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# *------------------------------------------------------------------
# | PROGRAM NAME: notifications.R
# | DATE: 29/03/2018
# | CREATED BY: David Granjon
# *----------------------------------------------------------------
# | PURPOSE: This UI code contains the datas to generate all
# | notifications in the network part. Needed by the
# | function generate_notification() of model_utils.R
# *-----------------------------------------------------------------
# | UPDATES: 29/03/2018 (last update)
# |
# |
# *------------------------------------------------------------------
notification_list <- list(
php1 = c(
paste(
"Welcome to the",
"<mark><font color=\"#FF0000\"><b>",
"primary-hyperparathyroidism",
"</b></font></mark>",
"(PHP1) case study.",
"Before going further, make sure that <b>regulations</b> are enabled,
and that Ca and Pi homeostasis are selected.",
"<hr>",
"The <b>next</b> and <b>back</b> buttons will walk you through the
consequences of PTH overproduction and regulatory pathways involved.",
"You can <b>hover</b> over",
"<mark><font color=\"#FF0000\"><b>",
"intestine,",
"</b></font></mark>",
"<mark><font color=\"#FF0000\"><b>",
"kidney,",
"</b></font></mark>",
"<mark><font color=\"#FF0000\"><b>",
"bone,",
"</b></font></mark>",
"and",
"<mark><font color=\"#FF0000\"><b>",
"PTHg",
"</b></font></mark>",
"nodes to display detailed views at the cellular levels.",
"External links to related content from <b>HSeT</b> are also provided
where appropriate (HSeT log-in required)",
sep = " "
),
paste(
"PTH increases <b>bone resorption</b>, Ca <b>reabsorption</b>
(in TAL and DCT/CNT ) and enhances vitamin D3 <b>conversion</b>
into its active form. Furthermore, it represses <b>Pi reabsorption</b>
in the proximal tubule.",
sep = " "
),
paste(
"1,25 vitamin D3 synthesis is enhanced by <b>PTH</b>, which
stimulates <b>Cyp27b1</b> and inhibits <b>Cyp24a1</b>. Active
vitamin D3 increases <b>intestinal absorption</b> of Ca and Pi,
<b>Ca reabsorption</b> in kidney (DCT/CNT) as well as <b>FGF23
synthesis</b> in bone. Besides, it represses <b>PTH
synthesis</b> in parathyroid glands.",
sep = " "
),
paste(
"FGF23 synthesis is mainly enhanced by vitamin D3 and to a
lesser extent by Pi. Its main role is to <b>prevent vitamin D3
toxicity</b> by repressing its synthesis (activates Cyp24a1 and
represses Cyp27b1, so antagonist of PTH). Additionally, it blunts
<b>Pi reabsorption</b> in the proximal tubule. The relationship
between PTH and FGF23 are still controversial, to date."
),
paste(
"Ca <b>represses PTH secretion</b> via the <b>calcium sensing
receptor</b> (CaSR) in parathyroid chief cells. It also reduces
the synthesis of the active form of vitamin D3. Finally, it
activates the CaSR in the kidney, thereby <b>lowering the
reabsorption of Ca</b> in the TAL."
),
paste(
"Since plasma Pi levels are decreased, the activation of PTH
synthesis by Pi is reduced, as well as the repression of
vitamin D3 conversion and the increase of FGF23 synthesis."
),
paste(
"Ionized plasma Ca concentration is",
"<mark><font color=\"#FF0000\"><b>",
"widely increased",
"</b></font></mark>",
"during PHP1,
mainly because of a higher intestinal absorption, bone resorption
and reabsorption in kidney. Inversely, Pi plasma concentration is",
"<mark><font color=\"#FF0000\"><b>",
"significantly reduced",
"</b></font></mark>",
"as a consequence of PTH and FGF23 effects
on its renal reabsorption. Ca and Pi are also known to regulate
hormonal synthesis, for example via the CaSR in parathyroid glands.",
sep = " "
)
),
hypopara = c(
paste(
"Welcome to the",
"<mark><font color=\"#FF0000\"><b>",
"hypoparathyroidism",
"</b></font></mark>",
"(PHP1) case study.",
"Before going further, make sure that <b>regulations</b> are enabled,
and that Ca and Pi homeostasis are selected.",
"<hr>",
"The <b>next</b> and <b>back</b> buttons will walk you through the
consequences of PTH deficiency and regulatory pathways involved.",
"You can <b>hover</b> over",
"<mark><font color=\"#FF0000\"><b>",
"intestine,",
"</b></font></mark>",
"<mark><font color=\"#FF0000\"><b>",
"kidney,",
"</b></font></mark>",
"<mark><font color=\"#FF0000\"><b>",
"bone,",
"</b></font></mark>",
"and",
"<mark><font color=\"#FF0000\"><b>",
"PTHg",
"</b></font></mark>",
"nodes to display detailed views at the cellular levels.",
"External links to related content from <b>HSeT</b> are also provided
where appropriate (HSeT log-in required)",
sep = " "
),
paste(
"Bone <b>resorption</b>, Ca <b>reabsorption</b> (in TAL and
DCT/CNT) and <b>vitamin D3 conversion</b> into its active
form are <b>decreased</b>. Furthermore, the repression of
<b>Pi reabsorption</b> in the proximal tubule is dampened."
