Clinical evaluation of ceramic inlays and onlays fabricated with two systems: five-year follow-up

This study evaluated the five-year clinical performance of ceramic inlays and onlays made with two systems: sintered Duceram (Dentsply-Degussa) and pressable IPS Empress (Ivoclar Vivadent). Eighty-six restorations were placed by a single operator in 35 patients with a median age of 33 years. The restorations were cemented with dual-cured resin cement (Variolink II, Ivoclar Vivadent) and Syntac Classic adhesive under rubber dam. The evaluations were conducted by two independent investigators at baseline, and at one, two, three, and five years using the modified United States Public Health Service (USPHS) criteria. At the five-year recall, 26 patients were evaluated (74.28%), totalling 62 (72.09%) restorations. Four IPS restorations were fractured, two restorations presented secondary caries (one from IPS and one from Duceram), and two restorations showed unacceptable defects at the restoration margin and needed replacement (one restoration from each ceramic system). A general success rate of 87% was recorded. The Fisher exact test revealed no significant difference between Duceram and IPS Empress ceramic systems for all aspects evaluated at different recall appointments (p>0.05). The McNemar chi-square test showed significant differences in relation to marginal discoloration, marginal integrity, and surface texture between the baseline and five-year recall for both systems (p<0.001), with an increased percentage of Bravo scores. However, few Charlie or Delta scores were attributed to these restorations. In conclusion, these two types of ceramic materials demonstrated acceptable clinical performance after five years

Human hemorrhagic pulmonary leptospirosis: pathological findings and pathophysiological correlations.

Abstract Background: Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil‘s syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease. Principal Findings: Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage. Conclusions: Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary noninflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease.

Design and control techniques of optical networks

The world of communication has changed quickly in the last decade resulting in the the rapid increase in the pace of peoples’ lives. This is due to the explosion of mobile communication and the internet which has now reached all levels of society. With such pressure for access to communication there is increased demand for bandwidth. Photonic technology is the right solution for high speed networks that have to supply wide bandwidth to new communication service providers. In particular this Ph.D. dissertation deals with DWDM optical packet-switched networks. The issue introduces a huge quantity of problems from physical layer up to transport layer. Here this subject is tackled from the network level perspective. The long term solution represented by optical packet switching has been fully explored in this years together with the Network Research Group at the department of Electronics, Computer Science and System of the University of Bologna. Some national as well as international projects supported this research like the Network of Excellence (NoE) e-Photon/ONe, funded by the European Commission in the Sixth Framework Programme and INTREPIDO project (End-to-end Traffic Engineering and Protection for IP over DWDM Optical Networks) funded by the Italian Ministry of Education, University and Scientific Research. Optical packet switching for DWDM networks is studied at single node level as well as at network level. In particular the techniques discussed are thought to be implemented for a long-haul transport network that connects local and metropolitan networks around the world. The main issues faced are contention resolution in a asynchronous variable packet length environment, adaptive routing, wavelength conversion and node architecture. Characteristics that a network must assure as quality of service and resilience are also explored at both node and network level. Results are mainly evaluated via simulation and through analysis.

On The Timing of Default Losses: When and Why?

At the light of what happened in 2010 and 2011, a lot of European countries founded themselves in a difficult position where all the credit rating agencies were downgrading debt states. Problem of solvency and guarantees on the states' bond were perceived as too risky for a Monetary Union as Europe is. Fear of a contagion from Greece as well was threatening the other countries as Italy, Spain, Portugal and Ireland; while Germany and France asked for a division between risky and riskless bond in order to feel more safe. Our paper gets inspiration by Roch and Uhlig (2011), it refers to the Argentinian case examined by Arellano (2008) and examine possible interventions as monetization or bailout as proposed by Cole and Kehoe (2000). We propose a model in which a state defaults and cannot repay a fraction of the old bond; but contrary to Roch and Uhlig that where considering a one-time cost of default we consider default as an accumulation of losses, perceived as unpaid fractions of the old debts. Our contributions to literature is that default immediately imply that economy faces a bad period and, accumulating losses, government will be worse-off. We studied a function for this accumulation of debt period by period, in order to get an idea of the magnitude of this waste of resources that economy will face when experiences a default. Our thesis is that bailouts just postpone the day of reckoning (Roch, Uhlig); so it's better to default before accumulate a lot of debts. What Europe need now is the introduction of new reforms in a controlled default where the Eurozone will be saved in its whole integrity and a state could fail with the future promise of a resurrection. As experience show us, governments are not interested into reducing debts since there are ECB interventions. That clearly create a distortion between countries in the same monetary union, giving to the states just an illusion about their future debtor position.

