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Integrated Chemical and Biological Evaluation of Linden Honeydew Honey from Bosnia and Herzegovina: Composition and Cellular Effects
No full textHoneydew honey (HH) is a distinctive type of honey known for its dark colour, high mineral and polyphenol content, and pronounced biological activity. This study continues previous research on beech and chestnut honeydew honeys by presenting a comprehensive analysis of linden honeydew honey (LHH) from Bosnia and Herzegovina—a variety that, until now, has not been characterised in detail. Physicochemical parameters confirmed its classification as HH, with high electrical conductivity (1.21 mS/cm) and low moisture (15.1%). GC-MS analysis revealed a unique volatile profile dominated by α-terpinolene (17.4%), distinguishing LHH from other HH types. The sample exhibited high total phenolic content (816.38 mg GAE/kg) and moderate antioxidant capacity (1.11 mmol TE/kg). Antimicrobial testing demonstrated strong activity against Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA), with lower efficacy against Gram-negative bacteria. No cytotoxic effects were observed in HaCaT keratinocytes at concentrations up to 60 mg/mL, and wound healing assays showed improved scratch closure reaching approximately 30% after 24 h and 41% after 48 h compared to the control. These results indicate that LHH possesses promising bioactive properties and potential for dermatological application. Further studies with broader sample sets are needed to explore variability and confirm the therapeutic relevance of LHH in comparison to other honeydew types
Delayed Intracerebral Hemorrhage after Deep Brain Stimulation for Parkinson’s Disease
No full textIntroduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for advanced Parkinson’s disease (PD), offering significant symptomatic relief. Although DBS is generally considered safe, it carries risks, including the potential for delayed complications such as intracerebral hemorrhage (ICH). Case Presentation: We present a rare case of a 67-year-old male with PD who developed delayed ICH after undergoing bilateral STN DBS. Initially, the patient showed no neurological deficits postoperatively, with imaging confirming correct lead placement and no signs of hemorrhage. However, on the second postoperative day, the patient developed sudden right-sided hemiparesis. A CT scan revealed ICH alongside the left lead. The hemorrhage was managed conservatively, and the patient underwent extensive physical therapy, leading to significant improvement. Over the next 2 weeks, the patient’s condition improved, and follow-up CT scans showed complete resolution of the ICH. At this point, the left lead stimulation was initiated, further improving the patient’s PD symptoms. This case illustrates the potential for delayed ICH following STN DBS, emphasizing the need for ongoing monitoring and individualized treatment strategies. Conclusion: This case underscores the importance of vigilant postoperative monitoring and individualized management strategies in STN DBS patients. Early detection and appropriate management of complications such as ICH are crucial for minimizing risks and ensuring optimal patient outcomes. The potential for delayed complications highlights the need for continuous follow-up, even in the absence of immediate postoperative issues
Genetic Testing for Monogenic Forms of Male Infertility Contributes to the Clinical Diagnosis of Men with Severe Idiopathic Male Infertility
No full textPurpose: In recent years, many genes have been associated with male infertility; however, testing of monogenic forms has not yet been clinically implemented in the diagnosis of severe forms of idiopathic male infertility, as the diagnostic utility has not been established yet. The aim of this study was therefore to answer if the implementation of genetic testing for monogenic forms of male infertility could contribute to the clinical diagnosis of men with severe forms of idiopathic male infertility. Materials and Methods: Based on the ClinGene curation protocol, we defined a panel of genes with sufficient evidence for the involvement with severe male infertility. We tested the 21-gene panel in a representative multicentric cohort of men with significantly impaired spermatogenesis. We performed whole exome sequencing on 191 infertile men with severe forms of idiopathic male infertility; non-obstructive azoospermia, and severe oligozoospermia (T, p.Arg926*; c.2817delG, p.Leu940fs), MSH4 (c.1392delG, p.Ile465fs; c.2261C>T, p.Ser754Leu), TEX15 (c.6848_6849delGA, p.Arg2283fs; c.6271dupA, p.Arg2091fs), and TEX14 (c.1021C>T, p.Arg341*) genes were found. Conclusions: In the present multicentric cohort study, a monogenic cause in 2.1% of infertile men was identified. These findings confirm the utility of monogenic testing and suggest the clinical use of monogenic testing for men with severe forms of idiopathic male infertility
