Factors influencing the prognosis of patients with acute cerebral infarction who received usual care: a multicenter prospective cohort study.

[Purpose] The prognostic factors for patients with acute stroke who received usual care (mobilization ≥48 h after admission) remain unclear. This study aimed to investigate the prognostic factors that predict functional outcomes using evaluations performed immediately after onset in patients with acute cerebral infarction who received usual care from admission until discharge. [Participants and Methods] Participants with acute cerebral infarction admitted to five acute care hospitals in Tokyo and Saitama, Japan and prescribed physical therapy were included. Participants information, functional evaluations, and progress were recorded during the first physical therapy session, mobilization, and discharge. Participants who received usual care were assigned to either the good- or poor-outcome group based on the Modified Rankin Scale at discharge. [Results] In total, 161 Participants receiving usual care (mobilization ≥48 h after admission) were included. Reinfarction and the First National Institutes of Health Stroke Scale score were identified as independent predictors of functional outcome at hospital discharge in participants who received usual care (median, 22.0 d). The cutoff NIHSS score was 4. [Conclusion] Our results provided evidence that the National Institutes of Health Stroke Scale score and reinfarction are useful predictors of functional outcomes in participants who received usual care.

Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis.

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is frequently complicated with rapidly progressive-interstitial lung disease (RP-ILD). The prognosis of MDA5-DM with RP-ILD is mostly poor despite intensive treatment with a combination of high-dose glucocorticoids and single conventional immunosuppressants. It was reported that the triple therapy (high-dose glucocorticoids, cyclophosphamide and tacrolimus) was more effective than a combination of high-dose glucocorticoids and stepwise addition of immunosuppressants. In addition, the efficacy of tofacitinib 10 mg/day for MDA5-DM with RP-ILD refractory to the triple therapy was suggested. However, the effect of those therapies was evaluated only in comparison to the historical control. Moreover, more importantly, there are still refractory patients even if treated with those therapies. In this case series, we report six MDA5-DM cases with RP-ILD in which the dose of tofacitinib was increased from 10 mg to 20 mg/day due to poor response to the triple therapy, followed by tofacitinib 10 mg/day. Four of six patients improved after dose escalation of tofacitinib, while two non-responders died. All six patients developed at least one infection including five cases of cytomegalovirus reactivation, one pulmonary aspergillosis, one herpes zoster and one herpes simplex keratitis. These cases suggest that the dose escalation of tofacitinib can be an option for MDA5-DM patients refractory to 10 mg/day of tofacitinib and other immunosuppressants although the risk of infection is a concern. The risk-benefit balance of the dose escalation of tofacitinib should be carefully assessed in each case.

Evolution of the alternative AQP2 gene: Acquisition of a novel protein-coding sequence in dolphins.

Taxon-specific de novo protein-coding sequences are thought to be important for taxon-specific environmental adaptation. A recent study revealed that bottlenose dolphins acquired a novel isoform of aquaporin 2 generated by alternative splicing (alternative AQP2), which helps dolphins to live in hyperosmotic seawater. The AQP2 gene consists of four exons, but the alternative AQP2 gene lacks the fourth exon and instead has a longer third exon that includes the original third exon and a part of the original third intron. Here, we show that the latter half of the third exon of the alternative AQP2 arose from a non-protein-coding sequence. Intact ORF of this de novo sequence is shared not by all cetaceans, but only by delphinoids. However, this sequence is conservative in all modern cetaceans, implying that this de novo sequence potentially plays important roles for marine adaptation in cetaceans.

Comparison of ancillary ligand effects between 2,2'-bipyridine and 2-(2'-pyridyl)phenyl in the linkage and bridging isomerism of 5-methyltetrazolato iridium(III) and/or rhodium(III) complexes.

Several new iridium(III) and rhodium(III) complexes bearing 5-methyltetrazolate (MeCN4(-)) have been prepared, and their structures in the crystals and in solution have been determined by X-ray analysis and by NMR spectroscopy, respectively. In the crystals of the mononuclear complexes, κN(2)-coordination of MeCN4(-) was observed when the ancillary ligand was 2,2'-bipyridine (bpy): [Cp*M(bpy)(MeCN4-κN(2))]PF6 (Cp* = η(5)-C5Me5; M = Ir: 1 and Rh: 2), while the corresponding complexes with 2-(2'-pyridyl)phenyl (ppy(-)) were confirmed to have the κN(1)-coordination of MeCN4(-): [Cp*M(ppy)(MeCN4-κN(1))] (M = Ir: 3 and Rh: 4). In solution, the Ir(III) complexes (1 and 3) were robust enough to maintain their molecular structures, but the Rh(III) complexes (2 and 4) existed as an equilibrium mixture of the κN(1)- and κN(2)-isomers. In addition to the Ir(III)-Ir(III) and Rh(III)-Rh(III) homodinuclear complexes bridged by MeCN4(-) (5-8), the corresponding heterodinuclear Ir(III)-Rh(III) complexes (9-12) were prepared using the mononuclear Ir(III) complexes (1 and 3) as precursors. The molecular structures of these dinuclear complexes were also characterised. Interestingly, both of the heterodinuclear complexes comprised of Cp*M(bpy)(2+) and Cp*M'(ppy)(+) fragments, [Cp*M(bpy)(µ-MeCN4)M'(ppy)Cp*](PF6)2 (M = Ir, M' = Rh: 10 and M = Rh, M' = Ir: 11), exhibited selective crystallisation of a specific µ-κN(1)(M'-ppy):κN(3)(M-bpy) isomer. In solution, the dinuclear complexes with a Rh-N(MeCN4) bond and more than one positive charge (6 and 9-11) showed a dissociation equilibrium, while monocationic MeCN4-bridged complexes (7, 8 and 12) were inactive for dissociation. Furthermore, the heterodinuclear complexes of 9-12, as well as the Rh(III)-Rh(III) complex of 8, exhibited a bridging isomerisation, which would proceed via a η(2):η(2)-intermediate without dissociation of Cp*M(bpy or ppy) fragments.