Engineering spacer specificity of the Cre/loxP system.

Translational research on the Cre/loxP recombination system focuses on enhancing its specificity by modifying Cre/DNA interactions. Despite extensive efforts, the exact mechanisms governing Cre discrimination between substrates remains elusive. Cre recognizes 13 bp inverted repeats, initiating recombination in the 8 bp spacer region. While literature suggests that efficient recombination proceeds between lox sites with non-loxP spacer sequences when both lox sites have matching spacers, experimental validation for this assumption is lacking. To fill this gap, we investigated target site variations of identical pairs of the loxP 8 bp spacer region, screening 6000 unique loxP-like sequences. Approximately 84% of these sites exhibited efficient recombination, affirming the plasticity of spacer sequences for catalysis. However, certain spacers negatively impacted recombination, emphasizing sequence dependence. Directed evolution of Cre on inefficiently recombined spacers not only yielded recombinases with enhanced activity but also mutants with reprogrammed selective activity. Mutations altering spacer specificity were identified, and molecular modelling and dynamics simulations were used to investigate the possible mechanisms behind the specificity switch. Our findings highlight the potential to fine-tune site-specific recombinases for spacer sequence specificity, offering a novel concept to enhance the applied properties of designer-recombinases for genome engineering applications.

Stress factors and food purchase prioritization during the pandemic of coronavirus disease 2019.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) pandemic confinement has an impact on stress levels, which causes changes in food purchase and consumption behaviors. The objective of this study is to associate food purchase prioritization with stress level during the COVID-19 pandemic confinement. METHODS: Multicenter, observational and cross-sectional study, an online questionnaire that included data on sociodemographic variables, stress factors and food purchase prioritization was disseminated through digital platforms and social networks. RESULTS: A number of 6357 participants were included, of whom 83.6% were female, 56.3% were from the middle socioeconomic level, 71.2% had completed higher education and 78.3% had a job. At greater stress levels it was observed a higher prioritization of canned foods (Odds ratio (OR): 1.91, 95% CI: 1.56; 2.34), sweets (OR: 1.58, 95% CI: 1.06; 2.34) and flours (OR: 1.45, 95% CI: 1.25; 1.68). While lower stress levels are associated with nuts (OR: 0.75, 95% CI: 0.66; 0.85), vegetables (OR: 0.82, 95% CI: 0.72; 0.94), and fruits (OR: 0.90, 95% CI: 0.80; 1.01), after adjusting for confounders. CONCLUSIONS: There is an association between food purchase prioritization and stress level during the COVID-19 confinement. At greater stress levels, individuals purchase more food, both healthy and unhealthy. The later may have a negative impact on people's health, leading to or further aggravating malnutrition by excess and nutrition-related noncommunicable diseases.

COVID-19 vaccine hesitancy prevalence in Mexico: A systematic review and metanalysis.

Background: Vaccine hesitancy (VH) is a recognized threat to public health that undermines efforts to mitigate disease burden. This study aims to gather available evidence regarding COVID-19 VH in Mexico, estimate the prevalence of VH, and its determinants to inform policymaking in this country. Methods: Following PRISMA guidelines, a systematic review of the MEDLINE literature, articles that estimated the prevalence of COVID-19 VH in Mexico were included in the analysis to obtain a pooled estimate. We used a binomial-normal model for meta-analysis of proportions (i.e., generalized linear mixed model) to perform the metanalysis. We then performed a narrative review of COVID-19 VH in Mexican subpopulations. Results: Seven studies met inclusion criteria. We estimated a pooled prevalence of COVID-19 VH of 16 % (95 % CI: 11-23 %) in Mexico. We found an association between VH and demographic characteristics, intrinsic vaccine factors, and beliefs. Subgroup analyses from specific studies suggested that patients with clinical conditions such as breast cancer or rheumatologic diseases had a higher prevalence of VH. Conclusions: VH is a highly complex and dynamic phenomenon in Mexico. Characterizing and understanding COVID-19 vaccine hesitancy in the Mexican population helps target future policy interventions to mitigate the spread and impact of infectious diseases. The implications of VH differ among groups that may be at higher risk of severe disease, underscoring the importance of prompt research among these groups as well as targeted interventions to address VH.

Food insecurity and sociodemographic factors in Latin America during the COVID-19 pandemic.

