MEDMAG
2024 EDITION
Content
Editor’s note Zain Hasan
1. What is copycat suicide, and what mechanisms can help to explain it? (Boran Sahin)
2. Thalidomide - the story of its complex chirality (Nathan Wolfson)
3. How important is it to prioritise a long, organic, healthy sleep? (Ibrahim Khan)
4. Understanding the brain (Zakariya Tanweer) 5. mRNA vaccines - the future of vaccinology (Shay Patel) 6. ELISA in microbiology (Arnav Dubey) 7.
PrefaceandEditor’s
Note
The outgoing MedSoc committee of 2023-24 is proud to finally present this year’s edition of MedMag. This years edition showed a particularly diverse range of captivating topics, from psychological and chemical phenomena to vaccinology, capturing the true foothold medicine seems to have anchored in nearly every scientific discipline. Whether your interests lie in humanities or you are a STEM geek, there will no doubt be something that captures your interest within the pages ahead.
I would like to thank every single contributor here for their hard work in producing these thoroughly scrutinised pieces of research, and I congratulate them on taking time to explore their interests in the medical profession. Though I write purely as an aspiring medic for the time being, I have taken great pleasure in exploring the social and scientific mix that medicine offers, and I, along with the rest of our outgoing committee, look forward to taking just one step closer to becoming a doctor in September.
But for now, happy reading, and we wish you all the best on your future endeavours!
Zain Hasan, Editor of MedMagThe MedSoc Committee, 2023-24
What is copycat suicide, and what mechanisms help to explain it?
Boran Sahin, L6H1What is copycat suicide?
Copycatsuicide,alsoknownastheWerthereffect,isthephenomenonthatresultsina noticeablespikeinsuicideafterthepublicisedlossofacelebrityororpublicfigure.The Werthereffectdisproportionatelyaffectsyoungpeople,whotendtobelessequippedto navigatetheintenseemotionthatcanfollowthelossofarolemodel.Althoughitisawholly preventablephenomenon,thereisstilllittleinthewayofawarenessinthepublicandmedia’s psyche,andthisiswhatIhopetoshedsomelightonwiththisarticle.
PerhapsthemostvisiblecaseinrecenttimesisthatofRobinWilliams.Afterhistragiclossin 2014,wewitnessedthemostpronouncedexampleoftheWerthereffectTherewasalmosta fourfoldincreaseincallstosuicidehotlines,andAmericanemergencyroomssawnearly4½ timesasmanypatientspresentingwithsignsofselfharmorfromattemptsontheirlives withinthetwodaysimmediatelyfollowingthenewsbreaking.
Copycatsuicideisuniqueinitsnature,asitisoneoftheonlydirectlyobservablephenomena thatdirectlyinvolvepublichealththatthegeneralpubliccanveryeasilymanipulate.Allit takesfortheWerthereffecttobemitigatedisforonenewspapertosetaprecedentof responsiblereportingguidelines.
What Mechanisms affect the Werther effect?
Atleastthreemechanismsmightexplaintheincreasesinthenumberofsuicidesassociated withreportingofsuicide:identificationwiththedeceasedperson,whichmightoccurmore frequentlywhenthereportedsuicidesareaboutindividualswithhighsocialstanding; increasedmediareportingofsuicideleadingtonormalisationofsuicideasanacceptableway tocopewithdifficulties;andinformationonsuicidemethods,whichmightinfluencethe choiceofsuicidemethodbyavulnerableindividual Astudyshowedthatmediareporting directlyafter13%increaseinsuicidesoverthefollowing1-2months.Thestudyalsoshowed thatwhenthemediareportedthespecificsuicidemethodsusedbycelebrities,thenumberof deathsinthepopulationusingthesamemethodincreasedby30%.(Samaritans,n.d.). Additionally,thereisabeliefthattheWerthereffectactstocatalysethosewhoarealready experiencingsuicidalthoughts
What steps do public health agencies need to take?
Thecurrentscaffoldingaroundmentalhealthtreatmentinthemajorityofthewestern hemisphereleavesalottobedesired.Inmany“developed”nations,thedefactomethodsof treatmentareusuallymedicinal;however,duetotheincrediblyintricatenatureofhuman mentalhealth,thisisoftena‘nuclearoption’.Themajorityofthosesufferingwiththeir mentalhealthwilllikelynotseeinstitutionalisationorheavycoursesofantidepressantsasan appropriatepathwaytotreatment,andsowillsimplynotseekouthelp.Thisisincredibly isolating,andoftenwillleadtothemostvulnerablepeopleinsocietybeingleftontheirown tosufferthroughtheirconditions.
Theknockoneffectsofthiscanbetremendous,ifleftunchecked,mentalhealthcrises, increasedsuicideratesanddrasticallyreducedpublichapinessscalesareamongtherealities wemayhavetocometoexpect.Perhapsmostdangerously,analreadystrugglingNHS wouldbegiventhepossiblyunbearableburdenofhavingtofurtherbolsteritsmentalhealth services.TheBMAstatesthat“TheGovernmentmusturgentlyaddressthatdemandfor mentalhealthservicesisoutpacingtheresourcesaffordedtothem.”(BMA,2023),howeverI wouldliketoputforwardthatthegovernment–andbyextensiontheNHS–arenotthe onlyagentsthatshouldbeheldresponsiblehereAspreviouslymentioned,themediaplaysa hugeroleindecidingthepublicperceptionaroundthesecrises.Itismybeliefthatthereis simplynotinanyformacomprehensivesetofguidelinestosafeguardthesevulnerable membersofoursocietyfromirresponsiblereporting.TheSamaritansregularlypublish statementswarningmediaoutletsonhowtorespondtocelebritysuicide,andthesewarnings areregularlyignored Itisthentheresponsibilityofthepublictostopsupportingthe capitalisationofthesevulnerabledemograpicsinordertobuymoreclicksonanarticle.
Ultimately,significantexpansionmustbemadetotheoptionsavailablethroughtheNHS whenItcomestoMentalhealthtreatmentoptions.TheNHScurrentlyspends8.31%ofits budgetonmentalhealthtreatment,howeverthemajorityofthisgoestowardsitssecure rehabilitation centres Addiitonaly, the8.31% figurealso includes spending on SEND patients.Thisallresultsinasimplyinadequateamountoffundingbeingleftoverfor‘minor mentalhealth’.Forthosewithlessseriousconditions,thereisfrequentlynorealalternativeto MedicationorTherapy.Thisthenmeansthatthemajorityofthosewithminormentalhealth conditions,thatcouldberenderedbeatriskwithminimalintervention,arenowatthe mercyofirresponsiblemediaagencies.
