Photo was taken per Silvia Ross, MS, RDN, CDN.
DO YOU ALWAYS HEAR YOU SHOULD TAKE PROBIOTICS ? You start taking probiotics from the stores, you might read some information such as " probiotics helps with digestion and more. " Are these good for you or how much do you really have to get daily?, How do different strains function in the human body? YOU MUST ASK YOURSELF ALL THESE QUESTIONS and MORE. Those same questions I have been asked throughout my professional career as a Registered Dietitian Nutritionist. I was exposed to the information of new research and regular inquiries from clients and patients regarding several matters, mostly on what are Probiotics, Prebiotics, Psychobiotics, Dysbiosis, Polyphenols, Omega 3 and their effects on an individual's overall health.
It is crucial for individuals to understand the structure of the different functionality of bacterial strains that can be beneficial or harmful to our human body. Therefore, I decided to write a blog using the collective information to answer all questions based on research and studies from prestigious reliable sources including reports obtained from an article published in the Food & Nutrition magazine of the March /April 2018 edition, page 19, "The Potential of Probiotics. Exploring the promising world of probiotics one species at a time" and from Stephens-Bogard et al's research "The Microbes at the Table: The Role of Gut Microbiome and Related Nutritional Interventions in the Treatment of Anorexia Nervosa." The latter study was published in the Integrative RDN magazine of the Spring 2017, volume 19, Issue 4th edition, which is a magazine from the Dietitians in Integrative and Functional Medicine (DIFM), a practice group of the Academy of Nutrition and Dietetics.
WHAT ARE PROBIOTICS?
"Probiotics are live bacteria and yeasts that are good for your health, especially your digestive system. We usually think of these as germs that cause diseases. But your body is full of bacteria, both good and bad. Probiotics are often called "good" or "helpful" bacteria because they help keep your gut healthy."(1)
Lactobacillus and Bifidobacterium are the principal probiotic groups.
THE EFFECTS OF PROBIOTICS IN OUR HEALTH AND OUR CHILDREN
We understand that we need a certain amount of BACTERIA KNOWN AS "INTESTINAL BACTERIA OR GOOD FLORA BACTERIA" for the proper function of the overall human body. YES
It is known that when a baby is in a sterile condition or environment while in the womb of his or her mother. However, during the transition of vaginal delivery, a baby is exposed to the microflora in the vaginal cavity.
I reviewed many articles and designed a completed comprehensive literature review of " the Association between Birth Rate and Age at Menarche, Birth Weight and Adult BMI, Age At Menarche, and Adult BMI" and conclude that if a woman is overweight or obese before or during pregnancy; their children are more likely to be overweight or obese in his or her adulthood.
It might be because an overweight or obese woman has a bacteria different from the bacteria of a slimmer person. Other studies also show that the delivery via vaginal or cesarian can contribute to the weight of the child and his or her adulthood.
Other researchers revealed higher levels of Lactobacillales and lower levels of Clostridium in the intestinal microbiota in preterm birth patients in contrast to term birth patients. On the other hand, In Kirihara et al study it shows the effects of probiotics on perinatal outcomes. It was a retrospective evaluation of "the effects of oral probiotics on perinatal outcome in patients at high risk of preterm birth." "Probiotics containing Streptococcus faecalis, Clostridium butyricum, and Bacillus mesentericus were administered for prophylaxis of bacterial vaginosis or treatment of constipation starting at 12.5 ± 4.1 weeks until delivery." Patients who were not administered probiotics are known as a control group. (2)
This study concluded that the probiotics group exhibited longer gestation, greater birth weight and reduce rates of chorioamnionitis ( "which is also known as intra-amniotic infection (IAI) is an inflammation of the fetal membranes (amnion and chorion) due to a bacterial infection."" Chorioamnionitis typically results from bacteria ascending into the uterus from the vagina and is most often associated with prolonged labor." 3) Another effect of the probiotic group was higher rates of normal vaginal flora compared to the non-probiotics group. The data showed that "probiotics significantly suppressed preterm birth before 32 weeks and tended to suppress chorioamnionitis/funisitis."(2) (“inflammation of the connective tissue of the umbilical cord, which may cause abortion.")(4 )
There are many strains of good Bacteria which are found mostly in certain foods. Their contribution and functionality to the human body are different to one another.
