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1.  Periodontal Disease: A Covert Source of Inflammation in Chronic Kidney Disease Patients 
The prevalence of atherosclerotic complications (myocardial infarction, stroke, and sudden death) is increased in end-stage renal disease (ESRD) patients, especially in haemodialysis patients. Increasing evidence suggests that both in general population and in dialysis patients, systemic inflammation plays a dominant role in the pathogenesis of atherosclerotic complications. In general population, also, evidence shows that moderate to severe periodontitis can contribute to inflammatory burden by increasing serum CRP levels and may increase the prevalence of atherosclerotic events. Moreover, the results of some new interventional studies reveal that effective phase I periodontal therapy may decrease serum CRP levels, the most important acute phase protein, monitored as a systemic marker of inflammation and endothelial dysfunction as well, used as an initial predictor of atherosclerotic events. Considering that moderate to severe periodontal diseases have a higher prevalence in CKD and in dialysis population and that periodontal examination is not part of the standard medical assessment, destructive periodontitis might be an ignored source of systemic inflammation in end-stage renal disease patients and may add to the chronic inflammatory status in CKD.
doi:10.1155/2013/515796
PMCID: PMC3690231  PMID: 23840952
2.  Antidiabetic Properties of Germinated Brown Rice: A Systematic Review 
Diet is an important variable in the course of type 2 diabetes, which has generated interest in dietary options like germinated brown rice (GBR) for effective management of the disease among rice-consuming populations. In vitro data and animal experiments show that GBR has potentials as a functional diet for managing this disease, and short-term clinical studies indicate encouraging results. Mechanisms for antidiabetic effects of GBR due to bioactive compounds like γ-aminobutyric acid (GABA), γ-oryzanol, dietary fibre, phenolics, vitamins, acylated steryl β-glucoside, and minerals include antihyperglycemia, low insulin index, antioxidative effect, antithrombosis, antihypertensive effect, hypocholesterolemia, and neuroprotective effects. The evidence so far suggests that there may be enormous benefits for diabetics in rice-consuming populations if white rice is replaced with GBR. However, long-term clinical studies are still needed to verify these findings on antidiabetic effects of GBR. Thus, we present a review on the antidiabetic properties of GBR from relevant preclinical and clinical studies, in order to provide detailed information on this subject for researchers to review the potential of GBR in combating this disease.
doi:10.1155/2012/816501
PMCID: PMC3529503  PMID: 23304216
3.  Nanoscale drug delivery systems and the blood–brain barrier 
The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain’s vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual’s age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.
doi:10.2147/IJN.S52236
PMCID: PMC3926460  PMID: 24550672
apoE; blood–brain barrier; CNS; drug targeting; liposomes; nanoparticles
4.  Exercise Induced Adipokine Changes and the Metabolic Syndrome 
Journal of Diabetes Research  2014;2014:726861.
The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.
doi:10.1155/2014/726861
PMCID: PMC3915640  PMID: 24563869
5.  Type I Interferons: Key Players in Normal Skin and Select Cutaneous Malignancies 
Interferons (IFNs) are a family of naturally existing glycoproteins known for their antiviral activity and their ability to influence the behavior of normal and transformed cell types. Type I Interferons include IFN-α and IFN-β. Currently, IFN-α has numerous approved antitumor applications, including malignant melanoma, in which IFN-α has been shown to increase relapse free survival. Moreover, IFN-α has been successfully used in the intralesional treatment of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In spite of these promising clinical results; however, there exists a paucity of knowledge on the precise anti-tumor action of IFN-α/β at the cellular and molecular levels in cutaneous malignancies such as SCC, BCC, and melanoma. This review summarizes current knowledge on the extent to which Type I IFN influences proliferation, apoptosis, angiogenesis, and immune function in normal skin, cutaneous SCC, BCC, and melanoma.
doi:10.1155/2014/847545
PMCID: PMC3913103  PMID: 24516470
6.  Bio-Mimic Optimization Strategies in Wireless Sensor Networks: A Survey 
Sensors (Basel, Switzerland)  2013;14(1):299-345.