Inconclusion,Itisourjointresponsibility,alongwithgovernmentalagencies,tobeginthe shifttowardbetter,moreequitablementalhealthtreatment.Wecannolongerstandbyas swathesofourpopulationarelefttosufferalone.InthewordsofRobinWilliams,“No matterwhatpeopletellyou,wordsandideascanchangetheworld”.
Thalidomide - the story of its complex chirality
Nathan Wolfson, L6H2Inmodernmedicine,thereisnoprocessmorerigorous,complexandcloselyscrutinised thanthetestingofdrugsbeforeapprovalandclinicalapplication.Itisaculminationof phasedtrials,improvementsandconsultingwithrandomisedgroupsinaculminationof 12.5yearsoftimeandonaverage,£1,150m.Itisdonetoensurethesafetyofpatientsof whomwillbeprescribednewmedicationsandtopreventanyunwarrantedsocialissuesthat couldariseasaresult.
Inthe1960’showever,adrugslippedthroughthenet,causingsocio-economiccatastrophe. Thalidomide,awidelyprescribedmedicationdesignedtoalleviatemorningsicknessbecame infamousafteritsusageledtoseverebirthdefectsinthousandsofinfants.Itleftnew-borns with‘phocomelia’,ararecongenitalanomalywheretheproximityofanextremityisabsent withthehandorfootattacheddirectlytothetrunk.Thisdisabledmanyandcausedlifechangingdamage,tothe(onaverage)60%thatdidn’tdiewithintheirfirstbirthday. (Rehman,ArfonsandLazarus,2011)
Tobegin,Thalidomideisanoralmedicationusedtotreatmanycancersandskindisorders. Itwasfirstmarketedin1957inWestGermany,whereitwasavailableoverthecounter, with its rationale for usage being its sedative or hypnotic properties. Chemically, Thalidomide is known as α-(N-phthalimido) glutarimide, with the formulae, C13H10N2O4andastructureconsistingofaphthalimidecore(acyclicimidederivedfrom aphthalicacid).Thiswasconnectedtoaglutarimidemoietybackbone,withtwoaromatic ringsattached,tofurtherstructuralcomplexity
Inthecompound,onesuchcarbon(C3)wasfoundtohavechiralproperties,meaningthe compoundhadtwoenantiomers,S-thalidomide,andR-thalidomide,thatexistinaracemic mixture.Enantiomersaremoleculesthataremirrorimagesofeachother.Heretheidea grewthatduetothistrait(opticalisomerism)andthefactthetwomoleculescannotbe superimposeddirectlyontopofeachother,theywouldhavedifferentpropertieswhen dissolvedinthebody.Onesuchenantiomerrelievessicknessandnausea,theotherjustso happenstobeassociatedwithteratogeniceffects(long-lastingabnormalities,usuallygrowth restriction).Acombinationthatwouldn’tbeforgotten.
ThemechanismssummarisedbelowshowtheprimarypropertiesthatmakeThalidomidea successfulantiemeticdrug.
Thalidomide(THD)hasbeenconsistentlyobservedinclinicalstudiestohavesedative properties These reduce the perception of nausea, showing a potential overlap in mechanismmuchlikepropofol,midazolamandolanzapine.THDisshowntoimpair cognitivefunctionthroughinvolvementofthecereblon-mediatedmodulationofthe calcium-activatedpotassiumchannelinthehippocampus.Thisleadstoreducedglutamate(a messengerthatinducesnausea-likebehaviour)release,affectingtransmissionofemetic pathways THDalsomodulatestheN-methyl-D-aparticacid(NMDA)pathway,which contributetoneuroprotectiveoutcomesandreductionoftransmissioninthenucleustractus solitarius,thisreducesthedownstreampathwaysresultinginsymptomsofnauseaand vomiting.
THD may alleviate reduced gastric motility induced by anti-cancer chemotherapy, potentiallythroughitsweakinhibitoryactivityonnitricoxidesynthase(NOS)and modulation of tumour necrosis factor alpha (TNFα) levels, which could prevent chemotherapy-inducedchangesingastricmotilityandsubsequentnausea.THDexhibits anti-inflammatoryaffectsbyreducingtheproductionoftumournecrosisfactoralpha (TNFα)andothercytokinessuchasIL-1β,IL-6,andIL-10.Thesearespecificallyseenin theS-enantiomerofTHDandhavearesponsecomparabletoaspirin.Thebuild-upof TNFαitknowntocausenauseaandthusitseffectivemodulationmitigatesemeticaffects
THDexertsamildanti-thyroideffectasobservedduetoareductionofiodineuptakein earlyhumanstudies.Elevatedthyroidhormonelevelsareassociatedwithpregnancyand specificallymorningsicknessandcanbeseentohaveacorrelation.Finally,elevatedblood levelsofGDF15havebeenassociatedwithnauseaandvomitinginpregnantwomen, implicatingGDF15intheinductionofvomiting,especiallyinlaterstagesofpregnancyand hyperemesisgravidarum.THDdirectlytargetsGDF15andmakesitpossibletomanageand mitigate.(Andrews,WilliamsandSanger,2022)
Thecombinationofthesechemicalpropertiesmakeitprimarilysuccessfulintreating sicknessnotonlyinapregnantpatientbutthosewhohadchemotherapy-inducedvomiting andother,likeproblems.However,howdidthedefectivepropertiesoccur?
Therearevaryingcauses,eachwithvaryinglevelsofscrutiny.Forinstance,uponstudiesof theregulationofover9000proteinsafterexposuretoTHD,researchersfoundMEIS2was ubiquitinatedbyCRBNbutupontreatmentwithTHD,becamere-expressed.Traditionally MEIS2,hasbeensuggestedtonegativelyregulatelimbgrowth.However,thisisstilltobe conclusivelyproveninanimalmodels.CD147isalsoknownasabindingcomplexfor CRBN.ItsdestabilisationduetoTHDexpressionreducescellproliferation,causinga reductioningrowth.
Inrecentstudies,ithasbeenshownthatSpaltLikeTranscriptionFactorhasbeendegraded asaresultofCRBNthalidomidetreatment.SALL4playsakeyroleinmaintainingthe pluripotentandself-renewalofembryonicstemcells(ESC’s),whichwhendegradedaffects growth.
