AS, producing several transcripts isoforms form a single gene, also increases the protein diversity. However, the evolution and manner for increasing protein variation differs between AS and GD. An important question is how are patterns of AS affected after a GD event. Here, we review the current knowledge of AS and GD, focusing on their evolutionary relationship. These two processes are now considered the main contributors to the increasing protein diversity and therefore their relationship is a relevant, yet understudied, area of evolutionary study.The protein diversity that exists today has resulted from various evolutionary processes. It is well known that gene duplication (GD) along with the accumulation of mutations are responsible, among other factors, for an increase in the number of different proteins. The gene structure in eukaryotes requires the removal of non-coding sequences, introns, to produce mature mRNAs. This process, known as  Organismal protein diversity has increased through evolution. This diversity has allowed organisms to adapt to different environments, to develop and to differentiate specialized tissues. GD, along with mutations, has been an important process to increase the protein diversity. The genome sequence of a variety of organisms has allowed the identification of paralogous genes produced by GD. Nevertheless, the vast amount of proteins cannot be solely explained by this process. Before the human genome was sequenced it was widely believed that the human genome would encode around 100,000 genes based on an estimate of the number of different proteins existing in human cells . SurprisThe vast number of genes in eukaryotic organisms is in large part due to GD. Several processes can occur in the cell that can lead to the duplication of genes. There are two GD classifications; SSD and WGD. SSD duplicates one or several genes while WGD increases significantly the offspring’s gene count compared to the parent. SSDs events may result from unequal cross-over (DNA-dependent) or retrotransposition (RNA-dependent). Both processes give rise to different gene structures. Retrotransposed genes become single exon genes while DNA-dependent duplications inherit gene structure and regulatory sequences (reviewed by Four models have been proposed to describe the evolution of duplicated, or paralogous genes. The model of neofunctionalization establish that one copy of the gene retains the ancestral function while the function of the other diverges into a new one. Subfunctionalization, or duplication-divergence-complementation propose that the ancestral gene function is partitioned between paralogs. Subfunctionalization was tested by Figure 1: ES, where a complete exon is absent from the primary transcript; AA, where the 3′ end of an intron changes; AD, where the 5′ splice site of the intron is different; IR, where a reported intron is not spliced and is part of the mature mRNA and MEE, where one of two exons is retained in a given isoform but not both exons. These AS events vary in their frequency among different eukaryotic organisms. In animals, ES is the most common AS event, which represents around 50% of all AS events, while in plants IR is the most frequent AS event (reviewed Alternative splicing is a post-transcriptional process that occurs in different stresses, developmental conditions and in different cell types (reviewed by reviewed .Nematodes and humans show high variation in cell types and both genomes code for a similar number of genes. However, 98% of human multiple-exon genes exhibit AS  while ASFigure 2. The independent model establishes the lack of relationship between GD and AS and therefore the number of isoforms in paralogs vs. non-duplicated genes would be similar. The functional sharing model illustrates the subfunctionalization of the paralogous genes, where one paralog would adopt certain number of ancestral AS events and the other paralog adopts the rest of the ancient isoforms. Therefore, in the functional sharing model the number of AS events per gene decreases in comparison with the non-duplicated genes. The last model is the accelerated AS model, where an increase in the number of AS events per gene results from a relaxed selection pressure for each paralogous gene.Transcript isoforms resulting from AS events can be viewed as having “internal-paralogs” in the same gene . These “Danio rerio (The most common AS event analyzed in paralogous genes is MEE. This AS event accounts for the particularity where given the possibility of two exons, one is maintained in one duplicated gene and lost in the other, and vice versa in the paralog. The first example found to have this pattern was the microphthalmia-associated transcription factor in io rerio . This isio rerio . To geneThe first attempt to generalize an evolutionary model for AS after GD was proposed by Caenorhabditis elegans, confirmed findings from previous analyses in mouse and human indicating that larger gene families had fewer AS events. However, these authors focused their work on an interaction network that consisted of ∼900 genes; they found a negative correlation between AS events and the connectivity in the network. This means that a gene with multiple connections to other genes, also known as a hub, had fewer AS events than genes connected to one or two genes. Further, they argued that duplication of hub genes was an uncommon phenomenon. Therefore AS, interpreted as an internal paralog, was unlikely to occur in hub genes.Arabidopsis thaliana and Oryza sativa. They analyzed several factors and characteristics of singletons vs. duplicated genes and found that singletons were less affected by AS than paralogs in both plant species; which contrasts with findings from animal studies. In agreement with these results, Plants are organisms with a tendency to have undergone WGDs throughout their evolutionary history; and are therefore particularly important in the study of AS and GD. A. thaliana looking for the qualitative and quantitative conservation of AS events in paralogs. Such conservation was higher in paralogous genes resulting from tandem duplications than from WGD-resulting paralogs. They found that IR, the most frequent AS event in plants, was also the event with highest conservation in A. thaliana. These results suggest that the fate of AS events after GD depends on the type of AS event and the type of GD.The two contrastingly AS evolutionary models, function sharing and independent, were discussed more recently by The relationship between GD and AS is far from being understood. Several models of this relationship have been proposed and examples of each have been demonstrated. The analysis of these processes is complex and therefore a generalization of an evolutionary model is a difficult task. The development and utilization of new technologies has allowed the identification of gene isoforms expressed in a tissue-specific or even a cell-specific manner in more model organisms . More stThe correct identification and classification of AS and GD is fundamental to improve the understanding of the evolution of both processes. AS events must be classified in terms of how they modify the primary transcript and the expression of unique isoforms in specific conditions, tissues and developmental stages. Future studies should also consider the percentage of affected genes and that the frequency of different AS event types varies between plants and animals. The classification of AS events should also be complemented by identifying and classifying GD events. The time elapsed after a GD event is an important factor in paralogous gene AS. In addition, this could be complemented with the mutation rates for each gene. These could give insights of the evolution of the paralogous genes. Besides classifying GD events as either SSD or WGD, researchers must also determine the way they were produced and the time since the duplication is necessary. For this classification, the comparison between species is important. There are a variety of model species, each uniquely qualifies as a study organism, for the different GD processes. Plants and teleost species in the animal kingdom, for example, are good models for the classification of WGD and SSD, respectively. Several organisms and a variety of tissues and conditions need to be analyzed with a characterization and classification of type of AS and GD in order to identify an evolutionary model of AS events after GD. These analyses could be complemented with other genome-wide analysis including isoforms quantification and proteomic studies . A singlAll authors listed, have made 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.