Objective: To understand the association of food insecurity with sociodemographic factors in a sample population in Latin America during the COVID-19 pandemic. Methods: This was a multicenter cross-sectional study conducted in 10 countries in Latin America using an online survey through various digital platforms from October 14, 2020 to February 15, 2021. Statistical analysis of data was performed by applying descriptive statistics, chi-square test, and logistic regression analysis. Results: Of a total of 6 357 surveys, 58.2% of respondents experienced food security, 29.3% were slightly food insecure, 9.2% were moderately food insecure, and 3.3% were severely food insecure. Concerning the association food insecurity and sociodemographic variables, there is a significant association in the variables studied, including area of residence, education level, occupation, number of persons in the household, household with children younger than 10 years of age, and socioeconomic level. Conclusions: These findings indicate that sociodemographic factors associated with food insecurity during the COVID-19 pandemic in Latin America were rural residence; complete and incomplete basic and secondary schooling; occupation (homemaker, unemployed, and self-employed); low, medium-low, and medium socioeconomic level; household with more than four persons; and household with children younger than 10 years of age.

Differences in vocal brain areas and astrocytes between the house wren and the rufous-tailed hummingbird.

The house wren shows complex song, and the rufous-tailed hummingbird has a simple song. The location of vocal brain areas supports the song's complexity; however, these still need to be studied. The astrocytic population in songbirds appears to be associated with change in vocal control nuclei; however, astrocytic distribution and morphology have not been described in these species. Consequently, we compared the distribution and volume of the vocal brain areas: HVC, RA, Area X, and LMAN, cell density, and the morphology of astrocytes in the house wren and the rufous-tailed hummingbird. Individuals of the two species were collected, and their brains were analyzed using serial Nissl- NeuN- and MAP2-stained tissue scanner imaging, followed by 3D reconstructions of the vocal areas; and GFAP and S100ß astrocytes were analyzed in both species. We found that vocal areas were located close to the cerebral midline in the house wren and a more lateralized position in the rufous-tailed hummingbird. The LMAN occupied a larger volume in the rufous-tailed hummingbird, while the RA and HVC were larger in the house wren. While Area X showed higher cell density in the house wren than the rufous-tailed hummingbird, the LMAN showed a higher density in the rufous-tailed hummingbird. In the house wren, GFAP astrocytes in the same bregma where the vocal areas were located were observed at the laminar edge of the pallium (LEP) and in the vascular region, as well as in vocal motor relay regions in the pallidum and mesencephalon. In contrast, GFAP astrocytes were found in LEP, but not in the pallidum and mesencephalon in hummingbirds. Finally, when comparing GFAP astrocytes in the LEP region of both species, house wren astrocytes exhibited significantly more complex morphology than those of the rufous-tailed hummingbird. These findings suggest a difference in the location and cellular density of vocal circuits, as well as morphology of GFAP astrocytes between the house wren and the rufous-tailed hummingbird.

Food insecurity and sociodemographic factors in Latin America during the COVID-19 pandemic / Inseguridad alimentaria y factores sociodemográficos en América Latina durante la pandemia de COVID-19 / Insegurança alimentar e fatores sociodemográficos na América Latina durante a pandemia de COVID-19

[ABSTRACT]. Objective. To understand the association of food insecurity with sociodemographic factors in a sample popu- lation in Latin America during the COVID-19 pandemic. Methods. This was a multicenter cross-sectional study conducted in 10 countries in Latin America using an online survey through various digital platforms from October 14, 2020 to February 15, 2021. Statistical analysis of data was performed by applying descriptive statistics, chi-square test, and logistic regression analysis. Results. Of a total of 6 357 surveys, 58.2% of respondents experienced food security, 29.3% were slightly food insecure, 9.2% were moderately food insecure, and 3.3% were severely food insecure. Concerning the association food insecurity and sociodemographic variables, there is a significant association in the variables studied, including area of residence, education level, occupation, number of persons in the household, house- hold with children younger than 10 years of age, and socioeconomic level. Conclusions. These findings indicate that sociodemographic factors associated with food insecurity during the COVID-19 pandemic in Latin America were rural residence; complete and incomplete basic and secondary schooling; occupation (homemaker, unemployed, and self-employed); low, medium-low, and medium socioeco- nomic level; household with more than four persons; and household with children younger than 10 years of age.

