Proteins[1].pptx proteins health and diseases

proteins health and diseases

1. Proteins – Health & Disease : Part 1 Dr. Sangaragomathy A M 1 st MDS, Dept. of Public Health Dentistry KLES Institute of Dental Sciences, Bengaluru

2. Contents Introduction Functions BIOCHEMISTRY & PHYSIOLOGY Classification Amino acids Structure of Proteins Sources & Dietary guidelines Digestion & Absorption Metabolism – Urea Cycle CLINICAL SIGNIFICANCE Assessment of Protein Intake Classification of Malnutrition Protein & Oral Health DENTAL APPLICATIONS Protein & oral health Proteins in treatment in dental diseases PUBLIC HEALTH SIGNIFICANCE Policies & Programs Conclusion References

3. introduction

4. proteins Word Origin – Greek word - Proteios – “ Primary ” Proteins are the basis of structure and function of life – constitute 50% of cellular dry weight – are the building blocks Elemental composition – C, H, O, N, S

5. functions STATIC FUNCTIONS Strength & Structure Fibrous proteins – (class of proteins) provide - Strength, Structure & Elasticity to tissues. Examples : Collagen, Elastin – Bone matrix, vascular system, organs Actin & Myosin - Muscles α- keratin – Epidermal tissues (Hair & nails) Fibrin – Blood clotting

6. DYNAMIC FUNCTIONS Globular proteins play a role here Growth & Maintenance Biochemical reactions – Enzymes, clotting factors Messenger - Hormones Immune function - Immunoglobulins Transport & Storage – Storage proteins – Ferritin (Iron) Transport protein (Haemoglobin) Balances fluids Provide energy

7. classification Functional Classification Chemical nature & solubility Nutritional classification

8. FUNCTIONAL CLASSIFICATION Structural proteins – Keratin (hair & nails), Collagen(bone) Catalytic proteins (Enzymes) - Hexokinase, Pepsin Transport proteins – Haemoglobin, serum Albumin Hormonal proteins – Insulin, Growth hormone Contractile proteins – Actin, Myosin Storage proteins – Ovalbumin, Glutelin Genetic proteins - Nucleoproteins Defence proteins – Immunoglobulins, Snake venom Receptor proteins – Hormones

9. CHEMICAL NATURE & SOLUBILITY Simple proteins – composed of only amino acid residues Globular (spherical) : Albumin, Globulin, Insulin Fibrous (scleroproteins) : Collagen, Keratin, Elastin, Actin, Myosin, Fibrin Conjugated proteins - contains non-protein moiety (prosthetic/conjugating group) Prosthetic groups include – lipid, carb, nucleic acid, metal Derived proteins – are denatured products of simple or conjugated proteins Primary derived proteins : from heat, acids, alkali Secondary derived proteins : hydrolytic products of proteins

10. Fibrous v/s Globular proteins

11. NUTRITIONAL CLASSIFICATION Complete protein – have all essential amino acids in required proportion to promote good growth. E.g. Egg albumin, Milk casein Partially complete protein – partially lack 1/more essential amino acids, promotes moderate growth. E.g. Wheat & rice proteins Incomplete protein - lack 1/more essential amino acids, don not promote growth at all. E.g. Gelatin

12. Complete Protein - Sources

13. Amino acids Essential (9) – Can’t be produced by body, obtained from diet Non-essential (11) - Naturally produced by body, not essential to acquire through dietary sources. Conditionally essential (7) – (subgroup) are produced by the body, yet in times of severe physical stress, growth, or trauma, may become depleted.

14. Structure 4 levels of organization Primary structure Secondary structure Tertiary structure Quaternary structure

15. PRIMARY STRUCTURE Linear sequence of amino acids Forming polypeptides Peptide bonds SECONDARY STRUCTURE Formed by twisting/ folding of polypeptide chains 2 types : α -helix – tightly packed coiled structure with amino acid chains extending outward from central axis. β - pleated sheet – fully extended polypeptide chains arranged in parallel/anti-parallel direction

16. TERTIARY STRUCTURE 3-D arrangement of protein Compact structure, hydrophobic sidechains at interior & hydrophilic groups on the surface QUARTERNARY STRUCTURE Composed of 2/more polypeptides – identical/unrelated Subunits – monomers/protomers 2 subunits: Dimer, 4 subunits: Tetramer E.g. Haemoglobin