Andfinally,thalidomidewasshowninstudiestodisruptsΔNp63/TAp63,contributingto teratogenicity Traditionally,theknockdownofthesecompoundshaveledtodefectsin zebrafish,whilstthenormalexpressionofthesegenesrestoreddownstreamtargetslike FGF8,whichreducedabnormalities.(Asatsuma-Okumura,ItoandHanda,2020)
Allofthiswasbecauseoftheunfortunatedifferenceinisomerresponsewithinthebody. The (R)-enantiomer had sedative effects whereas the (S)-isomer was teratogenic Thalidomidereducedthedevelopmentofembryobloodvessels,whichexplainswhyonly partsofthebabyweredeformed.Theyweregivenareducedbloodsupply,socould undergolessmitosisasaresult.
Fromthisdiscovery,researchersquestionedwhethertheisolationofthe(R)-enantiomer wouldhavemeantthatthedrugcouldfinallybeusedsafelywithinthebody,however foundtheconsequencetobegrave.Itwasfoundtheopticalisomerscouldshiftwithinthe body,toproduceundesiredoutcomes.
The shadow of effect from Thalidomide, forced researchers to consider the chiral componentsofcompoundsandtheirsignificantdifferenceofbehaviourwithinthebody. Today,THDiswidelyusedtolimittumourgrowth,asitconstrictsnewlyformedblood vesselgrowthwithinthebody,however,willalwayshaveamarkinhistoryduetoits oversight.
Forme,thisshowsthepinnaclebeliefattheheartofmedicine.Nomatter,howmuchwe research,orhowconfidentweare,thecomplexityofsciencewillalwaysstand AsIsit writingthisnow,therewillbepartsofmedicinenow,welookbackonwithembarrassment andshame.Medicineisnothingbutanart,sometwistingcreativitymixedwithmistakeand error.Yetthroughthesemistakes,welearn,andproblemsolve,inordertogivepatients,the treatmenttheydeserve.
“Medicine is a science of uncertainty and an art of probability”
- William Osler, founding professor of Johns Hopkins Hospital
How important is it to prioritise a long, organic, healthy sleep?
Ibrahim Khan, L6R1ITheaveragelifeexpectancyofhumanityis71years,meaningwewillspendanaverageof 23orsoyearssleeping,withoutknowingmuchaboutsleepitself,tothepointthat,I believe,manytakeitforgranted.Teenagersrequireatleast8hoursofsleepeverysingle night(SleepFoundation,2024),however,adolescentstendtogetonly6.5-7.5hoursofsleep per night (Better Health, nd), suggesting that we may fundamentally neglect the organizationofourownsleepcycle.Thisprojectwillattempttounderlinethescience behindagoodsleepschedule,theconsequencesofalackthereof,andthethreatstooursleep thataresurprisinglymoredangerousthanwemightthink.
Thefirstquestionthatwemustaskis“whatissleep?”.Oursleepisaconstantcyclebetween twodifferenttypesofsleep,REMandNREMsleep,duringwhichyouareunconscious,and yoursensoryactivityisinhibited.InChapter3ofhisbook“Whywesleep”(2017),Walker mentionsadiscoveryin1952whenEugeneAserinskynoticedthat,whenobservinghuman infant,therewereperiodsofsleepinwhichtheireyeswould“rapidlydartsidetoside underneaththeirlids”.ThisisknownasREMsleepandwasaccompaniedbyactiveand vigorousbrainwaveactivity.Thisperiodofsleepwasdistinctlyseparatedfromadifferent swathoftime,whentheeyeswouldstaystill,andthebrainwaveswouldbecomecalm: NREMsleep.Page47presentsthedifferencesbetweenthem.
Thisiswherewegettheabbreviations REM (rapid-eye movement) sleep and NREM(non-rapideyemovement)sleep from.Thesedistinctphasesofsleeprepeat throughout the night over and over again,nowknownasthesleepcycle. Belowisadiagramwhichshowsthatina typical8hoursofsleepatotaloffivefull sleep cycles will occur: the perfect amount(p.43).Yet,howmuchdoesa long, 8-hour sleep benefit our body comparedtoalackofsuch?Inhisbook, Walkerpresentsafewstudiesexplaining therangeofbenefitssleepoffers.
Image adapted from “Why We Sleep”, Matthew Walker (2017)
Yet,howmuchdoesalong,8-hoursleepbenefitourbodycomparedtoalackofsuch?In hisbook,Walkerpresentsafewstudiesexplainingtherangeofbenefitssleepoffers.
Inchapter6ofhisbook“Whywesleep”(2017)MatthewWalkerexplainsoneofsleep’s benefits,strengtheningmemory.Heandhisteamrecruitedagroupofhealthyadults, separatingthemintoa“napgroupandano-napgroup”(p 109)toseewhichonecould remembermorefacts.Bothgroups’memorieswereofsimilarability.Afterthisthenap grouptookaninety-minutesiestawhereastheno-napgroupstayedawake(p.110).Thenat 6PMonthesameday,anotherroundofintenselearningwithcommenced.Theno-nap groupbecameprogressivelyworseatlearningandthenapgrouphelda“20percent learningadvantage”overtheother,andevenimprovedintheircapacitytomemorisefacts. Whenanalysingthebrainwavesofparticipantsinthenapgroup,theresearchersfoundthat thememory-strengtheningphenomenawereinfactsleepspindles(electricalloopstoand frompartsofthebrain)shiftingtheirfactualmemories(p.111)fromthehippocampus, whichisthebrain’stemporarystoreformemory,tothecortex,whichisalongerterm, securechamberformemory.Fromthis,then,wefindsleepdeeplyfortifiesourmemory.
Moreover,inChapter7ofhisbook“Whywesleep”(2017),Walkerexploresanunintuitive benefitofagoodnight’ssleep,emotionalrationality.Hestudiedtwogroupsofhealthy adults(p.146),oneofwhichstayedawaketheentirenight,whereastheotherslept normally.Thefollowingday,bothgroupswereshown“onehundredpictures”,ranging fromemotionallyneutraltoemotionallynegativeandthushisteamcouldcomparethe increaseinneuralresponsetothemoreemotionallynegativetriggers,betweenthetwo groups. The sleep-deprived group showed a “60 percent amplification” (p. 147) in emotionalreactivityintheiramygdala,apartofthebrainusedfortriggeringouremotions, comparedtoa“modestdegreeofreactivity”forthegroupwhoweregiveagoodnight’s sleep.Withoutsleep,thebraincanreverttoapatternofuncontrolledreactivityand emotionalrationality.Sleepdeprivationcanleadtobullyinginchildren(p.148),aswellas generalaggression,andevensuicide.Thisoccursbecause,afteragood,fullnight’ssleep,the prefrontalcortex(p.147)(theregionassociatedwithrationalthoughtandlogicaldecisionmakingprocedures)becomes“stronglycoupledtotheamygdala”(theemotionalcentreof thebrain)inequilibrium.Yetafteralackofsleep,humanslosethisdelicatecoupling,and therefore,ouratavisticimpulsesaremuchmorelikelytotakeover.
