Veterinary medicine - Repository of PHD, master's thesis
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Expression of guanylate cyclase C in human prefrontal cortex depends on sex and feeding status
No full textIntroduction: Guanylate cyclase C (GC-C) has been detected in the rodent brain in neurons of the cerebral cortex, amygdala, midbrain, hypothalamus, and cerebellum.
Methods: In this study we determined GC-C protein expression in Brodmann areas (BA) 9, BA10, BA11, and BA32 of the human prefrontal cortex involved in regulation of feeding behavior, as well as in the cerebellar cortex, arcuate nucleus of hypothalamus and substantia nigra in brain samples of human 21 male and 13 female brains by ELISA with postmortem delay < 24 h.
Results: GC-C was found in all tested brain areas and it was expressed in neurons of the third cortical layer of BA9. The regulation of GC-C expression by feeding was found in male BA11 and BA10-M, where GC-C expression was in negative correlation to the volume of stomach content during autopsy. In female BA11 there was no correlation detected, while in BA10-M there was even positive correlation. This suggests sex differences in GC-C expression regulation in BA11 and BA10-M. The amount of GC-C was higher in female BA9 only when the death occurred shortly after a meal, while expression of GC-C was higher in BA10-O only when the stomach was empty. The expression of GC-C in female hypothalamus was lower when compared to male hypothalamus only when the stomach was full, suggesting possibly lower satiety effects of GC-C agonists in women.
Discussion: These results point toward the possible role of GC-C in regulation of feeding behavior. Since, this is first study of GC-C regulation and its possible function in prefrontal cortex, to determine exact role of GC-C in different region of prefrontal cortex, especially in humans, need further studies
Laryngeal Mask Airway in Neonatal Resuscitation: A Survey of the Union of European Neonatal and Perinatal Societies
No full textIntroduction: Laryngeal mask airway (LMA) use in neonatal resuscitation is limited despite existing evidence and recommendations. This survey investigated the knowledge and experience of healthcare providers on the use of the LMA and explored barriers and solutions for implementation.
Methods: This online, cross-sectional survey on LMA in neonatal resuscitation involved healthcare professionals of the Union of European Neonatal and Perinatal Societies (UENPS).
Results: A total of 858 healthcare professionals from 42 countries participated in the survey. Only 6% took part in an LMA-specific course. Some delivery rooms were not equipped with LMA (26.1%). LMA was mainly considered after the failure of a face mask (FM) or endotracheal tube (ET), while the first choice was limited to neonates with upper airway malformations. LMA and FM were considered easier to position but less effective than ET, while LMA was considered less invasive than ET but more invasive than FM. Participants felt less competent and experienced with LMA than FM and ET. The lack of confidence in LMA was perceived as the main barrier to its implementation in neonatal resuscitation. More training, supervision, and device availability in delivery wards were suggested as possible actions to overcome those barriers.
Conclusion: Our survey confirms previous findings on limited knowledge, experience, and confidence with LMA, which is usually considered an option after the failure of FM/ET. Our findings highlight the need for increasing the availability of LMA in delivery wards. Moreover, increasing LMA training and having an LMA expert supervisor during clinical practice may improve the implementation of LMA use in neonatal clinical practice
Is CYP2C Haplotype Relevant for Efficacy and Bleeding Risk in Clopidogrel-Treated Patients?
