Vitamin D has been a focus of attention in liver cancer due to its direct and indirect antineoplastic effects. This review critically evaluates data from recently published basic and clinical studies investigating the role of vitamin D in liver cancer. Basic studies indicate that vitamin D plays an important role in liver cancer development by suppressing the activity of hepatic stellate cells and Kupffer cells. Furthermore, vitamin D has a direct anti-proliferative, anti-angiogenic, proapoptotic, and prodifferentiative effect on liver cancer cells. Recent investigation suggested several interesting mechanisms of these actions, such as inactivation of Notch signaling, p27 accumulation, and tyrosine-protein kinase Met/extracellular signal-regulated kinases inhibition. On the other hand, data from clinical observational studies, although promising, are still inconclusive. Unfortunately, studies on the effect of vitamin D supplementation were generally focused on short-term outcomes of chronic liver diseases (liver enzyme levels or elastographic finding); therefore, there are still no reliable data on the effect of vitamin D supplementation on liver cancer occurrence or survival.

BACKGROUND During the COVID-19 pandemic, a multitude of surveys have analyzed the impact virus spreading on the everyday medical practice, including neurosurgery. However, none have examined the perceptions of neurosurgeons towards the pandemic, their life changes, and the strategies they implemented to be able to deal with their patients in such a difficult time. METHODS From April 2021 to May 2021 a modified Delphi method was used to construct, pilot, and refine the questionnaire focused on the evolution of global neurosurgical practice during the pandemic. This survey was distributed among 1000 neurosurgeons; the responses were then collected and critically analyzed. RESULTS Outpatient department practices changed with a rapid rise in teleservices. 63.9% of respondents reported that they have changed their OT practices to emergency cases with occasional elective cases. 40.0% of respondents and 47.9% of their family members reported to have suffered from COVID-19. 56.2% of the respondents reported having felt depressed in the last 1 year. 40.9% of respondents reported having faced financial difficulties. 80.6% of the respondents found online webinars to be a good source of learning. 47.8% of respondents tried to improve their neurosurgical knowledge while 31.6% spent the extra time in research activities. CONLCUSIONS Progressive increase in operative waiting lists, preferential use of telemedicine, reduction in tendency to complete stoppage of physical clinic services and drop in the use of PPE kits were evident. Respondents' age had an impact on how the clinical services and operative practices have evolved. Financial concerns overshadow mental health.

Introduction: In Sweden, during specialty training, the nurse anesthetist learns how to ensure patient safety in a health-care setting by implementing the surgical checklist measures during perioperative care. To date, there are still considerable shortcomings when it comes to implementing these patient safety measures in Swedish hospitals. Aim: The purpose of this study is to describe the use of the WHO surgical safety checklist (WHOSSC) by surgical teams, with special emphasis on nurse anesthetists to increase patient safety. Materials and Methods: This descriptive questionnaire-based study was performed between September 2018 and March 2019 and included 196 health-care professionals who completed the questionnaire. The survey was carried out among all the health-care professionals at two surgical units at a university hospital during the data collection period. Results: The results reveal that the majority of health-care staff in this study agree with the need to implement the WHOSSC during surgery and the necessity of doing so to ensure patient safety. However, it is not clear whether this checklist needs to be made a matter of routine at the clinics and whether this is possible in emergency situations. Conclusion: The nurse anesthetists, as members of the surgical team, use the list all the time in emergency situations and conclude, like other members of the team, that the list improves patient safety. Clearer procedures are needed during surgery regarding the usage of the checklist in practice, and there should be a designated person in the surgical team responsible for implementing the checklist.

Objectives. The present study aimed to assess changes in the perception of and willingness to participate in organ donation (OD) among immigrants from Bosnia and Herzegovina living in Sweden from the perspective of gender differences. Materials and Methods. A cross-sectional study with 60 participants born in Bosnia and Herzegovina and living in Sweden was performed. Data were collected using a self-administrative questionnaire, providing demographic characteristics, information about opinions, awareness, and knowledge on the donation process and religious approach to the subject, willingness to donate/receive organs, and possession of a donor card. Results. Our results showed significant differences between genders regarding the definition of transplantation (P<0.0001), information about OD (P<0.0001), knowledge (P<0.0001) and importance of OD (P<0.003), religious permitting (P=0.0001), and religious opposing (P=0.0007) to OD. Furthermore, a significant difference was observed regarding the preferred recipient (P=0.0062) and the possession of the donor card (P<0.0001). Regression analysis showed that female gender and higher income were statistically significant in prediction of positive attitudes toward OD (P=0.0027, P=0.0002, respectively). Conclusion. Change of social background and integration into Swedish society undoubtedly led to change in the attitudes toward OD, regardless of the perspective of gender differences. However, women were found to have more positive attitudes toward OD.

