UPSC Medical Science 2026 — Paper I

(a) 'Describe ... under the following headings' demands two clearly separated headed sub-answers: (i) the factors that make the hip joint stable, and (ii) the arterial supply of the upper end of the femur PLUS the mechanism by which avascular necrosis of the femoral head occurs. Omitting the AVN mechanism forfeits a large share of marks. (b) A case of post-thoracotomy right hemidiaphragmatic paradox requires (i) the anatomical explanation - iatrogenic right phrenic nerve injury and why a paralysed dome rises on inspiration - and (ii) an enumeration of the major diaphragmatic openings with their vertebral levels AND every structure traversing each. Both parts, and specifically the vertebral levels, must appear. (c) Obstructive (post-hepatic/cholestatic) jaundice from carcinoma head of pancreas. Three explicit sub-parts must be answered: (i) serum markers of cholestasis, (ii) the biochemical findings in serum, urine AND stool, and (iii) the mechanism of the greasy stools (steatorrhoea). All three samples must be covered in (ii). (d) Two linked demands: describe the sequential phases of the neuronal action potential with the underlying ionic conductance changes and typical voltages, and then state, comparatively, how conduction differs between myelinated and unmyelinated neurons. Both halves carry marks; a graph of membrane potential against time strengthens the first half. (e) The question explicitly requires a well-labelled diagram PLUS an explanation of the principal connections of the basal ganglia - afferents to the striatum, the direct and indirect (and hyperdirect) intrinsic circuits with their transmitters, and the efferent outflow to the thalamus and cortex. A written answer with no diagram cannot score full marks.

• Stability: deep acetabulum, labrum and transverse ligament, iliofemoral, pubofemoral and ischiofemoral ligaments, capsule, suction and muscles
• Iliofemoral (Y) ligament as the strongest, preventing hyperextension
• Supply: retinacular arteries from medial and lateral circumflex femoral (trochanteric anastomosis), artery of ligament of head, nutrient artery
• Avascular necrosis: retinacular vessels torn in intracapsular fracture or dislocation, head left ischaemic, collapse and osteoarthritis
• Right phrenic nerve (C3–C5) injury during hilar or mediastinal dissection, with its course over the pericardium
• Paradoxical movement explained: paralysed dome rises on inspiration as the normal side descends and intrathoracic pressure falls
• Openings with levels: caval T8, oesophageal T10, aortic T12
• Contents of each opening plus the minor passages: sympathetic trunk, splanchnic nerves, subcostal vessels, superior epigastric vessels
• Serum: conjugated bilirubin, markedly raised ALP and GGT, raised bile salts and cholesterol
• Urine: bilirubin present, urobilinogen absent
• Stool: pale, clay-coloured with no stercobilin and increased fat
• Steatorrhoea from absent bile salts (no emulsification or micelles) and, if the duct is blocked, lack of pancreatic lipase
• Resting potential about −70 mV, threshold about −55 mV, and voltage-gated Na+ channel opening for depolarisation with overshoot to about +35 mV
• Repolarisation by Na+ inactivation and K+ efflux, then after-hyperpolarisation
• Absolute and relative refractory periods; all-or-none spike
• Myelinated: saltatory conduction at nodes of Ranvier, fast and energy-saving; unmyelinated: continuous, slow
• Components: striatum, GPe, GPi, STN and substantia nigra (SNc and SNr)
• Afferents: corticostriatal glutamatergic, nigrostriatal dopaminergic, thalamostriatal
• Efferents: GPi/SNr inhibit the VA/VL thalamus, which excites the motor and premotor cortex
• Direct pathway (facilitates), indirect pathway through GPe and STN (inhibits), and dopamine acting on D1 and D2 neurons

