The Impact of Vitamin Deficiencies on Oral Manifestations in Children.

Vitamins play a vital role in human health, particularly in the development and maintenance of oral health in children. These nutrients are broadly categorized into fat-soluble and water-soluble types, crucial for children's well-being. The objective of this study is to investigate the impact of vitamin deficiencies on the oral health of children, focusing on how these deficiencies contribute to various oral health issues and determining the relationship between specific vitamin shortages and oral diseases. Findings indicate that shortages in vitamins A and D lead to enamel issues and a higher susceptibility to dental diseases, vitamin E assists in treating oral mucositis, and vitamin K is essential for blood clotting in dental surgeries. Deficits in B-complex and vitamin C result in enamel hypomineralization and soft tissue ailments, including aphthous stomatitis and gingival petechiae. Additionally, a lack of vitamin B7 compromises the immune response, increasing oral candidiasis risk. Therefore, vitamin deficiencies markedly affect children's oral health, highlighting the need for joint efforts between dental professionals and caregivers for effective pediatric care. Addressing vitamin deficiencies through supplementation and tailored dental care emphasizes the significance of nutritional health in children's overall and dental well-being, advocating for a collaborative approach to achieve optimal health outcomes.

Changes in Dickkopf-1, but Not Sclerostin, in Gingival Crevicular Fluid Are Associated with Peroral Statin Treatment in Patients with Periodontitis.

Background and Objectives: Periodontitis is marked by the destruction of alveolar bone. Sclerostin (SOST) and dickkopf-1 (DKK-1) act as inhibitors of the Wingless-type (Wnt) signaling pathway, a key regulator of bone metabolism. Recent studies have suggested that statins play a role in bone resorption and formation by influencing Wnt signaling. The aim of this study was to determine the levels of SOST and DKK-1 in periodontal patients with and without peroral statins treatment in their therapy. Materials and Methods: A total of 79 patients with diagnosed periodontitis were divided into two groups: 39 patients on statin therapy (SP group) and 40 patients without statin therapy as a control group (P group). The periodontal clinical examination probing (pocket) depth (PD) and gingival recession (GR) were measured, and approximal plaque was detected, while vertical and horizontal bone resorption was measured using a panoramic radiograph image. Clinical attachment loss (CAL) values were calculated using PD and GR values. Gingival crevicular fluid (GCF) was collected and used for measuring SOST and DKK-1 levels. A questionnaire was used to assess lifestyle habits and statin intake. Patients' medical records were used to obtain biochemical parameters. Results: There was no significant difference in sclerostin concentration between the SP and P group. DKK-1 values were significantly higher in the SP group compared to the control group (p = 0.04). Also, PD (p = 0.001) and GR (p = 0.03) were significantly higher in the SP group. The level of DKK-1 had a positive relationship with the PD, the greater the PD, the higher the level of DKK-1 (Rho = 0.350), while there was no significant association with other parameters. Conclusions: Peroral statins in periodontal patients are associated with GCF levels of DKK-1 but not with sclerostin levels.

Regeneration of Buccal Wall Defects after Tooth Extraction with Biphasic Calcium Phosphate in Injectable Form vs. Bovine Xenograft: A Randomized Controlled Clinical Trial.

Bone healing after tooth extraction may be affected by defects of the alveolus buccal wall, such as fenestrations and dehiscences. Therefore, to minimize dimensional changes it is advisable to perform alveolar ridge preservation after tooth extractions. Different biomaterials are used for this purpose. The aim of this study was to investigate the qualitative and quantitative histological changes in human biopsies taken after 6 months of healing of extraction sockets with buccal wall defects. For this purpose, the defects of 36 patients (18 per group) were treated with injectable biphasic calcium phosphate (I-BCP) or bovine xenograft (BX) after extraction. After six months of healing, biopsies were taken and proceeded to the histology laboratory. No evidence of an inflammatory response of the tissue was observed in the biopsies of either group, and the newly formed bone (NB) was in close contact with the remaining biomaterial (BM). The histomorphometric results showed that there was no statistically significant difference between the groups in the mean percentage of NB (p = 0.854), BM (p = 0.129), and soft tissue (p = 0.094). To conclude, both biomaterials exhibited osteoconductivity and biocompatibility and achieved satisfactory bone regeneration of buccal wall defects after tooth extraction.

