The prestressed near-surface mounted reinforcement (NSMR) using Fiber Reinforced Polymer (FRP) was developed to improve the load bearing capacity of ageing or degraded concrete structures. The NSMR using FRP was the subject of numerous studies of which a mere portion was dedicated to the long-term behavior under fatigue loading. Accordingly, the present study intends to examine the fatigue performance of the NSMR applying the anchoring system developed by Korea Institute of Construction and Building Technology (KICT). To that goal, fatigue test is performed on 6.4 m reinforced concrete beams fabricated with various concrete strengths and developed lengths of the Carbon Fiber Reinforced Polymer (CFRP) tendon. The test results reveal that the difference in the concrete strength and in the developed length of the CFRP tendon has insignificant effect on the strengthening performance. It is concluded that the accumulation of fatigue loading, the concrete strength and the developed length of the tendon will not affect significantly the strengthening performance given that sufficient strengthening is secured. Prestressed concrete (PSC) eases the control of the deflection and cracks in concrete structures by reducing the tensile stress through the introduction of a compressive force by means of tendons embedded in the tension zone of the structure. Ageing bridges may experience loss of their function and performance that should be recovered or improved by strengthening the structure. The strengthening of PSC girder bridge is achieved by enlarging the girder, external prestressing, carbon fiber bonding or steel plate bonding. The external bonding reinforcement (EBR) methods were applied to improve the performance by bonding the reinforcement on the tensile zone of the concrete member using an adhesive. This reinforcement took first the form of a plate made of steel that started to be replaced by Fiber Reinforced Polymer (FRP) since the mid of 1980s.The near-surface mounted reinforcement (NSMR) resembles the above mentioned external bonding reinforcement but embeds the FRP plate or bar in a groove cut with a definite depth in the concrete surface. De Lorenzis et al.  reportedIn view of the efficiency of FRP, both NSMR and EBR cannot exploit fully the maximum performance of FRP due to the premature occurrence of debonding at the reinforcement-concrete interface. As passive strengthening methods, their effect appears only under the application of additional live loads without clear improvement of the serviceability in term of cracking and deflection recovery. Accordingly, numerous researchers attempted the prestressed NSMR achieving the synergy of both NSMR and prestressing . For theIn particular, FRP is checked to apply in many sites because of strong points such as high strength, light weight, chemical resistance and need to secure reliability through real size test because of low applications, low construction cases, problems with design criteria ,5,6,7,8.Despite of the numerous studies related to NSMR using FRP, a very few of them studied the long-term behavior under fatigue loading . The repAccordingly, the present study intends to examine the fatigue behavior of the prestressed NSMR applying the anchoring device developed by KICT. The cumulated effect of the fatigue load on the strengthening performance is examined by means of a series of fatigue tests performed on 6.4 m reinforced concrete beams fabricated with various concrete strengths and developed lengths of the Carbon Fiber Reinforced Polymer (CFRP) tendon. The fatigue tests were conducted in two stages. The first stage applied 2 million loading cycles and the second stage applied static loading until failure of the specimens to measure the residual strength after the accumulation of fatigue.This study intends to examine the fatigue performance of the prestressed NSMR. To that goal, the specimens are designated as shown in As shown in The structural tests were executed in two stages. The first stage applied 2 million loading cycles and the second stage applied static loading until failure of the specimens to measure the residual strength after the accumulation of fatigue.y and 0.7fy, where fy is the steel yield stress. Accordingly, the present study adopted fatigue load ranging between 60 kN and 100 kN. In addition, the loading rate was set to 2.0 to 3.0 Hz. The fatigue test conducted using a dynamic actuator with capacity of 1000 kN to apply 2 million loading cycles. Static load of 100 kN was applied after 1, 1000, 5000, 10,000, 100,000, 1 million and 2 million cycles to measure the deflection, strain and cracks and examine the eventual progress of damage according to the accumulation of fatigue.The size of the fatigue load was determined with reference to the stress of the tensile member using the calculation method suggested by ACI, AASHTO and CSA ,17,18,19Static loading was performed by 4-point loading on all the specimens using static actuators  with capacity of 2000 kN to measure the deflection and strain according to the gradual increase of the load until failure. As shown in −6 and 6500 × 10−6 during the tensioning work.The tendon used in the fabrication of NSM specimens is a CFRP rod with diameter of 10 mm and its mechanical characteristics are arranged in The residual strength can be measured using the static loading results listed in The ductility of the specimens with respect to the concrete strength is shown in This study examined the strengthening performance of the prestressed NSMR according to the accumulation of fatigue loading. To that goal, fatigue test was performed on 6.4 m reinforced concrete beams fabricated with various concrete strengths and developed lengths of the CFRP tendon. The fatigue tests were conducted in two stages. The first stage applied 2 million loading cycles and the second stage applied static loading until failure of the specimens to measure the residual strength after the accumulation of fatigue. The following conclusions can be derived.The observation of the fatigue behavior with respect to the concrete strength revealed that the deflection exhibited the largest increase rate below 1000 cycles, increased gradually until 100,000 cycles and stabilized until 2 million cycles. The strain measured at the center of the CFRP tendon showed also similar tendency according to the accumulation of fatigue cycles. Moreover, the same tendency was also observed for the fatigue behavior according to the developed length of the tendon.The analysis of the strain developed during tensioning and the strain caused by the accumulation of fatigue revealed that all the specimens presented similar behavior and strain at the rupture of the tendon. In addition, the tendon could reach its tensile performance before rupture under the loading applied after the compressive failure of concrete. This indicated that the accumulation of the fatigue load had poor effect on the loss of the performance like the tension force of the CFRP tendon.The results of the static loading test with respect to the concrete strength showed that the accumulation of the fatigue load did not provoke damage nor performance loss of the prestressed NSMR specimens. Moreover, the test results of the specimens with concrete strengths of 30 MPa and 40 MPa appeared to be practically identical to those of a previous experiment without fatigue load accumulation. This indicated that the strengthening performance of the prestressed NSMR is insensitive to the accumulation of fatigue loading and the concrete strength given that sufficient strengthening is secured.The insignificance of the change in the performance provided by the specimens with developed lengths of 67%, 80% and 93% of the CFRP tendon demonstrated that the developed length of the tendon has practically no effect on the strengthening performance given that appropriate tensioning has been secured. However, an appropriate and sufficient developed length should be secured to prevent the anchor be installed outside the effective depth d in which case shear failure would occur due to the increase of inclined cracks.The analysis of the ductility with respect to the concrete strength and the developed length of the tendon provided results complying with those of previous research. All the specimens exhibited nearly the same ductility according to the concrete strength and the ductility appeared to increase with longer developed length of the tendon. Accordingly, adopting longer developed length of the tendon was recommended for securing stable ductile behavior.


Catechols are widely found in nature taking part in a variety of biological functions, ranging from the aqueous adhesion of marine organisms to the storage of transition metal ions. This has been achieved thanks to their (i) rich redox chemistry and ability to cross-link through complex and irreversible oxidation mechanisms, (ii) excellent chelating properties, and (iii) the diverse modes of interaction of the vicinal hydroxyl groups with all kinds of surfaces of remarkably different chemical and physical nature . TherefoThis Special Issue collects contributions from different laboratories working on both basic research and applications of bioinspired catechol systems presented by cutting edge specialists in this growing field. Taking advantage of its open access publication, this collection of papers, influenced by biomimetic approaches, will bring about new avenues for new research and innovative solutions in biomedicine and technology. Main topics addressed in the field of basic catechol chemistry include (i) a computational investigation by Barone et al.  of noncoIntegrating more than replacing the many excellent reviews, the present collection will provide the reader with a concise panorama of the status quo and perspectives in the increasingly expanding field of basic and applied research on bioinspired catechol systems. It is clear that the interest for catechol-based materials is experiencing a steady burst, perfectly represented by polydopamine . Several patents based on bioinspired catechol systems and different products are already commercialized and available the market. We believe that this special issue may fulfill an important function in promoting biomimetic catechol chemistry for an increasing range of applications.


