Medicina, Volume 55, Issue 6 (June 2019) – 97 articles

Background and Objectives: Electrocautery adenoidectomy (ECA) is a common procedure performed in paediatric otolaryngology. ECA has been preferred over curettage adenoidectomy due to its lower intraoperative bleeding rates, decreased procedure time, and higher subjective success. However, post-ECA symptoms of pain and halitosis have never been studied. The objective of our study was to identify the pattern of post-ECA halitosis and pain in the paediatric population. Materials and Methods: This is a single centre, prospective observational study that uses visual analogue scales (VAS) by parent proxy to assess post-ECA pain and halitosis in paediatric patients (age < 18) in South Australia. A total of 19 patients were enrolled in the study and followed for seven days. Results: Postoperative pain and halitosis reaches a peak 3 days post-ECA (median = 2 for pain; median = 6 for halitosis) but resolves 7 days post-ECA (median = 0 for both). Conclusions: Our study demonstrates that halitosis and pain occur over a seven-day period in patients undergoing ECA and will resolve post-operatively with simple analgesia and without antibiotics. Full article

Background and objectives. Stroke-induced mortality is the third most common cause of death in developed countries. Intense interest has focused on the recurrent ischemic stroke, which rate makes up 30% during first 5 years after first-ever stroke. This work aims to develop criteria for the prediction of acute recurrent cerebral ischemic hemispheric stroke (RCIHS) outcome on the basis of comprehensive baseline clinical, laboratory, and neuroimaging examinations. Materials and Methods. One hundred thirty-six patients (71 males and 65 females, median age 74 (65; 78)) with acute RCIHS were enrolled in the study. All patients underwent a detailed clinical and neurological examination using National Institutes of Health Stroke Scale (NIHSS), computed tomography of the brain, hematological, and biochemical investigations. In order to detect the dependent and independent risk factors of the lethal outcome of the acute period of RCIHS, univariable and multivariable regression analysis were conducted. A receiver operating characteristic (ROC) analysis with the calculation of sensitivity and specificity was performed to determine the prediction variables. Results. Twenty-five patients died. The independent predictors of the lethal outcome of acute RCIHS were: Baseline NIHSS score (OR 95% CІ 1.33 (1.08–1.64), p = 0.0003), septum pellucidum displacement (OR 95% CI 1.53 (1.17–2.00), p = 0.0021), glucose serum level (OR 95% CI 1.28 (1.09–1.50), p = 0.0022), neutrophil-to-lymphocyte ratio (OR 95% CI 1.11 (1.00–1.21), p = 0.0303). The mathematical model, which included these variables was developed and it could determine the prognosis of lethal outcome of the acute RCIHS with an accuracy of 86.8% (AUC = 0.88 ± 0.04 (0.88–0.93), p < 0.0001). Full article

Background and objectives: The aim of our study is to validate the registration of knee arthroplasty revisions in the Lithuanian Arthroplasty Register (LAR) and thus give an indication of the accuracy of the published revision rates. Materials and methods: A total of 4269 primary total knee arthroplasties (TKAs) registered in the LAR between 2013 and 2015 were included. Two years after surgery the patients were contacted by phone in order to inquire if they had been subject to revision. The information from the patients was then cross checked against what had been registered in the LAR, and in case of a revision not having been registered hospital charts were investigated. Thus, the patients were followed up with regarding revision and/or death until 2017. A true revision was defined as an addition, exchange, or removal of one or all components. Results: Out of 4269 primary TKAs, we managed to contact and interview 2769 patients. Nine small hospitals were not able to provide contact details (telephone numbers) for 533 patients (549 knees). Sixty-seven patients (67 knees) were deceased (data from the Lithuanian National Census Register) and a further 438 patients (565 knees) appeared to have a wrong or non-valid telephone number, leaving 3031 (3091 knees) patients being contacted. Of those, 262 patients (266 knees) refused to participate in the study which left 2769 responders (2825 knees). Sixty-one patients said that reoperation had been performed on the index knee within two years of their primary surgery. After checking with the clinics, 10 were surgical procedures on the knee but not true revisions by our criteria. Out of the 51 true revisions we found that 46 were registered to the LAR as revised, while five (9.8%) revisions were missing. Conclusions: We conclude that the Lithuanian Arthroplasty Register has a good completeness of registered revision TKAs as only 9.8% of revisions were missing. Full article

