Environmental effects on changes in gene expression

Posljednjih 10 do 15 godina ubrzani razvoj novih spoznaja u genetici ukazao je na potpuno nove mehanizme nastanka pojedinih bolesti, a posebno razvoja pojedinih kliničkih fenotipova. Promjene u epigenetskome profilu stanice mogu biti pozitivne i pogodovati izražavanju povoljnih gena, kao što su geni koji sudjeluju u staničnoj signalizaciji i suzbijanju onkogeneze. Međutim, promjene također mogu biti štetne i mijenjati funkcije važnih gena, što dovodi do bolesti. Nedavno je dokazano da se neki epigenetski biljezi mogu zadržavati tijekom mejoze i tako prenositi transgeneracijski. Najveći broj publiciranih radova odnosi se na mehanizme autoimunosti i karcinogenezu, no u zadnjih pet godina pojavljuju se i radovi koji se bave fenomenom međureakcije čimbenika okoliša i ekspresije bolesti za brojna druga stanja. U radu su analizirane dosadašnje spoznaje te njihov klinički značaj.In the last 10-15 years the rapid development of new knowledge in genetics pointed out entirely new mechanisms of development of certain diseases, in particular the development of some clinical phenotypes. Changes in the epigenetic profile of a cell can be positive and favor the expression of advantageus genes such as those linked to cell signaling and tumor suppression. However, they can also be detrimental and alter the functions of important genes, thereby leading to disease. Recent evidence has further highlighted that some epigenetic marks can be maintained across meiosis and be transmitted to the subsequent generation to reprogram developmental and cellular features. The largest number of published works refers to the mechanisms of carcinogenesis and autoimmunity, but in the last five years, there are also works that deal with the phenomenon of interplay of environmental factors and the expression of the disease for many other conditions. The article analyzes recent findings and their clinical significance

Environmental effects on changes in gene expression

Posljednjih 10 do 15 godina ubrzani razvoj novih spoznaja u genetici ukazao je na potpuno nove mehanizme nastanka pojedinih bolesti, a posebno razvoja pojedinih kliničkih fenotipova. Promjene u epigenetskome profilu stanice mogu biti pozitivne i pogodovati izražavanju povoljnih gena, kao što su geni koji sudjeluju u staničnoj signalizaciji i suzbijanju onkogeneze. Međutim, promjene također mogu biti štetne i mijenjati funkcije važnih gena, što dovodi do bolesti. Nedavno je dokazano da se neki epigenetski biljezi mogu zadržavati tijekom mejoze i tako prenositi transgeneracijski. Najveći broj publiciranih radova odnosi se na mehanizme autoimunosti i karcinogenezu, no u zadnjih pet godina pojavljuju se i radovi koji se bave fenomenom međureakcije čimbenika okoliša i ekspresije bolesti za brojna druga stanja. U radu su analizirane dosadašnje spoznaje te njihov klinički značaj.In the last 10-15 years the rapid development of new knowledge in genetics pointed out entirely new mechanisms of development of certain diseases, in particular the development of some clinical phenotypes. Changes in the epigenetic profile of a cell can be positive and favor the expression of advantageus genes such as those linked to cell signaling and tumor suppression. However, they can also be detrimental and alter the functions of important genes, thereby leading to disease. Recent evidence has further highlighted that some epigenetic marks can be maintained across meiosis and be transmitted to the subsequent generation to reprogram developmental and cellular features. The largest number of published works refers to the mechanisms of carcinogenesis and autoimmunity, but in the last five years, there are also works that deal with the phenomenon of interplay of environmental factors and the expression of the disease for many other conditions. The article analyzes recent findings and their clinical significance

Vrijednost mjerljivih i nemjerljivih značajka ultrazvučnog prikaza limfnih čvorova u otkrivanju zloćudnog zauzeća

