Distinct karyotypic and mutational landscape in trisomy AML.

Trisomy karyotype occurs in 5%-10% of AML. Its mutational landscape and prognostic significance are not well defined. A cohort of 156 trisomy AML patients was analysed, with reference to 615 cytogenetically normal (CN) AML patients. Trisomy AML showed distinct mutational landscape with more prevalent SMC1A, N/KRAS, ASXL1 and BCOR but fewer CEBPAbZIP and NPM1 mutations in patients ≤60, and fewer NPM1 mutations in those >60. NRAS mutations were associated with poor outcome in trisomy AML, whereas DNMT3A and FLT3-ITD mutations had neutral effect. Trisomy AML appeared biologically distinct from CN-AML.

Technical report: surgical preparation of human brain tissue for clinical and basic research.

BACKGROUND: The study of the distinct structure and function of the human central nervous system, both in healthy and diseased states, is becoming increasingly significant in the field of neuroscience. Typically, cortical and subcortical tissue is discarded during surgeries for tumors and epilepsy. Yet, there is a strong encouragement to utilize this tissue for clinical and basic research in humans. Here, we describe the technical aspects of the microdissection and immediate handling of viable human cortical access tissue for basic and clinical research, highlighting the measures needed to be taken in the operating room to ensure standardized procedures and optimal experimental results. METHODS: In multiple rounds of experiments (n = 36), we developed and refined surgical principles for the removal of cortical access tissue. The specimens were immediately immersed in cold carbogenated N-methyl-D-glucamine-based artificial cerebrospinal fluid for electrophysiology and electron microscopy experiments or specialized hibernation medium for organotypic slice cultures. RESULTS: The surgical principles of brain tissue microdissection were (1) rapid preparation (<1 min), (2) maintenance of the cortical axis, (3) minimization of mechanical trauma to sample, (4) use of pointed scalpel blade, (5) avoidance of cauterization and blunt preparation, (6) constant irrigation, and (7) retrieval of the sample without the use of forceps or suction. After a single round of introduction to these principles, multiple surgeons adopted the technique for samples with a minimal dimension of 5 mm spanning all cortical layers and subcortical white matter. Small samples (5-7 mm) were ideal for acute slice preparation and electrophysiology. No adverse events from sample resection were observed. CONCLUSION: The microdissection technique of human cortical access tissue is safe and easily adoptable into the routine of neurosurgical procedures. The standardized and reliable surgical extraction of human brain tissue lays the foundation for human-to-human translational research on human brain tissue.

Multifamily groups for patients with schizophrenia: an exploratory randomised controlled trial in Bosnia and Herzegovina.

BACKGROUND: Schizophrenia has a significant and lasting impact on the quality of life of patients and their families and is a leading cause of disability globally. Family interventions can be beneficial and may be particularly appropriate in settings with limited resources. We conducted an exploratory trial testing the effectiveness of a multifamily group intervention, which draws on the traditions of psychoeducation and trialogue, for improving the quality of life of patients with schizophrenia in Bosnia and Herzegovina. METHODS: We conducted an exploratory, randomised controlled trial with patients with schizophrenia attending an outpatient clinic in Sarajevo. Our primary outcome was improved quality of life at 6-month follow-up. Secondary outcomes included objective social outcomes, psychiatric symptoms and psychiatric hospitalisation measured at 6 and 12 months. Experiences of participants were assessed in post-intervention interviews. RESULTS: 72 patients were randomly assigned to either one of six multifamily groups or treatment as usual. Follow-up assessments were completed with 53 patients (74%) at 6 months and 55 patients (76%) at 12 months. The intervention significantly improved quality of life at 6 months (Cohen's d = 0.78, F = 6.37, p = 0.016) and 12 months (d = 1.08, F = 17.92, p < 0.001), compared with treatment as usual. Re-hospitalisation rates at 6 months and symptom levels also improved significantly whilst changes in other secondary outcomes failed to reach statistical significance. CONCLUSION: These findings suggest multifamily groups can be effective for improving the quality of life of patients with schizophrenia in Bosnia and Herzegovina. Further research is required to assess how multifamily groups may be scaled up in similar settings with limited resources.

NDUFA9 point mutations cause a variable mitochondrial complex I assembly defect.

