from pptx import Presentation
from pptx.util import Inches, Pt, Emu
from pptx.dml.color import RGBColor
from pptx.enum.text import PP_ALIGN, MSO_ANCHOR
from pptx.util import Inches, Pt
import copy

prs = Presentation()
prs.slide_width  = Inches(13.333)
prs.slide_height = Inches(7.5)
blank = prs.slide_layouts[6]

# ── Colour palette ──────────────────────────────────────────────
C_TITLE_BG   = RGBColor(0x1A, 0x3A, 0x5C)   # dark navy
C_TITLE_FG   = RGBColor(0xFF, 0xFF, 0xFF)
C_ACCENT     = RGBColor(0xF0, 0x A0, 0x00)   # amber accent bar
C_BOX_YELLOW = RGBColor(0xFF, 0xF0, 0xB0)    # cortisol box
C_BOX_GREY   = RGBColor(0xE0, 0xE0, 0xE0)    # cortisone box
C_BOX_GREEN  = RGBColor(0xC8, 0xE6, 0xC9)    # active/effect box
C_BOX_RED    = RGBColor(0xFF, 0xCC, 0xCC)    # AME/clinical box
C_BOX_BLUE   = RGBColor(0xBB, 0xDE, 0xFB)    # salivary / diag box
C_BOX_BORDER = RGBColor(0x33, 0x33, 0x33)
C_ARROW      = RGBColor(0x33, 0x33, 0x33)
C_REF_BG     = RGBColor(0xF5, 0xF5, 0xF5)
C_REF_TXT    = RGBColor(0x44, 0x44, 0x44)
C_WHITE      = RGBColor(0xFF, 0xFF, 0xFF)

# ── Helper: add a filled rectangle with centred text ────────────
def add_box(slide, x, y, w, h, fill_rgb, text, font_size=13,
            bold=False, font_rgb=RGBColor(0x11,0x11,0x11),
            border_rgb=C_BOX_BORDER, border_pt=1.0):
    shape = slide.shapes.add_shape(
        1,  # MSO_SHAPE_TYPE.RECTANGLE
        Inches(x), Inches(y), Inches(w), Inches(h)
    )
    shape.fill.solid()
    shape.fill.fore_color.rgb = fill_rgb
    shape.line.color.rgb = border_rgb
    shape.line.width = Pt(border_pt)
    tf = shape.text_frame
    tf.word_wrap = True
    tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    p = tf.paragraphs[0]
    p.alignment = PP_ALIGN.CENTER
    run = p.add_run()
    run.text = text
    run.font.size = Pt(font_size)
    run.font.bold = bold
    run.font.color.rgb = font_rgb
    return shape

# ── Helper: add arrow (connector line with arrowhead) ───────────
def add_arrow(slide, x1, y1, x2, y2):
    from pptx.oxml.ns import qn
    from lxml import etree
    cx = int((x2 - x1) * 914400)
    cy = int((y2 - y1) * 914400)
    sp_tree = slide.shapes._spTree
    xml = f"""
    <p:cxnSp xmlns:p="http://schemas.openxmlformats.org/presentationml/2006/main"
             xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main"
             xmlns:r="http://schemas.openxmlformats.org/officeDocument/2006/relationships">
      <p:nvCxnSpPr>
        <p:cNvPr id="99" name="Arrow"/>
        <p:cNvCxnSpPr/>
        <p:nvPr/>
      </p:nvCxnSpPr>
      <p:spPr>
        <a:xfrm>
          <a:off x="{int(x1*914400)}" y="{int(y1*914400)}"/>
          <a:ext cx="{cx}" cy="{cy}"/>
        </a:xfrm>
        <a:prstGeom prst="straightConnector1"><a:avLst/></a:prstGeom>
        <a:ln w="25400">
          <a:solidFill><a:srgbClr val="333333"/></a:solidFill>
          <a:headEnd type="none"/>
          <a:tailEnd type="arrow" w="med" len="med"/>
        </a:ln>
      </p:spPr>
    </p:cxnSp>"""
    sp_tree.append(etree.fromstring(xml))

