Associations between sleep habits and mental health status and suicidality in a longitudinal survey of monozygotic twin adolescents

Several epidemiological studies have indicated that there is a relationship between sleep habits, such as sleep duration, bedtime and bedtime regularity, and mental health status, including depression and anxiety in adolescents. However, it is still to be clarified whether the relationship is direct cause‐and‐effect or mediated by the influence of genetic and other traits, i.e. quasi‐correlation. To examine this issue, we conducted a twin study using a total of 314 data for monozygotic twins from a longitudinal survey of sleep habits and mental health status conducted in a unified junior and senior high school (grades 7–12), located in Tokyo, Japan. Three‐level hierarchical linear model analysis showed that both bedtime and sleep duration had significant associations with the Japanese version of the 12‐item General Health Questionnaire (GHQ‐12) score, suicidal thoughts and the experience of self‐harm behaviours when genetic factors and shared environmental factors, which were completely shared between co‐twins, were controlled for. These associations were statistically significant even after controlling for bedtime regularity, which was also associated significantly with the GHQ‐12 score. These suggest that the associations between sleep habits and mental health status were still statistically significant after controlling for the influence of genetic and shared environmental factors of twins, and that there may be a direct cause‐and‐effect in the relationship in adolescents. Thus, late bedtime and short sleep duration could predict subsequent development of depression and anxiety, including suicidal or self‐injury risk. This suggests that poor mental health status in adolescents might be improved by health education and intervention concerning sleep and lifestyle habits.     

Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced HCC who received sorafenib therapy.Relationships among baseline characteristics as well as AEoccurrence and tumor response,overall survival(OS),and treatment duration were analyzed.The nursingintervention program consisted of education regardingself-monitoring and AEs management,and telephoneRESULTS:A total of 37 patients were enrolled in the study,comprising 30 males(81%) with a median age of 71 years.The disease control rate at 3 mo was 41%,and the median OS and treatment duration were 259 and 108 d,respectively.Nursing intervention was given to 24 patients(65%).Every patient exhibited some kinds of AEs,but no patients experienced G4 AEs.Frequently observed AEs G2 included anorexia(57%),skin toxicity(57%),and fatigue(54%).Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years,presence of G2 skin toxicity,and absence of G2 hypoalbuminemia.The disease control rate in patients with G2 skin toxicity was 13/20(65%),which was significantly higher compared with that in patients with no or G1 skin toxicity.Multivariate analysis revealed that nursing intervention and G2 skin toxicity were independent significant predictors for longer treatment duration.CONCLUSION:Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC.Nursing intervention contributed to better adher-ence,which may improve the efficacy of sorafenib.     

Basal insulin requirement of youth with type 1 diabetes differs according to age

We investigated the percentage of total basal insulin dose to total daily insulin dose (%TBD) among Japanese youth of different ages with type 1 diabetes. The study enrolled 69 patients with type 1 diabetes who were treated with multiple daily injections of insulin. The participants were divided into the following age groups: group A, 0 to <10 years (n = 18); group B, 10 to <20 years (n = 31) and group C, 20 to <25 years (n = 20). We found no difference in the sex ratio, body mass index, and glycated hemoglobin and 2‐h postprandial C‐peptide levels among the three groups. Participants assigned to group B had a significantly higher percentage of total daily insulin dose than those in group A and group C (49.7 ± 10.4% vs 38.5 ± 13.7% and 38.3 ± 8.2%, P = 0.0005). In conclusion, the basal insulin requirements of Japanese youth with type 1 diabetes might have an age effect that is associated with puberty.     

Immunomodulatory aspects in the progression and treatment of oral malignancy

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.     

Association of Increased Indoleamine 2, 3‐Dioxygenase With Impaired Natural Killer Cell Activity in Hemodialysis Patients

Indoleamine 2, 3‐dioxygenase (IDO) suppresses adaptive immune response. However, there was no study to examine whether IDO activity is associated with immune parameters in dialysis patients. In this study, we estimated serum IDO activity by the kynurenine/tryptophan ratio (KTR), and compared KTR with natural killer (NK) cell activity, soluble interleukin‐2 receptor (sIL‐2R) and serum levels of trace elements such as selenium (Se) and zinc (Zn) that affect T‐cell function in 28 hemodialysis (HD) patients (age: 72 ± 13 years old, time on HD: 79 ± 89 months). NK cell activity was decreased in 35.7% of the patients. KTR values were almost 10‐times higher in HD patients (380.81 ± 385.46 mM/M) than those in the referred controls (32.9 ± 9.10 mM/M). KTR was lower in patients with impaired NK cell activity than those without (279 ± 111 vs. 565 ± 603 mM/M, P = 0.07). There was no relationship between KTR and sIL‐2R and Zn, while KTR was significantly and negatively correlated with serum Se levels that can impair cellular immunity (r = ?0.41, P < 0.05). Our findings suggest that increased IDO activity with Se deficiency may be associated with impaired NK cell function in HD patients.     

Esophageal motor dysfunction plays a key role in GERD with globus sensation - Analysis of factors promoting resistance to PPI therapy

Abstract Objective. Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy. Design. The subjects were 350 patients with globus sensation. All patients underwent both laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease. After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients were divided into PPI-responsive and PPI-resistant groups. Then we investigated esophageal motility in the PPI-resistant group by a multichannel intraluminal impedance and manometry study. Results. A total of 119 patients (55.6%) were resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal motility. They included 36 patients (66.4%) with ineffective esophageal motility, 9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with hypertensive lower esophageal sphincter. There were significant differences of upper esophageal sphincter pressure and esophageal body peristalsis between the patients with PPI-resistant LPRD and healthy controls matched for age and sex. Conclusion. Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal motility.     

Diabetic ketoacidosis accompanied by hypothermia: a case report

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus and is caused by insulin insufficiency. Hypothermia is defined as a core temperature of less than 35°C and is sometimes accompanied by DKA. We report two patients with diabetes who were admitted for DKA accompanied by hypothermia.