Interaction between APOE4 genotype and environmental risk factors in Alzheimer's disease

Alzheimer's disease (AD) is probably caused by both genetic and environmental risk factors. The major genetic risk factor is the E4 variant of apolipoprotein E gene called apoE4. Several risk factors for developing AD have been identified including lifestyle, such as dietary habits. The mechanisms behind the AD pathogenesis and the onset of cognitive decline in the AD brain are presently unknown. In this study we wanted to characterize the effects of the interaction between environmental risk factors and apoE genotype on neurodegeneration processes, with particular focus on behavioural studies and neurodegenerative processes at molecular level. Towards this aim, we used 6 months-old apoE4 and apoE3 Target Replacement (TR) mice fed on different diets (high intake of cholesterol and high intake of carbohydrates). These mice were evaluated for learning and memory deficits in spatial reference (Morris Water Maze (MWM)) and contextual learning (Passive Avoidance) tasks, which involve the hippocampus and the amygdala, respectively. From these behavioural studies we found that the initial cognitive impairments manifested as a retention deficit in apoE4 mice fed on high carbohydrate diet. Thus, the genetic risk factor apoE4 genotype associated with a high carbohydrate diet seems to affect cognitive functions in young mice, corroborating the theory that the combination of genetic and environmental risk factors greatly increases the risk of developing AD and leads to an earlier onset of cognitive deficits. The cellular and molecular bases of the cognitive decline in AD are largely unknown. In order to determine the molecular changes for the onset of the early cognitive impairment observed in the behavioural studies, we performed molecular studies, with particular focus on synaptic integrity and Tau phosphorylation. The most relevant finding of our molecular studies showed a significant decrease of Brain-derived Neurotrophic Factor (BDNF) in apoE4 mice fed on high carbohydrate diet. Our results may suggest that BDNF decrease found in apoE4 HS mice could be involved in the earliest impairment in long-term reference memory observed in behavioural studies. The second aim of this thesis was to study possible involvement of leptin in AD. There is growing evidence that leptin has neuroprotective properties in the Central Nervous System (CNS). Recent evidence has shown that leptin and its receptors are widespread in the CNS and may provide neuronal survival signals. However, there are still numerous questions, regarding the molecular mechanism by which leptin acts, that remain unanswered. Thus, given to the importance of the involvement of leptin in AD, we wanted to clarify the function of leptin in the pathogenesis of AD and to investigate if apoE genotype affect leptin levels through studies in vitro, in mice and in human. Our findings suggest that apoE4 TR mice showed an increase of leptin in the brain. Leptin levels are also increased in the cerebral spinal fluid of AD patients and apoE4 carriers with AD have higher levels of leptin than apoE3 carriers. Moreover, leptin seems to be expressed by reactive glial cells in AD brains. In vitro, ApoE4 together with Amyloid beta increases leptin production by microglia and astrocytes. Taken together, all these findings suggest that leptin replacement might not be a good strategy for AD therapy. Our results show that high leptin levels were found in AD brains. These findings suggest that, as high leptin levels do not promote satiety in obese individuals, it might be possible that they do not promote neuroprotection in AD patients. Therefore, we hypothesized that AD brain could suffer from leptin resistance. Further studies will be critical to determine whether or not the central leptin resistance in SNC could affect its potential neuroprotective effects.

Distribution and state of fishery resources in the Northern and Central Adriatic Sea using trawl surveys data

The Ecosystem Approach to Fisheries represents the most recent research line in the international context, showing interest both towards the whole community and toward the identification and protection of all the “critical habitats” in which marine resources complete their life cycles. Using data coming from trawl surveys performed in the Northern and Central Adriatic from 1996 to 2010, this study provides the first attempt to appraise the status of the whole demersal community. It took into account not only fishery target species but also by-catch and discharge species by the use of a suite of biological indicators both at population and multi-specific level, allowing to have a global picture of the status of the demersal system. This study underlined the decline of extremely important species for the Adriatic fishery in recent years; adverse impact on catches is expected for these species in the coming years, since also minimum values of recruits recently were recorded. Both the excessive exploitation and environmental factors affected availability of resources. Moreover both distribution and nursery areas of the most important resources were pinpointed by means of geostatistical methods. The geospatial analysis also confirmed the presence of relevant recruitment areas in the North and Central Adriatic for several commercial species, as reported in the literature. The morphological and oceanographic features, the relevant rivers inflow together with the mosaic pattern of biocenoses with different food availability affected the location of the observed relevant nursery areas.