Background and objectives: The purpose of the study is to correlate vascular calcification biomarkers osteoprotegerin (OPG) and 25-hydroxyvitamin D₃ (25-OH-D₃), indicators of arterial stiffness carotid-femoral pulse wave velocity (c-f PWV) and renal resistive index (RRI), with parameters of left ventricular function in heart failure patients versus control. Materials and methods: Our case-control study compared 60 patients with ischemic heart failure and reduced left ventricular ejection fraction (LVEF) (<40%) with a control group of 60 healthy age-matched subjects (CON). Serum levels of OPG and 25-OH-D₃ were determined by ELISA. Left ventricular volumes (LVESV, LVEDV) and LVEF were measured by echocardiography. C-f PWV was determined using the arteriograph device. RRI was measured by duplex Doppler. Peak systolic velocity (PSV) and minimum end-diastolic velocity (EDV) were determined using angle correction. The estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation. The Pearson’s correlation coefficient was used for interpretation of results. Results: OPG values were significantly higher in heart failure (HF) patients vs. CON (4.7 ± 0.25 vs. 1.3 ± 0.67 ng/mL, p < 0.001). 25-OH vitamin D₃ levels were significantly lower in HF patients vs. CON (20.49 ± 7.31 vs. 37.09 ± 4.59 ng/mL, p < 0.001). Multiple regression analysis considering 25-OH D3 as a dependent variable demonstrated indicators of vascular stiffness RRI, c-f PWV and vascular calcification biomarker OPG as predictors. OPG values were significantly correlated with cardiac parameters LVEDV (r = 0.862, p < 0.001), LVEF (r = −0.832, p < 0.001), and c-f PWV(r = 0.833, p < 0.001), and also with 25-OH-D₃ (r = −0.636, p < 0.001). RRI values were significantly correlated with cardiac parameters LVEDV (r = 0.586, p < 0.001) and LVEF (r = −0.587, p < 0.001), and with eGFR (r = −0.488, p < 0.001), c-f PWV(r = 0.640, p < 0.001), and 25-OH-D₃ (r = −0.732, p < 0.001). Conclusions: This study showed significant correlations between vitamin D deficit and vascular stiffness indicators in heart failure patients with reduced ejection fraction, demonstrating the importance of these examinations for a better evaluation of these patients. Together with the evaluation of renal function, the measurement of vascular stiffness indicators and biomarkers might play a key role in identifying patients at greater risk for worsening disease prognosis and for shorter life expectancy, who could benefit from vitamin D supplementation. The abstract was accepted for presentation at the Congress of the European Society of Cardiology, Munich, 2018. Full article

Background and Objectives: Radiation enteritis is a common side effect after radiotherapy for abdominal and pelvic malignancies. The aim of the present study was to investigate the protective effect of melatonin, known for its free radical scavenging ability, against radiotherapy-induced small intestinal oxidative damage. Materials and Methods: Thirty male Wistar rats were randomly assigned to six groups (5 rats in each) as follows: Group I (control group) rats received neither radiation nor melatonin; group II rats received only 8 Gy single dose of gamma radiation to their abdomen and pelvis regions; group III (administered with only 50 mg/kg melatonin); group IV (administered with only 100 mg/kg melatonin); group V (50 mg/kg melatonin + 8 Gy radiation), group VI (100 mg/kg melatonin + 8 Gy radiation). All rats were sacrificed after 5 days for biochemical assessments of their intestinal tissues. Results: Treatment with melatonin post irradiation significantly reduced malondialdehyde (MDA) levels as well as increased both superoxide dismutase (SOD) and catalase (CAT) activities of the irradiated intestinal tissues. In addition, melatonin administration with different doses pre irradiation led to protection of the tissues. Moreover, the 100 mg/kg dose was more effective compared to 50 mg/kg. Conclusions: The results of our study suggest that melatonin has a potent protective effect against radiotherapy-induced intestinal damage, by decreasing oxidative stress and increasing antioxidant enzymes. We recommend future clinical trials for more insights. Full article

Background and objectives: T regulatory lymphocytes (Treg) are one of the subsets of T-lymphocytes involved in the interaction of neoplastic tumors and the host immune system, and they may impair the immune reaction against cancer. It has been shown that Treg are increased in the peripheral blood of patients with various cancers. In colorectal cancer, the prognostic role of Treg remains controversial. Colorectal cancer is a heterogenous disease, with many variations stemming from its primary tumor location. The aim of this study is to analyse the relationship between the amount of Treg in the peripheral blood of patients with left-sided colorectal cancer in various stages of disease and long-term survival. Materials and Methods: A prospective analysis of 94 patients with left-sided colorectal cancer and a group of 21 healthy volunteers was carried out. Treg levels in peripheral blood were analysed using flow cytometry. Results: There was a statistically significant difference between the amount of Treg in the Ist and IInd TNM stages (p = 0.047). The number of Treg in the entire study group was significantly lower than in the control group (p = 0.008) and between patients in stages II and III and the control group (p = 0.003 and p = 0.018). The group of pT3+pT4 patients also had significantly lower Treg counts in their peripheral blood than the control group (p = 0.005). In the entire study group, the level of Treg cells in the peripheral blood had no influence on survival. The analysis of the TNM stage subgroups also showed no difference in survival between patients with “low” and “high” Treg counts. Conclusion: The absolute number of Treg in the peripheral blood of patients with left-sided colorectal cancer was significantly decreased in comparison to healthy controls, especially for patients with stage II+III disease. Treg presence in the peripheral blood had no impact on survival. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide, with approximately 630,000 new cases diagnosed each year. The development of low-cost and non-invasive tools for the detection of HNSCC using volatile organic compounds (VOCs) in the breath could potentially improve patient care. The aim of this study was to investigate the feasibility of selected ion flow tube mass spectrometry (SIFT-MS) technology to identify breath VOCs for the detection of HNSCC. Materials and Methods: Breath samples were obtained from HNSCC patients (N = 23) and healthy volunteers (N = 21). Exhaled alveolar breath samples were collected into FlexFoil^® PLUS (SKC Limited, Dorset, UK) sampling bags from newly diagnosed, histologically confirmed, untreated patients with HNSCC and from non-cancer participants. Breath samples were analyzed by Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) (Syft Technologies, Christchurch, New Zealand) using Selective Ion Mode (SIM) scans that probed for 91 specific VOCs that had been previously reported as breath biomarkers of HNSCC and other malignancies. Results: Of the 91 compounds analyzed, the median concentration of hydrogen cyanide (HCN) was significantly higher in the HNSCC group (2.5 ppb, 1.6–4.4) compared to the non-cancer group (1.1 ppb, 0.9–1.3; Benjamini–Hochberg adjusted p < 0.05). A receiver operating curve (ROC) analysis showed an area under the curve (AUC) of 0.801 (95% CI, 0.65952–0.94296), suggesting moderate accuracy of HCN in distinguishing HNSCC from non-cancer individuals. There were no statistically significant differences in the concentrations of the other compounds of interest that were analyzed. Conclusions: This pilot study demonstrated the feasibility of SIFT-MS technology to identify VOCs for the detection of HNSCC. Full article