[RESUMEN]. Objetivo. Determinar la asociación de la inseguridad alimentaria con factores sociodemográficos en una muestra de población de América Latina durante la pandemia de COVID-19. Métodos. Se llevó a cabo un estudio transversal multicéntrico en diez países de América Latina mediante una encuesta en línea a través de diversas plataformas digitales, entre el 14 de octubre del 2020 y el 15 de febrero del 2021. Se realizó un análisis estadístico de los datos usando procedimientos de estadística descriptiva, la prueba ji al cuadrado y un análisis de regresión logística. Resultados. En un total de 6 357 encuestas, el 58,2% de las personas encuestadas gozaba de seguridad ali- mentaria, el 29,3% tenía una inseguridad alimentaria leve, el 9,2% una inseguridad alimentaria moderada y el 3,3% una inseguridad alimentaria grave. Por lo que respecta a la asociación entre la inseguridad alimentaria y las variables sociodemográficas, hay una asociación significativa para algunas de las variables estudiadas, como la zona de residencia, el nivel de estudios, la actividad laboral, el número de personas en el hogar, el hogar con menores de 10 años y el nivel socioeconómico. Conclusiones. Estos resultados indican que los factores sociodemográficos asociados a la inseguridad alimentaria durante la pandemia de COVID-19 en América Latina fueron la residencia en zonas rurales; la edu- cación primaria y secundaria completa o no; la actividad laboral (trabajo doméstico, personas desempleadas y trabajadores autónomos); el nivel socioeconómico bajo, medio bajo, y medio; el hogar con más de cuatro personas; y el hogar con menores de 10 años.

[RESUMO]. Objetivo. Compreender a relação entre insegurança alimentar e fatores sociodemográficos em uma amostra populacional da América Latina durante a pandemia de COVID-19. Métodos. Estudo transversal multicêntrico realizado em 10 países da América Latina por meio de uma pesquisa on-line conduzida em diferentes plataformas digitais de 14 de outubro de 2020 a 15 de fevereiro de 2021. A análise estatística dos dados foi realizada por meio da aplicação de estatísticas descritivas, teste qui-quadrado e análise de regressão logística. Resultados. De um total de 6 357 questionários, 58,2% dos entrevistados afirmaram ter segurança alimentar, 29,3% indicaram um nível de insegurança alimentar leve, 9,2% tinham insegurança alimentar moderada e 3,3%, insegurança alimentar grave. No que diz respeito à relação entre insegurança alimentar e variáveis sociodemográficas, há uma relação significativa com as variáveis estudadas, incluindo área de residência, nível de escolaridade, ocupação, número de pessoas no domicílio, domicílio com crianças com menos de 10 anos de idade e nível socioeconômico. Conclusões. Os achados apontam que os fatores sociodemográficos associados à insegurança alimentar durante a pandemia de COVID-19 na América Latina foram residência em zona rural; ensino fundamental e médio completo e incompleto; ocupação (do lar, desempregado(a) e autônomo(a)); nível socioeconômico baixo, médio-baixo e médio; domicílio com mais de quatro pessoas; e domicílio com crianças menores de 10 anos de idade.

Use of an airway bundle to reduce unplanned extubations in a neonatal intensive care unit.

BACKGROUND: Following the opening of an infant cardiac neonatal intensive care unit, our aim was to determine a baseline UE rate and implement initiatives to target a goal less than 0.5 UEs/100 ventilator days. METHODS: We utilized the Model for Improvement. Key stakeholders included neonatal providers, nurses, and respiratory therapists. We focused on the creation of an airway bundle that addressed securement methods, communication and education. RESULTS: From October 2017 to January 2018, our baseline UE rate was 0.92 UEs/100 ventilator days. Subsequent to the implementation of an airway bundle with high compliance, we observed a significant change in the centerline (0.45 to 0.02 UEs/100 ventilator days) during the spring of 2021, followed by a period of 480 days with no UEs. CONCLUSION: In a unit where UEs were infrequent events, high compliance with an airway bundle led to a significantly sustained decrease in our UE rates.

The relapsed acute lymphoblastic leukemia network (ReALLNet): a multidisciplinary project from the spanish society of pediatric hematology and oncology (SEHOP).