17. sources Did you Know? Protein is not stored in the body, hence it is important to consume enough proteins everyday, to meet daily dietary requirements

18. Dietary guidelines RDA (2020) for protein is 0.83g/kg/day instead of 1g/kg/day (RDA 2010) EAR is 0.66 g/kg/day

19. Digestion Dietary proteins are denatured on cooking and therefore are easily digested Proteolytic enzymes are secreted as inactive zymogens – converted to active form in intestinal lumen – to prevent autodigestion of secretory acini Proteolytic enzymes are of 2 types: Endopeptidases : act on peptide bonds inside the protein molecule. E.g. pepsin, trypsin, chymotrypsin, elastase Exopeptidases : act on peptide bonds at end of polypeptide chain – carboxypeptidase (carboxy terminal), aminopeptidase (amino terminal)

20. Digestion of proteins are divided into 3 parts: Gastric digestion Pancreatic digestion Intestinal digestion GASTRIC HCl makes the pH optimum for pepsin action & denatures proteins Pepsin – breaks down proteins into proteoses & peptones Renin (chymosin) – curdling action of milk protein casein into Para casein – further broken down by pepsin

21. PANCREATIC Optimum pH(8) is provided by alkaline bile & pancreatic juice Pancreatic juice – (endopeptidases) – Trypsin, Chymotrypsin, Elastase, Carboxypeptidase Trypsin – Trypsinogen activated by enterokinase in intestinal microvillus membrane. This further activates other enzymes Chymotrypsin – Trypsin activates chymotrypsinogen. Trypsin & Chymotrypsin – degrade proteins into smaller peptides Carboxypeptidase – the smaller peptides are further hydrolysed to tripeptides & dipeptides by this enzyme.

22. INTESTINAL Complete Digestion of the small peptides to amino acids is done by intestinal juice – Succus entericus The luminal surface of intestinal epithelial cells contain Amino-peptidases – that release N-terminal amino acids .

23. absorption Absorption of proteins mainly occurs in the small intestine. Its an energy requiring process These transport systems are carrier mediated – there are 5 different carriers for different amino acids Clinical applications : Allergy – due to absorption of partially digested proteins (milk, fish), or induced by immune reaction to structure of the protein (gluten)

24. metabolism Dietary proteins & body proteins are broken down to amino acids – catabolic reactions Transamination – amino group of amino acid is removed to produce carbon skeleton (keto-acid) Amino group is excreted as urea Keto acid is used for – Gluconeogenesis, synthesis of Non-essential amino acids Amino acids in body amino acid pool is used for anabolic reactions.

25. CATABOLIC PATHWAY of amino acids Formation of Ammonia Detoxification/Disposal of Ammonia Formation of Urea Formation of Ammonia The amino group of amino acid is removed as ammonia. This is done by transamination & Trans-deamination. Transamination – exchange of amino acid between one amino acid and another keto acid to form a new alpha acid

26. Trans-deamination – All amino acids are first transaminated to glutamate- which is finally deaminated by glutamate dehydrogenase reaction in liver. This removes all the amino groups of all amino acids Ammonia is released in the process

27. Detoxification of Ammonia Ammonia is highly toxic- especially to the nervous system. Detoxification of ammonia is by conversion to urea and excretion through urine. First Line of defence (Trapping of Ammonia) Ammonia is immediately trapped by glutamic acid to form glutamine, especially in the brain cells. Glutamine is transported to liver – where the reaction is reversed by glutaminase to generate ammonia – that is immediately detoxified into urea.

28. Final Disposal Ammonia from all over the body thus reaches the liver Its then detoxified tp urea by liver cells, then excreted by kidneys Urea is the end product of protein metabolism Formation of Urea This occurs through the urea cycle AKA Krebs- Henseleit cycle / Ornithine cycle

29. Urea cycle Formation of Carbamoyl Phosphate 1 molecule of ammonia condenses with CO2 in presence of 2 ATP. Formation of Citrulline Carbamoyl group is transferred to NH2 group of ornithine. Citrulline is present in milk

30. Urea cycle Formation of Argininosuccinate 1 molecule of aspartate is added – provides 2 nd N atom of urea This needs hydrolysis of ATP to AMP level, so 2 high energy phosphate bonds are utilized

31. Urea cycle Formation of Arginine Argininosuccinate is cleaved to arginine and fumarate Formation of Urea Hydrolysis of arginine to urea and ornithine by arginase Ornithine maybe considered a catalyst – that enters the reaction and is regenerated

