Clear Targets Research Articles

Změna klimatu a limity odpovědnosti států

Climate change is now considered one of the greatest global challenges facing the world community. Climate change, or rather global warming, which is its main accelerator, is responsible for many of the negative impacts that people in different parts of the world are facing today. The world community is responding to climate change and setting clear targets to be achieved so that global warming begins to slow down and then returns to its natural equilibrium. However, this goal will not be achieved immediately, and certain parts of the world are already experiencing significant negative impacts that are affecting their human rights and fundamental freedoms. The question of responsibility, i.e., who is responsible for causing these negative impacts and who is responsible for addressing them, is still not closed. The so-called climate litigation, which has been spreading around the world since the middle of the last decade, could help to clarify it. Recently, human rights arguments have been emphasised in this litigation, and there is great potential that in the near future judicial and other decisions will eventually force states to act more effectively, especially on their international obligations and the potential liability consequences of non-compliance.

Climate Change Mitigation in Agriculture beyond 2030: Options for Carbon Pricing and Carbon Border Adjustment Mechanisms

SummaryIn the EU's climate policy, agriculture is covered as an Effort‐Sharing (ESR) sector, i.e. a sector beyond the Emission Trading System and LULUCF. Despite ambitious climate targets for the ESR sectors and an emerging focus on the need for agriculture to make a substantial contribution to climate change mitigation, agriculture has contributed much less to achieving climate targets than other ESR sectors in most EU Member States. A more radical mitigation instrument is required since the potential to increase climate efficiency in EU agriculture is limited. Carbon pricing is considered an effective instrument and is widely adopted in other sectors worldwide. Options on how to reduce related carbon leakage are discussed. Our recommendations for efficient climate change mitigation policy in agriculture are threefold. First, the agricultural sector needs more precise guidance and clear climate targets. Second, although preventing all conflicts between climate change mitigation actions and other policy goals is impossible and inefficient, a policy could minimise adverse effects. Third, since agricultural GHG emissions can only be minimised and compensated by negative emissions in other sectors, well‐defined intersectoral coordination is required.

Real-world experience with 11C-methionine positron emission tomography in the management of acromegaly.

L-[methyl-11C]-methionine-positron emission tomography (Met-PET) is a potentially important imaging adjunct in the diagnostic workup of pituitary adenomas, including somatotroph tumors. Met-PET can identify residual or occult disease and make definitive therapies accessible to a subgroup of patients who would otherwise require lifelong medical therapy. However, existing data on its use are still limited to small case series. Here, we report the largest single-center experience (n = 61) in acromegaly. A total of 189 cases of acromegaly were referred to our national Met-PET service in the last 12 years. For this analysis, we have reviewed outcomes in those 61 patients managed exclusively by our multidisciplinary team (single center, single surgeon). Referral indications were as follows: indeterminate magnetic resonance imaging (MRI; n = 38, 62.3%), occult residual (n = 14, 23.0%), (radio-)surgical planning (n = 6, 9.8%), and occult de novo tumor (n = 3, 4.9%). A total of 33/61 patients (54.1%) underwent PET-guided surgery. Twenty-four of 33 patients (72.7%) achieved complete biochemical remission following (re-)surgery. Insulin-like growth factor 1 levels were reduced to <2 × upper limit of normal (ULN) in 6 of the remaining 9 cases, 3 of whom achieved levels of <1.1 × ULN compared with mean preoperative levels of 2.4 × ULN (SD 0.8) for n = 9. Only 3 patients developed single new hormonal deficits (gonadotropic/thyrotropic insufficiency). There were no neurovascular complications after surgery. In patients with persistent/recurrent acromegaly or occult tumors, Met-PET can facilitate further targeted intervention (surgery/radiosurgery). This led to complete remission in most cases (24/33) or significant improvement with comparatively low risk of complications. L-[methyl-11C]-methionine-positron emission tomography should therefore be considered in all patients who are potential candidates for further surgical intervention but present no clear target on MRI.

