Disease-specific Effects Research Articles

Overview of the Efficacy of Using Probiotics for Neurosurgical and Potential Neurosurgical Patients.

This review delves into the emerging field of the gut microbiota-brain axis, emphasizing its bidirectional communication and implications for neurological health, particularly in trauma and neurosurgery. While disruptions in this axis can lead to dysbiosis and hinder neurological recovery, recent studies have highlighted the therapeutic potential of interventions like probiotics in targeting this axis. This review aims to focus on the efficacy of probiotic supplementation to support the gut microbiota-brain axis in trauma, neurosurgery, or pain based on the current clinical trials to assess the complex interplays among probiotics, the gut microbiota, and the central nervous system (CNS). This comprehensive literature review identified 10 relevant publications on probiotic interventions for various neurosurgical conditions across multiple countries. These studies demonstrated diverse outcomes, with significant improvements observed in gastrointestinal mobility, inflammatory responses, and infection rates, particularly in post-traumatic brain injury and spinal surgery. Probiotics also showed promise in mitigating antibiotic-associated diarrhea and modulating inflammatory cytokines. Despite the promising findings, the complex interplays among probiotics, the gut microbiota, and the central nervous system (CNS) call for cautious interpretation. Conflicting outcomes emphasize the need for better-designed trials to understand strain-specific and disease-specific effects accurately. In conclusion, probiotics offer a promising adjuvant therapy for neurosurgical patients, traumatic brain injuries, and post-spinal surgery. However, further well-designed randomized controlled trials are essential to elucidate the intricate relationship between microbiome-modulating interventions and the CNS via the gut microbiota-brain axis.

Abstract SY16-01: What IDH mouse models have taught us about hematological diseases, from leukemia to T cell lymphoma

Abstract SY16-01: What IDH mouse models have taught us about hematological diseases, from leukemia to T cell lymphoma

Baseline Health Status and its Association With Subsequent Cardiovascular Events in Patients With Atrial Fibrillation

BackgroundClinical practice guidelines recommend optimizing the health status of patients with atrial fibrillation (AF) as a primary treatment goal. Whether disease-specific health status is associated with subsequent clinical events is unknown. ObjectivesThe aim of this study was to investigate the association between health status and subsequent clinical events among patients with AF. MethodsUsing a prospective cohort study of patients with new-onset AF referred to 11 hospitals (n = 3,313, 68.4% men, mean age 67.8 ± 11.6 years), data were extracted from 3,296 patients (99.4%) who completed the disease-specific Atrial Fibrillation Effects on Quality-of-Life (AFEQT) questionnaire between 2012 and 2018. Factors associated with baseline AFEQT overall summary (OS) score and associations between major adverse cardiovascular or neurologic events (MACNE; a composite of all-cause death, stroke, or new-onset heart failure hospitalization) over 2 years were investigated. ResultsOverall, 517 participants (15.6%) had poor to fair health status (AFEQT OS <60), and 1,035 (31.2%) had fair to good health status (AFEQT OS 60 to <80) at baseline. Female sex, younger age, family history of AF, higher baseline heart rate, paroxysmal AF, initial visit to the emergency department, and history of heart failure were associated with lower AFEQT OS scores. Of those, 226 participants (6.8%) experienced MACNE; restricted cubic spline analysis with adjustment for factors associated with baseline AFEQT score showed a nonlinear increase in the risk for MACNE with AFEQT OS score <80. The strongest associations were observed for baseline AFEQT daily activity scores (for AFEQT daily activity score of <80 vs ≥80, HR: 1.65; 95% CI: 1.21-2.25). ConclusionsDiminished health status in patients with AF is common and is independently associated with subsequent adverse cardiovascular events.

Circular RNA as Therapeutic Targets in Atherosclerosis: Are We Running in Circles?

