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Isolated REM sleep behaviour disorder (iRBD) is characterised by dream enactment behaviours, such as kicking and punching while asleep, and vivid/violent dreams. It is now acknowledged as a prodromal phase of neurodegenerative disease—approximately 80% of people with iRBD will develop dementia with Lewy Bodies, Parkinson's disease or another degenerative brain disease within 10 years. It is important that neurologists and other clinicians understand how to make an early accurate diagnosis of iRBD so that affected people can have the opportunity to take part in clinical trials. However, making a diagnosis can be clinically challenging due to a variety of reasons, including delayed referral, symptom overlap with other disorders, and uncertainty about how to confirm a diagnosis. Several methods of assessment are available, such as clinical interview, screening questionnaires and video polysomnography or 'sleep study'. This review aims to support clinical neurologists in assessing people who present with symptoms suggestive of iRBD. We describe the usefulness and limitations of each diagnostic method currently available in clinical practice, and present recent research on the utility of new wearable technologies to assist with iRBD diagnosis, which may offer a more practical assessment method for clinicians. This review highlights the importance of thorough clinical investigation when patients present with suspected iRBD and emphasises the need for easier access to diagnostic procedures for accurate and early diagnosis. [ABSTRACT FROM AUTHOR]

This article reviews the first twelve months of the civil disobedience movement in Myanmar following the 1 February 2021 coup d'état and its many dynamics and manifestations. Myanmar's 'Spring Revolution' generated a shared sense of national unity—overcoming gender, ethnic, religious and class boundaries, but raising questions about the long-term sustainability of nonviolent civil resistance in a state where the military has for decades wielded political and economic power. Since the coup, Myanmar has been in turmoil, paralysed by instability which escalated after the military's deadly crackdown on pro-democracy activists. The article charts the growth of the Civil Disobedience Movement (CDM), its multiple methods of strategic resistance and non-cooperation, and the radicalisation of the resistance agenda. It analyses the formation of the Committee Representing the Pyidaungsu Hluttaw (CRPH), the creation of the interim National Unity Government (NUG), the founding of the National Unity Consultative Council (NUCC) and the inauguration of the People's Defence Force (PDF). It examines the implications for Myanmar when the crisis reached a more complex phase after the military's open use of force and terror on the broader civilian population prompted the NUG to declare war on the junta, and to urge ethnic armed organisations (EAOs) and newly formed anti-junta civilian militias (PDF) to attack the State Administration Council (SAC) as a terrorist organisation. The NUG now opposes the military junta by strategic and peaceful non-cooperation, armed resistance, and international diplomacy. This paper considers whether the predominantly nonviolent civil resistance movement's struggle for federal democracy and inclusive governance is laying the foundations for eventual transition to a fully democratic future or whether the cycles of violence will continue as the military continues to control power by using intimidation and fear. It notes that the coup has destroyed the economy and expanded Myanmar's human rights and humanitarian crises but has also provided the opportunity for Myanmar's people to explore diverse visions of a free, federal, democratic and accountable Myanmar. It finally examines the possibilities for future peaceful nation building, reconciliation, and the healing of the trauma of civil war. [ABSTRACT FROM AUTHOR]

Introduction: The social distancing (SD) adopted during the coronavirus disease 2019 (COVID-19) pandemic has transformed the internet from a convenience into a necessity. The behavioral changes caused by isolation range from adaptation of consumption, work, and teaching routines to altered leisure options to occupy idle time at home. Such transformations can be positive, expanding use of digital technologies (DT), but they can also have serious future physical and emotional consequences if there conscious use of technological devices is lacking. Objectives: The study aimed to validate the Behavioral Changes Scale on the Use of Digital Technologies During Social Distancing (BCSDTSD), an instrument for assessing behavioral changes related to use of DT during SD. Method: Validation of the BCSDTSD in five phases: 1. construction of an initial scale with 10 questions; 2. evaluation of the questions by a panel of experts; 3. application to 1,012 volunteers via the internet; 4. statistical analysis of the results; and 5. preparation of the validated final version of the BCSDTSD. Data were analyzed using the dplyr, psy, and paran packages and the REdaS statistical program. Three statistical criteria were used in the factor analysis (FA). Results: FA confirmed that all 10 questions in the questionnaire should be maintained, confirming its robust construction, and Cronbach's alpha demonstrated its internal consistency with a value of 0.725, which is satisfactory for first-application questionnaires. Conclusion: The BCSDTSD instrument was validated for assessment of behavioral changes related to the use of DT during SD. [ABSTRACT FROM AUTHOR]

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that hugin+ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of hugin+ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that hugin+ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide-dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep. [ABSTRACT FROM AUTHOR]

Summary: Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a sleep disorder that is characterised by dream enactment episodes during REM sleep. It is the strongest known predictor of α‐synuclein‐related neurodegenerative disease (αNDD), such that >80% of people with iRBD will eventually develop Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy in later life. More research is needed to understand the trajectory of phenoconversion to each αNDD. Only five 'gold standard' prevalence studies of iRBD in older adults have been undertaken previously, with estimates ranging from 0.74% to 2.01%. The diagnostic recommendations for video‐polysomnography (vPSG) to confirm iRBD makes prevalence studies challenging, as vPSG is often unavailable to large cohorts. In Australia, there have been no iRBD prevalence studies, and little is known about the cognitive and motor profiles of Australian people with iRBD. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study will investigate the prevalence of iRBD in Tasmania, an island state of Australia, using validated questionnaires and home‐based vPSG. It will also explore several cognitive, motor, olfactory, autonomic, visual, tactile, and sleep profiles in people with iRBD to better understand which characteristics influence the progression of iRBD to αNDD. This paper details the ISLAND Sleep Study protocol and presents preliminary baseline results. [ABSTRACT FROM AUTHOR]

• Microglia adopt a toxic pro-inflammatory profile and loss of homeostatic functions with age. • Dysfunctional microglia are associated with tau pathology in ageing and disease. • Pathological tau exacerbates age-related changes to microglia. • Sexually dimorphic roles of microglia may alter their contributions in tauopathies. Tauopathies are a group of neurodegenerative diseases that involve pathological changes to the tau protein. Neuroinflammation is a commonly reported feature of tauopathies that has been demonstrated to exacerbate tau pathology and, hence, neurodegeneration. Microglia can mediate the inflammatory response in order to maintain brain homeostasis. In the aged brain, microglia are reported to undergo morphological and functional changes, adopting a pro-inflammatory profile and loss of homeostatic functions. Dystrophic and dysfunctional microglia are associated with tau pathology in the healthy and diseased brain which is proposed to contribute to disease development and progression. Microglia have also been recently demonstrated to possess sexually dimorphic roles in the developing, adult and aged brain. The sex differences in microglial functionality suggest that microglia may contribute to tauopathies which may differ between sexes. This review highlights the detrimental loop between age-related microglial changes and tau pathology with implications for microglial sexual dichotomy. [ABSTRACT FROM AUTHOR]