32. Urea cycle Regulation: During starvation – activity of urea cycle enzymes is elevated to meet the increased rate of protein catabolism Disorders of Urea Cycle

33. Conclusion – part:1 Proteins are building blocks of the body, they provide various static and dynamic functions – essential for proper functioning of the human body. Our diet must provide adequate amounts of protein to achieve maximum growth potential – for dental as well as holistic growth of the body Proteins are not stored in the body, and we require several essential amino acids- which can be obtained through dietary intake alone – deficiency of which may manifest orally and systemically. Thorough understanding of the biochemistry, dietary sources, digestion, absorption and metabolism of proteins, enables us to tackle and prevent various public health problems prevalent in India, such as PEM, details of which will be dealt in the next part of the presentation.

34. references Biochemistry – U. Satyanarayana, U. Chakrapani, 5 th Edition https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243327/ https://www.brainkart.com/article/Classification-of-proteins_34014/ https://portlandpress.com/essaysbiochem/article/64/4/607/226177/Metabolism https://www.myfooddata.com/articles/complete-vegetarian-protein-foods.php

35. Proteins – Health & Disease : Part 2 Dr. Sangaragomathy A M 1 st MDS, Dept. of Public Health Dentistry KLES Institute of Dental Sciences, Bengaluru

36. Contents CLINICAL SIGNIFICANCE Assessment of Protein Status Excess & Deficiency of Proteins Classification of Malnutrition PEM DENTAL APPLICATIONS Protein & oral health Proteins & oral diseases PUBLIC HEALTH SIGNIFICANCE Sustainable Development Goal #2: Zero Hunger National Programs involving proteins Conclusion References

37. Clinical significance Assessment of Protein Status Deficiency of Proteins - Oral Manifestations, Treatment Excess of Proteins Classification of Malnutrition PEM

38. Assessment of protein status BIOCHEMICAL TESTS Important proteins which are much altered are albumin and globulin . Normal albumin levels are 3.5-5.5g/dl During Protein Energy Malnutrition (PEM) the levels may slowdown to 2.0-2.5g/dl AG Ratio, normal range : 1.5 – 2.5 albumin globulin ratio shows a tendency to decrease .

39. DEFICIENCY of protein Protein deficiency indicates a lack of body protein or a relative deficiency of one or several essential amino acids. CAUSES Primary cause is protein-deficient diet. Secondary protein deficiencies can be ascribed to six causes: Irregular food habits , e.g., in the case of chronic alcoholics. Chronic gastrointestinal disorders , such as celiac disease or enteritis

40. Disturbed protein metabolism , cirrhosis of liver, hormonal disorders or in some cases of diabetes. Continuous loss of protein ; chronic renal disease, bleeding or exudative gastroenteropathy. High losses of albumin into the urine are indicators of the nephrotic syndrome. Increased protein turnover , in case of infection, fever, or gastroenteritis. Enhanced protein catabolism , patients with severe injuries, burns, or postoperative stress. RISK GROUPS Developing countries – poor population (primarily children in 2 nd year of life) Developed societies – those who adhere to extreme diets, anorexia nervosa, bulimia nervosa

41. CLINICAL FEATURES Fatty liver Oedema Muscle wasting Reduced cardiac output & poor circulation Increased susceptibility to infections Impaired Renal functions – Nephrotic syndrome, Acute Renal Failure Impaired Pancreatic secretion Decreased production of digestive enzymes – impaired absorption & digestion of nutrients

42. Collagen - formation of dentin, cementum, periodontal ligaments, gingiva, oral mucosa, and bones such as the maxilla and mandible. Required for maintenance & repair of oral tissues Formation of antibodies to resist infection . Deficiency causes : Poor structural integrity & degeneration of dentition & supporting structures Delayed wound healing, Poor resistance to oral pathogens & increased susceptibility to Dental Caries Early childhood malnutrition- associated with Enamel Hypoplasia, caries of primary dentition & delayed exfoliation of primary teeth Chronic protein-energy malnutrition can reduce salivary gland function into adolescence ORAL MANIFESTATIONS

43. TREATMENT Dietary treatment depends on the cause of the deficiency. Mild protein deficiencies - increased oral intake of protein is sufficient. Nephrotic syndrome - intake of protein increased to 90–120g /day for adults, hepatic synthesis of albumin can compensate in part the urinary losses. Acute renal failure - protein intake should be only 20 g/ day , this reduces protein metabolism & production of urea. Special Feeding Methods Tube feeding - severe malnutrition, (when unable to eat) Parenteral nutrition – severe injuries /burns (small intestine is unable to digest & absorb)

44. EXCESS of protein Above RDA 0.8 g protein/kg body weight/day Extra protein may impose a metabolic burden on the bones, kidneys, and liver. The adverse effects associated with long-term high protein intake are : disorders of bone and calcium homeostasis, disorders of renal function, increased cancer risk disorders of liver function, precipitated progression of coronary artery disease. 

