Age-matched Subjects Research Articles

Lower osteoporotic-like vertebral fractural deformity (OLVF) prevalence and severity among older Thais and Indonesians than among older Chinese.

Chinese are known to have a lower vertebral fragility fracture risk than Caucasians. This study evaluates radiographic osteoporotic-like vertebral fractural deformity (OLVF) prevalence and severity among Chinese, Thai, Indonesian women and men. In an epidemiological study with community subjects, spine radiographs (T4-L5) were sampled for 195 Thai women (mean: 73.6 years), 202 Thai men (mean: 73.7 years), 236 Indonesian women (mean: 70.4 years), and 174 Indonesian men (mean: 70.2 years). Spine radiographs of age-matched subjects were also sampled for Chinese. OLVF classification included no OLVF (grade 0), and OLVFs with <20% (grade 0.5, minimal grade), ≥20-25% (grade 1, mild grade), ≥25%-1/3 (grade 1.5, moderate grade), ≥1/3-40% (grade 2, marked grade), ≥40%-2/3 (grade 2.5, severe grade), and ≥2/3 height loss (grade 3, collapsed grade). OLVF sum score (OLVFss) was calculated with each vertebra assigned a score of 0, -0.5, -1, -1.5, -2, -2.5, and -3 for no OLVF or OLVF grades 0.5-3. Osteoporosis prevalences were estimated based on OLVFss. For a woman, OLVFss ≤-1.0 and OLVFss ≤-1.5 were the thresholds to classify the case being osteoporotic according to the lowest T-score or femoral neck T-score respectively. For men, these thresholds were OLVFss ≤-2.5 and OLVFss ≤-3.0. Compared with Southeast Asians, Chinese had overall higher prevalences of all-inclusive OLVF, apparent OLVF, and OLVF among Chinese were more likely to be multiple. A trend was noted that Chinese women were more likely to have severe and collapsed grades OLVFs than Southeast Asian women, while such a trend was not noted for Chinese men vs. Southeast Asian men comparison. For men, the Chinese vs. Southeast Asians difference was that Chinese had a higher prevalence of milder OLVFs. For the Thais vs. Indonesians comparison, OLVFss (mean ± standard deviation) was -0.62±1.43 for Thai men, -0.47±0.98 for Indonesian men, -0.82±2.39 for Thai women, and -0.76±2.18 for Indonesian women. The lowest T-score based osteoporosis prevalence and femoral neck T-score based osteoporosis prevalence was 9.4% and 6.9% respectively for Thai men, and 6.9% and 2.9% for respectively Indonesian men; 19.5% and 14.9% respectively for Thai women, 18.9% and 14.5% respectively for Indonesian women. The prevalence and severity of radiographic OLVF show a weak trend of 'Chinese > Thais > Indonesians', both for older women and for older men. The results of the current study support the notion that 'populations from a warmer climate have better spine health'.

Power Spectral Density and Default Mode Network Connectivity in Generalized Epilepsy Syndromes: What to Expect from Drug-Resistant Patients.

Background: Recent studies have described unique aspects of default mode network connectivity in patients with idiopathic generalized epilepsy (IGE). A complete background in this field could be gained by combining this research with spectral analysis. Objectives: An important objective of this study was to compare linear connectivity and power spectral densities across different activity bands of patients with juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic-clonic seizures alone (EGTCSA), and drug-resistant IGE (DR-IGE) with healthy, age-matched controls. Methods: This was an observational case-control study. We performed EEG spectral analysis in MATLAB and connectivity analysis with LORETA for 39 patients with IGE and 12 drug-resistant IGE (DR-IGE) and healthy, age-matched subjects. We defined regions of interest (ROIs) from the default mode network (DMN) and performed connectivity statistics using time-varying spectra for paired samples. Using the same EEG data, we compared mean power spectral density (PSD) with epilepsy subgroups and controls across different activity bands. Results: We obtained a modified value for the mean power spectral density in the beta band for the JME group as follows. The connectivity analysis showed that, in general, there was increased linear connectivity in the DMN for the JAE, JME, and EGCTSA groups compared to the healthy controls. Reduced linear connectivity between regions of the DMN was found for DR-IGE. Conclusions: Spectral analysis of electroencephalography (EEG) for generalized epilepsy syndromes seems to be less informative than connectivity analysis for DMN. DMN connectivity analysis, especially for DR-IGE, opens up the possibility of finding biomarkers related to drug response in IGE.