Cancer cells are mainly dependent on glycolysis for their growth and survival. Dietary carbohydrates play a critical role in the growth and proliferation of cancer and a low-carbohydrate diet may help slow down the growth of tumours. However, the exact mechanisms behind this effect are unclear. This review study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene in the association between dietary carbohydrates and cancer. This study was carried out using keywords such as polymorphism and/or cancer and/or dietary carbohydrate and/or FTO gene. PubMed and Science Direct databases were used to collect all related articles published from 1990 to 2018.Recent studies showed that the level of FTO gene expression in cancer cells is dramatically increased and may play a role in the growth of these cells through the regulation of the cellular metabolic pathways, including the phosphoinositide 3-kinases/protein kinaseB (PI3K/AKT) signaling pathway. Dietary carbohydrate may influence the FTO gene expression by eliminating the inhibitory effect of adenosine monophosphate-activated protein kinase (AMPK) on the FTO gene expression. This review summarised what has been recently discovered about the effects of dietary carbohydrate on cancer cells and tried to determine the mediating role of the FTO gene in these effects. Recent studies suggested that healthy diet can play a major role in the prevention of cell malignancy, apoptosis of cancer cells and reduced tumour size –6. For eUntil recently not a lot has been found about the existing mechanisms by which dietary components affect the formation of cancer cells. The results of most studies suggest that some part of this effect may be due to the effects of dietary intake on the expression of some of the genes involved in the cell metabolism and division. The relation between gene variations and risk of cancer is well documented , 14. CanPubMed, PsycInfo and the Cochrane databases were searched to identify articles published in relevant fields. Appropriate keywords including carbohydrate, diet, FTO expression, FTO genotype, cancer, cell and metabolism  were used to collect the papers. All articles published in English from June 1990 to July 2018 were studied. Of the total 180 articles, 109 articles were excluded because they failed to address the role of the FTO gene in breast cancer and/ or obesity and 63 articles for lack of sufficient information on the mechanism of the effects of FTO gene on the breast cancer and obesity. Finally, eight articles were included. Of these studies, five studies were on the relationship between dietary carbohydrate and cancer, and five were related to the molecular mechanisms of dietary carbohydrate on FTO gene.Unlike normal cells, most malignant cells are dependent on the availability of sugar in the blood constantly for energy supply and to meet demands for their metabolism. These cells are unable to metabolise fatty acids and ketone bodies due to mitochondrial dysfunction. Previous studies reported the benefits of a low-carbohydrate diets on human body weight and general health . Ho et aMoulton et al. evaluated the effects of two different ratios of carbohydrate and protein in the early development of breast tissue carcinogenesis in an animal study . After tP < 0.05). The risk of breast cancer was associated with the consumption of carbohydrates with higher GIs (P for trend < 0.001).Sieri et al. conducted a cohort study and examined whether the glycemic load (GL) and the glycemic index (GI) are associated with the risk of breast cancer in women . A totalThe association between hyperglycemia and cancer risk was examined in 33,293 women and 31,304 men in northern Sweden . The resTan-Shalaby et al. examined the impact of the modified Atkins diet on cancer development. A total of 17 patients with advanced cancer, who had not undergone chemotherapy, were enrolled for the study . They reMoreover, the effect of ketogenic diet as a well-known low-carbohydrate diet on tumour growth was investigated and approved in several studies –39. ReduFTO gene is known for its role in obesity and diabetes . The assRecent studies on the relationship between the macronutrients intake and the level of FTO gene expression in the hypothalamus identified that dietary carbohydrates can affect the FTO gene expression level. However, the results in this area are contradictory and in some studies carbohydrate intake up-regulated the FTO gene expression, while in other studies it suppressed FTO gene expression . It is pThe possible mechanism behind the effect of the FTO gene on cancer risk has been studied recently. The FTO gene may act as a mediator for the phosphorylation of serine in location 473 of the AKT protein and its activation has a key role in the proliferation and differentiation of cells . It was Cancer cells are dependent on glycolysis for their growth and proliferation. Dietary carbohydrate is a significant factor and the association between blood glucose levels and cancer is well documented. But the exact mechanisms of this relationship remain unclear. Recent studies showed that dietary macronutrients may have an impact on cancer by altering the expression level of the genes associated with the metabolism of cancer cells (such as FTO). If we could improve the expression levels of the genes involved in growth, metabolism, and the function of cancer cells through changing our diet, we can hope to find a nutritionally applicable solution for the treatment and control of cancer in the future. Further research on the exact mechanism of the influence of FTO gene on the growth and proliferation of cancer cells may clarify the importance of this issue and the possibility of therapeutic use of dietary components in cancer.


The aim of this paper is to study experimentally the effect of marble powder and green sand as partial substitute for fine aggregate on the strength and durability of M40 grade concrete. The use of metakaolin as a pozzolanic admixture by using as binder replacement is also studied to assess the properties with respect to fresh and hardened state. Several formulations were prepared with constant water-binder ratio 0.4 and varying percentages of marble powder and green sand. The results indicated that the properties of concrete were much enhanced by extent incorporation of marble powder and green sand as fine aggregate and metakaolin for cement when compared to normal concrete. The microscopic studies also confirmed the viability of using green sand and marble powder as fine aggregates. Recent decades have witnessed the rapid demand for river sand as fine aggregate which is one of the most essential ingredients in the production of concrete . Modern Previous research works have previously investigated the effects of using foundry sand ,18,19 anHence the value of the present study lies on the fulfilling of the practical design requirements such as strength and durability of concrete mixes manufactured using replacements of fine aggregate by both marble powder and green sand. In addition the synergistic effect of marble powder and green sand together with a pozzolanic admixture (metakaolin) on the concrete properties addressed in detail thereby not only saving the exhaustion of natural aggregates but also reducing the efficiency of using industrial wastes as fine aggregate replacements.The main objective of this research is to investigate the feasibility of using marble powder and green sand as fine aggregate in concrete production. The effect of metakaolin replacement in cement is also investigated. The mechanical properties of the hardened concrete made of green sand and marble powder were studied at various ages. The microstructure and hydration products were also investigated to assess the impact of using green sand on marble powder as partial replacement for fine aggregate.Ordinary Portland cement (OPC) 43 grade conforming to Indian standard BIS 8112-1989  is used The concrete mixes were manufactured in the proportion of 1:2.08:3.57 corresponding for Binder: Fine aggregate: Coarse aggregate, as per BIS 10262-2009  referrinThe fresh state properties of the concrete mixes were determined using slump test conforming to IS1199-1959 and the hardened state properties were analyzed by conducting compressive strength on 150 mm concrete cube specimens, flexural strength test on 100 mm × 100 mm × 500 mm prism specimens and split tensile strength test on 150 mm diameter × 300 mm height cylindrical specimens at several ages conforming to BIS516-1959 . Impact The workability of the concrete mixesis conducted as shown in The flexural strength development of the concrete mixes at various ages of 14, 28, 56 and 90 days are shown in The splitting tensile strength test  setup on cylinder specimen is shown in The impact strength apparatus and specimens at failure is shown in The water absorption values of the concrete mixes with and without the fine aggregate replacement are provided in The XRD studies  done to The morphology of the concrete mixes as obtained from the Scanning Electron Microscope Equipment  and resu2 values are also shown in With the help of the experimental data, graphs were plotted between split tensile strength and flexural strength of concrete mixes at various ages. The linear relationship between split tensile strength and flexural strength is obtained through the predicted equation and their corresponding regression coefficient RThis study mainly aims at utilizing marble powder and green sand as partial substitute for fine aggregate and metakaolin for cement. From the experimental results obtained the following conclusions can be withdrawn.The workability of the concrete was very much influenced due to the addition of green sand and marble powder. The relative decrease in the workability was achieved due to the increase in amount of water required by the aggregates and the normal sand. Moreover decrease in the workability may also be caused due agglomeration and compounding effect exhibited by the metakaolin particles.An increase in the compressive strength of all the mixes occurred at various ages. The filler effect and the pozzolanic reaction of metakaolin with calcium hydrate also contributed to the increase in the strength of the concrete. This enables the use of marble and green sand as construction materials by minimizing the utilization of the river sand as fine aggregate and the reduced production of cement by replacing with metakaolin.The flexural strength of the concrete mixes was enhanced due to the fine aggregate replacement and metakaolin replacement. The use of marble powder and green sand within 15% was found to be optimum to increase the flexural strength of the concrete when used in combination with metakaolin as cement substitute.The splitting tensile of the concrete was also improved up to 15% beyond which the decrease in the reduction in the split tensile strength was observed. This shows that using 15% green sand and marble powder was found to be adequate as far as the strength parameters are concerned.The impact strength of the concrete was much enhanced for the concrete containing metakaolin as cement replacement and marble powder and green sand as fine aggregate replacement that proved to be efficient in absorbing the impact energy acting on the concrete.The use of marble powder and green sand as fine aggregate replacement created a favorable effect on reducing the porosity of the concrete. The reduction in the water absorption caused a decrease in the voids and is responsible for the improvement in the mechanical strength and impermeability properties of concrete. The addition of metakaolin caused stronger bonding of the cement paste and strengthens the adherence of the cement and the aggregates by the formation of CSH gel which is also responsible for the reduction in the porosity values.The X-ray diffraction studies also showed the minimal presence of calcium hydroxide that confirmed the consumption of calcium hydroxide in the hydration reaction which is responsible for the dense microstructure of the concrete by the addition of CSH gel. The reduced calcium hydroxide peaks inherits the formation of CSH gel that is responsible for the improved strength and durability of the concrete.The SEM images of the concrete also showed reduction in the voids in the concrete and the well distributed CSH gel that effectively bonded the fine aggregates with the cement matrix. The SEM micrographs are coherent for the obtained mechanical properties and the morphology of concrete mix and shows that the marble powder and green sand in combination with metakaolin can be used for making good quality concrete with higher strength.2 values indicate the conformity of the interrelationship between the variables.The prediction models obtained from the experimental data showed the relationship between various strength parameters of the concrete and the obtained RThe final conclusion can be withdrawn that when green sand and marble powder are used as fine aggregate replacement and metakaolin as partial substitute for cement the concrete mixture with high strength properties compared to that of the normal concrete can be obtained. The incorporation of these powdered fine aggregates instead of normal river sand proves to be beneficial to obtain concrete with higher strength. Moreover this type of concrete produced is also environment friendly and economically feasible by large utilization of the waste marble powder and green sand.


