Being pregnant, Miscarriage & Ladies’s Well being In Antiphospholipid Syndrome

This submit is a part of the Antiphospholipid Syndrome (APS) useful resource library that I’m build up on my web site for sufferers, as a affected person who’s lived with it for greater than 20 years myself. This text particularly will concentrate on all issues associated to the feminine intercourse and girls’s well being in Antiphospholipid Syndrome. It can cowl subjects similar to being pregnant, miscarriage, menstruation, menopause, danger elements, contraception and different normal information.

I’ve taken the time to analysis related medical journals, and likewise share my private experiences the place applicable. I hope you discover it helpful, whether or not as a affected person or as a supporter. If there are particular phrases used on this submit that you simply have been questioning about, similar to antiphospholipid antibodies (aPLs), correlations with different autoimmune illnesses similar to Lupus, the reversal protocol and extra, then I’d advocate that you simply take a look at the entire A – Z information plus different sources within the sequence under.

Antiphospholipid Syndrome Analysis: The A – Z Information as a Affected person

*Disclaimer: This text is supposed for academic functions, and is predicated on my private experiences as a affected person. While I’ve finished my utmost to be meticulous in analysis, I’m not a physician, and nothing on this article ought to be substituted for medical recommendation. Please seek the advice of your personal physician earlier than altering or including any new remedy protocols. This submit can also comprise affiliate hyperlinks. It can value you nothing to click on on them. I’ll get a small referral price from purchases you make, which helps with the upkeep of this weblog. Learn our Privateness Coverage web page for extra info. Thanks!

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Ladies’s Well being in Antiphospholipid Syndrome

The phrases for ‘girls’ and ‘feminine’ used on this article will largely be referring to those that have been assigned feminine at delivery, and can take into consideration genetic variations and their hyperlinks with autoimmunity. Females usually have two X chromosomes, whereas males have an X and Y chromosome. Females account for round 80% of all autoimmune illness instances as nicely, and up to date research have proven that particular X-linked genes could also be contributors to autoimmune illness. Based on Dou et al. (2024):

“To make the gene expression output roughly equal between females and males, each cell in a feminine’s physique epigenetically silences considered one of two X chromosomes by way of the motion of the lengthy non-coding RNA (lncRNA) Xist. Xist is an ∼17-kb lncRNA (19 kb in human) that’s transcribed solely from the inactive X chromosome and thus not expressed in males.”

While precisely how, when and the place continues to be sketchy, there isn’t any doubt that there might be additional Antiphospholipid Syndrome associated problems just by being feminine. In spite of everything, APS is a blood clotting autoimmune dysfunction, and as girls we get intervals each month on common, and likewise have to undergo the being pregnant course of if we so select to – all of which entails the immune system and blood.

Epidemiology of APS – Males vs Females

Antiphospholipid Syndrome is extra generally present in girls than in males, with a ratio of about 3.5:1. It is usually extra typically secondary APS (SAPS) in girls, whereas males are extra vulnerable to main APS (PAPS). Ladies current with strokes, livedo and complications extra often than in males. Whereas male PAPS sufferers current extra with myocardial infarction, mesenteric and hepatic vein thrombosis (Kaul and Hughes, 2023).

Different research have additionally proven better cerebrovascular illness in girls, while males had gastrointestinal involvement extra often (Jara et al., 2005). That is additionally an fascinating desk which exhibits the comorbidities related to APS and antiphospholipid antibodies (aPLs) positivity within the normal inhabitants, from a compilation of assorted analysis papers (p.s. hyperlink generally must be clicked twice to open for some unknown purpose). It contains the varied aPLs present in girls in various kinds of being pregnant incidents, ages when girls first skilled a stroke, sufferers with comorbidities, and extra (Dabit et al., 2021).

Learn this submit for extra info on how Antiphospholipid Syndrome can have an effect on all the physique.

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Menstruation & Antiphospholipid Syndrome

It isn’t uncommon for us girls to expertise heavier intervals while taking anticoagulants, or to see some blood clots discharged. One thing vital to learn about are ovarian cysts. Most of those cysts are widespread and innocent, and happen even in wholesome girls. They often get reabsorbed into the physique or are handed out, however generally they’ll rupture.