Diastolic dysfunction evaluation by cardiovascular magnetic resonance derived E, a, e': Comparison to echocardiography.

Transthoracic echocardiography (TTE) is the first-line and most useful imaging modality for evaluating diastolic dysfunction (DD). Cardiovascular magnetic resonance (CMR) has not been fully evaluated for this task. We investigated the utility of CMR for DD evaluation.Thirty-one patients with a recent TTE (within 4 months) were prospectively enrolled, along with 12 healthy age-matched subjects. CMR imaging was performed at 1.5 T to assess diastolic function by quantifying mitral inflow velocities (E and A), mitral annular velocities (e'), and left atrial volume (LAVi). Measurements by TTE and CMR were compared using regression. The diagnostic accuracy of CMR for DD was determined.CMR derived E, A, E/A, e' and E/e' all correlated moderately to strongly with TTE, and more strongly when comparing studies performed closer in time (E: r = 0.68, E deceleration time: r = 0.82, A: r = 0.78, e' r = 0.75, E/e': r = 0.80, p = 0.001; LAVi: r = 0.79, p < 0.001; E/A: r = 0.82, p < 0.001, n = 14 within 45 days). Using CMR criteria analogous to TTE, there was 82% (23/28) agreement regarding the presence of DD (95% CI [63 to 93%]), with 100% sensitivity and 75% specificity, and 71% (20/28) agreement in the absolute DD grade.CMR can evaluate diastolic function, with overall strong agreement to TTE.

Exacerbated mitochondrial dynamic abnormalities without evident tau pathology in rapidly progressive Alzheimer's disease.

Rapidly progressive Alzheimer's disease (rpAD) is a clinical subtype distinguished by its rapid cognitive decline and shorter disease duration. rpAD, like typical AD (tAD), is characterized by underlying neuropathology of amyloid plaques and neurofibrillary tangles. There is early evidence that the composition of amyloid plaques could vary between the rpAD and tAD. Differences in tau pathology between rpAD and tAD are also of interest. Additionally, mitochondrial dysfunction is a key early-stage change in tAD but has not yet been evaluated in rpAD. To deepen our understanding of the underlying pathophysiological processes specific to rpAD, we explore potential changes in tau pathology and mitochondrial dysfunction in rpAD compared to tAD. We performed immunohistochemical and immunoblot analyses of tau, phosphorylated tau, and key regulators of mitochondrial dynamics and bioenergetics in postmortem human temporal cortex tissues obtained from patients diagnosed with tAD or rpAD, and tissues from age-matched normal subjects. tAD was characterized by significant tau phosphorylation at the PHF1 epitope. Unexpectedly, rpAD showed milder PHF1 tau phosphorylation, similar to that of age-matched controls. Despite these differences in tau pathology, both tAD and rpAD exhibited a significant decrease in the key regulators of mitochondrial dynamics and bioenergetics compared to controls. However, the decline in mitochondrial dynamics regulators was more pronounced in rpAD. These findings suggest divergent pathological processes between tAD and rpAD, specifically in terms of tau pathology and mitochondrial dynamic abnormalities, which underscore the necessity for different approaches to understand and potentially treat various AD subtypes.

Bone fragility in Type 2 Diabetes Mellitus. Influence of sex and cardiovascular disease in a pilot study using metabolomics

