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The potential to integrate Forest therapy and Forest bathing (Shinrin-Yoku) with Nature-based mindfulness into public health programs
The term 'Forest therapy' covers both preventive and therapeutic interventions in the forest. It is increasingly used for health promotive activities that are also referred to in the literature as "Forest bathing" (jap. “Shinrin-Yoku”), forest walks, and forest healing as well as for therapeutic purposes like nature therapy. It involves consciously engaging in slow, multi-sensory, immersive experiences in forests and other natural and semi-natural environments to achieve mental and physical health and well-being. There is a growing body of evidence-based research demonstrating the physiological and psychological effects of forests on health. Physiological effects can be seen in improvements in blood pressure, heart rate, cortisol levels, pain relief, stress reduction, respiratory function, and general well-being. It has been confirmed to have psychological effects on symptoms of depression, and anxiety, improving quality of life, mood, emotional and physical burnout, self-perception and acceptance, concentration, and improving cognitive function. Shinrin-Yoku leads to a deepening of the relationship between man and nature, and to the 'invisible' world. Mindfulness in and with nature, on the other hand, is a new setting that involves the ability to observe both one's perceptions and those of nature in an open and non-judgmental experience. Research has shown that mindfulness indoors reduces symptoms of depression and anxiety, significantly reduces overall stress, and improves quality of life. This type of intervention has been shown to help improve chronic physical conditions, including cardiovascular and malignant diseases. The European Society of Hypertension has recognized the benefits of mindfulness and included it as a supportive, i.e., non-pharmacological therapy in the treatment guidelines for arterial hypertension in 2023. In this paper, the researchers argue using both methods in a combined outdoor setting as a comprehensive approach to lay the foundations for social prescribing to support usual healthcare, to improve health outcomes
Automated Morphological Classification and Quantification of Cerebrospinal Fluid Extracellular Vesicles via AFM and Machine Learning
Size-exclusion chromatography, AFM, Gwyddion, western blot, dynamic light scattering, machine learnin
Refined tamoxifen administration in mice by encouraging voluntary consumption of palatable formulations
Drug administration in preclinical rodent models is essential for research and the development of novel therapies. Compassionate administration methods have been developed, but these are mostly incompatible with water-insoluble drugs such as tamoxifen or do not allow for precise timing or dosing of the drugs. For more than two decades, tamoxifen has been administered by oral gavage or injection to CreERT2–loxP gene-modified mouse models to spatiotemporally control gene expression, with the numbers of such inducible models steadily increasing in recent years. Animal-friendly procedures for accurately administering tamoxifen or other water-insoluble drugs would, therefore, have an important impact on animal welfare. On the basis of a previously published micropipette feeding protocol, we developed palatable formulations to encourage voluntary consumption of tamoxifen. We evaluated the acceptance of the new formulations by mice during training and treatment and assessed the efficacy of tamoxifen-mediated induction of CreERT2–loxP-dependent reporter genes. Both sweetened milk and syrup-based formulations encouraged mice to consume tamoxifen voluntarily, but only sweetened milk formulations were statistically noninferior to oral gavage or intraperitoneal injections in inducing CreERT2-mediated gene expression. Serum concentrations of tamoxifen metabolites, quantified using an in-house-developed cell assay, confirmed the lower efficacy of syrup- as compared to sweetened milk-based formulations. We found dosing with a micropipette to be more accurate than oral gavage or injection, with the added advantage that the method requires little training for the experimenter. The new palatable solutions encourage voluntary consumption of tamoxifen without loss of efficacy compared to oral gavage or injections and thus represent a refined administration metho
Differences in Subjective Transition Outcomes Between Transgender and Gender-Diverse Individuals Who Completed Mandatory Psychiatric Assessment and Those Who Received Gender-Affirmative Medical Treatment in Croatia: A Cross-Sectional Online Survey
The aim of this study was to evaluate diferent aspects of transition outcomes in groups of transgender and gender diverse
(TGD) people based on their transition status. We divided the 70 TGD participants (19 individuals assigned male at birth and
51 assigned female at birth) into two groups: those who had completed their psychiatric and psychological evaluation (PPE),
which is mandatory in Croatia, and those who had undergone gender-afrming medical treatment (GAMT) (both genderafrming hormone treatment and gender-afrming surgery). The online survey included sociodemographic questions and a
custom-designed nine-item scale. The items were specifcally designed based on the DSM-5-TR criteria for gender dysphoria to assess subjectively perceived transition outcomes. We conducted a factor analysis of the scale followed by structural
equation modeling for confrmation. Chi-squared and Mann–Whitney U tests were used to compare group diferences. The
following three-factor structure was confrmed: better functioning, reduced body dysphoria, and satisfaction with decision.
A positive infuence of better functioning on satisfaction with the decision was found. In addition, our results showed that
TGD individuals who had undergone GAMT scored higher on better functioning than those who had just completed PPE.
