Age-matched Healthy Controls Research Articles

Renal Allograft Macrophage Infiltration in Antibody-Mediated Renal Allograft Rejection

Abstract Introduction/Objective Macrophages are involved in the pathogenesis and contribute to acute and chronic renal allograft injury. We evaluated CD163+ (M2) macrophage graft tissue infiltration and its correlation with clinical and histological prognostic factors. Urinary soluble CD163, circulating total, and monocyte-derived microparticles (MMPs) in plasma were also estimated and correlated with tissue M2 macrophage infiltration. Methods/Case Report The study included forty-five renal allograft recipients with for-cause graft biopsy, with Antibody-mediated Rejection (ABMR) (n=30) or no evidence of rejection (NER) (n=15), from Jan 2021-Dec 2023, along with fifteen age-matched healthy controls (HC). On immunohistochemistry, CD163 positive cells were counted in glomeruli and tubulointerstitium. Urinary sCD163 was done by ELISA. Flow cytometry quantified plasma MPs (AnnexinV+) and MMPs (CD14+/ AnnexinV+). Results (if a Case Study enter NA) The mean age of renal allograft recipients was 35±9yrs (all males). Mean s.creatinine in ABMR and NER was 3±2.6 and 2±0.5 mg/dl, respectively. ABMR had significantly more glomerular (16.2±13.7/10 glomeruli) and tubulointerstitial (183±108/10hpf) M2 macrophage (CD163+) cell infiltration than NER (4.8±4.7/10 glomeruli; 133.5±108/10hpf). Urinary sCD163 in ABMR was also significantly raised (0.89±0.63ng/ml) than in NER. It was not detectable in HC. Plasma MMPs were elevated in ABMR [25% of total MPs (1.62x104)] as compared to NER [8.2 % of total MPs (1.4x104)] and HC [7.8% of total MPs (1.2x104)]. In ABMR, the glomerular CD163+ cells correlated with urinary sCD163 levels (r=0.350, p=0.050) and circulating MMPs (r=0.526, p=0.002). Conclusion We found that in renal allograft recipients with ABMR, there is significantly higher graft biopsy glomerular CD163+ (M2) macrophage infiltration and elevated urinary sCD163 levels as compared to NER. The plasma circulating MMPs were also elevated in ABMR. Our findings suggest that monocyte activation plays a significant role in the pathogenesis and injury in ABMR. Non-invasive markers of monocyte activation can distinguish ABMR from NER in allograft recipients presenting with allograft dysfunction.

Associations between elevated uric acid and brain imaging abnormalities in pediatric patients with methylmalonic acidemia under 5 years of age

Methylmalonic acidemia (MMA) is the most common inborn organic acidemia, presenting multisystemic complications. Uric acid may have neurotoxic or neuroprotective effects due to its antioxidant or pro-inflammatory properties; however, its role in MMA brain injury remains unclear. We examined the correlation between the serum uric acid levels and brain imaging features of MMA. Data were collected from a cross-sectional study of 216 patients with MMA and 216 healthy matched controls aged 0–5 years in China. Serum uric acid levels were measured, and magnetic resonance imaging and computed tomography findings were retrieved from hospital records. Overall, 74.1% patients had brain abnormalities. Patients in the MMA group with abnormal brain imaging had higher serum uric acid levels than those in the MMA normal brain imaging and control groups. The area under the curve of serum uric acid was 0.74, 0.91, and 0.93 for MMA diagnosis with abnormal brain images, basal ganglia changes, and globus pallidus changes, respectively. Higher serum uric acid levels were independently associated with abnormal brain images. Children aged < 5 years with abnormal brain images in MMA exhibit elevated serum uric acid levels, serving as an effective auxiliary diagnostic indicator and independent risk factor for brain tissue injury.

Red blood cells from patients with ST-elevation myocardial infarction and elevated C-reactive protein levels induce endothelial dysfunction.