Type 2 diabetes mellitus (T2DM) is one of the most common worldwide metabolic disorders, characterized by insulin resistance (IR) and defective insulin secretion by pancreatic β-cells which leads to multiple complications such as bone fragility. This complication might be influenced by other factors such as gender and cardiovascular disease (CVD). However, it is unclear why a certain T2DM group develops bone fragility, and what the molecular mechanism is. Metabolomics is a powerful approach to the study of human metabolism, especially in complex diseases such as T2DM. Thus, this study aimed to identify significant metabolites associated with bone fragility in T2DM patients. To achieve this, 81 individuals were enrolled and classified as T2DM patients (D, n=28), T2DM with bone fragility (D-Frag, n=25), or age-matched non-diabetic subjects (ND, n=28) as the control group. Serum samples were collected and analyzed using liquid chromatography and gas chromatography, both coupled to mass spectrometry (LC-MS and GC-MS, respectively). Samples were compared within four different scenarios: 1) the classical comparison of D vs ND to corroborate previous studies; 2) D-Frag vs D to explore the metabolites mainly associated with bone fragility; 3) the same comparison using male data (MD-Frag vs MD) to study as a more homogeneous model of bone fragility as in women, bone fragility could be mainly associated with hormonal stage and pregnancy; and 4) MD-Frag-CVD vs MD-CVD to explore the influence of bone fragility in the male-based model with CVD considering that most of the T2DM patients suffer from CVD. After analysis of these scenarios, our results suggest that acylcarnitines and glycerophospholipids, among other metabolites, are involved in the development of bone fragility in T2DM.

Muscle spindle receptors and their impact on Parkinson´s disease and Cerebral Palsy subjects.

In some neurological conditions, like Parkinson's disease (PD) and Cerebral Palsy (CP), as well as with ageing, muscle spindles have been mentioned as participating in the pathological response of observed muscles. The aim of this review has therefore been to examine what is known about muscle spindle receptors, their function and how they are involved in regulating precise muscle movement in relation to these two conditions. Data from acoustic myography (AMG) studies with healthy controls (HC), CP and PD subjects have been re-examined with a view to identifying possible effects of changes in muscle movement which could be related to muscle spindle receptor function. Studies of muscle spindles have shown that during shortening and lengthening contractions the fusimotor system is activated differently with different discharge frequencies and sensitivities. With increasing age comes a loss of precise proprioception, something that coincides with a change in the AMG E-score towards lower values, indicating a reduced level of coordination and efficiency of muscle use. With PD and CP there is likewise a documented decrease in proprioception, also showing lower E-values than age-matched HC subjects. We conclude that the decrease in proprioception observed in these subjects must be partly due to a change in the muscle spindle / C-centre feedback system.

Cone Beam Computed Tomography Evaluation of Socket Healing After Third Molar Germ Extraction: A Case Series Study Including Adolescents with Osteogenesis Imperfecta Type I Treated with Bisphosphonates and Healthy Age-Matched Subjects

Bisphophonates (BPs) are widely used in Osteogenesis imperfecta (OI). Cone Beam Computed Tomography (CBCT) shows clinical usefulness in evaluating impacted teeth and adjacent structure relationships, extraction socket healing, bone mineral density (BMD) and BP-related jaw osteonecrosis (BRONJ). The aim of the study was to compare alveolar sockets and the adjacent bone area before and after third molar extraction in OI type I (OI-I) adolescents treated with BPs and age-matched healthy subjects (HSs) by CBCT. Methods: Five adolescents with genetically proven OI-I treated with BPs (three males and two females, mean age: 15.2 ± 1.78 years) and four age-matched healthy subjects (two males and two females, mean age: 15.5 ± 1.29 years) were included in this study. Eight Regions of Interest (ROIs) were evaluated: between 3.7 and 3.8 (ROI-1) and 4.7 and 4.8 (ROI-2); after 3.8 (ROI-3) and 4.8 (ROI-4); alveolar sockets 3.8 (ROI-5) and 4.8 (ROI-6); left (ROI-7) and right (ROI-8) cortical bone. Results: ROIs were evaluated on both sides of the mandible for all the subjects except one OI patient in which CBCTs were performed pre- and-post third molar extraction only on the right side. CBCT was performed 12.8 ± 4.60 and 11.5 ± 2.51 days before and 8.0 ± 1.41 and 7.7 ± 0.5 months after extraction in OI-I and HSs, respectively. BPs were discontinued 62.0 ± 36.5 months before extraction. None of the OI-I adolescents developed BRONJ. Statistically significant greater values were observed in OI-I for ROI-1 and -2 (p = 0.0464), ROI-3 and -4 (p = 0.0037) and ROI-7 and -8 (p = 0.0079) after extraction. Conclusions: This descriptive study confirms that, in OI-I adolescents treated with BPs, third molar extraction is safe, and socket healing occurs properly. In addition, it demonstrates that, if the same device and imaging conditions are used and comparisons to predetermined standard values are avoided, CBCT can be used to monitor BMD changes. The significant greater BMD observed for different ROIs in OI-I could reflect the increased secondary mineralization related to the BP-dependent reduction in bone turnover.

