Chronic Impairment Research Articles

Individual and Family Determinants for Quality of Life in Parents of Children With Inborn Errors of Metabolism Requiring a Restricted Diet: A Multilevel Analysis Approach

ABSTRACT Inborn errors of metabolism (IEMs) requiring a restricted diet can have a significant impact on both children and their caregivers. Previous research has shown conflicting findings in the quality of life (QoL) of caregivers specifically, as many factors can influence daily interactions: home care demands, the potential for acute health crises and hospitalization, dietary constraints, medications, and others. Influencing factors have previously been reported to include emotional, adaptive, and socioeconomic factors, and previous research has varied greatly in sample characteristics, methods of collecting data and measuring QoL, and methods of analysis. This study was performed to clarify previous findings and provide a clearer picture of QoL in parents of children with IEMs requiring a restricted diet compared with the general population based on parent self-report. The final analysis included 785 parents of 578 children with IEMs requiring a restricted diet. Quality of life was assessed using the World Health Organization Quality of Life–BREF and was compared with age- and sex-matched control subjects from the general population. Parents of children with IEMs requiring a restricted diet in this study population experienced a significantly lower QoL in the areas of physical health (mean, −6.09 [SD, 15.01]) and social relationships (mean, −6.82 [SD, 17.71]), as well as a significantly higher QoL in psychological health (mean, +3.10 [SD, 14.25]). Multivariate models were examined to determine factors responsible for these differences in QoL; parental anxiety was negatively associated with all QoL domains. Other factors negatively associated with at least 1 domain included being a father (physical health and social relationships), older parent (physical and psychological health), having an education higher than high school (psychological health), and using more social support–seeking coping strategies (physical health and environment). Factors positively associated with at least 1 domain included having an education level higher than high school (environment), being a working parent (physical and psychological health, environment), and using more positive thinking coping strategies (psychological health). Child-related factors negatively associated with parental QoL included having at least 1 disease complication (social relationships and environment) and a higher number of hospital medical providers (physical health). A child being older positively impacted parental QoL in the environment domain. It is not uncommon for parents of children with chronic diseases or impairments to experience a lower QoL. In this study, some aspects of QoL were enhanced by the demands of caregiving, and some were negatively impacted. Discrepancies in previous literature may be partially attributed to varying tests, variable characteristics within a sample (eg, longer time since diagnosis), or differences in analysis methods. The results in this study indicate a potential need for resources to support parents of children with IEMs requiring a restricted diet. Previous literature has shown efficacy in providing in-home health care professionals for occasional relief of caregiving duties for parents, as well as support groups of parents in similar situations. Parental anxiety in particular was shown to impact QoL negatively in all domains, and thus targeting interventions toward reducing parental anxiety might be one way to improve QoL. The adaptation of parents to their child's condition and to the demands of caregiving could explain some aspects of the QoL difference from the general population, but these differences should still be addressed to improve QoL.

Anemia and Associated Risk Factors in Pediatric Patients.

Anemia is the most common hematologic abnormality identified in children and represents a major global health problem. A delay in diagnosis and treatment might place patients with anemia at risk for the development of rare but serious complications, including chronic and irreversible cognitive impairment. Identified risk factors contributing to the development of anemia in children include the presence of nutritional deficiencies, environmental factors, chronic comorbidities, and congenital disorders of hemoglobin or red blood cells. Pediatricians, especially those in the primary care setting, serve a particularly critical role in the identification and care of those children affected by anemia. Prompt recognition of these risk factors is crucial for developing appropriate and timely therapeutic interventions and prevention strategies.

Trends in health service needs, utilization, and non-communicable chronic diseases burden of older adults in China: evidence from the 1993 to 2018 National Health Service Survey

