Non-coding RNA and cholesteatoma

Objective Cholesteatoma is a challenging chronic pathology of the middle ear for which pharmacologic therapies have not been developed yet. Cholesteatoma occurrence depends on the interplay between genetic and environmental factors while master regulators orchestrating disease progression are still unknown. Therefore, in this review, we will discuss the diagnostic and therapeutic potential of non-coding RNAs (ncRNA) as a new class of regulatory molecules. Methods We have comprehensively reviewed all articles investigating ncRNAs, specifically micro RNAs (miRNAs) and long ncRNAs (lncRNA/circRNA) in cholesteatoma tissue. Results Candidate miRNA approaches indicated that miR-21 and let-7a are the major miRNAs involved in cholesteatoma growth, migration, proliferation, bone destruction, and apoptosis. Regulatory potential for the same biological processes was also observed for miR-203a. The NF-kB/miR-802/PTEN regulatory network was in relation to observed miR-21 activity in cholesteatoma as well. High throughput approaches revealed additional ncRNAs implicated in cholesteatoma pathology. Competitive endogenous RNA (ceRNA) analysis highlighted lncRNA/circRNA that could be “endogenous sponge” for miR-21 and let-7a based on the hypothesis that RNA transcripts can communicate with and regulate each other by using shared miRNA response elements. Conclusion In this review, we summarize the discoveries and role of ncRNA in major pathways in cholesteatoma and highlight the potential of miRNA-based therapeutics in the treatment of cholesteatoma. Level of Evidence: NA

Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity

Fatty acids play a crucial role in obesity development and in the comorbidities of obesity in both adults and children. This study aimed to assess the impact of circulating fatty acids on biomarkers of metabolic health of adolescents living with obesity. Parameters such as blood lipids, redox status, and leukocyte telomere length (rLTL) were measured alongside the proportions of individual fatty acids. The Mann–Whitney U test revealed that individuals with obesity exhibited an unfavorable lipid and redox status compared to the control normal weight group. The group with obesity also had lower plasma n-3 polyunsaturated fatty acids (PUFAs) and a higher ratio of n-6 to n-3 PUFAs than the control group. They also had a shorter rLTL, indicating accelerated biological aging. There was an inverse association of rLTL and plasma n-6-to-n-3 PUFA ratio. Future studies should explore the impact of recommended nutrition plans and increased physical activity on these parameters to determine if these interventions can enhance the health and well-being of adolescents with obesity, knowing that early obesity can track into adulthood

Fizioterapija u operativnom liječenju tumora dojke

Tumori dojke javljaju se neovisno o dobi u rasponu od 25. do 80. godine života, a u nekim slučajevima čak i kasnije. Pretežito oboljevaju žene no možemo ih naći i u muškaraca. Osnovna je podjela na benigne i maligne. Maligni tumor dojke najzastupljenija je zloćudna bolest, te drugi na ljestvici uzroka smrti od tumora u žena. Iako nije poznato zbog čega nastaje, neki čimbenici povećavaju rizik za razvoj raka dojke: spol, dob, prekomjerna težina, pušenje, pozitivna obiteljska anamneza. Dojka je žlijezdani organ smješten na prednjoj strani prsnog koša, uključen u masno tkivo što ga sa svih strana okružuje. Glavne dijagnostičke metode za otkrivanje tumora dojke su anamneza, fizikalni pregled, mamografija. Fizikalni pregled se sastoji od pažljive inspekcije i palpacije u sjedećem i ležećem položaju bolesnice. Operativni zahvat je najčešći oblik liječenja. Pri tom zahvat uključuje intervenciju na limfnim čvorovima bilo da se radi o provjeri proširenosti bolesti ili o potrebi micanja zahvaćenih limfnih čvorova. Postoji nekoliko vrsta operacijskih zahvata. Poštednim operativnim zahvatom uklanjaju se tumor i okolni parenhim. Mastektomija je operacija uklanjanja cijele dojke. Moguće komplikacije operativnog liječenja jesu; dehiscencije šava i edem ruke nakon disekcije aksile, koji može prerasti i u tromboflebiti, smanjen mišićni tonus i izdržljivost, pogoršanje općeg stanja, hematom, ograničeni pokreti u ramenom obruču, prisutnost bolova u vratu i leima, limfedem. Nakon odabranih zahvata slijedi lječenje s ciljem sprečavanja povrata bolesti a ono ovisi o veličini tumora i zahvaćenom području. Ono uključuje radijsku terapiju dojke te sistemnu terapiju (kemoterapija, biološka terapija, hormonska terapija). Fizioterapija ima ulogu u prevenciji i otklanjanju posljedica kirurškog lječenja na funkcije zahvaćenog segmenta, te u postizanju kvalitete života liječenih na planu psihičke i socijalne integracije, zato je vrlo bitno s fizioterapijom započeti na vrijeme. Cilj fizioterapije ostvaruje se kroz tri faze: obnova, održavanje i razvitak maksimalne funkcionalne pokretljivosti i sposobnosti liječenih da se vrate u ADL i uspješna integracija u svakodnevnim aktivnostima i profesionalan život uz što manju ovisnost liječenih o pomoći drugih osoba. Pri tome se primjenjuju postupci: pozicioniranje bolesnika na krevetu, terapijske vježbe i tehnike za smanjenje boli, povećanje pokretljivosti, snage i izdržljivosti te specijalizirane metode, npr. limfna drenaža, PNF koncept (proprioceptivna neuromuskularna facilitacija) i Mulliganov koncept. Provode se vježbe disanja i relaksacije, vježbe istezanja. Program intervencije temeljen je na procjeni boli, pokretljivosti, mišićne snage, prisutnosti patološkog umora