Significance of cerebral microinfarcts in antiphospholipid syndrome: A population-based study.

Acute ischemic stroke (AIS) or transient ischemic attack (TIA) is the most common neurological manifestations of patients with antiphospholipid syndrome (APS). Incidental diffusion-weighted imaging (DWI) positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMI), are microscopic ischemic lesions, detectable on MRI for 10-14 days only. We aimed to look at the prevalence of acute incidental CMI in a cohort of patients with APS and their association with subsequent AIS or TIA. This is a population-based cohort study of adults with APS diagnosis using International Statistical Classification-9 (ICD-9) and supporting laboratory results between January 2014 and April 2020. We included any patient undergoing brain MRI (index event) during the year prior APS diagnosis or at any time point following diagnosis. Age-matched subjects with negative APS laboratory workup were used as a control group. In the first analysis, we compared acute incidental CMI prevalence in both groups. We then performed a second analysis among APS patients only, comparing patients with and without acute incidental CMI for AIS or TIA as the primary outcome. Cox proportional hazards models used to calculate hazards ratio (HR) and 4 years cumulative risk. 292 patients were included, of which, 207 patients with APS. Thirteen patients with APS had acute incidental CMI on MRI (6.3%), compared with none in the control group (p = 0.013). Following multivariable analysis, APS was the sole factor associated with acute incidental CMI (p = 0.026). During a median follow-up of 4 years (IQR 3.5, 4) in patients with APS, following multivariable analysis, acute incidental CMI was associated with subsequent AIS or TIA (HR 6.73 [(95% CI, 1.96-23.11], p < 0.01). Acute incidental CMI are more common among patients with APS than in patients with negative APS tests, and are associated with subsequent AIS or TIA. Detecting acute incidental CMI in patients with APS may guide etiological workup and reevaluation of antithrombotic regimen.

Impact of the scapular dyskinesia on balance and pulmonary health in young adults: Cross-sectional observational study

Purpose. To evaluate balance abilities and respiratory system health in undergraduate students (young adults) with scapular dyskinesia. Methods. 141 sedentary students [65 men (46.1%): 76 women (53.9%)] voluntarily participated in this cross-sectional, observational study that included participants with scapular dyskinesia (group-I; n = 76), and normal control, age-matched subjects (group-II; n = 65). The evaluated variables included scapular dyskinesia (including the dyskinesis side and type) evaluated by the Lateral scapular slide test (LSST), balance (including the overall limits of stability, the limit of stability at the right and the limit of stability at the left) evaluated by the Biodex Balance System, and the pulmonary health variables (including the forced vital capacity “FVC”, the forced expiratory volume in one second “FEV1”, the FEV1/FVC% ratio, the maximum voluntary ventilation “MVV”, peak expiratory flow rate “PEFr” and the estimated “lung age”) using portable spirometer. Results. Among the seventy-six participants with scapular dyskinesia, there were 31 (40.8%) participants with right-side dyskinesia, 21 (27.6%) participants with left-side dyskinesia, 24 (31.6) participants with bilateral dyskinesia. Results showed that there were significant differences between groups I and II in the overall limits of stability (P = 116-3), Limits of Stability “Rt side” (P = 4-2), “Limits of Stability (Lt side)” (P = 2-2), the FVC (P = 1-3), the FEV1 (P = 8-3), and the lung age (P = 1-3). Conclusion. The balance abilities and the pulmonary health variables are significantly deteriorated in young adults with scapular dyskinesis.

Screening of [18F]Florbetazine for Aβ Plaques and a Head-to-Head Comparison Study with [11C]Pittsburgh Compound-B ([11C]PiB) in Human Subjects.

