Stacked Up Against Us: Using Photovoice and Participatory Methods to Explore Structural Racism's Impact on Adolescent Sexual and Reproductive Health Inequities.

While structural racism has profound impacts on adolescent health, little is known about how youth synthesize racialized experiences and work to dismantle systems of oppression. This article provides an overview of a Youth Participatory Action Research study that used Photovoice and community mapping to explore how structural violence, like racism, impacts the sexual and reproductive health of historically excluded youth as they navigate unjust socio-political landscapes. Youth participants used photography and community maps to identify how the experience of bias, profiling, and tokenism impacted their ability to navigate complex social systems. With youth voices prioritized, participants explored ways to address structural racism in their lives. The importance of co-creating opportunities with and for youth in critical reflection of their lived experience is emphasized. Through an Arts and Cultural in Public Health framework, we provide an analysis of the ways structural racism functions as a gendered racial project and fundamental cause of adolescent sexual and reproductive health inequities, while identifying pathways toward liberation in pursuit of health and well-being.

Microbiota unbalance in relation to high-risk human papillomavirus cervical infection.

OBJECTIVES: To assess vaginal dysfunction using basic vaginal states and the presence of lactobacillary microbiota in patients with human papillomavirus (HPV) infection with no squamous intra-epithelial lesions (SIL), with low-grade squamous intra-epithelial lesions (L-SIL), and with high-grade squamous intra-epithelial lesions (H-SIL) or squamous cell carcinoma compared with a control group (HPV-negative); to establish the prevalence of bacterial vaginosis, candidiasis, and trichomoniasis in the different age groups; and to characterize the species of lactobacilli according to the type of lesion. METHODS: A cross-sectional study was carried out of patients who underwent clinical examination and collection of vaginal fornixes to study basic vaginal states and culture. Species identification of lactobacilli was performed by mass spectrometry. The results were analyzed using the χ2 and Fisher's tests; p<0.05 was considered significant. High-risk viral types were determined using a multiplex real-time polymerase chain reaction test. RESULTS: A total of 741 patients were analyzed and divided into three age groups: Group 1 aged 18-24 years (n=138), Group 2 aged 25-50 years (n=456), and Group 3 aged >50 years (n=147). All groups were further divided into an HPV-negative (control) group and an HPV-positive group without lesions, with L-SIL, or with H-SIL/squamous cell carcinoma. The prevalence of unbalanced basic vaginal states in patients with H-SIL/squamous cell carcinoma was 72.7% (p=0.03) in Group 1, 53.1% (p=0.05) in Group 2, and no cases of unbalance were detected in Group 3. The prevalence of bacterial vaginosis in women with H-SIL/squamous cell carcinoma in Group 1 was 54.5% and in Group 2 was 43.7%. Patients with H-SIL/squamous cell carcinoma had a prevalence of 21.4% of Lactobacillus crispatus, 42.9% of L. jensenii, and 14.3% of L. iners. CONCLUSIONS: A greater unbalance of vaginal microbiota was observed in patients with SIL, especially in those with H-SIL/squamous cell carcinoma. In this group, an increase in L. jensenii and L. iners compared with control was found. L. crispatus had a similar prevalence to the control group. It is important to characterize the lactobacilli species since the unbalance alters the vaginal microenvironment and acts as a co-factor in the persistence of HPV infection.

Respiratory and otolaryngological disorders in Down syndrome from one center in Brazil.

Down syndrome (DS) is the most common chromosomal condition. Anatomical and functional variations in the upper and lower airways are component manifestations of the syndrome and increase the risk of various medical problems. The objective of this study was to determine the prevalence of otorhinolaryngological and respiratory diseases in a DS outpatient clinic over a 3-year period. Medical records data from 1207 patients were retrospectively reviewed. Newborn Hearing Screening was positive in 7.1% of patients. Brainstem auditory evoked potential was performed in 1101 children and showed a hearing loss of 19.8% in the first year. It was positive in 21% of 1021 exams. Audiometry was altered in 64 of 994 exams (6.4%), showing a conductive loss in 90%. Adenotonsillectomy was performed in 308 (25.5%) patients, and 169 (14.0%) required serous otitis ventilation tubes. Asthma was observed in 140 (11.6%) patients, and allergic rhinitis in 544 (56.6%). There were hospitalizations for invasive infection in 480 (39.8%) children, and two (0.2%) patients had severe septicemia from pulmonary focus. Five (0.4%) infants had laryngotracheomalacia, and one patient had anomalous right tracheal bronchus. Recognizing the prevalence of respiratory and otorhinolaryngological disorders in patients with DS allows the promotion of optimal follow-up and early treatment, preventing the development of sequelae.

