Concomitant back pain as a predictor of outcome after single level lumbar micro-decompressive surgery - A study of 995 patients.

OBJECTIVE: To determine if preoperative leg pain and low back pain severity affected postoperative outcome. METHOD: Prospectively collected Spine-Tango data was analysed for 995 consecutive patients who underwent a primary, single level, lumbar micro-decompression/microdiscectomy at a single tertiary spinal centre. RESULT: At 3 months, 72% of patients were satisfied with the outcome of surgery. Pre-operative low back pain was a significant predictor of poor outcome (P < 0.01). CONCLUSION: Our study has shown that patients with a low back pain VAS of 6 or more have a significantly greater chance of a poor outcome following primary lumbar microdecompressive/microdiscectomy surgery.

Gamma Radiation-Induced Disruption of Cellular Junctions in HUVECs Is Mediated through Affecting MAPK/NF-κB Inflammatory Pathways.

Ionizing radiation-induced cardiovascular diseases (CVDs) have been well documented. However, the mechanisms of CVD genesis are still not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to gamma irradiation at different doses ranging from 0.2 Gy to 5 Gy. Cell viability, migration ability, permeability, oxidative and nitrosative stresses, inflammation, and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway activation were evaluated postirradiation. It was found that gamma irradiation at doses ranging from 0.5 Gy to 5 Gy inhibited the migration ability of HUVECs without any significant effects on cell viability at 6 h and 24 h postirradiation. The decreased transendothelial electrical resistance (TEER), increased permeability, and disruption of cellular junctions were observed in HUVECs after gamma irradiation accompanied by the lower levels of junction-related proteins such as ZO-1, occludin, vascular endothelial- (VE-) cadherin, and connexin 40. The enhanced oxidative and nitrosative stresses, e.g., ROS and NO2 - levels and inflammatory cytokines IL-6 and TNF-α were demonstrated in HUVECs after gamma irradiation. Western blot results showed that protein levels of mitogen-activated protein kinase (MAPK) pathway molecules p38, p53, p21, and p27 increased after gamma irradiation, which further induced the activation of the NF-κB pathway. BAY 11-7085, an inhibitor of NF-κB activation, was demonstrated to partially block the effects of gamma radiation in HUVECs examined by TEER and FITC-dextran permeability assay. We therefore concluded that the gamma irradiation-induced disruption of cellular junctions in HUVECs was through the inflammatory MAPK/NF-κB signaling pathway.

Serological and molecular detection of Mycoplasma pneumoniae in children with community-acquired lower respiratory tract infections.

This study was designed to evaluate the incidence of Mycoplasma pneumoniae infection in children with community-acquired lower respiratory tract infections (LRTIs). A total of 245 patients 6 months to 12 years of age were investigated for M. pneumoniae employing serological tests, polymerase chain reaction (PCR), nested PCR, and reverse transcription PCR (RT-PCR) on throat swab samples. Forty five (59.2%) children <5 years and 31 (40.7%) children ≥5 years age group were positive for M. pneumoniae infection, and this difference was statistically significant (P ≤ 0.01).Clinical and radiological findings across M.pneumoniae-positive and -negative cases were comparable. Serology, PCR, nested PCR, and RT-PCR together detected M. pneumoniae infection in 76 (31%) patients. Sensitivity, specificity, and positive and negative predictive values of PCR were 16.18%, 95.48%, 57.89%, and 74.78%, respectively, and those of serology were 57.89%, 74.78%, 16.18%, and 95.48%, respectively. Serological and molecular detection in combination is useful for rapid and reliable diagnosis of M. pneumoniae infections in children with LRTIs.

Mycoplasma pneumoniae infection and asthma in children.

A clinical association between exacerbation of asthma symptoms and Mycoplasma pneumoniae ( M. pneumoniae) infection has long been suspected. We studied 80 children aged 5-15 years; 50 with asthma (Group 1) and 30 without an acute exacerbation of asthma (Group 2) for detection of M. pneumoniae by serology and polymerase chain reaction (PCR) on nasopharyngeal aspirates. Our study confirms that lower respiratory tract infections with M. pneumoniae are frequently associated with exacerbations of asthma in children.