Background: Microglia are traditionally described as the immune cells of the brain and have an inflammatory role in Alzheimer's disease (AD). Microglial morphological and phenotypic shifts in AD have not been fully characterized; however, microglia are often described as either pro- or anti-inflammatory.Objective: To determine microglial if microglial morphology and phenotype changes with disease status.Methods: This study observed morphology through Iba1 immunohistochemistry on tissue sections encompassing the primary motor cortex and somatosensory barrel fields. Immunohistochemistry for pro-inflammatory markers: CD14 and CD40; and anti-inflammatory markers: CD16 and TREM2, was performed at 3, 6, and 12 months of age which correlated with pre-plaque, onset, and significant plaque load in APP/PS1 brains (n = 6) and compared to age-matched littermate controls (n = 6).Results: Microglia demonstrated a defined morphological shift with time. Deramified morphologies increased in the APP/PS1, at both 6 months (p < 0.0001) and 12 months (p < 0.0001). At 12 months, there were significantly lower numbers of ramified microglia (p < 0.001). Results indicated that microglia have a heterogenic marker immunoreactivity as CD16, TREM2, and CD40 were associated with an activated morphology at the same time points. All inflammatory markers were significantly upregulated at 12 months in the APP/PS1 mice (TREM2 (F (2,30)  = 10.75, p = 0.0003), CD40 (F (2,30)  = 15.86, p < 0.0001), CD14 (F (2,30)  = 6.84, p = 0.0036), and CD16 (F (2,30)  = 3.026, p = 0.0635)).Conclusion: Our data indicate that pro- and anti-inflammatory factors of microglia occur in APP/PS1 mice. [ABSTRACT FROM AUTHOR]

A central question in the circadian biology field concerns the mechanisms that translate ~24‐hr oscillations of the molecular clock into overt rhythms. Drosophila melanogaster is a powerful system that provided the first understanding of how molecular clocks are generated and is now illuminating the neural basis of circadian behavior. The identity of ~150 clock neurons in the Drosophila brain and their roles in shaping circadian rhythms of locomotor activity have been described before. This review summarizes mechanisms that transmit time‐of‐day signals from the clock, within the clock network as well as downstream of it. We also discuss the identification of functional multisynaptic circuits between clock neurons and output neurons that regulate locomotor activity. [ABSTRACT FROM AUTHOR]

There has been strong interest in the role of metals in neurodegeneration, and how ageing may predispose the brain to related diseases such as Alzheimer's disease. Recent work has also highlighted a potential interaction between different metal species and various components of the cytoskeletal network in the brain, which themselves have a reported role in age-related degenerative disease and other neurological disorders. Neurofilaments are one such class of intermediate filament protein that have a demonstrated capacity to bind and utilise cation species. In this study, we investigated the consequences of altering the neurofilamentous network on metal ion homeostasis by examining neurofilament light (NFL) gene knockout mice, relative to wildtype control animals, at adulthood (5 months of age) and advanced age (22 months). Inductively coupled plasma mass spectroscopy demonstrated that the concentrations of iron (Fe), copper (Cu) and zinc (Zn) varied across brain regions and peripheral nerve samples. Zn and Fe showed statistically significant interactions between genotype and age, as well as between genotype and region, and Cu demonstrated a genotype and region interaction. The most substantial difference between genotypes was found in Fe in the older animals, where, across many regions examined, there was elevated Fe in the NFL knockout mice. This data indicates a potential relationship between the neurofilamentous cytoskeleton and the processing and/or storage of Fe through ageing. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) has been identified as a risk factor for Alzheimer's disease (AD). However, how such neural damage contributes to AD pathology remains unclear; specifically, the relationship between the timing of a TBI relative to aging and the onset of AD pathology is not known. In this study, we have examined the effect of TBI on subsequent beta-amyloid (Aβ) deposition in APP/PS1 (APPSWE/PSEN1dE9) transgenic mice either before (3 months of age) or after the onset (6 months of age) of plaque pathology. Lateral fluid percussion injury (LFPI), a model of diffuse brain injury, was induced in APP/PS1 and C57Bl/6 wild-type (WT) littermates. LFPI caused a significant increase in both total (p < 0.001) and fibrillar (p < 0.001) Aβ plaque load in the cortex of 3-month-old APP/PS1 mice compared to sham-treated mice at 30 days post-injury. However, in the cortex of 6-month-old mice at 30 days post-injury, LFPI caused a significant decrease in total (p < 0.01), but not fibrillar (p > 0.05), Aβ plaque load compared to sham-treated mice. No Aβ plaques were present in any WT mice across these conditions. Glial fibrillary acidic protein immunolabeling of astrocytes and ionized calcium-binding adapter molecule 1 immunolabeling of microglial/macrophages was not significantly different (p < 0.05) in injured animals compared to sham mice, or APP/PS1 mice compared to WT mice. The current data indicate that TBI may have differential effects on Aβ plaque deposition depending on the age and the stage of amyloidosis at the time of injury. [ABSTRACT FROM AUTHOR]

Environmental enrichment (EE) has been consistently reported to enhance cognitive function in mouse models of neuropathology. Microglia, implicated in Alzheimer's disease pathology, may mediate this effect. The aim of the present study was to investigate the effect of EE on cognitive function and microglia in mouse models of aging and amyloidosis. Male wild-type (Wt) and APP/PS1 mice were randomly assigned to standard housing (SH) or EE from 12 to 18 months of age. Spatial memory testing was performed using the Y and Barnes maze. Immunohistochemical analysis of Aβ load, Iba1 and CD-68-labeled (phagocytic-type) microglia was examined between conditions. EE from 12 months of age was associated with improved short-term memory performance in APP/PS1 mice, despite no reductions to Aβ load. APP/PS1 mice in SH had significantly increased microglia occupying the neocortex and hippocampus (p = 0.02; p = 0.004, respectively) relative to Wt animals. Microglia labeling was not statistically different between EE-exposed APP/PS1 compared to Wt mice, indicating that EE may attenuate the increased microglial load in aging APP/PS1 mice. APP/PS1 mice from EE had significantly (p = 0.01) higher colocalization of Iba1 and CD-68 labeling, indicative of increased phagocytic microglia compared to mice from SH. The findings of the present study suggest that EE after substantial brain amyloidosis, has the potential to preserve domains of cognitive function, while having no effect on Aβ deposition. The current study demonstrates that EE may attenuate microglia in aging APP/PS1 mice, and may promote alterations in cellular phenotype. • Late-life EE was associated with improved short-term memory performance. • Increased microglia in neocortex and hippocampus in APP/PS1 mice was maintained in SH conditions but not EE. • In APP/PS1 animals, EE was associated with increased co-localisation of Iba1 and CD-68 in microglia. [ABSTRACT FROM AUTHOR]