THE STRAINS OF PROBIOTICS EFFECTS (5)
LACTOBACILLUS: Found in the gut and the urinary tracts. The most abundant bacteria in the VAGINA.(5)" Some research finding only about 40% of women having ecosystems dominated by D-lactic acid-producing species (Lactobacillus crispatus, L. gasser and L. jensenii)."
Photo from the Food & Nutrition magazine March /April 2018.
LADIES -These aerobic, lactic-forming Bacteria are mostly in our VAGINA to keep the YEAST known as "Candidiasis" in check.
It can be FOUND in YOGURT, FERMENTED FOODS,
LACTOBACILLUS ACIDOPHILUS (5-6)
-The most common species of LACTOBACILLUS.
__MAY treat for BOOSTNG IMMUNITY and EFFECTS on INCREASED WEIGHT, DECREASED GASTROINTESTINAL TRACT (GI) side effects of CONSTIPATION/PAIN/BLOATING/INFLAMMATION AND TRAVELER'S DIARRHEA, ANTIBIOTIC- ASSOCIATED DIARRHEA, OR AAD and CLOSTRIDIUM DIFFICILE, which is a common side effect of oral antibiotics.
__It can help with mood disorders by DECREASING ANXIETY/DEPRESSION.
__Reduces the incidence of eczema in infants when taken orally by their pregnant or breastfeeding mothers.
Possible Treatment for Bacterial Vaginosis
_ Ingestion or application of yogurt to the VAGINA can aid with YEAST INFECTIONS. (5)
---Certain yogurt, milk, miso, tempeh, pills, freeze-dried granules, powders and vaginal suppositories.
RECOMMENDATIONS: from 1 BILLION to 15 BILLION COLONY FORMING UNIT, OR CFU DAILY.
LACTOBACILLUS HELVETICUS with BIFIDOBACTERIUM LONGUM (5)
_ Have immune-boosting and ability to treat psychological conditions by lowering anxiety, depression, improving skin conditions such as ATOPIC DERMATITIS and overall health.
_ Improve the quality of sleep and increased serum calcium levels in elderly individuals.
_Commonly used in the fermentation of milk for the production of Swiss and Italian cheeses.
_FOUND IN: both are in KEFIR, CERTAIN YOGURTS, AND SUPPLEMENTS.
RECOMMENDATION: There is no recommended dosage as yet. Intake of 3 BILLION CFU DAILY shows improvement with Anxiety and Depression.
LACTOBACILLUS DELBRUECKII SUBSP. BULGARICUS with STREPTOCOCCUS THERMOPHILUS. (5)
__It has been shown to decrease length of stay and lower risk of infections in patients with traumatic brain injury in the ICU.
__100 BILLION CFU DAILY of the three species.
__Improvement in non-alcoholic fatty liver disease
__Taking 500 MILLION CFU of L. Bulgaricus and S. thermophilus daily.
_ Common in yogurt and work by feeding off the bacteria's byproducts. Found in supplements.
LACTOBACILLUS PLANTARUM (5)
__There is a significant improvement observed in psychological health by reducing anxiety, depression, symptoms of autism, lowering the BMI, decreasing blood pressure, decreasing cholesterol, reducing fat oxidation, reducing cardiovascular disease in smokers, increasing immunity, decrease allergy symptoms in children and metabolic conditions.
--Fermented vegetables ( kimchi, fermented beets, pickled cucumbers, pickled beans, sauerkraut, fermented juice drinks, green olives.
RECOMMENDATION: There is no exact dosage, but 3 BILLION to 10 BILLION CFU found in over-the-counter supplements.
LACTOBACILLUS REUTERI (5)
__Reduce inflammation, allergies, pro-inflammatory diseases, lower infections and inflammatory markers in diseases including rheumatoid arthritis, cystic fibrosis and general allergies including inflammation of the airways.
__It may also lessen eczema in children and may decrease dental caries.
__Certain fermented vegetables, dairy products, and oral supplements.
RECOMMENDATION: Ranged from 100 MILLION to BILLION CFU DAILY.
