distal myopathy

ls -la /tmp/workspace/ 2>/dev/null || echo "workspace empty or not found"

mkdir -p /tmp/workspace/distal-myopathy && python3 << 'PYEOF' from docx import Document from docx.shared import Pt, Inches, RGBColor from docx.enum.text import WD_ALIGN_PARAGRAPH from docx.oxml.ns import qn from docx.oxml import OxmlElement doc = Document() # ── Page margins (narrow for exam style) ────────────────────────────────────── from docx.shared import Cm section = doc.sections[0] section.page_width = Inches(8.27) # A4 section.page_height = Inches(11.69) section.left_margin = Cm(2.5) section.right_margin = Cm(2.5) section.top_margin = Cm(2.5) section.bottom_margin = Cm(2.0) # ── Default body style ───────────────────────────────────────────────────────── normal = doc.styles["Normal"] normal.font.name = "Times New Roman" normal.font.size = Pt(12) # Helper to set paragraph spacing def set_spacing(para, before=0, after=6, line=None): pf = para.paragraph_format pf.space_before = Pt(before) pf.space_after = Pt(after) if line: from docx.shared import Pt as Pts pf.line_spacing = Pts(line) # ── Title ────────────────────────────────────────────────────────────────────── title = doc.add_heading("DISTAL MYOPATHIES", level=1) title.alignment = WD_ALIGN_PARAGRAPH.CENTER title.runs[0].font.name = "Times New Roman" title.runs[0].font.size = Pt(16) title.runs[0].font.color.rgb = RGBColor(0, 0, 0) title.runs[0].font.bold = True set_spacing(title, before=0, after=4) # Source line src = doc.add_paragraph("(Based on Harrison's Principles of Internal Medicine, 22nd Edition)") src.alignment = WD_ALIGN_PARAGRAPH.CENTER src.runs[0].font.name = "Times New Roman" src.runs[0].font.size = Pt(10) src.runs[0].font.italic = True set_spacing(src, before=0, after=12) # ── Section heading helper ──────────────────────────────────────────────────── def add_section(doc, text): h = doc.add_heading(text, level=2) h.runs[0].font.name = "Times New Roman" h.runs[0].font.size = Pt(13) h.runs[0].font.color.rgb = RGBColor(0, 0, 0) h.runs[0].font.bold = True set_spacing(h, before=10, after=4) return h # ── Body paragraph helper ───────────────────────────────────────────────────── def add_body(doc, text, indent=False): p = doc.add_paragraph(text) p.style = doc.styles["Normal"] p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=6, line=14) if indent: p.paragraph_format.first_line_indent = Cm(1) return p # ── Bold inline helper ──────────────────────────────────────────────────────── def add_body_bold(doc, bold_text, rest_text): p = doc.add_paragraph() p.style = doc.styles["Normal"] p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=6, line=14) r1 = p.add_run(bold_text) r1.bold = True r1.font.name = "Times New Roman" r1.font.size = Pt(12) r2 = p.add_run(rest_text) r2.font.name = "Times New Roman" r2.font.size = Pt(12) return p # ═══════════════════════════════════════════════════════════════════════════════ # 1. INTRODUCTION # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "1. INTRODUCTION") add_body(doc, "Distal myopathies are a heterogeneous group of inherited muscle diseases characterised by " "preferential weakness and wasting of the distal limb muscles — the hands, wrist extensors, " "forearms, anterior tibial muscles, and gastrocnemii — in contrast to the proximal girdle " "weakness typical of most muscular dystrophies. Because distal weakness is more commonly " "associated with neuropathic disorders (hereditary neuropathies, motor neuron disease), " "distal myopathies are frequently misdiagnosed and may present a diagnostic challenge.", indent=True) add_body(doc, "The major distal myopathies are summarised in Harrison's Table 460-5 (Hereditary Distal " "Myopathies, Dystrophies). They differ in their age of onset, pattern of inheritance, " "specific muscles first involved, serum creatine kinase (CK) levels, muscle biopsy findings, " "and genetic aetiology. Some are allelic with forms of limb-girdle muscular dystrophy (LGMD), " "and the same gene mutation can produce a distal phenotype in one family member and a proximal " "phenotype in another.", indent=True) # ═══════════════════════════════════════════════════════════════════════════════ # 2. GENERAL DIAGNOSTIC APPROACH # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "2. GENERAL DIAGNOSTIC APPROACH") add_body(doc, "The initial diagnosis in a patient with distal weakness is often a hereditary or acquired " "neuropathy or motor neuron disease. The following investigations help establish a myopathic " "aetiology:") bullets = [ ("Serum Creatine Kinase (CK): ", "Levels are mildly elevated in most distal myopathies, " "but markedly elevated (often >2,000–10,000 IU/L) specifically in Miyoshi myopathy. " "A CK concentration over 500 IU/L in a patient with distal weakness should raise " "strong suspicion of a myopathic process. However, CK alone cannot exclude a myopathy, " "as it may be normal in some types (e.g., Welander, Udd)."), ("Electromyography (EMG): ", "EMG is the key tool to distinguish a distal myopathy from " "a neuropathic disorder. It shows myopathic motor unit potentials (short duration, " "low amplitude, polyphasic, early recruitment). Myotonic discharges are characteristically " "seen in myofibrillar myopathies. Repetitive nerve stimulation may be used to exclude " "myasthenia gravis, which can rarely present with predominantly distal weakness."), ("Nerve Conduction Studies (NCS): ", "Normal or near-normal, distinguishing distal myopathy " "from CMT and other neuropathies."), ("Muscle Biopsy: ", "Shows dystrophic features (fibre size variation, necrosis, regeneration, " "fibrosis). Rimmed vacuoles are a hallmark of Welander, Udd, Markesbery-Griggs, and GNE " "myopathies. In myofibrillar myopathies (MFM), Gomori trichrome stain reveals dense " "inclusions and amorphous material; electron microscopy shows myofibrillar disruption. " "Immunostaining for dysferlin is absent or reduced in Miyoshi type 1."), ("Genetic Testing: ", "Next-generation sequencing (NGS) panels encompassing multiple " "causative genes have improved diagnostic yield considerably over