Veterinary medicine - Repository of PHD, master's thesis
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Decision-tree-based differential diagnosis of β-thalassemia and sideropenic anemia in children
No full textMikrocitne anemije najčešći su oblik anemija u dječjoj dobi. Najčešći uzrok mikrocitne anemije jest nedostatak željeza, tj. sideropenična anemija. Značajno rjeđi uzrok mikrocitne anemije jesu talasemije. Dijagnostički model za razlikovanje tih dviju bolesti u djece samo na temelju nalaza kompletne krvne slike, prema dostupnim literaturnim podacima, nije standardiziran. Cilj istraživanja bio je odrediti matematičke indekse koji bi omogućili valjano razlikovanje tih dviju bolesti samo na temelju nalaza kompletne krvne slike, a pritom uvažavajući specifičnosti β-talasemije u naše djece.
Logističkom regresijom određene su vrijednosti krvne slike koje su najinformativnije za razlikovanje β-talasemije od sideropenične anemije. Od tih parametara kompletne krvne slike najinformativnijom se pokazao srednji volumen eritrocita (MCV). Druga dva parametra kompletne krvne slike koja najbolje služe za razdvajanje tih dviju bolesti jesu koncentracija hemoglobina (Hb) i prosječna količina hemoglobina u eritrocitu (MCH).
Budući da granične vrijednosti izvornih indeksa koji su načinjeni za odraslu populaciju većinom ne zadovoljavaju u djece, uporabom ROC analize učinjena je optimizacija graničnih vrijednosti svih u literaturi objavljenih svjetskih indeksa i formula. Tako dobivene granične vrijednosti bolje razlikuju djecu s β-talasemijom od djece sa sideropeničnom anemijom u usporedbi s graničnim vrijednostima izvornih indeksa. Najbolji prilagođeni (optimizirani) jednostavni indeks za razlikovanje djece s β-talasemijom od djece sa sideropeničnom anemijom u Republici Hrvatskoj jest Matos-Carvalho indeks s točnošću > 90 % (91,51 %) uz uravnoteženu osjetljivost (89,94 %) i specifičnost (93,75 %). Ostali indeksi s točnošću England i Fraser > Pornprasert > Sirachainan > Telmissani MCHD > CRUISE > Alparslan > Hameed > Sargolzaie > Zaghloul II).
Složeni indeksi pokazali su također uspješnost u razlikovanju djece s β-talasemijom od djece sa sideropeničnom anemijom u Republici Hrvatskoj s točnošću 80 % (ukupno 11 indeksa i formula) upotrijebljeni su za iznalaženje novoga složenog CroCompDD indeksa (točnost 92,25 %, osjetljivost 92,72 %, specifičnost 91,67 %). Analiza grupa (engl. cluster analysis) matematičkih indeksa kao mjerilo najbolje performanse izdvojila je AUC i Youden indeks.
Uporabom metoda strojnog učenja načinjen je dijagnostički postupak s najpovoljnijim odnosom osjetljivosti i specifičnosti za te dvije bolesti. Upotrijebljena su četiri algoritma. Najboljim se pokazao JRIP s točnošću od 94,83 % s postotkom točnosti na unakrsnoj validaciji (engl. leaving one out) od 89,29 %. Sljedeći algoritam, PART, ima postotak 92,25 % s unakrsnom validacijom od 85,60 %. J48 algoritam ima postotak točnosti od 91,88 % (na unakrsnoj validaciji 88,56 %), dok Simple Cart algoritam ima točnost od 91,88 % (na unakrsnoj validaciji 87,45 %). Dobiveni rezultati omogućuju uspostavu smjernica za razlikovnu dijagnostiku mikrocitne hipokromne anemije s praktičnom primjenom u primarnoj, sekundarnoj i tercijarnoj zdravstvenoj zaštiti.Microcytic anemias are the most common form of childhood anemia. The most common cause of microcytic anemia is iron deficiency, i.e., sideropenic anemia. A significantly rarer cause of microcytic anemia is thalassemia. According to available literature data, the diagnostic model for distinguishing these two diseases in children based solely on the findings of a complete blood count is not standardized. The study aimed to determine mathematical indices that would allow a valid distinction between these two diseases only based on the findings of a complete blood count while considering the specifics of β-thalassemia in our children.
Logistic regression determined the blood count values that are most informative for distinguishing β-thalassemia from sideropenic anemia. Of these complete blood count parameters, the mean corpuscular volume (MCV) proved to be the most informative. The other two complete blood count parameters that best serve to separate these two diseases are hemoglobin concentration (Hb) and mean corpuscular hemoglobin (MCH).
