Medicina, Volume 56, Issue 3 (March 2020) – 50 articles

Background and Objectives: Ficus benghalensis (FB) is a commonly found tree in Pakistan and its various parts have folkloric importance in managing neurological ailments. In the present study, methanolic extract of its bark has been tested on an experimental animal model to evaluate memory-enhancing, anxiolytic and antidepressant activities to validate the claimed therapeutic potential. Materials and Methods: Methanolic extract of freshly isolated bark was prepared and subjected to preliminary phytochemical studies and gas chromatography–mass spectrometry (GC–MS) analysis for the presence of phytocomponents. To evaluate its effect on spatial learning, passive-avoidance test–step through (PAT-ST), Y-maze and Morris water maze (MWM) tests were carried out. Open-field (OFT) and elevated plus maze (EPM) tests were employed to explore the anti-anxiety potential of FB while a forced swimming test (FST) was utilized to assess its anti-depressant prospective. FB doses of 100, 200 and 300 mg/kg with positive and negative controls given to Sprague Dawley (SD) rats. Results: phytochemical studies showed the presence of various phytoconstituents including alkaloids, flavonoids, terpenes, phenolics and anthraquinones. The presence of synephrine, aspargine, glucose, fructose and fatty acids was revealed by GC–MS analysis. FB administration led to significant improved memory retention when evaluated through passive avoidance (p < 0.05), Y-maze (p < 0.05) and Morris water maze (p < 0.05) tests in a scopolamine model of amnesic rats. When tested by open field and elevated plus maze tests, FB demonstrated anxiety-resolving characteristics (p < 0.05) as animals dared to stay in open areas more than a control group. Mobility time was increased and immobility time was reduced (p < 0.05–0.01) in rats treated with FB, unveiling the anti-depressant importance of F. benghalensis. Conclusion: methanolic extract of F. benghalensis bark furnished scientific proof behind folkloric claims of the memory improving, anxiety-reducing and depression-resolving characteristics of the plant. These activities might be possible due to interaction of its phytoconstituents with serotonergic, glutamatergic, cholinergic and GABAergic systems in the brain. Full article

Background and Objectives: The aim of this study was to explore the association between the cerebral autoregulation (CA) index, the pressure reactivity index (PRx), the patient’s clinical outcome, and the quality of arterial blood pressure (ABP(t)) and intracranial blood pressure (ICP(t)) signals by comparing two filtering methods to derive the PRx. Materials and Methods: Data from 60 traumatic brain injury (TBI) patients were collected. Moving averaging and FIR (Finite Impulse Response) filtering were performed on the ABP(t) and ICP(t) signals, and the PRx was estimated from both filtered datasets. Sensitivity, specificity, and receiver-operating characteristic (ROC) curves with the area under the curves (AUCs) were determined using patient outcomes as a reference. The outcome chosen for comparison among the two filtering methods were mortality and survival. Results: The FIR filtering approach, compared with clinical outcome, had a sensitivity of 70%, a specificity of 81%, and a level of significance p = 0.001 with an area under the curve (AUC) of 0.78. The moving average filtering method compared with the clinical outcome had a sensitivity of 58%, a specificity of 72%, and a level of significance p = 0.054, with an area under the curve (AUC) of 0.66. Conclusions: The FIR (optimal) filtering approach was found to be more sensitive for discriminating between two clinical outcomes, namely intact (survival) and impaired (death) cerebral autoregulation for TBI treatment decision making. Full article

Background and objectives: Although laparoscopic sleeve gastrectomy (LSG) is effective for obesity management, postoperative vitamin B12 (B12) deficiency is of major concern. In this cross-sectional study, we assessed the levels of B12 and its related functional biomarkers, namely, total homocysteine (tHcy), methylmalonic acid (MMA), folate, methylcitric acid (MCA), and hemoglobin (Hb), in one-year postoperative LSG patients and matched controls. Materials and Methods: Plasma B12, tHcy, MMA, folate, and MCA were measured in matched controls (n = 66) and patients (n = 71) using validated liquid chromatography-tandem mass spectrometry techniques and protocols in the United Arab Emirates (UAE). Results: The median B12 concentration in patients (177 pmol/L) was significantly lower (p < 0.001) than in the controls (334.7 pmol/L). The tHcy and MMA levels were significantly increased (p < 0.001 and p = 0.011, respectively) and folate levels were significantly decreased (p = 0.001) in the LSG patients compared to the controls. Interestingly, no significant difference in MCA levels were observed between the two groups. The levels of tHcy and MMA were concomitantly increased with the decreased folate levels in postoperative LSG patients when compared with the controls. The Hb levels were significantly lower in males and females in the patient group compared with those in the control group, respectively (p = 0.005 and p = 0.043). Conclusions: This is the first report of serum levels of B12 and its functional biomarkers in postoperative LSG patients among a local population from the UAE. Our findings revealed significant alterations of the B12 biomarkers, total B12, MMA, and tHcy in one-year postoperative LSG patients. Full article

The objective of this article is to discuss the inherent bias involved with artificial intelligence-based decision support systems for healthcare. In this article, the authors describe some relevant work published in this area. A proposed overview of solutions is also presented. The authors believe that the information presented in this article will enhance the readers’ understanding of this inherent bias and add to the discussion on this topic. Finally, the authors discuss an overview of the need to implement transdisciplinary solutions that can be used to mitigate this bias. Full article