(a) A classical Erb-Duchenne (upper trunk) palsy after a road traffic accident. Two explicit demands: (i) identify the site of the plexus lesion USING A DIAGRAM, and (ii) explain the anatomical basis of each motor and sensory deficit described - the adducted medially rotated arm, extended elbow, pronated forearm and sensory loss on the lateral forearm. (b(i)) 'Describe the role of various proteins regulating iron absorption, transport and storage' requires a protein-centred answer covering all three compartments - luminal/enterocyte uptake and export, plasma transport and cellular delivery, and intracellular storage - together with the regulatory proteins (hepcidin-ferroportin axis, IRE/IRP system). (b(ii)) Two linked demands: (a) explain the biochemical role of vitamin B6, i.e. the reactions catalysed by its coenzyme pyridoxal phosphate, and (b) explain the specific mechanism by which B6 deficiency mimics pellagra - the block at the PLP-dependent kynureninase step of the tryptophan-to-niacin pathway. The causal explanation in (b) carries heavy weight. (c(i)) Two demands of roughly equal weight: describe the functions of growth hormone (growth-promoting and metabolic, direct versus IGF-1 mediated) and write a note on the regulation of its secretion (GHRH, somatostatin, ghrelin, IGF-1 feedback, and the physiological stimuli and inhibitors). (c(ii)) A compact note strictly at RECEPTOR level: the structure of the insulin receptor, the ligand-induced autophosphorylation, and the downstream signalling limbs (IRS-PI3K-Akt and Ras-MAPK) with the key cellular outcome of GLUT4 translocation. General insulin actions on metabolism are not what is asked.

• Site: upper trunk (C5, C6) at Erb's point, shown on a plexus diagram
• Motor: deltoid, supraspinatus, infraspinatus and teres minor paralysed, giving adducted and medially rotated arm
• Biceps, brachialis and supinators paralysed with unopposed triceps and pronators, giving extended elbow and pronated forearm (waiter's tip)
• Sensory: C5–C6 dermatomes, with lateral forearm supplied by the lateral cutaneous nerve of the forearm (musculocutaneous)
• Absorption: Dcytb, DMT1, haem carrier protein and ferroportin with hephaestin
• Transport: transferrin and transferrin receptor 1 with endosomal release
• Storage: ferritin and haemosiderin
• Regulation: hepcidin–ferroportin axis and the IRE–IRP system
• PLP as the active coenzyme, with a Schiff base mechanism
• Reactions: transamination, decarboxylation (GABA, dopamine, serotonin, histamine), ALA synthase, trans-sulfuration, glycogen phosphorylase
• Kynureninase (PLP-dependent) converts 3-hydroxykynurenine to 3-hydroxyanthranilate in the tryptophan-to-niacin pathway
• Deficiency causes accumulation of 3-hydroxykynurenine and xanthurenic acid, less niacin and NAD, and so pellagra-like features
• Growth-promoting actions through IGF-1: bone, cartilage, muscle, protein anabolism
• Metabolic actions: lipolysis, anti-insulin (diabetogenic) effect, electrolyte retention
• Regulation: GHRH stimulation, somatostatin inhibition, ghrelin, IGF-1 feedback
• Stimuli (hypoglycaemia, sleep, exercise, stress, amino acids) and inhibitors (hyperglycaemia, obesity, glucocorticoids, REM sleep)
• Heterotetramer with extracellular α subunits that bind insulin and β subunits with tyrosine kinase activity
• Autophosphorylation of β subunits and phosphorylation of IRS proteins
• PI3K–Akt pathway with GLUT4 translocation and glycogen synthesis; Ras–MAPK pathway for growth
• Termination by internalisation, phosphatases and receptor down-regulation

