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Colin Tuft,1 Elie Matar,2 Zoe Menczel Schrire,2 Ronald R Grunstein,2,3 Brendon J Yee,1– 3 Camilla M Hoyos2,4 1Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney Medical School, Sydney, NSW, Australia; 3Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; 4School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, AustraliaCorrespondence: Camilla M Hoyos, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney Medical School, Sydney, NSW, Australia, Tel +61 2 9114 0409, Email camilla.hoyos@sydney.edu.auAbstract: Exogenous melatonin is commonly used for sleep disorders in older adults, and its use is increasing over time. It appears to have modest efficacy in treating insomnia and circadian rhythm sleep-wake disorders. Melatonin is commonly perceived to be a safe alternative to other hypnotics and is available without prescription in some jurisdictions. New evidence suggests that endogenous melatonin has pleomorphic effects on multiple organ systems, many of which are poorly understood. This narrative review summarizes the current evidence regarding the safety of melatonin in older adults (defined by age over 65 years). Melatonin appears to have a favorable safety profile in this population, however there is a dearth of evidence regarding the safety of prolonged use. There are several factors which increase the risk of adverse effects of melatonin in older adults, and these should be taken into consideration when prescribing to this population.Keywords: adverse effect, safety, insomnia, elderly, sleep wake phase disorder

Interstellar water ice is mainly amorphous, but the nature of its morphology still remains poorly known. The experimental study described in this work focuses on how relevant changes of the ice morphology result from atomic hydrogen exposure and subsequent recombination. We show that there is an exponential decrease in the porosity of the amorphous water ice sample following hydrogen-atom irradiation. These and other laboratory results lead us to suggest that water ice in space is almost certainly amorphous and non-porous (compact). [ABSTRACT FROM AUTHOR]

There has always been a great deal of interest in the formation of H2 as well as in the binding energy released upon its formation on the surface of dust grains. The present work aims at collecting experimental evidence for how the bond energy budget of H2 is distributed between the reaction site and the internal energy of the molecule. So far, the non-detection of excited nascent H2 in dense quiescent clouds could be a sign that either predictions of emission line intensities are not correct or the de-excitation of the newly formed molecules proceeds rapidly on the grain surface itself. In this Letter, we present experimental evidence that interstellar molecular hydrogen is formed and then rapidly de-excited on the surface of porous water ice mantles. In addition, although we detect ro-vibrationally excited nascent molecules desorbing from a bare non-porous (compact) water ice film, we demonstrate that the amount of excited nascent hydrogen molecules is significantly reduced no matter the morphology of the water ice substrate at 10 K (both on non-porous and on porous water ice) in a regime of high molecular coverage as is the case in dark molecular clouds. [ABSTRACT FROM AUTHOR]