Drosophila (25%), rodents (65%), and humans (90%) suggest that increasing complexity of the brain is accompanied by growing numbers of glial cells . The latter has recently emerged as an excellent model of the oscillatory network , as the normal diurnal oscillation of the key neurotransmitters like glutamate, GABA, dopamine and ATP adenosine, which underlie the circadian homeostasis, can be disrupted by excessive alcohol consumption. Considering the regulation of purinergic signaling and circadian oscillations by both neurons and astrocytes, as well as their interactions, they review the diverse mechanisms by which purinergic malfunction may contribute to circadian disruption or alcohol abuse.Another in-depth review, given by Duhart et al. show effects of human glioma cells  in the hypothalamic region on the circadian behavioral output in mice. Their report might be of relevance for glioma diagnosis as it provides the foundation work for future research aimed to understand the pathological consequences of astrocytic dysfunction in the circadian time-keeping, which have recently come to light as a major player in SCN , including the neuron-glia interactions that may impact the processing in the cerebellum. The authors show possible relation between neurons expressing the clock protein PERIOD  and Bergmann glia, which are demonstrated to express melatonin receptors.The research by Drosophila melanogaster . Górska-Andrzejak et al. bring attention to the glial cells located in the output of the circadian pacemaker in the neuropil of optic medulla and infer the possibility of interactions between Pigment Dispersing Factor (PDF) releasing clock neurons and the medulla glia expressing PDF receptors. Further characterization of the distal medulla glia by Krzeptowski et al. reveals two populations of cells that differ with respect to expression level of PER and the glial marker REPO. Interestingly, the authors have observed that the elevated levels of PER are characteristic for the ensheathing glia, but not the astrocyte-like ones , even though the latter are well-known to influence the circadian rhythms of Drosophila locomotor activity . Long and Giebultowicz additionally demonstrate that the rhythmic expression of PER dampens with advanced age in most of the glial subtypes. Thus, their study bring into focus the glia-related circadian changes that may significantly contribute to the loss of homeostasis in the aging brain.Functioning of both neuronal and glial oscillators is the foundation of the circadian plasticity of the visual system of Drosophila  emphasizes the important role of neuron-glial interactions in the structural plasticity of the circadian network. The article by Ceriani group  reveals the involvement of glial cells in the structural remodeling of neuronal pacemakers . It explains how the dynamic morphological changes of dense astrocytic meshwork might modulate the output activity of the neuronal oscillators to produce dimorphic behavior of females and males.Another study on Drosophila  corroborates the hypothesis that the circadian clock may also adopt post-transcriptional mechanisms regulating transposable elements (TEs) in order to ensure proper rhythmicity. Its authors argue that BELLE, a conserved DEAD-box RNA helicase that acts as an important piRNA-mediated regulator of TEs, is a putative clock component present in both the clock neurons and the glial cells of Drosophila brain  and influences circadian rhythmicity of Drosophila locomotor activity.Eventually, the last paper on All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Cytomegaloviruses (CMV) reorganize membranous system of the cell in order to develop a virion assembly compartment (VAC). The development starts in the early (E) phase of infection with the reorganization of the endosomal system and the Golgi and proceeds to the late phase until newly formed virions are assembled and released. The events in the E phase involve reorganization of the endosomal recycling compartment (ERC) in a series of cellular alterations that are mostly unknown. In this minireview, we discuss the effect of murine CMV infection on Rab proteins, master regulators of membrane trafficking pathways, which in the cascades with their GEFs and GAPs organize the flow of membranes through the ERC. Immunofluorescence analyzes of murine CMV infected cells suggest perturbations of Rab cascades that operate at the ERC. Analysis of cellular transcriptome in the course of both murine and human CMV infection demonstrates the alteration in expression of cellular genes whose products are known to build Rab cascades. These alterations, however, cannot explain perturbations of the ERC. Cellular proteome data available for human CMV infected cells suggests the potential role of RabGAP downregulation at the end of the E phase. However, the very early onset of the ERC alterations in the course of MCMV infection indicates that CMVs exploit Rab cascades to reorganize the ERC, which represents the earliest step in the sequential establishment of the cVAC. The seqThe development of cVAC is initiated immediately upon infection. It involves reorganization of the Golgi and the endosomal system in a proper sequence of required membranous structures around the cell center . The reoThe ERC represents one branch in the endosomal maturation and highly dynamic router of membrane flow that undergoes through a series of transitions regulated by the cascade recruitment of Rab proteins and their effectors . Thus, iA study in MCMV infected cells demonstrated that the endosomal rearrangement and dislocation of the Golgi are initiated already at 3–5 hpi . AnalysiMultiple studies on the organization of the cVAC during HCMV infection suggested that CMV infection reorganize REs into a perinuclear cluster that form the core of the cVAC . These sThe ERC represents a complex of heterogeneous subsets and functionally linked populations of REs that include relatively large perinuclear structures, tubular REs and a number of small transport intermediates . SeveralRab GTPases are master regulators of membrane traffic that control distinct steps in membrane flow by recruiting diverse effector proteins rev. by . InactivThe membrane flow into the ERC involve a transition of Rab5-positive EE/SEs to Rab11-REs and Arf6/Rab8-REs  and the The sequences of regulatory networks that control membrane flow through the ERC in uninfected cells as well as the sequence of alterations that lead to the final establishment of the cVAC in CMV infected cells are far from being completely understood. A small piece of evidence indicates that alteration of Rab recruitment is exploited by CMVs as an integral part of a complex mechanism that leads to the development of the cVAC.In uninfected fibroblasts, Rab proteins and their effectors are mainly cytosolic, and only those that decorate major endosomal organelles display distinguishable structures visible by conventional confocal microscopy Figure . Many trC. elegans epithelial cells Rab5 recruits an effector which promote interaction of Rab10 GEF with Rab10  when the cut-off value was adjusted to p < 0.1, whereas none of them was significant at the cut-off p < 0.05. Even upregulation of TBC1D30 observed at 18 hpi is insignificant at p < 0.05, because of the very low level of transcript in uninfected cells. However, these alterations, as well as most of the alterations observed in the previous study (One approach used by CMVs could be manipulation with the amount of proteins that shape membranous organelles, either by up- and down-regulation of transcription, translation or protein degradation. Transcriptome analysis of MCMV infected cells at 3 and 18 hpi Figure  demonstrus study , correlaus study .Given that most of altered Rab protein genes are upregulated, downregulation of Rab gene expression is not a mechanism that could explain membrane reshaping in the E-phase of infection. On the contrary, upregulation of some genes encoding GEFs and GAPs may correlate with the low recruitment of Rab13, Rab22a, and Rab35 and could explain some of the alterations observed in the E phase of MCMV infection. Thus, manipulation with the expression level of regulatory proteins could be a potential target of CMVs. This conclusion may be supported by observations from temporal quantitative proteome analysis in HCMV infected cells at the end of E phase , which dAltogether, immunofluorescence, proteome, and transcriptome analysis suggest that the main alteration of CMVs in the E phase of infection could be the recruitment of components of Rab cascades and that targeting of RabGAP proteins could be a mechanism exploited by CMVs in order to reshape membranous system of the cell.in vivo under physiological conditions (Analysis of the perinuclear endosomal aggregate that is established at the end of the E phase of CMV infection indicates that CMVs exploit Rab cascades to take over the control at the ERC trafficking routes and thereby initiate the establishment of the cVAC. Although a plethora of data in the last decade provided clues about Rab cascades, many components remain unidentified and functional networks that construct the cascades poorly characterized nditions . The anaPL conceived and coordinated the study, carried out image analysis, conceived figure presentation, and drafted the manuscript. HL and GZ coordinated the study, established immunofluorescence protocols, and carried out recycling analysis. LK, VP, NV, and SiJ carried out immunofluorescence and imaging studies. BL and StJ performed the transcriptome analysis. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


How to cite this article: Ali U. The Burden of Acute Kidney Injury in Indian Pediatric Intensive Care Units. Indian J Crit Care Med 2019;23(8):349. Acute kidney injury is a major game changer when it occurs in the setting of critical illness in children. It increases the risk of death independent of the severity of illness. In addition, one third of the AKI survivors carry the risk of future progression to chronic kidney disease. Zero deaths due to AKI by the year 2025 (0 by 25) is the ambitious global vision of the International Society of Nephrology. However, in many countries of the world including India we have not yet reached the starting post of understanding the total burden of AKI in children.The burden of AKI could be higher in Indian children when compared to developed nations due to a higher incidence of infectious illnesses, wider use of both allopathic and non-allopathic nephrotoxic medications and the probability of having a higher subset of children born with lower nephron numbers secondary to premature births or intrauterine growth retardation that make them more vulnerable to AKI during critical illness.The need of the hour is to have national or regional AKI prevalence studies to understand the extent of the problem and the regional differences in the predisposing conditions. Comparison of data is hampered by the prevalence of different methodologies for measuring serum creatinine and the use of different criteria for the diagnosis of AKIAs creatinine levels are physiologically low in infants and children due to lower muscle mass, it is important that serum creatinine is measured by enzymatic methods that measure true creatinine and avoid interference by other non-creatinine chromogens. Laboratories should validate their methodology by referencing to isotope dilution mass spectrometry (IDMS). This is already being done by some laboratories, but the standards need to become universal.Several diagnostic criteria are currently used in pediatrics for defining AKI. The most common ones are the AKIN, the p RIFLE and the KDIGO criteria. The KDIGO does not need GFR calculations. It allows the use of either relative or absolute increases in serum creatinine and can be used for both adults and children. The uniform adoption of KDIGO criteria for defining AKI will allow valid comparison of data from different institutions.1 Until we are able to get the big picture, these snaphots from different parts of the country contribute important jigsaw pieces to complete the larger puzzle of the etiology and outcome of AKI in critically ill Indian children.There have been several small, single centre reports from different parts of India describing the prevalence and outcome of AKI in children. This issue carries an interesting snapshot from a PICU in Eastern UP where 50% of the cohort had viral encephalitis as the underlying illness.