The use of elastic materials favours degradation of their surface. The period of their clinical usefulness is then shortened, and their further utilisation in the oral cavity may have the reverse effect. The surface properties of such material as well as the influence of the humidity on their surface are very important as they determine the prosthetic materials behavior in the mouth. The surface of such material should be resistant to water. Inverse gas chromatography is an accurate, sensitive technique for studying surface properties. Thanks to using a unique equipment specially designed for IGC technique, Surface Energy Analyzer, it was possible to characterize the surface at 0 and 80% of humidity. Our results show that increased humidity does not affect surface properties of studied prosthetic materials. Their ability to dispersive and specific interactions change in very limited degree. IGC experiment was also applied for the estimation of Hansen solubility parameters that indicate ability of a material to dispersive, polar, and hydrogen-bonding interactions. Relation between the surface characteristics and practical use of soft lining materials with implications for their clinical usefulness is also discussed. In dentistry, soft lining materials are used in patients in whom extremely difficult conditions of the basal seat area are found. Thanks to their flexibility properties, these materials make a cushioning, elastic layer of the mucous part of the denture, which is conducive to less traumatic transfer of occlusal forces onto the base. A removable denture lined with elastic material does not exert traumatic influence on the soft, rigid, and pressure-sensitive oral mucosa, is more comfortable and facilitates adaptation by the patient .Soft liners can be classified as temporary, for short-term use and definitive to obtain permanent cushion-like effect. Long-term soft lining materials may also be divided according to the chemical structure into silicone elastomers and plasticized acrylates and due to the way of polymerization into room-temperature and heat-temperature polymerized. Lining made with use of high-temperature polymerized materials can be performed only by dental technician in prosthetic laboratory (indirect method). Lining made with use of room-temperature polymerized materials can be done in a dentist’s office by a dentist, as well (direct method of lining).In the course of their utilisation, elastic materials are subject to a constant impact of the changeable and difficult conditions of the oral environment . While bThe soft lining materials used in the study are successfully applied in dentistry due to their desired physical and chemical properties. Biological durability, low toxicity, the ability to be moulded easily to obtain a required shape, the lack of macroscopic changes in the surface features, shape preservation for a possibly long period of time, low glass transition temperature, and good thermal and chemical resistance make these materials difficult to be replaced in clinical practice.Due to the strain resulting from the use in the oral cavity environment, changes in the micromorphology of their surface are, however, detected in images obtained with a scanning electron microscope. Surface degradation is observed as early as a few days after application, in the form of a network of longitudinally oriented grooves and cracks , 6. The Increased roughness of the elastic material surface may irritate the pressure-sensitive and often atrophic mucous membrane, and, at the same time, create optimal conditions for the colonisation and development of pathogenic microorganisms in the oral cavity environment. Changes of the surface features may lead to gradual spatial disintegration of the material and have a negative effect on the mechanical properties of the elastic materials, too , 9.The group of chemical compounds called plasticizers (softeners) which includes phtalans, aliphatic esters, polyesters, cyclic ethers, phosphates, etc., is responsible for the elasticity of soft lining materials. The plasticizers decrease in the glass transition temperature thanks to which the hard materials become rubbery and elastic. The plasticizers are loosely connected with a network of polymeric chains and that is why they usually dissolve or leach into the oral cavity, which causes the material to become hard just like the denture base acrylate .−1 day−1 1/2, respectively.It can be seen that all examined materials have different ability to intermolecular interactions. For polydimethylsiloxane group of materials—Molloplast B and Mollosil, we can observe similar values for components and total solubility parameter. These two materials has also similar value of 1/2 is observed for Silagum Comfort. Villacryl, representative of acrylic materials, shows the lower dispersion and polar HSP value, but it has the higher ability to interact through hydrogen bonding, as evidenced by the high values of KD parameter.The highest total solubility parameter—27.65 [MPa]For Silagum Soft, the largest capacity for dispersion interactions confirms the highest values of dispersion component of solubility parameter The HSP values for dental materials can be compared with water HSP, but it is hard to state exactly which data for water are correct—see Table 1.3 in Ref  and TablKA and KD represent surface ability to act as electron acceptor and donor, respectively, while HSPs Conclusions based on concerning the activity of soft lining materials based on HSPs results are in agreement with those reported earlier for surface parameters Table . One shoThe study gave different results of both surface parameters and Hansen Solubility Parameters, although these materials are classified into the same group in terms of their chemical composition. The diversity may be caused by different ways of preparing each material as well as mixing the components of the preparations. Molloplast B, which polymerises at high temperatures, is characterized by greater cross-linking of residual monomers; therefore, its surface is harder and more resistant to the influence of the external environment .The qualitative differences in the molecular composition, varying values of the surface energy and hydrophilicity may cause the investigated materials to be characterized by different biological properties. Nakamoto et al. have confirmed that the higher the surface energy, the greater the ability of microorganisms to adhere to the elastic liner surface .IGC proved to be an appropriate and useful technique for studying surface properties of the prosthetic materials and the stability of their surface under the influence of humidity. On the basis of IGC data obtained at different values of humidity, Silagum should be the most stable material taking into account the water influence. It also possesses the highest total solubility parameter value and potential for to non-polar and permanent dipole–permanent dipole interactions. The other tested prosthetic materials were characterized by the surface more sensitive to water, but the changes of the values of the IGC parameters under the influence of water were not large. Obtained Hansen solubility parameter data indicate greater potential for tested materials to the dispersive and polar intermolecular interactions.2] has been obtained for Silagum Comfort, which confirms strong hydrophobic properties of this material. The lowest values 2] have been obtained for Villacryl Soft. The high hydrophilicity of this material may deepen the mechanical surface irregularities (roughness) and impair the ability to deform elastically and flow , which may, in turn, encourage the adhesion of pathogenic microorganisms, including fungi from the Candida genus, to the surface of the elastic material [The solubility parameter is a thermodynamic description of the system and can, therefore, be used in assessing the impact of various conditions on the behavior of the tested materials and explanations of intermolecular phenomena. It is currently thought that bacterial adhesion is started by electrostatic attraction, hydrophobic reactions, and the Van der Waals forces between the bacterial cell membrane and the surface of the elastic material , 43. Thimaterial . The hydmaterial .The examined lignin materials seem to be relatively stable in water environment. These are characterized by relatively strong ability to dispersive interactions (high value of


Among the innovations for the treatment of type 1 diabetes, islet transplantation is a less invasive method of treatment, although it is still in development. One of the greatest barriers to this technique is the low number of pancreas donors and the low number of pancreases that are available for transplantation. Rodent models have been chosen in most studies of islet rejection and type 1 diabetes prevention to evaluate the quality and function of isolated human islets and to identify alternative solutions to the problem of islet scarcity. The purpose of this study is to conduct a review of islet xenotransplantation experiments from humans to rodents, to organize and analyze the parameters of these experiments, to describe trends in experimental modeling and to assess the viability of this procedure. In this study, we reviewed recently published research regarding islet xenotransplantation from humans to rodents, and we summarized the findings and organized the relevant data. The included studies were recent reports that involved xenotransplantation using human islets in a rodent model. We excluded the studies that related to isotransplantation, autotransplantation and allotransplantation. A total of 34 studies that related to xenotransplantation were selected for review based on their relevance and current data. Advances in the use of different graft sites may overcome autoimmunity and rejection after transplantation, which may solve the problem of the scarcity of islet donors in patients with type 1 diabetes. According to the International Diabetes Federation (IDF), diabetes mellitus currently affects 382 million people, with a projected increase to 592 million people by 2035 The etiology of type I diabetes mellitus is unknown; however, histopathological findings indicate an autoimmune destruction of ß-cells, an association with HLA alleles and environmental factors, such as exposure to bovine milk. Diabetes mellitus was historically considered a fatal disease that resulted in hyperglycemic coma. However, since the discovery of the therapeutic application of insulin in the 1920s, diabetes mellitus has become a chronic disease that causes many complications, including retinopathy, nephropathy, vasculopathy and neuropathy.In 1894, the first case of islet transplantation as a treatment for diabetes was described by Dr. Watson Williams and Hareshant. Notably, this case occurred before the insulin isolation of Banting, Best and Collip in 1921. In the early twentieth century, Dr. W. Williams attempted to implant sheep pancreatic fragments in the subcutaneous tissue of a 15-year-old male with ketoacidosis. However, the