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Abstract AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4−/− mice (KO) due to stenosis of Silvio’s aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4−/− mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.

Peptidergic systems show promise as targets for fighting tumors. While some peptides encourage the growth and spread of tumor cells and angiogenic mechanisms, others display antitumor properties. As such, peptide ligands and receptor antagonists could be used as antitumor agents alone or in conjunction with chemotherapy or radiotherapy. Peptide receptor antagonists can counteract the oncogenic effects of specific peptides by inducing apoptosis in various types of tumor cells, hindering cancer cell migration and inhibiting angiogenesis. Peptides and peptide receptor antagonists are not currently used in clinical practice as antitumor agents. Still, aprepitant, a neurokinin 1 receptor antagonist, is a promising candidate due to its ability to promote apoptosis in many cancer cells. However, to utilize aprepitant as an anticancer agent, the dosage must be increased and administered for a more extended period. Moving beyond current protocols for aprepitant’s use as an antiemetic is essential. Additionally, a common anticancer strategy with aprepitant is possible regardless of cancer cell type. Finally, combining aprepitant with chemotherapy or radiotherapy is encouraged.

Strategic regulatory development is essential to ensure that new innovations in nanotechnology-enabled health products (NHPs) successfully reach the market and benefit patients. Currently, the lack of specific regulatory guidelines for NHPs is considered one of the primary causes of the so-called “valley of death” in these products, impacting both current and future advancements. In this study, we have implemented a methodology to anticipate key trends in NHP development and compare them with the current regulatory landscape applicable to NHPs. This methodology relies on Horizon Scanning, a tool commonly used by policymakers to foresee future needs and proactively shape a regulatory framework tailored to those needs. Through the application of this methodology, different trends in NHP have been identified, notably NHPs for drug delivery and dental applications. Furthermore, the most disruptive elements involve NHPs that are multicomposite and multifunctional, harnessing nano-scale properties to combine therapeutic and diagnostic purposes within a single product. When compared with the regulatory landscape, current regulations are gradually adapting to accommodate emerging trends, with specific guidelines being developed. However, for the most disruptive elements, multicomposite and multifunctional NHPs, their novelty still poses significant regulatory challenges, requiring a strategic development of guidelines by regulatory agencies to ensure their safe and effective integration into healthcare practices. This study underscores the importance of proactive regulatory planning to bridge the gap between NHP innovation and market implementation.

The lack of specific regulatory guidelines for nanotechnology-enabled health products (NHPs) is hampering development and patient access to these innovative technologies. Namely, there is an urgent need for harmonized regulatory definitions and classification systems that allow establishing a standardized framework for NHPs regulatory assessment. In this work, a novel classification system for NHPs is proposed. This classification can be applied for sorting nano-based innovations and regulatory guidelines according to the type of NHPs they address. Said methodology combines scientific and regulatory principles and it is based on the following criteria: principal mode of action, chemical composition, medical purpose and nanomanufacturing approach. This classification system could serve as a useful tool to sensor the state of the art of NHPs which is particularly useful for regulators to support strategy development of regulatory guidelines. Additionally, this tool would also allow manufacturers of NHPs to align their development plans with their applicable guidelines and standards and thus fulfill regulators expectations.

IntroductionThe protection of children is a major driver of behavior among those in charge of their care. We evaluated whether compliance with preventive measures against SARS-CoV-2 infection among adults living with children was different from that of those not living with them, in 2020.MethodsWe used the COSMO-SPAIN (N = 867) and the nationally representative ENE-COVID (N = 29,926) surveys to estimate prevalence of compliance (95% confidence interval). Logistic model based standardization methods were applied to estimate standardized prevalence differences (SPrD) to the overall distribution of age, sex, education, history of COVID-19, and residence of other >60 yrs in the household.ResultsWe observed that adults living with children more frequently avoided bars (SPrDENE−COVID: 4.2%; 95% CI: 2.3–6.1), crowded places (SPrDCOSMO: 8.0%; 95% CI: 0.6–15.1) and did not use public transportation (SPrDENE−COVID: 4.9%; 95% CI: 3.0–6.7). They were also more worried about work and family conciliation (SPrDCOSMO: 12.2%; 95% CI: 4.8–19.5) and about closure of education centers (SPrDCOSMO: 26.5%; 95% CI: 19.4–33.6).DiscussionIn general, adults living with children adopted slightly more frequently social distancing measures.

Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins) in cancer development. Anticancer therapeutic strategies targeting the opioid peptidergic system and the main research lines to be developed regarding the topic reviewed are suggested. There is much to investigate about opioid peptides and cancer: basic information is scarce, incomplete, or absent in many tumors. This knowledge is crucial since promising anticancer strategies could be developed alone or in combination therapies with chemotherapy/radiotherapy.

Atrial flutter with 1:1 atrioventricular conduction is a cardiac arrhythmia difficult to diagnose, fatal in many cases, and unmanageable with drug therapy. A number of 17 patients presenting with this disease was studied. A percentage of 70.6 % presented with throbbings, 64.7 % with syncope and important symptoms such as dizziness, sweating, and angina pectoris. The episode was solved with the use of antiarrythmic agents by endovenous route or electrical cardioversion. Ten patients had associated cardiovascular diseases such as arterial hypertension, ischemic heart disease, and aortic stenosis. During the follow-up 5 patients were controlled with the use of antiarrythmic drugs. Eleven patients underwent electrophysiologic studies with diagnostic or therapeutic purposes. When the drugs failed to be effective or the crisis of 1:1 atrial flutter was execrable for the patient, an electrical fulguration of the flutter focus (five cases) was performed. Two patients needed antiarrythmic agents even after the procedure and are now asymptomatic. Three cases with nonsuccessful ablation of the focus or associated atrial fibrillation underwent a fulguration of the atrioventricular node. All patients had a satisfactory evolution. This entity is poorly tolerated presenting a great deal of symptoms and the diagnosis and prevention with drugs is very difficult with no pharmacologic therapeutic possibilities.

El flutter auricular con conducción auriculoventricular 1:1 es una arritmia cardiaca difícil de diagnosticar, fatal en muchos casos y rebelde al tratamiento medicamentoso. Se estudiaron 17 pacientes con esta entidad. El 70,6 % presentó palpitaciones, el 64,7 % síncope y el resto síntomas importantes como mareos, sudoración y angina. El episodio se yuguló con antiarrítmicos endovenosos o cardioversión eléctrica. Diez pacientes tenían enfermedades cardiovasculares asociadas como hipertensión arterial, cardiopatía isquémica y estenosis aórtica. En el seguimiento cinco pacientes fueron controlados con fármacos antiarrítmicos. A once se les realizaron estudios electrofisiológicos con objetivos diagnóstico o terapéuticos. Cuando los fármacos fueron inefectivos o la crisis de flutter auricular 1:1 ominosa para el paciente, se realizó fulguración eléctrica del foco del flutter (cinco casos), dos de ellos necesitaron antiarrítmicos, aún después del procedimiento y se han mantenido asintomáticos. A los tres casos con ablación del foco no exitosa o asociación de una fibrilación auricular se les fulguró el nodo auriculoventricular. Todos evolucionaron bien. Esta entidad es mal tolerada, muy sintomática de difícil diagnóstico y prevención con drogas, con posibilidades terapéuticas no farmacológicas. Atrial flutter with 1:1 atrioventricular conduction is a cardiac arrhythmia difficult to diagnose, fatal in many cases, and unmanageable with drug therapy. A number of 17 patients presenting with this disease was studied. A percentage of 70.6 % presented with throbbings, 64.7 % with syncope and important symptoms such as dizziness, sweating, and angina pectoris. The episode was solved with the use of antiarrythmic agents by endovenous route or electrical cardioversion. Ten patients had associated cardiovascular diseases such as arterial hypertension, ischemic heart disease, and aortic stenosis. During the follow-up 5 patients were controlled with the use of antiarrythmic drugs. Eleven patients underwent electrophysiologic studies with diagnostic or therapeutic purposes. When the drugs failed to be effective or the crisis of 1:1 atrial flutter was execrable for the patient, an electrical fulguration of the flutter focus (five cases) was performed. Two patients needed antiarrythmic agents even after the procedure and are now asymptomatic. Three cases with nonsuccessful ablation of the focus or associated atrial fibrillation underwent a fulguration of the atrioventricular node. All patients had a satisfactory evolution. This entity is poorly tolerated presenting a great deal of symptoms and the diagnosis and prevention with drugs is very difficult with no pharmacologic therapeutic possibilities.