),
paste(
"Less vitamin D3 is converted into 1,25 vitamin D3,
resulting in a <b>decrease of intestinal absorption</b> of
both Ca and Pi, a <b>decreased reabsorption</b> of Ca."
),
paste(
"FGF23 synthesis is <b>reduced</b> due to lower vitamin D3 levels.
Moreover, the elevation of Pi levels is <b>not enough to
compensate</b> the loss of vitamin D3 (effect on FGF23 synthesis)."
),
paste(
"Because of the <b>decreased levels of plasma Ca</b>, PTH secretion is
<b>less repressed</b>. Besides, more Ca is reabsorbed in the kidney
since CaSR is <b>less activated</b>. The inhibitory effect of Ca on
D3 synthesis is also <b>blunted</b>."
),
paste(
"Since plasma Pi levels are <b>increased</b>, the
activation of PTH synthesis by Pi is <b>increased</b>,
as well as the repression of vitamin D3 conversion and
the increase of FGF23 synthesis."
),
paste(
"Ionized plasma Ca concentration is",
"<mark><font color=\"#FF0000\"><b>",
"widely decreased",
"</b></font></mark>",
"since intestinal
absorption, resorption and reabsorption in kidney are
<b>substantially reduced</b>. Inversely, Pi plasma
concentration is",
"<mark><font color=\"#FF0000\"><b>",
"significantly enhanced",
"</b></font></mark>",
"as a consequence of PTH and FGF23 effects on its renal
reabsorption, which are lower. Besides, the Pi rise is
cannot compensate the loss of parathyroid function.",
sep = " "
)
),
hypoD3 = c(
paste(
"Welcome to the",
"<mark><font color=\"#FF0000\"><b>",
"vitamin D3 deficiency",
"</b></font></mark>",
"(PHP1) case study.",
"Before going further, make sure that <b>regulations</b> are enabled,
and that Ca and Pi homeostasis are selected.",
"<hr>",
"The <b>next</b> and <b>back</b> buttons will walk you through the
consequences of vitamin D3 deficiency and regulatory pathways involved.",
"You can <b>hover</b> over",
"<mark><font color=\"#FF0000\"><b>",
"intestine,",
"</b></font></mark>",
"<mark><font color=\"#FF0000\"><b>",
"kidney,",
"</b></font></mark>",
"<mark><font color=\"#FF0000\"><b>",
"bone,",
"</b></font></mark>",
"and",
"<mark><font color=\"#FF0000\"><b>",
"PTHg",
"</b></font></mark>",
"nodes to display detailed views at the cellular levels.",
"External links to related content from <b>HSeT</b> are also provided
where appropriate (HSeT log-in required)",
sep = " "
),
paste(
"1,25 vitamin D3 effects on PTH synthesis,
FGF23 synthesis and kidney are <b>reduced</b>."
),
paste(
"Plasma PTH concentration <b>increases</b> because of the
blunted repression by 1,25 vitamin D3, as well as the
<b>reduction</b> of ionized plasma Ca concentration
via the calcium sensing receptor. Thus, resorption is
<b>increased</b> in order to compensate the <b>reduced intestinal
absorption</b> of both Ca and Pi. Similarly, the elevation of
PTH levels aims at <b>increasing Ca reabsorption</b> as well
as decreasing Pi reabsorption in kidney. Besides, the increase
of PTH also <b>slightly counteract</b> the decrease of
vitamin D3 stocks."
),
paste(
"FGF23 synthesis is <b>reduced</b> as a result
of vitamin D3 deficiency."
),
paste(
"The reduction of plasma Ca levels cause an <b>increase of
PTH exocytosis</b> since CaSR is less activated. The decrease
of Ca inhibitory effect on D3 synthesis, as well as elevated
PTH levels are not enough significant to compensate for
25(OH)D3 deficiency. Finally, CaSR is less activated in the
kidney so as to <b>enhance Ca reabsorption</b>."
),
paste(
"Activation of PTH synthesis by Pi is <b>reduced</b>, as well
as its effect on D3 synthesis. Besides, FGF23 synthesis is
<b>less activated</b>"
),
paste(
"In summary, ionized plasma Ca concentration and Pi",
"<mark><font color=\"#FF0000\"><b>",
"remain quite stable",
"</b></font></mark>",
"as long as vitamin D3 stocks are not
totally depleted. However, they start to",
"<mark><font color=\"#FF0000\"><b>",
"decrease",
"</b></font></mark>",
"as soon as the level of vitamin D3 is
below a given",
"<mark><font color=\"#FF0000\"><b>",
"critical
threshold.",
"</b></font></mark>",
"Consequently, all fluxes
are significantly reduced."
)
)
)
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