Explaining the "parenting - callous-unemotional traits - antisocial behavior" axis in early adolescence: The role of affiliative reward.

In explaining the "parenting - callous-unemotional traits - antisocial behavior" axis, recent theoretical advances postulate a critical role for affiliative reward. Existing empirical studies focus on early childhood and the appetitive phase of the reward process (i.e. affiliation-seeking behavior) rather than the consummatory phase (i.e. affective rewards). This study focuses on experienced affiliative reward (i.e. companionship, intimacy, affection, and worth) in relation to parents and best friends in early adolescence. The Alabama Parenting Questionnaire, Network of Relationships Inventory, Inventory of Callous and Unemotional Traits, and Youth Self Report were completed by 1132 12-year-olds and analyzed via structural equation models. In this cross-sectional sample, parent-related affiliative reward mediated the path from perceived parenting practices to callousness and further to aggression and rule-breaking. Parent-related affiliative reward was also related to uncaring traits and further to aggression and rule-breaking. In contrast, friend-related affiliative reward was not a mediator in this theoretical causal chain and largely not related to perceived parenting practices or CU traits. Low parent-related experienced affiliative reward is a mechanism through which corporal punishment, poor monitoring, and low involvement translate into callousness, and therefore to aggression and rule-breaking. Friend-related affiliative reward does not yet play a role in early adolescence.

Positioning sulphonylureas in a modern treatment algorithm for patients with type 2 diabetes: Expert opinion from a European consensus panel.

The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second-line treatment after metformin and are often ranked at the same level as newer glucose-lowering medications. Strong evidence now shows that sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT-2is and GLP-1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT-2is and/or GLP-1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second-line agents continues to be acceptable in resource-constrained settings.

Clinical and genetic predictors of diabetes drug's response.

Diabetes is a major health problem worldwide. Glycemic control is the main goal in the management of type 2 diabetes. While many anti-diabetic drugs and guidelines are available, almost half of diabetic patients do not reach their treatment goal and develop complications. The glucose-lowering response to anti-diabetic drug differs significantly between individuals. Relatively little is known about the factors that might underlie this response. The identification of predictors of response to anti-diabetic drugs is essential for treatment personalization. Unfortunately, the evidence on predictors of drugs response in type 2 diabetes is scarce. Only a few trials were designed for specific groups of patients (e.g. patients with renal impairment or older patients), while subgroup analyses of larger trials are frequently unreported. Physicians need help in picking the drug which provides the maximal benefit, with minimal side effects, in the right dose, for a specific patient, using an omics-based approach besides the phenotypic characteristics.

Intercellular adhesion molecule-1 (ICAM-1) associates with 24-hour ambulatory blood pressure variability in type 2 diabetes and controls.

BACKGROUND AND AIM: Endothelial dysfunction is a common feature in hypertension and type 2 diabetes. Whether blood pressure (BP) variability is influencing serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) remains to be clarified. We aimed to assess the association between the circulating adhesion molecules and ambulatory blood pressure variability in patients with type 2 diabetes and controls. PATIENTS AND METHODS: The study included data from type 2 diabetes with controlled BP (n = 55), type 2 diabetes with uncontrolled BP (n = 55) and control subjects (n = 28). ICAM-1 and VCAM-1 were measured with specific enzyme-linked immunosorbent assay method. BP variability was assessed using standard deviation of mean systolic and diastolic BP evaluated during 24-hour ambulatory BP monitoring. RESULTS: The uncontrolled BP type 2 diabetes group had significantly higher serum ICAM-1 and VCAM-1 levels compared to controlled BP type 2 diabetes and control groups. In linear regression analysis, after adjustment, higher ICAM-1 was consistently associated with higher daytime and 24-hour diastolic BP variability, and daytime systolic BP variability in the study population. VCAM-1 was associated only with daytime systolic BP variability. CONCLUSIONS: Our study evaluating the association of serum ICAM-1 and VCAM-1 with 24-hour ambulatory BP variability in patients with type 2 diabetes and controls might offer better understanding of the mechanisms generating endothelial dysfunction. Elevated 24-hour ambulatory BP variability might induce endothelial activation by increasing circulating adhesion molecules levels.