No full textA recently discovered haplotype—CYP2C:TG—determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients with a poor (PM) or intermediate (IM) CYP2C19 metabolizer phenotype (vs. normal, NM; rapid, RM; or ultrarapid, UM). We investigated whether the CYP2C:TG haplotype affected efficacy/bleeding risk in clopidogrel-treated patients. Adults (n = 283) treated with clopidogrel over 3–6 months were classified by CYP2C19 phenotype based on the CYP2C19*2*17 genotype, and based on the CYP2C19/CYP2C cluster genotype, and regarding carriage of the CYP2:TG haplotype, and were balanced on a number of covariates across the levels of phenotypes/haplotype carriage. Overall, 45 (15.9%) patients experienced ischemic events, and 49 (17.3%) experienced bleedings. By either classification, the incidence of ischemic events was similarly numerically higher in PM/IM patients (21.6%, 21.8%, respectively) than in mutually similar NM, RM, and UM patients (13.2–14.8%), whereas the incidence of bleeding events was numerically lower (13.1% vs. 16.6–20.5%). The incidence of ischemic events was similar in CYP2C:TG carries and non-carries (14.1% vs. 16.1%), whereas the incidence of bleedings appeared mildly lower in the former (14.9% vs. 20.1%). We observed no signal to suggest a major effect of the CYP2C19/CYP2C cluster genotype or CYP2C:TG haplotype on the clinical efficacy/safety of clopidogrel
Correlation between the liver transection line localization and future liver remnant hypertrophy in associating liver partition and portal vein ligation for staged hepatectomy
No full textBackground and aims: Colorectal liver metastases (CRLMs) represent the most prevalent form of secondary liver tumors, and insufficient future liver remnant (FLR) often leads to unresectability. To tackle this challenge, various methods for stimulating liver hypertrophy have been developed including portal vein embolization (PVE), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and the newest one, liver venous deprivation (LVD). ALPPS was thoroughly studied over the last decade and it has been shown to induce rapid and intensive FLR hypertrophy. The objective of this study was to assess whether the localization of the liver transection line during the initial stage of ALPPS correlates with the degree of FLR hypertrophy.
Methods: A retrospective, multicentric study was conducted, and we analyzed all consecutive patients with CRLMs who underwent ALPPS over the eight-year period. Patients were categorized into two groups based on the type of resection-right trisectionectomy (ERH) or right hemihepatectomy (RH) respectively. The degree of hypertrophy (DH), its correlation with FLR and postoperative outcomes were assessed.
Results: The cohort consisted of 136 patients (72 in the ERH group and 64 in the RH group). Baseline characteristics, hypertrophy interval, and total liver volume showed no significant differences between the groups. DH was greater in the ERH group (83.2% vs. 62.5%, p = 0.025). A strong negative correlation was observed between FLR volume and DH in both groups. Postoperative outcomes and one-year survival were comparable between the groups.
Conclusions: FLR hypertrophy is influenced by the localization of the liver transection line in ALPPS. Furthermore, correlation analysis indicated that a smaller estimated FLR is associated with greater DH. No statistical difference in outcomes was noted between the groups
Real-world Outcomes of Dual HER2 Blockade Therapy in Metastatic HER2-Positive Breast Cancer: from Induction to Maintenance
No full textBackground and objective: Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab combined with taxane-based chemotherapy (Cht) has been the standard first-line treatment for HER2-positive metastatic breast cancer (mBC) for years, due to the impressive results of the CLEOPATRA study. Real-world (RW) studies have become critical for assessing treatment effectiveness and safety in real-life circumstances. The aim of this study was to analyze the treatment outcomes of first-line therapy for HER2-positive mBC in RW clinical practice, specifically focusing on the use of maintenance endocrine therapy (ET) in hormone receptor positive (HR-positive) patients.
Methods: This retrospective analysis included 106 HER2-positive mBC patients treated with trastuzumab and pertuzumab combined with taxane-based Cht from October 2015 to December 2020 at the University Hospital Centre Zagreb.
Results: At a median follow-up of 30 months, median progression-free survival (PFS) was 25 months for the total population (95% confidence interval [CI] 16 - not analyzed). Patients with de novo mBC had longer median PFS than patients with recurrent disease (not reached vs. 18 months; hazard ratio 1.99; 95% CI 0.69-3.64, p<0.022). Age, hormone receptor positivity, visceral involvement, number of Cht cycles and previous adjuvant trastuzumab did not impact PFS. Most HR-positive patients (N=55, 88.7%) received maintenance ET after induction Cht.
