Osteoporosis in the view of osteoimmunology: common feature underlined by different pathogenic mechanisms

Osteoporosis is a skeletal disorder characterized by low bone mineral density and microarchitectural changes with increased susceptibility to fractures, resulting in significant morbidity and mortality. Although it predominantly affects postmenopausal women, it is now well known that systemic bone loss is a common underlying feature of different metabolic, endocrine and inflammatory diseases. Investigations of osteoporosis as a complication of chronic inflammatory conditions revealed immune mechanisms behind the increased osteoclast bone resorption and impaired osteoblast bone formation. This concept was particularly emphasized after the research field of osteoimmunology emerged, focusing on the interaction between the immune system and bone. It is increasingly becoming evident that immune cells and mediators critically regulate osteoclast and osteoblast development, function and coupling activity. Among other mediators, receptor activator of nuclear factor-kB ligand (RANKL), receptor activator of nuclear factor-kB (RANK) and soluble decoy receptor osteoprotegerin (OPG) form a key functional link between the immune system and bone, regulating both osteoclast formation and activity as well as immune cell functions. Excessive production of inflammatory mediators exerts autocrine, paracrine and endocrine signaling effects on bone remodeling with the net increase in bone resorption locally, in diseases primarily affecting joints, bones or surrounding tissues, and systemically, causing osteoporosis in various chronic inflammatory diseases. This brief review particularly focuses on bone pathology in rheumatoid arthritis, as one of the most extensively studied conditions accompanied by local and systemic inflammation-induced bone loss

Association between CXCL9/10 polymorphisms and acute rejection of liver allograft

While increased serum concentrations of CXCL9/10 are associated with acute cellular rejection (ACR) occurrence, the association between CXCL9/10 single nucleotide polymorphisms (SNPs) and ACR after liver transplantation (LT) remains unknown. In the present case-control study, polymorphisms of CXCL9 (rs10336) and CXCL10 (rs3921) were determined by polymerase chain reaction in 215 liver transplant recipients. ACR was defined as biopsy proven within 6 months after LT. As selected SNPs were in 3'-UTR region, their possible association with protein synthesis was assessed by measuring the plasma concentration of CXCL9/10 in a cohort of 40 new transplant patients using ELISA. There was no association between CXCL9/10 genotypes and overall incidence of ACR. However, patients with CXCL9 genotype AA developed ACR earlier than patients with GG genotype (P = .003), with similar results for CXCL10 gene (CC vs GG; P = .005). There was no statistically significant difference in plasma concentrations of CXCL9/10 between the rejectors and the non-rejectors. Of note, patients with AA CXCL9 genotype had significantly higher CXCL9 plasma concentrations than patients with AG (P = .01) or GG genotype (P = .045).In conclusion, the SNPs of CXCL9 (rs10336) and CXCL10 (rs3921) are not associated with the incidence of ACR. However, patients with CXCL9 genotype AA developed ACR earlier and the same genotype was associated with greater plasma concentrations suggesting the involvement of CXCL9 mediated processes in ACR development

Knowledge, Attitudes and Behaviours Of Mostar University Students on the harmful effects of ultraviolet radiation exposure - A KAB study

Various reports suggest that adolescents seem to be obsessed with tanning. Existing evidence on attitudes demonstrate that young adults focus on improving appearance through a tan, with protective behaviors often being absent. The popularity of tanning, primarily among the young adult population, further promotes unsafe sun-related behaviors. The aim of this study was to determine the knowledge level of Mostar University students on the harmful effects of ultraviolet radiation (UVR), their attitudes and sun-related behaviors, and whether medical students are more likely to apply preventive measures against UVR in comparison with students from other faculties. The survey included a total of 140 undergraduate Mostar University students: 70 medical students and 70 non-healthcare-related faculty students. The data were collected by completing the personal design questionnaire created for this study. This study shows that Mostar University students have a high level of knowledge about UVR and skin cancer, but their behavior is not sufficiently preventive and appropriate to their knowledge. Medical students often use UV protection measures and employ more preventive behavior than that of other faculty students, but it is still at a low level of prevention. Findings concurred with existing evidence that the knowledge of associated risks from UVR was not sufficient to motivate safer sun-related practices. </p