When this occurs, it’s referred to as an Ovarian Cyst Rupture, and I can inform you from two first-hand experiences that it isn’t nice. I almost died each instances. This was additionally the explanation why my healthcare crew determined to place me on contraception (Nexplanon), to forestall additional episodes. A advantage of being on contraception, not less than for me, is that I’ve skilled lighter intervals with fewer interval cramps since then.

The Relation Between Oestrogen & APS

Or estrogen, relying on the place you come from! Oestrogen is a steroid hormone related to menstruation (Delgado and Lopez-Ojeda, 2023). There are a number of differing kinds – estrone (E1), estradiol (E2), estriol (E3), and etestrol (E4) – they usually collectively regulate the event and performance of the feminine reproductive system. Males additionally produce oestrogen, primarily within the testis (Harding and Heaton, 2022).

Past its position as a intercourse hormone, oestrogens and their receptors additionally play a job in modulating innate immune responses towards infections, from viral to bacterial, parasitic and fungal. They show anti-inflammatory results and likewise assist the physique with wound therapeutic and restore (Harding and Heaton, 2022). A strong hormone, little doubt!

Nonetheless, oestrogen additionally performs a job in ache flares for rheumatoid autoimmune issues, similar to SLE (Lupus) and Rheumatoid Arthritis. Oestrogens additionally improve the chance of each arterial and venous thrombosis, and affect nearly each cell within the physique. The technical rationalization, in line with Abou-Ismail et al. (2020):

“Estrogen results in elevated thrombin era and fibrin clot formation by growing the degrees of variable coagulation proteins and reducing the degrees of anticoagulant proteins.”

And in line with Manukyan et al. (2020):

“Our findings present the flexibility of E2 [high-17β-estradiol] to advertise proinflammatory and procoagulatory phenotype of innate immune cells in people with aPL [antiphospholipid antibodies] positivity. Our information highlights the numerous affect of feminine hormones on the activation of immune cells within the presence of aPL.”

Oestrogen additionally will increase the chance of blood clots when utilized in contraceptives or as postmenopausal hormone substitute remedy. This could additionally occur in males who use them as remedy for coronary illness, or in sex-change remedy (Rosendaal et al., 2002). Thus, it’s best to keep away from therapies and types of contraception that comprise oestrogen if in case you have Antiphospholipid Syndrome.

Ovarian Cyst Ruptures in Ladies with Antiphospholipid Syndrome

Ovarian cyst ruptures are extraordinarily painful and might be life-threatening. For girls with Antiphospholipid Syndrome who’re on some type of anticoagulation remedy, the blood thinning results of the remedy(s) can compound the issue. Let’s take a more in-depth have a look at how and why they occur.

Kinds of Useful Cysts

There are two kinds of purposeful cysts that your ovaries develop each month – a follicle cyst and a corpus luteum cyst. A follicular cyst happens when the follicle doesn’t rupture throughout ovulation. A corpus luteum cyst happens after the egg is launched, and the opening turns into blocked within the corpus luteum. Most purposeful ovarian cysts are innocent and resolve on their very own.

Nonetheless, an ovarian cyst rupture can happen generally throughout menstruation. For a wholesome feminine, often this will get handed out as a blood clot, or reabsorbed by the physique, with few to no incidences. If there are signs, they might embrace sudden belly or pelvic ache, ache with fever and vomiting, or indicators of shock and weak point.

Hemoperitoneum in Females with APS

For a feminine with Antiphospholipid Syndrome, such ruptures can generally trigger inside bleeding, no because of their blood thinning medicines. That is also called a hemoperitoneum, the place extra blood accumulates within the belly or pelvic cavity, and it’s a medical emergency.

This doesn’t occur each interval after all, however I’ve been unfortunate to have had two ovarian cyst rupture episodes that have been of life-threatening standing. The ache was acute and got here on abruptly. Inside 4 hours I used to be doubled over, swollen and bloated with ache, and needed to crawl to the hospital.

They are going to often do an belly ultrasound on the A&E/ER to verify totally free fluid. Emergency surgical procedure is often required, however typically averted for sufferers who’re on anticoagulants, till the blood thinning results of their medicines have been counteracted.