Endothelial dysfunction is an early consequence of vascular inflammation and a driver of coronary atherosclerotic disease leading to myocardial infarction. The red blood cells (RBCs) mediate endothelial dysfunction in patients at cardiovascular risk, but their role in patients with acute myocardial infarction is unknown. This study aimed to investigate if RBCs from patients with ST-elevation myocardial infarction (STEMI) induced endothelial dysfunction and the role of systemic inflammation in this effect. RBCs from patients with STEMI and aged-matched healthy controls were co-incubated with rat aortic segments for 18h followed by evaluation of endothelium-dependent (EDR) and -independent relaxation (EIDR). RBCs and aortic segments were also analyzed for arginase and oxidative stress. The patients were divided into groups depending on C-reactive protein (CRP) levels at admission. RBCs from patients with STEMI and CRP levels >2 mg/L induced impairment of EDR, but not EIDR, compared to RBCs from STEMI and CRP <2 mg/L and healthy controls. Aortic expression of arginase 1 was increased following incubation with RBCs from patients with STEMI and CRP >2, and arginase inhibition prevented the RBC-induced endothelial dysfunction. RBCs from patients with STEMI and CRP >2 had increased reactive oxygen species compared to RBCs from patients with CRP <2 and healthy controls. Vascular inhibition of NADPH oxidases and increased dismutation of superoxide improved EDR. RBCs from patients with STEMI and low-grade inflammation induce endothelial dysfunction through a mechanism involving arginase 1 as well and increased RBC and vascular superoxide by NADPH oxidases.

Unique Gut Microbiome and Metabolic Profiles in Chinese Workers Exposed to Dust: Insights from a Case-Control Study.

This study aimed to identify distinct gut microbiome and serum metabolic features in workers exposed to dust compared to healthy controls. A case-control study was conducted with dust-exposed workers without silicosis and age-matched healthy controls. Gut microbiome composition was analyzed using 16S rRNA sequencing, and serum and fecal metabolomic profiles were assessed by LC-MS. Dust-exposed workers showed higher levels of Blautia and Trichoderma and lower levels of Anaplasma, Aspergillus, Plasmodiophoromycetes, and Escherichia coli-Shigella. Metabolites such as indole-3-acetate and gentamicin C1a were downregulated, while adenine, 2-phenylacetamide, and 4-pyridoxic acid were upregulated. Blautia spp. were linked to altered metabolites in dust-exposed workers, suggesting microbiome-metabolite interactions that may affect silicosis progression. However, the small sample size and cross-sectional design limit generalizability, and further longitudinal studies are needed.

Ocular effects of synthetic cannabinoids: a case-control study.

To evaluate the ocular effects of "Bonzai", a synthetic cannabinoid (SC), in seropositive and seronegative users. Sixty eyes of 60 consecutive male patients with a history of "Bonzai" use and 30 eyes of 30 age-matched male healthy controls were enrolled in this case-control study. Patients with past "Bonzai" use were grouped as seropositive (n:30) and seronegative (n:30) according to urine toxicology tests. All groups were compared for blood pressures, intraocular pressure, foveal and parafoveal retinal thicknesses, subfoveal and parafoveal choroidal thicknesses, measurements of the peripapillary retinal nerve fibre layer (RNFL), and macular ganglion cell complex (GCC), subfoveal total choroidal, luminal and stromal areas, and choroidal vascularity index (CVI). No differences were noted in blood pressures between the groups (p > 0.05). The mean intraocular pressure was significantly lower in the seropositive group than in the other groups (p < 0.001). Foveal and retinal thicknesses, RNFL, and GCC measurements did not differ between the groups (p > 0.05). Subfoveal and parafoveal choroidal thicknesses and areas were lower in the seropositive group than in the other groups (p < 0.001, for all). CVI increased in both groups with "Bonzai" use compared to the control group (p < 0.001, for all). This study indicates that intraocular pressure may decrease, and choroidal changes may be observed in SC users. Further clinical studies with a larger sample size, especially using purified SC for therapeutic purposes, are needed to confirm the present findings, and further histopathologic studies are required to clarify the changes in the choroid despite SC seronegativity. NCT06235346.

