Attaining freshwater and estuarine-water soil saturation in an ecosystem-scale coastal flooding experiment.

Coastal upland forests are facing widespread mortality as sea-level rise accelerates and precipitation and storm regimes change. The loss of coastal forests has significant implications for the coastal carbon cycle; yet, predicting mortality likelihood is difficult due to our limited understanding of disturbance impacts on coastal forests. The manipulative, ecosystem-scale Terrestrial Ecosystem Manipulation to Probe the Effects of Storm Treatments (TEMPEST) experiment addresses the potential for freshwater and estuarine-water disturbance events to alter tree function, species composition, and ecosystem processes in a deciduous coastal forest in MD, USA. The experiment uses a large-unit (2000 m2), un-replicated experimental design, with three 50 m × 40 m plots serving as control, freshwater, and estuarine-water treatments. Transient saturation (5 h) of the entire soil rooting zone (0-30 cm) across a 2000 m2 coastal forest was attained by delivering 300 m3 of water through a spatially distributed irrigation network at a rate just above the soil infiltration rate. Our water delivery approach also elevated the water table (typically ~ 2 m belowground) and achieved extensive, low-level inundation (~ 8 cm standing water). A TEMPEST simulation approximated a 15-cm rainfall event and based on historic records, was of comparable intensity to a 10-year storm for the area. This characterization was supported by showing that Hurricane Ida's (~ 5 cm rainfall) hydrologic impacts were shorter (40% lower duration) and less expansive (80% less coverage) than those generated through experimental manipulation. Future work will apply TEMPEST treatments to evaluate coastal forest resilience to changing hydrologic disturbance regimes and identify conditions that initiate ecosystem state transitions.

Guidelines on radiographic imaging as part of root canal treatment: a systematic review with a focus on review imaging after treatment.

AIM: To identify guidelines on endodontics which make recommendations relating to post-root canal treatment radiological review imaging, to make an objective assessment of their quality using the AGREE tool and to examine the evidence cited in support of their recommendations. METHODOLOGY: The primary sources to identify published guidelines were MEDLINE (Ovid® ) and EMBASE. The search aim was to identify guidelines pertaining to the post-root canal treatment follow-up recommendations published from 1946 with the final search date being 26 June 2016. The primary search was supplemented by searching Internet search engines and several websites that might have guidelines. The guidelines obtained from the search end-result were assessed for quality and scientific evidence using the AGREE II instrument. Similarities and differences in the recommendations were identified. RESULTS: Thirty guidelines were identified, seven of which met the inclusion criteria. Two guidelines used and clearly described the methods for obtaining scientific evidence from which the recommendations were set. The recommendations varied, particularly as regards the timing of the first review radiograph. Some guidelines lacked supporting evidence. CONCLUSIONS: The recommendations for post-root canal treatment radiographic follow-up varied amongst the identified guidelines. However, the methodology for obtaining the scientific evidence was poorly described in most of the guidelines. Guideline development groups should use the AGREE II instrument as a guide to produce higher quality guidelines.

Efficient removal of arsenic (V) from water using steel-making slag.

This study describes the potential use of steel-making slag as an arsenic-removal medium. Systematic analysis of slag material revealed a composition of oxides of calcium, iron, silicon, and phosphorous. Under the experimental conditions of this study, the equilibrium time was shown to be 2 hours, and the removal capacity to be 99%, with an adsorbent loading capacity of 1.25g/l. The adsorption kinetics were shown to follow a pseudo-second-order rate equation, and the adsorption isotherm closely followed both the Langmuir and Freundlich isothermic models. Variations in solution pH levels demonstrated that with a decrease in the initial solution pH, the adsorption capacity decreases. This is attributed to the leaching of silica and phosphate from the slag to the solution, which imparted a competing effect for adsorption sites. However, with an alkaline pH, such leaching was reduced, and due to formation of calcium carbonate from the leached calcium from the slag material, the arsenic removal efficiency increased as it was co-precipitated with calcium carbonate.

