Lexical acquisition in progressive aphasia and frontotemporal dementia

We investigated the characteristics of language difficulty in frontotemporal dementia (FTD) by exposing these patients to a new verb in a naturalistic manner and then assessing acquisition of the grammatical, semantic, and thematic matrix information associated with the new word. We found that FTD patients have difficulty relative to healthy seniors in their acquisition of the new verb, but that progressive nonfluent aphasia (PNFA), semantic dementia (SD), and social/dysexecutive variant (SOC/EXEC) subgroups of FTD demonstrate relatively distinct impairment profiles. Specifically, PNFA patients showed relative difficulty assigning the new verb to its correct grammatical form class, reflecting compromised processing of the associated grammatical information. SD patients were impaired at associating the new word with its pictorial representation, suggesting impaired processing of the new verb's semantic attributes. SOC/EXEC patients showed their greatest difficulty judging violations of the new word's associated thematic roles, implying that limited executive resources underlie in part the difficulty in integrating grammatical and semantic information into a coherent thematic matrix. Similar impairment profiles were seen during a follow-up session one week after the initial evaluation. These deficits in lexical acquisition reflect the breakdown of a language-processing system that consists of highly interactive but partially dissociable grammatical, semantic, and resource-based components, leading to relatively distinct language-processing deficits in each subgroup of patients with FTD.     

Surgical stress and cytoskeletal changes in lens epithelial cells following manual and femtosecond laser-assisted capsulotomy

AIM: To study the effect of mechanical stress on the cytoskeleton in lens epithelial cells following conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS). METHODS: The cytoskeleton of the epithelial cells of the anterior lens capsules (ALC) removed by CPS and FLACS was examined by immunohistochemistry. Expression of the intermediate filament, glial fibrillary acidic protein (GFAP), and glutamine synthetase (GS) immunoreactivity were detected. In order to map the actin network of cells, fluorescently labeled phalloidin was used. The samples were examined using confocal laser scanning microscopy. RESULTS: GFAP expression was visible in a larger number of the epithelial cells after CPS compared to FLACS. In CPS sample’s epithelial cells, GFAP immunoreactivity indicated robust morphological change. Regarding the actin filaments, the presence of tubular elements connecting epithelial cells, regular actin pattern and marked cortical network after CPS were found. Following FLACS, the actin cytoskeleton of the epithelial cells remained densely structured, and the tubular elements were undetectable, however, the above-mentioned regular actin pattern and the marked cortical network were visible. CONCLUSION: The conventional removal of the ALC induces more robust changes of the cytoskeleton of the lens epithelial cells.     

Reclassification of adolescent hypertension by ambulatory blood pressure monitoring using adult norms and association with left ventricular hypertrophy

2017 pediatric blood pressure (BP) guidelines applied adult BP norms to define clinic hypertension (HTN) in patients ≥ 13 years. 2014 pediatric ambulatory BP monitor (ABPM) guidelines recommend age‐ and sex‐specific percentile norms for patients < 18 years. The authors evaluated reclassification of HTN when applying adult ABPM norms in patients ≥ 13 years and assessed the association of left ventricular hypertrophy (LVH) with HTN. Charts of patients 13–17 years with ABPM 9/2018–5/2019 were reviewed for sex, age, height, weight, BP medication, ABPM results, and left ventricular mass index (LVMI). American Heart Association 2005 (AHA 2005), AHA 2017 (AHA 2017), and European Society of Hypertension 2018 (ESH 2018) guidelines for adult ABPM were compared with 2014 AHA pediatric norms (pABPM). HTN was defined by each guideline using only ABPM. ABPM and clinic BP were used to classify white coat hypertension (WCH) and masked hypertension (MH). LVH was defined as LVMI > 51 g/m^2.7. 272 patients had adequate ABPM. 124 patients also had echocardiogram. All adult norms resulted in significant reclassification of HTN. LVMI correlated significantly with systolic BP only. The odds of a patient with HTN having LVH was significant using AHA 2005 (OR: 8.75 [2.1, 36.4], p = .03) and ESH 2018 (OR: 4.94 [1, 24.3], p = .002). Significant reclassification of HTN occurs with all adult norms. HTN is significantly associated with LVH using AHA 2005 and ESH 2018. Applying pediatric norms for ABPM while using adult norms for clinic BP causes confusion. Guideline selection should balance misdiagnosis with over‐diagnosis.     