BackgroundAging is associated with an increased prevalence of non-communicable chronic diseases (NCDs), functional impairments, and diverse demands for health services. This study analyzed the trends in older adults’ needs and utilization of health services from 1993 to 2018 in China, as well as chronic disease-related economic burdens.MethodsThe research data were collected from the six cross-sectional National Health Service Survey (NHSS), implemented every 5 years from 1993 to 2018. A multi-stage stratified random cluster sampling method has been adopted in the NHSS. The data on the older population's socio-economic characteristics, health service needs, and utilization were collected from the 6 waves National Health Service Survey (NHSS) 1993–2018. In the 2013 and 2018 NHSSs, EQ-5D-3L and visual analogue scale were used to evaluate the health condition. And the prevalence of NCDs and related Out-of-pocket (OOP) expenditures were collected. Functional dependency and impairment were collected in 2018. The Katz Activities of Daily Living scale was used to evaluate six functions, including self-feeding, dressing, bathing, transferring, toilet hygiene, and controlling bowel movements.ResultsThe two-week morbidity rate and prevalence of NCDs showed a rapid upward trend in older adults. With the development of health system reform and universal health insurance coverage, older adults' two-week medical consultation rate increased from 25.6% in 1993 to 40.1% in 2018, and the hospitalization rate rose from 6.1% to 24.9%. The difference in health service needs and utilization between urban and rural areas decreased, and the hospitalization rate in rural areas (26.3%) exceeded that in urban areas (23.6%) for the first time in 2018. Functional independence become more severe as aged. The proportion of severe functional impairment was 6.9% and 2% in the group aged 80 or over and group 70–79 years, respectively. Regarding disability status, 32.5% had hearing problems and 31.4% had visual impairment. The highest prevalence rates of NCDs in older adults were found in hypertension (36.9%), followed by diabetes (10.6%), cerebrovascular disease (5.4%), ischemic heart disease (4.5%), and intervertebral disc disease (4.2%). The average annual OOP expenditures attributed to NCDs increased from ¥2481.8 RMB in 2013 to ¥8255.9 RMB in 2018 for older adults. About 90.7% of older adults prefer to live in the residential community, leading to the demands for preventive healthcare (30.4%), medical treatment (14.1%), and elderly education (8.6%).ConclusionThe elevated risks of age-related impairments and chronic morbidities, and increased demands for preventive healthcare are critical public health issues. Policymakers should strengthen primary healthcare and move towards integrated delivery to improve access and quality of care for older adults. The integration of healthcare and social security constitutes an adaptive trend in meeting the multi-level demands of an aging society.

Long-chain omega-3 polyunsaturated fatty acids are reduced in neonates with substantial brain injury undergoing therapeutic hypothermia after hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Although therapeutic hypothermia is an effective treatment, substantial chronic neurological impairment often persists. The long-chain omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, offer therapeutic potential in the post-acute phase. To understand how PUFAs are affected by HIE and therapeutic hypothermia we quantified for the first time the effects of HIE and therapeutic hypothermia on blood PUFA levels and lipid peroxidation. In a cross-sectional approach, blood samples from newborns with moderate to severe HIE, who underwent therapeutic hypothermia (sHIE group) were compared to samples from newborns with mild HIE, who did not receive therapeutic hypothermia, and controls. The sHIE group was stratified into cerebral MRI predictive of good (n = 10), or poor outcomes (n = 10; nine developed cerebral palsy). Cell pellets were analyzed for fatty acid content, and plasma for lipid peroxidation products, thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal. Omega-3 Index (% DHA + EPA) was similar between control and HIE groups; however, with therapeutic hypothermia there were significantly lower levels in poor vs. good prognosis sHIE groups. Estimated Δ-6 desaturase activity was significantly lower in sHIE compared to mild HIE and control groups, and linoleic acid significantly increased in the sHIE group with good prognosis. Reduced long-chain omega-3 PUFAs was associated with poor outcome after HIE and therapeutic hypothermia, potentially due to decreased biosynthesis and tissue incorporation. We speculate a potential role for long-chain omega-3 PUFA interventions in addition to existing treatments to improve neurologic outcomes in sHIE.

Diabetic Retinopathy Screening Using Smartphone-Based Fundus Photography and Deep-Learning Artificial Intelligence in the Yucatan Peninsula: A Field Study.

To compare the performance of Medios (offline) and EyeArt (online) artificial intelligence (AI) algorithms for detecting diabetic retinopathy (DR) on images captured using fundus-on-smartphone photography in a remote outreach field setting. In June, 2019 in the Yucatan Peninsula, 248 patients, many of whom had chronic visual impairment, were screened for DR using two portable Remidio fundus-on-phone cameras, and 2130 images obtained were analyzed, retrospectively, by Medios and EyeArt. Screening performance metrics also were determined retrospectively using masked image analysis combined with clinical examination results as the reference standard. A total of 129 patients were determined to have some level of DR; 119 patients had no DR. Medios was capable of evaluating every patient with a sensitivity (95% confidence intervals [CIs]) of 94% (88%-97%) and specificity of 94% (88%-98%). Owing primarily to photographer error, EyeArt evaluated 156 patients with a sensitivity of 94% (86%-98%) and specificity of 86% (77%-93%). In a head-to-head comparison of 110 patients, the sensitivities of Medios and EyeArt were 99% (93%-100%) and 95% (87%-99%). The specificities for both were 88% (73%-97%). Medios and EyeArt AI algorithms demonstrated high levels of sensitivity and specificity for detecting DR when applied in this real-world field setting. Both programs should be considered in remote, large-scale DR screening campaigns where immediate results are desirable, and in the case of EyeArt, online access is possible.

Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression

Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2 (NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesis-related protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly, overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice. Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment.

Machine learning-based classification of chronic traumatic brain injury using hybrid diffusion imaging.

Traumatic brain injury (TBI) can cause progressive neuropathology that leads to chronic impairments, creating a need for biomarkers to detect and monitor this condition to improve outcomes. This study aimed to analyze the ability of data-driven analysis of diffusion tensor imaging (DTI) and neurite orientation dispersion imaging (NODDI) to develop biomarkers to infer symptom severity and determine whether they outperform conventional T1-weighted imaging. A machine learning-based model was developed using a dataset of hybrid diffusion imaging of patients with chronic traumatic brain injury. We first extracted the useful features from the hybrid diffusion imaging (HYDI) data and then used supervised learning algorithms to classify the outcome of TBI. We developed three models based on DTI, NODDI, and T1-weighted imaging, and we compared the accuracy results across different models. Compared with the conventional T1-weighted imaging-based classification with an accuracy of 51.7-56.8%, our machine learning-based models achieved significantly better results with DTI-based models at 58.7-73.0% accuracy and NODDI with an accuracy of 64.0-72.3%. The machine learning-based feature selection and classification algorithm based on hybrid diffusion features significantly outperform conventional T1-weighted imaging. The results suggest that advanced algorithms can be developed for inferring symptoms of chronic brain injury using feature selection and diffusion-weighted imaging.

Actuated Thumb Exoskeleton with Variable Axes of Rotation For Stroke Rehabilitation

Chronic hand impairment is very common amongst stroke survivors. More specifically, movement of the thumb is highly restricted causing a major decrease in the functionality of the entire hand. The non-orthogonal, non-intersecting joint axes of the thumb and the many actuating muscles involved make it very difficult to understand the thumb, let alone provide techniques for rehabilitation. Thus, an exoskeleton that incorporatesthe 5 anatomical Degrees of Freedom (DOF) of the thumb, both for actuation and measuring, was created in order to better understand motor control of the thumb, both in neurologically intact individuals and in stroke survivors. A mounting bracket was developed to affix the exoskeleton to a forearm brace. The exoskeleton was then tested to determine if it restricted movement. The movement space of the thumb was tracked both withthe thumb connected to the exoskeleton and for the free thumb using a Digital Motion Analysis System (DMAS). Neurologically intact subjects were able to cover an average of 72% of their normal thumb working space while wearing the exoskeleton. Most of the restriction occurred in the upper region of the workspace. Thus, the device seems to allow considerable freedom of movement of the thumb, particularly in the region of the workspace used for everyday tasks. Subjects remarked that thumb movement felt quite natural. Further research using this exoskeleton can be done to better understand the impairments that occur in the thumb and thus provide better insight into rehabilitation methods. For example, the use of a system including motors and flexible shafts to drive the joints of the exoskeleton which in turn drives the joints of the thumb might provide a successful mode of rehabilitation.

Interpretable Fuzzy System for Early Detection Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a chronic developmental impairment that impairs a person's ability to communicate and connect with others. In people with ASD, social contact and reciprocal communication are continually jeopardized. People with ASD may require varying degrees of psychological aid in order to gain greater independence, or they may require ongoing supervision and care. Early discovery of ASD results in more time allocated to individual rehabilitation. In this study, we proposed the fuzzy classifier for ASD classification and tested its interpretability with the fuzzy index and Nauck's index to ensure its reliability. Then, the rule base is created with the Gauje tool. The fuzzy rules were then applied to the fuzzy neural network to predict autism. The suggested model is built on the Mamdani rule set and optimized using the backpropagation algorithm. The proposed model uses a heuristic function and pattern evolution to classify dataset. The model is evaluated using the benchmark metrics accuracy and F-measure, and Nauck's index and fuzzy index are employed to quantify interpretability. The proposed model is superior in its ability to accurately detect ASD, with an average accuracy rate of 91% compared to other classifiers.

