ABSTRACT
BACKGROUND AND PURPOSE
Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing ...solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space DTI‐ALPS parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD).
METHODS
All 36 participants imaged on a Siemens 3.0T Tim Trio. Single‐SE diffusion weighted Echo‐planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI‐ALPS parameter was calculated in these regions and correlated with cognitive status, Mini‐Mental State Examination (MMSE), and ADASCog11 measures.
RESULTS
Significant correlations were found between DTI‐ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI‐ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028).
CONCLUSION
Further work is needed to determine the utility of DTI‐ALPS index in larger elderly cohorts and whether it measures glymphatic activity.
Ecological restoration is critical for climate and biodiversity resilience over the coming century. Today, there is strong evidence that wildlife can significantly influence the distribution and ...stoichiometry of elements across landscapes, with subsequent impacts on the composition and functioning of ecosystems. Consequently, any anthropogenic activity that modifies this important aspect of zoogeochemistry, such as changes to animal community composition, diet, or movement patterns, may support or hinder restoration goals. It is therefore imperative that the zoogeochemical effects of such anthropogenic modifications are quantified and mapped at high spatiotemporal resolutions to help inform restoration strategies. Here, we first discuss pathways through which human activities shape wildlife‐mediated elemental landscapes and outline why current frameworks are inadequate to characterize these processes. We then suggest improvements required to comprehensively model, validate, and monitor element recycling and redistribution by wildlife under differing wildlife management scenarios and discuss how this might be implemented in practice through a specific example in the southern Kalahari Desert. With robust ecological forecasting, zoogeochemical impacts of wildlife can thus be used to support ecological restoration and nature‐based solutions to climate change. If ignored in the restoration process, the effects of wildlife on elemental landscapes may delay, or even prevent, restoration success.
Drug allergy: A 2022 practice parameter update Khan, David A.; Banerji, Aleena; Blumenthal, Kimberly G. ...
Journal of allergy and clinical immunology,
December 2022, 2022-12-00, 20221201, Volume:
150, Issue:
6
Journal Article
DNA methylation among firefighters Zhou, Jin; Jenkins, Timothy G; Jung, Alesia M ...
PloS one,
03/2019, Volume:
14, Issue:
3
Journal Article
Peer reviewed
Open access
Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of ...cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood samples from 45 incumbent and 41 new recruit non-smoking male firefighters and analyzed the samples for DNA methylation using an Illumina Methylation EPIC 850k chip. Adjusting for age and ethnicity, we performed: 1) genome-wide differential methylation analysis; 2) genome-wide prediction for firefighter status (incumbent or new recruit) and years of service; and 3) Ingenuity Pathway Analysis (IPA). Four CpGs, including three in the YIPF6, MPST, and PCED1B genes, demonstrated above 1.5-fold statistically significant differential methylation after Bonferroni correction. Genome-wide methylation predicted with high accuracy incumbent and new recruit status as well as years of service among incumbent firefighters. Using IPA, the top pathways with more than 5 gene members annotated from differentially methylated probes included Sirtuin signaling pathway, p53 signaling, and 5' AMP-activated protein kinase (AMPK) signaling. These DNA methylation findings suggest potential cellular mechanisms associated with increased cancer risk in firefighters.
While dietary intake has previously been related to various indices of poor sleep (e.g., short sleep duration, poor sleep quality), to date, few studies have examined chrononutrition from the ...perspectives of the relationship between dietary intake and social jet lag and temporal sleep variability. Moreover, recently it has been suggested that previous methods of measuring social jet lag have the potential to lead to large overestimations. Together, this precludes a clear understanding of the role of nutritional composition in the pathophysiology of poor sleep, via social jet lag and temporal sleep variability, or vice versa. The aim of the present study was to determine the relationships between nutrient intake and social jet lag (using a revised index, taking account of intention to sleep and sleep onset and offset difficulties), and temporal sleep variability. Using a cross-sectional survey, 657 healthy participants (mean age 26.7 ± 6.1 years), without sleep disorders, were recruited via an online platform and completed measures of weekly dietary intake, social jet lag, temporal sleep variability, stress/sleep reactivity and mood. Results showed limited associations between nutritional composition and social jet lag. However, levels of temporal sleep variability were predicted by consumption of polyunsaturated fats, sodium, chloride and total energy intake. The results suggest further examinations of specific nutrients are warranted in a first step to tailoring interventions to manage diet and temporal variabilities in sleep patterns.
