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Introduction: The activities of Recover-E project, which belongs to Horizon 2020 financed programs, started in Montenegro in January 2018. The main project goals include: Establishing Community mental health team within Special Psychiatric Hospital Kotor; Selecting a group of 180 patients with severe mental illnesses (with or without comorbid substance abuse); Dividing them in to assertive community treatment and control group. At the end of 18 months period level of functioning between two subgroups (measured by WHODAS scale) will be compared, as well as health economic evaluation including readmission rate. Objectives: Goals of this research at the end of 5 months period of project activities are: Firstly to establish whether there is a significant difference in readmission rate between two subgroups and secondly to examine if patient's addiction status has also a significant influence at this outcome. Methods: Selected group of 89 study participants was recruited between the end of February 2019 and July 2019. Among themthere were 45 patients treated byCommunity mental health teamand 44 in control group (treatment as usual). 20 patients had dual diagnosis. Readmission rate (depending on study arm or addiction status) as a categorical variable was compared by Pearson's Chi Square test. Results: There was not statistically significant difference between treatment and control group in terms of readmission rate. However, the difference between patients with dual diagnosis and the those without substance abuse was with p value below 0.05. Conclusions: Further investigation is necessary. [ABSTRACT FROM AUTHOR]

Biochar, which is the product of biomass pyrolysis, has been suggested as a feed supplement to improve performance in livestock systems and reduce greenhouse gas emissions. The aim of the current study was to investigate in vitro and in vivo potential of biochar to favourably modify rumen fermentation (e.g., an increase in total Short Chained Fatty Acid (SCFA) concentration and a change in SCFA profile), reduce methane emission and increase sheep growth performance. Four concentrates were produced with biochar inclusion of 0, 10, 23 and 46 g/kg DM. The experimental diets for the in vitro experiments consisted of straw and concentrate in a 60:40 ratio and included measurements of total gas and methane (CH 4 ) production, pH, ammonia nitrogen, SCFA, and microbial assays (total bacteria and methanogenic archaea). Two in vivo experiments were performed where the animals received ad libitum forage with 0.4 kg concentrate daily. Experiment 1 investigated the daily DM intake of sheep while experiment 2 investigated daily growth rate and CH 4 emission of lambs. The inclusion of biochar had no impact on in vitro total gas production (ml/200 mg DM substrate) (P = 0.81) and CH 4 production (ml/200 mg DM substrate) (P = 0.93). In vitro total SCFA concentration increased (P < 0.05) while acetate to propionate ratio (A:P) tended to decrease (P = 0.05) with both doses of biochar. Total bacteria decreased with the highest biochar inclusion in vitro (P < 0.05). Sheep's DM intake (kg/d) increased when low and medium levels but not when a higher level of biochar was added to the diet (P < 0.001). The inclusion of biochar did not significantly impact the lamb's daily growth rate (g/d) (P = 0.61) or enteric CH 4 emissions (g/kg DM) (P = 0.43). We conclude that biochar supplementation had no favourable impacts on in vitro and in vivo CH 4 production or on lamb's growth rate. Further research with well-characterised biochar is needed to gain a better understanding of the potential of biochar as a feed additive for ruminant livestock., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Sleep insufficiency or decreased quality have been associated with Alzheimer's disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD., Methods: We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/electromyography headpieces into 6-month-old (plaque-free, n = 10) and 11-month-old (moderate plaque-burdened, n = 10) Tg2576 mice and age-matched wild-type (WT, 6 months old n = 10, 11 months old n = 10) mice and recorded vigilance states for 24 h., Results: Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-h period compared to WT mice at 6 but not at 11 months of age. Concomitantly, power in the delta frequency was decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, rendering a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 h in the overall sleep-wake phenotype at 11 months of age appears to be the result of changes in sleep-wake characteristics accompanying the healthy aging of WT mice., Conclusion: Therefore, our results indicate that at the plaque-free disease stage, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Sleep is crucial to restore body functions and metabolism across nearly all tissues and cells, and sleep restriction is linked to various metabolic dysfunctions in humans. Using exhaled breath analysis by secondary electrospray ionization high-resolution mass spectrometry, we measured the human exhaled metabolome at 10-s resolution across a night of sleep in combination with conventional polysomnography. Our subsequent analysis of almost 2,000 metabolite features demonstrates rapid, reversible control of major metabolic pathways by the individual vigilance states. Within this framework, whereas a switch to wake reduces fatty acid oxidation, a switch to slow-wave sleep increases it, and the transition to rapid eye movement sleep results in elevation of tricarboxylic acid (TCA) cycle intermediates. Thus, in addition to daily regulation of metabolism, there exists a surprising and complex underlying orchestration across sleep and wake. Both likely play an important role in optimizing metabolic circuits for human performance and health., Competing Interests: Declaration of interests M.K. and P.S. are co-founders of a company employing SESI-MS commercially, Deep Breath Intelligence (DBI)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Key Message: This review illustrates how far we have come since the emergence of GE technologies and how they could be applied to obtain superior and sustainable crop production. The main challenges of today's agriculture are maintaining and raising productivity, reducing its negative impact on the environment, and adapting to climate change. Efficient plant breeding can generate elite varieties that will rapidly replace obsolete ones and address ongoing challenges in an efficient and sustainable manner. Site-specific genome editing in plants is a rapidly evolving field with tangible results. The technology is equipped with a powerful toolbox of molecular scissors to cut DNA at a pre-determined site with different efficiencies for designing an approach that best suits the objectives of each plant breeding strategy. Genome editing (GE) not only revolutionizes plant biology, but provides the means to solve challenges related to plant architecture, food security, nutrient content, adaptation to the environment, resistance to diseases and production of plant-based materials. This review illustrates how far we have come since the emergence of these technologies and how these technologies could be applied to obtain superior, safe and sustainable crop production. Synergies of genome editing with other technological platforms that are gaining significance in plants lead to an exciting new, post-genomic era for plant research and production. In previous months, we have seen what global changes might arise from one new virus, reminding us of what drastic effects such events could have on food production. This demonstrates how important science, technology, and tools are to meet the current time and the future. Plant GE can make a real difference to future sustainable food production to the benefit of both mankind and our environment.