Lipidomics biomarkers in women with polycystic ovary syndrome (PCOS) using ultra-high performance liquid chromatography-quadrupole time of flight electrospray in a positive ionization mode mass spectrometry.

Polycystic ovary syndrome (PCOS), characterized by oligo-anovulation and androgen excess is considered a high-risk condition for metabolic disorders. Herein, untargeted metabolomics analysis was applied to women with PCOS, aiming to provide deeper insights into lipidomics biomarkers signature of PCOS, for better diagnosis and management. This was a cross-sectional study in which 15 Caucasian women with PCOS and 15 Caucasian healthy, age-matched women were enrolled. Lipidomics analysis was performed using Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Electrospray Mass Spectrometry. Partial Least Squares Discriminant Analysis retrieved the most important discriminative metabolites. Significantly increased levels of triacylglycerol (18:2/18:2/0-18:0) in addition to cholestane-3beta, 5alpha, 6beta-triol (18:0/0:0) and cholestane-5alpha (18:1/0:0) appeared as valuable variables to differentiate subjects with PCOS from controls. Acyl-carnitine 2-hydroxylauroylcarnitine was significantly elevated in PCOS in opposition to decreased phosphocholines metabolites (18:1/18:4, 18:3/18:2), to suggest a metabolic pattern linked to lipid peroxidation. A high fat intake or reduced fat energy consumption during nighttime due to diminished ability to switch to lipid oxidation during fasting time possibly contribute to hypertriglyceridemia found in PCOS. Furthermore, inflammatory mediators including metabolites of the prostaglandin (PG) E2 pathway and oxo-leukotrienes (LT) were increased in patients with PCOS. Potential lipidomics biomarkers were identified that could stratify between women with PCOS and healthy controls. The results show particular alterations in acylglycerols, PGs and LTs and phosphocholines and carnitine metabolites. The lipidomics profiles of PCOS indicate a higher risk of developing metabolic diseases.

Sleep duration and body mass index: moderating effect of self-perceived stress and age. Results of a cross-sectional population-based study.

PURPOSE: The objective of this analysis was to assess whether the association between sleep duration and BMI and between sleep duration and waist circumference is moderated by age and self-perceived stress. METHODS: We analyzed data from 2034 participants enrolled in 2014 in the cross-sectional study Obesity in Romania Study-study of the prevalence of obesity and related risk factors in Romanian general population (ORO study). RESULTS: Interaction between sleep duration, self-perceived stress and age, with BMI as dependent variable, was statistically significant after adjustment for demographic and lifestyle factors (p value for interaction 0.003). In participants without self-perceived stress, a linear negative association between sleep duration and BMI was observed only in those 18-39 years old (p = 0.049), with BMI decreasing in parallel with increased sleep duration. In participants with self-perceived stress, a U-shaped relationship was observed between BMI and sleep duration in those 40-64 years old, with higher BMI in those sleeping ≤ 6 h and ≥ 9 h/night compared to those sleeping > 6 and < 9 h/night (p = 0.002 and 0.005). Those ≥ 65 years old with self-perceived stress sleeping ≥ 9 h/night had a significantly higher BMI compared to those in other sleep duration categories (p = 0.041 vs. those sleeping ≤ 6 h/night and p = 0.013 vs. to those sleeping > 6 and < 9 h/night). No interaction between age, self-perceived stress and sleep duration, with waist circumference as dependent variable was observed. CONCLUSIONS: In our sample, the association between sleep duration and BMI was moderated by self-perceived stress and age.

Comparative Models of Biological and Social Pathways to Predict Child Growth through Age 2 Years from Birth Cohorts in Brazil, India, the Philippines, and South Africa.