The second time I had an ovarian cyst rupture, the nurses on the A&E have been slightly junior, so I needed to insist on the ultrasound. The senior physician later confirmed the analysis, and I used to be instantly positioned within the excessive emergency part, given sturdy painkillers, and injected with three various kinds of blood clotting brokers. RBC (purple blood cell) counts could fall, however this may be resulting from dehydration as nicely.

Learn this submit for extra info on reversal brokers and medicines associated to Antiphospholipid Syndrome.

Start Management as Prevention for Bleeding Threat in Ladies with Antiphospholipid Syndrome

On account of these ovarian cyst rupture episodes, my gynaecologist prompt contraception to forestall ovulation, which would scale back the possibilities of a reoccurrence.

There are a number of kinds of delivery controls, they usually comprise the hormones oestrogen, or progestin, or each. As talked about beforehand, oestrogen will increase the chance of blood clots. Research have additionally demonstrated that progestins together oral contraceptives additionally play a job to a lesser diploma (Rosendaal, 2002). You may view a desk of contraceptive suggestions for girls with APS right here (Sammaritano, 2021).

As I’ve many comorbidities similar to Lupus and Sjögren’s illness and am severely immunocompromised, my gynaecologist didn’t advocate intrauterine units (IUDs) both because of the increased probability for infections. I personally use Nexplanon, as prompt by my very own gynaecologist.

Etonogestrel (Implanon & Nexplanon) – What I Use for Start Management as a Feminine with APS

Etonogestrel is a progestin hormone beneath the model names of Implanon and Nexplanon. It comes within the type of a small implant, and your gynaecologist will make a small reduce in your arm to insert it subdermally. You’ll almost certainly have to do a reversal of your blood thinning remedy beforehand, simply in case of extreme bleeding. Your rheumatologist/physician and gynaecologist will work intently with you to do the reversal protocol, which you’ll be able to learn extra about right here.

What I like concerning the etonogestrel implant is that when it’s inserted, it lasts for 3 years and you may go about your life as per traditional. And do you have to want to attempt for being pregnant, you possibly can merely take away it and begin making an attempt just about instantly.

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Being pregnant with Antiphospholipid Syndrome

Being pregnant is a difficult and sensitive matter relating to Antiphospholipid Syndrome. I’ve identified individuals who have had miscarriages at 8 months, as a result of they didn’t know that that they had APS. The incidence of being pregnant loss for girls with Antiphospholipid Syndrome is reported to be between 34% – 76% (Xu et al., 2019).

Ladies with APS have to work intently with their rheumatologist, a high-risk gynaecologist, and their whole healthcare crew – earlier than even getting pregnant. Your healthcare crew ought to assess your danger elements, and work with you to implement preventive methods, in addition to give you a plan that’s tailor-made to your particular circumstances and well being standing (Andreoli et al., 2017).

So Why Not Display screen Each Lady Earlier than Being pregnant for Antiphospholipid Antibodies?

I used to suppose that each girl ought to be examined for APS earlier than being pregnant to avoid wasting us the grief of a miscarriage. However having finished extra analysis, I can perceive why it isn’t such a good suggestion to take action. Typically, asymptomatic sufferers shouldn’t be screened for aPLs as there’s a danger of false positivity of as much as 3 – 20% (Rand and Wolgast, 2012). This not solely topics the person to pointless remedy, however will increase the chance of bleeding problems.

Earlier than screening for aPLs, the affected person’s medical historical past (similar to recurrent miscarriages), in addition to comorbidities (similar to SLE), have to make sense medically too. False optimistic aPLs checks will also be triggered by many kinds of infections, similar to Lyme Illness, Syphilis and EBV (Rand and Wolgast, 2012).

Will I Move Antiphospholipid Syndrome on to My Youngster?

Like many different autoimmune illnesses, Antiphospholipid Syndrome is polygenic, the place a number of genes are concerned, and will also be influenced by environmental elements. The particular person contribution of every gene could even be unnoticeable, and requires a number of contributing elements to activate (Lvovs et al., 2012). While sure, the genes are nonetheless there, APS will not be generally inherited from mum or dad to baby, as in comparison with different situations similar to sickle cell anaemia or cystic fibrosis.

