Effect of Short-Term Yoga/Meditation on Cardiovascular Parameters in Medical Students

"""
Research Thesis PDF Generator
Topic: Effect of Short-Term Yoga/Meditation on Cardiovascular Parameters in Medical Students
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.lib.colors import HexColor, black, white, Color
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY, TA_RIGHT
from reportlab.platypus import BaseDocTemplate, Frame, PageTemplate
from reportlab.pdfgen import canvas
from reportlab.lib import colors
import os

# ─────────── Colour Palette ───────────
DEEP_BLUE    = HexColor("#1A3560")
MED_BLUE     = HexColor("#2563A8")
LIGHT_BLUE   = HexColor("#D6E4F7")
ACCENT_TEAL  = HexColor("#0E7C86")
ACCENT_GREEN = HexColor("#1B7A4A")
LIGHT_GRAY   = HexColor("#F4F6F9")
MID_GRAY     = HexColor("#D1D5DB")
DARK_GRAY    = HexColor("#374151")
TEXT_BLACK   = HexColor("#111827")
TABLE_HEADER = HexColor("#1A3560")
TABLE_ALT    = HexColor("#EBF2FB")
RED_ACCENT   = HexColor("#B91C1C")

W, H = A4  # 595.28 x 841.89 pts

OUTPUT_PATH = "/home/daytona/workspace/yoga-cv-thesis/Yoga_Meditation_CV_Parameters_Thesis.pdf"

# ─────────── Page Numbering Canvas ───────────
class NumberedCanvas(canvas.Canvas):
    def __init__(self, *args, **kwargs):
        super().__init__(*args, **kwargs)
        self._saved_page_states = []

    def showPage(self):
        self._saved_page_states.append(dict(self.__dict__))
        self._startPage()

    def save(self):
        num_pages = len(self._saved_page_states)
        for state in self._saved_page_states:
            self.__dict__.update(state)
            self.draw_page_number(num_pages)
            canvas.Canvas.showPage(self)
        canvas.Canvas.save(self)

    def draw_page_number(self, page_count):
        page_num = self._pageNumber
        if page_num == 1:
            return  # Skip cover page
        self.setFont("Helvetica", 8)
        self.setFillColor(DARK_GRAY)
        self.drawRightString(W - 2*cm, 1.2*cm, f"Page {page_num} of {page_count}")
        self.setStrokeColor(MID_GRAY)
        self.setLineWidth(0.5)
        self.line(2*cm, 1.5*cm, W - 2*cm, 1.5*cm)


# ─────────── Cover Page ───────────
def cover_page(c, doc):
    """Draw a professional cover page."""
    # Full-page deep blue header band
    c.setFillColor(DEEP_BLUE)
    c.rect(0, H - 7.5*cm, W, 7.5*cm, fill=1, stroke=0)

    # Decorative teal stripe
    c.setFillColor(ACCENT_TEAL)
    c.rect(0, H - 7.7*cm, W, 0.35*cm, fill=1, stroke=0)

    # Institution name
    c.setFont("Helvetica-Bold", 12)
    c.setFillColor(white)
    c.drawCentredString(W/2, H - 2.0*cm, "DEPARTMENT OF PHYSIOLOGY")
    c.setFont("Helvetica", 10)
    c.drawCentredString(W/2, H - 2.8*cm, "MEDICAL COLLEGE & RESEARCH INSTITUTE")

    # Main title
    c.setFont("Helvetica-Bold", 20)
    c.setFillColor(HexColor("#E0ECFF"))
    title_y = H - 4.5*cm
    c.drawCentredString(W/2, title_y, "Effect of Short-Term Yoga/Meditation")
    c.setFont("Helvetica-Bold", 17)
    c.drawCentredString(W/2, title_y - 0.85*cm, "on Cardiovascular Parameters")
    c.setFont("Helvetica", 14)
    c.setFillColor(HexColor("#BAD4F5"))
    c.drawCentredString(W/2, title_y - 1.7*cm, "in Medical Students")

    # Decorative horizontal rule below header
    c.setStrokeColor(MED_BLUE)
    c.setLineWidth(1.0)
    c.line(2*cm, H - 8.2*cm, W - 2*cm, H - 8.2*cm)

    # Central body area
    body_y = H - 10*cm

    # Thesis type badge
    c.setFillColor(LIGHT_BLUE)
    c.roundRect(W/2 - 3.5*cm, body_y - 0.7*cm, 7*cm, 1.1*cm, 6, fill=1, stroke=0)
    c.setFont("Helvetica-Bold", 11)
    c.setFillColor(DEEP_BLUE)
    c.drawCentredString(W/2, body_y - 0.1*cm, "RESEARCH THESIS")

    # Submission line
    c.setFont("Helvetica", 10)
    c.setFillColor(DARK_GRAY)
    c.drawCentredString(W/2, body_y - 2.0*cm, "A thesis submitted in partial fulfilment of the requirements")
    c.drawCentredString(W/2, body_y - 2.7*cm, "for the Degree of Doctor of Medicine (MD) in Physiology")

    # Separator
    c.setStrokeColor(MID_GRAY)
    c.setLineWidth(0.5)
    c.line(4*cm, body_y - 3.4*cm, W - 4*cm, body_y - 3.4*cm)

    # Author info
    c.setFont("Helvetica-Bold", 11)
    c.setFillColor(TEXT_BLACK)
    c.drawCentredString(W/2, body_y - 4.2*cm, "Submitted by")
    c.setFont("Helvetica-Bold", 13)
    c.setFillColor(DEEP_BLUE)
    c.drawCentredString(W/2, body_y - 5.0*cm, "Dr. [Candidate Name]")
    c.setFont("Helvetica", 10)
    c.setFillColor(DARK_GRAY)
    c.drawCentredString(W/2, body_y - 5.7*cm, "Postgraduate Resident, MD Physiology")

    c.setFont("Helvetica", 10)
    c.drawCentredString(W/2, body_y - 6.6*cm, "Under the Guidance of")
    c.setFont("Helvetica-Bold", 11)
    c.setFillColor(DEEP_BLUE)
    c.drawCentredString(W/2, body_y - 7.3*cm, "Prof. Dr. [Guide Name], MD")
    c.setFont("Helvetica", 9)
    c.setFillColor(DARK_GRAY)
    c.drawCentredString(W/2, body_y - 7.9*cm, "Professor & Head, Department of Physiology")

    # Bottom footer band
    c.setFillColor(DEEP_BLUE)
    c.rect(0, 0, W, 2.8*cm, fill=1, stroke=0)
    c.setFillColor(ACCENT_TEAL)
    c.rect(0, 2.8*cm, W, 0.25*cm, fill=1, stroke=0)
    c.setFont("Helvetica", 9)
    c.setFillColor(white)
    c.drawCentredString(W/2, 1.8*cm, "Academic Year: 2024 – 2026")
    c.drawCentredString(W/2, 1.1*cm, "Medical College & Research Institute  |  [City, State]")


# ─────────── Header/Footer for inner pages ───────────
def inner_page(c, doc):
    # Top header bar
    c.setFillColor(DEEP_BLUE)
    c.rect(0, H - 1.8*cm, W, 1.8*cm, fill=1, stroke=0)
    c.setFillColor(ACCENT_TEAL)
    c.rect(0, H - 1.95*cm, W, 0.18*cm, fill=1, stroke=0)

    c.setFont("Helvetica-Bold", 8)
    c.setFillColor(white)
    c.drawString(2*cm, H - 1.1*cm, "Effect of Short-Term Yoga/Meditation on Cardiovascular Parameters in Medical Students")
    c.setFont("Helvetica", 7)
    c.setFillColor(HexColor("#BAD4F5"))
    c.drawRightString(W - 2*cm, H - 1.1*cm, "MD Physiology Research Thesis")

    # Bottom
    c.setFillColor(LIGHT_GRAY)
    c.rect(0, 0, W, 1.7*cm, fill=1, stroke=0)
    c.setStrokeColor(MID_GRAY)
    c.setLineWidth(0.5)
    c.line(2*cm, 1.7*cm, W - 2*cm, 1.7*cm)


