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Neuroblastoma is the most common extracranial malignant tumor of childhood, accounting for 15% of all pediatric cancer deaths. Despite significant advances in our understanding of neuroblastoma biology, five-year survival rates for high-risk disease remain less than 50%, highlighting the importance of identifying novel therapeutic targets to combat the disease. MYCN amplification is the most frequent and predictive molecular aberration correlating with poor outcome in neuroblastoma. N-Myc is a short-lived protein primarily due to its rapid proteasomal degradation, a potentially exploitable vulnerability in neuroblastoma. AF1q is an oncoprotein with established roles in leukemia and solid tumor progression. It is normally expressed in brain and sympathetic neurons and has been postulated to play a part in neural differentiation. However, no role for AF1q in tumors of neural origin has been reported. In this study, we found AF1q to be a universal marker of neuroblastoma tumors. Silencing AF1q in neuroblastoma cells caused proteasomal degradation of N-Myc through Ras/ERK and AKT/GSK3β pathways, activated p53 and blocked cell cycle progression, culminating in cell death via the intrinsic apoptotic pathway. Moreover, silencing AF1q attenuated neuroblastoma tumorigenicity in vivo signifying AF1qs importance in neuroblastoma oncogenesis. Our findings reveal AF1q to be a novel regulator of N-Myc and potential therapeutic target in neuroblastoma.

Background: Household air pollution adversely affects human health and the environment, yet more than 40% of the world still depends on solid cooking fuels. The House Air Pollution Intervention Network (HAPIN) randomized controlled trial is assessing the health effects of a liquefied petroleum gas (LPG) stove and 18-month supply of free fuel in 3,200 households in rural Guatemala, India, Peru, and Rwanda. Aims: We conducted formative research in Guatemala to create visual messages that support the sustained, exclusive use of LPG in HAPIN intervention households. Method: We conducted ethnographic research, including direct observation (n = 36), in-depth (n = 18), and semistructured (n = 6) interviews, and 24 focus group discussions (n = 96) to understand participants' experience with LPG. Sixty participants were selected from a pilot study of LPG stove and 2-months of free fuel to assess the acceptability and use of LPG. Emergent themes were used to create visual messages based on observations and interviews in 40 households; messages were tested and revised in focus group discussions with 20 households. Results: We identified 50 codes related to household air pollution and stoves; these were reduced into 24 themes relevant to LPG stoves, prioritizing 12 for calendars. Messages addressed fear and reluctance to use LPG; preference of wood stoves for cooking traditional foods; sustainability and accessibility of fuel; association between health outcomes and household air pollution; and the need for inspirational and aspirational messages. Discussion: We created a flip chart and calendar illustrating themes to promote exclusive LPG use in HAPIN intervention households.

Sentinel surveillance plays a critical role in monitoring pathogen circulation, assessing potential threats for species conservation, and evaluating the risk of spillover to human populations. This study provides a comprehensive exploration of helminth parasites in the Mediterranean-distributed hedgehog species Atelerix algirus in Mallorca, Balearic Islands. Using an integrated approach that combines necropsies and morphological and molecular identifications using the COI gene, we identified 11 helminth taxa in 135 hedgehogs, representing half of those that died at the local wildlife hospital in Mallorca between 2019 and 2022. We report an overall A. cantonensis prevalence of 11.5% and confirm the first case of a subclinical neuroangiostrongyliasis infection in a wildlife host. Infection prevalences over the year revealed that only two species, the nematode A. cantonensis and the cestode Mathevotaenia sp., had a seasonal pattern, with most A. cantonensis cases occurring in autumn and, to a lesser extent, Mathevotaenia sp. cases in winter. This pattern is probably due to the higher abundance and greater activity of snails and slugs (intermediate hosts) during these seasons, with important implications for public health and strategies for prevention of neuroangiostrongyliasis. Other key findings include a high prevalence (88.1%) of the lungworm Crenosoma striatum and detection of the acanthocephalan Moniliformis saudi for the first time in A. algirus. We anticipate that our study will facilitate surveillance efforts and clarify species identities in future studies. Given the lethal effects of A. cantonensis infection in hedgehogs, further studies are needed to evaluate the threat this parasite represents to European wildlife.

Bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment are among the most common morbidities affecting preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, it is currently uncertain how BPD contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are involved in interorgan communication in diverse pathological processes. ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) is pivotal in inflammasome assembly and activation of inflammatory response. We assessed expression profiles of the alveolar macrophage (AM) markers CD11b, CD11c, and CD206 as well as ASC in EVs isolated from the plasma of preterm infants at risk for BPD at 1 week of age. We found that infants on higher fraction of inspired oxygen therapy (HO2⩾30%) had increased concentrations of AM-derived EV-ASC compared with infants on lower fraction of inspired oxygen (LO2<30%). To assess the function of these EVs, we performed adoptive transfer experiments by injecting them into the circulation of newborn mice. We discovered that mice that received EVs from infants on HO2 had increased lung inflammation, decreased alveolarization, and disrupted vascular development, the hallmarks of BPD. Importantly, these EVs crossed the blood–brain barrier, and the EVs from infants on HO2 caused inflammation, reduced cell survival, and increased cell death, with features of pyroptosis and necroptosis in the hippocampus. These results highlight a novel role for AM-derived EV-ASC in mediating the lung-to-brain cross-talk that is critical in the pathogenesis of BPD and brain injury and identify potential novel targets for preventing and treating BPD and brain injury in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Localized cutaneous leishmaniasis (LCL) is a serious public health problem in Southern Mexico. Six species of Phlebotominae (Diptera: Psychodidae) have been found to be infected with Leishmania (Leishmania) mexicana, the causative agent of LCL in the region. However, little is known about the biology and potential participation of Psathyromyia cratifer in the Leishmania transmission cycle in Mexico, and the Americas. The present study provides evidence of temporal infection caused by Leishmania in Psathyromyia cratifer as well as data on its population dynamics in a LCL endemic area during the well-known transmission cycle of Leishmania in Southern Mexico. Methodology/Principal findings: Individual specimens of Psathyromyia cratifer were collected in four sites over the course of five months (from November 2020 through March 2021) using animal-baited, human-baited, and light traps. The temporal activity pattern (month + hour) of Psathyromyia cratifer was assessed along with its relationship with environmental variables. Moreover, Leishmania DNA and blood meals were analyzed and detected in female sand flies. This evidenced an infection rate ranging from 8% to 83%, and the record of Homo sapiens and Ototylomys phyllotis as blood hosts of this sand fly species. High abundances of these sand flies in human-baited traps were recorded which revealed the marked anthropophilic behavior of Psathyromyia cratifer. As regards the transmission dynamics of the parasite within the region, it was observed that the potential highest epidemiological risk for Leishmania transmission by Psathyromyia cratifer occurred during the months of January and March. Conclusion: This is the first contribution ever made to both the population dynamic and the temporal Leishmania prevalence patterns in Psathyromyia cratifer. The resulting findings suggest that this sand fly specimen is the sixth potential vector of L. (L.) mexicana in Southern Mexico. Nonetheless, various biology, behavior, and ecology strands are yet to be addressed. The latter, to determine the role it plays in the transmission dynamics of the parasite within the region, and other areas of the country. Author summary: Psathyromyia cratifer is a species of Neotropical dipteran belonging to one of the most medically important groups worldwide wise, the Phlebotomine sand flies. Some sand fly species transmit Leishmania parasites to humans, which leads to one of the most common but neglected tropical diseases known as leishmaniasis. The data on life history traits and involvement of this species in the transmission of Leishmania, is yet limited. This research furnishes evidence about population dynamics and temporal Leishmania infection patterns in female Pa. cratifer specimens collected from four sites part of a transmission area in Yucatan, Mexico. Our findings suggest that females of this species are attracted to and feed on humans as well as an important Leishmania reservoir in the region. Although not all sites recorded infected individuals, the infection and temporal abundance of this species in most sites, were similar. Our findings suggest that this species could be a suspected vector of the parasite in the region, however, it is important to continue with incrimination studies that incorporate other sources of evidence. [ABSTRACT FROM AUTHOR]