Ophthalmological abnormalities in Down syndrome among Brazilian patients.

Down syndrome is the most common chromosomal disorder, affecting 1/700 live births. Among the clinical findings, one constant concern is the high prevalence of visual disorders that, if left untreated, can negatively affect child development. The aim of this study was to determine the prevalence of ophthalmological findings among patients who attended an outpatient clinic for patients with Down syndrome in southern Brazil between 2005 and 2016. A cross-sectional study including 1,207 patients medical records were done, which 492 (40.8%) had some ophthalmological disorder. These data were subjected to descriptive analysis using Statistica software. Among the 492 patients with any ophthalmological disease, the need for glasses was found in 434 (36%) patients, keratoconus in 254 (42.1%), congenital cataract in 27 (15.1%), nasolacrimal duct obstruction in 25 (2.0%), strabismus in 22 (1.9%), nystagmus in four (0.3%), and juvenile cataract in two (0.2%). Two young adults with keratoconus underwent corneal transplantation. Although the prevalence of an ophthalmological disease among the present sample (40.8%) was lower than described in the current literature, it still reinforced the importance of routine and early evaluations in infants. These should begin at 6 months of age and be repeated half-year until 2 years old, annually until 7 years old, biennial in adolescents, and triennial in adults and elderly. Our findings of a high frequency of keratoconus support a detailed corneal study in such patients for early detection and treatment.

Changes in Firearm and Medication Storage Practices in Homes of Youths at Risk for Suicide: Results of the SAFETY Study, a Clustered, Emergency Department-Based, Multisite, Stepped-Wedge Trial.

STUDY OBJECTIVE: We evaluate whether a counseling intervention implemented at the hospital level resulted in safer firearm and medication storage by caregivers of youths aged 10 to 17 years after their child's evaluation in the emergency department (ED) for a behavioral health concern. METHODS: We used a stepped-wedge clustered design rolled out at 4 hospital sites to assess primary preregistered outcomes (self-reported storage changes caregivers made to household firearms and medications), assessed by survey 2 weeks after the ED visit. Three logistic models provided estimates of the intervention effect: an unadjusted model, a model with hospital-level fixed effects, and a model that further adjusts for time. RESULTS: Of the 575 caregiver participants, 208 were firearm owners (123 in usual care, 85 in the intervention). Baseline (pre-ED visit) characteristics did not differ between usual care and intervention phases. During the 2-year study period, twice as many caregivers whose child visited the ED after (compared with before) a hospital adopted the intervention improved firearm storage and 3 times as many improved medication storage (odds ratio [OR]=2.1 [95% confidence interval {CI} 1.0 to ∞] and OR=3.0 [95% CI 2.2 to ∞], respectively). After adjusting for time, the intervention effect for medications persisted (OR=2.0 [95% CI 1.0 to ∞]); the effect on firearms did not (OR=0.7 [95% CI 0.1 to ∞]). CONCLUSION: To our knowledge, this study is the first controlled trial to estimate the effectiveness of an intervention on firearm and medication storage in homes of youths at elevated risk of suicide. We found evidence that caregivers' medication storage improved after their child's ED visit, with evidence suggestive of improvement for firearm storage.

