Brain Function and Marijuana: Are there Changes after Abstinence of Consumption? Preliminary Results.

BACKGROUND: The legalization of cannabis use and false claims about the plant Cannabis sativa to be considered a pharmaceutical product have been found to increase consumption, lower risk perception, and lead to more health problems, without reducing criminal activity. Brain function, typically assessed by neuropsychological tests, shows abnormalities with acute marijuana use, but inconsistent results have been published after abstinence, with a maximum follow-up of 28 days. Our previous research, using neuropsychological tests and brain perfusion single photon emission computed tomography (neuroSPECT), demonstrated consistent abnormalities in brain function among schoolchildren who consume marijuana compared to their non-consuming peers. The aim of this study is to investigate whether brain function changes in 20 adult marijuana users after 6 months of abstinence. METHODOLOGY: Comparison of neuropsychological tests (Rey Complex Figure; Porteus Maze; Four subtests of WAIS-IV Intellectual Tests; STROOP; D2) and perfusion neuroSPECT (functional images), obtained in relation to recent consumption and after 6 months of serial drug-screening test confirmed abstinence. RESULTS: In a one-year period (2020-2021) only five compliant participants were recruited. The COVID-19 pandemic was a limiting factor. Preliminary results of neuropsychological tests, functional brain perfusion images and limited statistical analysis are presented. The results of the neuropsychological tests of the three subjects who completed the abstinence period so far show some improvement in working memory and attention after abstinence. NeuroSPECT shows disorganized hypoperfusion of variable severity in relation to recent consumption, involving areas associated with cognitive function such as the posterior cingulate and temporal lobes, in our five initially enrolled patients, when compared to a normal database. Of these, only two participants have already been re-evaluated with neuroSPECT after 6 months of abstinence, one of whom showed some improvement on the post-abstinence images. CONCLUSION: We analyze the methodological challenges of this research, including the pandemic, to incorporate the appropriate corrections in the next phase of our investigation. Our final findings may provide clinicians and users with information about the long-term effects of marijuana use on brain function.

Late-in-life Exercise Ameliorates the Aging Trajectory Metabolism Programmed by Maternal Obesity in Rats: It is Never Too Late.

BACKGROUND: Maternal obesity (MO) has been shown to adversely affect metabolic, oxidative, reproductive, and cognitive function in offspring. However, it is unclear whether lifestyle modification can ameliorate the metabolic and organ dysfunction programmed by MO and prevent the effects of metabolic syndrome in adulthood. This study aimed to evaluate whether moderate voluntary exercise in the offspring of rats born to obese mothers can ameliorate the adverse effects of MO programming on metabolism and liver function in mid-adulthood. METHODS: Offspring of control (CF1) and MOF1 mothers were fed with a control diet from weaning. Adult males and females participated in 15 min exercise sessions five days/week. Metabolic parameters were analyzed before and after the exercise intervention. Liver oxidative stress biomarkers and antioxidant enzymes were analyzed before and after the intervention. RESULTS: Males showed that CF1ex ran more than MOF1ex and increased the distance covered. In contrast, females in both groups ran similar distances and remained constant but ran more distance than males. At PND 300 and 450, male and female MOF1 had higher leptin, triglycerides, insulin, and HOMA-IR levels than CF1. However, male MOF1ex had lower triglycerides, insulin, and HOMA-IR levels than MOF1. Improvements in liver fat and antioxidant enzymes were observed in CF1ex and MOF1ex males and females compared to their respective CF1 and MOF1 groups. CONCLUSION: These findings suggest that moderate voluntary exercise, even when started in mid-adulthood, can improve metabolic outcomes and delay accelerated metabolic aging in MO-programmed rats in a sex-dependent manner.

Impaired Ischemia-Reperfusion Responses in the Hearts of Aged Male and Female Offspring of Obese Rats.

