Neonates, although deficient in cell immunity, frequently reveal sepsis with augmented proinflammatory reactions. Here, we found that neonatal monocytes produced significantly higher TNF-α mRNA and protein than adult monocytes. Assessment of the transcriptional factor found no significant difference of NF-κB p65 level between neonatal and adult monocytes. Addition of Act D to access the half-life of TNF-α mRNA revealed no significant difference of the LPS-induced TNF-α mRNA half-life between them, whereas CHX increased neonatal TNF-α mRNA significantly. This suggests that a post-transcriptional mechanism involves the augmentation of TNF-α production by neonatal monocytes. To examine whether miRNA was involved in the post-transcriptional regulation, differential displays of miRNA array between neonatal and adult MNCs were performed, along with the discovery of hsa-miR-103, hsa-miR-125b, hsa-miR-130a, hsa-miR-454-3p, and hsa-miR-542-3p, which were greater than a twofold decrease or increase after LPS treatment for 4 h. The functional validation identified that miR-125b decreased significantly in association with higher TNF-α expression by neonatal monocytes after LPS stimulation. Transfection of the miR-125b precursor into neonatal monocytes significantly repressed the TNF-α mRNA and protein expression, suggesting that miR-125b negatively regulates TNF-α expression in neonatal monocytes. Modulation of miRNA expression may be used to regulate TNF-α production in newborns with altered proinflammatory reactions.

Introduction.  Diabetes is a common risk factor for overactive bladder (OAB) syndrome and erectile dysfunction (ED). Aim.  The study evaluated the risk factors of OAB and association of OAB and ED in type 2 diabetic men. Methods.  The diagnosis of ED and OAB was based on a self-administered questionnaire containing Sexual Health Inventory for Men (SHIM) and OAB symptom score (OABSS, 0-15, indicating increasing severity of symptoms), respectively. Main Outcome Measures.  The clinical variables and diabetes-associated complications, including ED, which are risk factors for OAB, were evaluated. Results.  Of 453 consecutive subjects attending outpatient diabetic clinic with a mean age of 60.6 years, 25.4%, 10.2%, 81.9%, and 28.3% reported having OAB, OAB wet, ED, and severe ED, respectively. The OABSS is inversely associated with SHIM (correlation coefficient-0.275). The patients with OAB have significantly lower SHIM score, testosterone level, and serum albumin level, have more proportion of severe ED, were older, and have longer duration of diabetes mellitus (DM). After adjustment for age and duration of DM, the presence of severe ED was associated with OAB (odds ratio [OR] = 1.58), and severe ED (OR = 2.36), SHIM score (OR = 0.92), and serum albumin level (OR = 0.24) were risk factors for OAB wet (patients with urgency incontinence, once a week or more). The OR of ED in patients with OAB or OAB wet compared with no OAB was 1.82, and 3.61, respectively. Among the OAB components, urgency incontinence has the strongest impact on ED (OR = 4.06), followed by nocturia, urgency, and frequency. About 15.1%(N = 68) without OAB and ED are younger and have shorter DM duration, lower systolic BP, and higher serum albumin level after multivariate analysis compared with patients with OAB or ED. Conclusion.  The presence of severe ED was significantly associated with OAB, especially OAB wet. The presence of OAB wet increased the risk and severity of ED. Liu R-T, Chung M-S, Chuang Y-C, Lee J-J, Lee W-C, Chang H-W, Yang KD, and Chancellor MB. The presence of overactive bladder wet increased the risk and severity of erectile dysfunction in men with type 2 diabetes. J Sex Med **;**:**-**.

Background. Kawasaki disease is characterized by systemic vasculitis of unknown etiology. Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions. Host innate immune response factors are involved in modulating the disease outcome. The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD. Methods. A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) of CLEC5A (rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay. The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test. Results. No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and patients. In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. Conclusions. This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The laboratory findings before and after intravenous immunoglobulin (IVIG) in KD have been discussed, but the characteristics of IVIG therapy still are unclear. This study aimed to compare laboratory data from patients with KD and enterovirus (EV) infection to evaluate the differences after IVIG therapy. The study enrolled 171 KD patients and 38 EV patients treated with a single dose of IVIG from 2003 to 2010. Laboratory data including total white blood cell counts (WBC) and hemoglobin (Hb), platelet, segment, lymphocyte, eosinophil, and monocyte levels were analyzed. Compared with the KD patients, the EV patients had higher Hb, lymphocyte, and monocyte levels and lower eosinophil levels before IVIG treatment (p < 0.05). After IVIG treatment, the KD patients had lower Hb and segment levels but higher platelet, lymphocyte, and eosinophil levels than the EV patients (p < 0.05). In the KD patients, the platelet, eosinophil, and monocyte levels increased after IVIG treatment, whereas Hb, WBC, and segment levels decreased significantly (p < 0.001). In the EV patients, eosinophil levels increased after IVIG treatment, whereas WBC and Hb levels decreased significantly (p < 0.05). The study results provide evidence that eosinophilia may be related to IVIG therapy in KD and EV patients. The KD patients had higher eosinophil levels both before and after IVIG therapy than the EV patients, which may have been due to the inflammatory mechanism of KD. The KD patients had higher platelet levels than the EV patients, suggesting that platelets are involved in the inflammatory response to KD.