Functional movement disorder (FMD) is a common manifestation of functional neurological disorder. FMD can occur alongside other neurological conditions, but especially in patients with established Parkinson's disease (PD). An interesting observation emerging across cohort studies and case series is that FMD can precede the diagnosis of PD, suggesting that FMD may itself be a prodromal symptom of neurodegeneration. Such a notion would have significant clinical implications for the assessment and management of people with FMD, particularly with respect to decisions around the use of auxiliary investigations, counselling, and follow-up. In this Viewpoint we review the evidence concerning the temporal relationship between FMD and PD. We discuss the potential explanations and mechanisms for FMD as a prodromal symptom of PD, and highlight clinical considerations and important outstanding questions in the field. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Neuroimaging studies in rapid eye movement sleep behavior disorder (RBD) can inform fundamental questions about the pathogenesis of Parkinson's disease (PD). Across modalities, functional magnetic resonance imaging (fMRI) may be better suited to identify changes between neural networks in the earliest stages of Lewy body diseases when structural changes may be subtle or absent. This review synthesizes the findings from all fMRI studies of RBD to gain further insight into the pathophysiology and progression of Lewy body diseases. A total of 32 studies were identified using a systematic review conducted according to PRISMA guidelines between January 2000 to February 2024 for original fMRI studies in patients with either isolated RBD (iRBD) or RBD secondary to PD. Common functional alterations were detectable in iRBD patients compared with healthy controls across brainstem nuclei, basal ganglia, frontal and occipital lobes, and whole brain network measures. Patients with established PD and RBD demonstrated decreased functional connectivity across the whole brain and brainstem nuclei, but increased functional connectivity in the cerebellum and frontal lobe compared with those PD patients without RBD. Finally, longitudinal changes in resting state functional connectivity were found to track with disease progression. Currently, fMRI studies in RBD have demonstrated early signatures of neurodegeneration across both motor and non-motor pathways. Although more work is needed, such findings have the potential to inform our understanding of disease, help to distinguish between prodromal PD and prodromal dementia with Lewy bodies, and support the development of fMRI-based outcome measures of phenoconversion and progression in future disease modifying trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Visual hallucinations are a common non-motor feature of Parkinson's disease and have been associated with accelerated cognitive decline, increased mortality and early institutionalisation. Despite their prevalence and negative impact on patient outcomes, the repertoire of treatments aimed at addressing this troubling symptom is limited. Over the last two decades, significant contributions have been made in uncovering the pathological and functional mechanisms of visual hallucinations, bringing us closer to the development of a comprehensive neurobiological framework. Convergent evidence now suggests that degeneration within the central cholinergic system may play a significant role in the genesis and progression of visual hallucinations. Here, we outline how cholinergic dysfunction may serve as a potential unifying neurobiological substrate underlying the multifactorial and dynamic nature of visual hallucinations. Drawing upon previous theoretical models, we explore the impact that alterations in cholinergic neurotransmission has on the core cognitive processes pertinent to abnormal perceptual experiences. We conclude by highlighting that a deeper understanding of cholinergic neurobiology and individual pathophysiology may help to improve established and emerging treatment strategies for the management of visual hallucinations and psychotic symptoms in Parkinson's disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Study Objectives: Idiopathic hypersomnia (IH) is a disorder of central hypersomnolence that results in excessive daytime sleepiness in the absence of another identifying cause. Case studies from sleep clinic patients may not be a fair representation of the wider IH population. This study aims to better characterize patients diagnosed with IH in Australia and New Zealand using online patient-driven survey data., Methods: A retrospective analysis of 686 participants from the Hypersomnolence Australia Patient Data Registry diagnosed with either IH (n = 554), narcolepsy type 1 (NT1, n = 54) or narcolepsy type 2 (NT2, n = 78) between January 2013 and October 2022 was performed., Results: Participants with IH reported additional sleep disorders such as OSA (16.4%) and restless legs syndrome (7.9%) and notable comorbidities included depression (46.2%) and anxiety (50%). There was a mean delay in diagnosis of 10 years in participants with IH, when compared to symptom onset. IH presents with unique but also overlapping symptomatology with NT2, with similar reporting of long daytime naps, unrefreshed sleep and automatic behavior. Modafinil was the most common medication (45.5%) used by participants with IH followed by dexamphetamine (44.2%). Most participants with IH reported receiving physician advice regarding positive lifestyle changes but recommend that newly diagnosed patients be given more advice about medication use., Conclusions: This study demonstrates a delay in IH diagnosis when compared to symptom onset and overlapping features of IH and NT2. It also highlights the heterogeneous presentation of IH and the value of large patient registries in future research., (© 2024 American Academy of Sleep Medicine.)

Background: Severe acute respiratory tract infections (SARI) pose a health threat to children and adults worldwide. The SARI surveillance program was initiated in 2018 in Bahrain to monitor the activity of respiratory pathogens. Salmaniya Medical Complex (SMC) was chosen as the sentinel site for the SARI surveillance program. This study aimed to describe the epidemiology of SARI patients admitted to SMC from 2018 to 2022., Methods: Patients meeting the World Health Organization definition of SARI and presenting with cough and fever within the last 10 days and admitted to SMC from January 2018 until December 2022 were included in the study. Epidemiological data on SARI cases were collected from SARI surveillance data and analyzed using SPSS version 25 and Excel., Results: A total of 1362 SARI cases were enrolled from January 2018 to the end of December 2022; the majority were males (57.7%, n = 786). The highest SARI incidence rates were recorded among individuals over 65 years old (155.5 per 100,000) in 2021 and among those under 5 years old (887 per 100,000) in 2020. About half of the patients had at least one comorbidity (54.0%, n = 735), with diabetes (23.0%, n = 313) and hypertension (17.2%, n = 234) being the most common. The highest number of cases was observed in 2021 (27%, n = 373), followed by 2018 (20%, n = 267). A viral pathogen was detected in 30.7% ( n = 418) of the SARI patients. The most prevalent pathogen was influenza A (11.5%, n = 156), followed by SARS-CoV-2 (9.7%, n = 132), respiratory syncytial virus (RSV) (5.1%, n = 69), and influenza B (3.9%, n = 53). The highest percentage of SARI cases was recorded in the winter months, mainly January (17%, n = 236). The percentages of influenza A and RSV cases were highest in December, at 22% ( n = 39) and 14% ( n = 25), respectively. Influenza B cases were recorded predominantly in March (9%, n = 11)., Conclusion: The incidence of SARI was highest among patients above 65 years old. The majority had comorbidities. Influenza and respiratory syncytial viruses were the most frequent causes of SARI, with influenza A being the most prevalent. December and January were the months with the highest SARI cases and viral detection rates. Promoting vaccination, timely testing, and prompt treatment, especially for the elderly and those with comorbidities, is key to reducing SARI-related morbidity and mortality, especially during peak seasons., Competing Interests: No financial or non-financial benefits have been received or will be received from any party directly or indirectly related to this article’s subject., (© 2024 Sayyad, Mohamed, Alajaimi, Matar, Hasan, Aldolabi, et al., Licensee HBKU Press.)