Fizioterapija u operativnom liječenju tumora dojke

Tumori dojke javljaju se neovisno o dobi u rasponu od 25. do 80. godine života, a u nekim slučajevima čak i kasnije. Pretežito oboljevaju žene no možemo ih naći i u muškaraca. Osnovna je podjela na benigne i maligne. Maligni tumor dojke najzastupljenija je zloćudna bolest, te drugi na ljestvici uzroka smrti od tumora u žena. Iako nije poznato zbog čega nastaje, neki čimbenici povećavaju rizik za razvoj raka dojke: spol, dob, prekomjerna težina, pušenje, pozitivna obiteljska anamneza. Dojka je žlijezdani organ smješten na prednjoj strani prsnog koša, uključen u masno tkivo što ga sa svih strana okružuje. Glavne dijagnostičke metode za otkrivanje tumora dojke su anamneza, fizikalni pregled, mamografija. Fizikalni pregled se sastoji od pažljive inspekcije i palpacije u sjedećem i ležećem položaju bolesnice. Operativni zahvat je najčešći oblik liječenja. Pri tom zahvat uključuje intervenciju na limfnim čvorovima bilo da se radi o provjeri proširenosti bolesti ili o potrebi micanja zahvaćenih limfnih čvorova. Postoji nekoliko vrsta operacijskih zahvata. Poštednim operativnim zahvatom uklanjaju se tumor i okolni parenhim. Mastektomija je operacija uklanjanja cijele dojke. Moguće komplikacije operativnog liječenja jesu; dehiscencije šava i edem ruke nakon disekcije aksile, koji može prerasti i u tromboflebiti, smanjen mišićni tonus i izdržljivost, pogoršanje općeg stanja, hematom, ograničeni pokreti u ramenom obruču, prisutnost bolova u vratu i leima, limfedem. Nakon odabranih zahvata slijedi lječenje s ciljem sprečavanja povrata bolesti a ono ovisi o veličini tumora i zahvaćenom području. Ono uključuje radijsku terapiju dojke te sistemnu terapiju (kemoterapija, biološka terapija, hormonska terapija). Fizioterapija ima ulogu u prevenciji i otklanjanju posljedica kirurškog lječenja na funkcije zahvaćenog segmenta, te u postizanju kvalitete života liječenih na planu psihičke i socijalne integracije, zato je vrlo bitno s fizioterapijom započeti na vrijeme. Cilj fizioterapije ostvaruje se kroz tri faze: obnova, održavanje i razvitak maksimalne funkcionalne pokretljivosti i sposobnosti liječenih da se vrate u ADL i uspješna integracija u svakodnevnim aktivnostima i profesionalan život uz što manju ovisnost liječenih o pomoći drugih osoba. Pri tome se primjenjuju postupci: pozicioniranje bolesnika na krevetu, terapijske vježbe i tehnike za smanjenje boli, povećanje pokretljivosti, snage i izdržljivosti te specijalizirane metode, npr. limfna drenaža, PNF koncept (proprioceptivna neuromuskularna facilitacija) i Mulliganov koncept. Provode se vježbe disanja i relaksacije, vježbe istezanja. Program intervencije temeljen je na procjeni boli, pokretljivosti, mišićne snage, prisutnosti patološkog umora

First patient in Serbia with biochemically and genetically diagnosed pyridoxine-dependent epilepsy