Legionella sheltonii sp. nov., a novel species isolated on a cruise ship during routine monitoring
No full textlike isolates, HB10 and PATHC038
, were isolated from a cold water distribution system on a cruise ship in 2017. The strains have been characterized by employing discriminatory genome typing, matrix-assisted laser desorption/ionization time-of-flight MS technique, fatty acid profiling and biochemical tests, thus identifying a new species in the genus
. Colonies displayed phenotypic characteristics typical of the family
, including a requirement for
-cysteine and testing catalase positive. Fatty acid methyl ester analysis showed that the predominant fatty acids detected in the studied strains are C16:0 iso, C16:1
7
, C16:0 and C15:0 anteiso. The obtained MIC values showed antimicrobial susceptibility to the antimicrobial drugs ciprofloxacin and erythromycin (0.8 and 2 µg ml
, respectively). The bacteria were also Gram-negative, rod-shaped, grew aerobically on buffered charcoal yeast extract agar and weakly grew on glycine-vancomycin-polymyxin-cycloheximide media at 36 °C with the ability to autofluoresce a blue-white colour when placed under a long-wavelength UV light (365 nm). The whole-genome sequencing performed displayed a G+C content of 38.2 mol%. The digital DNA–DNA hybridization analysis demonstrated a separation from the phylogenetically most related
, with 54.7% DNA–DNA relatedness. The identity percentage measured by average nucleotide identity between the PATHC038
strain and its respective closest species,
, was 93.9%, also confirming the distinctiveness of the novel species. The 16S rRNA gene,
and
sequences showed a similarity of 98.7, 98.4 and 96.2%, respectively, with
NCTC 11976
. Additionally, average amino acid identity and percentage of conserved proteins analyses further supported their classification as a novel species. The results obtained in this study confirm the status of an independent species. The name proposed for this species is
sp. nov. with PATHC038
(CCUG 76918T, ATCC TSD-370) as the type strain
Proteomic research of the stress response of Saccharomyces cerevisiae W303 yeast to metal ions eluted from orthodontic appliances
No full textGenetic Mechanisms of Yeast Response to Metal-Ion Induced Stress
No full textOvaj rad analizirao je učinak metalnih iona koje oslobađaju ortodontske naprave na kvasac Saccharomyces cerevisiae soj W303, korišten kao modelni organizam. Ortodontski materijali oslobađaju redoks-aktivne metalne ione poput željeza, nikla, aluminija, kroma i bakra, sposobne za stvaranje oksidacijskog stresa. Istraživanje je procijenilo održivost kvasca, njegovu proliferaciju i gensku ekspresiju primarnih antioksidacijskih (GPX2, SOD1, SOD2, CTT1), transkripcijskih faktora (YAP1, YAP5) i ostalih gena uključenih u metabolizam sumpora i redoks homeostazu (CCC, CYS3, CYS4, GSH1, GSH2, TSA1, TRR1). Stanična održivost mjerena je brojanjem stanica i fluorescentnim bojenjem, ističući smanjenje proliferacije i povećanje apoptoze nakon dulje izloženosti metalnim eluatima. Analiza genske ekspresije pokazala je različite odgovore na oksidacijski stres tijekom vremena, s početnom aktivacijom antioksidativne obrane nakon čega slijede prilagodbe povezane s homeostazom željeza. Ovi rezultati doprinose razumijevanju molekularnih mehanizama kojima metalni ioni oslobođeni iz ortodontskih materijala djeluju na oksidacijski stres i održivost stanica kvasca.This study analyzed the effect of metal ions released by orthodontic appliances on the yeast Saccharomyces cerevisiae strain w303, used as a model organism. Orthodontic materials release redox-active metal ions such as iron, nickel, aluminum, chromium, and copper, capable of generating oxidative stress. The study assessed yeast viability, its proliferation, and gene expression of primary antioxidant enzymes (GPX2, SOD1, SOD2, CTT1), transcription factors (YAP1, YAP5), and other genes involved in sulfur metabolism and redox homeostasis (CCC, CYS3, CYS4, GSH1, GSH2, TSA1, TRR1). Cell viability was measured by cell counting and fluorescent staining, highlighting a decrease in proliferation and an increase in apoptosis after prolonged exposure to metal eluates. Gene expression analysis showed different responses to oxidative stress over time, with an initial activation of antioxidant defenses followed by adaptations related to iron homeostasis. These results contribute to the understanding of the molecular mechanisms by which metal ions released from orthodontic materials affect oxidative stress and cell viability in yeast
