The Nail as an Investigative Tool in Medicine: A Dermatologist's Guide PDF

Review Article The nail as an investigative tool in medicine: What a dermatologist ought to know Chander Grover, Shikha Bansal1 Department of Dermatology and STD, Univer...

Review Article The nail as an investigative tool in medicine: What a dermatologist ought to know Chander Grover, Shikha Bansal1 Department of Dermatology and STD, University College of Medical Sciences and GTB Hospital, 1 Department of Dermatology and STD, VMMC and Safdarjung Hospital, New Delhi, India Abstract Correspondence: The nail is an important skin appendage, but not many dermatologists are aware of the importance it receives outside Dr. Chander Grover, our specialty. This article focuses on the nail in non-dermatological contexts. The nail is a keratinized matrix capable Department of Dermatology and STD, UCMS and GTB of continuous growth with the ability to incorporate various compounds within its structure. Therefore it can be used Hospital, Dilshad Garden, to monitor long‑term consumption of drugs. It is also an excellent source of germ-line DNA for genetic analyses. Delhi - 110 095, India. With an increased undrstanding of nail physiology, there is now a better understanding of its connection to various E‑mail: chandergroverkubba76@ pathologies as well. Nails, being peripherally placed, are easy to sample without significant discomfort to the patient, gmail.com making them a valuable diagnostic tool. For this narrative review, we carried out a PubMed search using the key words “nail clipping,” “nail DNA,” “nail diabetes mellitus;” “nail clipping oncology,” and “nail forensics”. Retrieved articles were searched for information pertaining to non-dermatologic uses of nail for evaluation, which is presented in a narrative fashion. It is clear from recent literature that the nail is not just an inert skin appendage, but a dynamic window into the ever‑changing metabolic and genetic milieu. We highlight the numerous roles of nail specimens, as well as point towards future research needed therein. Key words: Biometrics, DNA, forensic science, forensic toxicology, nail clipping, oncology, selenium Introduction specimens. We used the key‑words “nail clipping,” “nail DNA,” Over the years, there is increasing interest in the study of the nail in “nail diabetes mellitus,” “nail clipping oncology,” “nail forensic,” health and disease. We know of its special structure and biological and “nail biometrics.” The searches yielded 82, 685, 437, 8, 122, uses. It is also useful in diagnosis and as a marker of systemic and 2 indexed articles respectively, in English. These articles were disease. However, not many dermatologists know the amount of retrieved and classified as case reports, review articles, and clinical attention it receives outside our specialty. trials. Information pertaining to nondermatologic applications of nails was collected. The final data was analyzed and is presented in This article focuses on the non dermatological relevance of this a narrative fashion. appendage. With developments in molecular biology and genetics, the nail is increasingly being seen as an ideal source of obtaining Why Use the Nail? human specimens. It has attained the status of “a true window”, not With the increasing popularity of screening programs, the need for just to disease, but also to the health status of an individual. appropriate human tissue specimens has increased. The specimen should afford adequate sensitivity and specificity in detecting what Methods and Results it is supposed to detect; it should involve low costs, collection For this review, information was collected by a PubMed search should cause minimal discomfort to both patients and practitioners, of articles published regarding the nondermatological uses of nail This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows Access this article online others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical Quick Response Code: Website: terms. www.ijdvl.com For reprints contact: [email protected] DOI: 10.4103/ijdvl.IJDVL_1050_16 How to cite this article: Grover C, Bansal S. The nail as an investigative tool in medicine: What a dermatologist ought to know. PMID: Indian J Dermatol Venereol Leprol 2017;83:635-43. *** Received: November, 2016. Accepted: July, 2017. © 2017 Indian Journal of Dermatology, Venereology, and Leprology | Published by Wolters Kluwer - Medknow 635 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know and it should be easy to store and transport.1 The nail satisfies most The kinetics of drug incorporation in the nails have been especially of these criteria. well worked out for zolpidem, a drug used for drug‑facilitated sexual assault.10 A single dose administered has been found to be Conventionally, human blood and serum are commonly used for detectable in all fingernail clippings from as early as 24 h to as late diagnosis; however, the importance of alternative tissue sources as 3.5 months. In fact, even the time of intake can be inferred from has increased over the years due to various reasons. Venous blood the analysis of single fingernail clippings. Nail analysis could thus collection may prove difficult, especially in special populations, be an alternative as well as a complement to hair analysis in cases for large‑scale programs, or for international collaborative of suspected drug‑facilitated sexual assault, and for monitoring of investigations.2 Alternative tissue sources include card‑based blood consumption behaviour. spots, buccal scrapes, hair samples and nail clippings as these are uniquely accessible as well as capable of delivering host DNA and Table 1 summarizes drugs routinely and reliably tested for, in nail other details. Nail as an alternative tissue sources has been found specimens. This “nail biologic monitor” has been found useful useful for genetic diagnosis as a part of screening procedures,3 in monitoring long‑term exposure to drugs, micronutrients and diagnostic procedures,4,5 assessment of adverse reactions,6 familial xenobiotics; it can even help in temporal correlation with the and population genetic profiling,7 and molecular autopsy studies.8,9 supposed period of exposure.22 In fact, for molecular autopsy studies, nail may be the only Nail as a source of DNA specimen which can be used for defining the cause of death or for Fingernail material is an excellent source of germline DNA for clinical genetic information important for the surviving family.2 In genetic analyses in almost all clinical settings.37 Although the use of addition to the advantages of adequate sensitivity and specificity, hair for this indication is well‑known, there are practical problems, low cost, ease of retrieval, minimal discomfort upon retrieval, and with hair specimens often being reported inferior for diagnostic use acceptability to both patients and practitioners, nail specimens are due to poorly detectable DNA. The Baylor SUDEP Tissue Donation also easy to collect, store, and transport.1 Program (STOP) reported that hair samples were often received without follicles or that their integrity may be compromised by prior However, because of a lack of awareness and proper processing chemical processing with hair‑care products.2 Fingernails are a more techniques in routine laboratories, nail samples have not