Excessive synchronization of basal ganglia neurons at 20 Hz slows movement in Parkinson's disease

Excessive synchronization of neuronal activity at around 20 Hz is a common finding in the basal ganglia of patients with untreated Parkinson's disease (PD). Correlative evidence suggests, but does not prove, that this spontaneous activity may contribute to slowness of movement in this condition. Here we investigate whether externally imposed synchronization through direct stimulation of the region of the subthalamic nucleus at 20 Hz can slow motor performance in a simple unimanual tapping task and whether this effect is frequency selective. Tapping rates were recorded on 42 sides in 22 patients with PD after overnight withdrawal of medication. Tapping was performed without stimulation and during bilateral stimulation at 20 Hz, 50 Hz and 130 Hz. We found that tapping rates were slowed by 8.2+/-3.2% (p=0.014) during 20-Hz stimulation in subjects with relatively preserved baseline function in the task. This effect was frequency selective. The current data provide proof of the principle that excessive beta synchrony within the basal ganglia-cortical loop may contribute to the slowing of movements in Parkinson's disease.     

Reports of anaphylaxis after coronavirus disease 2019 vaccination,South Korea, 26 February to 30 April 2021

The South Korea mass vaccination programme administered 3.8 million doses of COVID-19 vaccinations between 26 February and 30 April 2021. After 173 suspected anaphylaxis reports to the nationwide monitoring system for adverse events following immunisation, 44 anaphylaxis cases were confirmed using Brighton Collaboration case definitions. The rates per million doses were 18.2 cases and 6.2 cases for Vaxzevria and Comirnaty, respectively. Median time of onset was 14 min after vaccination and most cases had recovered at the time of review.     

Postinfarction Inferior Ventricular Septal Rupture: Surgical Repair Through the Right Atrium

Abstract   Operative mortality of inferior postinfarct ventricular septal rupture (VSR) remains high. Previous reports have described a transatrial approach to access the VSR avoiding a ventriculotomy, thereby reducing the potential risks of myocardial damage, hemorrhage, and ventricular arrhythmias. The transatrial right ventricular patch or direct suture repair, however, is exposed to the left-to-right pressure gradient and is at risk of residual shunting. In this report, a transatrial approach is used, with direct suture of the VSR, patch exclusion of the right ventricle, and biological glue instillation to protect the patch from left ventricular pressures.     

A hybrid surgical transcatheter strategy for treating severe para-right atrioventricular valvular regurgitation in a patient with left atrial isomerism

Paravalvular leaks are a recognized complication of valve replacement surgery. We report a 47-year-old man with left atrial isomerism, interrupted left sided inferior caval vein with unilateral left sided superior caval vein, a common atrium, and anomalous pulmonary venous connection to the coronary sinus, who had recurrent severe para-right atrioventricular (AV) regurgitation with gross right heart failure following tricuspid valve (TCV) replacement. He underwent a hybrid surgery-transcatheter treatment strategy in the cardiac catheterization laboratory, which led to significant improvement in hemodynamics and symptoms. This to our knowledge is the first reported case of a minimally invasive approach to para-right sided AV valve regurgitation.     

Evaluation of the poly(ADP‐ribose) polymerase‐1 gene variants in Alzheimer's disease

Amyloid peptide is thought to play a critical role in neuronal death in Alzheimer's disease (AD), most likely through oxidative stress. Free radical‐related injury leads to DNA breaks, which subsequently activates the repair enzyme poly(ADP‐ribose) polymerase‐1 (PARP‐1). In this study, the relationship between genetic variants situated at the PARP‐1 gene and AD development was investigated. We performed a case and control study from a Taiwanese population enrolled 120 AD patients and 111 healthy controls by using a polymerase chain reaction restriction fragment length polymorphism approach for two PARP‐1 exonic polymorphisms, 414C/T (rs1805404) and 2456T/C (rs1136410), corresponding to protein residues at positions 81Asp/Asp and762Val/Ala. There were no significant differences in allele or genotype frequencies for either PARP‐1 gene variant between the case and control groups; however, upon analysis of the haplotype distribution, four haplotypes (Hts) were identified. We found that the distributions of Ht3‐TT and Ht4‐CC were significantly associated with an increased risk of AD (P<0.0001), whereas the Ht1‐TC haplotype showed a protective effect for cases compared with the control group (P<0.05). These results reveal that the PARP‐1 gene is highly associated with AD susceptibility and might contribute to a critical mechanism that mediates cell survival or death as a response to cytotoxic stress. J. Clin. Lab. Anal. 24:182–186, 2010. © 2010 Wiley‐Liss, Inc.     

Higher densities of Foxp3<Superscript>+</Superscript> regulatory T cells are associated with better prognosis in triple-negative breast cancer

Purpose

The role of Forkhead Box Protein 3 (Foxp3) expressing regulatory T cells (Tregs) in breast cancer remains unclear. We examined the abundance and localisation of total T cells, B cells and Tregs within samples from triple-negative breast cancers (TNBCs) and asked whether these parameters were associated with clinicopathological features of the cancer or clinical outcomes.

Methods

Samples from TNBCs diagnosed between 2003 and 2010 in Singapore were divided into “high” and “low” intra-tumoural or stromal groups, based on whether they had higher or lower than median densities of specific tumour-infiltrating lymphocyte populations (CD3⁺ total T cells, Foxp3⁺CD3⁺ Tregs, or CD20⁺ B cells) in the intra-tumoural space or stroma.

Results

Of the 164 samples, patients bearing tumours with high Tregs within their intra-tumoural, but not stromal, areas experienced significantly longer overall and disease-free survival compared to individuals with low Treg densities. These “high intra-tumoural Treg” tumours were also characterised by relatively higher frequencies of CD8⁺ T cells and CD20⁺ B cells, and expressed significantly higher levels of some genes associated with inflammation, immune cell functions and trafficking, altogether consistent with a more “immune-activated” tumour microenvironment, in contrast to tumours bearing lower densities of Tregs.

Conclusions

In summary, the combination of high densities of intra-tumoural Tregs, CD8⁺ T cells and CD20⁺ B cells represents a favourable prognostic panel in TNBCs. These data also indicate new avenues for further investigation on the interaction between immune cell types within the tumour microenvironment and highlight the potential of Treg density and localisation within tumours to affect clinical outcome.

     

Late onset diffuse lamellar keratitis associated with an epithelial defect in six eyes

PURPOSE: To report six cases of late onset diffuse lamellar keratitis associated with epithelial defects 2 to 12 months following uncomplicated laser in situ keratomileusis (LASIK). METHODS: Retrospective case series. RESULTS: The interface inflammation and epithelial defects were treated aggressively with topical corticosteroids and topical antibiotics with complete resolution over 1 to 2 weeks. There were no complications or loss of best spectacle-corrected visual acuity. These cases illustrate new understanding in the etiology of diffuse lamellar keratitis following lamellar surgery. CONCLUSION: Late onset diffuse lamellar keratitis in association with epithelial defects may occur following LASIK. Treatment with topical antibiotics and topical corticosteroids may result in uncomplicated, complete resolution.     

Rare intracanalicular ophthalmic aneurysm: endovascular treatment and review of the literature

This report outlines the diagnosis and endovascular management of a rare intracanalicular ophthalmic aneurysm in a patient presenting with progressive visual loss.