Maternal obesity predisposes offspring (F1) to cardiovascular disease. To evaluate basal heart function and ischemia-reperfusion (IR) responses in F1 males and females of obese mothers, female Wistar rats (F0) were fed chow or an obesogenic (MO) diet from weaning through pregnancy and lactation. Non-sibling F1 males and females were weaned to chow at postnatal day (PND) 21 and euthanized at PND 550. Offspring of MO mothers (MOF1) rarely survive beyond PND 650. Hearts were immediately isolated from euthanized F1s and subjected to 30 min ischemia with 20 min reperfusion. Retroperitoneal fat, serum triglycerides, glucose, insulin, and insulin resistance were measured. Baseline left ventricular developed pressure (LVDP) was lower in male and female MOF1 than in controls. After global ischemia, LVDP in control (C) male and female F1 recovered 78 and 83%, respectively, while recovery in MO male and female F1 was significantly lower at 28 and 52%, respectively. Following the IR challenge, MO hearts showed a higher functional susceptibility to reperfusion injury, resulting in lower cardiac reserve than controls in both sexes. Female hearts were more resistant to IR. Retroperitoneal fat was increased in male MOF1 vs. CF1. Circulating triglycerides and insulin resistance were increased in male and female MOF1 vs. CF1. These data show that MO programming reduces F1 cardiac reserve associated with age-related insulin resistance in a sex-specific manner.

Community-Based Prevention of Substance Use in Adolescents: Outcomes Before and During the COVID-19 Pandemic in Santiago, Chile.

A primary community prevention approach in Iceland was associated with strong reductions of substance use in adolescents. Two years into the implementation of this prevention model in Chile, the aim of this study was to assess changes in the prevalence of adolescent alcohol and cannabis use and to discuss the impact of the COVID-19 pandemic on the substance use outcomes. In 2018, six municipalities in Greater Santiago, Chile, implemented the Icelandic prevention model, including structured assessments of prevalence and risk factors of substance use in tenth grade high school students every 2 years. The survey allows municipalities and schools to work on prevention with prevalence data from their own community. The survey was modified from an on-site paper format in 2018 to an on-line digital format in a shortened version in 2020. Comparisons between the cross-sectional surveys in the years 2018 and 2020 were performed with multilevel logistic regressions. Totally, 7538 participants were surveyed in 2018 and 5528 in 2020, nested in 125 schools from the six municipalities. Lifetime alcohol use decreased from 79.8% in 2018 to 70.0% in 2020 (X2 = 139.3, p < 0.01), past-month alcohol use decreased from 45.5 to 33.4% (X2 = 171.2, p < 0.01), and lifetime cannabis use decrease from 27.9 to 18.8% (X2 = 127.4, p < 0.01). Several risk factors improved between 2018 and 2020: staying out of home after 10 p.m. (X2 = 105.6, p < 0.01), alcohol use in friends (X2 = 31.8, p < 0.01), drunkenness in friends (X2 = 251.4, p < 0.01), and cannabis use in friends (X2 = 217.7, p < 0.01). However, other factors deteriorated in 2020: perceived parenting (X2 = 63.8, p < 0.01), depression and anxiety symptoms (X2 = 23.5, p < 0.01), and low parental rejection of alcohol use (X2 = 24.9, p < 0.01). The interaction between alcohol use in friends and year was significant for lifetime alcohol use (ß = 0.29, p < 0.01) and past-month alcohol use (ß = 0.24, p < 0.01), and the interaction between depression and anxiety symptoms and year was significant for lifetime alcohol use (ß = 0.34, p < 0.01), past-month alcohol use (ß = 0.33, p < 0.01), and lifetime cannabis use (ß = 0.26, p = 0.016). The decrease of substance use prevalence in adolescents was attributable at least in part to a reduction of alcohol use in friends. This could be related to social distancing policies, curfews, and homeschooling during the pandemic in Chile that implied less physical interactions between adolescents. The increase of depression and anxiety symptoms may also be related to the COVID-19 pandemic. The factors rather attributable to the prevention intervention did not show substantial changes (i.e., sports activities, parenting, and extracurricular activities).

Facilitating Factors and Barriers to the Implementation of the Icelandic Prevention Model of Adolescent Substance Use in Chile: A Focus Group Study.