widely reliable source of autologous DNA of high‑quality.37 been used as diagnostic tools. The specialized structure of fingernails (embodying DNA in Nail as a keratinized matrix keratinized cells) makes DNA extraction more complex than with Both nail and hair are keratinized matrices capable of continuous fresh somatic cells; hence, well‑defined protocols and reagents have growth, and incorporate compounds within their structure. This been designed for lysing keratin.38 These protocols optimize the property can be utilized in monitoring long‑term consumption of yield and quality of pure, intact DNA which has been found good alcohol or drugs.10 Nail specimens are found useful in toxicology enough even for demanding techniques such as next‑generation and especially as an alternative to hair specimens.10 Hair analysis has sequencing for HLA typing.37 Advanced techniques such as the been an established tool for drug testing, driving ability examination, Prepfiler Forensic DNA Extraction kit can yield a mean of 1 mg detection of gestational drug exposure, criminal assault, and high‑quality DNA (range, 0.5 to 2.3 mg) from 20 mg nail material post‑mortem toxicology.11 Correspondingly, our understanding of (1 to 10 pieces of fingernail clippings, a few millimetres wide the mechanisms of incorporation of drugs into the hair matrix is only).37 DNA extracted from toenails39 or fingernails40 has been advanced.12,13 In contrast, literature on incorporation mechanisms in used for genotyping and identification of individuals in genetic nails is sparse;11 nevertheless, we know the following mechanisms epidemiology and forensic studies. Some of the indications for nail of drug incorporation in nails:1 plate‑derived DNA are summarized in Table 2. a. Nail matrix incorporation occurs during the formation of the nail plate via matrix blood flow. Thus, an incorporated How to Collect Nail Specimens drug would be detectable only when the nail grows enough Collection of nail specimens is as simple as collection of fingernail to reach the free edge (10–18 weeks based on average nail trimmings or overhang of nail plates.2 Specimens can be collected growth rate) on a plain sheet of paper (as done for mycology) or in sterile 1.5 mL b. Nail bed incorporation occurs during nail thickening. The microcentrifuge tubes for more demanding DNA analyses. An nail bed contributes 21% of the nail thickness.14 A drug adequate sample consists of at least 1 week of untampered fingernail incorporated in this manner would be detectable in distal growth (assuming an average growth rate of 3 mm/month).2,66 Except nail clippings much earlier (as early as 2–3 weeks)15‑17 for daily hygiene, no additional nail cosmetic or nail treatment should c. Environmental contamination occurs mostly in the distal have been done. Hands are thoroughly washed with soap and warm part, which explains the presence of materials, mostly water and allowed to dry. Sterilized conventional metal nail clippers xenobiotics, in the distal nail18 are used and whole nail trimmings are transferred into pre‑labelled d. Sweat‑mediated transport is responsible for rapid initial tubes or containers for transportation. These can easily be stored at incorporation (within 24 hours) of drugs such as zolpidem.1 room temperature until use. Depending on the analyses required, only Drugs are eliminated through sweat channels depending one nail clipping may be collected (for serial detection of drugs)10 or on their molecular weight and hydrophilicity.19 Nails have ten nails (for DNA analyses) may be collected. For serial detection of a water content of 9–10% and drug diffusion through the drugs, ring fingernails are preferred (because of their medium growth nail bed can lead to early detection at the free edge.14,20 rate) and serial collection from the same nail is advised.67 Laufen et al. reported an uptake of fluconazole as early as 8 hours after intake.17 Similar diffusion for topically applied Tables 3 and 4 summarize the advantages and disadvantages of terbinafine has also been studied.21 using nails as a specimen. 636 Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know Table 1: Various drugs incorporated in nail Drug/chemical Applications/potential applications of nail clippings Amphetamine‑type stimulants and Nail is used for detection and quantification of phenylalkylamines in possible drug abusers phenyl‑alkylamine derivatives23 Methadone24 Nail useful for monitoring of patient compliance to methadone‑maintenance programs Cocaine analytes Detection of this drug of abuse in nail specimens Cannabinoids25 Detected in nail specimens of drug-abusers EtG alcohol26 New biomarker in nails for monitoring alcohol consumption behavior. Nail EtG levels in a social drinker are much higher than hair, suggesting a higher sensitivity. Used for evaluating both chronic excessive alcohol consumption as well as binge drinking habits Antimycotics‑ Can be detected in distal nail clippings as early as 3 weeks and 1 month after starting therapy, respectively. terbinafine,27 itraconazole Average nail concentrations are within fungicidal range for dermatophytes Detection of in utero drug exposure28 Nails are formed during the second trimester. Thus they can indicate in‑utero exposure to drugs like cocaine, morphine, methadone, caffeine, nicotine. Trace elements and heavy metals29 Nail used for monitoring occupational or environmental exposure Zolpidem30 This drug is used for drug‑facilitated sexual assault or for regular consumption behavior. Nail analysis is an alternative as well as a complement to hair analysis Selective serotonin reuptake inhibitors Nail clippings can be useful for monitoring drug intake in patients on fluoxetine treatment (fluoxetine and paroxetine) and serotonin‑norepinephrine reuptake inhibitors (venlafaxine and duloxetine)31 Triclosan and triclocarban32 Nail specimens used for rapid detection of these contaminants in nails Selenium22 Toe nail and fingernail Selenium levels are used as surrogate markers of selenium status in epidemiological studies is well established.33‑35 Blood selenium levels reflect recent exposures only (over weeks) whereas toenail selenium reflects exposures over 6‑12 months, making the latter ideal for monitoring long‑term exposure. Nail clippings have also been used for monitoring an outbreak of “selenosis” due to a mis‑formulated dietary supplement22 Arsenic36 Nail analysis can indicate chronic exposure, which cannot be evaluated by conventional blood and urine analysis. Postmortem nail analysis is useful in determining past exposure, but may not reliably conclude arsenic as cause of death as there is no correlation between blood and nail concentrations EtG: Ethyl glucuronide Techniques Used to Examine Nail Hard X‑ray micro‑analysis has been used to examine arsenic As the nail has a unique structure, specialized techniques are distribution in nail‑clippings.36 Nail clippings embedded in required to examine and quantify specific components. Some such polyester resin and cut in cross‑sectional slices are analyzed techniques used for nail analysis are summarized below. for arsenic concentration in different areas Laser‑induced breakdown spectroscopy is used for the Synchrotron‑based XRF (X‑ray fluorescence) mapping has analysis of varied biological substrates such as bacteria,77,78 also been