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An estimated 990,000 new cases of gastric cancer are diagnosed worldwide each year. Surgical excision, the only chance for prolonged survival, is feasible in about 20% of cases. Even after surgery, the median survival is limited to 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. This led to clinical trials associating surgery with neoadjuvant or adjuvant treatments to improve tumor control and patient survival. The most studied modalities are perioperative chemotherapy and adjuvant chemoradiotherapy. To date, evidence has shown a survival benefit for postoperative chemoradiotherapy and for perioperative chemotherapy. Phase III trials are ongoing to compare these two modalities. The aim of this review is to synthesize current knowledge about adjuvant chemoradiotherapy in the management of gastric adenocarcinoma, and to consider its prospects by integrating modern radiotherapy techniques. Keywords: Gastric cancer, Adjuvant therapy, Chemoradiotherapy, IMRT, Adenocarcinoma

DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of ∼30–40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms.In the present study, we used Affymetrix oligonucleotide microarrays to analyze global gene expression in blood samples of 15 manifesting and 15 non-manifesting mutation carriers in order to identify a susceptibility profile beyond the GAG deletion which is associated with the manifestation of symptoms in DYT1 dystonia.We identified a genetic signature which distinguished between asymptomatic mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100% specificity. This genetic signature could correctly predict the disease state in an independent test set with a sensitivity of 87.5% and a specificity of 85.7%.Conclusively, this genetic signature might provide a possibility to distinguish DYT1 patients from asymptomatic mutation carriers.

Abstract In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline’s ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (Mpro) and papain-like protease (Plpro), as well as of the human transmembrane serine protease 2 (TMPRSS2), were selected as target cavities. Using active-site point-cloud comparisons, it was possible to identify two compounds—flufenamic acid and fusidic acid—which show strong inhibition of viral replication. The complexes from which fusidic acid and flufenamic acid were derived would not have been identified using classical sequence- and structure-based methods as they show very little structural (TM-score: 0.1 and 0.09, respectively) and very low sequence (~ 5%) identity to Mpro and TMPRSS2, respectively. Furthermore, a cavity-based off-target screening was performed using acetylcholinesterase (AChE) as an example. Using cavity comparisons, the human carboxylesterase was successfully identified, which is a described off-target for AChE inhibitors.

Abstract This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to g aγ ∼ 1.5 × 10 −11 GeV −1, and masses up to m a ∼ 0.25 eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups.

The effective and sustainable environmental performance of a business is a result of various factors and most important the integrated outcome of the environmental management. Likewise, the integration of environmental protection into the armed forces functions has also gain interest for the military sector internationally. Therefore, the environmental management system (EMS) is recognized as one of the most widely used tools. This study provides a review on environmental management issues related to the military activities and their assessment globally. The multitasking characteristics of the defence sector result in the need for the eco-friendly related issues to be directed in a holistic and integrated way, with the help of a certified environmental management system. North Atlantic Treaty Organization (NATO) itself and NATO countries, like USA, UK, Canada, Holland, Denmark, Czech Republic, Greece, as well as non-NATO countries like Sweden and Australia have an environmental management system structure in place to assist military environmental management and studies reveal that the armed forces could anticipate positive outcomes from environmental management system. A case-by-case approach, of the above, is examined and based on the results, appropriate recommendations are presented, which may contribute to the environmental management system considerations as the most important tool for effective management framework and most importantly to evaluate its effectiveness as a structure for the defence sector’s activities.

Abstract This paper reports on the development of a technology involving $$^{100}\hbox {Mo}$$ 100 Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( $$\sim 1~\hbox {kg}$$ ∼ 1 kg ), high optical quality, radiopure $$^{100}\hbox {Mo}$$ 100 Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2–0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of $$^{100}\hbox {Mo}$$ 100 Mo (3034 keV) is 4–6 keV FWHM. The rejection of the $$\alpha $$ α -induced dominant background above 2.6 MeV is better than $$8\sigma $$ 8 σ . Less than $$10~\upmu \hbox {Bq/kg}$$ 10 μ Bq/kg activity of $$^{232}\hbox {Th}\, (^{228}\hbox {Th})$$ 232 Th ( 228 Th ) and $$^{226}\hbox {Ra}$$ 226 Ra in the crystals is ensured by boule recrystallization. The potential of $$^{100}\hbox {Mo}$$ 100 Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only $$10~\hbox {kg}\times \hbox {d}$$ 10 kg × d exposure: the two neutrino double-beta decay half-life of $$^{100}\hbox {Mo}$$ 100 Mo has been measured with the up-to-date highest accuracy as $$T_{1/2}$$ T 1 / 2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] $$\times ~10^{18}~\hbox {years}$$ × 10 18 years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of $$^{100}\hbox {Mo}$$ 100 Mo .