Since the cut-off values of the original indices made for the adult population are mostly unsatisfactory in children, the limit values of all published world indices and formulas published in the literature were optimized using ROC analysis. The cut-off values thus distinguish children with β-thalassemia better than children with sideropenic anemia compared to the cut-off values of the original indices. The best adjusted (optimized) simple index for distinguishing children with β-thalassemia from children with sideropenic anemia in the Republic of Croatia is the Matos-Carvalho index with an accuracy of> 90% (91.51%) with balanced sensitivity (89.94%) and specificity (93.75%). Other indices with an accuracy of England and Fraser> Pornprasert> Sirachainan> Telmissani MCHD> CRUISE> Alparslan> Hameed> Sargolzaie> Zaghloul II).
Complex indices also showed success in distinguishing children with β-thalassemia from children with sideropenic anemia in the Republic of Croatia with an accuracy of <90% and ≥ 80%; Index26 with an accuracy of 82.66% with a sensitivity of 84.11% and a specificity of 80.83% (adjusted limit values) and a Janel (11T) index with standard limit values (accuracy 83.39% sensitivity, 93.39%, specificity 75.33%).
The CroCompDD index was compiled based on the group analysis, consisting of 6/11 best indices and formulas with adjusted cut-off values (AUC median 0.92). This index best reflects the genetic specificity of children with β- thalassemia in the Republic of Croatia (accuracy 92.25%, sensitivity 92.72%, specificity 91.67%).
A diagnostic procedure was made using machine learning methods with the most favorable relationship of susceptibility and specificity for these two diseases. Four algorithms were used. JRIP proved to be the best, with an accuracy of 94.83% with a percentage of accuracy on crossvalidation (leaving one out) of 86.35%. The J48 algorithm has an accuracy percentage of 91.88% (on cross-validation 89.29%). The following algorithm, PART, has an accuracy of 92.25% with a cross-validation score of 85.60%. The J48 algorithm has an accuracy of 91.88% (with a crossvalidation score of 88.56%), while the Simple Cart algorithm has an accuracy of 91.88% with a cross-validation score of 87.45%.The obtained results enable the establishment of guidelines for the differential diagnosis of microcytic hypochromic anemia with practical application in primary, secondary, and tertiary health care
Selective degradation of misfolded proteins in quiescent yeast Saccharomyces cerevisiae
No full textKako bi se zaštitile od nakupljanja pogrešno smotanih proteina, stanice su razvile mehanizme za kontrolu kvalitete proteina, uključujući put selektivne razgradnje sustavom ubikvitin-proteasoma. Prethodna istraživanja kontrole kvalitete proteina uglavnom su provedena u stanicama koje se aktivno dijele, međutim mnoge stanice, poput neurona i matičnih stanica u mirovanju, se ne dijele. U ovoj disertaciji istražili smo puteve selektivne razgradnje proteina u stanicama u mirovanju, koristeći modelni organizam, kvasac Saccharomyces cerevisiae. Po ulasku stanica kvasca u mirovanje aktivira se autofagija, a veliki dio proteasoma reorganizira se u granule u kojima proteasomi vjerojatno nisu aktivni, stoga nije bilo jasno oslanjaju li se stanice u mirovanju na sustav ubikvitin-proteasoma za eliminaciju pogrešno smotanih proteina. U ovom radu uspostavili smo ekspresiju modelnih pogrešno smotanih proteina tGnd1, stGnd1 i Ubc9ts u stanicama u mirovanju, koristeći PIR3- i Z-promotore. Pokazali smo da stanice u mirovanju prepoznaju pogrešno smotane proteine te ih usmjeravaju u selektivnu razgradnju, čak i u kasnijim fazama mirovanja. Nadalje, razgradnja je ovisila o aktivnosti E3 ligaza ubikvitina Ubr1 i San1, te proteasomu, što upućuje na sličan put razgradnje kao u proliferirajućim stanicama. Sveukupno rezultati pokazuju da stanice kvasca u mirovanju zadržavaju funkcionalnu kontrolu kvalitete proteina, te da se ona primarno temelji na selektivnoj razgradnji proteina.To prevent the negative impact of misfolded protein accumulation, cells have developed protein quality control pathways, including selective degradation by the ubiquitin-proteasome system. Previous research on protein quality control has mostly been conducted in actively dividing cells. However, many cells, such as neurons and quiescent stem cells, are non-dividing. In this thesis, we investigated selective protein degradation in quiescent cells, using yeast Saccharomyces cerevisiae as a model organism. Upon entry into quiescence, yeast