xenograft was rejected because of a lack of immunosuppressive techniques. In 1972, Dr. P. Lacey demonstrated the reversibility of diabetes in rodents by using islet implantation The first successes in islet allografts in the surgical treatment of diabetes occurred in 1990 with Scharp et al., who achieved insulin independence in a patient with type 1 diabetes mellitus for one month. However, many technical difficulties were found during the reproduction of this experiment.One of the greatest barriers to the development of islet transplantation is the low number of pancreas donors and the low number of pancreases that can be used for transplantation To supply the scarcity of islets, animal donors, such as pigs, could provide an alternative source of cells for transplantation In this context, to evaluate the quality and function of isolated human islets Manikandan et al. Although there have been many positive results related to the xenotransplantation of human islets to rodents, researchers have rarely achieved a breakthrough in the clinical treatment of islet transplantation, perhaps because of the differences between the human immune system and the rodent model. These differences have stimulated the development of humanized rodent models, which allow the detailed study of human immune system cells and transplanted human islets in vivo The purpose of this study is to review islet xenotransplantation experimental attempts from humans to rodents, to organize the parameters of these experiments and to analyze the viability of these procedures.We reviewed studies regarding islet xenotransplantation from humans to rodents. The relevant data from recently published studies from 2006 to 2016 were summarized and organized.The study designs of previous reviews and experimental studies were included.Donor participants were humans from whom islets were isolated and transplanted to rodents (recipient).The interventions were islet xenotransplantation from humans to rodents. There were different graft sites and types of islet recipients. In the present review, only the studies that relate to human to rodent islet xenotransplantation were selected.Several parameters were considered, namely, strain, gender, age and weight of the recipient, xenotransplantation site, graft survival time (follow up), number of transplanted islets and diabetes induction method.Articles discussing transplantation in porcine, tilapia and nonhuman primates (which are some of the more common species that are used for transplantation) were excluded from the review to focus on the articles that relate to islet xenotransplantation from humans to rodents. Studies using stem cells or that had an unclear methodology were excluded from our review.Research letters, articles not published in English and articles for which the full text was unavailable were not considered in this review.Following the PubMed search, we reviewed the references from the retrieved publications and obtained the entire text of the publications for potential inclusion in the review.Using the Medline database, the literature was searched for English-language articles that were published from January 2006 to January 2016.We performed a manual search of the references and contacted experts in the field.We searched for published articles by using the Medline database with the keywords "rodent islet transplantation".We also selected the most recent works that were published from January 2006 to January 2016 by using the following search terms: “(((((rodent human islet xenotransplantation) NOT tilapia) NOT porcine) NOT nonhuman primate) NOT pig) AND (“2006”[Date - Completion]: “2016”[Date - Completion])”.Articles that were published before 2006 were not included in the analysis because of a lack of information, relevance and current data.The data from each study were independently extracted by 3 of the authors. Disagreements were resolved by consensus. If no consensus was achieved, a fourth author was consulted.A total of 1,819 articles from 2006 to 2016 were found, but only 225 articles were related to xenotransplantation and were thus selected based on their relevance and current information. We selected 91 articles and analyzed them; 34 of these articles were had good methodological quality, such as updated information that is necessary for this review and a description of all comparative parameters related to islet xenotransplantation from human donors to rodents.According to the selected studies, C57BL/6 mice were the most used strains in xenograft experiments as islet recipients (22%), followed by NOD-SCID and BALB/c mice (14% each), SCID mice (8%), and NU/NU mice (6%). Syrian Golden hamsters, athymic nude Foxn1-nu mice, NOD/LtJ mice, NOD SCID gamma mice, Rowett rats, and SCID-Beige mice were the least commonly used recipients (3% each).The results are organized and displayed in Islet transplantation is an innovation for type 1 diabetes treatment that is less invasive and that has a 20-fold lower morbidity rate than pancreas transplantation Some studies have reported an 80% rate of insulin independence during the first postoperative year in the patients who were treated with islet transplantation. However, graft survival rates remain low The islet transplantation technique has been developed to provide an adequate supply of insulin, which solves the problem of donor shortage for diabetic patients We discuss the analyzed studies in more detail below.In this study, we reviewed the articles describing xenograft transplantation in rodents. The majority of the animals were between 9 and 16 weeks old and were male . See The standard diabetes induction method was the use of streptozotocin. The median dose was 170 mg/kg (50-250 mg/kg).The authors used different sites for the xenografts , but theThe highest graft survival time was more than 300 days, which was obtained by Brehm MA et al. It is important to note that in many studies, the recipients were sacrificed for histopathological analysis.We identified many variables on the analyzed studies. The characteristics of the xenotransplantation site are factors that can possibly influence the obtained results. Based on our analysis, it is possible to reproduce some of these studies and to modify additional variables to obtain better graft survival times. Nevertheless, one relevant limitation is that many studies did not describe the data that are essential to reproduce the described experiments, such as the strain, age and gender of the recipient animal and the diabetes induction method.Although immunosuppressive drugs may increase the survival rates of islet allotransplantation in rodents by reducing the side effects The viability of pancreatic islet transplantation could be determined in only a small number of studies because of a lack of the information that is necessary to perform this procedure.The survival rates in allograft experiments have increased with the use of novel graft sites. Different methodologies to conserve islets may overcome autoimmunity and rejection after transplantation and solve the problem of the scarcity of islet donors for patients with type 1 diabetes.Iuamoto LR, Franco AS, Suguita FY, Essu FF, Oliveira LT, Kato JM and Torsani MB were responsible for the literature review and manuscript writing. Iuamoto LR, Franco AS, Meyer A, Andraus W and D'Albuquerque LA were responsible for critical analysis. Iuamoto LR, Franco AS, Kato JM, Meyer A, Chaib E and D'Albuquerque LA were responsible for paper revision. Iuamoto LR, Franco AS, Meyer A, Chaib E, Andraus W and D'Albuquerque LA were responsible for manuscript review. Iuamoto LR and Meyer A were responsible for study design. Meyer A, Chaib E, Andraus W and D'Albuquerque LA were responsible for supervision of the study.


This research analyzes the role of prosocialness and trust in the use of water as a limited resource under situations of competition or cooperation. For this purpose, 107 participants played the role of farmers and made decisions about irrigating their fields in the web-based multiplayer game Irrigania. Before the simulation exercise, participants’ prosocialness and trust levels were evaluated and they were randomly assigned to an experimental condition (competition or cooperation). Repeated measures analysis, using the 10 fields and the experimental conditions as factors, showed that, in the cooperation condition, farmers and their villages used a less selfish strategy to cultivate their fields, which produced greater benefits. Under competition, benefits to farmers and their villages were reduced over time. Mediational analysis shows that the selfish irrigation strategy fully mediated the relationship between prosocialness and accumulated profits; prosocial individuals choose less selfish irrigation strategies and, in turn, accumulated more benefit. Moreover, moderation analysis shows that trust moderated the link between prosocialness and water use strategy by strengthening the negative effect of prosocialness on selection of selfish strategies. The implications of these results highlight the importance of promoting the necessary trust to develop prosocial strategies in collectives; therefore, the efficacy of interventions, such as the creation of cooperative educational contexts or organization of collective actions with groups affected by water scarcity, are discussed. Water has been and continues to be a source of political conflict, at times even violent conflict, a prospect which may worsen as populations grow, economies develop, and climatic conditions change” (p. 29). Water is an essential to human life common pool natural resource; therefore, it is a scarce and precious resource, particularly in places where there is a great shortage of water, mainly due to the climate, leading to serious problems for society and for the environment. Therefore, water scarcity and interdependent collective behavior in which individuals tend to maximize their personal benefit create the necessary conditions for considering water consumption as a social dilemma. In this sense, for example, applied research has explored the positive impact of interventions in real-world dilemmas related to water conservation by publishing data on private consumption , selfish strategies will mediate the relation between prosocialness and accumulated income, such that individuals with the most strongly prosocial disposition will use less selfish strategies, which will result in higher accumulated income.sine qua non of cooperation. When individuals mistrust the goodwill of another, they tend not to engage in prosocial behaviors or provide help. Trust is a dispositional variable that affects the decision to cooperate or defect in social dilemmas , trust will moderate the relation between prosocialness and selfish strategies, such that trust will strengthen the negative association between prosocial disposition and selfish strategies.SD = 2.18; range 18–27 years).The participants were 107 students of Environmental Sciences Degrees from the University of Córdoba, 70.5% women and 29.5% men. The mean age