Background and objectives: Bisphosphonates represent selective inhibitors of excess osteoblastic bone resorption that characterizes all osteopathies, targeting osteoclasts and their precursors. Their long-term administration in postmenopausal women suffering from osteoporosis has resulted in neural adverse effects. The current study focuses on the research of possible alterations in the femoral nerve, caused by bisphosphonates. We hypothesized that bisphosphonates, taken orally (per os), may produce degenerative changes to the femoral nerve, affecting lower-limb posture and walking neuronal commands. Materials and Methods: In order to support our hypothesis, femoral nerve specimens were extracted from ten female 12-month-old Wistar rats given 0.05 milligrams (mg) per kilogram (kg) of body weight (b.w.) per week alendronate per os for 13 weeks and from ten female 12-month-old Wistar rats given normal saline that were used as a control group. Specimens were studied using immunohistochemistry for selected antibodies NeuN (Neuronal Nuclear Protein), a protein located within mature, postmitotic neural nucleus, and cytosol and Sox10 (Sex-determining Region Y (SRY)—High-Motility Group (HMG)—box 10). The latter marker is fundamental for myelination of peripheral nerves. Obtained slides were examined under a light microscope. Results: Samples extracted from rats given alendronate were more Sox10 positive compared to samples of the control group, where the marker’s expression was not so intense. Both groups were equally NeuN positive. Our results are in agreement with previous studies conducted under a transmission electron microscope. Conclusions: The suggested pathophysiological mechanism linked to histological alterations described above is possibly related to toxic drug effects on Schwann and neuronal cells. Our hypothesis enhances the existing scientific evidence of degenerative changes present on femoral nerve following bisphosphonates administration, indicating a possible relationship between alendronate use and neuronal function. Full article

Background and objectives: To compare the medium- to long-term mechanical behavior of overdentures with two different retention systems: overdentures with Locator® axial retention, and vertical insertion overdentures with bar retention, used to rehabilitate edentulous maxillar. Material and Methods: This prospective study assessed patients presenting complete maxillary edentulism, rehabilitated by means of implant-supported overdentures (n = 20), 10 with Locator® axial retention (ODA group) and 10 with overdentures on bars (ODB group). Patients also completed a questionnaire to determine their satisfaction with treatment. Results: The mean follow-up time in both groups was 11.4 years, with follow-up times in both groups ranging from 5 to 14 years. The ODA group suffered mechanical complications such as retention loss, need for nylon retention insert changes, resin fracture, and need for relining. In the ODB group, prosthetic dental wear, screw loosening, and complete prosthetic failure were more common. A total of 19 implants failed (23.8%); of these, 11 were in the ODA group (failure rate = 27.5%) and eight in the ODB group (failure rate = 20%). The patient satisfaction questionnaire obtained a mean score of 7.9 out of 10 in the ODA group, and 9.75 in the ODB group. Conclusions: in rehabilitations of edentulous maxillar by means of implant-supported overdentures, both the systems assessed were shown to be effective in the medium to long term. Patients expressed a high level of satisfaction with the treatments received. Full article

Alarmins are endogenous mediators released by cells following insults or cell death to alert the host’s innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiological processes and inflammatory diseases including osteoporosis. The aim of the review was to evaluate the role of alarmins in osteoporosis. A bibliographic search of the published scientific literature regarding the role of alarmins in osteoporosis was organized independently by two researchers in the following scientific databases: Pubmed, Scopus, and Web of Science. The keywords used were combined as follows: “alarmins and osteoporosis”, “RAGE and osteoporosis”, “HMGB1 and osteoporosis”, “IL-1 and osteoporosis”, “IL 33 and osteopororsis”, “S100s protein and osteoporosis”. The information was summarized and organized in the present review. We highlight the emerging roles of alarmins in various bone remodeling processes involved in the onset and development of osteoporosis, as well as their potential role as biomarkers of osteoporosis severity and progression. Findings of the research suggest a potential use of alarmins as pharmacological targets in future therapeutic strategies aimed at preventing bone loss and fragility fractures induced by aging and inflammatory diseases. Full article

Traumatic brain injury represents physical damage to the brain tissue that induces transitory or permanent neurological disabilities. The traumatic injury activates an important inflammatory response, followed by a cascade of events that lead to neuronal loss and further brain damage. Maintaining proper ventilation, a normal level of oxygenation, and adequate blood pressure are the main therapeutic strategies performed after injury. Surgery is often necessary for patients with more serious injuries. However, to date, there are no therapies that completely resolve the brain damage suffered following the trauma. Stem cells, due to their capacity to differentiate into neuronal cells and through releasing neurotrophic factors, seem to be a valid strategy to use in the treatment of traumatic brain injury. The purpose of this review is to provide an overview of clinical trials, aimed to evaluate the use of stem cell-based therapy in traumatic brain injury. These studies aim to assess the safety and efficacy of stem cells in this disease. The results available so far are few; therefore, future studies need in order to evaluate the safety and efficacy of stem cell transplantation in traumatic brain injury. Full article