# ── Helper: slide-wide background ────────────────────────────────
def set_bg(slide, rgb):
    from pptx.oxml.ns import qn
    from lxml import etree
    bg = slide.background
    fill = bg.fill
    fill.solid()
    fill.fore_color.rgb = rgb

# ── Helper: text label (no box) ─────────────────────────────────
def add_label(slide, x, y, w, h, text, size=11, bold=False,
              align=PP_ALIGN.CENTER, rgb=RGBColor(0x33,0x33,0x33)):
    tb = slide.shapes.add_textbox(Inches(x), Inches(y), Inches(w), Inches(h))
    tf = tb.text_frame
    tf.word_wrap = True
    tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    p = tf.paragraphs[0]
    p.alignment = align
    run = p.add_run()
    run.text = text
    run.font.size = Pt(size)
    run.font.bold = bold
    run.font.color.rgb = rgb

# ══════════════════════════════════════════════════════════════════
# SLIDE 1 — Title slide
# ══════════════════════════════════════════════════════════════════
s1 = prs.slides.add_slide(blank)
set_bg(s1, RGBColor(0xF7, 0xF9, 0xFF))

# navy header bar
hdr = s1.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(2.2))
hdr.fill.solid(); hdr.fill.fore_color.rgb = C_TITLE_BG
hdr.line.fill.background()

add_label(s1, 0.3, 0.25, 12.7, 1.1,
          "CORTISOL METABOLISM", size=40, bold=True, rgb=C_TITLE_FG)
add_label(s1, 0.3, 1.3, 12.7, 0.7,
          "Liver  |  Kidney  |  Salivary Glands  |  Peripheral Tissues",
          size=18, rgb=RGBColor(0xBB, 0xCC, 0xFF))

add_label(s1, 1.5, 2.5, 10, 0.5,
          "Cortisol is secreted by the zona fasciculata of the adrenal cortex in response to ACTH.",
          size=14, rgb=RGBColor(0x22,0x22,0x55))
add_label(s1, 1.5, 3.1, 10, 0.5,
          "~90–95% circulates BOUND to cortisol-binding globulin (CBG) and albumin (liver-synthesised).",
          size=14, rgb=RGBColor(0x22,0x22,0x55))
add_label(s1, 1.5, 3.7, 10, 0.5,
          "~5% is FREE — the biologically active fraction.",
          size=14, rgb=RGBColor(0x22,0x22,0x55))
add_label(s1, 1.5, 4.3, 10, 0.5,
          "Key enzyme: 11β-Hydroxysteroid Dehydrogenase (11β-HSD) — two isoforms control tissue-level activity.",
          size=14, rgb=RGBColor(0x22,0x22,0x55))

# footer
add_label(s1, 0.2, 7.0, 12.9, 0.4,
          "References: Guyton & Hall (2021) p.950–954 | Lippincott Biochemistry 8e p.664–665 | Ganong's Review 26e p.3287 | Brenner & Rector's Kidney p.647 | Goldman-Cecil Medicine",
          size=8, rgb=RGBColor(0x88,0x88,0x88))

# ══════════════════════════════════════════════════════════════════
# SLIDE 2 — 11β-HSD isoforms comparison table
# ══════════════════════════════════════════════════════════════════
s2 = prs.slides.add_slide(blank)
set_bg(s2, RGBColor(0xF7, 0xF9, 0xFF))
hdr2 = s2.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(1.2))
hdr2.fill.solid(); hdr2.fill.fore_color.rgb = C_TITLE_BG; hdr2.line.fill.background()
add_label(s2, 0.3, 0.1, 12.7, 0.9, "The 11β-HSD Enzyme System — Pre-receptor Gatekeeper",
          size=26, bold=True, rgb=C_TITLE_FG)

