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This is a retrospective study to investigate the results of using zolpidem and lorazepam in persons with disorders of consciousness (DoC) and to provide practical information for clinical application and further studies. The cohort included 146 patients (11 hemorrhagic stroke, 87 traumatic brain injury (TBI), 48 anoxic brain injury (ABI)) admitted to a specialized DoC rehabilitation program. A positive trial indicated a patient responded to either zolpidem or lorazepam with prominent functional improvements necessitating routine use of the medication. Non-responders had equivocal or negative (i.e., went to sleep) responses. Eleven patients with a stroke who had either medication were all non-responders. Of the remaining 135 patients, 95 received at least one medication trial. The overall positive rate was 11.6% (11/95), with 6.3% (5/79) for zolpidem and 14.0% (6/43) for lorazepam. Among TBI patients, the positive rate of the zolpidem trial (10.2%, 5/49) was slightly higher than that of the lorazepam trial (6.9%, 2/29; p > 0.05). Among ABI patients, the positive rate of the lorazepam trial (28.6%, 4/14) was significantly higher than that of the zolpidem trial (0%, 0/30; p = 0.007). Following a positive trial, most patients were continued on the medications on a regular basis before eventual discontinuation. Our results suggested the etiology of DoC, considering traumatic vs. anoxic injuries, may serve in guiding the clinical application of these medications in the treatment of DoC and in future prospective studies. We advocate for screening all patients with DoC using zolpidem and/or lorazepam.The top-ranked cross-disorder risk gene CACNA1C is strongly associated with multiple neuropsychiatric dysfunctions. In a recent series of studies, we applied a genomically informed approach and contributed extensively to the behavioral characterization of a genetic rat model haploinsufficient for the cross-disorder risk gene Cacna1c. Because deficits in processing social signals are associated with reduced social functioning as commonly seen in neuropsychiatric disorders, we focused on socio-affective communication through 22-kHz and 50-kHz ultrasonic vocalizations (USV). Specifically, we applied a reciprocal approach for studying socio-affective communication in sender and receiver by including rough-and-tumble play and playback of 22-kHz and 50-kHz USV. U0126 ic50 Here, we review the findings obtained in this recent series of studies and link them to the key features of 50-kHz USV emission during rough-and-tumble play and social approach behavior evoked by playback of 22-kHz and 50-kHz USV. We conclude that Cacna1c haploinsufficiency in rats leads to robust deficits in socio-affective communication through 22-kHz and 50-kHz USV and associated alterations in social behavior, such as rough-and-tumble play behavior.Polyhydroxybutyrate-co-hydroxyvalerate (PHBV) is considered a suitable polymer for drug delivery systems and bone tissue engineering due to its biocompatibility and biodegradability. However, the lack of bioactivity and antibacterial activity hinders its biomedical applications. In this study, mesoporous bioactive glass nanoparticles (MBGN) were incorporated into PHBV to enhance its bioactivity, while cinnamaldehyde (CIN) was loaded in MBGN to introduce antimicrobial activity. The blank (PHBV/MBGN) and the CIN-loaded microspheres (PHBV/MBGN/CIN5, PHBV/MBGN/CIN10, and PHBV/MBGN/CIN20) were fabricated by emulsion solvent extraction/evaporation method. The average particle size and zeta potential of all samples were investigated, as well as the morphology of all samples evaluated by scanning electron microscopy. PHBV/MBGN/CIN5, PHBV/MBGN/CIN10, and PHBV/MBGN/CIN20 significantly exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli in the first 3 h, while CIN releasing behavior was observed up to 7 d. Human osteosarcoma cell (MG-63) proliferation and attachment were noticed after 24 h cell culture, demonstrating no adverse effects due to the presence of microspheres. Additionally, the rapid formation of hydroxyapatite on the composite microspheres after immersion in simulated body fluid (SBF) during 7 d revealed the bioactivity of the composite microspheres. Our findings indicate that this system represents an alternative model for an antibacterial biomaterial for potential applications in bone tissue engineering.Mitophagy plays a pro-survival or pro-death role that is cellular-context- and stress-condition-dependent. In this study, we revealed that cyclovirobuxine D (CVB-D), a natural compound derived from Buxus microphylla, was able to provoke mitophagy in lung cancer cells. CVB-D-induced mitophagy potentiates apoptosis by promoting mitochondrial dysfunction. Mechanistically, CVB-D initiates mitophagy by enhancing the expression of the mitophagy receptor BNIP3 and strengthening its interaction with LC3 to provoke mitophagy. Our results further showed that p65, a transcriptional suppressor of BNIP3, is downregulated upon CVB-D treatment. The ectopic expression of p65 inhibits BNIP3 expression, while its knockdown significantly abolishes its transcriptional repression on BNIP3 upon CVB-D treatment. Importantly, nude mice bearing subcutaneous xenograft tumors presented retarded growth upon CVB-D treatment. Overall, we demonstrated that CVB-D treatment can provoke mitophagy and further revealed that the p65/BNIP3/LC3 axis is one potential mechanism involved in CVB-D-induced mitophagy in lung cancer cells, thus providing an effective antitumor therapeutic strategy for the treatment of lung cancer patients.Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza viruses (HPIVs) are leading causes of respiratory disease in young children, the elderly, and individuals of all ages with immunosuppression. Vaccination strategies against these pneumoviruses and paramyxoviruses are vast in number, yet no licensed vaccines are available. Here, we review development of Sendai virus (SeV), a versatile pediatric vaccine that can (a) serve as a Jennerian vaccine against HPIV1, (b) serve as a recombinant vaccine against HRSV, HPIV2, HPIV3, and HMPV, (c) accommodate foreign genes for viral glycoproteins in multiple intergenic positions, (d) induce durable, mucosal, B-cell, and T-cell immune responses without enhanced immunopathology, (e) protect cotton rats, African green monkeys, and chimpanzees from infection, and (f) be formulated into a vaccine cocktail. Clinical phase I safety trials of SeV have been completed in adults and 3-6-year-old children. Clinical testing of SeVRSV, an HRSV fusion (F) glycoprotein gene recombinant, has also been completed in adults.
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