was 21.28 years . Participants took, on average, 15 min to complete the survey, and their anonymity was guaranteed. In a second phase, participants were randomly assigned to one of two experimental conditions (cooperation or competition) and, finally, in a third phase, participants played the Irrigania game. Participants took between 52 and 84 min to complete the 10 simulated years of the game.Game information was collected via record sheets that were designed so that each participant could register all of their decisions and achievements. On the record sheet, participants provided information related to the simulation, such as farmer name, village name, village group name, farmer’s decisions , and the outcomes of the simulation (net income per year and accumulated income).In the first phase of the experiment, participants completed an online questionnaire that was created with the Global Park survey program. They were informed that they would have to do a group task online with other participants. In this phase, and before the group tasks, the socio-demographic and dispositional variables were assessed .N = 52; competition N = 55). Participants in the cooperation condition could talk to each other with their village’ members about strategies and income whilst they were playing the game , in order to create a cooperative atmosphere  was measured using a short version of the Prosocialness Scale , which aTrust (α = 0.87) was measured by adapting the scale used by In order to measure analytical strategies and decision-making we used the Irrigania simulation game, in which a number of fields are allocated to players, and each player decides how to irrigate each of their fields every year.This was indexed as the difference between the number of fields under groundwater irrigation and the number of fields under rainfed agriculture (groundwater irrigation - rainfed agriculture), using the SPSS program. To generate the “selfish irrigation” measure, we selected groundwater irrigation and rainfed agriculture as the most extreme strategies, selfish and prosocial, respectively, while river water irrigation was not considered for the calculation.Annual income depended on weather conditions during the previous year, the type of irrigation chosen, and how the other farmers used the water resources. Accumulated income was calculated for years 1 through 10 as the sum of annual income through the 10 years.Data were analyzed using SPSS v21. Repeated measure analyses were used to scrutinize the changes over time in the overall sample and in each of the experimental conditions. ANOVAs were performed to explore differences between the cooperation and competition conditions. A mediational analysis was performed by using the Process procedure for SPSS  in orderF = 459.52, p < 0.001; η2 = 0.98; O = 1.00] over the accumulated incomes throughout the 10 years of the simulation for the complete sample as a whole, as well as a significant time effect for the evolution of accumulated incomes throughout the 10 years in both cooperation  and competition  conditions . When including the experimental condition as between-factor , the significant effect of time remain , a marginal main effect of the experimental condition is observed , and an interactive effect between time and the experimental condition is observed .The repeated measure analyses (by including the 10 years of accumulated incomes as repeated factor) revealed a significant overall time effect . Moreover, the average of net incomes was higher for individuals in the cooperation condition than for individuals in the competition condition .ANOVAs were used to assess whether the experimental condition (competition vs. cooperation) affected net and accumulated incomes. The results exhibited a significant effect on accumulated income in the 10th year, as well as on the average of net incomes over the 10 years. As expected, individuals in the cooperation competition accumulated higher incomes in the last year of the simulation than individuals in the competition condition . Moreover, as Figure 1 shows, the repeated measure analyses performed separately with each group showed that, in both the competition  and cooperation  conditions, individuals saw their incomes significantly reduce between the first and the 10th year. When doing a mixed ANOVA by including the experimental condition (cooperation vs. competition) as interpersonal factor (between factor), the results showed that the main effect of time remain , a main effect of the experimental condition is observed , and a interactive effect is observed showing that the reduction o net income is significantly greater for individuals in the competition condition . Hypothesis 2 was therefore partially confirmed.The repeated measure analyses (including the first and the 10th years of net incomes as factor) of the complete sample as a whole showed significant differences in the evolution of the net income from the first to the 10th years across the two conditions .We performed ANOVAs to evaluate the irrigation strategies followed by both the cooperation and competition experimental conditions. In the competition condition participants used a more selfish strategy, which resulted in a higher number of fields being irrigated with groundwater . On average, over the 10 years, individuals in the cooperation condition irrigated significantly more fields with rainfed agriculture than individuals in the competition condition .Participants in the cooperation condition cultivated a higher number of fields with rainfed agriculture and, thus, used a more prosocial strategy , and this could have contributed to the not expected reduction of the profits obtained by participants in the cooperation condition. Interestingly, despite the reduction of the incomes over time obtained with the prosocial strategy, participants in the cooperation condition continue to opt for the prosocial strategy; and this decision enhanced finally their benefits to the long-term. Once again, this result strengthens the idea of changing the predominant occidental competitive framework toward sharing resources by promoting cooperative environments for the benefit of individual, societies and the planet.In a cooperative situation, both individuals and groups obtain higher benefits, both net and accumulated, than in a competitive situation, a result in accordance with previous studies . MoreoveFurthermore, people usually base their own decisions, in part, on the decisions and behaviors they have observed in others, reciprocation providing one example of this . In our Our results seem to corroborate the theories which hold that selfish and self-sufficient behaviors are increased in competitive situations , and thaIn accordance with Most authors  agree thGiven that the results reinforce the thesis focused on the importance of generating confidence for developing less selfish strategies to solve social dilemmas , an impoFinally, the study showed that trust acts as a moderating variable on the relation between prosocialness and selection of selfish strategies, such that trust strengthens the negative effect of dispositional prosocialness on selection of selfish strategies. In other words, prosocialness predicts less selfish strategies, and low trust levels reinforce this relation, whereas high levels of trust do not significantly alter the effect of a prosocial disposition on the selection of selfish strategies. Therefore, proself individuals who lack trust in the prosocialness of others tend to use even more selfish strategies than proself individuals who place high trust in the prosocial disposition of others. The study seems to indicate that, in situations of perceived vulnerability and when dealing with common-pool natural resources, high trust levels are a prerequisite for engaging in cooperative pro-environmental behaviors, especially for individuals with low prosocial tendencies. This is in concordance with previous studies that have shown that trust promotes cooperation , as wellA larger and more heterogeneous particularly with respect to degree subject sample would have been advantageous. It would have been especially beneficial to have a sample of farmers, as they would probably have had more knowledge relevant to the theme of the simulation. In future investigations, it would be interesting to explore other variables that have been shown to have an effect on behavior in social dilemmas, such as self-efficacy. Investigating differences between students of science and arts degrees in terms of previous knowledge of environmental issues and prosocial disposition would also be useful.This investigation has explored the role of prosocialness and trust in people’s decision-making with respect to environmental issues specifically the use of water, a limited essential resource and the importance of cooperation in decision-making about common-pool resources. It has shown that there are significant differences between levels of pro-environmental behavior under cooperation and competition conditions. As discussed before, in cooperative conditions the water-use strategies chosen were less selfish and more prosocial and pro-environmental, and this, in turn, affected both net and accumulated income, such that they were higher in the cooperation condition than in the competition condition. This is due to the fact that, in the competition condition, groundwater irrigation was the most frequently used strategy and, while this produces a higher income in the short term, the cost is higher, and thus long-term over-use of this strategy will reduce profits. In the cooperation condition, participants focused more on the common wealth and made more use of rainfed agriculture, thus obtaining a higher income over the long term.Our study has demonstrated how irrigation strategy mediates the relation between prosocialness and cumulative incomes. Participants with a more prosocial disposition chose less selfish water consumption strategies, and obtained higher cumulative incomes than individuals who used more selfish irrigation strategies. On the other hand, it has shown that trust moderates the relation between prosocialness and selfish irrigation strategies, strengthening the negative association between these two variables. Prosocial individuals with high trust levels behave in an even less selfish way than prosocial individuals with low trust levels.In conclusion, we would like to reaffirm the relevance, highlighted by EC helped to the design of the project, she performed the statistical analyses, and she is the principal redactor of the paper. CT is the main researcher of the project in which the paper is framed, she designed the project, recollected the data with the co-authors, she has collaborated in the redaction of the paper. RG has collaborated in the data recollection and in the redaction of the paper. JS has designed the Irrigania Game used in the experiment, and has collaborated in the redaction of the paper. BL has collaborated in the redaction of the paper.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.