(a(i)) Two numbered sub-parts, both compulsory: (1) name the ligaments of the ovary and explain their role in ovarian torsion and the complications that follow, and (2) explain the SURGICAL importance of the anatomical relations of the ovarian fossa. The second part is a relations-plus-clinical-application question, not a bare list of boundaries. (a(ii)) Describe the MAJOR anatomical sites of portosystemic (portocaval) anastomosis and, at each site, LIST THE VEINS - both the portal tributary and the systemic vein it communicates with. Naming sites without naming the paired veins does not meet the demand. (b(i)) Two short demands: a precise definition of the genetic code, then an enumeration of its salient features with the specific facts (64 codons, 61 sense plus 3 stop, initiator AUG, degeneracy, wobble, non-overlapping and comma-free, near-universality with mitochondrial exceptions). (b(ii)) Define post-translational modification and then discuss the modifications ORGANISED BY THE AMINO ACID RESIDUE involved - serine/threonine/tyrosine, asparagine, proline and lysine, glutamate, cysteine, plus proteolytic processing - each with a named enzyme or clinical example. A residue-wise treatment is what the phrase 'involving various amino acids' demands. (c(i)) Two demands: describe ANY TWO methods of measuring cardiac output - with the governing equation and a worked illustration, not just the name - and then explain the role of the Frank-Starling law in cardiac contraction, i.e. its statement, its sarcomere-level mechanism and its physiological significance. (c(ii)) A tight note on the Golgi tendon organ covering BOTH its structure (site, capsule, in-series arrangement, Ib innervation, absence of motor supply) and its function (tension detection, autogenic inhibition through the Ib inhibitory interneuron, protective and force-regulating roles).

• Ligaments: suspensory (infundibulopelvic), ovarian ligament proper, mesovarium, tubo-ovarian
• Torsion on the vascular pedicle: venous then arterial obstruction, infarction, necrosis, peritonitis, loss of ovary
• Ovarian fossa boundaries: external iliac vessels, obliterated umbilical artery, ureter and internal iliac artery, uterine artery origin; floor obturator nerve and vessels
• Surgical points: ureter injury, obturator nerve and referred thigh pain, iliac vessel bleeding, lymph nodes
• Lower oesophagus: left gastric with oesophageal/azygos veins, causing varices
• Anal canal: superior rectal with middle and inferior rectal veins, causing haemorrhoids
• Umbilicus: paraumbilical with epigastric and thoracoepigastric veins, causing caput medusae
• Retroperitoneal (Retzius) and bare area of the liver: colic, duodenal and pancreatic veins with renal, lumbar, phrenic and gonadal veins
• Definition: triplet codons in mRNA specify the amino acid sequence
• 64 codons: 61 sense and 3 stop (UAA, UAG, UGA), initiator AUG
• Degenerate with wobble; unambiguous, non-overlapping, comma-free
• Nearly universal, with mitochondrial exceptions
• Definition of PTM as covalent change after or during translation
• Ser/Thr/Tyr phosphorylation and O-glycosylation; Asn N-glycosylation
• Pro/Lys hydroxylation (vitamin C, collagen), Glu γ-carboxylation (vitamin K), Cys disulphide bonds and prenylation
• Proteolytic processing (proinsulin, zymogens, signal peptides) and lysine modifications
• Fick principle CO = VO₂/(CaO₂ − CvO₂) with a worked example
• Indicator dilution or thermodilution, with the principle and area under the curve
• Frank–Starling law: force of contraction proportional to end-diastolic fibre length within physiological limits
• Role: matching right and left outputs, adjusting stroke volume to venous return, intrinsic control, and limits in failure
• Encapsulated receptor at the musculotendinous junction, in series with muscle fibres
• Collagen bundles with intertwined endings of Ib afferent fibres
• Senses tension; the Ib fibre excites inhibitory interneurons that inhibit the α motor neuron of the same muscle (autogenic inhibition)
• Protective role and the clasp-knife reflex; contrast with the muscle spindle

