Pediatric Insomnia.

Insomnia is the most common sleep disorder among all ages; unfortunately, however, child and adolescent insomnia is infrequently addressed. Given the importance of adequate sleep for proper brain development, pediatric populations are particularly vulnerable to the negative effects of insomnia. Therefore, proper clinical assessment and treatment of pediatric insomnia is crucial. This article is the result of a comprehensive literature review and serves as a guide to the disorder and how it presents differently across child development.

Myths and Evidence Regarding Melatonin Supplementation for Occasional Sleeplessness in the Pediatric Population.

Occasional sleeplessness in children is common, with as many as 25% of all healthy children experiencing a problem sleeping at some point over the course of their childhood. Occasional sleeplessness is poorly understood, has a significant impact on quality of life in children and their families, and is often challenging to manage. There is substantial evidence supporting the safe and effective use of the widely available dietary supplement melatonin for children with chronic conditions. This article summarizes the views expressed in a recent Consensus Panel meeting convened to evaluate the use of melatonin in children, as well as the published scientific literature related to the effectiveness and safety of melatonin, with a focus on occasional sleeplessness in healthy children. We provide an evidence-based framework for the implementation of a standard process to effectively manage occasional sleeplessness in children and adolescents. Unsubstantiated concerns in the past may have limited melatonin's use in children with conditions for which the supplement may support a better sleep pattern and, by doing so, may help to improve quality of life. Melatonin dietary supplements using high quality standards may be provided to children together with cognitive-behavioral therapy after proper sleep evaluation and after improved sleep hygiene, family education, and sleep diary activities have failed to resolve sleep difficulties. [Pediatr Ann. 2021;50(9):e391-e395.].

Pediatric Insomnia.

Insomnia is the most common sleep disorder among all ages; unfortunately, however, child and adolescent insomnia is infrequently addressed. Given the importance of adequate sleep for proper brain development, pediatric populations are particularly vulnerable to the negative effects of insomnia. Therefore, proper clinical assessment and treatment of pediatric insomnia is crucial. This article is the result of a comprehensive literature review and serves as a guide to the disorder and how it presents differently across child development.

Mental Health Promotion and Disease Prevention: It's About Time.

Over the past decade, our field has observed rapidly rising rates of mental illness in children and adolescents. The numbers are sobering. Nearly 50% of teens 13 to 18 years of age meet DSM criteria for at least 1 disorder and 27.6% meet criteria for a "severe disorder."1 Adverse childhood experiences affect more than 50% of children and predispose these individuals to not only academic and behavioral problems throughout their youth, but also future physical disability, such as obesity, hypertension, and diabetes, as adults.2 By 14 years of age, accidents, suicide, and homicide assert themselves as the leading causes of death among our youth, accounting for more than 85% of the mortality among teens and young adults and holding fast to that ranking until 35 years of age.3 Most addictive behavior starts in adolescence, accounting for the 3 greatest causes of preventable death-smoking, obesity, and alcohol abuse-that take the lives of approximately 1 million adults in the United States annually.4 In addition, if there were ever a statistic to be held on the tip of every psychiatrist's tongue, it would be that 50% of all mental illnesses begin by 14 years of age and 75% begin by 24 years.5.

Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain.

The self-assembly of micellar structures from diblock polymers that contain hydrophilic and hydrophobic domains has been of great interest for the encapsulation of drugs and other hydrophobic molecules. While most commercially used surfactants are derived from hydrocarbon sources, there have been recent efforts to replace these with biodegradable, nontoxic, biologically synthesized alternatives. Previous examples have primarily examined naturally occurring self-assembling proteins, such as silk and elastin-like sequences. Herein, we describe a new series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles that are 27 nm in diameter after enzymatic cleavage of a solubilizing protein tag. The sequences of the proteins are based on a human intrinsically disordered protein, which has been appended with a hydrophobic segment. The micelles were found to form across a broad range of pH, ionic strength, and temperature conditions, with critical micelle concentration (CMC) values in the low micromolar range, 3 orders of magnitude lower than the CMC of commonly used surfactant sodium dodecyl sulfate (SDS). The reported micelles were found to solubilize hydrophobic metal complexes and organic molecules, suggesting their potential suitability for catalysis and drug delivery applications. Furthermore, the inherent flexibility in the design of these protein sequences enables the encoding of additional functionalities for many future applications. Overall, this work represents a new biomolecular alternative to traditional surfactants that are based on nonrenewable and poorly biodegradable hydrocarbon sources.

Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing.

BACKGROUND: Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. METHODS: Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as 'damaging' or 'potentially damaging' by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. RESULTS: Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. CONCLUSION: The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases.

Exploring Interventions for Sleep Disorders in Adolescent Cannabis Users.