Mitochondrial respiratory chain complex I consists of 44 different subunits and contains 3 functional modules: the Q-, the N- and the P-module. NDUFA9 is a Q-module subunit required for complex I assembly or stability. However, its role in complex I biogenesis has not been studied in patient fibroblasts. So far, a single patient carrying an NDUFA9 variant with a severe neonatally fatal phenotype has been reported. Via exome sequencing, we identified a novel homozygous NDUFA9 missense variant in another patient with a milder phenotype including childhood-onset progressive generalized dystonia and axonal peripheral neuropathy. We performed complex I assembly analysis using primary skin fibroblasts of both patients. Reduced complex I abundance and an accumulation of Q-module subassemblies were present in both patients but more pronounced in the severe clinical phenotype patient. The latter displayed additional accumulation of P-module subassemblies, which was not present in the milder-phenotype patient. Lentiviral complementation of both patient fibroblast cell lines with wild-type NDUFA9 rescued complex I deficiency and the assembly defects. Our report further characterizes the phenotypic spectrum of NDUFA9 deficiency and demonstrates that the severity of the clinical phenotype correlates with the severity of the effects of the different NDUFA9 variants on complex I assembly.

Annual direct medical costs associated with diabetes-related complications in the event year and in subsequent years in Hong Kong.

AIM: To develop models to estimate the direct medical costs associated with diabetes-related complications in the event year and in subsequent years. METHODS: The public direct medical costs associated with 13 diabetes-related complications were estimated among a cohort of 128 353 people with diabetes over 5 years. Private direct medical costs were estimated from a cross-sectional survey among 1825 people with diabetes. We used panel data regression with fixed effects to investigate the impact of each complication on direct medical costs in the event year and subsequent years, adjusting for age and co-existing complications. RESULTS: The expected annual public direct medical cost for the baseline case was US$1,521 (95% CI 1,518 to 1,525) or a 65-year-old person with diabetes without complications. A new lower limb ulcer was associated with the biggest increase, with a multiplier of 9.38 (95% CI 8.49 to 10.37). New end-stage renal disease and stroke increased the annual medical cost by 5.23 (95% CI 4.70 to 5.82) and 5.94 (95% CI 5.79 to 6.10) times, respectively. History of acute myocardial infarction, congestive heart failure, stroke, end-stage renal disease and lower limb ulcer increased the cost by 2-3 times. The expected annual private direct medical cost of the baseline case was US$187 (95% CI 135 to 258) for a 65-year-old man without complications. Heart disease, stroke, sight-threatening diabetic retinopathy and end-stage renal disease increased the private medical costs by 1.5 to 2.5 times. CONCLUSIONS: Wide variations in direct medical cost in event year and subsequent years across different major complications were observed. Input of these data would be essential for economic evaluations of diabetes management programmes.

Childhood lead poisoning: an overview.

Childhood lead poisoning is a major public health concern in many countries. In 2015, the Hong Kong SAR Government and its citizens faced a major public health crisis due to the presence of lead in the drinking water of a number of public housing estates. Fortunately, no child was diagnosed with lead poisoning that required treatment with chelation. Lead is a ubiquitous, naturally occurring material that exists in air, dust, soil, and water. It is also widely present in industrial products including petrol, paints, ceramics, food cans, candies, cosmetics, traditional remedies, batteries, solder, stained glass, crystal vessels, ammunition, ceramic glazes, jewellry, and toys. It can also be found in human milk. There is no safe blood lead level and it may be impossible to completely eliminate lead from any city. Hence routine measurement of blood lead levels is not considered useful. Acute poisoning, especially with encephalopathy, deserves immediate medical treatment in hospital. Chelation therapy is recommended if blood lead level is 45 µg/dL or higher. For blood levels between 20 and 45 µg/dL, treatment is indicated if the child is symptomatic. For blood levels below 20 µg/dL in otherwise asymptomatic children, the principle of treatment is to provide long-term neurodevelopmental follow-up and counselling. In all cases, immediate removal of the source of lead exposure is vital. Even low levels of lead exposure can significantly impair learning, educational attainment, and neurodevelopment.

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: baseline data from the IMPaCT randomized controlled trial.

BACKGROUND: The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment. METHOD: Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18-65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria. RESULTS: High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS. CONCLUSIONS: In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: baseline data from the IMPaCT RCT study--Corrigendum.