Disruption of leptin signalling has been implicated as playing a role in the development of Alzheimer’s disease (AD). Leptin has previously been shown to be affected by amyloid-beta (Aβ)-related signalling; however, pathways that link leptin to the disease pathogenesis have not been determined. To characterize the association between increasing age-dependent Aβ levels with leptin signalling and the vulnerable brain regions in AD, we assessed the mRNA and protein expression profile of leptin and leptin receptor (Ob-Rb) at 9 and 18-month-age in APP/PS1 mice. Immunohistochemical labelling demonstrated that leptin and Ob-Rb proteins were localised to neocortical and hippocampal neurons in APP/PS1 and wildtype (WT) mice. Neuronal leptin and Ob-Rb immunolabelling was more prominent in the neocortex of both groups at 9 month of age, while, at 18 months, labelling was reduced in the hippocampus of APP/PS1 mice relative to WT. Immunoblotting analysis demonstrated decreased hippocampal leptin levels, concomitantly with an increased Ob-Rb levels, in APP/PS1 mice compared with WT controls at 18 month of age. While no leptin mRNA was found in either of the groups analysed, Ob-Rb mRNA was significantly decreased in the hippocampus of APP/PS1 mice at both ages analysed. In addition, a significant decreased protein kinase B (Akt) activity concomitantly with an upregulation of suppressor of cytokine signaling-3 (SOCS3) and protein-tyrosine phosphatase 1B (PTP1B) transcripts was present. Thus, these results collectively indicate alterations of leptin signalling in the hippocampus of APP/PS1 mice, providing novel insights about the pathways that could link aberrant leptin signaling to the pathological changes of AD. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to describe case management as experienced by patients with heart failure and their health professionals with the aim of understanding why case management might contribute in reducing hospital admissions. Background: Heart failure is a common cause of unplanned hospital admission. The evidence for case management in patients with heart failure for reducing admissions is promising. Design: Systematic review and qualitative evidence synthesis. Data source: Searches were conducted in Medline, Psychinfo, Kings Fund database and Cinahl from inception of each database to 16 February 2017. Review methods: Robust systematic review methodology was used to identify qualitative studies describing the experiences of patients with heart failure and healthcare providers of case management. Data were synthesized thematically, and analytic themes were developed. Findings: Five studies (six papers) from which nine descriptive themes were used to determine three analytic themes. This synthesis showed that case management provides positive quality of care for patients, increases perceived access to services and creates more time to ask questions and develop trusted relationships. For health professionals, case management enhanced care by improved relationships with both patients and colleagues although concerns remained around resources, training and inter-professional conflict. Conclusions: This synthesis emphasizes the importance of the quality of being cared for as a patient and caring as a health professional. Case management enhances communication between patients and health professionals, supports patient self-care and self-management and can be an important contributing factor in reducing unplanned admissions for patients with heart failure. [ABSTRACT FROM AUTHOR]

Aims and objectives: To explore an innovative primary healthcare gerontology nurse specialist role from the perspectives of older people and health professionals. Background: Primary care is struggling to meet the needs and demands of complex older people. New models which incorporate holistic assessment and care coordination are necessary. Design: A qualitative descriptive general inductive design was used. Methods: Older people at risk of health and functional decline were identified and received a comprehensive gerontology assessment and care coordination. Older adults (75 years+) enrolled within one of three primary healthcare practices in Auckland, New Zealand were eligible. Healthcare professionals directly involved with the primary healthcare gerontology nurse specialist model were invited for study participation. Face-to-face interviews were held with five older people and six health professionals were interviewed by telephone. A semistructured interview guide was used for all interviews. A general inductive approach was undertaken for analysis to systematically identify codes and themes. Results: Data analysis revealed two central themes from the older people perspective: “holistic expertise” and “communication.” Two main themes were identified from the health professional perspective: “competency” and “service delivery.” Results showed the gerontology nurse specialist role was highly regarded by both older people and the health professionals. The in-home comprehensive geriatric assessment was identified as greatly beneficial. Conclusions: The competence and care coordination of the gerontology nurse specialist reduced fragmentation and were deemed immensely valuable. Care coordination should be recognised as a key component to meeting the complex needs of at risk older people in the community. Relevance to clinical practice: The expert knowledge of the gerontology nurse specialist and in-home comprehensive geriatric assessment were crucial aspects of the new model. Equally important was the assimilation of primary and secondary care infrastructure to upskill and deliver mentorship to the gerontology nurse specialist. [ABSTRACT FROM AUTHOR]

Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APPSWE/PS1dE9) from 6 months of age. After 6 months of housing in standard laboratory cages, APPSWE/PS1dE9 ( n = 27) and healthy wildtype ( n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to Aβ plaque pathology in the neocortex or hippocampus of APPSWE/PS1dE9 mice. However, a significant increase in synaptophysin immunolabeled puncta in the hippocampal subregion, CA1, in APPSWE/PS1dE9 mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APPSWE/PS1dE9 mice exposed to EE, however, no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later-life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with Aβ deposition. [ABSTRACT FROM AUTHOR]

Diffuse axonal injury is a hallmark pathological consequence of non-penetrative traumatic brain injury (TBI) and yet the axonal responses to stretch injury are not fully understood at the cellular level. Here, we investigated the effects of mild (5%), very mild (0.5%) and repetitive very mild (2×0.5%) axonal stretch injury on primary cortical neurons using a recently developed compartmentalized in vitro model. We found that very mild and mild levels of stretch injury resulted in the formation of smaller growth cones at the tips of axons and a significantly higher number of collapsed structures compared to those present in uninjured cultures, when measured at both 24 h and 72 h post injury. Immunocytochemistry studies revealed that at 72 h following mild injury the axonal growth cones had a significantly higher colocalization of βIII tubulin and F-actin and higher percentage of collapsed morphology than those present following a very mild injury. Interestingly, cultures that received a second very mild stretch injury, 24 h after the first insult, had a further increased proportion of growth cone collapse and increased βIII tubulin and F-actin colocalization, compared with a single very mild injury at 72 h PI. In addition, our results demonstrated that microtubule stabilization of axons using brain penetrant Epothilone D (EpoD) (100 nM) resulted in a significant reduction in the number of fragmented axons following mild injury. Collectively, these results suggest that mild and very mild stretch injury to a very localized region of the cortical axon is able to trigger a degenerative response characterized by growth cone collapse and significant abnormal cytoskeletal rearrangement. Furthermore, repetitive very mild stretch injury significantly exacerbated this response. Results suggest that axonal degeneration following stretch injury involves destabilization of the microtubule cytoskeleton and hence treatment with EpoD reduced fragmentation. Together, these results contribute a better understanding of the pathogenesis of mild and repetitive TBI and highlight the therapeutic effect of microtubule targeted drugs on distal part of neurons using a compartmentalized culturing model. [ABSTRACT FROM AUTHOR]

