Survivin gene promoter polymorphism -31G/C as a risk factor for keratocystic odontogenic tumor development

Several single nucleotide polymorphisms in survivin gene promoters, notably -31G/C, have been shown to modulate the expression and activity of the survivin protein. Consequently, the -31G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The aim of this study was to investigate a possible association between the -31G/C polymorphism and the risk for keratocystic odontogenic tumor (KCOT) development. DNA from 52 biopsy specimens of KCOTs and from 82 buccal swabs of healthy individuals was subjected to PCR restriction fragment length polymorphism analysis to identify individual genotypes. The distribution of genotypes in KCOT and control groups, respectively, was: GG: 30 (57.7%) vs. 26 (31.7%); CG: 17 (32.7%) vs. 45 (54.9%); and CC: 5 (9.6%) vs. 11 (13.4%), respectively. These differences were statistically significant. The G allele was more common in the KCOT group than in the control group: 76 (74%) vs. 96 (59%), respectively. Logistic regression analysis showed that GC heterozygotes had a considerably decreased susceptibility for KCOTs compared with GG homozygotes. The same was true for GC+CC vs. GG. The GG genotype of the -31G/C polymorphism might be a risk factor for KCOT development.     

Analysis of granulysin-mediated cytotoxicity in peripheral blood of patients with psoriatic arthritis

The objective of the present study was to investigate possible changes in granulysin (GNLY)-mediated cytotoxicity of peripheral blood lymphocytes in psoriatic arthritis (PsA) patients with respect to different phases of the disease. We prospectively enrolled 25 PsA patients in the active phase, 26 PsA patients in remission and 24 healthy controls. The simultaneous detection of intracellular GNLY and cell surface antigens (CD3 and CD56) was performed with flow cytometry. GNLY apoptotic protein was visualised by immunocytochemistry. Natural killer (NK) cell cytotoxicity was analysed with a cytotoxicity assay against human erythroleukaemia K-562 cells. The percentage of GNLY(+) cells did not differ significantly between PsA patients in the acute phase and those in remission; however, it was always higher than in healthy examinees due to the increased percentage of GNLY(+) cells within T cells, NKT cells, and both, and in the CD56(+dim) and CD56(+bright) NK subsets. The mean fluorescence intensity for GNLY was higher in all lymphocyte subpopulations in the acute phase than in remission and in healthy controls. Accordingly, GNLY-mediated NK cell cytotoxicity against K-562 cells of active phase PsA patients was significantly higher than that in patients in remission or in healthy controls. These findings demonstrated the involvement of GNLY in the worsening of PsA and suggested that GNLY mediated the development of joint lesions.     

Prediction of a Good Response to Cardiac Resynchronization Therapy in Patients with Severe Dilated Cardyomyopathy: Could Conventional Echocardiography Be the Answer after All?

Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m² (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275)     

Efficient biodegradation of petroleum n-alkanes and polycyclic aromatic hydrocarbons by polyextremophilic Pseudomonas aeruginosa san ai with multidegradative capacity

Pseudomonas aeruginosa san ai, an alkaliphilic, metallotolerant bacterium, degraded individual selected petroleum compounds, i.e., n-alkanes (n-hexadecane, n-nonadecane) and polycyclic aromatic hydrocarbons (fluorene, phenanthrene, pyrene) with efficiency of 80%, 98%, 96%, 50% and 41%, respectively, at initial concentrations of 20 mg L⁻¹ and in seven days. P. aeruginosa san ai showed a high biodegradative capacity on complex hydrocarbon mixtures, the aliphatic and aromatic fractions from crude oil. The efficiency of P. aeruginosa san ai degradation of crude oil fractions in seven days reached stage 3–4 of the oil biodegradation scale, which ranges from 0 (no biodegradation) to 10 (maximum biodegradation). Identified metabolites concomitant with genomic and enzymatic data indicated the terminal oxidation pathway for the n-alkane degradation, and the salicylate and phthalate pathways for fluorene biodegradation. Polyextremophilic P. aeruginosa san ai, as a biosurfactant producer with multidegradative capacity for hydrocarbons, can be used in an improved strategy for environmental bioremediation of hydrocarbon-contaminated sites, including extreme habitats characterized by low or elevated temperatures, acidic or alkaline pH or high concentrations of heavy metals.