The prostate is surrounded by periprostatic adipose tissue (PPAT), the thickness of which has been associated with more aggressive prostate cancer (PCa). There are limited data regarding the functional characteristics of PPAT, how it compares to subcutaneous adipose tissue (SAT), and whether in a setting of localized PCa, these traits are altered by obesity or disease aggressiveness. PPAT and SAT were collected from 60 men (age: 42-78 years, BMI: 21.3-35.6 kg/m 2 ) undergoing total prostatectomy for PCa. Compared to SAT, adipocytes in PPAT were smaller, had the same basal rates of fatty acid release (lipolysis) yet released less polyunsaturated fatty acid species, and were more sensitive to isoproterenol-stimulated lipolysis. Basal lipolysis of PPAT was increased in men diagnosed with less aggressive PCa (Gleason score (GS) ≤ 3 + 4) compared to men with more aggressive PCa (GS ≥ 4 + 3) but no other measured adipocyte parameters related to PCa aggressiveness. Likewise, there was no difference in PPAT lipid biology between lean and obese men. In conclusion, lipid biological features of PPAT do differ from SAT; however, we did not observe any meaningful difference in ex vivo PPAT biology that is associated with PCa aggressiveness or obesity. As such, our findings do not support a relationship between altered PCa behavior in obese men and the metabolic reprogramming of PPAT.