In this study, the extraction efficiency of natural deep eutectic solvents (NADES) based on choline chloride as a hydrogen bond acceptor (HBA) and five different hydrogen bond donors (HBD; lactic acid, 1,4-butanediol, 1,2-propanediol, fructose and urea) was evaluated for the first time for the isolation of valuable bioactive compounds from Achillea millefolium L. The phytochemical profiles of NADES extracts obtained after ultrasound-assisted extraction were evaluated both spectrophotometrically (total phenolic content (TPC) and antioxidant assays) and chromatographically (UHPLC-MS and HPLC-UV). The results were compared with those obtained with 80% ethanol, 80% methanol, and water. The highest TPC value was found in the lactic acid-based NADES (ChCl-LA), which correlated with the highest antioxidant activity determined by the FRAP analysis. On the other hand, the highest antiradical potential against ABTS+• was determined for urea-based NADES. Phenolic acids (chlorogenic acid and dicaffeoylquinic acid isomers), flavones (luteolin and apigenin), and their corresponding glucosides were determined as the dominant individual phenolic compounds in all extracts. The antibacterial and antifungal properties of the extracts obtained against four bacterial cultures and two yeasts were evaluated using two methods: the agar dilution method to obtain the minimum inhibitory concentration (MIC) and the minimum bactericidal or fungicidal concentration (MBC or MFC), and the disc diffusion method. ChCl-LA had the lowest MIC and MBC/MFC with respect to all microorganisms, with an MIC ranging from 0.05 mg mL−1 to 0.8 mg mL−1, while the water extract had the weakest inhibitory activity with MIC and MBC/MFC higher than 3.2 mg mL−1.

There are activities in viticulture and mariculture that require extreme physical endurance from human workers, making them prime candidates for automation and robotization. This paper presents a novel, practical, heterogeneous, autonomous robotic system divided into two main parts, each dealing with respective scenarios in viticulture and mariculture. The robotic components and the subsystems that enable collaboration were developed as part of the ongoing HEKTOR project, and each specific scenario is presented. In viticulture, this includes vineyard surveillance, spraying and suckering with an all-terrain mobile manipulator (ATMM) and a lightweight autonomous aerial robot (LAAR) that can be used in very steep vineyards where other mechanization fails. In mariculture, scenarios include coordinated aerial and subsurface monitoring of fish net pens using the LAAR, an autonomous surface vehicle (ASV), and a remotely operated underwater vehicle (ROV). All robotic components communicate and coordinate their actions through the Robot Operating System (ROS). Field tests demonstrate the great capabilities of the HEKTOR system for the fully autonomous execution of very strenuous and hazardous work in viticulture and mariculture, while meeting the necessary conditions for the required quality and quantity of the work performed.

Cardiovascular diseases are the leading cause of death and the main cause of disability. In the last decade, homocysteine has been found to be a risk factor or a marker for cardiovascular diseases, including myocardial infarction (MI) and heart failure (HF). There are indications that vitamin B6 plays a significant role in the process of transsulfuration in homocysteine metabolism, specifically, in a part of the reaction in which homocysteine transfers a sulfhydryl group to serine to form α-ketobutyrate and cysteine. Therefore, an elevated homocysteine concentration (hyperhomocysteinemia) could be a consequence of vitamin B6 and/or folate deficiency. Hyperhomocysteinemia in turn could damage the endothelium and the blood vessel wall and induce worsening of atherosclerotic process, having a negative impact on the mechanisms underlying MI and HF, such as oxidative stress, inflammation, and altered function of gasotransmitters. Given the importance of the vitamin B6 in homocysteine metabolism, in this paper, we review its role in reducing oxidative stress and inflammation, influencing the functions of gasotransmitters, and improving vasodilatation and coronary flow in animal models of MI and HF.