It is challenging to explore properties of heavy elements as they can only be produced artificially. Here, the authors demonstrate a high resolution spectroscopy method, studying the properties of actinium, which can be extended to the study of other elements located at the end of the periodic table.

Advanced studies in cancer related pain have demonstrated that intrathecal administration of opioids has been much more effective than other drug-administrating routes.The most frequently used drug has been morphine which is the first opioid approved by the US Food and Drug Administration (FDA) for intra-spinal use.Practical conversion rules for different morphine administrating routes were given by Foley et al (1985).Those doses and concentrations are now recommended as a starting doseguideline for the initial phase of treatment.Dosage indicators should be assessed and individualized based on patient response, analgesic requirements and side effects.Therefore, we are herewith presenting findings from a study regardingmorphine doses compared to conversion doses (as per our algorithm) in chronic cancer pain during drug-administration by spinal route.

We present the first laboratory experiments of aerosol formation from oxidation of volatile organic species emitted by living plants, a process which for half a century has been known to take place in the atmosphere. We have treated white cabbage plants with methyl jasmonate in order to induce the production of monoterpenes and certain less-volatile sesqui- and homoterpenes. Ozone was introduced into the growth chamber in which the plants were placed, and the subsequent aerosol formation and growth of aerosols were monitored by measuring the particle size distributions continuously during the experiments. Our observations show similar particle formation rates as in the atmosphere but much higher growth rates. The results indicate that the concentrations of nonvolatile oxidation products of plant released precursors needed to induce the nucleation are roughly an order-of-magnitude higher than their concentrations during atmospheric nucleation events. Our results therefore suggest that if oxidized organics are involved in atmospheric nucleation events, their role is to participate in the growth of pre-existing molecular clusters rather than to form such clusters through homogeneous or ion-induced nucleation.

Introduction Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Patients are rarely examined in this population pretherapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. We present a protocol of a prospective longitudinal research study of adult patients in a single Australian haematology service undergoing CAR-T therapy. The study will describe neurocognitive features specific to ICANS, characterise the underlying syndrome, capture recovery, identify predictors of differential postinfusion outcomes and determine a set of cognitive instruments necessary to monitor patients acutely.Methods and analysis This is a prospective longitudinal study that comprises neuropsychological and neurological examinations occurring prior to CAR-T, during the acute post-treatment period, 28 days, 6 months and 12 months post infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires of psychopathology and accounts of subjective cognitive complaint.Ethics and dissemination This study aims to guide diagnosis, management and monitoring of neurocognitive features of CAR-T cell therapy. Results of this study will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. All procedures involving human subjects/patients were approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (21/145).

There remains limited understanding and mixed results around predictors of compulsive exercise, especially outside of eating disorder populations and settings. Research is also limited by operationalisation of compulsive exercise as a unidimensional construct, despite evidence that it is best understood and examined as multi-dimensional. Given that compulsive exercise is also observed in the general exercise population, increased understanding around predictors of compulsive exercise is needed. This study examined the relationship between dimensions of compulsive exercise (Compulsive Exercise Test) with obsessive and harmonious passion (the Passion Scale) and exercise identity (the Exercise Identity Scale) in a sample of N = 1184 Australian general exercisers. Correlation, regression and moderation analyses indicated that exercise identity was associated with all dimensions of compulsive exercise, although strength and direction of relationships varied. Harmonious passion was related to several dimensions of compulsive exercise and also moderated relationships between identity with weight-control exercise, mood improvement and lack of exercise enjoyment, whereas obsessive passion moderated the relationship between identity and lack of exercise enjoyment only. Results highlight that compulsive exercise dimensions have nuanced relationships with other variables and that examination of dimensions can increase understanding around compulsive exercise. Harmonious passion predicted more aspects of compulsive exercise than obsessive passion. Individuals with high exercise identity, and those with low harmonious passion may be more at risk of poor outcomes including compulsive exercise pathology and other related outcomes.

