Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2

We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line, CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin, suppressed the invasion in a dose-dependent manner. Similarly, pharmacological inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9 secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an important role to convert the cholangiocarcinoma cells to be more aggressive one.     

Steroid use for refractory hypotension in congenital diaphragmatic hernia

Purpose

Guidelines for diagnosis and treatment of adrenal insufficiency (AI) in newborns with congenital diaphragmatic hernia (CDH) are poorly defined.

Methods

From 2002 to 2016, 155 infants were treated for CDH at our institution. Patients with shock refractory to vasopressors (clinically diagnosed AI) were treated with hydrocortisone (HC). When available, random cortisol levels <10 μg/dL were considered low. Outcomes were compared between groups.

Results

Hydrocortisone was used to treat AI in 34% (53/155) of patients. That subset of patients was demonstrably sicker, and mortality was expectedly higher for those treated with HC (37.7 vs. 17.6%, p = 0.0098). Of the subset of patients with random cortisol levels measured before initiation of HC, 67.7% (21/31) had low cortisol levels. No significant differences were seen in survival between the high and low groups, but mortality trended higher in patients with high cortisol levels that received HC. After multivariate analysis, duration of HC stress dose administration was associated with increased risk of mortality (OR 1.11, 95% CI 1.02–1.2, p = 0.021), and total duration of HC treatment was associated with increased risk of sepsis (OR 1.04, 95% CI 1.005–1.075, p = 0.026).

Conclusion

AI is prevalent amongst patients with CDH, but prolonged treatment with HC may increase risk of mortality and sepsis.

     

Identification of psychological behaviours among children having parental HIV infection and their determinants in Myanmar: a comparative study with neighbourhood peers

Psychological impact is one of the direct and indirect consequences of HIV and AIDS on children. A national survey applying a cross-sectional comparative design was conducted among children aged 4–16 years with parental HIV infection and age-group matched neighbourhood peers without parental HIV infection to identify and compare their psychological behaviours and determinants. A multistage sampling method was used. Face-to-face interviews were conducted with parents/guardians of the children to obtain family characteristics and children’s psychological behaviours using the modified Strengths and Difficulties Questionnaire. Factor analysis identified three domains of psychological behaviours, namely social, emotional and conduct behaviours. Comparison of these behaviours was done using Chi-squared test with Rao–Scott adjustment. Determinants of these behaviours were identified using survey-weighted logistic regression adjusted for socio-demographic variables. A total of 1280 children with parental HIV infection and 1279 neighbourhood peers participated in the study. Social conditions of the two groups differed in terms of family displacement (24.6% vs. 8.9%, p < 0.001), family dispersion (12.4% vs. 3.7%, p < 0.001), and child displacement (10.3% vs. 3.5%, p < 0.001). Emotional behaviour was significantly different between the two groups (31.3% vs. 24.0%, p < 0.01) but no difference in social or conduct behaviours was evident. Children from extended families (adjusted odds ratio (AOR): 1.34, 95% CI: 1.07–1.67), females (AOR: 1.37, 95% CI: 1.07–1.75), orphans (AOR: 1.62, 95% CI: 1.29–2.05) and children who experienced family displacement (AOR: 1.38, 95% CI: 1.11–1.72) were more likely to have abnormal emotional behaviour. Children from extended families (AOR: 0.77, 95% CI: 0.62–0.97) had less chance of having abnormal conduct behaviour. In contrast, preschool (AOR: 2.73, 95% CI: 1.92–3.87) and out-of-school children (AOR: 1.47, 95% CI: 1.01–2.27) were more likely to have abnormal conduct behaviour. Development of long-term strategies for reducing the risk of behavioural problems among children with parental HIV infection is suggested.     

Velopharyngeal palsy: a case report]

Here we present a case of velopharyngeal palsy. An 18-year-old man had hyperemia in his left conjunctivum. One or two weeks later he experienced nasal speech and difficulty in swallowing. General physical examination was normal. The only abnormal neurological finding was palato-pharyngeal paralysis on the right side. MRI of the head and neck had no abnormalities. Acute and convalescent sera showed no rise in viral antibody titer. CSF examination was normal except for the increased IgG% and IgG.albumin index. Treatment consisted of glycerol and steroid, and his symptom improved within two or three weeks. We think immunological mechanism is important because CSF examination showed increased IgG% and IgG.albumin index in our case. Acquired and isolated velopharyngeal palsy is uncommon. Only 26 cases have been reported so far. This is the first case in Japan. The disease has some characteristics. This occurs in childhood and adolescence. Onset is sudden, consisting in rhinolalia and dysphagia. On examination there is asymmetry of the pharynx and deviation of the uvula contralateral to the affected side. There is no other neurological abnormalities. Complete spontaneous recovery is usual. In some cases viral infection is the cause, but in most cases the cause is unknown. In contrast, the disease with both acquired velopharyngeal palsy and vocal cord palsy is relatively common. This occurs in the middle aged or elderly people. In addition to dysphagia and hoarse voice, this disease often accompanies neurological abnormalities such as other cranial nerve palsy and meningitis, fever, and pain in the pharyngeal region. In most cases viral infection is the cause.