Architecture of sleep and the sleep cycle - adapted from “Why We Sleep”, Matthew Walker (2017)Gettingenoughsleep,perhapsmoreimportantly,isalsoavitalfactorincarsafety,asalack ofsleeppresentsasignificanthigherriskofcarcrashesinFact,almost20%ofseriouscar crashesareassociatedwithdriverfatigue(ColtenH.R.,Altevogt,B.M.,2006).
InPage139ofhisbook“WhyweSleep”(2017),Walkerpresentsabargraphshowing similarresults,modifiedfromanextensivestudyinWashingtonDC(AAAfoundation, 2016).
ThenextmajorpointImustgooveriswhat exactlydoImeanby“organic?Well,theway thatIwoulddefineorganic/naturalinthiscontext isatypeofsleepthatisnotsignificantlyaffected byanyartificialdrugsorexternalvariables.This includes,butisnotlimitedto,themostpopular drugintheentireworld,caffeine.Coffee,aswell asTeaandenergydrinkshavetakentheworldby storm as caffeine is the “most widely used psychoactivesubstanceintheworld,”(CAMH).
Essentially,ithasbecomethego-tosolutionwhenyou’refeelingtiredorstressed
Onereasonourbodyisreadytosleepatnightisthebuild-upofadenosine,which accumulateseverysecondweareawake,inducing“sleeppressure”,andmakesusfeelsleepy. Belowishowthecycleofourwakedrive(circadianrhythmandmelatonin),theother reasonwegetreadytogotosleep,worksalongsidethecycleofoursleeppressure,or adenosinelevels(Walker,M,WhyweSleep(2017),p31)
Caffeinecompeteswithadenosinemoleculesbybindingtotheadenosinereceptorsinour brain.hisinactivatesthereceptorsfrominteractingwithadenosine,blockingthenatural signalsofsleepcommunicatingwithourbrain,thusreducingsleepinessandkeepingus awake Whatmakescaffeinesothreateningtosleepisitshalf-lifeoffivetosevenhours ThismeansthatifIdrinkaredbullataround6PM,50%ofitscaffeinewillstillbeinmy systemfrom11PMtopotentially1AM!Halfthecaffeinefromthatdrinkisstillapowerful countertosleepiness.Moreover,whilstcaffeinedoesblockouradenosinereceptors,itdoes notinhibitadenosineaccumulation.Therefore,afterliverenzymesfinishbreakingdownall thecaffeineinoursystem(duringyoursleep),youradenosinereceptorswillbebombarded withahugeconcentrationofthepreviouslyaccumulatedadenosine,hittingyouwith suddenjoltofsleepinessjustafewhoursafterwakingup.Thisisknownasa“caffeine crash”,andsomemayevenresorttousingmorecaffeinetoresolvethis,whichwillsimply leadtoanothercaffeinecrash,startingadependencycycle.
AstudywaspublishedintheJournalofPaediatricPsychology,todetermineifcaffeine consumptionhadthepotentialtoadverselyaffectsleepqualityinyoungpeople,including thosewithMDD(MajorDepressiveDisorder)(WhalenD.J.,etal.,2007).Researchers askedeveryoneofits53participants,30ofwhichhadMDD,tocompleteasubjectivesleep reporttwiceaweekfor“fiveextendedweekends”acrossthetimeofthestudy,which includedbutwasnotlimitedto:“(a),sleepquality,...(c),timetofallasleep,and(g)total sleeptime”Thestudyintotalranfor8weeksResultsareshownbelow
Walker, M., Why we Sleep (2017)
Whalen D J, et al, 2007
Gettingenoughsleep,perhapsmoreimportantly,isalsoavitalfactorincarsafety,asalack ofsleeppresentsasignificanthigherriskofcarcrashesinFact,almost20%ofseriouscar crashesareassociatedwithdriverfatigue(ColtenH.R.,Altevogt,B.M.,2006).
InPage139ofhisbook“WhyweSleep”(2017),Walkerpresentsabargraphshowing similarresults,modifiedfromanextensivestudyinWashingtonDC(AAAfoundation, 2016).
Fromthedataabovewecanseethatmorefrequentuseofcaffeinateddrinksmaycorrelate toagenerallowersleepquality,accordingtothesubjectivejudgementoftheparticipants,as wellasincreasingthetimetakentofallasleepandincreasingtheeasetobewokenup.
Caffeinateddrinksarenottheonlyartificialmeanstoaffectsleep,however.Apopular methodoffallingasleep,ifyouconsistentlystrugglewithit,istheconsumptionofsleeping pills.Buthowdotheycomparetoanorganicnight’ssleep?
InChapter14ofhisbook“WhyWeSleep”,Walkerexplainsthatsleepmedicationsnever induceanynaturalsleep,andmerely“sedate”youbytargetingthereceptorswhichprevent thefiringofneurones:theyaresedatives(p.282).Becauseofthis,sleepinducedbypills severelylacksthelargerbrainwavesfoundinnaturalNREMsleep(p.283).Thisdipinsleep qualityleadstowakinggrogginess,whichmayincentivisepeopletodrinkmorecoffee throughtheday,whichcandisruptsleepatnight,causingthemtotakeanothersleepingpill thuscontinuingthis“viciouscycle”.And,ifpeoplesuddenlystoptakingmedication,they suffermuchworsesleepthanbefore(knownas“reboundinsomnia”).However,whatis mostconcerningwiththeuseofsleepmedicationisitscorrelationwithprematuredeath andcausingcancer!