The author regrets to announce that affiliation 8, in the above article (Gardner-Sood et al. 2015), contained an error in the author affiliation address and author surname, which were published in the approved article. The correct surname and affiliation address are given below. J. Eberhard, Clinical Psychiatric Research Center, Lund University, Skåne, Sweden

Spontaneous motion on two-dimensional continuous attractors.

Attractor models are simplified models used to describe the dynamics of firing rate profiles of a pool of neurons. The firing rate profile, or the neuronal activity, is thought to carry information. Continuous attractor neural networks (CANNs) describe the neural processing of continuous information such as object position, object orientation, and direction of object motion. Recently it was found that in one-dimensional CANNs, short-term synaptic depression can destabilize bump-shaped neuronal attractor activity profiles. In this article, we study two-dimensional CANNs with short-term synaptic depression and spike frequency adaptation. We found that the dynamics of CANNs with short-term synaptic depression and CANNs with spike frequency adaptation are qualitatively similar. We also found that in both kinds of CANNs, the perturbative approach can be used to predict phase diagrams, dynamical variables, and speed of spontaneous motion.

UV photodecomposition of zinc acetate for the growth of ZnO nanowires.

The thermal annealing of zinc precursors to form suitable seed layers for the growth of ZnO nanowires is common. However, the process is relatively long and involves high temperatures which limit substrate choice. In this study the use of a low temperature, ultra-violet (UV) exposure is demonstrated for photodecomposition of zinc acetate precursors to form suitable seed layers. Comparisons are made between ZnO nanowire growth performed on seed layers produced through thermal annealing and exposure to UV. The dependence of growth density and nanowire diameter on UV exposure time is investigated. Growth quality is confirmed with energy dispersive x-ray (EDX) and x-ray diffraction analyses. The chemical composition of the exposed layers is investigated with EDX and x-ray photoelectron spectroscopy (XPS). Atomic force microscopy (AFM) is utilized to investigate morphological changes with respect to UV exposure. The diameter and density of the resultant growth was found to be strongly dependent on the UV exposure time. UV exposure times of only 25-30 s led to maximum density of growth and minimum diameter, significantly faster than thermal annealing. EDX, XPS and AFM analyses of the seed layers confirmed decomposition of the zinc precursor and morphological changes which influenced the growth.

Timely thoracoscopic decortication promotes the recovery of paediatric parapneumonic empyema.

INTRODUCTION: Parapneumonic empyema is one of the most commonly encountered yet difficult to manage paediatric thoracic conditions. Conservative treatment with chest tube drainage and fibrinolytic agents had been proposed but operative decortication remains the gold standard for refractory cases. Thoracoscopic decortication has been advocated in recent years due to its superiority in terms of post-operative pain, cosmesis and other long-term results. However, few studies investigated the effect of timing on peri-operative outcomes. This study aims to explore the benefits of early decortication. METHODS: Retrospective study of all patients who underwent thoracoscopic decortication between 1999 and 2013 at a tertiary referral centre was performed. Data were extracted from respective medical records. Patients' demographics, peri-operative outcomes, length of hospitalization and post-operative complications were analysed. RESULTS: A total of 28 patients were identified, 12 males and 16 females. Average age of patients was 4.5 years (range 12 months-14 years). Right-sided empyema was involved in 14 of the patients. Patients who underwent operation within 2 weeks from symptom onset (n = 16) showed significant shorter post-operative hospital stay (mean 9.5 vs 20.4 days, p = 0.003) and total hospitalization duration (mean 19.3 vs 38.8 days, p < 0.001). Correlation study demonstrated a strong relation between delay in operation and prolonged hospitalization (r = 0.63, p = 0.001). The peri-operative and post-operative outcomes were similar. No major post-operative complication was encountered except one patient who required a second decortication for residual empyema. CONCLUSION: Thoracoscopic decortication is a safe and feasible procedure for parapneumonic empyema. Timely surgery is recommended as it promotes early recovery and shorter hospitalization.

Platelet Ca(2+) responses coupled to glycoprotein VI and Toll-like receptors persist in the presence of endothelial-derived inhibitors: roles for secondary activation of P2X1 receptors and release from intracellular Ca(2+) stores.