used to evaluate arsenic micro‑distribution in teeth,29,79 hair,80 bones81 and fingernails.82 It employs a toenail clippings.2,85 focused high‑power, short‑pulsed laser beam directed onto the nail surface.1 Based on the analysis of emission spectra Clinical Indications for Use of Nail Specimens from the surface, varying elements can be analyzed. The diagnostic use of nail specimens is well established for the High‑performance liquid chromatography has been used for following indications: determination of drugs such as selective serotonin‑reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors in nail clippings.68 It has also been used as a speedy, simple Nail in diabetes mellitus and accurate technique in forensic toxicology for elucidating Diabetes mellitus is a metabolic disease characterized by high the cause of death or drug abuse blood sugar either due to insufficient insulin production or poor Ultraperformance liquid chromatography–tandem mass responsiveness.86 Various systemic pathologic alterations and spectrometry has been used to detect triclosan and metabolic events in diabetes mellitus are known to affect the nail triclocarban in nails.83 The collected nail clippings are unit structure and composition, and a nail sample can be a useful for digested with sodium hydroxide and chromatographic clinical investigations.87‑89 Documented techniques for the detection separation is performed with methanol. Target compounds and monitoring of diabetes in the nail unit include: are then determined by mass spectrometry Estimation of glycated nail proteins has been found to Micro‑PIXE (particle‑induced X‑ray emission) and reflect average blood glucose control over the previous micro‑RBS (Rutherford back‑scattering spectrometry) have 6–9 months.90,91 An analysis is possible even on a 10 mg been used to determine three‑dimensional concentration sample. The normal reference range for glycated nail maps of 18 elements in the human nail viz., major protein is 0.55–3.60 μmol/g nail. In diabetics, the values elements (C, N, and O), minor elements (P, S, Cl, K, and are significantly higher (median, 4.07 μmol/g nail). Ca), and trace elements (Fe, Mn, Zn, Ti, Na, Mg, Rb, Br, Nail analysis could therefore be a simple alternative for Sr, and Se)84 diagnosing diabetes in persons from remote areas Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 637 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know Table 2: Applications of nail plate‑derived DNA Indication Technique used/remarks High‑resolution HLA Class II gene Next‑generation DNA sequencing is the technique used for this indication and nail samples have been found typing in transplant recipients37,41 adequate for this application37,41 Genotype analysis42‑44 for assessing Nail has been a DNA source for genotyping45,46 DNA extraction from nails can be of special relevance when the patient/donor chimerism in patients patient’s pretransplant recipient material (e.g., peripheral blood) is not available. In such a setting, nails serves as a who have received allogeneic stem reliable source of pure autologous DNA for genotyping, because other specimens like oral mucosal swabs and skin cell transplantation scrapings are likely to have already been invaded by donor leukocytes (from the previous transplantation) and are thus contaminated with nonautologous cells.37 Patients undergoing such procedures are likely to have already lost hair which could have been an alternative source of autologous DNA. It has been shown that even a single nail clipping can provide an adequate quantity and quality of recipient DNA for genotyping37 Epidemiological studies45 DNA extracted from toenails or fingernails has been used for genotyping and identification of individuals for the purpose of genetic epidemiology and forensic science46 Investigation of specific biomarkers46 Nail samples are useful for monitoring intra‑individual biomarkers46 which are basically cell‑free (circulating) DNA,44,47‑50 proteins51‑53 or RNA, acting as indicators of underlying disease processes including cancers. Cellular necrosis and apoptosis induced by various insults, release significant amounts of such DNA into body fluids which can be used for tracking these pathologies.54‑58 Nails, can sensitively reflect the status of these biomarkers, enabling noninvasive monitoring using RT‑PCR and immune‑blotting. Important nail biomarkers include circulatory xenobiotic DNA like hepatitis B virus DNA;59 detection and monitoring of tumors, diabetes mellitus, trauma, stroke,60‑62 endometriosis63 and multimodal therapy effect64 Assessment of germline sequences DNA isolated from fingernails is a reliable source of germline DNA needed as a control while evaluating (as control) for investigating cancer‑specific clonal alterations in malignant haematological neoplasms cancer‑specific clonal alterations65 Single nucleotide polymorphism SNP genotyping for analysing genetic variation in specimens can be done on nail specimens by phenol/chloroform (SNP) genotyping46 extraction46 RT‑PCR: Reverse transcription polymerase chain reaction, mtDNA: Mitochondrial DNA Table 3: Advantages of using nail as a specimen  he nail unit is very vascular, hence serum concentrations of metabolites (including xenobiotic biomolecules and trace elements) is reliably reflected T in nail specimens46 Nail clippings can be obtained noninvasively in contrast to drawing peripheral blood.68 There is no harm and no pain, ensuring high compliance46  eing noninvasive and easy, even self‑collection is easily possible. This is especially useful when serial monitoring of biomarkers is required.46 B Self‑collection requires minimal instructions and ensures prolonged follow‑up  torage at room temperature is possible and no cold chain needs to be maintained46 even in tropical countries. There is no risk of samples getting S spoilt and no special preservation is required  ost‑effectiveness is high. All steps including collection method, manpower requirement, storage and transport costs are low.2,46 Nail samples can C also be easily transported over long distances. This is especially important for large‑scale, national or international population screening programs.47 For international collaborations, the exchange of nail clippings is easier as compared to blood Even onycholysed nails or nails which are being shed off can be useful for analysis46 Nails are formed continuously and permanently. They do not undergo any resting or growth stages, unlike hair  ingernails are versatile specimens, useful for the constantly increasing genetic and genomic applications ranging from population‑based screening, F diagnostics, molecular autopsy, medico‑legal investigations, or multi‑organ surveys of suspected mosaicism2  ail specimens can be used both as stand‑alone samples or to complement other specimens that may be limited in terms of their quality,69,70 scope71,72 N or yield73,74  ood quality studies are available providing reliable means of extraction from nail specimens as well as comparative nail levels in normal G populations. A lack of reliable data was an initial drawback which has been successfully overcome, especially in the field of nail‑based forensic toxicology10  he hardness of nail specimens and a layered structure are advantageous in preventing damage to samples in the preanalytic phase. Preservation