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, 15% of patients will relapse; consequently, their survival rates decrease to below 50%. Therefore, several research and innovation studies are focusing on pediatric relapsed or refractory ALL (R/R ALL). Driven by this context and following the European strategic plan to implement precision medicine equitably, the Relapsed ALL Network (ReALLNet) was launched under the umbrella of SEHOP in 2021, aiming to connect bedside patient care with expert groups in R/R ALL in an interdisciplinary and multicentric network. To achieve this objective, a board consisting of experts in diagnosis, management, preclinical research, and clinical trials has been established. The requirements of treatment centers have been evaluated, and the available oncogenomic and functional study resources have been assessed and organized. A shipping platform has been developed to process samples requiring study derivation, and an integrated diagnostic committee has been established to report results. These biological data, as well as patient outcomes, are collected in a national registry. Additionally, samples from all patients are stored in a biobank. This comprehensive repository of data and samples is expected to foster an environment where preclinical researchers and data scientists can seek to meet the complex needs of this challenging population. This proof of concept aims to demonstrate that a network-based organization, such as that embodied by ReALLNet, provides the ideal niche for the equitable and efficient implementation of "what's next" in the management of children with R/R ALL.

BACE1 and SCD1 are associated with neurodegeneration.

Introduction: Proteolytic processing of amyloid protein precursor by ß-site secretase enzyme (BACE1) is dependent on the cellular lipid composition and is affected by endomembrane trafficking in dementia and Alzheimer's disease (AD). Stearoyl-CoA desaturase 1 (SCD1) is responsible for the synthesis of fatty acid monounsaturation (MUFAs), whose accumulation is strongly associated with cognitive dysfunction. Methods: In this study, we analyzed the relationship between BACE1 and SCD1 in vivo and in vitro neurodegenerative models and their association in familial AD (FAD), sporadic AD (SAD), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) using microscopy, biochemical, and mass SPECT approach. Results: Our findings showed that BACE1 and SCD1 immunoreactivities were increased and colocalized in astrocytes of the hippocampus in a rat model of global cerebral ischemia (2-VO). A synergistic effect of double BACE1/SCD1 silencing on the recovery of motor and cognitive functions was obtained. This neuroprotective regulation involved the segregation of phospholipids (PLs) associated with polyunsaturated fatty acids in the hippocampus, cerebrospinal fluid, and serum. The double silencing in the sham and ischemic groups was stronger in the serum, inducing an inverse ratio between total phosphatydilcholine (PC) and lysophosphatidylcholine (LPC), represented mainly by the reduction of PC 38:4 and PC 36:4 and an increase in LPC 16:0 and LPC 18:0. Furthermore, PC 38:4 and PC:36:4 levels augmented in pathological conditions in in vitro AD models. BACE1 and SCD1 increases were confirmed in the hippocampus of FAD, SAD, and CADASIL. Conclusion: Therefore, the findings suggest a novel convergence of BACE-1 and SCD1 in neurodegeneration, related to pro-inflammatory phospholipids.

Serotypes and antimicrobial resistance of Streptococcus pneumoniae in children under 5 years of age pre- and post-pneumococcal conjugate vaccine introduction in Paraguay.

Introduction. Streptococcus pneumoniae remains a major cause of mortality and morbidity worldwide in children <5 years of age, even with advances in vaccination programmes.Hypothesis/Gap Statement. Reviewing and reporting trends in the distribution of pneumococcal serotypes and antimicrobial resistance in Paraguay will be useful for decision-making in public health.Aim. This study analysed the serotype distribution and antimicrobial resistance of S. pneumoniae and the characteristics of pneumococcal disease in children <5 years old before and after the introduction of pneumococcal conjugate vaccines (PCVs).Methodology. A total of 885 isolates and 278 S. pneumoniae PCR-positive clinical specimens were referred to the Central Laboratory of Public Health (LCSP) within the meningitis and pneumonia laboratory based-surveillance network in the period 2006-2020. Conventional and molecular microbiological techniques were used for confirmation and characterization.Results. We identified 563 cases of pneumococcal disease in the pre-vaccination period, 325 cases in the post-PCV10 period and 275 cases in the post-PCV13 period. The serotypes covered by PCV10 decreased from 78.6-6.5 %. However, additional serotypes covered by PCV13 increased from 6.6-57.5% and non-PCV13 serotypes increased from 14.8-36.0 % (P<0.001) in the post-PCV13 period. In cases of meningitis, the rate of resistance to penicillin decreased after the introduction of conjugate vaccines. No resistance to ceftriaxone was found in any period. In cases without meningitis, the rate of resistance to penicillin and ceftriaxone decreased slightly. However, the rate of resistance to erythromycin and tetracycline increased and that to trimethoprim-sulfamethoxazole (SXT) decreased in the post-PCV13 period compared to the pre-PCV period. The multidrug resistance rate was 8.5 %.Conclusion. A change in the circulating serotypes and antimicrobial resistance to certain antibiotics was observed. Non-vaccine serotype circulation and multidrug resistance may compromise the success of the conjugate vaccines.

