In this randomized controlled pilot trial, we investigated the effects of a 6-month intake of hydrogen-rich water (HRW) on several molecular and phenotypic biomarkers of aging in older adults aged 70 years and over. Forty older adults (20 women) were randomly allocated in a parallel-group design to receive 0.5 L per day of HRW (15 ppm of hydrogen) or control drink (0 ppm of hydrogen) during a 6-month intervention period. The biomarkers assessed at baseline and 6-month follow up were molecular markers in the blood (DNA and chromosomes, nutrient sensing, protein, and lipid metabolism, oxidative stress and mitochondria, cell senescence, inflammation), brain metabolism, cognitive functioning, physical function and body composition, resting blood pressure, facial skin features, sleep outcomes, and health-related quality of life. The mean age, weight, and height of study participants were 76.0 ± 5.6 years, 78.2 ± 16.1 kg, height 167.5 ± 11.5 cm, respectively. A significant treatment vs. time interaction was found for telomere length (P = 0.049), with the length increased after HRW intervention (from 0.99 ± 0.15 at baseline to 1.02 ± 0.26 at follow up) and decreased after drinking control water (from 0.92 ± 0.27 to 0.79 ± 0.15). A marker of DNA methylation (Tet methylcytosine dioxygenase 2, TET2) expression at 6-month follow-up increased in both groups, yet the degree of elevation was significantly higher in HRW (from 0.81 ± 0.52 at baseline to 1.62 ± 0.66 at follow up) comparing to the control water (from 1.13 ± 0.82 to 1.76 ± 0.87) (P = 0.040). A strong trend for treatment vs. time interaction was found for a degree of DNA methylation (P = 0.166), with the methylation increased in the HRW group (from 120.6 ± 39.8 ng at baseline to 126.6 ± 33.8 ng at follow up) and decreased after taking control water (from 133.6 ± 52.9 ng to 121.2 ± 38.4 ng). HRW was superior to control water to increase brain choline and NAA levels in the left frontal grey matter, brain creatine at the right parietal white matter, and brain NAA at the right parietal mesial grey matter (P < 0.05). No significant differences were found between interventions for other outcomes (P > 0.05), except for a significantly improved chair stand performance after HRW intervention compared to the control water (P = 0.01). Owing to pleiotropic mechanisms of hydrogen action, this simple biomedical gas could be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening. The study was registered at ClinicalTrials.gov (NCT04430803).

Aim of study: This research aims to determine if there are statistically significant differences among provenances of silver fir (Abies alba Mill.) as one of the most important tree species in Bosnia and Herzegovina, to choose a provenance with the best productivity for further silvicultural activities of silver fir in the country. Material and methods: The height and diameter at breast height were measured, and the basal area and volume of silver fir trees were calculated in the silver fir provenance test. The test contains nine provenances from Bosnia and Hezegovina and was launched in 1991, with 5-year-old seedlings (3+2). The data were collected in 2013. Main results: Variance analysis for all traits showed statistically significant differences among provenances. Average breast height diameter in 27-year-old plants for all provenances amounted to 11.0 cm, average height 8.4 m, average basal area 0.010342 m, and average volume 0.070845 m Highlights: The research results confirmed the existence of variability among silver fir provenances in Bosnia and Herzegovina, considering the morphological indicators. Provenance Bosanski Petrovac showed the highest values of all traits, which implies it is the best provenance for the further activities on seed collecting and producing planting material for afforestation in Bosnia and Herzegovina.

To shift the paradigm towards Industry 4.0, maritime domain aims to utilize shared situational awareness (SSA) amongst vessels. SSA entails sharing various heterogeneous information, depending on the context and use case at hand, and no single wireless technology is equally suitable for all uses. Moreover, different vessels are equipped with different hardware and have different communication capabilities, as well as communication needs. To enable SSA regardless of the vessel’s communication capabilities and context, we propose a multimodal network architecture that utilizes all of the network interfaces on a vessel, including multiple IEEE 802.11 interfaces, and automatically bootstraps the communication transparently to the applications, making the entire communication system environment-aware, service-driven, and technology-agnostic. This paper presents the design, implementation, and evaluation of the proposed network architecture which introduces virtually no additional delays as compared to the Linux communication stack, automates communication bootstrapping, and uses a novel application-network integration concept that enables application-aware networks, as well as network-aware applications. The evaluation was conducted for several IEEE 802.11 flavors. Although inspired by SSA for vessels, the proposed architecture incorporates several concepts applicable in other domains. It is modular enough to support existing, as well as emerging communication technologies.

