Personalized music therapy combined with medication as treatment for tinnitus.

OBJECTIVE: This study aimed to investigate the effects of personalized music therapy in combination with medication as a treatment for tinnitus. PATIENTS AND METHODS: We retrospectively analyzed a total of 200 patients who were admitted to the Department of Otorhinolaryngology in our hospital from June 2018 to June 2019, with tinnitus as their primary complaint. Patients were divided into four groups based on their individual treatment methods: medication group (patients received medication only, n=40), tinnitus masking (TM) group (patients received medication plus TM, n=38), tinnitus re-training (TRT) group (patients received medication plus TRT, n=35), and personalized group (patients received medication plus personalized music therapy, n=30). The pure-tone audiometry (PTA), loudness visual analogue scale (VAS), and tinnitus handicap inventory (THI) for each patient were analyzed. RESULTS: There were statistically significant differences in the THI and VAS scores of all groups before and after treatment (p<0.05). Following nine and twelve months of treatment, the THI and VAS scores of the TRT group and the personalized group were significantly lower than those of the other two groups (p<0.05). The THI and VAS scores of the personalized group were significantly lower than those of the TRT group (p<0.05). Additionally, THI and VAS scores were statistically different at various measurement time points in each group (p<0.05). The clinical effective rate (85.37%) of the personalized group was higher than that of the other three groups (p<0.05). CONCLUSIONS: TM, TRT, or personalized music therapy, when combined with medication, are effective in treating patients with tinnitus. Among these methods, personalized music therapy may be the superior treatment after nine months of treatment.

Effects of rope skipping exercise on physical, cardiovascular fitness and exercise tolerance in adolescent students with moderate intellectual disability.

BACKGROUND: Adolescents with intellectual disabilities (ID) who live a sedentary lifestyle may lead to an increased risk of chronic cardiovascular disease in adulthood. The aim of this study is to investigate the effects of 8-week progressive rope skipping training on physical, cardiovascular fitness and exercise tolerance of high school students with moderate ID. METHODS: Thirty-four senior high school with ID (aged 15-18 years old) were randomised into experimental group received progressive skipping rope exercise (RS, n = 17) and control group no rope skipping exercise intervention group (CON, n = 17). The RS group were received progressive rope skipping exercise for 50 min each time, three times a week, for 8 weeks. The control group was not allowed to participate in intervention activities during the study period. The physical fitness, body composition, arterial stiffness index (ASI) and blood pressure were measured before and after the 8-week intervention. RESULTS: After the 8-week progressive skipping rope exercise intervention, the participants from the RS group increased in the 3-min step test, sit-up test, grip strength and sit and reach test, when compared to the baseline (P < 0.05). The RS group exhibited lower the area under curve of heart rate (HR) during post-exercise recovery (P < 0.05). The participants in the RS group showed significant decreases in systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP) and HR when compared to the baseline (P < 0.05). Change SBP has moderate positive correlation with change ASI. CONCLUSIONS: The results of this experiment suggest that progressive rope skipping exercise might improve physical fitness and promote cardiovascular health, as well as enhance exercise tolerance for adolescent students with moderate ID.

DNA binding properties and cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone.

OBJECTIVE: This study aims to investigate the CT-DNA (Calf thymus DNA) binding properties and HeLa cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone (HL2). MATERIALS AND METHODS: A series of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazonewere (HL2) were synthesized, and their structures were characterized through FT-IR, ESI-MS, elemental analysis, molar conductivities and X-ray diffraction. DNA binding properties between CT-DNA and metal complexes were investigated by UV-Vis spectrophotometry and viscosity titration. The toxicological properties of compounds on HeLa cell were measured in vitro. RESULTS: Ligand H2L1 or HL2 exhibits a tridentate and anion ligand and uses oxygen anion, nitrogen atom and sulfur atom to coordinate with metal ions. When coordinated with metal ions, the unit O=C-NH- of each ligand has been enolized and deprotonated into -O-C=N-. The suggested chemical formulas of metal complexes are: [Co(HL1)2], [Ni(HL1)2], [Cu(HL1)2], [Co(L2)2], [Cu(L2)2], [Zn(L2)2], [ScL2(NO3)2(H2O)2], [Pr(L2)2(NO3)] and [Dy(L2)2(NO3)]. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation with Kb of 104~105 L mol-1 compared to ethidium bromide [classical DNA intercalator, Kb(EB-DNA) = 3.068 × 104 L mol-1]; however, the groove pattern cannot be excluded. The coexistence of multiple binding modes may be a common form of drug binding to DNA. HeLa cell shows lower viabilities in the presence of [Ni(HL1)2] and [Cu(HL1)2] (*p < 0.05) compared to the other compounds, with the LC50 of 2.6 µmol L-1 and 2.2 µmol L-1, respectively. CONCLUSIONS: These compounds, especially [Ni(HL1)2] and [Cu(HL1)2], will be promising for anti-tumor drugs, which should be further studied.