For the past 20 years, many authors have focused their investigations on wireless sensor networks. Various issues related to wireless sensor networks such as energy minimization (optimization), compression schemes, self-organizing network algorithms, routing protocols, quality of service management, security, energy harvesting, etc., have been extensively explored. The three most important issues among these are energy efficiency, quality of service and security management. To get the best possible results in one or more of these issues in wireless sensor networks optimization is necessary. Furthermore, in number of applications (e.g., body area sensor networks, vehicular ad hoc networks) these issues might conflict and require a trade-off amongst them. Due to the high energy consumption and data processing requirements, the use of classical algorithms has historically been disregarded. In this context contemporary researchers started using bio-mimetic strategy-based optimization techniques in the field of wireless sensor networks. These techniques are diverse and involve many different optimization algorithms. As far as we know, most existing works tend to focus only on optimization of one specific issue of the three mentioned above. It is high time that these individual efforts are put into perspective and a more holistic view is taken. In this paper we take a step in that direction by presenting a survey of the literature in the area of wireless sensor network optimization concentrating especially on the three most widely used bio-mimetic algorithms, namely, particle swarm optimization, ant colony optimization and genetic algorithm. In addition, to stimulate new research and development interests in this field, open research issues, challenges and future research directions are highlighted.
doi:10.3390/s140100299
PMCID: PMC3926559  PMID: 24368702
wireless sensor networks; optimization; bio-mimetic algorithms; particle swarm optimization; ant colony optimization; genetic algorithm
7.  Automated Bone Age Assessment: Motivation, Taxonomies, and Challenges 
Bone age assessment (BAA) of unknown people is one of the most important topics in clinical procedure for evaluation of biological maturity of children. BAA is performed usually by comparing an X-ray of left hand wrist with an atlas of known sample bones. Recently, BAA has gained remarkable ground from academia and medicine. Manual methods of BAA are time-consuming and prone to observer variability. This is a motivation for developing automated methods of BAA. However, there is considerable research on the automated assessment, much of which are still in the experimental stage. This survey provides taxonomy of automated BAA approaches and discusses the challenges. Finally, we present suggestions for future research.
doi:10.1155/2013/391626
PMCID: PMC3876824  PMID: 24454534
8.  Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies 
Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.
PMCID: PMC3905635  PMID: 24592582
Blindness; Infections; Malnutrition; Vitamin A; South Asia
9.  Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and Diabetes: A Review 
Insulin resistance is a key factor in metabolic disorders like hyperglycemia and hyperinsulinemia, which are promoted by obesity and may later lead to Type II diabetes mellitus. In recent years, researchers have identified links between insulin resistance and many noncommunicable illnesses other than diabetes. Hence, studying insulin resistance is of particular importance in unravelling the pathways employed by such diseases. In this review, mechanisms involving free fatty acids, adipocytokines such as TNFα and PPARγ and serine kinases like JNK and IKKβ, asserted to be responsible in the development of insulin resistance, will be discussed. Suggested mechanisms for actions in normal and disrupted states were also visualised in several manually constructed diagrams to capture an overall view of the insulin-signalling pathway and its related components. The underlying constituents of medicinal significance found in the Stevia rebaudiana Bertoni plant (among other plants that potentiate antihyperglycemic activities) were explored in further depth. Understanding these factors and their mechanisms may be essential for comprehending the progression of insulin resistance towards the development of diabetes mellitus.
doi:10.1155/2013/718049
PMCID: PMC3845826  PMID: 24324517
10.  A Review of Microsatellite Markers and Their Applications in Rice Breeding Programs to Improve Blast Disease Resistance 
Over the last few decades, the use of molecular markers has played an increasing role in rice breeding and genetics. Of the different types of molecular markers, microsatellites have been utilized most extensively, because they can be readily amplified by PCR and the large amount of allelic variation at each locus. Microsatellites are also known as simple sequence repeats (SSR), and they are typically composed of 1–6 nucleotide repeats. These markers are abundant, distributed throughout the genome and are highly polymorphic compared with other genetic markers, as well as being species-specific and co-dominant. For these reasons, they have become increasingly important genetic markers in rice breeding programs. The evolution of new biotypes of pests and diseases as well as the pressures of climate change pose serious challenges to rice breeders, who would like to increase rice production by introducing resistance to multiple biotic and abiotic stresses. Recent advances in rice genomics have now made it possible to identify and map a number of genes through linkage to existing DNA markers. Among the more noteworthy examples of genes that have been tightly linked to molecular markers in rice are those that confer resistance or tolerance to blast. Therefore, in combination with conventional breeding approaches, marker-assisted selection (MAS) can be used to monitor the presence or lack of these genes in breeding populations. For example, marker-assisted backcross breeding has been used to integrate important genes with significant biological effects into a number of commonly grown rice varieties. The use of cost-effective, finely mapped microsatellite markers and MAS strategies should provide opportunities for breeders to develop high-yield, blast resistance rice cultivars. The aim of this review is to summarize the current knowledge concerning the linkage of microsatellite markers to rice blast resistance genes, as well as to explore the use of MAS in rice breeding programs aimed at improving blast resistance in this species. We also discuss the various advantages, disadvantages and uses of microsatellite markers relative to other molecular marker types.