# Table headers
cols = ["Feature", "11β-HSD Type 1", "11β-HSD Type 2"]
col_x = [0.3, 3.5, 8.0]
col_w = [3.0, 4.3, 4.9]
row_data = [
    ("Direction",    "Cortisone → Cortisol\n(Reductase — ACTIVATES)",
                     "Cortisol → Cortisone\n(Dehydrogenase — INACTIVATES)"),
    ("Cofactor",     "NADPH-dependent",           "NAD⁺-dependent"),
    ("Tissues",      "Liver, Adipose, Brain,\nSkin, Skeletal muscle",
                     "Kidney, Salivary glands,\nColon, Sweat glands, Placenta"),
    ("Net Effect",   "Amplifies glucocorticoid\naction locally",
                     "Protects mineralocorticoid\nreceptor from cortisol"),
    ("Clinical relevance",
                     "↑ in obesity → insulin\nresistance; cognitive decline",
                     "Deficiency → Apparent\nMineralocorticoid Excess (AME)"),
]
header_fills = [RGBColor(0x1A,0x3A,0x5C), RGBColor(0x2E,0x7D,0x32), RGBColor(0xC6,0x28,0x28)]
header_fgs   = [C_WHITE, C_WHITE, C_WHITE]

for ci, (col, cx, cw) in enumerate(zip(cols, col_x, col_w)):
    add_box(s2, cx, 1.3, cw, 0.55, header_fills[ci], col,
            font_size=14, bold=True, font_rgb=header_fgs[ci],
            border_rgb=RGBColor(0xFF,0xFF,0xFF), border_pt=1.5)

row_fills = [C_BOX_YELLOW, C_BOX_GREY, C_BOX_GREEN, C_BOX_BLUE, C_BOX_RED]
for ri, (label, v1, v2) in enumerate(row_data):
    ry = 1.9 + ri * 0.98
    add_box(s2, 0.3,  ry, 3.0, 0.88, RGBColor(0xEE,0xEE,0xEE), label,
            font_size=12, bold=True)
    add_box(s2, 3.5,  ry, 4.3, 0.88, row_fills[ri], v1,  font_size=11)
    add_box(s2, 8.0,  ry, 4.9, 0.88, row_fills[ri], v2,  font_size=11)

add_label(s2, 0.2, 7.0, 12.9, 0.4,
          "References: Guyton & Hall (2021) p.953–954 | Wikipedia: 11β-Hydroxysteroid dehydrogenase | Brenner & Rector's Kidney p.647",
          size=8, rgb=RGBColor(0x88,0x88,0x88))

# ══════════════════════════════════════════════════════════════════
# SLIDE 3 — Simple Flowchart: Cortisol Metabolism
# ══════════════════════════════════════════════════════════════════
s3 = prs.slides.add_slide(blank)
set_bg(s3, RGBColor(0xF7, 0xF9, 0xFF))
hdr3 = s3.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(1.1))
hdr3.fill.solid(); hdr3.fill.fore_color.rgb = C_TITLE_BG; hdr3.line.fill.background()
add_label(s3, 0.3, 0.1, 12.7, 0.85, "Cortisol Metabolism — Simple Flowchart",
          size=26, bold=True, rgb=C_TITLE_FG)

# Central cortisol box (top centre)
add_box(s3, 4.9, 1.2, 3.5, 0.75, C_BOX_YELLOW,
        "CORTISOL (Active)\nSecreted by Adrenal Cortex", font_size=12, bold=True)

# Arrow down-left to Kidney branch
add_arrow(s3, 5.0, 1.95, 2.2, 3.0)
# Arrow down-right to Liver/HSD1 branch
add_arrow(s3, 8.3, 1.95, 11.1, 3.0)
# Arrow straight down to Liver catabolism
add_arrow(s3, 6.65, 1.95, 6.65, 3.0)

# ── LEFT: Kidney / Salivary ──────────────────────────────────────
add_box(s3, 0.3, 3.0, 3.8, 0.75, C_BOX_BLUE,
        "Kidney | Salivary Glands\nColon | Sweat Glands", font_size=11, bold=True)
add_arrow(s3, 2.2, 3.75, 2.2, 4.5)
add_label(s3, 0.3, 3.78, 3.8, 0.65, "11β-HSD2\n(NAD⁺, Dehydrogenase)", size=10,
          rgb=RGBColor(0x77,0x00,0x00))
add_box(s3, 0.3, 4.5, 3.8, 0.65, C_BOX_GREY,
        "CORTISONE (Inactive)", font_size=12, bold=True)
add_arrow(s3, 2.2, 5.15, 2.2, 5.85)
add_box(s3, 0.3, 5.85, 3.8, 0.75, C_BOX_RED,
        "MR PROTECTED\n✗ Cannot activate Mineralocorticoid Receptor", font_size=10)