“Beta beams” produce collimated pure electron (anti)neutrino beams by accelerating beta active ions to high energies and having them decay in a racetrack shaped storage ring of 7 km circumference, the decay ring. EUROnu beta beams are based on CERN infrastructures and existing machines. Using existing machines may be an advantage for the cost evaluation, but will also constrain the physics performance. The isotope pair of choice for the beta beam is ^{6}He and ^{18}Ne. However, before the EUROnu studies one of the required isotopes, ^{18}Ne, could not be produced in rates that satisfy the needs for physics of the beta beam. Therefore, studies of alternative beta emitters, ^{8}Li and ^{8}B, with properties interesting for a beta beam have been proposed and have been studied within EUROnu. These alternative isotopes could be produced by using a small storage ring, in which the beam traverses a target, creating the ^{8}Li and ^{8}B isotopes. This production ring, the injection linac and the target system have been evaluated. Measurements of the cross section of the reactions to produce the beta beam isotopes show interesting results. A device to collect the produced isotopes from the target has been developed and tested. However, the yields of ^{8}Li and ^{8}B, using the production ring for production of ^{8}Li and ^{8}B, is not yet, according to simulations, giving the rates of isotopes that would be needed. Therefore, a new method of producing the ^{18}Ne isotope has been developed and tested giving good production rates. A 60 GHz ECRIS prototype, the first in the world, was developed and tested for ion production with contributions from EUROnu. The decay ring lattices for the ^{8}Li and ^{8}B have been developed and the lattice for ^{6}He and ^{18}Ne has been optimized to ensure the high intensity ion beam stability.

# Background In response to the COVID-19 pandemic, nations around the world introduced a range of behavioural interventions and restrictions in order to manage the spread of the virus. These included social distancing, lockdowns, and use of personal protective equipment, amongst others. The aim of the present paper is to examine some of the effects of these interventions on the psychological wellbeing and mental health of older adults, especially those with hearing loss. # Methods The present review focused on published peer reviewed studies focusing on older adults. Search engines included Google Scholar, SpringerLink Journals, ProQuest Central, and PubMed employing different combinations of search terms such as "COVID-19", "older adults", and "isolation". # Results Older adults were at risk of experiencing increased anxiety and depression and poorer wellbeing during lockdowns across nations, with those self-reporting loneliness reporting more severe symptomatology. Reductions in wellbeing were observed both amongst community-dwelling older adults and those living in residential care facilities. Use of personal protective equipment, especially masks, and social distancing requirements impacted communication amongst older adults with hearing loss, with this subgroup reporting increased depression, anxiety, and stress, with symptoms increasing with the severity of the hearing loss. # Conclusions While technology can help to mitigate the impacts of lockdowns and restrictions, limited access to devices and a range of challenges in upskilling older adults has impacted the utility of these technologies for promoting wellbeing. Education and training in the use of technologies and digital devices for both older adults and families might assist in promoting wellbeing, with increased accessibility needed in aged care facilities to further support the wellbeing of residents.

The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Fréjus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of μ^{+} and μ^{-} beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular ^{6}He and ^{18}Ne, also stored in a ring. The far detector is also the MEMPHYS detector in the Fréjus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive.

Behaviour changes (BCs) are common in young-onset dementia (YOD). Access to knowledgeable and age-appropriate support services is needed to assist with the appropriate management of BCs. We sought to investigate the types of YOD-related BCs that most commonly require support, the formal services being accessed for support, and the experiences of those seeking support in Australia. We employed a cross-sectional online questionnaire for individuals living with YOD as well as individuals providing informal or formal care for someone with YOD. Thirty-six questionnaire responses were recorded. Of the total sample, 83% reported YOD-related BCs requiring support, the most common being appetite/eating changes, followed by agitation/aggression and apathy/indifference. Seventy-six percent of these individuals had attempted to seek support from a formal service, with Dementia Australia, Dementia Support Australia, and general practitioners most commonly approached. Responses suggested that the support access pathway is suboptimal, with a lack of clarity about what services to approach for support and long wait times. Furthermore, 28% of participants had not gained access to support utilizing non-pharmacological strategies. Individuals who need support for YOD-related BCs demonstrated a high rate of help-seeking from formal support services; however, the support access pathway is slow, is difficult to navigate, and does not result in the best-practice management of BCs. Formal services resourced to provide efficient support with the implementation of behavioural strategies are needed, along with clear, accessible guidelines on the pathway to access them.

Abstract Background With increasing numbers of people living with dementia relying on family to care for them at home, there is an urgent need for practical and evidence-based programs to support carers in maintaining their mental health and well-being. The objective of this study was to evaluate the acceptability and feasibility of a modified STrAtegies for RelaTives (START) program delivered online (START-online). Method A mixed-methods non-blinded evaluation of START-online (using Zoom as videoconferencing platform) for acceptability and feasibility (completion rates and qualitative feedback through surveys and focus groups) and quantitative evaluation. This occurred at the National Ageing Research Institute, in metropolitan Victoria, Australia. Results Twenty-nine eligible carers were referred, 20 (70%) consented to the study. Of these, 16 (80%) completed all 8 sessions, 2 completed only 3 sessions, and 2 withdrew. Carers’ qualitative feedback indicated that the therapist interaction was valued, content and online delivery of the program was acceptable. Feedback was mixed on the appropriate stage of caring. Conclusion START-online was feasible and acceptable for carers, including those living outside of metropolitan areas who might otherwise be unable to access face-to-face programs. With the recent COVID-19 pandemic necessitating social distancing to avoid infection, interventions such as this one have increasing relevance in the provision of flexible services.