Molecular function of α7 nicotinic receptors as drug targets.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels involved in many physiological and pathological processes. In vertebrates, there are seventeen different nAChR subunits that combine to yield a variety of receptors with different pharmacology, function, and localization. The homomeric α7 receptor is one of the most abundant nAChRs in the nervous system and it is also present in non-neuronal cells. It plays important roles in cognition, memory, pain, neuroprotection, and inflammation. Its diverse physiological actions and associated disorders have made of α7 an attractive novel target for drug modulation. Potentiation of the α7 receptor has emerged as a novel therapeutic strategy for several neurological diseases, such as Alzheimer's and Parkinson's diseases, and inflammatory disorders. In contrast, increased α7 activity has been associated with cancer cell proliferation. The presence of different drug target sites offers a great potential for α7 modulation in different pathological contexts. In particular, compounds that target allosteric sites offer significant advantages over orthosteric agonists due to higher selectivity and a broader spectrum of degrees and mechanisms of modulation. Heterologous expression of α7, together with chaperone proteins, combined with patch clamp recordings have provided important advances in our knowledge of the molecular basis of α7 responses and their potential modulation for pathological processes. This review gives a synthetic view of α7 and its molecular function, focusing on how its unique activation and desensitization features can be modified by pharmacological agents. This fundamental information offers insights into therapeutic strategies.

Self-Reported Nutritional Status and Breakfast Characterization in Latin American University Students.

OBJECTIVE: To associate breakfast consumption frequency with self-reported nutritional status and dietary patterns of Latin American university students by human development. MATERIAL AND METHODS: This was a cross-sectional, multicenter observational study. University students from 11 Latin American countries (Argentina, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Mexico, Peru, Paraguay, Panama and Uruguay) were invited to participate by answering an online self-administered questionnaire on food consumption and sociodemographic indicators, associations were investigated using logistic regression. RESULTS: The logistic regression analysis showed significant associations between breakfast consumption and the crude model, models 2 and 3 in countries with very high and upper-middle/high human development. However, after adjustment in the most comprehensive model, the association is no longer statistically significant. In the fully adjusted model of the variables, a significant relationship was observed between breakfast consumption and both healthy and unhealthy dietary patterns. Specifically, students who typically consume breakfast exhibit greater consumption of oatmeal and fruits, as well as healthier dinner choices. Conversely, they exhibit lower consumption of fast food, sugary drinks, and juices. In particular, in highly developed countries, along with the mentioned foods, consumption of dairy was linked to breakfast consumption in a positive way, while alcohol consumption was negatively associated. CONCLUSION: University students who eat breakfast on a regular basis maintain a healthier diet in comparison to those who do not, irrespective of their country's level of human development.

The Need for Community-Responsive and Flexible Sex Ed for Historically Marginalized Youth.

Introduction: When it is offered, sexuality education in the USA is far from standardized. While studies have explored differences in delivery and type of sexuality education across the USA, sexual and reproductive health inequities persist among historically marginalized groups (Latino/a/x, Black, African American, LGBTQ +). There is a critical need to better understand the systemic barriers to receiving effective sexuality education in these communities. Methods: Participatory research methods were used in working with a community advisory board (CAB)-consisting of emerging adults and service providers from community-based organizations (CBOs) serving youth-to examine how structural barriers contribute to adolescent sexual and reproductive health (ASRH) inequities in Massachusetts. CAB meetings and semi-structured interviews were conducted in the cities of Springfield (n = 14) and Lynn (n = 9) between December 2020 and May 2021. Results: Inflexible funding guidelines, a related evidence-based curricular mandate, and a lack of community-responsive sexuality education fail to meet the sexual and reproductive health (SRH) needs of these youth. Conclusions: Current evidence-based mandates must be revisited to improve young people's access to quality sexuality information in public schools. To guarantee sexuality education curricula is centered in the context of the community and population in which it is implemented, collaboration between youth-serving CBOs and school districts could improve students' overall experience and social-emotional growth by providing comprehensive, positive, and community-responsive curricula. Policy Implications: Funders and programming should prioritize community responsiveness by financially supporting and developing and/or adapting evidence-based curricula to better match the community's needs, which can be completed through culture-centered training and community-based partnership.

Structural Racism and Its Influence On Sexual and Reproductive Health Inequities Among Immigrant Youth.

This community-based participatory research study explores the influence of structural racism on sexual and reproductive health (SRH) inequities among immigrant, including refugee, youth. We conducted interviews with emerging youth and youth service providers living in two communities in Massachusetts. Our results detail three major themes illustrating how structural racism influences SRH inequities among immigrant youth: (1) lack of culture-centered SRH supports for recently immigrated youth; (2) immigration enforcement and fear impacting access to adolescent SRH (ASRH) education and services; and (3) perceived ineligibility related to tenuous legal status as a barrier to accessing ASRH services. Conclusions: Findings illustrate the importance of rooting sexuality education curricula in a culture centered framework that recognizes local cultural understandings, acknowledges structural constraints faced by young people, and prioritizes youth agency and voice when engaging in this work. Raising awareness of SRH resources available to immigrant youth may expand access for this underserved population.