Characterization of the GBoV1 Capsid and Its Antibody Interactions

Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in several human cell types. Here, we report the capsid structure of GBoV1 determined to 2.76 Å resolution using cryo-electron microscopy (cryo-EM) and its interaction with mouse monoclonal antibodies (mAbs) and human sera. GBoV1 shares capsid surface morphologies with other parvoviruses, with a channel at the 5-fold symmetry axis, protrusions surrounding the 3-fold axis and a depression at the 2-fold axis. A 2/5-fold wall separates the 2-fold and 5-fold axes. Compared to HBoV1, differences are localized to the 3-fold protrusions. Consistently, native dot immunoblots and cryo-EM showed cross-reactivity and binding, respectively, by a 5-fold targeted HBoV1 mAb, 15C6. Surprisingly, recognition was observed for one out of three 3-fold targeted mAbs, 12C1, indicating some structural similarity at this region. In addition, GBoV1, tested against 40 human sera, showed the similar rates of seropositivity as HBoV1. Immunogenic reactivity against parvoviral vectors is a significant barrier to efficient gene delivery. This study is a step towards optimizing bocaparvovirus vectors with antibody escape properties.     

Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study

Purpose

CHIT1 is expressed by pulmonary macrophages, which is typically the site of entry for many environmental fungi that may increase the risk of pulmonary fungal infection and lead to hypersensitivity. The conserved expression of this gene in humans suggests its physiological importance in the mammalian lung.

Methods

The present study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients. DNA samples were extracted from blood, and the genotyping was done using polymerase chain reaction method.

Results

Statistical analysis revealed that the 24 bp duplication in CHIT1 gene polymorphism shows highly significant association in heterozygous (wild/dup) genotype with OR 1.74, 95 % CI (1.29–2.36), and p = 0.000. However, the homozygous mutant genotype (dup/dup) was found to be non-significant with OR 1.06, 95 % CI (0.69–1.63), and p = 0.786. The combination of both wild/dup and dup/dup was also found to be highly significant with OR 1.57, 95 % CI (1.18–2.11), and p = 0.002.

Conclusions

This is the first study conducted in India which reports a significant association between 24 bp duplication in CHIT1 gene polymorphism and asthma in the studied North Indian population.     

Formulation and Evaluation of Sustained Release Extrudes Prepared via Novel Hot Melt Extrusion Technique

The purpose of the present investigation is to emphasize the application of hot-melt extrusion technique (HMET) for the preparation of sustained release matrix formulation of highly dosed, freely soluble drugs. In this study, sustained release multiple unit dosage of venlafaxine hydrochloride (VH) was prepared by HMET. Custom design was used to screen the effect of four factors-type of polymer (ethylcellulose and eudragit RSPO) (X ₁), amount of polymer (X ₂), type of plasticizer (DBS, ATBC, TEC, and PEG) (X ₃), and plasticizer concentration (X ₄), on the drug release at 8 h (Y1) and machine torque (Y2). The experiments were carried out according to a four-factor 16-run statistical model and subjected to 12-h dissolution study in purified water. The significance of the model was indicated by ANOVA. Results of in vitro release study indicate that formulations prepared with higher amount of ethylcellulose and DBC show significant retardation at 8 h. The result shows that increase in concentration of polymer with the combination of water insoluble plasticizer (DBS and ATBC) has better sustained release while increasing concentration of TEC and PEG results faster in vitro release. Besides that increase in plasticizer concentration helps in reducing the melt temperature and machine torque. The in vivo study was performed, and formulations were compared using area under the plasma concentration-time curve (AUC_0-∞), time to reach peak plasma concentration (T_max), and peak plasma concentration (C_max). The drug release profiles of extrudes were found to fit both diffusion and surface erosion models. Further to this, scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction analysis of the hot-melt extrudates demonstrated that VH remained crystalline and was homogeneously dispersed throughout the polymer matrix.     

Improvement of Bioavailability and Anti-Inflammatory Potential of Curcumin in Combination with Emu Oil

The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund’s complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.