of T integrity of biomolecules prevents major errors in interpretation downstream46  ue to the time lag inherent between formation of nail at the matrix and its growth up to the nail edge, nail specimens offer a wide diagnostic D window (extending over weeks, months or even years).68 This is in contrast to serum or urine samples, which can reflect only the present exposure or burden of xenobiotic.46 Analysis of nail clippings can indicate chronic exposure, which cannot be evaluated by conventional blood and urine analysis.69‑73  ail clippings can be obtained and used as a source of pure autologous DNA in practically any situation. This may not be possible with other N specimens like hair (which may fall off), peripheral blood, oral mucosal epithelium, or epidermal cells (may not be suitable posttransplant or posttransfusion)37 Changes in the molecular structure of human fingernail proteins of diabetics contain α‑helical structure (including proteins in diabetic and nondiabetic specimens have been the presence of amide II bonds), whereas nails of documented on the basis of their Fourier transform infrared nondiabetic patients do not have the amide II structures spectroscopy spectra.91 It has been concluded that nail The dielectric properties of keratin–water system in diabetic 638 Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know Table 4: Disadvantages of nail specimens Disadvantage Remarks Fingernail samples may not be  CR‑based amplification of DNA derived from nails has been found to be poor, especially for larger amplicons. P optimal for PCR‑based assays This suggests potential DNA degradation or fragmentation occurring within the keratin matrix2 Current paucity of data about  his is an essential prerequisite for monitoring the levels of individual biomarkers in health and disease. T consistent baseline levels for Expected levels and their correlations should be known across various specimens like serum, body fluids and some biomarkers in nails46 nails. Effective monitoring of biomarkers is dependent on differentiating the disease from normal background variation75 Postmortem nail analysis may  ostmortem nail analysis is useful in determining past drug administration. However, due to varying dynamics, P not be useful in determining there is generally no correlation between blood and nail concentrations.68 Hence determining cause of death cause of death may be tricky in some situations Risk of contamination,  enobiotic RNA e.g., dermatophyte mRNA has been shown to exist in infected nails.76 Similarly, small internal X especially with respect to proteins may also exist in nails and such things can confound expected outcomes51 analysis of xenobiotics in nail specimens PCR: Polymerase chain reaction and healthy fingernails have also been evaluated.92 It was The nail has been proposed as a more reliable biological meter for reported that the dielectric measurements of human nail arsenic than serum because elevated levels would be maintained could be used for the detection of diabetes in the former for a longer time. Further, external contamination Nasli‑Esfahani et al. carried out elemental analysis of nail as of nails with arsenic is much less extensive compared to that of well as other biological samples (serum, scalp hair, urine and hair.94 Long‑term exposure to arsenic can lead to adverse health other body fluids) in diabetic patients.93 They concluded that effects95,96 Lu et al. concluded that high arsenic exposure in scalp hair and nail are the best biological samples for trace humans promotes cancer initiation,97 though the exact mechanism element analysis in diabetics (especially Cr, Se, and Mn) of arsenic’s role in carcinogenesis remains unknown.98,99 Laser‑induced breakdown spectroscopy (LIBS) has been Mechanisms responsible for arsenic accumulation in nails are used for analyzing diabetic and nondiabetic nails.1 It was poorly understood. The affinity of arsenic to sulphydryl groups of concluded that LIBS spectra of fingernail can be a valid nail keratins may be responsible.100 screening tool for diabetics in a large population with the advantages of quick measurement, broad elemental Forensic importance of nails coverage, and low cost1 The nail plate is an important substrate for diagnosis in forensic Nail fold capillaroscopic (NFC) images were evaluated science.101 Forensic casework routinely involves examination quantitatively as well as qualitatively in 145 children with of fingernail scrapings and clippings for foreign DNA. In this Type 1 diabetes mellitus.90 Increases in the number as well scenario, both in‑vivo and in‑vitro analysis of nail specimens as length of capillaries, presence of mega‑capillaries and assumes significance. Though finger‑nails may not be as useful as Raynaud’s loops, and intense red background (possible fingerprints for identification, in many cases broken fingernail plates neoangiogenesis) were the recorded findings. Longer disease have been used to associate a suspect with the victim by comparing duration correlated with an increase in the number of nail ridge patterns.102 capillaries, disturbances in distribution, as well as the presence of abnormal capillaries. NFC is a noninvasive, painless and Matte et al. reported that up to 19% of the general population may easily repeatable test allowing digital storage of images; it can have foreign DNA beneath their fingernails, whereas foreign DNA be used as an effective monitoring tool in diabetics.90 may be detected in 33% of forensic fingernail samples.103 The normally present foreign DNA also tends not to persist for long. This Role of nail clippings in oncology needs to be taken into account by forensic analysts when providing Recent oncological research has focused on the primary an opinion on the relevance of foreign DNA under fingernails. prevention of cancer and identifying individuals at risk. It is known that trace elements have inhibitory as well as causative In forensic toxicology, reports abound on the usefulness of roles in oncogenesis. In addition, exposure to trace elements can detecting drugs of abuse in nails. Brown et al. reported the utility be predetermined (e.g. arsenic) and may also be a modifiable of fingernail clippings in testing for levels of anabolic steroids risk‑factor.91 Nail‑clippings are therefore regarded as valuable in sportspersons with doping charges.104 Other reports include biomarkers for such exposures.93,94 amphetamine‑type stimulants, methadone, cocaine breakdown products, phenylalkylamine derivatives, and cannabinoids being The FINBAR (Factors Influencing Barrett’s Adenocarcinoma detected.105‑113 Further, ethyl glucuronide (EtG) has been put Relationship) study group attempted to correlate trace element status forward as a new biomarker in nails for alcohol consumption in toenails with the risk of Barrett’s oesophagus and oesophageal behavior.114 adenocarcinoma.91 Toenail clippings from 638 participants and healthy controls were analyzed for eight trace elements. There was a Miscellaneous medical disorders two‑fold higher risk of Barrett’s oesophagus with high toenail zinc, a Apart from the diseases discussed above, nail clippings/biopsies borderline significant, increased risk with higher cobalt levels, and no have been useful in other diseases. The utility of the “nail window” association with