The use of alcohol and other drugs is a major public health problem in adolescence. The implementation of evidence-based prevention strategies is still scarce in the global south. This study aimed to evaluate facilitators and barriers to the implementation of the Icelandic prevention model of adolescent substance use (IPM) in Chile. We conducted a qualitative study of stakeholders during the implementation process of the IPM in six municipalities of the Metropolitan Region of Santiago, Chile. We convened six focus groups with parents and professionals from schools and municipal prevention teams (38 participants). Recordings were transcribed and submitted to a six-step thematic analysis. The following facilitators emerged: Participants valued the contribution of the IPM to articulate existing programs and teams, its community focus, and the local data obtained through the survey. There were also several barriers: Those included resistance to adopting a foreign model, the tension between generating local strategies and looking for measures to ensure the fidelity of the implementation, socioeconomic differences between and within municipalities, low-risk perception and supervision of parents in Chile, and a culture that generally does not discourage adolescent substance use. Implementation of the IPM was largely accepted by the stakeholders who agreed with the community approach of the model. The main barriers to consider were related to cultural and socioeconomic factors that need to be addressed in further research and may limit the effects of the model in Chile.

Maternal Obesity Programs the Premature Aging of Rat Offspring Liver Mitochondrial Electron Transport Chain Genes in a Sex-Dependent Manner.

We investigated whether maternal obesity affects the hepatic mitochondrial electron transport chain (ETC), sirtuins, and antioxidant enzymes in young (110 postnatal days (PND)) and old (650PND) male and female offspring in a sex- and age-related manner. Female Wistar rats ate a control (C) or high-fat (MO) diet from weaning, through pregnancy and lactation. After weaning, the offspring ate the C diet and were euthanized at 110 and 650PND. The livers were collected for RNA-seq and immunohistochemistry. Male offspring livers had more differentially expressed genes (DEGs) down-regulated by both MO and natural aging than females. C-650PND vs. C-110PND and MO-110PND vs. C-110PND comparisons revealed 1477 DEGs in common for males (premature aging by MO) and 35 DEGs for females. Analysis to identify KEGG pathways enriched from genes in common showed changes in 511 and 3 KEGG pathways in the male and female livers, respectively. Mitochondrial function pathways showed ETC-related gene down-regulation. All ETC complexes, sirtuin2, sirtuin3, sod-1, and catalase, exhibited gene down-regulation and decreased protein expression at young and old ages in MO males vs. C males; meanwhile, MO females down-regulated only at 650PND. Conclusions: MO accelerates the age-associated down-regulation of ETC pathway gene expression in male offspring livers, thereby causing sex-dependent oxidative stress, premature aging, and metabolic dysfunction.

Parental practices and their association with alcohol and cannabis use among adolescents in Chile.

Background: Adolescent alcohol and cannabis use are common in Chile. The present study aimed to assess the relationship between perceived parenting practices and alcohol and cannabis use among adolescents in a Latin American context. Methods: We adapted and implemented a substance use prevention strategy in Chile, which included surveys of tenth-grade students from six municipalities in the Metropolitan Region of Greater Santiago. We assessed the reliability and factorial structure of the parenting scale with 16 items, which formed part of the survey. We dichotomized parenting scores into high (above the median) and low. The association of parenting practices with alcohol and cannabis use in adolescents was assessed using multivariate multilevel regression models. Results: A total of 7,538 tenth-grade students from 118 schools were included in the study. The 16-item scale of parenting practices showed good internal consistency (Omega total = 0.84), and three factors representing Relationship between parents and adolescents, Norms and monitoring, and Parents knowing their children's friends and the parents of their children's friends. High total scores of parenting were associated with lower odds of lifetime alcohol use (OR 0.57; 95% CI: 0.49-0.65), past-month alcohol use (OR 0.63; 95% CI: 0.57-0.70), lifetime drunkenness (OR 0.64; 95% CI: 0.58-0.72), and lifetime cannabis use (OR 0.54; 95% CI: 0.47-0.61). Above median scores on each parenting subscale were associated with significantly lower odds of substance use. The strongest associations were observed for the subscale Norms and monitoring. Interactions between parenting and gender showed a significantly stronger effect of parenting practices on alcohol and cannabis use among girls. Conclusion: Different types of parenting practices were associated with a lower prevalence of adolescent alcohol and cannabis use. Improving parenting practices has the potential to prevent adolescent substance use in Chile, especially among girls.