Persistence and compliance of deferoxamine versus deferasirox in Medicaid patients with sickle-cell disease.

WHAT IS KNOWN AND OBJECTIVE: Patients with sickle-cell disease (SCD) receiving chronic transfusions of red blood cells are at risk of developing serious adverse effects. Iron chelation therapy (ICT) helps eliminate iron overload by binding with plasma iron to form a non-toxic conjugate that can be safely excreted from the body. Two iron chelating agents are currently available in the United States: Deferoxamine (DFO) is an injectable formulation, and deferasirox (Exjade(®) ) is an oral suspension. This study compared the frequency of hospitalizations, persistence and compliance of patients with SCD from Medicaid programmes treated with DFO vs. deferasirox. METHODS: Health care claims from Medicaid Florida (1998-2007), Missouri (1993-2008) and New Jersey (1996-2008) were analysed. Patients with continuous enrolment for ≥6months prior to ICT initiation and ≥1 SCD diagnosis were included in the analysis. Patients were divided into four cohorts: patients treated with DFO (any-DFO group) and patients treated with deferasirox (any-deferasirox group); the latter was further divided into patients initiated on DFO and then switched to deferasirox (deferasirox switchers), and patients treated with deferasirox-only (deferasirox-only group). Frequency of hospitalization for crisis conditions related to SCD as well as length of stay pre- and post-ICT treatment initiation were assessed. Persistence was defined as time to drug discontinuation with ≥1 Rx gap, using Kaplan-Meier approach. Compliance was estimated using a medication possession ratio (MPR) based on the drug exposure approach. Adjusted analyses of persistence and compliance were also conducted. RESULTS: A total of 217 (mean age: 19·4years, 39·2 men), 275 (20·1years, 41·5% men), 105 (19·4years, 42·9% men) and 166 (20·4years, 41·6% men) patients were included in the any-DFO, any-deferasirox, deferasirox switchers and deferasirox-only groups, respectively. After ICT initiation, the any-deferasirox and deferasirox-only groups experienced a statistically significant reduction in the frequency of hospitalizations relative to pretreatment [any-deferasirox: from 0·09 to 0·06 hospitalizations per patient per month (pmpm), P=0·0105; deferasirox-only: from 0·11 to 0·07 hospitalizations pmpm, P=0·0188], whereas it remained stable in the any-DFO group at 0·08 hospitalizations pmpm (P=0·9483). The Kaplan-Meier rates of medication persistence assessed at 6 and 12months of follow-up were significantly lower for DFO patients (6 months: 0·34, 12months: 0·21) as compared to all deferasirox (0·51, 0·29, P=0·0002), deferasirox switchers (0·56, 0·37, P=0·0002) and deferasirox-only (0·47, 0·24, P=0·0176) patients. Similarly, compliance to treatment was significantly lower for patients treated with DFO (mean MPR: 0·64) compared with any-deferasirox (0·78, P<0·0001), deferasirox switchers (0·75, P=0·0002) and deferasirox-only (0·80, P<0·0001) patients. Adjusted analyses of persistence and compliance yielded similar results. WHAT IS NEW AND CONCLUSIONS: Based on a Medicaid population, patients treated with deferasirox were more compliant and persistent with their treatment than those treated with DFO. Frequency of hospitalizations was significantly reduced after treatment initiation for the any-deferasirox and deferasirox-only groups. Prospective studies controlling for potential clinical and treatment pattern differences between deferasirox and DFO patients are needed to assess whether the decreased hospitalizations after initiation of deferasirox are related to better treatment compliance.

Optimization of external (in air) particle induced gamma-ray emission (PIGE) methodology for rapid, non-destructive, and simultaneous quantification of fluorine, sodium, and phosphorus in nuclear waste immobilization matrices.