Pseudomonas aeruginosa san ai degraded individual selected petroleum compounds: n-hexadecane, n-nonadecane, fluorene, phenanthrene, and pyrene with high efficiency, at initial concentrations of 20 mg L⁻¹ and in seven days.     

Oxidative stress in schizophrenia patients treated with long-acting haloperidol decanoate

In this study the role of oxidative stress in schizophrenia was investigated by evaluating the relationship of oxidative stress markers with neurochemistry, psychopathology, and extrapyramidal symptoms. Antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and concentrations of malondialdehyde, protein carbonyls, nitrite, nitrate, glutathione, dopamine, noradrenaline, adrenaline, and serotonin were measured in 52 outpatients with DSM-IV diagnosis of schizophrenia treated with haloperidol decanoate. Psychopathology and extrapyramidal symptoms were assessed by positive and negative syndrome scale, global assessment of functioning, abnormal involuntary movement scale, Simpson Angus scale, and Barnes akathisia rating scale. Haloperidol dose was positively correlated with plasma protein carbonyls. Longer duration of illness was associated with decreased levels of glutathione peroxidase. Increased activity of superoxide dismutase was associated with increased levels of catalase, glutathione peroxidase, glutathione reductase and reduced glutathione, and decreased concentration of malondialdehyde, indicating joint action of various antioxidative systems. Increased levels of nitrite and noradrenaline were associated with decreased level of malondialdehyde. Akathisia was greater in patients with decreased catalase activity, indicating involvement of impaired antioxidant defense in developing extrapyramidal symptoms. These results confirm the hypothesis that oxidative stress is involved in pathophysiology of schizophrenia and severity of extrapyramidal symptoms.     

Circular and linear: a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells

It is a challenge to select the right target to treat conditions without affecting non-diseased cells. Cancer belongs to the top 10 causes of death in the world and it remains difficult to treat. Amongst cancer emerging targets, silent information regulator 1 (SIRT1) – a histone deacetylase – has shown many roles in cancer, ageing and metabolism. Here we report novel SIRT1 ligands that bind and modulate the activity of SIRT1 within cells and enhance its enzymatic activity. We developed a modified aptamer capable of binding to and forming a complex with SIRT1. Our ligands are aptamers, they can be made of DNA or RNA oligonucleotides, their binding domain can recognise a target with very high affinity and specificity. We used the systematic evolution of ligands by exponential enrichment (SELEX) technique to develop circular and linear aptamers selectively binding to SIRT1. Cellular consequences of the interaction were monitored by fluorescence microscopy, cell viability assay, stability and enzymatic assays. Our results indicate that from our pool of aptamers, circular AC3 penetrates cancerous cells and is recruited to modulate the SIRT1 activity. This modulation of SIRT1 resulted in anticancer activity on different cancer cell lines. Furthermore, this modified aptamer showed no toxicity on one non-cancerous cell line and was stable in human plasma. We have demonstrated that aptamers are efficient tools for localisation of internal cell targets, and in this particular case, anticancer activity through modulation of SIRT1.

We report novel SIRT1 ligands that bind and modulate the activity of SIRT1 within cells and enhance its enzymatic activity. From a pool of aptamers we identify circular AC3 as having anticancer activity.     

Validation of flavonoids as potential dipeptidyl peptidase III inhibitors: Experimental and computational approach

Fifteen flavonoids were studied for their inhibitory activity against human dipeptidyl peptidase III (hDPP III) combining an in vitro assay with an in silico molecular modeling study. All analyzed flavonoids showed inhibitory effects against hDPP III with the IC₅₀ values ranging from 22.0 to 437.2 μm . Our 3D QSAR studies indicate that the presence of hydrophilic regions at a flavonoid molecule increases its inhibitory activity, while the higher percentage of hydrophobic surfaces has negative impact on enzyme inhibition. Furthermore, molecular dynamics (MD) simulations of the complex of hDPP III with one of the most potent inhibitors, luteolin, were performed, and binding mode analysis revealed that the 3′ and 4′ hydroxyl group on B‐ring as well as 5 and 7 hydroxyl group on A‐ring helps luteolin to interact with the Asn391, Asn406, Tyr417, His450, Glu451, Val447, Glu512, Asn545, Gln566, and Arg572 residues. The MD results clearly provide valuable information explaining the importance of flavonoid hydroxyl groups in the mechanism for the binding pattern at the active site of hDPP III.     