Much attention has been paid lately to harnessing the diagnostic and therapeutic potential of non-coding circular ribonucleic acids (circRNAs) and micro-RNAs (miRNAs) for the prevention and treatment of cardiovascular diseases. The genetic environment that contributes to atherosclerosis pathophysiology is immensely complex. Any potential therapeutic application of circRNAs must be assessed for risks, benefits, and off-target effects in both the short and long term. A search of the online PubMed database for publications related to circRNA and atherosclerosis from 2016 to 2022 was conducted. These studies were reviewed for their design, including methods for developing atherosclerosis and the effects of the corresponding atherosclerotic environment on circRNA expression. Investigated mechanisms were recorded, including associated miRNA, genes, and ultimate effects on cell mechanics, and inflammatory markers. The most investigated circRNAs were then further analyzed for redundant, disparate, and/or contradictory findings. Many disparate, opposing, and contradictory effects were observed across experiments. These include levels of the expression of a particular circRNA in atherosclerotic environments, attempted ascertainment of the in toto effects of circRNA or miRNA silencing on atherosclerosis progression, and off-target, cell-specific, and disease-specific effects. The high potential for detrimental and unpredictable off-target effects downstream of circRNA manipulation will likely render the practice of therapeutic targeting of circRNA or miRNA molecules not only complicated but perilous.

A Comparison Between Early Presentation of Dementia with Lewy Bodies, Alzheimer's Disease, and Parkinson's Disease: Evidence from Routine Primary Care and UK Biobank Data.

The purpose of this study was to simultaneously contrast prediagnostic clinical characteristics of individuals with a final diagnosis of dementia with Lewy Bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD) compared with controls without neurodegenerative disorders. Using the longitudinal THIN database in the United Kingdom, we tested the association of each neurodegenerative disorder with a selected list of symptoms and broad families of treatments, and compared the associations between disorders to detect disease-specific effects. We replicated the main findings in the UK Biobank. We used data of 28,222 patients with PD, 20,214 with AD, 4,682 with DLB, and 20,214 healthy controls. All neurodegenerative disorders were significantly associated with the presence of multiple clinical characteristics before their diagnosis, including sleep disorders, falls, psychiatric symptoms, and autonomic dysfunctions. When comparing patients with DLB with patients with PD and patients with AD patients, falls, psychiatric symptoms, and autonomic dysfunction were all more strongly associated with DLB in the 5 years preceding the first neurodegenerative diagnosis. The use of statins was lower in patients who developed PD and higher in patients who developed DLB compared to patients with AD. In patients with PD, the use of statins was associated with the development of dementia in the 5 years following PD diagnosis. Prediagnostic presentations of falls, psychiatric symptoms, and autonomic dysfunctions were more strongly associated with DLB than PD and AD. This study also suggests that although several associations with medications are similar in neurodegenerative disorders, statin usage is negatively associated with PD but positively with DLB and AD as well as development of dementia in PD. ANN NEUROL 2023;94:259-270.

MEDEA randomised intervention study protocol in Cyprus, Greece and Israel for mitigation of desert dust health effects in adults with atrial fibrillation

IntroductionMediterranean countries experience frequent desert dust storm (DDS) events originating from neighbouring Sahara and Arabian deserts, which are associated with significant increase in mortality and hospital admissions, mostly from cardiovascular...

Cross-cultural adaptation and validation of Diabetes Quality of Life Brief Clinical Inventory in Turkish patients with type 2 diabetes mellitus

Purpose To translate and culturally adapt the Diabetes Quality of Life Brief Clinical Inventory (DQoL-BCI) into Turkish and assess the psychometric properties of the translated version. Methods A forward–backward translation process was conducted in conformity with international guidelines. A total of 150 patients with type 2 diabetes mellitus (T2DM) completed the Turkish version of DQoL-BCI (DQoL-BCI-Tr). The factor structure, test–retest reliability, and construct validity were evaluated. Results In the DQoL-BCI-Tr, the three-factor structure was found optimal and explained 68.7% of the variance. The DQoL-BCI-Tr showed excellent internal consistency (Cronbach’s alpha = 0.90) and test–retest reliability (ICC = 0.98). Cronbach’s alpha values ranged from 0.85 to 0.91 for subscales (satisfaction, worry, impact). A negative correlation was found between the total scores of the DQoL-BCI-Tr and the EuroQoL-5 dimensions (EQ-5D) indexes (r= −0.22, p < 0.01). The DQoL-BCI-Tr total score and satisfaction and worry subscale scores differentiated between groups defined by glycated hemoglobin (HbA1c>9%) and the use of insulin. Conclusions The study results showed that the DQoL-BCI-Tr can be served as a reliable and valid instrument to obtain information from Turkish patients with T2DM diagnosis, including satisfaction with treatment, the impact of the disease, and worry about the social/vocational issues. Implications for rehabilitation The Turkish version of the Diabetes Quality of Life Brief Clinical Inventory (DQoL-BCI) is a valid and reliable instrument. The DQoL-BCI Questionnaire in Turkish (DQoL-BCI-Tr) is an easy and quick way to determine satisfaction with treatment, impact of disease, and worry about the social/vocational issues. The DQoL-BCI-Tr is a reliable instrument for assessing disease-specific effects, emotional loads, and satisfaction of Turkish patients with type 2 diabetes in clinical and research settings.