Objectives: To describe implementation of an innovative gerontology nurse specialist role within one primary health organisation in Auckland, New Zealand. Quantitative outcomes of the screening tool as well as the nurse specialist assessment will be presented.Method: The intervention involved use of the Brief Risk Identification for Geriatric Health Tool (BRIGHT) to identify high-needs older people with subsequent comprehensive geriatric assessment (CGA) performed by the gerontology nurse specialist.Results: A total 384 of the 416 BRIGHTs were completed (92% response rate) and 15% of these were identified as high risk (n= 57). The BRIGHTs for high-risk older people revealed the highest scoring question was ‘needing help with housework’ (26%). The most frequent intervention by the gerontology nurse specialist was education (30%).Conclusions: The primary health care gerontology nurse specialist model delivers a proactive case finding and specialist gerontology intervention for older people at high risk of functional or health decline. [ABSTRACT FROM PUBLISHER]

Aims To present a methodological exemplar of integrating findings from a quantitative and qualitative review on the same topic to provide insight into components of care that contribute to supportive care that is acceptable to men with prostate cancer. Background Men with prostate cancer are likely to live a long time with the disease, experience side effects from treatment and therefore have ongoing supportive care needs. Quantitative and qualitative reviews have been published but the findings have yet to be integrated. Design Integration of quantitative and qualitative synthesized evidence. Data source Two previously published systematic reviews. Review methods Synthesized evidence on supportive care for men with prostate cancer was integrated from two previously published systematic reviews: a narrative quantitative review and a qualitative review with thematic synthesis. These two streams of synthesized evidence were synthesized using concurrent narrative summary. Data from both reviews were used to develop a set of propositions from which a summary of components of care that likely to contribute to supportive care acceptable to men with prostate cancer were identified. Results Nine propositions were developed which covered men's supportive care focusing on the role of health professionals. These propositions were used to compose nine components of care likely to lead to supportive care that is acceptable to men with prostate cancer. Some of these components are no/low cost such as developing a more empathic personalized approach, but more specific approaches need further investigation in randomized controlled trials, for example, online support. Conclusion This methodological exemplar demonstrates the integration of quantitative and qualitative synthesized data to determine components of care likely to lead to provision of supportive care acceptable to men with prostate cancer. [ABSTRACT FROM AUTHOR]

Metabolic homeostasis requires coordination between circadian clocks in different tissues. Also, systemic signals appear to be required for some transcriptional rhythms in the mammalian liver and the Drosophila fat body. Here we show that free-running oscillations of the fat body clock require clock function in the PDF-positive cells of the fly brain. Interestingly, rhythmic expression of the cytochrome P450 transcripts, sex-specific enzyme 1 (sxe1) and Cyp6a21, which cycle in the fat body independently of the local clock, depends upon clocks in neurons expressing neuropeptide F (NPF). NPF signaling itself is required to drive cycling of sxe1 and Cyp6a21 in the fat body, and its mammalian ortholog, Npy, functions similarly to regulate cycling of cytochrome P450 genes in the mouse liver. These data highlight the importance of neuronal clocks for peripheral rhythms, particularly in a specific detoxification pathway, and identify a novel and conserved role for NPF/Npy in circadian rhythms. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that results in motor dysfunction and death, generally from respiratory failure. 90% of ALS cases are sporadic with no known cause. Familial cases have been linked with mutations in several disparate classes of genes, including those involved in DNA/RNA metabolism, protein misfolding, oxidative stress and the cytoskeleton, leading to the proposition that ALS could be a multi-factorial disease. However, alterations in excitability have been reported in all types of ALS cases, and may be a common disease mechanism predisposing neurons to degeneration. Excitotoxicity has long been suspected as a mediator in the disease process, and may arise from changes in synaptic inputs, or alterations in the excitability of the neurons being stimulated. Although the glutamatergic system is widely recognised as a therapeutic avenue with the potential to extend lifespan and delay disease onset, the causes of altered excitability in ALS are currently unclear and warrant further investigation. This article reviews current evidence of alterations to excitatory and inhibitory signalling in the cortex and spinal cord, and in the intrinsic excitability of motor neurons, in ALS. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with the loss of cognitive function. Neurofilament (NF) triplet proteins, the major structural (intermediate filament) proteins of neurons, are expressed in a subset of pyramidal cells that show a high degree of vulnerability to degeneration in AD. Alterations in the NF triplet proteins in amyloid-beta (Aβ) plaque-associated dystrophic neurites (DNs) represent the first cytoskeletal aberration to occur in the neocortex in the earliest stages of AD. We generated transgenic APP/PS1 (APPswe/PSEN1dE9) mice on the neurofilament light knockout (NFL KO) background to explore the role of NFL deletion in the context of DN formation, synaptic changes, and other neuropathologic features. Our analysis demonstrated that NFL deficiency significantly increased neocortical DN pathology, Aβ deposition, synapse vulnerability, and microgliosis in APP/PS1 mice. Thus, NFs may have a role in protecting neurites from dystrophy and in regulating cellular pathways related to the generation of Aβ plaques. [ABSTRACT FROM AUTHOR]

Men with prostate cancer are likely to have a long illness and experience psychological distress for which supportive care may be helpful. This systematic review describes the evidence for effectiveness and cost-effectiveness of supportive care for men with prostate cancer, taking into account treatment pathway and components of interventions. MEDLINE, EMBASE, CINAHL, CENTRAL, and Psychinfo were searched from inception--July 2013 for randomized controlled trials and controlled trials. Two authors independently assessed risk of bias and extracted data. Twenty-six studies were included (2740 participants). Interventions were delivered pre and during ( n = 12), short-term ( n = 8), and longer term (18 months) ( n = 5) after primary treatment. No interventions were delivered beyond this time. Few trials recruited ethnic minorities and none recruited men in same sex relationships. Intervention components included information, education, health professional discussion, homework, peer discussion, buddy support, cognitive behavioral therapy, cognitive restructuring, psychoeducation, Reiki and relaxation. Most interventions were delivered for 5-10 weeks. Risk of bias of trials was assessed as unclear for most domains due to lack of information. The majority of trials measuring quality of life and depression found no effect. Relatively few trials measured anxiety, coping skills and self-efficacy, and the majority found no effect. No cost data were available. Trials of supportive care for men with prostate cancer cover a range of interventions but are limited by population diversity, inconsistent measurement and reporting of outcomes, and inability to assess risk of bias . Recommendations on design and conduct of future trials are presented. [ABSTRACT FROM AUTHOR]

Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APP SWE , PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24 h and 7 d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24 h or 7 d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p > 0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24 h PI or 7 d PI. There was a significant (p < 0.001) increase in cross-sectional cortical area occupied by Iba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p > 0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24 h PI (compared to sites distant to the injury and the corresponding area in sham mice; p < 0.01), but not after 7 d PI (p > 0.05). There was no significant effect of genotype on this response (p > 0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that causes synaptic degeneration. [ABSTRACT FROM AUTHOR]