(a(i)) Trace the CSF from its site of formation, through every ventricle and foramen, to its site of absorption, and then write specifically on the MECHANISM of absorption (pressure-dependent bulk flow through arachnoid villi acting as one-way valves, with the alternative routes). (a(ii)) A left occipital haemorrhage causing right homonymous hemianopia with macular sparing. The answer must (a) draw and label the ENTIRE visual pathway from retina to visual cortex and (b) use it to explain why the field loss is right-sided, homonymous, and why the macula is spared. (b(i)) Define GFR with its normal value, then discuss the DIFFERENT clearance tests used to measure it - the clearance formula, the properties of an ideal marker, inulin as the gold standard, creatinine clearance with its sources of error, and the radioisotopic, iohexol and cystatin C alternatives. (b(ii)) Two demands: describe the steps of PCR - the reaction components and the three thermal steps with their temperatures, durations and molecular events, repeated over cycles giving exponential amplification - and then state THREE specific applications in clinical medicine. Exactly three named, concrete applications are required. (c(i)) Name the three FUNCTIONAL divisions of the cerebellum with their anatomical and phylogenetic equivalents, and state the role of each - including the deep nucleus and the signature deficit of each division. A purely anatomical (lobar) answer does not meet the demand. (c(ii)) Discuss the two descending motor systems classified by their position in the spinal white matter and their termination in the ventral horn - the LATERAL (lateral corticospinal and rubrospinal) and the MEDIAL/ventromedial (anterior corticospinal, vestibulospinal, reticulospinal, tectospinal) groups - naming the tracts in each and stating their functions. (c(iii)) Two specified roles of oxytocin - in parturition (uterine receptor upregulation at term, augmentation of contractions, the Ferguson positive-feedback reflex, control of postpartum haemorrhage) and in lactation (the neuroendocrine milk-EJECTION or let-down reflex through myoepithelial cells). Both must be covered; milk secretion is prolactin's role, not oxytocin's.

• Formation by choroid plexuses (about 500 mL/day, total about 150 mL)
• Path: lateral ventricles, foramina of Monro, third ventricle, aqueduct, fourth ventricle, foramina of Magendie and Luschka, subarachnoid space
• Absorption through arachnoid villi into the superior sagittal sinus
• Mechanism: pressure-dependent bulk flow through one-way valve villi, with minor routes and the effect of blockage
• Diagram: retina, optic nerve, chiasma, optic tract, lateral geniculate body, optic radiation, visual cortex, correctly labelled
• Nasal fibres cross at the chiasma, so the left hemisphere carries the right visual field of both eyes
• Left cortical lesion gives loss of the right half of the field in both eyes (homonymous)
• Macular sparing from dual blood supply (posterior and middle cerebral arteries) at the occipital pole and large macular representation
• Definition and normal value about 125 mL/min (90–120 mL/min/1.73 m²)
• Clearance formula C = UV/P and the properties of an ideal marker
• Inulin as the gold standard and creatinine clearance with its errors (tubular secretion, muscle mass, drugs)
• Alternatives: radioisotopes (51Cr-EDTA, 99mTc-DTPA), iohexol and cystatin C
• Components: template, two primers, Taq polymerase, dNTPs, Mg²⁺ and buffer
• Steps: denaturation about 94–95 °C, annealing about 50–65 °C, extension about 72 °C
• 25–35 cycles giving exponential amplification (2ⁿ)
• Three named applications: infections (TB, HIV, COVID-19), genetic diseases, cancer or haematology (BCR-ABL)
• Vestibulocerebellum: flocculonodular lobe, equilibrium and vestibulo-ocular reflex
• Spinocerebellum: vermis and paravermis, tone, posture and execution of movement
• Cerebrocerebellum: lateral hemispheres, planning and coordination of skilled movement via dentate nucleus
• Inputs and outputs of each division, with the effect of a lesion
• Medial pathways: anterior corticospinal, vestibulospinal, reticulospinal, tectospinal
• Medial function: posture, balance, axial and proximal muscle control
• Lateral pathways: lateral corticospinal and rubrospinal
• Lateral function: skilled voluntary movement of distal limbs
• Made in the hypothalamic supraoptic and paraventricular nuclei, released from the posterior pituitary
• Parturition: uterine receptor upregulation, Ferguson reflex with positive feedback, uterine contraction
• Postpartum: uterine contraction and control of bleeding
• Lactation: suckling reflex to milk ejection by myoepithelial contraction; prolactin makes milk