FER garden data visualization on devices with iOS operating system

Sustavi interneta stvari mijenjaju našu svakodnevicu. Visoka razina umreženosti, brz prijenos podataka, precizno obrađivanje i ciljano grupiranje tih podataka samo su neki od razloga zašto Internet stvari postaje izrazito popularan. Tome doprinosi i činjenica da ga je moguće integrirati u brojna područja, od auto, građevinske, sportske pa do poljoprivredne industrije. Dodatnu vrijednost koju u njemu pronalazimo jest da ga je moguće pružiti na korištenje gotovo svima jer je krajnjem korisniku potreban samo funkcionalan mobilni uređaj. U ovom radu analiziran je Ekosustav umreženih uređaja i usluga za Internet stvari s primjenom u poljoprivredi za koji je izrađena mobilna iOS aplikacija po visokim standardima trenutne prakse. Omogućen je rad aplikacije u trenutcima kada korisnik nema internet, visoka razina sigurnosti pomoću napredne autorizacije i to je uz ostala unaprjeđenja izvedeno koristeći funkcijsko reaktivnu paradigmu.Internet of Things systems are changing our daily lives. High levels of connectability, fast data transfer, accurate processing and targeted grouping of data are just a few of the reasons why Internet of Things is becoming extremely popular. The fact that it can be integrated into so many areas, from the automotive, construction, sports to the agricultural industry, also contributes to its popularity. The additional value we find in it is that it can be provided for use by almost everyone because the end user only needs a functional mobile device. This paper analyses Ecosystem of networked devices and services for the Internet of Things with application in agriculture for which an iOS mobile app was developed according to the highest standards of current practice. The operation of the application is enabled in moments when the user does not have the Internet, a high level of security with advanced authorization and this, along with other improvements, is made using a functional reactive paradigm

FER garden data visualization on devices with iOS operating system

Sustavi interneta stvari mijenjaju našu svakodnevicu. Visoka razina umreženosti, brz prijenos podataka, precizno obrađivanje i ciljano grupiranje tih podataka samo su neki od razloga zašto Internet stvari postaje izrazito popularan. Tome doprinosi i činjenica da ga je moguće integrirati u brojna područja, od auto, građevinske, sportske pa do poljoprivredne industrije. Dodatnu vrijednost koju u njemu pronalazimo jest da ga je moguće pružiti na korištenje gotovo svima jer je krajnjem korisniku potreban samo funkcionalan mobilni uređaj. U ovom radu analiziran je Ekosustav umreženih uređaja i usluga za Internet stvari s primjenom u poljoprivredi za koji je izrađena mobilna iOS aplikacija po visokim standardima trenutne prakse. Omogućen je rad aplikacije u trenutcima kada korisnik nema internet, visoka razina sigurnosti pomoću napredne autorizacije i to je uz ostala unaprjeđenja izvedeno koristeći funkcijsko reaktivnu paradigmu.Internet of Things systems are changing our daily lives. High levels of connectability, fast data transfer, accurate processing and targeted grouping of data are just a few of the reasons why Internet of Things is becoming extremely popular. The fact that it can be integrated into so many areas, from the automotive, construction, sports to the agricultural industry, also contributes to its popularity. The additional value we find in it is that it can be provided for use by almost everyone because the end user only needs a functional mobile device. This paper analyses Ecosystem of networked devices and services for the Internet of Things with application in agriculture for which an iOS mobile app was developed according to the highest standards of current practice. The operation of the application is enabled in moments when the user does not have the Internet, a high level of security with advanced authorization and this, along with other improvements, is made using a functional reactive paradigm

Vitamin D in liver cancer: novel insights and future perspectives

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

Importance of genetic polymorphisms in liver transplantation outcomes

Although, liver transplantation serves as the only curative treatment for patients with end-stage liver diseases, it is burdened with complications, which affect survival rates. In addition to clinical risk factors, contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes. Determination of single nucleotide polymorphisms (SNPs) is one of the most important tools in development of personalized transplant approach. To provide a better insight in recent developments, we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation: Acute cellular rejection, development of new-onset diabetes mellitus and non-alcoholic fatty liver disease, hepatocellular carcinoma recurrence, and tacrolimus concentration variability. Reviewed studies confirmed previously established SNP prognostic factors, such as PNPLA3 rs738409 for non-alcoholic fatty liver disease development, or the role of CYP3A5 rs776746 in tacrolimus concentration variability. They also identified several novel SNPs, with a reasonably strong association, which have the potential to become useful predictors of post-transplant complications. However, as the studies were typically conducted in one centre on relatively low-to-moderate number of patients, verification of the results in other centers is warranted to resolve these limitations. Furthermore, of 29 reviewed studies, 28 used gene candidate approach and only one implemented a genome wide association approach. Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine

Diagnostic and Practical Value of Abbreviated Contrast Enhanced Magnetic Resonance Imaging in Breast Cancer Diagnostics