Chronic kidney disease acquired knowledge in a diabetic and hypertensive population using a translated and validated questionnaire.

Chronic kidney disease (CKD) is the progressive and irreversible functional and/or structural impairment of the kidney; its main etiologies include hypertension and diabetes. Mexico has the second highest prevalence of CKD worldwide with a high economic burden affecting public and private health systems. Patients with higher knowledge about CKD increase their adherence to preventive treatment. In this study we aim to describe the knowledge of CKD in a sample of Mexican high-risk population, comparing it with general Mexican population, medical students and nephrologists. A cross-sectional, observational study was performed divided in two phases: translation and validation of the knowledge questionnaire to Spanish, and cross-sectional survey to evaluate the knowledge of CKD in patients with diagnosis of diabetes and/or hypertension. We interviewed medical students, general population, and nephrologists to attain validation of the questionnaire in Spanish. The questionnaire was answered by 1,061 participants within the high-risk population. The results of the questionnaire were: 22/24, 18/24, 13.8/24, and 13.4/24 in nephrologists, medical students, normal subjects, and high-risk population, respectively. The questions with least correct answers were related to kidney functions and CKD risk factors. To our knowledge this is the first time a questionnaire for CKD knowledge is applied in Mexican population. These findings suggest poor understanding of kidney functions, risk factors, and symptoms of CKD. It is important not only to provide medical treatment to chronic illness but also awareness of the consequences of not achieving goals of treatment.

Determinants of COVID-19 vaccine hesitancy among pregnant persons.

BACKGROUND: Vaccines reduce the risk of contracting and developing complications from coronavirus disease 2019 (COVID-19). Pregnant people are at increased risk of disease-related complications but have a higher prevalence of vaccine hesitancy (VH) than their nonpregnant counterparts. OBJECTIVE: This study aimed to describe risk factors and COVID-19- and vaccine-related perspectives that lead to VH among pregnant people in Mexico to target strategies to increase vaccine acceptance in this population. METHODS: A cross-sectional survey-based study to evaluate risk factors and COVID-19- and vaccine-related perspectives associated with VH among pregnant people was conducted. Respondents were pregnant people of all ages attending a regular follow-up visit or admitted to labor and delivery in a third-level maternity hospital in Mexico. VH was defined as not having received a COVID-19 vaccine and either declining or being undecided to accept a vaccine during their pregnancy. We used bivariate and multivariable logistic regression models to estimate assess the relationship among demographic factors, COVID-19- and vaccine-related perspectives, and VH. RESULTS: A total of 1475 respondents completed the questionnaire; 216 (18%) were under the age of 18 years, and 860 (58%) had received at least one dose of a COVID-19 vaccine. In this sample, 264 (18%) were classified as vaccine hesitant. Key factors associated with VH were adolescence, having family as a primary source of information, first pregnancy, and history of vaccines in previous pregnancies. COVID-19 perspectives were also strongly associated with VH. CONCLUSIONS: Among pregnant people in Mexico, VH is associated with demographic factors, vaccination history, sources of information, and perceived risks to the fetus. This information is relevant to policy makers and health care professionals to identify those more likely to be hesitant and to inform strategies to increase vaccine uptake among pregnant people.

Rational engineering of glycosaminoglycan-based Dickkopf-1 scavengers to improve bone regeneration.