single-gene testing " "and are the current preferred approach."), ] for bold, rest in bullets: p = doc.add_paragraph(style="List Bullet") p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=4, line=14) r1 = p.add_run(bold) r1.bold = True r1.font.name = "Times New Roman" r1.font.size = Pt(12) r2 = p.add_run(rest) r2.font.name = "Times New Roman" r2.font.size = Pt(12) # ═══════════════════════════════════════════════════════════════════════════════ # 3. CLASSIFICATION # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "3. CLASSIFICATION") add_body(doc, "Distal myopathies are best classified by inheritance pattern and age of onset:") add_body_bold(doc, "A. Autosomal Dominant (AD), Late Onset (after age 35–40 years):", "") items_ad_late = [ "Welander distal myopathy (TIA1)", "Udd distal myopathy / Tibial muscular dystrophy (TTN/Titin)", "Markesbery-Griggs myopathy (ZASP/LDB3)", ] for item in items_ad_late: p = doc.add_paragraph(item, style="List Bullet") p.runs[0].font.name = "Times New Roman" p.runs[0].font.size = Pt(12) set_spacing(p, after=2) add_body_bold(doc, "B. Autosomal Dominant (AD), Early Onset (childhood to 3rd decade):", "") items_ad_early = [ "Laing distal myopathy (MYH7)", ] for item in items_ad_early: p = doc.add_paragraph(item, style="List Bullet") p.runs[0].font.name = "Times New Roman" p.runs[0].font.size = Pt(12) set_spacing(p, after=2) add_body_bold(doc, "C. Autosomal Recessive (AR), Early Onset (teens to 3rd decade):", "") items_ar = [ "Miyoshi myopathy type 1 (DYSF/Dysferlin)", "Miyoshi myopathy type 3 (ANO5/Anoctamin-5)", "GNE myopathy — Nonaka / hereditary IBM type 2 (GNE)", ] for item in items_ar: p = doc.add_paragraph(item, style="List Bullet") p.runs[0].font.name = "Times New Roman" p.runs[0].font.size = Pt(12) set_spacing(p, after=2) add_body_bold(doc, "D. Others (Autosomal Dominant):", "") items_other = [ "Williams myopathy (FLNC/Filamin C)", "Vocal cord and pharyngeal distal myopathy — VCPDM (MATR3/Matrin-3)", "KLHL9 myopathy, PLIN4 myopathy", ] for item in items_other: p = doc.add_paragraph(item, style="List Bullet") p.runs[0].font.name = "Times New Roman" p.runs[0].font.size = Pt(12) set_spacing(p, after=2) # ═══════════════════════════════════════════════════════════════════════════════ # 4. INDIVIDUAL SYNDROMES — CLINICAL FEATURES # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "4. INDIVIDUAL SYNDROMES — CLINICAL FEATURES") # 4a Welander add_body_bold(doc, "4a. Welander Distal Myopathy", "") add_body(doc, "Welander myopathy is an autosomal dominant condition that has only been reported in " "Scandinavian populations, where it is relatively common. Onset is in the fourth to fifth " "decade (age 40–60 years). It preferentially involves the wrist and finger extensors, " "presenting as finger and wrist drop. Foot drop develops later. The disease is not " "entirely restricted to muscle — careful evaluation may reveal mild distal hypesthesia " "and temperature loss due to some loss of small myelinated fibres. Despite this, " "electrodiagnostic testing shows little denervation and ample evidence of myopathy. " "Serum CK is normal or slightly elevated (2–3x normal). Muscle biopsy shows myopathic " "changes with characteristic rimmed vacuoles. Welander myopathy is caused by mutations " "in the TIA1 gene on chromosome 2p13, encoding a T-cell restricted intracellular antigen " "that is an RNA-binding protein. A particular TIA1 variant can cause a similar phenotype " "only in the presence of a second SQSTM1 mutation (which also links to Paget disease of bone).", indent=True) # 4b Udd add_body_bold(doc, "4b. Udd Distal Myopathy (Tibial Muscular Dystrophy)", "") add_body(doc, "Udd myopathy is an autosomal dominant, late-onset (fifth to seventh decade; typically " "after age 35) distal myopathy caused by mutations in the titin gene (TTN) on chromosome " "2q31. It is allelic with LGMD2J and hereditary myopathy with early respiratory failure " "(HMERF). The hallmark feature is progressive bilateral foot drop due to selective " "weakness of the anterior tibial muscles. Cardiomyopathy is rare, unlike other " "titinopathies. Serum CK is normal or only slightly elevated. Muscle biopsy characteristically " "demonstrates rimmed vacuoles.", indent=True) # 4c Markesbery-Griggs add_body_bold(doc, "4c. Markesbery-Griggs Myopathy", "") add_body(doc, "Markesbery-Griggs myopathy is an autosomal dominant condition caused by mutations in the " "ZASP/LDB3 gene. Onset is usually after age 35. The disease presents with progressive " "foot drop (anterior tibial weakness), and over time proximal leg weakness and distal arm " "weakness (wrist and finger extensors) develop. Cardiomyopathy (dilated or hypertrophic) " "is common, and the ECG may show conduction defects or arrhythmias. Serum CK is normal or " "slightly elevated. EMG demonstrates markedly increased insertional and spontaneous activity " "with fibrillation potentials, positive sharp waves, and characteristic myotonic discharges. " "Muscle biopsy shows rimmed vacuoles and myofibrillar disruption, classifying it as one " "of the myofibrillar myopathies (MFM). Dense inclusions and amorphous material are seen " "on Gomori trichrome staining.", indent=True) # 4d Laing add_body_bold(doc, "4d. Laing Distal Myopathy", "") add_body(doc, "Laing distal myopathy is an autosomal dominant disorder caused by mutations in the MYH7 " "gene (chromosome 14q11) encoding myosin heavy chain 7 (slow/beta cardiac myosin heavy chain), " "the major myosin isoform expressed in type 1 muscle fibres. It is distinguished from other " "AD distal myopathies by its early onset — childhood or early adult life (2nd–3rd decade). " "The characteristic feature is weakness of the anterior tibial muscles and neck flexors. " "Serum CK is normal or only slightly elevated. EMG is myopathic. Cardiomyopathy may be the " "initial symptom. Importantly, rimmed vacuoles are absent on muscle biopsy, distinguishing " "it from most other distal myopathies. MYH7 mutations also cause hyaline body myopathy.", indent=True) # 4e Miyoshi add_body_bold(doc, "4e. Miyoshi