Abstract Background Our objective was to explore what people receiving and providing care consider to be ‘good’ in-home care for people living with dementia. Methods We conducted 36 in-depth interviews and two focus groups with key stakeholders in Australia in the first quarter of 2018. Participants included those receiving care (4 people living with dementia, 15 family carers) or providing care (9 case managers, 5 service managers, 10 home care workers). Qualitative thematic analysis was guided by Braun and Clarke’s six-step approach. Results Consensus was reached across all groups on five themes considered as important for good in-home dementia care: 1) Home care workers’ understanding of dementia and its impact; 2) Home care workers’ demonstrating person-centred care and empathy in their care relationship with their client; 3) Good relationships and communication between care worker, person with dementia and family carers; 4) Home care workers’ knowing positive practical strategies for changed behaviours; 5) Effective workplace policies and workforce culture. The results contributed to the co-design of a dementia specific training program for home care workers. Conclusions It is crucial to consider the views and opinions of each stakeholder group involved in providing/receiving dementia care from home care workers, to inform workforce training, education program design and service design. Results can be used to inform and empower home care providers, policy, and related decision makers to guide the delivery of improved home care services. Trial registration ACTRN 12619000251123 .

Abstract Background Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home. Methods This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs’ sense of competence in dementia care provision. Discussion Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs. Trial registration anzctr.org.au ; ACTRN12619000251123. Registered on 20 February 2019.

Poor mental wellbeing not only affects an individual and their family, but it also affects the workplace and the society as a whole. Consequently, it is crucial to investigate approaches that can promote a positive mindset in order to enhance wellbeing. This study aimed to explore the association between gratitude, wellbeing, spirituality, and experiencing meaningful work. A sample of 197 participants (69.5% female) completed measures of gratitude, experiencing meaningful work, spirituality, and several wellbeing indices. Gratitude was significantly positively associated with happiness, life satisfaction, flourishing, positive affect, spirituality, and experiencing meaningful work. A mediation analysis revealed that the relationship between wellbeing and experiencing meaningful work was partially mediated by gratitude. Additionally, spirituality did not moderate the relationship between gratitude and experiencing meaningful work. Overall, the findings indicate that fostering a grateful mindset could enhance wellbeing and work engagement, which in turn could lead to the experience of meaningful work.

O-GlcNAcylation is an important post-translational and metabolic process in cells that must be carefully regulated. O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to proteins. OGT is a promising target in various pathologies such as cancer, immune system diseases, or nervous impairment. In our previous work we identified the 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives as promising compounds by a fragment-based drug design approach. Herein, we report the extension of this first series with several new fragments. As the most potent fragment, we identified 3b with an IC50 value of 116.0 μM. If compared with the most potent inhibitor of the first series, F20 (IC50 = 117.6 μM), we can conclude that the new fragments did not improve OGT inhibition remarkably. Therefore, F20 was used as the basis for the design of a series of compounds with the elongation toward the O-GlcNAc binding pocket as the free carboxylate allows easy conjugation. Compound 6b with an IC50 value of 144.5 μM showed the most potent OGT inhibition among the elongated compounds, but it loses inhibition potency when compared to the UDP mimetic F20. We therefore assume that the binding of the compounds in the O-GlcNAc binding pocket is likely not crucial for OGT inhibition. Furthermore, evaluation of the compounds with two different assays revealed that some inhibitors most likely interfere with the commercially available UDP-Glo™ glycosyltransferase assay, leading to false positive results. This observation calls for caution, when evaluating UDP mimetic as OGT inhibitors with the UDP-Glo™ glycosyltransferase assay, as misinterpretations can occur.