Background: The oncogenic receptor tyrosine kinase (RTK) ERBB2 is known to dimerize with other EGFR family members, particularly ERBB3, through which it potently activates PI3K signalling. Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast cancer patients for two decades. However, the lack of response and the rapid onset of relapse in many patients now question the assumption that the ERBB2/ERBB3 heterodimer is the sole relevant effector target of these therapies., Methods: Through a systematic protein-protein interaction screen, we have identified and validated alternative RTKs that interact with ERBB2. Using quantitative readouts of signalling pathway activation and cell proliferation, we have examined their influence upon the mechanism of trastuzumab- and pertuzumab-mediated inhibition of cell growth in ERBB2-amplified breast cancer cell lines and a patient-derived xenograft model., Results: We now demonstrate that inactivation of ERBB3/PI3K by these therapeutic antibodies is insufficient to inhibit the growth of ERBB2-amplified breast cancer cells. Instead, we show extensive promiscuity between ERBB2 and an array of RTKs from outside of the EGFR family. Paradoxically, pertuzumab also acts as an artificial ligand to promote ERBB2 activation and ERK signalling, through allosteric activation by a subset of these non-canonical RTKs. However, this unexpected activation mechanism also increases the sensitivity of the receptor network to the ERBB2 kinase inhibitor lapatinib, which in combination with pertuzumab, displays a synergistic effect in single-agent resistant cell lines and PDX models., Conclusions: The interaction of ERBB2 with a number of non-canonical RTKs activates a compensatory signalling response following treatment with pertuzumab, although a counter-intuitive combination of ERBB2 antibody therapy and a kinase inhibitor can overcome this innate therapeutic resistance.

Hybrid breeding in sunflowers based on CMS PET1 requires development of restorer lines carrying, in most cases, the restorer gene Rf1 . Markers for marker-assisted selection have been developed, but there is still need for closer, more versatile, and co-dominant markers linked to Rf1 . Homology searches against the reference sunflower genome using sequences of cloned markers, as well as Bacterial Artificial Chromosome (BAC)-end sequences of clones hybridizing to them, allowed the identification of two genomic regions of 30 and 3.9 Mb, respectively, as possible physical locations of the restorer gene Rf1 on linkage group 13. Nine potential candidate genes, encoding six pentatricopeptide repeat proteins, one tetratricopeptide-like helical domain, a probable aldehyde dehydrogenase 22A1, and a probable poly(A) polymerase 3 (PAPS3), were identified in these two genomic regions. Amplicon targeted next generation sequencing of these nine candidate genes for Rf1 was performed in an association panel consisting of 27 maintainer and 32 restorer lines and revealed the presence of 210 Single Nucleotide Polymorphisms (SNPs) and 67 Insertions/Deletions (INDELs). Association studies showed significant associations of 10 SNPs with fertility restoration ( p -value < 10 -4 ), narrowing Rf1 down to three candidate genes. Three new markers, one co-dominant marker 67N04&#95;P and two dominant markers, PPR621.5R for restorer, and PPR621.5M for maintainer lines were developed and verified in the association panel of 59 sunflower lines. The versatility of the three newly developed markers, as well as of three existing markers for the restorer gene Rf1 (HRG01 and HRG02, Cleaved Amplified Polymorphic Sequence (CAPS)-marker H13), was analyzed in a large association panel consisting of 557 accessions.

Chlorpyrifos is a widely used organophosphate pesticide (OP). In birds and mammals OP exhibits a toxic effect via inhibition of cholinesterases [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and through oxidative/nitrosative stress. In this study, the influence of chlorpyrifos on cholinesterase activity, parameters of oxidative stress [malondialdehyde (MDA); glutathione (GSH); superoxide dismutase (SOD); nitrite concentration (NO2-); hydrogen peroxide (H2O2)], and inflammatory parameter [activity of myeloperoxidase (MPO)] in the brain of Japanese quail (Coturnix japanica) was examined. The study was conducted on a total of 60 male Japanese quails (one control and 5 experimental groups, n = 10), 3 to 4 wk old. Quails were administered by gavage chlorpyrifos (CPF) for 7 consecutive da at doses of 0.375 mg/kg BW, 0.75 mg/kg BW, 1.5 mg/kg BW, 3 mg/kg BW, and 6 mg/kg BW. Our studies have shown that all doses of CPF significantly inhibited both cholinesterases in brain: AChE from 22.74 to 37.83% and BChE from 19.53 to 61.9%, and that inhibition was dose dependent. Also, CPF has led to an increase in the concentration of MDA, GSH, NO2-, and H2O2 and activity of SOD and MPO. Overall, these results support the hypothesis that CPF causes oxidative stress and inflammatory response. This research was carried out on quails because there is hardly any or not enough data about the neurotoxic effect of CPF and especially about its influence on oxidative stress in birds. This study is highly important because we are witnessing massive avian mortality in certain countries due to pesticides.