Risk Factors for Late-Onset Psychosis: A Case-Control Study.

The onset of schizophrenia occurs after the age of 40 in up to 20% of cases. We aim to depict risk factors for first-episode psychosis after the age of 40 by comparing late-onset psychosis (LOP) patients to healthy age-matched controls. In this case-control study using electronic health records, 142 individuals aged 40-65 years with an encounter for a first episode of psychosis between 2013 and 2021 were included. Four controls (N = 568) were matched to each case on age, sex, race, and year of encounter. Potential risk factors for the primary analysis were captured via structured data and text-mining of medical notes. Conditional logistic regression models were used to assess the odds of LOP with potential risk factors. After adjusting for all variables in the main analysis, odds for LOP were increased by immigration (OR 3.30, 95% CI, 1.56-6.98), depression (OR 3.58, 95% CI, 2.01-6.38), anxiety (OR 2.12, 95% CI, 1.20-3.75), cannabis use (OR 3.00, 95% CI, 1.36-6.61), alcohol use disorder (OR 5.46, 95% CI, 2.41-12.36), polysubstance use (OR 4.22, 95% CI, 1.30-13.7), severe trauma (OR 2.29, 95% CI, 1.08-4.48), and caregiver burden (OR 15.26, 95% CI, 3.85-60.48). Life stressors along with the effects of substance use and other psychiatric conditions may confer some risk to the development of LOP. Replication is required in independent prospective studies. Further research is necessary to truly parse out which of these factors belong on the causal pathway.

Contrastive Functional Connectivity Defines Neurophysiology-informed Symptom Dimensions in Major Depression.

Major depressive disorder (MDD) is a prevalent psychiatric disorder characterized by substantial clinical and neurobiological heterogeneity. Conventional studies that solely focus on clinical symptoms or neuroimaging metrics often fail to capture the intricate relationship between these modalities, limiting their ability to disentangle the complexity in MDD. Moreover, patient neuroimaging data typically contains normal sources of variance shared with healthy controls, which can obscure disorder-specific variance and complicate the delineation of disease heterogeneity. We employed contrastive principal component analysis to extract disorder-specific variations in fMRI-based resting-state functional connectivity (RSFC) by contrasting MDD patients (N=233) with age-matched healthy controls (N=285). We then applied sparse canonical correlation analysis to identify latent dimensions in the disorder variations by linking the extracted contrastive connectivity features to clinical symptoms in MDD patients. Two significant and generalizable dimensions linking distinct brain circuits and clinical profiles were discovered. The first dimension, associated with an apparent "internalizing-externalizing" symptom dimension, was characterized by self-connections within the visual network and also associated with choice reaction times of cognitive tasks. The second dimension, associated with personality facets such as extraversion and conscientiousness typically inversely associated with depression symptoms, is primarily driven by self-connections within the dorsal attention network. This "depression-protective personality" dimension is also associated with multiple cognitive task performances related to psychomotor slowing and cognitive control. Our contrastive RSFC-based dimensional approach offers a new avenue to dissect clinical heterogeneity underlying MDD. By identifying two stable, neurophysiology-informed symptom dimensions in MDD patients, our findings may enhance disease mechanism insights and facilitate precision phenotyping, thus advancing the development of targeted therapeutics for precision mental health.

Preliminary investigation of MMP8 (rs11225395) and MMP9 (rs3787268) polymorphisms association with breast cancer risk in pashtun women of Pakistan.