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Most of the medicinal products that are currently approved and used in clinical practice for neurodegenerative diseases, in particular Alzheimer’s disease, have a compensatory mechanism of action that enhances neurotransmitter signalling. It is an urgent need to develop new medicinal products combining cognitive-enhancing, neuroprotective, and disease-specific effects resulting from a multi-target mechanism of action including, in particular, prevention of glutamate-induced neuronal calcium uptake and stabilisation of microtubules.The aim of this study was to search for potentially neuroprotective and tauopathy-alleviating medicines amongst new thiouronium salt derivatives based on vicinal diamines.Materials and methods. The study investigated the ability of thiouronium salts to block glutamate-induced 45Ca2+ uptake by synaptosomes prepared from the brain of Wistar rats. The authors evaluated effects of these new compounds on polymerisation of a preparation of C57bl mouse brain tubulin and microtubule-associated proteins. The evaluation was carried out in the presence of guanosine triphosphate (GTP) and based on specific absorbance changes at 355 nm due to formation of microtubules. The authors analysed the structure of these microtubules, using negative staining followed by transmission electron microscopy. The IC50 determination and the statistical analysis were performed using standard software (Excel and PRISM 6.02).Results. The authors developed a screening algorithm for a number of new thiouronium salt derivatives based on vicinal diamines and studied biological activity of these derivatives by the effects on glutamate-induced calcium uptake by synaptosomes and on microtubule assembly processes. The authors identified compounds suppressing glutamate-induced calcium uptake by synaptosomes, i.e. compounds with neuroprotective potential. In addition, a number of new compounds were able to stimulate GTP-dependent microtubule assembly processes. The authors observed formation of microtubules with a normal structure in the presence of isopropyl-N’-[2-(benzoylamino)-1,2-diphenylethyl]-N-ethylimidothiocarbamate hydrobromide and considered the compound a promising scaffold for further optimisation.Conclusions. Chemical modification of thiouronium salts is a promising direction for developing effective neuroprotectors and microtubule stabilisers.

Pharmacokinetics of Antimicrobials in Children with Emphasis on Challenges Faced by Low and Middle Income Countries, a Clinical Review.

Effective antimicrobial exposure is essential to treat infections and prevent antimicrobial resistance, both being major public health problems in low and middle income countries (LMIC). Delivery of drug concentrations to the target site is governed by dose and pharmacokinetic processes (absorption, distribution, metabolism and excretion). However, specific data on the pharmacokinetics of antimicrobials in children living in LMIC settings are scarce. Additionally, there are significant logistical constraints to therapeutic drug monitoring that further emphasize the importance of understanding pharmacokinetics and dosing in LMIC. Both malnutrition and diarrheal disease reduce the extent of enteral absorption. Multiple antiretrovirals and antimycobacterial agents, commonly used by children in low resource settings, have potential interactions with other antimicrobials. Hypoalbuminemia, which may be the result of malnutrition, nephrotic syndrome or liver failure, increases the unbound concentrations of protein bound drugs that may therefore be eliminated faster. Kidney function develops rapidly during the first years of life and different inflammatory processes commonly augment renal clearance in febrile children, potentially resulting in subtherapeutic drug concentrations if doses are not adapted. Using a narrative review approach, we outline the effects of growth, maturation and comorbidities on maturational and disease specific effects on pharmacokinetics in children in LMIC.

Exercise-Boosted Mitochondrial Remodeling in Parkinson's Disease.

Parkinson's disease (PD) is a movement disorder characterized by the progressive degeneration of dopaminergic neurons resulting in dopamine deficiency in the striatum. Given the estimated escalation in the number of people with PD in the coming decades, interventions aimed at minimizing morbidity and improving quality of life are crucial. Mitochondrial dysfunction and oxidative stress are intrinsic factors related to PD pathogenesis. Accumulating evidence suggests that patients with PD might benefit from various forms of exercise in diverse ways, from general health improvements to disease-specific effects and, potentially, disease-modifying effects. However, the signaling and mechanism connecting skeletal muscle-increased activity and brain remodeling are poorly elucidated. In this review, we describe skeletal muscle-brain crosstalk in PD, with a special focus on mitochondrial effects, proposing mitochondrial dysfunction as a linker in the muscle-brain axis in this neurodegenerative disease and as a promising therapeutic target. Moreover, we outline how exercise secretome can improve mitochondrial health and impact the nervous system to slow down PD progression. Understanding the regulation of the mitochondrial function by exercise in PD may be beneficial in defining interventions to delay the onset of this neurodegenerative disease.