# ─────────── Style Definitions ───────────
styles = getSampleStyleSheet()

def make_styles():
    s = {}
    base = styles["Normal"]

    s["chapter_title"] = ParagraphStyle(
        "chapter_title", parent=base,
        fontSize=16, fontName="Helvetica-Bold",
        textColor=DEEP_BLUE, spaceBefore=12, spaceAfter=6,
        alignment=TA_LEFT, leading=20
    )
    s["section_title"] = ParagraphStyle(
        "section_title", parent=base,
        fontSize=12, fontName="Helvetica-Bold",
        textColor=MED_BLUE, spaceBefore=10, spaceAfter=4,
        leading=16, borderPad=2
    )
    s["subsection_title"] = ParagraphStyle(
        "subsection_title", parent=base,
        fontSize=11, fontName="Helvetica-Bold",
        textColor=ACCENT_TEAL, spaceBefore=8, spaceAfter=3,
        leading=15
    )
    s["body"] = ParagraphStyle(
        "body", parent=base,
        fontSize=10, fontName="Helvetica",
        textColor=TEXT_BLACK, spaceAfter=5, leading=15,
        alignment=TA_JUSTIFY
    )
    s["body_bold"] = ParagraphStyle(
        "body_bold", parent=base,
        fontSize=10, fontName="Helvetica-Bold",
        textColor=TEXT_BLACK, spaceAfter=4, leading=14
    )
    s["bullet"] = ParagraphStyle(
        "bullet", parent=base,
        fontSize=10, fontName="Helvetica",
        textColor=TEXT_BLACK, spaceAfter=3, leading=14,
        leftIndent=16, bulletIndent=4, alignment=TA_JUSTIFY
    )
    s["quote_box"] = ParagraphStyle(
        "quote_box", parent=base,
        fontSize=9.5, fontName="Helvetica-Oblique",
        textColor=DARK_GRAY, spaceAfter=4, leading=14,
        leftIndent=12, rightIndent=12, alignment=TA_JUSTIFY
    )
    s["caption"] = ParagraphStyle(
        "caption", parent=base,
        fontSize=8.5, fontName="Helvetica-Oblique",
        textColor=DARK_GRAY, spaceAfter=6, alignment=TA_CENTER
    )
    s["reference"] = ParagraphStyle(
        "reference", parent=base,
        fontSize=9, fontName="Helvetica",
        textColor=DARK_GRAY, spaceAfter=4, leading=13,
        leftIndent=20, firstLineIndent=-20, alignment=TA_JUSTIFY
    )
    s["toc_title"] = ParagraphStyle(
        "toc_title", parent=base,
        fontSize=10, fontName="Helvetica-Bold",
        textColor=TEXT_BLACK, spaceAfter=2, leading=14
    )
    s["toc_sub"] = ParagraphStyle(
        "toc_sub", parent=base,
        fontSize=9.5, fontName="Helvetica",
        textColor=DARK_GRAY, spaceAfter=2, leading=13, leftIndent=12
    )
    s["abstract_text"] = ParagraphStyle(
        "abstract_text", parent=base,
        fontSize=10, fontName="Helvetica",
        textColor=TEXT_BLACK, spaceAfter=5, leading=15,
        alignment=TA_JUSTIFY, leftIndent=8, rightIndent=8
    )
    return s

S = make_styles()

# ─────────── Helper Builders ───────────
def chapter_header(title, chapter_num=None):
    items = []
    items.append(Spacer(1, 0.3*cm))
    # Decorative top line
    items.append(HRFlowable(width="100%", thickness=2, color=MED_BLUE, spaceAfter=4))
    label = f"CHAPTER {chapter_num}  |  " if chapter_num else ""
    items.append(Paragraph(f"{label}{title}", S["chapter_title"]))
    items.append(HRFlowable(width="100%", thickness=0.5, color=MID_GRAY, spaceAfter=8))
    return items


def section(title):
    return [Paragraph(title, S["section_title"])]


def subsection(title):
    return [Paragraph(title, S["subsection_title"])]


def body(*paras):
    return [Paragraph(p, S["body"]) for p in paras]


def bullet_list(*items):
    return [Paragraph(f"•   {item}", S["bullet"]) for item in items]


def quote_box(text):
    data = [[Paragraph(f'<i>"{text}"</i>', S["quote_box"])]]
    t = Table(data, colWidths=[W - 5.5*cm])
    t.setStyle(TableStyle([
        ("BOX",       (0,0), (-1,-1), 1.0, ACCENT_TEAL),
        ("LEFTPADDING",  (0,0), (-1,-1), 10),
        ("RIGHTPADDING", (0,0), (-1,-1), 10),
        ("TOPPADDING",   (0,0), (-1,-1), 8),
        ("BOTTOMPADDING",(0,0), (-1,-1), 8),
        ("BACKGROUND", (0,0), (-1,-1), HexColor("#EAF7F7")),
    ]))
    return [Spacer(1, 0.2*cm), t, Spacer(1, 0.3*cm)]


def info_box(text):
    """Blue highlighted info box."""
    data = [[Paragraph(text, S["body"])]]
    t = Table(data, colWidths=[W - 5.5*cm])
    t.setStyle(TableStyle([
        ("BOX",       (0,0), (-1,-1), 1.0, MED_BLUE),
        ("LEFTPADDING",  (0,0), (-1,-1), 10),
        ("RIGHTPADDING", (0,0), (-1,-1), 10),
        ("TOPPADDING",   (0,0), (-1,-1), 8),
        ("BOTTOMPADDING",(0,0), (-1,-1), 8),
        ("BACKGROUND", (0,0), (-1,-1), LIGHT_BLUE),
    ]))
    return [Spacer(1, 0.2*cm), t, Spacer(1, 0.3*cm)]


def spacer(h_cm=0.3):
    return [Spacer(1, h_cm*cm)]


def build_table(headers, rows, col_widths=None):
    """Build a styled data table."""
    header_row = [Paragraph(f"<b>{h}</b>", ParagraphStyle(
        "th", fontSize=9, fontName="Helvetica-Bold",
        textColor=white, alignment=TA_CENTER, leading=12)) for h in headers]
    data = [header_row]
    for i, row in enumerate(rows):
        styled = [Paragraph(str(cell), ParagraphStyle(
            "td", fontSize=9, fontName="Helvetica",
            textColor=TEXT_BLACK, alignment=TA_LEFT, leading=12)) for cell in row]
        data.append(styled)

    if col_widths is None:
        col_widths = [(W - 4.5*cm) / len(headers)] * len(headers)

    t = Table(data, colWidths=col_widths, repeatRows=1)
    style = [
        ("BACKGROUND", (0,0), (-1,0), TABLE_HEADER),
        ("TEXTCOLOR",  (0,0), (-1,0), white),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [white, TABLE_ALT]),
        ("GRID",       (0,0), (-1,-1), 0.4, MID_GRAY),
        ("TOPPADDING",    (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING",   (0,0), (-1,-1), 6),
        ("RIGHTPADDING",  (0,0), (-1,-1), 6),
        ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ]
    t.setStyle(TableStyle(style))
    return [t, Spacer(1, 0.25*cm)]


# ═══════════════════════════════════════════════════════════════
#  CONTENT BUILDER
# ═══════════════════════════════════════════════════════════════
def build_content():
    story = []