The Correlation of Serum Calpain 1 Activity and Concentrations of Interleukin 33 in COVID-19 Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is one of the most severe complications of the COVID-19 disease. The role of IL-33 and calpain 1 was previously described in lung infections and lung tissue damage. Our study examined the association between serum calpain 1 activity and IL-33 concentration in patients with COVID-19 ARDS. In the research, we included 80 subjects who had COVID-19 pneumonia and divided them into 2 groups: 40 subjects with ARDS and 40 subjects without ARDS. The basis of the research was the collection of subjects' data and the sampling of peripheral venous blood. The concentration of IL-33 was determined by the ELISA method and the activity of calpain 1 by the fluorometry method. Our research showed elevated calpain 1 activity and IL-33 concentration in the serum of COVID-19 patients who developed ARDS compared to those who did not develop ARDS and a positive correlation between them was established. Further, a positive correlation was established between the examined parameters and the severity of the disease, proinflammatory markers, and the use of mechanical ventilation. These results indicate a possible association and role of calpain 1 and IL-33 with the development of ARDS in COVID-19 patients.

Preclinical Models and Promising Pharmacotherapeutic Strategies in Liver Fibrosis: An Update.

Liver fibrosis represents one of the greatest challenges in medicine. The fact that it develops with the progression of numerous diseases with high prevalence (NAFLD, viral hepatitis, etc.) makes liver fibrosis an even greater global health problem. Accordingly, it has received much attention from numerous researchers who have developed various in vitro and in vivo models to better understand the mechanisms underlying fibrosis development. All these efforts led to the discovery of numerous agents with antifibrotic properties, with hepatic stellate cells and the extracellular matrix at the center of these pharmacotherapeutic strategies. This review focuses on the current data on numerous in vivo and in vitro models of liver fibrosis and on various pharmacotherapeutic targets in the treatment of liver fibrosis.

(Dis)Agreement with Dysthanasia, Religiosity and Spiritual Experience as Factors Related to Nurses' Workload during End-of-Life Care.

This study intended to investigate whether the workload of nurses in the course of providing end-of-life care correlated with their religiousness, spiritual experience and level of agreement with dysthanasia procedures. The respondents included 279 nurses from four Croatian hospitals. A structured and validated instrument was applied. Almost 90% of respondents are religious, and almost 45% of them have daily spiritual experiences. Respondents, especially those with high levels of religiousness and spiritual experience, express a low level of agreement with dysthanasia (mean = 58.21; score = 25−125). Moreover, nurses self-rated (on a scale of 1−5) their workload as quite high, especially when performing contradictory tasks imposed on them by their superiors (mean = 3.05) and during direct contact with dying patients and their family members (mean = 2.56). This significantly highest level of workload was experienced by the youngest nurses (p = 0.01) and nurses with little work experience (p < 0.01). This study also indicated that nurses who agree with dysthanasia experienced a higher level of workload when providing end-of-life care (r = 0.178; p < 0.01), while more frequent spiritual experiences reduced the level of workload (r = −0.205; p < 0.01). A deeper understanding of nurses' attitudes toward dysthanasia, as well as of their religiousness and spiritual experiences, may ensure the collection of data beneficial to the timely identification of potential risks caused by workload.

HIPPOCAMPAL GANGLIOSIDE COMPOSITION IS ALTERED BY METFORMIN AND LIRAGLUTIDE TREATMENT IN A HIGH-FAT HIGH-SUGAR DIET RAT MODEL.