ABSTRACT The axon initial segment (AIS) plays a key role in initiation of action potentials and neuronal output. The plasma membrane of the AIS contains high densities of voltage-gated ion channels required for these electrical events, and much recent work has focused on defining the mechanisms for generating and maintaining this unique neuronal plasma membrane domain. The Kv2.1 voltage-gated potassium channel is abundantly present in large clusters on the soma and proximal dendrites of mammalian brain neurons. Kv2.1 is also a component of the ion channel repertoire at the AIS. Here we show that Kv2.1 clusters on the AIS of brain neurons across diverse mammalian species including humans define a noncanonical ion channel clustering domain deficient in Ankyrin-G. The sites of Kv2.1 clustering on the AIS are sites where cisternal organelles, specialized intracellular calcium release membranes, come into close apposition with the plasma membrane, and are also sites of clustering of γ-aminobutyric acid (GABA)ergic synapses. Using an antibody specific for a single Kv2.1 phosphorylation site, we find that the phosphorylation state differs between Kv2.1 clusters on the proximal and distal portions of the AIS. Together, these studies show that the sites of Kv2.1 clustering on the AIS represent specialized domains containing components of diverse neuronal signaling pathways that may contribute to local regulation of Kv2.1 function and AIS membrane excitability. J. Comp. Neurol. 522:2594-2608, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Neurofilaments (NFs) have been proposed to have a significant role in attempted axonal regeneration following a variety of forms of injury. The NF triplet proteins of the central nervous system are comprised of light (NF-L), medium (NF-M) and heavy (NF-H) chains and are part of the type IV intermediate filament family. We sought to define the role of NF-L in the neuronal response to trauma and regeneration by examining the effect of total absence of the NF-L protein on neuronal maturation and response to axotomy. This study utilized an in vitro model comprising relatively mature cortical murine neurons derived from either wild-type embryonic (E15) mice or mice with a genetic knockout of NF-L (NF-L KO). Whilst NF-L KO neurons developed to relative maturity at a comparable rate to wild-type control neurons, NF-L KO neurons demonstrated relatively increased expression of α-internexin and decreased expression of NF-M. Further, we demonstrate that α-internexin co-immunoprecipitates with the NF binding protein NDel1 in NFL-KO cortical neurons in vitro. Following localized axotomy, NF-L KO neurons demonstrated reduced amyloid precursor protein accumulation in damaged neurites as well as a significant reduction in the number of axons regenerating (4.79+/-0.58 sprouts) in comparison to control preparations (10.47+/−1.11 sprouts) (p<0.05). These studies indicate that NFs comprising NF-L have a dynamic role in the reactive and regenerative changes in axons following injury. [ABSTRACT FROM AUTHOR]

Highlights: [•] Motor neurons grow in a novel compartmented neuromuscular junction circuit model. [•] Cultured motor neurons recapitulate in vivo organisation. [•] Motor neuron cell bodies develop within a spinal-cord environment with glia. [•] Motor neuron axons extend towards skeletal muscle to form synapses. [•] Spinal cord and muscle environments physically and fluidically isolated. [ABSTRACT FROM AUTHOR]

α-Synuclein is a pre-synaptic chaperone and its accumulation contributes to differential cell loss in Parkinson's disease. Cytoplasmic expression of α-synuclein can directly modulate apoptotic pathways and contribute to cell survival, whereas induced over-expression of the protein causes oxidative stress through mitochondrial and cytosolic free-radical production. This study aimed to clarify the contribution of endogenous α-synuclein to oxidative stress and its association with cell death. Primary cortical neurons were derived from α-synuclein knock-out ( Snca-/-) and wild-type (C57BL/6; WT) mice and treated with in vitro models of oxidative-stress, complex I inhibition and excitotoxicity. Mitochondrial free radical production was determined in isolated mitochondria derived from each mouse strain. Snca-/- derived cortical cultures were more susceptible ( P < 0.05) to oxidative-stress, but not excitotoxicity. This result was determined by significant increases in cell death (Propidium-Iodide staining) after 6 h treatment in Snca-/- (45 % ± 2.7 SEM), relative to WT (33 % ± 3.9 SEM) cultures. α-Synuclein also confers significant ( P < 0.05) resistance to low-dose (5 nM) rotenone toxicity, with a twofold reduction in cell death in WT, compared with Snca-/- cortical neurons. The expression of α-synuclein had no effect on cortical glutathione levels, or the production of reactive oxygen intermediates in isolated mitochondria. These data indicate that endogenous levels of α-synuclein confer resistance to oxidative stress downstream of free radical production and scavenging. The current data suggest that α-synuclein prevents cytochrome c release and apoptosis through inhibition of the MAPK signalling pathway. [ABSTRACT FROM AUTHOR]

This article analyzes the preparation, consumption, and distribution of food in ISKCON, and the ways in which ISKCON has absorbed and remade the Hindu tradition of prasadam, transforming it into a major vehicle of proselytization, a sacred cuisine, a health cure, a worldwide charitable enterprise, and increasingly a successful method of fundraising. The article contextualizes ISKCON's food culture, arguing that it emerges from the encounters between Chaitanya Vaishnavism and modernity, and the shifting patterns of overlap between Hindu and Western culture. Like ISKCON itself, it is the result of an uneven process of creative adaptation to some aspects of modernity and of resistance to others. Analysis of Krishna's prasadam reveals a dynamic tension between traditionalism and the reappropriation of tradition. While ISKCON's cultural and religious context is undoubtedly Hindu, its revisioning of prasadam as an instrument of global mission is radical. Its "kitchen culture" has grown to incorporate eco-projects, free food distribution, mass food production, and large-scale catering. ISKCON claims that its food culture will restore human physical health and the health of the planet at a time when affluent nations are eating themselves to death. Its emphasis on ethically sourced food and sustainable lifestyles is therefore increasingly in harmony with international plans for environmental protection and climate change. [ABSTRACT FROM AUTHOR]

Abstract: Axonal degeneration is a prominent feature of amyotrophic lateral sclerosis (ALS) both in lower motor nerves as well as descending white matter axons in the spinal cord of human patients. Although the pathology of lower motor axonal degeneration has been described in both human ALS and related transgenic animal models, few studies have examined the pathological features of descending axon degeneration, particularly in mouse models of ALS. We have examined the degeneration of white matter tracts in the G93A mutant superoxide dismutase-1 (mSOD1+) mouse spinal cord white matter from 12weeks of age to end-stage disease. In a G93A mSOD1 mouse model where green fluorescent protein was expressed in neurons (mSOD1+/GFP+), degeneration of white matter tracts was present from the ventral to dorsolateral funiculi. This pattern of axonal pathology occurred from 16weeks of age. However, the dorsal funiculus, the site of the major corticospinal tract in mice, showed relatively less degeneration. Immunohistochemical analysis demonstrated that the neurofilament light chain (NFL) and neuronal intermediate filament protein alpha-internexin accumulated in axon swellings in the spinal white matter. Increased levels of alpha-internexin protein, in mSOD1+ mouse spinal cord tissue, were demonstrated by Western blotting. In contrast, degenerating axons did not show obvious accumulations of neurofilament medium and heavy chain proteins (NFM and NFH). These data suggest that white matter degeneration in this mouse model of ALS is widespread and involves a specific molecular signature, particularly the accumulation of NFL and alpha-internexin proteins. [Copyright &y& Elsevier]