Objective: People with neurocognitive disorders (NCDs) have an increased risk of epilepsy. However, most studies investigating the risk of seizures in people with NCDs are limited to those with Alzheimer's disease (AD) and vascular dementia (VD), and those who developed dementia after age 65 years. A knowledge gap exists regarding factors associated with development of epilepsy in people with younger-onset NCD, and those with non-AD and non-VD dementia subtypes. In this study, we aimed to identify the factors associated with the development of epilepsy in people with younger-onset NCDs of varied etiologies, the majority of whom had symptom onset prior to age 65 years.Participants and Methods: This was a retrospective study reviewing the medical records of consecutive people admitted with cognitive impairment to a tertiary neuropsychiatry unit between 1 January 2004 and 30 April 2019. People diagnosed with primary NCDs were included in the analysis. The prevalence and characteristics of epilepsy were described. The factors associated with developing epilepsy were identified in a binary logistic regression model.Results: A total of 427 people were included. One hundred fourteen had Alzheimer's disease, 104 frontotemporal dementia, 51 vascular dementia, 69 movement disorder-associated dementia, and 89 unspecified NCD. The median age on admission was 59 years (range 33–86) and 75.2% (n = 321/427) had young-onset NCD with onset before 65 years of age. 40/427 (9.4%) people had epilepsy, and epilepsy onset clustered between 2 years before and 6 years after the onset of cognitive decline in 80% (n = 32/40). The most frequent seizure type was focal to bilateral tonic-clonic seizure (35%, n = 14/40). Most of the people (94.7%, n = 36/38) achieved seizure freedom with one or two antiseizure medications. People with unspecified NCD (compared to frontotemporal dementia and movement disorder-associated dementia, age of onset of NCDs ≤50 years, and current smoking status were independently associated with higher risk of developing epilepsy.Conclusion: Epilepsy is common in people with younger-onset NCDs, and a high index of suspicion is warranted particularly for those with unspecified subtype and smoking status. Smoking reduction or cessation should be further investigated as a potentially modifiable factor for risk reduction.

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.

Does the "ideal" organization exist? Or do different workplace attributes attract different people? And if so, what attributes attract what types of employees? This study combines person-organization fit theory and a policy capturing methodology to determine (a) which attributes are the strongest predictors of perceived organization attractiveness in a sample of Australian job seekers, and (b) whether the magnitude of these predictive effects varies as a function of job seekers' personal values. The design of this study is a randomized experiment of Australian job seekers who responded to an online survey invitation. Each of the 400 respondents received a random subset of 8 of 64 possible descriptions of organizations. Each description presented an organization that scored either high or low on six attributes based on the Employer Attractiveness Scale: economic, development, interest, social, application, and environmental value. Multi-level modelling revealed that all six attributes positively predicted job seekers' ratings of organization attractiveness, with the three strongest predictors being social, environmental, and application value. Moderation analyses revealed that participants with strong self-transcendent or weak self-enhancement values were most sensitive to the absence of social, environmental, and application value in workplaces, down-rating organizations that scored low on these attributes. Our results demonstrate how job seekers' personal values shape preferences for different types of workplaces. Organizations may be able to improve recruitment outcomes by matching working conditions to the personal values of workers they hope to employ.

Psychosocial interventions targeting the specific needs of people affected by younger-onset dementia are lacking. Younger-onset dementia refers to dementia where symptom onset occurs at less than 65 years old. Because of its occurrence in middle age, the impact on spouses is particularly marked and dyadic-based interventions are recommended. Music And Psychology & Social Connections (MAPS) is a novel online intervention, informed by the theory of adaptive coping by Bannon et al. (2021) for dyads affected by younger-onset dementia. MAPS combines therapeutic songwriting, cognitive behaviour therapy, and a private social networking group that focuses on the dyads. This will be a randomised controlled trial with a waitlist control. The primary aims are to assess whether MAPS improves depressive, anxiety, and stress symptoms in caregivers, with secondary aims to assess whether MAPS improves depressive symptoms in people with younger-onset dementia. The trial also aims to assess dyadic social connectedness; caregiver coping skills; and neuropsychiatric symptoms in people with younger-onset dementia. We will recruit 60 dyads to participate in a group-based weekly online program for 8 weeks facilitated by a credentialed music therapist and psychologist. Sessions 1 and 8 will include both caregivers and people with younger-onset dementia and Sessions 2–7 will involve separate group sessions for caregivers and those with dementia. There will be focus groups for qualitative feedback. Due to its online administration, MAPS has the potential to reach many dyads affected by younger-onset dementia.

O-GlcNAcylation is an essential post-translational modification installed by the enzyme O-β-N-acetyl-d-glucosaminyl transferase (OGT). Modulating this enzyme would be extremely valuable to better understand its role in the development of serious human pathologies, such as diabetes and cancer. However, the limited availability of potent and selective inhibitors hinders the validation of this potential therapeutic target. To explore new chemotypes that target the active site of OGT, we performed virtual screening of a large library of commercially available compounds with drug-like properties. We purchased samples of the most promising virtual hits and used enzyme assays to identify authentic leads. Structure-activity relationships of the best identified OGT inhibitor were explored by generating a small library of derivatives. Our best hit displays a novel uridine mimetic scaffold and inhibited the recombinant enzyme with an IC50 value of 7 µM. The current hit represents an excellent starting point for designing and developing a new set of OGT inhibitors that may prove useful for exploring the biology of OGT.