"Your son needs help and we're gonna help him": A qualitative study of the experiences of gun-owning caregivers of adolescents receiving lethal means counseling in the emergency department.

Suicide attempts in adolescents are often transient and unpredictable, making preventative approaches crucial in reducing suicide deaths. One important approach is lethal means counseling (LMC), in which clinicians counsel caregivers to reduce access to methods used in suicide, specifically firearms and medications. Research on LMC has increasingly encouraged the use of the shared decision-making (SDM) model, which emphasizes information exchange, collaborative deliberation, and joint planning between caregivers and clinicians. We examine caregivers' experiences with LMC, using the SDM model as our analytic framework. We conducted qualitative interviews with 21 firearm-owning caregivers of adolescents who came to emergency departments (EDs) in Colorado for a behavioral health complaint. The implementation of LMC at these institutions had three central components: training for clinicians, materials (e.g., lockboxes and pamphlets) to support LMC, and the protocolization of LMC at the institution. Our semi-structured, hour-long interviews examined participants' reflections on and reactions to LMC provided in the ED and how that related to changes in their understanding of their medication and gun storage practices. We analyzed interviews using a phenomenological approach, focusing on experiences with LMC and informed by the tenets of the SDM model. Our analysis revealed that caregivers were receptive to the idea of LMC in the pediatric emergency care setting. Caregivers' engagement in LMC was reinforced by experiences with clinicians who sought to understand the circumstances of their household, shared the motivation behind LMC, and facilitated conversation around a shared concern for the child's safety. In contrast, counseling delivered mechanically and without considering the household context was tied to caregivers' confusion and alienation, both for LMC and their consideration of changes to home storage practices. These findings provide insight into adolescent caregivers' experiences with LMC implemented in EDs and how LMC may best be approached.

[Complete androgen insensitivity syndrome: diagnosis and multidisciplinary management]. / Síndrome de insensibilidad completa a los andrógenos: diagnóstico y manejo multidisciplinario.

Background: Complete androgen insensitivity syndrome (CAIS) is a sexual differentiation disorder, caused by a defect in the androgen receptor gene (AR; OMIM# 313700). It is characterized by the resistance of target tissues to the action of testosterone, which prevents normal male genital development. The objective is to describe a family case of CAIS and highlight the importance of multidisciplinary medical management and early diagnosis of this syndrome. Clinical case: We present two cases of SICA in a Mexican family. Case 1: 18-year-old female patient with primary amenorrhea and a history of surgery at an early age, without performing gonadectomy. Case 2: 11-year-old female patient who, due to the history of her sister, underwent surgery at that age. In both patients, absence of uterus and ovaries, hypoplastic vagina and male gonads is reported. The 46,XY karyotype was detected with the GTG and CBG band technique and fluorescent in situ hybridization with the presence of the Y chromosome in 100% of the cells analyzed. Although both patients were identified with their assigned sex, they were referred to the institution's psychiatric clinic. Conclusions: The importance of multidisciplinary management for the diagnosis of SICA at an early age is discussed, in order to make decisions regarding the treatment and management of patients, avoiding malignant transformation of the male gonads.

Introducción: el síndrome de insensibilidad completa a los andrógenos (SICA) es un desorden de la diferenciación sexual, causado por un defecto en el gen receptor de andrógenos (AR; OMIM# 313700). Se caracteriza por la resistencia de los tejidos diana a la acción de la testosterona, lo que impide el desarrollo genital masculino de manera normal. El objetivo es describir un caso familiar de SICA y destacar la importancia del manejo médico multidisciplinario y el diagnóstico temprano de este síndrome. Caso clínico: presentamos dos casos de SICA en una familia mexicana. Caso 1: paciente de 18 años con amenorrea primaria y antecedente de intervención quirúrgica a edad temprana, sin realizarle gonadectomía. Caso 2: paciente de 11 años que debido al antecedente de su hermana fue intervenida quirúrgicamente a esa edad. En ambas pacientes, se reporta ausencia de útero y ovarios, vagina hipoplásica y gónadas masculinas. El cariotipo 46,XY fue detectado con técnica de bandas GTG y CBG e hibridación in situ fluorescente con presencia del cromosoma Y en el 100% de las células analizadas. Aunque ambas se identificaban con su sexo de asignación, fueron referidas a consulta de psiquiatría de la institución. Conclusiones: se discute la importancia del manejo multidisciplinario para el diagnóstico de SICA a edades tempranas con la finalidad de tomar decisiones respecto al tratamiento y manejo de las pacientes y evitar la malignización de las gónadas masculinas.