6 Identifying research gaps and opportunities to enhance sustainable beef production

Abstract Sustainability has evolved and extended its influence across diverse sectors of the economy, including those in the beef supply chain. Public-facing companies predominantly emphasize environmental sustainability, especially climate-associated features, while beef producers continue to prioritize economic sustainability, hoping to to ensure their operation thrives into the next generation. Diversifying revenue and improving productivity are pivotal for safeguarding economic sustainability and fostering resilient production systems. Diversification is not new to beef producers; many have integrated ecosystem services into their operations to generate non-production revenue. The most valuable asset of a beef producer is the productivity of the land. Decision support tools need to be enhanced to allow producers to either capitalize on above average forage production to generate additional income, or to plan for alternative strategies when forage supply is forecast to be reduced. Because downstream beef supply chain participants prioritize environmental sustainability or reduction of scope 3 emissions, an emerging diversification opportunity for beef producers is to address this opportunity. While soil carbon initiatives have received attention, companies with substantial scope 3 emissions from beef production may value greenhouse gas (GHG) emissions from cattle more highly. Incentives for practices that reduce GHG emission from cattle can simultaneously reduce environmental impact associated with beef production and generate an additional revenue stream adjacent to beef production. Current opportunities to participate in these incentive programs are limited. Research can address the creation of functional protocols, and their intrinsic value. Clear targets, for gross emissions or emissions intensity, must be set but are not equivalent. In particular, research on effective/acceptable monitoring, reporting, and verification of emissions claims is imperative to functional markets. Innovation in emissions management and productivity gains can be integrated, so that goals of economic and environmental sustainability among value chain participants can be achieved. Maintaining a comprehensive perspective on sustainability solutions is essential to meeting the needs of humanity.

Range-wide genetic analysis of an endangered bumble bee (Bombus affinis, Hymenoptera: Apidae) reveals population structure, isolation by distance, and low colony abundance.

Declines in bumble bee species range and abundances are documented across multiple continents and have prompted the need for research to aid species recovery and conservation. The rusty patched bumble bee (Bombus affinis) is the first federally listed bumble bee species in North America. We conducted a range-wide population genetics study of B. affinis from across all extant conservation units to inform conservation efforts. To understand the species' vulnerability and help establish recovery targets, we examined population structure, patterns of genetic diversity, and population differentiation. Additionally, we conducted a site-level analysis of colony abundance to inform prioritizing areas for conservation, translocation, and other recovery actions. We find substantial evidence of population structuring along an east-to-west gradient. Putative populations show evidence of isolation by distance, high inbreeding coefficients, and a range-wide male diploidy rate of ~15%. Our results suggest the Appalachians represent a genetically distinct cluster with high levels of private alleles and substantial differentiation from the rest of the extant range. Site-level analyses suggest low colony abundance estimates for B. affinis compared to similar datasets of stable, co-occurring species. These results lend genetic support to trends from observational studies, suggesting that B. affinis has undergone a recent decline and exhibit substantial spatial structure. The low colony abundances observed here suggest caution in overinterpreting the stability of populations even where B. affinis is reliably detected interannually. These results help delineate informed management units, provide context for the potential risks of translocation programs, and help set clear recovery targets for this and other threatened bumble bee species.

CHOP-mediated Gasdermin E expression promotes pyroptosis, inflammation, and mitochondrial damage in renal ischemia-reperfusion injury