Occurrence and impact of domestic violence and abuse in gay and bisexual men: A cross sectional survey.

This cross-sectional survey measured adult experience and perpetration of negative and potentially abusive behaviours with partners and its associations with mental and sexual health problems, drug and alcohol abuse in gay and bisexual men attending a UK sexual health service. Of 532 men, 33.9% (95% CI: 29.4-37.9) experienced and 16.3% (95% CI: 13.0-19.8) reported carrying out negative behaviour. Ever being frightened of a partner (aOR 2.5; 95% CI: 2.0-3.1) and having to ask a partner's permission (aOR 2.7; 95% CI: 1.6-4.7) were associated with increased odds of being anxious. There were increased odds of cannabis use in the last 12 months amongst men who reported ever being physically hurt (aOR 2.4; 95% CI: 1.7-3.6). Being frightened (aOR 2.2; 95% CI: 1.5-3.2), being physically hurt (aOR 2.3; 95% CI: 1.4-3.8), being forced to have sex (aOR 2.5; 95% CI: 1.3-4.9) and experiencing negative behaviour in the last 12 months (aOR 1.7; 95% CI: 1.2-2.5) were associated with increased odds of using a Class A drugs in the last 12 months. Sexual health practitioners should be trained with regards to the risk indicators associated with domestic violence and abuse, how to ask about domestic violence and abuse and refer to support.

Xpert(®) MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children.

SETTING: A tertiary care teaching hospital in New Delhi, India. OBJECTIVE: To determine the sensitivity and specificity of the Xpert(®) MTB/RIF assay in paediatric pulmonary tuberculosis (PTB) using MGIT™ culture as gold standard. METHODS: After ethical approval had been obtained, 50 patients aged 0-14 years with suspected PTB were enrolled. Sputum/induced sputum and gastric lavage from the participants were sent for direct smear, MGIT culture and Xpert testing. Chest X-ray and tuberculin skin test (TST) were also performed. PTB diagnosis was made without considering Xpert results according to the Revised National Tuberculosis Control Programme (RNTCP) algorithm. The sensitivity and specificity of Xpert were calculated using culture as gold standard. RESULTS: Of 50 individuals with suspected PTB, 23 (46%) were diagnosed with PTB based on the RNTCP algorithm. Sixteen children from the PTB group (69.5%) were Xpert-positive. None in the 'not PTB' group were Xpert-positive. With culture as gold standard, Xpert sensitivity and specificity were respectively 91.6% (95%CI 59.7-99.5) and 86.8% (95%CI 71.1-95.05). CONCLUSION: In almost 70% of PTB cases, a definitive diagnosis could be made within 2 h using Xpert, establishing its role as a sensitive and specific point-of-care test.

Influenza A virus enhances its propagation through the modulation of Annexin-A1 dependent endosomal trafficking and apoptosis.

The influenza virus infects millions of people each year and can result in severe complications. Understanding virus recognition and host responses to influenza infection will enable future development of more effective anti-viral therapies. Previous research has revealed diverse yet important roles for the annexin family of proteins in modulating the course of influenza A virus (IAV) infection. However, the role of Annexin-A1 (ANXA1) in IAV infection has not been addressed. Here, we show that ANXA1 deficient mice exhibit a survival advantage, and lower viral titers after infection. This was accompanied with enhanced inflammatory cell infiltration during IAV infection. ANXA1 expression is increased during influenza infection clinically, in vivo and in vitro. The presence of ANXA1 enhances viral replication, influences virus binding, and enhances endosomal trafficking of the virus to the nucleus. ANXA1 colocalizes with early and late endosomes near the nucleus, and enhances nuclear accumulation of viral nucleoprotein. In addition, ANXA1 enhances IAV-mediated apoptosis. Overall, our study demonstrates that ANXA1 plays an important role in influenza virus replication and propagation through various mechanisms and that we predict that the regulation of ANXA1 expression during IAV infection may be a viral strategy to enhance its infectivity.