Background and objective: Magnetic resonance imaging (MRI) causes severe anxiety in some patients. Anxiety during MRI leads to prolongation of the procedure and deterioration of image quality, resulting in loss of labor and cost increase. The aim of this study was to investigate the effect of written and visual information on state anxiety in patients undergoing MRI. Material and Methods: A cross-sectional prospective study was conducted with 294 participants. The study was carried out between January 2019 and March 2019 at the Radiology Clinic of the tertiary university hospital. The participants were divided into 3 groups as group 1 (control group), group 2 (written information) and group 3 (visual information). The trait anxiety and state anxiety of the participants were measured by State-Trait Anxiety Inventory (STAI) inventory, which can measure both anxiety status. Results: There was no statistically significant difference between demographic characteristics and trait anxiety scores (p = 0.20) of all three groups. The state anxiety scores of group 3 were statistically lower than the group 2 (p < 0.001) and control group (p < 0.001). The state anxiety scores of group 2 were statistically lower than control group (p < 0.001). Conclusion: MRI anxiety can be reduced by visual and written information. Visual information may be more effective in reducing MRI anxiety than written information. Full article

Background and objectives: There is a paucity of research on the shape of internal jugular vein (IJV) and their association with an individual’s morphology and various chronic diseases. Therefore, this study aimed to analyze the anatomy of the IJV across various patients and to relate the differences in anatomy to basic patient characteristics. Materials and Methods: This retrospective study included a total of 313 patients who underwent contrast-enhanced neck computed tomography between January 2017 and December 2018. The circumferences of the right and left IJVs were measured at three locations (hyoid bone, cricoid cartilage, and first thoracic vertebra) and parameters affecting the size of the IJV were analyzed. Results: The right IJV was significantly larger than the left IJV at each position (p < 0.001), and the area of the lumen was the largest at the cricoid cartilage level (p < 0.001). After dividing the right IJV data into two groups (above and below the median area), multivariate logistic regression analysis showed that age (odds ratio (OR) 1.040; 95% confidence interval (CI) 1.022–1.058, p < 0.001) and body mass index (BMI, OR 1.080; 95% CI 1.011–1.154, p = 0.0.23) affected size. Conclusions: The right IJV is larger than the left and has a rhomboid morphology. Age and BMI are significant factors affecting the IJV size. Full article

Background and Objectives: Cardiovascular disease (CVD) prevention guidelines define targets for lifestyle and risk factors for patients at high risk of developing CVD. We assessed the control of these factors, as well as CVD risk perception in patients enrolled into the primary care arm of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE V) survey in Lithuania. Materials and Methods: Data were collected as the part of the EUROASPIRE V survey, a multicenter, prospective, cross-sectional observational study. Adults without a documented CVD who had been prescribed antihypertensive medicines and/or lipid-lowering medicines and/or treatment for diabetes (diet and/oral antidiabetic medicines and/or insulin) were eligible for the survey. Data were collected through the review of medical records, patients’ interview, physical examination and laboratory tests. Results: A total of 201 patients were enrolled. Very few patients reached targets for low-density lipoprotein cholesterol (LDL-C) (4.5%), waist circumference (17.4%) and body mass index (15.4%). Only 31% of very high CVD risk patients and 52% of high-risk patients used statins. Blood pressure target was achieved by 115 (57.2%) patients. Only 21.7% of patients at very high actual CVD risk and 27% patients at high risk correctly estimated their risk. Of patients at moderate actual CVD risk, 37.5% patients accurately self-assessed the risk. About 60%–80% of patients reported efforts to reduce the intake of sugar, salt or alcohol; more than 70% of patients were current nonsmokers. Only a third of patients reported weight reduction efforts (33.3%) or regular physical activity (27.4%). Conclusions: The control of cardiovascular risk factors in a selected group of primary prevention patients was unsatisfactory, especially in terms of LDL-C level and body weight parameters. Many patients did not accurately perceive their own risk of developing CVD. Full article

Helicobacter pylori (Hp) management has undoubtedly resulted in a notable economic burden on healthcare systems globally, including Greece. Its cost has never been estimated so far, especially during the recent 10-year unprecedented financial crisis. Direct medical and procedural costs for one attempt “outpatient” Hp eradication treatment were estimated as the following: (I) first-line regimens: 10 and 14 days standard triple, 10 and 14 days sequential, 10 and 14 days concomitant non-bismuth quadruple, 14 days hybrid, (II) second-line salvage regimens: 10 and 14 days levofloxacin-containing triple regimens. Treatment costs using prototypes and/or generic drugs were calculated. Drug prices were collected and confirmed from two official online medical databases including all medicines approved by the Greek National Organization for Medicines. Regimens based on generics were more affordable than prototypes and those including pantoprazole yielded the lowest prices (mean: 27.84 €). Paradoxically, 10-day concomitant and 14-day hybrid regimens (currently providing good (90–94%) first-line eradication rates in Greece) cost the same (mean: 34.76 €). The expenditures for Hp eradication treatment regimens were estimated thoroughly for the first time in Greece. These data should be taken into account by Public Health policymakers both in Greece and the European Union, aiming for a better and less expensive therapeutic approach. Full article