Most analyses of gaps in human resources for health (HRH) do not consider training and the transition of graduates into the labour market. This study aims to explore the labour market for Peru’s recent medical, nursing, and midwifery graduates as well as their transition into employment in the Ministry of Health’s (MOH) system.Data from four different datasets, covering 2007–2013, was used to characterize the patterns of recently trained physicians, nurses, midwives, and postgraduate-trained physicians that enter employment in the MOH system, and scenario analyses were used to describe how this rate of entry needs to adapt in order to fill current HRH shortages.HRH graduates have been increasing from 2007 to 2011, but the proportions that enter employment in the MOH system 2 years later range from 8 to 45% and less than 10% of newly trained medical specialists. Scenario analyses indicate that the gap for physicians and nurses will be met in 2027 and 2024, respectively, while midwives in 2017. However, if the number of HRH graduates entering the MOH system doubles, these gaps could be filled as early as 2020 for physicians and 2019 for nurses. In this latter scenario, the MOH system would still only utilize 56% of newly qualified physicians, 74% of nurses, and 66% of midwives available in the labour market.At 2013 training rates, Peru has the number of physicians, nurses, and midwives it needs to address HRH shortages and meet estimated HRH gaps in the national MOH system during the next decade. However, a significant number of newly qualified health professionals do not work for the MOH system within 2 years of graduation. These analyses highlight the importance of building adequate incentive structures to improve the entry and retention of HRH into the public sector. Changes in demography, epidemiology, and disability burden patterns create increasing pressure on healthcare systems and the roles of healthcare professionals . In ordeThe World Health Organization has defined the minimum threshold to provide essential maternal and child healthcare services as 23 physicians, nurses, and midwives per 10 000 population , as a loBenefiting from access to primary data sources, this study has three objectives: (1) to quantify how many recently trained physicians, nurses, and midwives enter the national health system of the Ministry of Health (MOH); (2) to describe how the rate of entry into Peru’s health sector should adapt in order to fill the HRH gap in physicians, nurses, and midwives at the primary care level, [NB: this gap has been defined by the MOH  as a difHealthcare in Peru is provided by the MOH, ESSALUD, Armed Forces and National Police, and the private sector. The publicly funded MOH system cares for approximately 60% of the population, while ESSALUD, a contribution-based social security system, covers approximately 30% , 10. FigIn terms of the offer of training for health professionals, there was a significant increase in the number of private universities created during the 1990s in Peru. Thus, the offer of university-level training has increased significantly . At the This study used four databases: (a) graduate numbers from university training programmes for physicians, nurses, and midwives for 2007–2011 were obtained from the National Assembly of Deaneries , the average uptake of employment over the time period was 28% for physicians, 37% for nurses, and 33% for midwives.Table Table This study reports on a particular point in the cycle of HRH planning: the transition from training to employment in the national health system, in a country where this sector provides care for 60% of the population. Results from this analysis of primary data show that at 2013 training rates, Peru has the number of physicians, nurses, and midwives it needs to meet the estimated HRH gap in the national MOH system during the next decade. This is explained by the number of HRH graduates, which has been increasing from 2007 to 2011 due to the additional offer of training provided by private universities [Shortages in HRH have been reported in Peru indicating substantial deficiencies in the total number of available healthcare professionals and medical specialists , 13. UsiThe differences in the proportion of graduates who enter SERUMS (nearly 100% of physicians vs. 62% of nurses and 85% of midwives over the time period) in the immediate year after graduation could indicate that nurses and midwives may have other options of immediate employment in the private sector or the social security system that do not require being posted in a remote and rural area and may even offer longer-term opportunities than the MOH.The average proportion of SERUMS healthcare professionals entering the MOH system has been consistently low, 28% of physicians, 38% of nurses, and 33% of midwives. To increase the number of healthcare professionals in the MOH system, strategies to raise the proportion of SERUMS-completed healthcare professionals and graduated medical specialists entering the MOH system need to be explored. In 2009, the Peruvian government instituted a strategy to increase the number of SERUMS positions at rural and remote outposts available to physicians [Entering employment in the MOH system from SERUMS is clearly not linear, but further investigation is needed to understand the specific barriers such as those on the supply side  or the In addition to the low proportions of SERUMS-completed healthcare professionals and medical specialists entering the MOH system, the workforce shortage is compounded by mismatched training competency. Peru has been able to meet its demand for training in healthcare professions, with 70% of graduates attending private universities, yet a massive disconnect remains between the primary care-level competencies developed in universities and those desired by the MOH . This miThese findings can be relevant to health systems in other countries, where quantity of HRH may not be critical but other constraints and barriers, fiscal or otherwise, exist . For exaThis study provides an assessment of the transition of healthcare professionals from university training, through SERUMS, and entry into the MOH system. It moves beyond merely quantifying HRH and signalling gaps in density to explore what happens to HRH within the local labour market and incorporates the complexity of various transition points. The main strength of this study included the ability to track individuals over time to assess if they ultimately become employed by the MOH system in the immediate year after completing their SERUMS, providing a robust exploration of trends over the time period. It makes use of primary data, rather than models or theoretical assumptions, and as such could be considered innovative. The focus of the study has international significance in relation to the market for physicians, nurses, and midwives in Peru, particularly in attracting new graduates into employment in the Ministry of Health’s (MOH) system. Nevertheless, this study has limitations. Data on HRH in this study accounts for those working for the MOH system, excluding those working for other sectors, such as ESSALUD and the private sector. Yet, because the MOH system covers the majority of the population, these findings still show evidence of matters causing the gap in healthcare professionals. Furthermore, the MOH’s databases shared with the authors did not include information on salaries, and no primary data sources on levels of HRH unemployment and migration existed to the knowledge of the authors. Projections were based on average rates for a period of 5 years. The analysis looked at the transition of HRH from graduation, to SERUMS, and then employment in the MOH system in the immediate years after but did not consider that professionals may join further on. However, it can be assumed that those employed by the MOH system are not employed by ESSALUD at the same time , although they might have a dual practice in the private sector. In spite of its limitations, the scenario projections included in this study may prove useful to policymakers in Peru and other countries in the same stage of development, to persuade them to use concurrent and synergic strategies to address gaps in HRH.Peru faces significant HRH shortages, and an analysis of its labour market shows a complex pattern with high availability of newly graduated HRH, and yet low entry into employment structures of the MOH system. These analyses provide evidence of the importance of understanding health labour market trends as a basis to build incentive structures for HRH to join the public national health system, not only in Peru but also in other countries investing in the development of their HRH.


Urban slums are characterised by unique challenging living conditions, which increase their inhabitants’ vulnerability to specific health conditions. The identification and prioritization of the key health issues occurring in these settings is essential for the development of programmes that aim to enhance the health of local slum communities effectively. As such, the present study sought to identify and prioritise the key health issues occurring in urban slums, with a focus on the perceptions of health professionals and community workers, in the rapidly growing city of Bangalore, India.The study followed a two-phased mixed methods design. During Phase I of the study, a total of 60 health conditions belonging to four major categories: - 1) non-communicable diseases; 2) infectious diseases; 3) maternal and women’s reproductive health; and 4) child health - were identified through a systematic literature review and semi-structured interviews conducted with health professionals and other relevant stakeholders with experience working with urban slum communities in Bangalore. In Phase II, the health issues were prioritised based on four criteria through a consensus workshop conducted in Bangalore.The top health issues prioritized during the workshop were: diabetes and hypertension (non-communicable diseases category), dengue fever (infectious diseases category), malnutrition and anaemia . Diarrhoea was also selected as a top priority in children. These health issues were in line with national and international reports that listed them as top causes of mortality and major contributors to the burden of diseases in India.The results of this study will be used to inform the development of technologies and the design of interventions to improve the health outcomes of local communities. Identification of priority health issues in the slums of other regions of India, and in other low and lower middle-income countries, is recommended.The online version of this article (10.1186/s12889-018-5194-2) contains supplementary material, which is available to authorized users. While rapid urbanization is emerging as a major challenge globally, the population of urban poor is expected to grow worldwide. Over 800 million people are thought to live in urban slums at present globally, with an estimation to double in the next 30 years . In Indipers comms.). This includes non-notified slums, which are not recognized formally by the government, and lack many vital services, facilities and amenities [Within this wider context, Bangalore is a rapidly expanding and developing city that is situated in the southern Indian state of Karnataka, and attracts a large number of migrants from surrounding rural areas . While tmenities .Urban slums are characterised by poverty, housing of poor structural integrity, overcrowding, poor access to water, sanitation and other facilities, and challenging living conditions overall, which impact their inhabitants directly and indirectly , 7. All Addressing the health challenges of urban slum communities is becoming an increasingly important consideration in global health . A cruciThe findings of this study are used to develop a mobile diagnostic and screening toolkit that will help to detect and address the major health challenges in these communities more effectively.A two-phased mixed methods design was used in the present study. The aim of Phase I of the study was to identify the health issues reported from urban