The killer of liver cancer – viral hepatitis

Viral hepatitis prevention and control knowledge points

First, basic knowledge

Viral hepatitis is a common infectious disease caused by a variety of hepatitis viruses.

Hepatitis viruses can be classified as type A, B, C, D and E.
Most cases of hepatitis A and hepatitis E are acute, and the prognosis is good.
The course of hepatitis B and C is complex and chronic, which can lead to cirrhosis or liver cancer.

The clinical manifestations of all types of viral hepatitis are similar, with fatigue, loss of appetite, hepatomegaly and abnormal liver function as the main symptoms in the acute phase, and jaundice in some cases.
Chronic infection may have mild or no clinical symptoms.

Second, the transmission way and prevention of viral hepatitis

Hepatitis A and E are transmitted through the digestive tract, while hepatitis B and C are transmitted through blood, mother-to-child and sexual transmission.

Hepatitis A and E are mainly transmitted through the digestive tract. Contamination of water or food can cause outbreaks.

Hepatitis B and C are mainly transmitted through blood, mother to child and sex.
For example, transfusion of blood and blood products contaminated with the virus, use of unsterilized syringes and needles (for injecting drugs, etc.), invasive medical or cosmetic devices (for tattoos, piercing of ears, etc.), and sharing of razors and toothbrushes;
Having unprotected sex with an infected person;
A pregnant woman with the virus can transmit it to her newborn.

The transmission way of Ding liver and second liver are similar, with second liver virus at the same time or on the basis of second liver virus infection ability is infected.

Inoculate second liver vaccine is the safest, effective measure that prevents second liver.

China implements free hepatitis B vaccine for newborns, and three doses should be given in accordance with the “0, 1, and 6 months” immunization program. The first dose should be given as early as 24 hours after birth.

Except the neonatal and adult high-risk groups such as the medical staff, often contact with blood and blood products, childcare facilities staff, often receive blood transfusions and blood products, low immune function, professional easy to occur outside of the injured, hepatitis b virus surface antigen positive gay sex, family members, men have more sex partners or injecting drug users and so on should also be hepatitis b vaccination.

  1. Mother-to-child blocking measures can effectively prevent mother-to-child transmission of hepatitis B.

The pregnant and puerpera with positive surface antigen of second liver virus is in the process of pregnancy or childbirth, may infect second liver virus to fetus or newborn.
The younger the age at the time of infection, the higher the risk of the transformation to chronic viral hepatitis, so it is of great significance to carry out mother-to-child hepatitis B blockade.

Pregnant women with positive HBsAg should ensure hospital delivery to minimize the exposure of the newborn to maternal blood.

Newborns born to pregnant women with positive surface antigen of hepatitis B virus should receive the first injection of hepatitis B vaccine as soon as possible within 24 hours after birth, at the same time, inject hepatitis B immunoglobulin, and complete subsequent doses of vaccination in accordance with the immunization procedures of hepatitis B vaccine.

Pregnant women with high hepatitis B viral load can receive standard antiviral treatment under the guidance of professional physicians.

Attention to diet, drinking water hygiene and vaccination can effectively prevent hepatitis A and hepatitis E.

Improve environmental sanitation, strengthen water and excrement management, improve water supply conditions;
Develop good personal hygiene habits, wash hands before meals, do not eat raw food, do not drink raw water, can effectively prevent hepatitis A and hepatitis E.

Vaccination is effective in preventing hepatitis A and E.
Hepatitis A vaccine has been included in the expanded national immunization program, and free vaccination is available to children aged 18 months.
Food is produced and managed the key crowd such as staff of staff of establishment of staff of staff of nursery institution, collective life also should inoculate armour liver vaccine.
Our country already has hepatitis E vaccine, can be vaccinated voluntarily at one’s own expense.

Cut off the transmission route, can effectively prevent hepatitis C.

There is no vaccine for hepatitis C, but it can be prevented with effective measures to cut off transmission.

Refuse drugs and do not share needles to inject drugs;
Put an end to illegal blood collection and supply;
Avoid unnecessary injections, blood transfusions and the use of blood products;
The risk of HCV infection can be significantly reduced by receiving injections, blood transfusions and using blood products at a proper health care facility.

