The associating behavior of a series of monodisperse poly(2-(dimethylamino)ethyl methacrylate)-b-poly(methacrylic acid) (PDMAEMA-b-PMAA) ampholytic diblock copolymers has been studied in water in the dilute regime as a function of pH and salt concentration. Dynamic light scattering (DLS) has been used to monitor the association behavior and transmission electron microscopy (TEM) to visualize the morphology of the aggregates. At and around the isoelectric point (IEP) of the ampholytic diblocks, strong electrostatic interactions occur and lead to the formation of insoluble complexes between negatively and positively charged blocks. These electrostatic interactions can be screened by the addition of salt, which leads to the partial dissolution of the material, according to Debye screening. For samples containing a major PDMAEMA block, spherical micelles are observed below the IEP. These micelles consist of a PMAA core surrounded by a water-soluble protonated PDMAEMA corona. At and above the IEP, these samples are insoluble. Spherical micelles are also formed below the IEP for samples containing a minor PDMAEMA block. These copolymers are insoluble at and around the IEP, whereas solubility is observed above the IEP with formation of aggregates of remarkable morphologies, including hollow spheres and complex compartmentalized aggregates. This aggregation is most favorable at high pH, and it cannot be accounted for only by electrostatic interaction between oppositely charged blocks. Indeed, short-range hydrophobic interaction between uncharged PDMAEMA blocks seems to play a key role in the association process. This is emphasized by quaternized poly(2-(dimethylamino)ethyl methacrylate)-b-poly(methacrylic acid) ampholytic copolymers which are carrying a permanent positive charge on the aminated monomeric units and do not form these particular aggregates.
The pathophysiologic mechanisms of Guillain-Barré syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. OBJECTIVE To identify specific clinical features of GBS associated with ZIKV infection. DESIGN, SETTING, AND PARTICIPANTS During the ZIKV epidemic in Puerto Rico, prospective and retrospective strategies were used to identify patients with GBS who had neurologic illness onset in 2016 and were hospitalized at all 57 nonspecialized hospitals and 2 rehabilitation centers in Puerto Rico. Guillain-Barré syndrome diagnosis was confirmed via medical record review using the Brighton Collaboration criteria. Specimens (serum, urine, cerebrospinal fluid, and saliva) from patients with GBS were tested for evidence of ZIKV infection by real-time reverse transcriptase-polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. In this analysis of public health surveillance data, a total of 123 confirmed GBS cases were identified, of which 107 had specimens submitted for testing; there were 71 patients with and 36 patients without evidence of ZIKV infection. Follow-up telephone interviews with patients were conducted 6 months after neurologic illness onset; 60 patients with and 27 patients without evidence of ZIKV infection participated. MAIN OUTCOMES AND MEASURES Acute and long-term clinical characteristics of GBS associated with ZIKV infection. RESULTS Of 123 patients with confirmed GBS, the median age was 54 years (age range, 4-88 years), and 68 patients (55.3%) were male. The following clinical features were more frequent among patients with GBS and evidence of ZIKV infection compared with patients with GBS without evidence of ZIKV infection: facial weakness (44 [62.0%] vs 10 [27.8%]; P < .001), dysphagia (38 [53.5%] vs 9 [25.0%]; P = .005), shortness of breath (33 [46.5%] vs 9 [25.0%]; P = .03), facial paresthesia (13 [18.3%] vs 1 [2.8%]; P = .03), elevated levels of protein in cerebrospinal fluid (49 [94.2%] vs 23 [71.9%]; P = .008), admission to the intensive care unit (47 [66.2%] vs 16 [44.4%]; P = .03), and required mechanical ventilation (22 [31.0%] vs 4 [11.1%]; P = .02). Six months after neurologic illness onset, patients with GBS and evidence of ZIKV infection more frequently reported having excessive or inadequate tearing (30 [53.6%] vs 6 [26.1%]; P = .03), difficulty drinking from a cup (10 [17.9%] vs 0; P = .03), and self-reported substantial pain (15 [27.3%] vs 1 [4.3%]; P = .03). CONCLUSIONS AND RELEVANCE In this study, GBS associated with ZIKV infection was found to have higher morbidity during the acute phase and more frequent cranial neuropathy during acute neuropathy and 6 months afterward. Results indicate GBS pathophysiologic mechanisms that may be more common after ZIKV infection.
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