LACTOBACILLUS RHAMMOSUS GG OR LGG (5)
__Survives in the GI tract compared to other species of Lactobacillus.
__ The most effective Bacteria for treating infections of diarrhea, and acute diarrhea in children.
__Promotes Vaginal health (with L. reuteri) treat pediatric conditions.
__Prevents dental caries, improve infant neurological health, and lower the risk of developing ADD or ADHD.
__ Lowers the risk of Bacterial Vaginosis and promote the growth of beneficial bacteria.
__ Using vaginal suppository,it may decrease the risk of yeast infection.
__Kefir and certain brands of kombucha drinks, supplements, and powders.
RECOMMENDATION: 10 BILLION CFU- There is no recommendation for children with compromised immune systems ( based on American Academy of Pediatrics).
LACTOBACILLUS CASEI (5)
__The gut-brain axis by improving neurological ( lower anxiety and depression in people with chronic fatigue syndrome) and mental health.
__ Improve mood, cognition in individuals with autism.
__Improve multiple sclerosis and cognition.
__supplements, chewable forms for children, in some dairy, non-dairy yogurts, kefir, kvass, and fermented beverage.
RECOMMENDATION: 100 MILLION TO 8 BILLION CFU DAILY
__ Inhabitat in the mouth, gut, and vagina.
__The first bacteria to live in the GI tract.
__ HELPS WITH the digestion of foods ( produces short-fatty acids and lowers inflammation through the stimulation of immune cells).
BIFIDOBACTERIUM BIFIDUM (5)
__Optimizes immunity and improve eczema in infants.
__Treats certain GI conditions, including constipation, IBS, ulcerative colitis and H. Pylori.
__Yogurt, kefir, buttermilk, miso, tempeh, pickles, cured meats, kimchi, certain wine, vinegar, sauerkraut, sourdough bread, and oral supplements.
RECOMMENDATION: There is no recommended dosage but seeing benefits by taking 1 BILLION CFU DAILY.
BIFIDOBACTERIUM INFANTIS (5)
__Mental health ( anxiety, depression, and autism spectrum disorder )and possess anti-inflammatory properties.
__ Found some dairy including yogurt but common in oral supplements.
RECOMMENDATION: There is no recommended dosage as noted.
SACCHAROMYCES BOULARDII (5)
__You can make Kombucha with the yeast.
__Treat many GI tract conditions including diarrhea in children and infants with feeding tubes, traveler's diarrhea or diarrhea caused due to C. diff and effective in adults for ADD.
__Kombucha and oral supplements.
RECOMMENDATION: Ranging dosage of 250 to 1,000 MILLIGRAMS DAILY FOR TWO TO FOUR WEEKS IN ADULTS with diarrhea.
___250 to 750 MILLIGRAMS DAILY FOR children- not exceeding more than five days.
WHAT ARE PSYCHOBIOTIC? (6)
" As proposed by Sarkar et al, includes probiotics and prebiotics that work synergistically to confer mental health benefits to the host."(4)
Research has revealed that there is approximated 100 to 350 trillion microorganisms. These microorganisms with their genes are called the human microbiome. They are recognized to be fundamental. The greatest microbial communities location is in the Gastrointestinal tract (GI).
Research suggests that there are five major microbial species, which are the center microbiome that consists of 14 different classes in the human GI tract. There also is enough evidence that shows that a person's microbiome is individually unique. (4)
Figure: Profile of the Human Gastrointestinal Microbiomes found on the Integrative RDN Spring 2017 volume 19, Issue 4 edition.
What is Dysbiosis? (6)
They are "perturbations, alterations, or imbalances in the diversity and/or composition of microorganisms in the human microbiome. Gut dysbiosis refers to imbalances in the GI tract."
Their research continues to highlight the importance of diet in regulating the structure of the GI microbiome and associated effects on human health including decreasing weight. As the treatment for overweight or obese individuals or increasing weight, or as the treatment for malnutrition or underweight individuals, and individuals with Anorexia Nervosa (AN).
Based on the collective information gathered from the study of "The Potential of Probiotics. Exploring the promising world of probiotics, one species at a time," shows that some strains of specific bacteria and possible infection of GROUP A STREPTOCOCCI INFECTION can be related to the development of AN.
Dysbiosis can also occur in the vagina!
A test can be used to determined if there are any vaginal imbalances.