The aim of the study was to assess diagnostic value and utility of selected morphological features in predicting lymph node (LN) malignancy using B-mode, Doppler ultrasonography and multivariate settings in a tertiary radiological referral center. The study included 123 patients having undergone ultrasound-guided fine-needle aspiration and cytologic analysis (FNAC) of cervical, axillary and inguinal LNs. Each LN was characterized by long/L and short/T-axis, shape, margins, echogenicity, cortical thickness, vascularization, and examiner’s subjective impression. Within the limitations of FNAC, altered shape and vascularization had relatively high specificity and positive predictive value (>80%), whereas subjective impression had high sensitivity and negative predictive value (100%) for malignancy. The cut-off levels for different features of LN by ROC analysis were as follows: long-axis 23 mm, short-axis 11 mm, L/T ratio 2.19, and maximal cortical thickness 5.1 mm. On multivariate analysis (adaptive regression splines, n=108), the addition of long-axis, L/T ratio, age and sex considerably improved diagnostic accuracy (88%), sensitivity (margins + vascularization) and specificity (subjective impression) of the diagnostic model. The combination of morphological and demographic features could improve diagnostic accuracy, usually with a trade-off between the sensitivity and specificity of the predictive model. The performance may depend on the level of expertise and institutional settings.Cilj istraživanja bio je odrediti dijagnostičku vrijednost i korisnost odabranih morfoloških značajka u predviđanju malignosti limfnog čvora (LČ) upotrebom B-moda, Dopplerova ultrazvuka i multivarijatnih postavka u tercijarnom radiološkom referentnom centru. U 123 bolesnika je učinjena ultrazvučno vođena aspiracijska punkcija i citološka analiza LČ vrata, pazuha i prepona. Svaki LČ je opisan uzdužnim/L i poprečnim/T promjerom, oblikom, rubom, ehogenošću, debljinom kore, vaskularizacijom i subjektivnim dojmom pregledavatelja. Unutar ograničenja citološke analize, izmijenjen oblik i vaskularizacija su imali visoku specifičnost i pozitivnu prediktivnu vrijednost (>80%), dok je subjektivni dojam imao visoku osjetljivost i negativnu prediktivnu vrijednost (100%) za malignost. Optimalne granične vrijednosti za različite značajke LČ dobivene analizom ROC su bile 23 mm za uzdužni promjer, 11 mm za poprečni promjer, 2,19 za omjer L/T i 5,1 mm za maksimalnu debljinu korteksa. U multivarijatnoj analizi (adaptive regression splines, n=108) dodatak uzdužnog promjera, omjera L/T, dobi i spola semikvalitativnim obilježjima LČ značajno je povećao dijagnostičku točnost (88%), osjetljivost (rubovi + vaskularizacija, 87%) i specifičnost (subjektivni dojam, 83%) konačnog dijagnostičkog modela. U zaključku, kombinacija morfoloških i demografskih značajka može poboljšati dijagnostičku točnost, obično uz kompromis između osjetljivosti i specifičnosti prediktivnog modela. Učinkovitost može ovisiti o razini stručnosti i institucionalnim postavkama

Manjak lizosomske kisele lipaze u djece: vlastita iskustva i nova mogućnost enzimskoga nadomjesnog liječenja [Lysosomal acid lipase deficiency in children: our experience and a novel possibility of enzyme replacement therapy]

Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early

LYSOSOMAL ACID LIPASE DEFICIENCY IN CHILDREN: OUR EXPERIENCE AND A NOVEL POSSIBILITY OF ENZYME REPLACEMENT THERAPY

Manjak lizosomske kisele lipaze autosomno je recesivno nasljedna bolest s dva klinička fenotipa. Wolmanova bolest počinje u ranoj dojenačkoj dobi i brzo je progresivna. Zbog masivnog nakupljanja kolesterolskih estera i triglicerida u crijevima, jetri, slezeni i drugim stanicama monocitno-makrofagnog reda dolazi do malapsorpcije, hepatosplenomegalije, zatajenja jetre i smrti u prvoj godini života. Bolest nakupljanja kolesterolskih estera može se očitovati od rane dječje do kasne odrasle dobi, varijabilna je tijeka i progresije. Glavna su obilježja različito izražena jetrena bolest, uključujući cirozu i zatajenje jetre, hiperkolesterolemija i rana ateroskleroza. Karakterističan je patohistološki nalaz mikrovezikularne steatoze i fibroze, a patognomoničan je ultrastrukturni nalaz kristala kolesterolskih estera. Dijagnozu potvrđuju mjerenje enzimske aktivnosti i/ili analiza gena. Liječenje je donedavno bilo suportivno i simptomatsko. Klinička istraživanja enzimskoga nadomjesnog liječenja pokazuju vrlo ohrabrujuće rezultate. Prikazujemo dojenče s Wolmanovom bolešću i dvoje djece s bolešću nakupljanja kolesterolskih estera s ciljem skretanja pozornosti na bolesti zbog manjka lizosomske kisele lipaze i što ranijeg početka optimalne skrbi.Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early