Walkerreferstoastudyexaminingwhethertheincreaseduseofsleepingpillsincreased mortalityrisk(KripkeD.F,etal.,2012)(p.286).Researchersexaminedover10,000patients whousedsleepmedicationandcomparedthemto20,000individualsofsimilarage,health, gender,backgroundetcwhowerenottakinganysleepingpills,andcontrolledforother healthfactorswhichcouldaffectmortality.Kripkefoundthatfrequentuseofsedativesdid significantlyincreasemortalityrate,aswellascancerrisks:Participantswhotook18-132 pillsandthosewhotookover132pillsperyearwere1.2and1.35timesmorelikelyto developcancerrespectively.
Inconclusion,agoodsleepscheduleisessentialtoourwell-being,fromdecreasingrisksof carcrashes,to.Weshouldbecautiouswithhowmuchcaffeineweconsumewhichcould disruptoursleepscheduleandrhythm.Despitebeingprescriptiondrugs,poorsleepers shouldalsosteerawayfromtheuseofsleepingpillsandmedicationduetotheirsurprising sideeffectsandrisks.Cognitivebehaviouraltherapyforinsomnia(CBT-I),currently acceptedbythemedicalcommunityasaprimarytreatment(p.290),ismuchbetterifyou findtroublesleeping.Thisinvolvesthereductionofcaffeineandalcoholintake,screentime inthebedroom,establishingaregularbedtimeetc.(p.291),tonaturallyimproveyoursleep qualityandability.
Thankyouforreading,andremember,getsomegoodsleeptonight!
Understanding the Brain
Zakariya Tanweer, L6M2
Asdeterministictheoriesaboutfree-willbecomeincreasinglypopular,manyheadsare turnedtothescientificcommunityforanswers,echoingtheIsraeliteswaitprophecyfrom thebottomofmountSinai.YetwhilstMosesbroughtdownthetencommandmentsfrom itspeak,neuroscientistsarestilltryingtofindawaytoscalethemountain.AsSaskiaDe Vries,Ph.D.,aneuroscientistattheAlleninstitutedescribesit,understandingthebrain“it’s abitlikefishinginthedark”Inthisessay,Iwillbeexploringthereasonswhythebrainis sohardtounderstand,andtheworkthat’sbeingdonetountangleit,oneneuronatatime.
Oneofthebiggestproblemsscientistsface,isthesheercomplexityofthehumanbrain.The averageadultbrainhasaround86,000,000,000neurons(thesameorderasthenumberof starsintheMilkyWay)Onaverageeachoneoftheseneuronshasaround7,000synapses Thatputsthesynapsecountataround600,000,000,000,000(around1quadrillionin childrenbeforesynapticpruningbegins).That’snottomentionthefactthateachsynapseis notabinarytransistor,havingsomewherebetween10and100,000switchesinit.Thereare alsolikelyhundredsoftypesofneurons,somanythatscientistsstilldon’tknowhowmany differentkindsthereare.Andthat’sjustneurons…
Thebrainalsohasmorethan400milesofbloodvessel,whichhasonlyrecentlybeen mappedbyresearchersatStanfordUniversity.TonyWyss-Corray(Ph.D.ofneurology), saysthat“Whileneuronsarethecomputationalunitsofthebrain,thebloodvesselsarethe infrastructure grid providing them the necessary energy”. We can’t disregard their functionalimportanceeither!
Thenthereareglia(derivingfromtheGreek,meaningglue):non-neuronalcellsthat maintain the signalling abilities of neurons, and define synaptic contacts (creating connectionsbetweenneurons).Therearethreetimesasmanygliainthebrainasneurons, butweknowverylittleaboutglia(evenlessthanwedoaboutneurons)!Estimatessuggest thatthehumanbraincanholdabout25petabytesofdata,soit’ssafetosaythatthesheer magnitudeofneurologicalcomplexityinthebrainissufficientforthehardtimescientists arehavingdecipheringit,butitdoesn’tstopthere.
A bone fide obstacle
Sadly,gainingaccesstothebrainisnoeasyfeat.Theimmediatebarrierstoresearchare8 bonesthatformtheneurocranium,obstructingaccess.Asaresult,alargeamountof sophisticatedtechnologyhasbeendevelopedtotacklethisproblem(Note:thefollowing methodsapartfromSingle-UnitrecordingandNeuropixelconcernmappingregionsofthe brainandcannotidentifytheactivityofspecificneurons):
An EEG, or electroencephalography involves placing electrodes on the scalp and a conductivegel,eitherwithindividualwiresstemmingfromeachelectrode,oracap/netin whichtheelectrodesareembedded.Highdensityarrays(typicallyusedinthecapornet setup),cancontainupto256electrodes.Inpracticalapplication,thisnon-invasiveapproach isn’talwayssufficient.Forexample,ifapatientmustundergoanevaluationforepilepsy, oftentheyneedacraniotomy(wheretheboneflapisremovedtoaccessthebrain),before theelectrodescanbeinsertednearthebrainsurfacetoperformanelectrocorticographyor ECoG.Despitetheirtechnicalprecision,sadlyEEG’shaveprettylowspecialresolutiondue tothedistortionsufferedwhentheelectricalsignalsinyourbraininteractwithyourskull. Magnetoencephalographyontheotherhandrecordsmagneticfieldsproducedbyelectrical signalsinthebrain.MEGisreferencefree,contrarytoEEGs,wherethepositionsof electrons(references)needtobesufficientlydefinedifyouwantmeaningfuldata.Magnetic fieldsalsosufferlessdistortionthanelectricalfieldsbytheneurocranium,soMEGshavea higherspecialresolutionandthebrainactivityobservedcanbelocalisedtoaparticular regionwithhigheraccuracy.
FunctionalMagneticResonanceImagingworksabitdifferently,calculatingbrainactivity bymeasuringbloodflow,asthetwoareproportional.Whenaparticularsectionofyour brainperformsanintensivetask,higherbloodflowisrequired,tosupplyitsincreased demand.FMRIalsohastwomaindrawbacksthough.Firstly,usingbloodflowasametric doesn’tyieldpreciseresults,becauseitisalready“tooclosetomaximumactivation”.That meansthatbloodflowisalreadyincrediblyhighandclosetoitsmaximum,asourbrain performsitsgeneralmodaltasks,thatthediscrepanciesinbrainactivitywhenstimulatedare verysmall,makingithardtomakeaccuratepredictions
Anothernon-invasiveneuralimagingmethodisNIRS(Near-infraredspectroscopy).Its functionisbestunderstoodinlightofanexample:intercranialbleeding.Near-infraredlight isdirectedtowardsthebrain.Innon-injuredpatients,thebrainabsorbsNIRlightevenly, butwhenbleedingoccurs,ahighconcentrationofbloodcausesNIRtobeabsorbedmore inthesectionofthebrainsustaininganinjurythanotherparts,causingadecreaseinaNIR lightdeflectedtoascanner,inthatregion.JustasdiscussedinFMRIs,bloodconcentration correlatestoneuralactivity,soNIRScancalculatetheincreaseinabsorptionofNIRlight accordingtoincreaseinbloodflow(andhaemoglobinconcentration).Althoughmore portablethanFMRIs,NIRScanonlyscancorticalbraintissue(ontheoutside),whereas FMRIscanmeasureactivitythroughoutthebrain.
