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Abstract Background A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects. Methods CRiB2 is a two-arm, assessor-blind, multi-site, randomised controlled trial (RCT) comparing CR to treatment-as-usual (TAU). Participants are people with a diagnosis of BD, aged between 18 and 65, with no neurological or current substance use disorder, and currently euthymic. 250 participants will be recruited through primary, secondary, tertiary care, and the community. Participants will be block-randomised (1:1 ratio, stratified by site) to continue with their usual care (TAU) or receive a 12-week course of therapy and usual care (CR + TAU). The intervention comprises one-on-one CR sessions with a therapist supplemented with independent cognitive training for 30–40 h in total. Outcomes will be assessed at 13- and 25-weeks post-randomisation. Efficacy will be examined by intention-to-treat analyses estimating between-group differences in primary (i.e., psychosocial functioning at week 25 measured with the Functional Assessment Short Test) and secondary outcomes (i.e., measures of cognition, mood, patient-defined goals, and quality of life). Global cognition, metacognitive skills, affect fluctuation, and salivary cortisol levels will be evaluated as putative mechanisms of CR through mediation models. Discussion This study will provide a robust evaluation of efficacy of CR in people with BD and examine the putative mechanisms by which this therapy works. The findings will contribute to determining the clinical utility of CR and potential mechanisms of action. Trial registration Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331 . Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting.

Wastewater treatment plants (WWTP) have extensive energy processes that undermine their economic and environmental performance. In this context, the integration of wastewater treatment with other biochemical processes such as co-digestion of sludge with organic wastes, and production of value-added products at their downstream processes will shift conventional WWTPs into biorefinery platforms with better sustainability performance. The sustainability of such a biorefinery platform has been investigated herein using an economic and life cycle assessment approach. This WWTP-based biorefinery treats wastewater from Copenhagen municipality, co-digests the source-sorted organic fraction of municipal solid waste and sludge, and upgrades biogas into biomethane using a hydrogen-assisted upgrading method. Apart from bioenergy, this biorefinery also produces microbial protein (MP) using recovered nutrients from WWTP's reject water. The net environmental savings achieved in two damage categories, i.e., −1.07 × 10−2 species.yr/FU in ecosystem quality and −1.68 × 106 USD/FU in resource scarcity damage categories along with high potential windows for the further environmental profile improvements make this biorefinery platform so encouraging. Despite being promising in terms of environmental performance, the high capital expenditure and low gross profit have undermined the economic performance of the proposed biorefinery. Technological improvements, process optimization, and encouraging incentives/subsidies are still needed to make this platform economically feasible. HIGHLIGHTS A biorefinery for microbial protein and bioenergy production has been developed.; Wastewater treatment and anaerobic digestion of sludge incorporated in biorefinery.; Microbial production had lower environmental profile than soybean meal.; High CAPEX undermined the economic feasibility of MP production.;

Telomerase activity coincides with lengthening of the ends of chromosomes known as telomeres. Telomere length is used as a marker for cellular aging. Telomeres shorten over time as cells divide, and certain bioactive compounds such as gold nanoparticles (AuNPs) may slow the shortening of telomeres by increasing telomerase activity. The objective of the present study is to assess the effect of AuNPs on telomerase activity and telomere length in human fibroblasts. Telomerase activity was measured using enzyme-linked immunosorbent assay (ELISA) in primary human lung fibroblasts (IMR90) and using quantitative PCR-based telomeric repeat amplification protocol (Q-TRAP) in primary human dermal fibroblasts, neonatal (HDFn). Telomere length was determined by Telomere Analysis Technology (TAT®)assay in HDFn. In IMR90, all AuNP treatments showed significant increases in telomerase activity when compared to earlier passages. HDFn treated with AuNPs at 0 ppm, 0.05 ppm, 0.5 ppm, or 5 ppm did not show significant differences in telomerase activity compared to the control group. Significant differences in telomere length in HDFn were observed at 2 weeks of 0.05 and 0.5 ppm AuNPs under oxidative culture conditions as compared to the control group. The study showed preliminary evidence that AuNPs may increase telomerase activity and decelerate the shortening of telomeres in human fibroblasts, suggesting its potential anti-aging effects, which warrants further investigation.