Cancer is an important public issue around the world. Among types of cancer, lung and colorectal cancer are the most common in men while breast and cervical cancer are the most common in women. Detection of early stage cancer via screening can significantly reduce the mortality and prolong life. Although cancer prevention and control has been served as the national priority, individual’s utilization of cancer screening services is low due to limited knowledge of cancer screening and ineffective patient-provider commutation, especially in minority populations. In this symposium, we will examine three scenarios that highlight the challenges of cancer screenings in minority populations. First, we will share the results from a mixed method study that investigate the knowledge and attitudes towards Low Dose Computed Tomography lung cancer (LDCT) screening and assess the smoking cessation needs for African Americans who receive LDCT screening in an effort to reduce the health burden of lung cancer. The next study will discuss how the characteristics of older Chinese adults from the United States and Taiwan are associated cancer screening communication with physicians . Lastly, we will share the results from a cross-sectional study that analyzed 10 years data of National Health Interview Survey to examine the difference in LDCT screening eligibility among Asian American  smokers. The discussant will summarize with an overview of the topic, and comment on the disparities of cancer screening in older minority populations.


As it approaches a decade since Frontiers in Endocrinology was launched, the Chief Editors have commissioned a series of articles to reflect the continuing dynamic evolution of the science at the Frontiers of Endocrinology. These articles highlight recent breakthroughs or advances, new technologies, or challenges in the field of endocrinology. As with any dynamic field the frontiers are ever changing and these articles exemplify some of the recent developments together with some of the new questions and challenges for the future. The articles cover many different areas of endocrinology including issues involved in some of the biggest health challenges facing today's society such as stress, obesity, reproduction, cancer, and aging.Carpentier et al. review the challenges that have been encountered in the subsequent decade of research into BAT in humans. They address key questions such as the true extent of BAT in humans; whether the original imaging techniques underestimated the total mass of BAT and to what extent “beiging” of white adipocytes, with the induction of UCP1, can occur in humans. These are critical questions that could establish whether beige and brown adipocytes in humans could be an effective target to bring about changes in energy expenditure that are of therapeutic benefit.The greatest challenge to health provision in virtually every country across the globe is obesity; the scale of the epidemic threatens to outstrip resources in even the richest of societies . The burStengel and Taché.In addition to the advances in our understanding of energy expenditure there have been major progress in our knowledge of the endocrine controls of energy intake via hormones that control hunger and satiety and hence determine food intake . Life wiMa and Vella and Laferrère and Pattou have reviewed the potential new insights into metabolic endocrinology that these observations may provide. The clues from the anatomical differences between the different surgical procedures are reviewed by Ma and Vella. They describe how such anatomical distinctions can provide insights into the various hormonal pathways and in particular the interactions between regions of the gut and the pancreas. They also touch on other interesting, less well-appreciated effects, such as how the surgery and endocrine changes can alter the perception of sweet-taste and hence alter calorie intake. The most studied surgical intervention is Roux-enY gastric bypass and Laferrère and Pattou review these studies with an emphasis on what these studies have revealed regarding the gut endocrine system. They highlight the many new questions raised in relation to the role of satiety hormones, incretins, and bile acids. Our concepts of bile acids have been transformed from being regarded as just soaps that aid in the uptake of dietary fats to being a previously unappreciated complex endocrine system.The management of obesity remains a huge health challenge. Numerous dietary and lifestyle changes have been proposed and all have achieved modest weight loss that is invariably soon regained. The pharmaceutical industry has invested considerably in developing medications to treat the huge potential market with a long trail of failures with many concerns regarding adverse effects and long-term safety . While nJacobsen et al. provide an overview of the development of strategies to prevent this and avoid the need for lifelong treatment. In order to prevent type I diabetes it is important to understand the natural history of the development of the autoimmunity that results in pancreatic beta cell destruction and the onset of type 1 diabetes. The challenges of studying populations prior to the disease onset and how this is being addressed around the world are described. These studies have informed the various trials for primary prevention in subjects at risk and secondary prevention in those already exhibiting evidence of autoimmunity. To date these studies have had limited success and new and future strategies are discussed.While the obesity epidemic has added to the focus on type 2 diabetes it has also become clear that there has been a 3% annual increase in the incidence of type 1 diabetes and Eiden and Jiang review how new observations of adrenal chromaffin cells have contributed to our understanding of how we coordinate response to stress. The adrenal medulla has conventionally been considered the source of epinephrine to coordinate the cardiovascular, neuronal, and metabolic responses to stress. In this overview they describe recent observations of sympathetic nervous system regulation of chromaffin cell function and its secretion of not just epinephrine but also a rich cocktail of novel bioactive peptides. This new evidence is synthesized into a broader understanding of how metabolic, cardiovascular, and inflammatory responses are integrated. They also highlight interesting new questions that have arisen from this work; such as whether the sensory nervous system and immune/inflammatory systems are looped-in together via the adrenal medullary stress response and what are the broader endocrine functions of the many bioactive peptides secreted from the chromaffin cells.In a fine exposition of how studying one component can help inform on how inter-connected the endocrine system has become; Franks and Hardy. They focus on recent advances regarding the role of androgens in the development of polycystic ovary syndrome (PCOS), which remains the most common endocrine disorder in women of reproductive age.Population control and reproductive health remain major health issues globally. The important role of androgens both in ovarian follicle selection to ensure mono-follicular ovulation in women and in the normal cyclical secretion of estrodiol is reviewed by Kristensen and Andersen discuss the many issues and challenges with extending this technique to more broader applications. Using this technique to restore fertility to women with anovulatory PCOS is discussed. The many issues surrounding the more controversial application of the technique to enable healthy women to postpone childbearing into their more advanced years is also addressed.One of the recent advances in techniques for maintaining fertility in women has been ovarian tissue cryopreservation (OTC) and transplantation. Originally developed to assist prepubertal girls and young women faced with reductions in the ovarian reserve due to pathologies, such as malignancies, or due to aggressive therapies that damage the ovary, Karras et al.. The ongoing questions regarding the role of VDBP in important clinical issues such as preeclampsia, preterm birth, and gestational diabetes are discussed.During pregnancy a woman's endocrine system kicks into overdrive with most hormones adapting to enable the mother to meet the additional metabolic demands and to provide an optimal environment in which the fetus can develop. Among all of these hormonal changes vitamin D plays an under-appreciated role both in ensuring adequate calcium availability for fetal bone development and in enhancing maternal tolerance to the presence of paternal and fetal alloantigens. Recent advances in our understanding of the part played by vitamin D-binding protein (VDBP) in facilitating these roles is reviewed by Moody et al.. The development of agents that target receptors for bombesin, neurotensin, vasoactive intestinal peptide, and somatostatin are described in relation to the detection and treatment of both endocrine and non-endocrine cancers.Neuropeptide G protein-coupled receptors (GPCRs) are over-expressed in many different cancers; not just the relatively rare neuroendocrine tumors but also in some common cancers such as small cell lung cancers. The potential targeting of specific GPCRs for the development of novel cancer therapies is reviewed by Alrezk et al.. These are challenging cancers to treat and although most can be cured by surgery on rare occasions they metastasize and for these there are currently no approved treatments. The potential of systemic therapies, that have largely been developed to treat other cancers, is reviewed by Jimenez. Different strategies that have been designed to target each of the accepted “hallmarks” are discussed in relation to their application to treating PCCs and PGLs. These include different strategies to inhibit angiogenesis, cell proliferation, invasion, and metastasis, to enhance the induction of cell death and the recently developed immunotherapies.Recent advances in the genetics, biochemical characterization, and imaging of pheochromocytomas (PCCs) and paragangliomas (PGLs) are reviewed by Sahli et al.. The limitations of current genetic markers, their cost-effectiveness and the next generation of tests currently being evaluated are discussed.As more and more people survive into advanced ages the problems of the elderly become an increasing burden on clinical services. The prevalence of thyroid nodules in people over the age of 60 years is extremely high (50–70%) and although most of these are benign (85–95%) it is important to distinguish the few that can become malignant and require surgery. The current status of molecular markers for the differential diagnosis of malignant, vs. benign, thyroid nodules is reviewed by Ramchand and Seeman. The relative merits of antiresorptive and anabolic therapies are discussed as are the alternative strategies of combining these therapies or using them sequentially.Another common ailment associated with aging is osteopenia, which leads to the high prevalence of fractures seen in the elderly population. The challenges of identifying individuals at risk of fractures and the uses and limitations of current therapies for osteopenia are discussed by The increasing speed of technological advances provides endocrinologists with ever more powerful tools for investigation, diagnosis and treatment. As the pressures of modern lifestyles involve major changes in how we live and eat and demographics markedly increase the elderly population the challenges endocrinologists face in the clinic are constantly evolving. This collection of articles illustrates the variety of these challenges across the different specialties within endocrinology and the dynamic nature of modern endocrinology.Both authors have made a substantial, direct and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A selection of polar organic compounds was investigated for their biodegradation on a laboratory scale fixed-bed bioreactor and the decline of the parent compounds besides the formation of metabolites was monitored. Of particular interest was the investigation into the degradation of pesticides, especially isoproturon (IPU), surfactants and industrial by-products of chemical synthesis. The results from the laboratory degradation experiments are compared to findings in groundwater.