VITAMIN B12 DEFICIENCY IN CHILDREN – UNDERESTIMATED DANGER IN THE LIGHT OF NEW KNOWLEDGE

Vitamin B12 (kobalamin) ima dva aktivna oblika, adenozilkobalamin i metilkobalamin, koji imaju ključnu ulogu u dvama važnim metaboličkim putovima u ljudi i njihov je manjak odgovoran za kliničke teškoće u bolesnika. Kobalamin je nuždan tijekom cijelog života, no njegova dovoljna količina posebno je bitna u fetalno i dojenačko doba, kada je iznimno važan za normalan rast i razvoj djeteta, kao i za normalan razvoj središnjega živčanog sustava. Zbog vrlo složenog prometa i metabolizma njegov se manjak može očitovati pri raznim prirođenim i stečenim poremećajima. Klinička slika kojom se očituje manjak vitamina B12 obično je nespecifična, nosi velik rizik od trajnih posljedica za bolesnika, a najčešće se vrlo jednostavno liječi ako se na vrijeme prepozna. U Republici Hrvatskoj poremećaji metabolizma kobalamina u djece prerijetko se otkrivaju. Zato je cilj ovog rada skrenuti pozornost na nove spoznaje o metabolizmu kobalamina, prikazati bolesnike s tipičnim kliničkim tijekom i laboratorijskim nalazima te dati smjernice za brzo dijagnosticiranje i liječenje poremećaja vitamina B12 u djece.Vitamin B12 (cobalamin) has two active forms, adenosylcobalamin and methylcobalamin which have a key role in two important metabolic pathways in humans and their deficiency is responsible for clinical problems. Cobalamin is essential during whole life, but its sufficient amount is extra important in fetal and neonatal period, when it is essential for normal child growth and development as well as for normal development of the central nervous system. Because of very complex transport and metabolism, its deficiency can be manifested in numerous congenital and acquired disorders. Vitamin B12 deficiency mostly has non-specific clinical features, it carries a great risk of permanent consequences, but most frequently it is easily curable if diagnosed on time. In Croatia cobalamin deficiency in children has been diagnosed too rarely. Accordingly, the aim of this paper is to point to the recently gained knowledge on cobalamin metabolism, present typical case reports and to provide guidelines for rapid and proper diagnostic and therapeutic approach

Nutrition as a Significant Factor in Fitness and Recreation : Undergraduate Thesis

Sjedilački način života, razvoj tehnologije, brza i obilna prehrana te ubrzani način života, doveo je do pretilosti i porasta kroničnih bolesti, a funkcionalne i motoričke sposobnosti su na zabrinjavajuće niskoj razini. Fitnes se kao pojam u svakodnevnom životu često koristi, a označava stanje dobrog tjelesnog i mentalnog zdravlja, dobre tjelesne kondicije nastale kao rezultat redovitog tjelesnog vježbanja, pravilne prehrane i brige o svom zdravlju. Osjećati se zdravo, zadovoljno i sposobno za obavljanje svakodnevnih zadaća trebao bi biti cilj svakog pojedinca, ali i društva u cjelini. U današnje vrijeme, svaki malo ozbiljniji rekreativac, a pogotovo vrhunski sportaš, vodi brigu o svom režimu prehrane. Ukoliko prehrana nije pravilna, naročito u sportaša mlađih dobnih kategorija, dolazi ne samo do nepravilnosti u razvoju već i do narušavanja zdravlja. Pristup prehrani treba biti individualan, odnosno ovisi o dobi, spolu, vrsti sporta, broju treninga, te socijalnom i zdravstvenom statusu pojedinca.Sedentary lifestyle, advances in technology, fast and abundant food consumption and fast-paced life have all lead to obesity and an increased number of chronic diseases, while functional and motor abilities have reached alarmingly low levels. Fitness as a term is used often in everyday life. It means being physically and mentally healthy, being in good physical shape due to bodily training, healthy diet and personal health care. Feeling healthy, satisfied and capable of fulfilling everyday demands should be the goal of not only every human being, but also the society as a whole. In this day and age even amateur athletes, not to mention professional athletes, concern themselves with proper nutrition and dietary regimen. Inadequate nutrition, especially with younger athletes, can result in unhealthy development and poor health. Nutrition should be personalized meaning it should depend on the individual’s age and gender, type of sport, number of trainings, social and health state

Diagnostic of Anthropological Status in Recreation and Fitness : Undergraduate Thesis