PETorPositronEmissionTopographyscansmightbethemostwell-knownformof neuroimaging,butitisn’tverydifferentinthemechanismbywhichitisenacted.Whilst FMRIandNIRSarenon-invasivemeasurementsofblood-flow,lookingatmagneticfields andlightabsorptionreflectively,PETscansindirectlymeasurebloodflowtothebrain invasively,withatracer:Oxygen-15 Becauseofits2-minutehalf-life,oxygen-15must enterthebody,directlyfromtheamedicalcyclotron(aparticleacceleratorthatcan bombardatomswithcyclotronbeamstoproduceisotopes).Aringofdetectorsinthescan tracesthetracerandgeneratesa3Dimageaccordingly.
A new hope (but neurological complexity strikes back)
ImaginetryingtotransportallthegrainsofsandonabeachinPortsmouthtoBlackpool withonlyapairofchopsticks.NowimagineyouhadanarmyofJCBdiggerstodothe samejob…That’snotneuropixel.Neuropixelsaremorelikeifyouweretogiveyoua spooninstead,stillprettyslow,butdefinitelybetterthanchopsticks.Whilsttraditional singleunitrecordingmethodsonlyallowscientiststotestoneneuronatatime,neuropixel canrecordafewhundred,with1000recordingsitesarrangedinto2rowsona1cmlong probe.
Aswithallnewtech,neuropixelhasgaugedalotofattentionandpraise,butitdoesn’t defeatthequestion:isitpossibletomapoutthebrain?Rememberthereareeighty-six billionneuronsinourbrains,andwhilstneuropixeliscertainlypowerful,itdefinitelyisn’t sufficientforaddressingthebrain’scomplexity.Thisisalsonotingthatelectrodescanonly reallyreachthecorticaltissue,togoanydeeperintothebrainwouldrequirecuttingthe brainopen,compromisingitsstructuralintegrityandthefunctionoftheoutercortex,with greatramificationsforactivityinotherpartsofthebrain.
Thenthere’stheethicalissues:doesbrainresearchseektore-enforcedeterministicbiases andgivecausalclosuretoourthought,anddoesthatmeanthatwehavenofreewill,only predeterminedneuralsignals?Iwasalwaysgoingtowritethisessay.Youwerealways goingtoreadit.Doesthatinturnmeanthattherecanbenomoralaccountabilityforour actionsifweneverhadchoice,onlyitsillusion?
AmIoverthinkingit?
Canweeventhinkaboutthinking?
Isthisonetoomanyrhetoricalquestions?
“If the human brain were so simple that we could understand it, we would be so simple that we couldn’t” ~Emerson Pugh
mRNA vaccines - the future of vaccinology?
Shay Patel, 10M2The2023NobelPrizeinPhysiologyandMedicinewasawardedtoDrewWeissmanand KatalinKarikófordiscoveriesleadingtothedevelopmentofthemessengerribonucleicacid (mRNA)vaccine(Karlén,2023)Untilrecently,traditionalvaccineshavebeenbasedonan inactivatedorweakenedvirus,whichwasdesignedtostimulatetheimmunesystemto releaseantibodies.Theweakenedviruswouldnotcauseadiseaseasitnormallywould,but stillpromptthesameimmuneresponse(BBC,n.d.).Sincethebodycanthenrecognisea specificpathogen,itcanbefoughtofmoreeffectively.
Lymphocytesareatypeofwhitebloodcell,andproduceantibodiesagainstapathogen.The antigensfoundonpathogensareusedas‘markers’foundontheirsurfacemembranes,to whichtheantibodiescanstick.(Bangham,2021).Theseantibodiescanstoppathogensin threeways:theycausethepathogentoburst,theyagglutinatethepathogentofacilitate theiringestionbythephagocytes(amoreabundanttypeofwhitebloodcellwhichengulfs thebacteriainatemporaryvacuoleandreleasesenzymestodigestit),ortheyneutralizethe toxinsproducedbythepathogen.Regardlessofthemethod,aftertheinfection,some lymphocytesdevelopintomemorycells,remaininginthebloodformanyyearssoour bodiesrecogniseitquicker,massproducingantibodiesatafasterrate,asseeninFigure1. Thisprocessisknownassecondaryimmuneresponse(Miyasaka,2022).
Microbiology: Health and Disease, 2022
Overthepastthirtyyears,inanattemptto reduce costs, vaccines have utilised only certainpartsofavirusratherthanthewhole structure,typicallyproteinsorsugarsfrom the surface. However, in both methods, scientistshavehadtodependonusingthe virus to develop the respective vaccine. Unfortunately, this form of development reliesonthecultivationofcellsonalarge scale,makingitbothexpensiveandtime consuming(WHO,2020)
DuringtheoutbreakofCOVID-19,promptingthegrowthofa$10bnindustry,therewasa growingrealisationthatvaccinationsforthemasswouldnotbesustainablegiventhecosts, anditwouldtaketimetodevelopvaccinesbasedonaninactivevirusgiventhesudden outbreakAsaresult,alternativeroutesfordevelopingavaccinewerepursued,onebeingthe utilisation of mRNA. Such methods were utilized in the development of the Pfizer/BioNTechVaccineandtheModernavaccine(UniversityofAuckland,2021).
How does an mRNA vaccine work?
Typically,mRNAcarriesacopyofthedeoxyribonucleicacid(DNA)basesequencefrom thenucleustothecytoplasm,whereitattachestoaribosome(Figure2).Theinstructions carriedbythemRNAareusedforproteinsynthesis,assemblingtheaminoacidsusingthe basesequencetobuildproteins(BBC,n.d.).