Effects of different nutritional strategies on intestinal inflammation in pigs

Intestinal health is essential for the health of the body since the gastro-intestinal mucosa is the main site of interaction with the external environment, as well as the major area colonized by the microbiota. Intestinal health relies on proper barrier function, epithelial integrity and related mechanisms of protection (mucous layer, tight junctions, immune and inflammatory system). In pigs, during the weaning transition, intestinal inflammation and barrier integrity play a crucial role in regulating intestinal health and, consequently, pig’s health, growth and productivity. The aim of the project was to assess the impact of different nutritional strategies on the intestinal health of weaning piglets with reference to the inflammatory status and epithelial integrity. Therefore, in vivo trials were conducted to test the in-feed supplementation with zinc, tributyrin, or organic acids and nature-identical compounds (NIC) to weaning piglets. All the dietary interventions positively impacted the intestinal inflammatory status and, as a consequence, improved epithelial integrity by modulating tight junctions proteins (zinc or tributyrin) or by enhancing barrier properties measured with Ussing chambers (organic acids and NIC). These findings highlight that intestinal inflammation and barrier function are strictly linked, and that the control of inflammation is essential for adequate barrier function. In addition, in zinc trial and organic acids and NIC trial, better intestinal health could successfully result in better growth performance, as aimed for pig production improvement. To conclude, this work shows that dietary supplementation with bio-active substances such as zinc, tributyrin or organic acids and NIC may improve intestinal health of weaning piglets modulating intestinal inflammatory stress and barrier integrity and allowing better piglet’s health, growth and productivity.

Geological and hydrogeological features affecting migration, multi-phase partitioning and degradation of chlorinated hydrocarbons through unconsolidated porous media.

Chlorinated solvents are the most ubiquitous organic contaminants found in groundwater since the last five decades. They generally reach groundwater as Dense Non-Aqueous Phase Liquid (DNAPL). This phase can migrate through aquifers, and also through aquitards, in ways that aqueous contaminants cannot. The complex phase partitioning to which chlorinated solvent DNAPLs can undergo (i.e. to the dissolved, vapor or sorbed phase), as well as their transformations (e.g. degradation), depend on the physico-chemical properties of the contaminants themselves and on features of the hydrogeological system. The main goal of the thesis is to provide new knowledge for the future investigations of sites contaminated by DNAPLs in alluvial settings, proposing innovative investigative approaches and emphasizing some of the key issues and main criticalities of this kind of contaminants in such a setting. To achieve this goal, the hydrogeologic setting below the city of Ferrara (Po plain, northern Italy), which is affected by scattered contamination by chlorinated solvents, has been investigated at different scales (regional and site specific), both from an intrinsic (i.e. groundwater flow systems) and specific (i.e. chlorinated solvent DNAPL behavior) point of view. Detailed investigations were carried out in particular in one selected test-site, known as “Caretti site”, where high-resolution vertical profiling of different kind of data were collected by means of multilevel monitoring systems and other innovative sampling and analytical techniques. This allowed to achieve a deep geological and hydrogeological knowledge of the system and to reconstruct in detail the architecture of contaminants in relationship to the features of the hosting porous medium. The results achieved in this thesis are useful not only at local scale, e.g. employable to interpret the origin of contamination in other sites of the Ferrara area, but also at global scale, in order to address future remediation and protection actions of similar hydrogeologic settings.

LoneStar : Design and evaluation of an energy-efficient, disk-based archival storage system

Bandlaufwerke waren bisher die vorherrschende Technologie, um die anfallenden Datenmengen in Archivsystemen zu speichern. Mit Zugriffsmustern, die immer aktiver werden, und Speichermedien wie Festplatten die kostenmäßig aufholen, muss die Architektur vor Speichersystemen zur Archivierung neu überdacht werden. Zuverlässigkeit, Integrität und Haltbarkeit sind die Haupteigenschaften der digitalen Archivierung. Allerdings nimmt auch die Zugriffsgeschwindigkeit einen erhöhten Stellenwert ein, wenn aktive Archive ihre gesamten Inhalte für den direkten Zugriff bereitstellen. Ein band-basiertes System kann die hierfür benötigte Parallelität, Latenz und Durchsatz nicht liefern, was in der Regel durch festplattenbasierte Systeme als Zwischenspeicher kompensiert wird.rnIn dieser Arbeit untersuchen wir die Herausforderungen und Möglichkeiten ein festplattenbasiertes Speichersystem zu entwickeln, das auf eine hohe Zuverlässigkeit und Energieeffizienz zielt und das sich sowohl für aktive als auch für kalte Archivumgebungen eignet. Zuerst analysieren wir die Speichersysteme und Zugriffsmuster eines großen digitalen Archivs und präsentieren damit ein mögliches Einsatzgebiet für unsere Architektur. Daraufhin stellen wir Mechanismen vor um die Zuverlässigkeit einer einzelnen Festplatte zu verbessern und präsentieren sowie evaluieren einen neuen, energieeffizienten, zwei- dimensionalen RAID Ansatz der für „Schreibe ein Mal, lese mehrfach“ Zugriffe optimiert ist. Letztlich stellen wir Protokollierungs- und Zwischenspeichermechanismen vor, die die zugrundeliegenden Ziele unterstützen und evaluieren das RAID System in einer Dateisystemumgebung.