Quality of life in Down syndrome in Brazil: a cross-sectional study.

BACKGROUND: Down syndrome is the most commonly genetic cause of developmental delay and intellectual disability, affecting 1:700 live births. It is associated with heart disease and recurrent infections, among other complications that greatly impair the patient's quality of life. OBJECTIVE: To evaluate the major factors associated with quality of life in a cohort of patients with Down syndrome. METHODS: We assessed 1,187 patients with Down syndrome, older than 4 years old, with an adaptation of the Personal Outcomes Scale validated for Portuguese language, interviewing patients, parents, and caregivers. RESULTS: A bad quality of life was reported in 56.4% of the sample. The main factors associated with better quality of life were female sex, first medical visit before 4 months old, higher parental education, a professionally active mother, and prenatal care. The main factors associated with worse quality of life were family history of alcohol abuse and psychiatric disorders and comorbidity with autism and epilepsy. CONCLUSION: Clinical comorbidities such as autism and epilepsy carry a heavy burden among patients with Down syndrome, while factors related to family support, such as employment status and educational background of the parents, enhance quality of life. The factors associated with quality of life among patients with Down syndrome should be adequately evaluated in medical consultation and targeted in public health policies.

ANTECEDENTES: A síndrome de Down é a mais comum causa identificável de atraso de desenvolvimento e deficiência intelectual, afetando 1 a cada 700 nascidos vivos. Está associada a cardiopatias, infecções recorrentes e outras complicações que impactam significativamente a qualidade de vida dos pacientes. OBJETIVO: Avaliar os principais fatores associados a qualidade de vida em uma coorte de pacientes com Síndrome de Down. MéTODOS: Avaliamos 1.187 pacientes com síndrome de Down com mais de 4 anos de idade utilizando uma adaptação da versão validada para o português da Escala Pessoal de Resultados, entrevistando pacientes, pais e cuidadores. RESULTADOS: Uma má qualidade de vida foi encontrada em 56.4% da amostra. Os principais fatores associados à melhor qualidade de vida foram sexo feminino, primeira consulta médica antes dos 4 meses de idade, maior nível educacional dos pais, mãe profissionalmente ativa e atenção pré-natal. Os principais fatores associados à pior qualidade de vida foram o histórico familiar de abuso de álcool e distúrbios psiquiátricos, além de comorbidade com autismo e epilepsia. CONCLUSãO: As comorbidades clínicas como autismo e epilepsia levam a um maior impacto entre os pacientes com síndrome de Down, enquanto fatores relacionados ao apoio familiar, como situação profissional e formação educacional dos pais, estão associados à melhor qualidade de vida. Os fatores associados à qualidade de vida de pacientes com síndrome de Down devem ser adequadamente avaliados em consulta médica e alvo de políticas públicas de saúde.

Vaginal States: Detection of Conversion Processes in Women Using Contraception and Characterization of Vaginal Lactobacillus Species.