Succinic acid (SA) is a valuable platform chemical that can be converted into biodegradable plastics, resins, solvents, etc. The emerging biological routes for SA production are gaining more attention because they exploit the natural abilities of bacteria to fixate carbon dioxide (CO2). On the other hand, an inexpensive organic carbon source that can fulfill the energetic requirements of the microbial strain is also a significant challenge for industrial SA production. The current work presents a holistic techno-economic analysis of SA production using sugar-rich residual streams and biogas as raw materials. Simulation results showed that by establishing an integrated process, high SA production can be simultaneously achieved with biogas upgrading. The CO2 provided from biogas and carbohydrates, which are provided from organic by-products is converted into two products: biomethane (CH4 > 95%, a clean biofuel), and SA. The mass and energy balances and techno-economic indicators were simulated and calculated using SuperPro Designer®. The total capital investment and the total production cost for a facility producing 1000 tSA/year were estimated to be EUR 5,211,000 and EUR 2,339,000 per year, respectively. The total revenue was calculated to be EUR 2,811,000 per year, while the revenue due to biomethane produced, namely, 198,150 Nm3 corresponded to EUR 205,284 per year. The return on investment, payback period, and internal rate of return of the project were found to be 11.68%, 8.56 years, and 11.11%, respectively.

The beauty industry is actively searching for solutions to prevent skin aging. Some of the crucial elements protecting cells from the aging process are telomere shortening, telomerase expression, cell senescence, and homeostasis of the redox system. Modification of these factors using natural antioxidants is an appealing way to support healthy skin aging. Therefore, in this study, we sought to investigate the antiaging efficacy of a specific combination of four botanical extracts (pomegranate, sweet orange, Cistanche and Centella asiatica) with proven antioxidant properties. To this end, normal human dermal fibroblasts were used as a cell model and the following studies were performed: cell proliferation was established by means of the MTT assay and the intracellular ROS levels in stress-induced premature senescence fibroblasts; telomere length measurement was performed under standard cell culture conditions using qPCR and under oxidative stress conditions using a variation of the Q-FISH technique; telomerase activity was examined by means of Q-TRAP; and AGE quantification was completed by means of ELISA assay in UV-irradiated fibroblasts. As a result, the botanical blend significantly reversed the H2O2-induced decrease in cell viability and reduced H2O2-induced ROS. Additionally, the presence of the botanical ingredient reduced the telomere shortening rate in both stressed and non-stressed replicating fibroblasts, and under oxidative stress conditions, the fibroblasts presented a higher median and 20th percentile telomere length, as well as a lower percentage of short telomeres (

Telomere length, a hallmark of cellular senescence, decreases with age and is associated with age-related diseases. Environmental factors, including dietary and lifestyle factors, can affect the rate at which telomeres shorten, and telomere protection prevents this from happening. The protection of telomeres by natural molecules has been proposed as an antiaging strategy that may play a role in treating age-related diseases. This study investigated the effect of a cycloartane-type triterpene glycoside (astragaloside IV). Astragaloside IV is one of the primary compounds from the aqueous extract of Astragalus membranaceus, and it provides telomere protection both in vitro and in vivo. In a study cohort with 13 participants, telomere length in human skin samples was analyzed after daily treatment for 4 weeks. A comparison of the average median telomere length between the treatment and control groups (5342 bp vs. 4616 bp p = 0.0168) showed significant results. In the second clinical cohort with 20 participants, skin parameters at baseline and after 4 and 8 weeks were measured in vivo. The results show that the product improved hydration by 95%, the skin appeared brighter by 90%, and wrinkle visibility was reduced by 70%. The combination of biologically active compounds in the cream possesses telomere-protecting properties and notable antioxidant activity in vitro and in vivo.