Myopathy", "") add_body(doc, "Miyoshi myopathy is an autosomal recessive distal myopathy with onset in the second to " "third decade (adolescence). It is unique among distal myopathies in that weakness begins " "in the posterior compartment — specifically the foot plantar flexors and gastrocnemii — " "rather than the anterior tibial muscles. This causes severe gastrocnemius atrophy producing " "a thin, tapering calf. Patients are unable to stand on their toes, and walk up stairs in " "a clumsy, jerky fashion. The illness is progressive; ultimately hip weakness develops and " "ambulation may become difficult in midlife.", indent=True) add_body(doc, "The most diagnostically important feature is a markedly elevated serum CK — often several " "thousand IU/L — even before the patient becomes symptomatic. Muscle biopsy shows dystrophic " "changes but no rimmed vacuoles. Miyoshi myopathy type 1 is caused by DYSF mutations " "(same gene as LGMD2B), while type 3 is caused by ANO5 mutations (same gene as LGMD2L). " "This intra-family variability — some members having a distal (Miyoshi) pattern and others " "a proximal (LGMD2B) pattern with the same DYSF mutation — is well recognised.", indent=True) # 4f GNE add_body_bold(doc, "4f. GNE Myopathy (Nonaka Myopathy / Autosomal Recessive Hereditary IBM Type 2)", "") add_body(doc, "GNE myopathy (previously called Nonaka distal myopathy and autosomal recessive hereditary " "inclusion body myopathy, hIBM2) is an autosomal recessive, early adult-onset (less than " "30 years) distal myopathy caused by mutations in the GNE gene on chromosome 9p1-q1. GNE " "encodes UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase, a bifunctional " "enzyme critical in sialic acid biosynthesis. Mutations lead to secondary reduction in " "sialic acid production, which is thought to underlie the myopathic process.", indent=True) add_body(doc, "The clinical phenotype resembles Markesbery-Griggs and Udd myopathies, with predominant " "anterior tibial and extensor forearm weakness. However, a distinctive feature is relative " "quadriceps sparing (unlike sporadic IBM where the quadriceps is prominently involved). " "Serum CK is moderately elevated (3–10x normal). Muscle biopsy shows rimmed vacuoles and " "on electron microscopy, 15- to 18-nm tubular filaments identical to IBM — but without " "the inflammatory infiltrate that characterises sporadic IBM.", indent=True) # 4g Vocal cord add_body_bold(doc, "4g. Vocal Cord and Pharyngeal Distal Myopathy (VCPDM)", "") add_body(doc, "This autosomal dominant myopathy is caused by mutations in the MATR3 gene encoding " "Matrin-3. It typically presents in the third to fourth decade with preferential weakness " "of ankle dorsiflexion and wrist/finger extension. The distinguishing feature is vocal cord " "weakness (dysphonia) and pharyngeal weakness (dysphagia) in addition to limb involvement. " "Management of dysphagia and ptosis parallels treatment of oculopharyngeal muscular dystrophy.", indent=True) # ═══════════════════════════════════════════════════════════════════════════════ # 5. MYOFIBRILLAR MYOPATHIES (MFM) — RELATIONSHIP TO DISTAL MYOPATHIES # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "5. MYOFIBRILLAR MYOPATHIES (MFM)") add_body(doc, "Myofibrillar myopathies (MFMs) are a clinically and genetically heterogeneous group of " "muscular dystrophies that can present with prominent distal or proximal weakness. They can " "be inherited in an autosomal dominant or recessive pattern. Causative genes include DES " "(desmin), ZASP/LDB3, MYOT (myotilin), FLNC (filamin C), BAG3, and CRYAB (alphaB-crystallin).", indent=True) add_body(doc, "Key laboratory features: serum CK is mildly to moderately elevated; EMG demonstrates " "an irritable myopathy with fibrillation potentials and characteristic myotonic discharges; " "muscle biopsy shows dense inclusions and amorphous material best seen on Gomori trichrome " "stain with myofibrillar disruption on electron microscopy; immunostaining shows abnormal " "accumulation of desmin and other proteins. MFMs are frequently associated with " "cardiomyopathy (dilated or hypertrophic) and cardiac arrhythmias — sometimes fatal — " "as well as respiratory muscle involvement.", indent=True) # ═══════════════════════════════════════════════════════════════════════════════ # 6. DIFFERENTIAL DIAGNOSIS # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "6. DIFFERENTIAL DIAGNOSIS") add_body(doc, "Distal myopathies must be distinguished from the following conditions that present " "with distal weakness:") diffs = [ ("Hereditary neuropathies (CMT): ", "Nerve conduction studies show slowing (demyelinating) " "or reduced amplitudes (axonal); EMG shows denervation potentials (fibrillations, " "positive sharp waves at rest with chronic neurogenic motor units on voluntary activation)."), ("Motor neuron disease (ALS): ", "Widespread denervation on EMG, fasciculations, UMN signs."), ("Myotonic dystrophy type 1: ", "Facial weakness, cataracts, endocrine involvement, " "grip and percussion myotonia; myotonic discharges on EMG."), ("Sporadic Inclusion Body Myositis (IBM): ", "Older age; finger flexor and quadriceps " "involvement (quadriceps not spared — contrasts with GNE myopathy); inflammatory " "infiltrate on biopsy."), ("Distal FSHD: ", "Scapular winging and facial weakness."), ("Myasthenia gravis: ", "Can rarely present with distal weakness — repetitive nerve " "stimulation is helpful."), ] for bold, rest in diffs: p = doc.add_paragraph(style="List Bullet") p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=4, line=14) r1 = p.add_run(bold) r1.bold = True r1.font.name = "Times New Roman" r1.font.size = Pt(12) r2 = p.add_run(rest) r2.font.name = "Times New Roman" r2.font.size = Pt(12) # ═══════════════════════════════════════════════════════════════════════════════ # 7. TREATMENT # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "7. TREATMENT") add_body(doc, "There is currently no disease-modifying therapy for any hereditary distal myopathy. " "Management remains symptomatic and supportive:") treatments = [ ("Ankle-Foot