Monteggia described a fracture of the proximal third of the ulna with anterior dislocation of the radial head from both the proximal radioulnar and radiocapitellar joints. The key treatment principle in Monteggia fractures is stable anatomic alignment of the ulna. We present an uncommon case of a Monteggia fracture-dislocation with an unreducable anterior dislocation of the radial head and associated with a lesion of the lateral collateral ligament of the elbow. The patient in our report had a successful clinical outcome and functional range of motion after rigid fixation of the ulnar shaft fracture and exploration of the elbow joint, reduction of the radial head and repair of the lateral collateral ligament. This case is unusual because of the association of a complete tear of the external collateral ligament of the elbow. The original fracture pattern described by Monteggia is a fracture of the proximal third of the ulna with anterior dislocation of the radial head. Proximal radius was dislocated from both the proximal radioulnar (RU) and radiocapitellar (RC) joints. The main step in the surgical treatment of Monteggia fractures is anatomic reduction and stable osteosynthesis. Once this step is properly achieved, radial head is automatically reduced in most of the cases. Open reduction is only necessary in the rare cases of incarceration of soft parts or a bone fragment. We report a case of a Monteggia fracture were open reduction of the radial head was performed. This case is unusual because of the association of a complete tear of the external collateral ligament of the elbow.A 42-year-old patient presents in the emergency ward with a fresh closed trauma from the left forearm, following a road accident. Physical examination showed swelling of the elbow and upper forearm and an obvious deformity. The patient was neuro-vascularly intact in that extremity. Initial plain radiographic studies of the left forearm revealed a displaced fracture involving the ulna shaft and a dislocation of the radial head. This radiological finding, also called Monteggia fracture-dislocation type 1, was associated with a radial styloid fracture . PosteriIn 1814 Monteggia reported a particular injury pattern associating a fracture of the proximal third of the shaft of the ulna, with a dislocation of the radial head from both the superior radio-ulnar and the radio-humeral joints . Dislocawe have described the management of a rare lesion in which there was buttonholing of the radial head through the anterior capsule associated with a rupture and incarceration of the annular ligament, causing the radiocapitellar dislocation to be irreducible (even after fixation of the ulnar fractures). The anatomic reduction of the ulna determines the reduction of the radial head spontaneously in 93% of the cases. In the other 7%, open reduction typically needs to be performed.The authors declare no competing interests.


The data was obtained from a field survey aimed at measuring the patterns of utilization of mental healthcare services among people living with mental illness. The data was collected using a standardized and structured questionnaire from People Living with Mental Illness (PLMI) receiving treatment and the care-givers of People Living with Mental Illness. Three psychiatric hospitals in Ogun state, Nigeria were the population from which the samples were taken. Chi-square test of independence and correspondence analysis were used to present the data in analyzed form. Specification TableSignificance of the data•The central theme is the study of utilization of mental healthcare facilities among people living with mental illness.•The data could be useful in monitoring the extent to which the mental health services are available and utilized.•The study can be replicated to other countries with similar demographic factors.•The data can be used in the overall study of mental health.1The data is a summary of responses from a field survey. Structured questionnaires were administered to People Living with Mental Illness (PLWMI) and their caregivers and the aim is to measure the patterns of utilization of mental healthcare services among PLWMI.Only those receiving treatments and the care-givers (in the case of very unstable patients) were considered. Also, those residents in the study areas that are of Yoruba origin were considered. Adults younger than 18 years were excluded from the study.The pattern of utilization mental healthcare services in this context was determined by the perceived use of the mental healthcare services by the respondents, frequency of use, frequency of taking prescribed medications and the perceived obstacle of using the available mental healthcare services. These are shown in 2Mental illness has been believed by numerous experts to be caused amongst others by depression, alcohol and substance abuse, stress, violence against women or minors, post-traumatic stress disorder, women׳s infertility and biological factors. Mental health in particular requires special help, care and management. The treatment may come as psychotherapy and medications which are available in mental healthcare services. The availability of mental health services determines their patterns of usage or utilization Utilization is connected with ease of use, excellence service, good customer relations, affordable fees charge, management and socio-economic factors.Questionnaire was used in this article to measure the pattern of utilization of mental healthcare services in Psychiatric hospitals located in three local Government areas of Ogun state, Nigeria. The utilization of the mental healthcare services in the demographics of the study area in particular and Nigeria in general are historically low due to long distance, unavailability of medications, stigmatization, epileptic or skeletal services, poor road networks, poverty and dearth of skilled psychiatrics 2.1Chi-square test of independence was used to determine the association between the measure of utilization of mental healthcare services and the socio-demographics of the respondents and is presented in Remarks: P-value less than 0.05 imply association.2.2The correlational studies are important to reveal the strength and nature of the observed linear relationship that exist between the measure of utilization and the socio-demographic variables. These are presented in 2.3Correspondence analysis is performed to visually display the contributions of the income of the respondents to the hindrance from using mental health services. Details on correspondence analysis can be found in The results are presented as follows: Correspondence table , model sRemarks: The data was explained by two dimensions. Distance seems not to be perceived hindrance to utilization of mental healthcare services in the studied area.


The implementation of these approaches impels its potential effect on the economy of particular countries and also reduces unnecessary overburden on the environment. This contribution aims to provide an overview of some of the most recent trends, challenges, and applications in the field of biomaterials derived from sustainable resources.Biomaterials and sustainable resources are two complementary terms supporting the development of new sustainable emerging processes. In this context, many interdisciplinary approaches including biomass waste valorization and proper usage of green technologies,  The interplay between biomaterials and renewable resources has provided a window of opportunity for the development of novel sustainable emerging strategies within the past few years. Humans used biomaterials in ancient times without actually knowing it. In recent times, a great deal of attention has been paid to their development from sustainable resources driven by the need to develop increasingly more sustainable alternatives to traditional materials. The urgent need for sustainable energy development depends on the advancements of green technologies and increasingly on biocompatible materials with properties comparable to existing materials because they are the way toward a more sustainable future.2 sequestration )In view of the relevant properties and biological activities of these extracts and exopolysaccharides, advanced applications for extracted polysaccharides and related compounds from tobacco as well as from other sources  were envisaged .The first initiative related to the utilization of such polysaccharides as sacrificial templates for the production of a wide range of nanomaterials including nanocrystals of metal oxides. Preliminary research results from the group indicated that the utilization of pure polysaccharides including starch and alginic acid as templates in a dry ball milling methodology could lead to advanced nanocrystals of metal oxides (ZnO) in high purities and with a highly crystalline nature  38]. Im. Im38]. These results were initial proof-of-concept from pure polysaccharides but in some cases algae-extracted polysaccharides show a remarkable potential as replacement of pure compounds in the proposed technologies .i.e., biomass and residues) to produce controllable and well defined nanostructures is the way forward in this regard. In some cases, the challenge lies in the possibility to carefully control the properties of the synthesized biomaterials , but these issues have been occasionally circumvented in cases depending on the biomaterial synthetic protocol and/or the selected future application. As an example, the presence of heteroatoms including Nitrogen or Boron can improve the electrochemical performance. In some other cases, the formation of nanocomposites or the presence of another substrate/starting material  can lead to advanced materials with high-end applications such as electrodes in energy storage devices  where physical properties like conductivity, flexibility, transparency, and mechanical strength are compulsorily needed. These biomaterials with customized composition and porosity can be suitable as electrodes in supercapacitor cells as well as adsorbents for CO2 sequestration. From personal experience, a deep knowledge in the structure and composition of the starting material  is key to lead future advances in the field of sustainable biomaterials for different applications.The development of economic and environmentally benign processes for the scale-up production of materials, chemicals, and fuels is one of the challenges for the 21st century. Selected examples for bio(nano)material designs in view of their future applications clearly illustrates the potential of such bio-derived materials including carbonaceous materials and biocompatible nano-composites from natural sources in a wide range of applications. The use of low cost and alternative renewable precursors structures, therefore technologies and chemistries still require a significant amount of work in the future. In any case, innovative and emerging green technologies for the design of biomaterials can lead the way toward an economical and sustainable society for the betterment of mankind as illustrated by the key examples included in this contribution, which we sincerely hope can stimulate further work within the scientific community.


The author Elena Scherrer was inadvertently omitted from the list of authors during the submission process of the paper "Diagnosis and Prediction of Neuroendocrine Liver Metastases: A Protocol of Six Systematic Reviews" :e60). The author Elena Scherrer  should have been added after Tobias Buerge in the original published manuscript. This error was corrected in the online version of the paper on the JMIR Research Protocols website on April 28, 2014 along with the publication of this correction notice. This correction notice has been sent to PubMed and the correct full-text has been resubmitted to Pubmed Central and other full-text repositories.