Single Nucleotide polymorphisms (SNPs) in MMP8 and MMP9 have been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check MMP8 (rs11225395) and MMP9 (rs3787268) polymorphism with breast cancer risk in the selected population. This study, consisting of 300 breast cancer patients and 168 gender and age-matched healthy controls was subjected to confirm MMP8 and MMP9 polymorphisms. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using the T-ARMS-PCR protocol. Based on our study results, significant associations were observed between the MMP8 rs11225395 risk allele (G) and increased breast cancer risk, with the G allele frequency higher in patients (65%) compared to controls (51%) (OR = 1.752, 95% CI = 1.423-3.662, p = 0.002). Genotypes GG (OR = 4.218, p = 0.005) and AG (OR = 7.286, p = 0.0001) of MMP8 rs11225395 were also significantly associated with elevated breast cancer risk. Similarly, MMP9 rs3787268 exhibited a higher frequency of the risk allele (A) in breast cancer cases (81%) compared to controls (41%), correlating strongly with increased risk (OR = 6.320, p = 0.0001). Genotypes AA (OR = 14.500, p = 0.0001) and AG (OR = 2.429, p = 0.077) of MMP9 rs3787268 containing the risk allele showed significant associations with heightened breast cancer risk. Subgroup analyses based on age, disease progression, tumor size, and grade revealed noteworthy associations for both MMP8 rs11225395 and MMP9 rs3787268. MMP8 rs11225395 genotypes displayed significant correlations with age (p = 0.066), disease progression (p = 0.0001), larger tumor size (p = 0.005), and higher tumor grade (p = 0.006). Similarly, MMP9 rs3787268 genotypes were significantly associated with age (p = 0.001), disease progression (p = 0.010), larger tumor size (p = 0.018), and higher tumor grade (p = 0.037). Logistic regression analyses further underscored these genetic variants' potential role as biomarkers in breast cancer, particularly in relation to specific hormone receptor statuses such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) positivity. The results revealed significant associations between the mutant alleles and genotypes of MMP8 (rs11225395) and MMP9 (rs3787268) with increased breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

Metataxonomic and Immunological Analysis of Feces from Children with or without Phelan-McDermid Syndrome.

Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by a developmental delay and autism spectrum disorder (ASD)-like behaviors. Emerging research suggests a link between gut microbiota and neuropsychiatric conditions, including PMS. This study aimed to investigate the fecal microbiota and immune profiles of children with PMS compared to healthy controls. Fecal samples were collected from children diagnosed with PMS and age-matched healthy controls. The bacterial composition was analyzed using 16S rRNA gene sequencing, while short-chain fatty acids (SCFAs) were quantified through gas chromatography. Immunological profiling was conducted using a multiplex cytokine assay. Significant differences were observed in the gut microbiota composition between PMS patients and controls, including a lower abundance of key bacterial genera such as Faecalibacterium and Agathobacter in PMS patients. SCFA levels were also reduced in PMS patients. Immunological analysis revealed higher levels of several pro-inflammatory cytokines in the PMS group, although these differences were not statistically significant. The findings indicate that children with PMS have distinct gut microbiota and SCFA profiles, which may contribute to the gastrointestinal and neurodevelopmental symptoms observed in this syndrome. These results suggest potential avenues for microbiota-targeted therapies in PMS.

Resting-state EEG spectral and fractal features in dementia with Lewy bodies with and without visual hallucinations

ObjectiveComplex visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB), though they may not occur in all patients. Power spectral density (PSD) analysis of resting-state EEG (rs-EEG) shows associations between some frequency bands (e.g., θ), individual alpha frequency (IAF) and VH. However, new tools that improve early differential diagnosis and symptom-based stratification with higher sensitivity and specificity, even within the DLB population, are desirable. We aimed to assess differences in rs-EEG data between DLB patients with VH (DLB-VH+) and without VH (DLB-VH-), comparing innovative non-linear approaches with more traditional linear ones. MethodsWe retrospectively analyzed rs-EEG recordings of DLB-VH+, DLB-VH-, Alzheimer’s disease patients and age-matched healthy controls. EEG was analyzed using the nonlinear Higuchi’s Fractal Dimension (FD) measure, and the results were compared with those of entropy and standard linear methods based on PSD and IAF. ResultsOnly the FD measure could discriminate between DLB-VH+ and DLB-VH-. ConclusionsIn conclusion, rs-EEG differences between DLB-VH+ and DLB-VH- are better characterized by FD analysis than by a more traditional power spectrum approach. SignificanceThis suggests that the presence of complex VH is associated with less complex brain dynamics at rest, as reflected by the FD measure.