Background and objectives: Impacted third molars (ITM) are the most commonly-impacted teeth. There is a risk for ITM to cause a number of pathological conditions, and external root resorption (ERR) of adjacent teeth is one of the most prevalent. Retaining or prophylactic extraction of ITM is a polemic topic. External root resorption of adjacent teeth is one of possible indications for prophylactic removal of ITM. The aim of this study was to assess the relationship between external root resorption (ERR) on the distal aspect of second molars’ roots and positional parameters of ITM. Methods: Cone beam computed tomography scans of 109 patients (41 males, 68 females; mean age 26.4 ± 7.9 years) with 254 ITM (131 in the maxilla and 123 in the mandible) were retrospectively analyzed. Positional parameters of ITM (mesio-distal position, angulation, impaction depth, and available eruption space) were evaluated. The presence, location, and depth of ERR of adjacent second molars were assessed. Results: Analysis showed a relationship between ITM impaction depth, mesial inclination angle, and the presence of ERR. Mesial inclination angle of more than 13.6° increased the odds of ERR occurrence by 5.439 (95% CI, 2.97–9.98). ITM presence at the level of ½ of roots of the adjacent second molar or more apically increased the odds of ERR occurrence by 2.218 (95% CI, 1.215–4.048). No significant correlation was detected between the occurrence of ERR and patient age, gender, or the available eruption space in the mandible. Depth of ERR did not depend on its location. Conclusions: Incidence of ERR in second molars is significantly associated with mesial inclination and a deep position of ITM. Full article

Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a potent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of antioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous melatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley male rats were split into three equal groups and given carbon tetrachloride (CCl₄), 2 g/kg (CCl₄ group) or the same dose of CCl₄ and melatonin, 10 mg/kg (CCl₄/melatonin group) or saline (control group). The effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in serum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in all three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine and thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in serum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations were decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate dehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum: NO₂-by 37.9%; NO₃-by 29.2%. There was no significant difference in content NO₂-in the liver, but concentration of NO₃-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both in serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in serum, nor in liver. The histopathological liver lesions observed in the CCl₄/melatonin group were less severe than those seen in the CCl₄ group. Conclusions: we demonstrated an ameliorating effect of melatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and histopathological lesions in the liver in rats with CCl₄-induced hepatitis. Full article

Psychotherapy with suicidal patients is inherently challenging. Psychodynamic psychotherapy focuses attention on the patient’s internal experience through the creation of a therapeutic space for an open-ended exploration of thoughts, fears, and fantasies as they emerge through interactive dialogue with an empathic therapist. The Boston Suicide Study Group (M.S., M.J.G., E.R., B.H.), has developed an integrative psychodynamic approach to psychotherapy with suicidal patients based on the authors’ extensive clinical work with suicidal patients (over 100 years combined). It is fundamentally psychodynamic in nature, with an emphasis on the therapeutic alliance, unconscious and implicit relational processes, and the power of the therapeutic relationship to facilitate change in a long-term exploratory treatment. It is also integrative, however, drawing extensively on ideas and techniques described in Dialectical Behavioral Therapy (DBT), Mentalization Based Treatment (MBT), Cognitive-Behavioral Therapy (CBT), as well on developmental and social psychology research. This is not meant to be a comprehensive review of psychodynamic treatment of suicidal patients, but rather a description of an integrative approach that synthesizes clinical experience and relevant theoretical contributions from the literature that support the authors’ reasoning. There are ten key aspects of this integrative psychodynamic treatment: 1. Approach to the patient in crisis; 2, instilling hope; 3. a focus on the patient’s internal affective experience; 4. attention to conscious and unconscious beliefs and fantasies; 5. improving affect tolerance; 6. development of narrative identity and modification of "relational scripts"; 7. facilitation of the emergence of the patient’s genuine capacities; 8. improving a sense of continuity and coherence; 9 attention to the therapeutic alliance; 10. attention to countertransference. The elements of treatment are overlapping and not meant to be sequential, but each is discussed separately as an essential aspect of the psychotherapeutic work. This integrative psychodynamic approach is a useful method for suicide prevention as it helps to instill hope, provides relational contact and engages the suicidal patient in a process that leads to positive internal change. The benefits of the psychotherapy go beyond crisis intervention, and include the potential for improved affect tolerance, more fulfilling relational experiences, emergence of previously warded off experience of genuine capacities, and a positive change in narrative identity. Full article