45. malnutrition

46. Protein energy malnutrition According to WHO “an imbalance between the supply of protein and energy and the body's demand for them to ensure optimal growth and function”. M ajor public health problem in India. Affects particularly preschool children (<6 years) Impairs physical to cognitive growth and increased susceptibility to infection. PEM is measured in terms of underweight (low weight for age), stunting (low height for age) and wasting (low weight for height).

47. Kwashiorkor Inadequate protein intake Marasmus Inadequate intake of both protein & energy

48. ORAL MANIFESTATIONS OF PEM Angular stomatitis Atrophic glossitis Atrophy of salivary glands, xerostomia – increased dental caries . Enamel dysplasia due to malnutrition in the first years of life. Delayed Eruption of teeth Periodontal disease develops more rapidly - due to limited defensive capacity

49. HEALTH PROMOTION 1. Measures directed to pregnant and lactating women (education , distribution of supplements); 2. Promotion of breast-feeding; 3 . Development of low cost weaning foods : the child should be made to eat more food at frequent intervals; 4. Measures to improve family diet; 5. Nutrition education - Promotion of correct feeding practices; 6. Home economics; 7. Family planning and spacing of births; and 8. Family environment. PREVENTION OF PEM

50. SPECIFIC PROTECTION 1. Child' s diet - protein & energy rich foods. Milk, eggs, fresh fruits should be given if possible; 2. Immunization; 3. Food fortification. EARLY DIAGNOSIS AND TREATMENT l. Periodic surveillance; 2. Early diagnosis of any lag in growth; 3. Early diagnosis and treatment of infections & diarrhea; 4 . Development of programs for early rehydration of children with diarrhea; 5. Development of supplementary feeding programs during epidemics; 6. Deworming of heavily infested children. REHABILITATION 1. Nutritional rehabilitation services; 2. Hospital treatment; and 3. Follow-up care.

51. PREVALENCE OF PEM PEM is measured in terms of underweight (low weight for age), stunting (low height for age) and wasting (low weight for height). Data on nutritional indicators in the country are captured periodically under the National Family Health Survey (NFHS) conducted by the Ministry of Health and Family Welfare. As per the recent NFHS-5 (2019-21) report, the nutrition indicators for children under 5 years have improved as compared with NFHS-4 (2015-16). Stunting has reduced from 38.4% to 35.5%, Wasting has reduced from 21.0% to 19.3% Underweight prevalence has reduced from 35.8% to 32.1%.

52. GOVERNMENT INITIATIVES Supplementary Nutrition Programme under Anganwadi Services & POSHAN Abhiyaan - rejuvenated and converged as ‘ Saksham Anganwadi and POSHAN 2.0 ’ (Mission Poshan 2.0). Poshan 2.0 focuses on Maternal Nutrition, Infant and Young Child Feeding Norms, Treatment of MAM/SAM and Wellness through AYUSH. Steps have been taken to improve nutritional quality and testing in accredited labs, strengthen delivery and leverage technology under the 'Poshan Tracker'

53. Dental applications Proteins & oral health Proteins & oral diseases

54. Proteins & oral health Protein plays a vital role in oral health – B uilding block for bone & periodontium, Maintains integrity of oral mucosa S upports wound healing M aintains normal immune function, Protects against Demineralization of enamel

55. Role of Amino acids Amino acids have a range of impacts on oral tissues; R educes bacterial colonization of oral tissues & modulates inflammatory response, which Re duces gingivitis and mucositis, Reduces risk of dental decay by enhancing the properties of saliva in neutralizing acids

56. Role of Collagen Large family of triple helical proteins Basic framework of extracellular matrix providing support & to from cells and tissues. Important for angiogenesis, morphogenesis, cell adhesion, repair, and regeneration. Synthesis, degradation, followed by replacement with new fibers, is necessary for constant remodeling of the connective tissue Degradation is necessary in physiological processes ( development and tissue repair ) pathological processes ( tumorigenesis and metastasis )

57. Role of collagen F oundational matrix of teeth & connective tissues. Principal component of bone, connective tissue, muscles, tendons, cartilage and oral mucosa, dentin, cementum, pulp & periodontal ligament (PDL) Tooth Eruption – PDL fibroblasts contract and transmit a contractile force transmitted through collagen fiber bundles Promotes w ound healing – P ost-extraction sites, benefit from collagen's wound-healing properties. C ollagen membranes - bone grafting for implants - guide bone regeneration - successful implant integration.