Positron emission tomography (PET) imaging of amyloid-β (Aβ) has emerged as a crucial strategy for early diagnosis and monitoring of therapeutic advancements targeting Aβ. In our previous first-in-human study, we identified that [18F]Florbetazine ([18F]92), featuring a diaryl-azine scaffold, exhibits higher cortical uptake in Alzheimer's disease (AD) patients compared to healthy controls (HC). Building upon these promising findings, this study aimed to characterize the diagnostic potential of [18F]92 and its dimethylamino-modified tracer [18F]91 and further compare them with the benchmark [11C]PiB in the same cohort of AD patients and age-matched HC subjects. The cortical accumulation of these tracers was evident, with no significant radioactivity retention observed in the cortex of HC subjects, consistent with [11C]PiB images (correlation coefficient of 0.9125 and 0.7883 between [18F]Florbetazine/[18F]91 and [11C]PiB, respectively). Additionally, quantified data revealed higher standardized uptake value ratios (SUVR) (with the cerebellum as the reference region) of [18F]Florbetazine/[18F]91 in AD patients compared to the HC group ([18F]Florbetazine: 1.49 vs 1.16; [18F]91: 1.33 vs 1.20). Notably, [18F]Florbetazine exhibited less nonspecific bindings in myelin-rich regions, compared to the dimethylamino-substituted [18F]91, akin to [11C]PiB. Overall, this study suggests that [18F]Florbetazine displays superior characteristics to [18F]91 in identifying Aβ pathology in AD. Furthermore, the close agreement between the uptakes in nontarget regions for [18F]Florbetazine and [11C]PiB in this head-to-head comparison study underscores its suitability for both clinical and research applications.

Delineating excess comorbidities in idiopathic pulmonary fibrosis: an observational study

BackgroundOur study examined whether prevalent and incident comorbidities are increased in idiopathic pulmonary fibrosis (IPF) patients when compared to matched chronic obstructive pulmonary disease (COPD) patients and control subjects without IPF or COPD.MethodsIPF and age, gender and smoking matched COPD patients, diagnosed between 01/01/1997 and 01/01/2019 were identified from the Clinical Practice Research Datalink GOLD database multiple registrations cohort at the first date an ICD-10 or read code mentioned IPF/COPD. A control cohort comprised age, gender and pack-year smoking matched subjects without IPF or COPD. Prevalent (prior to IPF/COPD diagnosis) and incident (after IPF/COPD diagnosis) comorbidities were examined. Group differences were estimated using a t-test. Mortality relationships were examined using multivariable Cox proportional hazards adjusted for patient age, gender and smoking status.ResultsAcross 3055 IPF patients, 38% had 3 or more prevalent comorbidities versus 32% of COPD patients and 21% of matched control subjects. Survival time reduced as the number of comorbidities in an individual increased (p < 0.0001).In IPF, prevalent heart failure (Hazard ratio [HR] = 1.62, 95% Confidence Interval [CI]: 1.43–1.84, p < 0.001), chronic kidney disease (HR = 1.27, 95%CI: 1.10–1.47, p = 0.001), cerebrovascular disease (HR = 1.18, 95%CI: 1.02–1.35, p = 0.02), abdominal and peripheral vascular disease (HR = 1.29, 95%CI: 1.09–1.50, p = 0.003) independently associated with reduced survival. Key comorbidities showed increased incidence in IPF (versus COPD) 7–10 years prior to IPF diagnosis.InterpretationThe mortality impact of excessive prevalent comorbidities in IPF versus COPD and smoking matched controls suggests that multiorgan mechanisms of injury need elucidation in patients that develop IPF.

Quantitative susceptibility mapping in the brain reflects spatial expression of genes involved in iron homeostasis and myelination.