The cyclotide T20K inhibits the proliferation of human immune cells and is currently in clinical trials for multiple sclerosis. Here, we provide novel functional data and mechanistic insights into structure–activity relationships of T20K. Analogs with partial or complete reduction of the cystine knot had loss of function in proliferation experiments. Similarly, an acyclic analog of T20K was inactive in lymphocyte bioassays. The lack of activity of non-native peptide analogs appears to be associated with the ability of cyclotides to interact with and penetrate cell membranes, since cellular uptake studies demonstrated fast fractional transfer only of the native peptide into the cytosol of human immune cells. Therefore, structural differences between cyclic and linear native folded peptides were investigated by NMR to elucidate structure–activity relationships. Acyclic T20K had a less rigid backbone and considerable structural changes in loops 1 and 6 compared to the native cyclic T20K, supporting the idea that the cyclic cystine knot motif is a unique bioactive scaffold. This study provides evidence that this structural motif in cyclotides governs bioactivity, interactions with and transport across biological membranes, and the structural integrity of these peptides. These observations could be useful to understand the structure–activity of other cystine knot proteins due to the structural conservation of the cystine knot motif across evolution and to provide guidance for the design of novel cyclic cysteine-stabilized molecules.

In this paper, we solve the problem of learning a generalized Nash equilibrium (GNE) in merely monotone games. First, we propose a novel continuous semi-decentralized solution algorithm without projections that uses first-order information to compute a GNE with a central coordinator. As the second main contribution, we design a gain adaptation scheme for the previous algorithm in order to alleviate the problem of improper scaling of the cost functions versus the constraints. Third, we propose a data-driven variant of the former algorithm, where each agent estimates their individual pseudogradient via zeroth-order information, namely, measurements of their individual cost function values. Finally, we apply our method to a perturbation amplitude optimization problem in oil extraction engineering.

Parkinson’s disease (PD) causes a progressive decline of motor and cognitive functions, often affecting postural control. Training through virtual reality has been shown to be effective in improving this condition. This study aims to analyse the effects of the Kinect Adventures! games in postural control of people with PD. Ten individuals diagnosed with idiopathic PD, in stages I to III of the Hoehn & Yahr scale, aged between 48 and 73 years, were selected. Fourteen training sessions of one hour each, twice a week, were performed. Individuals were evaluated pre, post-intervention and 30 days after the last session of intervention by a force platform that measured the oscillation area (COP) and velocity (VOS) of the centre of pressure in ten different sensory conditions and the Limits of Stability (LOS). LOS showed a statistically significant increase immediately after the training the 14 sessions, as were observed and there were no significant changes in COP and VOS immediately after the intervention or 30 days after the end of training. The results of this study indicate that the training with Kinect Adventures! Games improve the postural control of people with PD, by increasing the LOS. Keywords: Parkinson disease; postural balance; virtual reality exposure therapy; video game

Os acidentes com animais peçonhentos têm importância na saúde pública, sendo fundamental ações educativas para prevenção, diagnóstico e tratamentos. No Brasil, os soros hiperimunes são preconizados para o tratamento dos acidentados. Esses produtos são produzidos por laboratórios oficiais seguindo requisitos das Boas Práticas de Fabricação (BPF) e distribuídos gratuitamente pelo Sistema Único de Saúde. Buscando atender uma demanda da sociedade, o projeto de extensão “Kaizen: Formação de recursos humanos e o aperfeiçoamento contínuo profissional, institucional e social sobre animais peçonhentos e a produção de soros na saúde pública” estabeleceu uma parceria entre o Instituto Vital Brazil (IVB) e o Curso de Farmácia da Universidade Federal do Rio de Janeiro (UFRJ-Macaé) para o desenvolvimento de ciclos de ações educativas para diferentes públicos. O primeiro ciclo foi realizado pela universidade e direcionado aos colaboradores do IVB envolvendo conteúdos das BPF. O segundo ciclo foi realizado pelo IVB para o público de Macaé e municípios limítrofes com a participação de estudantes de ensino fundamental, médio e superior, além de agentes de combate de endemias, exército brasileiro, defesa civil, centro de zoonoses e guarda ambiental. Após a realização das ações, formulários de avaliação foram fornecidos aos participantes, observando-se alto grau de satisfação. Dessa forma, as ações contribuíram para o aprimoramento do conhecimento das BPF, além de ampliar os espaços de construção do conhecimento e aprendizagem para evitar os acidentes com animais peçonhentos, assim como nos tratamentos e produção dos soros hiperimunes e distribuição na saúde pública.