Conclusion: This retrospective study provides additional data on patient characteristics, treatment and outcomes of RW HER2-positive mBC patients treated with pertuzumab and trastuzumab as first-line therapy. In our institution, maintenance ET after induction Cht has become standard clinical practice
The Impact of Newly Diagnosed Early Breast Cancer on Psychological Resilience, Distress Levels, and the Perception of Health
No full textConfronting a breast cancer diagnosis, along with complex and challenging treatment procedures, is an extremely stressful experience. Psychological resilience is the ability to maintain or restore normal functioning while facing adversity. We aimed to explore the impact of an early breast cancer diagnosis on psychological resilience, distress, and perception of health. A cross-sectional study was conducted, including 50 patients newly diagnosed with early breast cancer and 67 healthy women with screening mammograms graded 1 or 2 using a Breast Imaging Reporting and Data System. The levels of distress, perception of health, and psychological resilience were assessed using the depression, anxiety, and stress scale, the SF 36-Item Health Survey 1.0, and the Connor–Davidson RISC-25 scale. Differences between variables were examined using the t-test and chi-square test for interval and categorial variables. The surveys were conducted within four weeks of a breast cancer diagnosis. Patients with breast cancer reported a deterioration of their health relative to the previous year and significantly higher levels of psychological resilience, while there was no significant difference between the groups in levels of stress, anxiety, or depression. The process of diagnosis with early breast cancer may activate psychological dynamic processes which are involved in the effective adaptation to acute stress, leading to higher resilience levels in breast cancer patients compared to healthy controls
Gene RAD50, STARD3, ORMDL3 and IL6R polymorphisms in asthmatic patients
No full textUnatoč značajnom medicinskom napretku u posljednjih nekoliko desetljeća, astma se još uvijek smatra izazovom. Ovo je prva slučaj-kontrola studija gena kandidata u Hrvatskoj kojoj je cilj razjasniti genomski kontekst pojave astme u odraslih. Hipoteza istraživanja je bila da su polimorfizmi gena IL6R (1q21.3), RAD50 (5q31.1), STARD3 i ORMDL3 (17q12-21.1) povezani s ranijom pojavom bolesti, težom astmom, većim brojem egzacerbacija te alergijskim oblikom astme. U istraživanju je sudjelovalo 235 ispitanika s astmom težine 1-4 (od blage do teške astme) po GINA kriterijima. Našlo se da su polimorfizmi RS2897443 i RS2244012 (RAD50) rizični čimbenik za razvoj nosne polipoze, RS1877031 (STARD3) rizični je čimbenik za pojavu astme u djece i razvoj nosne polipoze, ali djeluje zaštitno na prisutnost astme i pojavu bolesti u odraslih te nastanak T2 alergijskog i eozinofilnog fenotipa. RS3744246 gena ORMDL3 nosi povećan rizik za prisutnost astme u odraslih iako je uz njega ona bolje kontrolirana dok su za SNP gena IL6R, RS4129267, nađene samo asocijacije na razini pojedinih genotipova za prisutnost astme u odraslih i visoke vrijednosti krvne eozinofilije i FeNO-a. Zaključno, astma je kompleksna bolest i ovdje se dokazalo da spoznaje o genetskoj podlozi patofizioloških procesa dobivenih iz dječjih populacija nisu nužno i odraz situacije u populaciji odraslih.Despite significant medical advances in recent decades, asthma is still considered a challenge. This is the first candidate genes case-control study in Croatia that aims to clarify the genomic context of asthma in adults. The research hypothesis was that IL6R (1q21.3), RAD50 (5q31.1), STARD3 and ORMDL3 (17q12-21.1) gene polymorphisms were associated with an earlier disease onset, more severe asthma, a greater number of exacerbations and an allergic asthma phenotype. A total of 235 subjects with asthma, stage 1-4 (from mild to severe asthma) according to GINA criteria, took part in this research. It was found that the polymorphisms RS2897443 and RS2244012 (RAD50) are a risk factor for the development of nasal polyposis, RS1877031 (STARD3) is a risk factor for the onset of asthma and the development of nasal polyposis in children, but has a protective effect on the presence of asthma and the onset of the disease in adults and the occurrence of T2 allergic and eosinophilic phenotype. RS3744246 of the ORMDL3 gene carries an increased risk for the presence of asthma in adults, although it conffers a better controlled variant, while for the SNP of the IL6R gene, RS4129267, the only associations were found at the level of individual genotypes for the presence of asthma in adults and high values of blood eosinophilia and FeNO. In conclusion, asthma is a complex disease and here it has been proven that the knowledge about the genetic basis of pathophysiological processes in asthma obtaine
Systematic Review of Current Audiological Treatment Options for Patients with Treacher Collins Syndrome (TCS) and Surgical and Audiological Experiences of an Otorhinolaryngologist with TCS
No full textTreacher Collins syndrome (TCS) is a rare congenital craniofacial condition that affects approximately one out of fifty thousand births. Different ratios of TCS patients have conductive hearing loss: 88%1 vs. 91.4–100.00%2. For this reason, it was examined which hearing solutions can be used with this condition and how effective they are. A systematic literature review was conducted, which showed that the bone-anchored hearing aid (BAHA, OSIA), the bone conduction implant (Bonebridge) or the active implant of the middle ear (Soundbridge) are reliable methods for the treatment of conductive hearing loss in TCS patients. After the implantation of all available hearing solutions, improved hearing and speech comprehension were observed. Additionally, a statement regarding the treatment of TCS and a personalized point of view of a clinical expert with TCS were provided. However, due to the small amount of data, no general recommendations can be given for the treatment of hearing loss in TCS patients; therefore, it is advised to collect more data on hearing solutions for TCS patients in future research
Candidate-gene studies related to drug pharmacokinetics, pharmacodynamics, safety, and efficacy in the era of extensive technological developments: could we empower them by more efficient implementation of established epidemiological concepts?