Matched Unrelated Donor Hematopoietic Cell Transplant with Increased Donor Inhibitory KIR Improves Survival in a Pediatric Acute Leukemia: A CIBMTR Cohort Analysis

Natural killer (NK) cells potentially mediate innate immunity early after hematopoietic cell transplantation (HCT). NK cells posses an array of activating and inhibitory receptors on their surface, including killer immunoglobulin-like receptor (KIR) and which interact with KIR-ligands (KIRL) on target cells. The impact of NK cell mediated alloreactivity in pediatric HCT is not well characterized. In this study, we explored a mathematical approach to quantify KIR-KIRL combinations to assess clinical outcomes in a cohort of pediatric patients who underwent HLA-matched unrelated donor (MUD) HCT for acute leukemia including AML and ALL. This retrospective study was performed on deidentified donor and recipient demographic and clinical outcomes data provided by the Center for International Blood and Marrow Transplant Research (CIBMTR). KIR-KIRL interaction values were assigned as previously (Krieger et. al 2021, Bone Marrow Transplantation). Briefly donor inhibitory (iKIR) and activating (aKIR) KIR- recipient KIRL interactions, accounting for missing KIR-L (mKIR), were summed up, using a system of matrices. The study cohort was comprised of 686 pediatric donor-recipient pairs (DRP) who underwent MUD HCT for AML (N=355) and ALL (N=333) and had neutrophil engraftment (Table 1). This cohort of pediatric patients was aged 0-18 years (average 11). All patients received T cell replete grafts; 26% received in vivo T cell depletion, with either anti-thymocyte globulin (ATG) or alemtuzumab. The majority, 77% received a bone marrow graft and 90% received myeloablative conditioning. The effect of all 3 KIR-KIRL interaction scores (absolute values of iKIR, mKIR and aKIR) on clinical outcomes were evaluated. Higher donor iKIR score was associated with improvement in overall survival (OS) SHR 0.73 (multivariate P=0.003) and relapse-free survival (RFS), SHR 0.8 (P=0.019); grade 3-4 acute GVHD was lower in patients transplanted with higher iKIR or mKIR scores (iKIR; SHR 0.58 (P=0.013); mKIR SHR 0.6 (P=0.041)). Higher aKIR scores, were not significantly associated with any clinical outcomes examined. As in previous analysis, the iKIR and mKIR scores were added to give an IM-KIR score, which was dichotomized for analysis into those DRP with an IM KIR score of 5 (IM = 5), and those with an IM-KIR score of 2, 3 or 4 (IM < 5). Of note, KIR haplotype A patients always have an IM KIR score of 4, and are thus categorized among IM<5 donors. In this cohort of pediatric patients transplanted for both AML and ALL, those transplanted with IM=5 donors demonstrated improved OS, SHR 0.75 (P = 0.027), RFS, SHR 0.79 (P=0.05) and grade 3-4 aGVHD incidence, SHR 0.37 (P= 0.003) in multivariate analysis. We next examined outcomes in patients with ALL and AML to understand disease specific effects. Patients transplanted for AML with IM=5 donors had an improvement in OS, SHR 0.62 (P=0.01), as well as RFS, SHR 0.70 (p=0.033) (Fig. 1). There was a trend towards relapse risk reduction in this cohort SHR 0.67 (univariate P=0.048). Patients transplanted for ALL with IM=5 donors demonstrated a marked decrease in grade 3-4 acute GVHD incidence SHR, 0.31 (P=0.017). This large pediatric study confirms that unrelated DRPs with donor haplotype B genotypes and a higher inhibitory KIR content (regardless of KIR ligand status), confer significant improvement in overall survival and severe aGVHD after MUD HCT. Those patients transplanted for AML experienced an improvement in OS and RFS despite the lower event rate observed in pediatric-age patients, the majority of whom receive myeloablative preparatory regimens without the use of in vivo T cell depletion. This challenges the notion that KIR are irrelevant to pediatric donor selection. Future clinical trials evaluating donor selection for URD HCT should include this measure to evaluate its value prospectively. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