Background: Early growth faltering accounts for one-third of child deaths, and adversely impacts the health and human capital of surviving children. Social as well as biological factors contribute to growth faltering, but their relative strength and interrelations in different contexts have not been fully described. Objective: The aim of this study was to use structural equation modelling to explore social and biological multidetermination of child height at age 2 y in longitudinal data from 4 birth cohort studies in low- and middle-income countries. Methods: We analyzed data from 13,824 participants in birth cohort studies in Brazil, India, the Philippines, and South Africa. We used exploratory structural equation models, with height-for-age at 24 mo as the outcome to derive factors, and path analysis to estimate relations among a wide set of social and biological variables common to the 4 sites. Results: The prevalence of stunting at 24 mo ranged from 14.0% in Brazil to 67.7% in the Philippines. Maternal height and birthweight were strongly predictive of height-for-age at 24 mo in all 4 sites (all P values <0.001). Three social-environmental factors, which we characterized as "child circumstances," "family socioeconomic status," and "community facilities," were identified in all sites. Each social-environmental factor was also strongly predictive of height-for-age at 24 mo (all P values <0.001), with some relations partly mediated through birthweight. The biological pathways accounted for 59% of the total explained variance and the social-environmental pathways accounted for 41%. The resulting path coefficients were broadly similar across the 4 sites. Conclusions: Early child growth faltering is determined by both biological and social factors. Maternal height, itself a marker of intergenerational deprivation, strongly influences child height at 2 y, including indirect effects through birthweight and social factors. However, concurrent social factors, many of which are modifiable, directly and indirectly contribute to child growth. This study highlights opportunities for interventions that address both biological and social determinants over the long and short term.

Parenting and the Adjustment of Children Born to Gay Fathers Through Surrogacy.

Findings are presented on a study of 40 gay father families created through surrogacy and a comparison group of 55 lesbian mother families created through donor insemination with a child aged 3-9 years. Standardized interview, observational and questionnaire measures of stigmatization, quality of parent-child relationships, and children's adjustment were administered to parents, children, and teachers. Children in both family types showed high levels of adjustment with lower levels of children's internalizing problems reported by gay fathers. Irrespective of family type, children whose parents perceived greater stigmatization and children who experienced higher levels of negative parenting showed higher levels of parent-reported externalizing problems. The findings contribute to theoretical understanding of the role of family structure and family processes in child adjustment.

The role of age of disclosure of biological origins in the psychological wellbeing of adolescents conceived by reproductive donation: a longitudinal study from age 1 to age 14.

BACKGROUND: The question of whether children should be told of their biological origins is one of the most controversial issues regarding the birth of children through donated eggs, sperm, embryos or surrogacy. METHODS: In the sixth phase of this longitudinal study when the children were aged 14 years, family relationships and adolescent adjustment were examined in 87 families created through reproductive donation and 54 natural conception families. The quality of family relationships was assessed by standardised interview with mothers and by standardised questionnaires and an observational measure with mothers and adolescents. Adolescent adjustment was assessed using standardised questionnaires. Systematic information on whether and when parents had told children about their biological origins was obtained at earlier phases of the study. RESULTS: There were no overall differences between disclosing families and either nondisclosing or natural conception families. However, within the disclosing families, more positive family relationships and higher levels of adolescent wellbeing were found for adolescents who had been told about their biological origins before age 7. CONCLUSIONS: The earlier children born through reproductive donation are told about their biological origins, the more positive are the outcomes in terms of the quality of family relationships and psychological wellbeing at adolescence.

Does executive function mediate the path from mothers' depressive symptoms to young children's problem behaviors?

This study investigated the mediation role played by children's executive function in the relationship between exposure to mild maternal depressive symptoms and problem behaviors. At ages 2, 3, and 6years, 143 children completed executive function tasks and a verbal ability test. Mothers completed the Beck Depression Inventory at each time-point, and teachers completed the Strengths and Difficulties Questionnaire at child age 6. Longitudinal autoregressive mediation models showed a mediation effect that was significant and quite specific; executive function (and not verbal ability) at age 3 mediated the path between mothers' depressive symptoms (but not general social disadvantage) at the first time-point and children's externalizing and internalizing problems at age 6. Improving children's executive functioning might protect them against the adverse effects of exposure to maternal depressive symptoms.