Blockage of calcium-sensing receptor improves chronic intermittent hypoxia-induced cognitive impairment by PERK-ATF4-CHOP pathway

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is involved in cognitive impairment of children. Chronic intermittent hypoxia (CIH) is considered as the critical pathophysiological mechanism of OSAHS. Calcium sensitive receptor (CaSR) mediated apoptosis in many neurological disease models by endoplasmic reticulum stress (ERS)-related pathway. However, little is known about the role of CaSR in OSAHS-induced cognitive dysfunction. In this study, we explored the effect of CaSR on CIH-induced cognitive impairment and possible mechanisms on regulation of PERK-ATF4-CHOP pathway in vivo and in vitro. CIH exposed for 9 h in PC12 cells and resulted in the cell apoptosis, simulating OSAHS-induced neuronal injury. CIH upregulated the level of CaSR, p-PERK, ATF4 and CHOP, contributing to the cell apoptosis. Treated with CaSR inhibitor (NPS-2143) or p-PERK inhibitor (GSK2656157) before CIH exposure, CIH-induced PC12 cell apoptosis was alleviated via inhibition of CaSR by downregulating p-PERK, ATF4 and CHOP. In addition, we established CIH mice model. With CIH exposure for 4 weeks in mice, more spatial memory errors were observed during 8-arm radial maze test. CIH significantly increased apoptotic cells in hippocampus via upregulating cleaved Caspase-3 and downregulating ratio of Bcl-2 to Bax. Besides, treatment of CaSR inhibitor alleviated the hippocampal neuronal apoptosis following CIH with downregulated p-PERK, ATF4 and CHOP, suggesting that CaSR contributed to CIH-induced neuronal apoptosis in hippocampus via ERS pathway. Sum up, our results demonstrated that CaSR accelerated hippocampal apoptosis via PERK-ATF4-CHOP pathway, holding a critical function on CIH-mediated cognitive impairment. Conversely, inhibition of CaSR suppressed PERK-ATF4-CHOP pathway and alleviated cognitive impairment.

Grip strength cut-points from the Swiss DO-HEALTH population

BackgroundWhile grip strength (GS) is commonly assessed using a Dynamometer, the Martin Vigorimeter was proposed as an alternative method especially in older adults. However, its reference values for Swiss older adults are missing. We therefore aimed to derive sex- and age-specific GS cut-points for the dominant and non-dominant hand (DH; NDH) using the Martin Vigorimeter. Additionally, we aimed to identify clinically relevant weakness and assess convergent validity with key markers of physical function and sarcopenia in generally healthy Swiss older adults.MethodsThis cross-sectional analysis includes baseline data from Swiss participants enrolled in DO-HEALTH, a 3-year randomized controlled trial in community-dwelling adults age 70 + . For both DH and NDH, 4 different definitions of weakness to derive GS cut-points by sex and age category (≤ 75 vs. > 75 years) were used: i) GS below the median of the 1st quintile, ii) GS below the upper limit of the 1st quintile, iii) GS below 2-standard deviation (SD) of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers (i.e. individuals without major chronic diseases, disabilities, cognitive impairment or mental health issues) and iv) GS below 2.5-SD of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers. To assess the proposed cut-points’ convergent validity, we assessed their association with gait speed, time to complete the 5 Times Sit-To-Stand (5TSTS) test, and present sarcopenia.ResultsIn total, 976 participants had available GS at the DH (mean age 75.2, 62% women). According to the 4 weakness definitions, GS cut-points at the DH ranged from 29–42 and 25–39 kPa in younger and older women respectively, and from 51–69 and 31–50 kPa in younger and older men respectively. Overall, weakness prevalence ranged from 2.0% to 19.3%. Definitions of weakness using the median and the upper limit of the 1st GS quintile were most consistently associated with markers of physical performance. Weak participants were more likely to have lower gait speed, longer time to complete the 5TSTS, and sarcopenia, compared to participants without weakness.ConclusionsIn generally healthy Swiss older adults, weakness defined by the median or the upper limit of the 1st GS quintile may serve as reference to identify clinically relevant weakness. Additional research is needed in less healthy populations in order to derive representative population-based cut-points.Trial registrationClinicalTrials.gov Identifier: NCT01745263.