LC-MS/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are known to be able to modulate immune responses, possess tissue-protective properties, and exhibit healing capacities with therapeutic potential for various diseases. The ability of MSCs to secrete various cytokines and growth factors provides new insights into autoimmune-diseases such as rheumatoid arthritis (RA). RA is a systemic autoimmune disease that affects the lining of synovial joints, causing stiffness, pain, inflammation, and joint erosion. In recent years, MSCs-based therapies have been widely proposed as promising therapies in the treatment of RA. However, the mechanism involved in disease-specific therapeutic effects of MSCs on RA remains unclear. To clarify the mechanism involved in effects of MSCs on RA, proteomic profiling was performed using an RA mouse model before and after treatment with MSCs. In this study, treatment efficacy of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) was confirmed using a type II collagen-induced arthritis (CIA) mouse model. Results of measuring incidence rates of arthritis and clinical arthritis index (CAI) revealed that mice administrated with hUCB-MSCs had a significant reduction in arthritis severity. Proteins that might affect disease progression and therapeutic efficacy of hUCB-MSC were identified through LC-MS/MS analysis using serum samples. In addition, L-1000 analysis was performed for hUCB-MSC culture medium. To analysis data obtained from LC-MS/MS and L-1000, tools such as ExDEGA, MEV, and DAVID GO were used. Results showed that various factors secreted from hUCB-MSCs might play roles in therapeutic effects of MSCs on RA, with platelet activation possibly playing a pivotal role. Results of this study also suggest that SERPINE1 and THBS1 among substances secreted by hUCB-MSC might be key factors that can inhibit platelet activation. This paper is expected to improve our understanding of mechanisms involved in treatment effects of stem cells on rheumatoid arthritis.

Characterization of Adrenal miRNA-Based Dysregulations in Cushing's Syndrome.

MiRNAs are important epigenetic players with tissue- and disease-specific effects. In this study, our aim was to investigate the putative differential expression of miRNAs in adrenal tissues from different forms of Cushing’s syndrome (CS). For this, miRNA-based next-generation sequencing was performed in adrenal tissues taken from patients with ACTH-independent cortisol-producing adrenocortical adenomas (CPA), from patients with ACTH-dependent pituitary Cushing’s disease (CD) after bilateral adrenalectomy, and from control subjects. A confirmatory QPCR was also performed in adrenals from patients with other CS subtypes, such as primary bilateral macronodular hyperplasia and ectopic CS. Sequencing revealed significant differences in the miRNA profiles of CD and CPA. QPCR revealed the upregulated expression of miR-1247-5p in CPA and PBMAH (log2 fold change > 2.5, p < 0.05). MiR-379-5p was found to be upregulated in PBMAH and CD (log2 fold change > 1.8, p < 0.05). Analyses of miR-1247-5p and miR-379-5p expression in the adrenals of mice which had been exposed to short-term ACTH stimulation showed no influence on the adrenal miRNA expression profiles. For miRNA-specific target prediction, RNA-seq data from the adrenals of CPA, PBMAH, and control samples were analyzed with different bioinformatic platforms. The analyses revealed that both miR-1247-5p and miR-379-5p target specific genes in the WNT signaling pathway. In conclusion, this study identified distinct adrenal miRNAs as being associated with CS subtypes.

Attention-deficit/hyperactivity and obsessive-compulsive symptoms in adult patients with primary restless legs syndrome

Comorbidity between Restless Legs Syndrome and Attention-Deficit/Hyperactivity Disorder remains a matter of debate. This putative association, possibly reflecting a shared brain iron homeostasis and dopaminergic dysfunction, supports the hypothesis of a neurodevelopmental component in Restless Legs Syndrome pathogenesis. The aim of this study was to investigate Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms prevalence in adult patients with primary Restless Legs Syndrome compared to another ill group of patients with obstructive sleep apnea syndrome to control for the disease specific effects on psychiatric symptoms and a healthy individuals control group. Clinical data were obtained through standardized and validated self-administrated questionnaires evaluating Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms frequencies in 139 outpatients with idiopathic Restless Legs Syndrome, 111 patients with treated obstructive sleep apnea syndrome and 136 healthy subjects. Our findings demonstrate a higher prevalence of Attention-Deficit/Hyperactivity Disorder symptoms among both male and female patients with Restless Legs Syndrome, compared to obstructive sleep apnea syndrome patients and healthy subjects (33.3 and 43.5%, respectively, p < 0.001). Only women presented a strong relationship between Attention-Deficit/Hyperactivity Disorder and Restless Legs Syndrome severity (p < 0.001). Male and female in the three groups showed similar Obsessive-Compulsive Disorder symptom prevalence. These findings indicate that Attention-Deficit/Hyperactivity Disorder symptoms among adult patients with Restless Legs Syndrome populations are a robust phenomenon. These data provide arguments in favor of an enlargement of the clinical neuropsychological presentation of Restless Legs Syndrome and question the role of decreased brain iron of these psychiatric symptoms.