Based on Barinotti et al. (2020):

“The etiology of APS continues to be unknown, however equally to different autoimmune illnesses, it appears to be linked to a fancy interaction between genetic predisposition, antigenic stimuli, and the presence of particular autoantibodies.” ….. “APS is a fancy uncommon illness with the good majority of the instances being sporadic. Not often, the situation has been reported to run in households.”

There may be nonetheless a lot to be understood as to how Antiphospholipid Syndrome finally develops, however in line with Ortiz-Fernández and Sawalha (2019), current research have recognized a few of the genetic elements that contribute to APS, similar to: “antigen receptor-mediated signaling, interferon-gamma-mediated signaling, T cell receptor signaling, and regulation of B cell receptor signaling pathways”. Genetic susceptibility to APS can be depending on ethnic, gene-gene, gene-environment, and a large number of different elements which can be nonetheless not fully understood (Horita and Merrill, 2004).

Treatment Interactions Throughout Being pregnant with Antiphospholipid Syndrome

You will need to inform your medical crew earlier than even making an attempt for being pregnant, as sure medicines that you simply’re on is perhaps dangerous to both your self or the foetus. Some medicines take some time to be fully eradicated out of your bodily system as nicely. Your physician will often change you to a safer various for being pregnant, and monitor you intently for antagonistic results.

Listed here are some vital medicines to be aware of in relation to APS and being pregnant. When you’ve got different medicines that you simply take for different continual sicknesses, they need to even be taken into consideration.

Warfarin & Being pregnant

Warfarin remedy ought to be paused throughout being pregnant, as it may be dangerous to foetuses. Aside from a uncommon illness referred to as Foetal Warfarin Syndrome (Starling et al., 2012), warfarin also can trigger different problems throughout being pregnant similar to developmental issues or haemorrhages (Abadi et al., 2002).

Hydroxychloroquine, Low Molecular Weight Heparin (LMWH) & Aspirin in Pregnant APS Sufferers

Current research have additionally proven that the present customary for being pregnant in APS sufferers, which makes use of aspirin and LMWH, are restricted in efficacy of late-term being pregnant problems. Apparently, hydroxychloroquine, which is an anti-malarial drug generally used to deal with Lupus (SLE), confirmed advantages for APS sufferers in being pregnant.

A research on 176 pregnancies (96 with aPLs) mirrored the next fee of dwell births, and a decrease prevalence of aPLs-related being pregnant morbidity while on hydroxychloroquine (Sciascia et al., 2016). One other European multicentre research of 35 APS sufferers who have been placed on hydroxychloroquine, confirmed a lower in being pregnant losses from 81% to 19%, as in comparison with earlier utilization of aspirin and/or LMWH solely (Mekinian, 2015).

These findings by Marchetti et al. (2014) clarify why hydroxychloroquine could also be helpful for APS sufferers who’re pregnant:

“Right here, we noticed that HCQ fully reversed the results of the plasma of APS sufferers (free from anti–annexin V antibodies) and the anti‐β2GP1 antibodies on trophoblastic cell fusion and differentiation.”

One thing fascinating I discovered while doing analysis on this matter, is that in Japan, APS-complicated pregnancies from the utilization of LMWH will not be coated by medical insurance coverage. Thus, unfractionated heparin (UFH) and/or low-dose aspirin (LDA) are used as an alternative (Deguchi et al., 2017). As well as, there may be additionally one thing often known as aspirin-heparin resistant APS (AHRAPS), the place different therapies similar to high-dose intravenous immunoglobulin (IVIG) could should be included (Arumugham and Rayi, 2023).

Do you have to have an interest to study extra, this paper by Schreiber and Hunt (2019) does a superb job of itemizing out the administration of APS throughout being pregnant. You may also study extra about warfarin, LMWH and different medicines associated to APS on this submit.

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Being pregnant Problems with Antiphospholipid Syndrome

While it’s important to not fear your self sick(er), it’s also vital to concentrate on potential being pregnant problems on account of Antiphospholipid Syndrome, in an effort to higher care and advocate for your self. These problems can come up from a mixture of things – from the illness itself, comorbidities, hormonal modifications, decreased mobility, stage of being pregnant, and technique of supply, with caesarean part carrying the next danger of thrombosis than vaginal supply (Lee et al., 2021).