doi:10.3390/ijms141122499
PMCID: PMC3856076  PMID: 24240810
simple sequence repeats; marker development and application; blast resistance; marker assisted selection; rice breeding
11.  Early intervention in the treatment of rheumatoid arthritis: focus on tocilizumab 
Tocilizumab is a fully humanized monoclonal antibody against interleukin-6 receptors that was approved for the treatment of patients with rheumatoid arthritis (RA). Several lines of evidence, obtained both from conventional disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors, have supported the concept of “window of opportunity” as showing that these therapies consistently work better in early disease as compared to established RA. This review addresses the question of whether a window of opportunity gained with conventional DMARDs and TNF inhibitors can also be achieved with tocilizumab. To this end, data regarding the use of tocilizumab in early RA patients are summarized. Currently available data suggest that the earlier the treatment with tocilizumab, the better the clinical outcome can be, which may have implications for various aspects of RA treatment strategies.
doi:10.2147/TCRM.S35784
PMCID: PMC3810895  PMID: 24179334
rheumatoid arthritis; tocilizumab; early intervention
12.  Renal trauma imaging: Diagnosis and management. A pictorial review 
Polish Journal of Radiology  2013;78(4):27-35.
Summary
Background
The purpose of this review is to illustrate and discuss the spectrum of imaging findings, particularly computed tomography (CT), of blunt and penetrating renal trauma, based on our own materials, according to the American Association for Surgery of Trauma (AAST) renal injury grading scale. The article also indicates the conditions in which interventional radiology procedures can be applied for the management of renal trauma.
Material/Method
Cases for this pictorial review were selected from the imaging material collected at the Radiology Department of Hamad Medical Corporation during a 14-year period from 1999 to 2012. The material includes 176 cases (164 males and 12 females) with confirmed blunt or penetrating renal trauma. Following abdominal trauma, all patients had a CT examination performed on admission to the hospital and/or during hospitalization. The most representative and illustrative cases of renal trauma were reviewed according to CT findings and were categorized according to the AAST grading system.
Discusion
The review describes a spectrum of imaging presentations with special emphasis on the 5 grades of renal injury on a CT according to the AAST scale.
The most representative cases were illustrated and discussed with indications of possible interventional radiology treatment. Two groups of patients not included in the AAST grading system were presented separately: those with preexisting renal abnormalities and those with sustained iatrogenic renal injury.
Conclusions
Proper application of renal trauma grading scale is essential for selecting the patients for conservative treatment, surgery or interventional radiology procedure.
doi:10.12659/PJR.889780
PMCID: PMC3908505  PMID: 24505221
kidney; injury; trauma; computed tomography; ultrasound; embolization
13.  Exercise and the Aging Endothelium 
Journal of Diabetes Research  2013;2013:789607.
The endothelium plays a critical role in the maintenance of cardiovascular health by producing nitric oxide and other vasoactive materials. Aging is associated with a gradual decline in this functional aspect of endothelial regulation of cardiovascular homeostasis. Indeed, age is an independent risk factor for cardiovascular diseases and is in part an important factor in the increased exponential mortality rates from vascular disease such as myocardial infarction and stroke that occurs in the ageing population. There are a number of mechanisms suggested to explain age-related endothelial dysfunction. However, recent scientific studies have advanced the notion of oxidative stress and inflammation as the two major risk factors underlying aging and age-related diseases. Regular physical activity, known to have a favorable effect on cardiovascular health, can also improve the function of the ageing endothelium by modulating oxidative stress and inflammatory processes, as we discuss in this paper.
doi:10.1155/2013/789607
PMCID: PMC3747387  PMID: 23984434
14.  Emerging role of G protein-coupled receptors in microvascular myogenic tone 
Cardiovascular Research  2012;95(2):223-232.