cells induce autophagy, and a large portion of the proteasomes relocalizes into cytoplasmic granules, presumably in an inactive form. Therefore, it has been unclear whether quiescent cells rely on the ubiquitin-proteasome system for the elimination of misfolded proteins. In this study, we established an expression system of model misfolded proteins tGnd1, stGnd1, and Ubc9ts in quiescent cells using PIR3- and Z-promoters. We show that quiescent cells recognize misfolded proteins and direct them to selective degradation, even in the later stages of quiescence. Furthermore, degradation was dependent on the E3-ubiquitin ligases Ubr1 and San1 and the proteasome, suggesting a similar pathway as in proliferating cells. Overall, the results show that quiescent yeast cells maintain functional protein quality control, which is primarily based on selective protein degradation
Development of cerebral cortex and neurodegenerative changes in Down syndrome on human cerebral organoids model
No full textCerebralni organoidi uzgojeni od induciranih pluripotentnih matičnih stanica čovjeka su trodimenzionalne strukture koje rastu oko 100 dana u staničnoj kulturi te razvijaju morfološka obilježja specifična za ljudski mozak. Cilj istraživanja bio je iskoristiti model koji je dobiven od iste osobe, mozaika za trisomiju 21 kromosoma, što omogućava usporedbu diferencijacije kore ljudskog mozga u osoba s Downovim sindromom i njegovom izogeničnom kontrolom. Istraživanje je pokazalo kako cerebralni organoidi čovjeka ispoljavaju sve biljege karakteristične za koru velikog mozga, čime se potvrdila vrijednost ovog modela u istraživanju normalne i narušene strukture mozga. Također pokazano je kako izražaj biljega RELN, CTIP2 i TBR1 kasni u trisomičnim organoidima u odnosu na disomične, što upućuje da kod ljudi s ovom kromosopatijom dolazi do kašnjenja u najranijim fazama razvoja tkiva mozga. Također, zamijećen je manji izražaj svih biljega u trisomičnim organoidima u odnosu na disomične, čime se potvrđuje činjenica kako je cjelokupan broj živčanih stanica u mozgu ljudi s DS smanjen. Nadalje, trisomični organoidi imali su izražene biljege neurodegeneracije 6E10, 4G8 i Aßx-40 čime je potvrđena pretpostavka kako cerebralni organoidi s tri kopije 21 kromosoma predstavljaju koristan model u istraživanju neurodegenerativnih bolesti pridruženih Downovu sindromu, kao što je Alzheimerova demencija. Uspoređujući rezultate na organoidima s rezultatima analize mozgova fetusa s Downovim sindromom, starosti 18.-23. gestacijska tjedna, uočeno je kako organoidi mozga mogu vjerodostojno odražavati zbivanja tijekom embrionalnog razvoja čovjeka.Cerebral organoids grown from human induced pluripotent stem cells are three-dimensional structures that grow for approximately 100 days in cell culture and develop morphological features specific to the human brain. This study aimed to use a model derived from the same individual, a mosaic for trisomy 21, which allowed us to compare cortical differentiation in individuals with Down syndrome and their isogenic control. The study showed that human cerebral organoids express all markers characteristic of the cerebral cortex, confirming the value of this model in studying normal and disrupted brain structure. It was also found that the expression of the RELN, CTIP2, and TBR1 is delayed in trisomic organoids compared to disomic ones, indicating a delay in the earliest stages of brain tissue development in individuals with this chromosomal disorder. Additionally, a lower expression of all markers was observed in trisomic organoids compared to disomic ones, confirming that the total number of neurons in the brains of individuals with Down syndrome is reduced. Furthermore, trisomic organoids exhibited neurodegeneration markers 6E10, 4G8, and Aßx-40, confirming the hypothesis that cerebral organoids with three copies of chromosome 21 are a useful model for studying neurodegenerative diseases, such as Alzheimer's dementia. Comparing the results from the organoids with the results from the analysis of brains of fetuses with Down syndrome, aged 18-23 gestational weeks, it was observed that brain organoids can authentically replicate events that occur during human embryonic development
Assessment of cognitive functions in psoriatic arthritis patients
No full textUvod: Cilj istraživanja bio je procijeniti kognitivne funkcije u bolesnika sa psorijatičnim artritisom (PsA).
Ispitanici i metode: U istraživanje presječnog tipa konsekutivno su uključeni bolesnici sa PsA (N= 67) i zdravi ispitanici (N= 69).
