Abstract Background Posttraumatic stress disorder is characterized by an overactive noradrenergic system conferring core posttraumatic stress disorder symptoms such as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine oxidase A gene exonI/intronI region was investigated for the first time regarding its role in posttraumatic stress disorder risk and severity. Methods Monoamine oxidase A methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells in a total sample of N=652 (441 male) patients with current posttraumatic stress disorder, patients with remitted posttraumatic stress disorder, and healthy probands (comparison group) recruited at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. Posttraumatic stress disorder severity was measured by means of the Clinician-Administered Posttraumatic Stress Disorder Scale and its respective subscores representing distinct symptom clusters. Results In the male, but not the female sample, patients with current posttraumatic stress disorder displayed hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553, GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder patients and healthy probands. Symptom severity (Clinician-Administered Posttraumatic Stress Disorder Scale scores) in male patients with current posttraumatic stress disorder significantly correlated with monoamine oxidase A methylation. This applied particularly to symptom clusters related to reexperiencing of trauma (cluster B) and hyperarousal (cluster D). Conclusions The present findings suggest monoamine oxidase A gene hypermethylation, potentially resulting in enhanced noradrenergic signalling, as a disease status and severity marker of current posttraumatic stress disorder in males. If replicated, monoamine oxidase A hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of posttraumatic stress disorder guiding personalized treatment decisions on the use of antiadrenergic agents.

Eleven social bonding groups were conducted with a total of 136 participants of which 79 (56.4%) were women and 57 (40.7%) were men. Without exception, both genders reported positive experiences; furthermore, 42.3% of them express that the social bonding group space is a setting where common issues can be resolved and where personal growth can be enhanced. In fact, 39.0% believe that the group allows them to relieve the weight of their problems and lower stress levels. According to 29.4% of the interviewees, it also improves peer-esteem among participants. The study shows that incorporating social bonding groups in all of the school learning processes presents positive impact as they make the students socialize and share their emotional states or general unrests brought on by family conflicts or other risk factors. Therefore, this therapy provides students with opportunities to build their self-esteem and improve their resilience.

We consider the possibility that the primordial curvature perturbation is direction-dependent. To first order this is parameterised by a quadrupolar modulation of the power spectrum and results in statistical anisotropy of the CMB, which can be quantified using `bipolar spherical harmonics'. We compute these for the Planck DR2-2015 SMICA map and estimate the noise covariance from Planck Full Focal Plane 9 simulations. A constant quadrupolar modulation is detected with 2.2 σ significance, dropping to 2σ when the primordial power is assumed to scale with wave number k as a power law. Going beyond previous work we now allow the spectrum to have arbitrary scale-dependence. Our non-parametric reconstruction then suggests several spectral features, the most prominent at k ∼ 0.006 Mpc−1. When a constant quadrupolar modulation is fitted to data in the range 0.005 ⩽ k/Mpc−1 ⩽ 0.008, its preferred directions are found to be related to the cosmic hemispherical asymmetry and the CMB dipole. To determine the significance we apply two test statistics to our reconstructions of the quadrupolar modulation from data, against reconstructions of realisations of noise only. With a test statistic sensitive only to the amplitude of the modulation, the reconstructions from the multipole range 30 ⩽ ℓ ⩽ 1200 are unusual with 2.1σ significance. With the second test statistic, sensitive also to the direction, the significance rises to 6.9σ. Our approach is easily generalised to include other data sets such as polarisation, large-scale structure and forthcoming 21-cm line observations which will enable these anomalies to be investigated further.

SB5 is a biosimilar agent for adalimumab (ADA). The aim of this study was to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of SB5 in comparison with reference ADA in patients with rheumatoid arthritis (RA).

This paper intends to bring attention of both scientific and general audience to the status quo of the existing, residential building stock in Bosnia and Herzegovina, highlighting its energy savings potential. The research results presented in this text may be applicable on two levels: on a larger scale, the policy makers may use this data in the process of development of strategic and EE measures implementation plans, while, on a smaller scale, the individual users may gain practical insight into the benefits of energy saving measures and implement them in their own households. Moreover, the exposed data may be subject to further evaluations, studies and comparisons, while the presented methodology can be used by other researchers in countries where there have not been research activities on the existing residential buildings stock from the EE perspective.

