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Madalina Patron,1,2,* Mattias Neset,1,2,* Mariia Mielkozorova,2,* Daniel G Bisson,1,3,* Marie Vigouroux,4 Juan Pablo Cata,5,6 Pablo M Ingelmo,4,7,8 Jean A Ouellet,1,3 Lisbet Haglund,1,3,* Svetlana V Komarova1,2,* 1Shriners Hospital for Children, Montreal, Canada; 2Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Canada; 3Orthopaedic Research Laboratory, Department of Surgery, McGill University, Montreal, Canada; 4Edwards Family Interdisciplinary Center for Complex Pain, Montreal Children’s Hospital, Montreal, QC, Canada; 5Department of Anesthesia and Perioperative Medicine, The University of Texas – MD Anderson Cancer Center, Houston, TX, USA; 6Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA; 7Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada; 8Research Institute, McGill University Health Center, Montreal, Canada*These authors contributed equally to this workCorrespondence: Svetlana V Komarova, Shriners Hospital for Children, 1003 Decarie Boulevard, Montreal, Quebec, H4A 0A9, Canada, Tel +1 514 282-7153, Email svetlana.komarova@mcgill.caPurpose: Pain is an understudied physiological effect of spaceflight. Changes in inflammatory and tissue degradation markers are often associated with painful conditions. Our aim was to evaluate the changes in markers associated with tissue deterioration after a short-term spaceflight.Patients and Methods: Plasma levels of markers for systemic inflammation and tissue degeneration markers were assessed in two astronauts before and within 24 h after the 17-day Axiom Space AX-1 mission.Results: After the spaceflight, C-reactive protein (CRP) was reduced in both astronauts, while INFγ, GM-CSF, TNFα, BDNF, and all measured interleukins were consistently increased. Chemokines demonstrated variable changes, with consistent positive changes in CCL3, 4, 8, 22 and CXCL8, 9, 10, and consistent negative change in CCL8. Markers associated with tissue degradation and bone turnover demonstrated consistent increases in MMP1, MMP13, NTX and OPG, and consistent decreases in MMP3 and MMP9.Conclusion: Spaceflight induced changes in the markers of systemic inflammation, tissue deterioration, and bone resorption in two astronauts after a short, 17-day, which were often consistent with those observed in painful conditions on Earth. However, some differences, such as a consistent decrease in CRP, were noted. All records for the effect of space travel on human health are critical for improving our understanding of the effect of this unique environment on humans.Keywords: spaceflight, astronaut, cytokine, interleukin, chemokine, bone turnover

The mitochondrial calcium uniporter channel (MCUC) mediates mitochondrial calcium entry, regulating energy metabolism and cell death. Although several MCUC components have been identified, the molecular basis of mitochondrial calcium signaling networks and their remodeling upon changes in uniporter activity have not been assessed. Here, we map the MCUC interactome under resting conditions and upon chronic loss or gain of mitochondrial calcium uptake. We identify 89 high-confidence interactors that link MCUC to several mitochondrial complexes and pathways, half of which are associated with human disease. As a proof-of-concept, we validate the mitochondrial intermembrane space protein EFHD1 as a binding partner of the MCUC subunits MCU, EMRE, and MCUB. We further show a MICU1-dependent inhibitory effect of EFHD1 on calcium uptake. Next, we systematically survey compensatory mechanisms and functional consequences of mitochondrial calcium dyshomeostasis by analyzing the MCU interactome upon EMRE, MCUB, MICU1, or MICU2 knockdown. While silencing EMRE reduces MCU interconnectivity, MCUB loss-of-function leads to a wider interaction network. Our study provides a comprehensive and high-confidence resource to gain insights into players and mechanisms regulating mitochondrial calcium signaling and their relevance in human diseases., (© 2024. The Author(s).)

The threat of viral influenza infections has sparked research efforts to develop vaccines that can induce broadly protective immunity with safe adjuvants that trigger robust immune responses. Here, we demonstrate that subcutaneous or intranasal delivery of a seasonal trivalent influenza vaccine (TIV) adjuvanted with the Quillaja brasiliensis saponin-based nanoparticle (IMXQB) increases the potency of TIV. The adjuvanted vaccine (TIV-IMXQB) elicited high levels of IgG2a and IgG1 antibodies with virus-neutralizing capacity and improved serum hemagglutination inhibition titers. The cellular immune response induced by TIV-IMXQB suggests the presence of a mixed Th1/Th2 cytokine profile, antibody-secreting cells (ASCs) skewed toward an IgG2a phenotype, a positive delayed-type hypersensitivity (DTH) response, and effector CD4 + and CD8 + T cells. After challenge, viral titers in the lungs were significantly lower in animals receiving TIV-IMXQB than in those inoculated with TIV alone. Most notably, mice vaccinated intranasally with TIV-IMXQB and challenged with a lethal dose of influenza virus were fully protected against weight loss and lung virus replication, with no mortality, whereas, among animals vaccinated with TIV alone, the mortality rate was 75%. These findings demonstrate that TIV-IMXQB improved the immune responses to TIV, and, unlike the commercial vaccine, conferred full protection against influenza challenge., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Silveira, Rivera-Patron, Deshpande, Sienra, Checa, Moreno, Chabalgoity, Cibulski and Baz.)

