Functional Disturbances Research Articles

Emerging Roles of Vitamin B12 in Aging and Inflammation.

Vitamin B12 (cobalamin) is an essential nutrient for humans and animals. Metabolically active forms of B12-methylcobalamin and 5-deoxyadenosylcobalamin are cofactors for the enzymes methionine synthase and mitochondrial methylmalonyl-CoA mutase. Malfunction of these enzymes due to a scarcity of vitamin B12 leads to disturbance of one-carbon metabolism and impaired mitochondrial function. A significant fraction of the population (up to 20%) is deficient in vitamin B12, with a higher rate of deficiency among elderly people. B12 deficiency is associated with numerous hallmarks of aging at the cellular and organismal levels. Cellular senescence is characterized by high levels of DNA damage by metabolic abnormalities, increased mitochondrial dysfunction, and disturbance of epigenetic regulation. B12 deficiency could be responsible for or play a crucial part in these disorders. In this review, we focus on a comprehensive analysis of molecular mechanisms through which vitamin B12 influences aging. We review new data about how deficiency in vitamin B12 may accelerate cellular aging. Despite indications that vitamin B12 has an important role in health and healthy aging, knowledge of the influence of vitamin B12 on aging is still limited and requires further research.

Alterations in spatiotemporal characteristics of dynamic networks in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is characterized by altered patterns of brain functional connectivity (FC). However, the nature and extent of alterations in the spatiotemporal characteristics of dynamic FC in JME patients remain elusive. Dynamic networks effectively encapsulate temporal variations in brain imaging data, offering insights into brain network abnormalities and contributing to our understanding of the seizure mechanisms and origins. Resting-state functional magnetic resonance imaging (rs-fMRI) data were procured from 37 JME patients and 37 healthy counterparts. Forty-seven network nodes were identified by group-independent component analysis (ICA) to construct the dynamic network. Ultimately, patients' and controls' spatiotemporal characteristics, encompassing temporal clustering and variability, were contrasted at the whole-brain, large-scale network, and regional levels. Our findings reveal a marked reduction in temporal clustering and an elevation in temporal variability in JME patients at the whole-brain echelon. Perturbations were notably pronounced in the default mode network (DMN) and visual network (VN) at the large-scale level. Nodes exhibiting anomalous were predominantly situated within the DMN and VN. Additionally, there was a significant correlation between the severity of JME symptoms and the temporal clustering of the VN. Our findings suggest that excessive temporal changes in brain FC may affect the temporal structure of dynamic brain networks, leading to disturbances in brain function in patients with JME. The DMN and VN play an important role in the dynamics of brain networks in patients, and their abnormal spatiotemporal properties may underlie abnormal brain function in patients with JME in the early stages of the disease.

Biallelic loss of function variants in FUZ result in an orofaciodigital syndrome

Orofaciodigital syndrome is a distinctive subtype of skeletal ciliopathies. Disease-causing variants in the genes encoding the CPLANE complex result in a wide variety of skeletal dysplasia with disturbed ciliary functions. The phenotypic spectrum includes orofaciodigital syndrome and short rib polydactyly syndrome. FUZ, as a part of the CPLANE complex, is involved in intraflagellar vesicular trafficking within primary cilia. Previously, the variants, c.98_111+9del and c.851G>T in FUZ were identified in two individuals with a skeletal ciliopathy, manifesting digital anomalies (polydactyly, syndactyly), orofacial cleft, short ribs and cardiac defects. Here, we present two novel variants, c.601G>A and c.625_636del in biallelic state, in two additional subjects exhibiting phenotypic overlap with the previously reported cases. Our findings underscore the association between biallelic loss of function variants in FUZ and skeletal ciliopathy akin to orofaciodigital syndrome.