The advantages of new generation antipsychotics in the treatment of psychotic disorders
No full textPsihotični poremećaji, osobito shizofrenija, predstavljaju kompleksna stanja koja zahtijevaju dugotrajno i individualizirano farmakološko liječenje. Unatoč širokoj dostupnosti antipsihotika prve, druge i treće generacije, terapijski odgovori često su ograničeni, osobito u liječenju negativnih i kognitivnih simptoma, dok nuspojave poput ekstrapiramidnih smetnji i metaboličkih poremećaja dodatno smanjuju suradljivost pacijenata. S ciljem poboljšanja učinkovitosti i sigurnosnog profila terapije, razvijene su nove molekule i inovativni oblici primjene antipsihotika koji ciljaju različite receptorske sustave izvan dopaminergičkog puta. U ovom radu analizirani su novi i eksperimentalni antipsihotici, uključujući KarXT (xanomelin/trospium), inhalacijski loksapin, transdermalni asenapin, brilaroksazin, emraklidin, ulotaront i pimavanserin. Prikazane su njihove farmakodinamske značajke, klinička učinkovitost, profil nuspojava te potencijalna uloga u suvremenoj psihofarmakoterapiji. Rad ističe važnost daljnjih istraživanja i personaliziranog pristupa u odabiru antipsihotične terapije.Psychotic disorders, particularly schizophrenia, are complex conditions that require long-term and individualized pharmacological treatment. Despite the availability of first, second, and third generation antipsychotics, therapeutic responses often remain limited, especially in addressing negative and cognitive symptoms. Additionally, adverse effects such as extrapyramidal symptoms and metabolic disturbances frequently reduce patient adherence. In an effort to enhance treatment efficacy and safety, new antipsychotic molecules and innovative drug delivery systems have been developed, many of which target non-dopaminergic receptor pathways. This paper provides an overview of recent and experimental antipsychotics, including KarXT (xanomeline/trospium), inhaled loxapine, transdermal asenapine, brilaroxazine, emraclidine, ulotaront, and pimavanserin. Their pharmacodynamic properties, clinical efficacy, side effect profiles, and potential roles in modern psychopharmacology are discussed. The paper highlights the importance of ongoing research and a personalized approach in optimizing antipsychotic treatment
Treatment approaches for patients with multiple sclerosis during pregnancy and breastfeeding
No full textMultipla skleroza (MS) autoimuna je neurodegenerativna bolest koja najčešće pogađa žene u reproduktivnoj dobi. Tradicionalno se trudnoća smatrala rizičnim razdobljem za žene s MS-om, no novija istraživanja pokazuju kako trudnoća u većini slučajeva ima povoljan učinak na tijek bolesti. Tijekom trudnoće dolazi do prirodne imunosupresije, što smanjuje rizik od relapsa. Nasuprot tome, postpartalno razdoblje karakterizira porast rizika od ponovnog aktiviranja bolesti.
Liječenje MS-a u trudnoći i tijekom dojenja izazov je zbog ograničenih podataka o sigurnosti lijekova koji modificiraju tijek bolesti (DMT). Lijekovi kao što su interferon beta i glatiramer acetat imaju najviše podataka o sigurnosti, dok se visoko učinkoviti lijekovi poput natalizumaba i anti-CD20 protutijela mogu koristiti u žena s agresivnijim oblicima bolesti uz oprez i individualiziran pristup.
Planiranje trudnoće kod žena s MS-om uključuje procjenu bolesti, prilagodbu terapije i pravovremenu edukaciju. Isključivo dojenje potencijalno smanjuje rizik od postpartalnih relapsa, iako su rezultati još uvijek nedovoljno jasni. Cilj ovog rada bio je prikazati trenutno dostupne spoznaje o liječenju žena s MS-om u trudnoći i dojenju te naglasiti važnost interdisciplinarne suradnje i potrebu za dodatnim istraživanjima u ovoj specifičnoj populaciji bolesnica.Multiple sclerosis (MS) is a chronic autoimmune disease that primarily affects women of reproductive age. While pregnancy was once discouraged in women with MS, current evidence suggests that pregnancy is generally safe and may even reduce disease activity due to natural immunosuppressive mechanisms. However, the postpartum period is associated with an increased risk of relapses. Managing MS during pregnancy and breastfeeding is complex due to limited safety data on disease-modifying therapies (DMTs). Interferon beta and glatiramer acetate have the most established safety profiles, while highly effective treatments such as natalizumab and anti-CD20 monoclonal antibodies may be considered for women with highly active disease, provided a case-by-case evaluation is done.
