Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer’s disease

The neurofibrillary tangles (NFT) and amyloid‐ß plaques (AP) that comprise Alzheimer’s disease (AD) neuropathology are associated with neurodegeneration and microglial activation. Activated microglia exist on a dynamic spectrum of morphologic subtypes that include resting, surveillant microglia capable of converting to activated, hypertrophic microglia closely linked to neuroinflammatory processes and AD neuropathology in amnestic AD. However, quantitative analyses of microglial subtypes and neurons are lacking in non‐amnestic clinical AD variants, including primary progressive aphasia (PPA‐AD). PPA‐AD is a language disorder characterized by cortical atrophy and NFT densities concentrated to the language‐dominant hemisphere. Here, a stereologic investigation of five PPA‐AD participants determined the densities and distributions of neurons and microglial subtypes to examine how cellular changes relate to AD neuropathology and may contribute to cortical atrophy. Adjacent series of sections were immunostained for neurons (NeuN) and microglia (HLA‐DR) from bilateral language and non‐language regions where in vivo cortical atrophy and Thioflavin‐S‐positive APs and NFTs were previously quantified. NeuN‐positive neurons and morphologic subtypes of HLA‐DR‐positive microglia (i.e., resting [ramified] microglia and activated [hypertrophic] microglia) were quantified using unbiased stereology. Relationships between neurons, microglia, AD neuropathology, and cortical atrophy were determined using linear mixed models. NFT densities were positively associated with hypertrophic microglia densities (P < 0.01) and inversely related to neuron densities (P = 0.01). Hypertrophic microglia densities were inversely related to densities of neurons (P < 0.01) and ramified microglia (P < 0.01). Ramified microglia densities were positively associated with neuron densities (P = 0.02) and inversely related to cortical atrophy (P = 0.03). Our findings provide converging evidence of divergent roles for microglial subtypes in patterns of neurodegeneration, which includes hypertrophic microglia likely driving a neuroinflammatory response more sensitive to NFTs than APs in PPA‐AD. Moreover, the accumulation of both NFTs and activated hypertrophic microglia in association with low neuron densities suggest they may collectively contribute to focal neurodegeneration characteristic of PPA‐AD.     

Genetic landscape of human platelet antigen variants in the Indian population analysed from 1029 whole genomes

Genetic variants in human platelet antigens (HPAs) considered allo- or auto antigens are associated with various disorders, including neonatal alloimmune thrombocytopenia, platelet transfusion refractoriness and post-transfusion purpura. Although global differences in genotype frequencies were observed, the distributions of HPA variants in the Indian population are largely unknown. This study aims to explore the landscape of HPA variants in India to provide a basis for risk assessment and management of related complications. Population-specific frequencies of genetic variants associated with the 35 classes of HPAs (HPA-1 to HPA-35) were estimated by systematically analysing genomic variations of 1029 healthy Indian individuals as well as from global population genome datasets. Allele frequencies of the most clinically relevant HPA systems in the Indian population were found as follows, HPA-1a – 0.884, HPA-1b – 0.117, HPA-2a – 0.941, HPA-2b – 0.059, HPA-3a – 0.653, HPA-3b – 0.347, HPA-4a – 0.999, HPA-4b – 0.0010, HPA-5a – 0.923, HPA-5b – 0.077, HPA-6a – 0.998, HPA-6b – 0.002, HPA-15a – 0.582 and HPA-15b – 0.418. This study provides the first comprehensive analysis of HPA allele and genotype frequencies using large scale representative whole genome sequencing data of the Indian population.     

Osteopontin: a marker for invasive oral squamous cell carcinoma but not for potentially malignant epithelial dysplasias

This study aimed to evaluate and correlate osteopontin (OPN) expression in oral squamous cell carcinoma (OSCC) and potentially malignant disorders including oral leukoplakia and oral submucous fibrosis (OSMF). Expression of OPN was investigated in 140 samples including OSCC, oral leukoplakia, and OSMF with or without dysplasia and normal oral mucosa. By using immunohistochemistry. Both intercellular and intracellular staining of the keratinocytes was considered to be positive, and intensity grading was assessed. Statistical analysis was done using analysis of variance. OPN positivity was detected in 85% cases of OSCC, 55% cases of oral leukoplakia, 35% cases of OSMF, and 60% cases of normal mucosa. These study highlights OPN as a biomarker for malignancy in the form of invasion but not to study progression from dysplasia to malignant transformation.     

Proteomic Analyses of the Effects of Drugs of Abuse on Monocyte-Derived Mature Dendritic Cells

Drug abuse has become a global health concern. Understanding how drug abuse modulates the immune system and how the immune system responds to pathogens associated with drug abuse, such hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1), can be assessed by an integrated approach comparing proteomic analyses and quantitation of gene expression. Two-dimensional (2D) difference gel electrophoresis was used to determine the molecular mechanisms underlying the proteomic changes that alter normal biological processes when monocyte-derived mature dendritic cells were treated with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins including those that modulate apoptosis, protein folding, protein kinase activity, and metabolism and proteins that function as intracellular signal transduction molecules. Proteomic data were validated using a combination of quantitative, real-time PCR and Western blot analyses. These studies will help to identify the molecular mechanisms, including the expression of several functionally important classes of proteins that have emerged as potential mediators of pathogenesis. These proteins may predispose immunocompetent cells, including dendritic cells, to infection with viruses such as HCV and HIV-1, which are associated with drug abuse.     

