Survivin Expression in Placentas with Intrauterine Growth Restriction

Background/Objectives: Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5–10% of all pregnancies and it is a leading cause of perinatal morbidity and mortality. During the initial phases of placentation, complex interlinked processes including cell proliferation, differentiation, apoptosis and the invasion of trophoblasts occur. Alterations in the regulation of these processes lead to placental dysfunction. Survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in cell proliferation balance and apoptosis, thus leading to proper placental development. This study aimed to evaluate survivin expression in placentas from IUGR and healthy pregnancies to explore its potential as a biomarker for the early diagnosis, prevention, and treatment of IUGR. Methods: Survivin presence was determined in 153 archival formalin-fixed and paraffin-embedded placental tissues from IUGR (N = 122) and uncomplicated (N = 31) term pregnancies. Tissue microarrays (TMAs) were constructed, and survivin expression was assessed using immunohistochemistry (IHC). Survivin levels were quantified using positive cell proportion (PCP) scores and immunoreactive scores (IRS), with statistical significance determined using mean values, standard deviation (SD), standard error, and Student’s t test in instances of normal distribution, and when this was not the case, the Mann–Whitney test. Chi-square tests, Fisher exact tests, and t-tests (p < 0.05) were used to compare categorical variables. Results: Our results suggested the significantly higher expression of survivin validated with PCP (p < 0.001) and IRS (p < 0.002) in placentas with IUGR compared to placentas from non-complicated term pregnancies. Conclusions: Increased survivin expression in IUGR placentas points to its potential role as a key indicator of placental dysfunction. By signaling early pathological changes, survivin may offer a valuable tool for the early detection of IUGR, potentially allowing for timely clinical interventions that could reduce the risk of serious outcomes, including stillbirth. To fully establish survivin’s clinical value, further research is needed to validate its diagnostic accuracy and to explore its involvement in molecular pathways that may be targeted for therapeutic benefit

Patients with Higher Pulse Wave Velocity Are More Likely to Develop a More Severe Form of Knee Osteoarthritis: Implications for Cardiovascular Risk

Background/Objectives: Knee osteoarthritis (KOA) is a progressive degenerative joint disease characterised by low-grade inflammation and is associated with increased cardiovascular (CV) risk and arterial stiffness. Pulse wave velocity (PWV) is a quantitative measure of arterial stiffness and an important tool for detecting subclinical arterial calcification and CV risk. This study aimed to determine whether PWV can distinguish radiographically mild KOA (Kellgren–Lawrence grades 1-2) from severe KAO (Kellgren–Lawrence grades 3-4) in terms of CV risk factors. Methods: A total of 223 postmenopausal women with KOA participated in this cross-sectional study. Assessments included anthropometry, laboratory analyses, blood pressure and PWV measurements, a 6 min walk test, pain evaluation using a visual analogue scale (VAS), and completion of the International Physical Activity Questionnaire (IPAQ). Results: PWV was significantly higher in the severe KOA group (10.53 m/s vs. 8.78 m/s, p 8.4 m/s, compared to the group with PWV ≤ 8.4 m/s. Conversely, eGFR, the 6 min walk test and physical activity of patients were reduced in the group with PWV > 8.4 m/s. A patient with a PWV > 8.4 m/s has a 1.77 times higher chance of developing a more severe form of the disease than a patient with a lower PWV. Conclusions: Patients with a higher PWV are more likely to develop a more severe form of KOA, which is associated with increased cardiovascular risk

Impact of Light Pollution on the Development of Obesity by Influencing the Quality of Sleep : Graduation Thesis

The increasing prevalence of light pollution has been recognized as a significant environmental factor influencing sleep quality and metabolic health. This thesis investigates the hypothesis that light pollution contributes to obesity development by dysrupting sleep patterns. Exposure of artificial light at night interferes with the circadian rhythm, leading to melatonin suppression, fragmented sleep, delayed sleep onset and hormonal imbalances. Leptin, ghrelin and cortisol are mostly affected by ALAN and contribute to increased hunger and appetite, weight gain, fat accumulation and insulin resistance. This paper shows recent evidence, by presenting several studies and review papers linking higher obesity rates to light pollution. This thesis underlines the importance of recognizing light pollution as a modifiable risk factor in the obesity epidemic and advocates for integrated approaches to combine environmental, lifestyle and interventions to improve human health