Development and validation of a novel nomogram to predict chronic total occlusion before coronary angiography.

OBJECTIVE: Some previous studies have analyzed potential predictors related to the high incidence rate of coronary artery disease (CAD) and established a relevant nomogram for CAD in patients before coronary angiography (CAG). Nevertheless, there are still few models to predict chronic total occlusion (CTO). In this study, we aimed to construct a risk model and nomogram that could effectively predict the probability of CTO before CAG. PATIENTS AND METHODS: In total, the derivation set (n=1,105) and the validation set (n=368), which included patients with CAG diagnosis of CTO, were collected. A statistical difference test was performed for clinical, demography, echocardiography, medication history, laboratory indexes, and angiography. Univariate and multivariate logistic regression analysis were performed to determine the independent risk factors that affect the diagnosis of CTO. A nomogram was established and validated based on the independent predictors. The area under the curve (AUC), the calibration curve, and the decision curve analysis (DCA) were used to evaluate the nomogram. RESULTS: The incidence of CTO within CAD was 21.5%. Univariate and multivariate logistic regression analysis revealed that risk factors for gender (male), neutrophil percentage (NE%), hematocrit (HCT), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), ejection fraction (EF), troponin I (TnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independent predictors of CTO. A nomogram was constructed incorporating these independent predictors with good discrimination (0.746 in the C-index) and external validation (0.741 in the C-index). The calibration curves and the DCA showed the reliability and accuracy of this clinical prediction model. CONCLUSIONS: The nomogram, composed of gender, NE%, HCT, TC, HDL, EF, TnI, and NT-proBNP, can be used for the prediction of CTO in CAD patients, which opens a great possibility of enriching the means to predict the prognosis of these patients in clinical practice. More studies are needed to validate the effectiveness of this nomogram in other populations.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Identifying pulmonary nodules or masses on chest radiography using deep learning: external validation and strategies to improve clinical practice.

AIM: To test the diagnostic performance of a deep learning-based system for the detection of clinically significant pulmonary nodules/masses on chest radiographs. MATERIALS AND METHODS: Using a retrospective study of 100 patients (47 with clinically significant pulmonary nodules/masses and 53 control subjects without pulmonary nodules), two radiologists verified clinically significantly pulmonary nodules/masses according to chest computed tomography (CT) findings. A computer-aided diagnosis (CAD) software using a deep-learning approach was used to detect pulmonary nodules/masses to determine the diagnostic performance in four algorithms (heat map, abnormal probability, nodule probability, and mass probability). RESULTS: A total of 100 cases were included in the analysis. Among the four algorithms, mass algorithm could achieve a 76.6% sensitivity (36/47, 11 false negative) and 88.68% specificity (47/53, six false-positive) in the detection of pulmonary nodules/masses at the optimal probability score cut-off of 0.2884. Compared to the other three algorithms, mass probability algorithm had best predictive ability for pulmonary nodule/mass detection at the optimal probability score cut-off of 0.2884 (AUCMass: 0.916 versus AUCHeat map: 0.682, p<0.001; AUCMass: 0.916 versus AUCAbnormal: 0.810, p=0.002; AUCMass: 0.916 versus AUCNodule: 0.813, p=0.014). CONCLUSION: In conclusion, the deep-learning based computer-aided diagnosis system will likely play a vital role in the early detection and diagnosis of pulmonary nodules/masses on chest radiographs. In future applications, these algorithms could support triage workflow via double reading to improve sensitivity and specificity during the diagnostic process.

The role of innate lymphoid cells in nasal inflammation and cancer.