Black cumin (Nigella sativa L. [N.sativa]) seed extracts demonstrated numerous beneficial biological effects including, among others, antidiabetic, anticancer, immunomodulatory, antimicrobial, anti-inflammatory, antihypertensive, and antioxidant activity. To better understand the phytochemical composition of N. sativa seeds, methanol seed extracts were analyzed for phenolic acid and flavonoid content. Furthermore, we tested N. sativa methanol, n-hexane, and aqueous seed extracts for their inhibitory activity against butyrylcholinesterase (BChE) and catalase (CAT) as well as for antimicrobial activity against several bacterial and a yeast strains. The phenolic content of N. sativa was analyzed using ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The inhibition of BChE was assessed by modified Ellman's method, and the inhibition of CAT was determined by monitoring hydrogen peroxide consumption. The extracts were tested against Bacillus subtilis, Staphylococcus aureus, Salmonella enterica, and Escherichia coli using the agar diffusion method. The UHPLC-MS/MS method allowed the identification and quantification of 23 phenolic compounds within 15 minutes. The major components found in N. sativa seed extract were sinapinic acid (7.22 ± 0.73 µg/mg) as a phenolic acid and kaempferol (11.74 ± 0.92 µg/mg) as a flavonoid. All extracts showed inhibitory activity against BChE, with methanol seed extract demonstrating the highest inhibitory activity (inhibitory concentration 50% [IC50] 79.11 ± 6.06 µg/ml). The methanol seed extract also showed strong inhibitory activity against CAT with an IC50 value of 6.61 ± 0.27 µg/ml. Finally, the methanol extract exhibited considerable inhibitory activity against the tested microbial strains. Overall, this is the first study to investigate the ability of black cumin seed extracts to inhibit CAT. Our results indicate that N. sativa seed can be considered as an effective inhibitor of CAT activity.

Diabetic retinopathy (DR) is a complication of diabetes characterized by vascular permeability, increased tissue ischemia, and angiogenesis. One of the most important proteins involved in angiogenesis is vascular endothelial growth factor (VEGF, also known as VEGFA). A previous study demonstrated that two single nucleotide polymorphisms (SNPs), rs6921438 and rs10738760, account for nearly half the variation in circulating VEGF levels. The aim of our study was to assess the association between rs6921438 and rs10738760 and DR in Slovenian patients with type 2 diabetes mellitus (T2DM). This case-control study enrolled 1037 unrelated Slovenian individuals (Caucasians) with T2DM. DR group included 415 T2DM patients with DR, while control group included 622 T2DM patients with no clinical signs of DR. The clinical and laboratory data were obtained from the medical records of the patients. The genotyping of rs6921438 and rs10738760 SNPs was carried out with real-time PCR assays. Significant differences were observed between patients with DR and controls in the duration of diabetes (p < 0.001), insulin therapy (p < 0.001), glycated hemoglobin (p = 0.001), body mass index (p = 0.002), total cholesterol (p = 0.002), and low-density lipoprotein cholesterol (p < 0.001). However, we did not observe significant differences in the genotype and allele distribution of the two SNPs, between DR and control group (p < 0.05). Logistic regression analysis showed that rs6921438 and rs10738760 were not independent genetic risk factors for DR in the co-dominant model adjusted for the above-mentioned clinical and laboratory data. In conclusion, VEGF-related SNPs rs10738760 and rs6921438 are not associated with DR in our group of Slovenian patients (Caucasians) with T2DM.

Liquid impinging jet at the bottom of the annular cavity is a typical case in the process industry. The jet could have an impact at the bottom center or its peripheral section. The profiled annular cylindrical cavity with the installed electricity heater source is investigated in this paper. Thermal contact irreversibility and liquid drag irreversibility are generated within the profiled cavity. Through analytical modeling and experimental verification, a valid model of the entropy generation is established for both states. The results show that the total entropy between the liquid and the bottom is many times greater for the case of the central jet impingement. Within the annular vertical walls are the locations of the maximum or minimum of the entropy. The effectiveness of the liquid heating is greater in the peripheral impact of the liquid. The method and the results are the basis for optimizing the profiled cavity in various optimization geometry parameters. The optimal geometry of the annular cavity exists in such a way that the balance between thermal irreversibility and liquid drag irreversibility leads to the total minimum rate of the entropy generation for the annular cavity.