BACKGROUND: The vaginal microenvironment, regulated by an immune system, can be protected or altered by many factors, including contraceptive methods. OBJECTIVE: The objective of this study is to evaluate the impact of contraceptive methods on the basic vaginal states (BVSs) and to identify culturable vaginal Lactobacillus species. METHODS: This is a prospective, consecutive, longitudinal, and descriptive study. The vaginal contents of 208 women were sampled prior to initiating contraception and six months later. The BVSs were established using the balance of vaginal content (BAVACO) methodology that evaluates microbiota and vaginal inflammatory reaction (VIR). Lactobacillus species were characterized by biochemical tests and mass spectrometry. The following contraceptive methods were evaluated: combined oral contraceptive pill (COCP), condom (CON) and rhythm method (RHYT). McNemar's test was used. RESULTS: Of the 208 women, 171 attended both examinations. In the COCP group (n=127), 83 vaginal contents maintained a normal microbiota, 1 sample became dysbiotic, and 37/43 dysbiotic microbiota samples reverted to normal (p<0.0001). A conversion to BVS with VIR was detected in the CON group (n=31) (p=0.001). The RHYT group (n=13) maintained its initial BVSs. The predominant Lactobacillus species found were L. crispatus and L. gasseri, with a trend toward a positive association between L. crispatus and COCP (OR=2.82; p=0.058). CONCLUSION: Hormone administration corrected the dysbiosis and preserved a normal BVS. The CON increased the VIR. The protection of the microbiota observed in the rhythm method probably responds to a systemic hormonal influence. The trend toward a positive association between COCP and L. crispatus, with its protective properties, evidenced an effective hormonal relationship.

Biochemical profiling study in umbilical cord blood in mothers with metabolic disorders.

BACKGROUND: During pregnancy metabolic disorders that affect differently the fetus, are known. These could be early or late disorders. OBJECTIVES: To analyze different biochemical parameters in umbilical cord blood (UCB) of healthy and pathological newborns from mothers with metabolic disorders. MATERIALS AND METHODS: Samples from UCB (121) were analyzed of newborn from mothers with metabolic disorders who attended at Obstetrics Division. Patients were consecutive, prospective and transversally studied. Newborn were classified as healthy (n = 65) and pathological (n = 56). The maternal metabolic disorders were gestational or non-gestational diabetes, glucose intolerance, insulin resistance and/or obesity).The disorders of the pathological newborns were intrauterine growth restriction (IUGR) and/or fetal distress. Glucose (Glu), urea, creatinine, uric acid (UA), total bilirubin (TB), total proteins (TP), albumin (Alb), transaminases (ALT/AST), alkaline-phosphatase (ALP), gammaglutamyltranspeptidase (GGT), creatinkinasa (CK), lactatedehydrogenase, amylase (amy), pseudocholinesterase, iron, calcium, phosphorus, magnesium (Mg), sodium, potassium, chlorine, cholesterol (Chol), HDL-Chol, LDL-Chol, triglycerides (TG), high sensitivity C reactive protein (hsCRP) were determined by recommended methods. T-Student's and Mann Withney tests were applied, p < .05. RESULTS: Pathological neonates (n: 56) showed a significant decrease in maternal gestation weeks (GW) and in newborn weight (NW) with respect to healthy newborns (n: 65) from mothers with metabolic disorders (p < .0001). Pathological neonates from mothers with metabolic pathologies (n: 56) showed significant increases in Chol, TG, TB (p < .01), LDL-Chol, UA, Mg, hsCRP, ALP levels (p < .05) and significant decreases in TP, Alb (p < .0001) and Glu, ALT, CK, GGT, amy (p < .05) in UCB with respect to healthy newborns. CONCLUSIONS: In pathological newborn, the decrease in GW and NW would be related to IUGR that accompany these metabolic disorders. The increases observed of the analyzed parameters would be related to cellular destruction associated to maternal pathology and decreases of the parameters to IUGR with hepatic immaturity.

Physical Discipline, Deprivation, and Differential Risk of Developmental Delay Across 17 Countries.

OBJECTIVE: Parenting behaviors have been studied largely in isolation with regard to child development in cross-national contexts. We examine and compare the relative strength of association between physical discipline and deprivation with risk of children's socioemotional and cognitive developmental delay in a cross-national sample. METHOD: The sample was drawn from the UNICEF Multiple Indicator Cluster Survey. Analyses used observations with data on parental physical discipline, parenting behaviors associated with deprivation, and child developmental outcomes. The present analysis included 29,792 children aged 36-59 months across 17 countries. Using the Early Child Development Index, risk for cognitive or socioemotional developmental delay was indicated if a child could not accomplish 2 or more items within that specific subdomain. Overall risk for delay was indicated if a child was at risk in either subdomain. Associations among discipline, deprivation, and delay were assessed using multivariable logistic regression. RESULTS: Five of the 7 exposures were associated with risk of overall developmental delay. Physical discipline (odds ratio [OR] = 1.49 [95% CI = 1.39, 1.59]; p < .001) had the largest association with risk for socioemotional delay. Not having books (OR = 1.62 [95% CI = 1.42, 1.84]; p < .001) and not counting with the child (OR = 1.47 [95% CI = 1.32, 1.64]; p < .001) had the largest associations with risk of cognitive delay. CONCLUSION: The exposures of physical discipline and deprivation measured here have distinct associations with risk of socioemotional and cognitive delay cross-nationally. Programmatic and clinical interventions should seek to act on adversities that are relevant to the targeted delay.