While there are specific tips sketched out for the administration of APS throughout being pregnant, extra research nonetheless should be finished in an effort to decide the very best plan of action. Thus, it’s crucial to make sure that your being pregnant care is individualised based mostly in your medical historical past, comorbidities similar to SLE, way of life elements and extra.

Trophoblasts

Being pregnant problems don’t simply stem from a single issue; Antiphospholipid Syndrome can assault from totally different pathways. For one, they’ll work together with trophoblasts, which intrude with vitamins transmitted to the embryo within the placenta. Aside from vitamins, trophoblasts additionally produce quite a few progress elements and hormones that help wholesome foetal and placental improvement (Wang and Zhao, 2010).

Based on a research by Mulla et al. (2009):

“Our findings counsel that early being pregnant loss and late obstetric problems in APS could come up from anti-β2GPI Abs appearing on first trimester trophoblast cells, thereby triggering placental irritation and cell demise.”

That means to say that antiphospholipid antibodies set off an inflammatory response within the placenta, which interferes with trophoblasts. Research have discovered that hydroxychloroquine, an anti-malarial drug generally used to deal with Lupus (SLE), has helpful results towards this.

Preeclampsia

Preeclampsia can be related to Antiphospholipid Syndrome, and will also be related to shallow cytotrophoblast invasion (Skoura et al., 2022). Preeclampsia manifests as hypertension and generally with protein within the urine (proteinuria). It’s important to work together with your obstetrician intently, as this could be a lethal situation.

Venous Thromboembolism (VTE)

One other extreme complication of being pregnant for APS sufferers is venous thromboembolism (VTE), particularly within the legs (DVTs). This could manifest systemically with delicate to life-threatening signs, from ache and swelling, to blood clots within the lungs (pulmonary embolism). Left-sided DVTs are additionally extra widespread at 70% – 90%, because of the involvement of sure veins throughout being pregnant. VTE can be nonetheless a danger in the course of the postpartum interval (Varrias et al., 2023).

Typically, LMWH is used for the prevention and remedy of VTEs in pregnant girls, though that will depend on the person as nicely. Listed here are some tips based mostly on observational research and extrapolation from Bates et al. (2012).

Learn extra about cardiovascular and pulmonary embolisms typically relation to APS right here.

Intrauterine Progress Restriction (IUGR)

Intrauterine Progress Restriction (IUGR) – also called Foetal Progress Restriction – is one other being pregnant complication with APS, the place the foetus is estimated to be under the tenth percentile for its gestational age. Ladies with APS have been discovered to have the next fee of IUGR, with anticardiolipin (aCL) positivity extremely related to it (Xi et al., 2020).

In one other systematic meta-analysis, anticardiolipin antibodies (aCLs) and anti-beta2 glycoprotein 1 antibodies (anti-β2GP1) have been additionally discovered to be related to IUGR, while lupus anticoagulant (LA) didn’t improve the possibilities of it (Xu et al., 2022). This additional demonstrates the complexity of antiphospholipid antibodies and APS typically, as every sort of antibody impacts the physique otherwise, but are all indicators in the direction of an Antiphospholipid Syndrome analysis.

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Miscarriages & Antiphospholipid Syndrome

Sadly, many ladies solely uncover that they’ve Antiphospholipid Syndrome after recurrent miscarriages. Based on Di Prima et al. (2011):

“Obstetric problems are the hallmark of antiphospholipid syndrome. Recurrent miscarriage, early supply, oligohydramnios, prematurity, intrauterine progress restriction, Foetal misery, Foetal or neonatal thrombosis, pre-eclampsia/eclampsia, HELLP syndrome, arterial or venous thrombosis and placental insufficiency are essentially the most extreme APS-related complication for pregnant girls.”

Foetal loss over 10 weeks of gestation is extra widespread in girls with Antiphospholipid Syndrome, though about half of recurrent miscarriages happen in the course of the first trimester. The lupus anticoagulant additionally performs an enormous position in recurrent miscarriages earlier than the twenty fourth week of gestation (Di Prima et al., 2011).

The fee of profitable births is greater than 80% though there are nonetheless dangers, similar to preeclampsia and preterm supply (Abrahams et al., 2017). I can’t emphasise this sufficient, however this can be very vital to work intently with a high-risk obstetrician and your whole healthcare crew all through your being pregnant journey.