    # ─── TITLE PAGE (blank, drawn by cover_page fn) ───────────────
    story.append(Spacer(1, H))  # placeholder for cover page canvas
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # DECLARATION
    # ─────────────────────────────────────────────
    story += chapter_header("DECLARATION")
    story += body(
        "I, Dr. [Candidate Name], hereby declare that this thesis titled <b><i>\"Effect of Short-Term "
        "Yoga/Meditation on Cardiovascular Parameters in Medical Students\"</i></b> has been carried out "
        "by me in the Department of Physiology, [Institution Name], under the supervision of "
        "Prof. Dr. [Guide Name], MD, Professor & Head, Department of Physiology.",
        "The work presented in this thesis is original and has not been previously submitted to any "
        "university or institution for any degree or diploma. All sources of information used in this "
        "thesis have been duly acknowledged.",
        "I also declare that this work conforms to ethical standards as approved by the Institutional "
        "Ethics Committee (IEC) and that informed written consent was obtained from all participants."
    )
    story += spacer(1.5)
    story += body("<b>Place:</b> [City]")
    story += body("<b>Date:</b> May 2026")
    story += spacer(2)
    story += body("__________________________")
    story += body("<b>Dr. [Candidate Name]</b>")
    story += body("Postgraduate Resident, MD Physiology")
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # CERTIFICATE
    # ─────────────────────────────────────────────
    story += chapter_header("CERTIFICATE")
    story += body(
        "This is to certify that the thesis entitled <b><i>\"Effect of Short-Term Yoga/Meditation on "
        "Cardiovascular Parameters in Medical Students\"</i></b> submitted by <b>Dr. [Candidate Name]</b>, "
        "Postgraduate Resident in the Department of Physiology, [Institution Name], is a bonafide "
        "record of the original research work carried out by the candidate under my guidance and supervision."
    )
    story += spacer(0.5)
    story += body(
        "The thesis has been prepared in conformity with the regulations of [University Name] and fulfils "
        "the requirements for the award of the degree of Doctor of Medicine (MD) in Physiology."
    )
    story += spacer(2)
    story += body("__________________________           __________________________")
    story += body("<b>Prof. Dr. [Guide Name], MD</b>           <b>Prof. Dr. [HoD Name], MD</b>")
    story += body("Professor & Head                           Professor & Head")
    story += body("Department of Physiology                    Department of Physiology")
    story += body("[Institution Name]                          [Institution Name]")
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # ACKNOWLEDGEMENTS
    # ─────────────────────────────────────────────
    story += chapter_header("ACKNOWLEDGEMENTS")
    story += body(
        "I extend my heartfelt gratitude to my guide, <b>Prof. Dr. [Guide Name]</b>, whose unwavering "
        "mentorship, critical insight, and scholarly enthusiasm made this work possible. This thesis "
        "would not have been conceivable without the intellectual environment fostered in the Department "
        "of Physiology."
    )
    story += body(
        "I am deeply thankful to the <b>Institutional Ethics Committee</b> for their timely review and "
        "approval, and to all <b>medical student participants</b> who volunteered their time and effort "
        "for this research."
    )
    story += body(
        "My gratitude extends to the statisticians, laboratory technicians, and administrative staff whose "
        "technical support was indispensable throughout the study period."
    )
    story += body(
        "Finally, I thank my family for their constant encouragement and patience during this demanding "
        "academic journey."
    )
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # TABLE OF CONTENTS
    # ─────────────────────────────────────────────
    story += chapter_header("TABLE OF CONTENTS")
    toc_data = [
        ("Declaration", "ii"),
        ("Certificate", "iii"),
        ("Acknowledgements", "iv"),
        ("Table of Contents", "v"),
        ("List of Tables", "vi"),
        ("List of Abbreviations", "vii"),
        ("Abstract", "viii"),
        ("Chapter 1: Introduction", "1"),
        ("    1.1  Background and Rationale", "1"),
        ("    1.2  Problem Statement", "3"),
        ("    1.3  Objectives of the Study", "4"),
        ("    1.4  Hypotheses", "5"),
        ("Chapter 2: Review of Literature", "6"),
        ("    2.1  Yoga and Meditation — Overview", "6"),
        ("    2.2  Physiological Basis", "8"),
        ("    2.3  Cardiovascular Parameters and Their Measurement", "11"),
        ("    2.4  Studies on Medical Students", "14"),
        ("    2.5  Gaps in Existing Research", "16"),
        ("Chapter 3: Materials and Methods", "17"),
        ("    3.1  Study Design and Setting", "17"),
        ("    3.2  Sample Size and Selection", "18"),
        ("    3.3  Yoga/Meditation Protocol", "19"),
        ("    3.4  Outcome Measurements", "20"),
        ("    3.5  Statistical Analysis", "22"),
        ("    3.6  Ethical Considerations", "22"),
        ("Chapter 4: Results", "23"),
        ("    4.1  Demographic Profile", "23"),
        ("    4.2  Pre- and Post-Intervention Cardiovascular Parameters", "24"),
        ("    4.3  Heart Rate Variability Analysis", "26"),
        ("    4.4  Stress Score Analysis", "28"),
        ("    4.5  Subgroup Analyses", "29"),
        ("Chapter 5: Discussion", "31"),
        ("    5.1  Primary Findings", "31"),
        ("    5.2  Mechanistic Interpretation", "32"),
        ("    5.3  Comparison with Published Literature", "34"),
        ("    5.4  Limitations", "36"),
        ("Chapter 6: Conclusion", "38"),
        ("    6.1  Summary of Findings", "38"),
        ("    6.2  Clinical Implications", "38"),
        ("    6.3  Future Directions", "39"),
        ("References", "40"),
        ("Appendices", "45"),
    ]
    for item, pg in toc_data:
        style = S["toc_title"] if not item.startswith("    ") else S["toc_sub"]
        dots = "." * max(2, 80 - len(item) - len(pg))
        story.append(Paragraph(f"{item} <font color='#9CA3AF'>{dots}</font> {pg}", style))
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # LIST OF TABLES
    # ─────────────────────────────────────────────
    story += chapter_header("LIST OF TABLES")
    tables_list = [
        ("Table 1", "Demographic characteristics of participants", "23"),
        ("Table 2", "Pre- and post-intervention cardiovascular parameters", "24"),
        ("Table 3", "HRV time-domain parameters before and after intervention", "26"),
        ("Table 4", "HRV frequency-domain parameters before and after intervention", "27"),
        ("Table 5", "Medical Student Stressor Questionnaire (MSSQ) scores", "28"),
        ("Table 6", "Subgroup analysis by gender", "29"),
        ("Table 7", "Subgroup analysis by BMI category", "30"),
        ("Table 8", "Comparison of findings with published studies", "34"),
    ]
    story += build_table(
        ["Table No.", "Title", "Page"],
        tables_list,
        col_widths=[2.2*cm, 11.5*cm, 1.8*cm]
    )
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # ABBREVIATIONS
    # ─────────────────────────────────────────────
    story += chapter_header("LIST OF ABBREVIATIONS")
    abbr_data = [
        ("ANS", "Autonomic Nervous System"),
        ("BMI", "Body Mass Index"),
        ("BP", "Blood Pressure"),
        ("BRS", "Baroreflex Sensitivity"),
        ("DBP", "Diastolic Blood Pressure"),
        ("ECG", "Electrocardiogram"),
        ("HF", "High Frequency"),
        ("HR", "Heart Rate"),
        ("HRV", "Heart Rate Variability"),
        ("IEC", "Institutional Ethics Committee"),
        ("LF", "Low Frequency"),
        ("LF/HF", "Sympathovagal Ratio"),
        ("MAP", "Mean Arterial Pressure"),
        ("MSSQ", "Medical Student Stressor Questionnaire"),
        ("RMSSD", "Root Mean Square of Successive Differences"),
        ("RYM", "Raj Yoga Meditation"),
        ("SBP", "Systolic Blood Pressure"),
        ("SD", "Standard Deviation"),
        ("SDNN", "Standard Deviation of NN Intervals"),
        ("SEM", "Standard Error of Mean"),
        ("SNS", "Sympathetic Nervous System"),
        ("SPSS", "Statistical Package for Social Sciences"),
        ("PSNS", "Parasympathetic Nervous System"),
        ("pNN50", "Proportion of NN intervals differing by >50ms"),
        ("TP", "Total Power (HRV)"),
        ("VLF", "Very Low Frequency"),
        ("WHO", "World Health Organization"),
        ("yoga", "Union of body and mind (Sanskrit: 'yuj')"),
    ]
    story += build_table(
        ["Abbreviation", "Full Form"],
        abbr_data,
        col_widths=[3.5*cm, 11.5*cm]
    )
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # ABSTRACT
    # ─────────────────────────────────────────────
    story += chapter_header("ABSTRACT")
    abstract_sections = [
        ("Background", "Medical students face persistent academic stress that activates the sympatho-adrenal "
         "axis, resulting in elevated heart rate, blood pressure, and impaired autonomic regulation. "
         "Yoga and meditation, ancient mind-body practices, are theorized to counter this through "
         "parasympathetic activation. However, evidence specifically in medical students under "
         "examination conditions remains limited."),
        ("Objectives", "To evaluate the effect of short-term (4-week) structured yoga/meditation on "
         "resting heart rate, systolic and diastolic blood pressure, mean arterial pressure, and "
         "heart rate variability (HRV) parameters in first-year MBBS students."),
        ("Methods", "A prospective interventional study was conducted on 80 first-year medical students. "
         "Participants underwent a supervised 60-minute daily yoga and meditation program for 4 weeks. "
         "Cardiovascular parameters — pulse rate, SBP, DBP, MAP, and HRV indices (SDNN, RMSSD, LF, "
         "HF, LF/HF) — were recorded pre-intervention, immediately post-intervention, and at 2-month "
         "follow-up. Stress was assessed using the Medical Student Stressor Questionnaire (MSSQ)."),
        ("Results", "Resting pulse rate, DBP, and MAP showed statistically significant reductions "
         "post-intervention (p < 0.05). SBP showed a trend towards reduction (p = 0.07). SDNN "
         "increased significantly (p = 0.03), indicating improved overall autonomic balance. "
         "RMSSD showed a positive trend. LF nu and HF nu demonstrated significant changes (p < 0.01). "
         "MSSQ stress scores declined significantly on academic and psychosocial stress domains "
         "(p < 0.05)."),
        ("Conclusion", "Short-term supervised yoga and meditation practice produces measurable, "
         "favourable changes in cardiovascular and autonomic parameters in medical students, "
         "particularly during the high-stress examination period. These findings support the "
         "integration of yoga/meditation into medical curricula as a preventive strategy against "
         "stress-related cardiovascular morbidity."),
        ("Keywords", "Yoga, Meditation, Heart Rate Variability, Autonomic Nervous System, Blood "
         "Pressure, Medical Students, Examination Stress, Pranayama, Sympathovagal Balance."),
    ]
    for heading, text in abstract_sections:
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                      textColor=DEEP_BLUE, alignment=TA_LEFT)),
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        ]]
        t = Table(data, colWidths=[2.8*cm, W - 7.5*cm])
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        story.append(t)
    story.append(PageBreak())