Forefoot inflammation in recent-onset ACPA-positive and ACPA-negative RA: clinically similar, but different in underlying inflamed tissues

ObjectivesAlthough joint swelling is traditionally interpreted as synovitis, recent imaging studies showed that there is also inflammation of tenosynovium and intermetatarsal bursae in the forefoot. We aimed to increase our...

Application of computational fluid dynamics to investigate pathophysiological mechanisms in exercise-induced laryngeal obstruction.

The underlying pathophysiological mechanisms of exercise-induced laryngeal obstruction (EILO) remain to be fully established. It is hypothesized that high inspiratory flow rates can exert a force on laryngeal airway walls that contribute to its inward collapse causing obstruction. Computational fluid dynamics (CFD) presents an opportunity to explore the distribution of forces in a patient-specific upper airway geometry. The current study combined exercise physiological data and CFD simulation to explore differences in airflow and force distribution between a patient with EILO and a healthy matched control. Participants underwent incremental exercise testing with continuous recording of respiratory airflow and laryngoscopic video, followed by an MRI scan. The respiratory and MRI data were used to generate a subject-specific CFD model of upper respiratory airflow. In patient with EILO, the posterior supraglottis experiences an inwardly directed net force, whose magnitude increases nonlinearly with larger flow rates, with slight changes in the direction toward the center of the airway. The control demonstrated an outwardly directed force at all regions of the wall, with a magnitude that increases linearly with larger flow rates. A comparison is made between the CFD results and endoscopic visualization of supraglottic collapse, and a very good agreement is found. The current study presents the first hybrid physiological and computational approach to investigate the pathophysiological mechanisms of EILO, with preliminary findings showing great potential, but should be used in larger sample sizes to confirm findings.NEW & NOTEWORTHY The current study is the first to use a hybrid combined computational fluid dynamics (CFD) and exercise physiology approach to investigate pathophysiology in exercise-induced laryngeal obstruction (EILO). The hybrid methodology is a promising approach to explore the pathophysiological mechanisms underlying the condition. Notable differences occur in the distribution of airflow and wall forces between the EILO and control participants, which align with symptoms and visual observations.

Rehabilitation Response in Tremor- and Non-Tremor-Dominant Parkinson Disease: A Task-fMRI Study.

Tremor-dominant (TD) and nontremor-dominant (NTD) Parkinson's disease (PD) showed different responses to rehabilitation. However, the neural mechanism behind this remains unclear. This cohort study explores changes in motor function, brain activation, and functional connectivity following 2 weeks of rehabilitation in TD-PD and NTD-PD patients, respectively. A total of 11 TD-PD patients, 24 NTD-PD patients, and 21 age-matched healthy controls (HCs) were included. At baseline, all participants underwent functional magnetic resonance imaging (fMRI) while performing the foot tapping task. Motor symptoms, gait, balance, and task-based fMRI were then evaluated in patients before and after rehabilitation. Compared to HCs, TD-PD patients showed increased activity in the left inferior frontal gyrus and the right insula, and NTD-PD patients showed increased activations in the left postcentral gyrus and decreased within-cerebellar connectivity at baseline. Rehabilitation improved motor function in PD patients regardless of motor subtype. TD-PD patients showed increased recruitments of the sensorimotor cortex and the bilateral thalamus after rehabilitation, and NTD-PD patients showed increased cerebellar activation and within-cerebellar connectivity that was associated with better motor performance. This study demonstrated that rehabilitation-induced brain functional reorganization varied by motor subtypes in PD, which may have important implications for making individualized rehabilitation programs. ClinicalTrials.gov identifier: ChiCTR1900020771.