slums through a systematic literature review and semi-structured interviews with health professionals, community workers and other relevant stakeholders, while Phase II involved the prioritization of these health issues through a consensus workshop. In addition to the data extracted from the literature and interviews, data gathered from a community health centre situated in a slum area in Bangalore and a community consultation activity were used to gain additional insights to complement and enrich the findings of the literature review and interviews. Figure health, disease, healthcare and health problems combined in all possible configurations with the terms slums, urban slums and poverty areas. Two researchers (AW and SA) screened and scored the initial set of titles retrieved based on pre-defined inclusion and exclusion criteria independently. At the beginning of the search, studies from any location were included if they focused on health issues in urban slum setting, so as to get a general overview of the various health issues that exist in the urban slums globally. However, studies were only included in the final analysis if they focused specifically on health issues in urban slum settings in India. Articles that focused exclusively on rural slums, had a veterinary focus, were not written in English, were duplicated, or focussed exclusively on risk factors were excluded. Articles were assigned a score of 0 points if they failed to meet the inclusion criteria, 1 point if they met the criteria partially, and 2 points when they met the inclusion criteria fully. The scores of both researchers were summed and titles scoring a total of two or more points in the first round were examined during the screening of abstracts. When no abstract could be retrieved, the title was scored again. The scores of both researchers were added, and when the total score equalled two or more, the publication was selected for full text analysis. Relevant information, including the health issues mentioned, the specific geographic focus, the target demographic, the study design and the sample size, were extracted from the text. Quality assessment of the publications retrieved was outside the scope of the present study. Cohen’s Kappa was calculated to determine the level of agreement between the two reviewers in the title and abstract assessments.A systematic literature search was performed to identify publications that focus on health issues in urban slums in India. The databases Pubmed, Embase, Cinahl, Cochrane and Google Scholar were searched for records up to August 2016 using the following terms: Semi-structured interviews were conducted to gain insight into the health issues in urban slums with a specific focus on the city of Bangalore. Relevant stakeholders with experience working with urban slum communities in Bangalore, including health professionals and community health workers, were recruited through a snowball sampling strategy. The objectives and procedures of the interviews were described via an e-mail invitation to potential participants. The interviews were conducted via video conference at a time convenient to the participant, and with the aid of a semi-structured interview topic guide. Interviews were conducted on an individual basis, or in small groups, depending on the availability and preferences of participants. The interviews lasted approximately 30–45 min. All participants provided verbal consent prior to the interviews and were given assurances about the maintenance of their anonymity and data confidentiality. All interviews were audio-recorded and summarised following each discussion, with the summaries being shared with the interviewees afterwards for confirmation.A list of all the health issues mentioned in either the literature or by interviewees was compiled and examined. The health issues were then categorised into four main themes: 1) non-communicable diseases; 2) infectious diseases; 3) maternal and women’s reproductive health; and 4) child health. This categorisation was not mutually exclusive; each health issue could be listed under more than one category if appropriate.During the second phase of the study, a workshop was conducted in Bangalore in October 2016 to reach a consensus with the participants on the priority health issues for the local urban slum communities. The majority of participants were interviewees from the first phase, in addition to experts who were invited to participate in the workshop due to their expertise in developing health technologies for low income settings. Preliminary findings from Phase I were shared with the participants. Scoring sheets listing the health conditions identified were prepared for each disease category, and participants were asked to score the health issues in each category based on four criteria: prevalence of the health issue in urban slums (refers to how common it is in urban slum communities they work with); seriousness of the health issue ; feasibility of diagnosing/screening for it in the field (refers to the likelihood of being able to screen for the condition in the field); and how beneficial it would be to detect the issue early . These criteria were selected considering the overarching objective of the wider project to which the study belongs . The definitions of the scoring criteria were discussed with the participants prior to the prioritisation exercise so that participants shared a similar perception of each of the criteria. Participants were asked to assign a score between 0 and 5 to each health issue; where 1 is the lowest score, 5 is the highest and 0 is “I don’t know”. For example, assigning a score of 1 to a particular health issue for the seriousness of health issue criterion indicates that the health issue is relatively less serious with reference to the urban slum community. All criteria were given equal weight in the calculation of scores, and the average score assigned to each health issue was calculated by summing the scores assigned to a particular health issue by all participants and dividing this total score by the number of participants. Health issues were then ranked from highest score to lowest in all four categories, based on their average score.Figure n = 35) of the studies assessed were observational, of which 27 were cross-sectional. The literature examined included five qualitative studies, five reviews, six studies of mixed methods design, one quasi-experimental study and five studies where the study design did not fit the categories mentioned above. Sample sizes ranged from four to 62,239 and the participants belonged to a range of different age groups. Children were the most studied group in the literature, with 50% of the studies (n = 30) reporting health issues exclusively in children. Their health issues were also mentioned in studies that reported health outcomes across a range of age groups (n = 9). A total of 12 studies focused solely on women’s health issues, whereas only two studies focused specifically on men’s health problems and one study focused on the older people. With regard to the geographic regions of the studies, 38% of the studies (n = 23) were conducted in urban slums located in the Northern region of India, compared to 13 studies in the Western region, nine in the East, three in the South and two in the Central region. A summary of the findings of the literature can be found in an additional file [see Additional file Overall, 59% ((insert after the results of Phase 1). In total, 57 health issues were identified from the literature (see the first column of Table n = 28) identified in the literature can be classified as non-communicable diseases, whereas twenty-four issues can be classified as infectious diseases. Several of the health issues identified from the sources examined (n = 16) were endocrine, nutritional and metabolic diseases, such as diabetes and nutritional deficiencies. Almost half of the conditions (n = 12) mentioned in children were infectious in nature, while a third were nutrition-related (n = 8). Diseases of the genito-urinary system, pregnancy-related problems and nutrition-related conditions, such as anaemia and malnutrition, were the main health issues mentioned with regard to women’s maternal and reproductive health.Table A total of 19 participants who work closely with local communities in 5 large urban slums  in Bangalore were interviewed - six health professionals ; ten community health workers ; and three other participants .n = 18) can be classified as non-communicable conditions. One of the participants stated that “chronic conditions like diabetes and hypertension can be found in almost every family”, reflecting the prevalence of such health issues in the context of urban slums in Bangalore. Thirteen of the health issues can be classified as infectious conditions. These conditions were referred to in many interviews as acute conditions, viral diseases, seasonal infections and monsoon related infections. For example, one participant stated, “During our work with people in the slums, we encountered a lot of infectious monsoon-related diseases like chikungunya, malaria and dengue fever”. Children were identified by many participants as one of the groups most vulnerable to health issues in urban slums. Diarrhoea (mentioned in 17 interviews) and malnutrition (mentioned in 12 interviews) were the most frequently reported health problems in children, followed by acute respiratory infections (mentioned in 11 interviews). One of the participants stated that “In child health, malnutrition is a major issue due to lots of reasons like lack of food availability, food insecurity and lack of money to buy food”. Women were also identified as a major group on which the burden of ill health falls, and were reported to be the most frequent visitors to outpatient clinics in the local community health centres. This is illustrated by the observation of by one of the participants that “70 % of (our) patients in the clinic are women”. Reproductive tract infections (mentioned in 14 interviews) and anaemia (mentioned in 11 interviews) were the most commonly mentioned health issues for women.A total of 37 health issues were reported as major problems in urban slums in Bangalore during the interviews .Non-communicable diseasesMalnutrition, diabetes and hypertension were selected as the top health priorities in the category of non-communicable diseases in terms of both their prevalence and the feasibility of screening for them in the field. However, malnutrition was not seen as one of the top five health issues in terms of the potential benefits of screening for it early in the field, while neither hypertension nor diabetes was selected as a top priority with regard to seriousness of the health condition. Some conditions scored highly on one or two criteria, but not on other criteria. Cancer, renal problems and coronary heart diseases, for instance, were amongst the top five priority health issues in terms of their seriousness, but not with regard to any other criteria.Infectious diseasesDengue fever was identified as one of the top five infectious health issues for all four criteria, followed by diarrhoea and sexually transmitted infections (STIs), which were prioritised in terms of three criteria. The remaining health issues in this category were selected as top health priorities in one or two criteria only.Maternal and women’s reproductive healthMalnutrition and anaemia were scored as the top two priority health issues in the maternal and women’s reproductive health category, in terms of all four criteria. Vitamin deficiencies was perceived as a highly prevalent and serious, but was not selected as one of the top priorities in terms of feasibility of screening and benefits of early screening in the field. Other conditions were prioritised under only one criterion, including obesity for the prevalence of the health issue criterion, and urinary tract infections (UTIs) for the feasibility to screen for in the field criterion.Child healthDiarrhoea was selected as the top health priority for children on all criteria, followed by malnutrition, anaemia and sepsis.A total of fourteen participants - three