58. EPITHELIAL STRUCTURAL PROTEINS Maintain the integrity of epithelial tissues and function as a protective barrier. Keratin proteins - predominant cytoskeletal component of epithelia, attached to the plasma membrane via desmosomes , Desmosomes contain 2 types of transmembrane proteins - desmoglein and desmocollins , that are members of the cadherin family. Desmosomal cadherins - linked to the keratin cytoskeleton via several cytoplasmic plaque proteins, ( desmoplakin and plakoglobin (-y-catenin) Additional differentiation markers - including filaggrin a nd trichohyalin , that associate with the keratin cytoskeleton during terminal differentiation

59. Role of saliva COMPONENTS Mucin (Carbohydrate rich glycoprotein) Antibacterial components Lactoferrin Kallikrein Lysozyme Peroxidase Thiocyanate Digestive enzymes Ptyalin/amylase Maltase Lipase Free amino acids, peptides, growth factors

60. Role of saliva FUNCTIONS Mechanical Lubrication (mucin) Protective layer of glycoproteins – prevent microbial adhesion Dilutes hot & other irritant materials – preventing trauma Antimicrobial Glycoproteins aggregate microbes – preventing adhesion to oral tissues Immunoglobulins – IgA, IgG, IgM – prevent bacterial adhesion Peroxidase – bactericidal Lysozyme – breakdown bacterial cell wall Lactoferrin – inhibits bacterial multiplication

61. Role of saliva Digestive Amylase/Ptyalin – starch to disaccharides Lipase – important for lipid digestion in newborns Buffering action Glycoproteins having negatively charged residues & Sialin ( salivay polypeptide) Gustation Gustin – development & maturation of taste buds

62. Role of saliva Tissue repair & Blood coagulation Epidermal growth factors Blood coagulating factors (IX, VII, platelet factor) Endocrine function Parotin – promotes mesenchymal tissue growth, decreases serum calcium levels

63. Proteins & oral diseases Proteins & Dental Caries Proteins & Periodontal Diseases Proteins & Oral Cancer Synthetic proteins in Treatment of Dental diseases

64. Proteins & dental caries

65. Proteins & dental caries

66. Proteins & periodontal diseases

67. Proteins & periodontal diseases

68. Proteins & periodontal diseases

69. Proteins & oral cancer

70. Proteins & oral cancer

71. Proteins & oral cancer

72. Proteins & oral cancer

73. Proteins & oral cancer

74. Synthetic proteins in dental treatment Dentistry now harnesses synthetic proteins for tissue regeneration & dental material enhancement. The balance of dental enamel between demineralization & remineralization impacts caries formation - presence of hydroxyapatite and salivary peptides influence enamel health- use of salivary protein-inspired peptides for enhanced remineralization. S ynthetic proteins like bone morphogenetic proteins- for bone regeneration. Applications include Bacterial Biofilm in hibition Enamel remineralization Bone regeneration Stimulation of Dentin-Pulp Complex

75. Synthetic proteins in dental treatment BACTERIAL BIOFILM INHIBITION Over 2000 Antimicrobial Peptides (AMPs)- inhibit bacterial biofilm formation. The construction of the bioactive molecule phosphoserine-histatin 5 (Sp-H5) creates electrostatic attractive forces between positively charged amino acids (Lys12, Arg13, Lys14, Lys18, and Arg23) and the negatively charged phosphate anion of hydroxyapatite. These forces inhibit the adhesion of S. mutans and promote enamel remineralization. Specifically, Arg13, Lys14, Lys18, and Arg23 interact with the negatively charged phosphate anion of hydroxyapatite to inhibit S. mutans adhesion and facilitate enamel remineralization

76. Synthetic proteins in dental treatment ENAMEL REMINERALIZATION P roteins such as amelogenin , dentin phosphoprotein, or synthetic peptides with physiological properties like salivary proteins; promote a supersaturated state of calcium and phosphate ions in demineralized areas. Amelogenins assemble into nanospheres, globular aggregates, and nanochains during enamel formation, which favors the formation of HA crystals.