Lifestyle factors, dietary patterns, and social determinants of social and eating jetlag: A cross-sectional survey.

Social jetlag (SJL) and, more recently, eating jetlag have been linked with an increased risk of non-communicable diseases. Here we aim to investigate lifestyle factors (diet, eating behavior, smoking, perceived stress, time spent sedentary/day) and social determinants (education level, employment status, and place of residence) associated with SJL corrected for sleep duration (SJLsc) and eating jetlag. Self-declared data on age, gender, lifestyle, and eating behavior were collected online from March 2021 to February 2022 of 432 adults. Principal component analysis was used to extract three dietary patterns (Prudent, Western, and Risky). Prevalence of SJLsc was 35.2%, with no significant difference between men and women (p = 0.558). Adults with SJLsc had significantly larger eating jetlag (56.0 min vs 41.2 min, p = 0.001). Increasing SJLsc duration was associated with an increased adherence to a Risky dietary pattern (standardized ß coefficient = .165, p = 0.012); increasing eating jetlag duration was associated with an increased adherence to a Western dietary pattern (standardized ß coefficient = .127, p = 0.039) and a shorter sleep duration (standardized ßcoefficient = -0.147, p = 0.011). Among social determinants analyzed, only being a student or employed was associated with eating jetlag (standardized ß coefficient = 0.125, p = 0.044), while none displayed any relationship with SJLsc. Our survey provides evidence on a risky behavior among young persons with SJLsc and eating jetlag, characterized by a higher alcohol consumption, and a diet rich in processed meat and high-fat food, eating during nights, and shorter sleep duration with potential long-term negative health outcomes.

Does maternal depression predict young children's executive function? - a 4-year longitudinal study.

BACKGROUND: Building on reports that parental maltreatment and neglect adversely affect young children's executive function (EF), this longitudinal study examined whether exposure to a more common risk factor, mothers' depressive symptoms, predicted individual differences in EF at school-age. METHODS: We followed up at age 6 a socially diverse sample of 126 children (78 boys, 48 girls) for whom direct observations of mother-child interactions have been shown to predict gains in EF between the ages of 2 and 4. We used an EF latent factor based on scores from three tasks (Beads, Day/Night, Tower of London) that tapped working memory, inhibitory control and planning, as well as a latent growth model of mothers' Beck Depression Inventory factor scores at four time-points, and included age 6 verbal ability as a covariate in all analyses. RESULTS: The intercept and slope for mothers' depressive symptoms each predicted unique variance in EF at age 6; these predictive effects remained significant when we also included: (a) age 2 working memory, (b) maternal education and (c) direct observations of maternal positive control at ages 2 and 6. CONCLUSION: Our findings suggest that early exposure to mothers' depressive symptoms adversely affects children's developing EF, and that the chronicity of this exposure may matter.

Children born through reproductive donation: a longitudinal study of psychological adjustment.

BACKGROUND: Parenting and children's adjustment were examined in 30 surrogacy families, 31 egg donation families, 35 donor insemination families, and 53 natural conception families. METHODS: Parenting was assessed at age 3 by a standardized interview designed to assess quality of parenting and by questionnaire measures of anxiety, depression, and marital quality. Children's adjustment was assessed at ages 3, 7, and 10 using the Strengths and Difficulties Questionnaire (SDQ). RESULTS: Although children born through reproductive donation obtained SDQ scores within the normal range, surrogacy children showed higher levels of adjustment difficulties at age 7 than children conceived by gamete donation. Mothers who had kept their child's origins secret showed elevated levels of distress. However, maternal distress had a more negative impact on children who were aware of their origins. CONCLUSIONS: The absence of a gestational connection to the mother may be more problematic for children than the absence of a genetic link.