As the Australian population ages the demand for nursing care which focuses on responding to the needs of the older person will increase. Few newly graduated Registered Nurses (RNs) currently enter the aged care workforce and few select a career in caring for older people; yet older people are the largest patient group in most health care environments. This research, conducted by the Australian Hartford Consortium of Gerontological Nursing Excellence (Aus-HCGNE), explored how care of the older person is currently taught in Australian schools of nursing (SoN). The interview guide included questions about: whether care of the older person is taught in separate subjects or integrated across the curriculum; academics’ qualifications; subject content; and aged care clinical placements. The head of each of the 33 Australian schools of nursing was contacted, invited to participate and asked to nominate the appropriate academics (undergraduate/curriculum co-ordinators) who would be the most appropriate person to participate in the interview. These academics were then contacted, written informed consent was obtained, interviews were scheduled and completed. This research is timely given the current Royal Commission into Aged Care Quality and Safety in Australia, one focus of which is nurses in residential aged care in respect to numbers, education and competence. This research will be completed by mid-2019. The results will be fed back to SoN to inform the development of their curricula and the preparation of future RNs who will undoubtably need to be expert in the care of older people across the health sector.


Economic analysis can be a guide to determining the level of actions taken to reduce nitrogen (N) losses and reduce environmental risk in a cost-effective manner while also allowing consideration of relative costs of controls to various groups. The biophysical science of N control, especially from nonpoint sources such as agriculture, is not certain. Widespread precise data do not exist for a river basin (or often even for a watershed) that couples management practices and other actions to reduce nonpoint N losses with specific delivery from the basin. The causal relationships are clouded by other factors influencing N flows, such as weather, temperature, and soil characteristics. Even when the science is certain, economic analysis has its own sets of uncertainties and simplifying economic assumptions. The economic analysis of the National Hypoxia Assessment provides an example of economic analysis based on less than complete scientific information that can still provide guidance to policy makers about the economic consequences of alternative approaches. One critical value to policy makers comes from bounding the economic magnitude of the consequences of alternative actions. Another value is the identification of impacts outside the sphere of initial concerns. Such analysis can successfully assess relative impacts of different degrees of control of N losses within the basin as well as outside the basin. It can demonstrate the extent to which costs of control of any one action increase with the intensity of application of control.


Thunnus albacares) fishery” This paper presents data associated with the benchmarking of the Fair Trade USA (FT USA) Capture Fisheries Standard and the Marine Stewardship Council (MSC) Fisheries Standard against the Food and Agriculture Organization's Voluntary Guidelines for Securing Sustainable Small-Scale Fisheries in the Context of Food Security and Poverty Eradiation (FAO Voluntary Guidelines). Benchmarking was used to determine the extent to which these standards, which promote sustainability in different ways, align with the FAO Voluntary Guidelines. The data represent a comprehensive analysis of these standards and are useful for beginning to understand the appropriateness of these standards for small-scale fisheries in developing regions of the world. For further interpretation and discussion please see “A tale of two standards: A case study of the Fair Trade USA certified Maluku handline yellowfin tuna ( For guidelines that were comprised of several aspects, the guidelines were further broken down into sub-guidelines. For each guideline and sub-guideline, both the FTUSA and MSC standards were assessed to determine if there were requirements or components of the certification program equivalent to the FAO Voluntary Guidelines. A stoplight methodology was used to indicate if the respective standard did or did no fulfill a guideline of the FAO Voluntary Guidelines. Green was used to indicate explicit alignment, yellow for partial fulfillment of the guideline and red if the standard did not meet the respective guideline at all. Thus the production of the benchmarking data involved the authors judging the requirements of the standards against the FAO Voluntary Guidelines. Note that criteria that were considered outside the scope of a marine certification program were ignored. For example, the FAO includes land aspects in the first guideline (5.2), but they were ignored in the analysis.


In the biomedical field, human organ repair and regeneration represent a very important and challenging tasks  control of intrinsical multifunctional properties for enhanced bioactivity and drug/gene delivery; (2) Control of bioactivity and biodegradation; and (3) understanding molecular mechanism of nanomaterials controlling tissue regeneration. This Research Topic has attracted a series of papers that show the recent advances in the synthesis and biomedical application of bioactive nanomaterials especially bioactive glass nanoparticles, and provide new insights on designing bioactive nanomaterials. In this Research Topic, The editors hope that the Research Topic “Multifunctional Bioactive Nanomaterials for Tissue Regeneration” will contribute to the progress of research and development activities in the field of novel bioactive nanomaterials for regenerative medicine, inspiring future work leading to the expansion of the biomedical applications of such bioactive nanomaterials.BL proposed the Research Topic and editorial and in charge of 2 manuscript for review process. AB revised the topic and editorial. XC was in charge of 1 manuscript for review process. All authors listed have made a substantial, direct and intellectual contribution to the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Tetanus is a vaccine-preventable disease of significant public health importance especially in developing countries. The WHO strategy for the elimination of maternal and neonatal tetanus recommends the promotion of clean delivery practices, systematic immunization of pregnant women and those in the reproductive age (15-49 years) and surveillance for neonatal tetanus. Implementation of the recommended strategy with the support of WHO, UNICEF and other partners has led to significant decline in number of cases and deaths due to NT over the last decades. The coverage with the second or more dose of tetanus toxoid-containing vaccines (TT2+) a proxy for Protection at Birth (PAB) for the WHO African region has risen from 62% in 2000 to 77% by 2015 Reported cases of NT declined from 5175 in 2000 to 1289 in 2015.The goal of eliminating maternal and neonatal tetanus by 2015 was missed, but some progress has been made. By the end of 2016, 37 out of 47 (79%) of the WHO AFR member states achieved elimination. The 10 member states remaining need additional support by all partners to achieve and maintain the goal of MNTE. Innovative ways of implementing the recommendations need to be urgently considered. Clostridium tetani bacteria whose resistant spores are present in soil and the environment. The causative organism is harboured by humans and animals that excrete the bacteria and spores. Once in a suitable anaerobic environment such as a contaminated wound, the bacteria multiply, releasing tetanus toxin, which is responsible for the symptoms and outcomes of the diseaseTetanus is a non-communicable disease caused by a potent neurotoxin produced by Despite decades of efforts to control and eliminate the disease, it still remains a major public health problem especially in remote areas with poor health care delivery and among the poor and illiterate populations. For instance a study in Benin City, Nigeria, identified lack of awareness of antenatal care services among the target population, under-utilisation of antenatal service, non-immunisation with tetanus toxoid vaccines, negative cultural beliefs, primordial cord care, lack of economic and decision making empowerment of the target population and lack of government commitment towards elimination of neonatal tetanus, as contributing towards the burden of neonatal tetanus in the areaIn the late 1980s, the World Health Organization (WHO) estimated that about 787,000 newborn babies died from tetanus within the first 28 days of their lives. The most recent estimate for 2015 has shown a decline in the estimated NT deaths to 34,000, which is a 96% declineThe WHO defines neonatal tetanus elimination as the occurrence at the district level of less than 1 case of NT per 1000 live births annually. Maternal and neonatal tetanus is thus considered eliminated when neonatal tetanus cases are below the defined threshold.The WHO strategy recommends the promotion of clean delivery practices, aimed at minimizing bacterial contaimination. It also reccomends systematic immunization of pregnant women and those in the reproductive age (15-49 years) with a tetanus toxoid-containing vaccine. Additonally, it reccomends theprovision of at least 3 doses of tetanus toxoid to women of reproductive age that reside in areas classified as being at high risk through supplemental immunization activities’ (SIAs). The vaccination will ensure that women have high enough antibodies to pass to their unborn babies during pregnancy to prevent the disease in the first few weeks after delivery when the risk is highest, in the event of bacterial contamination. Finally, case-based surveillance is used to identify NT cases and deaths as well as for risk assessment of populationsProgress in elimination has been slow and the AFR region missed its target by end-2015, due to slow implementation of the recommendations of the elimination strategy. As at end of 2016, ten of the remaining 18 countries where NT remains a public health problem  are in the African region. The manuscript summarizes the progress made in MNTE, highlights the challenges and suggets ways to acelerate the elimintion of the disease.The review of the progress made in the elimination of maternal and neonatal tetanus in the African Region of the World Health Organization is based on the evaluation of the implementation of the WHO strategy for MNTE by Member States.The key components of the strategy are the promotion of clean delivery practices, systematic immunization of pregnant women and those in the reproductive age (15-49 years) with a tetanus toxoid-containing vaccine in routine immunization, or provision of at least 3 doses of tetanus toxoid through SIAs to women of reproductive age that reside in areas classified as being at high risk for MNT and the use of case-based surveillance to identify NT cases and deaths.The coverage with the second dose of tetanus toxoid (TT2+) in pregnant women serves as a proxy for Protection at Birth (PAB). WHO and UNICEF obtain data from countries, which together with surveys is used to establish an estimate of the coverage with TT2The results presented reflect data obtained on the implementation of these activities by member States as reported in the WHO/UNICEF Joint Reporting Form.The high-risk approach targets areas prioritized as at risk of maternal and neonatal tetanus. These countries have been conducting at least three rounds of SIAs. Between 2000 and 2015 a total of 78,985,175 women of reproductive age received at least two doses of Tetanus Toxoid in 31 countries of the WHO African Region.The level of skilled delivery remains low and needs to be increased to sustain the gains achieved towards elimination. Skilled delivery rates rose from 36% in 2000 to 49% in 2015 in East and Southern Africa regions while it moved from 36% to 54% within the same period in West and Central African regions of UNICEF indicating that skilled delivery rate is still low in countries of the WHO African regionThe member states of the AFR region have made remarkable progress towards achievement of the goal of MNTE. Of the 41 countries that attained MNTE from 2000 to 2016 out of 59 priority countries globally, 28 (68%) are in the AFR region. This is in addition to the nine countries that were already classified as having achieved elimination in 1999. These countries are also being supported to sustain their efforts so as to maintain their MNT elimination status. This support and guidance include a shift from the use of TT-only vaccine to Td vaccine given as a booster in schools and to pregnant women during antenatal care.The remaining 10 member states that are yet to attain MNTE have their plans of action as part of the comprehensive multi-year plan for immunization and are at different levels of strategic implementation of their planned activities to achieve elimination.Despite the apparent progress made in MNTE some challenges have been identified. The lack of awareness of antenatal services, under-utilisation of services and the sub-optimal integration of services with immunisation. These challenges lead to missed opportunities including non-immunisation with tetanus toxoid during antenatal care services. Other challenges are negative cultural beliefs, primordial cord care, lack of economic and decision making, empowerment of the target population and lack of government commitment towards elimination of neonatal tetanus, all affect the pace of eliminationEfforts are continuing through the scale up of the Reaching Every District approach in member states where most have adopted the 5-dose schedule in their immunization programmes to improve coverage with at least two protective doses of TT-containing vaccine. Based on the WHO strategic guidance countries have carried out surveillance and prioritized high-risk districts for NT cases. Using the surveillance and other core and surrogate data obtained the countries conduct at least three rounds of TT SIAs targeting women of reproductive age (15-49 years of age) in all districts classified as being at high risk for MNT. The aim of vaccination is to reach at least 80% of all women of reproductive age with three doses of the vaccine. Vaccination will ensure that the women have high enough antibodies against tetanus toxin to pass on to unborn children during pregnancy, which will protect against disease in the first few weeks of life when the risk is highest. Member states have implemented this strategy to ensure that targeted women in high-risk districts were reached. About 79 million women of reproductive age in the AFR region received at least two doses of TT from 2000 to 2015.An important component of the MNTE strategy is surveillance for cases and deaths due to NT. The Integrated Disease Surveillance and Response (IDSR) is the main strategy that is being followed for disease notification, reporting, and action in the region. Efforts are ongoing to integrate NT surveillance into the active acute flaccid paralysis (AFP) surveillance for Polio using the vast infrastructure already in place. However, more cases are being documented through the IDSR than through the case-based surveillance for NT and cases are not followed by the appropriate response. Additionally, a significant number of the NT cases being reported through routine surveillance have been found not to be truly NT cases during programme reviews, pre-validation assessments or validation surveys, but more cases compatible with neonatal infections especially neonatal sepsis. More needs to be done in surveillance to obtain reproducible data which will inform programme implementation.Although vaccination of pregnant women or women of reproductive age stands out as the most important intervention, regular antenatal check-ups, safe and clean deliveries also significantly contribute to the prevention of neonatal tetanusThe shortage of midwives, cultural preferences of the location of births, economic factors and attitude of health staff are, among others, some of the reasons for the low skilled attendants at birth rate in AFR region.The goal of eliminating maternal and neonatal tetanus by 2015 has been achieved by 35 out of 47 (75%) of the WHO African Region member states. Two more countries attained MNTE in 2016, and the remaining 10 member states need to be supported to use the high-risk approach, including increasing funding, to achieve the elimination goal while those that have achieved the goal need to sustain the gains through the implementation of appropriate strategies depending on their local context.The manuscript has provided a brief update on the progress made in MNTE. However the paper is limited to only information obtained from the JRF, including coverage data which is not obtained from coverage surveys. The degree of accuracy of data is therefore limited. In addition, data may not have come from all parts of the countries including remote hard to reach or populations with poor access to health services, which are also the high risk areas for MNTE. Rumours have circulated in some countries of the regions in the past, which have alleged that the vaccine against tetanus is meant to control birth. Attention should therefore also be paid to communicating factually and effectively about the immense value of vaccination of women of childbearing age in preventing disease and deaths from NT. Effective reporting about vaccine safety particularly among adolescents will minimize hesitancy which can cause reduction in coverage.Additionally, surveillance for NT needs to improve substantially to include local response vaccination in the area that identified NT cases and community surveillance. This will help to bring the countries back on track to meeting the overall goal of MNT elimination.