Quantitative susceptibility mapping (QSM) is an MRI modality used to non-invasively measure iron content in the brain. Iron exhibits a specific anatomically varying pattern of accumulation in the brain across individuals. The highest regions of accumulation are the deep grey nuclei, where iron is stored in paramagnetic molecule ferritin. This form of iron is considered to be what largely contributes to the signal measured by QSM in the deep grey nuclei. It is also known that QSM is affected by diamagnetic myelin contents. Here, we investigate spatial gene expression of iron and myelin related genes, as measured by the Allen Human Brain Atlas, in relation to QSM images of age-matched subjects. We performed multiple linear regressions between gene expression and the average QSM signal within 34 distinct deep grey nuclei regions. Our results show a positive correlation (p < .05, corrected) between expression of ferritin and the QSM signal in deep grey nuclei regions. We repeated the analysis for other genes that encode proteins thought to be involved in the transport and storage of iron in the brain, as well as myelination. In addition to ferritin, our findings demonstrate a positive correlation (p < .05, corrected) between the expression of ferroportin, transferrin, divalent metal transporter 1, several gene markers of myelinating oligodendrocytes, and the QSM signal in deep grey nuclei regions. Our results suggest that the QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.

Vitamin D and it’s Association with FokI VDR Polymorphism in Patients with Asthma-COPD Overlap

Background: Asthma-COPD overlap is a new phenotype in respiratory ailments. It has been shown that this group of patients might possess vitamin D3 deficiency. The association of vitamin D receptor (VDR) gene polymorphism with serum vitamin D status in ACO patients has not been investigated yet. Objective: To assess the association of VDR gene polymorphism (FokI) with serum vitamin D status in patients with Asthma-COPD overlap. Methods: This cross-sectional study was carried out in the Department of Physiology of Bangabandhu Sheikh Mujib Medical University, Dhaka, from January 2018 to July 2018 on 23 (twenty-three) patients (aged ≥40 years) with ACO. For comparison, 24 (twenty-four) apparently healthy age, smoking duration and BMI matched subjects were selected. For all participants single nucleotide polymorphism of VDR gene FokI (rs10735810) was done by DNA extraction, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Vitamin D3 was measured by using automated analyzer: ARCHITECT Plus ci4100. The results were expressed as mean with standard error (mean±SEM) and frequency distribution. The data were statistically analyzed by Graphpad prism (Version 7) using independent sample ‘t’ test, two sample proportion test, Fisher exact test and ANOVA test. In the interpretation of results, ≤0.05 level of probability (p) was accepted as significant. Results: The mean±SEM of serum 25(OH)D were 16.37±0.78 and 18.46±1.01 ng/ml in control and study groups, respectively. The frequency distribution of FokI genotype was 86.95% (FF), 8.69% (Ff), 4.35% (ff) and 91.66% (FF), 4.17% (Ff), 4.17% (ff) in ACO patients and healthy subjects, respectively. When FoKI VDR SNP was analyzed with serum vitamin D status in patients with ACO, statistically no association was seen. Conclusions: FokI VDR SNP is not associated with serum vitamin D status in patients with ACO. J Rang Med Col. March 2024; Vol. 9, No. 1: 22-27

Predicting the cognitive impairment with multimodal ophthalmic imaging and artificial neural network for community screening

Background/aimsTo investigate the comprehensive prediction ability for cognitive impairment in a general elder population using the combination of the multimodal ophthalmic imaging and artificial neural networks.MethodsPatients with cognitive impairment and...

Determinants of hand pulse wave velocity and hand pulse transit time in healthy adults

Arterial pulse wave velocity (PWV) is recognized as a convenient method to assess peripheral vascular stiffness. This study explored the clinical characteristics of hand PWV (hPWV) and hand pulse transit time (hPTT) in healthy adults (sixty males = 42.4 ± 13.9 yrs; sixty-four females = 42.8 ± 13.9 yrs) voluntarily participated in this study. The arterial pulse waveform and the anatomical distance from the radial styloid process to the tip of the middle finger of both hands were recorded in the sitting position. The hPWV was calculated as the traversed distance divided by hPTT between those two points. Male subjects showed significantly greater hPWV, systolic blood pressure, and pulse pressure than age-matched female subjects, while the hPTT was not significantly different between genders. Multiple linear regression analysis showed that gender is a common determinant of hPWV and hPTT, and that age and heart rate (HR) were negatively correlated with hPWV and hPTT, respectively. We conclude that male subjects have greater hPWV than female subjects. Ageing is associated with decreased hPWV, while increased HR is associated with a smaller hPTT. The hPWV and hPTT might be used as non-invasive indices to characterise the ageing and arterial stiffness of peripheral blood vessels.