Background and Objectives: To evaluate in vitro the fracture resistance and fracture type of computer-aided design and computer-aided manufacturing (CAD-CAM) materials. Materials and Methods: Discs were fabricated (10 × 1.5 mm) from four test groups (N = 80; N = 20 per group): lithium disilicate (LDS) group (control group): IPS e.max CAD^®; zirconium-reinforced lithium silicate (ZRLS) group: VITA SUPRINITY^®; polymer-infiltrated ceramic networks (PICN) group: VITA ENAMIC^®; resin nanoceramics (RNC) group: LAVA™ ULTIMATE. Each disc was cemented (following the manufacturers’ instructions) onto previously prepared molar dentin. Samples underwent until fracture using a Shimadzu^® test machine. The stress suffered by each material was calculated with the Hertzian model, and its behavior was analyzed using the Weibull modulus. Data were analyzed with ANOVA parametric statistical tests. Results: The LDS group obtained higher fracture resistance (4588.6 MPa), followed by the ZRLS group (4476.3 MPa) and PICN group (4014.2 MPa) without statistically significant differences (p < 0.05). Hybrid materials presented lower strength than ceramic materials, the RNC group obtaining the lowest values (3110 MPa) with significant difference (p < 0.001). Groups PICN and RNC showed greater occlusal wear on the restoration surface prior to star-shaped fracture on the surface, while other materials presented radial fracture patterns. Conclusion: The strength of CAD-CAM materials depended on their composition, lithium disilicate being stronger than hybrid materials. Full article

Background and objectives: Pulmonary hypertension (PH) is characterized by the vasoconstriction and abnormally proliferative vascular cells. The available allopathic treatment options for PH are still not able to cure the disease. Alternative medicine is becoming popular and drawing the attention of the general public and scientific communities. The entomogenous fungus Yarsagumba (Cordyceps sinensis) and its biologically active ingredient cordycepin may represent the therapeutic option for this incurable disease, owing to their anti-inflammatory, vasodilatory and anti-oxidative effects. Methods: In this study, we investigated whether Yarsagumba extract and cordycepin possess anti-proliferative and vasorelaxant properties in the context of PH, using 5-bromo-2’-deoxyuridine assay and isolated mice lungs, respectively. Results: Our results revealed that Yarsagumba extract and its bioactive compound cordycepin significantly attenuated the proliferation of human pulmonary artery smooth muscle cells derived from donor and PH subjects. In isolated murine lungs, only Yarsagumba extract, but not cordycepin, resulted in vasodilatation, indicating the probable existence of other bioactive metabolites present in Yarsagumba that may be responsible for this outcome. Conclusion: Future comprehensive in vivo and in vitro research is crucially needed to discover the profound mechanistic insights with regard to this promising therapeutic potency of Yarsagumba extract and to provide further evidence as to whether it can be used as a strategy for the treatment of PH. Full article

Background and Objectives: Masticatory limitations on the dietary habits of edentulous subjects restrict their access to adequate nutrition, exposing them to a greater risk of protein energy malnutrition. The aim of this study is to verify the existence of an association between Masticatory Performance (MP) and nutritional changes in the elderly. Materials and Methods: 76 participants were enrolled. MP testing was performed using the two-color chewing gum mixing test. The system used reveals the extent to which the two differently colored chewing gums mix, and allows discrimination between different MPs. The assessment of the participants’ nutritional statuses was carried out through a food interview. Anthropometric parameters were collected, and bioimpedance analysis was performed. Results: Mean MP was 0.448 ± 0.188. No statistically significant differences were detected between male and female subjects (p > 0.05). According to the Body Mass Index (BMI), obese patients had a lower MP than overweight and normal weight subjects (0.408 ± 0.225, 0.453 ± 0.169 and 0.486 ± 0.181, respectively). MP values were lower both in male and female subjects with a waist circumference above the threshold than those below it (0.455 ± 0.205 vs. 0.476 ± 0.110, respectively, in males and 0.447 ± 0.171 vs. 0.501 ± 0.138, respectively, in females). No relationship was noticed between MP and bioimpedance parameters (p > 0.05). Conclusions: A statistically significant relation was observed between MP and the number of missing teeth. A reduced MP could worsen nutritional parameters. A reduced MP did not seem to negatively affect bioimpedance parameters. Full article

In this paper we introduce a mechanistic model through which exercise may enhance episodic memory, specifically via attenuating proactive and retroactive memory interference. We discuss the various types of memory, different stages of memory function, review the mechanisms behind forgetting, and the mechanistic role of exercise in facilitating pattern separation (to attenuate memory interference). Full article

Background and Objectives: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (GSTP1). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of GSTP1*Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including GSTP1*IIe105Val rs1695 or GSTM1 and GSTT1 deletion polymorphisms. Materials and Methods: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. Results: We found that carriers of either GSTP1*Val (rs1138272) or GSTP1*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89–8.40, p < 0.001 and OR = 1.8, 95%CI: 1.19–2.73, p = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with GSTP1*C haplotype, represented by both variant alleles (GSTP1*Val rs1695 + GSTP1*Val rs1138272), had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56–11.65, p < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (GSTM1*active, GSTT1*null, GSTP1*Val rs1695 and GSTP1*Val rs1138272) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55–8.61, p = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05–44.93, p < 0.001). Conclusion: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially GSTP1, highlighting the role of gene–gene interactions in human susceptibility to this cancer. Full article