In clinical practice, renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), often leading to acute renal failure or end-stage renal disease (ESRD). The current understanding of renal IRI mechanisms remains unclear, and effective therapeutic strategies and clear targets are lacking. Therefore, the need to find explicit and effective ways to reduce renal IRI remains a scientific challenge. The current study explored pyroptosis, a type of inflammation-regulated programmed cell death, and the role of Gasdermins E (GSDME)-mediated pyroptosis, mitochondrial damage, and inflammation in renal IRI. The analysis of human samples showed that the expression levels of GSDME in normal human renal tissues were higher than those of GSDMD. Moreover, our study demonstrated that GSDME played an important role in mediating pyroptosis, inflammation, and mitochondrial damage in renal IRI. Subsequently, GSDME-N accumulated in the mitochondrial membrane, leading to mitochondrial damage and activation of caspase3, which generated a feed-forward loop of self-amplification injury. However, GSDME knockout resulted in the amelioration of renal IRI. Moreover, the current study found that the transcription factor CHOP was activated much earlier in renal IRI. Inhibition of BCL-2 by CHOP leaded to casapse3 activation, resulting in mitochondrial damage and apoptosis; not only that, but CHOP positively regulated GSDME thereby causing pyroptosis. Therefore, this study explored the transcriptional mechanisms of GSDME during IRI development and the important role of CHOP/Caspase3/GSDME mechanistic axis in regulating pyroptosis in renal IRI. This axis might serve as a potential therapeutic target.

Estimating surrogates, utility graphs and indicator sets for soil capacity and security assessments using legacy data

Context Legacy data from prior studies enable preliminary analysis for soil security assessment which will inform future research questions. Aims This study aims to utilise the soil security assessment framework (SSAF) to evaluate the capacity of soil in fulfilling various roles and understand the underlying drivers. Methods The framework entails: (1) defining a combination of role(s) × dimension(s) and identifying a target indicator (a soil property that can be used to evaluate a particular role × dimension combination) or a surrogate indicator (an alternative indicator when there is not a clear target indicator); (2) transforming the indicator into a unitless score (ranging from 0 to 1) using a utility graph based on expert knowledge; (3) fitting the remaining soil properties (potential indicators) into utility graphs and weighing them using (a) ordination and (b) regression method. The application of this framework is demonstrated in evaluating two soil roles: nutrient storage and habitat for biodiversity (with pH and microbial DNA Shannon’s diversity index as surrogates, respectively) for an area in the lower Hunter Valley region, New South Wales, Australia. Key results The regression model provides utility estimates that were similar to those obtained from surrogates, in comparison to the utility derived from the ordination model. Conclusions This study provides a methodological pathway to examine the capacity and drivers of fulfilling different soil roles. The standardisation of this method opens the door to a complete quantification under the SSAF. Implications Indicators derived from a legacy dataset can be used for soil security assessment.

Rhizopus oryzae causes the leaf rot disease of Epimedium sagittatum in Guizhou, China.