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners., (© 2024. The Author(s).)

Background: Recent consensus research criteria have identified a 'psychiatric onset' form of prodromal dementia with Lewy bodies (DLB) characterised by prominent late-onset psychiatric symptoms. Although recognised as important to raise the index of diagnostic suspicion, evidence regarding this cohort was deemed too limited to impose formal criteria. We reviewed the published literature on psychiatric-onset DLB to identify key clinical characteristics and evidence gaps to progress our understanding of this entity., Methods: Medline, PubMed and Embase were searched for relevant articles containing longitudinal follow-up of patients initially presenting with a psychiatric illness who subsequently developed DLB according to the diagnostic criteria available at the time., Results: Two cohort studies (18 and 21 patients) along with 12 case series (13 cases) were identified totalling 52 patients (63% female). Initial psychiatric presentation occurred at a mean of 63 years (range 53-88), with depression being the most frequently reported psychiatric presentation (88%). Psychotic presentations were less common on presentation (11%) but became more prevalent throughout the prodromal period before the diagnosis of DLB (83%). Relapses of the psychiatric disease were common occurring in 94% (32/34) of patients. Parkinsonism, cognitive fluctuations, visual hallucinations, and REM sleep behaviour disorder were uncommonly reported at initial presentation (3.8%)., Conclusions: Psychiatric-onset DLB is characterized by a female predominant relapsing-remitting psychiatric illness presenting with affective symptoms but later developing psychotic features prior to the onset of DLB. Additional prospective studies including other neurodegenerative cohorts with harmonised assessments are required to inform definitive diagnostic criteria for this condition., (© 2023. The Author(s).)