Cognitive impairment and therapeutic response in resistant depression

ObjectivesTherapeutic response in depression is a major challenge since more than one third of patients are not in remission after two attempts of antidepressant treatment and will present a treatment-resistant depression. In order to better adapt therapeutic strategies for treatment-resistant patients, predictive indicators and markers of therapeutic response still need to be identified. In parallel, patients with depression exhibit disturbances in cognitive functioning. This study aims to describe and compare cognitive performances collected at inclusion of patients presenting treatment-resistant depression who will be responders at 6 months to those of non-responders, and to evaluate the predictive value of cognitive indicators on clinical therapeutic response at 6 months after a therapeutic modification. MethodsObservational study. Patients were evaluated at the clinical (HDRS and BDI-II) and cognitive levels using standardized tools assessing memory, executive functions, attention, and social cognition, prior to a change in antidepressant treatment. Six months after inclusion, they were reassessed and classified into two groups based on the presence or absence of therapeutic response, defined by a 50% improvement on HDRS and BDI-II. The cognitive scores collected at inclusion were then compared. Additionally, univariate logistic regression models were used. ResultsThirty patients were included in this study. Only 13 could be evaluated at 6 months. Among these patients, four had responded to the new treatment while nine were non-responders. Both groups of patients presented deviant cognitive performances compared to norms on tests evaluating executive functions and attention. Statistical analyses did not reveal any difference between the cognitive performances of responders and non-responders at 6 months. Regression analyses showed no association between cognitive scores and therapeutic response at 6 months. ConclusionExecutive functioning plays a significant role in treatment-resistant depression. In order to improve the understanding and identification of subtypes of depression, cognitive indicators should be systematically integrated into future research.

Astrocytic HILPDA promotes lipid droplets generation to drive cognitive dysfunction in mice with sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is manifested as a spectrum of disturbed cerebral function ranging from mild delirium to coma. However, the pathogenesis of SAE has not been clearly elucidated. Astrocytes play important roles in maintaining the function and metabolism of the brain. Most recently, it has been demonstrated that disorders of lipid metabolism, especially lipid droplets (LDs) dyshomeostasis, are involved in a variety of neurodegenerative diseases. The aim of this study was to investigate whether LDs are involved in the underlying mechanism of SAE. The open field test, Y-maze test, and contextual fear conditioning test (CFCT) were used to test cognitive function in SAE mice. Lipidomics was utilized to investigate alterations in hippocampal lipid metabolism in SAE mice. Western blotting and immunofluorescence labeling were applied for the observation of related proteins. In the current study, we found that SAE mice showed severe cognitive dysfunction, including spatial working and contextual memory. Meanwhile, we demonstrated that lipid metabolism was widely dysregulated in the hippocampus by using lipidomic analysis. Furthermore, western blotting and immunofluorescence confirmed that LDs accumulation in hippocampal astrocytes was involved in the pathological process of cognitive dysfunction in SAE mice. We verified that LDs can be inhibited by specifically suppress hypoxia-inducible lipid droplet-associated protein (HILPDA) in astrocytes. Meanwhile, cognitive dysfunction in SAE was ameliorated by reducing A1 astrocyte activation and inhibiting presynaptic membrane transmitter release. The accumulation of astrocytic lipid droplets plays a crucial role in the pathological process of SAE. HILPDA is an attractive therapeutic target for lipid metabolism regulation and cognitive improvement in septic patients.

Identification of urine biomarkers of endometriosis-Protein mass spectrometry.

Endometriosis is a chronic inflammatory disease that leads to a series of pathological reactions. The basis is a changed proinflammatory activated immune system, which results in more pronounced oxidative stress, disturbed function of proteolysis and cell apoptosis. These processes are crucial in the development of the disease because their dysfunctional activities cause the progression of the disease. It is believed that the proteins excreted in the urine interact with each other and promote pathological processes in endometriosis. We analyzed the urine proteome of patients and aimed to detect a potential protein biomarker for endometriosis in the urine proteome. We collected urine samples from 16 patients with endometriosis and 16 patients in the control group with functional ovarian cysts. The diagnosis for all patients was confirmed through pathohistological analysis. After the preanalytical preparation of the urine, chromatography and mass spectrometry (LC-MS/MS) used the technology of urine proteome analysis. The main finding was a significantly different concentration of 14 proteins in the urine samples. We recorded a considerably higher concentration of proteins that have a significant role in activating the immune system (SELL), iron metabolism (HAMP) and cell apoptosis (CHGA) in endometriosis compared to controls. Proteins having an antioxidant function (SOD1) and a role in proteolysis of the extracellular matrix (MMP-9) were significantly reduced in endometriosis compared to controls. Consistent with the known pathogenesis of endometriosis, the study results complement the pathological responses that occur with disease progression.