The following behaviors can also be effective in preventing hepatitis C:

Do not share needles or other tools such as tattoos and piercings with others, and do not share personal belongings such as razors and toothbrushes that may cause bleeding with others.
Use condoms correctly and avoid unsafe sex.

If women infected with HCV wish to have children, it is best to become pregnant after the cure of HCV.

  1. Hepatitis B and C can not be transmitted by contact with daily work and life.

Hepatitis B and C viruses are not transmitted through the respiratory and digestive tracts.
Therefore, daily work, study and life contacts such as shaking hands, hugging, working in the same office, sharing office supplies, living in the same dormitory, eating in the same restaurant and sharing toilets without blood exposure will not be infected with hepatitis B or hepatitis C virus.
The hepatitis B and C viruses were not found to be transmitted by blood-sucking insects such as mosquitoes and bedbugs.

Three, viral hepatitis detection

Have suspected viral hepatitis symptom or easy to infect crowd, should take the initiative to medical institution check.

Hepatic of A and liver of E are acute come on more, if have unclean food history or patient close contact history, accompany suspect viral hepatitis symptom, if whole body is weak, appetite drops, nauseous vomit, abdominal distend, liver area is not well, urine color deepens, should visit a doctor to medical institution as soon as possible check.

Suggest susceptible population (such as traumatic treatment, blood transfusion, are Shared syringes, sexual partners, organ transplantation, use disinfection instruments of the unknown tattoo, tattoo eyeline, pedicure behavior such as personnel, HIV, hepatitis b and hepatitis c patients by a spouse or children) and unexplained abnormal liver biochemical examination active hepatitis b and c inspections to the formal medical institutions, understand their infection status, achieve early discovery, early diagnosis and early treatment.

IV. Treatment of viral hepatitis

Viral hepatitis patient should comply with doctor’s advice, undertake standardized treatment, avoid by all means stop medicine by oneself or credulous false advertisement.

The vast majority of hepatitis A and hepatitis E are acute viral hepatitis, and most patients can recover completely within half a year after timely and standardized treatment.
A small number of serious patients have the risk of liver failure, should be paid attention to.

Second liver turns easily chronic, there is no effective medicine to be able to clear second liver virus completely at present, but classics standard antiviral treatment, can limit restrain virus replication, delay and reduce liver damage, prevent the occurrence of liver cirrhosis, liver cancer and its complications, improve life quality and prolong life.

Patients should establish confidence, maintain patience, follow the doctor’s advice, actively cooperate with the treatment, and insist on regular examination, to ensure the treatment effect.
On the contrary, arbitrary drug selection, random drug change, self-withdrawal, and not on time return examination, may cause virus resistance, disease rebound or recurrence.
In the process of diagnosis and treatment do not believe in excessive publicity and false advertising, so as not to cause illness delay and economic losses.

Hepatitis C is also easy to turn chronic, after the standard full course of antiviral treatment, the vast majority of patients can be cured.

All viral hepatitis patients should avoid drinking, smoking, irrational drug use and other behaviors that aggravate liver damage.

V. Rights and Obligations

Prevention and treatment of viral hepatitis is the common responsibility of the whole society.

At present, the situation of viral hepatitis prevention and control in China is grim, with a large base of chronic viral hepatitis patients accumulated for a long time, acute viral hepatitis occasionally occurring, and the risk of transmission still exists.
Prevention and control of viral hepatitis requires close departmental collaboration and the understanding, participation and support of the public.

Efforts should be made to eliminate social discrimination against those infected with hepatitis B.

“About further standardize the enrollment and employment physical examination project Hepatitis b surface antigen carriers and employment rights notice requirements, all kinds of education institutions at all levels, unit of choose and employ persons in the citizens’ admission, employment, medical, shall not be required to carry out the project detection of hepatitis b, shall not be required to provide hepatitis b project inspection report, also may not ask whether for hepatitis b surface antigen carriers.
Medical and health institutions at all levels shall not provide hepatitis B testing services in the physical examination for enrollment or employment.
No educational institution at any level or of any kind shall refuse to enroll students or require them to drop out of school on the grounds that they carry hepatitis B surface antigen.

Except for the special occupation that the national health committee approves and gives to announce, healthy physical examination is not required to detect second liver project because of the person being examined, the unit of choose and employ persons must not refuse to recruit with laborer to carry second liver surface antigen for (employ) use or dismiss, dismiss.