Abstract Background/Aims Gout is a major cause of morbidity with a significant increase in UK hospitalisation identified over the last decade due to acute flare. Patient and physician education ...alongside a treat-to-target approach with urate-lowering therapy (ULT) are fundamental in its management. Despite being commonly encountered by clinicians, a survey conducted at Imperial College Healthcare NHS trust (ICHNT) demonstrated 49% of responders did not feel confident managing the condition. This project aimed to create a guideline for the management of acute gout at ICHNT to aid prompt diagnosis and effective management. Increasing the proportion of patients commencing ULT through engagement with local primary care networks was prioritised to improve patient outcomes and reduce subsequent hospital attendances. Methods A trust wide guideline for the management of acute gout was created with input from stakeholders (including emergency and acute medicine physicians) and informed by rheumatology clinicians and current guidelines. Latest recommendations from NICE, BSR and EULAR were consulted alongside local guidelines in place across London. An emphasis was placed upon education and initiation of ULT to improve management of acute and chronic gout to prevent future hospital attendances. Staff within the rheumatology department were consulted to agree on timing of ULT initiation and an effective pathway for implementation. Results Through review of local, national and international guidelines, discrepancies in gout management were identified, most notably variation in the timing of ULT initiation (e.g. during the acute presentation, after flare resolution or after subsequent flare). This was reflected in the practice of clinicians within the rheumatology department at ICHNT. Agreed consensus brought the trust guideline predominantly in line with current NICE guidance for management of acute gout with ULT commenced in patients 2-4 weeks after resolution of flare. Initially, this led to delegation of ULT initiation to general practitioners, however, this resulted in concerns over treatment delays and added pressure on an already stretched service. Follow-up within secondary care was also considered, but capacity issues exist. As a next step, a pilot for a pharmacy-led follow-up service within primary care is planned using standardised protocols supported by secondary care. Conclusion The implementation of a local guideline on the management of acute gout is helpful for clinicians from a non-rheumatology background to facilitate prompt diagnosis and effective management of this common, but often poorly treated, condition. A successful pathway to prevent future flares is more challenging, not only due to discrepancies in current guidelines on timing of ULT initiation but also in creating capacity for follow-up and treatment implementation. This continuing project aims to explore alternative pathways such as a pharmacy-led service that improves patient outcomes and reduces future burden upon healthcare services. Disclosure E. Mabey: None. H. Wilson-Morkeh: None. B. Ellis: None.
Engineered cardiac tissues that can be directly produced from human induced pluripotent stem cells (hiPSCs) in scalable, suspension culture systems are needed to meet the demands of cardiac ...regenerative medicine. Here, we demonstrate successful production of functional cardiac tissue microspheres through direct differentiation of hydrogel encapsulated hiPSCs. To form the microspheres, hiPSCs were suspended within the photocrosslinkable biomaterial, PEG-fibrinogen (25 million cells/mL), and encapsulated at a rate of 420,000 cells/minute using a custom microfluidic system. Even at this high cell density and rapid production rate, high intra-batch and batch-to-batch reproducibility was achieved. Following microsphere formation, hiPSCs maintained high cell viability and continued to grow within and beyond the original PEG-fibrinogen matrix. These initially soft microspheres (<250 Pa) supported efficient cardiac differentiation; spontaneous contractions initiated by differentiation day 8, and the microspheres contained >75% cardiomyocytes (CMs). CMs responded appropriately to pharmacological stimuli and exhibited 1:1 capture up to 6.0 Hz when electrically paced. Over time, cells formed cell-cell junctions and aligned myofibril fibers; engineered cardiac microspheres were maintained in culture over 3 years. The capability to rapidly generate uniform cardiac microsphere tissues is critical for advancing downstream applications including biomanufacturing, multi-well plate drug screening, and injection-based regenerative therapies.
