An ALK2 inhibitor, BLU-782, prevents heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease driven by gain-of-function variants in activin receptor-like kinase 2 (ALK2), the most common variant being ALK2R206H. In FOP, ALK2 variants display increased and dysregulated signaling through the bone morphogenetic protein (BMP) pathway resulting in progressive and permanent replacement of skeletal muscle and connective tissues with heterotopic bone, ultimately leading to severe debilitation and premature death. Here, we describe the discovery of BLU-782 (IPN60130), a small-molecule ALK2R206H inhibitor developed for the treatment of FOP. A small-molecule library was screened in a biochemical ALK2 binding assay to identify potent ALK2 binding compounds. Iterative rounds of structure-guided drug design were used to optimize compounds for ALK2R206H binding, ALK2 selectivity, and other desirable pharmacokinetic properties. BLU-782 preferentially bound to ALK2R206H with high affinity, inhibiting signaling from ALK2R206H and other rare FOP variants in cells in vitro without affecting signaling of closely related homologs ALK1, ALK3, and ALK6. In vivo efficacy of BLU-782 was demonstrated using a conditional knock-in ALK2R206H mouse model, where prophylactic oral dosing reduced edema and prevented cartilage and heterotopic ossification (HO) in both muscle and bone injury models. BLU-782 treatment preserved the normal muscle-healing response in ALK2R206H mice. Delayed dosing revealed a short 2-day window after injury when BLU-782 treatment prevented HO in ALK2R206H mice, but dosing delays of 4 days or longer abrogated HO prevention. Together, these data suggest that BLU-782 may be a candidate for prevention of HO in FOP.

Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy: A Multicenter Pilot Randomized Clinical Trial.

Importance: Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge. Objective: To examine the effect of 48 and 72 hours of whole-body hypothermia after mild HIE on cerebral magnetic resonance (MR) biomarkers. Design, Setting, and Participants: This open-label, 3-arm RCT was conducted between October 31, 2019, and April 28, 2023, with masked outcome analysis. Participants were neonates at 6 tertiary neonatal intensive care units in the UK and Italy born at or after 36 weeks' gestation with severe birth acidosis, requiring continued resuscitation, or with an Apgar score less than 6 at 10 minutes after birth and with evidence of mild HIE on modified Sarnat staging. Statistical analysis was per intention to treat. Interventions: Random allocation to 1 of 3 groups (1:1:1) based on age: neonates younger than 6 hours were randomized to normothermia or 72-hour hypothermia (33.5 °C), and those 6 hours or older and already receiving whole-body hypothermia were randomized to rewarming after 48 or 72 hours of hypothermia. Main Outcomes and Measures: Thalamic N-acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by cerebral MR imaging and thalamic spectroscopy between 4 and 7 days after birth using harmonized sequences. Results: Of 225 eligible neonates, 101 were recruited (54 males [53.5%]); 48 (47.5%) were younger than 6 hours and 53 (52.5%) were 6 hours or older at randomization. Mean (SD) gestational age and birth weight were 39.5 (1.1) weeks and 3378 (380) grams in the normothermia group (n = 34), 38.7 (0.5) weeks and 3017 (338) grams in the 48-hour hypothermia group (n = 31), and 39.0 (1.1) weeks and 3293 (252) grams in the 72-hour hypothermia group (n = 36). More neonates in the 48-hour (14 of 31 [45.2%]) and 72-hour (13 of 36 [36.1%]) groups required intubation at birth than in the normothermic group (3 of 34 [8.8%]). Ninety-nine neonates (98.0%) had MR imaging data and 87 (86.1%), NAA data. Injury scores on conventional MR biomarkers were similar across groups. The mean (SD) NAA level in the normothermia group was 10.98 (0.92) mmol/kg wet weight vs 8.36 (1.23) mmol/kg wet weight (mean difference [MD], -2.62 [95% CI, -3.34 to -1.89] mmol/kg wet weight) in the 48-hour and 9.02 (1.79) mmol/kg wet weight (MD, -1.96 [95% CI, -2.66 to -1.26] mmol/kg wet weight) in the 72-hour hypothermia group. Seizures occurred beyond 6 hours after birth in 4 neonates: 1 (2.9%) in the normothermia group, 1 (3.2%) in the 48-hour hypothermia group, and 2 (5.6%) in the 72-hour hypothermia group. Conclusions and Relevance: In this pilot RCT, whole-body hypothermia did not improve cerebral MR biomarkers after mild HIE, although neonates in the hypothermia groups were sicker at baseline. Safety and efficacy of whole-body hypothermia should be evaluated in RCTs. Trial Registration: ClinicalTrials.gov Identifier: NCT03409770.