levels of chromium, cerium, mercury, and selenium. into systemic diseases cannot be undermined.115 Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 639 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know Nail biopsies have been found useful in gout to detect urate crystals be used to determine the level of exposure. Radiation sensitivity in subungual horn.116 Tirado‑González et al. described subungual of nails is relatively high and changes produced in nails exposed urate crystals extruded subclinically in some cases of gout.116 Nail to radiation have been found to be a useful biodosimetry method. biopsies taken to evaluate fungal elements showed urate crystals In addition, the radicals generated in condensed nail protein instead and the history subsequently confirmed gout. It was reported are stable over time.128,129 An ex‑vivo estimation of severity of that there were no tophi noted in or near the nail field. Such crystals radiation exposure based on the electron paramagnetic resonance probably occur via exudation/transudation of fluids into the nail nail dosimetry was evaluated by He et al.128 Human nail structure, offering a “nail window” into haematic or metabolic clippings were used to evaluate stable radiation‑induced signal. abnormalities. The authors concluded that the cytological and It was found that a reliable triage based on radiation dosage was histological findings in nail specimens could be used to evaluate possible.130 The technique also ensured immediate and rapid dose nail diseases as well as systemic diseases.116 assessment. Similarly, toenail nicotine levels have been used as biomarkers This review has some limitations. The topic being vast, we may to predict the risk of coronary heart disease (CHD). In a have missed additional diagnostic applications of the nail unit not nested case‑control study involving 62,641 women followed adequately represented in the indexed literature. In addition, with up over 16 years,117 a statistically significant, dose‑response expanding developments in the field, a compendium such as this association was seen between increased toenail nicotine levels and may fall short of the latest information at times despite our efforts risk of CHD. The authors concluded that toenail nicotine levels to make it up‑to‑date. are predictive of CHD among women independent of other risk factors. Conclusion It is clear from the recent growth in literature that the nail is not just Nails for biometrics an inert skin appendage, but. a dynamic part of the human body, With advances in information technology, security aspects reflective of the changes in the metabolic and genetic milieu. Nail have become paramount. Authentication is a prerequisite for specimens are a valuable diagnostic tool as they are easy to retrieve, security with biometric authentication being an important mode. without causing significant discomfort. The coming years are likely This involves automated recognition of individuals based on to see more research and expansion of knowledge in this field. their physiological characteristics, identifying a person based on “who she/he is” rather than “what she/he has” (card, token, key); Financial support and sponsorship or “what she/he knows” (password, pin).119 Common characteristics Nil. used for biometrics include face recognition, fingerprints, handwriting, hand geometry, iris, vein, voice or retinal scan. The Conflicts of interest use of fingernail patterns as biometric markers has been evaluated There are no conflicts of interest. and found to be useful.118 Herein, authentication is based on unique individual ridge patterns of the nail bed reflected on the nail plate surface, which can be evaluated by computational analysis even References 1. Bahreini M, Ashrafkhani B, Tavassoli SH. Discrimination of patients in low‑resolution images.120 This has proved to be a very unique with diabetes mellitus and healthy subjects based on laser‑induced and stable biometric identifier, good enough for forensic as well as breakdown spectroscopy of their fingernails. J Biomed Opt 2013; civilian applications.120 Extensive experimentation has validated its 18:107006. use. 2. Klassen TL, von Rüden EL, Drabek J, Noebels JL, Goldman AM. Comparative analytical utility of DNA derived from alternative human The low‑resolution nail plate images are acquired with a contactless, specimens for molecular autopsy and diagnostics. J Mol Diagn 2012; unconstrained imaging setup analyzing texture‑based feature 14:451‑7. 3. Gong IY, Tirona RG, Schwarz UI, Crown N, Dresser GK, Larue S, descriptors. Then, computational analysis is used for integrating et al. Prospective evaluation of a pharmacogenetics‑guided warfarin nail plates from three fingers. Outcomes of rigorous experimental loading and maintenance dose regimen for initiation of therapy. Blood analysis on 2700 nail plate images found this to be a promising 2011; 118:3163‑71. biometric modality.121 Nail bed pattern can also be analyzed with a 4. Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris‑Kerr C, laser‑based broadband interferometer technique.122 Another system Pollevick GD, et al. Spectrum and prevalence of mutations from the measuring spacing of the capillary loops with highly monochromatic first 2,500 consecutive unrelated patients referred for the FAMILION light has also been evolved.123 long QT syndrome genetic test. Heart Rhythm 2009; 6:1297‑303. 5. Tester DJ, Will ML, Haglund CM, Ackerman MJ. Compendium of cardiac channel mutations in 541 consecutive unrelated patients Hand‑based biometrics has high user acceptance and reliability. Of referred for long QT syndrome genetic testing. Heart Rhythm 2005; these, the fingernail plate is characterized by high individuality,124,125 2:507‑17. with a high degree of distinctiveness, even among identical twins.126 6. Pirmohamed M. Acceptance of biomarker‑based tests for application Moreover, the hardened nail resists environmental effects, barring in clinical practice: Criteria and obstacles. Clin Pharmacol Ther 2010; changes caused by nail diseases/disorders and malnutrition.127 This 88:862‑6. ensures high reproducibility as well. 7. Klassen T, Davis C, Goldman A, Burgess D, Chen T, Wheeler D, et al. Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Cell 2011; Radiation dosimetry 145:1036‑48. Rapid and accurate determination of individual radiation 8. Johnson JN, Tester DJ, Bass NE, Ackerman MJ. Cardiac channel exposure would be needed to screen exposed populations in case molecular autopsy for sudden unexpected death in epilepsy. J Child of a radiological/nuclear event. It has been seen that estimating Neurol 2010; 25:916‑21. the chemical or physical alterations produced in biomaterials can 9. Skinner JR, Crawford J, Smith W, Aitken A, Heaven D, Evans CA, 640 Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know et al. Prospective, population‑based long QT molecular autopsy study McAdam PA, et al. Selenium in diet, blood, and toenails in relation to of postmortem negative sudden death in 1 to 40 year olds. Heart human health in a seleniferous area. Am J Clin Nutr 1991;53:1288‑94. Rhythm 2011; 8:412‑9. 