Most mental health services for trauma‐exposed children and adolescents were not originally developed for refugees. Information is needed to help clinicians design services to address the ...consequences of trauma in refugee populations. We compared trauma exposure, psychological distress, and mental health service utilization among children and adolescents of refugee‐origin, immigrant‐origin, and U.S.‐origin referred for assessment and treatment by U.S. providers in the National Child Traumatic Stress Network (NCTSN). We used propensity score matching to compare trauma profiles, mental health needs, and service use across three groups. Our sample comprised refugee‐origin youth (n = 60, 48.3% female, mean age = 13.07 years) and propensity‐matched samples of immigrant‐origin youth (n = 143, 60.8% female, mean age = 13.26 years), and U.S.‐origin youth (n = 140, 56.1% female, mean age = 12.11 years). On average, there were significantly more types of trauma exposure among refugee youth than either U.S.‐origin youth (p < .001) or immigrant youth (p ≤ .001). Compared with U.S.‐origin youth, refugee youth had higher rates of community violence exposure, dissociative symptoms, traumatic grief, somatization, and phobic disorder. In contrast, the refugee group had comparably lower rates of substance abuse and oppositional defiant disorder (ps ranging from .030 to < .001).This clinic‐referred sample of refugee‐origin youth presented with distinct patterns of trauma exposure, distress symptoms, and service needs that merit consideration in services planning.
Resumen
Spanish s by the Asociación Chilena de Estrés Traumático (ACET)
La mayoría de los servicios mentales para niños y adolescentes expuestos a trauma no fueron originalmente desarrollados para refugiados. Se necesita información para ayudar a los clínicos a diseñar servicios que aborden las consecuencias del trauma en poblaciones de refugiados. Comparamos la exposición al trauma, la angustia psicológica y la utilización de servicios mentales entre niños y adolescentes de grupos refugiados, inmigrantes y de origen americano para la evaluación y tratamiento por los proveedores americanos en la Red Nacional de Estrés Traumático infantil (RNETI). Usamos la puntuación de pares de propensión para comparar los perfiles de trauma, necesidades de salud mental y uso de servicios en los tres grupos. La muestra comprendió jóvenes refugiados (n = 60, 48,3% femenino, edad promedio = 13.7 años) ymuestras de pares de propensión de jóvenes inmigrantes (n = 143, 60,8%, femenino, edad promedio = 13.26 años) y jóvenes de origen americano (n = 140 56,1%, femenino, edad promedio = 12.11 años). En promedio, hubo significativamente más tipos de exposición a traumas entre los jóvenes refugiados que en los jóvenes de origen americano (p<.001) o jóvenes inmigrantes (p<.001). Comparados con los jóvenes de origen americano, los jóvenes refugiados tuvieron mayores tasas de exposición a violencia comunitaria, síntomas disociativos, duelo traumático, somatización y trastorno fóbico. En contraste, el grupo de refugiados tuvo en comparación tasas más bajas de abuso de sustancias y trastorno oposicionista desafiante (ps que van desde .030 a < .001). Esta muestra clínica referida de jóvenes refugiados presentados con patrones distintivos de exposición a trauma, síntomas de angustia y necesidades de servicio, merecen una consideración en la planificación de los servicios.