The effect of Dulaglutide on glycemic and weight control in patients with type 2 diabetes.

Background and aims: The objectives of type 2 diabetes treatment are to achieve adequate long-term glycemic control and to reduce the risk associated with comorbidities and complications. Once-weekly Dulaglutide showed a reduction in cardiovascular risk associated with diabetes in addition to improved glycemic control and bodyweight reduction in several clinical trials. We aimed to investigate the effect of Dulaglutide 1.5 mg on glycemic and weight control in type 2 diabetes patients inadequately controlled by antihyperglycemic treatment in real-world clinical practice. Methods: We retrospectively reviewed the medical records of 50 patients with type 2 diabetes inadequately controlled by previous treatment and newly initiated on Dulaglutide. The data were collected at 6 months (n=50) and 12 months (n=40) after Dulaglutide therapy initiation. Results: Dulaglutide treatment resulted in significant improvement of glycated hemoglobin (-1.3 %; p<0.001) after 6 months and after 12 months (-2.0 %; p<0.001). Significant bodyweight reduction was found after 6 months (-2.0 kg; p=0.002) and 12 months (-3.5 kg; p=0.001) of Dulaglutide treatment initiation. In addition, a reduction in insulin dose was observed. Conclusions: Our clinical data showed that Dulaglutide 1.5 mg significantly improved glycemic and bodyweight control at 6 and 12 months after treatment initiation in patients with type 2 diabetes inadequately controlled by previous antihyperglycemic treatment.

Social and Metabolic Determinants of Prevalent Hypertension in Men and Women: A Cluster Analysis from a Population-Based Study.

Essential hypertension (HTN) has a complex spectrum of pathophysiological determinants and current guidelines provide limited information on high-risk groups that should be targeted for its primary prevention. The objective of our research was to identify clusters of social and metabolic factors associated with prevalent HTN in men and women from a population-based survey in Romania. Of the 1477 participants in the main study, 798 with complete data were analyzed here. Using two-step cluster analysis, one high-risk cluster in women and two high and intermediate risk for prevalent HTN in men were identified. Older age, rural area, lower education, and higher burden of metabolic factors characterized clusters with higher risk, while intermediate risk in men was characterized by a more metabolically healthy phenotype in younger individuals. In logistic regression, men in Cluster 1 vs. those in Cluster 3 had an odds ratio (OR) of 9.6 (95%CI: 4.6; 20.0), p < 0.001 for prevalent HTN, while OR for Cluster 2 vs. Cluster 3 was 3.2 (95%CI: 1.4; 7.4), p = 0.005. In women, the OR for HTN was 10.2 (95%CI: 5.7; 18.5) if assigned to Cluster 2 vs. Cluster 1, p < 0.001. These results pointed out the subgroups and communities that the primary prevention of HTN should be prioritized in.

Early adolescents' perceptions of parenting practices and mental health problems: A network approach.

This study aims to identify possible primary targets for the parenting programs designed to reduce (or prevent) the mental health problems of adolescents. We used network analysis to estimate networks for parenting practices and for the interplay between parenting practices and adolescents' mental health problems. A community sample of early adolescents (10-13 years old, N = 1,125) reported both parenting (Alabama Parenting Questionnaire, Child Global Report) and mental health outcomes (Youth Self-Report). The behavior "You stay out later than you are supposed to and your parents don't know it" was the most central in the parenting practices network. Poor monitoring and conduct problems were the main paths through which parenting practices and youths' mental health influenced each other. Regarding the interplay between parenting practices and adolescent mental health, the network for males had a significantly higher connectivity (p = .035) than that for females. Although in the early stages, the network approach promises to provide a better understanding of parenting practices and their interaction with the mental health problems of adolescents. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Length of Hospital Stay, Hospitalization Costs, and Their Drivers in Adults with Diabetes in the Romanian Public Hospital System.