This review summarizes the available literature on the intersection of adolescent cannabis use and sleep disturbances, along with interventions for adolescent cannabis users who suffer sleep impairments. Adolescents are susceptible to various sleep disorders, which are often exacerbated by the use of substances such as cannabis. The relationship between cannabis and sleep is bidirectional. Interventions to improve sleep impairments among adolescent cannabis users to date have demonstrated limited efficacy, although few studies indicating the benefits of behavioral interventions-such as Cognitive Behavior Therapy for Insomnia or Mindfulness Based Stress Reduction-appear promising in the treatment of sleep disorders, which are present for users of cannabis. Further research is necessary to elucidate the precise mechanisms by which cannabis use coexists with sleep impairments, along with effective interventions for those users who suffer sleep difficulties.

Impact of a sleep course on sleep, mood and anxiety symptoms in college students: A pilot study.

OBJECTIVE: To examine the impact of a sleep course on sleep-related behaviors, mood, and anxiety in college students. PARTICIPANTS: Participants were 145 students enrolled in either the sleep course (n = 70) or a psychology course (n = 75); data were collected in September 2014, November 2014, and February 2015. METHODS: Sleep characteristics and symptoms of depression and anxiety were assessed using validated questionnaires and sleep logs. Linear, logistic and proportional odds regression models were used to test course effects. RESULTS: In November, sleep course students reported significant differences in sleep hygiene (SHI; p < .001), perceived sleep latency (PSQI; p < .05), and circadian sleep phase (MEQ; p < .05), compared to controls. In February, the sleep course students maintained most of the aforementioned gains and reported fewer symptoms of depression (CES-D; p = .05) and anxiety (BAI; p < .05). CONCLUSIONS: These positive preliminary results indicate that focused education has the potential to improve sleep among college students.

Almost Psychiatry: The Impact of Teaching Child and Adolescent Mental Health Studies to Undergraduate College Students.

OBJECTIVE: The Child and Adolescent Mental Health Studies (CAMS) program is housed in a Liberal Arts undergraduate college of a large research university. Psychiatrists, clinical psychologists, and social workers at the university's medical center teach the courses. The purpose of this study is to evaluate the extent to which CAMS encourages graduates of the program to pursue a career in child and adolescent mental health (CAMH). METHODS: In 2015-2016, graduates of the CAMS program were invited to participate in a mixed methods study. In addition to statistical analyses, qualitative thematic analyses were performed to interpret free-text responses. RESULTS: Forty-five percent (314/702) of invited graduates completed the online survey. Interviews were conducted with 11% (34/314) of participants by study staff over the phone. Quantitative results suggested that 81% (149/185) of participants enrolled in educational programs after graduation due to an interest in CAMH. A significantly higher proportion of the total sample (t = 3.661, p < .001) reported that they changed their career goals while undergraduate students compared to those who did so after graduation. Results of qualitative interviews with 34 participants uncovered five key themes unique to CAMS that may explain the program's influence on graduates' career choices and career development: practitioners-as-instructors, instructor mentorship, novel course content, experiential learning opportunities, and career training and skills. CONCLUSIONS: Quantitative and qualitative results indicated that teaching college undergraduate students about CAMH encourages them to set career goals within the field. These findings suggest the utility of implementing similar programs at other undergraduate colleges.

Reoperation risk following the first operation for internal herniation in patients with laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most commonly used surgical procedure in the treatment of morbid obesity in Denmark. Internal herniation (IH) and intermittent internal herniation (IIH) are probably the most common late complications in patients with LRYGB. The aim of this study was to investigate a possible increased risk of subsequent operations after an initial IH or IIH event. METHODS: This long-term follow-up study of patients who had surgery for an initial IH or IIH event in 2006-2011, based on the Danish National Patient Registry (NPR), was performed to 2013. During this period, mesenteric defects were not closed routinely during LRYGB. RESULTS: Data were retrieved from 12 221 patients with LRYGB from the NPR. A total of 383 patients had surgery for an initial IH or IIH event. Some 102 patients (26·6 (95 per cent c.i. 22·5 to 31·3) per cent) had a second operation. Twenty-seven (26·5 (18·9 to 35·8) per cent) of these 102 patients had a third operation, and five (19 (8 to 37) per cent) of the 27 had a fourth operation. Of the 383 patients diagnosed with an initial IH or IIH event, 72 (18·8 per cent) had a second IH/IIH event, 14 (3·7 per cent) had a third event, and three (0·8 per cent) a fourth event requiring surgery. CONCLUSION: Patients who have surgery for IH or IIH have a substantial risk of needing further operations.

A design thinking framework for healthcare management and innovation.

The business community has learned the value of design thinking as a way to innovate in addressing people's needs--and health systems could benefit enormously from doing the same. This paper lays out how design thinking applies to healthcare challenges and how systems might utilize this proven and accessible problem-solving process. We show how design thinking can foster new approaches to complex and persistent healthcare problems through human-centered research, collective and diverse teamwork and rapid prototyping. We introduce the core elements of design thinking for a healthcare audience and show how it can supplement current healthcare management, innovation and practice.

The prognostic value of lymph node ratio in a national cohort of rectal cancer patients.