External (in air) PIGE methodology has been optimized for rapid quantification of fluorine, sodium, and phosphorus in fluorapatite waste immobilization matrices for Molten Salt Reactor (MSR). The present methodology addresses the issue of distinguishing hydroxyapatite and fluorapatite phases through XRD patterns. Fluctuations in proton beam current have been monitored by prompt γ-ray from nitrogen (2312 keV) through 14N(p,p'γ)14N nuclear reaction and have successfully been applied as a new method of current normalization, for the first time, in external PIGE method with lower Compton background and negligible spectral interference. The proposed method was also compared with the earlier method of current normalization using 165 keV (181T(p,p'γ)181Ta) from the Tantalum window used for obtaining "in air" beam. For the fluctuation of beam current within 5-10 nA, nitrogen from air can be used as an effective current normalizer. Moreover, the uncertainty (within ±3%) was also improved in the present method of current normalization. Fluorine can be estimated from trace to major concentrations using 197 keV (19F(p,p'γ)19F) γ-ray with highest sensitivity as compared to other prompt γ-rays (110 keV and 1236 keV). The matrix effect in PIGE was also eliminated by diluting the sample in cellulose. The method was validated using the synthetic samples (Ca10(PO4)6F2, Na2Eu2Ca6(PO4)6F2, Na1.5Eu1.5Ca7(PO4)6F2, Na1Eu1Ca8(PO4)6F2, Na0.5Eu0.5Ca9(PO4)6F2, and Sr10(PO4)6F2). The results were found to be satisfactory and in good agreement with stoichiometric amounts. Elements such as Na, P, and Ca were determined in the fluorapatite samples using PIGE and EDXRF, respectively, as a part of chemical quality control. Moreover, in external PIGE, 1266 keV γ-ray (31P(p,p'γ)31P) provides more accurate P concentrations in the samples.

A high-resolution computed tomography based scoring system to predict ease of electrode insertion in cochlear implantation.

OBJECTIVE: This study aimed to formulate a scoring system based on high-resolution computed tomography scans to predict ease of electrode insertion during cochlear implantation via posterior tympanotomy in paediatric patients. METHOD: A scoring system Cochlear Implantation Radiological Assessment Score (CIRAS) was formulated based on six parameters. This score was correlated with intra-operative findings, and receiver operating characteristic analysis was performed to determine the optimal cut-off score to predict difficulty of surgery and to establish the inherent validity of the scoring system by area under curve. RESULTS: Receiver operating characteristic analysis showed that optimal cut-off score was 8 (93.1 per cent specificity and 56.52 per cent sensitivity), and area under the curve was 0.828. Patients with CIRAS of more than 8 had significantly higher time for surgery (p < 0.05). CONCLUSION: CIRAS is an easy to administer tool by utilising classical axial and coronal sections, without any numerical measures. Pre-operative assessment by this score gives a good idea of intra-operative challenges.

Endoscopic epitympanic exploration in mucosal chronic otitis media: is canal wall up mastoidectomy really needed?

OBJECTIVE: To compare endoscopic epitympanic exploration with conventional canal wall up (cortical) mastoidectomy for mucosal chronic otitis media in terms of post-operative outcomes. METHODS: Seventy-six patients diagnosed with chronic otitis media (mucosal variety) were randomly assigned to two treatment groups: endoscopic epitympanic exploration and conventional canal wall up (cortical) mastoidectomy. The groups were compared in terms of: post-operative anatomical outcomes (graft uptake), middle-ear physiological outcomes (post-operative tympanometry), audiological outcomes (air-bone gap), surgical time, post-operative pain, vertigo, and long-term complications such as retraction pocket and re-perforation. RESULTS: There was a statistically significant difference between the groups in terms of mean air-bone gap at 12 months, surgical time, and median post-operative pain measured at 6 hours (p < 0.05). No statistically significant differences were noted in terms of: graft uptake at 1, 3 and 6 months, mean air-bone gap at 3 and 6 months, tympanometry at 3, 6 and 12 months, vertigo at 1 week, or long-term complications. CONCLUSION: Endoscopic epitympanic exploration resulted in significantly better long-term audiological outcomes, shorter operating time and less pain compared with conventional canal wall up (cortical) mastoidectomy.