Cervical Spine Vibration Modifies Oculomotor Function in Young Adults with Traumatic Brain Injury

ObjectiveThe purpose of this study was to investigate if vibrational interference of spinal proprioception affects oculomotor function, visual attention and processing, and selective attention in individuals with mild traumatic brain injury (mTBI) compared to healthy age-matched controls. MethodsThis study was a parallel design, single-session intervention with 20 young adults with mTBI and 20 age-matched controls. Each completed a battery of computerized eye-tracking assessments (CEAs), including egocentric localization, fixational stability, smooth pursuit, saccades, Stroop, and the vestibulo-ocular reflex (VOR), and then had their cervical spine function (flexion-relaxation ratio) recorded at baseline. Spinal vibration (100 Hz) was applied to the cervical spine and the CEA battery was repeated. CEA outcomes were compared to baseline and between mTBI and control groups. ResultsFollowing cervical vibration, significant pre to post-differences were seen in both the mTBI and control group for egocentric localization, fixation stability, pursuit, saccades, Stroop, and VOR. At baseline, there was a significant difference between the mTBI and control groups across many CEA measures, with the mTBI group performing more poorly in egocentric localization, pursuit, saccades, Stroop, and VOR. The mTBI group also had a poorer flexion-relaxation ratio than the control group. ConclusionCervical spine vibration improved cognitive and oculomotor performance in the mTBI group for VOR, Stroop, and pursuit, but had mixed effects on the control group. These findings suggest that some optometric mTBI symptoms may result from spinal or proprioceptive dysfunction, as altering proprioceptive input appears to positively impact visual outcomes.

Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies

BackgroundPhenotypic heterogeneity and unpredictability of individual disease progression present enormous challenges in ultrarare renal ciliopathies. The tubular-derived glycoprotein Dickkopf-related protein 3 (DKK3) is a promising biomarker for kidney fibrosis and prediction of kidney function decline. Here, we measured urinary (u)DKK3 levels in 195 pediatric renal ciliopathy patients to assess its potential as a discriminative and prediction marker. MethodsUDKK3 concentration was measured in 357 spot urine samples from 247 individuals including 52 healthy age-matched controls. Disease entities comprised nephronophthisis (NPH) (n=37), autosomal recessive polycystic kidney disease (ARPKD) (n=61), Bardet Biedl syndrome (BBS) (n=57) and hepatocyte nuclear factor 1 beta (HNF1B)-nephropathy (n=40). Results were correlated with chronic kidney disease (CKD) stage and annual estimated glomerular filtration rate (eGFR) decline. ResultsMedian uDKK3/creatinine ratios in all disease entities were significantly higher compared with healthy controls (11pg/mg uDKK3/crea, p<0.001): NPH 1.219pg/mg, HNF1B 731pg/mg, BBS 541pg/mg and ARPKD 437pg/mg. A significant correlation of CKD stage with uDKK3 levels was observed for all disease entities (p<0.0001) with no other clinical parameter having a relevant impact. In our cohort, uDKK3 values >4.700 pg/mg were associated with a significantly greater annual eGFR loss independently of diagnosis and eGFR (p=0.0029). While we observed a trend towards lower uDKK3 levels in glomerulopathies compared to renal ciliopathies, there was no discriminative difference between individual ciliopathy entities (p=0.2637). ConclusionIn renal ciliopathies uDKK3 is a marker to assess disease severity and estimate short-term kidney function decline.