Design, Synthesis, and Functional Evaluation of a Novel Series of Phosphonate-Functionalized 1,2,3-Triazoles as Positive Allosteric Modulators of α7 Nicotinic Acetylcholine Receptors.

The α7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel widely distributed in the central nervous system, mainly in the hippocampus and cortex. The enhancement of its activity by positive allosteric modulators (PAMs) is a promising therapeutic strategy for cognitive deficits and neurodegenerative disorders. With the aim of developing novel scaffolds with PAM activity, we designed and synthesized a series of phosphonate-functionalized 1,4-disubstituted 1,2,3-triazoles using supported copper nanoparticles as the cycloaddition reaction catalyst and evaluated their activity on α7 receptors by single-channel and whole-cell recordings. We identified several triazole derivatives that displayed PAM activity, with the compound functionalized with the methyl phosphonate group being the most efficacious one. At the macroscopic level, α7 potentiation was evidenced as an increase of the maximal currents elicited by acetylcholine with minimal effects on desensitization, recapitulating the actions of type I PAMs. At the single-channel level, the active compounds did not affect channel amplitude but significantly increased the duration of channel openings and activation episodes. By using chimeric and mutant α7 receptors, we demonstrated that the new α7 PAMs share transmembrane structural determinants of potentiation with other chemically nonrelated PAMs. To gain further insight into the chemical basis of potentiation, we applied structure-activity relationship strategies involving modification of the chain length, inversion of substituent positions in the triazole ring, and changes in the aromatic nucleus. Our findings revealed that the phosphonate-functionalized 1,4-disubstituted 1,2,3-triazole is a novel pharmacophore for the development of therapeutic agents for neurological and neurodegenerative disorders associated with cholinergic dysfunction.

Fetal coenzyme Q10 deficiency in intrahepatic cholestasis of pregnancy.

AIM: Intrahepatic cholestasis of pregnancy (ICP) is considered a high-risk condition because it may have serious consequences for the fetus health. ICP is characterized by the accumulation of bile acids in maternal serum which contribute to an imbalance between the production of reactive oxygen species and the antioxidant defenses increasing the oxidative stress experienced by the fetus. Previously, it was reported a significant decrease in plasma coenzyme Q10 (CoQ10) in women with ICP. CoQ10 is a redox substance integrated in the mitochondrial respiratory chain and is recognized as a potent antioxidant playing an intrinsic role against oxidative damage. The objective of the present study was to investigate the levels of CoQ10 in umbilical cord blood during normal pregnancy and in those complicated with ICP, all of them compared to the maternal ones. METHODS: CoQ10 levels and bile acid levels in maternal and umbilical cord blood levels during normal pregnancies (n=23) and in those complicated with ICP (n=13), were investigated. RESULTS: A significant decrease in neonate CoQ10 levels corrected by cholesterol (0.105±0.010 vs. 0.069±0.011, P<0.05, normal pregnancy vs. ICP, respectively), together with an increase of total serum bile acids (2.10±0.02 vs. 7.60±2.30, P<0.05, normal pregnancy vs. ICP, respectively) was observed. CONCLUSIONS: A fetus from an ICP mother is exposed to a greater risk derived from oxidative damage. The recognition of CoQ10 deficiency is important since it could be the starting point for a new and safe intervention strategy which can establish CoQ10 as a promising candidate to prevent the risk of oxidative stress.

Child discipline in low- and middle-income countries: Socioeconomic disparities at the household- and country-level.