The WNT signaling pathway is a central regulator of bone development and regeneration. Functional alterations of WNT ligands and inhibitors are associated with a variety of bone diseases that affect bone fragility and result in a high medical and socioeconomic burden. Hence, this cellular pathway has emerged as a novel target for bone-protective therapies, e.g. in osteoporosis. Here, we investigated glycosaminoglycan (GAG) recognition by Dickkopf-1 (DKK1), a potent endogenous WNT inhibitor, and the underlying functional implications in order to develop WNT signaling regulators. In a multidisciplinary approach we applied in silico structure-based de novo design strategies and molecular dynamics simulations combined with synthetic chemistry and surface plasmon resonance spectroscopy to Rationally Engineer oligomeric Glycosaminoglycan derivatives (REGAG) with improved neutralizing properties for DKK1. In vitro and in vivo assays show that the GAG modification to obtain REGAG translated into increased WNT pathway activity and improved bone regeneration in a mouse calvaria defect model with critical size bone lesions. Importantly, the developed REGAG outperformed polymeric high-sulfated hyaluronan (sHA3) in enhancing bone healing up to 50% due to their improved DKK1 binding properties. Thus, rationally engineered GAG variants may represent an innovative strategy to develop novel therapeutic approaches for regenerative medicine.

Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder.

OBJECTIVE: Body dysmorphic disorder (BDD) is an often-severe condition in which individuals are preoccupied by misperceptions of their appearance as defective or ugly. Only serotonin reuptake inhibitors and cognitive-behavioral therapy have been demonstrated efficacious in randomized controlled trials. Psilocybin is a psychedelic drug with growing evidence for safety and efficacy in treatment of depression. This study aimed to pilot test the feasibility, tolerability, safety, and efficacy of psilocybin treatment of adults with BDD. METHODS: In this open-label trial, 12 adults (8 women, 4 men) with moderate-to-severe non-delusional BDD that had been unresponsive to at least one serotonin reuptake inhibitor trial received a single oral dose of psilocybin 25 mg. There was no control group. Psychological support was provided before, during, and after the dosing session. The primary outcome measure for efficacy was the Yale-Brown Obsessive Compulsive Disorder Scale Modified for BDD (BDD-YBOCS) score during 12 weeks of assessments after dosing. RESULTS: All participants completed dosing and all follow-up assessments. BDD-YBOCS scores decreased significantly over 12 weeks of follow-up (p < .001) with a large effect size (partial eta squared = 0.54), and significant changes from baseline were present at week 1 and persisted through week 12. Secondary efficacy measures of BDD symptoms, conviction of belief, negative affect, and disability also improved significantly, and no serious adverse events occurred. At week 12, seven participants (58%) were rated responders, based on ≥30% decrease in BDD-YBOCS. CONCLUSION: This study provides promising preliminary support for psilocybin as a treatment of BDD, warranting future controlled studies.

Dipeptide-Derived Alkynes as Potent and Selective Irreversible Inhibitors of Cysteine Cathepsins.

The potential of designing irreversible alkyne-based inhibitors of cysteine cathepsins by isoelectronic replacement in reversibly acting potent peptide nitriles was explored. The synthesis of the dipeptide alkynes was developed with special emphasis on stereochemically homogeneous products obtained in the Gilbert-Seyferth homologation for C≡C bond formation. Twenty-three dipeptide alkynes and 12 analogous nitriles were synthesized and investigated for their inhibition of cathepsins B, L, S, and K. Numerous combinations of residues at positions P1 and P2 as well as terminal acyl groups allowed for the derivation of extensive structure-activity relationships, which were rationalized by computational covalent docking for selected examples. The determined inactivation constants of the alkynes at the target enzymes span a range of >3 orders of magnitude (3-10 133 M-1 s-1). Notably, the selectivity profiles of alkynes do not necessarily reflect those of the nitriles. Inhibitory activity at the cellular level was demonstrated for selected compounds.

Descripción del bienestar social y prevalencia del consumo de alcohol en jóvenes de Ciudad del Carmen, México / Description of social welfare and prevalence of alcohol consumption in young people in Ciudad del Carmen, México

Introducción: la juventud ha sido considerada una etapa de mayor riesgo ante conductas saludables o no saludables, asimismo una etapa de menor control parental y un incremento en las actividades sociales que configura el estilo de vida de esta población. Objetivo: analizar la relación del bienestar social y el consumo de alcohol en jóvenes Método: investigación cuantitativa de tipo correlacional realizada en 279 jóvenes de Ciudad del Carmen Campeche, se utilizó un muestreo no probabilístico por conveniencia, como instrumentos de medición se utilizó una cédula de datos personales y de consumo de alcohol y la escala de Bienestar Social de Keyes. Resultados: la prevalencia global (U= 5483.50, p=.026) y en el último año (U= 8432.00, p=.038) muestra diferencias significativas, siendo mayor las puntuaciones en los jóvenes que no han consumido alcohol. Se identificó una relación negativa y significativa del bienestar social y el número de bebidas alcohólicas consumidas (rs=-727, p=.001). Conclusión: los resultados permitieron comprender el grado de bienestar social de los jóvenes, siendo un elemento crucial para su crecimiento y desarrollo para la vida adulta, además se constató la magnitud del consumo de alcohol en esta población, el cual representa un problema de salud pública. (AU)