Pojmovi vezani uz dijagnostiku uglavnom su povezani s područjem biomedicine i zdravstva, ali često ih možemo susresti i u drugim područjima čovjekovog djelovanja (Škorić i Bartoluci, 2011). Sportska dijagnostika je dio kineziologije koja je zahvaljujući brzom napretku tehnologije, postala neizostavni dio trenažnog procesa. Dijagnostika u sportu provodi se terenskim testovima i/ili testovima u laboratorijskim uvjetima. U sportsku rekreaciju uključene su različite sportske aktivnosti čiji su programi prilagođeni dobnim skupinama i potrebama pojedinca, te imaju pozitivan učinak na ljudski organizam. Planiranje i programiranje trenažnog procesa odvija se na temelju rezultata dobivenih dijagnostičkim procedurama. Proces započinje inicijalnim testiranjem i služi kao početna točka. Daljnji tranzitivni dijagnostički postupci važni su za praćenje napretka provedenog programa.Terms related to diagnostics and diagnosis are mainly associated with the field of medicine and health care, but they can frequently be found in other areas of human activity (Škorić and Bartoluci, 2011). Sports diagnostics is a part of kinesiology which, due the rapid progress of technology, has become an indispensable part of a training process. Diagnostics in sports is performed by means of field and/or laboratory tests. Sports recreation includes various sports activities whose programs are tailored to suit age groups and individual needs, thus having a positive effect on the human body. Planning and programming of the training process is based on the results obtained by diagnostic procedures. The process begins with initial testing and serves as a starting point. Further transitive diagnostic procedures are important for monitoring the progress of the implemented program

Nutrition as a Significant Factor in Fitness and Recreation : Undergraduate Thesis

Sjedilački način života, razvoj tehnologije, brza i obilna prehrana te ubrzani način života, doveo je do pretilosti i porasta kroničnih bolesti, a funkcionalne i motoričke sposobnosti su na zabrinjavajuće niskoj razini. Fitnes se kao pojam u svakodnevnom životu često koristi, a označava stanje dobrog tjelesnog i mentalnog zdravlja, dobre tjelesne kondicije nastale kao rezultat redovitog tjelesnog vježbanja, pravilne prehrane i brige o svom zdravlju. Osjećati se zdravo, zadovoljno i sposobno za obavljanje svakodnevnih zadaća trebao bi biti cilj svakog pojedinca, ali i društva u cjelini. U današnje vrijeme, svaki malo ozbiljniji rekreativac, a pogotovo vrhunski sportaš, vodi brigu o svom režimu prehrane. Ukoliko prehrana nije pravilna, naročito u sportaša mlađih dobnih kategorija, dolazi ne samo do nepravilnosti u razvoju već i do narušavanja zdravlja. Pristup prehrani treba biti individualan, odnosno ovisi o dobi, spolu, vrsti sporta, broju treninga, te socijalnom i zdravstvenom statusu pojedinca.Sedentary lifestyle, advances in technology, fast and abundant food consumption and fast-paced life have all lead to obesity and an increased number of chronic diseases, while functional and motor abilities have reached alarmingly low levels. Fitness as a term is used often in everyday life. It means being physically and mentally healthy, being in good physical shape due to bodily training, healthy diet and personal health care. Feeling healthy, satisfied and capable of fulfilling everyday demands should be the goal of not only every human being, but also the society as a whole. In this day and age even amateur athletes, not to mention professional athletes, concern themselves with proper nutrition and dietary regimen. Inadequate nutrition, especially with younger athletes, can result in unhealthy development and poor health. Nutrition should be personalized meaning it should depend on the individual’s age and gender, type of sport, number of trainings, social and health state

Diagnostic of Anthropological Status in Recreation and Fitness : Undergraduate Thesis

Pojmovi vezani uz dijagnostiku uglavnom su povezani s područjem biomedicine i zdravstva, ali često ih možemo susresti i u drugim područjima čovjekovog djelovanja (Škorić i Bartoluci, 2011). Sportska dijagnostika je dio kineziologije koja je zahvaljujući brzom napretku tehnologije, postala neizostavni dio trenažnog procesa. Dijagnostika u sportu provodi se terenskim testovima i/ili testovima u laboratorijskim uvjetima. U sportsku rekreaciju uključene su različite sportske aktivnosti čiji su programi prilagođeni dobnim skupinama i potrebama pojedinca, te imaju pozitivan učinak na ljudski organizam. Planiranje i programiranje trenažnog procesa odvija se na temelju rezultata dobivenih dijagnostičkim procedurama. Proces započinje inicijalnim testiranjem i služi kao početna točka. Daljnji tranzitivni dijagnostički postupci važni su za praćenje napretka provedenog programa.Terms related to diagnostics and diagnosis are mainly associated with the field of medicine and health care, but they can frequently be found in other areas of human activity (Škorić and Bartoluci, 2011). Sports diagnostics is a part of kinesiology which, due the rapid progress of technology, has become an indispensable part of a training process. Diagnostics in sports is performed by means of field and/or laboratory tests. Sports recreation includes various sports activities whose programs are tailored to suit age groups and individual needs, thus having a positive effect on the human body. Planning and programming of the training process is based on the results obtained by diagnostic procedures. The process begins with initial testing and serves as a starting point. Further transitive diagnostic procedures are important for monitoring the progress of the implemented program