Background and objectives: Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients’ outcome. Materials and Methods: Immunohistochemical analysis of TGF-β1, Smad2, and Smad4 expression was performed on 404 urothelial bladder cancer samples, incorporated in tissue microarrays. Expression status was correlated with clinicopathological and follow-up data. The median follow-up was 61 months. Results: High expression of TGF-β1, Smad2, and Smad4 was detected in 68.1%, 31.7% and 45.2% of the tumors, respectively. TGF-β1 overexpression was significantly associated with high tumor grade, and advanced pathologic stage (p < 0.001, respectively). Conversely, high Smad2 and Smad4 expression was linked to low tumor grade (p = 0,003, p = 0.048, respectively), and low tumor stage (p < 0.001, p = 0.003, respectively). Smad2 showed an inverse correlation with variant morphology and divergent differentiation of urothelial tumors (p = 0.014). High TGF-β1 correlated directly, while Smad2 and Smad4 correlated inversely to cancer-specific death (p = 0.043, p = 0.003, and p = 0.022, respectively). There was a strong relationship between Smad2 and Smad4 expression (p < 0.001). Survival analyses showed that high Smad2 and Smad4 expression was associated with longer overall survival (p = 0.003, p = 0.034, respectively), while in multivariate regression analysis TGF-β1 manifested as an independent predictor of poor outcome. Conclusions: Unraveling the complex roles and significance of TGF-β signaling in urothelial bladder cancer might have important implications for therapy of this disease. Assessment of TGF-β pathway status in patients with urothelial bladder cancer may provide useful prognostic information, and identify patients that could have the most benefit from therapy targeting TGF-β signaling cascade. Full article

Background and Objectives: Teeth decay and plaque are complicated problems created by oral pathogens. Tecoma stans (L.) and Cassia javanica (L.) are two ornamental evergreen plants widely distributed in Egypt. These plants are traditionally used for oral hygienic purposes. This study aims to elucidate the volatile oil constituents obtained from the flowers of these plants and evaluate the antimicrobial activity of these volatile oils against specific oral pathogens in comparison to chlorhexidine. Materials and Methods: The flowers obtained from both plants were extracted by n-hexane. GC-MS spectrometry was used to identify the constituents. Minimum inhibitory concentrations (MICs) were measured using tetrazolium salt (2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) (XTT). Results: GC-MS analysis revealed the presence of 32 and 29 compounds, representing 100% of the volatile constituents of Tecoma stans and Cassia javanica, respectively. The GC-MS analysis showed more than 60% of the volatile oil constituents are represented in both plants with different proportions. Chlorhexidine exerted stronger activity than tested plants against all microorganisms. Cassia javanica flower extract was more active against all tested microorganisms than Tecoma stans. Of note was the effect on Streptococcus mutans, which was inhibited by 100% at 12.5 and 25 µg/mL of Cassia javanica and Tecoma stans, respectively. The growth of Lactobacillus acidophilus was also completely inhibited by 25 µg/mL of the Cassia javanica extract. MIC90 and MIC were also calculated, which revealed the superiority of Cassia javanica over Tecoma stans against all tested oral pathogens. Conclusion: Cassia javanica flower volatile oils showed a potential anti-oral pathogen activity at relatively low concentrations. Also, Cassia javanica and Tecoma stans demonstrated a strong activity against tooth decay’s notorious bacteria Streptococcus mutans. Both plants can be potential substituents to chlorhexidine. Formulating the constituents of these plants in toothpastes and mouthwashes as anti-oral pathogen preparations can be an interesting future plan. Full article

Background and objectives: Gastric cancer (GC) is one of the deadliest malignancies, with the underlying pathophysiological mechanisms still not completely understood. In this study, we aimed to investigate the signal transducer and activator of transcription 3 (STAT3) moleculeconnection with the pathological features of GCs, and the expression of cell adhesive molecules (E-cadherin and β-catenin) and angiogenesis-related factors (vascular endothelial growth factor (VEGF), HIF1α, and CD31)). Materials and Methods: This study comprised 136 cases of GCs with data related to the patients’ demographic characteristics (age, gender) and pathological features (tumor location, gross type, Laurens’ type of GC, histological differentiation, invasion depth, lymphovascular invasion and the presence of metastases) which were correlated with STAT3 expression. Additionally, STAT3 expression and the expression of adhesive molecules and angiogenesis-related factors were studied by immunohistochemical methods. Results: The expression of STAT3 was found to be significantly associated with the occurrence of poorly differentiated GCs in the lower portion of the stomach and with the presence of distant metastases. Interestingly, none of the investigated parameters related to cell adhesion or to angiogenesis were found to be related to the expression of STAT3. Conclusions: The lack of significant differences between the studied STAT3 expression and some of the molecules associated with different cancer features might be due to the characteristics of the studied population sample associated with the origin, heterogeneity, and cancer pathophysiological background. Nonetheless, the results of our study suggest that STAT3 could be a useful marker for the presence of distant GC metastases, which further indicates that STAT3 action might involve some other signaling molecules/pathways that warrant further elucidation. Full article