OBJECTIVE: The innate lymphoid cells (ILCs) are a recently discovered type of innate immune cell. The functions of these cells resemble different T-cell subtypes. These cells play important roles in local injury, inflammation, pathogen infection, or tumours. However, there have been few studies focusing on the role of ILCs in nasal diseases. MATERIALS AND METHODS: We reviewed the literature about the roles of ILCs in nasal inflammation, tissue remodeling, and cancer. RESULTS: The ILCs represent a newly identified family of innate immune cells. These cells play important roles in inflammation, immune responses, tissue remodeling, and cancer immunity. The ILCs, especially ILC2s, play important roles in CRSwNP and AR. ILC2s may be involved in the pathogenesis of eosinophilic inflammation in non-allergic nasal diseases, such as non-allergic CRSwNP and non-allergic rhinitis. ILCs also play pro-tumor or anti-tumor roles in cancer immunity for head and neck cancer. CONCLUSIONS: LC2s may be a useful therapeutic target for CRSwNP and AR. ILCs may also represent new therapeutic targets to activate anti-tumor immunity in head and neck cancer.

MiR-21 inhibitor improves locomotor function recovery by inhibiting IL-6R/JAK-STAT pathway-mediated inflammation after spinal cord injury in model of rat.

OBJECTIVE: To investigate the function of miRNA-21 and interleukin-6 receptor/Janus Kinase-Signal transducer and activator of transcription (IL-6R/JAK-STAT) pathway in microglia on inflammatory responses after spinal cord injury (SCI). MATERIALS AND METHODS: This study first detected respectively the protein level of inflammatory factor inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) by Western blotting after transfection of miR-21 or administration of miR-21 inhibitor in activated microglia cells of rat in vitro. The quantitative Real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of IL-6R under two different interventions. Next, we established a model of spinal cord injury in rat and inspected miR-21 and IL-6R in SCI rat by qRT-PCR. In addition, the protein levels of iNOS and TNF-α in SCI rat were detected by Western blotting. MiR-21 inhibitor was injected into the injured area of SCI rat to delve into the function of miR-21 down-expression on iNOS and TNF-α expression by Western blot as well as the RNA levels of IL-6R, JAK and STAT3 by qRT-PCR. Furthermore, the SCI rat with movement and coordination of hindlimbs was observed by Basso-Beattie-Bresnahan locomotor rating scale (BBB scale) after miR-21 down-expression. RESULTS: Compared with the microglia transfected with miR-21, the execution of inhibitor in microglia effectively relieved the expression of IL-6R and the breakout of iNOS and TNF-α. Meanwhile, the increase of miR-21 was significantly observed in SCI rat along with significant improvement of inflammatory response-related factors including iNOS and TNF-α. After that, we injected SCI rat with miR-21 inhibitor into the spinal cord injury area and found the inhibition of miR-21 decreased the protein levels of iNOS and TNF-α. Simultaneously, down-expression of miR-21 evidently declined the RNA levels of IL-6R, JAK, and STAT3 in SCI rat. Compared with the sham-operated rat, the movement and coordination of hindlimbs of the SCI group displayed dramatic dysfunction. However, miR-21 down-expression elevated the movement and coordination of hindlimbs of the SCI rat than those of the only injury group. CONCLUSIONS: Inhibition of miR-21 can promote the recovery of spinal cord injury by down-regulating IL-6R/JAK-STAT signaling pathway and inhibiting inflammation.

Rehydration before wet fixation in conventional body fluid cytology - An 18-year experience.

PURPOSE: In conventional cytology, preparation of a specimen by wet fixation for Papanicolaou stain is potentially subject to dry effect or cell loss which may make cytologic interpretation difficult or even impossible. We have been routinely making an additional smear for rehydration with normal saline (rehydration method) before wet fixation to overcome the above shortcomings. METHODS: We reviewed malignant pleural effusion and ascites 15 cases each in our cytology laboratory over the past 1 year. Four slides of each specimen were made. Two were air-dried for Liu's stain (a Romanowsky stain) and the other two were wet-fixed for Papanicolaou stain. The air-dried smears were also served as retained cellularity control. One of the two wet-fixed smears was processed as a control of preservation of nuclear detail whereas the other one stayed air-dried for 10 minutes and then covered with normal saline (rehydration method) for 80 seconds before wet fixation. RESULTS: There was minor cell loss (P = .032). The cells appeared larger with good preservation of nuclear detail (P < .0001 by two-sided Wilcoxon rank sum test) but no red blood cells retained on the slide after rehydration. CONCLUSION: The rehydration method can effectively minimise cell loss, enlarge and preserve the cytological features of malignant cells with haemolysis. This method is simple, practical and good for cytological screening for tumour cells and interpretation especially in a bloody smear. We recommend that the rehydration method be part of traditional cytopreparatory work of wet fixation for Papanicolaou stain in conventional body fluid cytology.

