Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling

Although conventional therapies for acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) are effective in inducing remission, many patients relapse upon treatment. Hence, there is an urgent need for novel therapies. PIM kinases are often overexpressed in AML and DLBCL and are therefore an attractive therapeutic target. However, in vitro experiments have demonstrated that intrinsic resistance to PIM inhibition is common. It is therefore likely that only a minority of patients will benefit from single agent PIM inhibitor treatment. In this study, we performed an shRNA-based genetic screen to identify kinases whose suppression is synergistic with PIM inhibition. Here, we report that suppression of p38α (MAPK14) is synthetic lethal with the PIM kinase inhibitor AZD1208. PIM inhibition elevates reactive oxygen species (ROS) levels, which subsequently activates p38α and downstream AKT/mTOR signaling. We found that p38α inhibitors sensitize hematological tumor cell lines to AZD1208 treatment in vitro and in vivo. These results were validated in ex vivo patient-derived AML cells. Our findings provide mechanistic and translational evidence supporting the rationale to test a combination of p38α and PIM inhibitors in clinical trials for AML and DLBCL

Challenges in the Analysis of Historic Concrete:Understanding the Limitations of Techniques, the Variability of the Material and the Importance of Representative Samples

The number of historically-significant concrete structures which require conservation and repair is ever-increasing. The use of unsuitable proprietary materials has led to poor quality repairs of historically-significant structures in the United Kingdom, some of which have resulted in damage to the historic character of the structure and accelerated deterioration of the substrate. As a result, the approach to the repair of historic concrete structures has shifted from the use of mass-produced proprietary repair materials to purpose-made ‘like-for-like’ replacements which, theoretically, have similar mechanical and aesthetic properties. In order to create like-for-like repair materials, the original mix proportions and water/cement (w/c) ratio of the substrate have to be established. However, there are concerns regarding the accuracy of existing techniques and standards used for the analyses of hardened concrete. Furthermore, due to a lack of available material, analyses are often carried out on samples that are much smaller than the minimum requirement for a representative sample, or from areas which are not representative. This paper discusses these issues and hopes to provide information to conservators and analysts on the limitations of techniques, the variability of the material and the importance of representative samples

Acute pancreatitis: a study of urine trypsinogen-2 measurement as a screening test

Background: Usefulness of urine trypsinogen-2 as screening test for acute pancreatitis in Indian population.Methods:We prospectively compared the urinary trypsinogen-2 dipstick test and serum amylase assays in 100 consecutive patients with acute abdominal pain at the emergency department. Urine samples were obtained on admission and tested for the dipstick. The diagnosis of acute pancreatitis was made on the basis of a typical clinical picture and serum amylase at least more than threefold the upper reference limit (300 IU) and/or radiological evidence (Abdominal X ray/ultrasonography/contrast enhanced CT).Results: 1. Urine trypsinogen-2 dipstick test was having 100% sensitivity and 85.71% specificity in diagnosing acute pancreatitis in Indian population. 2. Serum amylase was having 61.36% sensitivity and 78.57% specificity in diagnosing acute pancreatitis. 3. Sensitivity and specificity of urine trypsinogen-2 dipstick test is more than that of serum amylase in diagnosing acute pancreatitis which is statistically proved to be significant (P <0.05).Conclusion:Detection of trypsinogen-2 in urine is a simple office test in diagnosing acute pancreatitis in emergency department. As the sensitivity and specificity are high, detection of urine trypsinogen-2 in urine can be used as a screening test, which will definitely help in early diagnosis and prompt treatment of acute pancreatitis.

Engineering Performance of a New Siloxane-Based Corrosion Inhibitor

This paper presents an evaluation of a new non-toxic corrosion inhibitor on selected engineering properties of concrete mixes with different cementitious materials following a corrosion and durability study on concrete samples. Corrosion inhibitors consist of powders or solutions which are added to concrete when mixed to prevent or delay corrosion of steel by their reaction with ferrous ions to form a stable and passive ferric oxide film on the steel surface. The new inhibitor functions slightly differently and its corrosion inhibition effect is due to the formation of a siloxane coating on the steel surface. Therefore, the performance of the new inhibitor in concrete mixes manufactured with CEM I, PFA and GGBS cements was compared against a well known and established corrosion inhibitor on the market, namely calcium nitrite in terms of their effect on workability (measured in terms of slump), compressive strength, freeze–thaw durability and macro-cell corrosion. The results from this experimental programme have demonstrated that the new inhibitor is effective in reducing or slowing down corrosion. In addition, it was found that CEM I concrete containing the new inhibitor was less penetrable to chlorides than that without. A similar set of results was obtained for the freeze– thaw resistance, but the compressive strength was found to decrease with the addition of the new inhibitor. In the case of concretes containing PFA and GGBS, the new inhibitor was found to be less effective. Further, long-term investigations are recommended to assess the effectiveness over time

The Synoptic Characteristics, Causes, and Mechanisms of Kahlaa Tornado in Iraq on 14th April 2016