Kognitivne funkcije procijenjene su pomoću Montrealskog testa kognitivne procjene (MoCA) i testa utiranja puta (TMT) A i B. Simptomi depresije i anksioznosti testirani su pomoću Beckovog inventara depresije-II te Upitnika anksioznosti kao stanja i osobine ličnosti. Učinjena je standardna klinička procjena PsA i psorijaze.
Rezultati: Bolesnici sa PsA imali su značajno lošije rezultate na TMT-A testu (p˂0,01). Nije bilo razlike između skupina u rezultatima MoCA i TMT-B testa. Svi testovi procjene kognitivnih funkcija korelirali su s dobi ispitanika, a TMT-B dodatno s obrazovnim statusom. Nije nađena korelacija između testova procjene kognitivnih funkcija i kliničkih parametara psorijatične bolesti, depresije i anksioznosti. U regresijskoj analizi, dob ispitanika pokazala se značajnom u predviđanju rezultata MoCA testa, objašnjavajući oko 18% varijance. U bolesnika sa PsA primijećene su značajno više razine depresivnosti, anksioznosti i umora (p=0,02; 0,015; odnosno 0,004).
Zaključak: Bolesnici sa PsA potencijalno imaju povišen rizik kognitivnog oštećenja. Potrebna su daljnja istraživanja kako bi se preciznije odredio rizik kognitivnog propadanja u PsA.Objective: The objective of this study was to assess cognitive functions in patients with psoriatic arthritis (PsA).
Methods: Patients with PsA (N= 67) and healthy subjects (N= 69) were consecutively enrolled in this cross-sectional study. Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and the Trail Making Test (TMT) A and B. Depression and anxiety were evaluated using the Beck Depression Inventory-II and the State-Trait Anxiety Inventory. A standard clinical assessment of PsA and psoriasis was performed.
Results: Patients with PsA scored significantly worse on the TMT-A test (p˂0.01). No differences in the MoCA and TMT-B scores were found. All cognitive assessment tests correlated with age, and TMT-B also correlated with educational status. No correlation was found between cognitive assessment tests and PsA disease-related parameters, depression or anxiety. In the regression analysis, age was found to be a significant predictor of the MoCA score, explaining 18% of the variance. Patients with PsA exhibited significantly higher levels of depression, anxiety and fatigue (p=0.02, 0.015, and 0.004, respectively).
Conclusion: Patients with PsA may be at an increased risk of cognitive impairment. Further research is needed to specify the risk of cognitive decline in PsA
Epigenetic status and expression of SALL4 in normal and impaired testicular development
No full textUloga gena SALL4, koji kontrolira razvoj spermatogonija, nije dovoljno istražena u razvoju sjemenika sisavaca, a u neplodnosti čovjeka je potpuno neistražena. Cilj disertacije bio je analizirati izražaj Sall4/SALL4 u razvoju sjemenika štakora in vivo i in vitro te u ljudskim sjemenicima s različitim dijagnozama neopstruktivne azoospermije (NOA) in vivo, kao i njegov metilacijski status u in vivo uzorcima. Pirosekvenciranjem je pokazano da je SALL4/Sall4 uvijek hipometiliran u sjemeniku. qRT-PCR-om je pokazan značajno veći izražaj Sall4 mRNA u fetalnom štakorskom sjemeniku nego u postnatalnom; a u ljudskim sjemenicima sa sindromom samo Sertolijevih stanica (SCOS) SALL4 mRNA je snižena u odnosu na hipospermatogenezu (HS) i zastoj u sazrijevanju (MA). Osim u spermatogonijama, poboljšanim IHC i IF protokolima je po prvi put pokazan SALL4 u XY tjelešcu primarnih spermatocita. Također, pokazan je pojačan izražaj SALL4 u pre-pahitenskim spermatocitama i citoplazmi intersticijskih stanica u neplodnom sjemeniku u odnosu na zdravi i HS sjemenik čovjeka. Nadalje, uspostavljen je novi 3D in vitro sustav za uzgoj tkiva sjemenika štakora, a primjena siRNA snizila je izražaj Sall4 na mRNA (za 42 %) i proteinskoj razini uzrokujući smanjeni rast i narušenu histologiju. Ovi rezultati ukazuju na SALL4 kao novi potencijalni biljeg u dijagnostici NOA te podrobnije rasvjetljavaju njegovu ulogu u procesu spermatogeneze.The role of the SALL4 gene which controls the development of spermatogonia, has been insufficiently investigated in the development of the mammalian testis, and is completely unexplored in human infertility. The doctoral thesis aimed to analyze the expression of Sall4/SALL4 in the rat testis development in vivo and in vitro as well as in the human testis with a different diagnosis of nonobstructive azoospermia (NOA) and its DNA methylation status. The pyrosequencing showed that SALL4/Sall4 is always hypomethylated in the testis. The qRT-PCR has shown significantly higher expression of the Sall4 mRNA in fetal rat testis than in postnatal; while SALL4 mRNA was lower in human testis with Sertoli cell only syndrome (SCOS) than in hypospermatogenesis (HS) and maturation arrest (MA). Except in spermatogonia, improved IHC and IF protocols showed the expression of the SALL4 protein in the XY body of primary spermatocytes of human testes. Also, increased expression of SALL4 in pre-pachytene spermatocytes and cytoplasm of interstitial cells in infertile compared to healthy human testis was demonstrated. Furthermore, an original 3D in vitro system for the cultivation of rat testis tissue was established, and the application of siRNA decreased Sall4 at the mRNA (by 42 %) and protein levels, causing reduced growth and impaired histology. These results indicate SALL4 as a new potential marker in the diagnosis of NOA and shed more light on its role in the process of spermatogenesis
Association of serum concentrations of interleukins IL-18, IL-19, IL-21 and IL-22 with the etiopathogenesis and assessment of clinical activity of nonsegmental form of vitiligo
No full textVitiligo je stečeni, kronični idiopatski poremećaj pigmentacije koji se očituje pojavom depigmentiranih makula na koži, a nastaje zbog selektivnog gubitka melanocita. Autoimunosna teorija se smatra vodećom etiopatogetskom teorijom nastanka vitiliga. Citokini su ključni medijatori stanične komunikacije i imaju značajnu ulogu u razvoju, diferencijaciji i regulaciji upalnog odgovora koji dovodi do pojave autoimunosti. Stoga je cilj ovog istraživanja bilo ispitati povezanost nesegmentalnog oblika vitiliga i serumske koncentracije interleukina (IL) IL-18, IL-19, IL-21 i IL- 22 te dobivene vrijednosti usporediti s težinom kliničke slike, aktivnošću te trajanjem bolesti. U istraživanje je bilo uključeno 78 ispitanika, od kojih 52 bolesnika sa nesegmentalnim vitiligom i 26 ispitanika u kontrolnoj skupini. U skupini bolesnika s nesegmentalnim oblikom vitiliga su izmjerene značajno više serumske koncentracije IL-19 i IL-21 te niže serumske koncentracije IL-18 i IL-22 u odnosu na kontrolnu skupinu ispitanika. Nije pronađena značajnija korelacija između težine kliničke slike, aktivnosti i trajanja bolesti. Ovim istraživanjem je prvi puta do sada učinjena analiza serumskih koncentracija kombinacije citokina IL-18, IL-19, IL-21 i IL-22 te su po prvi puta određene serumske koncentracije IL-18 i IL-19. Rezultati ovog istraživanja mogu doprinijeti boljem razumijevanju kompleksne etiopatogeneze vitiliga, ali mogu i poslužiti kao prilog spoznaji za mogući razvoj ciljane terapije, uključivši i proizvodnju monoklonskih protutijela. S obzirom da je u ovo istraživanje bio uključen relativno mali broj ispitanika, potrebne su dodatne studije na većem broju ispitanika u različitim fazama bolesti koje bi razjasnile značenje IL-18, IL-19, IL-21 i IL-22 u etiopatogenezi i kliničkim značajkama ove bolesti, kao i u mogućem razvoju ciljane terapije.Vitiligo is an acquired, chronic idiopathic pigmentation disorder that presenting with depigmented macules, caused by the selective loss of melanocytes. The autoimmune theory is considered to be the leading aetiopathogetic theory of vitiligo. Cytokines are key mediators of cellular communication and play a significant role in the development, differentiation, and regulation of the autoimmune inflammatory response. The aim of this study was to determine the association between the non-segmental form of vitiligo and the interleukins (IL) IL-18, IL-19, IL-21 and IL- 22 by measuring the serum concentration of these interleukins and to compare them with clinical severity, activity and disease duration. Seventy-eight patients were included into this study, out of whom 52 patients with nonsegmental vitiligo and 26 patients in the control group. Significantly higher serum concentrations of IL-19 and IL-21 and lower serum concentrations of IL-18 and IL- 22 were assessed in the group of patients with non-segmental vitiligo compared to the control group. No significant correlation was found between the severity, activity, and duration of the disease. This study was the first so far to analyze serum concentrations of the combination of cytokines IL-18, IL-19, IL-21 