Blood flow autoregulation results from the ability of resistance arteries to reduce or increase their diameters in response to changes in intravascular pressure. The mechanism by which arteries maintain a constant blood flow to organs over a range of pressures relies on this myogenic response, which defines the intrinsic property of the smooth muscle to contract in response to stretch. The resistance to flow created by myogenic tone (MT) prevents tissue damage and allows the maintenance of a constant perfusion, despite fluctuations in arterial pressure. Interventions targeting MT may provide a more rational therapeutic approach in vascular disorders, such as hypertension, vasospasm, chronic heart failure, or diabetes. Despite its early description by Bayliss in 1902, the cellular and molecular mechanisms underlying MT remain poorly understood. We now appreciate that MT requires a complex mechanotransduction converting a physical stimulus (pressure) into a biological response (change in vessel diameter). Although smooth muscle cell depolarization and a rise in intracellular calcium concentration are recognized as cornerstones of the myogenic response, the role of wall strain-induced formation of vasoactive mediators is less well established. The vascular system expresses a large variety of Class 1 G protein-coupled receptors (GPCR) activated by an eclectic range of chemical entities, including peptides, lipids, nucleotides, and amines. These messengers can function in blood vessels as vasoconstrictors. This review focuses on locally generated GPCR agonists and their proposed contributions to MT. Their interplay with pivotal Gq-11 and G12-13 protein signalling is also discussed.
doi:10.1093/cvr/cvs152
PMCID: PMC3888209  PMID: 22637750
Myogenic tone; G protein-coupled receptors; Gq-11; G12-13; Rho; TRP channels
15.  Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss 
Rheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.
doi:10.1155/2013/701305
PMCID: PMC3674653  PMID: 23762095
16.  Developmental dysplasia of the hip in the newborn: A systematic review 
World Journal of Orthopedics  2013;4(2):32-41.
Developmental dysplasia of the hip (DDH) denotes a wide spectrum of conditions ranging from subtle acetabular dysplasia to irreducible hip dislocations. Clinical diagnostic tests complement ultrasound imaging in allowing diagnosis, classification and monitoring of this condition. Classification systems relate to the alpha and beta angles in addition to the dynamic coverage index (DCI). Screening programmes for DDH show considerable geographic variation; certain risk factors have been identified which necessitate ultrasound assessment of the newborn. The treatment of DDH has undergone significant evolution, but the current gold standard is still the Pavlik harness. Duration of Pavlik harness treatment has been reported to range from 3 to 9.3 mo. The beta angle, DCI and the superior/lateral femoral head displacement can be assessed via ultrasound to estimate the likelihood of success. Success rates of between 7% and 99% have been reported when using the harness to treat DDH. Avascular necrosis remains the most devastating complication of harness usage with a reported rate of between 0% and 28%. Alternative non-surgical treatment methods used for DDH include devices proposed by LeDamany, Frejka, Lorenz and Ortolani. The Rosen splint and Wagner stocking have also been used for DDH treatment. Surgical treatment for DDH comprises open reduction alongside a combination of femoral or pelvic osteotomies. Femoral osteotomies are carried out in cases of excessive anteversion or valgus deformity of the femoral neck. The two principal pelvic osteotomies most commonly performed are the Salter osteotomy and Pemberton acetabuloplasty. Serious surgical complications include epiphyseal damage, sciatic nerve damage and femoral neck fracture.