Nivolumab effectively inhibit platinum-resistant ovarian cancer cells via induction of cell apoptosis and inhibition of ADAM17 expression.

OBJECTIVE: Nivolumab is an anti-PD-1 (anti-programmed death-1) monoclonal antibody. It has achieved an overall response rate of 17% in Phase 1 clinical trial for patient with platinum-resistant ovarian cancer (PROC). However, its underlying mechanism has not been fully explored yet. The aim of the study is to investigate the efficiency of nivolumab to inhibit PROC cells and its possible mechanism. MATERIALS AND METHODS: Firstly, methylthiazolyl tetrazolium bromide (MTT) assay was performed to determine the IC50 values of cisplatin in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The results showed that IC50 (half maximal inhibitory concentration) values of cisplatin were significantly decreased in a time-dependent manner in A2780, A2780/DDP, SKOV3, and SKOV3/DDP cells. Secondly, MMT assay was used once again to measure anti-tumor effects of nivolumab in A2780/DDP cells. The results showed that anti-tumor effects of nivolumab increased in a dose- and time-dependent manner. Thirdly, A2780/DDP cells were treated with nivolumab in combination with cisplatin for 48 h. RESULTS: The results demonstrated that nivolumab increased the anti-tumor effects of cisplatin in A2780/DDP cells. Notably, the combined treatment effectively reversed cisplatin resistance in PROC cells. Also, nivolumab induced cell apoptosis and cell-cycle arrest in G0/G1 phase in PROC cells. FACS and Western blot were performed to measure cell apoptosis and Bcl-2 and Bax expression respectively. The results showed that combined treatment significantly increased cell apoptosis rate, down-regulated Bcl-2, and unregulated Bax expression in PROC cells. Additionally, the expression levels of ADAM17 were significantly decreased in a dose-dependent manner in PROC cells, which were treated with nivolumab. CONCLUSIONS: Therefore, all the results demonstrated that the combined treatment with nivolumab and cisplatin effectively inhibited PROC cells via induction of cell apoptosis and inhibition of ADAM17 expression.

Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections.

It has been proposed that inactivated probiotics may modulate the host immune system and contribute to mitigation of viral infections. This study demonstrated that administration of heat-killed Enterococcus faecalis, a widely used probiotic, can protect host animals against viral infections. The influenza-mediated morbidity and lung inflammation in E. faecalis-treated mice decreased significantly compared with those of the control mice. Furthermore, we found that the protection is associated with production of monocyte chemoattractant protein-1 (MCP-1). The intratracheal injection of a recombinant mouse MCP-1 protein abrogated the antiviral effects elicited by pretreatment with E. faecalis. CC chemokine receptor 2 (CCR2) is a receptor for MCP-1, and the intraperitoneal administration of a CCR2 antagonist effectively inhibited viral pathogenicity. The reduced pathogenicity was also observed in CCR2-deficient mice. Finally, E. faecalis significantly attenuated neuropathogenicity induced by another RNA virus, enterovirus 71. This study demonstrates that killed probiotics can reduce viral disease severity and identify that the MCP-1 pathway might act as a key mediator in the improved antiviral immune response. Our findings suggest that MCP-1 and its related signaling pathway can serve as critical therapeutic targets for development of new antiviral strategies.

The lipid profile in obese asthmatic children compared to non-obese asthmatic children