The prevalence, consequences, and outcome of perinatal asphyxia in term and late preterm live-born neonatesA A case-control study from Iran

Background: Despite several investigations reporting the prevalence of asphyxia in developed and developing countries, very few studies from Iran have demonstrated the rate of neonatal asphyxia and its affecting factors. Objectives: This study aimed to determine the prevalence of asphyxia, its consequences, and neonatal outcomes among Iranian term and late preterm live-born neonates. Methods: A case-control study was conducted in three hospitals; Vali-e-Asr, Yas, and Ziaean from April 2019 to March 2020. The case group included neonates with a history of perinatal asphyxia. Twice gestational age-matched subjects without such a history also entered the study as the control group. All maternal and neonatal data were collected from participants’ medical records. Determining the prevalence of neonatal asphyxia was the primary outcome of the present study. Results: Totally 48 subjects as the case and control groups were included and 16 asphyxiated cases were observed equal to 3.3 per 1000 live-born neonates. Concerning the type of delivery, cesarean section in the control group and vaginal delivery in the case group were the most frequent types of delivery (p=0.041). Comparing neonatal variables, the results showed a significant difference regarding the groups’ genders (p=0.036). Apgar scores in the case group were also significantly lower than the control group (p=0.0001). More cases also required PPV compared to the controls (12 vs. 0; p=0.0001). Hypoxic-ischemic encephalopathy (HIE) grade 1 was also significantly more frequent in the case group than the controls (p=0.0001). The means of pH and base excess in the case group were significantly lower than the control group (p=0.0001). Conclusion: The results showed the prevalence rate of asphyxia among term and late preterm participants was 3.3 cases per 1000 live-born neonates. Apgar scores&lt;5 accompanied with metabolic acidosis, HIE, and requirement of PPV could be predictive variables for perinatal asphyxia. Observing such clinical risk factors may indicate the need of early diagnosis and timely interventions to improve neonatal outcomes.

Automated Evaluation of Ellipsoid Zone At-Risk Burden for Detection of Hydroxychloroquine Retinopathy.

Screening for hydroxychloroquine (HCQ) retinopathy is crucial to detecting early disease. A novel machine-learning-based optical coherence tomography (OCT) biomarker, Ellipsoid Zone (EZ) At-Risk, can quantitatively measure EZ alterations and at-risk areas for progressive EZ loss in a fully automated fashion. The purpose of this analysis was to compare the EZ At-Risk burden in eyes with HCQ toxicity to eyes without toxicity. IRB-approved image analysis study of 83 subjects on HCQ and 44 age-matched normal subjects. SD-OCT images were reviewed for evidence of HCQ retinopathy. A ML-based, fully automatic measurement of the percentage of the macular area with EZ At-Risk was performed. The mean age for HCQ subjects was 67.1 ± 13.2 years and 64.2 ± 14.3 years for normal subjects. The mean EZ At-Risk macular burden in the "toxic" group (n = 38) was significantly higher (10.7%) compared to the "non-toxic" group (n = 45; 2.2%; p = 0.023) and the "normal" group (1.4%; p = 0.012). Additionally, the amount of EZ At-Risk burden was significantly correlated with the HCQ dose based on the actual (p = 0.016) and ideal body weight (p = 0.033). The novel biomarker EZ-At Risk was significantly higher in subjects with evidence of HCQ retinopathy as well as significantly associated with HCQ dose. This novel biomarker should be further evaluated as a potential screening tool for subjects on HCQ.

Insight into antiphospholipid syndrome: the role and clinical utility of neutrophils extracellular traps formation