BACKGROUND Concerns have been raised about how the transmission of emerging infectious diseases from patients to healthcare workers (HCWs) and vice versa could be recognized and prevented in a timely manner. An effective strategy to block transmission of pandemic H1N1 (2009) influenza in HCWs is important. METHODOLOGY/PRINCIPAL FINDINGS An infection control program was implemented to survey and prevent nosocomial outbreaks of H1N1 (2009) influenza at a 2,600-bed, tertiary-care academic hospital. In total, 4,963 employees at Kaohsiung Chang Gung Memorial Hospital recorded their temperature and received online education on control practices for influenza infections. Administration records provided vaccination records and occupational characteristics of all HCWs. Early recognition of a pandemic H1N1 (2009) influenza case was followed by a semi-structured questionnaire to analyze possible routes of patient contact, household contact, or unspecified contact. Surveillance spanned August 1, 2009 to January 31, 2010; 51 HCWs were confirmed to have novel H1N1 (2009) influenza by quantitative real-time reverse transcription polymerase chain reaction. Prevalence of patient contact, household contact, or unspecified contact infection was 13.7%(7/51), 13.7%(7/51), and 72.5%(37/51), respectively. The prevalence of the novel H1N1 infection was significantly lower among vaccinated HCWs than among unvaccinated HCWs (p<0.001). Higher viral loads in throat swabs were found in HCWs with patient and household contact infection than in those with unspecified contact infection (4.15 vs. 3.53 copies/mL, log(10), p = 0.035). CONCLUSION A surveillance system with daily temperature recordings and online education for HCWs is important for a low attack rate of H1N1 (2009) influenza transmission before H1N1 (2009) influenza vaccination is available, and the attack rate is further decreased after mass vaccination. Unspecified contact infection rates were significantly higher than that of patient contact and household contact infection, highlighting the need for public education of influenza transmission in addition to hospital infection control.

PURPOSE: Kawasaki disease (KD) is a systemic febrile vasculitis complicated by coronary artery lesions (CAL). Anemia is common in patients with KD and is associated with a prolonged duration of active inflammation. Hepcidin is a central modulator of inflammation-associated anemia, acting via control of iron absorption and a direct inhibitory effect on erythropoiesis. The aims of this study were to investigate the role of inflammation-induced hepcidin in the development of anemia, the occurrence of CAL formation, and IVIG treatment response in patients with KD. METHODS: Eighty-six KD patients and 30 febrile controls were enrolled. Levels of interleukin (IL)-6 and serum hepcidin were measured in sera by enzyme-linked immunosorbent assay. Hemoglobin and serum iron levels were also measured. RESULTS: Hemoglobin and iron levels were lower in KD patients than in controls (p < 0.001 and p = 0.009, respectively). Serum hepcidin and IL-6 levels were higher in KD patients than in controls (both p < 0.001) before intravenous immunoglobulin (IVIG) treatment. After IVIG treatment, serum hepcidin, IL-6, and hemoglobin levels decreased significantly (all p < 0.001). In addition, the serum hepcidin levels before IVIG treatment were negatively correlated with hemoglobin levels after IVIG treatment (R = -0.188, p = 0.046) and positively correlated with the changes of hemoglobin levels after IVIG treatment (R = 0.269, p = 0.015). Furthermore, serum hepcidin levels were negatively correlated with serum iron levels (R = -0.412, p = 0.002), which were positively correlated with hemoglobin levels (R = 0.210, p = 0.045). Additionally, the change of hepcidin levels was associated with IVIG treatment response and the occurrence of CAL formation. CONCLUSIONS: Inappropriately raised hepcidin levels impair iron metabolism and are associated with decreased hemoglobin levels in KD patients. Inflammation-induced hepcidin is associated with the development of anemia and disease outcomes in patients with KD.