  1. While people infected with viral hepatitis enjoy their rights, they should also assume their obligations to others and society.

An infected person with viral hepatitis should abide by the relevant provisions of the Law of the People’s Republic of China on the Prevention and Treatment of Infectious Diseases, accept relevant measures for the prevention and control of infectious diseases from disease prevention and control institutions and medical institutions in accordance with the law, and provide relevant information truthfully.
Before they are cured or before they are cleared of suspicion of infectious diseases, they shall not engage in work that is prohibited by laws, administrative regulations and the administrative department of health under the State Council from engaging in work that is likely to cause the spread of infectious diseases.

According to the implementation rules of the Regulations on the Administration of Public Health, the operators of public places shall organize the employees to carry out health examination every year, and the employees can only take up their posts after obtaining effective health certificates.
Personnel suffering from hepatitis A or hepatitis E shall not engage in work directly serving customers before they are cured.

Hepatitis B patients with antiviral treatment, we should be more active response

We are all familiar with Li Lanjuan, an academician of the Chinese Academy of Engineering.
During the COVID-19 epidemic last year, a large number of Chinese medical elites, including academicians Li Lanjuan and Zhong Nanshan, were calm and forgot all about food and sleep to race against the epidemic, which can be called the “magic needle in the sea” in the fight against the epidemic, and made outstanding contributions to the great victory in the fight against the epidemic.
Academician Li Lanjuan specializes in the prevention and treatment of emerging infectious diseases and has unique insights into various types of hepatitis.
Academician Li pointed out that antiviral treatment for hepatitis B patients should be more active, do our best to improve the condition and prolong the life of patients.

In clinical practice, we often encounter a few patients with second liver, do not know what is antiviral treatment, antiviral treatment should how to do, what to notice.
By this topic, the doctor and everyone say.

In general, the development of hepatitis B virus in the human body needs to go through four stages:

(1) Immune tolerance period.
This stage is mainly reflected in the infant period, although the virus settled down in the body, but the infant’s immune system is still in the early stage of development, very imperfect, so between the immune system and the virus “well water does not break the river”, peaceful.
There is a lot of virus in the baby, but because the virus and the immune system “coexist peacefully”, it is reflected in the liver function is all right.
At this stage, it is not appropriate to carry out antiviral treatment, if the treatment is not necessary, the effect is likely to be counterproductive, not only the drug effect is not good, there may be resistance and complications, the gain outweighs the loss, the risk is greater.

(2) Immune clearance period.
With the powerful, the body’s immune system development of hepatitis b virus was sensitive, and hepatitis b virus fantasy of “long-term coexistence” gone, the body’s immune system to the hepatitis b virus attack, main land within the liver, both sides you come to me to, it inevitably in the liver of liver cell damage, reflected in liver meritorious service is the number of hepatitis b virus is very high, liver meritorious service is not normal again, this time can antiviral treatment.

(3) Immune control period.
As the immune system is bolstered by antiviral treatment, and as scientific treatments are adhered to, both quantity and quality of the virus are falling.
Antiviral therapy achieved stage success.
The virus is dormant for a while, and the fight between the immune system and the virus enters a truce.
During the truce, the virus’s own metabolism is replaced, part of the virus is gradually “destroyed and swallowed” by the immune system and antiviral drugs, and the virus population is slowly reduced.
This period of time is variable, but relatively long, the power of immune control, mainly derived from drugs, or rely on the body’s immune system.

(4) Immune reactivation period.
Hepatitis b virus (HBV) if by chance the opportunity to grow again, once the immune system, the two sides met again lit “war”, this time the virus is likely to be changed, change, or “weapons” may upgrade, can’t adapt to the body’s immune system, namely before using drug control also of no help, this leads to resistance, can only change medicine, or use the more advanced drugs.
During the immune reactivation period, some patients may not take the initiative to make diagnosis and treatment, or appear drug resistance on the basis of the original treatment. No matter how the situation changes, antiviral treatment is necessary at this stage.

At present, there are mainly long-acting interferon and first-line nucleoside drugs for antiviral treatment, which have both advantages and disadvantages. However, considering the safety degree of medication, maintenance of work and life order, the number of patients, and the affordability range, we choose first-line nucleoside drugs for antiviral treatment, which is better.