Background and objectives: With improved diagnostic means of early breast cancer, the percentage of cases with metastasis in axillary lymph nodes has decreased from 50–75% to 15–30%. Lymphadenectomy and sentinel lymph node biopsy are not treatment procedures, as they aim at axillary nodal staging in breast cancer. Being surgical interventions, they can lead to various complications. Therefore, recently much attention has been paid to the identification of non-invasive methods for axillary nodal staging. In many countries, ultrasound is a first-line method to evaluate axillary lymph node status. The aim of this study was to evaluate the prognostic value of ultrasound in detecting intact axillary lymph nodes and to assess the accuracy of ultrasound in detecting a heavy nodal disease burden. The additional objective was to evaluate patients’ and tumor characteristics leading to false-negative results. Materials and Methods: A total of 227 women with newly diagnosed pT1 breast cancer were included to this prospective study conducted at the Breast Surgery Unit, Clinic of Surgery, Hospital of Lithuanian University of Health Sciences Kauno Klinikos, between May 1, 2016, and May 31, 2018. All patients underwent preoperative axillary ultrasound examination. Ultrasound data were compared with the results of histological examination. The accuracy and true-negative rate of ultrasound were calculated. The reasons of false-negative results were analyzed. Results: Of the 189 patients who had normally appearing axillary lymph nodes on preoperative ultrasound (PAUS-negative), 173 (91.5%) patients were also confirmed to have intact axillary lymph nodes (node-negative) by histological examination after surgery. The accuracy and the negative predictive value of ultrasound examination were 84.1% and 91.5%, respectively. In ≥3 node-positive cases, the accuracy and the negative predictive value increased to 88.7% and 98.3%, respectively. In total, false-negative results were found in 8.5% of the cases (n = 16); in the PAUS-negative group, false-negative results were recorded only in 1.6% of the cases (n = 3). The results of PAUS and pathological examination differed significantly between patients without and with lymphovascular invasion (LV0 vs. LV1, p < 0.001) as well as those showing no human epidermal growth factor receptor 2 (HER2) expression and patients with weakly or strongly expressed HER2 (HER2(0) vs. HER2(1), p = 0.024). Paired comparisons revealed that the true-negative rate was significantly different between the LV0 and LV1 groups (91% vs. 66.7%, p < 0.05), and the false-negative rate was statistically significant different between the HER2(0) and HER2(1) groups (10.5% vs. 1.2%, p < 0.05). Evaluation of other characteristics showed both the groups to be homogenous. Conclusions: Negative axillary ultrasound excluded axillary metastatic disease in 91.5% of the patients. PAUS had an accuracy of 88.7% in detecting a heavy nodal disease burden. With the absence of lymphovascular invasion (LV0), we can rely on PAUS examination that axillary lymph nodes are intact (PAUS-negative), and this patients’ group could avoid sentinel lymph node biopsy. Patients without HER2 expression are at a greater likelihood of false-negative results; therefore, the findings of ultrasound that axillary lymph nodes are intact (PAUS-negative results) should be interpreted with caution. Full article

Background: Left ventricular assist device (LVAD) therapy has improved the clinical outcomes in advanced heart failure patients, however, this may differ between countries. We aimed to compare outcomes between Japanese and US LVAD cohorts. Methods: For 416 consecutive LVAD patients who received HeartMate II LVAD implantation and completed a one-year follow-up, age-matched Japanese patients (the Japanese registry for mechanically assisted circulatory support (J-MACS) group) and the US patients were compared for their clinical outcomes. Results: 154 J-MACS patients and 77 US patients were compared. Survival, free from hemocompatibility-related adverse events (HRAEs) in the J-MACS was statistically comparable with the US (75% vs. 63%, p = 0.79). J-MACS had more disabling strokes than the US (0.221 vs. 0.052/patient-year, p = 0.005), whereas there was less nonsurgical bleeding (0.045 vs. 0.117/patient-year, p = 0.024). The net hemocompatibility score was statistically comparable between the groups (1.54 vs. 1.19 points/patient, p = 0.99). Post-LVAD prothrombin time with international normalized ratio (INR) <1.5 (odds ratio 4.07) was a risk factor for HRAEs in J-MACS, whereas INR >3.0 (odds ratio 5.71) was a risk factor in the US (p < 0.05 for both). Conclusion: In the age-matched cohorts, the J-MACS group experienced more strokes, while the US group had more bleedings. “Tailor-made” therapeutic strategy might be required for each country, given the unique variation of HRAE incidence among each country. Full article