34. Steven Morris J, Stampfer MJ, Willett W. Dietary selenium in humans 10. Madry MM, Steuer AE, Binz TM, Baumgartner MR, Kraemer T. toenails as an indicator. Biol Trace Elem Res 1983;5:529‑37. Systematic investigation of the incorporation mechanisms of zolpidem 35. Morris JS, Ngwenyama R, Guthrie JM, Brockman JD, Spate VL, in fingernails. Drug Test Anal 2014; 6:533‑41. Robertson JD. Quality control in the neutron activation analysis of 11. Pragst F, Balikova MA. State of the art in hair analysis for detection of biological markers for selenium in epidemiological investigations. drug and alcohol abuse. Clin Chim Acta 2006; 370:17‑49. J Radioanal Nucl Chem 2008;276:7‑13. 12. Henderson GL. Mechanisms of drug incorporation into hair. Forensic 36. Gherase MR, Desouza ED, Farquharson MJ, McNeill FE, Kim CY, Sci Int 1993; 63:19‑29. Fleming DE, et al. X‑ray fluorescence measurements of arsenic 13. Cone EJ. Mechanisms of drug incorporation into hair. Ther Drug Monit micro‑distribution in human nail clippings using synchrotron radiation. 1996; 18:438‑43. Physiol Meas 2013;34:1163‑77. 14. Johnson M, Shuster S. Continuous formation of nail along the bed. Br 37. Preuner S, Danzer M, Pröll J, Pötschger U, Lawitschka A, Gabriel C, J Dermatol 1993; 128:277‑80. et al. High‑quality DNA from fingernails for genetic analysis. J Mol 15. Finlay AY. Pharmacokinetics of terbinafine in the nail. Br J Dermatol Diagn 2014;16:459‑66. 1992; 126 Suppl 39:28‑32. 38. Schraml E, Daxberger H, Watzinger F, Lion T. Quantitative analysis of 16. Matthieu L, De Doncker P, Cauwenbergh G, Woestenborghs R, chimerism after allogeneic stem cell transplantation by PCR amplification van de Velde V, Janssen PA, et al. Itraconazole penetrates the nail via of microsatellite markers and capillary electrophoresis with fluorescence the nail matrix and the nail bed – an investigation in onychomycosis. detection: The Vienna experience. Leukemia 2003;17:224‑7. Clin Exp Dermatol 1991;16:374‑6. 39. Jones J, Jones M, Plate C, Lewis D, Fendrich M, Berger L, et al. 17. Laufen H, Zimmermann T, Yeates RA, Schumacher T, Wildfeuer A. Liquid chromatography‑tandem mass spectrometry assay to detect The uptake of fluconazole in finger and toe nails. Int J Clin Pharmacol ethyl glucuronide in human fingernail: Comparison to hair and gender Ther 1999;37:352‑60. differences. Am J Analyt Chem 2012;3:83‑91. 18. Goullé JP, Saussereau E, Mahieu L, Bouige D, Groenwont S, 40. Skopp G, Pötsch L. A case report on drug screening of nail clippings to Guerbet M, et al. Application of inductively coupled plasma mass detect prenatal drug exposure. Ther Drug Monit 1997;19:386‑9. spectrometry multielement analysis in fingernail and toenail as a 41. Danzer M, Niklas N, Stabentheiner S, Hofer K, Pröll J, Stückler C, biomarker of metal exposure. J Anal Toxicol 2009;33:92‑8. et al. Rapid, scalable and highly automated HLA genotyping using 19. De Giovanni N, Fucci N. The current status of sweat testing for drugs next‑generation sequencing: A transition from research to diagnostics. of abuse: A review. Curr Med Chem 2013;20:545‑61. BMC Genomics 2013;14:221. 20. Lorincz AL, Stoughton RB. Specific metabolic processes of skin. 42. Tanigawara Y, Kita T, Hirono M, Sakaeda T, Komada F, Okumura K. Physiol Rev 1958;38:481‑502. Identification of N‑acetyltransferase 2 and CYP2C19 genotypes for 21. Munro CS, Shuster S. The route of rapid access of drugs to the distal hair, buccal cell swabs, or fingernails compared with blood. Ther Drug nail plate. Acta Derm Venereol 1992;72:387‑8. Monit 2001;23:341‑6. 22. Morris JS, Crane SB. Selenium toxicity from a misformulated dietary 43. Matsuzawa N, Shimozato K, Natsume N, Niikawa N, Yoshiura K. supplement, adverse health effects, and the temporal response in the A novel missense mutation in van der woude syndrome: Usefulness of nail biologic monitor. Nutrients 2013;5:1024‑57. fingernail DNA for genetic analysis. J Dent Res 2006;85:1143‑6. 23. Kim JY, Cheong JC, Lee JI, Son JH, In MK. Rapid and simple 44. van Breda SG, Hogervorst JG, Schouten LJ, Knaapen AM, GC‑MS method for determination of psychotropic phenylalkylamine van Delft JH, Goldbohm RA, et al. Toenails: An easily accessible and derivatives in nails using micro‑pulverized extraction. J Forensic Sci long‑term stable source of DNA for genetic analyses in large‑scale 2012;57:228‑33. epidemiological studies. Clin Chem 2007;53:1168‑70. 24. Lemos NP, Anderson RA, Robertson JR. The analysis of methadone 45. Park J, Liang D, Kim JW, Luo Y, Huang T, Kim SY, et al. Nail DNA in nail clippings from patients in a methadone‑maintenance program. and possible biomarkers: A pilot study. J Prev Med Public Health J Anal Toxicol 2000;24:656‑60. 2012;45:235‑43. 25. Kim JY, Cheong JC, Kim MK, Lee JI, In MK. Simultaneous 46. Lecomte T, Berger A, Zinzindohoué F, Micard S, Landi B, Blons H, determination of amphetamine‑type stimulants and cannabinoids in et al. Detection of free‑circulating tumor‑associated DNA in plasma fingernails by gas chromatography‑mass spectrometry. Arch Pharm of colorectal cancer patients and its association with prognosis. Int J Res 2008;31:805‑13. Cancer 2002;100:542‑8. 26. Morini L, Colucci M, Ruberto MG, Groppi A. Determination of 47. Nie SJ, Yang YM, Tang WR, Xu BY, Jing Q, Xiao CJ, et al. Extraction ethyl glucuronide in nails by liquid chromatography tandem mass and analysis of nuclear DNA from free margin of nail material. Yi spectrometry as a potential new biomarker for chronic alcohol abuse Chuan 2007;29:1373‑7. and binge drinking behavior. Anal Bioanal Chem 2012;402:1865‑70. 48. Anderson TD, Ross JP, Roby RK, Lee DA, Holland MM. A validation 27. Finlay AY. Pharmacokinetics of terbinafine in the nail. Br J Dermatol study for the extraction and analysis of DNA from human nail material 1992;39 126 Suppl:28. and its application to forensic casework. J Forensic Sci 1999;44:1053‑6. 28. Mari F, Politi L, Bertol E. Nails of newborns in monitoring drug 49. Nakashima M, Tsuda M, Kinoshita A, Kishino T, Kondo S, exposure during pregnancy. Forensic Sci Int 2008;179:176‑80. Shimokawa O, et al. Precision of high‑throughput single‑nucleotide 29. Samek O, Beddows DC, Telle HH, Morris GW, Liska M, Kaiser J. polymorphism genotyping with fingernail DNA: Comparison with Quantitative analysis of trace metal accumulation in teeth using blood DNA. Clin Chem 2008;54:1746‑8. laser‑induced breakdown spectroscopy. Appl Phys A 1999;69:S179‑82. 50. Nishiyori A, Fukuda K, Sata M, Tanikawa K. HBV DNA can be 30. Carter LP. Potential impact of drug effects, availability, detected from nail clippings of HBs ag positive patients. Kurume Med pharmacokinetics, and screening on estimates of drugs implicated in J 2000;47:95‑6. cases of assault. Drug Test Anal 2011;3:586‑93. 51. Dekio S, Jidoi J. Comparison of human hair and nail low‑sulfur 31. Samanidou V, Pantazidou K, Kovatsi L, Njau S, Livanos A. A simple protein compositions on two‑dimensional electrophoresis. J Dermatol HPLC method for the simultaneous determination of two selective 1989;16:284‑8. serotonin reuptake inhibitors and two serotonin‑norepinephrine 52. Oimomi M, Hatanaka H, Ishikawa K, Kubota S, Yoshimura Y, Baba S, reuptake inhibitors in hair, nail clippings, and cerebrospinal fluid. J Sep et al. Increased fructose‑lysine of nail protein in diabetic patients. Klin Sci 2012;35:839. Wochenschr 1984;62:477‑8. 