# ── CENTRE: Liver catabolism ─────────────────────────────────────
add_box(s3, 4.9, 3.0, 3.5, 0.7, C_BOX_YELLOW,
        "LIVER (Catabolism)", font_size=12, bold=True)
add_arrow(s3, 6.65, 3.7, 6.65, 4.4)
add_label(s3, 4.9, 3.72, 3.5, 0.65,
          "5α/5β-Reductase + 3α-HSD", size=10, rgb=RGBColor(0x00,0x55,0x00))
add_box(s3, 4.9, 4.4, 3.5, 0.7, C_BOX_GREEN,
        "THF / allo-THF / THE\n(Tetrahydro metabolites)", font_size=11)
add_arrow(s3, 6.65, 5.1, 6.65, 5.75)
add_label(s3, 4.9, 5.12, 3.5, 0.6,
          "Glucuronide conjugation", size=10, rgb=RGBColor(0x00,0x55,0x00))
add_box(s3, 4.9, 5.75, 3.5, 0.65, C_BOX_BLUE,
        "URINE EXCRETION\n(Water-soluble conjugates)", font_size=11)

# ── RIGHT: Liver HSD1 / Amplification ────────────────────────────
add_box(s3, 9.2, 3.0, 3.9, 0.75, C_BOX_GREY,
        "Liver | Adipose | Brain\nSkin | Skeletal Muscle", font_size=11, bold=True)
add_arrow(s3, 11.15, 3.75, 11.15, 4.45)
add_label(s3, 9.2, 3.78, 3.9, 0.65, "11β-HSD1\n(NADPH, Reductase — ACTIVATES)", size=10,
          rgb=RGBColor(0x00,0x44,0x88))
add_box(s3, 9.2, 4.45, 3.9, 0.7, C_BOX_YELLOW,
        "CORTISOL (Active)\n→ Glucocorticoid Receptor (GR)", font_size=11, bold=True)
add_arrow(s3, 11.15, 5.15, 11.15, 5.8)
add_box(s3, 9.2, 5.8, 3.9, 0.8, C_BOX_GREEN,
        "↑ Gluconeogenesis  ↑ Lipolysis\n↓ Immune response  ↑ Protein catabolism",
        font_size=10)

add_label(s3, 0.2, 7.0, 12.9, 0.4,
          "References: Guyton & Hall (2021) p.950–954 | Lippincott Biochemistry 8e p.664–665 | Ganong's Review 26e p.3287 | Brenner & Rector's Kidney p.647",
          size=8, rgb=RGBColor(0x88,0x88,0x88))

# ══════════════════════════════════════════════════════════════════
# SLIDE 4 — Kidney in detail
# ══════════════════════════════════════════════════════════════════
s4 = prs.slides.add_slide(blank)
set_bg(s4, RGBColor(0xF7, 0xF9, 0xFF))
hdr4 = s4.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(1.1))
hdr4.fill.solid(); hdr4.fill.fore_color.rgb = C_TITLE_BG; hdr4.line.fill.background()
add_label(s4, 0.3, 0.1, 12.7, 0.85, "Kidney — Role of 11β-HSD2",
          size=26, bold=True, rgb=C_TITLE_FG)

points_kidney = [
    ("11β-HSD2 in distal tubule / cortical collecting duct",
     "Converts cortisol → cortisone (NAD⁺-dependent)"),
    ("Why it matters",
     "Cortisol circulates at ~1000× the concentration of aldosterone\nbut BOTH have equal affinity for the mineralocorticoid receptor (MR)"),
    ("Normal state",
     "11β-HSD2 inactivates cortisol → only aldosterone activates MR\n→ normal Na⁺ reabsorption, K⁺ excretion, blood pressure"),
    ("If 11β-HSD2 fails (AME / Licorice abuse)",
     "Cortisol floods MR → Na⁺ retention, hypertension, hypokalemia\nSuppressed renin, angiotensin II and aldosterone"),
    ("Diagnostic marker",
     "Urinary free cortisol : cortisone (UFF:UFE) ratio\n↑ ratio = impaired renal 11β-HSD2 activity"),
]