The concepts underlying hypertrophic cardiomyopathy (HCM) pathogenesis have evolved greatly over the last 60 years since the pioneering work of the British pathologist Donald Teare, presenting the autopsy findings of “asymmetric hypertrophy of the heart in young adults”. Advances in human genome analysis and cardiac imaging techniques have enriched our understanding of the complex architecture of the malady and shaped the way we perceive the illness continuum. Presently, HCM is acknowledged as “a disease of the sarcomere”, where the relationship between genotype and phenotype is not straightforward but subject to various genetic and nongenetic influences. The focus of this review is to discuss key aspects related to molecular mechanisms and imaging aspects that have prompted genotype–phenotype correlations, which will hopefully empower patient-tailored health interventions. Full article

Background and Objectives: Several studies inspected the impact of P2X7 polymorphisms on individual susceptibility to tuberculosis (TB), but the findings are still controversial and inconclusive. To achieve a more precise estimation, we conducted a meta-analysis of all eligible studies on the association between P2X7 polymorphisms and TB risk. Materials and Methods: Relevant studies were identified by searching the PubMed, Web of Science, Scopus and Google scholar databases up to November 2018. Twenty-four full-text articles were included in our meta-analysis. The strength of association between P2X7 polymorphisms and TB risk was evaluated by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models. Results: The findings of this meta-analysis revealed that the rs3751143 variant significantly increased the risk of TB in heterozygous codominant (OR = 1.44, 95%CI = 1.17–1.78, p = 0.0006, AC vs. AA), homozygous codominant (OR = 1.87, 95% CI = 1.40–2.49, p = 0.0004, CC vs. AA), dominant (OR = 1.50, 95% CI = 1.22–1.85, p = 0.0002, AC + CC vs. AA), recessive (OR = 1.61, 95% CI = 1.25–2.07, p = 0.001, CC vs. AC + AA), and allele (OR = 1.41, 95% CI = 1.19–1.67, p < 0.0001, C vs. A) genetic models. Stratified analysis showed that rs3751143 increased the risk of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in all genetic models. Furthermore, the rs3751143 increased risk of TB in the Asian population. The findings did not support an association between the rs2393799, rs1718119, rs208294, rs7958311, and rs2230911 polymorphisms of P2X7 and TB risk. Conclusions: The findings of this meta-analysis suggest that P2X7 rs3751143 polymorphism may play a role in susceptibility to TB in the Asian population. More well-designed studies are required to elucidate the exact role of P2X7 polymorphisms on TB development. Full article

Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure. Full article

Several researchers have analyzed the alterations of the methionine cycle associated with liver disease to clarify the pathogenesis of human hepatocellular carcinoma (HCC) and improve the preventive and the therapeutic approaches to this tumor. Different alterations of the methionine cycle leading to a decrease of S-adenosylmethionine (SAM) occur in hepatitis, liver steatosis, liver cirrhosis, and HCC. The reproduction of these changes in MAT1A-KO mice, prone to develop hepatitis and HCC, demonstrates the pathogenetic role of MAT1A gene under-regulation associated with up-regulation of the MAT2A gene (MAT1A:MAT2A switch), encoding the SAM synthesizing enzymes, methyladenosyltransferase I/III (MATI/III) and methyladenosyltransferase II (MATII), respectively. This leads to a rise of MATII, inhibited by the reaction product, with a consequent decrease of SAM synthesis. Attempts to increase the SAM pool by injecting exogenous SAM have beneficial effects in experimental alcoholic and non-alcoholic steatohepatitis and hepatocarcinogenesis. Mechanisms involved in hepatocarcinogenesis inhibition by SAM include: (1) antioxidative effects due to inhibition of nitric oxide (NO•) production, a rise in reduced glutathione (GSH) synthesis, stabilization of the DNA repair protein Apurinic/Apyrimidinic Endonuclease 1 (APEX1); (2) inhibition of c-myc, H-ras, and K-ras expression, prevention of NF-kB activation, and induction of overexpression of the oncosuppressor PP2A gene; (3) an increase in expression of the ERK inhibitor DUSP1; (4) inhibition of PI3K/AKT expression and down-regulation of C/EBPα and UCA1 gene transcripts; (5) blocking LKB1/AMPK activation; (6) DNA and protein methylation. Different clinical trials have documented curative effects of SAM in alcoholic liver disease. Furthermore, SAM enhances the IFN-α antiviral activity and protects against hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic hepatitis B virus (HBV) infection. However, although SAM prevents experimental tumors, it is not curative against already established experimental and human HCCs. The recent observation that the inhibition of MAT2A and MAT2B expression by miRNAs leads to a rise of endogenous SAM and strong inhibition of cancer cell growth could open new perspectives to the treatment of HCC. Full article