Background and Objectives: Abnormal concentrations of bioelements (magnesium, manganese, chromium, copper, zinc) have been associated with physical and emotional dysfunctions, including depression. This association, however, has not been analyzed in testosterone deficiency syndrome (TDS) or patients with depressiveness, i.e., when individual symptoms do not form the picture of a full-syndrome depressive disorder. This study aimed to assess the relationship between concentrations of selected bioelements and the incidence of depressive symptoms in men aged 50 years and older with a concurrent testosterone deficiency syndrome. Material and Methods: Blood samples were taken from 314 men; the mean age of the population was 61.36 ± 6.38 years. Spectrophotometric method for biochemical analysis of magnesium (Mg), manganese (Mn), chromium (Cr), copper (Cu), and zinc (Zn) was used. The diagnosis of testosterone deficiency syndrome (TDS) was based on the total testosterone (TT), free testosterone (FT), estradiol (E2), and dehydroepiandrosterone sulfate (DHEAS) levels by ELISA. Each participant completed the Androgen Deficiency in Aging Male (ADAM) questionnaire, as well as the Beck Depression Inventory (BDI-Ia) measuring the severity of depressive symptoms. Results: Emotional disturbances manifested as depressive symptoms were diagnosed in 28.7% of all participants and testosterone deficiency syndrome in 49.3%. In the TDS group, the analysis showed a significant correlation between the level of manganese (R = 0.225, p = 0.005) and chromium (R = 0.185, p = 0.021) with the incidence of depression. Conclusions: The results of our study demonstrated a relationship between manganese and chromium concentrations with the incidence of depression in men aged 50 years and older with a concurrent testosterone deficiency syndrome. This may indicate that there is a correlation between these bioelements, as well as emotional disorders manifested as depressive symptoms in aging men with a diagnosed testosterone deficiency. Full article

Isolated hydatid cysts of the pancreas are rare lesions, even in endemic regions. In this report, we present the case of a 76-year-old patient who was admitted to our clinic with a diagnosis of a cystic lesion in the tail of the pancreas. On preoperative computed tomography (CT) and magnetic resonance (MR) examination, the cyst was characterized as a mucinous cystadenoma. A laparoscopic distal pancreatectomy followed. A histopathological examination revealed a large hydatid cyst in the tail of the pancreas. Full article

Controversies related to the concept and practice of responsible authorship and its misuse have been among the most prominent issues discussed in the recent literature on research integrity. Therefore, this paper aims to address the factors that lead to two major types of unethical authorship, namely, honorary and ghost authorship. It also highlights negative consequences of authorship misuse and provides a critical analysis of different authorship guidelines, including a recent debate on the amendments of the International Committee of Medical Journal Editors (ICMJE) authorship definition. Empirical studies revealed that honorary authorship was the most prevalent deviation from the responsible authorship standards. Three different modalities of honorary authorship were distinguished: gift authorship, guest authorship, and coercive authorship. Prevalence of authorship misuse worldwide and in Europe was alarmingly high, covering approximately one third of all scientific publications. No significant differences were reported in authorship misuse between different health research disciplines. The studies conducted in North America highlighted the most effective means to cope with unethical authorship. These were training in publishing ethics, clear authorship policies developed by medical schools, and explicit compliance with the authorship criteria required by the medical journals. In conclusion, more empirical research is needed to raise awareness of the high prevalence of authorship misuse among scientists. Research integrity training courses, including publication ethics and authorship issues should be integrated into the curricula for students and young researchers in medical schools. Last but not least, further discussion on responsible authorship criteria and practice should be initiated. Full article

Background and Objective: Investigating the use of radiofrequency myolysis (RFM) for the treatment of fibroids through less invasive access by combining transvaginal ultrasound, hysteroscopy and laparoscopy. Materials and Methods: Fifty-four premenopausal women with 106 symptomatic uterine myomas. Patients underwent RFM in three ways: Vaginal Ultrasound-guided RFM (VU-RFM), Laparoscopic RFM (L-RFM) and Hysteroscopic-RFM (H-RFM). The mean patient age was 43 years; 52 symptomatic uterine myomas were subserosal, 44 intramural and 10 submucosal. The outcomes evaluated at 1 and 12 months after RFM were myoma size (volume-diameter), “Uterine Fibroid Symptom and Quality of Life (UFS-QOL)” questionnaire and a 10-point Visual Analogue Scale (VAS). The therapy was completed with a single ablation in all patients, no complication was registered. The average number of fibroids treated per intervention was two with the use of different accesses: 64/106 VU-RFMs (60.4%), 32/106 L-RFMs (30.2%) and 10/106 H-RFMs (9.4%). Results: Volume and diameter of fibroids were significantly reduced by, respectively, 51.3% and 20.1% in the first 30 days post-intervention (p < 0.001) up to a maximum of 73.5% and 37.1% after the second follow-up visit at 12 months (p < 0.001). A similar trend was shown in terms of disability with a progressive and significant reduction of symptoms (menorrhagia, dysmenorrhea, dyspareunia and pollakiuria) demonstrated by percentage variation of UFS-QOL Symptom Severity and VAS scores to −74.3% and −45.3% as well as −84.9% and −74.3%, respectively, at 1 and 12 months after RFM (p < 0.001). An overall improvement in the quality of life was also demonstrated by a significant increase in the UFS-QOL total score of +38.2% in the first 30 days post-intervention up to +44.9% after the second follow-up visit at 12 months (p < 0.001). The overall average surgery time of the RFM for each patient was 48 minutes, and the time to treat each fibroid by Vaginal Ultrasound-guided RFM (23 min) was found to be significantly less than those of laparoscopy or hysteroscopy (respectively 35 and 34 min) (p < 0.05). An electromagnetic virtual needle tracking system (VNTS) was successfully tested during the RFM procedures, and real-time contrast-enhanced ultrasound (CEUS) has proven to be effective in determining the duration of myolysis through the identification of eventual residual areas of enhancement within the fibroids. Conclusion: Radiofrequency can be considered a minimally invasive and safe procedure for the treatment of uterine myomas through the customization and possible combination of transvaginal, laparoscopic or hysteroscopic accesses. The standardization of the ablation technique with pre-intervention biopsy and new technologies such as VNTS and CEUS spares healthy uterine tissue and may change the future management of symptomatic uterine fibroids. Full article