77. Synthetic proteins in dental treatment BONE REGENERATION V arious peptides have been investigated for their potential to promote bone tissue formation or accelerate healing in dental Currently, various growth factors (GFs) have been assessed, to promote local bone regeneration such as bone morphogenetic protein (BMP), platelet-derived growth factor (PDGF), parathyroid hormone(PTH) peptides,

78. Synthetic proteins in dental treatment STIMULATION OF DENTIN PULP COMPLEX Cell-based tissue engineering promotes microenvironments that facilitate odontogenic differentiation for the regeneration of the dentin-pulp complex. Utilizing synthetic proteins for dental pulp regeneration involves - strategic use of signaling molecules and the activation of vital signal transduction pathways, such as Wnt /-catenin and BMP/Smad. These pathways enhance various stem cell functions, such as migration, proliferation, odontoblastic differentiation, and the promotion of nerve and blood vessel regeneration

79. Public health significance SDG #2 : Zero Hunger – India’s status National Programs aimed at improving protein intake

80. Sdg #2: zero hunger Zero Hunger: End hunger, Achieve Food Security, Improved Nutrition, Promote Sustainable Agriculture

81. Sdg #2: zero hunger Target 2 : By 2030, end all forms of malnutrition, including achieving, by 2025, the internationally agreed targets on stunting and wasting in children under 5 years of age, and address the nutritional needs of adolescent girls, pregnant and lactating women and older persons Prevalence of stunting among children under 5 years of age Prevalence of malnutrition among children under 5 years of age, by type (wasting and overweight) Prevalence of anemia in women aged 15 to 49 years, by pregnancy status (percentage)

82. Sdg #2: zero hunger GLOBAL HUNGER INDEX

83. Sdg #2: zero hunger Status of India since 2014 A ccording to Global Hunger Index 2019, the rank of India is 102 out of 117 nations and categorized as a nation with serious hunger level.

84. Sdg #2: zero hunger PROGRESS IN INDIA The proportion of children under 5 years with stunted growth has reduced from 50% in 2000 to 31.7% in 2022

85. National programs Integrated Child Development Services (ICDS) provides 500 Kcal, with 12-15 g of protein per day to children and up to 25 g of protein for adolescent girls Balwadi Nutrition Program - 300kcal and 10gm protein for 270 days in a year Mid Day Meal Scheme (MDM) - provides 300 Kcal & 8-12 g of protein per day.  Special Nutrition Programme (SNP) – Preschool children : 300kcal and 10-12g protein Pregnant & lactating mothers :500kcal and 25 g protein

86. Conclusion – part:2 Proteins play an important role in formation & maintenance of various systemic & oral structures, hence adequate consumption of proteins is essential. Various proteins are used as biomarkers to predict the susceptibility of various dental diseases, and synthetic proteins are widely used to various dental treatments. India is facing the  double burden  of malnutrition, with the rise in non-communicable diseases, it is important to have a balance in the quality and quantity of macro-nutrients. There has been a  declining  trend in the consumption of protective foods like pulses and milk. The inclusion of  high -protein foods in a diet has been strongly associated with improving insulin response and reducing diabetes. Various government initiatives have aimed at improving protein consumption to address major public health problems such as PEM.

87. references https://doi.org/10.1016/B0-12-227055-X/00987-1 https://www.agd.org/docs/default-source/self-instruction-(gendent)/gendent_nd17_aafp_pflipsen.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045293/ Khaliq, Asif & Wraith, Darren & Nambiar, Smita & Miller, Yvette. (2022). A review of the prevalence, trends, and determinants of coexisting forms of malnutrition in neonates, infants, and children. BMC Public Health. 22. 10.1186/s12889-022-13098-9. https://www.redalyc.org/journal/7039/703973446002/html/ https://india.un.org/en/sdgs/2/progress#sdg-tab-content https://www.globalhungerindex.org/ranking.html https://www.globalhungerindex.org/methodology.html https://www.rjor.ro/wp-content/uploads/2016/07/ORAL-MANIFESTATIONS-OF-NURITIONAL-DISEASES-IN-CHILDREN1.pdf