for i, (title, body) in enumerate(points_kidney):
    ry = 1.25 + i * 1.12
    add_box(s4, 0.4, ry, 4.5, 0.95, C_BOX_BLUE, title, font_size=12, bold=True)
    add_box(s4, 5.1, ry, 7.9, 0.95, C_BOX_GREY, body, font_size=11)

add_label(s4, 0.2, 7.0, 12.9, 0.4,
          "References: Guyton & Hall (2021) p.953 | Ganong's Review 26e p.3287 | Brenner & Rector's Kidney p.647 | Goldman-Cecil Medicine",
          size=8, rgb=RGBColor(0x88,0x88,0x88))

# ══════════════════════════════════════════════════════════════════
# SLIDE 5 — Liver in detail
# ══════════════════════════════════════════════════════════════════
s5 = prs.slides.add_slide(blank)
set_bg(s5, RGBColor(0xF7, 0xF9, 0xFF))
hdr5 = s5.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(1.1))
hdr5.fill.solid(); hdr5.fill.fore_color.rgb = C_TITLE_BG; hdr5.line.fill.background()
add_label(s5, 0.3, 0.1, 12.7, 0.85, "Liver — Dual Role in Cortisol Metabolism",
          size=26, bold=True, rgb=C_TITLE_FG)

# Two columns
add_label(s5, 0.3, 1.15, 6.0, 0.5, "ROLE 1: ACTIVATION (11β-HSD1)",
          size=16, bold=True, rgb=RGBColor(0x1A,0x3A,0x5C))
add_label(s5, 7.0, 1.15, 6.0, 0.5, "ROLE 2: CATABOLISM & EXCRETION",
          size=16, bold=True, rgb=RGBColor(0x1A,0x3A,0x5C))

left_pts = [
    "Liver expresses 11β-HSD1 (NADPH reductase)",
    "Converts cortisone → active cortisol",
    "Amplifies glucocorticoid signalling locally",
    "↑ Gluconeogenesis (6–10× baseline)",
    "↑ Glycogen storage",
    "↑ Expression of gluconeogenic enzymes\n(PEPCK, G6Pase) via GR-mediated transcription",
    "↑ 11β-HSD1 in obesity → contributes to\ninsulin resistance & metabolic syndrome",
]
right_pts = [
    "5β-reductase (and 5α-reductase) reduce ring A",
    "→ Dihydrocortisol → Tetrahydrocortisol (THF)",
    "Cortisone → Tetrahydrocortisone (THE) via 5β-reductase",
    "Glucuronide (mainly) or sulfate conjugation",
    "Water-soluble conjugates excreted in urine",
    "Ratio (THF + allo-THF) : THE reflects\nhepatic 11β-HSD1 activity",
    "CBG (cortisol-binding globulin) also\nsynthesised by liver — liver disease ↓ CBG",
]

for i, pt in enumerate(left_pts):
    ry = 1.75 + i * 0.72
    b = s5.shapes.add_shape(1, Inches(0.3), Inches(ry), Inches(6.0), Inches(0.62))
    b.fill.solid(); b.fill.fore_color.rgb = C_BOX_YELLOW
    b.line.color.rgb = C_BOX_BORDER; b.line.width = Pt(0.75)
    tf = b.text_frame; tf.word_wrap = True; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    p = tf.paragraphs[0]; p.alignment = PP_ALIGN.LEFT
    run = p.add_run(); run.text = "• " + pt
    run.font.size = Pt(11); run.font.color.rgb = RGBColor(0x11,0x11,0x11)
    tf.margin_left = Pt(6)

for i, pt in enumerate(right_pts):
    ry = 1.75 + i * 0.72
    b = s5.shapes.add_shape(1, Inches(7.0), Inches(ry), Inches(6.1), Inches(0.62))
    b.fill.solid(); b.fill.fore_color.rgb = C_BOX_GREEN
    b.line.color.rgb = C_BOX_BORDER; b.line.width = Pt(0.75)
    tf = b.text_frame; tf.word_wrap = True; tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    p = tf.paragraphs[0]; p.alignment = PP_ALIGN.LEFT
    run = p.add_run(); run.text = "• " + pt
    run.font.size = Pt(11); run.font.color.rgb = RGBColor(0x11,0x11,0x11)
    tf.margin_left = Pt(6)

add_label(s5, 0.2, 7.0, 12.9, 0.4,
          "References: Guyton & Hall (2021) p.2055–2071 | Lippincott Biochemistry 8e p.664–665 | Goldman-Cecil Medicine p.443",
          size=8, rgb=RGBColor(0x88,0x88,0x88))