Orthoses (AFO): ", "For foot drop — preserve ambulation and prevent falls."), ("Cock-Up Splints: ", "For wrist drop — maintain hand function in conditions with " "finger and wrist extensor involvement (e.g., Welander, Markesbery-Griggs)."), ("Occupational Therapy: ", "For loss of hand function in upper limb-predominant types."), ("Cardiology Monitoring and Management: ", "Regular echocardiography and ECG monitoring " "in MFM and Laing myopathy. Cardiomyopathy (dilated/hypertrophic) and arrhythmias " "may require pharmacological management or device implantation (pacemaker/ICD)."), ("Respiratory Monitoring: ", "Particularly in MFM — diaphragmatic involvement may " "require non-invasive ventilatory support (BiPAP)."), ("Dysphagia Management: ", "For VCPDM — dietary modification, speech therapy; " "management parallels oculopharyngeal muscular dystrophy."), ("Physical Therapy: ", "Range-of-motion exercises to prevent contractures."), ("Genetic Counselling: ", "For affected individuals and family members."), ] for bold, rest in treatments: p = doc.add_paragraph(style="List Bullet") p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=4, line=14) r1 = p.add_run(bold) r1.bold = True r1.font.name = "Times New Roman" r1.font.size = Pt(12) r2 = p.add_run(rest) r2.font.name = "Times New Roman" r2.font.size = Pt(12) # ═══════════════════════════════════════════════════════════════════════════════ # 8. SUMMARY TABLE # ═══════════════════════════════════════════════════════════════════════════════ add_section(doc, "8. SUMMARY TABLE — HEREDITARY DISTAL MYOPATHIES (Harrison's Table 460-5)") table = doc.add_table(rows=1, cols=6) table.style = "Table Grid" # Header row hdr = table.rows[0].cells headers = ["Disorder", "Inheritance", "Gene/Protein", "Onset", "First Muscles", "Key Feature"] for i, h in enumerate(headers): hdr[i].text = h for run in hdr[i].paragraphs[0].runs: run.bold = True run.font.name = "Times New Roman" run.font.size = Pt(9) # Background shading tc = hdr[i]._tc tcPr = tc.get_or_add_tcPr() shd = OxmlElement('w:shd') shd.set(qn('w:val'), 'clear') shd.set(qn('w:color'), 'auto') shd.set(qn('w:fill'), 'D9D9D9') tcPr.append(shd) rows_data = [ ["Welander", "AD", "TIA1", "4th–5th decade", "Wrist/finger extensors (hands first)", "Rimmed vacuoles; Scandinavians only"], ["Udd (Tibial)", "AD", "TTN / Titin", "5th–7th decade", "Anterior tibial → foot drop", "Allelic with LGMD2J; rare cardiomyopathy"], ["Markesbery-Griggs", "AD", "ZASP (LDB3)", "After age 35", "Anterior tibial → foot drop", "Cardiomyopathy common; MFM features"], ["Laing", "AD", "MYH7", "Childhood–3rd decade", "Anterior tibial + neck flexors", "Early onset; NO rimmed vacuoles"], ["Williams", "AD", "FLNC / Filamin C", "Teens–5th decade", "Lower extremity (proximal or distal)", "MFM features; cardiomyopathy"], ["VCPDM", "AD", "MATR3 / Matrin-3", "3rd–4th decade", "Ankle dorsiflexors + wrist extensors", "Vocal cord + pharyngeal weakness"], ["Miyoshi 1", "AR", "DYSF / Dysferlin", "2nd–3rd decade", "Gastrocnemius (toe-stand impossible)", "CK markedly elevated; allelic with LGMD2B"], ["Miyoshi 3", "AR", "ANO5 / Anoctamin-5", "2nd–3rd decade", "Plantar flexors", "Allelic with LGMD2L"], ["GNE (Nonaka)", "AR", "GNE", "2nd–3rd decade (<30 yrs)", "Anterior tibial + forearm extensors", "Quadriceps sparing; rimmed vacuoles; no inflammation"], ] for rowdata in rows_data: row = table.add_row().cells for i, cell_text in enumerate(rowdata): row[i].text = cell_text for run in row[i].paragraphs[0].runs: run.font.name = "Times New Roman" run.font.size = Pt(9) # ── Conclusion ───────────────────────────────────────────────────────────────── add_section(doc, "9. CONCLUSION") add_body(doc, "Distal myopathies constitute an important and often underdiagnosed group of inherited " "muscle diseases. The key to diagnosis lies in recognising that distal weakness may be " "myopathic in origin — a markedly elevated CK (especially in Miyoshi myopathy), " "a myopathic EMG pattern, and characteristic biopsy findings (rimmed vacuoles, " "absence of denervation) help distinguish them from neuropathies. Each syndrome has " "a characteristic clinical profile: onset age, the specific muscle group first affected " "(hands in Welander, gastrocnemius in Miyoshi, anterior tibial in most others), " "and associated features such as cardiomyopathy in MFM and Laing myopathy or vocal " "cord/pharyngeal involvement in VCPDM. Genetic testing with NGS panels is now the " "preferred diagnostic tool. While no disease-modifying therapy exists, symptomatic " "management with orthoses, occupational therapy, cardiac surveillance, and respiratory " "monitoring substantially improves quality of life.", indent=True) # ── Reference ───────────────────────────────────────────────────────────────── ref = doc.add_paragraph() ref.alignment = WD_ALIGN_PARAGRAPH.LEFT set_spacing(ref, before=14, after=4) r = ref.add_run("Reference: ") r.bold = True r.font.name = "Times New Roman" r.font.size = Pt(10) r2 = ref.add_run( "Harrison's Principles of Internal Medicine, 22nd Edition (2025), McGraw-Hill Medical. " "Chapter 460 — Muscular Dystrophies and Other Muscle Diseases. " "Table 460-5: Hereditary Distal Myopathies, Dystrophies." ) r2.font.name = "Times New Roman" r2.font.size = Pt(10) # ── Save ────────────────────────────────────────────────────────────────────── out_path = "/tmp/workspace/distal-myopathy/Distal_Myopathies_NTR_Essay.docx" doc.save(out_path) print(f"Saved: {out_path}") PYEOF

python3 -c " from docx import Document doc = Document('/tmp/workspace/distal-myopathy/Distal_Myopathies_NTR_Essay.docx') for i, p in enumerate(doc.paragraphs[:30]): if p.text.strip(): print(f'[{p.style.name}] {p.text[:100]}') "