OBJECTIVE: To analyze the prognostic implications of the lymph node ratio (LNR) in curative resected rectal cancer. SUMMARY BACKGROUND DATA: It has been proposed that the LNR has a high prognostic impact in colorectal cancer, but the lymph node ratio has not been evaluated exclusively for rectal cancer in a large national cohort study. METHODS: All 6793 patients in Denmark diagnosed with stage I to III adenocarcinoma of the rectum, and so treated in the period from 2003 to 2011, were included in the analysis. The cohort was divided into two groups according to whether or not neo-adjuvant treatment had been given. RESULTS: In a multivariate analysis the pN status, ypN status and lymph node yield were found to be independent prognostic factors for overall survival, irrespective of neo-adjuvant therapy. The LNR was also found to be a significant prognostic factor with a Hazard Ratio ranging from 1.154 (95% CI: 0.930-1.432) (LNR: 0.01-0.08) to 2.974 (95% CI: 2.452-3.606) (LNR > 0.5) in the group of patients who had surgery to begin with and from 1.381 (95% CI: 0.891-2.139) (LNR: 0.01-0.08) to 2.915 (95% CI: 2.244-3.787) (LNR > 0.5) in the group of patients who had neo-adjuvant treatment. CONCLUSIONS: The LNR reflects the influence on survival from N-status and the lymph node yield and since LNR was shown to be a significant prognostic predictor for overall survival in patients with curatively resected stage III rectal cancer irrespective of neo-adjuvant therapy we recommend that the introduction of LNR should be considered for rectal cancer in a revised TNM classification.

CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer.

BACKGROUND: Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion, and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk. METHODS: Tumor samples were obtained from colon cancer patients. Biopsies from tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction or in formalin and paraffin embedded (FFPE) for immunohistochemical staining. CDX2 mRNA expression was evaluated by RT-qPCR. FFPE sections were stained for MLH1, MSH2, MSH6, PMS2, and CDX2. RESULTS: A total of 191 patient samples were included in the study and analyzed by immunohistochemistry. Of these samples, 97 were further evaluated by RT-qPCR. There was no significant difference in CDX2 mRNA expression between tumor and normal tissues. CDX2 mRNA expression was significantly lower in right-sided tumors (p<0.05), poorly differentiated tumors (p<0.05), and MMR-deficient tumors (p<0.05). Similarly, CDX2 protein expression was more often low or absent in right-sided tumors (p<0.01), poorly differentiated tumors (p<0.001), and MMR-deficient tumors (p<0.001). Low CDX2 protein or mRNA expression was not associated with recurrence risk. CONCLUSION: We found that CDX2 downregulation is associated with MMR deficiency, right-sided tumors, and poor differentiation at both the mRNA and protein level. Whether CDX2 plays an active role in tumor progression in MSI/MMR-deficient tumors remains to be elucidated.

Psychiatry's Next Generation: Teaching College Students About Mental Health.

OBJECTIVE: The authors describe an integrated area of study for undergraduate college students that targets an increase in knowledge of mental health issues in children, adolescents, and emerging adults; encourages mental health service utilization on college campuses; and exposes young minds to the possibilities of working with children and adolescents in the mental health field. METHODS: An overview of the program is provided, including the resources required to oversee and manage the program, student requirements, a description of the role that clinicians and researchers play as the program faculty, and an explanation of the tuition model. RESULTS: The program currently includes 40 courses with an annual enrollment of over 3000 students, resulting in departmental revenues that currently exceed $11 million per year. Student evaluations of the courses are very positive, and in a program survey students reported that their participation in the program had a positive impact on their life (84.2%) and impacted their career choice (60.2%). CONCLUSIONS: The benefits of the program include a valuable outreach to college students regarding the importance of seeking help for mental health issues, a positive influence on early career decision-making, opportunities for clinical and research educators to develop their scholarly areas of interest, and a significant source of departmental discretionary revenues.

The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review.

INTRODUCTION: Homeobox genes are often deregulated in cancer. They can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. It is implicated in differentiation, proliferation, cell-adhesion, and migration. CDX2 has been proposed as a tumor suppressor in colorectal cancer but its role is still controversial. This systematic review were undertaken in order to clarify CDX2s role in colorectal cancer. METHODS: A literature search was performed in the MEDLINE database from 1966 to February 2014. Only studies in which all or a part of the experimental design were performed on human colorectal cancer tissue were included. Thus, studies solely performed in cell-lines or animal models were excluded. RESULTS: Fifty-two articles of relevance were identified. CDX2 expression was rarely lost in colorectal cancers, however the expression pattern may often be heterogeneous within the tumor and can be selectively down regulated at the invasive front and in tumor buddings. Loss of CDX2 expression is probably correlated to tumor grade, stage, right-sided tumor location, MMR-deficiency, CIMP, and BRAF mutations. The CDX2 gene is rarely mutated but the locus harboring the gene is often amplified and may suggest CDX2 as a linage-survival oncogene. CDX2 might be implicated in cell proliferation and migration through cross-talk with the Wnt-signaling pathway, tumor-stroma proteins, and inflammatory cytokines. CONCLUSION: A clear role for CDX2 expression in colorectal cancer remains to be elucidated, and it might differ in relation to the underlying molecular pathways leading to the cancer formation.