EVALUATION OF ORGANOLEPTIC &IN-VITRO BIOAVAILABILITY PROPERTIES OF IRON FORTIFIED YOGURT

Yogurt is a fermented dairy product formed by the action of Lactobacillus spp. with the help of lactic acid fermentation procedure.In India major cause of anaemia is dietary iron deficiency.Iron deficiency causes poor cognitive performance, behavioural abnormalities, poor physical growth of children, disturbed immune function, lack of physical activity and poor work performance in all age groups. Worldwide dairy foods are most popular nutritious product so dairy foods may be used as a vehicle of food fortification. The iron compound which are used as a food fortificant should contain highly bioavailable iron and the physical chemical characteristics of the fortified food product should be similar to non-fortified product. In the present study yogurt was fortified with ammonium ferrous sulphate, ferrous sulphate, iron-casein complex in three different concentrations (20mg, 30mg, 40 mg iron) /kg milk sample. Sensory evaluation and In-vitro bioavailability study of yogurt samples were analyzed at 1st, 4th, 7th day of storage. Statistical analysis of the study shows ferrous sulphate and iron-casein complex fortified yogurt enhances the iron absorption compared to ammonium ferrous sulphate fortified yogurt.

BMP4 in Human Endometrial Stromal Cells Can Affect Decidualization by Regulating FOXO1 Expression.

Recurrent spontaneous abortion (RSA) is defined as the loss of 2 or more consecutive intrauterine pregnancies with the same sexual partner in the first trimester. Despite its significance, the etiology and underlying mechanisms of RSA remain elusive. Defective decidualization is proposed as one of the potential causes of RSA, with abnormal decidualization leading to disturbances in trophoblast invasion function. To assess the role of bone morphogenetic protein 4 (BMP4) in decidualization and RSA. Decidual samples were collected from both RSA patients and healthy controls to assess BMP4 expression. In vitro cell experiments utilized the hESC cell line to investigate the impact of BMP4 on decidualization and associated aging, as well as its role in the maternal-fetal interface communication. Subsequently, a spontaneous abortion mouse model was established to evaluate embryo resorption rates and BMP4 expression levels. Our study identified a significant downregulation of BMP4 expression in the decidua of RSA patients compared to the normal control group. In vitro, BMP4 knockdown resulted in inadequate decidualization and inhibited associated aging processes. Mechanistically, BMP4 was implicated in the regulation of FOXO1 expression, thereby influencing decidualization and aging. Furthermore, loss of BMP4 hindered trophoblast migration and invasion via FOXO1 modulation. Additionally, BMP4 downregulation was observed in RSA mice. Our findings highlighted the downregulation of BMP4 in both RSA patients and mice. BMP4 in human endometrial stromal cells was shown to modulate decidualization by regulating FOXO1 expression. Loss of BMP4 may contribute to the pathogenesis of RSA, suggesting potential avenues for abortion prevention strategies.

