in Asia, in conjunction with a higher incidence of the disease in Asian descendants compared with other ethnic populations in the United States and Europe, suggests that genetic predisposition might play an important role in the susceptibility to this disease.
Although genetic association studies have been widely performed in KD, several studies have produced inconsistent results. Some genes were proposed in one population; however, the findings could not be replicated in another population. In addition, the genes that are responsible for KD susceptibility may not be involved in CAL formation. First, some studies were performed in a small sample size that may not have been able to provide sufficient power to detect minor genetic effects. Second, it is becoming clear that there are different genetic backgrounds within populations that, due to variations in allele frequencies or heterogeneity of the phenotypes, may also influence the results. Thus, the environmental factors or infectious agents between countries should also be considered carefully.6. Genetic polymorphisms of the ITPKC signaling pathway in Kawasaki diseaseA major advancement in the genetic study of KD was made by the discovery of ITPKC in the RIKEN SNP center Japan. In 2008, Onouchi and colleagues first identified a functional polymorphism of ITPKC (rs28493229) that significantly associated with the susceptibility of KD and CAL in both Japanese and US children. Thus, in the model of Onouchi et al., ITPKC is a negative regulator of T cells, and it may function as a calcium channel modulator that is involved in controlling immune systems.
Interestingly, replication studies in the Taiwanese populations are strikingly controversial.
Their results indicated that the C allele of rs28493229 is associated with KD susceptibility.
The activation of SOC can be controlled by the expression level of IP3, which is the substrate of ITPKC protein. AsITPKCis involved in the Ca2+-dependent NFAT signaling in T cells, genetic association studies between calcium pathways and susceptibility of KD were performed. Modified linkage analysis completed on data generated by SNP arrays and RNA interference screening led to an important finding.
A single missense mutation in ORAI1 was found in patients with severe combined immune deficiency syndrome.
In 2011, genetic polymorphisms of ORAI1 were reported to associate with the risk and recurrence of calcium nephrolithiasis [130] and HLA-B27-positive AS [131]. In theKD study, no significant association between OARI1 genotypes ORAI1 andKDclinical parameters (such as CAL formation or IVIG treatment responses) was found. However, a novel genetic polymorphism in the STIM1 gene was detected that associated with CAL formation in KD patients (data not shown).
As STIM1 is a key initiator of SOC, DNA sequencing for the STIM1 gene family in a larger population may be helpful to identify novel polymorphisms. Future studies are needed to address the mechanism by which calcium signaling contributes to the development of KD. Genetic polymorphisms of the TGF- signaling pathway in Kawasaki diseaseTGF- is an important molecule that is involved in the regulation of cytokine expression and immune response. It has been shown that TGF--mediated signaling pathways are mainly via transcription factors, Smads, which include at least 3 common proteins: Smad2, Smad3, and Smad4. The binding of TGF- to its receptor results in the phosphorylation of Smad2 or Smad3, which heterodimerizes with Smad4. The formation of the Smad complex further translocates to the nulclus to regulate activation of the target genes. In the cardiovascular system, which is an important target of KD, TGF- signaling is involved in the pathogenesis of multiple cardiovascular diseases via aberrant vascular remodeling.
Low expression levels of endogenous TGF- activity in the blood may contribute to the development of atherosclerotic cardiovascular disease. In 2011, a large genetic study revealed a significant association between the polymorphisms in TGF- pathways and KD susceptibility or CAL formation in the European and US populations. It was confirmed that genetic polymorphisms of SMAD as well as TGFB2 contribute to the susceptibility of KD. These observations, in combination with those of the recent study, support the importance of TGF- pathways for the susceptibility or severity of KD.8. Although the function of NAALADL2 remains unclear, mutations in the gene may be involved in the development of Cornelia de Lange syndrome. Furthermore, the PELI1gene locus in the 2p13.3 region was confirmed to associate with the development of CAL in KD patients. The results suggested that BLK (encoding B-lymphoid tyrosine kinase) and CD40 are novel susceptibility genes for KD. Hence, the results from independent groups support a significant role of immune-related genes such as CD40 for KD and CAL formation. ConclusionSeveral major advances have been made in understanding the genetic effects of the susceptibility and clinical status of KD over the past decade.
Although the exact functional role of these genes in KD is still unclear, at present, these loci could provide a new direction for future studies.



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