Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction.

Reactive oxygen species (ROS), a by-product of aerobic life, are highly reactive molecules with unpaired electrons. The excess of ROS leads to oxidative stress, instigating the peroxidation of polyunsaturated fatty acids (PUFA) in the lipid membrane through a free radical chain reaction and the formation of the most bioactive aldehyde, known as 4-hydroxynonenal (4-HNE). 4-HNE functions as a signaling molecule and toxic product and acts mainly by forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and lipids. The mitochondria have been implicated as a site for 4-HNE generation and adduction. Several studies clarified how 4-HNE affects the mitochondria's functions, including bioenergetics, calcium homeostasis, and mitochondrial dynamics. Our research group has shown that 4-HNE activates mitochondria apoptosis-inducing factor (AIFM2) translocation and facilitates apoptosis in mice and human heart tissue during anti-cancer treatment. Recently, we demonstrated that a deficiency of SOD2 in the conditional-specific cardiac knockout mouse increases ROS, and subsequent production of 4-HNE inside mitochondria leads to the adduction of several mitochondrial respiratory chain complex proteins. Moreover, we highlighted the physiological functions of HNE and discussed their relevance in human pathophysiology and current discoveries concerning 4-HNE effects on mitochondria.

Bilingual Supports for Clinicians: Where Do We Go From Here?

Purpose The purpose of this study was to identify and define the support needs of bilingual speech-language pathologists working in one urban school district and to investigate the experiences of the clinicians engaged in a professional learning community (PLC) format within their public school system. Method Twenty-three bilingual speech-language pathologists met in a PLC over the course of 5 months, with a total of four sessions that were a mix of in person and virtual. The participants engaged in group discussions and activities alongside their peers to address self-identified areas of support and need. Additionally, initial and final focus group and exit slip data following the PLC were collected to inform the discussion topics of the PLC and gather final impressions. Constant comparative analysis was utilized to analyze focus group and exit slip data. Results When looking across the experiences of the clinicians in the district, the three themes that emerged from the data were systemic obstacles, professional obstacles, and supports. The three themes that emerged from the speech-language pathologists' experiences in the PLC included their positive experiences, the challenges with participation, and the positive outcomes from exposure to new techniques and earning platforms. Conclusion The findings of this study suggest that bilingual clinicians benefit from a PLC model when addressing specific areas of need.

How Funerals Accomplish Family: Findings From a Mass-Observation Study.

The article analyses how potentially conflicting frames of grief and family operate in a number of English funerals. The data come from the 2010 Mass-Observation directive "Going to Funerals" which asked its panel of correspondents to write about the most recent funeral they had attended. In their writings, grief is displayed through conventional understandings of family. Drawing on Randall Collins, we show how the funeral stratifies mourners into family or nonfamily, a stratification accomplished-by family and nonfamily-through both outward display and inner feeling. The funerals described were more about a very traditional notion of family than about grief; family trumped grief, or at least provided the frame through which grief could be written about; and perceptions of "family" prompted emotions which in turn defined family. The funerals were portrayed as a distinct arena privileging family over the fluid and varied personal attachments highlighted in both the new sociology of personal life and in the concept of disenfranchised grief.

Effects of Treatment Delay on Efficacy of Tecovirimat Following Lethal Aerosol Monkeypox Virus Challenge in Cynomolgus Macaques.

Background: Tecovirimat (ST-246) is being developed as an antiviral therapeutic for smallpox for use in the event of an accidental or intentional release. The last reported case of smallpox was 1978 but the potential for use of variola virus for biowarfare has renewed interest in smallpox antiviral therapeutics. Methods: Cynomolgus macaques were challenged with a lethal dose of monkeypox virus (MPXV) by aerosol as a model for human smallpox and treated orally with 10 mg/kg tecovirimat once daily starting up to 8 days following challenge. Monkeys were monitored for survival, lesions, and clinical signs of disease. Samples were collected for measurement of viremia by quantitative real-time polymerase chain reaction, and for white blood cell counts. Results: Survival in animals initiating treatment up to 5 days postchallenge was 100%. In animals treated starting 6, 7, or 8 days following challenge, survival was 67%, 100%, and 50%, respectively. Treatment initiation up to 4 days following challenge reduced severity of clinical manifestations of infection. Conclusions: Tecovirimat treatment initiated up to 8 days following a lethal aerosol MPXV challenge improves survival and, when initiated earlier than 5 days after challenge, provides protection from clinical effects of disease, supporting the conclusion that it is a promising smallpox antiviral therapeutic candidate.

Funerals against death.

While anthropological studies in non-Western societies show how funerals protect the community from the threat of death, sociological studies of British funerals have so far focused on meanings for the private family. The article reports on results from a Mass Observation directive - the first British study to focus specifically on the entire funeral congregation - and shows how attendees experience the contemporary life-centred funeral as a symbolic conquest of death. While the eulogy's accuracy is important, even more so - at least for some - is its authenticity, namely that the speaker has personal knowledge of the deceased. Whereas Davies analyses the power of professionally delivered ritual words against death, our data reveals how admired is the courage exercised by non-professionals in speaking against death, however faltering their words. Further, the very presence of a congregation whose members have known the deceased in diverse ways embodies a configurational eulogy, which we term relationships against death. We thus argue that funerals symbolically conquer death not only through words delivered by ritual specialists, but also through those who knew the deceased congregating and speaking.