Epimedium sagittatum is a collective term for herbaceous plants belonging to the family Berberidaceae. Their dried leaves and stems have significant therapeutic effects on tumor inhibition, hypertension control, and coronary heart disease (Ke et al. 2023; Zhao et al. 2019). In 2021 and 2022, plants with similar leaf rot symptoms ranging from 30% to 55% was observed on E. sagittatum in Congjiang County, Guizhou province. The initial symptoms of the disease manifest locally on the leaf, with yellowing on the surface edge of the affected tissue, browning in the middle part, and brown-white discoloration in the innermost part (Supplementary Figure S1B). As the disease progresses, the entire infected leaf gradually softens, while the veins remain intact (Supplementary Figure S1C). Ultimately, the leaf withers and dehisces. The nine samples with typical symptoms were collected from Congjiang County, Guizhou province (26.598°N, 106.707°E). Twenty-seven fungi were isolated, including ten isolates of Rhizopus and seventeen isolates of seven other genera. On isolate YYH-CJ-17 many sporangia were formed and turned to a brown-gray to black color on potato dextrose agar medium (PDA) after culturing 5 days under dark at 25 ℃ (Supplementary Figure S2A and S2B). The branches of mycelium were finger-shaped or root-shaped. The sporangium was spherical or nearly spherical, 60-250 µm in diameter, and sporangiospores were elliptical or spherical and 4-8 µm in diameter. The obtained 547 bp ITS fragment (accession OR225970) and 1231 bp EF-1α region (accession OR242258) from isolate YYH-CJ-17 were compared with NR database using the BLAST tool provided by NCBI, which revealed more than 99.5% identity (query cover more than 98%) with the sequences of ITS (accessions MF522822.1) and EF-1α (accession AB281541.1) of Rhizopus oryzae Went & H.C. Prinsen Geerlings (Gao et al. 2022; Zhang et al. 2022). The phylogenetic tree constructed with the ITS and EF-1α gene sequences demonstrates that strain YYH-CJ-17 clusters with R. oryzae in the same branch and the bootstrap value was greater than 99% (Supplementary Figure S3). Based on the morphological characteristics and ITS and EF-1a sequences, the isolate YYH-CJ-17 is identified as R. oryzae. Pathogenicity tests were performed on detached healthy leaves and living plants of E. sagittatum. Healthy leaves of E. sagittatum were subjected to inoculation with isolate YYH-CJ-17 with 5 × 105 CFU mL-1 concentration in sterile culture dishes. The progression of the disease was marked by the gradual softening of the infected leaves and the expansion of the lesions, which ultimately produced black-brown sporangium (Supplementary Figure S4A). Furthermore, the E. sagittatum living plants were sprayed with 5 × 105 CFU mL-1 conidial suspension of isolate YYH-CJ-17, with ddH2O as a negative control, and then were cultivated at 25℃ and 90% humidity for 21 days in the greenhouse. This assay found that the E. sagittatum leaves treated with isolate YYH-CJ-17 exhibited the same symptoms observed on plants in fields (Supplementary Figure S4B). The fungus re-isolated from the inoculated leaves were identified as R. oryzae by ITS sequencing and were blasted with NR database, which highest matched with the sequence of ITS (accessions MF522822.1) mentioned above, thus fulfilling Koch's postulates. R. oryzae has been identified as a causative agent of a diverse array of host diseases, including leaf mildew of tobacco, fruit rot of yellow oleander and pears, and soft rot of bananas (Farooq et al. 2017; Khokhar et al. 2019; Kwon et al. 2012; Pan et al. 2021). To the best of our knowledge, this is the first report of leaf rot on E. sagittatum caused by R. oryzae in China, which will provide clear prevention and management target for the leaf rot disease of E. sagittatum.

Archetypal representations of dilemmas concerning invasive alien species management—A case of invasive Lantana camara in the protected areas of Nilgiri Biosphere Reserve, India

AbstractThis multi‐site case study on the invasive alien plant Lantana camara in protected areas of Nilgiri Biosphere Reserve, India, addresses the reasons for inadequate institutional responses from stakeholders in managing the species despite the seriousness. The study uses thematic analysis and qualitative systems approach. The themes are converted into a qualitative‐system‐dynamics model and are then abstracted into system archetypes. The study identified three major themes: the dilemma involving stakeholders, the dilemma of alternative and commercial use of Lantana, and the Lantana management conundrum. The study translated these dilemmas into four generalisable archetypes: ‘drifting goals’, ‘modified‐shifting‐the‐burden’, ‘fixes‐that‐fail’ and ‘substitution rebound’. The latest is a novel contribution to the systems literature. Practically, the study helps understand the recurring undesired behavioural patterns in invasive species management and suggests policy and governance changes to tackle them. The study also points towards building stakeholder relationship protocols, focussing on fundamental solutions and having clear Lantana management targets.

Projected health and economic effects of the increase in childhood obesity during the COVID-19 pandemic in England: The potential cost of inaction.

The prevalence of overweight and obesity in young children rose sharply during the COVID-19 pandemic. Here we estimate the potential future health and economic effects of these trends in England. Using publicly available annual Body Mass Index (BMI) data from 2006-2022, we calculated the increase in overweight/obesity prevalence (BMI ≥85th reference percentile) during the COVID-19 pandemic among children aged 4-5 and 10-11, and variation by deprivation and ethnicity. We projected the impact of child BMI trends on adult health measures to estimate added lifelong medical and social costs. During 2020-2021 there were steep increases in overweight and obesity prevalence in children. By 2022, overweight and obesity prevalence in children aged 4-5 returned to expected levels based on pre-pandemic trends. However, overweight and obesity prevalence in children aged 10-11 persisted and was 4 percentage points (p<0.001) higher than expected, representing almost 56,000 additional children. The increase was twice as high in the most compared with the least deprived areas. The additional lifelong healthcare cost in this cohort will amount to £800 million with a cost to society of £8.7 billion. We did not find an increase in maternal obesity associated with the COVID-19 pandemic, however, prevalence grew faster in the post pandemic period. The return of overweight and obesity prevalence to pre-pandemic trends in children aged 4-5 provides a clear policy target for effective intervention to tackle this growing and serious population health concern.

Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss.

There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL.

Perspektif Ekonomi Islam Terhadap Pendistribusian Zakat Di Baznas Karangasem Bali

Zakat distribution is the distribution, distribution, delivery of goods or services to many people or several places. The distribution of zakat has clear and directed targets and objectives according to the basis stated in the Al-Qur'an which is applied to the form of zakat distribution. The method used in this research is a descriptive method using a qualitative approach which aims to describe zakat institutions in a comprehensive and comprehensive manner through observation, interviews and documentation. The results of this research explain that the forms of distribution of zakat funds carried out by zakat institutions to improve community welfare are consumptive distribution and productive distribution so that they are able to improve people's living standards. The targets of zakat distribution carried out by BAZNAS Karangasem Bali are eight asnaf, namely the needy, poor, amil, converts, riqab, gharimin, fisabilillah, and ibn sabil. The steps for distributing zakat carried out by BAZNAS Karangasem Bali are planning, implementation and supervision. So, with distribution in the form of empowerment and the right targets and good stages at BAZNAS Karangasem Bali, it has succeeded in improving the welfare of the community.

Stress and burnout amongst mental health professionals in Singapore during Covid-19 endemicity.

The COVID-19 pandemic has exerted a huge emotional strain on mental health professionals (MHP) in Singapore. As Singapore transited into an endemic status, it is unclear whether the psychological strain has likewise lessened. The aims of this study were to investigate the levels of stress and burnout experienced by MHP working in a tertiary psychiatric hospital in Singapore during this phase of COVID-19 endemicity (2022) in comparison to the earlier pandemic years (2020 and 2021) and to identify factors which contribute to as well as ameliorate stress and burnout. A total of 282 MHP participated in an online survey in 2022, which included 2 validated measures, namely the Perceived Stress Scale and the Oldenburg Burnout Inventory (OLBI). Participants were also asked to rank factors that contributed the most to their stress and burnout. Between-group comparisons were conducted regarding stress and burnout levels among MHP across different demographic groupings and working contexts. In addition, OLBI data completed by MHP in 2020 and 2021 were extracted from 2 published studies, and trend analysis was conducted for the proportion of MHP meeting burnout threshold across 3 time points. We found that the proportion of MHP meeting burnout threshold in 2020, 2021 and 2022 were 76.9%, 87.6% and 77.9% respectively. Professional groups, age, years of experience and income groups were associated with stress and/or burnout. High clinical workload was ranked as the top factor that contributed to stress and burnout while flexible working arrangement was ranked as the top area for improvement so as to reduce stress and burnout. As such, policy makers and hospital management may want to focus on setting clear mental health targets and facilitate manageable clinical workload, build manpower resiliency, optimize resources and provide flexible work arrangements to alleviate stress and burnout among MHP.