Glial Cells in Spinal Muscular Atrophy: Speculations on Non-Cell-Autonomous Mechanisms and Therapeutic Implications

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous deletions or mutations in the SMN1 gene, leading to progressive motor neuron degeneration. While SMA has been classically viewed as a motor neuron-autonomous disease, increasing evidence indicates a significant role of glial cells—astrocytes, microglia, oligodendrocytes, and Schwann cells—in the disease pathophysiology. Astrocytic dysfunction contributes to motor neuron vulnerability through impaired calcium homeostasis, disrupted synaptic integrity, and neurotrophic factor deficits. Microglia, through reactive gliosis and complement-mediated synaptic stripping, exacerbate neurodegeneration and neuroinflammation. Oligodendrocytes exhibit impaired differentiation and metabolic support, while Schwann cells display abnormalities in myelination, extracellular matrix composition, and neuromuscular junction maintenance, further compromising motor function. Dysregulation of pathways such as NF-κB, Notch, and JAK/STAT, alongside the upregulation of complement proteins and microRNAs, reinforces the non-cell-autonomous nature of SMA. Despite the advances in SMN-restorative therapies, they do not fully mitigate glial dysfunction. Targeting glial pathology, including modulation of reactive astrogliosis, microglial polarization, and myelination deficits, represents a critical avenue for therapeutic intervention. This review comprehensively examines the multifaceted roles of glial cells in SMA and highlights emerging glia-targeted strategies to enhance treatment efficacy and improve patient outcomes

Predictive and prognostic role of immune system cells, PD-1, PDL-1 and heat shock proteins in patients with triple negative, HER-2 positive and neoadjuvant treated breast cancer: istraživački podaci

Istraživanje je osmišljeno kao retrospektivna opservacijska analitička studija tri različite ispitivane skupine. Prvu skupinu će činiti bolesnice s trostruko negativnim, a drugu skupinu s HER-2 pozitivnim karcinomom dojke, operirane na Zavodu za opću i onkološku kirurgiju KBC-a Rijeka i Odjelu za opću i abdominalnu kirurgiju OB Pula u vremenskom razdoblju od 2008. do 2016. godine. U trećoj skupini bi bile bolesnice s lokalno uznapredovalim rakom dojke koje su na Klinici za radioterapiju i onkologiju KBC-a Rijeka liječene neoadjuvantnom kemoterapijom i bioterapijom te operirane na Zavodu za opću i onkološku kirurgiju KBC-a Rijeka u periodu 2016.-2020. Cilj istraživanja prve i druge skupine je izvršiti imunohistokemijsku karakterizaciju tumorskog upalnog infiltrata u trostruko negativnom i HER-2 pozitivnom karcinomu dojke, kao i odrediti prisutnost PD-1/PDL-1 i heat shock proteina u imunološkim i tumorskim stanicama. Namjera je analizirati odnos CD8, CD4, CD20, FOXP3, CD56 pozitivnih stanica, s tumorom povezanih makrofaga, te ekspresije PD-1/PDL-1 i heat shock proteina prema prognostičkim čimbenicima, prije svega pT, pN, pTNM i histološkom gradusu. Uslijediti će analiza međuodnosa upalnih stanica i ekspresije navedenih proteina, odnosno utvrđivanje njihovog potencijalnog prognostičkog značaja. Cilj istraživanja treće skupine je utvrditi mogući prediktivni značaj kliničkih, histoloških i imunohistokemijskih karakteristika tumora, ekspresije PD-1/PDL-1 i heat shock proteina u imunološkim i tumorskim stanicama u odgovoru na neoadjuvantno liječenje uz imunohistokemijsku karakterizaciju limfocitnog upalnog infiltrata. Nadalje cilj je ispitati međuodnos upalnih stanica s patohistološkim osobinama tumora. Osim navedenog, za skupinu kod koje nije došlo do potpunog odgovora na neoadjuvantno liječenje, cilj je provesti imunohistokemijsku karakterizaciju imunološkog odgovora u materijalu nakon završenog neoadjuvantnog liječenja, odrediti prisutnost PD-1 i PDL-1 i heat shock proteina te usporediti s odgovorom na neoadjuvantno liječenje.Nakon što se pregledom informatičkih baza podataka, Vegasoft i IBIS, pronađu slučajevi prema uključnim kriterijima istraživanja, sirovi podaci se pohranjuju na odvojenu i zaštićenu lokaciju od lokacije radnih verzija istraživačkih podataka. Podaci će se obraditi i pripremiti za statističku analizu

Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments. This narrative review explores their effectiveness, mechanisms of action, safety profiles, and current challenges in RA care. Tetracyclines have demonstrated significant immunomodulatory effects, including the inhibition of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), which are critical in RA pathology. Clinical trials, including double-blind, placebo-controlled studies, have shown efficacy in reducing RA symptoms, particularly in early and refractory cases. However, their use remains limited by inconsistent evidence, small sample sizes, and concerns about antimicrobial resistance. Current guidelines for RA management do not explicitly recommend tetracyclines due to these limitations, although off-label use may be considered in specific cases. The use of tetracycline for RA is restricted by drug interactions causing bacterial resistance alongside unpredictable patient responses, hence the necessity for prudence in its prescription within a clinical setting. To overcome these limitations, the development of safer compounds, in-depth in silico analyses, and integration with personalized medicine approaches are needed. Overall, tetracyclines show promise as adjunct therapies in RA management due to their dual anti-inflammatory and immunomodulatory actions. This review highlights the need for further research to address gaps in evidence, including the development of modified tetracyclines with reduced antimicrobial effects and improved safety profiles, as well as the integration of personalized medicine approaches to optimize patient outcomes

Hypoplastic left heart syndrome (HLHS) becomes of age: Assessing the young adult with HLHS including the neoaorta/aortic arch

Hypoplastic left heart syndrome (HLHS) is one of the most complex congenital heart defects (CHD), characterized by a hypoplastic left ventricle (LV), dominant right ventricle (RV) and small left-sided heart structures. The introduction of the Norwood operation has significantly improved outcomes, with 5-year survival reported up to 65 %. Despite these advances, post-operative morbidity and mortality remain high, and the long-term complications in adult survivors represent a challenge. The number of HLHS patients with Fontan circulation is expected to double in the next 20 years, leading to a growing population requiring specialized care from adult congenital heart disease (ACHD) teams. This article reviews current management strategies for HLHS, outlines potential long-term complications, and highlights existing knowledge gaps. Specific considerations in this population include the assessment of the neo-aorta and aortic arch, and systemic RV dysfunction in the setting of a Fontan circulation. The proposed surveillance strategy emphasizes the need for vigilant monitoring and timely intervention to treat the complications unique to this population, ensuring better outcomes for HLHS patients reaching adulthood

The Influence of Breast Density and Compression Force on Women’s Perception of Pain During Mammography

Cilj: Razumijevanje stupnja nelagode tijekom mamografskih pregleda i optimizacija sile kompresije korištene u različitim projekcijama temelj su radiološkim tehnolozima kako bi individualno pristupili oslikavanju dojki. Cilj ovog istraživanja je unaprjeđenje prakse mamografskog oslikavanja te poboljšanje iskustva žena. Ispitanici i metode: U ovo prospektivno istraživanje uključeno je 99 ispitanica koje su u razdoblju od 22. svibnja do 30. lipnja 2023. bile podvrgnute mamografskom pregledu u Kliničkom bolničkom centru Rijeka. Za statističku analizu korišten je Kolmogorov-Smirnovljev test kojim je ispitana normalnost distribucije numeričkih vrijednosti. U slučaju normalne distribucije korištena je aritmetička sredina te standardna devijacija, dok je u slučaju odstupanja numeričkih vrijednosti od normalne razdiobe korišten medijan i interkvartilni raspon. Razlika u normalno distribuiranim numeričkim varijablama među različitim kategorijama gustoće dojki ispitana je testom ANOVA. Razlika u varijabli boli koja odstupa od normalne razdiobe među dvjema dobnim skupinama, ispitana je Mann-Whitneyevim U-testom. Razlika u zastupljenosti ispitanica prema kvalitativnim obilježjima ispitana je testom χ2. Svi su testovi provedeni na razini statističke značajnosti p < 0,05. Za obradu podataka korišten je program Statistica 14.0.0.15 (TIBCO Software Inc.). Rezultati: Najčešće zastupljena kategorija gustoće tkiva dojke među ispitanicama je kategorija B. Medijan boli na skali od 0 do 10 je 5. Prosječna sila kompresije na desnu dojku u CC projekciji je 98,80 N, dok je za lijevu dojku 97,62 N. Prosječna sila kompresije na lijevu dojku u MLO projekciji iznosila je 118,86 N, a na desnu 114,81 N. Zaključak: Ovo istraživanje pridonosi razumijevanju čimbenika koji utječu na percipiranu razinu nelagode ispitanica prilikom mamografskog oslikavanja te optimizaciju postupka uz poboljšanje dijagnostičke vrijednosti procedure.Aim:Understanding the degree of discomfort during mammographic examinations and optimizing the compression force used in different projections are fundamental for radiologic technologists to individually approaching breast imaging. The aim of this study is to enhance mammographic imaging practices and improve patient experience. Participants and methods: This prospective study included 99 participants who underwent mammographic examination at the Clinical Hospital Center Rijeka from May 22 to June 30, 2023. The Kolmogorov-Smirnov test was used for statistical analysis to assess the normality of the distribution of numerical values. For normally distributed data, the mean and standard deviation were used, while the median and interquartile range were used for data that deviating from a normal distribution. The differences in normally distributed numerical variables among different categories of breast density were examined using the ANOVA test. The difference in the pain variable, which deviated from normal distribution between two age groups, was examined using the Mann-Whitney U test. The difference in the representation of participants based on qualitative features was examined using the χ2 test. All tests were conducted at a statistical significance level of