Background Neurobiological research frequently implicates inflammatory and neurogenic components with core aspects of bipolar disorder. Even in periods of symptom remission (euthymia), individuals with bipolar disorder experience cognitive impairments, which are increasingly being proposed as an outcome for interventions; identifying biomarkers associated with cognitive impairment in people with bipolar disorder could advance progress in this therapeutic field through identifying biological treatment targets. Aims We aimed to identify proteomic biomarker correlates of cognitive impairment in individuals with euthymic bipolar disorder. Method Forty-four adults with a bipolar disorder diagnosis in euthymia underwent a battery of cognitive assessments and provided blood for biomarkers. We examined a comprehensive panel of inflammatory and trophic proteins as putative cross-sectional predictors of cognition, conceptualised according to recommended definitions of clinically significant cognitive impairment (binary construct) and global cognitive performance (continuous measure). Results A total of 48% of the sample met the criteria for cognitive impairment. Adjusting for potentially important covariates, regression analyses identified lower levels of three proteins as significantly and independently associated with cognitive deficits, according to both binary and continuous definitions (interleukin-7, vascular endothelial growth factor C and placental growth factor), and one positively correlated with (continuous) global cognitive performance (basic fibroblast growth factor). Conclusions This study identifies four candidate markers of cognitive impairment in bipolar disorder, none of which have been previously compared with cognitive function in participants with bipolar disorder. Pending replication in larger samples and support from longitudinal studies, these markers could have implications for treating cognitive dysfunction in this patient population.

Biosynthesis of n-caproate from waste streams rich in acetate and ethanol through chain elongation has offered a potentially sustainable way for future production of liquid biofuels. However, most of the waste streams that fit with the purpose (e.g., digestate) are also rich in ammonium which at high concentration may cause toxic effects on the bioconversion process. This study aims to develop a robust, efficient, and cost-effective chain elongation process with high caproate productivity and tolerance to high ammonia concentration, through immobilization of Clostridium kluyveri on biomass particles as immobilization material. The threshold ammonia concentration for suspended cells cultivation was 2.1 g/L, while it was higher than 5.0 g/L for the wheat straw immobilized system. The caproate production process was dependent on the selected carriers and was performing in the order of: wheat straw > grass straw > saw dust. The biofilm immobilized on the wheat straw showed good reuse capability for caproate production under high ammonia concentration. Moreover, the lag phase for caproate production was shortened from 72 to 30 h after 8 times reuse. These results proved that caproate production and tolerance of chain elongation to ammonia toxicity could be enhanced via cell immobilization. This study offers insight into future development of efficient and cost-effective chain elongation system for production of caproate and other value-added products. Keywords: Caproate, Chain elongation, Biofilm, Ammonia, Clostridium kluyveri, Wheat straw

In this work, potassium iodide (KI) and graphene oxide (GO) were utilized to promote the selectivity of photocatalytic process for alkali lignin oxidation over ZnO. Different concertation of GO was added during the microwave synthesis procedure of ZnO, and the characterization results revealed that graphene can shift the conduction band to more reducing potential, resulting to higher production of superoxide anion radicals (O2−) compared to OH. Response Surface Methodology revealed the most suitable interaction among loading of GO, KI and irradiation time on lignin and total phenolic compound (TPC) degradation. Specifically, the optimal conditions (i.e. maximum lignin (52%) and minimum TPC (55%) degradation) were at [KI] = 0.64 mM; GO content into ZnO 1.2 mg/mL; 240 min of irradiation time. The results showed that higher addition of graphene into structure of ZnO could preserve more phenolics from degradation due to less production of OH. Furthermore, the addition of KI at optimized conditions could enhance the selectivity of degradation of lignin and phenolics via producing I radicals and quenching the excess amount of generated OH, respectively. The lower generation of OH at optimized conditions was quantitatively confirmed by a photoluminescence simplified technique. In addition, the effect of the photocatalytic process on substrate's anaerobic degradability was examined in order to evaluate the suitability of the pretreated solution for energy recovery. Indeed, besides the higher TPC concentration, the biogas production of treated straw at optimized conditions was increased by 35% compared to the untreated sample. Keywords: UV/Iodide, Lignin degradation, Graphene, Phenolics