Emerging data have linked certain features of clinical prostate cancer (PCa) to obesity and, more specifically, increased adiposity. Whereas the large number of clinical studies and meta-analyses that have explored the associations between PCa and obesity have shown considerable variability, particularly in relation to prostate cancer risk, there is an accumulating weight of evidence consistently linking obesity to greater aggressiveness of disease. In probing this association mechanistically, it has been posited that peri-prostatic adipose tissue (PPAT), a significant component of the prostate microenvironment, may be a critical source of fatty acids and other mitogens and thereby influences PCa pathogenesis and progression. Notably, several recent studies have identified secreted factors from both PPAT and PCa that potentially mediate the two-way communication between these intimately linked tissues. In the present review, we summarize the available literature regarding the relationship between PPAT and PCa, including the potential biological mediators of that relationship, and explore emerging areas of interest for future research endeavours., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Successful application of somatic hybridization in sunflower breeding is limited by low regeneration percentage from fusion products. The effect of pre-treatment media composition on shoot regeneration from electrofusion products of wild and cultivated sunflower was investigated in this paper, with the aim to determine if there is room for improvement of the existing regeneration protocols in order to make them less genotype-dependent. Protoplasts isolated from hypocotyls of two inbred lines of cultivated sunflower were electrofused with mesophyll protoplasts of H. mollis and H. maximiliani . The regeneration was induced only on calluses that were grown on the media with low auxin and high cytokinin contents during the development of calluses from microcalluses (pre-treatment), with silver nitrate as a medium component. Regeneration from fusion products was induced by treatment with a high concentration of TDZ or 2,4 D for a short period of time.

The plant regeneration from sunflower protoplast was achieved by protocols that considerably differ with respect to basal medium and concentration of growth regulators added. In most cases regeneration was restricted to a small proportion of genotypes. In this experiment, sunflower inbred line Ha-74A, with a high regeneration ability was used for protoplast isolation from etiolated hypocotyls. Isolated protoplasts were embedded in agarose droplets and cultured according to different regeneration protocols. The best results were obtained when protoplasts were cultured on L4 medium followed by transfer of regenerated microcalluses to solid regeneration media. Shoot regeneration was achieved by culture of calluses on SE regeneration medium after the treatment with 2.2 μM thidiazuron.

Purpose: The goals of the work described in this article were to translate and adapt into Serbian the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48), and to evaluate the psychometric properties of the translation., Methods: Translation/backtranslation, cultural adaptation, and pretesting were performed first. For validity, internal consistency, and sensitivity testing, the Serbian version was administered to a sample of 67 adolescents with epilepsy., Results: All subscales (Epilepsy Impact, Memory/Concentration, Attitudes toward Epilepsy, Physical Functioning, Stigma, Social Support, School Behavior, and Health Perceptions) contributed significantly to the summary measure. Mean scores for the subscales ranged from 75.4 to 91.3, and showed a tendency to decrease as illness severity increased. Internal consistency reliability (Cronbach's alpha) was 0.92 for the entire questionnaire., Conclusions: The QOLIE-AD-48 Serbian version is a valid and reliable instrument for health-related quality-of-life assessment in youths with epilepsy. It can be administered in 15 minutes, and can be used in clinical practice, as well as in quality-of-life research.