Background and objective: Changing to a different spirometry reference equation can result in misinterpretation of spirometric findings. Currently, there is limited data about any discordance between the interpretations of airway obstruction (AO) using the Global Lungs Initiative (GLI) 2012 and the currently employed Thai reference equations (Siriraj) in Thai adults. Therefore, this study aimed to determine differences in diagnosis around AO and classification of the severity of AO using the GLI2012 and Siriraj reference equations in Thai adults. Materials and Methods: We analyzed spirometric results from Thai adults aged 40–80 years old (n = 2084), which were collected at the Lung Health Center, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand between January 2005 and December 2015. The diagnoses concerning the AO were interpreted using the GLI2012 and Siriraj reference equations. The severity of AO in each case was classified into five grades, including mild, moderate, moderately severe, severe, or very severe. McNemar’s test was used to analyze differences in diagnosis of AO and classification of the level of severity. The Kappa statistic was used to determine agreements of diagnosis of AO and classification of severity between the two reference equations. Results: There were significant differences in both diagnosis of AO and their classifying severity level between the two reference equations (p-value < 0.001). However, the levels of agreement between the two reference equations were moderate to very good in different age and sex groups (Kappa values ranged from 0.62 to 0.78 for the diagnosis of AO and 0.54 to 0.89 for the classification of severity). Conclusions: Changing from the Siriraj to the GLI2012 reference equations underestimates the proportion of airway obstruction in Thai adults. Full article

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around −36 mV, and entrapment efficiency of around 60%. The in vitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for in vitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC). Full article

Background and Objective: During the last few years, a trend has been noted towards embryos being transferred at the blastocyst stage, which has been associated with improved rates regarding implantation and clinical pregnancy in comparison to cleavage stage embryo transfers. There is a limited number of studies investigating this notion in oocyte donation cycles employing cryopreserved embryos. The aim of this study is to evaluate the implantation potential and clinical pregnancy rates between the day 3 cleavage stage and blastocyst stage embryo transfers in oocyte donation cycles employing vitrified embryos. Methods: This is a retrospective evaluation of oocyte donation frozen–thawed transfers completed in our clinic from January 2017 to December 2017. Intracytoplasmic sperm injection was conducted for all oocytes. Following fertilization, all embryos were cryopreserved either at the cleavage or blastocyst stage. Embryo transfer of two embryos was performed under direct sonographic guidance in all cases. Results: Our results confirmed a 55.6% clinical pregnancy (CP) resulting from day 3 embryo transfers, a 68.8% CP from day 5, and 71.4% CP from day 6. Significantly improved pregnancy rates were related to embryo transfers at the blastocyst stage when compared to cleavage stage transfers (68.9% and 55.6% respectively, p = 0.016). The risk with regards to multiple pregnancies was similar. Conclusion: Our findings indicate that in oocyte donation cycles employing vitrified embryos, embryo transfer at the blastocyst stage is accompanied with a significant improvement in pregnancy rates and merits further investigation. Full article

Infective endocarditis is a serious condition, which is associated with high mortality in elderly patients. Gemella haemolysans (GH) is a microorganism from the Streptococcus family, rarely involved in infective endocarditis. Here, we present a case of Gemella haemolysans endocarditis in an 86-year-old patient, successfully treated by antibiotics and surgery following a pre-treatment comprehensive geriatric assessment (CGA). This case is discussed in the context of a review of all published cases of Gemella haemolysans endocarditis. We illustrate the benefit of a systematic pre-treatment comprehensive geriatric assessment in elderly patients with infective endocarditis. Full article

Background and objectives: Adipose tissue and skeletal muscle secrete adiponectin, a hormone abundantly secreted by adipocytes, that through the adiponectin receptor, regulate glucose and lipid metabolism. Adiponectin appears to protect skeletal muscles from inflammatory damage induced by oxidative stress. It has been suggested that decreased adiponectin levels could be associated with pathologic conditions, including obesity and diabetes. Furthermore, some studies suggest that exercise could have a beneficial effect by increasing adiponectin levels, but this observation remains controversial. It is also unknown if physical exercise modifies adiponectin expression in skeletal muscles. The aim of this study was to investigate the effect of chronic exercise on serum adiponectin and adiponectin expression in slow-twitch (soleus) and fast-twitch (plantaris) muscles in healthy rats. Materials and methods: Two-month-old male Wistar rats were randomly divided into three groups with n = 6 in each group: control (C), moderate-intensity training (MIT), and high-intensity training (HIT). The rats were conditioned to run on a treadmill for the 8-week period. Forty-eight hours after the last session, blood samples were collected for adiponectin measurements and total RNA was isolated from plantaris and soleus muscles to measure by RT-qPCR adiponectin receptor 1 and adiponectin mRNA expression level. Results: MIT and HIT groups had reduced adiponectin protein levels in serum and the plantaris muscle, but not changes in adiponectin protein were observed in the soleus muscle. No significant differences in Adiponectin receptor 1 (AdipoR1) gene expression were observed following intense or moderate exercise in either muscle group studied. Conclusions: Our study shows that decreasing levels of circulating adiponectin is a result of physical exercise and should not be generalized as a predictive marker of disease. Full article