A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression Among University Students: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT. Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors. Design, Setting, and Participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022. Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435). Main Outcomes and Measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline. Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P = .003) or treatment as usual (40.0% [2.7%]; P = .001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P = .007; self-guided i-CBT: 25.4% [8.8%]; P = .004; treatment as usual: 31.0% [9.4%]; P = .001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P = .14; treatment as usual: 53.0% [6.0%]; P = .25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P = .001; treatment as usual: 41.8% [3.2%]; P < .001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P = .07). Conclusions and Relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04780542.

Programming Mechanism of Adipose Tissue Expansion in the Rat Offspring of Obese Mothers Occurs in a Sex-Specific Manner.

We investigated whether excessive retroperitoneal adipose tissue (AT) expansion programmed by maternal obesity (MO) affects adipocyte size distribution and gene expression in relation to adipocyte proliferation and differentiation in male and female offspring (F1) from control (F1C) and obese (F1MO) mothers. Female Wistar rats (F0) ate a control or high-fat diet from weaning through pregnancy and lactation. F1 were weaned onto a control diet and euthanized at 110 postnatal days. Fat depots were weighed to estimate the total AT. Serum glucose, triglyceride, leptin, insulin, and the insulin resistance index (HOMA-IR) were determined. Adipocyte size and adipogenic gene expression were examined in retroperitoneal fat. Body weight, retroperitoneal AT and adipogenesis differed between male and female F1Cs. Retroperitoneal AT, glucose, triglyceride, insulin, HOMA-IR and leptin were higher in male and female F1MO vs. F1C. Small adipocytes were reduced in F1MO females and absent in F1MO males; large adipocytes were increased in F1MO males and females vs. F1C. Wnt, PI3K-Akt, and insulin signaling pathways in F1MO males and Egr2 in F1MO females were downregulated vs. F1C. MO induced metabolic dysfunction in F1 through different sex dimorphism mechanisms, including the decreased expression of pro-adipogenic genes and reduced insulin signaling in males and lipid mobilization-related genes in females.

High-fat diet consumption by male rat offspring of obese mothers exacerbates adipose tissue hypertrophy and metabolic alterations in adult life.

Obese mothers' offspring develop obesity and metabolic alterations in adulthood. Poor postnatal dietary patterns also contribute to obesity and its comorbidities. We aimed to determine whether in obese mothers' offspring an adverse postnatal environment, such as high-fat diet (HFD) consumption (second hit) exacerbates body fat accumulation, metabolic alterations and adipocyte size distribution. Female Wistar rats ate chow (C-5 %-fat) or HFD (maternal obesity (MO)-25 %-fat) from weaning until the end of lactation. Male offspring were weaned on either control (C/C and MO/C, maternal diet/offspring diet) or HFD (C/HF and MO/HF) diet. At 110 postnatal days, offspring were killed. Fat depots were excised to estimate adiposity index (AI). Serum glucose, triglyceride, leptin, insulin, insulin resistance index (HOMA-IR), corticosterone and dehydroepiandrosterone (DHEA) were determined. Adipocyte size distribution was evaluated in retroperitoneal fat. Body weight was similar in C/C and MO/C but higher in C/HF and MO/HF. AI, leptin, insulin and HOMA-IR were higher in MO/C and C/HF v. C/C but lower than MO/HF. Glucose increased in MO/HF v. MO/C. C/HF and MO/C had higher triglyceride and corticosterone than C/C, but lower corticosterone than MO/HF. DHEA and the DHEA/corticosterone ratio were lower in C/HF and MO/C v. C/C, but higher than MO/HF. Small adipocyte proportion decreased while large adipocyte proportions increased in MO/C and C/HF v. C/C and exacerbated in MO/HF v. C/HF. Postnatal consumption of a HFD by the offspring of obese mothers exacerbates body fat accumulation as well as the decrease of small and the increase of large adipocytes, which leads to larger metabolic abnormalities.