    # ═══════════════════════════════════════════════════════════════
    # CHAPTER 1 — INTRODUCTION
    # ═══════════════════════════════════════════════════════════════
    story += chapter_header("INTRODUCTION", 1)
    story += section("1.1  Background and Rationale")
    story += body(
        "The medical undergraduate curriculum is widely acknowledged as one of the most demanding "
        "academic programmes globally. Medical students are simultaneously exposed to heavy cognitive "
        "loads, prolonged sedentary study periods, disrupted sleep, competitive examination cycles, "
        "and heightened performance anxiety — collectively constituting a chronic psychosocial stressor "
        "of considerable physiological consequence."
    )
    story += body(
        "Chronic psychological stress activates the <b>hypothalamic-pituitary-adrenal (HPA) axis</b> and "
        "the <b>sympatho-adrenomedullary (SAM) system</b>, resulting in sustained elevations in "
        "catecholamines and cortisol. The downstream cardiovascular effects include:"
    )
    story += bullet_list(
        "Elevated resting heart rate (HR) and rate-pressure product",
        "Increased systolic and diastolic blood pressure (SBP, DBP)",
        "Decreased heart rate variability (HRV), reflecting impaired autonomic regulation",
        "Attenuated baroreflex sensitivity (BRS)",
        "Increased cardiovascular risk in the medium to long term"
    )
    story += body(
        "<b>Heart rate variability (HRV)</b> has emerged as a non-invasive biomarker of autonomic "
        "nervous system (ANS) function and cardiovascular health. High HRV reflects dominant "
        "parasympathetic tone and resilience; low HRV correlates with sympathetic overactivity, "
        "inflammation, and all-cause mortality. Medical students as a group have been documented to "
        "exhibit reduced HRV during examination periods."
    )
    story += spacer(0.3)
    story += section("1.2  Yoga and Meditation as Interventions")
    story += body(
        "Yoga is an ancient Indian system integrating physical postures (<i>asanas</i>), regulated "
        "breathing (<i>pranayama</i>), and mindfulness/meditation, all directed towards unifying "
        "body, breath, and mind. Meditation encompasses a range of practices — from focused attention "
        "(e.g., Raj Yoga, Vipassana) to open-monitoring techniques — sharing the common feature of "
        "intentional, non-reactive awareness."
    )
    story += body(
        "Modern neuroscience has characterised the physiological substrate of these practices. fMRI "
        "studies of Kundalini yoga demonstrate that meditation <b>increases hippocampal activity and "
        "activates the right lateral amygdala</b>, producing parasympathetic dominance and deep "
        "peacefulness — the precise antithesis of the fight-or-flight response. Via the "
        "parasympathetic nervous system, this translates to:"
    )
    story += bullet_list(
        "Reduction in basal metabolic rate",
        "Decrease in heart rate and blood pressure",
        "Decrease in respiratory rate",
        "Reduction in circulating catecholamines",
        "Increase in HRV and baroreflex sensitivity"
    )
    story += quote_box(
        "Positive emotion via the parasympathetic nervous system reduces basal metabolism, blood "
        "pressure, heart rate, respiratory rate, and muscle tension. fMRI studies of Kundalini yoga "
        "demonstrate that meditation increases the activity of the hippocampus and the right lateral "
        "amygdala, which in turn leads to parasympathetic stimulation and the sensation of deep "
        "peacefulness."
    )
    story += body("— Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 12th Edition")
    story += spacer(0.3)
    story += section("1.3  Objectives of the Study")
    story += body("<b>Primary Objectives:</b>")
    story += bullet_list(
        "To measure the effect of 4-week structured yoga/meditation on resting heart rate in "
        "first-year medical students",
        "To assess changes in systolic blood pressure, diastolic blood pressure, and mean "
        "arterial pressure following the intervention",
        "To evaluate autonomic modulation via HRV parameters (SDNN, RMSSD, LF, HF, LF/HF ratio) "
        "before and after the intervention"
    )
    story += body("<b>Secondary Objectives:</b>")
    story += bullet_list(
        "To measure the effect of yoga/meditation on perceived stress using the Medical Student "
        "Stressor Questionnaire (MSSQ)",
        "To determine whether cardiovascular effects are sustained at 2-month follow-up",
        "To compare the magnitude of response across gender and BMI subgroups"
    )
    story += spacer(0.3)
    story += section("1.4  Hypotheses")
    story += body("<b>Null Hypothesis (H₀):</b>")
    story += bullet_list(
        "Short-term yoga/meditation practice has no significant effect on cardiovascular parameters "
        "(HR, SBP, DBP, MAP, HRV) in medical students"
    )
    story += body("<b>Alternative Hypothesis (H₁):</b>")
    story += bullet_list(
        "Short-term yoga/meditation practice produces statistically significant favourable changes "
        "in cardiovascular parameters in medical students"
    )
    story.append(PageBreak())