Background People with bipolar disorder have moderate cognitive difficulties that tend to be more pronounced during mood episodes but persist after clinical remission and affect recovery. Recent evidence suggests heterogeneity in these difficulties, but the factors underlying cognitive heterogeneity are unclear. Aims To examine whether distinct cognitive profiles can be identified in a sample of euthymic individuals with bipolar disorder and examine potential differences between subgroups. Method Cognitive performance was assessed across four domains (i.e. processing speed, verbal learning/memory, working memory, executive functioning) in 80 participants. We conducted a hierarchical cluster analysis and a discriminant function analysis to identify cognitive profiles and considered differences in cognitive reserve, estimated cognitive decline from premorbid cognitive functioning, and clinical characteristics among subgroups. Results Four discrete cognitive profiles were identified: cognitively intact (n = 25; 31.3%); selective deficits in verbal learning and memory (n = 15; 18.8%); intermediate deficits across all cognitive domains (n = 30; 37.5%); and severe deficits across all domains (n = 10; 12.5%). Cognitive decline after illness onset was greater for the intermediate and severe subgroups. Cognitive reserve scores were increasingly lower for subgroups with greater impairments. A smaller proportion of cognitively intact participants were using antipsychotic medications compared with all other subgroups. Conclusions Our findings suggest that individuals with cognitively impaired profiles demonstrate more cognitive decline after illness onset. Cognitive reserve may be one of the factors underlying cognitive variability across people with bipolar disorder. Patients in the intermediate and severe subgroups may be in greater need of interventions targeting cognitive difficulties.

Background: There is evidence that cognitive remediation (CR) is moderately effective in improving cognitive and functional difficulties in people with schizophrenia. However, there is still a limited understanding of what influence different treatment responses. Aim: To identify moderators influencing CR response in people with schizophrenia. Methods: This systematic review follows PRISMA guidelines. Searches were conducted up to January 2019 on PubMed and PsychInfo to identify randomized controlled trials of CR reporting analyses of moderators of treatment response. All papers were assessed for methodological quality and information on sample size, intervention and control condition, moderators, outcomes, effect of moderator on outcomes and demographic characteristics from each study was extracted and critically summarised. Results: Thirty-six studies were included, considering 2737 participants. Study participants consisted on average of people in their late-thirties, mostly men, with over 10 years of illness. The review identified moderators that could be grouped into five categories: demographics, biological, cognitive and functional, psychological, and illness-related characteristics. The assessment of methodological quality showed that many studies had a high risk of bias. Conclusions: There was no high-quality replicated evidence which identifies reliable moderators of CR response. Many moderators were not replicated or presented in single, underpowered studies. Studies also investigated moderators independently despite their potential to overlap (e.g. age and education). Future research should concentrate on evaluating, with sound studies, the role moderators may play in affecting CR treatment response. This information can inform who will benefit most from the therapy and help to improve the benefits of CR. Keywords: Cognitive remediation, Cognition, Moderator, Schizophrenia, Psychosis

Biological biogas upgrading with H2 derived from excess renewable electricity was modeled and simulated in PROII® (AVEVA Group plc, Cambridge, UK). An economic analysis was performed for a biogas plant processing 100,000 tons of biomass (substrate) per year. The biogas and biomethane production simulation results were validated with laboratory experimental data, as well as full-scale data obtained from biogas plants. A biomethane production cost of 0.47 €/Nm3 was calculated, while the minimum biomethane selling price for NPV = 0 was equal to 0.66 €/Nm3, considering a H2 price of 1.0 €/kg. The feasibility analysis indicated that the H2-related costs were the major contributor to the capital and operation costs due to high expenses associated with the in-situ H2 storage facility and the purchasing of H2, respectively. Compared to conventional upgrading methods, biological biogas upgrading has a higher capital and production cost, which can be reduced by increasing the plant capacity. The sensitivity analysis showed that the profitability is very sensitive to biomethane prices, capital investment, and the H2 price.

Emergency Medical Responders (EMRs) work in potentially traumatic situations as part of their job. To enable them to do so requires a degree of resilience (i.e., the ability to bounce back from exposure to disruptive events). Taking a mixed-methods approach, the proposed study addresses the question of whether a reflective journal intervention will impact EMRs’ resilience to support positive outcomes. Data will be collected in four EU countries. The Connor-Davidson Resilience Scale will be administered for pre- and post-intervention assessment, while qualitative data will be collected for further analysis.