# ══════════════════════════════════════════════════════════════════
# SLIDE 6 — Salivary Glands
# ══════════════════════════════════════════════════════════════════
s6 = prs.slides.add_slide(blank)
set_bg(s6, RGBColor(0xF7, 0xF9, 0xFF))
hdr6 = s6.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(1.1))
hdr6.fill.solid(); hdr6.fill.fore_color.rgb = C_TITLE_BG; hdr6.line.fill.background()
add_label(s6, 0.3, 0.1, 12.7, 0.85, "Salivary Glands — Cortisol Metabolism & Diagnostic Use",
          size=26, bold=True, rgb=C_TITLE_FG)

sal_pts = [
    ("11β-HSD2 present in salivary gland epithelium",
     "Converts cortisol → cortisone\nProtects salivary mineralocorticoid receptors (regulate Na⁺/K⁺ in saliva)"),
    ("Salivary cortisol = FREE cortisol only",
     "Unlike serum (90–95% protein-bound)\nSaliva contains only the unbound, biologically active fraction"),
    ("Diagnostic — Late-night salivary cortisol",
     "Gold-standard non-invasive screen for Cushing's syndrome\nNormal: low at midnight; Cushing's: remains elevated"),
    ("Salivary cortisol : cortisone ratio",
     "Reflects local 11β-HSD2 activity\nHigh ratio = impaired inactivation (enzyme overwhelmed or deficient)"),
    ("Advantages of salivary sampling",
     "Non-invasive, stress-free, suitable for children, outpatients & research\nStable at room temperature for several hours"),
]

for i, (title, body) in enumerate(sal_pts):
    ry = 1.25 + i * 1.12
    add_box(s6, 0.4, ry, 4.5, 0.95, C_BOX_BLUE, title, font_size=12, bold=True)
    add_box(s6, 5.1, ry, 7.9, 0.95, C_BOX_GREY, body, font_size=11)

add_label(s6, 0.2, 7.0, 12.9, 0.4,
          "References: Guyton & Hall (2021) p.953 | Salivary Biomarkers Review, Univ. of Liverpool (2021) | Ganong's Review 26e p.3287",
          size=8, rgb=RGBColor(0x88,0x88,0x88))

# ══════════════════════════════════════════════════════════════════
# SLIDE 7 — Clinical Correlations
# ══════════════════════════════════════════════════════════════════
s7 = prs.slides.add_slide(blank)
set_bg(s7, RGBColor(0xF7, 0xF9, 0xFF))
hdr7 = s7.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(1.1))
hdr7.fill.solid(); hdr7.fill.fore_color.rgb = C_TITLE_BG; hdr7.line.fill.background()
add_label(s7, 0.3, 0.1, 12.7, 0.85, "Clinical Correlations",
          size=26, bold=True, rgb=C_TITLE_FG)

clin = [
    ("Apparent Mineralocorticoid\nExcess (AME)",
     "Genetic deficiency of 11β-HSD2\nCortisol activates renal MR\nHypertension + Hypokalemia + Suppressed aldosterone",
     C_BOX_RED),
    ("Licorice Abuse",
     "Glycyrrhetinic acid inhibits 11β-HSD2\nSame picture as AME\nReversible on stopping licorice",
     C_BOX_RED),
    ("Cushing's Syndrome",
     "Extreme cortisol excess overwhelms 11β-HSD2\nCortisol spills into MR → Na⁺ retention\nAlso adrenal diabetes, central obesity",
     C_BOX_RED),
    ("Obesity / Metabolic Syndrome",
     "↑ Adipose 11β-HSD1 → excess local cortisol\nContributes to insulin resistance, dyslipidaemia\nTarget for drug development (11β-HSD1 inhibitors)",
     C_BOX_YELLOW),
    ("Cushing's Screening",
     "Late-night salivary cortisol — validated first-line test\nUrinary free cortisol / 24-hr UFC\nLow-dose dexamethasone suppression test",
     C_BOX_BLUE),
    ("Diagnostic Ratios",
     "(THF + allo-THF) : THE → hepatic 11β-HSD1\nUFF : UFE (urinary) → renal 11β-HSD2\nSalivary cortisol : cortisone → salivary 11β-HSD2",
     C_BOX_GREEN),
]