Introduction: youth has been considered a stage of greater risk for healthy or unhealthy behaviors had a stage of less parental control and an increase in social activities that make up the lifestyle of this population. Objective: to analyze the relationship between social well-being and alcohol consumption in young people Method: correlational-type quantitative research carried out on 279 young people from Ciudad del Carmen Campeche, a non-probabilistic sample was obtained for convenience, as measurement instruments a certificate of personal and alcohol consumption data and the Keyes Social Welfare scale. Results: the global prevalence (U= 5483.50, p=.026) and in the last year (U= 8432.00, p=.038) show significant differences, the proportions being higher in young people who have not consumed alcohol. A negative and significant relationship was identified between social well-being and the number of alcoholic beverages consumed (rs=-727, p=.001). Conclusion: the results allowed us to understand the degree of social well-being of young people, being a crucial element for their growth and development for adult life, in addition, the magnitude of alcohol consumption in this population was verified, which represents a public health problem. (AU)

Organic Compounds and Antibiotic-Resistant Bacteria Behavior in Greywater Treated by a Constructed Wetland.

Laundry greywater is considered as an alternative source of non-potable water, as it is discharged in approximately 70% of homes. Because this water contains compounds such as biodegradable and recalcitrant organic matter, surfactants, and microbiological compounds, it must be treated prior to reuse. Therefore, the objective of this study was to assess the behavior of organic matter and antibiotic-resistant bacteria (ARB) in greywater treated by a constructed wetland (CW). The results show that the organic matter removal efficiencies were 67.19%, 50.15%, and 63.57% for biological oxygen demand (BOD5), chemical oxygen demand (COD) and total organic carbon (TOC), respectively; these efficiencies were not significant (p > 0.05). In addition, the CW allows the distribution of TOC and ionic compounds in the fractions below 1000 Da to increase by 5.03% and 13.05%, respectively. Meanwhile, the treatment of microbiological compounds generated non-significant removals (p > 0.05), along with increases in bacteria resistant to the antibiotics ciprofloxacin (CIP) and ceftriaxone (CTX) of 36.34%, and 40.79%, respectively. In addition, a strong association between ARB to CIP, CTX, cationic and non-ionic surfactants was determined, indicating the role of surfactants in ARB selection. It is suggested that disinfection systems should be employed prior to the reuse of the treated water.

Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection.

In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aß. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.

Efficacy and Safety of Erenumab, Galcanezumab, and Fremanezumab in the Treatment of Drug-Resistant Chronic Migraine: Experience in Real Clinical Practice.

BACKGROUND: Due to the recent introduction of new biologic drugs for chronic migraine, a global evaluation in real clinical practice is necessary. OBJECTIVE: The objective was to evaluate the effectiveness and safety in real clinical practice of drugs targeting the calcitonin gene-related peptide receptor (CGRPr) in patients with chronic migraine. METHODS: Single-center, restrospective study (2019-2022), including patients with chronic migraine treated with erenumab, galcanezumab, or fremanezumab. Effectiveness variables were recorded, namely, number of migraine headache days per month (MHD), Migraine Disability Assessment Scale (MIDAS) score, and Headache Impact Test-6 (HIT-6) score, assessing changes at week 12, 24 from baseline. Toxicity was recorded following the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. RESULTS: In all, 104 patients were included (46.2% erenumab, 41.3% galcanezumab, 12.5% fremanezumab). A reduction in MHD, MIDAS, and HIT-6 was achieved at weeks 12 and 24 with erenumab (p75% at week 24 than those intensified; P = 0.041). There was no difference in efficacy (P = 0.154) or improvement in quality of life (P = 0.783, P = 0.150), but there was greater toxicity (P < 0.001) among nonresponders with erenumab 70 mg versus erenumab 140 mg. CONCLUSIONS: The results confirm the effectiveness and safety of anticalcitonin gene-related peptide (CGRP) drugs in real clinical practice. However, the study shows little benefit from erenumab intensification, with similar effectiveness and worse tolerability than the standard dose.