Effectiveness of programs that offer individualized, multifactorial support to community-dwelling older people with ongoing health and social care needs: a systematic review protocol.

The objective of this review is to assess the effectiveness of programs that offer individualized, multifactorial support to community-dwelling older people with ongoing health and social care needs and to report how these programs affect quality of life and health system outcomes. As people age, they often have multiple chronic conditions and functional impairment, and as a result, they need support to live well. Nursing homes and other residential facilities provide care for people with such needs; however, they can be expensive and older people generally prefer to remain at home, in their community. There is growing interest in programs that offer individualized, multifactorial support in the community for people with complex health and social care needs. This review will focus on the effectiveness of programs that offer individualized, multifactorial support in the community for people over the age of 60 who are identified as having ongoing health and social care needs. The review will assess quality of life and health system outcomes, such as hospital admission. This review will be conducted in accordance with the JBI methodology for systematic reviews of effectiveness. Ten databases will be searched for published and unpublished studies. Titles, abstracts, and full-text studies will be screened by 2 or more independent reviewers and assessed for methodological validity using the standard JBI critical assessment tools. Relevant data will be extracted using the JBI data extraction tools. The data will then be synthesized and reported using measures of evidence certainty. PROSPERO CRD42022324061.

Heart failure and the heart-brain axis.

In heart failure (HF) strong haemodynamic and neuronal signalling feedback interactions between the heart and the central nervous system (CNS) exist that are able to mutually provoke acute or chronic functional impairment. Cerebral injury secondary to HF may include acute stroke, cognitive decline and dementia and depressive disorders. Also brain stem functions are involved in the cardiac-cerebral interaction in HF as neurohormonal control and neuronal reflex circuits are known to be impaired or imbalanced in HF. In turn, impaired cerebral functions may account for direct and indirect myocardial injury and may contribute to symptomatic severity of HF, to disease progression and to increased mortality. Despite the clinical and pathophysiologic significance of the heart-CNS interaction, this relevant field of HF comorbidity is clinically under-recognized with regard to both diagnostic workup and treatment efforts. Here, principal aspects of pathophysiologic heart-CNS interactions related to HF are discussed such as stroke, effects on cognitive function, on depressive disorder and neurovegetative control and neuronal cardiovascular reflex regulation. Aspects of (limited) treatment options for cerebral functional interactions in HF are examined.

The effects of general anesthetics on mitochondrial structure and function in the developing brain.

The use of general anesthetics in modern clinical practice is commonly regarded as safe for healthy individuals, but exposures at the extreme ends of the age spectrum have been linked to chronic cognitive impairments and persistent functional and structural alterations to the nervous system. The accumulation of evidence at both the epidemiological and experimental level prompted the addition of a warning label to inhaled anesthetics by the Food and Drug Administration cautioning their use in children under 3 years of age. Though the mechanism by which anesthetics may induce these detrimental changes remains to be fully elucidated, increasing evidence implicates mitochondria as a potential primary target of anesthetic damage, meditating many of the associated neurotoxic effects. Along with their commonly cited role in energy production via oxidative phosphorylation, mitochondria also play a central role in other critical cellular processes including calcium buffering, cell death pathways, and metabolite synthesis. In addition to meeting their immense energy demands, neurons are particularly dependent on the proper function and spatial organization of mitochondria to mediate specialized functions including neurotransmitter trafficking and release. Mitochondrial dependence is further highlighted in the developing brain, requiring spatiotemporally complex and metabolically expensive processes such as neurogenesis, synaptogenesis, and synaptic pruning, making the consequence of functional alterations potentially impactful. To this end, we explore and summarize the current mechanistic understanding of the effects of anesthetic exposure on mitochondria in the developing nervous system. We will specifically focus on the impact of anesthetic agents on mitochondrial dynamics, apoptosis, bioenergetics, stress pathways, and redox homeostasis. In addition, we will highlight critical knowledge gaps, pertinent challenges, and potential therapeutic targets warranting future exploration to guide mechanistic and outcomes research.

Lifestyle and Pharmacological Interventions and Treatment Indications for the Management of Obesity in Children and Adolescents.