National estimates of hospitalization diagnoses and costs were determined using the 2016 HCUP Kids' Inpatient Database. Children and youth with autism were hospitalized over 45,000 times at over $560 million in costs and 260,000 inpatient days. The most frequent principal diagnoses for hospitalizations of children and youth with autism were epilepsy, mental health conditions, pneumonia, asthma, and gastrointestinal disorders, which resulted in almost $200 million in costs and 150,000 inpatient days. Mental health diagnoses accounted for 24.8% of hospitalizations, an estimated $82 million in costs, and approximately 94,000 inpatient days. Children and youth with autism were more likely hospitalized for epilepsy, mental health diagnoses, and gastrointestinal disorders, and less likely for pneumonia and asthma compared to other children and youth., (©AAIDD.)

Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multiproteomic approach to demonstrate the regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca 2+ /H + exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca 2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca 2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Objectives: The objective of this study was to characterize the changes in timeliness and completeness of disease case reporting in Texas in response to an increasing number of foodborne illnesses and high-consequence infectious disease investigations and the Texas Department of State Health Services' new state-funded epidemiologist (SFE) program., Methods: We extracted electronic disease case reporting data on 42 conditions from 2012 through 2016 in all local health department (LHD) jurisdictions. We analyzed data on median time for processing reports and percentage of complete reports across time and between SFE and non-SFE jurisdictions using Mann-Whitney t tests and z scores., Results: The median time of processing improved from 13 days to 10 days from 2012 to 2016, and the percentage of disease case reports that were complete improved from 19.6% to 27.7%. Most reports were for foodborne illnesses; both timeliness (11 to 7 days) and completeness (20.9% to 23.5%) improved for these reports., Conclusions: Disease reporting improvements in timeliness and completeness were associated with the SFE program and its enhancement of epidemiologic capacity. SFEs were shown to improve surveillance metrics in LHDs, even in jurisdictions with a high volume of case reports. Adding epidemiologist positions in LHDs produces a tangible outcome of improved disease surveillance.

Objective: Hurricane evacuation is one of the strategies employed by emergency management and other agencies to reduce morbidity and mortality associated with hurricanes. However, factors associated with residents' evacuation decision-making have been inconsistent. In this study, we conducted a statistical meta-analysis to identify factors associated with hurricane evacuation as well as moderators of the evacuation decision., Methods: A systematic literature search identified 36 studies published between 1999 and 2018. Pooled estimates were calculated using random-effects models, and heterogeneity across studies was checked using both Q and I 2 statistics. Meta-regression methods were used to identify moderators. Publication bias was assessed using both visual (funnel plots) and statistical methods., Results: Mobile home residence, perception of risk, female sex, and Hispanic ethnicity were statistically associated with hurricane evacuation, while geographic region modified the relationship between Hispanic race and evacuation., Conclusions: Agencies responsible for preparedness may utilize these findings to identify specific population sub-groups for hurricane evacuation communication and other interventions. Future studies should consider statistical interactions and explore opportunities for research translation to emergency officials.

Objectives: In response to increasing caseloads of foodborne illnesses and high consequence infectious disease investigations, the Texas Department of State Health Services (DSHS) requested funding from the Texas Legislature in 2013 and 2015 for a new state-funded epidemiologist (SFE) program., Methods: Primary cross-sectional survey data were collected from 32 of 40 local health departments (LHDs) via an online instrument and analyzed to quantify roles, responsibilities, and training of epidemiologists in Texas in 2017 and compared to similar state health department assessments., Results: Sixty-six percent of SFEs had epidemiology-specific training (eg, master's in public health) compared to 45% in state health department estimates. For LHDs included in this study, the mean number of epidemiologists per 100 000 was 0.73 in medium LHDs and 0.46 in large LHDs. SFE positions make up approximately 40% of the LHD epidemiology workforce of all sizes and 56% of medium-sized LHD epidemiology staff in Texas specifically., Conclusions: Through this program, DSHS increased epidemiology capacity almost twofold from 0.28 to 0.47 epidemiologists per 100 000 people. These findings suggest that capacity funding programs like this improve epidemiology capacity in local jurisdictions and should be considered in other regions to improve general public health preparedness and epidemiology capacity.

Background: This study seeks to determine what handwashing facilities are available to workers, predominantly in the manufacturing and service industries, to find out if their workplace has the appropriate resources to conduct proper handwashing and how that affects handwashing satisfaction., Methods: This cross-sectional study surveyed U.S. adult workers ( N = 241) on their workplace handwashing equipment and facilities. The associations between demographic characteristics, consistent handwashing, and handwashing satisfaction were evaluated using Fisher's exact test., Findings: Eighty-eight percent of respondents reported consistent handwashing. Pulling a handle to exit the restroom was negatively associated with handwashing satisfaction ( p = .004) and having difficulty with an automatic faucet or dispenser was negatively marginally significant in its association with handwashing consistency ( p = .10)., Conclusion/applications to Practice: Greater understanding of the available equipment in workplace restroom facilities and how to improve selection and use of that equipment may improve workers' handwashing experiences.