(a(i)) Three explicitly named headings for methotrexate must all appear - therapeutic indications (malignant and non-malignant), drug interactions (with the mechanism of each), and side effects. A brief statement of the antifolate mechanism frames the answer but does not substitute for any of the three. (a(ii)) Three explicitly named headings for furosemide must all appear - therapeutic indications, drug interactions (with the mechanism of each) and side effects. A one-line statement of its action on the Na+-K+-2Cl- cotransporter of the thick ascending limb frames the answer. (b(i)) Two directives: 'Enumerate' four antigen-presenting cells (a bare list suffices) and 'Describe in brief' the two major antigen processing pathways. Both the cytosolic/MHC class I and the endocytic/MHC class II pathway must be covered with their end-point T-cell partner. (b(ii)) Two parts: 'Enumerate' any two types of effector T cells (naming with their lineage marker and function) and define/explain Treg cells - their phenotype, origin and suppressive mechanisms. (c) A clinical vignette with three explicit sub-parts: (i) state the single most probable diagnosis from fever, chills, throbbing peri-knee pain and an X-ray lytic focus rimmed by sclerosis in a 16-year-old; (ii) describe the pathogenesis of that condition; (iii) enumerate four complications. All three must be answered; the diagnosis must be committed to, not hedged. (d) Two linked demands: describe the laboratory diagnosis of acute lymphoblastic leukaemia (blood counts, smear, marrow, cytochemistry, ancillary tests) and set out its immunophenotypic classification (B-lineage and T-lineage subtypes with their defining markers). (e) Three forensic-medicine demands: classify thermal injuries (by agent and by depth), state precisely how the total body surface area burnt is calculated in an ADULT (Wallace's Rule of Nines with percentages), and give the various causes of death in burns grouped as immediate, early and delayed.

• Mechanism: dihydrofolate reductase inhibition (antifolate)
• Indications: ALL, choriocarcinoma, osteosarcoma, plus rheumatoid arthritis, psoriasis and ectopic pregnancy
• Interactions: NSAIDs, penicillins and probenecid (reduced excretion), co-trimoxazole (additive antifolate)
• Adverse effects: myelosuppression, mucositis, hepatotoxicity, pneumonitis, teratogenicity; leucovorin rescue
• Action: NKCC2 inhibition in the thick ascending limb
• Indications: pulmonary oedema, heart failure, ascites and oedema, renal failure, hypertension, hypercalcaemia
• Interactions: aminoglycosides and cisplatin (ototoxicity), NSAIDs (blunted effect), digoxin (hypokalaemia), lithium
• Adverse effects: hypovolaemia, hypokalaemia, hyponatraemia, metabolic alkalosis, ototoxicity, hyperuricaemia
• APCs: dendritic cells, macrophages, B cells, and Langerhans or Kupffer cells
• Endogenous pathway: proteasome, TAP, MHC class I to CD8+ T cells
• Exogenous pathway: endosome, MHC class II with CLIP and HLA-DM to CD4+ T cells
• Both pathways with their T-cell partner
• Two effector T cells with cytokines or function (Th1, Th2, Th17 or CD8+ CTL)
• Treg phenotype: CD4+ CD25+ FOXP3+
• Origin: thymic (natural) and peripheral (induced)
• Suppression by IL-10, TGF-β, CTLA-4 and IL-2 consumption; role in self-tolerance
• Diagnosis committed to: haematogenous pyogenic osteomyelitis (Brodie's abscess, S. aureus) of the metaphysis
• Pathogenesis: haematogenous seeding of the metaphysis, suppuration, raised pressure, subperiosteal spread
• Sequestrum, involucrum and cloacae; reactive sclerosis from a low-virulence infection explains the rim
• Four complications: septicaemia, septic arthritis, chronic osteomyelitis, pathological fracture, amyloidosis or Marjolin's ulcer
• Blood count and smear: anaemia, thrombocytopenia, lymphoblasts
• Marrow: 20% or more lymphoblasts; FAB L1, L2, L3
• Cytochemistry: MPO and Sudan black negative, PAS positive, TdT positive; flow cytometry, cytogenetics, CSF examination
• Classification: B-lineage (CD19, CD22, CD79a, CD10) with pro-B, common, pre-B and mature B; T-lineage (cytoplasmic CD3, CD7, CD2, CD5, CD1a) with pro-T to mature T
• Classification by agent (dry heat, moist heat, cold) and by depth (Dupuytren's six degrees)
• Rule of nines: head and neck 9%, each upper limb 9%, trunk front 18% and back 18%, each lower limb 18%, perineum 1%
• Immediate causes of death: neurogenic shock, asphyxia and burn shock
• Early and delayed causes: renal failure, toxaemia, septicaemia, pneumonia, embolism, tetanus, contractures