Background: Several countries, including Bahrain, used wastewater surveillance for disease activity monitoring. This study aimed to determine the presence of SARS-CoV-2 in untreated wastewater and to correlate it with the disease spread., Methods: A retrospective review was conducted for all wastewater samples tested for SARS-CoV-2 in public health laboratories from November 2020 to October 2022. Samples were collected weekly between February and October 2022 from different areas across Bahrain. Real-time polymerase chain reaction was used to test for the presence of SARS-CoV-2 in wastewater, and the results were correlated with the number of COVID-19 cases in the same area., Results: Of 387 wastewater samples, 103 (26.6%) samples tested positive for SARS-CoV-2. In late 2020, of 42 samples collected initially, four (9.5%) samples tested positive for SARS-CoV-2 in the four locations that hosted COVID-19 isolation facilities. Between February and October 2022, 345 specimens of wastewater were tested, and 99 (28.7%) were positive. The highest detection rate was in February, June, and July (60%, 45%, and 43%, respectively), which corresponded to COVID-19 peaks during 2022, and the lowest detection rate was in August and September (11% and 0%, respectively), corresponding to the low number of COVID-19 cases., Conclusion: The detection rate of SARS-CoV-2 in wastewater samples from Bahrain was high and was significantly correlated with the number of reported COVID-19 cases. Wastewater surveillance can aid the existing surveillance system in monitoring SARS-CoV-2 spread., Competing Interests: No financial or non‐financial benefits have been received or will be received from any party directly or indirectly related to this article's subject., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Isolated rapid eye movement sleep behaviour disorder (iRBD) is a sleep disorder characterized by the loss of rapid eye movement sleep muscle atonia and the appearance of abnormal movements and vocalizations during rapid eye movement sleep. It is a strong marker of incipient synucleinopathy such as dementia with Lewy bodies and Parkinson's disease. Patients with iRBD already show brain changes that are reminiscent of manifest synucleinopathies including brain atrophy. However, the mechanisms underlying the development of this atrophy remain poorly understood. In this study, we performed cutting-edge imaging transcriptomics and comprehensive spatial mapping analyses in a multicentric cohort of 171 polysomnography-confirmed iRBD patients [67.7 ± 6.6 (49-87) years; 83% men] and 238 healthy controls [66.6 ± 7.9 (41-88) years; 77% men] with T1-weighted MRI to investigate the gene expression and connectivity patterns associated with changes in cortical thickness and surface area in iRBD. Partial least squares regression was performed to identify the gene expression patterns underlying cortical changes in iRBD. Gene set enrichment analysis and virtual histology were then done to assess the biological processes, cellular components, human disease gene terms, and cell types enriched in these gene expression patterns. We then used structural and functional neighbourhood analyses to assess whether the atrophy patterns in iRBD were constrained by the brain's structural and functional connectome. Moreover, we used comprehensive spatial mapping analyses to assess the specific neurotransmitter systems, functional networks, cytoarchitectonic classes, and cognitive brain systems associated with cortical changes in iRBD. All comparisons were tested against null models that preserved spatial autocorrelation between brain regions and compared to Alzheimer's disease to assess the specificity of findings to synucleinopathies. We found that genes involved in mitochondrial function and macroautophagy were the strongest contributors to the cortical thinning occurring in iRBD. Moreover, we demonstrated that cortical thinning was constrained by the brain's structural and functional connectome and that it mapped onto specific networks involved in motor and planning functions. In contrast with cortical thickness, changes in cortical surface area were related to distinct genes, namely genes involved in the inflammatory response, and to different spatial mapping patterns. The gene expression and connectivity patterns associated with iRBD were all distinct from those observed in Alzheimer's disease. In summary, this study demonstrates that the development of brain atrophy in synucleinopathies is constrained by specific genes and networks., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Severe acute respiratory tract infection (SARI) is a major global health threat. This study aimed to examine risk factors associated with poor outcomes in patients with SARI., Methods: All patients who met World Health Organization's (WHO) SARI case definition and were admitted to Salmaniya Medical Complex from January 2018 to December 2021 were included. Epidemiological and virological data were obtained and analyzed., Results: Of 1159 patients with SARI included, 731 (63.1%) patients were below 50 years, and 357 (30.8%) tested positive for viral pathogens. The most prevalent virus was Flu-A ( n  = 134, 37.5%), SARS-CoV2 ( n  = 118, 33%), RSV ( n  = 51, 14.3%), Flu B ( n  = 49,13.7%), other viruses ( n  = 3, 0.8%), and combined infection ( n  = 2, 0.6%). Six hundred fifty-eight (56.8%) patients had comorbidities, mainly diabetes ( n  = 284, 43%) and heart disease ( n  = 217, 33%). 183 (16%) patients were admitted to ICU, 110 (9%) needed mechanical ventilation, and 80 (7%) patients died.The odds of ICU admission were higher for patients with hematological (OR 5.9, 95% CI 3.1-11.1) and lung diseases (OR 2.7, 95% CI 1.6-4.6). The odds of mechanical ventilation were higher among patients with lung disease (OR 3.1, 95% 1.7-5.5). The mortality odds were higher among patients above 50 (OR 2.4, 95% CI 1.4-4.1) and chronic kidney disease (OR 2.5, 95% CI 1.1-5.2)., Conclusions: Being 50 years or above or having kidney, lung, or heart diseases was associated with worse SARI outcomes. Efforts and actions in developing better strategies to vaccinate individuals at high risk and early diagnosis and treatment should help in reducing the burden of SARI., Competing Interests: No financial or non‐financial benefits have been received or will be received from any party directly or indirectly related to this article's subject., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease., (© 2022 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Parkinsonism and dystonia co-occur across many movement disorders and are most encountered in the setting of Parkinson's disease. Here we aim to explore the shared neurobiological underpinnings of dystonia and parkinsonism through the clinical lens of the conditions in which these movement disorders can be seen together. Foregrounding the discussion, we briefly review the circuits of the motor system and the neuroanatomical and neurophysiological aspects of motor control and highlight their relevance to the proposed pathophysiology of parkinsonism and dystonia. Insight into shared biology is then sought from dystonia occurring in PD and other forms of parkinsonism including those disorders in which both can be co-expressed simultaneously. We organize these within a biological schema along with important questions to be addressed in this space., (Copyright © 2023. Published by Elsevier Inc.)