Alergia alimentar autodeclarada em idosos no Brasil: prevalência e características clínicas ­ Protocolo de estudo / Self-reported food allergy among older Brazilians: prevalence and clinical characteristics ­ a study protocol

Nas últimas décadas tem se observado um aumento expressivo na prevalência de alergia alimentar (AA), com frequência estimada em adultos de 3% a 8%, sendo ainda mais relevante quando se avalia a AA autodeclarada (variação de 3% a 35%). Entretanto, são poucos os dados publicados sobre a prevalência de AA em idosos, e no Brasil tais dados são inexistentes. O objetivo principal deste protocolo de estudo é conhecer a prevalência de AA autodeclarada em idosos (≥ 60 anos) brasileiros. Trata-se de estudo epidemiológico transversal que utiliza questionário padronizado e validado para a língua portuguesa. Entre os vários aspectos investigados, serão avaliados quais alimentos e sintomas são os mais relacionados à AA nestes indivíduos. Os dados obtidos serão transcritos a planilha Excel para realização da análise estatística. A obtenção dessas informações permitirá compará-las às existentes, assim como estabelecer planos de abordagem destes pacientes.

In recent decades, there has been a significant increase in the prevalence of food allergies, reaching an estimated frequency of 3% to 8% in adults and even higher in self-reports (from 3% to 35%). However, published data on the prevalence of food allergies among older adults are scarce, and in Brazil they are non-existent. The main objective of this study was to investigate the prevalence of self-reported food allergy among older Brazilians (≥ 60 years). This cross-sectional epidemiological study protocol involves a questionnaire that was developed, standardized, and validated in Portuguese. The investigated aspects will include the foods and symptoms most commonly associated with food allergy in this population. The data will be input into an Excel spreadsheet for statistical analysis. Obtaining this data will allow comparison of the results with previous data and help establish treatment plans for these patients.

Resveratrol Supplementation in Obese Pregnant Rats Improves Maternal Metabolism and Prevents Increased Placental Oxidative Stress.

Maternal obesity (MO) causes maternal and fetal oxidative stress (OS) and metabolic dysfunction. We investigated whether supplementing obese mothers with resveratrol improves maternal metabolic alterations and reduces OS in the placenta and maternal and fetal liver. From weaning through pregnancy female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating until 19 days' gestation (dG), half the rats received 20 mg resveratrol/kg/d orally (Cres and MOres). At 19dG, maternal body weight, retroperitoneal fat adipocyte size, metabolic parameters, and OS biomarkers in the placenta and liver were determined. MO mothers showed higher body weight, triglycerides and leptin serum concentrations, insulin resistance (IR), decreased small and increased large adipocytes, liver fat accumulation, and hepatic upregulation of genes related to IR and inflammatory processes. Placenta, maternal and fetal liver OS biomarkers were augmented in MO. MOres mothers showed more small and fewer large adipocytes, lower triglycerides serum concentrations, IR and liver fat accumulation, downregulation of genes related to IR and inflammatory processes, and lowered OS in mothers, placentas, and female fetal liver. Maternal resveratrol supplementation in obese rats improves maternal metabolism and reduces placental and liver OS of mothers and fetuses in a sex-dependent manner.

The alcohol prevention magnitude measure: Application of a Spanish-language version in Santiago, Chile.