Background Bhutan is a small landlocked country located between India and China that is largely rural and Buddhist. As the nation develops and adopts more Western practices, the nature of the relationship between its young people and alcohol is developing as well. Objectives The present study examines how problematic alcohol use relates to parenting styles and distress in a sample of predominantly tertiary students. Methods For this study, 245 young adults completed self-report measures of parenting style, distress, and alcohol-related problems. Results Strong correlations were found indicating that more dysfunctional parenting styles were associated with greater distress and problematic alcohol use. Further analyses to evaluate the relationship between parenting styles and alcohol use found no role for moderation but a significant mediation which indicated that more dysfunctional parenting styles were associated with greater distress which in turn was associated with greater problematic alcohol use. Conclusions These findings replicate those found in Western countries and imply that the same vulnerabilities to problematic alcohol use are also present in Bhutan.

Guided by self-determination theory, we investigated the potential impact of work climate on employee motivation, and pro-environmental behavior (PEB) inside and outside of the workplace. We found that in workplaces with stronger pro-environmental climates and at least moderate levels of autonomy support, employees reported higher levels of autonomous motivation to engage in PEB. In turn, autonomously motivated employees engaged in more PEBs, both inside and outside the workplace. Controlled motivation played a more limited role in predicting employee PEBs. Overall, our findings suggest work climates that support pro-environmental actions and employee autonomy may not only foster PEBs within the workplace but also lay the foundation for PEBs in other non-workplace settings.

Postpartum depression (PPD) is a prevalent mental illness affecting women, and less commonly, men in the weeks and months after giving birth. Despite the high incidence of PPD in Australia, rates for help-seeking remain low, with stigma and discrimination frequently cited as the most common deterrents to seeking help from a professional source. The present study sought to investigate PPD stigma in a sample of parents and to examine the effects of an intervention on stigma and help-seeking behaviour. A total of 212 parents aged 18–71 years (M = 36.88, 194 females) completed measures of personal and perceived PPD stigma and attitudes towards seeking mental health services and were randomly assigned to one of four groups: an intervention group (video documentary or factsheet related to PPD) or a control group (video documentary or factsheet not related to PPD). Results showed that there were no effects for type of intervention on either personal or perceived PPD stigma scores. No effect was found for help-seeking propensity. Males had higher personal PPD stigma than females and older age was associated with lower personal PPD stigma. Familiarity with PPD was associated with perceived PPD stigma in others but not personal PPD stigma. More work needs to be conducted to develop interventions to reduce PPD stigma in the community.

Objective: Stillbirth devastates families and leaves them struggling to grieve the death of their baby in a society that expects grief symptoms to decrease over time. Previous research has suggested that increased memory sharing opportunities can lead to positive mental health outcomes. The aim of the current study was to examine people’s perceptions of stillbirth as well as the perceived appropriateness of affected parents sharing memories of their child. In addition, we examined whether manipulating empathy would have an effect on people’s perceptions of stillbirth.Method: Participants included 200 Australian men and women 18 to 74 years of age (M = 36.76, SD = 12.59) randomly allocated to one of three experimental conditions (i.e., low empathy, high empathy, and control). The high empathy group watched a video about stillbirth and was instructed to imagine how the people portrayed felt; the low empathy group watched the same video but was instructed to remain detached; and the control group watched an unrelated video. Participants were then asked how much money they would be willing to donate to a fictional stillbirth organization, followed by the completion of questionnaires measuring (a) perceptions of stillbirth, (b) empathy, and (c) the appropriateness of parents sharing memories of a stillborn child with different groups of people over time.Results: The empathy manipulation had an effect on empathy and the willingness to help effected parents (high empathy vs. control). However, empathy did not have an effect on participants’ perceptions toward stillbirth nor appropriateness of sharing memories. The appropriateness of sharing memories decreased as time passed and social distance increased.Discussion: Individuals who have experienced stillbirth need to be aware that societal expectations and their own expectations in relation to sharing memories may not correspond to each other and that they may need to educate their social group about their need to share memories. Removing the taboo surrounding stillbirth is vital for both parents and those to whom they would wish to communicate.

Objectives To examine maternal functioning and wellbeing as important aspects of a family’s adaptation to chronic paediatric conditions, in particular, children with diabetes. Method This cross-sectional study investigated the difference between the perceived quality of life of mothers of children with diabetes (n = 63) and mothers of children without diabetes (n = 114). The study also examined the role of self-efficacy, relationship satisfaction, number of social support providers, and satisfaction with social support in predicting quality of life. Results Mothers who had a child with diabetes had lower quality of life measured by general health, vitality, social functioning, role-emotional, and mental health than mothers that did not have a child with diabetes. Self-efficacy, relationship satisfaction, and social support were significant predictors of quality of life (mental health domain). Conclusion In order to enhance their psychological wellbeing, mothers of children with diabetes require adequate psychosocial support. Other implications for research and potential interventions are discussed.