Due to the ageing population, there is an increased demand for home care services. Restorative care is one approach to improving home care services, although there is little evidence to support its use in the community setting. The objective of this trial was to evaluate the impact of a restorative home care service for community-dwelling older people. The study was a cluster randomised controlled trial undertaken at a home care agency in New Zealand. The study period was from December 2005 to May 2007. Older people were interviewed face-to-face at baseline, four and 7 months. A total of 186 older people who received assistance from a home care agency participated in the study, 93 received restorative home care and 93 older people received usual home care. The primary outcome measure was change in health-related quality of life (measured by the Short Form 36 [SF36] Health Survey). Secondary outcomes were the physical, mental, and social well-being of older people (Nottingham Extended Activities of Daily Living, Timed Up and Go, Mastery scale, Duke Social Support Index). Findings revealed that compared with usual care, the intervention demonstrated a statistically significant benefit in health-related quality of life (SF36) at 7 months for older people (mean difference 3.8, 95% CI −0.0 to 7.7, P = 0.05). There were no changes in other scale measurements for older people in either group over time. There was a statistically significant difference in the number of older people in the intervention group identified for reduced hours or discharge (29%) compared with the control group (0%) ( P < 0.001). In conclusion, a restorative home care service may be of benefit to older people, and improves home care service efficacy. [ABSTRACT FROM AUTHOR]

The objective of the present study was to verify the response of patients with panic disorder (agoraphobia) to existing cognitive-behavior therapy models (CBT) of two respiratory subtypes of panic disorder (PD): respiratory subtype (RS) and non respiratory subtype (NRS). We randomly selected a sample of 50 patients diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders. The medication used was tricycle or selective serotonin reuptake inhibitor antidepressants. Seventy-seven point six percent of the patients from both groups showed RS and 22.4% the NRS. The RS patients responded satisfactorily to the treatment with techniques of CBT decreasing anxiety, breathing symptoms and panic attacks. According to the global functioning assessment scale, RS patients improved from 55.8 to 70.9 in comparison with NRS ones. [ABSTRACT FROM AUTHOR]

Paid caregivers possess an essential role in home care services. However, recruitment and retention issues are extensive within this workforce, largely in relation to poor working conditions. This article primarily focuses on the qualitative data extracted from a large randomised controlled trial in New Zealand and is supported by some quantitative findings. The aim was to explore paid caregiver perceptions of a restorative home care intervention in comparison with usual home care. The purpose of the qualitative exploration was to gather rich descriptive data that highlight differences between the two services with an emphasis on the workforce viewpoint. Four focus groups were undertaken with paid caregivers, two at baseline (4 and 5 participants in the control and intervention groups, respectively) and two at 14 months (eight participants in each focus group). Focus group data were collected in December 2005 and February 2007. A general inductive approach was used to analyse focus group transcripts. Two themes emerged from both the control and intervention focus groups: relationship with older people and issues with home care service delivery. A further two themes were pertinent to the intervention group: job satisfaction and preintervention. Findings revealed the intervention had a substantial positive impact on paid caregiver job satisfaction in comparison with usual care. This appeared to be due to improved training, increased support and supervision, and more flexibility. The intervention resulted in positive changes from the paid caregiver perspective and substantially reduced turnover in comparison with usual home care. However, both groups identified the need for further improvements to their working conditions. In addition, the need to regulate this vulnerable workforce is discussed. [ABSTRACT FROM AUTHOR]

Objective: This study in cognitive-behavioural therapy (CBT) was to demonstrate the preparation of the patient with panic disorder for agoraphobic exposures. Techniques have been used for exhibitions interceptive their own bodily sensations and in vivo exposure to feared situations or places. Methodology: 50 individuals divided in two Groups of 25 participants each one. Group 1 undertook 10 weekly, individual sessions of CBT of one hour duration with use of medication. Group 2, control, only used medication without CBT. The medication prescribed consisted of tricyclic anti-depressants and selective inhibitors of the re-uptake of serotonin. At the beginning and at the end of the medical and psychological interventions evaluation instruments were applied. Results: We observed a significant difference between baseline and final in a group 1, such as: reduction in panic attacks, anticipatory anxiety, agoraphobia avoidance and fear of bodily sensations. In the global assessment of functioning scale, an increase in the overall well-being of 60.8% to 72.5% among patients in group 1 with therapy, unlike the second group 2 without therapy. Conclusion: The procedures used for exposures, were considered essential in the preparation of patients with panic disorder, to be able to face up to panic attacks and subsequent agoraphobic situations. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a genetic, degenerative, and progressive central nervous system disease. It is characterized by motor abnormalities and cognitive and psychiatric symptoms. Objective. To describe the precise degree of clinical severity of patients with HD through a new neurocognitive assessment. Methods. Unprecedented battery of computerized tests, CNSVS (Central Nervous System Vital Signs), was applied at three different moments in 2008, 2009, and 2010. The accurate and reliable CNSVS objectively provided the cognitive state of patients and allowed for the evaluation of disease progression. Case Report. P., 26, female, without any medication, with normal psychomotor development is a parent carrier of HD. In 2008, she was diagnosed with HD in accordance with the Medical Genetics Laboratories. Conclusion. The tests may be useful to reveal the exact measure of the current evolutionary stage of HD patients, allowing for more efficient planning of treatment and future procedures, such as the medication, therapy, and physical activity to be administered. [ABSTRACT FROM AUTHOR]

Abstract: While functional recovery after injury is limited, it has become evident that the mature central nervous system does retain some ability to regenerate. This study investigated the intrinsic capacity of relatively mature cortical neurons (21 days in vitro) to respond to axonal loss. Neurons, growing as clusters on poly-l-lysine, were completely sheared of axons through chemical and mechanical disruption and transferred to either an intact astrocyte monolayer or a substrate of poly-l-lysine. Injured neurons exhibited a regenerative sprouting response that was independent of neuronal cell division or neural progenitors, as demonstrated by negative bromodeoxyuridine (BrdU) and the neuronal precursor intermediate filament nestin, labeling. At 24 h after injury, neurons had extended appropriately polarized neurites, demonstrated by compartmentalized microtubule-associated proteins MAP2 and tau immunolabeling. Newly sprouting axons were tipped by growth cones; however, growth cones on the tips of sprouting axons (mean area, 26.32 ± 2.20 μm) were significantly (p < 0.05) smaller than their developmental counterparts (mean area, 48.64 ± 5.9 μm), independent of substrate. Furthermore, live imaging indicated that regenerating neurons exhibited distinct axonal dynamics, with a significant (p < 0.05) reduction (70%) in pausing, considered vital for interstitial branching and pathfinding, relative to developmental growth cones. This study indicates that mature cultured cortical pyramidal and interneurons have the intrinsic potential to survive, extend processes, and reestablish neurite polarity following significant physical damage. These results may aid in defining the cellular basis of neuronal structural plasticity and defining the role of astrocyte reactivity in the response to trauma. [Copyright &y& Elsevier]