According to the above four stages, the route selection of antiviral therapy is predicted as follows:

1, if the patient belongs to the “big three Yang”, the number of viruses is high, B ultrasound examination is normal, no family history of liver cancer, no need for antiviral treatment, but it is best to do an examination every 3 to 6 months.

2, if the patient is “big 3 this world”, the virus number is high, the test result is normal, but the lineal within three generations have cancer, especially cancer of the liver, or have a family history of cancer of the liver, it suggested that antiviral treatment, efficacy and choice for strong first-line nucleoside drugs, such as entecavir and tenofovir, TAF, reduce the risk of drug resistance.

3, if the patient belongs to the “small three Yang”, abnormal liver function examination, abnormal elevation of transaminase, and determined to be caused by hepatitis B virus, belongs to the state of the disease attack, immediate antiviral treatment, the earlier the better, with first-line nucleoside drugs.

  1. If the patient belongs to the “minor three Yang”, there are 5 different situations, only 1 of which does not need antiviral treatment, and the other 4 should be treated quickly.

(1) the patient “small three Yang”, virus detection negative, liver function is normal, without liver fibrosis phenomenon, this is the carrier of second liver virus, do not need treatment.

(2) The patient underwent liver puncture examination and was diagnosed as grade 2 inflammation. The liver fibrosis reached stage 2 or above, and the patient received immediate antiviral treatment.

(3) the patient “small 3 this world”, check virus 2 times continuously is greater than equal to 5 power, although transaminase is normal, or rise value is less, also want antiviral treatment, because be “small 3 this world” hepatitis broke out.

(4) Male patients with “minor three Yang” status, age over 40 years old, two consecutive tests for the virus greater than or equal to the fourth power, need antiviral treatment.

(5) Patients with transaminase values above 60 for 3 consecutive months, tested positive for virus for 3 consecutive times, need antiviral treatment.

Doctors suggest that: for antiviral treatment, patients should first make clear which stage they belong to, which kind of situation, save the diagnosis data of previous examinations, for doctors to make judgment and develop treatment plan.
Secondly, it is recommended to use first-line nucleoside drug therapy, which is not only to prevent drug resistance, but also the most worrisome choice in long-term treatment.
Again, pay attention to regular examination, standard medication, timely detection of physical improvement or abnormal conditions, to ensure that the antiviral treatment continues to be effective.

General Anesthesia Is “You Die Once”?

Introduction: Recently, a 27-year-old girl in Foshan, Guangdong Province, died in a hotel due to acute respiratory and circulatory dysfunction caused by sevoflurane poisoning, which has attracted much attention. So what exactly is sevoflurane?
Sevoflurane as a class of gas is an inhaled general anesthetic, and today we’re going to talk about general anesthetics, what happens to the body after the injection, is that what other people say?
It’s like dying once and waking up stupid and demented?

First, what happens to the body after an anesthetic enters the body?
Take a look

Anesthesia is one of the important findings of the 19th century, scientists at that time, always want to relieve the pain of the method, is the most commonly used to anesthesia, anesthesia method, there were great, it means that the patient sticks to knock dizzy, have blood, with the patient of bloodletting method in patients with shock, and opium and alcohol method, let the patient to forget the pain.

Later scientists discovered the drug after one hundred years of development, gradually launched inhalation intravenous and conform to the anesthesia different anesthetic methods, such as when you respiratory inhalation or intravenous static drug, it will lead to brain central nervous, in the human brain nerve will receive the people to get their information, the various parts of the body after consolidation and work out the movement and induction.

Type in simple terms, central nerve is responsible for generating the psychological activities and the animal behavior and actions, and the purpose of anesthesia is to confuse it, let it have no way to control actions, there is no way to get their information, each place perception when animals meet with dangerous things, for example, can choose automatic to avoid, it is a reflex action, and the reflex action is processed by the central nervous.

After the injection of anesthetic will be “confuse” central nervous, there is no way to muscles work in this way, people will slowly disappear from awake to the consciousness, and loss of pain, muscle relaxation, heart rate, blood pressure can have varying degrees of decline, so often inject anesthetic need external help breathing breathing machine, anesthesia, depth of sleep than people sleeping at ordinary times greater depth, surgical operation, the pain will not lead to he woke up, so someone will describe general anesthesia, like a dead after a time, but it is exaggerated.