Copper oxide-based cathode for direct NADPH regeneration.

Nearly a fourth of all enzymatic activities is attributable to oxidoreductases, and the redox reactions supported by this vast catalytic repertoire sustain cellular metabolism. In many biological processes, reduction depends on hydride transfer from either reduced nicotinamide adenine dinucleotide (NADH) or its phosphorylated derivative (NADPH). Despite longstanding efforts to regenerate NADPH by various methods and harness it to support chemoenzymatic synthesis strategies, the lack of product purity has been a major deterrent. Here, we demonstrate that a nanostructured heterolayer Ni-Cu2O-Cu cathode formed by a photoelectrochemical process has unexpected efficiency in direct electrochemical regeneration of NADPH from NADP+. Remarkably, two-thirds of NADP+ was converted to NADPH with no measurable production of the inactive (NADP)2 dimer and at the lowest reported overpotential [- 0.75 V versus Ag/AgCl (3 M NaCl) reference]. Sputtering of nickel on the copper-oxide electrode nucleated an unexpected surface morphology that was critical for high product selectivity. Our results should motivate design of integrated electrolyzer platforms that deploy this heterogeneous catalyst for direct electrochemical regeneration of NADH/NADPH, which is central to design of next-generation biofuel fermentation strategies, biological solar converters, energy-storage devices, and artificial photosynthesis.

Prolonged intra-operative thermal exposure in endoscopic ear surgery: is it really safe?

OBJECTIVE: The aim of this study was to assess change in temperature, audiometric outcomes and post-operative complications following exposure to different light sources during endoscopic ear surgery. METHOD: A total of 64 patients diagnosed with chronic otitis media with central perforation and pure conductive hearing loss underwent endoscopic type 1 tympanoplasty. The patients were randomised into two groups based on the light source used: xenon or light-emitting diode. Temperature was measured using a K type thermocouple at the promontory and round window niche. Mean temperature change with respect to operating time, mean audiometric change, incidence of vomiting in the first 24 hours, vertigo and tinnitus at the end of the first week were observed. RESULTS: Mean temperature change showed a statistically significant difference with increasing length of operating time with the xenon light source and when the two light sources were compared for a particular time interval. Mean audiometric change showed statistically significant deterioration at higher frequencies (4, 6 and 8 kHz) with the xenon light source but only at 8 kHz for the light emitting diode source. When the mean audiometric change was compared between light sources for a particular frequency, statistical significance was found at 4, 6 and 8 kHz. Post-operative complications were vomiting, vertigo and tinnitus (p-values of 0.042, 0.099 and 0.147, respectively, between two groups). CONCLUSION: Light emitting diodes are associated with less significant middle-ear temperature rises and audiometric changes at higher frequencies when compared to xenon light sources. Hence, xenon should be replaced with cooler light sources.

Reduced Global Efficiency and Random Network Features in Patients with Relapsing-Remitting Multiple Sclerosis with Cognitive Impairment.