Prevalence and Factors Associated with Depression,Anxiety and Stress in IBD Patients Undergoing Intravenous Biological Therapy during the COVID-19 Pandemic-Montenegro Experience

Throughout its duration, the coronavirus disease 2019 (COVID-19) pandemic has been affecting lives worldwide and has had a sizeable impact on mental health, particularly for those who already suffer from a chronic illnesses. Depression, Anxiety and Stress (DAS) are common psychiatric comorbidities in inflammatory bowel disease (IBD) patients. This study aims to determine the prevalence and risk factors for moderate and severe symptoms of DAS in IBD patients have been undergoing intravenous biological therapy (IvBTh) during the COVID-19 pandemic. The study was conducted between September 1^st and November 30^th, 2020 at the Clinical Center of Montenegro-IBD unit, where all patients from Montenegro received the registered IvBTh. This case control study consists of 94 IBD patients that completed a validated questionnaire Depression, Anxiety and Stress Score-21 (DASS-21). A total of 59 patients received tumor necrosis factor alpha inhibitors (anti-TNF therapy), while 35 received anti-integrin therapy. After we calculated the DASS-21 score, we divided the patients into two groups: those who had moderate and severe symptoms (if they had any of the mentioned DASS-21 subscale score above limit for moderate or more severe symptoms: DASS-21 Depression, higher than 14; DASS-21 Anxiety, higher than 10 and DASS-21 Stress, higher than 19) and those who did not have significant symptoms (DASS-21 subscale score did not exceed the limit). We also examined demographic data, data on IBD characteristics and COVID-19 data and their impact on mental disorders. Standard statistical processing tests were used to identify risk factors for examined mental disorders. Following the DASS-21 criteria, we diagnosed the least moderate depression in 19.1%, anxiety in 14.9% and stress in 20.2% patients. The multivariate analysis indicated there to be a statistically significant relation of being higher at risk of developing depression, anxiety and stress when suffering from an active form of IBD (OR 6.487; 95% Cl 1.220–34.500, P = 0.028). Almost one third (30.9%) of patients have at least one of the examined mental disorders during the COVID-19 pandemic. Particular attention and efforts must be better focused on patients who suffer from an active form of IBD during the ongoing COVID-19 pandemic.     

An early shoulder repositioning program in birth-related brachial plexus injury: a pilot study of the Sup-ER protocol

Background

Birth-related brachial plexus injury (BRBPI) occurs in 1.2/1,000 births in British Columbia. Even in children with “good” recovery, external rotation (ER) and supination (Sup) are often weaker, and permanent skeletal imbalance ensues. A preventive early infant shoulder passive repositioning program was created using primarily a novel custom splint holding the affected arm in full ER and Sup: the Sup-ER splint. The details of the splint and the shoulder repositioning program evolved with experience over several years. This study reviews the first 4 years.

Methods

A retrospective review of BCCH patients managed with the Sup-ER protocol from 2008 to 2011 compared their recovery scores to matched historical controls selected from our database by two independent reviewers.

Results

The protocol was initiated in 18 children during the study period. Six were excluded due to the following: insufficient data points, non-compliance, late splint initiation, and loss to follow-up. Of the 12 matches, the Sup-ER group final score at 2 years was better than controls by 1.18 active movement scale (AMS) points (p = 0.036) in Sup and 0.96 AMS points in ER (but not statistically significant (p = 0.13)). Unexpectedly, but importantly, during the study period, zero subjects were assessed to have the active functional criteria to indicate brachial plexus reconstruction, where previously we operated on 13 %.

Conclusions

Early application of passive shoulder repositioning into Sup and ER may improve outcomes in function of the arm in infants with BRBPI. A North American multi-site randomized control trial has been approved and has started recruitment.