Usual vulval intraepithelial neoplasia in HIV-positive women - a case series.

Usual or undifferentiated type vulval intraepithelial neoplasia (VIN) is more common in young women and is usually associated with high-risk human papillomavirus infection. It is associated with the development of basaloid or warty squamous cell carcinoma. Studies have shown that HIV-positive women have an increased risk of VIN and invasive vulval carcinoma, but there is a paucity of data about this cohort of women. The objective of this study was to describe the clinical features and treatment responses of HIV-positive women diagnosed with VIN in a specialist vulval dermatology clinic. HIV-positive women diagnosed with VIN from 2007 to 2013 were retrospectively identified. Data were collected on demographics, clinical features, treatments and outcomes. Seven cases were retrospectively identified. The median CD4 cell count at presentation was 500 cells/mm3 (range 59-761). Five had multifocal VIN. Five were treated with imiquimod alone, one had surgical excision and one patient was treated with imiquimod and surgery. Five of the seven had complete resolution of disease. HIV-positive patients with VIN had good responses to treatment with imiquimod. They were likely to be stable on combination antiretroviral therapy at presentation, have multifocal disease and concurrent vaginal, anal or cervical intraepithelial neoplasia.

Gene Microarray Analyses of Daboia russelli russelli Daboiatoxin Treatment of THP-1 Human Macrophages Infected with Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model were investigated using whole-genome microarrays. Gene expression profiles were compared between infected THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx) or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential upregulation of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4), transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the tolllike receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B. pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment of human macrophages infected with B. pseudomallei.

Blood levels of isoniazid in Indian children with tuberculosis.

BACKGROUND: Under the Revised National Tuberculosis Control Program (RNTCP) in India children are receiving antituberculosis treatment (ATT) as per a weight band system. In this children may be receiving antituberculosis drugs in doses which may be more or less than that recommended in mg/kg body weight doses. The recommended dose of isoniazid (INH) for intermittent therapy under the RNTCP is 8-12 mg/kg body weight and by the World Health Organization (WHO) for daily therapy is 10-15 mg/kg body weight. AIMS: To evaluate the blood levels and pharmacokinetics of INH, in children suffering from tuberculosis, at doses administered under the weight band system of the Revised National Tuberculosis Control Program (RNTCP) 2009 of India. DESIGN: Prospective, open label, non-randomized single-dose study conducted in 20 children in the age group 5-12 years attending the outpatient, chest clinic of a tertiary care hospital. RESULTS: Group I (n = 8) included children who received INH in a dose of 10 mg/kg body weight or more and Group II (n = 12) included those who received INH in a dose less than 10 mg/kg body weight. The mean peak INH concentration (Cmax) was 6.03 ± 1.4 µg/mL and this was achieved in 2 hours (Tmax). The mean serum INH concentration was significantly higher in children who received INH in dose more than 10 mg/kg (Group I) as compared to those who received INH in doses lesser than 10 mg/kg body weight (Group II) at all-time points except at 2 hours (P < 0.05). The Cmax was also lower in Group II patients in comparison to Group I patients. Area under the concentration time curve (AUC) was significantly lower in Group II patients (P value 0.002). The elimination half-life of INH was 4.3 ± 0.4 h, elimination rate constant 0.16 ± 0.01/h, the volume of distribution 44.05 ± 5.3 L and clearance 7.1 ± 0.8 L/h. CONCLUSIONS: Lower blood levels and AUC of INH were achieved in children receiving doses of INH lesser than 10 mg/kg body weight. Long elimination half-life of INH is indicative of a slower rate of metabolism. Lower INH levels despite a slower rate of drug metabolism indicate caution with the INH doses being administered to children for intermittent therapy under the RNTCP.

Paediatric idiopathic myelofibrosis.