Sustainable and Eco-Friendly DLC Fabrication for Replacing Chrome on a Gravure Cylinder Surface.

This paper evaluates the potential of diamond-like carbon (DLC) as a durable surface protection to replace the chromium (Cr) layer, which is traditionally applied to gravure print cylinders and other components through a galvanic electroplating process. The fabrication of DLC is more eco-friendly and could reduce the environmental hazard posed by hexavalent chromium in liquid form that is used in Cr application and better adhere to environmental regulations. This could encourage businesses to bring the DLC fabrication process in-house, sharing resources such as materials, labor, and equipment, to help reduce costs. Four DLC variants (standard DLC, A-DLC, S-DLC, and organic silica) and chrome were analyzed and tested for their surface properties and durability. Data suggest that both standard DLC and S-DLC had higher surface free energy, allowing for good ink wetting on the surface when compared to chrome. In addition, the standard DLC and S-DLC surfaces are generally smoother than the chrome, resulting in lower relative hydrophilicity and allowing for easier removal of ink in the nonimage regions with the doctor blade. The elcometer adhesion test demonstrated that the bond strength of the DLC variants to their base layer was comparable to the bond strength of chrome, indicating that the adhesion strength of the two materials was similar. Furthermore, in the abrasion test, the wear on the standard DLC surface and the corresponding wear on the lamella tip of the metal doctor blades were notably lower than that observed on chrome. This distinction is particularly evident in each of the test trials, specifically run 1, which involved 2,000,000 wiping actions of a metal doctor blade in the presence of abrasive TiO2 ink pigments. Statistical analysis on standard DLC versus chrome suggests that DLC fabrication is effective and durable on plain and patterned surfaces. Therefore, from a sustainable and eco-friendly perspective, standard DLC and S-DLC would be good alternative durable surfaces for print cylinders and other components used in various industries due to superior wear resistance properties.

Pancreatic Insufficiency, Digestive Enzyme Supplementation, and Postnatal Growth in Preterm Babies.

BACKGROUND: Optimising postnatal growth facilitates better long-term neonatal neurodevelopmental outcomes. Early postnatal growth is often hindered by a variety of factors unique to the extrauterine environment and digestive immaturity both contributing to reduced enteral feed tolerance during the first few days and weeks after birth. Preterm infants display varying levels of pancreatic insufficiency that are related to gestational age and providing digestive enzyme supplementation, may be one way in which to improve postnatal growth in enterally fed preterm babies. SUMMARY: In this review, we explore which exocrine pancreatic enzymes are deficient in preterm babies, the methods by which exocrine pancreatic function is measured, potential avenues by which digestive enzyme replacement might improve postnatal growth failure, and which babies might benefit most from this intervention. KEY MESSAGES: Pancreatic exocrine function exhibits developmental immaturity in extremely preterm infants and may contribute to postnatal growth failure. Stool elastase is a simple, non-invasive method of assessing pancreatic function in preterm infants. Available evidence does not currently support routine use of digestive enzyme supplementation in preterm infants.

A Scoping Review on Gender/Sex Differences in COVID-19 Vaccine Intentions and Uptake in the United States.

OBJECTIVE: To explore the empirical literature on gender/sex differences in vaccine acceptance among U.S.-based adults and adolescents in approximately the first 2 years of the pandemic. DATA SOURCE: Embase, Medline, PsycINFO, EBSCO, CINAHL, Web of Science. STUDY INCLUSION AND EXCLUSION CRITERIA: Peer-reviewed studies conducted in the U.S. with those aged 12 and older, published in English before January 12, 2022, examining the relationship between gender/sex on COVID-19 vaccine intentions and/or uptake. DATA EXTRACTION: Three authors screened studies and extracted data. DATA SYNTHESIS: Univariate and multivariate results are summarized. RESULTS: A total of 53 studies met inclusion criteria (48 intentions, 7 uptake), using mostly cross-sectional designs (92.5%) and non-random sampling (83.0%). The majority of studies supported men's greater intentions to vaccinate compared to women, and men's greater vaccine uptake in univariate analyses, but most multivariate analyses supported no gender differences in uptake. Few studies examined gender beyond binary categories (women/men), highlighting a gap in the studies inclusive of transgender or gender-diverse populations in analyses. CONCLUSION: Women may have been more hesitant to get the vaccine than men early in the pandemic, but these differences may not translate to actual behavior. Future research should include non-binary/transgender populations, explore the gender-specific reasons for hesitancy and differences by sub-populations, utilize more rigorous designs, and test gender-sensitive public health campaigns to mitigate vaccine concerns.

