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Background: Rural populations in the USA demonstrate a high degree of vaccine hesitancy, particularly surrounding COVID-19 vaccines. Objectives: Following the successful implementation of a COVID-19 vaccination campaign with a rural-based health system in New York state, the goal of this project was to develop a large community-academic partnership with multiple rural-based community organisations to implement an additional COVID-19 vaccination campaign tailored to rural audiences. Methods: Campaign materials were created and refined with several collaborators across multiple ruralbased hospitals, health centres and community organisations. Campaign effectiveness was examined through an analysis of New York state vaccination data. Lessons learned: This project shows that larger community-academic partnerships involving multiple organisations can be achieved and utilised to address complex public health issues such as vaccine hesitancy. Conclusions: Larger and longer-term community-academic partnerships can be leveraged to combat a wide range of public health issues and enable a personalised focus on specific communities.

Previous studies found an impact of language familiarity on face recognition in 9- and 12-month-olds. Own race faces are better recognized when associated with native language, whereas for other race faces, it is with non-native language. The aim of this study is to investigate if language familiarity can also influence abstract pattern recognition. We tested 9- to 12-month-old monolingual infants with a visual paired-comparison task. During a 30-s familiarization phase, infants were shown an image of abstract patterns associated with an auditory soundtrack of a speaker reciting a story either in their native (French) or in a non-native language (German). After the familiarization, the familiar and a new abstract pattern were displayed side by side for the recognition test. We found a significant preference for the novel object in the native language condition but not in the non-native condition. These results suggest that language familiarity effects on infant memory are not specific to faces but also influence, on a larger scale, how infants process their immediate visual environment.

The World Health Organization Global Hearts initiative (HEARTS) and technical package aim to improve the primary health care management of hypertension and other risk factors for cardiovascular disease at the population level. This study describes the first HEARTS implementation pilot project in Guatemala’s Ministry of Health (MOH) primary health care system. This pilot began in April 2022 in six primary health care facilities in three rural indigenous municipalities. The project consisted of HEARTS-aligned strategies adapted to enhance program sustainability in Guatemala. Outcomes were defined using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. The primary reach outcome was treatment count, defined as the absolute number of patients per month receiving medication treatment for hypertension. The primary effectiveness outcomes were mean systolic blood pressure (BP), mean diastolic BP, and proportion of patients with BP control (

Abstract One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models accurately mimicking the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside neurons that synthesize catecholamines. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkinson’s, Alzheimer’s and apparently healthy aging individuals. However, this brain pigment is not taken into consideration in current animal models because common laboratory species, such as rodents, do not produce neuromelanin. Here we generate a tissue-specific transgenic mouse, termed tgNM, that mimics the human age-dependent brain-wide distribution of neuromelanin within catecholaminergic regions, based on the constitutive catecholamine-specific expression of human melanin-producing enzyme tyrosinase. We show that, in parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model could help explore new research avenues in brain aging and neurodegeneration.

Abstract Morphogenesis requires building stable macromolecular structures from highly dynamic proteins. Muscles are anchored by long-lasting integrin adhesions to resist contractile force. However, the mechanisms governing integrin diffusion, immobilization, and activation within developing tissues remain elusive. Here, we show that actin polymerization-driven membrane protrusions form nanotopographies that enable strong adhesion at Drosophila muscle attachment sites (MASs). Super-resolution microscopy reveals that integrins assemble adhesive belts around Arp2/3-dependent actin protrusions, forming invadosome-like structures with membrane nanotopographies. Single protein tracking shows that, during MAS development, integrins become immobile and confined within diffusion traps formed by the membrane nanotopographies. Actin filaments also display restricted motion and confinement, indicating strong mechanical connection with integrins. Using isolated muscle cells, we show that substrate nanotopography, rather than rigidity, drives adhesion maturation by regulating actin protrusion, integrin diffusion and immobilization. These results thus demonstrate that actin-polymerization-driven membrane protrusions are essential for the formation of strong integrin adhesions sites in the developing embryo, and highlight the important contribution of geometry to morphogenesis.

Abstract Partially autonomous vehicles can help minimize human errors. However, being free from some driving subtasks can result in a low vigilance state, which can affect the driver’s attention towards the road. The present study first tested whether drivers of partially autonomous vehicles would benefit from the addition of auditory versions of the messages presented in variable message signs (VMS), particularly, when they find themselves in a monotonous driving situation. A second aim was to test whether the addition of auditory messages would also produce an indirect effect on the driver’s vigilance, improving performance on other driving subtasks not related to the message processing. Forty-three volunteers participated in a driving simulator study. They completed two tasks: (a) a VMS task, where they had to regain manual control of the car if the VMS message was critical, and (b) a car-following task, where they had to pay attention to the preceding car to respond to occasional brake events. Behavioral and EEG data were registered. Overall, results indicated that the addition of audio messages helped drivers process VMS information more effectively and maintain a higher level of vigilance throughout the driving time. These findings would provide useful information for the development of partially automated vehicles, as their design must guarantee that the driver remains attentive enough to assume control when necessary.