ThemRNAvaccinesintroduceanmRNAsequencewhichhadbeendevelopedina laboratory(invitro-transcribedmRNA),whichinturnisusedasatemplatetomakeapiece oftheproteinfromtherespectivevirus.ThesinglestrandedmRNA,however,cannotbe injecteddirectlyintothebloodstreamduetoitsvulnerabilitytoenzymesandthermal instability.Therefore,mRNAvaccineswoulduselipidnanoparticles(fattydroplets)that wrapthemRNAinaprotectivebubble,whichmergewithcellstodeliverthemRNA.
TheribosomesincellsusetheadministeredmRNAtobuildtheprotein,causingnoharmto therecipient.Theimmunesystemisthenabletorecognisetheproteinandisawareitdoes notbelonginthebody(Perenkov,etal.,2023).Similartothereactionfromatraditional vaccine,theimmunesystemcreatesantibodieswhichdestroytheprotein,andifthevirus entersthebodyagain,theimmunesystemwillrecognizethepresenceofthesameprotein andattackthevirusquicklyandeffectively.
The Development of the Vaccine
Scientistshavebeensearchingforalternativestothetraditionalvaccinesincethe1950s,and onlyduringthe1980sweremethodsofproducingmRNAwithoutcultivatingcells introduced(Dolgin,2021).Theselaboratory-producedmRNAmoleculeswerecalledin vitro-transcribedmRNA,andthereseemedanobviousandsimpleimplementationofthem intohealthcareandvaccinology.
Sincethen,however,scientistshavestruggledtoimplementthemintovaccines.Twoofthe outstandinghindranceswerethatmRNAisunstableanddifficulttotransportincells,but moreimportantwasthefactthatanyinvitro-transcribedmRNAcausedinflammatory responsesintherecipient(Karlén,2023).Itseemedobviousgiventheinflammatoryreaction thatroutesotherthanmRNAmustbepursued,andthatmRNAwassimplynotviable. However,KatalinKarikóandDrewWeissmanbothnotedthefactthattheinflammatory responsewasidenticaltohowwerespondtomRNAfrombacteria.(Young,2023).
Lumen, 2021
As it turned out, they found that by modifying the nucleosides(thebuildingblocksofmRNA)oftheinvitrotranscribedmRNA,theycouldchangetheeffectithadon ourbody.Theytestedmakingsmallmodificationstoeach ofthefournucleosides:Adenine,Uracil,Guanineand Cytosine(Granados-Riveron&Aquino-Jarquin,2021).
Impressively,theyfoundthatbymodifyingtheUracilnucleotidetheycouldremovethe inflammatoryresponse,and,moreover,theycouldincreasetheproductionrateofthe proteins by the ribosome (Pardi & Weissman, 2023). Uridine was replaced with pseudouridine(anisomerofuridineinwhichtheuracilisattachedviaacarbon-carbonbond ratherthannitrogen-carbonglycosidicbond),whichhadbeenmodifiedtoenhanceRNA stabilityanddecreaseanti-RNAimmuneresponse(Figure3).Bydoingthis,theyhad discoveredamethodtomakeinvitro-transcribedmRNAwhichheldthebasesequenceto buildaproteininsidethebodyquicklyandreliably,and,mostimportantly,promptedno harmfulinflammatoryresponses.
mRNA Vaccines during COVID-19
ThevirusresponsibleforcausingCOVID-19isSARS-CoV-2.By2010,therewerealready multiplecompaniesworkingonthedevelopmentonmRNAvaccinesandtheybeganto attract interest (Chaudhary, et al., 2021). With the coronavirus pandemic being as widespreadandabundantasitwas,thetraditionalvaccinewouldhavehadextraordinarily largecostsontopofalongtimeperiodforproduction.
Fortunately,by2020thereweretwobasemRNAvaccineswhichcouldbeusedfor COVID-19. Sitting on the surface of the SARS-CoV-2 virus are spike proteins (a glycoproteinwhichprojectsfromthemembraneandbindstoreceptors),asdepictedin Figure4(Huang,etal.,2020).Thesespikeproteinsfacilitatedthebindingofthevirusto cells(Theoharides&Conti,2021).
ThemRNAvaccinecontainedaninvitro-transcribedmRNAwhichheldthebasesequence forproducingthesespikeproteins.Theribosomeswouldthenbuildtheseproteinsusingthe informationcarriedbythemRNA,andasthesespikeproteinsattachtothesurfaceofthe cell,thebody’simmunesystemwouldreacttothembyreleasingantibodies(National HumanGenomeResearchInstitute,2021) Therefore,thenexttimesuchspikeproteins fromSARS-CoV-2bindtocells,theantibodieswillattackthem(Pardi,etal.,2018).
Thesevaccineswereshowntobe95%effective,andthecostsofthesecomparedtothe traditionalvaccineweremuchlower(UKHealthSecurityAgency,2022).Moreover,the speedatwhichthesevaccinesweredevelopedandimplementedwasfarsuperiortothatof thetraditionalvaccine,resultantlyhavingagreaterglobalreach,asillustratedinFigure5. ThesemethodswereutilizedforthedevelopmentofthePfizer/BioNTechVaccineaswellas theModernaVaccine,whichhadamuchgreaterworldwideconsumptioncomparedto otherCOVID-19vaccinessuchasCodagenix,whichisbasedonaweakenedvirus; Valneva,whichisbasedonaninactivatedvirus(BritishSocietyforImmunology,2023);and theOxford-AstraZenecavaccinewhichisbasedonaweakenvirusofthecommoncold (BBC,2021)
Conclusion – do these Vaccines have a Future?
Basedonthesuccessthevaccinehadduringthe COVID-19pandemic,themRNAvaccineisno doubt one of the most effective and rapidly produced vaccines, and the success it found duringtheoutbreakoffersanargumentforit havingaplaceinthefutureofvaccinology.The vaccinesbasedonmRNAweredevelopedquickly andeffectively,reducingthenumberofdeath ratesduringtheCOVID-19pandemicsignificantly. BBC, 2021 Consequently,thereisrisingdemandforthemtobeimplementedagainstotherviruses.
Beyondthis,thereispotentialformRNAvaccinestobeusedastreatmentagainstother healthcareissues–therehavebeendevelopmentsshowingpossibletherapeuticoptionsfor majordiseasessuchascancer,wheretheimmunesystemcanbepresentedwithpiecesof thegeneticcodefromthespecificcancersoitcanonlyattackthetumour(BBC,n.d.). Withthisinmind,thefutureforthemRNAvaccineisnotonlyhopeful,butvast.The discoveriesofDrewWeissmanandKatalinKarikóhavenodoubtchangedthecourseof vaccinology,givingrisetoapromisingfutureandopeningitformoreapplicationswhich arefaster,cheaperandmoreeffective.