Clinical outcomes of Staphylococcus capitis isolation from neonates, England, 2015-2021: a retrospective case-control study.

OBJECTIVE: Staphylococcus capitis, a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day mortality for the detection of S. capitis versus other CoNS species. METHODS: In this retrospective case-control study, we included hospitalised infants with any CoNS species detected from a normally sterile body site up to 90 days of age. We linked English laboratory reports from the Second Generation Surveillance System database, mortality data from the Personal Demographics Service, and neonatal unit admissions from the National Neonatal Research Database. In primary analysis, multivariable logistic regression was used, with two co-primary outcomes: survival to discharge and death within 30 days of positive specimen date. Sensitivity analyses using multiply imputed datasets followed. RESULTS: We identified 16 636 CoNS episodes relating to 13 745 infants. CoNS episodes were highest among infants born extremely preterm (22-27 weeks) and with extremely low birth weight (400-999 g). In primary analysis, there were no differences in survival to discharge (p=0.71) or 30-day mortality (p=0.77) between CoNS species. In sensitivity analyses, there were no differences in outcomes between infection with four of the most common CoNS species (Staphylococcus epidermidis, S. capitis, Staphylococcus haemolyticus and Staphylococcus warneri) but the remaining CoNS species were at higher risk of adverse outcomes when treated in aggregate. CONCLUSION: Infants with S. capitis detected from sterile site samples did not experience significant differences in either survival to discharge or 30-day mortality compared with infants with detection of other common CoNS species.

The effect of rotational velocity on rotational traction across a range of artificial turf surface systems.

Mechanical testing by sporting governing bodies ensures artificial turf surfaces conform with performance standards. Rotational traction is measured using two equivalent devices: a rotational traction tester (RTT) and a lightweight rotational traction tester (LRTT). The devices differ in target rotational velocity; 72 deg/s for the RTT and 30 deg/s for the LRTT. The purpose of this study was to investigate the influence of rotational velocity on peak torque during rotational traction testing. An automated rotational traction tester examined nine rotational velocities between 10 and 210 deg/s, and ten artificial turf surface systems with a range of performance infill materials, infill depths and carpet specifications. Rotations at 10 deg/s produced the lowest peak torques on nine of the ten surfaces. Infill materials with intrinsic viscoelastic properties produced significantly higher peak torques at higher rotational velocities, whereas less elastic infill materials saw no significant increase in peak torque. A mean difference in peak torque of 2.6 Nm was found between the target velocities of the RTT and LRTT. The results support the synchronisation of target velocities for the RTT and LRTT. During standards testing, trials completed below a particular velocity should be repeated to negate velocity effects on peak torque.

Public Health Students' Perspectives on the Future of Public Health Education.

Our society faces an uncertain future and the field of public health will have an important role to play in shaping this future. This article introduces the special issue The Future of Health Education & Behavior which is focused on perspectives and research led by student authors. Our call for papers encouraged student perspectives that envisioned, challenged, and critiqued the future for health education and behavior. We summarize the articles included in this issue which cover topics such as gaps or future directions for public health training programs, perspectives on pressing issues facing our society, and empirical articles on critical public health topics. Many of the articles in the special issue point boldly to a future that more directly and critically confronts systems of oppression and moves away from a traditional emphasis on individual-level behaviors. These articles can help our field evolve and adapt to fully address the most pressing issues of our time.

Trends in coagulase-negative staphylococci (CoNS), England, 2010-2021.

Objective: To review the epidemiology of coagulase-negative staphylococci (CoNS) in England over the recent 12 year period. Methods: Laboratory-confirmed CoNS reported from sterile sites in patients in England to the UK Health Security Agency (UKHSA) between 2010 and 2021 were extracted from the national laboratory database and analysed. Results: Overall, 668 857 episodes of CoNS were reported. Unspeciated CoNS accounted for 56 % (374 228) of episodes, followed by Staphylococcus epidermidis (26 %; 174 050), S. hominis (6.5 %; 43 501) and S. capitis (3.9 %; 25 773). Unspeciated CoNS increased by 8.2 % (95 % CI, 7.1-9.3) annually between 2010 and 2016, then decreased annually by 6.4 % (95 % CI: -4.8 to -7.9) until 2021. Speciated CoNS increased by 47.6 % (95 % CI, 44.5-50.9) annually between 2010 and 2016 and increased annually by 8.9 % (95 % CI: 5.1 to 12.8) until 2021. Antimicrobial susceptibility profiles differed by species. Conclusions: Reports of CoNS from normally sterile body sites in patients in England increased between 2010 and 2016 and remained stable between 2017 and 2021. There has been a striking improvement in species-level identification of CoNS in recent years. Monitoring trends in CoNS epidemiology is crucial for development of observational and clinical intervention studies on individual species.