doi:10.5312/wjo.v4.i2.32
PMCID: PMC3631949  PMID: 23610749
Developmental dysplasia of the hip; Congenital; Pavlik harness; Ultrasound screening; Pelvic osteotomy
17.  Potential Mechanisms of Exercise in Gestational Diabetes 
Gestational diabetes mellitus (GDM) is defined as glucose intolerance first diagnosed during pregnancy. This condition shares same array of underlying abnormalities as occurs in diabetes outside of pregnancy, for example, genetic and environmental causes. However, the role of a sedentary lifestyle and/or excess energy intake is more prominent in GDM. Physically active women are less likely to develop GDM and other pregnancy-related diseases. Weight gain in pregnancy causes increased release of adipokines from adipose tissue; many adipokines increase oxidative stress and insulin resistance. Increased intramyocellular lipids also increase cellular oxidative stress with subsequent generation of reactive oxygen species. A well-planned program of exercise is an important component of a healthy lifestyle and, in spite of old myths, is also recommended during pregnancy. This paper briefly reviews the role of adipokines in gestational diabetes and attempts to shed some light on the mechanisms by which exercise can be beneficial as an adjuvant therapy in GDM. In this regard, we discuss the mechanisms by which exercise increases insulin sensitivity, changes adipokine profile levels, and boosts antioxidant mechanisms.
doi:10.1155/2013/285948
PMCID: PMC3649306  PMID: 23691290
18.  Unconscious learning processes: mental integration of verbal and pictorial instructional materials 
SpringerPlus  2013;2:105.
This review aims to provide an insight into human learning processes by examining the role of cognitive and emotional unconscious processing in mentally integrating visual and verbal instructional materials. Reviewed literature shows that conscious mental integration does not happen all the time, nor does it necessarily result in optimal learning. Students of all ages and levels of experience cannot always have conscious awareness, control, and the intention to learn or promptly and continually organize perceptual, cognitive, and emotional processes of learning. This review suggests considering the role of unconscious learning processes to enhance the understanding of how students form or activate mental associations between verbal and pictorial information. The understanding would assist in presenting students with spatially-integrated verbal and pictorial instructional materials as a way of facilitating mental integration and improving teaching and learning performance.
doi:10.1186/2193-1801-2-105
PMCID: PMC3612179  PMID: 23556145
Learning processes; Conscious processes; Unconscious processes; Mental representation; Instructional material; Working memory; Emotion; Motivation
19.  Telepointer technology in telemedicine : a review 
Telepointer is a powerful tool in the telemedicine system that enhances the effectiveness of long-distance communication. Telepointer has been tested in telemedicine, and has potential to a big influence in improving quality of health care, especially in the rural area. A telepointer system works by sending additional information in the form of gesture that can convey more accurate instruction or information. It leads to more effective communication, precise diagnosis, and better decision by means of discussion and consultation between the expert and the junior clinicians. However, there is no review paper yet on the state of the art of the telepointer in telemedicine. This paper is intended to give the readers an overview of recent advancement of telepointer technology as a support tool in telemedicine. There are four most popular modes of telepointer system, namely cursor, hand, laser and sketching pointer. The result shows that telepointer technology has a huge potential for wider acceptance in real life applications, there are needs for more improvement in the real time positioning accuracy. More results from actual test (real patient) need to be reported. We believe that by addressing these two issues, telepointer technology will be embraced widely by researchers and practitioners.
doi:10.1186/1475-925X-12-21
PMCID: PMC3610246  PMID: 23496940
Telepointer; Telemedicine; Cursor pointer; Hand pointer; Laser pointer; Sketching pointer
20.  Role of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth 
The fight against diseases spread by mosquitoes and other insects has enormous environmental, economic and social consequences. Chemical insecticides remain the first line of defence but the control of diseases, especially malaria and dengue fever, is being increasingly undermined by insecticide resistance. Mosquitoes have a large repertoire of P450s (over 100 genes). By pinpointing the key enzymes associated with insecticide resistance we can begin to develop new tools to aid the implementation of control interventions and reduce their environmental impact on Earth. Recent technological advances are helping us to build a functional profile of the P450 determinants of insecticide metabolic resistance in mosquitoes. Alongside, the cross-responses of mosquito P450s to insecticides and pollutants are also being investigated. Such research will provide the means to produce diagnostic tools for early detection of P450s linked to resistance. It will also enable the design of new insecticides with optimized efficacy in different environments.
doi:10.1098/rstb.2012.0429
PMCID: PMC3538419  PMID: 23297352
mosquito; malaria; dengue; pyrethroids; oxidases; detoxification
21.  Epoxy Coenzyme A Thioester Pathways for Degradation of Aromatic Compounds 
Applied and Environmental Microbiology  2012;78(15):5043-5051.