Abstract: There has been growing interest in the axon as the initial focus of pathological change in a number of neurodegenerative diseases of the central nervous system. This review concentrates on three major neurodegenerative conditions – amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer''s disease – with emphasis on key cellular changes that may underlie early axonal dysfunction and pathology and, potentially, the degeneration of neurons. In particular, this review will address recent data that indicate that the main pathological stimuli for these conditions, though often not definitively determined, result in an initial perturbation of the axon and its cytoskeleton, which then results in slow neuronal degeneration and loss of connectivity. The identification of a degenerative process initiated in the axon may provide new therapeutic targets for early intervention to inhibit the grim outcomes related to the progression of these diseases. [Copyright &y& Elsevier]

Islam is a religion of vast dimensions which has inspired great civilizations and today offers many men and women comfort and ethical guidance. In this paper I suggest that the tension between the Qur'an accepted as the perfect timeless word of God and the encultured dynamic Islam of nearly a quarter of the world's population results in contending perspectives of women's role and rights. The Qur'an gives men and women spiritual parity, but there are verses in the Qur'an that some feminists find difficult to reconcile with the modern rights of women. Most Islamic feminists make a clear distinction between cultural practices (what actually happens to embodied women) and the pure word of God. There are profound differences in the status of women within and between predominantly Muslim countries. In some countries it is illegal for women to drive a car, or to move freely outside the home, in others women have become heads of state. The decision to wear the veil, often a sign of empowerment in Europe, is in parts of the Islamic world obligatory. Voices representing an exclusivist, literalist understanding of Islam have entered the mainstream of Muslim lives due in part to the fact that Wahhabism imposes a narrow, sectarian view of Islam, and the Saudi government with its massive oil wealth propagates this puritanical form of Islam across the world. Some traditionalist maulanas and maulvis are concerned above all with women's modesty and enforce customs that refine, purify and protect their chastity. They, like some Islamic feminists, position Islamic rights and roles for women with regard to the exoticized and eroticized 'other' -- in this case Western civilization, Western imperialism and the rise of Western feminism. 'The West' becomes for traditional interpreters a kind of contemporary jahilya. There are also many progressive Muslim scholars who seek to articulate a historically accurate, non-idealized, now challenged, now challenging, view of Islam with an uncompromising emphasis on social justice, equality and pluralism (Safi 2008: 215). This paper argues that the ongoing, postcolonial battle against Western 'imperialism' demands epistemological humility. Nevertheless, women are fighting for basic human rights and freedoms in parts of the Islamic world where the State, religious authorities (the ulema) and the patriarchal family assume the right of legal and moral surveillance. In considering the nature of violence to Muslim women in Pakistan and the UK, I hope to show that accusations of orientalism should not deter us from recognizing the courage of women activists who themselves risk imprisonment and of the struggle of women victims of rape and domestic violence to overcome feelings of shame and dishonour. I argue that both the private and public spheres need to be made safe for all Muslim women, and not just a professional elite. This can only be achieved by a fuller recognition of women's rights encapsulated in law and all aspects of public life. [ABSTRACT FROM AUTHOR]

As in the adage that 'a conservative is just a liberal who has been mugged', many presume that punitive public attitudes are derived from the direct experience of crime and victimization. People become 'fed up' with criminality and seek to strike back at lawbreakers. Social theories of punitiveness, on the other hand, typically portray punitiveness as a form of scape-goating in which offenders are just a stand-in population, masking more abstract anxieties. This survey was designed to explore both of these hypotheses with a sample (N = 940) of the British public. A multivariate analysis of survey responses finds that factors such as concerns about the economy and the state of 'the youth today' account for a substantial proportion of the effect of actual crime concerns on punitiveness. Crime-related factors, such as victimization experiences or anxieties about crime, on the other hand, do not appear to be strong predictors of punitiveness in this sample. [ABSTRACT FROM AUTHOR]

• Rare variants, gene-environment and gene-gene interactions, and epigenetic mechanisms or modulators can explain the missing heritability of Alzheimer's disease. • Recent studies focused on combinations of variants that may contribute to AD risk, typically calculated as a polygenic risk score; Polygenic risk score can improve AD clinical risk prediction method. • APOE ε4 risk variants are neither necessary nor sufficient for the progression of AD. As a result, most epistasis studies have instead focused on the potential interactive role that APOE may have on common gene variants by gene-gene interaction. • Few studies have used longitudinal data to explore gene-environment/lifestyle interactions throughout AD course, especially in the preclinical phase of the disease. • This paper reviewed epigenetic mechanisms linked with AD; epigenetic alterations occur concurrently with memory formation and retrieval; there is increasing interest in epigenetic alterations in late-onset AD. Alzheimer's disease (AD) is a complex neurological disorder of uncertain aetiology, although substantial research has been conducted to explore important factors related to risk of onset and progression. Both lifestyle (e.g., complex mental stimulation, vascular health) and genetic factors (e.g., APOE, BDNF, PICALM, CLU, APP, PSEN1, PSEN2, and other genes) have been associated with AD risk. Despite more than thirty years of genetic research, much of the heritability of AD is not explained by measured loci. This suggests that the missing heritability of AD might be potentially related to rare variants, gene-environment and gene-gene interactions, and potentially epigenetic modulators. Moreover, while ageing is the most substantial factor risk for AD, there are limited longitudinal studies examining the association of genetic factors with decline in cognitive function due to ageing and the preclinical stages of this condition. This review summarises findings from currently available research on the genetic factors of ageing-related cognitive change and AD and suggests some future research directions. [ABSTRACT FROM AUTHOR]

This article will address individual differences in punitiveness or `get tough' attitudes towards lawbreakers, but will do so by looking in depth at the nature of worldviews that have been identified as decidedly forgiving. The aim is to generate new hypotheses through a grounded narrative analysis regarding a dimension of public sensibilities towards crime— leniency— about which we know very little. I conclude that social identity is an important aspect of merciful worldviews, and that a precondition of a forgiving orientation may be a focus on individual agency. This analysis is supported by quantitative tests of new hypotheses to emerge. This article contributes to the more complex picture of differentiated public opinion to crime and criminal justice that has emerged recently in the literature. [ABSTRACT FROM AUTHOR]