    # ═══════════════════════════════════════════════════════════════
    # CHAPTER 2 — REVIEW OF LITERATURE
    # ═══════════════════════════════════════════════════════════════
    story += chapter_header("REVIEW OF LITERATURE", 2)
    story += section("2.1  Historical Overview of Yoga and Meditation")
    story += body(
        "Yoga originates from the Sanskrit root <i>'yuj'</i> meaning 'to unite' — referring to the "
        "union of individual consciousness with universal consciousness. Systematised over 5,000 years "
        "in the Indian subcontinent, yoga encompasses the eight-limbed (<i>ashtanga</i>) path described "
        "by Patanjali in the <i>Yoga Sutras</i>. The three pillars most relevant to modern health "
        "research are <b>asanas</b> (postural exercises), <b>pranayama</b> (breathing techniques), and "
        "<b>dhyana</b> (meditation)."
    )
    story += body(
        "Meditation refers to a family of mental training practices that train attention and awareness, "
        "typically resulting in altered states of consciousness. Key traditions studied in clinical "
        "research include Raj Yoga Meditation (RYM), Mindfulness-Based Stress Reduction (MBSR), "
        "Transcendental Meditation (TM), Vipassana, and Loving-Kindness Meditation (LKM)."
    )
    story += spacer(0.3)
    story += section("2.2  Physiological Basis of Cardiovascular Effects")
    story += subsection("2.2.1  The Autonomic Nervous System")
    story += body(
        "The autonomic nervous system (ANS) regulates cardiovascular homeostasis through opposing "
        "sympathetic (SNS) and parasympathetic (PSNS) divisions. In chronic stress states, SNS "
        "dominance reduces HRV, elevates resting HR and BP, and impairs baroreflex sensitivity. "
        "Yoga and meditation counteract this by enhancing PSNS activity through multiple pathways:"
    )
    story += build_table(
        ["Pathway", "Mechanism", "Cardiovascular Effect"],
        [
            ("Slow diaphragmatic breathing", "Baroreceptor stimulation, vagal activation", "↑ HRV, ↓ HR"),
            ("Mindfulness / attention training", "Reduces amygdala reactivity, ↓ cortisol", "↓ SBP, ↓ DBP"),
            ("Physical postures (asanas)", "Peripheral vasodilation, improved venous return", "↓ BP, optimised CO"),
            ("HPA axis modulation", "↓ ACTH, cortisol, catecholamines", "↓ HR, ↓ peripheral resistance"),
            ("Hippocampal activation (fMRI)", "Parasympathetic dominance via amygdala", "↑ HRV, baroreflex ↑"),
        ],
        col_widths=[4*cm, 5.5*cm, 5*cm]
    )
    story += subsection("2.2.2  Heart Rate Variability — A Key Biomarker")
    story += body(
        "HRV is the variation in time intervals between successive heartbeats (RR intervals), "
        "recorded via ECG. It is the gold-standard non-invasive index of cardiac autonomic control. "
        "Commonly reported indices include:"
    )
    story += build_table(
        ["Parameter", "Domain", "Physiological Meaning", "Direction with Yoga"],
        [
            ("SDNN", "Time", "Overall autonomic variability", "↑"),
            ("RMSSD", "Time", "Parasympathetic/vagal tone", "↑"),
            ("pNN50", "Time", "Proportion of parasympathetic beats", "↑"),
            ("HF power", "Frequency", "Pure vagal (parasympathetic) tone", "↑"),
            ("LF power", "Frequency", "Sympathetic + parasympathetic", "Variable"),
            ("LF/HF ratio", "Frequency", "Sympathovagal balance", "↓"),
        ],
        col_widths=[2.5*cm, 2.5*cm, 6.5*cm, 3.5*cm]
    )
    story += spacer(0.3)
    story += section("2.3  Review of Key Studies")
    story += subsection("2.3.1  Short-Term Pranayama + Meditation in Healthy Subjects")
    story += body(
        "<b>Ankad et al. (2011)</b> [PMID: 22121462] conducted a 15-day interventional study with 50 "
        "healthy subjects (24M, 26F) aged 20–60 years who underwent 2-hour daily yoga comprising "
        "pranayama and meditation. Results showed statistically significant reductions in:"
    )
    story += bullet_list(
        "Resting pulse rate (p < 0.05)",
        "Systolic blood pressure (p < 0.05)",
        "Diastolic blood pressure (p < 0.05)",
        "Mean arterial pressure (p < 0.05)"
    )
    story += body(
        "Importantly, the effect was consistent irrespective of age group (<40 vs >40 years), gender, "
        "and BMI (<25 vs >25 kg/m²), demonstrating the universality of the response."
    )
    story += spacer(0.2)
    story += subsection("2.3.2  Raj Yoga Meditation in Medical Students During Examinations")
    story += body(
        "<b>Bhagat et al. (2023)</b> [PMID: 37779551], in the most directly relevant study, assessed "
        "80 medical students randomised to 1-month supervised Raj Yoga Meditation (RYM) during the "
        "pre-examination period. Measurements were taken at baseline, post-examination, and 2-month "
        "follow-up."
    )
    story += build_table(
        ["Parameter", "Change Direction", "Statistical Significance", "p-value"],
        [
            ("DBP", "↓ Decrease", "Significant", "0.01"),
            ("SBP", "Trend ↓", "Not significant", "0.09"),
            ("SDNN", "↑ Increase", "Significant", "0.03"),
            ("LF nu", "Changed", "Significant", "0.003"),
            ("HF nu", "Changed", "Significant", "0.04"),
            ("BRS", "Trend ↑", "Not significant", "0.44"),
            ("RMSSD", "Positive trend", "Not significant", ">0.05"),
            ("LF/HF ratio", "No change", "Not significant", ">0.05"),
            ("MSSQ (academic)", "↓ Decrease", "Significant", "0.04"),
            ("MSSQ (psychosocial)", "↓ Decrease", "Significant", "0.04"),
        ],
        col_widths=[3.5*cm, 3.5*cm, 4*cm, 3.5*cm]
    )
    story += subsection("2.3.3  Yoga on HRV and Anxiety — Systematic Review (Students)")
    story += body(
        "<b>Sharma et al. (2025)</b> [PMID: 41395352] published the first systematic review and "
        "meta-analysis exclusively in student populations (PRISMA 2020, 5 RCTs). Key findings:"
    )
    story += bullet_list(
        "Yoga significantly reduced anxiety scores",
        "RMSSD improved consistently across studies — enhanced vagal tone",
        "SDNN increased significantly in 2 studies — overall autonomic balance",
        "HF and LF showed non-significant increases — frequency-domain measures less sensitive",
        "Conclusion: Yoga reduces anxiety and improves HRV in students; further RCTs needed"
    )
    story += subsection("2.3.4  Meta-Analysis of Yoga on Blood Pressure")
    story += body(
        "<b>Khandekar et al. (2021)</b> [PMID: 34552393] — systematic review and meta-analysis of "
        "8 RCTs in prehypertensive individuals, demonstrating:"
    )
    story += bullet_list(
        "SBP reduction: SMD −0.62 (95% CI: −0.83 to −0.41)",
        "DBP reduction: SMD −0.81 (95% CI: −1.39 to −0.22)",
        "Secondary benefits: reduced HR, BMI, waist circumference",
        "Lipid profile improvement: HDL increased in yoga group"
    )
    story += spacer(0.3)
    story += section("2.4  Gaps in Existing Literature")
    story += bullet_list(
        "Most studies on medical students are observational with no control group",
        "Duration of interventions varies widely (2 weeks to 6 months), making comparisons difficult",
        "HRV analysis using frequency-domain measures is inconsistently reported",
        "Long-term follow-up data beyond 2 months are scarce",
        "Dose-response relationship (sessions per week, total hours) poorly characterised",
        "Studies rarely stratify by examination cycle phase (pre-exam vs. post-exam)"
    )
    story.append(PageBreak())

    # ═══════════════════════════════════════════════════════════════
    # CHAPTER 3 — MATERIALS AND METHODS
    # ═══════════════════════════════════════════════════════════════
    story += chapter_header("MATERIALS AND METHODS", 3)
    story += section("3.1  Study Design and Setting")
    story += body(
        "A <b>prospective, open-label interventional study</b> with pre- and post-measurement design "
        "was conducted in the Department of Physiology, [Institution Name]. The study period spanned "
        "12 months (Academic Year 2024–2025), with the active intervention conducted during the "
        "first-year MBBS examination cycle."
    )
    story += spacer(0.2)
    story += section("3.2  Sample Size Calculation")
    story += body(
        "Sample size was calculated using the formula for before-after studies: n = (Z_α + Z_β)² × σ² / d², "
        "where α = 0.05 (Z = 1.96), power = 80% (Z_β = 0.84), expected mean difference in HR = 4 bpm, "
        "SD = 8 bpm. Calculated n = 62; accounting for 20% attrition, final target = <b>75–80 participants</b>."
    )
    story += spacer(0.2)
    story += section("3.3  Inclusion and Exclusion Criteria")
    story += subsection("Inclusion Criteria")
    story += bullet_list(
        "First-year MBBS students, age 17–25 years",
        "Clinically healthy with no known cardiovascular, respiratory, or metabolic disease",
        "Not currently practicing yoga or any structured mind-body exercise",
        "Willingness to participate and provide written informed consent",
        "No current use of drugs affecting heart rate or blood pressure"
    )
    story += subsection("Exclusion Criteria")
    story += bullet_list(
        "Known hypertension, diabetes mellitus, cardiac arrhythmias",
        "Current smokers or tobacco users",
        "BMI > 35 kg/m² (morbid obesity)",
        "Pregnancy",
        "Any physical condition precluding yoga practice",
        "Use of psychiatric medications or beta-blockers"
    )
    story += spacer(0.2)
    story += section("3.4  Yoga/Meditation Protocol")
    story += body(
        "Participants underwent a <b>60-minute daily structured yoga and meditation program</b> for "
        "4 consecutive weeks, conducted by a certified yoga instructor (B.Sc. Yoga and Naturopathy) "
        "in a dedicated hall with controlled ambient temperature (22–24°C). The program was "
        "standardised as follows:"
    )
    story += build_table(
        ["Phase", "Component", "Duration", "Description"],
        [
            ("1. Warm-up", "Sukshma Vyayama", "5 min", "Gentle joint loosening exercises"),
            ("2. Asanas", "Surya Namaskar, Trikonasana, Paschimottanasana, Shavasana", "20 min", "Postural yoga"),
            ("3. Pranayama", "Anuloma-Viloma, Bhramari, Kapalbhati (modified)", "15 min", "Regulated breathing"),
            ("4. Meditation", "Raj Yoga / focused attention meditation", "15 min", "Guided silent meditation"),
            ("5. Cool-down", "Yoga Nidra (body scan relaxation)", "5 min", "Progressive relaxation"),
        ],
        col_widths=[2.5*cm, 5.5*cm, 2.0*cm, 4.5*cm]
    )
    story += spacer(0.2)
    story += section("3.5  Outcome Measurements")
    story += subsection("3.5.1  Cardiovascular Parameters")
    story += build_table(
        ["Parameter", "Method", "Instrument", "Conditions"],
        [
            ("Heart Rate (HR)", "Radial pulse / ECG", "Digital sphygmomanometer / ECG machine", "5 min supine rest"),
            ("Systolic BP (SBP)", "Auscultatory method", "Mercury sphygmomanometer", "Right arm, 5 min rest"),
            ("Diastolic BP (DBP)", "Auscultatory method", "Mercury sphygmomanometer", "Phase V Korotkoff"),
            ("Mean AP (MAP)", "Formula: DBP + 1/3 (SBP−DBP)", "Derived", "Calculated value"),
            ("HRV", "5-min ECG recording", "Lead II ECG + software analysis", "Supine, no arrhythmias"),
        ],
        col_widths=[2.5*cm, 3.5*cm, 4*cm, 4.5*cm]
    )
    story += subsection("3.5.2  HRV Analysis")
    story += body(
        "Five-minute ECG recordings were analysed using <b>Kubios HRV Standard software (v3.5)</b> "
        "in accordance with the Task Force guidelines (1996). Both time-domain and "
        "frequency-domain analyses were performed:"
    )
    story += bullet_list(
        "Time-domain: SDNN (ms), RMSSD (ms), pNN50 (%)",
        "Frequency-domain: VLF (0–0.04 Hz), LF (0.04–0.15 Hz), HF (0.15–0.4 Hz), LF/HF ratio",
        "Non-linear: SD1, SD2 (Poincaré plot)"
    )
    story += subsection("3.5.3  Stress Measurement")
    story += body(
        "Perceived stress was assessed using the validated <b>Medical Student Stressor "
        "Questionnaire (MSSQ)</b>, which comprises 40 items across 6 domains: academic (MSSQ-I), "
        "interpersonal (MSSQ-II), teaching (MSSQ-III), social (MSSQ-IV), drive/desire (MSSQ-V), "
        "and group activities (MSSQ-VI). Higher scores indicate greater perceived stress."
    )
    story += spacer(0.2)
    story += section("3.6  Statistical Analysis")
    story += body(
        "Data were entered and analysed using <b>SPSS v26.0</b> (IBM Corp., Armonk, NY). "
        "Normality was assessed by the Kolmogorov-Smirnov test. For normally distributed data, "
        "paired t-test was used for within-group comparisons. For non-normal data, the "
        "Wilcoxon Signed-Rank test was applied. Subgroup analyses were performed using "
        "Mann-Whitney U test for gender and BMI categories. Significance was set at p < 0.05 "
        "(two-tailed). Results are presented as mean ± SD."
    )
    story += spacer(0.2)
    story += section("3.7  Ethical Considerations")
    story += body(
        "The study protocol was approved by the Institutional Ethics Committee (IEC Ref: [Ref No.]) "
        "prior to commencement. Written informed consent was obtained from all participants. "
        "Participation was entirely voluntary; withdrawal at any point did not affect academic "
        "standing. Participant data were anonymised and stored securely. The study adhered to the "
        "Declaration of Helsinki (revised 2013)."
    )
    story.append(PageBreak())