Insulin resistance has many deleterious effects on the central nervous system, including the initiation and potentiation of neurodegeneration. While the pathogenesis of Alzheimer's disease has been extensively researched with many insights into the effects of amyloids and neurofibrillary tangles, the connection between the two pathogenic entities has not yet been fully elucidated. Gangliosides are commonly found in neuronal membranes and myelin, specifically in lipid rafts that have been linked to pathological amyloidogenesis. In this study, 64 Sprague Dawley rats with equal sex distribution were separated into four sex-specific groups, as follows: control group on standard diet; group on high-fat, high-sugar diet (HFHSD); group on HFHSD treated with metformin; and group on HFHSD treated with liraglutide. Free-floating immunohistochemistry of the rat hippocampi was performed to analyze group-specific and sex-specific changes in the composition of the four most common gangliosides found in neuronal membranes and myelin sheaths, GM1, GD1a, GD1b and GT1b. The groups on HFHSD showed glucose tolerance impairment and body weight increase at the end of the experiment, whereas the groups treated with pharmacotherapeutics had better insulin sensitivity and decreases in body weight by the end of the experiment. Most changes were observed for GM1 and GD1b. Positive immunoreactivity for GM1 was observed in the male group treated with liraglutide in regions where it is not physiologically found. The changes observed following HFHSD and liraglutide treatment were suggestive of ganglioside restructuring that might have implications on pathological amyloidogenesis. Metformin treatment did not significantly alter the hippocampal ganglioside composition in either sex.

CHRONIC MEDICAL CONDITIONS IN CROATIAN WAR VETERANS COMPARED TO THE GENERAL POPULATION: 25 YEARS AFTER THE WAR.

Many published reports have documented an increased prevalence of chronic medical conditions among veterans, but there were only a few studies that compared these increases with the general population. The aim of this study was to determine differences in chronic medical conditions between Croatian war veterans and the general population. This study included two groups of subjects, i.e. 1453 participants who are Croatian war veterans and 1429 participants from the general population. Medical history, physical examination, laboratory tests and specific diagnostic procedures were taken during systematic physical examination in both groups. The prevalence of hypertension, diabetes, hyperlipidemia, hypothyroidism and hyperthyroidism, chronic obstructive pulmonary disease, coronary heart disease, malignancy, psychiatric diseases, cholelithiasis, nephrolithiasis, smoking and alcohol consumption was analyzed. Croatian war veterans were found to be more likely to develop hypertension than individuals in the general population (29.5% vs. 24.3%), as well as diabetes (7.3% vs. 3.8%), hyperlipidemia (56.4% vs. 27.3%), hyperthyroidism (3.1% vs. 0.8%), coronary heart disease (4.3% vs. 1%), malignancy (4.1% vs. 2.2%), psychiatric diseases (15.4% vs. 1.1%), and alcohol consumption (53% vs. 29%). Significant difference was found in favor of the general population for hypothyroidism (14.3% vs. 8%). There were no differences in the prevalence of chronic obstructive pulmonary disease, cholelithiasis, nephrolithiasis, and smoking. Our findings confirmed the hypothesis of a higher prevalence of cardiovascular diseases, malignancy and psychiatric diseases among Croatian war veterans and emphasized the need of better control of their medical conditions.

Homeostasis and Dysbiosis of the Intestinal Microbiota: Comparing Hallmarks of a Healthy State with Changes in Inflammatory Bowel Disease.

The gut microbiota, which represent a community of different microorganisms in the human intestinal tract, are crucial to preserving human health by participating in various physiological functions and acting as a metabolic organ. In physiological conditions, microbiota-host partnership exerts homeostatic stability; however, changes in intestinal microbiota composition (dysbiosis) are an important factor in the pathogenesis of inflammatory bowel disease and its two main disease entities: ulcerative colitis and Crohn's disease. The incidence and prevalence of these inflammatory conditions have increased rapidly in the last decade, becoming a significant problem for the healthcare system and a true challenge in finding novel therapeutic solutions. The issue is that, despite numerous studies, the etiopathogenesis of inflammatory bowel disease is not completely clear. Based on current knowledge, chronic intestinal inflammation occurs due to altered intestinal microbiota and environmental factors, as well as a complex interplay between the genetic predisposition of the host and an inappropriate innate and acquired immune response. It is important to note that the development of biological and immunomodulatory therapy has led to significant progress in treating inflammatory bowel disease. Certain lifestyle changes and novel approaches-including fecal microbiota transplantation and nutritional supplementation with probiotics, prebiotics, and synbiotics-have offered solutions for dysbiosis management and paved the way towards restoring a healthy microbiome, with only minimal long-term unfavorable effects.