BACKGROUND A better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF) is important in alerting clinicians of severe dengue and improving management. METHODS AND FINDINGS Of 309 adults with DHF, 10 fatal patients and 299 survivors (controls) were retrospectively analyzed. Regarding causes of fatality, massive gastrointestinal (GI) bleeding was found in 4 patients, dengue shock syndrome (DSS) alone in 2; DSS/subarachnoid hemorrhage, Klebsiella pneumoniae meningitis/bacteremia, ventilator associated pneumonia, and massive GI bleeding/Enterococcus faecalis bacteremia each in one. Fatal patients were found to have significantly higher frequencies of early altered consciousness (≤24 h after hospitalization), hypothermia, GI bleeding/massive GI bleeding, DSS, concurrent bacteremia with/without shock, pulmonary edema, renal/hepatic failure, and subarachnoid hemorrhage. Among those experienced early altered consciousness, massive GI bleeding alone/with uremia/with E. faecalis bacteremia, and K. pneumoniae meningitis/bacteremia were each found in one patient. Significantly higher proportion of bandemia from initial (arrival) laboratory data in fatal patients as compared to controls, and higher proportion of pre-fatal leukocytosis and lower pre-fatal platelet count as compared to initial laboratory data of fatal patients were found. Massive GI bleeding (33.3%) and bacteremia (25%) were the major causes of pre-fatal leukocytosis in the deceased patients; 33.3% of the patients with pre-fatal profound thrombocytopenia (<20000/µL), and 50% of the patients with pre-fatal prothrombin time (PT) prolongation experienced massive GI bleeding. CONCLUSIONS Our report highlights causes of fatality other than DSS in patients with severe dengue, and suggested hypothermia, leukocytosis and bandemia may be warning signs of severe dengue. Clinicians should be alert to the potential development of massive GI bleeding, particularly in patients with early altered consciousness, profound thrombocytopenia, prolonged PT and/or leukocytosis. Antibiotic(s) should be empirically used for patients at risk for bacteremia until it is proven otherwise, especially in those with early altered consciousness and leukocytosis.

Kawasaki disease (KD) is an acute multi-system vasculitis syndrome of unknown etiology occurring mostly in infants and children younger than 5 years of age. In developed countries, it is the leading cause of acquired heart disease in children. However, KD remains a mysterious disease. Some viruses potentially causing the condition have been isolated, but the results have not been able to be reproduced. This article reviews and summarizes different aspects of KD and provides updated information on diagnosis and treatment. The supplementary criteria for incomplete presentation of KD patients suggested by the American Heart Association, treatment (including tumor necrosis factor-alpha antagonist, methylprednisolone pulse therapy, statins, plasma exchange, and cytotoxic agents) for those with intravenous immunoglobulin treatment failure, and other experiences are also included in this review.

Aims:  Some guidelines or studies consider haematuria an indication for renal biopsy or a potential cause of albuminuria that precludes accurate assessment of urinary albumin excretion. This study examined the justification of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and its associations with other diabetes-related variables. Methods:  Between May and November 2008, patients with Type 2 diabetes at a single centre with data on urinary albumin excretion and urinalysis in the same urine sample were recruited. Urinary albumin excretion was determined by urine albumin/creatinine ratio in spot urine. Diagnosis of haematuria was made by positive urine occult blood from 1+ to 4+ and/or presence of more than nine red blood cells/ml in urinalysis. Demographic, anthropometric, clinical and laboratory variables and diabetes-associated complications were analysed. Results:  In total, 743 patients were enrolled. Prevalence of haematuria among patients with normoalbuminuria, microalbuminuria, or macroalbuminuria was 8.7%(n = 13), 16.1%(n = 67) and 35.8%(n = 64), respectively. Urine albumin/creatinine ratio was significantly higher, while macroalbuminuria was more common in patients with haematuria (n = 144) than in those without (n = 599). Multiple regression analysis identified urine albumin/creatinine ratio (odds ratio 1.33, P = 0.01) and macroalbuminuria (odds ratio 2.66, P = 0.01) as the only independent predictors of haematuria. Moreover, urine albumin/creatinine ratio was an independent predictor of haematuria in the macroalbuminuria subgroup (odds ratio 1.30, P = 0.04). Conclusions:  Increased urine albumin/creatinine ratio and macroalbuminuria were the only independent predictors of haematuria in patients with Type 2 diabetes, raising questions on the justifications of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and including haematuria as an indication for renal biopsy in those with macroalbuminuria. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

A skewed T-helper (T(h))1/T(h)2 immune response is considered to be the major cause of allergic disorders. Overproduction of T(h)2 cytokines, which promote recruitment and activation of mast cells and eosinophils, plays a key part in the pathogenesis of allergic asthma. The mechanisms by which omalizumab is effective in asthma treatment are not yet fully understood. A 16-year-old girl who was experiencing frequent asthma attacks in spite of daily administration of budesonide (640μg) and montelukast (10mg) was given omalizumab (375mg) at intervals of 2 weeks, to prevent a visit to the emergency room. Plasma levels of T(h)1 cytokines [interferon (IFN)-γ and interleukin (IL)-12p70], T(h)2 cytokines (IL-4 and IL-13), other proinflammatory and regulatory cytokines [IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β], chemokines [monocyte chemotactic protein (MCP)-1, chemokine ligand (CCL)7, and CCL17], and soluble Fas ligand (sFasL) were measured before treatment and after treatment for 8 weeks. She showed a good clinical response to omalizumab: her lung function parameters improved and the use of β2-agonist decreased. No emergency room visits were required after omalizumab treatment for 8 weeks. Plasma levels of sFasL and TGF-β showed obvious increases after omalizumab therapy. IL-12p70 levels were decreased as compared to the corresponding baseline levels. These findings suggest that the effects of omalizumab in asthma treatment are not restricted to the regulation of the skewed T(h)1/T(h)2 cytokine immune response, and sFasL-mediated apoptosis and regulatory T-cell (Treg)-mediated TGF-β seem to have important roles in the therapeutic effects of omalizumab.