Mechanisms of vibration-induced structural myocardial remodeling

The review analyzes literature data on structural changes in the heart of patients with vibration disease, as detected by echocardiographic methods. Particularly, it highlights concentric remodeling of the left ventricle chambers and disturbances in diastolic function. The review also discusses a 1.2-fold decrease in heart structure intensity compared to healthy individuals (p 0.05). Furthermore, it examines changes in morphometric and bioenergetic parameters of cardiomyocytes under different experimental vibration modes (7 and 56 sessions at a frequency of 8 Hz), confirming the disruptions in the relationship between the spatial configuration of the heart cavities, contractile ability, and energy supply potential. Loss of cardiac myofibrils represents the transition from myocardial hypertrophy to decompensation, accompanied by an increase in degenerative (dystrophic) signs such as the loss of sarcomeres in cardiomyocytes. Understanding these pathological (morphological) processes requires consideration of various mediators that regulate cell metabolism, proliferation, growth, and survival, including stromal interaction molecule, calcium ATPase of the endo(sarco)plasmic reticulum, inositol-1,4,5-triphosphate receptor, protein that forms CRAC channels, and transient receptor potential canonical. The degradation system of the extracellular matrix, including matrix metalloproteinases and tissue inhibitors, plays a crucial role in structural cardiac remodeling. This system regulates the rate of mRNA synthesis on the DNA matrix by binding to specific DNA regions that control cardiac nutrition and plasticity. The review suggests that these findings can help explain some patterns of cardiac remodeling development in patients with vibration disease and determine the direction of pathogenetically based therapy. This therapy should consider not only the vibration-protective effect of drugs but also their ability to inhibit and regress myocardial remodeling.

Functional mapping of the lower urinary tract by epidural electrical stimulation of the spinal cord in decerebrated cat model

Several neurologic diseases including spinal cord injury, Parkinson’s disease or multiple sclerosis are accompanied by disturbances of the lower urinary tract functions. Clinical data indicates that chronic spinal cord stimulation can improve not only motor function but also ability to store urine and control micturition. Decoding the spinal mechanisms that regulate the functioning of detrusor (Detr) and external urethral sphincter (EUS) muscles is essential for effective neuromodulation therapy in patients with disturbances of micturition. In the present work we performed a mapping of Detr and EUS activity by applying epidural electrical stimulation (EES) at different levels of the spinal cord in decerebrated cat model. The study was performed in 5 adult male cats, evoked potentials were generated by EES aiming to recruit various spinal pathways responsible for LUT and hindlimbs control. Recruitment of Detr occurred mainly with stimulation of the lower thoracic and upper lumbar spinal cord (T13-L1 spinal segments). Responses in the EUS, in general, occurred with stimulation of all the studied sites of the spinal cord, however, a pronounced specificity was noted for the lower lumbar/upper sacral sections (L7-S1 spinal segments). These features were confirmed by comparing the normalized values of the slope angles used to approximate the recruitment curve data by the linear regression method. Thus, these findings are in accordance with our previous data obtained in rats and could be used for development of novel site-specific neuromodulation therapeutic approaches.

Unlocking mitochondrial drug targets: The importance of mitochondrial transport proteins.

A disturbed mitochondrial function contributes to the pathology of many common diseases. These organelles are therefore important therapeutic targets. On the contrary, many adverse effects of drugs can be explained by a mitochondrial off-target effect, in particular, due to an interaction with carrier proteins in the inner membrane. Yet this class of transport proteins remains underappreciated and understudied. The aim of this review is to provide a deeper understanding of the role of mitochondrial carriers in health and disease and their significance as drug targets. We present literature-based evidence that mitochondrial carrier proteins are associated with prevalent diseases and emphasize their potential as drug (off-)target sites by summarizing known mitochondrial drug-transporter interactions. Studying these carriers will enhance our knowledge of mitochondrial drug on- and off-targets and provide opportunities to further improve the efficacy and safety of drugs.