Obesity is a multifactorial chronic impairment that further decreases quality of life and life expectancy. Worldwide, childhood obesity has become a pandemic health issue causing several comorbidities that frequently present already in childhood, including cardiovascular (hypertension, dyslipidemia), metabolic (Type 2 diabetes mellitus, fatty liver disease, metabolic syndrome), respiratory, gastrointestinal and musculoskeletal disorders. In addition, obese children frequently experience stress and psychosocial symptoms, including mood disorders, anxiety, prejudice and low self-esteem. Given that cardiovascular risk factors and pediatric obesity have the tendency to pertain into adulthood, obesity management, including weight control and physical activity, should start before the late teens and certainly before the first signs of atherosclerosis can be detected. This review aims to concisely present options for childhood obesity management, including lifestyle modification strategies and pharmacological treatment, as well as the respective treatment indications for the general practitioner.

Sesamol Mitigates Chronic Iron Overload-Induced Cognitive Impairment and Systemic Inflammation via IL-6 and DMT1 Regulation.

Excessive iron contributes to oxidative damage and cognitive decline in Alzheimer's disease. Sesamol, a compound in sesame oil that exhibits both anti-inflammatory and neuroprotective properties, is examined in this study for its ability to alleviate cognitive impairments in iron overload mice model. An iron overload model is established by intraperitoneally injecting dextran iron (250mgkg-1 body weight) twice a week for 6 weeks, while sesamol (100mgkg-1 body weight) is administered daily for the same length of time. The results demonstrate that sesamol protects spatial working memory and learning ability in iron overload mice, and inhibits neuronal loss and brain atrophy induced by iron overload. Moreover, sesamol significantly decreases interleukin-6 and malondialdehyde, and increases glutathione peroxidase 4 in the brains of iron overload mice. Additionally, sesamol maintains iron homeostasis in the brain by regulating the expressions of transferrin receptors, divalent metal transporter 1, and hepcidin, and reducing iron accumulation. Furthermore, sesamol suppresses disturbed systemic iron homeostasis and inflammation, particularly liver interleukin-6 expression. These findings suggest that sesamol may be effective in mitigating neuroinflammatory responses and cognitive impairments induced by iron overload, potentially through its involvement in mediating the liver-brain axis.

Mood Symptoms and Chronic Fatigue Syndrome Due to Relapsing-Remitting Multiple Sclerosis Are Associated with Immune Activation and Aberrations in the Erythron.

Multiple sclerosis (MS) is a chronic autoimmune and neuroinflammatory disease of the central nervous system characterized by peripheral activation of immune-inflammatory pathways which culminate in neurotoxicity causing demyelination of central neurons. Nonetheless, the pathophysiology of relapsing-remitting MS (RRMS)-related chronic fatigue, depression, anxiety, cognitive impairments, and autonomic disturbances is not well understood. The current study aims to delineate whether the remitted phase of RRMS is accompanied by activated immune-inflammatory pathways and if the latter, coupled with erythron variables, explain the chronic fatigue and mood symptoms due to RRMS. We recruited 63 MS patients, 55 in the remitted phase of RRMS and 8 with secondary progressive MS, and 30 healthy controls and assessed erythron variables, and used a bio-plex assay to measure 27 serum cytokines. A significant proportion of the MS patients (46%) displayed activation of the immune-inflammatory response (IRS) and compensatory immune response (CIRS) systems, and T helper (Th)1 and Th17 cytokine profiles. Remitted RRMS patients showed increased chronic fatigue, depression, anxiety, physiosomatic, autonomic, and insomnia scores, which could partly be explained by M1 macrophage, Th1, Th-17, growth factor, and CIRS activation, as well as aberrations in the erythron including lowered hematocrit and hemoglobin levels. Around 50% of remitted RRMS patients show activation of immune-inflammatory pathways in association with mood and chronic-fatigue-like symptoms. IRS and CIRS activation as well as the aberrations in the erythron are new drug targets to treat chronic fatigue and affective symptoms due to MS.

Identifying and understanding how people living with a lower-grade glioma engage in self-management