Background: Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer's disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10–20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. Methods: Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50–92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30–40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50–100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. Discussion: This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. Trial registration: ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered. [ABSTRACT FROM AUTHOR]

During 1992-93, 2544 isolates from blood cultures, comprising 52% Gram-negative bacilli, 24% Staphylococcus aureus, 15% other staphylococci, 7% Enterococcus faecalis and 2% E. faecium, were consecutively collected and identified in 30 laboratories in 21 European countries. In addition 2512 urine isolates, comprising 82% Gram-negative bacilli, 3% S. aureus, 4% other staphylococci and 11% enterococci were collected. The bacteria were sent to 3 laboratories for susceptibility testing by the microdilution method in Mueller-Hinton broth. The MICs of penicillins and aztreonam for all susceptible Gram-negative bacilli were 0.25-8 mg/l, penems 0.032-2 mg/l, cefotaxime, ceftazidime and cefpirome or cefepime 0.032-0.25 mg/l, gentamicin, tobramycin and netilmicin 0.125-2 mg/l, amikacin 0.5-4 mg/l, ciprofloxacin 0.016-1 mg/l, trimethoprim 0.25-1 mg/l and tetracycline 1-2 mg/l. For susceptible staphylococci the MICs of erythromycin were 0.25-0.5 mg/l, clindamycin 0.125-0.25 mg/l, methicillin 2-8 mg/l, vancomycin and trimethoprim 1-4 mg/l, ciprofloxacin 0.25-1 mg/l, gentamicin and tobramycin 0.25-1 mg/l. For the enterococci the MICs of ampicillin and vancomycin were 2-4 mg/l and of imipenem, teicoplanin and trimethoprim 0.5-1 mg/l. The antibiotic resistance rates varied between laboratories, being lower in northern Europe, except for the penems, cefpirome and cefepime, which showed uniformly lower resistance rates. Compared to the earlier European studies the resistance rates to β-lactam antibiotics among the Gram-negatives have not changed except with an increase to cefotaxime and ceftazidime in central Europe. Resistance to aminoglycosides had also increased in central Europe from 7-8% to 20-21%, but decreased in southern Europe from 22-24% to 13-14% among the blood isolates and from 12-28% to 6-7% among the urine isolates. There was an increase in resistance to ciprofloxacin and gentamicin in staphylococci from southern Europe. The prevalence of MRSA was significant in central and southern Europe. It is of importance that collaborative national and international studies on the incidence of antibiotic resistance are being performed on a repetitive basis. [ABSTRACT FROM AUTHOR]

Presents an abbreviated account of an experiment in the in-service teacher education (INSET) provision in the area of multicultural education. Background on the INSET program; Consultations on the project; Schools selected for the project; Course conferences; Curriculum development.

Explores the diverse and contradictory ways in which the term spirituality is employed in writings about religion. Question on the reason behind the popularity of the term; Insights of contemporary anthropology; Analysis of the work of Michael Carrithers; Investigation of ideas associated with spirituality.

The calcium binding protein parvalbumin is expressed in interneurons of two main morphologies, the basket and chandelier cells, which target perisomatic domains on principal cells and are extensively interconnected in laminar networks by synapses and gap junctions. Beyond its utility as a convenient cellular marker, parvalbumin is an unambiguous identifier of the key role that these interneurons play in the fundamental functions of the cortex. They provide a temporal framework for principal cell activity by propagating gamma oscillation, providing coherence for cortical information processing and the basis for timing-dependent plasticity processes. As these parvalbumin networks mature, they are physically and functionally stabilised by axonal myelination and development of the extracellular matrix structure termed the perineuronal net. This maturation correlates with the emergence of high-speed, highly energetic activity and provides a coherent foundation for the unique ability of the cortex to cross-correlate activity across sensory modes and internal representations. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the most common form of dementia, is preceded by years of silent pathological change. Our objective was to examine the associations between modifiable dementia risk factors, cognition, and plasma phosphorylated p-tau 181, a hallmark biomarker of AD in a large-scale community cohort. Participants (n = 738, mean age 65.41 years) from the Island Study Linking Ageing and Neurodegenerative Disease responded to online assessments collecting demographics, adherence to dementia risk factors and cognitive function, and provided a blood sample for analysis. We found less education was significantly associated with lower cognitive scores. Modifiable dementia risk factors were not associated with plasma p-tau 181. Further, we did not observe any significant relationships between plasma p-tau 181 and cognition. Nonmodifiable factors such as age, education, sex, and apolipoprotein E epsilon 4 displayed significant associations with cognition and plasma p-tau 181. In a cognitively healthy community cohort of Tasmanian Australians, we did not observe any associations between modifiable risk factors for dementia and plasma p-tau 181. Nonmodifiable risk factors were associated with both cognition and plasma p-tau. This contributes to a growing body of evidence investigating confounding factors in the interpretation of blood-based biomarkers for dementia. [ABSTRACT FROM AUTHOR]

This article explores whether a relational approach to peacebuilding, shared multireligious perspectives and widening networks can bring sources of strength which enable positive peacebuilding and create grassroots, cross-community peace. While religious peacebuilding organizations have become the object of a burgeoning literature, the role of multireligious organisations in peacebuilding has received far less attention. The purpose of this paper is to redress this lack. By examining the influence, challenges and benefits of multireligious approaches to transnational peacebuilding, we hope to develop a sharper and more critically nuanced understanding of the potential role of multireligious organisations in global peacebuilding, and consider what, if anything, distinguishes them from secular and other faith-based organisations. We do so by analysing the impact of a project carried out in Myanmar by Religions for Peace. The project provides three case studies which offer unique opportunities to consider the limits and potential of multireligious grassroots interventions in conflict contexts with very different histories and cultural configurations. [ABSTRACT FROM AUTHOR]

The 'risk assessment' in peacebuilding has become a standard, if sometimes slightly formulaic and performative, element of project design and written proposals. Largely driven by donor requirements and organisational procedures, the relatively new discipline and practice recognised as 'Religious Peacebuilding' has taken on many of the elements of 'secular' peacebuilding, including the risk assessment. This means that organisations increasingly have to attempt to understand the associated risks to projects with a religious dimension often without any specific guidelines, and in many cases, any relevant knowledge or previous experience of working with religious actors in peacebuilding. Consequently, the primary objective of this paper is to propose the first risk assessment framework for peacebuilding projects which explicitly focus on religious dimensions and actors. The framework is based on analysis of case studies and project evaluations from a number of contexts; and has the potential to make a tangible difference to the efficacy and impact of peacebuilding projects in a variety of post-conflict contexts. This paper will also briefly consider how the proposed framework relates to contemporary theoretical debates concerning the instrumentalization of religion, and increasing technocracy in peacebuilding theory and practice. [ABSTRACT FROM AUTHOR]