Both groups consistently scored high on satisfaction with the decision, with no statistically signifcant diferences between
them. Our fndings suggest that TGD individuals view gender-afrming medical care as benefcial to their overall functioning
CCR5 Δ32 and CTLA-4 +49 A/G Gene Polymorphisms and Interferon-β Treatment Response in Croatian and Slovenian Multiple Sclerosis Patients
The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-β treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and non-responders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-β therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-β treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients
The Re-Emergence of Neuroinvasive Flaviviruses in Croatia During the 2022 Transmission Season
(Re-)emerging arboviruses, such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), and Usutu virus (USUV), are continuously increasing in incidence. We analyzed the epidemiological characteristics of flavivirus infections in humans, sentinel animals, and mosquitoes detected in the 2022 transmission season in Croatia. From April to November 2022, 110 hospitalized patients with neuroinvasive diseases (NID) were tested for the presence of arboviruses. RT-qPCR was used to detect TBEV, WNV, and USUV RNA. An ELISA and virus neutralization tests were used for the detection of flavivirus antibodies. TBEV infection was confirmed in 22 patients with NID. WNV NID was detected in six patients. TBE showed male predominance (81.8%; male-to-female ratio of 4.5:1). All but one WNV patients were males. TBE occurred from April to August, with the majority of patients (83.3%) being detected during the May–June–July period. WNV infections were recorded in August and September. In addition to human cases, asymptomatic WNV infections (IgM positive) were reported in 10 horses. For the first time in Croatia, WNV NID was observed in one horse that presented with neurological symptoms. Furthermore, USUV was confirmed in one dead blackbird that presented with neurological symptoms. A total of 1984 mosquitoes were collected in the City of Zagreb. Two Ae. albopictus pools tested positive for flavivirus RNA: one collected in July (USUV) and the other collected in August (WNV). A phylogenetic analysis of detected human and avian strains confirmed WNV lineage 2 and the USUV Europe 2 lineage. The presented results confirm the endemic presence of neuroinvasive flaviviruses in continental Croatia. The continuous monitoring of virus circulation in humans, sentinel animals, and mosquitoes is needed to reduce the disease burden
Susceptibility of Mouse Brain to MCMV Infection and Neuroinflammation During Ontogeny
Human cytomegalovirus (HCMV) rarely infects the brain following infection of adult individuals. However, the virus readily infects the brain during congenital HCMV (cHCMV) infection, frequently causing severe neurodevelopmental and neurological sequelae. Interestingly, although the incidence of cHCMV infection is 0.5–1%, the proportion of congenitally infected individuals in which the virus manages to gain access to the brain is unknown. In this study, we used infection of mice with mouse cytomegalovirus (MCMV), the most commonly used experimental system for modeling HCMV disease in humans, to determine the impact of age on the susceptibility of the brain to cytomegalovirus infection and infection-mediated neuroinflammation. We demonstrate that infection of mice during various stages of neonatal development can lead to CMV neuroinvasion and inflammation. In contrast, MCMV infection does not result in MCMV neuroinvasion and neuroinflammation in weanling and adult mice. The obtained results establish a basis for elucidating the mechanisms of CMV neuroinvasion and the deleterious inflammatory response during ontogeny
Endothelial Dysfunction and Cardiovascular Disease: Hyperbaric Oxygen Therapy as an Emerging Therapeutic Modality?
Maintaining the physiological function of the vascular endothelium and endothelial glycocalyx is crucial for the prevention of cardiovascular disease, which is one of the leading causes of morbidity and mortality worldwide. Damage to these structures can lead to atherosclerosis, hypertension, and other cardiovascular problems, especially in individuals with risk factors such as diabetes and obesity. Endothelial dysfunction is associated with ischemic disease and has a negative impact on overall cardiovascular health. The aim of this review was to comprehensively summarize the crucial role of the vascular endothelium and glycocalyx in cardiovascular health and associated thrombo-inflammatory conditions. It highlights how endothelial dysfunction, influenced by factors such as diabetes, chronic kidney disease, and obesity, leads to adverse cardiovascular outcomes, including heart failure. Recent evidence suggests that hyperbaric oxygen therapy (HBOT) may offer therapeutic benefits in the treatment of cardiovascular risk factors and disease. This review presents the current evidence on the mechanisms by which HBOT promotes angiogenesis, shows antimicrobial and immunomodulatory effects, enhances antioxidant defenses, and stimulates stem cell activity. The latest findings on important topics will be presented, including the effects of HBOT on endothelial dysfunction, cardiac function, atherosclerosis, plaque stability, and endothelial integrity. In addition, the role of HBOT in alleviating cardiovascular risk factors such as hypertension, aging, obesity, and glucose metabolism regulation is discussed, along with its impact on inflammation in cardiovascular disease and its potential benefit in ischemia–reperfusion injury. While HBOT demonstrates significant therapeutic potential, the review also addresses potential risks associated with excessive oxidative stress and oxygen toxicity. By combining information on the molecular mechanisms of HBOT and its effects on the maintenance of vascular homeostasis, this review provides valuable insights into the development of innovative therapeutic strategies aimed at protecting and restoring endothelial function to prevent and treat cardiovascular diseases