Background: Although MRI is the most efficient method of detecting breast cancer, its standard protocol is time-consuming and expensive. The objective of this study was to compare the diagnostic accuracy of the modified innovative abbreviated MRI protocol (AMRP) and the standard magnetic resonance protocol (SMRP) when detecting breast cancer. Methods: The research involved 477 patients referred for breast MRI due to suspected lesions. They were randomly assigned to the AMRP group (N = 232) or the SMRP group (N = 245). The AMRP comprised one native (contrast-free) and four post-contrast dynamic sequences of T1-weighted volume imaging for breast assessment (VIBRANT) and 3d MIP (maximum intensity projection) lasting for eight minutes. All the patients underwent a core biopsy of their lesions and histopathological analysis. Results: The groups were comparable regarding the pre-screening and post-diagnostic characteristics and were of average (±SD) age at breast cancer diagnosis of 53.6 ± 12.7 years. There was no significant difference between the two protocols in terms of specificity or sensitivity of breast cancer diagnosis. The sensitivity (95% Cis) of the AMRP was 99.05% (96.6–99.9%), and its specificity was 59.09% (36.4–79.3%), whereas the sensitivity of the SMRP was 98.12% (95.3–99.5%) and its specificity was 68.75% (50.0–83.9%). Most of the tumors comprised one solid lesion in one of the breasts (77.3%), followed by multicentric tumors (16%), bilateral tumors (4.3%), and multifocal tumors (1.7%). The average size of tumors was approximately 14 mm (ranging from 3 mm to 72 mm). Conclusion: Our innovative AMR protocol showed comparable specificity and sensitivity for the diagnosis of breast cancer when compared to SMRP, which is the “gold standard” for histopathological diagnosis. This can lead to great savings in terms of the time and cost of imaging and interpretation

NOTCH3 rs1043996 Polymorphism Is Associated with the Occurrence of Alcoholic Liver Cirrhosis Independently of PNPLA3 and TM6SF2 Polymorphisms

Alcoholic liver cirrhosis (ALC) is the most common indication for liver transplantation (LT) in Croatia and presents a risk factor for the development of hepatocellular carcinoma (HCC). However, genetic susceptibility has not yet been systematically studied. We aimed to investigate the contribution of the risk polymorphisms PNPLA3 rs738409, EGF rs4444903, TM6SF2 rs58542926, MTHFR rs1801133, previously identified in other populations and, additionally, the contribution of Notch-related polymorphisms (NOTCH1 rs3124591, NOTCH3 rs1043996 and rs1044116, NOTCH4 rs422951). The study included 401 patients. The ALC group consisted of 260 LT candidates, 128 of whom had histopathologically confirmed HCC, and 132 of whom were without HCC. The control group included 141 patients without liver disease. Genotyping was performed by PCR using Taqman assays. The patients’ susceptibility to ALC was significantly associated with PNPLA3 rs738409, TM6SF2 rs58542926, and NOTCH3 rs1043996 polymorphisms. These polymorphisms remained significantly associated with ALC occurrence in a logistic regression model, even after additional model adjustment for sex and age. Cirrhotic patients with the PNPLA3 GG genotype demonstrated higher activity of ALT aminotransferases than patients with CC or CG genotypes. The susceptibility to the development of HCC in ALC was significantly associated with PNPLA3 rs738409 and EGF rs4444903 polymorphisms, and logistic regression confirmed these polymorphisms as independent predictors

LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib

Recent studies have established a concept of tumour necrosis factor-α (TNF-α)/Fas signalling crosstalk, highlighting TNF-α as a critical cytokine in sensitizing hepatocytes to death induced by Fas activation. However, in the exact inflammatory response, besides TNF-α, many other mediators, that might modulate apoptotic response differentially, are released. To resolve the issue, we studied the effects of lipopolysaccharide (LPS), one of the crucial inductors of inflammation in the liver, on apoptotic outcome. We show that LPS-induced inflammation diminishes the sensitivity of hepatocytes to Fas stimulus in vivo at caspase-8 level. Analysis of molecular mechanisms revealed an increased expression of various pro-inflammatory cytokines in non-parenchymal liver cells and hepatocyte-specific increase in Bcl-xL, associated with signal transducer and activator of transcription 3 (Stat3) phosphorylation. Pre-treatment with ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, prevented the LPS-induced Stat3 phosphorylation and restored the sensitivity of hepatocytes to Fas-mediated apoptosis. Furthermore, ruxolitinib pre-treatment diminished the LPS-induced Bcl-xL up-regulation without an inhibitory effect on LPS-induced expression of pro-inflammatory cytokines. In summary, although the reports are showing that the effects of isolated pro-inflammatory mediators, such as TNF-α or neutrophils, are pro-apoptotic, the overall effect of inflammatory milieu on hepatocytes in vivo is Stat3-dependent desensitization to Fas-mediated apoptosis