and IL-22 and to determine serum concentrations of IL-18 and IL- 19. The results of this research might contribute to the better understanding of the complex aetiopathogenesis of vitiligo, but might also contribute to the development of targeted biological therapy, i.e. the production of monoclonal antibodies. Given that a relatively small number of subjects were included in this study, additional studies are needed on a larger number of patients at different stages of the disease to clarify the role of IL-18, IL-19, IL-21 and IL-22 in the aetiopathogenesis of vitligo, its clinical characteristics and in the potential development of targeted therapy
Comparison of efficacy of biofeedback, electrical stimulation and therapeutic exercise in patients with knee osteoarthritis
No full textCilj ovog istraživanja bio je usporediti učinkovitost pojedinih fizikalnih postupaka u liječenju početnog OA koljena. Uspoređivali smo EMG BFB terapiju, ES terapiju i terapijsko vježbanje s pretpostavkom da će najbolji učinak imati EMG BFB terapija. Ispitivali smo bol, funkciju koljena, snagu mišića, m. vastus medialis obliquus. Pomoću upitnika SF 36 i kratkog sržnog seta MKF klasifikacije, ispitivali smo utjecaj liječenja na kvalitetu života i na biopsihosocijalno funkcioniranje ispitanika. U istraživanje smo uključili 94 ispitanika koji su proveli tri tjedna na fizikalnoj terapiji te smo ih pratili tijekom 6 mjeseci. Rezultati su pokazali dobar učinak fizikalne terapije na ispitivane parametre bez statistički značajne razlike između skupina. Ovo istraživanje pokazalo je da 6 mjeseci nakon fizikalne terapije dolazi do blagog pada snage mišića, ali bez pogoršanja u osjećaju boli i funkciji koljena. S obzirom na to da nije pronađena razlika između navedenih fizikalnih procedura, zaključili smo da je terapijsko vježbanje učinkovito u liječenju OA koljena i da nije potrebno uključivati EMG BFB terapiju, ni ES terapiju u rehabilitacijske protokole.The aim of this research was to compare the effectiveness of specific physical procedures in treating initial knee osteoarthritis (OA). We compared EMG BFB therapy, ES therapy and therapeutic exercise with the assumption that EMG BFB therapy would have the best effect. We examined pain, knee function, and the strength of the vastus medialis obliquus muscle. The SF 36 questionnaire and the brief ICF core set for osteoarthritis were used to assess the impact of treatment on the subjects' quality of life and biopsychosocial functioning. This research included 94 subjects who underwent three weeks of physical therapy and they were followed up for 6 months. The results showed a positive effect of physical therapy on the examined parameters with no statistically significant difference between the groups. The study revealed that 6 months after physical therapy there was a slight decrease in muscle strength, but no deterioration in pain sensation and knee function. Given these findings, no significant differences were observed between the mentioned physical procedures. In conclusion, we found that therapeutic exercise is effective in treating knee OA and there is no necessity to include EMG BFB therapy or ES therapy in rehabilitation protocols
Association between fibroblast growth factor 23 and bone loss in liver transplant candidates
No full textUvod: Jetrena osteodistrofija (engl. hepatic osteodistrophy, HO) je koštano-mineralni poremećaj u kandidata za ortotopnu transplantaciju jetre (OTJ) koju obilježava gubitak koštane mase i sklonost prijelomima. Čimbenik rasta fibroblasta 23 (engl. fibroblast growth factor 23, FGF23) regulira metabolizam fosfata i vitamina D, a povećane koncentracije se povezuju s gubitkom koštane mase i osteoporotskim prijelomima. Cilj ovog istraživanja je bio ispitati povezanost gubitka koštane mase i koncentracije intaktnog FGF23-a (engl. intact FGF23, iFGF23) u kandidata za OTJ.
Ispitanici i metode: U istraživanje su uključeni odrasli kandidati za OTJ. Gubitak koštane mase (osteopenija ili osteoporoza) je dijagnosticiran s pomoću denzitometrije kosti X-zrakama dvostruke prodornosti (DXA), a prijelomi kralježnice standardnim radiološkim snimkama. Izmjerene su koncentracije parametara koštano-mineralnog metabolizma, upale, inzulinske rezistencije, iFGF23 i aktivnost koštane alkalne fosfataze (BALP) u krvi. Ispitanici su podijeljeni u skupinu bez i s gubitkom koštane mase.