ELISA testing in microbiology
Arnav Dubey, L6J1Inthefieldofmicrobiology,Enzyme-LinkedImmunosorbentAssay(ELISA)isapivotal techniquethatexhibitsexceptionalsensitivityandspecificityindetectingandquantifyinga widerangeofsubstances,includingantibodiesandproteinsThisarticleexploresthebasic principlesofELISAtesting,itsdifferenttypes,applications,anditsprofoundsignificancein microbiologyresearchanddiagnostics.ELISAisanimmunologicalassaythatishighly reliableanddependsontheinteractionbetweenantigensandantibodies.Theassayusually consistsoffouressentialelements:asolidphasethatprovidesasurfaceforantigensor antibodiestobindto,anantigenorantibodyofinterest,asecondaryantibodylinkedtoan enzyme,andasubstrateusedfordetectingtheenzyme.
ELISA variants
In direct ELISA,antigensofinterestareimmobilizedontoasurfaceandlabelledprimary antibodiesthatdirectlyrecognizetheantigenareadded,enablingthevisualizationand quantificationofboundantigensDirectELISAisasimpletechniquefordetectingpurified antigens,widelyusedfordeterminingtheexistenceofspecificantigenssuchasthe detectionofaparticularviralproteininasample.
UnlikedirectELISA,the indirect methodusestwoantibodies.Theantigenisimmobilized, andanunlabelledantibody,specifictotheantigen,isintroducedNext,anenzyme-labelled secondaryantibodythatbindstotheprimaryantibodyisadded.Theamplifiedsignalfrom theenzyme-linkedsecondaryantibodycanbindtomultipleprimaryantibodiesatonce. IndirectELISAisahighlysensitiveandversatiletechniquefordetectingantibodiesina sample,suchasidentifyingthepresenceofantibodiesagainstaspecificpathogen.
Next, sandwich ELISA usestwospecificantibodies.Thefirstantibody,immobilizedon thesurface,capturestheantigenofinterestpresentwithinthesample.Thesecondenzymelabelledantibodythenbindstodifferentsitesontheantigen,forminga"sandwich"withthe antigenlocatedbetweenthetwoantibodies.SandwichELISAishighlyspecificand sensitive;itisutilizedwhendetectingantigenswithmultipleepitopes,likecertainproteins orbiomarkers,orwhenthetargetantigenispresentinlowconcentrations.
Finally, competitive ELISA involvesacompetitionbetweenanunlabelledantigenfrom thesampleandalabelledantigen(oranalyte)forbindingsitesonalimitedquantityof immobilizedantibody.Theamountoflabelledantigendetectedisinverselyproportionalto theconcentrationofanalyteinthesample.CompetitiveELISAisusefulinmeasuringthe concentrationofspecificcompoundsinsamples,suchassmallmoleculesorhormonesItis typicallyemployedindrugdevelopmentandtoxicologystudies.
EachELISAvariantoffersdistinctbenefitsandischosenbasedonresponsetoassay requirementssuchassensitivity,specificity,andtypeofmoleculedetected(antigenor antibody).Thesevariationsenableresearchersandclinicianstopreciselyidentifyand evaluateanextensivevarietyofsubstances,playingacriticalroleindiagnosticandresearch advancementswithinmicrobiologyandotherfields.
Inmicrobiologyresearchthefirstprocessispathogenidentification.Tohelpinthe diagnosisofinfectiousdisorders,ELISAisusedtodetectantigenspresentinclinicalsamples. Forexample,identifyingthesurfaceproteinsorelementsofbacteriaorviruses,suchasthe hepatitisBsurfaceantigenortheHIVp24antigen.Thenthereisantibodydetection,the presenceandquantityofantibodiesinbiologicalsamplescanbeascertainedwiththeaidof ELISAUnderstandinghowtheimmunesystemreactstoillnessesorimmunisationsrequires knowledgeofthis.Forinstance,evaluatingimmunologicalresponseorstatebylookingfor antibodies against microbial antigens. Then it is biomarker analysis, biomarkers for microbialinfectionsorillnessescanbemeasuredusingELISA.Totrackthecourseofa diseaseoranindividual'sreactiontotreatment,biomarkerssuchascytokines,certain proteins,orenzymescanbeexamined
ELISAtestingisveryimportantinmicrobiologydiagnostics.IthelpsinAutoantibody detection,Autoantibodiesfoundinautoimmuneillnessescanbeidentifiedwiththeuseof ELISA.Byidentifyingantibodiesthattargetself-antigens,itaidsinthediagnosisofdiseases suchasautoimmunehepatitis,systemiclupuserythematosus(SLE),andrheumatoidarthritis. Italsohelpscancerbiomarkers,whendetectingcertainproteinsorantigenslinkedto differenttypesofcancer,ELISAisessential.WithELISA,biomarkerssuchasHER2/neu, CA-125,andprostate-specificantigen(PSA)canbeevaluatedforcancerdevelopment trackingorearlyidentification.Italsocanhelpveterinarydiagnostics;Animalinfectious illnessdiagnosisisaccomplishedinveterinarymedicineusingELISA-basedassaysTheyaid intheidentificationofdiseasesthatharmpetsoranimals,enablingthepropermanagement andcontrolofdisease.ELISAisavitaltechniqueinmicrobiologydiagnosticsbecauseofits scalability, dependability, and capacity to identify certain molecules. Infections, autoimmunediseases,malignancies,allergies,anddiseasedevelopmentcanallbeprecisely diagnosedbyhealthcareprofessionalsandresearcherswithitshelp,leadingtobetterpatient outcomesandmoreefficientpatienttreatment.
VariationsinsensitivityandspecificityareamongtheconstraintsthatELISAfaces,despite itswidespreaduse.However,continuousdevelopmentslikeasautomation,microfluidic platforms,andmultiplexELISAareovercomingthesedrawbacks,increasingproductivity, andshorteningassaydurations.Inmicrobiology,ELISAisstillavitaltoolforresearchand diagnosticsbecausetoitsversatilityandsensitivity.Understandingmicrobialpathogens, diseasemechanisms,andtherapeuticinterventionsarecontinuallybeingadvancedbyit becauseofitsversatility,accuracy,andapplicability.
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