BACKGROUND: In the past month, an estimated eight of ten children worldwide have experienced violent discipline. Understanding the economic and social contexts in which parents are more likely to use particular disciplinary practices is necessary to reduce violence against children. Critical examination of disciplinary practices and beliefs in cross-country analysis of low- and middle-income countries (LMICS) has been limited. OBJECTIVE: To estimate the association of country-level stressors and household-level economic stressors with disciplinary behaviors and beliefs. PARTICIPANTS AND SETTING: Using Multiple Indicator Cluster Survey data between 2010 and 2013, 231,221 parents from 32 LMICS were included. METHODS: The prevalence of past-month nonviolent discipline, physical discipline, psychological aggression, belief in the utility of physical discipline, and incongruence of disciplinary practice and belief were estimated. Country-level prevalence was regressed on country-level stressors (economic burden, economic inequality, human security, and human development). Individual-level disciplinary practices and beliefs were regressed on household wealth. RESULTS: Country-level stressors predicted psychological and physical discipline use and belief in the utility of physical discipline. Lower household wealth was associated with increased violent disciplinary practice and belief. Lower household wealth was associated with increased likelihood of using violent discipline, even when the caregiver did not believe in its utility (OR = 1.63 [1.34, 1.98]). CONCLUSIONS: Discipline use and belief in LMICS should be understood within the context of salient societal and household stressors.Parental disciplinary beliefs and practices reflect complex interplay with broader social, political and economic contexts and should not be taken to be defined by monolithic views of culture.

Flavonoids as positive allosteric modulators of α7 nicotinic receptors.

The use of positive allosteric modulators (PAM) of α7 nicotinic receptors is a promising therapy for neurodegenerative, inflammatory and cognitive disorders. Flavonoids are polyphenolic compounds showing neuroprotective, anti-inflammatory and pro-cognitive actions. Besides their well-known antioxidant activity, flavonoids trigger intracellular pathways and interact with receptors, including α7. To reveal how the beneficial actions of flavonoids are linked to α7 function, we evaluated the effects of three representative flavonoids -genistein, quercetin and the neoflavonoid 5,7-dihydroxy-4-phenylcoumarin- on whole-cell and single-channel currents. All flavonoids increase the maximal currents elicited by acetylcholine with minimal effects on desensitization and do not reactivate desensitized receptors, a behaviour consistent with type I PAMs. At the single-channel level, they increase the duration of the open state and produce activation in long-duration episodes with a rank order of efficacy of genistein > quercetin ≥ neoflavonoid. By using mutant and chimeric α7 receptors, we demonstrated that flavonoids share transmembrane structural determinants with other PAMs. The α7-PAM activity of flavonoids results in decreased cell levels of reactive oxygen species. Thus, allosteric potentiation of α7 may be an additional mechanism underlying neuroprotective actions of flavonoids, which may be used as scaffolds for designing new therapeutic agents.

Early childhood exposure to non-violent discipline and physical and psychological aggression in low- and middle-income countries: National, regional, and global prevalence estimates.

BACKGROUND: Advocates for children's rights have recommended the elimination of all forms of violent discipline given its detrimental effects on children's development. Yet, little is known about the global prevalence of various forms of discipline, including physical and psychological aggression, as well as alternative forms of non-violent discipline, especially in low- and middle-income countries (LMICs). OBJECTIVE: This study aims to obtain national, regional, and global prevalence estimates of the percentage and number of 2- to- 4-y-olds in LMICs exposed to these disciplinary practices by their caregivers. PARTICIPANTS AND SETTING: We use data collected between 2010 and 2016 from 107,063 2- to- 4-y-old children living in 49 LMICs as part of the Multiple Indicator Cluster Survey (MICS). METHODS: Using the best-fitting model based on cross-validation techniques, we performed predictive modeling to generate country-level prevalence estimates for 131 LMICs in 2013, as well as 95% confidence intervals around these estimates. RESULTS: We estimate that 296.2 million 2- to- 4-y-olds (95% CI 256.9, 300.9) were exposed to non-violent discipline in 2013, which corresponds to 83.9% of the population. Furthermore, 220.4 million (95% CI 138.1, 283.7) and 230.7 million (95% CI 128.4, 300.6) children were exposed to aggressive physical and psychological discipline, respectively, which corresponds to prevalence of 62.5% and 65.4%. We also identify a high heterogeneity in the estimates across and within regions, finding a higher prevalence of both violent disciplinary methods in South Asia and Sub-Saharan Africa. CONCLUSIONS: These results suggest the need for new policies and programs to minimize violent discipline around the world.