health professionals, four community workers, four technology experts and three other participants with experience working in health projects in urban slums - completed the prioritization exercise carried out during the consensus workshop in Bangalore. Participants scored a total of 28 health issues in the non-communicable diseases category, 24 health issues in the infectious diseases category, 14 health issues in the maternal and women’s reproductive health category and 28 health issues in the child health category. Table Aside from the examination of literature and stakeholder interviews, additional insights were gained through data gathered from a community health centre, and a community consultation activity in a prominent slum area in Bangalore, in order to enrich the findings of the study.The data from the community health centre consisted of the numbers of patients that visited the clinic, as well as an indication of the nature of their ailment, and indicated that the majority of the 23,056 patients examined at the clinic over a period of two years were reported to have complaints related to diabetes, hypertension and/or heart disease (61.4%), while 36.2% were reported to have central nervous system-related complaints, 26.9% musculoskeletal issues, 26.3% dental issues, 11.9% gynaecological issues, 11.2% ophthalmological issues and 10.8% respiratory issues. Other health issues reported from the clinic data include gastrointestinal issues, dermatological issues, obstetric issues, issues requiring surgery, endocrine issues, urological issues, nutritional issues and psychiatric issues.The community consultation session sought to explore the local community perceptions of health and the health issues they face. Approximately 30–40 people participated in this activity, during which they were invited to share their thoughts on the main health issues faced by them, their families and neighbours. Overall, the perspective communicated by the local community initially was that they do not face many health issues. However, following further discussion, the health complaints that were reported during the community consultation session include cold, fever, dental caries and infections, asthma, otitis media, respiratory tract infections, diabetes, blood pressure, anaemia, spontaneous abortion/miscarriages, epilepsy, tuberculosis, kidney stones, thyroid problems, nephrotic issues, accidents, stroke and reproductive morbidities. Although diarrhoea was mentioned, the community did not see this as a major problem below one year of age. Further, they indicated that they only go to the hospital when there is a major crisis. It should be noted that these conditions were referred to using local terminology, with the discussion facilitated and interpreted by doctors and health workers who work with the community on a regular basis.This study aimed to identify the priority health issues in urban slums in Bangalore, India. Malnutrition and anaemia were identified as top priorities for women and children. This finding was expected, as these conditions top the list for factors contributing to the disease burden in India overall , particuNevertheless, the frequency of being reported in the literature is not necessarily a reflection of the prevalence of a particular health issue among the urban slum communities in Bangalore. On the contrary, it might indicate a publication bias or the prominence of that health issue in a region or at a given point in time. In this study, several conditions were identified as priorities in the workshop despite not receiving much attention in either or both of the data sources during the first phase of the study. For instance, dengue fever was selected as a top priority in the infectious diseases category for all four criteria during the prioritisation exercise. Given that it is a seasonal or epidemic health issue, it is possible that seasonality was taken into account when scoring the criteria for this condition. Sepsis was also selected as a priority health condition in the child health category for three criteria, which is in line with the WHO statistical profile of India that lists neonatal sepsis as one of the main causes of mortality in children under the age of five . FurtherThis study also demonstrated an equal distribution of health issues across infectious and non-communicable disease categories in both data sources examined in the first phase of the study, which might indicate that both types of health issues are of almost equal importance in urban slums in Bangalore. This is contrary to the common belief that infectious diseases would be more dominant in these areas  due to pWomen and children were found to be the most studied demographic groups in the literature review, and were also identified by interviewees as the most vulnerable groups in the slums. This is consistent with several national and international reports, which reveal large inequities in the health and mortality rates of women and children in Low and Lower Middle-Income Countries (LMICs).It would have been beneficial to compare the results of this study with priority health issues in slums in other parts of India, and the world, to understand the similarities and variations of health issues in different settings. However, studies on priority health issues in urban slums are scarce. The vast majority of studies that examine the health status of urban slum dwellers focus on reporting the prevalence of specific health issues or causes of ill health in slums and so do not provide a suitable comparison.One of the main strengths of this study is that it followed a mixed methods approach, which helped to gain a better understanding of the health issues in urban slums in Bangalore than would be obtained by a single method of data collection. For instance, several health issues identified from the literature were not mentioned in any of the interviews, and would have been missed in the prioritisation activity if only one data source was used. Further, the perceptions of the local slum community expressed during the community consultation session with regard to their health provided additional, and unexpected insights, that would have otherwise been missed. For example, they did not regard diarrhoea as a serious health problem among children below the age of one year, despite the fact that diarrhoea can be life threatening at this age and was identified as a priority health issue for the local urban slum community during the prioritization exercise. Certain health issues can become “normalised” due to their high prevalence and close association with the challenging living conditions in slums, and the fact that there is often little that slum dwellers can do to address them. Therefore, it was important to engage with local communities, and better understand their perceptions of health and priorities in order to develop future interventions based on their needs.One of the limitations of the study was the sampling strategy utilized for the interviews. Snowball sampling was used to recruit participants as it would have otherwise been difficult to identify interviewees within the local context. This might have introduced some bias into the health issues identified in the interviews as the sample is not necessarily a clear representation of all people working in health-related projects in the slums. However, it is anticipated that using other data sources (e.g. examination of the literature) to identify the health issues in urban slums may have overcome this bias partially. Also, the professional background of the participants might have influenced the health conditions identified, particularly in the case of the technology experts as their area of expertise was different to the remaining participants. However, by comparing their results to the rest of the group, no considerable difference was observed which may be due the fact that many of them were familiar with urban slum settings and health challenges of these settings through other initiatives.Although there are similarities in the living conditions of urban slums in different regions, and the findings of the present study may be useful to stakeholders working with urban slum communities outside of Bangalore, extrapolation to other slums within India and elsewhere should be done with caution, as all slums have their own unique characteristics, challenges and health issues. Also, the priority health conditions identified were based on criteria relevant to the objective of the wider project to which this study belongs . This might need to be taken into consideration when interpreting the results of the prioritisation exercise as there might be other criteria that are relevant to the local communities.The study was of exploratory in nature and aimed to identify and prioritise health conditions occurring in the urban slums of Bangalore. Hence, identifying and addressing factors contributing to the burden of ill health in these communities was beyond the scope of this study. However, it is noteworthy that this study is linked to a large initiative called “Health in Slums” which aims at improving the health and wellbeing of urban slums communities in Bangalore and include other projects that address some of the challenging living conditions faced by these communities.Following the completion of the present study, a preliminary prototype of the toolkit was developed by the project team. This initial prototype has been field tested and evaluated through a pilot study in one large slum, and it is expected that it will be refined and developed further through future projects.Urban slums have unique characteristics in terms of the challenging living conditions that make their inhabitants vulnerable to specific health issues. Identification of the priority health issues in urban slums is a necessary step in ensuring that any intervention that aims to improve the health status of the local urban slum communities is based on their needs, and that resources are allocated to the most important health issues. In this study, several health issues were selected as top priorities for the urban slums of Bangalore, India. The results of this study can be used to inform the design of interventions to improve the health status of local urban slum communities in Bangalore. Further, its findings are being used by the research team to develop a screening and diagnostic toolkit to address the priority health issues identified through the present study.Additional file 1:Summary of the findings of the literature. 59 articles were examined in full. The following table summarises the findings of these articles which include the objective of the study, its location, the target demographics, the study design, the sample size and the health issues mentioned in each study. (DOCX 29 kb)