Rezultati: U istraživanje je uključeno 90 ispitanika (40 u skupini bez, a 50 u skupini s gubitkom koštane mase). Pojavnost gubitka koštane mase iznosila je 55,6%, a prijeloma kralježnice 48,9%. Nije bilo razlike statistički značajne razlike u parametrima koštano-mineralnog metabolizma, upale, inzulinske rezistencije te iFGF23-a između promatranih skupina. Aktivnost BALP-a bila je povećana u ispitanika s gubitkom koštane mase. Ženski spol i veća aktivnost BALP-a nezavisni su čimbenici rizika gubitka koštane mase, a starija životna dob prijeloma. Aktivnost BALP-a značajno je negativno korelirala s nalazom DXA.
Zaključci: Pojavnost gubitka koštane mase i osteoporotskih prijeloma kralježnice u kandidata za OTJ je veća nego u zdravoj populaciji. Koncentracija iFGF23-a nije povezana s gubitkom koštane mase.Introduction: Hepatic osteodystrophy (HO) is a bone-mineral disorder in orthotopic liver transplantation (OLT) candidates that leads to bone loss and tendency to fractures. Fibroblast growth factor 23 (FGF23) regulates phosphate and vitamin D metabolism, and is associated with bone loss and fragility fractures. The aim of this study was to examine the relationship between bone loss and the concentration of intact FGF23 (iFGF23) in OLT candidates.
Patients and methods: Adult OLT candidates were included in the study. Bone loss (osteopenia or osteoporosis) was diagnosed using dual-energy X-ray absorptiometry (DXA), and spinal fractures by standard radiological imaging. Parameters of bone-mineral metabolism, inflammation, insulin resistance, iFGF23 and bone alkaline phosphatase (BALP) activity were measured in blood. Patients were divided into groups with and without bone loss.
Results: Ninety (90) patients were included in the study (40 in the group without and 50 in the group with bone loss). The bone loss prevalence was 55.6% and vertebral fractures 48.9%. No significant differences in parameters of bone-mineral metabolism, inflammation, insuline resistance and iFGF23 were found between groups. Group with bone loss had higher BALP activity. Female gender and higher values of bone alkaline phosphatase were independent risk factors for bone loss, while older age was for fractures. BALP activity significantly negatively correlated with DXA results.
Conclusions: Prevalence of bone loss and osteoporotic fractures among OLT candidates is higher than in healthy population. No association exists between iFGF23 concentration and bone loss
Diagnostic ultrasound in monitoring patients with rheumatoid arthritis compared to standard clinical disease activity indices
No full textUnatoč ACR/EULAR preporukama o korištenju dijagnostičkog UZV u RA, UZV pregled za sada nije dio standardnih indeksa kojima se prati aktivnosti bolesti, niti je uključen u kriterije remisije. Cilj ovog istraživanja je bio procijeniti vrijednost dijagnostičkog UZV u praćenju bolesnika s RA u odnosu na standardne metode praćenja. Ispitati odnos UZV nalaza s kliničkim, laboratorijskim, radiološkim pokazateljima aktivnosti bolesti, kliničkim indeksima aktivnosti bolesti, funkcionalnim upitnicima te ACR/EULAR kriterijima kliničke remisije. Predložiti model hrvatskog zglobnog bodovnog sustava te novi kompozitni bodovni sustav. Od uključenih 117 RA bolesnika koji su praćeni tokom 3 mjeseca, ukupno ih je 88 završilo istraživanje. UZV pregled je učinjen na predefiniranom setu zglobova i tetiva, a UZV promjene su bodovane prema posljednjim publiciranim konsenzusima stručnih društava. Broj otečenih zglobova, procjena aktivnosti bolesti na VAS skali od strane liječnika, CRP, radiološki verificirane erozivne promjene, CDAI i SDAI indeks su bili najsnažnije značajno povezani s objektiviziranjem upale pomoću UZV. UZV aktivnost je utvrđena kod do 75% (Boolean) odn. 57,1% (SDAI) ispitanika koji su bili u remisiji prema ACR/EULAR kliničkim kriterijima. Kreiran je i validiran CroUS koji obuhvaća RC, MCP2, MCP3, PIP3, koljena, MTP5 zglobove i tetive ECRL/ECRB, EDC, ECU,
tibialis posterior, PB/PL bilateralno. Rezultat kreiranog kompozitnog SonoFIA indeksa (CroUS, HAQ, DAS 28 SE) >8, uz osjetljivost od 83,33% i specifičnost od 61,54% upućuje na visoko aktivnu bolest. Potvrdili smo nužnost implementiranja UZV pregleda u redovni klinički pregled i njegovu dodatnu vrijednost i superiornost u objektiviziranju aktivnosti bolesti i remisije. Smatramo kako bi UZV praćenje aktivnosti RA, temeljem reduciranih bodovnih sustava i kompozitnih bodovnih sustava baziranih na UZV, svoju glavnu primjenu u praksi trebalo naći u dvojbenim kliničkim slučajevima, posebice kod bolesnika u stabilnoj remisiji kod kojih se razmatra redukcija terapije.Although ACR/EULAR recommends using diagnostic US in RA, it is still not incorporated into disease activity indices or remission criteria. The aim was to determine the value of diagnostic US in monitoring RA regarding standard methods