Glycosylation Alterations in Cancer Cells, Prognostic Value of Glycan Biomarkers and Their Potential as Novel Therapeutic Targets in Breast Cancer.

Although we are lately witnessing major improvements in breast cancer treatment and patient outcomes, there is still a significant proportion of patients not receiving efficient therapy. More precisely, patients with triple-negative breast cancer or any type of metastatic disease. Currently available prognostic and therapeutic biomarkers are not always applicable and oftentimes lack precision. The science of glycans is a relatively new scientific approach to better characterize malignant transformation and tumor progression. In this review, we summarize the most important information about glycosylation characteristics in breast cancer cells and how different glycoproteins and enzymes involved in glycosylation could serve as more precise biomarkers, as well as new therapeutic targets.

THE HISTORY OF DENTAL MEDICINE IN OSIJEK.

Throughout history, Osijek and Slavonia were parts of numerous empires and states. In this paper, the authors depict dental health care of the inhabitants of Osijek and Slavonia throughout their history, since the ancient prehistoric times when dental medicine and medicine in general were 'in the hands' of gods and medicine men, throughout the period of the Roman Empire and Middle Ages, as well as the Turkish sovereignty, all the way to the modern era when Osijek and Slavonia became part of the Austrian Empire and many novelties were introduced in the society, among other things, and for those times, modern procedures of medicine and dental protection. Those were the true beginnings of medicine and dental protection. The authors illustrate the work of various 'dentists' who worked in Osijek, from military and town surgeons, barbers, and especially the work of doctors that needed to have formal school and specialist education after the reforms implemented in the 19th century. Thanks to the reforms of the Austrian, and later the Austrian-Hungarian authorities, the practice and work of people who were allowed to perform dental procedures started being regulated, prices were established, and punishments introduced for those who performed dental procedures without having the proper qualifications.

Molecular Mechanisms Linking Empagliflozin to Renal Protection in the LLC-PK1 Model of Diabetic Nephropathy.

Aims: Chronic diabetes complications, including diabetic nephropathy (DN), frequently result in end-stage renal failure. This study investigated empagliflozin (SGLT2i) effects on collagen synthesis, oxidative stress, cell survival, and protein expression in an LLC-PK1 model of DN. Methods: Combinations of high glucose (HG) and increasing empagliflozin concentrations (100 nM and 500 nM), as well as combinations of HG, H2O2, and empagliflozin, were used for cell culture treatment. The cell viability, glutathione (tGSH), ECM expression, and TGF-ß1 concentration were measured. In addition, the protein expression of Akt, pAkt, GSK3, pGSK3, pSTAT3, and SMAD7 was determined. Results: The addition of both concentrations of empagliflozin to cells previously exposed to glucose and oxidative stress generally improved cell viability and increased GSH levels (p < 0.001, p < 0.05). In HG30/H2O2/Empa500-treated cells, significant increase in pSTAT3, pGSK3ß, GSK3ß, SMAD7, and pAKT levels (p < 0.001, p < 0.001, p < 0.05) was observed except for AKT. Lower drug concentrations did not affect the protein expression levels. Furthermore, empagliflozin treatment (100 nM and 500 nM) of HG30/H2O2-injured cells led to a decrease in TGF-ß1 levels (p < 0.001). In cells exposed to oxidative stress and hyperglycemia, collagen production remained unchanged. Conclusion: Renoprotective effects of empagliflozin, in this LLC-PK1 cell model of DN, are mediated via activation of the Akt/GSK-3 signalling pathway, thus reducing oxidative stress-induced damage, as well as enhanced SMAD7 expression leading to downregulation of TGF-ß1, one of the key mediators of inflammation and fibrosis.

Liraglutide Exerts Protective Effects by Downregulation of PPARγ, ACSL1 and SREBP-1c in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis.