As Jason Hawrelak ND, BNat (Hons), PhD, FNHAA, MASN, FACN, Chief Research Officer at Probiotic Advisor stated, "A simple pH test strip (with accurate gradations between pH 3.5-5.5) is all that is needed for an initial screen for vaginal dysbiosis – with a pH >4.5 a clear indication of a dysbiotic ecosystem in pre-menopausal women."
BACTERIA THAT ARE FOUND IN THE GI TRACT OF THE AN INDIVIDUALS (6)
__ANAEROBE METHANOBREVIBACTER SMITHII
---These species are adaptive to a low caloric intake.
--- creates an environment in the GI tract that optimizes the conversion of nutrients into calories.
------ DYSBIOSIS occurs in AN individuals: lower concentration of total bacteria including LACTOBACILLUS PLANTARUM, CLOSTRIDIUM LEPTUM, CLOSTRIDIUM COCOIDES, BACTEROIDES FRAGILES, AND STREPTOCOCCUS.
__Another Bacteria also found in the GI tract in AN and Autism spectrum disorder (ASD) and psychiatric conditions associated:
---increased levels of CLOSTRIDIA
Treatment Onset and After Weight Restoration. (6)
---Perturbations in the family RUMINOCOCCEAE (GENUS PARABACTEROIDS) _ also associated with inflammation such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)
__The GUT microbiome communicates with the nervous, endocrine, immune, and digestive system.
__The structure and functionality of the microbiome can affect physical and mental health by providing the blood-brain barrier (BBB).
__Regulates the moving through of oxygen, nutrients, neurotransmitters, and cytokines into the cerebrospinal fluid (CSF) and protects it from harmful bacteria and chemicals.
__ The GI tract sense biological and chemical agents coming from the environment.
___The cells and proteins of the immune and endocrine systems act as sentinels and deliver signals that help protect the brain in an unbalanced state.
Figure: Communication Pathways in the GUT- Brain Axis found on the Integrative RDN Spring 2017 volume 19, Issue 4 edition.
DYSREGULATION OF HUNGER AND SATIETY IN PATIENTS WITH AN (6)
Possible DUE TO:
_____Development of autoantibodies against APPETITE-REGULATING NEUROPEPTIDES (ARNP):
---Ghrelin ("a 28-amino-acid peptide hormone that is secreted primarily by stomach cells with lesser amounts secreted by other cells (as of the pancreas) and acts to stimulate appetite and the secretion of growth hormone." (5) and other words increase weight. ) and a-melanocyte-stimulating hormone (a-MSH) ("are produced by cells in the pars intermedia of the anterior lobe of the pituitary gland"). (7)
___Concentrations of GHRELIN relates to EATING DISORDERS -2 (EDI-2) in individuals with AN.
___The autoantibodies generated against microorganisms in the GI tract.
__LACTOCOCCUS LACTIS AND BIFIDOBACTERIUM LONGUM stimulate the productions of ARNPs.
FOUND in food and supplements: cheeses -colby, cheddar, cottage, cream, blue, as fermented milk products such as sour cream and buttermilk.
"A VARIETY OF MICROBIAL AGENTS CAN SUPPORT GI HEALTH" (6)
SHOW POSITIVE EFFECTS:
11 SPECIES OF PROBIOTIC BACTERIA AND PROBIOTIC MIXES on 8 different diseases.
____Emotional regulation, and the decrease in anxiety, depression and sad mood
--LACTOBACILLUS species are BACTERIA FOUND IN THE GI TRACT OF THE OBESE PEOPLE.
- LACTOBACILLUS PLANTARUM AND BIFIDOBACTERIUM INFANTIS
___PSYCHOTROPIC BACTERIA - Regulate host Mental Health by the production of proinflammatory cytokines, and communicating with the brain via the vagus nerve: LACTOBACILLUS RHAMNOUSUS and BIFIDOBACILLUS RHAMNOSUS AND BIFIDOBACTERIUM INFANTIS.
SEE BELOW FOR DIFFERENT STRAINS THAT CAN CONTRIBUTE WEIGHT GAIN OR DECREASE WEIGHT, MAY DECREASE ANXIETY/ DEPRESSION, DECREASE GASTROINTESTINAL TRACT (GI) side effects of CONSTIPATION/ PAIN/ BLOATING/ INFLAMMATION AND DIARRHEA. (6)
THE STRAINS OF MICROORGANISM THAT MAY INCREASE WEIGHT.
