Polyanionic Receptors for Carboxylates in Water.

Receptors for carboxylate anions have many possible biomedical applications, including mimicry of the vancomycin group of antibiotics.  However, binding carboxylates in water, the biological solvent, is highly challenging due to the hydrophilicity of these polar anions.  Here we report, for the first time, the recognition of simple carboxylates such as acetate and formate in water by synthetic receptors with charge-neutral binding sites.  The receptors are solubilised by polyanionic side-chains which, remarkably, do not preclude anion binding.  The tricyclic structures feature two identical binding sites linked by polyaromatic bridges, capable of folding into closed, twisted conformations.  This folding is hypothesised to preorganise the structures for anion recognition, mimicking the process which generates many protein binding sites.  The architecture is suitable for elaboration into enclosed structures with potential for selective recognition of biologically relevant carboxylates.

Operative Treatment of Acromial and Scapular Spine Fracture Nonunions Complicating Reverse Total Shoulder Arthroplasty.

BACKGROUND: Fractures of the acromion and spine can have a major impact on the outcome of reverse shoulder arthroplasty (RSA) with respect to pain, motion, and function. Reports on internal fixation for these fractures are isolated to small series or case reports with variable outcomes. The purpose of this study was to report on the outcome of open reduction and internal fixation (ORIF) of acromion or spine fractures encountered before or after RSA and describe our evolution of fixation techniques. METHODS: Between 2011 and 2023, 22 fractures or nonunions of the acromion or spine of the scapula underwent ORIF at a single institution and were followed for a minimum of 1 year. In 16 shoulders, fractures occurred after RSA, whereas 5 shoulders underwent ORIF prior to RSA. One shoulder had undergone prior failed ORIF elsewhere and revision ORIF was performed at our institution. There were 10 males and 12 females with a mean age of 67 (SD=15.1) years. Fixation strategies included single (n=11) and double plate fixation (n=11). Kruskal-Wallis one-way analyses of variance were used to analyze continuous variables and Chi-square tests employed for categorical variables. RESULTS: Of the 5 fractures treated with ORIF pre-RSA, 1 shoulder suffered an additional fracture medial to the hardware and 1 required additional bone grafting for incomplete union at the time of RSA. These 5 shoulders all underwent RSA uneventfully, but one fracture experienced late displacement of the scapular spine nonunion, leading to plate removal. Of the 16 post-RSA ORIF shoulders, radiographic union was confirmed in 14 and substantial residual inferior angulation identified in 3. New fractures occurred after ORIF in 5 shoulders. For patients who underwent ORIF after RSA, pain scores improved from a mean of 8 to 1.9 points, with more modest elevation gains (58.2° to 91.3° pre- and postoperatively, respectively). CONCLUSIONS: ORIF of acromion and scapular spine fractures or nonunions in the setting of RSA have the potential to lead to union. When these fractures and nonunions are encountered prior to RSA, ORIF allows for uneventful RSA implantation, but secondary displacement may occur. ORIF seems to lead to improvements in pain, but more modest improvements in motion and function. Our fixation strategy has evolved to (1) dual plating, (2) spanning the whole length of the spine with one of the plates, (3) use of hook features under the acromion or os trigonum if possible, and (4) liberal use of bone graft.

Management of the peri-intubation period in patients with pulmonary arterial hypertension and respiratory failure.

PURPOSE OF REVIEW: The endotracheal intubation of patients with pulmonary arterial hypertension (PAH) in respiratory distress is a highly morbid procedure that can precipitate hemodynamic collapse. Here we review our strategy for confronting this difficult clinical situation. RECENT FINDINGS: There are no clinical trials that explore best practices in the management of patients with PAH and respiratory failure. Here we provide a practical approach to respiratory support, inopressor and pulmonary vasodilator selection, hemodynamic considerations, point-of-care ultrasound monitoring, and endotracheal intubation in patients with PAH in respiratory failure.

Apolipoprotein L1 (APOL1) renal risk variant-mediated podocyte cytotoxicity depends on African haplotype and surface expression.

Homozygous Apolipoprotein L1 (APOL1) variants G1 and G2 cause APOL1-mediated kidney disease, purportedly acting as surface cation channels in podocytes. APOL1-G0 exhibits various single nucleotide polymorphisms, most commonly haplotype E150K, M228I and R255K ("KIK"; the Reference Sequence is "EMR"), whereas variants G1 and G2 are mostly found in a single "African" haplotype background ("EIK"). Several labs reported cytotoxicity with risk variants G1 and G2 in KIK or EIK background haplotypes, but used HEK-293 cells and did not verify equal surface expression. To see if haplotype matters in a more relevant cell type, we induced APOL1-G0, G1 and G2 EIK, KIK and EMR at comparable surface levels in immortalized podocytes. G1 and G2 risk variants (but not G0) caused dose-dependent podocyte death within 48h only in their native African EIK haplotype and correlated with K+ conductance (thallium FLIPR). We ruled out differences in localization and trafficking, except for possibly greater surface clustering of cytotoxic haplotypes. APOL1 surface expression was required, since Brefeldin A rescued cytotoxicity; and cytoplasmic isoforms vB3 and vC were not cytotoxic. Thus, APOL1-EIK risk variants kill podocytes in a dose and haplotype-dependent manner (as in HEK-293 cells), whereas unlike in HEK-293 cells the KIK risk variants did not.

Novidades nas Convolvulaceae da flora amazônica

Summary During a study of the Neotropical Convolvulaceae several novelties were found in Amazonia. Among these records is a new conbination (Ipomoea leprieurii D. Austin), two new species (Ipomoea carajasensis D. Austin and I. cavalcantei D Austin), and two South American taxa previously unknown in Amazonia (Operculina sericantha (Miguel) v. Ooststroom and Merremia wurdackii Austin & Staples).

Resumo Durante um estudo da Convolculaceae na zona neotropical, encontraram-se algumas novidades na Amazônia Legal. Entre essas, estão um nome novo (Ipomoea leprieurii D. Austin), duas espécies novas de (I. carajasense D. Austin e I. cavalcantei D Austin), e duas espécies antes desconhecidas na Amazônia (Operculina sericantha (Miguel) v. Ooststroom e Merremia wurdackii Austin & Staples).