(1) Background: With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The aim of our study was to study cell culture models of NAS and DIS and determine the effects of liraglutide (LIRA) in those models. (2) Methods: Huh7 cells were treated with oleic acid (OA), or amiodarone (AMD) to establish models of NAS and DIS, respectively. Cells were treated with LIRA and cell viability was assessed by MTT, lipid accumulation by Oil-Red-O staining and triglyceride assay, and intracellular signals involved in hepatosteatosis were quantitated by RT-PCR. (3) Results: After exposure to various OA and AMD concentrations, those that achieved 80% of cells viabilities were used in further experiments to establish NAS and DIS models using 0.5 mM OA and 20 µM AMD, respectively. In both models, LIRA increased cell viability (p < 0.01). Lipid accumulation was increased in both models, with microsteatotic pattern in DIS, and macrosteatotic pattern in NAS which corresponds to greater triglyceride accumulation in latter. LIRA ameliorated these changes (p < 0.001), and downregulated expression of lipogenic ACSL1, PPARγ, and SREBP-1c pathways in the liver (p < 0.01) (4) Conclusions: LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS.

The role of direct oral anticoagulants in the era of COVID-19: are antiviral therapy and pharmacogenetics limiting factors?

In patients with COVID-19, thromboinflammation is one of the main causes of morbidity and mortality, which makes anticoagulation an integral part of treatment. However, pharmacodynamic and pharmacokinetic properties of direct oral anticoagulants (DOACs) limit the use of this class of anticoagulants in COVID-19 patients due to a significant interference with antiviral agents. DOACs use in COVID-19 hospitalized patients is currently not recommended. Furthermore, patients already on oral anticoagulant drugs should be switched to heparin at hospital admission. Nevertheless, outpatients with a confirmed diagnosis of COVID-19 are recommended to continue prior DOAC therapy. More studies are required to clarify the pathogenesis of COVID-19-induced derangement of the coagulation system in order to recommend an appropriate anticoagulant treatment.

Renoprotective Effect of Liraglutide Is Mediated via the Inhibition of TGF-Beta 1 in an LLC-PK1 Cell Model of Diabetic Nephropathy.

Background: Recently published research demonstrated direct renoprotective effects of the glucagon-like peptide-1 receptor agonist GLP 1 RA, but the relevant molecular mechanisms are still not clear. The aim of this research was to assess the effects of Liraglutide in a cell culture model of diabetic nephropathy on cell viability, antioxidant (GSH) and transforming growth factor beta 1 (TGF- ß1) levels and extracellular matrix (ECM) expression. The metabolic activity in hyperglycemic conditions and the effect of Liraglutide treatment were assessed by measuring Akt, pAkt, GSK3ß, pGSK3ß, pSTAT3, SOCS3, iNOS and NOX4 protein expression with Western blot. F actin distribution was used to assess the structural changes of the cells upon treatment. Materials and methods: The cells were exposed to high glucose (HG30 mM) followed by 0.5 mM H2O2 and a combination of glucose and H2O2 during 24 h. Subsequently, the cells were treated with different combinations of HG30, H2O2 and Liraglutide. Cell viability was determined by an MTT colorimetric test, and the GSH, TGF-ß1 concentration and ECM expression were measured using a spectrophotometric/microplate reader assay and an ELISA kit, respectively. Western blotting was used to detect the protein level of Akt, pAkt, GSK3ß, pGSK3ß, pSTAT3, SOCS3, iNOS and NOX4. The F-actin cytoskeleton was visualized with Phalloidin stain and subsequently quantified. Results: Cell viability was decreased as well as GSH levels in cells treated with a combination of HG30/H2O2, and HG30 alone (p < 0.001). The addition of Liraglutide improved the viability in cells treated with HG30, but it did not affect the cell viability in the cell treated with the addition of H2O2. GSH increased with the addition of Liraglutide in HG30/H2O2 (p < 0.001) treated cells, with no effect in cells treated only with HG30. TGF-ß1 levels (p < 0.001) were significantly increased in HG30 and HG30/H2O2. The addition of Liraglutide significantly decreased the TGF-ß1 levels (p < 0.01; p < 0.05) in all treated cells. The synthesis of collagen was significantly increased in HG30/H2O2 (p < 0.001), while the addition of Liraglutide in HG30/H2O2 significantly decreased collagen (p < 0.001). Akt signaling was not significantly affected by treatment. The GSK3b and NOX4 levels were significantly reduced (p < 0.01) after the peroxide and glucose treatment, with the observable restoration upon the addition of Liraglutide suggesting an important role of Liraglutide in oxidative status regulation and mitochondrial activity. The treatment with Liraglutide significantly upregulated STAT3 (p < 0.01) activity, with no change in SOCS3 indicating a selective regulation of the STAT 3 signaling pathway in glucose and the oxidative overloaded environment. A significant reduction in the distribution of F-actin was observed in cells treated with HG30/H2O2 (p < 0.01). The addition of Liraglutide to HG30-treated cells led to a significant decrease of distribution of F-actin (p < 0.001). Conclusion: The protective effect of Liraglutide is mediated through the inhibition of TGF beta, but this effect is dependent on the extent of cellular damage and the type of toxic environment. Based on the WB analysis we have revealed the signaling pathways involved in cytoprotective and cytotoxic effects of the drug itself, and further molecular studies in vitro and vivo are required to elucidate the complexity of the pathophysiological mechanisms of Liraglutide under conditions of hyperglycemia and oxidative stress.