Background and objective: Although obesity is associated with an increased risk of peptic ulcer disease (PUD), no study has evaluated the association of PUD with sarcopenia. The aim of this study was to evaluate the association of sarcopenia and obesity with PUD. Material and Methods: Data from the Korean National Health and Nutrition Examination Survey (KNHANES) IV and V for 2007–2012 were used. PUD history, dietary, alcohol consumption, smoking, physical activity patterns, and other socioeconomic factors were analyzed. Sarcopenia index (appendicular skeletal muscle mass (kg) ÷ body mass index (kg/m2)) and body fat mass were determined by dual-energy X-ray absorptiometry. Univariate and multivariate analyses were performed to evaluate the association of sarcopenia with the prevalence of PUD. Results: The 7092 patients were divided into the sarcopenic obesity (SO, n = 870), sarcopenic non-obesity (n = 2676), non-sarcopenic obesity (NSO, n = 2698), and non-sarcopenic non-obesity (NSNO, n = 848) groups. The prevalence of PUD in these groups was 70 (7.9%), 170 (7.4%), 169 (6.3%), and 47 (3.8%), respectively (p < 0.001). A crude analysis revealed that the prevalence of PUD was 2.2-fold higher in the SO group than in the NSNO group (odds ratio (OR), 2.2; 95% confidence interval (CI), 1.5–3.2), the significance of which remained after adjustment for age, sex, body mass index, and HOMA-IR (homeostatic model assessment insulin resistance) score (OR, 1.9; 95% CI, 1.3–2.7). Conclusion: In conclusion, in this nationally representative cohort, the combination of muscle and fat mass, as well as obesity, was associated with an increased risk of PUD. Full article

Complement deficiencies are rare and often underdiagnosed primary immunodeficiencies that may be associated with invasive bacterial diseases. Serious infections with encapsulated organisms (mainly Streptococcus pneumoniae, but also Neisseria meningitides and Haemophilus influenzae type B) are frequent in patients with a deficiency of the second component of complement (C2), but no data are available on long-term follow-up. This study aimed to evaluate the long-term clinical outcome and the importance of an early diagnosis and subsequent infection prophylaxis in C2 deficiency. Here, we report the 21-year follow-up of a whole family which was tested for complement parameters, genetic analysis and biochemical measurements, due to recurrent pneumococcal meningitis in the elder brother. The two sons were diagnosed with homozygous type 1 C2 deficiency, while their parents were heterozygous with normal complement parameters. For the two brothers, a recommended vaccination program and antibiotic prophylaxis were prescribed. During the long-term follow-up, no severe/invasive infections were observed in either patient. At the age of 16, the younger brother developed progressive hypogammaglobulinemia of all three classes, IgA, IgM and IgG. A next generation sequencing panel excluded the presence of gene defects related to primary antibody deficiencies. Our data show that early diagnosis, use of vaccinations and antibiotic prophylaxis may allow a normal life in hereditary C2 deficiency, which can be characterized using functional and genetic methods. Moreover, a periodical check of immunoglobulin serum levels could be useful to detect a possible hypogammaglobulinemia. Full article

Approximately 10% of all breast cancer (BC) cases are familial and caused by inheritance of mutant BRCA1, BRCA2, or some other genes from the same DNA reparation pathway. Genetic counseling in families with cancer history is a powerful means for early cancer detection and active risk reduction through preventive interventions. This is the first report of the rare inherited BRCA2 frameshift-deletion mutation c.3847_3848delGT in one Lithuanian pedigree with the intense familial history of BC. Three BRCA2-positive blood relatives with BC of different biological types were identified in this pedigree with the same type mutation. All three cases were diagnosed with advanced stage ductal carcinoma. Markedly, polymorphic cells and numerous mitoses were identified in BC from the cases. Two patients from the family were diagnosed with the triple negative tumors, while one case had early onset of the hormone positive BC. Despite the variation in clinical and biological presentation of BC, all cases showed a good response to conventional treatment. In conclusion, the strong influence of BRCA2 mutation on the onset of BC of various biological types reveals the complexity of genetic counselling in families with BC history. Full article