IFNG is constitutively expressed by esophagus-resident CD8+ T cells and is poised to mediate a disease-specific effect via its action on IFNGR+ eosinophils during active EoE

Recent whole tissue RNA sequencing (RNAseq) and other bulk assays indicate that type I and II interferon responses are upregulated in active eosinophilic esophagitis (EoE), a Th2-biased inflammatory disease, but the cellular signaling network is unresolved.

"Is It Removed During Dialysis?"-Cognitive Dysfunction in Advanced Kidney Failure-A Review Article.

Cognitive impairment is independently associated with kidney disease and increases in prevalence with declining kidney function. At the stage where kidney replacement therapy is required, with dialysis or transplantation, cognitive impairment is up to three times more common, and can present at a younger age. This is not a new phenomenon. The cognitive interactions of kidney disease are long recognized from historical accounts of uremic encephalopathy and so-called “dialysis dementia” to the more recent recognition of cognitive impairment in those undergoing kidney replacement therapy (KRT). The understanding of cognitive impairment as an extra-renal complication of kidney failure and effect of its treatments is a rapidly developing area of renal medicine. Multiple proposed mechanisms contribute to this burden. Advanced vascular aging, significant multi-morbidity, mood disorders, and sleep dysregulation are common in addition to the disease-specific effects of uremic toxins, chronic inflammation, and the effect of dialysis itself. The impact of cognitive impairment on people living with kidney disease is vast ranging from increased hospitalization and mortality to decreased quality of life and altered decision making. Assessment of cognition in patients attending for renal care could have benefits. However, in the context of a busy clinical service, a pragmatic approach to assessing cognitive function is necessary and requires consideration of the purpose of testing and resources available. Limited evidence exists to support treatments to mitigate the degree of cognitive impairment observed, but promising interventions include physical or cognitive exercise, alteration to the dialysis treatment and kidney transplantation. In this review we present the history of cognitive impairment in those with kidney failure, and the current understanding of the mechanisms, effects, and implications of impaired cognition. We provide a practical approach to clinical assessment and discuss evidence-supported treatments and future directions in this ever-expanding area which is pivotal to our patients' quality and quantity of life.

Sex‐differences in neural responses to experimental pain in Alzheimer's disease

AbstractBackgroundPeople with Alzheimer’s disease (AD) generally receive less analgesic medications and verbally report pain less frequently than age‐matched healthy controls (Scherder 2005). Studies have also shown that people with AD exhibit differences in neural responses to acute experimental pain relative to controls (Monroe 2017). Several studies demonstrate that women report more pain than men and are at a greater risk for mismanagement of pain irrespective of cognitive status (Fillingim 2009). Thus, this study aimed to investigate sex differences in the neurophysiological response (fMRI) to experimental thermal pain in people with AD when compared to controls. We hypothesized that women with AD would have increased activation in brain regions related to the cognitive and emotional processing of pain.MethodThe sample consisted of 73 adults (age 65‐97), 36 adults with AD and 37 adults in a healthy control comparison group. In this study, 52.05% of the participants were female, matched across age and AD status. Experimental thermal perceptions for mild and moderate pain were collected prior to scanning. Stimuli were applied to the thenar eminence of the right hand. During fMRI, percepts were passively delivered during four runs, trials included 16 seconds of stimulus with 24 seconds of rest. Whole brain analysis for a sex by diagnostic group interaction was explored mild and moderate pain conditions. Standard SPM12 approaches were used for all analyses.ResultWe found significant main effects of both AD and sex in each pain condition indicating significant differences in brain activation for both males and females with AD compared to male and female controls (all p’s &lt; 0.05), however there was no significant sex by AD group interaction in either contrast comparison.ConclusionWhile there are significant effects of both sex and AD on neural responses to pain, there was no significant evidence of a unique effect of sex on neural responses in AD. This work suggests that differences in pain responses by sex is relevant to consider in addition to disease specific effects. Sex differences seen in healthy cohorts may not persist to the same degree the Alzheimer’s disease brain.