(a(i)) Two demands: give a precise definition of inflammation, then describe (not merely list) the cardinal features of acute inflammation - naming each Latin sign and explaining the vascular and cellular mechanism that produces it. (a(ii)) Two parts: describe the pathogenesis of SECONDARY (post-primary/reactivation) pulmonary tuberculosis - why it occurs, why it is apical, and how pre-existing hypersensitivity shapes the lesion - and then enumerate exactly five microscopic (histological) features of tuberculosis occurring in AIDS. (b(i)) 'Elaborate the mechanism of action' means set out HOW bacteria become resistant - the four or five biochemical mechanisms, each with a named drug-organism example - and the genetic basis by which resistance is acquired and spread. (b(ii)) Three demands in one short note: NAME the third-generation cephalosporins (parenteral and oral), STATE their therapeutic indications, and STATE their side effects. Naming is compulsory, not optional. (c(i)) Three numbered sub-parts, all compulsory: (1) name five clinically important Candida species, (2) write the laboratory diagnosis of candidiasis (specimen, microscopy, culture, identification tests), and (3) mention a seromarker for INVASIVE candidiasis. (c(ii)) Two demands: describe IN BRIEF any five clinical manifestations of Aspergillus infection (each needs the host setting and a defining feature, not just a name), and mention ONE specific antigen test used for diagnosis.

• Definition: local response of vascularised tissue to injury, bringing cells and plasma proteins
• Rubor and calor from vasodilatation and increased blood flow (histamine, NO, prostaglandins)
• Tumor from increased vascular permeability and exudate; dolor from bradykinin and prostaglandins; functio laesa
• Cellular events: margination, rolling, adhesion, diapedesis, chemotaxis and phagocytosis
• Reactivation or reinfection in a sensitised host, precipitated by immunosuppression
• Apical location from high oxygen tension and poor lymph drainage
• Type IV hypersensitivity: caseation, cavitation and bronchogenic spread with hilar nodes spared
• AIDS: poorly formed or absent granulomas, few giant cells and lymphocytes, extensive necrosis and numerous acid-fast bacilli
• Enzymatic inactivation (β-lactamase, aminoglycoside-modifying enzymes)
• Altered target (PBP2a in MRSA, D-Ala-D-Lac in VRE, gyrase, ribosomal methylation)
• Reduced permeability (porin loss) and active efflux
• Genetic basis: mutation and horizontal transfer by conjugation, transduction, transformation
• Parenteral: cefotaxime, ceftriaxone, ceftazidime, cefoperazone
• Oral: cefixime, cefpodoxime, cefdinir
• Indications: meningitis, gonorrhoea, typhoid fever, sepsis, Pseudomonas (ceftazidime), pneumonia
• Side effects: hypersensitivity, diarrhoea and superinfection, biliary sludge (ceftriaxone), bleeding and disulfiram-like reaction (cefoperazone)
• Species: C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, C. krusei (or C. auris)
• Specimens and direct microscopy showing budding yeast with pseudohyphae
• Culture on Sabouraud agar and CHROMagar; germ tube test, chlamydospores, sugar tests, MALDI-TOF
• Seromarker: (1→3)-β-D-glucan (or mannan antigen)
• Five manifestations from ABPA, aspergilloma, invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, sinusitis, otomycosis, keratitis
• ABPA with asthma, eosinophilia and raised IgE
• Aspergilloma in a pre-existing cavity with haemoptysis; invasive disease in neutropenia with the halo sign
• Galactomannan antigen test (ELISA on serum or BAL)