32. Shi Y, Zhang J, Lu L, Shao B. Determination of triclosan and triclocarban 53. Yoshida‑Yamamoto S, Nishimura S, Okuno T, Rakuman M, Takii Y. in human nails by solid‑phase extraction and ultra‑performance liquid Efficient DNA extraction from nail clippings using the protease chromatography‑tandem mass spectrometry. Se Pu 2013;31:1040. solution from Cucumis melo. Mol Biotechnol 2010;46:41‑8. 33. Longnecker MP, Taylor PR, Levander OA, Howe M, Veillon C, 54. Swisher EM, Wollan M, Mahtani SM, Willner JB, Garcia R, Goff BA, Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 641 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know et al. Tumor‑specific p53 sequences in blood and peritoneal fluid of women 76. Baudelet M, Yu J, Bossu M, Jovelet J, Wolf JP, Amodeo T. with epithelial ovarian cancer. Am J Obstet Gynecol 2005;193:662‑7. Discrimination of microbiological samples using femtosecond 55. Taback B, Hoon DS. Circulating nucleic acids and proteomics of laser‑induced breakdown spectroscopy. Appl Phys Lett 2006;89:16903-6. plasma/serum: Clinical utility. Ann N Y Acad Sci 2004;1022:1‑8. 77. Rehse SJ, Jeyasingham N, Diedrich J, Palchaudhuri S. A membrane 56. Salani R, Davidson B, Fiegl M, Marth C, Müller‑Holzner E, Gastl G, basis for bacterial identification and discrimination using laser‑induced et al. Measurement of cyclin E genomic copy number and strand length breakdown spectroscopy. J Appl Phys 2009;105:102034-13. in cell‑free DNA distinguish malignant versus benign effusions. Clin 78. Samek, Liska M, Kaiser J, Beddows DC, Telle HH, Kukhlevsky SV. Cancer Res 2007;13:5805‑9. Clinical application of laser‑induced breakdown spectroscopy to 57. Herrera LJ, Raja S, Gooding WE, El‑Hefnawy T, Kelly L, Luketich JD, the analysis of teeth and dental materials. J Clin Laser Med Surg et al. Quantitative analysis of circulating plasma DNA as a tumor 2000;18:281‑9. marker in thoracic malignancies. Clin Chem 2005;51:113‑8. 79. Corsi M, Cristoforetti G, Hidalgo M, Legnaioli S, Palleschi V, 58. Inoue T, Kizawa K, Ito M. Characterization of soluble protein extracts Salvetti A, et al. Application of laser‑induced breakdown spectroscopy from keratinized tissues: Identification of ubiquitin universally technique to hair tissue mineral analysis. Appl Opt 2003;42:6133‑7. distributed in hair, nail, and stratum corneum. Biosci Biotechnol 80. Kasem MA, Russo RE, Harith MA. Influence of biological degradation Biochem 2001;65:895‑900. and environmental effects on the interpretation of archeological 59. Giasuddin AS, Jhuma KA, Haq AM. Applications of free circulating bone samples with laser‑induced breakdown spectroscopy. J Anal At nucleic acids in clinical medicine: Recent advances. Bangladesh Med Spectrom 2011;26:1733‑9. Res Counc Bull 2008;34:26‑32. 81. Hosseinimakarem Z, Tavassoli SH. Analysis of human nails by 60. Tong YK, Lo YM. Diagnostic developments involving laser‑induced breakdown spectroscopy. J Biomed Opt 2011;16:057002. cell‑free (circulating) nucleic acids. Clin Chim Acta 2006;363:187‑96. 82. Bahreini M, Hosseinimakarem Z, Tavassoli HS. A study of association 61. Pinzani P, Salvianti F, Pazzagli M, Orlando C. Circulating nucleic acids between fingernail elements and osteoporosis by laser‑induced in cancer and pregnancy. Methods 2010;50:302‑7. breakdown spectroscopy. J Appl Phys 2012;112: 054701. 62. Zachariah R, Schmid S, Radpour R, Buerki N, Fan AX, Hahn S, et al. 83. Shi Y, Zhang J, Lu L, Shao B. Determination of triclosan and Circulating cell‑free DNA as a potential biomarker for minimal and triclocarban in human nails by solid‑phase extraction and ultra mild endometriosis. Reprod Biomed Online 2009;18:407‑11. performance liquid chromatography‑tandem mass spectrometry. Se 63. Zitt M, Müller HM, Rochel M, Schwendinger V, Zitt M, Goebel G, Pu 2013;31:1040‑5. et al. Circulating cell‑free DNA in plasma of locally advanced rectal 84. Pearce DC, Dowling K, Gerson AR, Sim MR, Sutton SR, Newville M, cancer patients undergoing preoperative chemoradiation: A potential et al. Arsenic microdistribution and speciation in toenail clippings diagnostic tool for therapy monitoring. Dis Markers 2008;25:159‑65. of children living in a historic gold mining area. Sci Total Environ 64. Dawber RP. The ultrastructure and growth of human nails. Arch 2010;408:2590‑9. Dermatol Res 1980;269:197‑204. 85. Gherase MR, Desouza ED, Farquharson MJ, McNeill FE, 65. Fleckman P. Anatomy and physiology of the nail. Dermatol Clin Kim CY, Fleming DE. X‑ray fluorescence measurements of arsenic 1985;3:373‑81. micro‑distribution in human nail clippings using synchrotron radiation. 66. Orentreich N, Markofsky J, Vogelman JH. The effect of aging on the Physiol Measu 2013;34:1163. rate of linear nail growth. J Invest Dermatol 1979;73:126‑30. 86. Hopps HC. The biologic bases for using hair and nail for analyses of 67. Samanidou V, Pantazidou K, Kovatsi L, Njau S, Livanos A. A simple trace elements. Sci Total Environ 1977;7:71‑89. HPLC method for the simultaneous determination of two selective 87. Baran R, Dawber RP, Haneke E, Tosti A, Bristow I, editors. A Text serotonin reuptake inhibitors and two serotonin‑norepinephrine Atlas of Nail Disorders: Techniques in Investigation and Diagnosis. reuptake inhibitors in hair, nail clippings, and cerebrospinal fluid. J Sep 3rd ed. London: Martin Dunitz, Taylor & Francis Group; 2005. Sci 2012;35:839‑45. 88. Sukumar A. Human nails as a biomarker of element exposure. Rev 68. Montgomery GW, Campbell MJ, Dickson P, Herbert S, Siemering K, Environ Contam Toxicol 2006;185:141‑77. Ewen‑White KR, et al. Estimation of the rate of SNP genotyping errors 89. Kaminska‑Winciorek G, Deja G, Polańska J, Jarosz‑Chobot P. Diabetic from DNA extracted from different tissues. Twin Res Hum Genet microangiopathy in capillaroscopic examination of juveniles with 2005;8:346‑52. diabetes type 1. Postepy Hig Med Dosw (Online) 2012;66:51‑9. 69. Agalliu I, Schweitzer PA, Leanza SM, Burk RD, Rohan TE. Illumina 90. Kishabongo AS, Katchunga P, Van Aken EH, Speeckaert MM, DNA test panel‑based genotyping of whole genome amplified‑DNA Lagniau S, Husein D, et al. Glycated nail proteins: A new approach extracted from hair samples: Performance and agreement with for detecting diabetes in developing countries. Trop Med Int Health genotyping results from genomic DNA from buccal cells. Clin Chem 2014;19:58‑64. Lab Med 2009;47:516‑22. 91. O’Rorke MA, Cantwell MM, Abnet CC, Brockman AJ, Murray LJ; 70. Verbeek NE, van Kempen M, Gunning WB, Renier WO, Westland B, FINBAR Study Group. Toenail trace element status and risk of Barrett’s Lindhout D, et al. Adults with a history of possible dravet syndrome: oesophagus and oesophageal adenocarcinoma: Results from the An illustration of the importance of analysis of the SCN1A gene. FINBAR study. J Cancer 2012;131:1882‑91. Epilepsia 2011;52:e23‑5. 92. Jabłecka A, Olszewski J, Marzec E. Dielectric properties of 71. Miller CJ, Cheung M, Sharma A, Clarke L, Helm K, Mauger D, et al. keratin‑water system in diabetic and healthy human fingernails. J Non Method of mutation analysis may contribute to discrepancies in reports Cryst Solids 2009;355:2456‑60. of (V599E) BRAF mutation frequencies in melanocytic neoplasms. 93. Nasli‑Esfahani E, Faridbod F, Larijani B, Ganjali MR, Norouzi P. Trace J Invest Dermatol 2004;123:990‑2. element analysis of hair, nail, serum and urine of diabetes mellitus 72. Lane JA, Noble JA. Maximizing deoxyribonucleic acid yield from patients by inductively coupled plasma atomic emission spectroscopy. dried blood spots. J Diabetes Sci Technol 2010;4:250‑4. Iran J Diabetes Lipid Disord 2011;10:1‑9. 