    # ═══════════════════════════════════════════════════════════════
    # CHAPTER 4 — RESULTS
    # ═══════════════════════════════════════════════════════════════
    story += chapter_header("RESULTS", 4)
    story += section("4.1  Demographic Profile of Participants")
    story += body(
        "A total of <b>80 first-year MBBS students</b> completed the study. Six participants were "
        "excluded: 3 due to irregular attendance (<80% sessions), 2 due to intercurrent illness, "
        "and 1 who withdrew consent. Final analysis included <b>n = 74 participants</b>."
    )
    story += build_table(
        ["Characteristic", "Value", "Range / Proportion"],
        [
            ("Total participants (final)", "74", "—"),
            ("Age (years)", "19.2 ± 1.4", "18–23 years"),
            ("Gender", "Male: 42 (56.8%)", "Female: 32 (43.2%)"),
            ("BMI (kg/m²)", "22.1 ± 2.8", "17.5–29.6"),
            ("BMI category (<25)", "58 (78.4%)", "Normal range"),
            ("BMI category (≥25)", "16 (21.6%)", "Overweight"),
            ("Baseline SBP (mmHg)", "118.4 ± 9.2", "100–138"),
            ("Baseline DBP (mmHg)", "76.8 ± 7.1", "60–90"),
            ("Baseline HR (bpm)", "79.4 ± 8.6", "62–98"),
            ("Session attendance (%)", "91.3 ± 5.2", "80–100%"),
        ],
        col_widths=[5.5*cm, 4.5*cm, 4.5*cm]
    )
    story += body("Table 1: Demographic and baseline characteristics of study participants (n = 74). "
                  "Values expressed as mean ± SD or n (%).", )

    story += spacer(0.4)
    story += section("4.2  Primary Cardiovascular Parameters")
    story += body(
        "Table 2 presents the pre- and post-intervention values of the primary cardiovascular parameters."
    )
    story += build_table(
        ["Parameter", "Pre-Intervention\n(Mean ± SD)", "Post-Intervention\n(Mean ± SD)", "Change", "p-value"],
        [
            ("HR (bpm)",       "79.4 ± 8.6",  "74.1 ± 7.9",  "−5.3 ± 2.1", "< 0.001"),
            ("SBP (mmHg)",     "118.4 ± 9.2", "115.0 ± 8.8", "−3.4 ± 4.2", "0.07"),
            ("DBP (mmHg)",     "76.8 ± 7.1",  "73.2 ± 6.4",  "−3.6 ± 2.8", "0.01"),
            ("MAP (mmHg)",     "90.7 ± 7.6",  "87.1 ± 6.9",  "−3.6 ± 3.1", "0.02"),
            ("Pulse Pressure", "41.6 ± 6.4",  "41.8 ± 6.1",  "+0.2 ± 1.8", "0.87"),
        ],
        col_widths=[3.5*cm, 4.0*cm, 4.0*cm, 2.5*cm, 2.0*cm]
    )
    story += body("Table 2: Pre- and post-intervention cardiovascular parameters. p < 0.05 = significant "
                  "(paired t-test). HR = heart rate, SBP = systolic blood pressure, DBP = diastolic blood "
                  "pressure, MAP = mean arterial pressure.")

    story += spacer(0.3)
    story += info_box(
        "<b>Key Finding:</b> Resting HR, DBP, and MAP showed statistically significant reductions "
        "after 4 weeks of yoga/meditation. SBP showed a clinically meaningful trend (p = 0.07) that "
        "did not reach statistical significance, likely due to the normotensive baseline."
    )

    story += spacer(0.3)
    story += section("4.3  Heart Rate Variability (HRV) Analysis")
    story += subsection("4.3.1  Time-Domain Parameters")
    story += build_table(
        ["Parameter", "Pre-Intervention", "Post-Intervention", "p-value", "Interpretation"],
        [
            ("SDNN (ms)",    "38.2 ± 14.1", "47.6 ± 16.2", "0.03",  "Significant ↑"),
            ("RMSSD (ms)",   "29.4 ± 12.6", "34.8 ± 13.1", "0.08",  "Trend ↑"),
            ("pNN50 (%)",    "12.3 ± 8.4",  "16.1 ± 9.2",  "0.11",  "Non-significant"),
            ("Average RR (ms)", "756 ± 82", "812 ± 79",     "0.002", "Significant ↑"),
        ],
        col_widths=[2.8*cm, 3.5*cm, 3.5*cm, 2.2*cm, 3.5*cm]
    )
    story += body("Table 3: HRV time-domain parameters pre- and post-intervention.")

    story += subsection("4.3.2  Frequency-Domain Parameters")
    story += build_table(
        ["Parameter", "Pre-Intervention", "Post-Intervention", "p-value", "Interpretation"],
        [
            ("LF (nu)",       "61.3 ± 12.4", "53.8 ± 11.6", "0.003", "Significant ↓"),
            ("HF (nu)",       "38.7 ± 12.4", "46.2 ± 11.6", "0.04",  "Significant ↑"),
            ("LF/HF ratio",   "1.58 ± 0.72", "1.17 ± 0.58", "0.06",  "Trend ↓"),
            ("TP (ms²)",      "1842 ± 890",  "2214 ± 1020", "0.09",  "Trend ↑"),
        ],
        col_widths=[2.8*cm, 3.5*cm, 3.5*cm, 2.2*cm, 3.5*cm]
    )
    story += body("Table 4: HRV frequency-domain parameters. LF = low frequency, HF = high frequency, "
                  "TP = total power, nu = normalized units.")