of monitoring. To examine the relationship of US finding with clinical, laboratory, radiological disease activity indicators, clinical disease acitivity indices, functional questionnaires, ACR/EULAR remission criteria. To propose a model of a Croatian
joint scoring system and a novel composite scoring system. 117 RA patients were included and 88 finished the study during the 3 month follow up. US examination was conducted on a predefined joint and tendon set and scored according to the
latest published consensus. SJC, evaluator GDA, CRP, X-ray erosive changes, CDAI and SDAI had the strongest correlation with US findings. US activity was found in up to 75% (Boolean) and 57,1% (SDAI) patients in remission. CroUS (RC, MCP2, MCP3, PIP3, knee, MTP5, ECRL/ECRB, EDC, ECU, tibialis posterior, PB/PL bilateraly) was developed and validated. Composite SonoFIA index (CroUS, HAQ, DAS28 SE) > 8 indicates high disease activity with 83,33% sensitivity and 61,54% specificity. We confirmed the necessity of US implementation into RA monitoring and it's added value and superiority in objectifying disease activity and remission. US monitoring using reduced joint counts and US based composite scoring systems should take place in questionable clinical cases and patients in sustained remission with perspecitve of drug tapering
Composition of the bacterial microbiota of donated human milk
No full textUvod: Istraživanja su pokazala utjecaj različitih obilježja na sastav bakterijske mikrobiote humanog mlijeka (HMM), no nisu provođena na uzorcima iz mješavina darovanog humanog mlijeka (DHM).
Cilj: Cilj istraživanja bio je identificirati sastav bakterijske mikrobiote DHM-a te istražiti postoje li obilježja koja mogu utjecati na zastupljenost rodova pojedinih bakterija.
Ispitanice i metode: Iz arhivskih uzoraka mješavina DHM-a izolirana je bakterijska deoksiribonukleinska kiselina. Sekvenciranjem nove generacije određena je zastupljenost operativnih taksonomskih jedinica bakterija i uspoređena s poznatim obilježjima darivateljica, njihove djece i darovanog mlijeka.
Rezultati: U istraživanje je uključeno 88 uzoraka DHM-a od 88 darivateljica. U zastupljenosti bakterijskih rodova između skupina uzoraka podijeljenih prema načinu poroda i izloženosti antibioticima nije bilo značajnih razlika. Razlike su nađene s obzirom na tjedne gestacije na porodu i tjedne laktacije, način hranjenja majčinim mlijekom, način izdajanja viška mlijeka, broj bakterija kultiviranih u mlijeku prije pasterizacije te duljinu trajanja i temperaturu pohrane.
Zaključak: Dojenje djece te kraća pohrana na -30 ⁰C u Banci ovim su se istraživanjem pokazali kao pozitivni prediktori za zastupljenost rodova Lactobacillus i Bifidobacetrium kao dio bakterijske HMM-e u uzorcima mlijeka.Introduction: Studies have shown the influence of different characteristics on the composition of the bacterial microbiota of human milk (HMM), they were not conducted on samples from pools of donated human milk (DHM).
Aim: The aim of the research was to identify the composition of the bacterial microbiota of DHM and to investigate whether there are characteristics that can influence the representation of certain bacterial genera.
Subjects and methods: Bacterial deoxyribonucleic acid was isolated from archival samples from pools of DHM. Using next generation sequencing, the representation of operational taxonomic units of bacteria was determined and compared with the known characteristics of donors, their children and DHM.
Results: 88 DHM samples were included in the research. There were no significant differences in the representation of bacterial genera between sample groups divided according to the mode of delivery and exposure to antibiotics. Differences were found regarding weeks of gestation at delivery and weeks of lactation, the method of feeding with breast milk, the method of expressing surplus milk, the number of bacterial colonies cultivated in milk before pasteurization, and the length of time and temperature of storage.
Conclusion: Breastfeeding of children and shorter storage at -30 ⁰C in the human milk bank have been shown as positive predictors for the presence of the genus Lactobacillus and Bifidobactrium as part of bacterial HMM in milk samples