Pediatric myelofibrosis is a rare disorder. It is usually secondary to other diseases. Rarely, when no underlying cause is found, it is termed idiopathic. We present here, a rare case of idiopathic myelofibrosis in a 10 year old male child. Bone marrow aspirate was dilute. Bone biopsy showed marrow fibrosis, with grade 2-3 reticulin fibres, with no evidence of granuloma, parasite or infilterative disorder. Acid fast bacillus stain was negative. Iliac lymph node biopsy showed reactive sinus histiocytosis with extramedullary hematopoeisis. Thus, diagnosis of pediatric idiopathic primary myelofibrosis was made. Idiopathic pediatric myelofibrosis should be suspected in a child with progressive pallor, hepatosplenomegaly and dry tap on bone marrow aspiration and marrow fibrosis on bone biopsy, after exclusion of secondary causes.

Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells.

BACKGROUND: Constitutive activation of signal transducer and activator of transcription signalling 3 (STAT3) has been linked with survival, proliferation and angiogenesis in a wide variety of malignancies including hepatocellular carcinoma (HCC). METHODS: We evaluated the effect of lupeol on STAT3 signalling cascade and its regulated functional responses in HCC cells. RESULTS: Lupeol suppressed constitutive activation of STAT3 phosphorylation at tyrosine 705 residue effectively in a dose- and time-dependent manner. The phosphorylation of Janus-activated kinases (JAKs) 1 and 2 and Src was also suppressed by lupeol. Pervanadate treatment reversed the downregulation of phospho-STAT3 induced by lupeol, thereby indicating the involvement of a phosphatase. Indeed, we observed that treatment with lupeol increased the protein and mRNA levels of SHP-2, and silencing of SHP-2 abolished the inhibitory effects of lupeol on STAT3 activation. Treatment with lupeol also downregulated the expression of diverse STAT3-regulated genes and decreased the binding of STAT3 to VEGF promoter. Moreover, the proliferation of various HCC cells was significantly suppressed by lupeol, being associated with substantial induction of apoptosis. Depletion of SHP-2 reversed the observed antiproliferative and pro-apoptotic effects of lupeol. CONCLUSIONS: Lupeol exhibited its potential anticancer effects in HCC through the downregulation of STAT3-induced pro-survival signalling cascade.

Non-response to the intensive phase of anti-tuberculosis treatment in children: evaluation and outcome [Short Communication].

The present study evaluates the causes for the persistence of symptoms and radiological signs after at least 2 months of intensive anti-tuberculosis treatment in children. In this prospective observational study, 26 paediatric patients with partial or no response to anti-tuberculosis treatment after the 2-month intensive phase were enrolled. After a detailed history and workup, it was found that 9 (34.6%) patients had a wrong initial diagnosis, while 12 (46.2%) had either received inadequate treatment or had complications requiring prolonged treatment; 5 (19.2%) failed to respond. Failure to respond to anti-tuberculosis treatment in paediatric tuberculosis seems to be over-diagnosed.

Improved sexual history taking in the 2012 BASHH asymptomatic screening re-audit.

Effective asymptomatic screening for sexually transmitted infections is an important public health service because a significant proportion of sexually transmitted infections do not present with symptoms. In 2009, the National Audit Group of the British Association of Sexual Health and HIV (BASHH) audited the management of asymptomatic patients and recommended increased documentation about oral and anal sex, regional strategies for nucleic acid amplification test (NAAT) use for gonorrhoea, improved screening for hepatitis B in men who have sex with men and an increase in screening for HIV. The 2012 audit used web-based forms to collect submissions from 180 consultant-led centres (65% response rate) that included episodes of care from 6669 asymptomatic patients. An improvement was demonstrated for all the areas measured during the 2009 audit. A doubling of gonorrhoea testing using NAATs was seen and yet 10% of asymptomatic patients continued to have microscopy despite these tests not being recommended by BASHH guidelines. This audit recommends universal adoption of gonorrhoea NAATs across the United Kingdom.

Post-infectious glomerulonephritis following infective endocarditis: Amenable to immunosuppression.

Glomerulonephritis develops in about 20% patients with infective endocarditis (IE), but is mostly asymptomatic. Heavy proteinuria or derangement of kidney functions is uncommon. We report here a child with IE and proliferative glomerulonephritis who manifested as significant proteinuria that recovered on treatment with immunosupressants.