Background: Endocrine disrupting air pollutants such as sulphur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), fine particle matter (PM2.5), and ozone (O3) can affect thyroid gland function on the level of synthesis, metabolism, and the action of its hormones. Objective: The aim of this study was to establish whether increased air pollution could contribute to an increased incidence of autoimmune thyroid diseases (AITD). Methods: A retrospective analysis was conducted of the medical records of 82000 patients at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. The target group of this study comprised a total of 174 patients from the Lukavac area. Daily data on concentrations of air pollutants were collected from the air quality monitoring station located in Lukavac. The study covered the period from 2015 to 2020. Results: The results of the monitoring confirmed the presence of air pollutants in concentrations above the permitted limits throughout the entire observed period. Concentrations of PM2.5, SO2, NO2, CO, and O3 were in the range of 1.90–431.40 μg/m3, 3.60-620.50 μg/m3, 3.40-66.20 μg/m3, 48.00-7002.00 μg/m3, and 0.70-89.40 μg/m3, with means of 64.08 μg/m3, 77.48 μg/m3, 22.57 μg/m3, 1657.15 μg/m3, and 31.49 μg/m3, respectively. During the six-year period, 174 cases of AITD were registered, of which 150 (86.21%) were women and 24 (13.79%) men. Hashimoto’s thyroiditis was found in 33 patients (18.97%), whilst 141 patients (81.03%) were diagnosed with atrophic thyroiditis. The highest total incidence of autoimmune thyroiditis was recorded in 2017, when it reached 99.49, 95% CI. Conclusion: The effects of chronic exposure to a mixture of air pollutants on the function of the thyroid gland are still not sufficiently well-known, but the numerical tendency towards a higher incidence of AITD in this study, albeit without statistical significance (p>0.05), still underlines the need for additional research.

Simple Summary Oral cavity is the most common site of head and neck cancer which is ranked as the eighth most common cancer worldwide. Oral cancer treatment is often associated with significant morbidity and is sometimes ineffective. These cancers, mainly due to tobacco and alcohol consumption, can develop from oral potentially malignant disorders, the most common of which is oral leukoplakia. Some of these oral potentially malignant disorders disappear, while others will transform to oral cancer. Patients may also develop cancer in the field of cancerization. Unfortunately, except for the surgical excision of lesions with dysplasia, there is no effective intervention to effectively prevent transformation or cancer development in the field of cancerization. Moreover, no standardized biomarker has been clearly identified as sufficient to predict malignant transformation. In this article, several experts discuss the main challenges in oral cancer prevention, in particular the need (i) to define new a new classification system integrating cellular and molecular features aiming (ii) at better identifying patients at high risk of malignant transformation, and (iii) at developing treatment strategies to prevent their malignant transformation of oral potentially malignant disorders. Abstract Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD. In this perspective paper, several experts discuss the main challenges in oral cancer prevention, in particular the need to (i) to define an OPMD classification system by integrating new pathological and molecular characteristics, aiming (ii) to better identify OPMD at high risk of malignant transformation, and (iii) to develop treatment strategies to eradicate OPMD or prevent malignant transformation.

We collected 1,671 Dermacentor reticulatus ticks from 17 locations in the Czech Republic, Slovakia, and Hungary. We found 47.9% overall prevalence of Rickettsia species in ticks over all locations. Sequence analysis confirmed that all tested samples belonged to R. raoultii, the causative agent of tick-borne lymphadenopathy.