Kennedy Terminal Ulcer – the Beginning of the End (a Case Report)

Cilj: prikazati rijedak slučaj promjene kože nazvan Kennedyjev ulkus (KTU), koji se javlja u bolesnika u terminalnom stadiju života te naglasiti važnost ovog entiteta u kliničkoj praksi. Prikaz slučaja: Sedamdesetogodišnjoj bolesnici, koja je bila na palijativnom liječenju u stacionaru, utvrđena je rana na sakrumu za koju se zbog njezinih posebnih karakteristika, izgleda, lokalizacije te brzine progresije posumnjalo da se radi o posebnom entitetu i vrsti rane, odnosno o Kennedyjevu ulkusu. Kennedyjev terminalni ulkus neizbježno je oštećenje kože koje se javlja kao dio procesa umiranja. Oskudna literatura sugerira da se Kennedyjevi terminalni ulkusi javljaju iznenada, obično su kruškolikog oblika, locirani u sakralno/kokcigealnoj regiji, crvenožute ili crne boje, izgledom slični abraziji, a javljaju se nedugo prije smrti. Unatoč sveobuhvatnoj njezi i svakodnevnoj brizi i tretmanu, promjena na koži vrlo je brzo progredirala u ulkus IV. stupnja, a bolesnica je nakon sedam dana preminula. Zaključak: U svakodnevnoj praksi o Kennedyjevu terminalnom ulkusu vrlo se malo zna i velik se broj takvih promjena ne otkriva te ih se pogrešno evidentira kao dekubitalne rane. Potrebna su daljnja istraživanja o fenomenu oštećenja kože kod svih palijativnih bolesnika te dodatna edukacija medicinskih djelatnika kako bi se što više pridonijelo ublažavanju boli i dostojanstvenom životu umiruće osobe, ali i ostalih sudionika uključenih u brigu o terminalnom bolesniku.Aim: to present Kennedy terminal ulcer (KTU), a rare case of skin injury that occurs in patients in their terminal stage of life, and to emphasize the importance of this entity in clinical practice. Case report: A 70-year-old woman who was undergoing palliative treatment in the hospital, was diagnosed with a wound on the sacrum. Due to its special characteristics, such as appearance, location, and speed of progression, the wound was suspected not to be an ordinary pressure ulcer but a special entity, the so-called Kennedy terminal ulcer. Kennedy terminal ulcer is an inevitable skin breakdown or deterioration that occurs as part of the dying process. Kennedy terminal ulcers appear suddenly, are usually pear-shaped, located in the sacral/coccygeal region, red – yellow, or black in colour, abrasion-like in appearance, and occur shortly before death. Despite comprehensive care and daily care and treatment, the change on the skin progressed very quickly into a grade IV ulcer, and the patient died after seven days. Conclusion: In everyday practice, very little is known about Kennedy’s terminal ulcer and a many of such changes are not detected and are incorrectly recorded as decubitus wounds. Further research is needed on the phenomenon of skin damage in all palliative patients, as well as for other members involved in the care of dying patient