Background and Objectives: In general, patients with rheumatoid arthritis (RA) are ignorant of the physician’s role and of RA-related feet problems. The aim of our study was to validate a questionnaire on the knowledge of different aspects of overall foot health in patients with RA. Materials and Methods: A cross-sectional descriptive analysis was carried out between March 2017 and April 2017. A questionnaire was designed and validated through the Delphi method to evaluate the knowledge about the illness, the repercussions on feet, medical podiatry care, and the role of the medical podiatrist. Results: After being checked by a panel of experts, all the items obtained a Cronbach’s alpha over 0.70. Conclusions: The content of this questionnaire about the knowledge of different aspects of medical podiatry health in patients with RA has internal consistency. Full article

Background and Objectives: Bacterial urinary tract infection (UTI) is the most common ailment affecting all age groups in males and females. The commercial antibiotics usage augments antibiotics resistance and creates higher recurrence rates of such communal infections. Hence, this study is aimed at investigating the antibacterial and antioxidant potentials of 15 common spices against 11 UTI-causing bacterial pathogens. Materials and Methods: The antioxidant potential of the methanolic extracts was analyzed as contents of total phenols and flavonoids; radical scavenging, total reducing power, the ferric reducing power assay. Urinary pathogens were subjected to spice extracts to investigate antibacterial assays. Results: Preliminary phytochemical study of spices was performed to find those containing alkaloids, flavonoids, phenolic compounds, and steroids that can be recognized for their noteworthy bactericidal effects. The outcome of the antioxidative potential from the four methods demonstrated the sequence of potent antioxidant activity: Acorus calamus > Alpinia galanga > Armoracia rusticana > Capparis spinosa > Aframomum melegueta. The total polyphenols and flavonoids in the studied species positively correlated with their antioxidant properties. The four most effective spices (A. calamus, A. galanga, A. rusticana, and C. spinosa) had a zone of inhibition of at least 22 mm. A. calamus, A. melegueta, and C. spinosa had the lowest minimum inhibitory concentration (MIC) value against Enterobacter aerogenes, Staphylococcus aureus and Proteus mirabilis. All 15 spices had the lowest minimum bactericidal concentration (MBC) value against most of the pathogenic bacteria. Conclusion: The four highly potent and unique spices noted for the in vitro control of UTI-causing pathogens could be pursued further in the development of complementary and alternative medicine against UTI-causing pathogens. Full article

Background and objectives: Boxing is a popular combat sport that requires high intensity and cooperation. However, there are limited data about the influence of boxing matches on blood parameters. The purpose of the present study was to investigate the match-induced changes in the metabolic, hormonal, and inflammatory status in male elite boxers. Materials and methods: High-level 20 male boxers with more than 5 years experience in boxing voluntarily participated in this study. Venous blood samples of the boxers, before and after combat, were taken for determination of the plasma parameters. Results: Our results indicated that a 9-min boxing match caused significant increases in plasma energy fuels (glucose and lactate), metabolic hormones (insulin, adrenocorticotropic hormone (ACTH), cortisol, and growth hormone), inflammatory markers (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α)), muscle damage indicators (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), and oxidative stress marker (SOD). A decrease in total oxidant status (TOS) was also considered. However, there were no significant alterations in the plasma levels of androgenic hormone (free and total testosterone), anabolic hormone (IGF-1), lipids (total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)), kidney function markers (creatinine and urea), and minerals (iron (Fe) and magnesium (Mg)). Conclusion: Elevations in the level of energy fuels and metabolic hormones of the boxers could be taken as a reflection of high-energy turnover during combat performance. The increases in inflammatory and tissue damage indicators may possibly be an indication of traumatic injury. Understanding the biochemical changes that occur during boxing match could be valuable to optimize the performance improvement of the athletes. Full article

Background and objective: We investigated the ability of preoperative serum values of red blood cell distribution width (RDW), neutrophil lymphocyte ratio (NLR) and plateletcrit (PCT) to predict Fuhrman grades (FG) and tumor stages of renal cell carcinoma in patients who underwent radical nephrectomy. Materials and methods: Records of 283 patients that underwent radical or partial nephrectomy of renal masses at our clinic between January 2010 and April 2018, whose pathology results indicated renal cell carcinoma (RCC), and who had their FG and T1–4 N0M0 identified were retrospectively evaluated. The patients were divided into two groups based on their FG as low (I–II) and high (III–IV) and their T stages were similarly grouped as limited to kidney (pT1–pT2) and not limited to kidney (pT3–pT4). Results: Mean RDW, NLR, PCT cut-off values of the patients for FG and T stage were 15.65%, 3.54, 0.28% and 14.35%, 2.69, 0.28%, respectively. The RDW and NLR were determined to be statistically significant predictors of a pathologically high FG, whereas the PCT value was not a statistically significant predictor of high FG (p = 0.003, p = 0.006, p = 0.075, respectively). The relationship of RDW, NLR and PCT values with a limited to the kidney pathological T stage revealed statistically significant correlations for all three values. Conclusions: We determined that only RDW and NLR were markers predicting FG, while PCT had no prognostic value. On the other hand, all three of these values were associated with a limited to the kidney pathological T stage in patients who underwent nephrectomy due to renal masses and whose pathologies suggested RCC. Full article