Cathelicidin in Urinary Tract Diseases: Diagnostic, Prognostic and Therapeutic Potential of an Evolutionary Conserved Antimicrobial Protein
Despite being one of the most common infectious diseases, urinary tract infections (UTIs) still represent a challenge for clinicians to diagnose and treat, especially in the era of growing antibiotic resistance among uropathogenic bacteria. Recent studies investigating the pathophysiology of UTIs have discovered the prominent role of antimicrobial peptides in the urinary tract defense system. Cathelicidin is an evolutionary conserved antimicrobial peptide encoded by one single gene in humans. Except for being stored in neutrophil cytoplasmic granules, cathelicidin is produced by uroepithelial cells rapidly upon contact with a uropathogen, even before leukocytes invade the urinary tract. In addition to its bactericidal effect, cathelicidin acts as a chemoattractant for multiple immune cells and a potent inductor of numerous cytokine synthesis. Such a crucial role in the initial pathogenesis of a UTI makes cathelicidin a potential biomarker for an early UTI diagnosis. Indeed, multiple studies over the last two decades have proved the potential clinical utility of cathelicidin as a UTI diagnostic biomarker. Furthermore, since patients after the resolution of a UTI have been found to express a lower urinary cathelicidin level than healthy controls, decreased cathelicidin levels have been suggested as a risk factor for developing UTI recurrence. Therefore, measuring cathelicidin levels in urine might help in distinguishing patients with a higher risk for a recurrent UTI. Interestingly, except in UTIs, cathelicidin has also been evaluated in other urinary tract diseases and proposed as a biomarker for diagnosing severe vesicoureteral reflux (VUR) and for recognizing renal scar development in patients with VUR. Finally, a prominent role in UTI pathogenesis also makes cathelicidin an attractive therapeutic target for treating UTIs and, lately, different therapeutic agents up-regulating cathelicidin expression have been investigated in this matter. Therefore, the present review aims to summarize the current body of knowledge on the diagnostic, prognostic and therapeutic potential of cathelicidin in urinary tract diseases. For this purpose, three databases (Scopus, Medline and Web of Science) were extensively searched to cover all the published articles. This exhaustive review will update clinicians on the contemporary state of knowledge about the potential clinical utility of cathelicidin in urinary tract diseases and hopefully encourage further research, resulting in improvement in the current management of urinary tract diseases
The Importance of the Peer Review Process in Journals with a Lower Impact Factor
Recenzijski postupak nije samo administrativni korak u publikaciji znanstvenih i stručnih radova, već predstavlja temelj kvalitete i dugoročne održivosti znanstvene zajednice. Unatoč manjoj vidljivosti časopisa nižeg čimbenika odjeka na globalnoj razini, recenzijski postupak osigurava očuvanje visokih znanstvenih standarda te temeljitu provjeru ispravnosti i relevantnosti rukopisa. Recenzijski postupak ključan je u održavanju integriteta znanstvene komunikacije, posebno u časopisima koji se bore za prepoznatljivost u širem znanstvenom prostoru. Osim poboljšanja kvalitete istraživačkih radova, recenzijski postupak igra i ključnu ulogu u održavanju etičkih standarda unutar znanstvene zajednice. Časopisi s nižim čimbenikom odjeka često objavljuju radove koji se bave specifičnim temama ili regionalnim pitanjima koja su zanemarena u većim međunarodnim časopisima. U kontekstu hrvatskog jezika i lokalnog istraživačkog okruženja, ovaj proces omogućuje ne samo održavanje visoke razine znanstvene produkcije već i jačanje zajedništva među istraživačima, čime se pridonosi razvoju cijele znanstvene zajednice u Hrvatskoj. U maloj hrvatskoj znanstvenoj zajednici, gdje je broj istraživača i institucija često ograničen, kvalitetna recenzija može značajno utjecati na razvoj znanstvene komunikacije i reputaciju domaćih časopisa.The peer review process is not merely an administrative step in the publication of scientific and professional manuscripts; it is the foundation of quality and long-term sustainability within the scientific community. Despite the limited global visibility of journals with lower impact factors, the peer review process ensures the preservation of high scientific standards and a thorough examination of the accuracy and relevance of manuscripts. Peer review is essential for maintaining the integrity of scientific communication, particularly in journals striving for recognition in the broader scientific arena. Beyond enhancing the quality of research articles, peer review also plays a crucial role in upholding ethical standards within the scientific community. Journals with lower impact factors often publish works that address specific topics or regional issues overlooked by larger international journals. In the context of the Croatian language and the local research environment, this process not only maintains a high level of scientific output but also strengthens collaboration among researchers, thereby contributing to the development of the entire scientific community in Croatia. In Croatia’s small scientific community, where the number of researchers and institutions is often limited, high-quality peer review can significantly impact the advancement of scientific communication and the reputation of domestic journals