TIPS in Variceal Bleeding: New and Old Indications

Variceal bleeding is one of the most dreaded complications of cirrhosis and its occurrence is associated with significant morbidity and mortality. During the past 30 years preventative therapies have reduced the risk of the first variceal bleed. Once variceal bleeding occurs use of pharmacologic and endoscopic therapies prevent rebleeding in most patients. The existing recommendations are that TIPS only be used in those patients who fail medical therapy. We reviewed recent literature focusing on the role of early TIPS in management of acute variceal hemorrhage and prevention of re-bleeding.     

Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors

N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP(C)), a key copper-binding protein in the CNS. Acute ablation of PrP(C) by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrP(C) interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ(1-42) (10 nM-5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ(1-42), copper chelators, or PrP(C) inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrP(C), one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ(1-42) might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrP(C)-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.     

Dynamics of a bacterial multidrug ABC transporter in the inward- and outward-facing conformations

The study of membrane proteins remains a challenging task, and approaches to unravel their dynamics are scarce. Here, we applied hydrogen/deuterium exchange (HDX) coupled to mass spectrometry to probe the motions of a bacterial multidrug ATP-binding cassette (ABC) transporter, BmrA, in the inward-facing (resting state) and outward-facing (ATP-bound) conformations. Trypsin digestion and global or local HDX support the transition between inward- and outward-facing conformations during the catalytic cycle of BmrA. However, in the resting state, peptides from the two intracellular domains, especially ICD2, show a much faster HDX than in the closed state. This shows that these two subdomains are very flexible in this conformation. Additionally, molecular dynamics simulations suggest a large fluctuation of the Cα positions from ICD2 residues in the inward-facing conformation of a related transporter, MsbA. These results highlight the unexpected flexibility of ABC exporters in the resting state and underline the power of HDX coupled to mass spectrometry to explore conformational changes and dynamics of large membrane proteins.     

Primary cheiloplasty on an elderly man: case report and review of the literature

It is rare for surgeons in the United States to perform primary repair of a cleft lip on an adult. However, in developing nations with limited specialized health care, late presentation for primary cheiloplasty occurs due to limitations in access to care, lack of awareness of treatment availability, and inability to afford treatment. Oral and maxillofacial surgeons who participate in humanitarian surgical mission trips to the developing world may encounter this subpopulation of cleft patients. The following case report describes the repair of an incomplete bilateral cleft lip in a 68-year-old man performed during a mission trip to rural Bangladesh. Based on an extensive literature search, this is the oldest patient to have undergone primary cheiloplasty reported in the English-language surgical literature.     

A CTAB-mediated antisolvent vapor route to shale-like Cs4PbBr6 microplates showing an eminent photoluminescence

Compared with nanoscale quantum dots (QDs), the large-sized perovskite crystals not only possess better stability but also are convenient for application exploration. Herein, we develop a facile and efficient antisolvent vapor-assisted recrystallization approach for the synthesis of large-sized Cs₄PbBr₆ perovskite crystal microplates. In this method, for the first time, the shale-like Cs₄PbBr₆ microplates with lateral dimensions of hundreds of microns are fabricated by employing cetyltriethylammnonium bromide (CTAB) as a morphology-directing agent. FESEM, TEM, and AFM characterizations indicate that the as-obtained shale-like Cs₄PbBr₆ microplates are actually formed by 6–8 nm thick Cs₄PbBr₆ nanosheets with orientational stacking. Importantly, such highly crystalline Cs₄PbBr₆ microplates with shale-like morphology exhibit a narrow and intense green PL emission with a 59% PL quantum yield. Moreover, the planar structure of shale-like Cs₄PbBr₆ microplates makes it easy to form a preferred orientation on a substrate, which endow them with promising potential in optoelectronic devices such as lighting and displays.

Highly luminescent shale-like Cs₄PbBr₆ microplates with hundreds of microns in lateral dimension and formed by thin nanosheets with orientational stacking.