Aromatic compounds (biogenic and anthropogenic) are abundant in the biosphere. Some of them are well-known environmental pollutants. Although the aromatic nucleus is relatively recalcitrant, microorganisms have developed various catabolic routes that enable complete biodegradation of aromatic compounds. The adopted degradation pathways depend on the availability of oxygen. Under oxic conditions, microorganisms utilize oxygen as a cosubstrate to activate and cleave the aromatic ring. In contrast, under anoxic conditions, the aromatic compounds are transformed to coenzyme A (CoA) thioesters followed by energy-consuming reduction of the ring. Eventually, the dearomatized ring is opened via a hydrolytic mechanism. Recently, novel catabolic pathways for the aerobic degradation of aromatic compounds were elucidated that differ significantly from the established catabolic routes. The new pathways were investigated in detail for the aerobic bacterial degradation of benzoate and phenylacetate. In both cases, the pathway is initiated by transforming the substrate to a CoA thioester and all the intermediates are bound by CoA. The subsequent reactions involve epoxidation of the aromatic ring followed by hydrolytic ring cleavage. Here we discuss the novel pathways, with a particular focus on their unique features and occurrence as well as ecological significance.
doi:10.1128/AEM.00633-12
PMCID: PMC3416408  PMID: 22582071
22.  Burns in Tanzania: morbidity and mortality, causes and risk factors: a review 
Burn injuries in low and middle income countries still remain a significant health problem, even though numbers of burn injuries in high income countries have decreased showing that such events are not “accidents” but are usually preventable. WHO states that the vast majority (over 95%) of fire-related burns occur in low and middle income countries. Burn injuries are a major cause of prolonged hospital stays, disfigurement, disability, and death in Africa Region. Evidence shows that prevention strategies can work. However prevention strategies need to be tailored to the specific environment taking into account local risk factors and available resources. An examination of the patterns and causes of burns should allow site specific recommendations for interventions. This literature review, specific to the United Republic of Tanzania, was conducted by researching PubMed, SafetyLit, and African Journals on Line data bases for primary sources using key words plus . Two sets of student data collected as part of Bachelor’s degree final dissertations at Muhimbili University of Health and Allied Sciences were used. In all, twenty two primary sources were found. Risk factors for burn morbidity in Tanzania are: 1/ a young age, especially years 1-3, 2/ home environment, especially around cooking fires, 3/ epilepsy, during seizures, and 4/ perceived inevitability of the incident. It was expected that ground level cooking fires would be found to be a risk factor, but several studies have shown non-significant results about raised cooking fires, types of fuel used, and cooking appliances. Risk factors for burn mortality are: being male, between 20-30 years of age, and being punished for alleged thieving by community mobs. An important factor in reducing burn morbidity, especially in children, is to educate people that burns are preventable in most cases and that most burns occur in the home around cooking fires. Children need to be kept away from fires. Epileptics should be monitored for medication and kept away from cooking fires as well. Community members need to be encouraged to bring wrong doers to the police.