Does pain intensity after total knee arthroplasty depend on somatosensory functioning in knee osteoarthritis patients? A prospective cohort study

The objective of this study is to determine whether the change in pain intensity over time differs between somatosensory functioning evolution profiles in knee osteoarthritis (KOA) patients undergoing total knee arthroplasty (TKA). This longitudinal prospective cohort study, conducted between March 2018 and July 2023, included KOA patients undergoing TKA in four hospitals in Belgium and the Netherlands. The evolution of the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale pain over time (baseline, 3 months, and 1 year post-TKA scores) was the outcome variable. The evolution scores of quantitative sensory testing (QST) and Central Sensitization Inventory (CSI) over time (baseline and 1 year post-TKA scores) were used to make subgroups. Participants were divided into separate normal, recovered, and persistent disturbed somatosensory subgroups based on the CSI, local and widespread pressure pain threshold [PPT] and heat allodynia, temporal summation [TS], and conditioned pain modulation [CPM]. Linear mixed model analyses were performed. Two hundred twenty-three participants were included. The persistent disturbed somatosensory functioning group had less pronounced pain improvement (based on CSI and local heat allodynia) and worse pain scores 1 year post-TKA (based on CSI, local PPT and heat allodynia, and TS) compared to the normal somatosensory functioning group. This persistent group also had worse pain scores 1 year post-TKA compared to the recovered group (based on CSI). The study suggests the presence of a “centrally driven central sensitization” subgroup in KOA patients awaiting TKA in four of seven grouping variables, comprising their less pain improvement or worse pain score after TKA. Future research should validate these findings further. The protocol is registered at clinicaltrials.gov (NCT05380648).

Pure total flavonoids from Citrus ameliorate NSAIDs-induced intestinal mucosal injury via regulation of exosomal LncRNA H19 and protective autophagy

IntroductionNon-steroid anti-inflammatory drugs (NSAIDs) are a class of prescription drugs with antipyretic, analgesic, anti-inflammatory, and antiplatelet effects. However, long-term use of NSAIDs will disrupt the intestinal mucosal barrier, causing erosion, ulcers, bleeding, and even perforation. Pure total flavonoids from Citrus (PTFC) is extracted from the dried peel of Citrus, showing a protective effect on intestinal mucosal barrier with unclear mechanisms. MethodsIn the present study, we used diclofenac (7.5 mg kg−1, i.g.) to induce a rat model of NSAIDs-related intestinal lesions. PTFC (50, 75, 100 mg·kg−1 d−1, i.g.) was administered 9 days before the initial diclofenac administration, followed by co-administration on the last 5 days. Exosomes were identified by western blotting and transmission electron microscopy (TEM), and then co-cultured with IEC-6 cells. The expression of long non-coding RNA (lncRNA) H19, autophagy-related 5 (Atg5), ZO-1, Occludin, and Claudin-1 were detected by quantitative real-time PCR (qRT-PCR). The expression of light chain 3 (LC3)-I, LC3-II, ZO-1, Occludin and Claudin-1 proteins was tested by western blotting. The localization of both exosomes and autophagosomes was examined by immunofluorescent technique. ResultsThe treatment of PTFC attenuated intestinal mucosal mechanical barrier function disturbance in diclofenac-induced NSAIDs rats. IEC-6 cells co-cultured with NSAIDs rats-derived exosomes possessed the lowest levels of protective autophagy, and severe intestinal barrier injuries. Cells co-cultured with the exosomes extracted from rats administrated PTFC exhibited an improvement of autophagy and intestinal mucosal mechanical barrier function. The prevention effect was proportional to the concentration of PTFC administered. ConclusionPTFC ameliorated NSAIDs-induced intestinal mucosal injury by down-regulating exosomal lncRNA H19 and promoting autophagy.

Control preoperative anxiety with self-relaxation

Anxiety experienced by preoperative patients is a normal response, but when the anxiety response causes disturbances in physiological and psychological function, this becomes an abnormal response. The impact of anxiety before surgery can have an impact on the operation so that it must be postponed. Action is needed to overcome the anxiety experienced by the patient. One that can by givingSelf relaxound therapy, that is by providing a combination of relaxation interventionsmaybeandnature sound developed by researchers which is done by perception and self-suggestion while listening to natural sounds and deep breathing exercises. The aim of this research is to determine the effect of relaxationself relaxound on patient anxiety before laparotomy surgery. This type of research uses quantitative research, by designquasi experiment using a non planequivalent without control group. This research was carried out in the surgical inpatient room on 32 respondents. Anxiety measurement uses a questionnaireZung Self Rating Scale. Data analysis usingPaired Sample T test with a significance limit of 0.05. The results of the analysis obtained a p value = 0.000 (α 0.05), which shows that there is a significant effect between therapyself relaxound with patient anxiety. Psychological problems are closely related to surgery, for this the researchers suggestSelf relaxound therapy can be considered as a nursing procedure for every preoperative patient.

