Intact working memory in non‐manifesting LRRK2 carriers – an fMRI study

Cognitive impairments are prevalent in patients with Parkinson's disease. Mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinsonism. Non‐manifesting carriers of the G2019S mutation in the LRRK2 gene were found to have lower executive functions as measured by the Stroop task. This exploratory study aimed to assess whether the cognitive impairment in non‐manifesting carriers is specific for executive functions or includes other cognitive domains such as working memory. We recruited 77 non‐manifesting first‐degree relatives of Parkinson's disease patients (38 carriers). A block‐design fMRI N‐back task, with 0‐back, 2‐back and 3‐back conditions, was used in order to assess working memory. Participants were well matched on the Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test, Unified Parkinson's Disease Rating Scale part III, digit span, age, gender and Beck Depression Inventory. The task achieved the overall expected effect in both groups with longer reaction times and lower accuracy rates with increasing task demands. However, no whole‐brain or region‐of‐interest between‐groups differences were found on any of the task conditions. These results indicate that non‐manifesting carriers of the G2019S mutation in the LRRK2 gene have a specific cognitive profile with executive functions, as assessed by the Stroop task, demonstrating significant impairment but with working memory, as assessed with the N‐back task, remaining relatively intact. These finding shed light on the pre‐motor cognitive changes in this unique ‘at risk’ population and should enable more focused cognitive assessments of these cohorts.     

The Use of Colchicine in Cardiovascular Diseases: A Systematic Review

The medicinal properties of colchicine have been recognized for centuries. Although previously used for gout and familial Mediterranean fever, its immune-modulating, anti-inflammatory, and antifibrotic effects are increasingly recognized as beneficial in the treatment of cardiovascular disorders. In this systematic review, we summarize the current evidence on colchicine's effectiveness in 1) pericarditis, 2) coronary artery disease, and 3) atrial fibrillation. We also discuss the safety, potential adverse effects, and common drug interactions that should be considered during use.     

Hemodynamic effects of hypothyroidism induced by methimazole in normal and portal hypertensive rats

Portal hypertension is accompanied by a hyperdynamic circulatory state that shares some similarities with thyrotoxicosis. This study was conducted in order to investigate the hemodynamic effects of hypothyroidism in a rat model with portal hypertension induced by partial portal vein ligation (PVL). Four groups of 10 rats each were studied: normal control and hypothyroid rats, and PVL control and hypothyroid rats. Hypothyroidism was induced by methimazole 0.04% in drinking water. Hemodynamic measurements were performed using the radioactive microsphere technique. Induction of hypothyroidism was confirmed by elevated TSH levels. In the PVL groups, hypothyroidism ameliorated the hyperdynamic circulation. Portal venous inflow and portal pressure dropped significantly: 7.1±0.2 vs 4.8±0.3 ml/min/100 g body wt (P<0.01) and 13.4±0.9 vs 10.9±0.8 mm Hg; (P<0.01), respectively. In normal rats, hypothyroidism was manifested by a hypodynamic circulatory state. These results demonstrate that hypothyroidism induced by methimazole is followed by amelioration of the hyperdynamic circulation, normalization of portal venous inflow, and reduction of portal pressure.     

Pseudo-Chediak-Higashi anomaly in acute myeloid leukaemia. An electron microscopical study.

2 cases of acute myeloid leukaemia with inclusion bodies are presented. The inclusions were found mainly in the blast cells but could also be encountered in lymphocytes and plasma cells. Cytochemical and ultrastructural studies showed a great resemblance of these inclusions to the ones found in Chediak-Higashi anomaly, i.e., high acid phosphatase activity, varying in size of inclusions from clusters of small granules to hugh inclusion, sometimes found in vacuoles, featuring fusion of lysosomes.     

"Under-the-plate" reduction band technique

We compared the value of 7.5 Nm external rotation stress in diagnosing tibiofibular syndesmotic injuries of the ankle on lateral radiographs with radiostereometric analysis (RSA) in 10 cadaveric legs. After sectioning 2 ligaments, RSA showed an increase in posterior translation and external rotation of the fibula. This increase in posterior translation was smaller than the posterior displacement of the fibula on the lateral radiograph, and RSA showed mainly an increase in external rotation of the fibula that can not be measured on conventional radiographs. We conclude that instability of the syndesmosis in cadaveric ankles can be detected with 7.5 Nm external rotation stress RSA, but that external rotation stress lateral radiography is unreliable.     

The GBA-370Rec Parkinson's disease risk haplotype harbors a potentially pathogenic variant in the mitochondrial gene SLC25A44

GBA variations are common risk factors for Parkinson's disease (PD), and are found in 21.7% of Ashkenazi PD patients (AJ-PD), 4.23% of them carry an allele, 370Rec, which is different from the common GBA-N370S allele. Using whole-genome-sequencing of 370Rec carriers, N370S carriers, and non-carriers, we characterize the unique 370Rec haplotype in AJ-PDs, and show that it harbors a missense variant replacing the highly conserved methionine-27 with valine in the transmembrane domain of the mitochondrial SLC25A44.     

Left circumflex coronary artery occlusion after mitral valve annuloplasty: "a stitch in time"

The left circumflex coronary artery is susceptible to injury during mitral valve surgery because of its proximity to the mitral valve annulus. We report the case of a 73-year-old woman who had undergone mitral valve repair and experienced a perioperative myocardial infarction due to occlusion of the left circumflex coronary artery. After percutaneous coronary intervention, a fistulous communication had developed between the stented portion of the left circumflex coronary artery and the left atrium, which, to our knowledge, is the first report of such a complication. The patient underwent successful mitral valve replacement. Although injuries to the left circumflex coronary artery are rare during mitral valve surgery, we believe that increasing awareness of the risk will help to prevent potentially fatal complications. We also recommend that surgeons gather as much detail as possible about the patient's anatomy before operation, use careful and meticulous surgical techniques, and use transesophageal echocardiography to look for wall-motion abnormalities before closing the incision.