PMCID: PMC3560491  PMID: 23386982
Burn injury; burn mortality; burn morbidity; Africa; Tanzania
23.  Tolerance of anaerobic conditions caused by flooding during germination and early growth in rice (Oryza sativa L.) 
Rice is semi-aquatic, adapted to a wide range of hydrologies, from aerobic soils in uplands to anaerobic and flooded fields in waterlogged lowlands, to even deeply submerged soils in flood-prone areas. Considerable diversity is present in native rice landraces selected by farmers over centuries. Our understanding of the adaptive features of these landraces to native ecosystems has improved considerably over the recent past. In some cases, major genes associated with tolerance have been cloned, such as SUB1A that confers tolerance of complete submergence and SNORKEL genes that control plant elongation to escape deepwater. Modern rice varieties are sensitive to flooding during germination and early growth, a problem commonly encountered in rainfed areas, but few landraces capable of germination under these conditions have recently been identified, enabling research into tolerance mechanisms. Major QTLs were also identified, and are being targeted for molecular breeding and for cloning. Nevertheless, limited progress has been made in identifying regulatory processes for traits that are unique to tolerant genotypes, including faster germination and coleoptile elongation, formation of roots and leaves under hypoxia, ability to catabolize starch into simple sugars for subsequent use in glycolysis and fermentative pathways to generate energy. Here we discuss the state of knowledge on the role of the PDC-ALDH-ACS bypass and the ALDH enzyme as the likely candidates effective in tolerant rice genotypes. Potential involvement of factors such as cytoplasmic pH regulation, phytohormones, reactive oxygen species scavenging and other metabolites is also discussed. Further characterization of contrasting genotypes would help in elucidating the genetic and biochemical regulatory and signaling mechanisms associated with tolerance. This could facilitate breeding rice varieties suitable for direct seeding systems and guide efforts for improving waterlogging tolerance in other crops.
doi:10.3389/fpls.2013.00269
PMCID: PMC3719019  PMID: 23888162
anaerobic germination; alcoholic fermentation; ALDH; pyruvate dehydrogenase bypass; hypoxia; direct seeding; flooding; submergence tolerance
24.  Entonox® inhalation to reduce pain in common diagnostic and therapeutic outpatient urological procedures: a review of the evidence 
INTRODUCTION
Entonox® (50% nitrous oxide and 50% oxygen; BOC Healthcare, Manchester, UK) is an analgesic and anxiolytic agent that is used to successfully reduce pain and anxiety during dental, paediatric and emergency department procedures. In this article we review the application and efficacy of Entonox® in painful local anaesthesia urological procedures by performing a systematic review of the literature.
METHODS
A MEDLINE® search was performed using the terms ‘nitrous oxide’, ‘Entonox’, ‘prostate biopsy’, ‘flexible cystoscopy’ and ‘extracorporeal shock wave lithotripsy’. English language publications of randomised studies were identified and reviewed.
RESULTS
The search yielded five randomised studies that investigated the clinical efficacy of Entonox® as an analgesic for day case urological procedures. Three randomised controlled trials (RCTs) investigated Entonox® in transrectal ultrasonography guided prostate biopsy. All three reported significant reductions in pain score in the Entonox® versus control groups. One RCT reported significant reduction in pain during male flexible cystoscopy in the Entonox® group compared with the control group. One RCT, which examined the use of Entonox® during extracorporeal shock wave lithotripsy, found its use significantly decreased the pain score compared with the control group and this was comparable to intravenous pethidine.
CONCLUSIONS
Evidence from varied adult and paediatric procedures has shown Entonox® to be an effective, safe and patient acceptable form of analgesia. All published studies of its use in urological day case procedures have found it to significantly reduce procedural pain. There is huge potential to use this cheap, safe, effective analgesic in our current practice.
doi:10.1308/003588412X13171221499702
PMCID: PMC3954179  PMID: 22524905
Urology; Analgesia; Pain
25.  Waterlogging Tolerance of Crops: Breeding, Mechanism of Tolerance, Molecular Approaches, and Future Prospects 
BioMed Research International  2012;2013:963525.
Submergence or flood is one of the major harmful abiotic stresses in the low-lying countries and crop losses due to waterlogging are considerably high. Plant breeding techniques, conventional or genetic engineering, might be an effective and economic way of developing crops to grow successfully in waterlogged condition. Marker assisted selection (MAS) is a new and more effective approach which can identify genomic regions of crops under stress, which could not be done previously. The discovery of comprehensive molecular linkage maps enables us to do the pyramiding of desirable traits to improve in submergence tolerance through MAS. However, because of genetic and environmental interaction, too many genes encoding a trait, and using undesirable populations the mapping of QTL was hampered to ensure proper growth and yield under waterlogged conditions Steady advances in the field of genomics and proteomics over the years will be helpful to increase the breeding programs which will help to accomplish a significant progress in the field crop variety development and also improvement in near future. Waterlogging response of soybean and major cereal crops, as rice, wheat, barley, and maize and discovery of QTL related with tolerance of waterlogging, development of resistant variety, and, in addition, future prospects have also been discussed.
doi:10.1155/2013/963525
PMCID: PMC3591200  PMID: 23484164

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