python3 << 'PYEOF' from docx import Document from docx.shared import Pt, Inches, Cm, RGBColor from docx.enum.text import WD_ALIGN_PARAGRAPH from docx.oxml.ns import qn from docx.oxml import OxmlElement doc = Document() # ── Page setup ───────────────────────────────────────────────────────────────── section = doc.sections[0] section.page_width = Inches(8.27) section.page_height = Inches(11.69) section.left_margin = Cm(2.5) section.right_margin = Cm(2.5) section.top_margin = Cm(2.5) section.bottom_margin = Cm(2.0) # ── Default Normal style ─────────────────────────────────────────────────────── normal = doc.styles["Normal"] normal.font.name = "Times New Roman" normal.font.size = Pt(12) # ── Helpers ──────────────────────────────────────────────────────────────────── def set_spacing(para, before=0, after=6, line=None): pf = para.paragraph_format pf.space_before = Pt(before) pf.space_after = Pt(after) if line: pf.line_spacing = Pt(line) def add_section(title_text): h = doc.add_heading(title_text, level=2) h.runs[0].font.name = "Times New Roman" h.runs[0].font.size = Pt(13) h.runs[0].font.color.rgb = RGBColor(0, 0, 0) h.runs[0].font.bold = True set_spacing(h, before=10, after=4) return h def add_body(text, indent=False): p = doc.add_paragraph(text) p.style = doc.styles["Normal"] p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=6, line=14) if indent: p.paragraph_format.first_line_indent = Cm(1) return p def add_mixed(bold_part, rest_part, bullet=False, indent=False): if bullet: p = doc.add_paragraph(style="List Bullet") else: p = doc.add_paragraph() p.style = doc.styles["Normal"] p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=5, line=14) if indent and not bullet: p.paragraph_format.first_line_indent = Cm(1) r1 = p.add_run(bold_part) r1.bold = True; r1.font.name = "Times New Roman"; r1.font.size = Pt(12) r2 = p.add_run(rest_part) r2.font.name = "Times New Roman"; r2.font.size = Pt(12) return p def add_bullet(text): p = doc.add_paragraph(text, style="List Bullet") p.alignment = WD_ALIGN_PARAGRAPH.JUSTIFY set_spacing(p, before=0, after=4, line=14) for run in p.runs: run.font.name = "Times New Roman"; run.font.size = Pt(12) return p def shade_cell(cell, fill="D9D9D9"): tc = cell._tc tcPr = tc.get_or_add_tcPr() shd = OxmlElement('w:shd') shd.set(qn('w:val'), 'clear') shd.set(qn('w:color'), 'auto') shd.set(qn('w:fill'), fill) tcPr.append(shd) # ══════════════════════════════════════════════════════════════════════════════ # TITLE # ══════════════════════════════════════════════════════════════════════════════ title = doc.add_heading("NEUROMUSCULAR JUNCTION (NERVE-MUSCLE JUNCTION)", level=1) title.alignment = WD_ALIGN_PARAGRAPH.CENTER title.runs[0].font.name = "Times New Roman" title.runs[0].font.size = Pt(16) title.runs[0].font.color.rgb = RGBColor(0, 0, 0) title.runs[0].font.bold = True set_spacing(title, before=0, after=4) src = doc.add_paragraph("(Based on Guyton & Hall Textbook of Medical Physiology / Harrison's Principles of Internal Medicine)") src.alignment = WD_ALIGN_PARAGRAPH.CENTER src.runs[0].font.name = "Times New Roman" src.runs[0].font.size = Pt(10) src.runs[0].font.italic = True set_spacing(src, before=0, after=12) # ══════════════════════════════════════════════════════════════════════════════ # 1. INTRODUCTION # ══════════════════════════════════════════════════════════════════════════════ add_section("1. INTRODUCTION") add_body( "The neuromuscular junction (NMJ), also called the nerve-muscle junction or motor end plate, " "is the specialised chemical synapse formed between the terminal of a motor neuron and a " "skeletal muscle fibre. It is the site where electrical signals from the nervous system are " "converted into mechanical contraction of muscle. Understanding the structure and function " "of the NMJ is fundamental to the physiology of voluntary movement and to the " "pathophysiology of diseases such as myasthenia gravis, Lambert-Eaton myasthenic syndrome, " "and the mechanism of action of neuromuscular blocking agents used in anaesthesia.", True) add_body( "Skeletal muscle fibres are innervated by large myelinated nerve fibres arising from alpha " "motoneurons in the anterior horns of the spinal cord (or cranial nerve motor nuclei). " "Each nerve fibre, after entering the muscle belly, branches and stimulates from three to " "several hundred skeletal muscle fibres. Each nerve ending makes a single junction with " "the muscle fibre near its midpoint. The action potential initiated at the NMJ travels in " "both directions toward the muscle fibre ends, causing uniform contraction. Only about 2% " "of muscle fibres receive more than one such junction.", True) # ══════════════════════════════════════════════════════════════════════════════ # 2. STRUCTURE # ══════════════════════════════════════════════════════════════════════════════ add_section("2. STRUCTURE OF THE NEUROMUSCULAR JUNCTION") add_body( "The NMJ has three anatomical components: the presynaptic terminal (nerve terminal), " "the synaptic cleft, and the postsynaptic membrane (motor end plate on the muscle fibre).") add_mixed("2a. Presynaptic Terminal (Axon Terminal): ", "The motor nerve fibre loses its myelin sheath as it approaches the muscle fibre and " "divides into a number of terminal boutons (terminal knobs). Each terminal bouton " "invaginates into the surface of the muscle fibre but lies outside the plasma membrane. " "The entire structure of branching terminals is called the motor end plate. It is covered " "by Schwann cells that insulate it from surrounding fluids. The axon terminal contains:") items_pre = [ "Numerous mitochondria — supply ATP for synthesis of acetylcholine (ACh).", "Approximately 300,000 synaptic vesicles per end plate — each vesicle stores acetylcholine (one quantum ≈ 5,000–10,000 ACh molecules).", "Active zones on the presynaptic membrane — linear dense bars flanked by voltage-gated calcium (Ca²⁺) channels, which are the sites of vesicle docking and exocytosis.", "Proteins involved in vesicle docking and fusion: SNARE proteins (synaptobrevin, syntaxin, SNAP-25), synapsin, synaptotagmin (the Ca²⁺ sensor).", ] for item in items_pre: add_bullet(item) add_mixed("2b. Synaptic Cleft: ", "The space between the presynaptic nerve terminal and the postsynaptic muscle membrane is " "the synaptic cleft, approximately 20–30 nanometres wide. The cleft contains:") items_cleft = [ "Acetylcholinesterase (AChE) — enzyme attached to the basal lamina within the synaptic cleft that