Lactic acid can be derived from microbial fermentation and be used as a platform chemical in various industrial applications. This study aims to investigate the challenges involved in combining a low-cost, heterogeneous feedstock, such as a mixture of candy-waste and digestate, with an optimized downstream strategy to achieve maximum recovery of high-purity lactic acid, targeting low energy consumption. To achieve this goal, four membrane separation technologies, namely microfiltration, nanofiltration, monopolar, and bipolar electrodialysis, were combined to design two purification processes. Microfiltration served as the pre-purification step, followed by either process A, which combined nanofiltration and bipolar electrodialysis, or process B, a combination of monopolar and bipolar electrodialysis. The findings emphasized the importance of pH as a control factor. Nanofiltration at pH 2.8 and monopolar electrodialysis at pH 4.0 led to increased lactic acid recovery. Moreover, it was observed that process B resulted in 1.09-fold higher lactic acid recovery than process A. However, process A had a 1.19-fold lower specific energy consumption, and the presence of ions in the final solution was reduced by 5-fold. In both processes lactic acid was separated from sugars and organic acids. Overall, the findings of this study suggest that membrane separation technology is a viable method for separating lactic acid produced from a mixture of residual candy-waste and digestate. [Display omitted] • Nanofiltration at pH 2.8 was efficient for lactic acid recovery. • Monopolar electrodialysis at pH 4.0 led to the highest lactic acid recovery. • Monopolar electrodialysis led to higher lactic acid recovery than nanofiltration. • Nanofiltration was less energy-demanding than monopolar electrodialysis. • Lactic acid titer reached 115 g L-1 after fed-batch monopolar electrodialysis. [ABSTRACT FROM AUTHOR]

Trace metals are indispensable for the metalloenzymes involved for efficient H 2 /CO 2 biomethanation. In-depth understanding of trace metals requirements of methanogens cannot only lead to robust and stable operation, but also can enhance CH 4 productivity. In this study, the effect of Fe, Mn, Co, Ni, Cu, Zn, Se, Mo and W on the H 2 /CO 2 biomethanation was examined. In a period of nutrient deprivation, suppression of hydrogenotrophic archaea was revealed at higher feed gas rates, leading to a significant drop in CH 4 content and a concomitant rise in acetic acid concentration. After nutrient supplementation, the increase in Co, Ni and Fe concentrations were pivotal factors for enhanced methanogenic activity, leading to a CH 4 content of more than 98% in the outlet biogas and a sharp drop in acetic acid concentration. Moreover, mathematical modeling was employed to simulate the influence of the most prominent element, iron, on the biomethanation process. The amended BioModel demonstrated that Fe limitation suppresses hydrogenotrophic archaea which consequently leads to H 2 accumulation and growth of homoacetogenic bacteria. [Display omitted] • Effect of nutrients deficiency on H 2 /CO 2 biomethanation was experimentally assessed. • Effect of iron on the biomethanation process was modeled. • Lack of iron impaired hydrogenotrophs and enhanced homoacetogenic activity. • Nutrients supplementation using digested manure avoided acetate accumulation. • Nutrients replenishment recovered hydrogenotrophs and decreased homoacetogenesis. [ABSTRACT FROM AUTHOR]

Competition for H 2 between homoacetogenic bacteria and methanogenic archaea is commonly faced in biological biogas upgrading process reducing the potential for high methane production capacities. In the present work, different feeding regimes were examined using anaerobic inocula that were adapted and non-adapted to the gaseous feedstock. Adapted inoculum could compensate the increased pressure at all examined levels and especially, produced above 95% of the theoretical methane without accumulating acetate at 0.2 atm. On the contrary, acetate accumulation was detected when a non-adapted inoculum was used. Microbial adaptation to elevated pressures can be applied as a means to improve production capacities. Thermodynamic analysis showed that hydrogenotrophic methanogenesis had always lower permissive H 2 partial pressures (3.20–7.46 Pa) compared to homoacetogenesis (0.43–0.85 Pa) at the examined pH (neutral vs alkaline) and pressure levels (i.e., 0.2–2.0 atm). An unstructured kinetic model was developed to study the influence of the examined variables in the hydrogenotrophic, homoacetogenesis and aceticlastic pathways. The kinetic parameters of the proposed model were estimated from experimental results and the goodness of the fitting was assessed by the coefficient of determination which indicated that the model describes efficiently the dynamics of the different compounds involved in the investigated pathways. [Display omitted] • Biological CO 2 and H 2 capturing is competitive between homoacetogens and methanogens. • Adaptation to substrate can avoid accumulation of acetate. • Methanogens had lower permissive H 2 partial pressures than homoacetogens. • Substrate competition between homoacetogens and methanogens was modeled. [ABSTRACT FROM AUTHOR]