Because even anesthetic injections, also need the anesthesiologist continuously append the anesthetic, for depth of anesthesia, the test of the level of the anesthesiologist, if less, so central nervous not be overwhelmed, or pain, will happen if you give more, the system will directly strike will die, of course, some people will wake up in the process of from anesthesia, they will feel pain during the operation and suture of asphyxia feeling, and limbs, but there was no way to respond, this is the amount of anesthetic to the consequences.

About 5 percent of people wake up from anesthesia, and the resulting psychological problems can leave them in pain for a lifetime.

Two, after the baby accepts general anesthesia, can become stupid become dementia?
What you want to know, here it is

China, about 800 ~ 9 million babies need to accept the whole body paralysis, short time of anesthesia for the baby’s brain won’t affect, and anesthesia effect is short for human, reversible, recoverable, so don’t be stupid not become dementia, and part of anesthetics can also through the liver may also through the breath.

Anesthetics have short-term amnesia effect, so at the time of anesthesia early injection, often appear short memories forget, is not a name and address, this kind of phenomenon such as long-term memory to forget, so the anesthetic will not lead to a dull boy, of course for the elderly and the poor people, drug metabolism ability, anesthetic will also cause life is affected, but the night it will return to normal in a few months later, it has to do with the level of the anesthesiologist.

After all, brain cells need sufficient nutrients, so if the brain hypoxia, 5 minutes will greatly affect the brain function, but will not affect people’s intelligence, and anesthesiologists are generally professionally trained, and will not cause brain hypoxia caused by mistake injection.

Conclusion: There are a lot of rumors about anesthesia on the Internet, we must distinguish them carefully. Secondly, in order to avoid the tragedy, we must go to the regular hospital when seeking medical treatment.

Rapid spread of covid mutant virus

On February 26, the new coronavirus b1526 spread rapidly in the United States.
The virus was first found in New York in November 2020, and then researchers have been checking out the existence of the mutated virus from patients. The number of cases of infection rose sharply from December 2020 to February this year, especially in the New York area.
Currently, 890 thousand people are diagnosed in New York’s covid, accounting for nearly 10% of the total in the United States. New York, the largest city in the United States, directly affects the economy, finance, media and politics in the United States. If the virus will infect or lead to severe infection again, New York will become the most serious disaster area in COVID-19.
It has been found that the mutant virus b1526 has stronger vaccine resistance and may weaken the human immune response to the virus. For this mutant strain, vaccine manufacturers are constantly developing and producing corresponding vaccines.

A new strain of the virus found in California has a higher rate of transmission and fatality

On 25 February, the German RKI reported 11,869 new cases of new crown infections and 385 deaths.
The seven-day infection rate rose again to 61.7 per 100,000 inhabitants.
A coronavirus is not a novel to be taken lightly. As soon as you feel you can relax, it is immediately attacked.

More worrisome is that a virus variant named Cal.20C has been detected for the first time in the United States in California, which has aroused the great concern of researchers at the University of San Francisco (UCSF).
Studies have shown that this variant of the virus is more lethal and transmissible, and more dangerous.

The strain was not present in September 2020, but now more than 50% of cases have been reported.
From the fall of 2020 to the end of 2021, researchers collected more than 2,000 cases of the cal.20c variant detected in California.

“This is a very worrying situation,” he said. “Our data suggest that it is more contagious and has a higher rate of severe illness and resistance to neutralizing antibodies.”
Charles Chiu, an epidemiologist at the University of San Francisco and an expert on virus sequencing, told Science magazine.

Cal.20c accounted for 21.3 percent of the 2,172 gene samples examined by the panel from 44 counties in California.
The researchers also screened 324 cases and confirmed that compared with normal cases, patients with the mutated virus were 4.8 times more likely to suffer severe illness and a whopping 11 times more likely to die.

Other virologists, however, said that the study’s sample size was too small and that more data were needed to truly assess the risk of CAL.20c.

We do not know if the strain will reach Germany, but the strain B.1.1.7 from the UK is already present in a high proportion in Germany, and the South African strain has also spread to the Franco-German border province of Mosel.

The French government now requires non-commuter immigrants to show a negative test for the virus starting in March.
Cross-border commuters are exempt from showing virus test results for reasons of work, but the French government has called for them to work from home as much as possible.

The French province of Moselle borders the German states of Rhiphal and Saarland, which are closing shops and slowly opening schools, while the Germans are closing neither.