The Stigma Related to Ladies’s Well being in Antiphospholipid Syndrome, and the Perceived Incapability to Conceive

I’ve at all times identified that I wish to be a mom – since I used to be 14 in reality. In my younger teenage thoughts, I’d get married at 27, have a number of kids, and commit myself to bringing them up in addition to I can. I used to be ready to undergo by means of all pains and dangers to take action. Sadly, life doesn’t work that approach. It isn’t to be dictated – it units the course and tempo, and you may both select to adapt, or battle double.

I’m now 38, with neither companion nor baby. My organic clock is ticking, however there may be nothing I can do about it. In spite of everything, marriage and/or being pregnant takes two palms to clap. Companions and potential companions have additionally written me off resulting from my multitude of continual sicknesses; they don’t even wish to start with the slightest risk of me being unable to conceive.

It is a phenomenological research that may resonate with you, if in case you have skilled foetal loss as a girl with Antiphospholipid Syndrome (Mahmoud et al., 2020). It illustrates the social burdens felt by sufferers, with some marriages ending in divorce resulting from expectations from husbands and mother-in-laws. The psychological struggling of the affected person is big as nicely, with many ladies feeling unhappy and pissed off. Some select to delay subsequent pregnancies, and plenty of dwell in fixed worry because of the unpredictability.

It will be significant for healthcare professionals to coach their sufferers on potential problems, from the bodily to emotional. In my view, it’s also the duty of family members to coach themselves on girls’s well being in Antiphospholipid Syndrome, and to know that it isn’t their companion’s fault. As a affected person, know that you’re not alone, and that you’re not to be blamed.

Ongoing Analysis on Recurrent Miscarriages in APS

A scientific assessment and meta-analysis has been finished to attempt to decide which antiphospholipid antibodies play an even bigger position in recurrent miscarriages for feminine sufferers with APS. While it has been discovered that anticardiolipin antibodies, lupus anticoagulant, anti-β2-glycoprotein I antibodies and antiphosphatidylserine (which is nearly all of them…) are associated to recurrent miscarriages, extra research nonetheless should be finished to study extra about what they honestly do (da Silva Santos et al., 2017).

As much as 15% of unexplained stillbirths is perhaps resulting from aPLs (antiphospholipid antibodies), with girls with lupus anticoagulant or who’re ‘triple apL optimistic’ on the highest danger (Herrera et al., 2017).

Menopause and Antiphospholipid Syndrome

There are usually not many research finished on APS and menopause however typically, menopause is a interval of immune modifications inside the feminine physique, amongst different occasions. Ranges of oestrogen and DHEA sulfate lower, which can result in: a rise in proinflammatory cytokines, a lower in sure anti-inflammatory cytokines, decreased lymphocyte ranges (CD4+ T cells and B cells), and a lower in cytotoxic exercise of NK cells (Bove, 2013).

Relying on the person, sort of autoimmune illnesses they’ve, and different elements similar to epigenetics and surroundings, the menopause transition can happen fairly otherwise. There are some studies of decreased frequency of ache flares in sufferers with SLE, but on the identical time, better harm accrual in affected organs (Bove, 2013).

In a single managed research, premenopausal girls with APS/SLE have been additionally discovered to have an elevated danger of atherosclerosis, which is a buildup of fat, ldl cholesterol and different substances in and on the artery partitions (Vlachoyiannopoulos et al., 2003). As per Mayo Clinic, while atherosclerosis is usually thought of a coronary heart drawback, it will probably additionally happen in some other artery within the human physique. The plaque not solely trigger the arteries to slim, they might additionally burst and result in blood clots. Study extra about cardiovascular manifestations in APS sufferers right here.

Conclusion to Ladies’s Well being in Antiphospholipid Syndrome

I hope that this text gives you with the added information to raised take care of your self as a feminine with Antiphospholipid Syndrome. From menstruation to baby delivery to menopause – the journey of womanhood is intertwined with blood, so it’s important to concentrate on how APS can work together with every stage of your life.

Ought to you’ve got any questions, corrections, experiences, or extra information to share – be at liberty to go away a remark under so we are able to all study collectively. Don’t neglect to take a look at the opposite posts within the sequence listed under, too!

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References:

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