How frequent is routine use of probiotics in UK neonatal units?

OBJECTIVE: There is a lack of UK guidance regarding routine use of probiotics in preterm infants to prevent necrotising enterocolitis, late-onset sepsis and death. As practices can vary, we aimed to determine the current usage of probiotics within neonatal units in the UK. DESIGN AND SETTING: Using NeoTRIPS, a trainee-led neonatal research network, an online survey was disseminated to neonatal units of all service levels within England, Scotland, Northern Ireland and Wales in 2022. Trainees were requested to complete one survey per unit regarding routine probiotic administration. RESULTS: 161 of 188 (86%) neonatal units responded to the survey. 70 of 161 (44%) respondents routinely give probiotics to preterm infants. 45 of 70 (64%) use the probiotic product Lactobacillus acidophilus NCFM/Bifidobacterium bifidum Bb-06/B. infantis Bi-26 (Labinic™). 57 of 70 (81%) start probiotics in infants ≤32 weeks' gestation. 33 of 70 (47%) had microbiology departments that were aware of the use of probiotics and 64 of 70 (91%) had a guideline available. Commencing enteral feeds was a prerequisite to starting probiotics in 62 of 70 (89%) units. The majority would stop probiotics if enteral feeds were withheld (59 of 70; 84%) or if the infant was being treated for necrotising enterocolitis (69 of 70; 99%). 24 of 91 (26%) units that did not use probiotics at the time of the survey were planning to introduce them within the next 12 months. CONCLUSIONS: More than 40% of all UK neonatal units that responded are now routinely administering probiotics, with variability in the product used. With increased probiotic usage in recent years, there is a need to establish whether this translates to improved clinical outcomes.

Police Violence: Reducing the Harms of Policing Through Public Health-Informed Alternative Response Programs.

Police violence is a public health issue in need of public health solutions. Reducing police contact through public health-informed alternative response programs separate from law enforcement agencies is one strategy to reduce police perpetration of physical, emotional, and sexual violence. Such programs may improve health outcomes, especially for communities that are disproportionately harmed by the police, such as Black, Latino/a, Native American, and transgender communities; nonbinary residents; people who are drug users, sex workers, or houseless; and people who experience mental health challenges. The use of alternative response teams is increasing across the United States. This article provides a public health rationale and framework for developing and implementing alternative response programs informed by public health principles of care, equity, and prevention. We conclude with recommendations for public health researchers and practitioners to guide inquiries into policing as a public health problem and expand the use of public health-informed alternative response programs. (Am J Public Health. 2023;113(S1):S37-S42. https://doi.org/10.2105/AJPH.2022.307107).

Antiracism and Community-Based Participatory Research: Synergies, Challenges, and Opportunities.

Structural racism causes stark health inequities and operates at every level of society, including the academic and governmental entities that support health research and practice. We argue that health research institutions must invest in research that actively disrupts racial hierarchies, with leadership from racially marginalized communities and scholars. We highlight synergies between antiracist principles and community-based participatory research (CBPR), examine the potential for CBPR to promote antiracist research and praxis, illustrate structural barriers to antiracist CBPR praxis, and offer examples of CBPR actions taken to disrupt structural racism. We make recommendations for the next generation of antiracist CBPR, including modify health research funding to center the priorities of racially marginalized communities, support sustained commitments and accountability to those communities by funders and research institutions, distribute research funds equitably across community and academic institutions, amplify antiracist praxis through translation of research to policy, and adopt institutional practices that support reflection and adaptation of CBPR to align with emergent community priorities and antiracist practices. A critical application of CBPR principles offers pathways to transforming institutional practices that reproduce and reinforce racial inequities. (Am J Public Health. 2023;113(1):70-78. https://doi.org/10.2105/AJPH.2022.307114).

Fear of Deportation and Associations with Mental Health Among Michigan Residents of Middle Eastern & North African Descent.

Anti-immigrant rhetoric and immigration policy enforcement in the United States over the last 2 decades has increased attention to fear of deportation as a determinant of poor health. We describe its association with mental health outcomes among Middle East and North African (MENA) residents of Michigan. Using a convenience sample of MENA residents in Michigan (n = 397), we conducted bivariate and multiple variable regression to describe the prevalence of deportation worry and examine the relationship between deportation worry and depressive symptoms (PHQ-4 scores). We found that 33% of our sample worried a loved one will be deported. Deportation worry was associated with worse mental health (p < 0.01). Immigration policies are health policies and deportation worry impacts mental and behavioral health.