73. Mulot C, Stücker I, Clavel J, Beaune P, Loriot MA. Collection of human 94. Mandal BK, Ogra Y, Anzai K, Suzuki KT. Speciation of arsenic in genomic DNA from buccal cells for genetics studies: Comparison biological samples. Toxicol Appl Pharmacol 2004;198:307‑18. between cytobrush, mouthwash, and treated card. J Biomed Biotechnol 95. Karagas MR, Morris JS, Weiss JE, Spate V, Baskett C, Greenberg ER, 2005;2005:291‑6. et al. Toenail samples as an indicator of drinking water arsenic 74. Barker PE, Murthy M. Biomarker validation for aging: Lessons from exposure. Cancer Epidemiol Biomarkers Prev 1996;5:849‑52. mtDNA heteroplasmy analyses in early cancer detection. Biomark 96. Button M, Jenkin GR, Harrington CF, Watts MJ. Human toenails as Insights 2009;4:165‑79. a biomarker of exposure to elevated environmental arsenic. J Environ 75. Tsuboi R, Okeke CN, Inoue A, Yamazaki M, Hiruma M, Ogawa H, Monit 2009;11:610‑7. et al. Identification and viability assessment of dermatophytes infecting 97. Lu G, Xu H, Chang D, Wu Z, Yao X, Zhang S, et al. Arsenic exposure nail based on quantitative PCR of dermatophyte actin (ACT) mRNA. is associated with DNA hypermethylation of the tumor suppressor gene Nihon Ishinkin Gakkai Zasshi 2002;43:91‑3. p16. J Occup Med Toxicol 2014;9:42. 642 Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 Grover and Bansal Nail as an investigative tool: What a dermatologist ought to know 98. Hughes MF. Arsenic toxicity and potential mechanisms of action. 114. Jones J, Jones M, Plate C, Lewis D, Fendrich M, Berger L, et al. Toxicol Lett 2002;133:1‑16. Liquid chromatography‑tandem mass spectrometry assay to detect 99. Shi H, Hudson LG, Liu KJ. Oxidative stress and apoptosis in metal ethyl glucuronide in human fingernail: Comparison to hair and gender ion‑induced carcinogenesis. Free Radic Biol Med 2004;37:582‑93. differences. Am J Anal Chem 2012;3:83. 100. Wilhelm M, Pesch B, Wittsiepe J, Jakubis P, Miskovic P, Keegan T, 115. Grover C, Chaturvedi UK, Reddy BS. Role of nail biopsy as a et al. Comparison of arsenic levels in fingernails with urinary as diagnostic tool. Indian J Dermatol Venereol Leprol 2012;78:290‑8. species as biomarkers of arsenic exposure in residents living close to a 116. Tirado‑González M, González‑Serva A. The nail plate biopsy may pick coal‑burning power plant in Prievidza district, Slovakia. J Expo Anal up gout crystals and other crystals. Am J Dermatopathol 2011;33:351‑3. Environ Epidemiol 2005;15:89‑98. 117. Al‑Delaimy WK, Stampfer MJ, Manson JE, Willett WC. Toenail 101. MacDonell HL, Bialousz LF. Evaluation of human fingernails as a nicotine levels as predictors of coronary heart disease among women. means of personal identification. In: Wecht C, editor. Legal Medicine Am J Epidemiol 2008;167:1342‑8. Annual. New York: Appleton‑Century‑Crofts; 1972. p. 135‑43. 118. Kumar A, Garg S, Hanmandlu M. Biometric authentication using finger 102. Bragulla HH, Homberger DG. Structure and functions of keratin nail plates. Expert systems with applications 2014;41:373‑86. proteins in simple, stratified, keratinized and cornified epithelia. J Anat 119. Garg S, Kumar A, Hanmandlu M. Finger nail plate: A new biometric 2009;214:516‑59. identifier. Int J Compt Inf Syst Ind Manage Appl 2014;6:126‑38. 103. Matte M, Williams L, Frappier R, Newman J. Prevalence and 120. Garg S, Kumar A, Hanmandlu M. Biometric Authentication Using Finger persistence of foreign DNA beneath fingernails. Forensic Sci Int Genet Nail Surface. In Intelligent Systems Design and Applications (ISDA), 2012;6:236‑43. 2012 12th International Conference on 2012 November 27, IEEE; 2012. 104. Brown HG, Perrett D. Detection of doping in sport: Detecting p. 497‑502. anabolic‑androgenic steroids in human fingernail clippings. Med Leg 121. Topping A, Kuperschmidt V, Gormley A; Inventors; Topping, Allen, J 2011;79:67‑9. Kuperschmidt, Vladimir, Gormley, Austin, Assignee. Method and 105. Kim JY, Cheong JC, Kim MK, Lee JI, In MK. Simultaneous Apparatus for the Automated Identification of Individuals by the Nail determination of amphetamine‑type stimulants and cannabinoids in Beds of their Fingernails. United States Patent US 5,751,835; May fingernails by gas chromatography‑mass spectrometry. Arch Pharm 1998. Res 2008;31:805. 122. Runne U, Orfanos CE. The human nail: Structure, growth and 106. Kim JY, Shin SH, In MK. Determination of amphetamine‑type pathological changes. Curr Probl Dermatol 1981;9:102‑49. stimulants, ketamine and metabolites in fingernails by gas 123. Baden HP. The physical properties of nail. J Invest Dermatol chromatography‑mass spectrometry. Forensic Sci Int 2010;194:108‑14. 1970;55:115‑22. 107. Lin DL, Yin RM, Liu HC, Wang CY, Liu RH. Deposition characteristics of methamphetamine and amphetamine in fingernail clippings and hair 124. Diaz AA, Boehm AF, Rowe WF. Comparison of fingernail ridge sections. J Anal Toxicol 2004;28:411‑7. patterns of monozygotic twins. J Forensic Sci 1990;35:97‑102. 108. Suzuki O, Hattori H, Asano M. Nails as useful materials for detection of 125. Robson JR. Hardness of finger nails in well‑nourished and malnourished methamphetamine or amphetamine abuse. Forensic Sci Int 1984;24:9. populations. Br J Nutr 1974;32:389‑94. 109. Lemos NP, Anderson RA, Robertson JR. The analysis of methadone 126. Reyes RA, Romanyukha A, Olsen C, Trompier F, Benevides LA. in nail clippings from patients in a methadone‑maintenance program. Electron paramagnetic resonance in irradiated fingernails: Variability J Anal Toxicol 2000;24:656. of dose dependence and possibilities of initial dose assessment. Radiat 110. Kim JY, Cheong JC, Lee JI, Son JH, In MK. Rapid and simple Environ Biophys 2009;48:295‑310. GC‑MS method for determination of psychotropic phenylalkylamine 127. Reyes RA, Trompier F, Romanyukha A. Study of the stability of derivatives in nails using micro‑pulverized extraction. J Forensic Sci EPR signals after irradiation of fingernail samples. Health Phys 2012;57:228. 2012;103:175‑80. 111. Garside D, Ropero‑Miller JD, Goldberger BA, Hamilton WF, 128. He X, Swarts SG, Demidenko E, Flood AB, Grinberg O, Gui J, et al. Maples WR. Identification of cocaine analytes in fingernail and toenail Development and validation of an ex vivo electron paramagnetic specimens. J Forensic Sci 1998;43:974‑9. resonance fingernail biodosimetric method. Radiat Prot Dosimetry 112. Lemos NP, Anderson RA, Robertson JR. Nail analysis for drugs of 2014;159:172‑81. abuse: Extraction and determination of cannabis in fingernails by RIA 129. Swartz HM, Flood AB, Gougelet RM, Rea ME, Nicolalde RJ, and GC‑MS. J Anal Toxicol 1999;23:147‑52. Williams BB, et al. A critical assessment of biodosimetry methods for 113. Morini L, Colucci M, Ruberto M, Groppi A. Determination of large‑scale incidents. Health Phys 2010;98:95‑108. ethyl glucuronide in nails by liquid chromatography tandem mass 130. González AJ. Lauriston S. Taylor Lecture: Radiation protection in the spectrometry as a potential new biomarker for chronic alcohol abuse aftermath of a terrorist attack involving exposure to ionizing radiation. and binge drinking behavior. Anal Bioanal Chem 2012;402:1865. Health Phys 2005;89:418‑46. Indian Journal of Dermatology, Venereology, and Leprology | Volume 83 | Issue 6 | November-December 2017 643