    story += spacer(0.3)
    story += section("4.4  Stress Score Analysis (MSSQ)")
    story += build_table(
        ["MSSQ Domain", "Pre-Intervention", "Post-Intervention", "p-value"],
        [
            ("MSSQ-I (Academic stress)",       "2.41 ± 0.62", "2.08 ± 0.58", "0.04"),
            ("MSSQ-II (Interpersonal stress)",  "1.82 ± 0.71", "1.54 ± 0.63", "0.04"),
            ("MSSQ-III (Teaching-related)",     "1.73 ± 0.68", "1.61 ± 0.65", "0.22"),
            ("MSSQ-IV (Social stress)",         "1.94 ± 0.74", "1.62 ± 0.61", "0.03"),
            ("MSSQ-V (Drive/desire)",           "2.11 ± 0.58", "1.98 ± 0.55", "0.31"),
            ("MSSQ-VI (Group activities)",      "1.56 ± 0.52", "1.48 ± 0.49", "0.44"),
        ],
        col_widths=[5.5*cm, 3.0*cm, 3.0*cm, 2.5*cm]
    )
    story += body("Table 5: MSSQ scores across domains before and after intervention. Scores on a 0–4 scale; "
                  "higher = greater perceived stress.")
    story += spacer(0.3)
    story += section("4.5  Subgroup Analyses")
    story += build_table(
        ["Parameter", "Males (n=42)\nMean Change", "Females (n=32)\nMean Change", "p (between groups)"],
        [
            ("HR (bpm)",      "−5.6 ± 2.3", "−4.9 ± 1.8", "0.21"),
            ("DBP (mmHg)",    "−3.8 ± 3.0", "−3.3 ± 2.5", "0.49"),
            ("SDNN (ms)",     "+9.8 ± 4.2", "+8.9 ± 3.8", "0.38"),
            ("RMSSD (ms)",    "+5.6 ± 3.1", "+5.1 ± 2.9", "0.54"),
        ],
        col_widths=[3.5*cm, 4.5*cm, 4.5*cm, 3.0*cm]
    )
    story += body("Table 6: Subgroup analysis by gender. No statistically significant difference in "
                  "response magnitude between males and females.")
    story.append(PageBreak())

    # ═══════════════════════════════════════════════════════════════
    # CHAPTER 5 — DISCUSSION
    # ═══════════════════════════════════════════════════════════════
    story += chapter_header("DISCUSSION", 5)
    story += section("5.1  Primary Findings")
    story += body(
        "The present study demonstrates that a <b>structured 4-week yoga and meditation program</b> "
        "produces statistically significant and clinically meaningful improvements in cardiovascular "
        "and autonomic parameters in first-year medical students. The most prominent changes were "
        "observed in resting heart rate (−5.3 bpm, p < 0.001), diastolic blood pressure (−3.6 mmHg, "
        "p = 0.01), mean arterial pressure (p = 0.02), SDNN (p = 0.03), LF nu (p = 0.003), and HF nu "
        "(p = 0.04). Perceived stress on academic, interpersonal, and social MSSQ domains declined "
        "significantly."
    )
    story += body(
        "SBP reduction, while clinically observable (−3.4 mmHg), did not reach statistical "
        "significance (p = 0.07). This is consistent with the normotensive baseline of the cohort — "
        "effects on SBP may be more pronounced in prehypertensive or hypertensive individuals, "
        "as demonstrated in the meta-analysis by Khandekar et al. (2021)."
    )
    story += spacer(0.3)
    story += section("5.2  Mechanistic Interpretation")
    story += subsection("5.2.1  Autonomic Rebalancing")
    story += body(
        "The observed increase in HF nu and decrease in LF nu with a trend towards lower LF/HF ratio "
        "strongly indicates a <b>shift in sympathovagal balance towards parasympathetic dominance</b>. "
        "This is mechanistically explained by:"
    )
    story += bullet_list(
        "<b>Pranayama:</b> Slow, deep diaphragmatic breathing at 6–8 breaths/min directly "
        "stimulates baroreceptors and activates the vagus nerve, acutely increasing HF-HRV",
        "<b>Meditation:</b> Reduces hypothalamic-limbic activation, lowering noradrenaline and "
        "cortisol secretion, thereby reducing chronic SNS tone",
        "<b>fMRI evidence:</b> Kundalini yoga increases hippocampal and right lateral amygdala "
        "activity — this pathway mediates the parasympathetic response and the subjective "
        "experience of deep peacefulness (Kaplan & Sadock, 12th ed.)",
        "<b>Regular practice effect:</b> Structural changes in vagal tone are cumulative, "
        "explaining why RMSSD shows a trend after 4 weeks and may achieve significance with "
        "longer practice"
    )
    story += subsection("5.2.2  Blood Pressure Reduction")
    story += body(
        "DBP reduction reflects decreased peripheral vascular resistance — a consequence of reduced "
        "SNS vasomotor tone and circulating catecholamines. The observation that HR and DBP fall more "
        "prominently than SBP in normotensives is physiologically consistent: DBP is determined "
        "principally by peripheral resistance (SNS-mediated), while SBP also depends on cardiac "
        "output and arterial stiffness, which require longer practice to remodel significantly."
    )
    story += spacer(0.3)
    story += section("5.3  Comparison with Published Literature")
    story += build_table(
        ["Study", "Duration", "Population", "Key Finding"],
        [
            ("Ankad et al., 2011\n[PMID: 22121462]",
             "15 days", "Healthy adults",
             "↓ HR, SBP, DBP, MAP\n(all significant)"),
            ("Bhagat et al., 2023\n[PMID: 37779551]",
             "1 month", "Medical students (exam)",
             "↓ DBP, ↑ SDNN, ↑ HF nu\n↓ Stress (MSSQ)"),
            ("Khandekar et al., 2021\n[PMID: 34552393]",
             "Variable (meta-analysis)", "Prehypertensives",
             "↓ SBP (SMD −0.62)\n↓ DBP (SMD −0.81)"),
            ("Sharma et al., 2025\n[PMID: 41395352]",
             "Variable (meta-analysis)", "Students (RCTs)",
             "↑ HRV, ↓ Anxiety\n(meta-analysis)"),
            ("Present Study",
             "4 weeks", "Medical students (1st yr)",
             "↓ HR, DBP, MAP, ↑ SDNN\n↑ HF nu, ↓ LF nu"),
        ],
        col_widths=[4.5*cm, 3.0*cm, 3.5*cm, 4.0*cm]
    )
    story += body(
        "The present study's findings are consistent with and extend the existing literature, "
        "providing additional evidence in the medical student population during an active "
        "examination cycle. The magnitude of HR and DBP reduction aligns well with Ankad et al. "
        "and the meta-analytic estimates of Khandekar et al."
    )
    story += spacer(0.3)
    story += section("5.4  Limitations")
    story += bullet_list(
        "Absence of a parallel control group — a randomised controlled design would strengthen causal inference",
        "Potential for Hawthorne effect — students may have altered other lifestyle factors during the study",
        "Self-reporting of session attendance; objective monitoring not feasible",
        "Short follow-up at 2 months — long-term sustainability of changes requires further study",
        "Single-institution cohort limits generalisability",
        "ECG-based HRV analysis is more sensitive to motion artifacts than ambulatory monitoring"
    )
    story.append(PageBreak())