Pediatric Dermatitis Seborrhoica - A Clinical and Therapeutic Review

Abstract Pediatric dermatitis seborrhoica (DS) is a common inflammatory disorder of infancy and adolescence distinct from atopic dermatitis. We performed a narrative review on clinical and therapeutic aspects of the disease. The prevalence varies geographically and can reach up to 10%. There is a slight male predominance. Although etiopathology is not well known, both endogenous and exogenous factors contribute. Skin microbiome and its interaction with sebaceous gland function is crucial. The inflammatory pathways include innate immune function and skin barrier disturbances. Malassezia spp. and certain bacteria are increased in lesional skin. DS develops in different clinical subtypes, from localized cephalic to disseminated disease with a risk of erythroderma and eczema herpeticatum. Treatment consists of skin care and topical and rarely systemic medical therapy. Cornerstones of treatment are antifungals and mild corticosteroids. Targeted treatment is on the horizon. Pediatric DS is a common disorder important in the differential diagnosis of skin problems in infants and and children. Due to better understanding of its pathogenesis, new treatment options are developed.

Relationship between oral function and respiratory disturbance index in patients with obstructive sleep apnea syndrome

Relationship between oral function and respiratory disturbance index in patients with obstructive sleep apnea syndrome

Crocin, the compound of the dried stigma of Crocus sativus L (saffron), restores doxorubicin-induced disturbances in kidney functioning, oxidative stress, inflammation, renal tissue morphology and TGF-β signalling pathways

Doxorubicin (Dox), an anthracycline antibiotic, is a chemotherapeutic drug for several cancer treatments. However, its clinical usage has been restricted because of severe side effects, including nephrotoxicity. This study aimed to demonstrate the possible nephroprotective effects of crocin (Cr) against Dox-induced oxidative stress, renal inflammation, renal morphology and transforming growth factor-β (TGF-β) signalling pathways in Dox-exposed rats. Hence, the rats were injected for 15 d consecutively with saline, six different injections of Dox until the cumulative dose reached 12 mg/kg., daily Cr (40 mg/kg), and Dox + Cr combination. Cr increased the activities of superoxide dismutase (SOD) and catalase (CAT), GSH content and suppressed inflammation and oxidative stress in Dox-exposed rats. Our results were confirmed by immunohistochemical findings that Cr treatment ameliorates the expressions of IL1β and TGF-β in Dox-induced nephrotoxicity. Conclusionally, Cr exhibits adequate nephroprotective effects against Dox-induced nephrotoxicity on rat kidney architecture and tissue function by stabilising cellular redox homeostasis, reducing renal fibrosis and suppressing inflammation.

Mitochondrial Fission in Nickel Nanoparticle-Induced Reproductive Toxicity: An In Vitro GC-1 Cell Study.

Reproductive disorders and declining fertility rates are significant public health concerns affecting birth rates and future populations. Male infertility, often due to spermatogenesis defects, may be linked to environmental pollutants like nickel nanoparticles (Ni NPs). Ni NPs are extensively utilized across different industries. Nevertheless, their potential adverse effects cannot be overlooked. Previous studies have linked the reproductive toxicity induced by Ni NPs with disturbances in mitochondrial function. Mitochondrial division/fusion dynamics are crucial to their proper function, yet little is known about how Ni NPs perturb these dynamics and whether such perturbation contributes to the impairment of the male reproductive system. Herein, we demonstrated that the exposure of Ni NPs to the mouse-derived spermatogonia cell line (GC-1 cells) triggered DRP1-mediated mitochondrial division and the enhanced impairment of mitochondria, consequently promoting mitochondria-dependent cell apoptosis. Notably, both the mitochondrial division inhibitor (Mdivi-1) and lentiviral-transfected cells with low expression of Dnm1l-DK in these cells could mitigate the toxic effects induced by Ni NPs, pointing to the potential role of mitochondrial dynamics in Ni NP-induced reproductive toxicity. Collectively, our work contributes to the understanding of the mechanisms by which Ni NPs can impact male reproductive function and identifies mitochondrial division as a potential target for intervention.