Insulin Resistance in Hypercalciuric Calcium Kidney Stone Patients

Rational and ObjectiveDiabetes and uric acid kidney stones are strongly associated. Patients with calcium kidney stones also have higher risk of developing diabetes compared to non-kidney stone patients yet this has not been further investigated. We aimed to characterize insulin resistance in calcium kidney stone patients. Study DesignObservational Setting & PopulationThis study was performed in the University of Chicago Clinical Research Center. Kidney stone patients (N=42) were selected for having idiopathic hypercalciuria and calcium stones with no other medical conditions and controls (N=27) were healthy. ExposuresAll participants presented to the Clinical Research Center in a fasting state and at least 2 timed fasting blood and urine were collected prior to a fixed breakfast. Six additional timed blood and urine collections were performed after breakfast. OutcomesWe compared fasting and fed indices of insulin resistance between the groups. Analytic ApproachWe used t-tests and multivariable linear regression models. A sensitivity analysis removing all patients who had ever been on a thiazide diuretic was also performed. ResultsIn separate multivariable linear models, kidney stone patients had higher fasting serum insulin (24 (3 to 46pmol/L), p=0.03) and higher homeostatic model of insulin resistance (HOMA-IR) (1.0 (0.2 to 1.8), p=0.02). In separate multivariable linear models, kidney stone patients had higher fed serum glucose (10 (2 to 18mg/dL), p=0.01). Results were similar in a sensitivity analysis removing all patients who had ever been on a thiazide diuretic. There were no differences in urine composition based on HOMA-IR levels. LimitationsSingle institution. Small sample size limited subanalyses by different calcium stone types. ConclusionsCalcium kidney stone patients without diabetes or other medical conditions demonstrated signs of insulin resistance compared to healthy matched controls.

Biomarker Profiles in Serum and CSF for Early Diagnosis of Selected Neurodegenerative Diseases

Biomarker research and justification for neurodegenerative illnesses have seen enormous efforts over the last ten years. Bio-fluid-based biomarkers have been believed to provide a better and easier approach to detecting biomarkers for diagnosing nervous system pathologies. Objectives: To evaluate the diagnostic potential of certain biomarkers in serum and cerebrospinal fluid to diagnose Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease at an initial stage. Methods: 280 participants were taken and distributed into four groups, comprising, 70 patients with early-stage Alzheimer’s disease, 70 with early-stage Parkinson’s disease, 70 with early-stage Huntington’s disease, and 70 age-matched healthy controls. Blood and cerebrospinal fluid samples were drawn and medical history was taken from the patients. Serum and cerebrospinal fluid levels of amyloid-beta (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), alpha-synuclein, huntingtin protein, and neuro-filament light chain were evaluated using enzyme-linked immunosorbent assays. Results: Alzheimer’s disease patients showed reduced serum Aβ42 (80.4 ± 15.6 pg/mL) and elevated t-tau (140.5 ± 18.2 pg/mL). Parkinson’s disease patients had raised serum alpha-synuclein (12.5 ± 2.3 ng/mL) and neuro-filament light chain. Huntington’s disease patients showed significant increases in serum huntingtin protein (8.2 ± 2.0 ng/mL). These profiles indicate efficacy in early diagnosis. Conclusions: It was concluded that Aβ42 and tau effectively detect Alzheimer’s disease, while Parkinson’s disease patients can be effectively diagnosed with Serum and cerebrospinal fluid levels of the neuro-filament light chain. Similarly, huntingtin protein and neuro-filament light chain are sensitive enough to detect Huntington’s disease at its early stages.

Exploring Scotopic Microperimetry as an Outcome Measure in Choroideremia.