Background and Objectives: This study evaluated the clinical characteristics of the acute coronary syndromes (ACS) in chronic kidney disease (CKD) patients and established prognostic values of the biomarkers and echocardiography. Materials and Methods: 273 patients admitted to the cardiology department of the Clinical County Emergency Hospital of Oradea, Romania, with ACS diagnosis were studied. Two study groups were formed according to the presence of CKD (137 patients with ACS + CKD and 136 with ACS without CKD). Kidney Disease: Improving Global Outcomes (KDIGO) threshold was used to assess the stages of CKD. Results: Data regarding the medical history, laboratory findings, biomarkers, echocardiography, and coronary angiography were analysed for both groups. ACS parameters were represented by ST-segment elevation myocardial infarction (STEMI), which revealed a greater incidence in subjects without CKD (43.88%); non-ST-segment elevation myocardial infarction (NSTEMI), characteristic for the CKD group (28.47%, with statistically significance p = 0.04); unstable angina and myocardial infarction with nonobstructive coronary arteries (MINOCA). Diabetes mellitus, chronic heart failure, previous stroke, and chronic coronary syndrome were more prevalent in the ACS + CKD group (56.93%, p < 0.01; 41.61%, p < 0.01; 18.25%, p < 0.01; 45.26%, p < 0.01). N-terminal pro b-type natriuretic peptide (NT-proBNP) was statistically higher (p < 0.01) in patients with CKD; Killip class 3 was evidenced more frequently in the same group (p < 0.01). Single-vessel coronary artery disease (CAD) was statistically more frequent in the ACS without CKD group (29.41%, p < 0.01) and three-vessel CAD or left main coronary artery disease (LMCA) were found more often in the ACS + CKD group (27.01%, 14.6%). Conclusions: Extension of the CAD in CKD subjects revealed an increased prevalence of the proximal CAD, and the involvement of various coronary arteries is characteristic in these patients. Biomarkers and echocardiographic elements can outline the evolution and outcomes of ACS in CKD patients. Full article

The main arguments in support of researching anxiety and depression in patients with chronic somatic diseases are the prevalence of affective disorders in the population, somatic conditions as risk factors of affective disorders and the search for effective preventative and therapeutic strategies. The aim of the study was to determine the association between the functional status, selected sociodemographic characteristics and prevalence as well as severity of anxiety and depression in patients with multiple sclerosis (MS), Parkinson’s disease (PD) and history of stroke (S). Material and methods: Eighty participants (44 women and 36 men) with MS (n = 22), PD (n = 31) and history of stroke (n = 27) were enrolled. All participants completed a questionnaire consisting of metrics, the Katz Index of Independence in Activities of Daily Living and the Hospital Anxiety and Depression Scale (HADS). Results: Fifty-five per cent of all participants did not present with anxiety or depression, 20% scored above the diagnostic threshold on the anxiety scale and 26% scored above the diagnostic threshold on the depression scale. Subgroup analysis revealed that anxiety and depression sufferers were 13.64% and 13.64% of MS patients, respectively; 22.58% and 35.48% of PD patients, respectively; and 22.22% and 25.93% of stroke survivors, respectively. There was a significant correlation between depression and independence level in the entire group and between depression and marital status in stroke survivors. Conclusions: Although depression and anxiety are highly prevalent in patients with neurological conditions, the disorder has a very individual nature and is not associated with the patient’s age, duration of a condition or concomitant diseases. Screening for depression and anxiety as a part of comprehensive approach may increase treatment efficacy in neurological patients Full article

Background and Objectives: Cirrhosis is a liver disease that causes about one million deaths annually worldwide. The estimated cirrhosis prevalence ranges from 4.5–9.5% in the general population. Up to 40% of cirrhotic patients are asymptomatic and may be diagnosed late. Studies have described the importance of the functions of the liver and autonomic nervous system (ANS) and their relationship. There is limited information available on non-alcoholic cirrhosis and heart rate variability (HRV), which is a measure of the ANS. This study aimed to evaluate cardiac autonomic modulation through HRV in non-alcoholic cirrhosis individuals reported in previous observational and clinical trial studies. Materials and Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement using the Medline, Scopus, and Web of Science electronic databases. Five studies were identified and reviewed. Results: HRV was decreased in patients with non-alcoholic cirrhosis, even in the first stage. Conclusions: HRV could be used as a complementary method to improve both the diagnosis and prognosis of non-alcoholic cirrhosis. Full article

Background and objective: Lyme disease, also known as Lyme borreliosis (LB), is a tick-borne infectious disease caused by the spirochete bacteria Borrelia. The risk of infection depends on the geographical area, ecological factors, and human behavior. Clinical manifestations of Lyme borreliosis have a wide range, but the most frequent clinical symptom, which is also a diagnostic symptom, is a skin rash called erythema migrans (EM). The disease is very common worldwide. In Lithuania, the disease frequency is 99.9 cases per 100,000 population (Centre for Communicable Diseases and AIDS, Lithuania, 2017). The main aim of this study was to obtain the baseline characteristics of the disease regarding the infected Lithuanian population. Materials and Methods: We analyzed data from the Centre for Communicable Diseases and AIDS about all Lyme disease (A69.2) diagnosed patients over a three-year period (from 2014 to 2016) in Lithuania. Results: In 2014–2016, 7424 (crude incidence rate 85.4) cases with LB were diagnosed in Lithuania. Most of them (4633 (62.4%)) were identified in women. Older people were more likely to suffer from LB. Urban residents were 2.6 times more often affected that those living in villages. Tick bites were primarily observed in high season months, from May to September (90%), with the highest peak in July. There was a higher number of observed tick bites (p = 0.003) in the urban residents. Erythema migrans occurred in 75.6% LB cases, while other symptoms did not exceed a quarter of all LB cases. There were 7353 (99.6%) cases where LB was confirmed via clinical symptoms and/or laboratory tests. Also, 1720 (23.2%) patients were tested for LB immunoglobulins. Conclusions: This study found a high incidence of Lyme disease in Lithuania. We elucidated the baseline characteristics regarding the infected Lithuanian population which may ease medical clinicians’ work on new Lyme diagnoses. Full article