for i, (title, body, fill) in enumerate(clin):
    col = i % 2
    row = i // 2
    cx = 0.3 + col * 6.6
    ry = 1.2 + row * 2.0
    add_box(s7, cx, ry, 3.0, 1.7, C_TITLE_BG, title, font_size=13, bold=True,
            font_rgb=C_WHITE, border_rgb=C_WHITE)
    add_box(s7, cx + 3.1, ry, 3.4, 1.7, fill, body, font_size=10)

add_label(s7, 0.2, 7.0, 12.9, 0.4,
          "References: Ganong's Review 26e p.3287 | Brenner & Rector's Kidney p.647 | Guyton & Hall (2021) p.953–954 | Liverpool Salivary Biomarkers Review (2021)",
          size=8, rgb=RGBColor(0x88,0x88,0x88))

# ══════════════════════════════════════════════════════════════════
# SLIDE 8 — References
# ══════════════════════════════════════════════════════════════════
s8 = prs.slides.add_slide(blank)
set_bg(s8, RGBColor(0xF7, 0xF9, 0xFF))
hdr8 = s8.shapes.add_shape(1, Inches(0), Inches(0), Inches(13.333), Inches(1.1))
hdr8.fill.solid(); hdr8.fill.fore_color.rgb = C_TITLE_BG; hdr8.line.fill.background()
add_label(s8, 0.3, 0.1, 12.7, 0.85, "References", size=26, bold=True, rgb=C_TITLE_FG)

refs = [
    "1.  Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. 14th ed. Elsevier; 2021. pp. 950–954.",
    "2.  Ferrier DR. Lippincott Illustrated Reviews: Biochemistry. 8th ed. Wolters Kluwer; 2022. pp. 664–665.",
    "3.  Barrett KE, et al. Ganong's Review of Medical Physiology. 26th ed. McGraw-Hill; 2019. p. 3287.",
    "4.  Yu ASL, et al. Brenner and Rector's The Kidney. 11th ed. Elsevier; 2020. p. 647.",
    "5.  Goldman L, Schafer AI. Goldman-Cecil Medicine. 26th ed. Elsevier; 2020. Chapter 203.",
    "6.  Chapman K, Holmes M, Seckl J. 11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of\n    Tissue Glucocorticoid Action. Physiol Rev. 2013;93(3):1139–1206. PMC3962546.",
    "7.  New MI, et al. 11β-Hydroxysteroid Dehydrogenase and Its Role in Apparent Mineralocorticoid Excess.\n    Pediatr Res. 1997;41(1):25–29.",
    "8.  Clow A, et al. Salivary Biomarkers of Health and Disease from Childhood to Older Adults.\n    University of Liverpool Repository; 2021.",
    "9.  Wikipedia: 11β-Hydroxysteroid dehydrogenase. Accessed July 2026.\n    https://en.wikipedia.org/wiki/11%CE%B2-Hydroxysteroid_dehydrogenase",
]

for i, ref in enumerate(refs):
    ry = 1.2 + i * 0.67
    tb = s8.shapes.add_textbox(Inches(0.5), Inches(ry), Inches(12.5), Inches(0.6))
    tf = tb.text_frame; tf.word_wrap = True
    p = tf.paragraphs[0]; p.alignment = PP_ALIGN.LEFT
    run = p.add_run(); run.text = ref
    run.font.size = Pt(12); run.font.color.rgb = C_REF_TXT

# ══════════════════════════════════════════════════════════════════
# SAVE
# ══════════════════════════════════════════════════════════════════
out = "/tmp/workspace/cortisol-ppt/Cortisol_Metabolism.pptx"
prs.save(out)
print(f"Saved: {out}")

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/cortisol-ppt/build_ppt.py'