Health Determinants: Healthy People of the UAE 2025 – 2035 Plan

Purpose: The goal of the Healthy People initiative is to improve the health of the nation as a whole by directing efforts that are made at the national level to promote health and prevent sickness (Healthy People, 2023). &#x0D; Methodology: This been a white paper the study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low-cost advantage as compared to field research. The current study looked into already published studies and reports as the data was easily accessed through online journals and libraries.&#x0D; Findings: The study found out that promoting a healthier and more informed generation requires health literacy in youngsters. The study also found out that the reduction of obesity among police officers would enhance both their general well-being and their effectiveness at work. The study indicated that a comprehensive road safety program targeting car accidents should be implemented to reduce road accidents&#x0D; Unique Contribution to Theory, Practice and Policy: Primary school’s teachers should integrate health education as a regular part of the curriculum, The police department should establish clear and realistic goals and incentives for police officers to participate in the health and wellness programs and drivers should undergo regular training and testing to ensure they follow the traffic rules and regulations. Education authorities should support and facilitate health literacy instruction in primary schools, by providing adequate resources and training, The United Arab Emirates (UAE) government should allocate more funds and resources to support individualized health and wellness programs for police officers, as well as to raise awareness about the risks of obesity and the benefits of physical activity and healthy eating. The government should develop and implement a national road safety strategy that sets clear goals and targets for reducing car accident fatalities and injuries. This strategy should be evidence-based and regularly updated.

Effects of scutellarin on the mechanism of cardiovascular diseases: a review.

Cardiovascular diseases represent a significant worldwide problem, jeopardizing individuals' physical and mental wellbeing as well as their quality of life as a result of their widespread incidence and fatality. With the aging society, the occurrence of Cardiovascular diseases is progressively rising each year. However, although drugs developed for treating Cardiovascular diseases have clear targets and proven efficacy, they still carry certain toxic and side effect risks. Therefore, finding safe, effective, and practical treatment options is crucial. Scutellarin is the primary constituent of Erigeron breviscapus (Vant.) Hand-Mazz. This article aims to establish a theoretical foundation for the creation and use of secure, productive, and logical medications for Scutellarin in curing heart-related illnesses. Additionally, the examination and analysis of the signal pathway and its associated mechanisms with regard to the employment of SCU in treating heart diseases will impart innovative resolving concepts for the treatment and prevention of Cardiovascular diseases.

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multi-faceted illness. Heterogenous onset and clinical presentation with additional comorbidities make it difficult to diagnose, characterize, and successfully treat. Current treatment guidelines focus on symptom management, but with no clear target or causative mechanism, remission rates are low, and fewer than 5% of patients return to their pre-morbid activity levels. Therefore, there is an urgent need to undertake robust clinical trials to identify effective treatments. This review synthesizes insights from clinical trials exploring pharmacological interventions and dietary supplements targeting immunological, metabolic, gastrointestinal, neurological, and neuroendocrine dysfunction in ME/CFS patients which require further exploration. Additionally, the trialling of alternative interventions in ME/CFS based on reported efficacy in the treatment of illnesses with overlapping symptomology is also discussed. Finally, we provide important considerations and make recommendations, focusing on outcome measures, to ensure the execution of future high-quality clinical trials to establish clinical efficacy of evidence-based interventions that are needed for adoption in clinical practice.

Reflecting on the conceptual core and developing a short version of international posture

International posture (IP) is a construct postulated by Yashima (2002) to capture attitudes toward international communities, including readiness to approach and communicate with intercultural partners, interest in international affairs, and willingness to go overseas to stay and work, which are believed to relate to L2 learning motivation. A recent comprehensive review of 66 studies by Botes et al. (2020) identified IP's usefulness and raised certain issues. To address these concerns, this study aims to develop a short version of IP, while maintaining the conceptual core of the original construct, namely: a) Focusing on motivation to learn an L2 as a lingua franca without a clear target population to identify with; b) Addressing both integrative and instrumental motives to learn an L2 that can coexist in learners; and c) Capturing multiple dimensions that comprise the overarching concept of IP. We report the process of developing a 10-item short version of IP with exploratory factor analyses, validation of item selection, and confirmatory factor analyses of the 10 selected items, which show the same structures as the original longer version. Subsequently, correlations as well as structural equation modeling procedures confirmed the nomological position and construct validity of the short scale vis-à-vis motivation-related constructs.

Mind shift I: Fructus Aurantii - Rhizoma Chuanxiong synergistically anchors stress-induced depression-like behaviours and gastrointestinal dysmotility cluster by regulating psycho-immune-neuroendocrine network

BackgroundResearchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PurposeMDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. Study designAcute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. Methods/resultsHere, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. ConclusionBrain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.