rapidly degrades ACh, terminating synaptic transmission.", "Laminin and other extracellular matrix proteins that anchor the NMJ architecture.", "Agrin — secreted by the nerve terminal into the basal lamina; crucial for clustering of acetylcholine receptors on the postsynaptic membrane.", ] for item in items_cleft: add_bullet(item) add_mixed("2c. Postsynaptic Membrane (Motor End Plate): ", "The muscle membrane at the NMJ is thickened and thrown into junctional folds (subneural " "clefts), which greatly increase the surface area available for ACh binding. Key features:") items_post = [ "Nicotinic acetylcholine receptors (nAChRs, NM type) — concentrated at the crests of the junctional folds (density ~10,000/μm²), directly opposite the active zones of the presynaptic terminal.", "Voltage-gated sodium channels — located at the depths of the junctional folds; responsible for generating the muscle action potential from the end plate potential.", "Rapsyn — anchoring protein that clusters nAChRs at the postsynaptic density.", "MuSK (muscle-specific kinase) — receptor tyrosine kinase essential for postsynaptic differentiation; activated by agrin via LRP4.", ] for item in items_post: add_bullet(item) # ══════════════════════════════════════════════════════════════════════════════ # 3. NICOTINIC ACETYLCHOLINE RECEPTOR # ══════════════════════════════════════════════════════════════════════════════ add_section("3. NICOTINIC ACETYLCHOLINE RECEPTOR (nAChR)") add_body( "The nicotinic acetylcholine receptor at the NMJ (NM subtype) is a ligand-gated ion " "channel composed of five glycoprotein subunits arranged symmetrically around a central " "pore. The structure differs between foetal and adult muscle:", True) add_mixed("Foetal receptor: ", "2α + β + δ + γ subunits (total molecular weight ~275,000 Da).") add_mixed("Adult receptor: ", "2α + β + δ + ε subunits (the γ subunit is replaced by ε after birth).") add_body( "The five subunits form a cylindrical transmembrane channel. The channel is normally " "closed. Binding of two acetylcholine molecules to the two α subunits causes a " "conformational change that opens the central pore to a diameter of approximately " "0.65 nanometres. This channel is cation-selective — it allows Na⁺, K⁺, and Ca²⁺ to " "pass freely, but negative charges at the channel mouth repel Cl⁻ ions. In practice, " "the dominant current is inward Na⁺ (driven by a large electrochemical gradient of ~160 mV " "inward) with a smaller outward K⁺ current. Patch-clamp studies have shown that a single " "open channel can conduct 15,000–30,000 Na⁺ ions per millisecond.", True) # ══════════════════════════════════════════════════════════════════════════════ # 4. SEQUENCE OF EVENTS IN NEUROMUSCULAR TRANSMISSION # ══════════════════════════════════════════════════════════════════════════════ add_section("4. SEQUENCE OF EVENTS IN NEUROMUSCULAR TRANSMISSION") add_body("The process of neuromuscular transmission proceeds through the following steps:") steps = [ ("Step 1 — Arrival of Action Potential at Nerve Terminal: ", "An action potential travels down the myelinated motor axon by saltatory conduction " "and reaches the presynaptic terminal. Depolarisation of the terminal membrane is the " "triggering event."), ("Step 2 — Influx of Calcium Ions (Ca²⁺): ", "Depolarisation of the presynaptic terminal opens voltage-gated Ca²⁺ channels " "(P/Q-type Ca²⁺ channels) located on either side of the dense bars in the active zones. " "Ca²⁺ flows into the terminal down its steep electrochemical gradient. This calcium " "influx is the obligatory trigger for neurotransmitter release."), ("Step 3 — Synthesis of Acetylcholine: ", "ACh is synthesised in the cytoplasm of the axon terminal from choline and acetyl-CoA " "by the enzyme choline acetyltransferase (ChAT). Choline is taken up from the synaptic " "cleft via a high-affinity Na⁺/choline co-transporter (ChT1). Synthesised ACh is " "packaged into synaptic vesicles along with ATP and proteoglycan for storage."), ("Step 4 — Exocytosis of Acetylcholine (Quantal Release): ", "Ca²⁺ entering the terminal activates Ca²⁺-calmodulin-dependent protein kinase, which " "phosphorylates synapsin proteins anchoring vesicles to the cytoskeleton. This frees " "the vesicles, which then dock at active zone release sites via SNARE proteins " "(synaptobrevin on vesicle; syntaxin and SNAP-25 on terminal membrane). The Ca²⁺ " "sensor synaptotagmin triggers membrane fusion and exocytosis. Each action potential " "causes approximately 125 vesicles to release their contents. Release is quantal — the " "smallest unit of release is one vesicle (one quantum)."), ("Step 5 — Diffusion Across the Synaptic Cleft: ", "Released ACh diffuses across the 20–30 nm synaptic cleft and binds to nicotinic " "acetylcholine receptors (NM subtype) concentrated at the crests of the junctional folds " "of the motor end plate. The diffusion time is extremely short (< 1 ms)."), ("Step 6 — Opening of Ion Channels and Generation of End Plate Potential (EPP): ", "Binding of two ACh molecules to the two α subunits of the nAChR opens the ion channel. " "This allows massive Na⁺ influx (and some K⁺ efflux), producing a localised " "depolarisation of the motor end plate called the end plate potential (EPP). The EPP " "is not an all-or-none response — it is a graded local potential of approximately " "50–75 mV amplitude under normal conditions. Importantly, the EPP has a large safety " "factor — it is much greater than the threshold needed to trigger an action potential."), ("Step 7 — Generation of Muscle Action Potential: ", "The EPP depolarises the adjacent perijunctional muscle membrane, activating " "voltage-gated Na⁺ channels. This generates a full action potential that propagates " "bidirectionally along the entire muscle fibre membrane (sarcolemma) and down the " "T-tubule system, ultimately triggering excitation-contraction coupling and muscle " "contraction via calcium release from the sarcoplasmic reticulum."), ("Step 8 — Termination — Degradation of Acetylcholine: ", "ACh in the synaptic cleft is rapidly hydrolysed by