摘要
Traditional and Simplified Chinese s by AsianSTSS
Traditional Chinese
標題: 透過難民、移民及美國藉的兒童臨床樣本, 比較創傷經歷、心理需要和
心理治療服務使用模式
撮要: 大部分現有為受創兒童及青少年提供的心理治療服務都不是專為難民而設。臨床治療師需要更多數據為難民設計治療, 治理創傷對他們的影響。本研究樣本為獲美國醫療單位轉介去國家兒童創傷壓力網絡(NCTSN), 接受評估和治療的兒童及青少年。我們比較難民、移民及美國藉的兒童及青少年的創傷經歷、心理悲痛和心理治療服務的使用模式。我們利用傾向評分匹配法, 比較三組樣本的創傷剖象、心理需要和治療服務使用。樣本包括難民青少年 (n = 60, 48.3% 女性, 平均年齡 = 13.07 歲), 及採用了傾向評分匹配法的青少年移民樣本 (n = 143, 60.8% 女性, 平均年齡 = 13.26 歲), 及美國藉青少年樣本 (n = 140, 56.1% 女性, 平均年齡 = 12.11 歲)。平均來說, 相比美國藉青少年(p < .001)和青少年移民(p < .001), 難民青少年顯著地反映更多種創傷經歷。與美國藉青少年相比, 難民青少年有較高水平的社群暴力經歷、離解症狀、創傷後悲傷、軀體化和恐懼症, 但有較低水平的濫用藥物狀況和對抗性蔑視失常 (ps 值域為 .030 至 < .001)。本研究的難民青少年樣本展現明顯的創傷經歷、悲痛症狀和心理治療服務需要的模式, 醫療單位日後設計治療時值得考慮這些數據。
Simplified Chinese
标题: 透过难民、移民及美国藉的儿童临床样本, 比较创伤经历、心理需要和心理治疗服务使用模式
撮要: 大部分现有为受创儿童及青少年提供的心理治疗服务都不是专为难民而设。临床治疗师需要更多数据为难民设计治疗, 治理创伤对他们的影响。本研究样本为获美国医疗单位转介去国家儿童创伤压力网络(NCTSN), 接受评估和治疗的儿童及青少年。我们比较难民、移民及美国藉的儿童及青少年的创伤经历、心理悲痛和心理治疗服务的使用模式。我们利用倾向评分匹配法, 比较三组样本的创伤剖象、心理需要和治疗服务使用。样本包括难民青少年 (n = 60, 48.3% 女性, 平均年龄 = 13.07 岁), 及采用了倾向评分匹配法的青少年移民样本 (n = 143, 60.8% 女性, 平均年龄 = 13.26 岁), 及美国藉青少年样本 (n = 140, 56.1% 女性, 平均年龄 = 12.11 岁)。平均来说, 相比美国藉青少年(p < .001)和青少年移民(p < .001), 难民青少年显著地反映更多种创伤经历。与美国藉青少年相比, 难民青少年有较高水平的社群暴力经历、离解症状、创伤后悲伤、躯体化和恐惧症, 但有较低水平的滥用药物状况和对抗性蔑视失常 (ps 值域为 .030 至 < .001)。本研究的难民青少年样本展现明显的创伤经历、悲痛症状和心理治疗服务需要的模式, 医疗单位日后设计治疗时值得考虑这些数据。
Telomeres are highly conserved regions of DNA that protect the ends of linear chromosomes. The loss of telomeres can signal an irreversible change to a cell's state, including cellular senescence. ...Senescent cells no longer divide and can damage nearby healthy cells, thus potentially placing them at the crossroads of cancer and ageing. While the epidemiology, cellular and molecular biology of telomeres are well studied, a newer field exploring telomere biology in the context of ecology and evolution is just emerging. With work to date focusing on how telomere shortening relates to individual mortality, less is known about how telomeres relate to ageing rates across species. Here, we investigated telomere length in cross-sectional samples from 19 bird species to determine how rates of telomere loss relate to interspecific variation in maximum lifespan. We found that bird species with longer lifespans lose fewer telomeric repeats each year compared with species with shorter lifespans. In addition, phylogenetic analysis revealed that the rate of telomere loss is evolutionarily conserved within bird families. This suggests that the physiological causes of telomere shortening, or the ability to maintain telomeres, are features that may be responsible for, or co-evolved with, different lifespans observed across species.
This article is part of the theme issue ‘Understanding diversity in telomere dynamics'.
PDF