So the seven-day infection figure in France is 200, and in the province of Moselle it’s even over 300.
However, the governors of the German states of Saarland and Rheinphalia have no plans to close their borders for now.
So if you need to work in France through these two states recently, you should pay attention to the policy changes.

On the federal side, the long blockade caused the government to pay high subsidies for it, which put a heavy burden on the national Treasury.
In 2021, the federal government will assume €180 billion in new debt.

The SPD’s candidate for chancellor, Olaf Schulz, who is now deputy chancellor and finance minister, recently announced that he would raise taxes in his next term, mainly for so-called “high earners”.

High-income and rich people will be affected, while low – and middle-income people will get relief.
In an interview with the Rheinposten newspaper, he said: “I agree with the overwhelming majority of citizens that we must make the tax system fairer and that those who earn a lot of money should contribute more to the community.”
(Is this called taking from the rich and giving to the poor or is it called “fairness”?)

Mr Schulz, by contrast, argues that the abolition of the solidarity tax, now demanded by the CDU and the FDP, is “against the people”.
Only 1.35 million citizens will have to pay the tax after its partial abolition this year.
Mr Schulz said the federation would not give up its 11 billion euro annual revenue.
(Standing against the people?
The federal government?)

For Schultz, of course, taxing “high earners” does not mean a quick way out of the debt crisis.
He wants to continue the current federal monetary policy with high credit spending to prepare for the future.

The economy minister, Peter Altmaier, favors selling state assets to pay the debt rather than raising taxes.

Newborns infected with a novel novel coronavirus: viral load 51,000 times higher than other patients

With the emergence of novel coronavirus vaccine, this thought that the epidemic will be better, but did not think that the mutant novel coronavirus is coming again, the United States a newborn body detected a new variant of the virus.

According to foreign media reports, a new variant novel coronavirus was found in a newborn with severe COVID-19 received by Children’s National Medical Center in Washington, US, and its viral load was much higher than that of other patients.

Researchers said the new strain of the virus came from a severely ill newborn born in September last year at Children’s National Medical Center in Washington, the United States, after sequencing the virus genome of the sample recently discovered the new strain.
Astonishingly, the viral load of the sample was 51,418 times higher than the other samples.

It is unclear how high the risk of transmission of the new variant is, but other studies of the novel coronavirus variant in children have found eight additional cases of the variant in the mid-Atlantic region of the United States.

Roberta Debiasi, chief of the division of infectious diseases at Children’s National Medical Center in Washington, noted that the mutated virus has an entirely new structure of the spike protein, which may make it more infectious.

It is not clear whether the new mutation is related to the high viral load in newborn samples, but it is presumed that they are closely related.
Of course, this could also be a coincidence, so further study of the mutated virus is needed.

Children with CoviD-19 had a lower incidence of severe illness, and these younger children were less likely to be infected with novel coronavirus, according to the data.
At present, the mechanism of the effect of novel coronavirus on children and infants remains to be further studied.

But in the past five months, according to the American Academy of Pediatrics and the Association of Children’s Hospitals, there has been a “dramatic increase” in the number of children infected with novel coronavirus. Severe cases in children are rare but persist, and there are serious and long-term side effects, including brain damage.

South Korea extends UK flight ban for another two weeks to guard against entry of mutant novel coronavirus

On February 24 news, South Korea central prevention epidemic countermeasure this department expresses on 24 days, to prevent mutation coronavirus to pass into territory strictly, the ban that Han government decides to take in the light of British flight extends two weeks again to next month 11 days.

South Korea has suspended flights to and from the UK since December 23 and has extended the measure several times.
The mutant novel coronavirus found in the UK was found in 94 countries and territories as of December 15, according to WHO data.
Of the 128 mutated cases in South Korea, 109 were infected with the strain found in Britain.

A new strain of Covid-19 virus has been found in Nigeria, spreading to many countries

A new strain of COVID-19 virus, known as B.1.525, has been found in Nigeria and has spread to several other countries, and has not yet been classified as a strain of concern, the director of Nigeria’s Centre for Disease Control, Ikowizu, said in Abuja on February 22.
It has been reported that the B.1.525novel coronavirus variant contains a gene variant called E484K, which has been found in countries including Brazil, South Africa, Denmark and the United States.