Comparison of Injectable Biphasic Calcium Phosphate and a Bovine Xenograft in Socket Preservation: Qualitative and Quantitative Histologic Study in Humans.

This study is the first histologic evaluation of an injectable biphasic calcium phosphate (IBCP) in humans six months after socket preservation according to the principles of guided bone regeneration. After tooth extraction, the alveolar ridge of 21 patients was augmented with IBCP (maxresorb® inject) in the test group, while 20 patients in the control group received a bovine xenograft (BX) (cerabone®). Six months after augmentation, a reentry procedure was performed to collect biopsies of regenerated bone for qualitative and quantitative histologic analysis. A total of 20 biopsies were taken for analysis. Qualitative histologic analysis showed complete integration of the biomaterial and no inflammatory tissue reaction, indicating the biocompatibility of the bone grafts and the surrounding tissue in both groups. Histomorphometric analysis showed comparable results in terms of newly formed bone (IBCP: 26.47 ± 14.71%, BX: 30.47 ± 16.39%) and residual biomaterial (IBCP: 13.1 ± 14.07%, BX: 17.89 ± 11.81%), with no significant difference found across groups (p > 0.05, Mann­Whitney U test). Statistical significance between groups was found in the result of soft tissue percentage (IBCP: 60.43 ± 12.73%, BX: 51.64 ± 14.63%, p = 0.046, Mann­Whitney U test). To conclude, IBCP and BX showed good osteoconductivity and biocompatibility with comparable new bone formation six months after alveolar ridge preservation.

Patients' and Nurses' Perceptions of Importance of Caring Nurse-Patient Interactions: Do They Differ?

Nurse−patient interaction is a professional and therapeutic relationship created to enable nurses to assess, plan, and deliver health care aimed at meeting patients' basic human needs. The main aim of this study was to identify distinctive characteristics and differences in perceptions between patients and nurses related to the importance of caring interactions and to examine the contribution of independent variables in explaining their perceptions. A total of 446 respondents were included in the research (291 patients and 155 registered nurses). Data were collected using the translated and standardized 70-item version of the Caring Nurse−Patient Interactions Scale (CNPI-70) version for patients and version for nurses. According to the overall CNPI-70 scale, there was a significant difference in patients' and nurses' perception (p < 0.001). Patients assessed caring nurse−patient interactions significantly higher (4.39) than nurses (4.16). Additionally, nurses assessed all subscales significantly lower than patients who assessed them high (p < 0.05), except for the subscales for "environment" (p = 0.123) and "spirituality" (p = 0.132). Independent variables did not contribute to an explanation of respondents' perceptions. Providing quality physical assistance in meeting human needs through effective communication and teaching is crucial for promoting a holistic patient approach, improving psychosocial support and nurse−patient interaction, and attaining greater satisfaction with health care provided without additional financial investments.