Choroideremia is an X-linked outer retinal degeneration. Early symptoms include nyctalopia and progressive visual field loss, but visual acuity is preserved until late disease stages. Dark-adapted two-color fundus-controlled perimetry (also known as scotopic microperimetry) has been developed to enable spatial assessment of rod and cone photoreceptor function. This study explores the use of scotopic microperimetry in patients with choroideremia. Twenty patients with choroideremia and 21 age-matched healthy controls completed visual acuity and scotopic microperimetry testing, which used the Scotopic Macular Integrity Assessment (S-MAIA) microperimeter. A subset of participants completed repeat scotopic testing to enable Bland-Altman repeatability analyses. Test reliability was assessed using fixation stability, fixation losses, and assessment of the rod-free zones. Pointwise sensitivity, mean sensitivity, and volume sensitivity indices were analyzed. False positive responses were the main source of poor test reliability, indicated by stimuli responses in the physiological blind spot and lack of rod-free mapping. Scotopic cyan and red sensitivities were significantly reduced in choroideremia participants (n = 17) compared to healthy controls (n = 16) (P < 0.01, Mann-Whitney U test). Scotopic cyan sensitivity was statistically lower than scotopic red sensitivity in both healthy controls and choroideremia (P < 0.01, Wilcoxon signed rank test). Interpretation of scotopic cyan-red differences should be used with caution due to high test-retest variability. Scotopic microperimetry could be a useful outcome measure in patients with early choroideremia. Careful selection of test grid design and sensitivity indices is required. Scotopic microperimetry may be a useful outcome measure in clinical trials for patients with early stage choroideremia.

Evaluation of Oxidative Stress activity, DNA Damage and Global DNA Methylation among Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is a serious threat to global medicine as more than two million get CKD yearly. However, the understanding of DNA damage, DNA methylation in chronic kidney disease (CKD) remains elusive. The study goal was to establish whether homocysteine (Hcy), oxidative DNA damage (ODD), glutathione peroxidase (GPX3) and 5-methylcytosine (5mC) could be used as a potential marker of CKD. Measurements of Hcy, ODD, and GPX3 levels were done by commercial enzyme linked immunosorbent assay (ELISA) kits of 60 patients with chronic kidney disease (age range 20-87 years) and 30 age-matched healthy controls. DNA extracted from blood of patients was used to evaluate the global 5-methylcytosine (5mC) levels by the MethylFlashTM methylated DNA quantification Kit (Epigentek, USA). Results indicated a highly significant rise in Hcy and ODD in CKD patients in contrast to the healthy controls group. Although GPX3 level reduced in CKD patients, there was no significant difference between the patients and healthy controls. This research results also revealed significant rise in global 5mC level in CKD patients in comparison to the healthy controls. There is a potential role of homocysteine, oxidative DNA damage and global 5mC to be used as a biomarker for the progression of CKD.

The potential effects of metformin and/or sitagliptin on leptin/adiponectin ratio in diabetic obese patients: a new therapeutic effect.

To explore how metformin, alone or in conjunction with sitagliptin, affects the leptin/adiponectin ratio in obese type 2 diabetes mellitus patients. The case-control study was conducted from March to August 2021 at the Department of Clinical Pharmacology, College of Medicine, Mustansiriyah University, Baghdad, Iraq, and comprised adult, obese type 2 diabetes mellitus patients of either gender and age-matched healthy controls. The MT group included patients taking metformin 1g/day, MTS group had patients taking metformin 1g/day plus sitagliptin 100mg/day, and the control group comprised healthy subjects. Serum levels of human leptin and adiponectin were recorded along with body mass index, blood pressure, lipid profile and glycaemic indices. Data was analysed using SPSS 20. Of the 90 subjects, 62(69%) were patients; 36(40%) in MT group and 26(29%) in MTS. The control group had 28(31%) individuals. The mean age of the patient groups was 48.62±8.17 years, and male: female ratio was 49:41, mean age of controls was 47.64± 5.77 years with the same male to female ratio as that of the patients. Leptin levels were higher in patients compared to controls (p=0.002), and leptin levels were lower in MTS (89.93±9.51) than MT group (93.69±13.69). Patients in MT (30.57±6.31) and MTS (32.99±7.10) groups had lower adiponectin levels than controls (48.83±9.21) (p=0.001). MT and MTS patients had a greater leptin-to-adiponectin ratio than controls (p=0.0001). Leptin-to-adiponectin ratio could be a viable marker for assessing risks related to type 2 diabetes mellitus and other health conditions.