Our previous study discussed crystallin family induction in an experimental rat model of retinal detachment. Therefore, we attempted to evaluate the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, as well as its association with the intrinsically neuroprotective protein Fas-apoptotic inhibitory molecule 2 (FAIM2). Separation of retina and RPE was induced in rat and mouse eyes by subretinal injection of hyaluronic acid. Retinas were subsequently analyzed for the presence αA-crystallin (HSPB4) and αB-crystallin (HSPB5) proteins using immunohistochemistry and immunoblotting. Photoreceptor death was analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and cell counts. The 661W cells subjected to FasL were used as a cell model of photoreceptor degeneration to assess the mechanisms of the protective effect of αA-crystallin and its dependence on its phosphorylation on T148. We further evaluated the interaction between FAIM2 and αA-crystallin using a co-immunoprecipitation assay. Our results showed that α-crystallin protein levels were rapidly induced in response to retinal detachment, with αA-crystallin playing a particularly important role in protecting photoreceptors during retinal detachment. Our data also show that the photoreceptor intrinsically neuroprotective protein FAIM2 is induced and interacts with α-crystallins following retinal detachment. Mechanistically, our work also demonstrated that the phosphorylation of αA-crystallin is important for the interaction of αA-crystallin with FAIM2 and their neuroprotective effect. Thus, αA-crystallin is involved in the regulation of photoreceptor survival during retinal detachment, playing a key role in the stabilization of FAIM2, serving as an important modulator of photoreceptor cell survival under chronic stress conditions.

Abstract The Neolithic (i.e., farming and stockbreeding) spread from the Near East across Europe since about 9000 years before the common era (BCE) until about 4000 yr BCE. It followed two main routes, namely a sea route along the northern Mediterranean coast and an inland one across the Balkans and central Europe. It is known that the dispersive behavior of farmers depended on geography, with longer movements along the Mediterranean coast than along the inland route. In sharp contrast, here we show that for both routes the percentage of farmers who interbred with hunter-gatherers and/or acculturated one of them was strikingly the same (about 3.6%). Therefore, whereas the dispersive behavior depended on the proximity to the Mediterranean sea, the interaction behavior (incorporation of hunter-gatherers) did not depend on geographical constraints but only on the transition in the subsistence economy (from hunting and gathering to farming) and its associated way of life. These conclusions are reached by analyzing the clines of haplogroup K, which was virtually absent in hunter-gatherers and the most frequent mitochondrial haplogroup in early farmers. Similarly, the most frequent Y-chromosome Neolithic haplogroup (G2a) displays an inland cline that agrees with the percentage of interbreeding reported above.

Abstract Background To our knowledge, only one study has examined the association between glucose variability (GV) and mortality in the elderly population with diabetes. GV was assessed by HbA1c, and a J-shaped curve was observed in the relationship between HbA1c thresholds and mortality. No study of GV was conducted during the COVID-19 pandemic and its lockdown. This study aims to evaluate whether GV is an independent predictor of all-cause mortality in patients aged 75 years or older with and without COVID-19 who were followed during the first year of the COVID-19 pandemic and its lockdown measures. Methods This was a retrospective cohort study of 407,492 patients from the AGED-MADRID dataset aged 83.5 (SD 5.8) years; 63.2% were women, and 29.3% had diabetes. GV was measured by the coefficient of variation of fasting plasma glucose (CV-FPG) over 6 years of follow-up (2015–2020). The outcome measure was all-cause mortality in 2020. Four models of logistic regression were performed, from simple (age, sex) to fully adjusted, to assess the effect of CV-FPG on all-cause mortality. Results During follow-up, 34,925 patients died (14,999 women and 19,926 men), with an all-cause mortality rate of 822.3 per 10,000 person-years (95% confidence interval (CI), 813.7 to 822.3) (739 per 10,000; 95% CI 728.7 to 739.0 in women and 967.1 per 10,000; 95% CI 951.7 to 967.2 in men). The highest quartile of CV-FPG was significantly more common in the deceased group (40.1% vs. 23.6%; p

The objective of this paper was to analyze the contents of opinion and news articles related to the city of Boulders sugar-sweetened beverage excise tax campaigns in Boulders only local newspaper. We searched for articles in The Daily Camera related to the sugar-sweetened beverage tax, published from January 2016 to December 2018. We conducted a content analysis, categorizing 152 relevant articles by type, authors, and frames (pro, anti, neutral) on the basis of the preponderance of arguments, themes, and use of evidence. The majority of articles were opinion (n=92) versus news (n=60). Most articles were pro-frame (n=78) versus anti-frame (n=37) and neutral frame (n=37). Pro-frame articles were more likely to cite evidence in support of arguments or the professional credentials/experience of the authors. The most frequent pro-frame themes were health, benefits of the revenues, equity, and unethical tactics of the industry. The most frequent anti-frame themes were economic consequences, claims that the measure was confusing, government overreach, and purported ineffectiveness of taxes. The leveraging of local issues by the beverage industry was observed. Themes identified in the news regarding Boulders successful sugar-sweetened beverage tax may appear in future sugar-sweetened beverage policy campaigns and should be anticipated.