BACKGROUND: The Alcohol Prevention Magnitude Measure (APMM) is an instrument to monitor and improve substance use prevention at the community level developed in Sweden. The aim of this study was to produce and apply a Spanish-language version of the APMM. METHOD: We translated and adapted the APMM using an expert panel. We retained 37 indicators in five dimensions, with total scores ranging from 0 to 100 points and 0 to 20 in each dimension. The instrument was administered to the prevention coordinators in six socioeconomically heterogeneous municipalities of Santiago de Chile, during the pilot implementation of a community-based prevention model in 2019 and 2020. We calculated median scores for the instrument and each dimension. We tested for differences between 2019 and 2020 using the Wilcoxon Test and between municipalities with the Friedman Test. RESULTS: The Spanish version of the APMM was acceptable to stakeholders. The median scores were 49.3 (range: 34.0 to 64.0) in 2019 and 67.3 (range 55.5 to 80.5) in 2020. The median scores for Staff and budget were 14.0 in 2019 and 2020, for Prevention policy 5.0 in 2019 and 16.0 in 2020, for Cooperation with key agents 12.0 in both years, for Supervision and alcohol licenses 4.3 in 2019 and 9.0 in 2020, and for Prevention activities 11.0 in 2019 and 15.0 in 2020. The scores in the dimensions Prevention policy and Supervision and alcohol licenses significantly increased in 2020. The differences between the municipalities were not significant. CONCLUSIONS: Improvements of the prevention index between 2019 and 2020 in the dimension Prevention policies may be related to the intervention. Improvements in Supervision and alcohol licenses could be related to curfew policies in the context of the COVID-19 pandemic. The Spanish version of the APMM deserves larger scale testing in Latin America.

Study protocol for pragmatic trials of Internet-delivered guided and unguided cognitive behavior therapy for treating depression and anxiety in university students of two Latin American countries: the Yo Puedo Sentirme Bien study.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent among university students and predict impaired college performance and later life role functioning. Yet most students do not receive treatment, especially in low-middle-income countries (LMICs). We aim to evaluate the effects of expanding treatment using scalable and inexpensive Internet-delivered transdiagnostic cognitive behavioral therapy (iCBT) among college students with symptoms of MDD and/or GAD in two LMICs in Latin America (Colombia and Mexico) and to investigate the feasibility of creating a precision treatment rule (PTR) to predict for whom iCBT is most effective. METHODS: We will first carry out a multi-site randomized pragmatic clinical trial (N = 1500) of students seeking treatment at student mental health clinics in participating universities or responding to an email offering services. Students on wait lists for clinic services will be randomized to unguided iCBT (33%), guided iCBT (33%), and treatment as usual (TAU) (33%). iCBT will be provided immediately whereas TAU will be whenever a clinic appointment is available. Short-term aggregate effects will be assessed at 90 days and longer-term effects 12 months after randomization. We will use ensemble machine learning to predict heterogeneity of treatment effects of unguided versus guided iCBT versus TAU and develop a precision treatment rule (PTR) to optimize individual student outcome. We will then conduct a second and third trial with separate samples (n = 500 per arm), but with unequal allocation across two arms: 25% will be assigned to the treatment determined to yield optimal outcomes based on the PTR developed in the first trial (PTR for optimal short-term outcomes for Trial 2 and 12-month outcomes for Trial 3), whereas the remaining 75% will be assigned with equal allocation across all three treatment arms. DISCUSSION: By collecting comprehensive baseline characteristics to evaluate heterogeneity of treatment effects, we will provide valuable and innovative information to optimize treatment effects and guide university mental health treatment planning. Such an effort could have enormous public-health implications for the region by increasing the reach of treatment, decreasing unmet need and clinic wait times, and serving as a model of evidence-based intervention planning and implementation. TRIAL STATUS: IRB Approval of Protocol Version 1.0; June 3, 2020. Recruitment began on March 1, 2021. Recruitment is tentatively scheduled to be completed on May 30, 2024. TRIAL REGISTRATION: ClinicalTrials.gov NCT04780542 . First submission date: February 28, 2021.