No full textUltrasound assessment of diaphragm mobility in patients with systemic sclerosis with and without interstitial lung disease
No full textSistemska skleroza (SSc) kronična je multisistemska autoimuna bolest nepoznate etiologije. Bolest često zahvaća pluća (SSc-ILD) i gastrointestinalni sustav. Dijafragma je glavni mišić u fiziologiji disanja te sudjeluje u više od 70 % minutne ventilacije.
Cilj ove disertacije bio je procijeniti je li dijafragmalna pokretljivost, debljina i frakcija zadebljanja (DTF) reducirana u bolesnika koji boluju od SSc-ILD-a u odnosu na pacijente bez ILD-a.
U ovome presječnom istraživanju istražena je povezanost ultrazvukom mjerene pokretljivosti, debljine dijafragme i DTF pacijenata sa SSc-ILD-om i bez ILD-a s kliničkim parametrima poput plućne funkcije, Warrickovim skorom, gastroezofagealnim simptomima, promjerima jednjaka, modificiranim Rodnanovim kožnim testom (mRSS) i modificiranom skalom dispneje britanskog Medicinskog istraživačkog vijeća (mMRC).
Rezultati istraživanja pokazali su da bolesnici sa SSc-ILD-om imaju manju pokretljivost dijafragme pri dubokom disanju odnosu na bolesnike bez ILD-a. Bolesnici koji imaju smanjenu pokretljivost dijafragme imaju više vrijednosti mMRC skale dispneje, viši mRSS, niže vrijednosti plućne funkcije, viši Warrickov skor te šire promjere jednjaka. Nije utvrđena značajna razlika u debljini dijafragme i DTF. Tri pacijenta (6 %) sa SSc su imali smanjenu debljinu dijafragme. Medijan vrijednosti DTF bio je 48 %. UZV dijafragme je korisna, neinvazivna metoda za procjenu funkcije dijafragme u bolesnika sa SSc.Systemic sclerosis (SSc) is a chronic multisystem autoimmune disease of unknown etiology. The disease often affects lungs (SSc-ILD) and the gastrointestinal system. The diaphragm is the main muscle in the physiology of respiration and is responsible for more than 70 % of minute ventilation.
The aim of this dissertation was to evaluate whether diaphragmatic mobility, thickness and thickening fraction (DTF) is reduced in patients suffering from SSc-ILD compared to patients without ILD.
In this cross-sectional study, the association of ultrasound-measured mobility, diaphragm thickness, and DTF of patients with SSc-ILD and without ILD with clinical parameters such as lung function, Warrick score, gastroesophageal symptoms, esophageal diameters, modified Rodnan skin score (mRSS) and modified British Medical Research Council (mMRC) dyspnea scale was investigated.
The research results demonstrated that patients with SSc-ILD have lower mobility of the diaphragm during deep breathing compared to patients without ILD. Patients who have reduced diaphragm mobility have higher mMRC dyspnea scale results, higher mRSS, lower pulmonary function results, higher Warrick score and wider esophageal diameters. No significant difference was found in diaphragm thickness and DTF. Three patients (6 %) with SSc had reduced diaphragm thickness. The median DTF value was 48 %. Ultrasound of the diaphragm is a useful, non-invasive method for evaluating diaphragm function in patients with SSc