BACKGROUND: A relationship between asthma and obesity has been documented in children and adolescents. An alternate day calorie restriction diet has been reported to improve asthma symptoms by decreasing levels of serum cholesterol and triglycerides, reducing markers of oxidative stress and increasing levels of the antioxidant uric acid. Therefore, to investigate the lipid profile in asthmatic children may be important in asthma control treatment. MATERIALS AND METHODS: One hundred and sixty newly diagnosed persistent asthmatic children were selected to participate in the study. They were divided into four groups based on their body mass index (BMI): Group I normal weight (BMI=20-24.9 kg/m2, n = 30); Group II under-weight (BMI < 20 kg/m2, n = 30); Group III overweight (BMI=25-30 kg/m2, n = 25); and Group IV obese (BMI > 30 kg/m2, n=25). Fasting blood sugar, fasting insulin, and HbA1c were measured to exclude the possibility of pre-diabetes. Lipid profile measurements included total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apo-A1, apo-B and triglycerides. RESULTS: There were no significant differences in the levels of apo-A1, apo-B, triglycerides, cholesterol and LDL in all four groups. Only the level of HDL was higher in GIV>GIII>GII>GI (75.84±13.95, 68.56±15.28, 64.17±13.93, 63.17±14.34mg/dl, respectively). There were no cases of pre-diabetes in any of the four groups. CONCLUSION: Hypercholesterolaemia and hypertriglyceridaemia were not found in any of the persistent asthmatic children, and thus they are not high risk factors for asthma. Similarly, there were no differences in apo-A1 and apo-B between any of the BMI groups. No differences were found in LDL levels, however HDL levels were increased in all four groups, indicating that allergic sensitisation may have occurred. Controlling body weight and restricting calorie intake may be as important as appropriate pharmacological management in controlling asthma

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An unusual case of focal segmental glomerulosclerosis presenting with retropharyngeal edema.

INTRODUCTION: Acute neck swelling with pharyngeal signs often triggers emergency consultation. Treatment and diagnosis are usually multidisciplinary. Failing to find a possible etiology may lead to misdiagnosis. CASE PRESENTATION: A young man presented to the emergency room with a 4-day history of cough, neck swelling and sore throat. Laboratory testing showed a leukocyte count of 9200 without left shift. Mild elevated CRP with 1.7 was noted and computed tomography (CT) showed fluid accumulation in the retropharyngeal space and neck edema down to thyroid region. Antibiotic was prescribed and admitted to infection ward under the impression of deep neck infection. During hospitalization, needle aspiration was performed where water fluid was collected without pus. Investigations showed massive proteinuria, hypoalbuminemia and hypercholesterolemia. The early focal segmental glomerulosclerosis was found by renal biopsy. After prednisolone 60mg daily and albumin supplement, the neck swelling, swallowing pain and general edema had completely resolved. DISCUSSION: The purpose of this case is to raise awareness of nephrotic syndrome as an unusual but possibly cause of retropharyngeal edema. We highlight the diagnostic features that will allow the physicians to make the correct diagnosis, avoid unnecessary incision and drainage, and commence effective treatment early in the disease course.

The lipid profile in obese asthmatic children compared to non-obese asthmatic children.

BACKGROUND: A relationship between asthma and obesity has been documented in children and adolescents. An alternate day calorie restriction diet has been reported to improve asthma symptoms by decreasing levels of serum cholesterol and triglycerides, reducing markers of oxidative stress and increasing levels of the antioxidant uric acid. Therefore, to investigate the lipid profile in asthmatic children may be important in asthma control treatment. MATERIALS AND METHODS: One hundred and sixty newly diagnosed persistent asthmatic children were selected to participate in the study. They were divided into four groups based on their body mass index (BMI): Group I normal weight (BMI=20-24.9kg/m(2), n=30); Group II under-weight (BMI<20kg/m(2), n=30); Group III overweight (BMI=25-30kg/m(2), n=25); and Group IV obese (BMI>30kg/m(2), n=25). Fasting blood sugar, fasting insulin, and HbA1c were measured to exclude the possibility of pre-diabetes. Lipid profile measurements included total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apo-A1, apo-B and triglycerides. RESULTS: There were no significant differences in the levels of apo-A1, apo-B, triglycerides, cholesterol and LDL in all four groups. Only the level of HDL was higher in GIV>GIII>GII>GI (75.84±13.95, 68.56±15.28, 64.17±13.93, 63.17±14.34mg/dl, respectively). There were no cases of pre-diabetes in any of the four groups. CONCLUSION: Hypercholesterolaemia and hypertriglyceridaemia were not found in any of the persistent asthmatic children, and thus they are not high risk factors for asthma. Similarly, there were no differences in apo-A1 and apo-B between any of the BMI groups. No differences were found in LDL levels, however HDL levels were increased in all four groups, indicating that allergic sensitisation may have occurred. Controlling body weight and restricting calorie intake may be as important as appropriate pharmacological management in controlling asthma.

Prolonged postprocedural outbreak of Mycobacterium massiliense infections associated with ultrasound transmission gel.

Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case-control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case-control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p <0.05) with acquiring the outbreak strain. Isolates from the cases and unopened bottles of ultrasound transmission gel were all of strain ST48 and indistinguishable or closely related by pulsed-field gel electrophoresis. After replacement of contaminated gel, no new cases were detected during 18 months' follow-up. This investigation identified the use of contaminated gel as the common source causing an outbreak on a larger scale than had been recognized. Our findings halted production by the manufacturer and prompted revision of hospital guidelines.

Prognostic significance of NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia.

Distinct microRNA (miRNA) and mRNA signatures were reported in nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML). However, it remains unknown whether the mutation participates in the dynamic interaction between miRNA and mRNA. In this study, we aimed to investigate the role of NPM1 mutation in modulating miRNA-mRNA regulation (MMR). From the sample-paired miRNA/mRNA microarrays of 181 de novo AML patients, we found that MMR was dynamic and could be affected by NPM1 mutation. By a systematic framework, we identified 493 NPM1 mutation-modulated MMR pairs, where the strength of MMR was significantly attenuated in patients carrying NPM1 mutations, compared to those with wild-type NPM1. These miRNAs/mRNAs were associated with pathways implicated in cancer and known functions of NPM1 mutation. Such modulation of MMR was validated in two independent cohorts as well as in cells with different NPM1 mutant burdens. Furthermore, we showed that the regulatory strength of nine MMR pairs could predict patients' outcomes. Combining these pairs, a scoring system was proposed and shown to predict survival in discovery and validation data sets, independent of other known prognostic factors. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which a novel prognostic marker is proposed in AML.

Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection.

The most severe form of virus-induced inflammation at the ocular surface is epidemic keratoconjunctivitis (EKC), often caused by group D human adenoviruses (HAdVs). We investigated the dynamics and mechanisms of changes in natural killer (NK) cell types in the human ocular mucosal surface in situ over the course of infection. In the acute phase of infection, the mature CD56(dim)NK cells that comprise a major subpopulation in the normal human conjunctiva are replaced by CD56(bright)NK cells recruited to the ocular surface by chemokines produced by the infected epithelium, and NKG2A-expressing CD56(dim) and CD56(bright) NK cells become the major subpopulations in severe inflammation. These NK cells attracted to the mucosal surface are however incapable of mounting a strong antiviral response because of upregulation of the inhibitory ligand human leukocyte antigen-E (HLA-E) on infected epithelium. Furthermore, group D HAdVs downregulate ligands for activating NK cell receptors, thus rendering even the mature NKG2A(-)NK cells unresponsive, an immune-escape mechanism distinct from other adenoviruses. Our findings imply that the EKC-causing group D HAdVs utilize these multiple pathways to inhibit antiviral NK cell responses in the initial stages of the infection.

Risk of Parkinson's disease following anxiety disorders: a nationwide population-based cohort study.

BACKGROUND AND PURPOSE: Anxiety is potentially a pre-motor symptom of Parkinson's disease (PD). Our aim was to investigate the association between anxiety and subsequent PD risk in a population-based sample. METHODS: A total of 174 776 participants, who were free of prior PD, dementia and stroke, were enrolled from Taiwan National Health Insurance Research Database between 1 January 2005 and 31 December 2005. The association between anxiety at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities, especially depression, and concomitant medication use was adjusted in the proportional hazards models. RESULTS: Over an average follow-up of 5.5 years, 2258 incident PD cases were diagnosed. After adjusting for age, sex, comorbidities and concomitant medication use, patients with anxiety were more likely to develop PD than subjects without anxiety [adjusted hazard ratio (HR) 1.38; 95% confidence interval (CI) 1.26-1.51]. Anxiety severity was dose-dependently associated with increased likelihood of PD: crude HR 1.27 (95% CI 1.11-1.44) for mild anxiety, 1.35 (95% CI 1.19-1.53) for moderate anxiety and 2.36 (95% CI 2.13-2.62) for severe anxiety (P < 0.0001). Results were similar after adjustment for age, sex, comorbid depression and other PD risk factors, and in the sensitivity analyses excluding participants with comorbid depression or with a PD diagnosis <3 years after anxiety diagnosis, and controlling for Charlson's scores. CONCLUSIONS: The likelihood of developing PD was greater amongst patients with anxiety than patients without anxiety, and the severity of anxiety correlated with risk of PD.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.