Síndrome de bandas amnióticas en el desarrollo de las hendiduras faciales. Reporte de caso clínico / Amniotic band syndrome in the development of facial clefts. Clinical case report

Introducción: el síndrome de bandas amnióticas abarca una variedad de anomalías congénitas que incluyen la deformación, disrupción y malformación de múltiples órganos. Este síndrome tiene diferentes manifestaciones clínicas al nacimiento, como anillos formados por la constricción de las bandas, amputaciones de extremidades y malformaciones craneofaciales. La incidencia es de aproximadamente 1 en 1,200-15,000 nacidos vivos. Objetivo: realizar la descripción de un paciente femenino de 4 meses de edad que acude al servicio de cirugía oral y maxilofacial del Hospital del Niño DIF Pachuca, Hidalgo, México. La paciente presenta deformidad en la región geniana que se extiende desde el labio superior hasta la región infraorbitaria de lado derecho, pit paracomisural derecho y fisura Tessier 7. Conclusión: se da el diagnóstico final de deformidad maxilofacial a causa del síndrome de bandas amnióticas y la paciente recibe tratamiento médico-quirúrgico con un resultado satisfactorio.

Backgrond: Amniotic band syndrome encompasses a variety of congenital anomalies which include deformation, disruption, or malformation of multiple organs, exhibiting different clinical manifestations at birth, such as rings formed by the constriction of the bands, limb amputations and craniofacial malformations. The incidence is approximately 1 in 1,200-15,000 live births. Objective: To describe a 4-month-old female patient who attends the oral and maxillofacial surgery service of the Hospital del Niño DIF Pachuca, Hidalgo, Mexico, presenting a deformity in the genian region that extending from the upper lip to the infraorbital region on the right side, right paracommissural pit and Tessier fissure 7. Conclusion: In the final diagnosis of maxillofacial deformity due to amniotic band syndrome, medical-surgical treatment is received with a satisfactory result.

DHA Supplementation of Obese Rats throughout Pregnancy and Lactation Modifies Milk Composition and Anxiety Behavior of Offspring.

We investigated if supplementing obese mothers (MO) with docosahexaenoic acid (DHA) improves milk long-chain polyunsaturated fatty acid (LCPUFA) composition and offspring anxiety behavior. From weaning throughout pregnancy and lactation, female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating and through lactation, half the mothers received 400 mg DHA kg-1 d-1 orally (C+DHA or MO+DHA). Offspring ate C after weaning. Maternal weight, total body fat, milk hormones, and milk nutrient composition were determined. Pups' milk nutrient intake was evaluated, and behavioral anxiety tests were conducted. MO exhibited increased weight and total fat, and higher milk corticosterone, leptin, linoleic, and arachidonic acid (AA) concentrations, and less DHA content. MO male and female offspring had higher ω-6/ ω-3 milk consumption ratios. In the elevated plus maze, female but not male MO offspring exhibited more anxiety. MO+DHA mothers exhibited lower weight, total fat, milk leptin, and AA concentrations, and enhanced milk DHA. MO+DHA offspring had a lower ω-6/ω-3 milk intake ratio and reduced anxiety vs. MO. DHA content was greater in C+DHA milk vs. C. Supplementing MO mothers with DHA improves milk composition, especially LCPUFA content and ω-6/ω-3 ratio reducing offspring anxiety in a sex-dependent manner.

Interoception and alcohol addiction: Vagotomy induces long-lasting suppression of relapse-type behavior.

Drug addictions are chronic mental disorders characterized by compulsive drug seeking and drug use, despite their negative consequences. It is a priority to find therapeutic alternatives to prevent relapse, as there are still no treatments that can ensure abstinence. One of the neural systems implicated in the appearance of the states of discomfort that motivate relapse is the interoceptive system, which oversees our internal body states. However, less attention has been given to the peripheral components of the interoceptive system and their role in addictions. Within these pathways, the vagus nerve represents one of the main visceral afferents of the interoceptive system. We hypothesized that the interruption of visceral afferent pathways would decrease the motivational effects of the drug, thereby either decreasing or preventing drug cravings. To test this idea, we used rats of a high-alcohol-drinking line and measured the effect that vagus nerve resection had on the relapse-like alcohol drinking, expressed as the alcohol deprivation effect, a phenomenon that has been linked to addiction-related events such as alcohol cravings. We found that even though vagotomy completely eliminates the effect of alcohol deprivation, it has no impact on water consumption or animal weight. These results give us valuable information about the relationship between the autonomic nervous system and alcohol use disorders and allow us to propose new clinical research that might have translational options.