An inflexible adherence to food rules mediates the longitudinal association between shape/weight overvaluation and binge eating

Understanding factors that account for the persistence of binge eating is necessary for developing effective early intervention and treatment approaches. The cognitive-behavioral model of eating disorders proposes that judgements of self-worth contingent upon weight and shape encourage adoption of multiple demanding rules related to food, eating and dieting, in turn increasing vulnerability to binge eating. However, there is limited longitudinal evidence supporting this hypothesized sequence of events. This study tested whether the longitudinal association between shape/weight overvaluation and binge eating is mediated by an inflexible adherence to food rules. Participants were 1760 adult women recruited from an online eating disorder platform who were invited to complete study measures at baseline (T1), 3-month follow-up (T2), and 6-month follow-up (T3). Path analysis was conducted to test the hypothesized associations. Missing data were handled using multiple imputation techniques. A significant indirect effect emerged, in that higher overvaluation scores at T1 predicted increased inflexible adherence to food rules at T2, which in turn predicted increased binge eating symptoms at T3. Findings offer support for the predictions outlined by the cognitive-behavioral model of eating disorders and highlight clear targets for early intervention and treatment.

A mixed-methods approach utilising electronic health records to examine antimicrobial prescription surrounding gastrointestinal clinical presentations in dogs and cats.

Systemically-administered antimicrobials are often prescribed in canine and feline gastrointestinal clinical presentations. Responsible use of antimicrobials, particularly those considered Highest Priority Critically Important Antimicrobials (HPCIAs) is vital to tackle antimicrobial resistance. Although practice-level prescription guidance is available, further strategies based on a greater understanding of antimicrobial prescription at the population-level are needed. Here, we used a mixed-methods approach, harnessing veterinary electronic health records (EHRs) to characterise the use of antimicrobials in canine and feline gastrointestinal presentations, and to explore justification and reasoning around antimicrobial prescribing, particularly of HPCIAs. This observational study used 23,337 EHRs complemented with veterinary practitioner-completed questionnaires, from canine and feline gastrointestinal consultations from 225 volunteer UK veterinary practices between April 2014 and September 2018. A total of 83.4% (95% confidence interval (CI) 82.6-84.3) gastrointestinal presentations were reported as mild, with non-haemorrhagic diarrhoea and vomiting the most frequently reported clinical signs. Systemically-administered antimicrobials occurred in 28.6% of canine (95% CI 26.9-30.3) and 22.4% of feline (95% CI 20.4-24.4) gastrointestinal consultations, with HPCIA prescription occurring more frequently in cats. Results of multivariable analysis showed the presence of non-haemorrhagic diarrhoea (canine Odds Ratio (OR) 2.1, 95% CI 1.9-2.3; feline OR 1.8, 95% CI 1.5-2.1), haemorrhagic diarrhoea (canine OR 4.2, 95% CI 3.8-4.7; feline OR 3.1, 95% CI 2.4-3.8), and moderate/severe presentations (canine OR 1.9, 95% CI 1.7-2.8; feline OR 2.0, 95% CI 1.7-2.5) were positively associated with receiving a systemically-administered antimicrobial. Thematic analysis of clinical narrative content of 516 gastrointestinal consultations where HPCIAs were prescribed allowed the identification of ten factors underpinning reasoning or decision-making for HPCIA prescription: perceived animal/owner compliance; owner's expectations; perceived risk of infection; clinical signs; recent clinical history; perceived positive previous response to antimicrobial therapy; geriatric patients and euthanasia; concomitant conditions; diagnostic testing and the behavioral trend to trial antimicrobial therapy empirically in gastrointestinal cases. No explicit justification for HPCIA prescription was recorded in 77% of cases. Improving recorded justification represents a clear target for stewardship programmes. By utilising a complementary mixed-methods approach to EHRs, this study unlocks previously untapped data recorded within EHRs. These results can help inform targeted interventions, contributing towards enhanced antimicrobial stewardship.