(a(i)) Two demands: CLASSIFY neurotoxic poisons (the standard forensic classification into cerebral, spinal and peripheral, with examples under each) and then DISCUSS IN BRIEF, for acute opiate poisoning, three specified heads - clinical features, treatment, and postmortem findings. All three heads must appear. (a(ii)) A brief note on 'atypical drowning' - define drowning, then explain each recognised atypical variety (dry drowning, immersion syndrome, secondary drowning, shallow-water drowning) with its mechanism, and state the medico-legal importance. (b(i)) A vignette with two numbered sub-parts: (1) commit to the single most probable diagnosis for a 60-year-old man with an irregular plaque at the base of the tongue whose biopsy shows atypical cells forming keratin pearls, and (2) describe the pathogenesis of that condition, covering both the tobacco/alcohol and the HPV pathways. (b(ii)) Two demands: enumerate FIVE differences between benign and malignant tumours (best set out as a table on the classical parameters) and then describe the mechanisms by which tumour cells escape immune surveillance. (c(i)) A comparative short note: state the ADVANTAGES of liposomal amphotericin B over conventional (deoxycholate) amphotericin B - toxicity, dosing, pharmacokinetics and clinical usefulness - with at least a passing mention of its drawback. (c(ii)) Two heads only: the therapeutic INDICATIONS of thiazide diuretics and their ADVERSE EFFECTS. A one-line mechanism is acceptable as a lead-in, but the marks lie in the two lists, each made specific. (c(iii)) Three heads on a single drug: the therapeutic indications of metformin, its MECHANISM OF ACTION (which is the pivot of the question - 'elaborate'), and its side effects.

• Classification: cerebral (somniferous, inebriant, deliriant), spinal (strychnine, gelsemium) and peripheral (curare, conium)
• Clinical features: pinpoint pupils, coma and respiratory depression
• Treatment: airway and ventilation, naloxone, gastric lavage with potassium permanganate, charcoal
• Postmortem: non-specific cyanosis, visceral congestion, pulmonary oedema, needle marks; chemical analysis
• Definition of drowning as asphyxia from submersion in liquid
• Dry drowning through laryngeal spasm with no water in the lungs
• Immersion syndrome by vagal inhibition; submersion of an unconscious person
• Secondary (delayed) drowning and shallow-water drowning, with medico-legal importance
• Diagnosis committed to: squamous cell carcinoma of the base of the tongue
• Tobacco and alcohol pathway: carcinogens, field change, TP53, CDKN2A and cyclin D1 changes
• HPV pathway: types 16 and 18, E6 degrading p53 and E7 inactivating Rb, p16 overexpression
• Progression from dysplasia to carcinoma in situ and invasion, with nodal spread
• Five differences: growth rate, growth pattern and capsule, differentiation, mitoses, metastasis
• Loss of MHC class I and antigen loss (immunoediting)
• Checkpoint ligands (PD-L1, CTLA-4), lack of costimulation
• Immunosuppressive factors and cells (TGF-β, IL-10, Tregs, MDSCs) and Fas ligand
• Much less nephrotoxicity
• Fewer infusion reactions and less hypokalaemia
• Higher doses (3–5 mg/kg/day) and single or short-course regimens
• Better tissue distribution through the reticuloendothelial system; high cost as the drawback
• Indications: hypertension, oedema, hypercalciuria and calcium stones, nephrogenic diabetes insipidus
• Electrolyte effects: hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia
• Metabolic effects: hyperuricaemia, hyperglycaemia, dyslipidaemia
• Other effects: hypovolaemia, sulphonamide allergy, digoxin toxicity, ineffective when GFR is low
• Indications: type 2 diabetes (first line), prediabetes, PCOS
• Mechanism: AMPK activation and mitochondrial complex I inhibition, reduced hepatic gluconeogenesis
• Increased peripheral insulin sensitivity and reduced intestinal glucose absorption, without insulin secretion
• Side effects: gastrointestinal upset, lactic acidosis, vitamin B12 deficiency, and contraindications (renal impairment)