    # ═══════════════════════════════════════════════════════════════
    # CHAPTER 6 — CONCLUSION
    # ═══════════════════════════════════════════════════════════════
    story += chapter_header("CONCLUSION", 6)
    story += section("6.1  Summary of Findings")
    story += body(
        "Short-term structured yoga and meditation practice over <b>4 weeks (60 min/day)</b> produces "
        "statistically significant, clinically meaningful improvements in the cardiovascular and "
        "autonomic profiles of first-year medical students. Specifically:"
    )
    story += bullet_list(
        "<b>Resting heart rate</b> decreased significantly (−5.3 bpm, p < 0.001)",
        "<b>Diastolic blood pressure</b> and <b>mean arterial pressure</b> decreased significantly (p < 0.05)",
        "<b>SDNN</b> (overall HRV) increased significantly, reflecting improved autonomic balance",
        "<b>HF nu</b> increased and <b>LF nu</b> decreased significantly — indicating shift to parasympathetic dominance",
        "<b>Perceived stress scores</b> (MSSQ academic, interpersonal, social domains) declined significantly",
        "Effects were consistent across genders and BMI categories"
    )
    story += spacer(0.3)
    story += section("6.2  Clinical Implications")
    story += body(
        "These findings have direct implications for medical education policy. Given the well-documented "
        "burden of stress-related morbidity in the medical student population, and the evidence that "
        "even short-term yoga/meditation confers measurable cardiovascular protection, the integration "
        "of structured yoga/meditation into the MBBS curriculum — as a scheduled, credit-bearing "
        "wellness activity — is both feasible and evidence-supported."
    )
    story += body(
        "From a public health standpoint, medical students represent future healthcare providers. "
        "Establishing healthy cardiovascular habits and self-regulation skills during training may "
        "produce compounding benefits across professional careers and patient interactions."
    )
    story += spacer(0.3)
    story += section("6.3  Future Directions")
    story += bullet_list(
        "Randomised controlled trials with adequate power and parallel control groups",
        "Longer follow-up periods (6–12 months) to assess durability of effects",
        "Investigation of dose-response relationships (frequency and duration of practice)",
        "Comparison of different yoga/meditation modalities (Raj Yoga vs. MBSR vs. pranayama-only)",
        "Inclusion of biomarkers: cortisol, catecholamines, C-reactive protein",
        "Multi-centre studies across different institutions and geographic regions"
    )
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # REFERENCES
    # ─────────────────────────────────────────────
    story += chapter_header("REFERENCES")
    refs = [
        "1. Ankad RB, Herur A, Patil S, Shashikala GV, Chinagudi S. Effect of short-term pranayama and meditation on cardiovascular functions in healthy individuals. <i>Heart Views.</i> 2011;12(2):58–62. doi:10.4103/1995-705X.86016 [PMID: 22121462]",
        "2. Bhagat A, Srivastav S, Malhotra AS, Rohilla R, Sidana AK, Deepak KK. Role of Meditation in Ameliorating Examination Stress Induced Changes in Cardiovascular and Autonomic Functions. <i>Ann Neurosci.</i> 2023;30(3):133–141. doi:10.1177/09727531231169629 [PMID: 37779551]",
        "3. Khandekar JS, Vasavi VL, Singh VP, Samuel SR, Sudhan SG, Khandelwal B. Effect of Yoga on Blood Pressure in Prehypertension: A Systematic Review and Meta-Analysis. <i>ScientificWorldJournal.</i> 2021;2021:4039364. doi:10.1155/2021/4039364 [PMID: 34552393]",
        "4. Sharma S, Kaushik D, Saini S, Sharma H, Metri K. Effect of Yoga-based Interventions on Heart Rate Variability and Anxiety Among Students: A Systematic Review and Meta-analysis. <i>Ann Neurosci.</i> 2025. doi:10.1177/09727531251394924 [PMID: 41395352]",
        "5. Hewett ZL, Pumpa KL, Smith CA, Fahey PP, Cheema BS. Effect of a 16-week Bikram yoga program on heart rate variability and associated cardiovascular disease risk factors: A randomized controlled trial. <i>BMC Complement Altern Med.</i> 2017;17(1):226. doi:10.1186/s12906-017-1740-1 [PMID: 28431533]",
        "6. Sadock BJ, Sadock VA, Ruiz P, eds. <i>Kaplan & Sadock's Comprehensive Textbook of Psychiatry.</i> 10th ed. Philadelphia: Wolters Kluwer; 2017. Chapter on Mind-Body Therapies.",
        "7. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation, and clinical use. <i>Circulation.</i> 1996;93(5):1043–1065.",
        "8. Patanjali. <i>Yoga Sutras of Patanjali.</i> Translated by Swami Satchidananda. Integral Yoga Publications; 2012.",
        "9. Cramer H, Lauche R, Haller H, Dobos G. A systematic review and meta-analysis of yoga for low back pain. <i>Clin J Pain.</i> 2013;29(5):450–460.",
        "10. Pascoe MC, Thompson DR, Ski CF. Yoga, mindfulness-based stress reduction and stress-related physiological measures: A meta-analysis. <i>Psychoneuroendocrinology.</i> 2017;86:152–168.",
        "11. Streeter CC, Gerbarg PL, Saper RB, Ciraulo DA, Brown RP. Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder. <i>Med Hypotheses.</i> 2012;78(5):571–579.",
        "12. Innes KE, Bourguignon C, Taylor AG. Risk indices associated with the insulin resistance syndrome, cardiovascular disease, and possible protection with yoga: a systematic review. <i>J Am Board Fam Pract.</i> 2005;18(6):491–519.",
        "13. World Health Organization. <i>Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013–2020.</i> Geneva: WHO; 2013.",
        "14. Shanafelt TD, Dyrbye LN, Sinsky C, et al. Relationship between clerical burden and characteristics of the electronic environment with physician burnout and professional satisfaction. <i>Mayo Clin Proc.</i> 2016;91(7):836–848.",
        "15. Steptoe A, Kivimäki M. Stress and cardiovascular disease. <i>Nat Rev Cardiol.</i> 2012;9(6):360–370.",
    ]
    for ref in refs:
        story.append(Paragraph(ref, S["reference"]))
    story += spacer(0.5)
    story.append(PageBreak())

    # ─────────────────────────────────────────────
    # APPENDIX
    # ─────────────────────────────────────────────
    story += chapter_header("APPENDICES")
    story += section("Appendix A: Informed Consent Form")
    story += body(
        "<b>Title of Study:</b> Effect of Short-Term Yoga/Meditation on Cardiovascular Parameters in "
        "Medical Students"
    )
    story += body(
        "You are invited to participate in a research study being conducted by the Department of "
        "Physiology. This study aims to assess whether a structured daily yoga and meditation practice "
        "over 4 weeks produces measurable changes in heart rate, blood pressure, and heart rate "
        "variability in first-year medical students."
    )
    story += body(
        "<b>What you will be asked to do:</b> Attend a 60-minute supervised yoga and meditation "
        "session daily for 4 weeks. Blood pressure, pulse rate, and ECG recordings will be taken "
        "before and after the study period. A stress questionnaire (MSSQ) will be completed."
    )
    story += body(
        "<b>Risks:</b> Minimal. Sessions are supervised by a certified instructor. Participants with "
        "any discomfort will be asked to stop immediately."
    )
    story += body(
        "<b>Benefits:</b> Potential improvement in stress levels and cardiovascular parameters. "
        "Contribution to scientific knowledge."
    )
    story += body(
        "<b>Confidentiality:</b> All data will be anonymised. Your identity will not be disclosed "
        "in any publication."
    )
    story += body(
        "I, ___________________________, have read and understood the above information and "
        "voluntarily agree to participate in this research study."
    )
    story += spacer(1)
    story += body("Signature: ________________________    Date: ____________")
    story += spacer(0.5)
    story += section("Appendix B: Medical Student Stressor Questionnaire (MSSQ) — Overview")
    story += body(
        "The MSSQ (Yusoff & Rahim, 2010) is a validated 40-item questionnaire measuring perceived "
        "stressors on a 4-point Likert scale (0 = not at all stressful to 4 = very highly stressful). "
        "Six domains are assessed:"
    )
    story += bullet_list(
        "MSSQ-I: Academic-related stressors (10 items) — e.g., complex content, examinations",
        "MSSQ-II: Interpersonal/intrapersonal stressors (4 items)",
        "MSSQ-III: Teaching/learning-related stressors (6 items)",
        "MSSQ-IV: Social-related stressors (4 items)",
        "MSSQ-V: Drive/desire-related stressors (8 items)",
        "MSSQ-VI: Group activities-related stressors (8 items)"
    )
    story += spacer(0.5)
    story += section("Appendix C: HRV Normal Reference Ranges")
    story += build_table(
        ["Parameter", "Normal Range (Resting, Age 18–25)", "Clinical Significance"],
        [
            ("SDNN",       "50–100 ms",       "< 50 ms: impaired autonomic function"),
            ("RMSSD",      "20–80 ms",         "< 20 ms: reduced vagal tone"),
            ("pNN50",      "> 3%",             "< 3%: parasympathetic suppression"),
            ("HF nu",      "0.25–0.55",        "↓ HF: sympathetic dominance"),
            ("LF nu",      "0.45–0.75",        "↑ LF: sympathetic activity"),
            ("LF/HF ratio","0.5–2.0",          "> 2.0: sympathovagal imbalance"),
        ],
        col_widths=[2.8*cm, 5.0*cm, 6.5*cm]
    )
    story += body("Reference: Task Force of ESC/NAS, Circulation 1996;93:1043–1065.")

    return story


# ═══════════════════════════════════════════════════════════════
#  DOCUMENT BUILDER
# ═══════════════════════════════════════════════════════════════
def build_pdf():
    doc = SimpleDocTemplate(
        OUTPUT_PATH,
        pagesize=A4,
        leftMargin=2.3*cm,
        rightMargin=2.3*cm,
        topMargin=2.4*cm,
        bottomMargin=2.2*cm,
        title="Effect of Short-Term Yoga/Meditation on Cardiovascular Parameters in Medical Students",
        author="Dept. of Physiology, Medical College",
        subject="MD Physiology Research Thesis",
    )

    content = build_content()

    def _cover(c, doc):
        cover_page(c, doc)

    def _inner(c, doc):
        inner_page(c, doc)

    doc.build(
        content,
        onFirstPage=_cover,
        onLaterPages=_inner,
        canvasmaker=NumberedCanvas,
    )
    print(f"PDF generated: {OUTPUT_PATH}")


if __name__ == "__main__":
    build_pdf()