For the past few decades, the Eastern Mediterranean Region has been one area of the world profoundly shaped by war and political instability. On-going conflict and destruction have left the region struggling with innumerable health concerns that have claimed the lives of many. Wars, and the chaos they leave behind, often provide the optimal conditions for the growth and re-emergence of communicable diseases. In this article, we highlight a few of the major re-emerging vaccine preventable diseases in four countries of the Eastern Mediterranean Region that are currently affected by war leading to a migration crisis: Iraq, South Sudan, Syria, and Yemen. We will also describe the impact these infections have had on patients, societies, and national health care services. This article also describes the efforts, both local and international, which have been made to address these crises, as well as future endeavors that can be done to contain and control further devastation left by these diseases. The Evolution and Eradication of Infectious Diseases, stated that “it seems reasonable to anticipate that within some measurable time … all the major infections will have disappeared”  Eastern Mediterranean Region (EMR) is one area of the world that is currently undergoing major political and economic upheaval. Of the 22 countries that comprise the region, Iraq, South Sudan, Syria, and Yemen, are four countries currently undergoing continuous conflict leading to mass displacement. These countries, in addition to the migratory routes undertaken by refugees to neighboring countries, are mapped in Figure In this review, we will highlight the delicate interplay between war, displacement, and the re-emergence of once eradicated vaccine-preventable diseases (VPDs), namely cholera, measles, and polio, as illustrated in Table Vibrio cholerae. Just like other infectious diseases, cholera can easily spread in areas of poor sanitation with contaminated water supplies such as refugee camps. There have been seven cholera pandemics since the seventeenth century, and most outbreaks have been closely linked to conflict and economic crises : a member of the ountries . In 1997ountries . With waIn the past three decades, Iraq has undergone many political calamities, leaving the country into a constant state of insecurity. In 2003, the country was thrown into political upheaval that was compounded with United States involvement. Although the Iraq War officially ended in 2011, conflict has continued to involve different religious and ethnic factions, contributing to a crackdown in social order with almost 3 million people internally displaced by 2017 . ThroughPrior to the eruption of the Gulf Wars in the 1980s, Iraq provided free health care to its people in 172 hospitals and 1,200 primary health care centers located throughout the country . Since tIn 2000, about 61% of Iraqi children were fully vaccinated . Just 1 During the 1980s, polio immunization was mandatory in the country. In the 1990s and until 2003, national polio vaccination campaigns were held annually, and vaccination rates reached those similar to the pre-Gulf War era . In the In the early 1980s, Iraq adopted the WHO Expanded Program on Immunization (EPI) leading to a decrease in the annual number of measles cases from 39,000 to 9,400 . The couAdequate vaccination is crucial to achieve herd immunity and prevent the occurrence of outbreaks. A study conducted in 2012 showed that even those who had received one dose of the MCV vaccine had a 3.7 times lower risk of contracting measles compared to those who had never received it . Some ofAfter decades of civil war in Sudan, South Sudan finally seceded and declared its independence in 2011, making it the world’s youngest nation. Although the separation was followed by a period of peace, by 2013 civil unrest resurfaced among different ethnic and political factions, eventually leading to one of the worst refugee crises of the modern world. By 2017, of the nearly 13 million South Sudanese citizens, almost 2 million people have been internally displaced, and with another 1.4 million refugees in neighboring countries, mainly Uganda and Ethiopia . In addiPrior to the eruption of war, Sudan employed a government-run Public Health System that was the only provider of health services. After 2011, a three-layered health system structure was adopted consisting of Primary Health Care Units (PHCU), Primary Health Care Centers (PHCC), and hospitals . In 2006With the rising refugee and migration crisis in the country, the health care system has suffered major setbacks. Currently, the country has one of the worst health indicators worldwide, with life expectancy at the age of 54 years. The health care system is also suffering from a severe shortage of health professionals with one physician for every 65,574 people . DespiteOne recent survey found that the percentage of fully immunized children was only 7.3%, with the percentage of partially immunized children not much higher . In 2000Another disease that has flourished in South Sudan in recent years is cholera. Although endemic to the country, a devastating outbreak of the disease has claimed the lives of 320 people and afflicted 17,785 others since June 2016 . When itDespite their successes, vaccination campaigns are not sufficient to solve the growing problem. Access to health care services is often impeded and the presence of refugees and displaced people in rural areas, away from major cities serves only to compound the problem. In addition, an on-going famine in the country has left almost a million people on the brink of starvation, leaving those inflicted immunocompromised and unable to fight off an otherwise mild infection .Similarly, the chaos created by wars and conflict make proper surveillance and monitoring systems of vaccination programs a difficult, yet necessary task. In June 2017, the South Sudanese government announced the death of 15 children due to contaminated measles vaccines . InadequDuring the 1960s, Syria underwent major political upheaval with the establishment of a socialist government. Despite the political reforms, the country enjoyed relative economic stability, which reflected well on the health care system. During that time, health care primarily consisted of a government-run system that provided citizens with access to nationwide primary health care services . PoliticSince 2011, the country has been at the center of a political crisis that has taken the world by storm. More than 5 years after the start of the Syrian Civil War, the world has witnessed one of the worst refugee crises seen since WWII . A recenOther than the direct casualties of war, the Syrian crisis has claimed many victims from basic health care issues that otherwise could have been prevented. Hospitals and ambulances were the frequent targets of missiles and explosions, leading to a crumbling of any health care infrastructure previously present. More than 700 medical workers have been killed since the start of the war in 2011 and more than 60 health care facilities have been destroyed in the past year alone . InternaIn Syria, prior to the outbreak of the war, the last documented case of polio was reported in 1999. The lack of proper immunization, coupled with contaminated living conditions, led to the re-emergence of polio after many years of obscurity, with the first case documented in October 2013, and eventually reaching 35 cases within the same year . The wilBy 2014, the WHO announced that polio had become a Public Health Emergency of International Concern . These dFactors that may jeopardize this success include continued conflict, inability to reach besieged areas, and the rapidity by which the disease can spread in poor living conditions. Continued efforts need to be made by both international and local groups to ensure continued immunizations against devastating diseases such as polio. In 2010, a case of polio reported in the Republic of Congo revealed a mutated virus in a previously immunized individual. While there have been no reports in Syria of mutated polio virus infections in vaccinated individuals, it is imperative to keep in mind that effective eradication of the disease will need to take into account possible antigenetic variants that can continue to persist despite adequate vaccination measures .In March 2015, Yemen underwent major political upheaval when war broke out between different religious factions. Since then, thousands have been killed and many more have been displaced. Yemen, which had a fragile health care system prior to the onset of war, did not have the infrastructure to withstand these changes and is currently on the brink of collapse. Prior to the war, Yemen had one of the highest rates of childhood malnutrition worldwide . In the Prior to the war, Yemen had a relatively stable vaccination rate reaching 70–80% of the target population . By NoveOn October 6, 2016, health authorities in Yemen announced an outbreak of cholera. By the end of December of the same year, there had been 163 confirmed cases, with 96 associated deaths . By JuneVulnerable groups include children and the elderly, in addition to immunosuppressed people and those with multiple comorbidities. A failing sewage system, continued conflict and inadequate health care facilities are only a few of the reasons contributing to this problem. Malnutrition, which is a significant consequence of the Yemen War, has further contributed to this outbreak. Without adequate assistance from both local and international relief agencies, cholera is expected to claim many more lives.In 2013, the WHO developed a document titled “Vaccination in acute humanitarian emergencies: a framework for decision making” aimed at helping aid agencies and policy makers with a systematic method of vaccinating in times of humanitarian crises, that is developed to take epidemiological and contextual factors into account . The WHOAdequate monitoring of vaccination, through the use of EPI cards and other validated recall methods, is crucial to ensure adequate surveillance of vaccination rates and coverage . ApproprDelayed identification and treatment contribute to the spread of infectious diseases, making them even harder to control. Health care volunteers may unknowingly become carriers of diseases and transmit them back to their home countries. With globalization and the advent of international travel, diseases that were once restricted to a particular community now threaten to inflict communities worldwide . Speedy While immediate medical attention is in dire need, there is a need to re-focus efforts toward long-term public health measures that are likely to benefit people for years to come. Post-conflict Needs Assessments (PCNAs), which are multilateral exercises needed to evaluate the health care services in affected areas, should be undertaken by international organizations in collaboration with national governments . FinanciMany health facilities in the aforementioned countries have been destroyed by conflict, and the lack of the electricity and running water makes the operation of any health care infrastructure difficult to achieve. Security concerns prevent volunteer workers and patients from venturing out of safe zones in search of health services. Wars also often drive highly educated professionals such as nurses and doctors to flee, leaving the country with a shortage of medical workers that are unable to shoulder the burden of a large, ailing population. Medical equipment and facilities are as scarce as those that operate them. Any future talks about re-building these countries’ health care systems need to include sustainable investments in infrastructure.In addition to infrastructure, it is important that health care providers choose appropriate methods for approaching those in need of medical care. For example, refugees have been shown to be less likely than others to seek health care. The costs of vaccination were cited as a major barrier for seeking health care among Syrian refugees in Jordan . Also, lPolio, measles, and cholera are but a few of the re-emerging vaccine preventable diseases that continue to pose a significant health burden in developing countries and in regions of political instability. While reports of war tend to focus on the casualties caused by airstrikes and ammunition, the long-term health consequences caused by inadequate prevention and treatment of communicable diseases are often ignored. War-affected countries rely on the efforts of the international community to recognize that the re-emergence of vaccine-preventable diseases is a global threat that requires a multinational approach. Until the political situations are resolved in these war-torn countries, infectious diseases will continue to spread and inflict vulnerable populations. We are now more than a decade into the twenty-first century, and re-emerging infectious diseases in times of war continue to pose a real and frightening threat to mankind.As no animals or humans were involved in this research endeavor, institutional review board approval was not required.IH provided the idea and supervised the whole process from inception to the final editing and submission of the manuscript. RR is the first author and did the literature search and wrote the whole manuscript. SS, NC, SC, and AL did the literature, drafted the paper, and critically revised it for important intellectual content. All authors gave final approval of the version to be published.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.