Background Neuropathic pain (NP) is one of the most frequent spinal cord injury (SCI) complications. Pain, quality of life, and functionality are associated and can lead to pain catastrophization. Pharmacological management of patients with NP secondary to SCI is widely known and there is increasing evidence in the area. Nevertheless, nonpharmacological management is not fully elucidated since its efficacy is inconclusive. Objective We hypothesize that (1) hydrotherapy is effective in reducing NP secondary to SCI. Additionally, our secondary hypotheses are that (2) hydrotherapy decreases the catastrophization of NP, and that (3) hydrotherapy improves life quality and minimizes the degree of disability, when compared to physical therapy. Methods A sample of approximately 20 participants will be randomly assigned to either the intervention (hydrotherapy) or control group (standard physical therapy). Both interventions will be administered twice a week over a 9-week period (18 sessions in total). Primary outcomes are changes in neuropathic pain perception and pain catastrophization. Secondary outcomes are changes in disability and quality of life scores. They will be assessed at baseline and follow-up at 4 weeks after discharge. Validated Spanish language scales that will be used are the following: Numerical Pain Rating Scale, Pain Catastrophization, Health-related Quality of life, and the World Health Organization’s Disability Assessment Schedule 2.0. Generalized mixed linear models will be used for comparing baseline and postintervention means of each group and their differences, together with 95% CIs and P values. A P value of less than .05 will be considered significant. Results Recruitment began in April 2019, and we recruited the last participants by December 2019, with 10 individuals assigned to hydrotherapy and 8 to physical therapy (control). Results from this study will be disseminated via scientific publication, in ClinicalTrials.gov, and in national and international conferences in the latter half of 2022. Conclusions This trial will explore the effects of hydrotherapy on neuropathic pain, together with functionality and quality of life, in patients with SCI. Furthermore, this study aims to evaluate these therapeutic modalities, including perception variables, and mental processes, which may affect the clinical condition and rehabilitation outcomes in these patients. Hydrotherapy is likely to be a safe, efficient, and cost-effective alternative to the current standard of care for NP secondary to SCI, with comparable results between the two. Trial Registration ClinicalTrials.gov NCT04164810; https://clinicaltrials.gov/ct2/show/NCT04164810 International Registered Report Identifier (IRRID) DERR1-10.2196/37255

Aim To determine the predictive value of phosphorylated human epidermal growth factor receptor 2 (pHER2Y1248) status in breast cancer (BC) patients undergoing trastuzumab-based adjuvant therapy. Methods Immunohistochemical status of pHER2Y1248, EGFR/HER1, HER3, and HER4 was determined in 124 consecutive HER2-positive BC patients (median age [range] = 57 years [49.0-64.0]) treated at the University Hospital for Tumors, Zagreb, between 2008 and 2011. The median follow-up was 84 months (60.0-84.0). Prognostic factors of disease free survival (DFS) rate were evaluated with Kaplan-Meier/log-rank test and Cox regression analysis. Results pHER2Y1248, HER1, HER3, and HER4 were expressed in 66.1%, 9.7%, 70.2%, and 71.0% of patients, respectively. Disease progression (DP) was observed in 17.1% of pHER2Y1248-positive and 47.6% of pHER2Y1248-negative BCs (P = 0.001). Kaplan-Meier analysis showed a worse five-year DFS in pHER2Y1248-negative patients who were older than 60 years (P < 0.001) and had positive lymph node status (P < 0.001); tumor size >2.0 cm (P < 0.001); higher histological grade (P < 0.001); HER2E intrinsic subtype (P < 0.001), negative hormone receptors (P < 0.001); negative HER1 status (P < 0.001), positive HER3 (P = 0.002); and/or positive HER4 (P = 0.002) status. The only negative prognostic factor for five-year DFS in multivariate Cox regression analysis was pHER2Y1248-negative (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.8-7.2, P < 0.001) and lymph node-positive status (HR 3.6, 95% CI 1.3-9.8, P = 0.014). Conclusion pHER2Y1248 predicts sensitivity to trastuzumab and a better five-year DFS regardless of any other prognostic parameter. In HER2-positive BC patients. Non-phosphorylated HER2Y1248 is a strong predictor of trastuzumab resistance and a poor DFS.

The last several years have seen a strong growth of telerobotic technologies with promising implications for many areas of learning. HCI has contributed to these discussions, mainly with studies on user experiences and user interfaces of telepresence robots. However, only a few telerobot studies have addressed everyday use in real-world learning environments. In the post-COVID 19 world, sociotechnical uncertainties and unforeseen challenges to learning in hybrid learning environments constitute a unique frontier where robotic and immersive technologies can mediate learning experiences. The aim of this workshop is to set the stage for a new wave of HCI research that accounts for and begins to develop new insights, concepts, and methods for use of immersive and telerobotic technologies in real-world learning environments. Participants are invited to collaboratively define an HCI research agenda focused on robot-mediated learning in the wild, which will require examining end-user engagements and questioning underlying concepts regarding telerobots for learning.