A temática fechamento de escola do campo tem sido fortemente discutida nos últimos anos em vários trabalhos científicos, sendo também fator de preocupação por parte das comunidades localizadas em área rural. Este artigo analisa a política de municipalização do ensino fundamental e de nucleação de escolas, indicando que tal política é o principal motivador do fechamento de milhares de escolas do campo no Brasil e de dezenas de escolas no Município de Passos Maia. Além disso, está elaboração apresenta dados sobre as escolas que foram fechadas no Município de Passos Maia e aponta os impactos negativos que a comunidade Conquista de Sepé obteve ao ser fechada sua escola local. Conclui-se, dessa forma, que fechar as Escolas do Campo provoca a destituição da organização social e da vivência comunitária. Nesta direção é que se localiza a afirmação de que Escola do Campo é “vida na comunidade”, por compreende-se que o fechamento/extinção de escolas do campo leva ao fechamento/extinção das comunidades rurais.  Como instrumentos metodológicos, para a elaboração do trabalho, foram utilizados estudo bibliográfico e entrevistas.

The main aim of the study was to empirically investigate and understand the effects that autonomy has on job satisfaction and job performance in Bosnia and Herzegovina. The empirical data was obtained from a questionnaire of 242 people living and working in Bosnia and Herzegovina. Once the data was collected, data analysis was conducted to assure validity and reliability through items’ loadings and Cronbach’s Alpha values.Furthermore, the scales were tested for convergent validity through partial least-square path modelling using SmartPLS 3 software. The results indicated that the effects of autonomy on job performance and job satisfaction were significant and had positive relationship.

The main objective of the study was to determine the developmental abilities of preschool children before and after six months of speech therapy treatment, and to examine the impact of the time of initiation of speech therapy treatment on the developmental abilities of children. The sample consisted of 35 children (20 male children and 15 female children), and all respondents reported early intervention due to speech and language difficulties. The age of the respondents ranged from 25 to 60 months. After conducting interviews with parents, taking anamnestic data, professional speech therapy diagnosticobservational procedure and determining speech-language disorders, the children underwent speech therapy treatment. After six months, a final assessment was made and the results showed statistically significant progress in all variables describing developmental abilities in children. The predictor “Time of treatment initiation” also had a statistically significant impact on all tested variables of developmental abilities of preschool children. The results showed that speech therapy treatment enables significant progress in all developmental areas in children, i.e. that progress in one development area follows the development of other areas.

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update on NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

Speech detection threshold (SDT) depends on audibility alone, whereas speech recognition threshold (SRT) requires the stimuli to be heard and identified. The aim of the study was to determine the difference between SDT and SRT, and to analyze the correlation between pure tone thresholds and speech thresholds. Difference between SDT and SRT was ≤ 12 dB in majority of cases (p = .018). SDT was strongly correlated with the best pure tone threshold. Pearson correlation coefficient was the highest in “Inverted U” shape (r = .99). There was strong correlation between SRT and PTA (500-2000), PTA (500-4000), and PTA (500-1000), especially in Rising configuration (r = .997, r = .992 r = .989, respectively), as well as, between SRT and frequency of 1000 Hz (r = .989). SRT is in the highest correlation with PTA (500, 1000, 2000 Hz) and with the hearing threshold at frequency of 1000 Hz.

Aim of this paper was to determine the frequency of congenital anomalies in a sample of newborns of Tuzla Canton and as well as their distribution according to gender, mother’s age and marital distance category. Research was undertaken using the retrospective analysis on the Clinic for Gynecology and Obstetrics of University Clinical Center in Tuzla. By analyzing medical documentation of 17223 newborns, we determined the frequency of congenital anomalies of 5.24%. Highest frequency of congenital anomalies was found in the newborns whose mothers are older than 35. It was found that the frequency of congenital anomalies in the observed population is within the range of variation of this parameter with data from the literature.