A pilot trial of integrating the Patient-Reported Outcome Measurement Information System (PROMIS®) into rheumatology care.

Utilising Patient-Reported Outcomes Measurement Information System (PROMIS®) questionnaires can enhance clinical care by measuring longitudinal changes in symptom severity as reported by the patient. The aim of this pilot study was to assess the feasibility and impact of incorporating PROMIS® questionnaires at the point-of-care in rheumatology practice. Patients with rheumatic diseases and decrements in ≥1 PROMIS® domain (pain intensity, physical function, or sleep disturbance) were stratified by their concerning domain, then randomised to either receive an interpretation of their PROMIS® scores prior to their rheumatology appointment (Arm 1) or to usual care (Arm 2) (ClinicalTrials.gov ID: NCT05026853). The primary outcome was the documentation of PROMIS® scores in the electronic medical record (EMR). Secondary outcomes include recommendations made by physicians based on PROMIS® scores, patient-provider communication, and change in the most concerning PROMIS® domain score from baseline to 12 weeks. 110 patients were enrolled. 55 were randomised to receive report cards (Arm 1), of which 46 received the report card, and 55 received usual care (Arm 2). Documentation of PROMIS® scores in the EMR was 50% higher in Arm 1 (12.7% in Arm 2, p<0.0001). More recommendations were made based on PROMIS® scores for Arm 1 patients. There was no significant difference in post-visit PROMIS® score improvement between Arm 1 and Arm 2. Providing PROMIS® report cards to patients and healthcare providers increased score documentation in the EMR. Increased recommendations made based on PROMIS® scores in Arm 1 suggest that having a score interpretation might help direct medical decision-making.

Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study.

To examine hemodynamic and functional connectivity alterations and their association with neurocognitive and mental health indices in patients with chronic mild traumatic brain injury (mTBI). Resting-state functional MRI (rs-fMRI) and neuropsychological assessment of 37 patients with chronic mTBI were performed. Intrinsic connectivity contrast (ICC) and time-shift analysis (TSA) of the rs-fMRI data allowed the assessment of regional hemodynamic and functional connectivity disturbances and their coupling (or uncoupling). Thirty-nine healthy age- and gender-matched participants were also examined. Patients with chronic mTBI displayed hypoconnectivity in bilateral hippocampi and parahippocampal gyri and increased connectivity in parietal areas (right angular gyrus and left superior parietal lobule (SPL)). Slower perfusion (hemodynamic lag) in the left anterior hippocampus was associated with higher self-reported symptoms of depression (r = - 0.53, p = .0006) and anxiety (r = - 0.484, p = .002), while faster perfusion (hemodynamic lead) in the left SPL was associated with lower semantic fluency (r = - 0.474, p = .002). Finally, functional coupling (high connectivity and hemodynamic lead) in the right anterior cingulate cortex (ACC)) was associated with lower performance on attention and visuomotor coordination (r = - 0.50, p = .001), while dysfunctional coupling (low connectivity and hemodynamic lag) in the left ventral posterior cingulate cortex (PCC) and right SPL was associated with lower scores on immediate passage memory (r = - 0.52, p = .001; r = - 0.53, p = .0006, respectively). Uncoupling in the right extrastriate visual cortex and posterior middle temporal gyrus was negatively associated with cognitive flexibility (r = - 0.50, p = .001). Hemodynamic and functional connectivity differences, indicating neurovascular (un)coupling, may be linked to mental health and neurocognitive indices in patients with chronic mTBI.