BACKGROUND AND PURPOSE: Graph theory uses structural similarity to analyze cortical structural connectivity. We used a voxel-based definition of cortical covariance networks to quantify and assess the relationship of network characteristics to cognition in a cohort of patients with relapsing-remitting MS with and without cognitive impairment. MATERIALS AND METHODS: We compared subject-specific structural gray matter network properties of 18 healthy controls, 25 patients with MS with cognitive impairment, and 55 patients with MS without cognitive impairment. Network parameters were compared, and predictive value for cognition was assessed, adjusting for confounders (sex, education, gray matter volume, network size and degree, and T1 and T2 lesion load). Backward stepwise multivariable regression quantified predictive factors for 5 neurocognitive domain test scores. RESULTS: Greater path length (r = -0.28, P < .0057) and lower normalized path length (r = 0.36, P < .0004) demonstrated a correlation with average cognition when comparing healthy controls with patients with MS. Similarly, MS with cognitive impairment demonstrated a correlation between lower normalized path length (r = 0.40, P < .001) and reduced average cognition. Increased normalized path length was associated with better performance for processing (P < .001), learning (P < .001), and executive domain function (P = .0235), while reduced path length was associated with better executive (P = .0031) and visual domains. Normalized path length improved prediction for processing (R 2 = 43.6%, G2 = 20.9; P < .0001) and learning (R 2 = 40.4%, G2 = 26.1; P < .0001) over a null model comprising confounders. Similarly, higher normalized path length improved prediction of average z scores (G2 = 21.3; P < .0001) and, combined with WM volume, explained 52% of average cognition variance. CONCLUSIONS: Patients with MS and cognitive impairment demonstrate more random network features and reduced global efficiency, impacting multiple cognitive domains. A model of normalized path length with normal-appearing white matter volume improved average cognitive z score prediction, explaining 52% of variance.

Diagnostic efficacy of cone beam computed tomography in paediatric dentistry: a systematic review.

PURPOSE: To determine in which clinical situations it is indicated or contra-indicated to prescribe cone beam computed tomography (CBCT) for paediatric patients. METHODS: Systematic review of in vivo paediatric research studies of diagnostic efficacy using CBCT, with supplementary searches for guideline documents on CBCT and for systematic reviews permitting inclusion of ex vivo and adult studies. RESULTS: After screening, 190 publications were included, mostly case studies. No systematic reviews were found of in vivo paediatric research. Fourteen studies of diagnostic efficacy were identified. The supplementary searches found 18 guideline documents relevant to the review and 26 systematic reviews. The diagnostic efficacy evidence on CBCT was diverse and often of limited quality. There was ex vivo evidence for diagnostic accuracy being greater using CBCT than radiographs for root fractures. The multiplanar capabilities of CBCT are advantageous when localising dental structures for surgical planning. Patient movement during scanning is more common in children which could reduce diagnostic efficacy. CONCLUSIONS: No strong recommendations on CBCT are possible, except that it should not be used as a primary diagnostic tool for caries. Guidelines on use of CBCT in the paediatric age group should be developed cautiously, taking into account the greater radiation risk and the higher economic costs compared with radiography. CBCT should only be used when adequate conventional radiographic examination has not answered the question for which imaging was required. Clinical research in paediatric patients is required at the higher levels of diagnostic efficacy of CBCT.

Correction to: Diagnostic efficacy of cone beam computed tomography in paediatric dentistry: a systematic review.

In the original publication of the article the fifth author's name "A. Littlewood" was submitted as "A. Littewood" which was left unnoticed in the later stages. The correct name is as published in this erratum.

Does tranexamic acid improve intra-operative visualisation in endoscopic ear surgery? A double-blind, randomised, controlled trial.

OBJECTIVE: To assess the effect of tranexamic acid on intra-operative bleeding and surgical field visualisation. METHODS: Fifty patients undergoing various endoscopic ear surgical procedures, including endoscopic tympanoplasty, endoscopic atticotomy or mastoidectomy, endoscopic ossiculoplasty, and endoscopic stapedotomy, were randomly assigned to: a study group that received tranexamic acid or a control group which received normal saline. The intra-operative bleeding and operative field visualisation was graded using the Das and Mitra endoscopic ear surgery bleeding and field visibility score, which was separately analysed for the external auditory canal and the middle ear. RESULTS: The Das and Mitra score was better (p < 0.05) in the group that received tranexamic acid as a haemostat when working in the external auditory canal; with respect to the middle ear, no statistically significant difference was found between the two agents. Mean values for mean arterial pressure, heart rate and surgical time were comparable in both groups, with no statistically significant differences. CONCLUSION: Tranexamic acid appears to be an effective haemostat in endoscopic ear surgery, thus improving surgical field visualisation, especially during manipulation of the external auditory canal soft tissues.

Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression.

Deciphering the BCR-ABL-independent signaling exploited in chronic myeloid leukemia (CML) progression is an important aspect in cancer stem-cell biology. CML stem-cell compartment is dynamic as it progresses to terminal blast crisis where myeloid and lymphoid blasts fail to differentiate. We demonstrate cross-regulation of signaling network involving Sonic hedgehog (Shh), Wnt, Notch and Hox for the inexorable blastic transformation of CD34(+) CML cells. Significant upregulation in Patched1, Frizzled2, Lef1, CyclinD1, p21 (P < or =0.0002) and downregulation of HoxA10 and HoxB4 (P< or =0.0001) transcripts in CD34(+) cells distinguish blast crisis from chronic CML. We report Shh-dependent Stat3 activation orchestrates these mutually interconnected signaling pathways. Stimulation of CD34(+) CML cells with either soluble Shh or Wnt3a did not activate Akt or p44/42-mitogen activated protein kinase (MAPK) pathways. Interestingly, unlike dominant negative Stat3beta, introduction of constitutive active Stat3 in CD34(+) CML cells induces cross-regulation in gene expression. Additionally, Shh and Wnt3a-dependent regulation of cyclin-dependent kinase inhibitors (CDKI) in CML suggests their role in the network. Taken together, our findings propose that deregulation in the form of hyperactive Shh and Wnt with repressed Notch and Hox pathways involving Stat3, Gli3, beta-catenin, CyclinD1, Hes1, HoxA10 and p21 might act synergistically to form an important hub in CML progression.

Interplay between human papilloma virus infection and p53 gene alterations in head and neck squamous cell carcinoma of an Indian patient population.

AIM: To investigate the complex interplay between human papilloma virus (HPV) infection and p53 gene alteration in 92 head and neck squamous cell carcinoma (HNSCC) and 28 leukoplakia samples from eastern India. METHODS: DNA isolated from the patient samples was subjected to HPV detection, loss of heterozygosity (LOH) analysis of the chromosome 17p region harbouring p53, genotyping at the p53 codon 72 locus and sequencing of the entire p53 gene to identify somatic mutations. Codon 72 heterozygotes carrying the p53 mutation were further cloned and resequenced to identify the allele harbouring the mutation. RESULTS: HPV positivity in the HNSCC samples was 69%; 21% of the HNSCC were found to harbour p53 mutations in the coding region of the gene. The absence of the p53 mutation in HPV positive tumours was statistically significant compared to the HPV negative tumours (p = 0.01), but the same did not hold true for p53 LOH (p = 1.0). Among the germline p53 codon 72 heterozygotes, the Pro allele was preferentially lost (p = 0.02) while the Arg allele was mutated in the majority of cases. The risk of HPV mediated tumourigenesis increased with the increase in number of Arg alleles at the codon 72 locus. CONCLUSION: It is proposed that genetic and epigenetic alteration of p53 follow distinct pathways during the development of HNSCC from normal epithelium via dysplasia. The p53 mutation and HPV mediated p53 inactivation possibly constitute two independent pathways of tumourigenesis.

Efficacy and Safety of Mycobacterium indicus pranii as an adjunct therapy in Category II pulmonary tuberculosis in a randomized trial.

Prolonged treatment of tuberculosis (TB) often leads to poor compliance, default and relapse, converting primary TB patients into category II TB (Cat IITB) cases, many of whom may convert to multi-drug resistant TB (MDR-TB). We have evaluated the immunotherapeutic potential of Mycobacterium indicus pranii (MIP) as an adjunct to Anti-Tubercular Treatment (ATT) in Cat II pulmonary TB (PTB) patients in a prospective, randomized, double blind, placebo controlled, multicentric clinical trial. 890 sputum smear positive Cat II PTB patients were randomized to receive either six intra-dermal injections (2 + 4) of heat-killed MIP at a dose of 5 × 108 bacilli or placebo once in 2 weeks for 2 months. Sputum smear and culture examinations were performed at different time points. MIP was safe with no adverse effects. While sputum smear conversion did not show any statistically significant difference, significantly higher number of patients (67.1%) in the MIP group achieved sputum culture conversion at fourth week compared to the placebo (57%) group (p = 0.0002), suggesting a role of MIP in clearance of the bacilli. Since live bacteria are the major contributors for sustained incidence of TB, the potential of MIP in clearance of the bacilli has far reaching implications in controlling the spread of the disease.