Reports on dengue outbreaks at hospitals are extremely rare. Here the authors analyze a dengue outbreak at the Teaching Hospital-Kandy (THK), Sri Lanka. Our hypothesis was that the present outbreak of dengue was due to nosocomial infections. Our objectives were to illustrate epidemiological evidence for nosocomial dengue infections among THK workers and comparison of dengue incidence of hospital workers of wards that treat dengue patients with workers of other wards, to ascertain whether most nosocomial dengue incidences occur closer to where dengue patients are treated and vector larvae were detected, and to draw the attention of the medical community to the significance of hospital outbreaks, making suggestions on how to improve dengue preventive work at the THK. We calculated weekly dengue incidences for the hospital workers and for the surrounding Kandy district population, plotted epicurves, and compared them. We also compared these with the temporal changes of numbers of patients who were admitted for other illnesses and then diagnosed with dengue and the numbers of containers with vector mosquito larvae found on hospital premises. Dengue incidence of the hospital workers for the 24-week study period (2388 per 100000 population) was significantly high when compared to incidence of the district (151 per 100000 population). Peaks of dengue incidence in hospital workers, the numbers of patients hospitalized for other illnesses contracting dengue, and numbers of containers with vector larvae occurred in the same week. The peak dengue incidence of the Kandy district happened six weeks later. There was no evidence to indicate blood contact causing dengue among hospital workers. The outbreak was controlled while dengue was rising in the district. This evidence indicates a probable nosocomial dengue outbreak. This outbreak adversely affected hospital workers, patients, and the community. We propose some measures to prevent such outbreaks. Aedes, breed mainly in manmade water containers [Dengue is a mosquito-borne emerging viral fever that can be life-threatening. The vector mosquitoes, genusntainers . Approxintainers . Despitentainers –5. Therentainers . We usedntainers . There iUsing data from the Sri Lanka Department of Census and Statistics and the Ministry of Health, we estimated the notified dengue case incidence of the Kandy district for 2015 (the previous year) to give an idea of background to the reader. It was 93 per 100000 population. THK is usually the hospital that manages the largest number of dengue cases in the Central Province. Dengue incidence in Kandy is usually high during mid-November to mid-February and again in May-September , 9. The  Aedes vector indices are high in Kandy [ Aedes vector by past studies [Workers of the THK and other large Sri Lankan hospitals in cities are at a greater risk of contracting dengue than the general population based upon the following facts:in Kandy , 11 and in Kandy . Hospita studies , 10, 12. studies .The THK  premises cover 14.6 hectares. During the month of May 2016, 57107 inpatients were managed at THK, the outpatient department (OPD) has treated 32553 patients, and the clinics have treated 77258 patients. The total number of employees in same month was 5569 including student nurses. Dengue patients are usually treated in two pediatric and six internal medicine wards. In the THK air conditioning is limited mainly to intensive care units (ICUs) and operating theatres and mosquito screens are not in place. Therefore vectors can fly in to and out of wards. Most dengue patients treated here are residents of the Kandy district. A hospital dengue preventive program has been active since 2012, in addition to the national and municipal council programs.Main objective: illustrating epidemiological evidence for nosocomial infections among THK workersComparison of weekly dengue incidence of THK workers with that of the Kandy district populationComparison of dengue incidence of hospital workers of wards that treat dengue patients with workers of wards without dengue patients. Expecting more workers to get dengue in the former Aedes larvae were detected within the hospital and observe whether most nosocomial dengue occurs closer to where dengue patients are treated and larvae were detectedTo map the distribution of probable nosocomial dengue cases among hospital workers and patients hospitalized for other illnesses and then contracted dengue and sites whereTo draw the attention of the medical community to the significance of hospital outbreaks of dengue by discussing how the present outbreak affected our hospital and the communityMaking suggestions on how to improve dengue preventive work at the THK.This is a retrospective, descriptive study. Our hypothesis was that the present outbreak of dengue among hospital workers was due to nosocomial  infections. Our objectives were as follows:Dengue cases are diagnosed and managed at the THK based on the criteria of the 2012 national guidelines of the Health Ministry of Sri Lanka , which a Aedes mosquito larvae found on the hospital premises by the surveys conducted in the hospital during our study period were obtained from the Medical Officer of Public Health and the Public Health Inspector (PHI) of the THK. Those surveys covered the entire THK premises and were conducted with the help of the national Anti-Malaria Campaign (AMC) personnel according to their standard procedures. Identification of the species of larvae was confirmed by trained personnel of AMC. To get a basic idea of the impact of this, we gathered information on how this outbreak affected THK workers, patients, and the community by speaking to some THK workers, patients, and the Medical Officer of Health of Kandy city .We gathered data from patients' notes and records at the infections control unit of the hospital from April 1st 2016 to September 16th 2016 period. The number of THK workers treated for dengue at THK, the buildings they work in most of the time, and the number of patients who contracted dengue while hospitalized for another illness (and the buildings where they were managed) were noted. The number (count) of hospital employees in May 2016 was obtained from the THK office and each relevant ward, and the estimated midyear population of the Kandy district for 2015 was obtained from the Sri Lanka Department of Census and Statistics. The reported number of dengue cases of the Kandy district during this period was obtained from the weekly epidemiology reports of the health ministry of Sri Lanka. The locations of the containers positive for Aedes larvae at THK are good supportive evidence. Thus we studied temporal changes of numbers and locations of such patients and larvae for the period of the outbreak. We created a graph employing Microsoft Excel charts and created a spot map also for that. Then we estimated dengue incidence for the THK workers, THK workers who work at units treating dengue patients, and the rest of THK workers and for the population of the Kandy district and looked for statistically significant differences between them by calculating odds ratio and comparison of proportions between those groups. We employed Openepi 3.01 software for that.We estimated weekly dengue incidences for 100000, for the populations of hospital workers and the Kandy district population, created epicurves using Microsoft Excel 2007 software, and looked for evidence of nosocomial infections. We looked for supportive evidence for nosocomial dengue as well. Patients hospitalized for other illnesses developed dengue while at the hospital during the same period and presence ofEpicurves of The peak of the dengue incidence of THK workers occurred six weeks before the peak incidence of the Kandy district population. The differences in magnitudes of the dengue incidences of the two populations are also clearly seen in 133 THK workers and 2132 people of the Kandy district contracted dengue infections during the study period. The dengue incidences of THK worker population and the Kandy district population for the period of study (24 weeks) were 2388 and 151 per 100000 population respectively. When the comparison of proportions of dengue patients of the THK and the Kandy district was performed using Openepi 3.01 software, the P value was <0.001.The temporal sequence of dengue incidences of the THK workers, the Kandy district population, the counts of patients admitted to THK for other illnesses and then diagnosed of dengue, and the counts of containers positive for Aedes mosquito larvae found in the hospital premises are illustrated in  Aedes larvae was found at THK premises during our study period.The graph of the count of patients admitted to THK for other diseases and then diagnosed of dengue each week shows the same temporal sequence pattern as the graph of weekly dengue incidences of the THK workers and both have peaks in the week ending June 3rd favoring the idea that both groups contracted dengue from the THK premises. Both graphs differ from the pattern of weekly dengue incidences of the Kandy district population. The peak of the dengue incidence of THK workers coincides with the week where the highest number of containers with Aedes larvae were detected, also showing the duration of outbreak .Monthly total numbers of dengue patients warded at THK are depicted in 2. During the period of April 1st–September 