Wavelet-based sparse functional linear model with applications to EEGs seizure detection and epilepsy diagnosis

In epilepsy diagnosis or epileptic seizure detection, much effort has been focused on finding effective combination of feature extraction and classification methods. In this paper, we develop a wavelet-based sparse functional linear model for representation of EEG signals. The aim of this modeling approach is to capture discriminative random components of EEG signals using wavelet variances. To achieve this goal, a forward search algorithm is proposed for determination of an appropriate wavelet decomposition level. Two EEG databases from University of Bonn and University of Freiburg are used for illustration of applicability of the proposed method to both epilepsy diagnosis and epileptic seizure detection problems. For this data considered, we show that wavelet-based sparse functional linear model with a simple classifier such as 1-NN classification method leads to higher classification results than those obtained using other complicated methods such as support vector machine. This approach produces a 100 % classification accuracy for various classification tasks using the EEG database from University of Bonn, and outperforms many other state-of-the-art techniques. The proposed classification scheme leads to 99 % overall classification accuracy for the EEG data from University of Freiburg.     

Biexponential diffusion tensor analysis of human brain diffusion data.

Several studies have shown that in tissues over an extended range of b-factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b-factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b-factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast-diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow-diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas.     

Hyperdense pericardial effusion in dermatomyositis and contrast induced nephropathy

Pericardial involvement in dermatomyositis is rare and usually asymptomatic. In many instances, a diagnosis of pericardial involvement is not found until autopsy. Renal failure associated with connective tissue disorders can result in or potentially exaggerate pericardial inflammation. We report an unusual case of high-density pericardial effusion in a patient with dermatomyositis consequent upon contrast nephropathy as demonstrated by computed tomography. High-density pericardial effusion can be a result of an insidious cause such as pericardial inflammation rather than the more usual causes such as coronary or cardiac perforation.     

Does exercise evoke neurological symptoms in healthy subjects?

Concussion is a common injury in collision sports and is evidenced by a variety of signs and symptoms. The recording of neurological symptoms is an important component of screening for a concussion and in return-to-play decisions. However similar symptoms are prevalent in the general population and are reported to be associated with participation in physical activities. The purpose of this study was to document the neurological symptoms reported by healthy individuals following controlled bouts of exercise. A crossover randomised design with 2 levels of exercise intensity, moderate intensity and high intensity, each of 15 min duration was used. Participants completed a standardised postconcussion symptom checklist prior to exercise (pre), immediately following exercise (post-1) and again after 15 min of rest (post-2). 60 participants were recruited into the study. A summed symptom score was calculated and analysed with a 2-way repeated measures ANOVA procedure. The intensity × time interaction (F_2,118 = 23.94, p < 0.001) demonstrated a significant increase in symptom scores for the high intensity condition immediately following exercise (p < 0.001). Although the moderate intensity showed a similar trend this was not significant. These findings suggest that sports medicine professionals need to be aware of the effect of exercise on symptom reporting when assessing and in making return-to-play decisions.     

Reporting of dose–volume specifications for “Martinez Universal Perineal Interstitial Template–based interstitial high-dose-rate brachytherapy for gynecological cancers” according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes

PurposeThe study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy.Methods and MaterialsForty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017–2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed.ResultsHigh-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm³ bladder and rectum were 2.9 Gy and 2.8 Gy. The mean TRAK was 0.16 cGy per fraction per hour at 1 m. TRAK values showed significant correlation with various isodose volumes (TRAK and V100: r = 0.943 p < 0.0005; and TRAK and V50: r = 0.953; p < 0.0005). A positive correlation was observed between TRAK and the number of needles (r = 0.746; p < 0.0005). At a median followup of 16 months, 4 of 42 patients (9.5%) had local recurrences.ConclusionsOur study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.     

Improvement of Dermatochalasis and Periorbital Rhytides With a High-Energy Pulsed CO2 Laser: A Retrospective Study

Background. Upper eyelid dermatochalasis is typically treated with excisional blepharoplasty. The role of the CO₂ laser previously had been confined to that of a vaporizing, incisional, or hemostatic tool. Over the past several years, however, ablative CO₂ laser skin resurfacing has been popularized as an adjunctive treatment to blepharoplasty to minimize periorbital rhytides through its vaporizing as well as skin-tightening action.
Objective. To evaluate the safety and efficacy of a high-energy pulsed CO₂ laser as a stand-alone treatment for dermatochalasis and periorbital rhytides.
Methods. Sixty-seven patients (skin phototypes I–IV) with mild-to-severe upper eyelid dermatochalasis and periorbital rhytides received periocular CO₂ laser skin treatment. Global assessment scores of dermatochalasis and rhytides were determined by a side-by-side comparison of periocular photographs preoperatively and 1, 3, and 6 months postoperatively. In addition, caliper measurements of upper eyelids before and 1, 3, and 6 months after treatment were obtained.
Results. Both dermatochalasis and periorbital rhytides were significantly improved after periocular CO₂ laser skin resurfacing. Patients with more severe dermatochalasis and rhytides showed greater improvement after CO₂ laser treatment than did those with mild or moderate involvement. Side effects were limited to erythema and transient hyperpigmentation. No scarring, hypopigmentation, or ectropion were observed.
Conclusions. Periocular skin resurfacing with a CO₂ laser can safely and effectively improve upper eyelid dermatochalasis and periorbital rhytides.