acetylcholinesterase (AChE), " "an enzyme embedded in the basal lamina. AChE cleaves ACh into choline and acetate " "within a few milliseconds. The resulting choline is recaptured into the presynaptic " "terminal via the Na⁺/choline co-transporter for re-synthesis of ACh. This rapid " "removal prevents sustained depolarisation and allows the motor end plate to repolarise " "and be ready for the next impulse. A small amount of ACh also diffuses away from " "the cleft and is no longer available to act on the membrane."), ] for bold, rest in steps: add_mixed(bold, rest, bullet=True) # ══════════════════════════════════════════════════════════════════════════════ # 5. END PLATE POTENTIAL # ══════════════════════════════════════════════════════════════════════════════ add_section("5. END PLATE POTENTIAL (EPP)") add_body( "The end plate potential (EPP) is the localised, graded depolarisation of the motor end " "plate resulting from ACh-induced opening of nAChRs. Key features:", True) epp_points = [ "Amplitude: Normally 50–75 mV — well above the threshold (~20–30 mV) needed to trigger a muscle action potential.", "Safety factor: The EPP is 3–4 times larger than what is strictly necessary to fire an action potential. This safety factor is reduced in myasthenia gravis.", "Miniature end plate potentials (MEPPs): Small (~0.5–1 mV), spontaneous depolarisations occur at rest due to the spontaneous fusion of single vesicles releasing one quantum of ACh. MEPPs are the electrophysiological correlate of quantal release.", "Graded nature: The EPP is proportional to the amount of ACh released. It is NOT propagated — it passively spreads to adjacent membrane, where it activates voltage-gated Na⁺ channels to generate the all-or-none muscle action potential.", ] for pt in epp_points: add_bullet(pt) # ══════════════════════════════════════════════════════════════════════════════ # 6. FACTORS AFFECTING NMJ TRANSMISSION # ══════════════════════════════════════════════════════════════════════════════ add_section("6. FACTORS AFFECTING NEUROMUSCULAR TRANSMISSION") add_mixed("A. Factors Enhancing Transmission:", "") enhance = [ "Increased extracellular Ca²⁺ concentration → greater Ca²⁺ influx → more ACh release.", "Anticholinesterase drugs (neostigmine, pyridostigmine) — inhibit AChE → prolong ACh in cleft → enhanced EPP. Used therapeutically in myasthenia gravis.", "Repeated stimulation at high frequency — can cause post-tetanic facilitation (transient enhancement after high-frequency stimulation).", ] for e in enhance: add_bullet(e) add_mixed("B. Factors Impairing Transmission:", "") impair = [ "Decreased extracellular Ca²⁺ or increased Mg²⁺ → reduces Ca²⁺ influx → less ACh release.", "Nondepolarising neuromuscular blocking agents (e.g., vecuronium, rocuronium, atracurium) — compete with ACh for nAChR binding sites → block EPP generation.", "Depolarising neuromuscular blocking agents (e.g., succinylcholine) — act as ACh analogues → persistent end plate depolarisation → desensitisation of nAChRs → flaccid paralysis.", "Botulinum toxin — cleaves SNARE proteins (synaptobrevin, syntaxin, SNAP-25) → prevents vesicle fusion → blocks ACh exocytosis.", "Aminoglycoside antibiotics (e.g., gentamicin) — reduce Ca²⁺-mediated ACh release.", "Organophosphate compounds — irreversibly inhibit AChE → ACh accumulates → depolarising block.", ] for im in impair: add_bullet(im) # ══════════════════════════════════════════════════════════════════════════════ # 7. DISEASES OF THE NMJ # ══════════════════════════════════════════════════════════════════════════════ add_section("7. DISORDERS OF THE NEUROMUSCULAR JUNCTION") add_body("Diseases of the NMJ are classified by the site of the defect:") nmj_diseases = [ ("Myasthenia Gravis (MG): ", "Autoimmune disorder caused by antibodies against nAChRs (85%) or MuSK (10%). " "Antibodies reduce the number of functional receptors by complement-mediated destruction, " "receptor crosslinking, and internalisation. The EPP amplitude is reduced, and with " "repeated stimulation the EPP may fall below threshold → fatigable weakness. " "Clinically: ptosis, diplopia, dysarthria, dysphagia, proximal limb weakness; " "characteristic fatigability. EMG: decremental response on repetitive nerve stimulation. " "Treatment: acetylcholinesterase inhibitors (pyridostigmine), immunosuppression " "(prednisolone, azathioprine), thymectomy, plasmapheresis, IVIG, rituximab."), ("Lambert-Eaton Myasthenic Syndrome (LEMS): ", "Autoimmune disorder (often paraneoplastic — small cell lung carcinoma) caused by " "antibodies against presynaptic voltage-gated Ca²⁺ channels (VGCC). Reduced Ca²⁺ " "influx → reduced ACh release. EMG: incremental response on high-frequency repetitive " "stimulation (contrasts with MG). Weakness is proximal, with autonomic features " "(dry mouth, constipation, erectile dysfunction). Treatment: 3,4-diaminopyridine " "(blocks K⁺ channels → prolongs depolarisation → more Ca²⁺ influx → more ACh release)."), ("Botulism: ", "Botulinum toxin (Clostridium botulinum) cleaves SNARE proteins → prevents ACh vesicle " "fusion and exocytosis. Causes descending flaccid paralysis, starting with cranial nerve " "palsies (diplopia, dysarthria), progressing to respiratory failure."), ("Congenital Myasthenic Syndromes (CMS): ", "Rare, hereditary NMJ disorders caused by mutations in genes encoding NMJ proteins " "(e.g., AChR subunits, AChE, rapsyn, MuSK, ChAT, DOK7, GFPT1). Onset in infancy/childhood."), ("Organophosphate Poisoning: ", "Irreversible inhibition of AChE → accumulation of ACh → initial fasciculations and " "depolarising block → flaccid paralysis and SLUDGE features (salivation, lacrimation, " "urination, defaecation, GI cramps, emesis). Treated with atropine and pralidoxime (2-PAM)."), ] for bold, rest in nmj_diseases: add_mixed(bold, rest, bullet=True) # ══════════════════════════════════════════════════════════════════════════════ # 8. NEUROMUSCULAR BLOCKING AGENTS (Clinical Relevance) # ══════════════════════════════════════════════════════════════════════════════ add_section("8. NEUROMUSCULAR BLOCKING AGENTS (Pharmacological Relevance)") add_body( "Knowledge of NMJ physiology directly underpins the use of muscle relaxants in clinical " "practice (anaesthesia, intensive care, controlled ventilation):", True) nmba_table = doc.add_table(rows=1, cols=4) nmba_table.style = "Table Grid" hdr = nmba_table.rows[0].cells for i, h in enumerate(["Type", "Examples", "Mechanism", "Reversal"]): hdr[i].text = h for run in hdr[i].paragraphs[0].runs: run.bold = True; run.font.name = "Times New Roman"; run.font.size = Pt(10) shade_cell(hdr[i]) rows_nmba = [ ["Nondepolarising", "Vecuronium, rocuronium, atracurium, pancuronium", "Competitive antagonists at nAChR — prevent ACh binding → block EPP → flaccid paralysis", "Anticholinesterases (neostigmine, pyridostigmine) + glycopyrrolate/atropine; sugammadex for rocuronium/vecuronium"], ["Depolarising", "Succinylcholine (suxamethonium)", "ACh agonist at nAChR → persistent depolarisation → phase I (depolarising) block → receptor desensitisation → phase II block", "No pharmacological reversal — relies on plasma cholinesterase hydrolysis; prolonged block with pseudocholinesterase deficiency"], ] for rd in rows_nmba: row = nmba_table.add_row().cells for i, txt in enumerate(rd): row[i].text = txt for run in row[i].paragraphs[0].runs: run.font.name = "Times New Roman"; run.font.size = Pt(9) # ══════════════════════════════════════════════════════════════════════════════ # 9. SUMMARY TABLE # ══════════════════════════════════════════════════════════════════════════════ add_section("9. SUMMARY — KEY MOLECULES AT THE NMJ") sum_table = doc.add_table(rows=1, cols=3) sum_table.style = "Table Grid" sh = sum_table.rows[0].cells for i, h in enumerate(["Molecule / Structure", "Location", "Function"]): sh[i].text = h for run in sh[i].paragraphs[0].runs: run.bold = True; run.font.name = "Times New Roman"; run.font.size = Pt(10) shade_cell(sh[i]) sum_rows = [ ["Acetylcholine (ACh)", "Synaptic vesicles in presynaptic terminal", "Neurotransmitter; binds nAChR → opens ion channel"], ["Choline acetyltransferase (ChAT)", "Presynaptic terminal cytoplasm", "Synthesises ACh from choline + acetyl-CoA"], ["Synaptic vesicles (~300,000/end plate)", "Presynaptic terminal", "Store and release ACh by exocytosis"], ["SNARE proteins (synaptobrevin, syntaxin, SNAP-25)", "Vesicle and presynaptic membrane", "Mediate vesicle docking and fusion for ACh exocytosis"], ["Synaptotagmin", "Synaptic vesicle membrane", "Ca²⁺ sensor; triggers SNARE-mediated fusion"], ["Voltage-gated Ca²⁺ channels (P/Q-type)", "Presynaptic active zones", "Open on depolarisation → Ca²⁺ influx → ACh release"], ["Synaptic cleft (20–30 nm)", "Between nerve terminal and motor end plate", "Space through which ACh diffuses"], ["Acetylcholinesterase (AChE)", "Basal lamina of synaptic cleft", "Degrades ACh → choline + acetate; terminates transmission"], ["nAChR (NM type)", "Crests of junctional folds on postsynaptic membrane", "Ligand-gated cation channel; binding of 2 ACh → opens pore → Na⁺ influx → EPP"], ["MuSK / Agrin / LRP4", "Postsynaptic membrane / basal lamina", "Clustering and maintenance of postsynaptic nAChRs"], ["Rapsyn", "Postsynaptic cytoskeleton", "Anchors nAChR clusters at the postsynaptic density"], ["Voltage-gated Na⁺ channels", "Depths of junctional folds and perijunctional sarcolemma", "Generate the muscle action potential from the EPP"], ] for rd in sum_rows: row = sum_table.add_row().cells for i, txt in enumerate(rd): row[i].text = txt for run in row[i].paragraphs[0].runs: run.font.name = "Times New Roman"; run.font.size = Pt(9) # ══════════════════════════════════════════════════════════════════════════════ # 10. CONCLUSION # ══════════════════════════════════════════════════════════════════════════════ add_section("10. CONCLUSION") add_body( "The neuromuscular junction is an exquisitely organised chemical synapse that ensures " "reliable one-to-one transmission from motor neuron to muscle fibre. The sequence of " "events — action potential arrival → Ca²⁺ influx → quantal ACh exocytosis → ACh " "diffusion → nAChR activation → EPP generation → muscle action potential → " "excitation-contraction coupling — is tightly regulated. The enormous safety factor " "of the EPP ensures that neuromuscular transmission is fail-safe under normal conditions. " "Disruption of any step in this pathway — whether by autoimmunity (myasthenia gravis, " "LEMS), bacterial toxins (botulinum toxin), organophosphates, or pharmacological blockade " "— results in clinically significant weakness. A thorough knowledge of NMJ physiology " "is therefore essential for understanding neuromuscular diseases and their rational treatment.", True) # ── Reference ────────────────────────────────────────────────────────────────── rp = doc.add_paragraph() rp.alignment = WD_ALIGN_PARAGRAPH.LEFT set_spacing(rp, before=14, after=4) rr1 = rp.add_run("References: ") rr1.bold = True; rr1.font.name = "Times New Roman"; rr1.font.size = Pt(10) rr2 = rp.add_run( "1. Guyton AC, Hall JE. Textbook of Medical Physiology, 14th Ed. Chapter 7 — " "Excitation of Skeletal Muscle: Neuromuscular Transmission and Excitation-Contraction Coupling. " "2. Ganong WF. Review of Medical Physiology, 26th Ed. Chapter 6 — Neuromuscular Junction. " "3. Costanzo LS. Physiology, 7th Ed. Chapter 1 — Neuromuscular Junction. " "4. Harrison's Principles of Internal Medicine, 22nd Ed. (2025) — Chapter on Neuromuscular Disorders." ) rr2.font.name = "Times New Roman"; rr2.font.size = Pt(10) # ── Save ─────────────────────────────────────────────────────────────────────── import os os.makedirs("/tmp/workspace/nmj-essay", exist_ok=True) out = "/tmp/workspace/nmj-essay/Neuromuscular_Junction_NTR_Essay.docx" doc.save(out) print(f"Saved: {out}") PYEOF

python3 -c " from docx import Document doc = Document('/tmp/workspace/nmj-essay/Neuromuscular_Junction_NTR_Essay.docx') headings = [p.text for p in doc.paragraphs if 'Heading' in p.style.name and p.text.strip()] print('SECTIONS:') for h in headings: print(' -', h) print() print('Total paragraphs:', len(doc.paragraphs)) print('Total tables:', len(doc.tables)) "