In this study, an analysis of the synoptic characteristics, causes and mechanisms of Kahlaa tornado event was carried out. This tornado occurred on 10:30 UTC (1:30 pm Iraq Local Time) on 14 April 2016 to the north of Kahlaa town in Maysan governorate. We analyzed surface and upper charts, weather conditions, the damage indices, the dynamical features and the instability of the tornado. The analysis showed that there was a low pressure system which was an extension of the Monsoon low in addition to a supercell thunderstorm and a jet stream aloft. The cold trough and high relative vorticity at 500 hPa level, the humid warm wind blowing from the south and the dry cold wind from the north contributed to the initiation of the tornado. According to the damage amount, Kahlaa tornado can be classified as EF2 degree (considerable) on Enhanced Fujita scale. Three indices were calculated to estimate the instability of the tornado. The values of the convective available potential energy (CAPE), K-index, and lifted index were (≥2500 J/kg), (35.3 oC), and (-7), respectively. All these indices confirmed the instability required to form severe thunderstorm essential to tornado formation. Although the forecasting of tornadoes occurrence is difficult, there would be indications that may lead to expect of occurrence. These may include the availability of moisture, heat, and significant wind direction changes with altitude. However, the vital factors were the existence of high instability and a supercell thunderstorm

Accommodative-Convergence Mechanism failure in HIV-Positive Non Presbyopic Patient on Highly Active Anti-Retroviral Therapy: A case report

Purpose: Accommodative-convergence mechanism failure could occur in non presbyopic HIV- sero positive patients on Highly Active Anti-Retroviral&nbsp; Therapy (HAART). This could be due to either direct neuronal infection by HIV, pathologic changes of the lens or the ciliary body or adverse effects of some individual drugs constituting the HAART regimen on the cranial nerves which play vital roles in the mechanism of accommodation and convergence. Case report: This is a case report of an accommodative- convergence mechanism failure in HIV positive non presbyopic 32-year-old male patient&nbsp; that was on HAART for more than five years. He presented with distance visual acuity (VA) of OD: 6/9 +2, OS: 6/9, and near visual acuity (NVA) of N24 both eyes, 3Δ esophoria at distance and 4Δ esophoria at near. Amplitude of accommodation (AA) was 3.50D and accommodative&nbsp; convergence/accommodation (AC/A) ratio was 6/1. Following comprehensive evaluation, his refractive correction was OD: Plano/-0.50DC X 180 6/5 and OS: Plano/-0.50DC X 90 6/5 at distance with near addition (Add) 2.50D N5. This was prescribed for regular wear in form of D-Top bifocal lens. Conclusion: These findings showed that HIV sero-positive adults on HAART could develop accommodativeconvergence mechanism failure, which may be characterized by low amplitude of accommodation, receded near point of convergence and high non presbyopic reading addition. These conditions may be under-recognized and need for reading addition of a non presbyopic age is often overlooked. Key Words: Accommodative-Convergence, HIV, Lateral Phoria, Refractive error

Detection of Trypanozoon trypanosomes infections on Glossina fuscipes fuscipes (Diptera: Glossinidae) using polymerase chain reaction (PCR) technique in the Blue Nile State, Sudan

Tsetse flies transmit many species of trypanosomes in Africa, some of which are human and livestock pathogens of major medical and socio-economic impact. Identification of trypanosomes is essential to assess the disease risk imposed by particular tsetse populations. The present study was carried out to determine the trypanosomal infection rate of tsetse flies (Glossina fuscipes fuscipes) in the Blue Nile State of Sudan. A polymerase chain reaction (PCR) assay was used because of the inherent difficulty of speciating trypanosomal parasites in the fly. Our results show that 4.44% (8/180) of the flies were positive for a Trypanosoma brucei group. Three of eight positive flies reacted with primers for Trypanosoma b. rhodesiense. We did not detect flies infected with T. b. gambiense. Thus, the burden of flies harboring T. b. rhodesiense and T. b. brucei trypanosomes were 1.67 and 2.78%, respectively. This is the first evidence of T. b. rhodesiense in the Yabus District. Thus, HAT case-detection active surveillance and tsetse fly control campaigns should be conducted before the establishment of human settlement, investment of natural resources into agricultural and animal husbandry.Key words: Glossina fuscipes fuscipes, Trypanosoma brucei, T. b. gambiense, T. b. rhodesiense, infection rate, PCR technique, Blue Nile State

A Systemic Review of Iron Deficiency Anemia in Adults and the Clinical Management of Diagnosis and Treatment

Iron deficiency is the most frequent cause of anaemia worldwide. It impairs quality of life, increases asthenia and can lead to clinical worsening of patients. In addition, iron deficiency has a complex mechanism whose pathologic pathway is recently becoming better understood. The discovery of hepcidin has allowed a better clarification of iron metabolism regulation. Furthermore, the ratio of concentration of soluble transferrin receptor to the log of the ferritin level, has been developed as a tool to detect iron deficiency in most situations. Therefore, the problem of this research lies in exploring the cause of iron deficiency that always be sought because the underlying condition can be serious. This review will summarize the current knowledge regarding diagnostic algorithms for iron deficiency anemia. The majority of aetiologies occur in the digestive tract, and justify morphological examination of the gut. First line investigations are upper gastrointestinal endoscopy and colonoscopy, and when negative, the small bowel should be explored; newer tools such as video capsule endoscopy have also been developed. The treatment of iron deficiency is aetiological if possible and iron supplementation whether in oral or in parenteral form