Acute respiratory insufficiency associated with the ingestion of central nervous system depressants]

The study of twenty patients with poisoning by central nervous system depressant drugs is reported. The authors emphasized clinical aspects, complications and mainly the lung function impairment. Barbiturates were the most common drugs, at least in 60% of the cases, used alone or in combination with sedatives and tranquilizers. In 55% of patients the amount of the drug ingested could not be measured. In 60% of the cases we didn't know the period of time between drug ingestion by the patients and their admission to the hospital. On admisson all patients were in coma. The coma was of varying degrees and the deeper the coma the worse was lung function and complications were more frequent. Whenever a cardiovascular collapse was present there was also a high mortality rate. The authors emphasized the importance of a follow-up of these patients in intensive care units, mainly with cardiovascular and ventilatory support.     

CD81 is essential for the formation of membrane protrusions and regulates Rac1-activation in adhesion-dependent immune cell migration

CD81 (TAPA-1) is a member of the widely expressed and evolutionary conserved tetraspanin family that forms complexes with a variety of other cell surface receptors and facilitates hepatitis C virus entry. Here, we show that CD81 is specifically required for the formation of lamellipodia in migrating dendritic cells (DCs). Mouse CD81(-/-) DCs, or murine and human CD81 RNA interference knockdown DCs lacked the ability to form actin protrusions, thereby impairing their motility dramatically. Moreover, we observed a selective loss of Rac1 activity in the absence of CD81, the latter of which is exclusively required for integrin-dependent migration on 2-dimensional substrates. Neither integrin affinity for substrate nor the size of basal integrin clusters was affected by CD81 deficiency in adherent DCs. However, the use of total internal reflection fluorescence microscopy revealed an accumulation of integrin clusters above the basal layer in CD81 knockdown cells. Furthermore, β1- or β2-integrins, actin, and Rac are strongly colocalized at the leading edge of DCs, but the very fronts of these cells protrude CD81-containing membranes that project outward from the actin-integrin area. Taken together, these data suggest a thus far unappreciated role for CD81 in the mobilization of preformed integrin clusters into the leading edge of migratory DCs on 2-dimensional surfaces.     

Fragmented QRS Complexes on 12‐Lead ECG: A Marker of Cardiac Sarcoidosis as Detected by Gadolinium Cardiac Magnetic Resonance Imaging

Background: Fragmented QRS complexes (fQRS) on a 12‐lead ECG are a marker of myocardial scar in patients with coronary artery disease. Cardiac sarcoidosis is also associated with myocardial granuloma formation and scarring. We evaluated the significance of fQRS on a 12‐lead ECG compared to Gadolinium‐delayed enhancement images (GDE) in cardiac magnetic resonance imaging (CMR). Method and results: The ECGs of patients (n = 17, mean age: 52 ± 11 years, male: 53%) with established diagnosis of sarcoidosis who underwent a CMR for evaluation of cardiac involvement were studied. ECG abnormalities included bundle branch block, Q wave, and fQRS. fQRS, Q wave, and bundle branch block were present in 9 (53%), 1 (6%), and 4 (24%) patients, respectively. The sensitivity and specificity of fQRS for detecting abnormal GDE were 100% and 80%, respectively. Sensitivity and specificity of Q waves were 11% and 100%, respectively. Conclusions: fQRS on a 12‐lead ECG in patients with suspected cardiac sarcoidosis are associated with cardiac involvement as detected by GDE on CMR.     

Effects of a 24‐hr‐shift‐related short‐term sleep deprivation on cardiac function: A cardiac magnetic resonance‐based study

Fatigue and sleep deprivation are common phenomena, especially among medical professionals and shift workers. Studies have proven that short episodes of sleep deprivation can lead to sympathetic hyperactivity with an elevation in blood pressure, heart rate, and an increased secretion of stress hormones (e.g. cortisol, noradrenaline, thyroid hormones). In this study investigating cardiac strain in 20 healthy subjects undergoing short‐term sleep deprivation, it could be shown for the first time that 24‐hr‐shift‐related short‐term sleep deprivation leads to a significant increase in cardiac contractility, blood pressure, heart rate and stress hormone secretion. These findings may help better understand how workload and shift duration affect public health, and lay the foundation for further investigations.     

Clarification of glycosylphosphatidylinositol anchorage of OTOANCORIN and human OTOA variants associated with deafness

Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remain poorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G>C and p.Gln589ArgfsX55 [NM_144672.3]) . The pathogenic potential of c.1320 + 5 G>C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild‐type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol‐specific phospholipase C‐induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI‐anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI‐anchorage.