Benefits of COVID-19 non-pharmaceutical interventions on the prevention of other notifiable infectious diseases

Benefits of COVID-19 non-pharmaceutical interventions on the prevention of other notifiable infectious diseases

Joint mapping of cardiovascular diseases: comparing the geographic patterns in incident acute myocardial infarction, stroke and atrial fibrillation, a Danish register-based cohort study 2014\u201315

BackgroundDisease mapping aims at identifying geographic patterns in disease. This may provide a better understanding of disease aetiology and risk factors as well as enable targeted prevention and allocation of resources. Joint mapping of multiple diseases may lead to improved insights since e.g. similarities and differences between geographic patterns may reflect shared and disease-specific determinants of disease. The objective of this study was to compare the geographic patterns in incident acute myocardial infarction (AMI), stroke and atrial fibrillation (AF) using the unique, population-based Danish register data.MethodsIncident AMI, stroke and AF was modelled by a multivariate Poisson model including a disease-specific random effect of municipality modelled by a multivariate conditionally autoregressive (MCAR) structure. Analyses were adjusted for age, sex and income.ResultsThe study included 3.5 million adults contributing 6.8 million person-years. In total, 18,349 incident cases of AMI, 28,006 incident cases of stroke, and 39,040 incident cases of AF occurred. Estimated municipality-specific standardized incidence rates ranged from 0.76 to 1.35 for AMI, from 0.79 to 1.38 for stroke, and from 0.85 to 1.24 for AF. In all diseases, geographic variation with clusters of high or low risk of disease after adjustment was seen. The geographic patterns displayed overall similarities between the diseases, with stroke and AF having the strongest resemblances. The most notable difference was observed in Copenhagen (high risk of stroke and AF, low risk of AMI). AF showed the least geographic variation.ConclusionUsing multiple-disease mapping, this study adds to the results of previous studies by enabling joint evaluation and comparison of the geographic patterns in AMI, stroke and AF. The simultaneous mapping of diseases displayed similarities and differences in occurrence that are non-assessable in traditional single-disease mapping studies. In addition to reflecting the fact that AF is a strong risk factor for stroke, the results suggested that AMI, stroke and AF share some, but not all environmental risk factors after accounting for age, sex and income (indicator of lifestyle and health behaviour).

Prognostic impact of nutritional and inflammation-based risk scores in follicular lymphoma in the era of anti-CD20 targeted treatment strategies

BackgroundThe composition of the tumor microenvironment (TME) is conditioned by immunity and the inflammatory response. Nutritional and inflammation-based risk scores have emerged as relevant predictors of survival outcome across a variety of hematological malignancies.MethodsIn this retrospective multicenter trial, we ascertained the prognostic impact of established nutritional and inflammation-based risk scores [Glasgow Prognostic Score (GPS), C-reactive–protein/albumin ratio (CAR), neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), and prognostic index (PI)] in 209 eligible patients with histologically confirmed CD20+ follicular lymphoma (FL) of WHO grade 1 (37.3%), 1–2 (16.3%), 2 (26.8%) or 3A (19.8%) admitted to the participating centers between January 2000 and December 2019. Characteristics significantly associated with overall or progression-free survival (OS, PFS) upon univariate analysis were subsequently included in a Cox proportional hazard model.ResultsIn the study cohort, the median age was 63 (range 22–90 years). The median follow-up period covered 99 months. The GPS and the CAR were identified to predict survival in FL patients. The GPS was the only independent predictor of OS (p < 0.0001; HR 2.773; 95% CI 1.630–4.719) and PFS (p = 0.001; HR 1.995; 95% CI 1.352–2.944) upon multivariate analysis. Additionally, there was frequent occurrence of progression of disease within 24 months (POD24) in FL patients with a calculated GPS of 2.ConclusionThe current results indicate that the GPS predicts especially OS in FL patients. Moreover, GPS was found to display disease-specific effects in regard to FL progression. These findings and potential combinations with additional established prognosticators should be further validated within prospective clinical trials.