Introduction. Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive inborn error of metabolism present with early-onset seizures resistant to common anticonvulsants. PDE has been shown to be caused by a defect of a α-aminoadipic semialdehyde dehydrogenase (also known as ALDH7A1 or antiquitin) in the cerebral lysine degradation pathway. Its deficiency results in accumulation of α-aminoadipic semialdehyde (α-AASA), piperideine -6-carboxylate and pipecolic acid, which serve as diagnostic markers in urine, plasma and cerebrospinal fluid of the disease. α-Aminoadipic semialdehyde dehydrogenase is encoded by the ALDH7A1 or antiquitin gene and definite confirmation of diagnosis of PDE is made by genetic analysis. Case report. We present a first patient in Serbia who was diagnosed clinically, biochemically and genetically. We suspected PDE due to drug-resistant seizures in the seventh day of life when we attempted with pyridoxine. Since that time the patient has taken pyridoxine and the seizures have not recured. Our patient had markedly elevated α- AASA in urine while on treatment with individual dosages of pyridoxine. Molecular-genetical analysis identified mutations of the ALDH7A1 (antiquitin) gene. Conclusion. α-AASA is reliable marker to select PDF patient for molecular analysis of the ALDH7A1(antiquitin) gene. Diagnosis is confirmed by molecular- genetical analysis and pyridoxine withdrawal is no longer needed to establish the diagnosis of „definite“ PDE

Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634)

Introduction. The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy’s father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years

Reference values of capillary blood saturation in neonates and its difference from pulse oximetry

Introduction Haemoglobin saturation is an obligatory oxygen parameter in the assessment of neonatal oxygenation. Although, pulse oximetry is currently one of the major methods in the determination of haemoglobin saturation, capillary blood saturation is still present in the diagnostic process. As well known, haemoglobin saturation value of capillary blood is insufficiently accurate, but not as much as the difference in relation to the values determined by pulse oximetry. Until now published studies have reported that capillary samples are obtained according to a protocol by the principle of free blood outflow, which is practically almost unachievable in the neonate. Objective Determination of the reference values of oxygen saturation (ScO2) and partial pressure (pcO2) of capillary blood by squeezing of the foot. The determination of difference between ScO2 and pulse oximetry (SpO2). Methods In 134 term newborns, we determined SpO2 . Subsequently, we measured the values of ScO2 and pcO2 from the same extremity. While withdrawing a capillary sample, we exerted multiple squeezing of the foot. The mean value of ScO2, pcO2, SpO2 and the difference between ScO2 and SpO2 were determined. Results Mean ScO2 value was 80.5}8.5%, pcO2 was 48.2}11.4 mm Hg and SpO2 was 98}1.9%. The difference between ScO2 and SpO2 values was 17.5}8.6% (t=23.568; p=0.000). Conclusion There is a statistically highly significant difference between the values of ScO2 and SpO2. Having the knowledge of this difference can increase the accuracy of clinical evaluation and further diagnostics. Comparison in up-to-now conducted studies suggests that the squeezing of the foot for obtaining a capillary sample in relation to free blood outflow does not bear any significant influence on the resultant values of haemoglobin saturation.

Expression of Toll-Like Receptors 2, 4 and Nuclear Factor Kappa B in Mucosal Lesions of Human Otitis: Pattern and Relationship in a Clinical Immunohistochemical Study

Objectives: The objectives were to detect and compare the expression of toll-like receptors (TLRs) 2, 4 and nuclear factor kappa B in mucosal lesions of chronic otitis. Methods: Fifty-five tissue samples obtained from children and adults operated on for otitis were investigated by semiquantitative immunohistochemical methods using polyclonal antibodies for TLR 2, 4 and NFkB. Kruskal-Wallis, Mann-Whitney, and Kendalls tau rank correlation tests were used. Results: Stronger expression of TLR2, 4 was found in inflamed mucosa than in the control for children and adults (TLR2: H = 23.86, P LT .001; TLR4: H = 22.80, P LT .001) (TLR2: H = 17.53, P LT .001; TLR4: H = 11.99, P LT .001); in cholesteatoma perimatrix compared to tubotympanic lesions in children (TLR2: H = 11.06, P = .004; TLR4: H = 10.61, P = .005) and adults (TLR2: H = 10.73, P =.013; TLR4: H = 9.65, P = .021). No differences were found in NFkB expression (H = 0.042, P = .99). Significant correlations were found for all pairs of molecules in cholesteatoma and tubotympanic mucosa of adults (TLR2, 4: P = .002, P LT .001; TLR2-NfkB: P = .032, P = .021; TLR4-NFkB: P =.035, P = .0013), only TLR4-NFkB in tubotympanic otitis of children (P = .026). Conclusions: Toll-like receptors 2, 4 and NFkB mediate inflammation in cholesteatoma and mucosal lesions of tubotympanic otitis in children and adults. Significant correlations between all pairs of molecules in all samples were detected in adults, but only TLR4-NFkB in children

SUMMARY

Introduction Haemoglobin saturation is an obligatory oxygen parameter in the assessment of neonatal oxygenation. Although, pulse oximetry is currently one of the major methods in the determination of haemoglobin saturation, capillary blood saturation is still present in the diagnostic process. As well known, haemoglobin saturation value of capillary blood is insufficiently accurate, but not as much as the difference in relation to the values determined by pulse oximetry. Until now published studies hav