Family planning, preconception counseling, and timely treatment adjustments are essential to reduce risks for both mother and child. Exclusive breastfeeding may provide some protective effect against postpartum relapses, though further research is needed to confirm this association.
This thesis aimed to present current knowledge on MS treatment during pregnancy and lactation, emphasizing the importance of individualized care and the urgent need for more clinical research to inform treatment decisions in this population
Sacral neuromodulation
No full textSakralna neuromodulacija predstavlja modernu, minimalno invazivnu terapijsku metodu za liječenje funkcionalnih poremećaja mokraćnog i probavnog sustava, a pogotovo u bolesnika koji imaju slab terapijski odgovor na standardne oblike liječenja. Ova metoda funkcionira tako da se električnom stimulacijom sakralnih živaca, osobito korijene živaca S3, modulira neuralna komunikacija između leđne moždine i zdjeličnih organa. Iako točan mehanizam djelovanja još uvijek nije u potpunosti jasan, brojna istraživanja govore da ova metoda ima pozitivan učinak na motorni i senzorni odgovor zdjeličnih organa. Indikacije za ovu vrstu terapije jesu prekomjerno aktivan mokraćni mjehur, retencija urina bez mehaničkog uzroka, fekalna inkontinencija te kronični bolovi u zdjelici. Unatoč dokazanim kliničkim prednostima, primjena SNM u kliničkoj praksi je i dalje ograničena zbog visoke cijene samog zahvata, potrebe za dugoročnim praćenjem bolesnika nakon zahvata i varijabilnoj dostupnosti ove metode u zdravstvenim sustavima različitih zemalja. Upravo zato što mehanizam djelovanja nije potpuno poznat također utječe na ograničenu upotrebu ove metode. Potrebna su dodatna istraživanja kako bi se poboljšala selekcija bolesnika odnosno definirale indikacije, smanjili troškovi te omogućila veća dostupnost ove terapijske metode koja potencijalno mijenja i poboljšava kvalitetu života bolesnika.Sacral neuromodulation is a modern, minimally invasive therapeutic method for the treatment of functional disorders of the urinary and digestive systems, especially in patients who have a poor therapeutic response to standard forms of treatment. This method works by modulating neural communication between the spinal cord and pelvic organs by electrical stimulation of the sacral nerves, especially the S3 nerve roots. Although the exact mechanism of action is still not completely clear, numerous studies show that this method has a positive effect on the motor and sensory response of the pelvic organs. Indications for this type of therapy are overactive bladder, urinary retention without a mechanical cause, fecal incontinence and chronic pelvic pain. Despite proven clinical advantages, the application of SNM in clinical practice is still limited due to the high cost of the procedure itself, the need for long-term follow-up of patients after the procedure and the variable availability of this method in the healthcare systems of different countries. The fact that the mechanism of action is not fully understood also affects the limited use of this method. Additional research is needed in order to improve the selection of patients, i.e. to define the indications, reduce costs and enable greater availability of this therapeutic method, which potentially changes and improves the quality of life of patients
Improvement of Oxidative Stability and Antioxidative Capacity of Virgin Olive Oil by Flash Thermal Pretreatment—Optimization Process
No full textFlash thermal pretreatment (FTT) is a promising technique for enhancing virgin olive oil (VOO) quality. This study investigated the effects of FTT, both cooling (15–25 °C) and heating (30–40 °C), on phenolics, tocopherols, fatty acid composition, oxidative stability (OSI), antioxidant capacity (AC), and volatile composition in VOOs from three Croatian varieties: Istarska Bjelica, Levantinka, and Oblica. A full factorial experimental design was used with two independent variables: treatment temperature and olive variety. Olive pastes were treated after crushing and before malaxation. Data were evaluated using ANOVA, partial least squares (PLS) regression, and response surface methodology (RSM). Istarska Bjelica showed the highest OSI improvement (+16%) mostly linked to elevated phenolic compounds. Levantinka exhibited moderate responses, with slight OSI and AC declines. Oblica was most sensitive to heating, showing OSI and AC reductions (up to 28%), despite increased oleocanthal and olacein. RSM identified optimal FTT temperatures for each variety: 18.9 °C (Istarska Bjelica), 15.4 °C (Levantinka), and 15.5 °C (Oblica). These findings support variety-specific FTT as an effective strategy to improve VOO functional and sensory quality