Associations of attitudes and social norms with experiences of intimate partner violence among married adolescents and their husbands in rural Niger: a dyadic cross-sectional study.

BACKGROUND: Prior cross-sectional research suggests that both men's and women's attitudes towards intimate partner violence (IPV) are predictive of women's IPV experience, although this can vary greatly by context. In general, women who have experienced IPV are likely to report attitudes accepting of it. Men who perpetrate IPV may also report attitudes accepting of it, although some research has found that there is not always an association. Studies that investigate these dynamics often conflate attitudes with social norms, or use attitudes as a proxy for social norms, given that valid measures on social norms are usually lacking. Here we conduct a secondary data analysis to ask how are men's and women's IPV-related attitudes associated with women's reports of IPV and how are men's and women's perceived social norms associated with women's reports of IPV. METHODS: Dyadic data were collected from a representative sample of married adolescent girls and their husbands in 48 rural villages of the Dosso region of Niger (N = 1010). Assessments included logistic regression analyses of husbands' and wives' reports of individual attitudes towards IPV, and social norms based on husbands' and wives' perceptions of their communities' beliefs related to gender roles and acceptability of IPV. RESULTS: Eight percent of women in this sample reported IPV. We found that, consistent with other research, wives who have reported IPV are more likely to report attitudes in support of IPV, while for husbands whose wives report IPV, that relationship is insignificant. On the other hand, husbands who report that people in their community believe there are times when a woman deserves to be beaten are more likely to have perpetrated IPV, while for wives there is no association between the community norm and IPV reporting. Finally, wives who report that people in their community hold inequitable gender norms in general are more likely to have experienced IPV, while for husbands, community gender norms are not predictive of whether their wives have reported IPV. CONCLUSIONS: Our results are evidence that IPV prevention interventions focused solely on individual attitudes may be insufficient. Targeting and assessment of social norms are likely critical to advancing understanding and prevention of IPV.

Controlling unequal surface energy results caused by test liquids: the case of UV/O3 Treated PET.

Ultraviolet/ozone (UV/O3) treatment has been reported to be an effective method to modify properties such as wettability, adhesion or adsorption of plastic surfaces. The change in the surface is measured by contact angle analysis, which employs liquids and their surface tensions (ST) to estimate the surface energy (SE). We found two different practices in the scientific community: (1) the majority of researchers adopted the ST value of liquids from the literature, while (2) other researchers conducted real-time measurements in the lab under ambient conditions prior to SE estimation. To the best of our knowledge, there is no study that compares the difference between the two practices. One study was found to show different SE methods generating unequal SE values for the same substrate. However, there was no definitive conclusion backed by general thermodynamics rules. In this study, we presented (1) a statistical significance test that showed the literature and experimental ST values are significantly different, and studied (2) the effect of different liquid pairs on the SE estimation for UV/O3 treated poly(ethylene terephthalate) (PET) substrate. Modification techniques such as atmospheric pressure plasma or chemical modification were studied previously to examine PET's wettability and the SE. The UV/O3 treatment was studied to improve adhesion and to modify its chemical properties for adsorption. In contrast, we studied (3) the effect of UV/O3 on wettability at different timeframes and addressed (4) how to control unequal SE based on a method that was refined on a rigorous thermodynamic three-phase system. It must be noted that this method can be generalized to other types of solid surfaces to estimate thermodynamically self-consistent SE values. This work also provides (5) a web-based calculator that complements computational findings available to the readership in the data availability section.

Possible In Utero Transmission of SARS-CoV-2 and Severe Respiratory Disease in a Preterm Infant.

Severe acute respiratory syndrome coronavirus 2 infections are uncommon in newborn infants. This report describes possible in utero transmission of the B.1.1.7 (alpha) variant in a preterm infant born at 31 weeks' gestational age who presented with severe respiratory disease. The infant was treated with high-frequency oscillatory ventilation, antiviral medications, and corticosteroids and transitioned to noninvasive respiratory support on day 33. By day 63, she was off positive pressure support and breathing room air and she was discharged from the hospital on day 70. She demonstrated normal growth and development at a 6-month follow-up visit. Placental histopathology revealed placentitis characterized by loss of intervillous spaces resulting from fibrin deposition and inflammatory cell infiltration. Optimum management strategies for treating infants with severe acute respiratory syndrome coronavirus 2 infection have yet to be determined.