THE STRAINS OF MICROORGANISM THAT MAY DECREASE ANXIETY/ DEPRESSION, DECREASE WEIGHT, DECREASE GASTROINTESTINAL TRACT (GI) side effects of CONSTIPATION/ PAIN/ BLOATING/ INFLAMMATION AND DIARRHEA.
THE STRAINS OF MICROORGANISM THAT MAY DECREASE WEIGHT.
THE STRAINS OF MICROORGANISM THAT MAY DECREASE ANXIETY/ DEPRESSION, NO WEIGHT CHANGE Noted, DECREASE GASTROINTESTINAL TRACT (GI) side effects of CONSTIPATION/ PAIN/ BLOATING/ INFLAMMATION AND DIARRHEA.
THE STRAINS OF MICROORGANISM THAT MAY DECREASE ANXIETY/ DEPRESSION, AND INCREASE WEIGHT.
THE STRAINS OF MICROORGANISM THAT MAY DECREASE ANXIETY/ DEPRESSION.
Please see below for PROBIOTIC BACTERIA AND YEAST that Modulate Weight, GI Symptoms, and MOOD. (6)
Figure: Taken from The Integrative RDN from Spring 2017 volume 19, Issue 4 edition.
Figure: Taken from The Integrative RDN from Spring 2017 volume 19, Issue 4 edition.
Figure: Taken from The Integrative RDN from Spring 2017 volume 19, Issue 4 edition.
WHAT ARE PREBIOTICS?(5)
___Galacto-oligosaccharides (FOS), fructooligosaccharides (FOS), inulin and lactulose, starch, pectin, and human milk oligosaccharides.
___ These prebiotics can enhance the function of Probiotics. They FEED the PROBIOTICS by stimulating their growth and activity.
____ Can affect positively to the host physiology.
___FUNCTIONAL FOODS: cheese, yogurt, fresh milk, kimchi, cabbage, fermented fish, and Chinese paocai.
___ PRODUCE gamma- aminobutyric acid ( GABA).
__ Increases the synaptic transmission velocity causing an increase in EMOTIONAL DYSREGULATION, ANXIETY, AGITATION, PANIC ATTACKS AND ADDITIVE BEHAVIOURS.
The Neurotransmitters SEROTONIN AND DOPAMINE.
___Can be synthesized by GI Bacteria from TRYPTOPHAN and PHENYLALANINE.
FOUND in FOODS:
___POULTRY, SEAFOOD, BEEF, PORK, EGGS WHITE, LEGUMES, NUTS, AND SEEDS.
WHAT ARE POLYPHENOLS?(5)
_ A large class of plant-based compounds such as phenolic acids, flavonoids, lignans, and stilbenes.
_They promote the growth of beneficial bacteria including BIFIDOBACTERIUM SPP.
_ A DIET RICH of OMEGA 3 may HELP TO maintain the normal brain function and cognitive processing, low anxiety, optimization of emotional regulation, and decrease depression.
_ Positive CNS effect: Anti-inflammatory, anti-oxidant, and enzymatic modulation of phenolic compounds accounts.
_ Green and black tea have been shown to delay the growth of dysbiotic HELICOBACTER PYLORI, STAPHYLOCOCCUS AUREUS, SALMONELLA TYPHIMURIUM, and LISTERIA MONOCYTOGENES BACTERIA.
___ BERRIES, CITRUS, RED WINE, COFFEE, TEA, AND COCOA.
WHAT ARE OMEGA 3 FATTY ACIDS - N-3s? (5)
___ An unsaturated fatty acid in fish oils, with three double bonds at particular positions in the hydrocarbon chain.
___It is an anti-inflammatory, Synaptic plasticity, monoaminergic
( DOPAMINE AND SEROTONIN) neurotransmission, modulating HPA axis activity, reduce central and peripheral inflammation.
__ Improve Anxiety, depression, emotional reactivity, and impulse control, perfectionism, and cognitive behaviors.
___ Omega 3 promotes the growth of strains of LACTOBACILLUS.
__ LACTOBACILLI can regulate N-3s absorption.
__ N-3S increase growth of BIFIDOBACTERIA.
__ Reduce growth of dysbiotic enteric bacteria.
____COLD-WATER FATTY FISH, NUTS, AND SEEDS (CHIA, HEMP, FLAX), FORTIFIED FOODS, FORTIFIED FOODS, DIETARY OMEGA 3 SUPPLEMENTS
( EICOSAPENTAENOIC ACID (EPA), and DOCOSAHEXAENOIC ACID (DHA).