Background and objective: The assessment of physical fitness has become a necessary issue in epidemiological studies, since a reduction in fitness is directly associated with early mortality. Therefore, the development of simple, accurate, and inexpensive methods is necessary to measure physical fitness. This study aimed to determine the reliability and validity of the criteria and constructs of the International Fitness Scale (IFIS), Portuguese version, in Brazilian pediatric populations. Methods: A total of 190 children aged 3–10 years and 110 adolescents aged 11–17 years were enrolled in an observational study of reliability and validity. For reliability, the participants completed a questionnaire twice (with an interval of 15 days). To test the criterion validity, we analyzed the agreement between the questionnaire and physical tests (20-m shuttle run test, handgrip strength, standing long jump tests, 4 × 10-m shuttle run test, and back-saver sit and reach test), and the construct validity was estimated by agreement between the questionnaire and high blood pressure. The reliability was analyzed by kappa coefficients. The agreement between the testing and retesting of the questionnaire was evaluated by kappa coefficients. We applied a 2 × 2 table to estimate the specificity, sensitivity, and accuracy of the questionnaire. Results: The mean age of the children was 6.7 years (n = 190), and for the adolescents it was 14.6 years (n = 110). The questionnaire reliability showed an almost perfect score (κ ≥ 0.93 in children and κ ≥ 0.88 in adolescents). The questionnaire showed moderate criterion validity (κ ≥ 0.40 in children and adolescents) as well as moderate construct validity (κ ≥ 0.40) in the components of general conditioning, cardiorespiratory capacity, muscular strength, and speed/agility in children and in the components of cardiorespiratory capacity, muscle strength, and speed/agility in adolescents. The questionnaire was a sensitive method for measuring physical fitness. Conclusions: The Portuguese version of the IFIS is a reliable and valid method for measuring physical fitness in pediatric populations. Full article

Background and objectives: Urinary tract infections (UTIs) are the third most common infections in humans, representing a significant factor of morbidity, both among outpatients and inpatients. The pathogenic role of Citrobacter, Enterobacter, and Serratia species (CES bacteria) has been described in UTIs. CES bacteria present a therapeutic challenge due to the various intrinsic and acquired resistance mechanisms they possess. Materials and Methods: The aim of this study was to assess and compare the resistance trends and epidemiology of CES pathogens in UTIs (RECESUTI) in inpatients and outpatients during a 10-year study period. To evaluate the resistance trends of isolated strains, several antibiotics were chosen as indicator drugs based on local utilization data. 578 CES isolates were obtained from inpatients and 554 from outpatients, representing 2.57 ± 0.41% of all positive urine samples for outpatients and 3.02 ± 0.40% for inpatients. E. cloacae was the most prevalent species. Results: The ratio of resistant strains to most of the indicator drugs was higher in the inpatient group and lower in the second half of the study period. ESBL-producing isolates were detected in 0–9.75% from outpatient and 0–29.09% from inpatient samples. Conclusions: Resistance developments of CES bacteria, coupled with their intrinsic non-susceptibility to several antibiotics, severely limits the number of therapeutic alternatives, especially for outpatients. Full article

Asthma is one of the most important medical and social problems of our time due to the prevalence and the complexity of its treatment. Chronic inflammation that is characteristic of asthma is accompanied by bronchial obstruction, which involves various lipid mediators produced from n-6 and n-3 polyunsaturated fatty acids (PUFAs). The review is devoted to modern ideas about the PUFA metabolites—eicosanoids (leukotrienes, prostaglandins, thromboxanes) and specialized pro-resolving lipid mediators (SPMs) maresins, lipoxins, resolvins, protectins. The latest advances in clinical lipidomics for identifying and disclosing the mechanism of synthesis and the biological action of SPMs have been given. The current views on the peculiarities of the inflammatory reaction in asthma and the role of highly specialized metabolites of arachidonic, eicosapentaenoic and docosahexaenoic acids in this process have been described. The possibility of using SPMs as therapeutic agents aimed at controlling the resolution of inflammation in asthma is discussed. Full article

Regarding cancer as a genetic multi-factorial disease, a number of aspects need to be investigated and analyzed in terms of cancer’s predisposition, development and prognosis. One of these multi-dimensional factors, which has gained increased attention in the oncological field due to its unelucidated role in risk assessment for cancer, is diet. Moreover, as studies advance, a clearer connection between diet and the molecular alteration of patients is becoming identifiable and quantifiable, thereby replacing the old general view associating specific phenotypical changes with the differential intake of nutrients. Respectively, there are two major fields concentrated on the interrelation between genome and diet: nutrigenetics and nutrigenomics. Nutrigenetics studies the effects of nutrition at the gene level, whereas nutrigenomics studies the effect of nutrients on genome and transcriptome patterns. By precisely evaluating the interaction between the genomic profile of patients and their nutrient intake, it is possible to envision a concept of personalized medicine encompassing nutrition and health care. The list of nutrients that could have an inhibitory effect on cancer development is quite extensive, with evidence in the scientific literature. The administration of these nutrients showed significant results in vitro and in vivo regarding cancer inhibition, although more studies regarding administration in effective doses in actual patients need to be done. Full article