ObjectiveDelay in seeking diagnosis of dementia is common in China. Misinformation and poor knowledge about dementia may contribute to it. The study was designed to explore the nationwide dementia literacy among older adults in urban China and to investigate the factors associated with overall dementia literacy.MethodsIn a cross-sectional study, a convenience sample of 3,439 community-dwelling old adults aged 60 and over was recruited from 34 cities in 20 provinces between June 20 and August 20, 2014. All participants were administered the face-to-face mental health literacy questionnaire, which included the prevalence, symptoms, intention, and options for treatment of dementia. Stepwise multivariate regression analysis was used to explore factors associated with overall dementia literacy.ResultsThe response rate was 87.4%. The overall dementia literacy was 55.5% (SD = 20.9%) among all respondents. The correct response rate was higher for questions on symptoms (58.7–89.6%), but lower for questions on the prevalence (22.2%) and choosing appropriate professional care personnel (22.2%). Being male [OR = 1.256, 95% CI (1.022–1.543)], having lower per capita annual income [OR = 1.314, 95% CI (1.064–1.623)], lower education [OR = 1.462, 95% CI (1.162–1.839)], and suspected depression [OR = 1.248, 95% CI (1.009–1.543)] were negatively associated with overall dementia literacy.ConclusionDementia literacy among community-dwelling older adults in urban China remains very low, in particular about the impact of dementia and appropriate treatment personnel. Community educational programs aiming to close this knowledge gap are encouraged to focus on those in the population at highest risk of low dementia literacy.

An experiment was conducted to test for the presence of prejudice towards obesity and whether weight controllability beliefs information reduces this prejudice and impacts on a person’s own healthy eating self-efficacy. The experiment randomly allocated 346 participants (49 males) into one of three conditions: controllable contributors toward obesity condition (e.g., information about personal control about diet and exercise); uncontrollable contributors toward obesity condition (e.g., information about genes, factors in society); and a control condition with no information given. Prejudice was present in 81% of the sample. High prejudice was predicted by low self-efficacy for exercise and weight. Weight controllability beliefs information had no significant effect on prejudice levels or exercise or healthy eating self-efficacy levels. Future research directions are discussed.

Objectives. The current study investigated mental health literacy in an Australian sample to examine sex differences in the identification of and attitudes towards various aspects of mental illness.Method. An online questionnaire was completed by 373 participants (M = 34.87 years). Participants were randomly assigned either a male or female version of a vignette depicting an individual exhibiting the symptoms of one of three types of mental illness (depression, anxiety, or psychosis) and asked to answer questions relating to aspects of mental health literacy.Results. Males exhibited poorer mental health literacy skills compared to females. Males were less likely to correctly identify the type of mental illness, more likely to rate symptoms as less serious, to perceive the individual as having greater personal control over such symptoms, and less likely to endorse the need for treatment for anxiety or psychosis.Conclusion. Generally, the sample was relatively proficient at correctly identifying mental illness but overall males displayed poorer mental health literacy skills than females.