Inhibition of Ca(2+) mobilization by cyclic nucleotides is central to the mechanism whereby endothelial-derived prostacyclin and nitric oxide limit platelet activation in the intact circulation. However, we show that ∼ 50% of the Ca(2+) response after stimulation of glycoprotein VI (GPVI) by collagen, or of Toll-like 2/1 receptors by Pam(3)Cys-Ser-(Lys)(4) (Pam(3)CSK(4)), is resistant to prostacyclin. At low agonist concentrations, the prostacyclin-resistant Ca(2+) response was predominantly because of P2X1 receptors activated by ATP release via a phospholipase-C-coupled secretory pathway requiring both protein kinase C and cytosolic Ca(2+) elevation. At higher agonist concentrations, an additional pathway was observed because of intracellular Ca(2+) release that also depended on activation of phospholipase C and, for TLR 2/1, PI3-kinase. Secondary activation of P2X1-dependent Ca(2+) influx also persisted in the presence of nitric oxide, delivered from spermine NONOate, or increased ectonucleotidase levels (apyrase). Surprisingly, apyrase was more effective than prostacyclin and NO at limiting secondary P2X1 activation. Dilution of platelets reduced the average extracellular ATP level without affecting the percentage contribution of P2X1 receptors to collagen-evoked Ca(2+) responses, indicating a highly efficient activation mechanism by local ATP. In conclusion, platelets possess inhibitor-resistant Ca(2+) mobilization pathways, including P2X1 receptors, that may be particularly important during early thrombotic or immune-dependent platelet activation.

Ultrafine particles generated from coloring with scented markers in the presence of ozone.

High concentrations of ultrafine particles (UFPs) have been previously reported during school art activities. This is possibly due to secondary organic aerosols (SOAs) formed from reactions between ozone and volatile organic compounds emitted from art products. Four brands of markers, three scented and one unscented, were tested inside a stainless steel chamber at eight different ozone concentrations between 0 and 300 ppb. Out of the 32 tested markers, only the lemon- and orange-scented markers from one brand reacted with ozone to form UFPs. Limonene, pinene, and several other terpenes were identified as ingredients of ink in SOA-forming markers. Coloring with one lemon-scented marker for 1 min without ozone generated on average approximately 26 ± 4 ppb of limonene inside the chamber. At 150 ppb ozone, using one lemon marker for 1 min formed on average 7.7 × 10(10) particles. The particle size distribution indicated an initial mode of 15 nm which grew to 40 nm. At 50 ppb ozone and below, no significant SOA formation occurred. The number of particles formed is moderately correlated with the mass of ink used (R(2)  = 0.68). Based on these data, scented markers are not likely a strong source of SOA under normal indoor ozone levels.

Association between tuberculosis infections and non-pulmonary malignancies: a nationwide population-based study.

BACKGROUND: In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections. METHODS: Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections. RESULTS: After a follow-up period of 28 866 person-years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90-2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54-1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin's disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis. CONCLUSION: Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.

Differential-phase-shift quantum key distribution using heralded narrow-band single photons.

We demonstrate the first proof of principle differential phase shift (DPS) quantum key distribution (QKD) using narrow-band heralded single photons with amplitude-phase modulations. In the 3-pulse case, we obtain a quantum bit error rate (QBER) as low as 3.06% which meets the unconditional security requirement. As we increase the pulse number up to 15, the key creation efficiency approaches 93.4%, but with a cost of increasing the QBER. Our result suggests that narrow-band single photons maybe a promising source for the DPS-QKD protocol.

Flexographic printing-assisted fabrication of ZnO nanowire devices.

In this study, the use of flexographic printing was investigated for low cost, high volume production of devices incorporating nanowires through the printing of zinc acetate precursors on a substrate used to form zinc oxide (ZnO) seeds for the growth of nanowires using a hydrothermal growth technique. The printing of precursors allows the selective area growth of ZnO nanowires, which has implications in high-yield production of devices incorporating ZnO nanowires. The work presented here achieved printed line widths of <60 µm with low edge distortion (<3 µm) using a printing plate with a line width of 50 µm. The hydrothermally grown ZnO nanowires show uniform density of growth over the printed area with nanowire diameters between 40 and 60 nm on both silicon and polyimide substrates. Energy-dispersive x-ray spectra showed contamination-free crystals with a 1:1 (zinc to oxygen) stoichiometry. Crystal orientation is along the c-axis with high quality crystalline structure shown using x-ray diffraction spectroscopy and high resolution transmission electron microscopy. A ZnO nanowire gas sensor, fabricated using the flexographic printing technique, is demonstrated. Such a printing-assisted fabrication offers low cost, high volume production of devices incorporating ZnO nanowires, ranging from gas sensors to field emission devices.