PurposeLower-grade gliomas (LGG) are mostly diagnosed in working-aged adults and rarely cured. LGG patients may face chronic impairments (e.g. fatigue, cognitive deficits). Self-management can improve clinical and psychosocial outcomes, yet how LGG patients self-manage the consequences of their tumour and its treatment is not fully understood. This study, therefore, aimed to identify and understand how LGG patients engage in the self-management of their condition.MethodsA diverse group of 28 LGG patients (age range 22–69 years; male n = 16, female n = 12; mean time since diagnosis = 8.7 years) who had completed primary treatment, were recruited from across the United Kingdom. Semi-structured interviews were conducted. Informed by a self-management strategy framework developed in cancer, directed content analysis identified and categorised self-management types and strategies used by patients.ResultsOverall, 20 self-management strategy types, comprising 123 self-management strategies were reported; each participant detailed extensive engagement in self-management. The most used strategy types were ‘using support’ (n = 28), ‘creating a healthy environment’ (n = 28), ‘meaning making’ (n = 27), and ‘self-monitoring’ (n = 27). The most used strategies were ‘accepting the tumour and its consequences’ (n = 26), ‘receiving support from friends (n = 24) and family’ (n = 24), and ‘reinterpreting negative consequences’ (n = 24).ConclusionsThis study provides a comprehensive understanding of the strategies used by LGG patients to self-manage their health and wellbeing, with a diverse, and substantial number of self-management strategies reported.Implications for Cancer SurvivorsThe findings will inform the development of a supported self-management intervention for LGG patients, which will be novel for this patient group.

Neurofunctional correlates of a neurorehabilitation system based on eye movements in chronic stroke impairment levels: A pilot study.

Rehabilitation after a stroke is widely considered fundamental to improve secondary functional impairments. Accessible methods based on motor learning, motor transfer and virtual environments are necessary to help to improve stroke patients' quality of life. Continuing the line of our previous studies, this work investigated the effect of our new and innovative game-based virtual reality training using the control of virtual objects with gaze in three chronic stroke survivors. All participants performed an eye-controlled virtual training task for 4 weeks. Pre- and post-training evaluation were carried out with the Fugl-Meyer Assessment for upper extremity scale as well as performing a tracking task inside an MRI scanner with a MRI-compatible eye-tracker or a joystick. Neural results for each participant show the increase of activity in the motor cortex, basal ganglia and cerebellum for both effectors (hand or eye). These promising results have a potential application as a new game-based neurorehabilitation approach to enhance the motor activity of stroke patients.

Improvement in Quality of Life With the Use of a Technological System Among Patients With Chronic Disease Followed Up in Primary Care (TeNDER Project): Protocol for a Randomized Controlled Trial.

Among chronic diseases, cognitive, neurological, and cardiovascular impairments are becoming increasingly prevalent, generating a shift in health and social needs. Technology can create an ecosystem of care integrated with microtools based on biosensors for motion, location, voice, and expression detection that can help people with chronic diseases. A technological system capable of identifying symptoms, signs, or behavioral patterns could provide notification of the development of complications of disease. This would help the self-care of patients with chronic disease and save health care costs, promoting the autonomy and empowerment of patients and their caregivers, improving their quality of life (QoL), and providing health professionals with monitoring tools. The main objective of this study is to evaluate the effectiveness of a technological system (the TeNDER system) to improve quality of life in patients with chronic diseases: Alzheimer disease, Parkinson disease, and cardiovascular disease. A multicenter, randomized, parallel-group clinical trial will be conducted with a follow-up of 2 months. The scope of the study will be the primary care health centers of the Community of Madrid belonging to the Spanish public health system. The study population will be patients diagnosed with Parkinson disease, Alzheimer disease, and cardiovascular disease; their caregivers; and health professionals. The sample size will be 534 patients (380 in the intervention group). The intervention will consist of the use of the TeNDER system. The system will monitor the patients by means of biosensors, and their data will be integrated into the TeNDER app. With the information provided, the TeNDER system will generate health reports that can be consulted by patients, caregivers, and health professionals. Sociodemographic variables and technological affinity will be measured, as will views on the usability of and satisfaction with the TeNDER system. The dependent variable will be the mean difference in QoL score between the intervention and control groups at 2 months. To study the effectiveness of the TeNDER system in improving QoL in patients, an explanatory linear regression model will be constructed. All analyses will be performed with the 95% CI and robust estimators. Ethics approval for this project was received on September 11, 2019. The trial was registered on August 14, 2020. Recruitment commenced in April 2021, and the expected results will be available during 2023 or 2024. This clinical trial among patients with highly prevalent chronic illnesses and the people most involved in their care will provide a more realistic view of the situation experienced by people with long-term illness and their support networks. The TeNDER system is in continuous development based on a study of the needs of the target population and on feedback during its use from the users: patients, caregivers, and primary care health professionals. ClinicalTrials.gov NCT05681065; https://clinicaltrials.gov/ct2/show/NCT05681065. DERR1-10.2196/47331.