Antiphospholipid syndrome (APLS) is a systemic immune dysregulation distinguished by repetitive complications and pregnancy loss in the absence of definite etiology. Most research focuses on the laboratory detection and clinical features of APLS, but its precise etiology remains to be deeply explored. NETosis is a newly developed theory in the pathophysiology of APLS which may serve as the missing bridge between coagulation and inflammation reaching the disease progression and severity. We aimed in this study to navigate the prognostic role of NETosis in thrombotic APLS. Our study included 49 newly diagnosed APLS patients (both 1ry and 2ry) who met clinical and laboratory criteria as per the international consensus statement on the update of the classification criteria for definite APLS and were sub-classified according to the occurrence of thrombotic events in thrombotic and non-thrombotic types. In addition, 20 sex and age-matched reactive subjects and 20 sex and age-matched healthy volunteer controls were enrolled. NETosis formation was assessed by measuring serum Myeloperoxidase (MPO) and Histones level using the enzyme-linked immunosorbent assay (ELISA) technique. Both MPO and Histones levels were able to discriminate among APLS cases from normal controls, showing significant cutoffs of > 2.09 ng/ml for MPO and > 1.45 ng/ml for Histones (AUC values were 0.987and 1.000, respectively). These values can be used as predictors for NETosis pathophysiology in APLS patients. Additionally, these markers demonstrated a significant association with several prognostic indicators, including thrombosis, higher PT and INR, and lower hemoglobin (Hb) levels which are supposed to be ameliorated by using NETs inhibitors. In conclusion, we suggest that measuring NETosis markers, MPO, and Histones, in the early course of APLS using proposed cutoff values will facilitate the timely initiation of anti-NETosis therapy and improve the overall prognosis, particularly for patients with thrombotic APLS.

Correlation between neutrophil to lymphocyte ratio and disease activity in patients with rheumatoid arthritis.

Objective: To figure out correlation between neutrophils to lymphocyte ratio in rheumatoid arthritis and its relationship with the disease severity. Study Design: Prospective study. Setting: Department of Rheumatology Fauji Foundation Hospital, Rawalpindi, Pakistan. Period: July 1st to December 31st, 2021. Material &amp; Methods: Study population included rheumatoid arthritis patients fulfilling American college for rheumatology criteria. On the basis of disease activity score-28 (DAS-28), the subjects were categorised into active and remission groups. The control group consisted of healthy age and gender matched subjects. Relationship between neutrophils to lymphocytes ratio with disease activity was analyzed. Data was analysed using SPSS 21. Results: 140 patients with RA were evaluated along with 70 healthy control subjects. NLR was higher in active RA (1.99±0.84) as compared to RA with remission (1.76±0.41) and controls (1.77±0.79). p value&lt;0.05 was obtained which was statistically significant. NLR is significantly correlated with CDAI and SDAI (r=0.24, p=0.04 each). CRP and ESR were also significantly higher in active RA patients compared to those in remission (p&lt;0.005 and p&lt;0.00 respectively) and control group. Conclusion: The neutrophil to lymphocyte ratio is a measure derived from a simple blood test. An elevated NLR is often considered an indicator of systemic inflammation. High NLR values may suggest increased inflammation and immune system activation, which are key features of RA. NLR may serve as a less expensive and easily accessible marker to detect inflammation in RA. It can be utilized in future as disease assessment tool.

Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study

The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson’s disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical symptoms longitudinally after dopamine replacement therapy in early, optimally-controlled PD patients with and without zonisamide treatment using positron emission tomography (PET). We enrolled sixteen PD patients (Hoehn and Yahr stage 1–2), and age-matched normal subjects. PD patients were randomly divided into two groups: one (zonisamide+) that did and one (zonisamide−) that did not undergo zonisamide therapy. Annual changes in neuroinflammation ([11C]DPA713 PET), dopamine transporter availability ([11C]CFT PET) and clinical severity were examined. Voxelwise differentiations in the binding of [11C]DPA713 (BPND) and [11C]CFT (SUVR) were compared with normal data and between the zonisamide+ and zonisamide− PD groups. The cerebral [11C]DPA713 BPND increased with time predominantly over the parieto-occipital region in PD patients. Comparison of the zonisamide+ group with the zonisamide− group showed lower levels in the cerebral [11C]DPA713 BPND in the zonisamide+ group. While the striatal [11C]CFT SUVR decreased longitudinally, the [11C]CFT SUVR in the nucleus accumbens showed a higher binding in the zonisamide+ group. A significant annual increase in attention score were found in the zonisamide+ group. The current results indicate neuroinflammation proceeds to the whole brain even after anti-parkinsonian therapy, but zonisamide coadministration might have the potential to ameliorate proinflammatory responses, exerting a neuroprotective effect in more damaged nigrostriatal regions with enhanced attention in PD.