Pistachio (Pistacia vera L.) is an economically important tree nut. Due to its nutritional properties and health benefits, it is considered a healthy food and thus widely consumed worldwide. However, fungal contamination of the commodities has received considerable attention because of possible contamination by toxigenic fungi, important source of mycotoxins, resulting from secondary metabolism and hazards to health consumer. Members of the genus Aspergillus, mainly Aspergillus flavus and Aspergillus niger, are reported as occurring most frequently on pistachio nuts, because able to grow in the presence of low amounts of water and to produce mycotoxins (aflatoxins and ochratoxins), that are well known for their harmful health effects on humans. Monitoring the contaminating fungal species is particularly worthy of note also in climate change scenario, allowing to notice changes in fungal population composition through the time. This study aimed to contribute to collect data about fungal population and mycotoxins occurred in pistachio samples collected in Turkey: prevalence of 2 species, A. flavus and Aspergillus tubingensis, was assessed. The A. flavus strains consisted of a mixed population of aflatoxin producers and non-producing strains in vitro, with evidence of a new genotype in gene cluster within strains of aflatoxin non-producing chemotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Mutations in the X-linked CDKL5 gene underlie a severe epileptic encephalopathy, CDKL5 deficiency disorder (CDD), characterized by gross motor impairment, autistic features and intellectual disability. Absence of Cdkl5 negatively impacts neuronal proliferation, survival, and maturation in in vitro and in vivo models, resulting in behavioral deficits in the Cdkl5 KO mouse. While there is no targeted therapy for CDD, several studies showed that treatments enabling an increase in brain BDNF levels give rise to structural and behavioral improvements in Cdkl5 KO mice. P021, a tetra-peptide derived from the biologically active region of the human ciliary neurotrophic factor (CNTF), was found to enhance neurogenesis and synaptic plasticity by promoting an increase in BDNF expression in preclinical models of brain disorders, such as Alzheimer's disease and Down syndrome, resulting in a beneficial therapeutic effect. Considering the positive actions of P021 on brain development and cognition associated with increased BDNF expression, the present study aimed to evaluate the possible beneficial effect of treatment with P021 in an in vitro and in vivo model of CDD., Methods: We used SH-CDKL5-KO cells as an in vitro model of CDD to test the efficacy of P021 on neuronal proliferation, survival, and maturation. In addition, both young and adult Cdkl5 KO mice were used to evaluate the in vivo effects of P021, on neuroanatomical and behavioral defects., Results: We found that P021 treatment was effective in restoring neuronal proliferation, survival, and maturation deficits, as well as alterations in the GSK3β signaling pathway, features that characterize a human neuronal model of CDKL5 deficiency. Unexpectedly, chronic in vivo P021 treatment failed to increase BDNF levels and did not improve neuroanatomical defects in Cdkl5 KO mice, resulting in limited behavioral benefit., Conclusions: At present, it remains to be understood whether initiating the treatment prenatally, or prolonging the duration of treatment will be necessary in order to achieve similar results in vivo in CDD mice to those obtained in vitro., Competing Interests: Declarations. Ethics approval and consent to participate: All the experiments were conducted in accordance with the Italian and European Community law for the use of experimental animals and with the approval of the National Bioethical Committee (approval number: n° 184/2022-PR). Consent for publication: Not applicable. Competing interests: KI is cofounder and Chief Scientific Officer of Phanes Biotech Inc. and has several patents on the composition and the use of P021 and is in the process of developing P021 as a therapeutic drug for the treatment of Alzheimer’s disease and related neurodegenerative disorders. Other authors declare no conflicts of interest related to this article., (© 2024. The Author(s).)

Purpose: The aims of this study were (1) to assess the test-retest reliability of the primary near infrared spectroscopy (NIRS) variables (i.e., StO 2 , T[Hb], [HbO 2 ] and [HHb]) during cycling and (2) to investigate potential influences of exercise intensity and adipose tissue thickness (ATT) on this reliability., Methods: 21 men and 20 women completed twelve constant work rate tests (6 min) at six different exercise intensities with each intensity performed twice. NIRS variables were measured at the vastus lateralis. The coefficient of variance (CV%), the intraclass correlation coefficient (ICC), mean bias and limits of agreement (LoA) were determined for reliability purposes., Results: The reliability of baseline values were acceptable to very good (CV% range: 5.83 - 21.96%). The reliability of end-values (CV% range: 0.02 - 25.02%, ICC range: 0.0 - 0.935) and amplitudes (CV% range: 0.46 - 5099%, ICC range: 0.0 - 0.887) were more variable. In general, the mean biases of end-values and amplitudes showed wide limits of agreement. A homogeneous influence of exercise intensity on reliability could not be established but reliability measures appeared to be lower in people with a lower skinfold thickness. Moreover, the NIRS signals decreased with increasing ATT but stabilized upon reaching a cut-off of 8 mm ATT. In addition, ATT did have a significant influence on [HHb] amplitude. In participants with ATT < 8 mm, higher amplitudes were observed with increasing intensity whereas in participants with ATT > 8 mm, there were no differences between the intensities., Conclusion: The study reveals variable results with regards to reliability and there was no consistent influence of exercise intensity on reliability. Participants with a lower skinfold thickness showed stronger reliability. Moreover, NIRS signals decrease when ATT exceeds 8 mm. Careful consideration is necessary when interpreting NIRS signals in such cases., Competing Interests: Declarations. Conflict of interest: Results of the present study are presented clearly, honestly and without fabrication, falsifcation or inappropriate data manipulation. No conficts of interest, fnancial or otherwise, are declared by the authors. Ethical approval: This study was approved by the Ethical Committee of the Ghent University Hospital (Ghent, Belgium) and the University of Verona Ethics Committee for Research on Human Subjects (Verona, Italy) in compliance with de Declaration of Helsinki (1964). Consent to participate: Informed consent for participation in this study was received from all subjects. Consent for publication: Consent for publication of the current study results was received from all subjects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)