The role of indigenous people in national development processes: Participation and marginalisation of indigenous Bedouin in South Sinai tourism development

The Bedouin of South Sinai have been significantly affected by the politics of external powers for a long time. However, never had the interest of external powers in Sinai been so strong as since the Israeli-Egyptian wars in the second half of the 20th century when Bedouin interests started to collide with Egypt’s plans for a development of luxury tourism in South Sinai. rnrnThe tourism boom that has started in the 1980s has brought economic and infrastructure development to the Bedouin and tourism has become the most important source of income for the Bedouin. However, while the absolute increase of tourists to Sinai has trickled down to the Bedouin to some extent, the participation of Bedouin in the overall tourism development is under-proportionate. Moreover, the Bedouin have become increasingly dependent on monetary income and consequently from tourism as the only significant source of income while at the same time they have lost much of their land as well as their self-determination.rnrnIn this context, the Bedouin livelihoods have become very vulnerable due to repeated depressions in the tourism industry as well as marginalization. Major marginalization processes the Bedouin are facing are the loss of land, barriers to market entry, especially increasingly strict rules and regulations in the tourism industry, as well as discrimination by the authorities. Social differentiation and Bedouin preferences are identified as further factors in Bedouin marginalization.rnrnThe strategies Bedouin have developed in response to all these problems are coping strategies, which try to deal with the present problem at the individual level. Basically no strategies have been developed at the collective level that would aim to actively shape the Bedouin’s present and future. Collective action has been hampered by a variety of factors, such as the speed of the developments, the distribution of power or the decay of tribal structures.rnWhile some Bedouin might be able to continue their tourism activities, a large number of informal jobs will not be feasible anymore. The majority of the previously mostly self-employed Bedouin will probably be forced to work as day-laborers who will have lost much of their pride, dignity, sovereignty and freedom. Moreover, with a return to subsistence being impossible for the majority of the Bedouin, it is likely that an increasing number of marginalized Bedouin will turn to illegal income generating activities such as smuggling or drug cultivation. This in turn will lead to further repression and discrimination and could escalate in a serious violent conflict between the Bedouin and the government.rnrnDevelopment plans and projects should address the general lack of civil rights, local participation and protection of minorities in Egypt and promote Bedouin community development and the consideration of Bedouin interests in tourism development.rnrnWether the political upheavals and the resignation of president Mubarak at the beginning of 2011 will have a positive effect on the situation of the Bedouin remains to be seen.rn

Frontal white matter integrity is related to psychomotor retardation in major depression

Altered frontal white matter integrity has been reported in major depression. Still, the behavioral correlates of these alterations are not established. In healthy subjects, motor activity correlated with white matter integrity in the motor system. To explore the relation of white matter integrity and motor activity in major depressive disorder, we investigated 21 medicated patients with major depressive disorder and 21 matched controls using diffusion tensor imaging and wrist actigraphy at the same day. Patients had lower activity levels (AL) compared with controls. Fractional anisotropy (FA) differed between groups in frontal white matter regions and the posterior cingulum. AL was linearly associated with white matter integrity in two clusters within the motor system. Controls had an exclusive positive association of FA and AL in white matter underneath the right dorsal premotor cortex. Only patients had a positive association within the posterior cingulum. Furthermore, patients had negative associations of FA and AL underneath the left primary motor cortex and within the left parahippocampal gyrus white matter. These differences in the associations between structure and behavior may contribute to well-known impaired motor planning or gait disturbances in major depressive disorder. Therefore, signs of psychomotor slowing in major depressive disorder may be linked to changes of the white matter integrity of the motor system.

Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells

Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destruction of liver cells by the host's own immune response. Similarly, after infection with lymphocytic choriomeningitis virus (LCMV) in mice, the adaptive immune response causes liver cell damage, choriomeningitis and destruction of lymphoid organ architecture. The immunopathological sequel during LCMV infection has been attributed to cytotoxic CD8(+) T cells. However, we now show that during LCMV infection CD4(+) T cells selectively induced the destruction of splenic marginal zone and caused liver cell damage with elevated serum alanin-transferase (ALT) levels. The destruction of the splenic marginal zone by CD4(+) T cells included the reduction of marginal zone B cells, marginal zone macrophages and marginal zone metallophilic macrophages. Functionally, this resulted in an impaired production of neutralizing antibodies against LCMV. Furthermore, CD4(+) T cells reduced B cells with an IgM(high)IgD(low) phenotype (transitional stage 1 and 2, marginal zone B cells), whereas other B cell subtypes such as follicular type 1 and 2 and germinal center/memory B cells were not affected. Adoptive transfer of CD4(+) T cells lacking different important effector cytokines and cytolytic pathways such as IFNγ, TNFα, perforin and Fas-FasL interaction did reveal that these cytolytic pathways are redundant in the induction of immunopathological sequel in spleen. In conclusion, our results define an important role of CD4(+) T cells in the induction of immunopathology in liver and spleen. This includes the CD4(+) T cell mediated destruction of the splenic marginal zone with consecutively impaired protective neutralizing antibody responses.

Assessment of endothelium and inflammatory response at the onset of reperfusion injury in hand surgery

Background Activation of the endothelium, complement activation and generation of cytokines are known events during ischemia-reperfusion (I/R) that mediate tissue injury. Our aim was to elucidate their respective participation at the onset of the reperfusion phase. Tourniquet application in hand surgery causes short-term ischemia, followed by reperfusion and was therefore used as the model in this study. Methods Ten patients were included in the study after obtaining informed consent. A tourniquet was placed on the upper arm and inflated to 250 mmHg for 116 ± 16 min, during which the surgery was performed. Venous blood and tissue samples from the surgical area were taken at baseline as well as 0, 2, and 10 min after reperfusion and analyzed for the following parameters: Endothelial integrity and/or activation were analyzed by measuring heparan sulfate and syndecan-1 in serum, and vWF, heparan sulfate proteoglycan as well as CD31on tissue. Complement activation was determined by C3a and C4d levels in plasma, levels of C1-inhibitor in serum, and IgG, IgM, C3b/c, and C4b/c deposition on tissue. Cytokines and growth factors IL-5, IL-6, IL-7, IL-8, IL-10, IL-17, G-CSF, GM-CSF, MCP-1, TNFα, VEGF, and PDGF bb were measured in the serum. Finally, CK-MM levels were determined in plasma as a measure for muscle necrosis. Results Markers for endothelial activation and/or integrity as well as complement activation showed no significant changes until 10 min reperfusion. Among the measured cytokines, IL-6, IL-7, IL-17, TNFα, GM-CSF, VEGF, and PDGF bb were significantly increased at 10 min reperfusion with respect to baseline. CK-MM showed a rise from baseline at the onset of reperfusion (p < 0.001) and dropped again at 2 min (p < 0.01) reperfusion, suggesting ischemic muscle damage. Conclusions In this clinical model of I/R injury no damage to the endothelium, antibody deposition or complement activation were observed during early reperfusion. However, an increase of pro-inflammatory cytokines and growth factors was shown, suggesting a contribution of these molecules in the early stages of I/R injury.

The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells

The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome

Defects in urothelial integrity resulting in leakage and activation of underlying sensory nerves are potential causative factors of bladder pain syndrome, a clinical syndrome of pelvic pain and urinary urgency/frequency in the absence of a specific cause. Herein, we identified the microRNA miR-199a-5p as an important regulator of intercellular junctions. On overexpression in urothelial cells, it impairs correct tight junction formation and leads to increased permeability. miR-199a-5p directly targets mRNAs encoding LIN7C, ARHGAP12, PALS1, RND1, and PVRL1 and attenuates their expression levels to a similar extent. Using laser microdissection, we showed that miR-199a-5p is predominantly expressed in bladder smooth muscle but that it is also detected in mature bladder urothelium and primary urothelial cultures. In the urothelium, its expression can be up-regulated after activation of cAMP signaling pathways. While validating miR-199a-5p targets, we delineated novel functions of LIN7C and ARHGAP12 in urothelial integrity and confirmed the essential role of PALS1 in establishing and maintaining urothelial polarity and junction assembly. The present results point to a possible link between miR-199a-5p expression and the control of urothelial permeability in bladder pain syndrome. Up-regulation of miR-199a-5p and concomitant down-regulation of its multiple targets might be detrimental to the establishment of a tight urothelial barrier, leading to chronic pain.