16th, 2016, 47% dengue cases of the THK were serologically (dengue NS1 antigen or IgM antibody for dengue) confirmed. The job categories of the 133 affected THK workers were as follows; 18 doctors, 39 nurses, 43 minor staff members , 19 student nurses and nursing tutors, and 14 workers of various other categories.The eight wards that manage dengue patients plus the OPD and emergency treatment unit have 504 workers. Out of that 17 had dengue. Out of 5065 other workers of the THK, 116 had dengue during our study period. The dengue incidence per 100000 population of workers of units treating dengue and rest of the THK workers were 3373 and 2291, respectively. Nevertheless there was no statistically significant difference in dengue incidence between the two categories . Out of 2352 beds of the THK (that include few cots and incubators) 115 (<5%) were in the areas relatively protected from mosquito access such as ICUs and the premature baby unit. They were distributed among buildings A, B, C, P, X, and MWhen asked about their concerns and views regarding this outbreak during first week of June 2016, 100 THK workers of all levels of hierarchy said that they were very worried about possibility of them contracting dengue. The first author in July 2016 asked all 48 staff members of one internal medicine ward how many times they contracted an illness that needed hospitalization as a probable result of working at the hospital (according to the best of their knowledge) during the last one year. No one had any such illness during the last year other than four members who were hospitalized with dengue in June. THK administration had to mobilize additional manpower from other wards to wards overcrowded with dengue patients where few workers are also on leave with dengue. The first author observed and some of these workers also agreed to taking some time to become familiarized with their new wards. In June 2016, the first author asked 33 patients who presented in late stages of several illnesses to an internal medicine ward for the reason for delay. One-third said fear of contracting dengue prevented them from coming earlier but aggravation of symptoms and inability to afford private treatment made them to come late. At the same month, some nondengue patients in internal medicine wards overcrowded with dengue patients went against medical advice telling fear of contracting dengue as the reason. In July 2016, 14 clinic patients on regular medical clinic follow-up who defaulted that clinic in June said fear of contracting dengue kept them away. The Medical Officer of Health of Kandy city personally communicated that she has noticed a rise of reported dengue cases from the immediate neighborhood of the hospital in May/June and believes that dengue has spread from the hospital.At the THK and most other hospitals of Kandy, dengue is diagnosed clinically as well by considering the patterns of the serial changes in platelet count, leucocytes count, hematocrit, and liver transaminases , 14. Som Aedes vector.As described above, different temporal patterns of dengue incidences in the epicurves  indicate Aedes larvae also peaked in the same week of peak dengue incidence of THK workers indicating high vector density. We think the plausible explanation for the whole picture is an outbreak of nosocomial  dengue.The intrinsic incubation period (IIP) of dengue virus is usually considered 4-6 days . The ave Aedes during that week. During the first week of June THK dengue control program was intensified with outside help. Surveillance for mosquito breeding places conducted more frequently and vigorously in June and July. That also contributed to the identification of many containers positive for Aedes larvae were found there. Some of them appear to be infected when coming for ward work or from another student nurse or a worker with dengue viremia. Most patients diagnosed with dengue while being managed for another illness were also from the buildings near the building where dengue patients were managed  the number of patients exceeds the number of beds in internal medicine and pediatric wards and many patients do not always utilize the nets provided. Once a probable nosocomial dengue case is identified, thermal fogging is employed to kill infected vectors in the vicinity. From the first week of June all these control measures were intensified with outside help; for example, fogging of the THK premises was performed twice a week for two months. Placement of ovitraps in selected locations to monitor the vector was introduced later. Considering results of some past studies we think that creation of additional barriers against dengue transmission inside the hospital by installation of screens against mosquitoes especially in units where dengue patients are managed and application of topical mosquito repellents to all potential dengue patients always and to the hospital workers during epidemics too may be useful. . For exa helpful .Even though a much larger number of dengue patients were managed at the hospital in July and the weather was conducive for dengue transmission, infections among THK workers got controlled. The decline of dengue incidence of THK workers while that of the surrounding Kandy population rose further supports the idea that nosocomial dengue occurred and indicates that even during the height of an epidemic in the community, vigorous preventive methods can control nosocomial dengue at hospitals, and that is an important lesson to remember. Further strengthening of THK dengue preventive program with wider participation of all stake holders based upon IMV principals may be useful in prevention of further outbreaks. Dearth of funds for preventive work is a key issue in implementing additional preventive measures in Sri Lanka and in most other countries severely affected by dengue although prevention is better than treatment. According to one study, hospital management of an adult with dengue fever and severe dengue hemorrhagic fever, respectively, cost the health ministry of Sri Lanka about 196 and 887 US dollars but the expenditure on dengue prevention per year per reported case of dengue was only 97 US dollars in 2012 . Hospita Aedes vector. One Indian team in 2008 responding to an article in the Lancet journal reported of 21 serologically confirmed cases of nosocomial dengue in healthcare workers and suspected possible aerosol transmission [In 2009, 37 hospital workers and 21 patients being treated for other diseases acquired confirmed dengue from the National Hospital of Sri Lanka-Colombo [smission . Howeversmission . A Banglsmission . Both prsmission . Many hesmission . We beliThe magnitude of this outbreak motivated us to give a basic idea of its impact. The information we gathered by talking to those who were affected is very basic. However it may help others to foresee what to expect in future outbreaks in other hospitals. The media highlighted this outbreak and sensationalized a death of one hospital worker as negligence. That led to anxiety among THK workers and to the practice of defensive medicine by some of them. Further studies may help identify dengue as an occupational hazard of workers in large hospitals in endemic countries. During the height of this outbreak, the THK administration had to mobilize additional manpower to wards treating dengue patients. Some Kandy residents had a transient fear of utilizing the hospital. According to the Medical Officer of Health of the Kandy city dengue has spilled to the immediate neighborhood of the hospital. Transportation methods and hubs are known contributors of the global spread of dengue . The preVector breeding sites were all over the THK premises. Dengue virus can get vertically transmitted in the vector , 13. PatHospitalized dengue cases are only a fraction of total dengue cases. THK workers who were treated for dengue at other hospitals were not counted. Some patients who appeared to be infected while being treated at THK for other illnesses (and some bystanders who stayed with their sick children), went home, and were then diagnosed with dengue within less than six days were not counted. Some hospital workers and patients who developed fever at the hospital may have got infected outside the hospital. The diagnosis of dengue in all cases of THK and Kandy district was not serologically confirmed. Other factors such as window space available for vectors to fly in and out of each building and practices like using mosquito repellents may also have influenced the number of cases in different buildings but these factors were not assessed. Investigations of each and every hospital staff member and all dengue patients for a longer period may give a better picture of the situation but that task is beyond the capability of the authors.The mid-2016 dengue outbreak at the THK affected hospital workers and users severely and is probably a nosocomial dengue outbreak. Such major outbreaks are likely to adversely affect the hospital workers, the smooth functioning of the hospital, and the communities they serve especially at a height of dengue epidemic, as was the case at the THK. Nonetheless such outbreaks can be controlled with additional effort. We have to generate more information on this issue from similar hospitals to confirm the findings of the present study and take steps to prevent dengue outbreaks at hospitals.