____ OMEGA 3 FATTY ACIDS: are alpha-linolenic acid (ALA).
Found in plant oils such as flaxseed, soybean, and canola oils.
The safety of probiotics considered in reviews and clinical DATA which have drawn consideration to isolated cases of human bacteremia. (9-11)
However, there is available data register that state that there are no harmful effects observed in controlled clinical studies with lactobacilli and bifidobacteria.(12)
TAKE WHAT YOU LEARNED INTO PRACTICE
It is essential that we have knowledge and understanding of the different strains, the structure of probiotics and potential effects, whenever we opt for consuming foods and supplements.
FOODS: YOGURT, MISO, LASSI, TEMPEH, KEFIR, SPARKLING PROBIOTIC DRINKS, PROBIOTIC JUICES, FERMENTED PRODUCTS such as APPLE VINEGAR WITH THE MOTHER, PICKLED CUCUMBER, PICKLED GINGER, SAUERKRAUT, GREEN OLIVES, PICKLED BEANS, NATTO, KAVS, FERMENTED VEGETABLES, SOY SAUCE, KIMCHI, KOMBUCHA, some cheeses such as SWISS CHEESE, SOURDOUGH BREAD and MORE. (5)
___NEW FOOD PRODUCTS formulated with the addition of probiotic cultures.
Various types of cheese, ice creams, milk-based desserts, powdered milk for newborn infants, butter, mayonnaise, powder products or capsules, and fermented food of vegetable origin.(13)
___It is always a good idea to discuss with your healthcare provider about getting the appropriate labs to determine any nutrient deficiency, EKG, bone density and a nutrition-focused assessment.
___I CAN measure YOUR BONE DENSITY IN POUNDS, HYDRATION, MUSCLE % AND FAT % IN MY PRACTICE.
___ For stabilization to improve weight without iatrogenic refeeding syndrome. An integrative approach can include supplemental probiotics and N-3s. (5)
__ As consumption of foods improves, it is always a good idea to start with foods sources, prebiotics, probiotics, N-3s, and phenolic compounds.
_ A good idea is to cultivate a fermentable food such as (kombucha, yogurt or Kefir. (5)
__ Start first with foods, BUT if fermented foods may cause a GI tract distress, or if you are not able to consume foods with probiotics. Then move toward taking oral supplements. (5)
__ You can always verify for GOOD SUPPLEMENT QUALITY.
____A 3 party organization test and reviews the NUTRITIONAL SUPPLEMENTS. The prestigious Manufacturing practices (GMP) by NSF International. (5)
___ There are guidelines that support criteria and methodology for the evaluation of probiotics. In order to recognize and establish data need to be available to substantiate health claims. (14)
__ These guidelines are available in Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food.14
_Other studies show that probiotics can help with: eradication of VRE (15), prevention of ADD (16), constipation (17), IBS (18), decreased rates of RTIs (19), decreased rates of vaginal candidiasis (20), decreased abdominal adiposity and body weight (21), hepatic encephalopathy (22), improved H. pylori eradication (23)and more.
__RECOMMENDATION: Start taken the minimum dose for some strains is 10(9) CFU/day, it is a best practice to take supplements that contain bacteria in concentrations >10(9) CFU/dose. Unless other researchers has demonstrated differently data on specific strain contained in the supplement is effective in smaller amounts.24
_ Probiotics must be taken with a dairy like food or grain or after for optimal survivor in the colon. 24
_10 (8) bacteria provided in a dairy base led to greater number of live bacteria in colon than 10(10) bacterias provided in a capsule. 25
__EXCESSIVE INTAKE OF ORAL SUPPLEMENTS may cause GI tract discomfort including the development of flatulence, bloating, constipation or diarrhea. (5)
Family can start by measuring the portion of a calorically-appropriate meal plan with the help of a Registered Dietitian Nutritionist starting today. BOOK YOUR CONSULTATION NOW.
Figure: Taken from The Integrative RDN from Spring 2017 volume 19, Issue 4 edition.
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