(a(i)) Three numbered sub-parts, all compulsory: (1) enumerate five human malaria parasites, (2) describe the rapid diagnostic test for malaria - its principle, target antigens and advantages - and (3) mention the malaria vaccine(s) available. (a(ii)) Two demands: DISCUSS the role of antibody-dependent enhancement in the pathogenesis of SEVERE dengue - the immunological mechanism and the clinical consequences it explains - and write in brief the laboratory diagnosis of dengue, organised by day of illness. (b(i)) Three demands: DEFINE injury as laid down in the Bharatiya Nyaya Sanhita (quote the statutory wording), ENUMERATE the various mechanical injuries in their standard classification, and write a brief note on the 'concealed punctured wound' with its sites and medico-legal significance. (b(ii)) Four demands: define identification, describe the PRIMARY and the SECONDARY characteristics (identifiers) separately, name the surest single test for identifying an individual, and JUSTIFY that choice - the 'why' carries marks of its own. (c(i)) 'Discuss the management of complicated (severe) Plasmodium falciparum malaria' - recognise severe malaria by its defining criteria, give the specific antimalarial with its exact dose regimen, state how therapy is completed, and cover supportive/ICU care including what must be avoided. (c(ii)) Two heads only: the therapeutic indications of primaquine (with the dose regimen for each) and its side effects, including the contraindications that follow from them.

• Five species: P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi
• RDT: immunochromatographic lateral-flow test on finger-prick blood, result in 15–20 minutes
• Antigens HRP-2 (P. falciparum), pLDH and aldolase; advantages of speed, no microscope or electricity, suitability for remote areas
• Vaccines: RTS,S/AS01 and R21/Matrix-M against P. falciparum circumsporozoite protein
• ADE: secondary infection with a different serotype, or infant with maternal antibody
• Cross-reactive non-neutralising antibody, Fcγ-receptor uptake by monocytes and macrophages, higher viral load
• Cytokine release, plasma leakage, thrombocytopenia, DHF and DSS
• Diagnosis by day: NS1 antigen and RT-PCR in days 1–5; IgM ELISA and IgG from day 5
• Definition: any harm illegally caused to any person in body, mind, reputation or property (BNS section 2(14))
• Classification: abrasion, contusion, laceration, incised, punctured, firearm wounds (and chop wounds or fractures)
• Concealed punctured wound: thin sharp instrument, tiny opening in a hidden site
• Sites and medico-legal significance: scalp, axilla, orifices, fontanelle, nape; missed injury, natural-death label, deep organ injury
• Definition: determination of individual identity of a person or remains
• Primary: age, sex, stature, race; fingerprints, dental records, DNA
• Secondary: scars, moles, tattoos, deformities, hair and eye colour, handwriting, clothing and effects
• Surest test: DNA fingerprinting, with reasons of uniqueness, stability, tiny sample, use on decomposed remains
• Recognition of severe malaria: cerebral malaria, severe anaemia, renal failure, pulmonary oedema, hypoglycaemia, shock
• IV artesunate 2.4 mg/kg at 0, 12, 24 h then daily; alternatives artemether IM or quinine with doxycycline
• Completion with a full 3-day oral ACT after at least 24 h of parenteral treatment
• Supportive care: glucose, anticonvulsants, transfusion, dialysis, ventilation; avoid fluid overload and steroids
• Radical cure of P. vivax and P. ovale (hypnozoites): 0.25 mg/kg for 14 days
• Gametocidal single dose in P. falciparum
• Adverse effects: haemolysis in G6PD deficiency, methaemoglobinaemia, GI upset
• Contraindications: G6PD deficiency, pregnancy, infants under 6 months