Gene expression profiling reveals the profound upregulation of hypoxia-responsive genes in primary human astrocytes.

Oxygen is vital for the development and survival of mammals. In response to hypoxia, the brain initiates numerous adaptive responses at the organ level as well as at the molecular and cellular levels, including the alteration of gene expression. Astrocytes play critical roles in the proper functioning of the brain; thus the manner in which astrocytes respond to hypoxia is likely important in determining the outcome of brain hypoxia. Here, we used microarray gene expression profiling and data-analysis algorithms to identify and analyze hypoxia-responsive genes in primary human astrocytes. We also compared gene expression patterns in astrocytes with those in human HeLa cells and pulmonary artery endothelial cells (ECs). Remarkably, in astrocytes, five times as many genes were induced as suppressed, whereas in HeLa and pulmonary ECs, as many as or more genes were suppressed than induced. More genes encoding hypoxia-inducible functions, such as glycolytic enzymes and angiogenic growth factors, were strongly induced in astrocytes compared with HeLa cells. Furthermore, gene ontology and computational algorithms revealed that many target genes of the EGF and insulin signaling pathways and the transcriptional regulators Myc, Jun, and p53 were selectively altered by hypoxia in astrocytes. Indeed, Western blot analysis confirmed that two major signal transducers mediating insulin and EGF action, Akt and MEK1/2, were activated by hypoxia in astrocytes. These results provide a global view of the signaling and regulatory network mediating oxygen regulation in human astrocytes.

Stacking dependence of carrier transport properties in multilayered black phosphorous.

We present the effect of different stacking orders on carrier transport properties of multi-layer black phosphorous. We consider three different stacking orders AAA, ABA and ACA, with increasing number of layers (from 2 to 6 layers). We employ a hierarchical approach in density functional theory (DFT), with structural simulations performed with generalized gradient approximation (GGA) and the bandstructure, carrier effective masses and optical properties evaluated with the meta-generalized gradient approximation (MGGA). The carrier transmission in the various black phosphorous sheets was carried out with the non-equilibrium green's function (NEGF) approach. The results show that ACA stacking has the highest electron and hole transmission probabilities. The results show tunability for a wide range of band-gaps, carrier effective masses and transmission with a great promise for lattice engineering (stacking order and layers) in black phosphorous.

MicroRNAs as biomarkers of resilience or vulnerability to stress.

Identifying novel biomarkers of resilience or vulnerability to stress could provide valuable information for the prevention and treatment of stress-related psychiatric disorders. To investigate the utility of blood microRNAs as biomarkers of resilience or vulnerability to stress, microRNAs were assessed before and after 7days of chronic social defeat in rats. Additionally, microRNA profiles of two important stress-regulatory brain regions, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA), were assessed. Rats that displayed vulnerability to subsequent chronic stress exhibited reductions in circulating miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p, and miR-532-5p levels. In contrast, rats that became resilient to stress displayed reduced levels of miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p compared to controls. In the mPFC, miR-126a-3p and miR-708-5p levels were higher in vulnerability compared to resilient rats. In the BLA, 77 microRNAs were significantly altered by stress but none were significantly different between resilient and vulnerable animals. These results provide proof-of-principle that assessment of circulating microRNAs is useful in identifying individuals who are vulnerable to the effects of future stress or individuals who have become resilient to the effects of stress. Furthermore, these data suggest that microRNAs in the mPFC but not in the BLA are regulators of resilience/vulnerability to stress.