The aim of this analysis was to assess the costs associated with the hospitalizations of persons with diabetes in a Romanian public hospital. We performed a retrospective "top-down" cost analysis of all adult patients discharged from a tertiary care hospital with an ICD-10 primary or secondary code of diabetes mellitus (type 1, type 2, or specific forms) between 1 January 2015 and 31 December 2018. All costs were adjusted with the annual inflation rates and converted to EUR. We included 16,868 patients with diabetes and 28,055 episodes of hospitalization. The total adjusted hospitalization cost in the analyzed period was EUR 26,418,126.8 and the adjusted median cost/episode of hospitalization was EUR 596.5. The mean length of a hospital stay/episode was 7.3 days. In the multivariate regression analysis, higher adjusted average costs/episodes of hospitalization and longer lengths of hospital stays were associated with increasing age, the presence of cardiovascular diseases, chronic kidney disease, and foot ulcerations. Moreover, a significant association between the average cost/episode of hospitalization and the length of hospital stay was observed (ß = 0.704, p < 0.001). This study shows the burden on Romanian public hospitals of inpatient diabetes care and the main drivers of the costs.

E-Selectin Is Associated with Daytime and 24-Hour Diastolic Blood Pressure Variability in Type 2 Diabetes.

E-selectin is an endothelial cell adhesion molecule involved in vascular inflammation. Elevated E-selectin has been reported in patients with high blood pressure and diabetes. Given the increasing clinical relevance of parameters derived from ambulatory blood pressure monitoring, further investigation of their relationships with E-selectin is of interest. In this study, we aimed to investigate the association between serum E-selectin, office blood pressure and 24 h ambulatory blood pressure parameters in patients with type 2 diabetes. Blood pressure variability was assessed by computing the standard deviation of mean systolic and diastolic blood pressure separately for daytime and nighttime during 24 h ambulatory blood pressure monitoring in a cohort of patients with type 2 diabetes (n = 132). Additionally, were assessed nighttime systolic dipping and pulse pressure separately for daytime, nighttime, and 24 h. Serum E-selectin was measured using the enzyme-linked immunosorbent assay technique. We found that E-selectin was consistently associated with 24 h diastolic blood pressure variability (r = 0.238; p = 0.019) and daytime diastolic blood pressure variability (r = 0.258; p = 0.012), after adjustment for confounding factors. No association of E-selectin with office blood pressure and other 24 h ambulatory blood pressure parameters was observed. In conclusion, endothelial activation indicated by elevated serum E-selectin is associated with increased ambulatory diastolic blood pressure variability in patients with type 2 diabetes.

Variability in Sleep Timing and Dietary Intake: A Scoping Review of the Literature.

The objective of this scoping review was to summarize previous studies which examined the effect of day-to-day variability in sleep timing and social jetlag (SJL) on dietary intake. A systematic literature search was conducted in PubMed, Embase, and Clarivate Analytics Web of Science and we identified 22 records. No difference in caloric and macronutrient intake between SJL groups was observed in studies that enrolled healthy young adults. However, studies that enrolled participants with obesity and obesity-related chronic conditions reported a higher caloric intake and a higher intake of carbohydrates, total fat, saturated fats, and cholesterol in participants with SJL than in those without. Most studies reported a lower quality of diet, a delayed mealtime, and eating jetlag in participants with SJL vs. those without SJL. No correlation of day-to-day variability in sleep timing with average caloric intake was observed, but bed-time variability was negatively associated with diet quality. Methodological issues have been identified in sources assessed including study design, power calculation, population enrolled, and tools/metrics used for sleep timing variability assessment. Future well powered longitudinal studies, with clear protocols, standardized metrics, including all age groups from general population are needed to clarify the dietary intake consequences of variability in sleep timing.

The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus.

Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its associations with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the composition of gut microbiota, but it is unclear how this, in turn, may influence metabolism. The main objective of this review is to evaluate the pathogenetic association between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.