Preventive and Protective Properties of Pertussis Vaccines: Current Situation and Future Challenges

Pertussis, more commonly known as whooping cough, is a potentially fatal respiratory disease caused by Bordetella pertussis. Two different types of vaccines provide effective protection: killed whole-cell vaccines (wPV) and more recently available acellular vaccines (aPVs) formulated with specific components. Disturbingly, while the vaccines are widely used, the incidence of disease is increasing in several developed countries that have switched from wPV to an aPV. It is suggested that the single most important underlying cause suggested for the resurgence is transmission through asymptomatic infections. While both vaccines protect against disease, a newly developed baboon model has shown that they do not prevent infection. Importantly, wPV-vaccinated animals appeared to clear an infection more rapidly than those vaccinated with aPV, which can relate to the period of possible disease transmission. To ultimately control whooping cough, it is clear that a more effective vaccine is needed that can prevent both disease and transmission. Modifications underway include the elimination of LPS from wPVs to improve their safety profiles and augmentation of aPVs with other bacterium proteins to increase immunogenicity and the longevity of protection. In the interim, vaccinations with aPV during pregnancy appear to protect newborns, the most susceptible to deadly pertussis

Object Manipulation in Virtual Reality Under Increasing Levels of Translational Gain

Room-scale Virtual Reality (VR) has become an affordable consumer reality, with applications ranging from entertainment to productivity. However, the limited physical space available for room-scale VR in the typical home or office environment poses a significant problem. To solve this, physical spaces can be extended by amplifying the mapping of physical to virtual movement (translational gain). Although amplified movement has been used since the earliest days of VR, little is known about how it influences reach-based interactions with virtual objects, now a standard feature of consumer VR. Consequently, this paper explores the picking and placing of virtual objects in VR for the first time, with translational gains of between 1x (a one-to-one mapping of a 3.5m*3.5m virtual space to the same sized physical space) and 3x (10.5m*10.5m virtual mapped to 3.5m*3.5m physical). Results show that reaching accuracy is maintained for up to 2x gain, however going beyond this diminishes accuracy and increases simulator sickness and perceived workload. We suggest gain levels of 1.5x to 1.75x can be utilized without compromising the usability of a VR task, significantly expanding the bounds of interactive room-scale VR

Long noncoding RNAs: a missing link in osteoporosis

Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly in the vertebrae and the hip. This condition and associated morbidity and mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides that are not translated into proteins, but play important regulatory roles in transcriptional and post-transcriptional regulation. Their contribution to disease onset and development is increasingly recognized. Herein, we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools. Firstly, current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication, fragility fractures, is reviewed. We analyze evidence of their roles in osteogenesis, osteoclastogenesis, and bone fracture healing events from human and animal model studies. Secondly, the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis. Finally, we conclude debating the possibilities, persisting difficulties, and future prospects of using lncRNAs in the treatment of osteoporosis.This project has been supported by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-031402—R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF. Authors would like to thank to FCT DL 57/2016/CP1360/CT0008 (M.I.A.) and SFRH/BD/112832/2015 (J.H.T)

Designing immersive sustainable food experiences in augmented reality: a consumer participatory co-creation approach

In light of the current debate on the impact of our current food system on climate change and related mitigation strategies, addressing the acceptance of sustainability aspects within consumer behavioral issues is of vital importance. However, the field remains mute on how those strategies can be designed and employed effectively to stimulate sustainable food consumption behavior. Immersive narrative design is a promising approach to engaging consumers in this context. Within this study, we shed light on how to create immersive, impactful, interactive narratives in augmented reality (AR) together with consumers. We propose a novel approach to how those stories can be planned, utilizing participatory design methods. Within a step-wise process, we develop the storyboard together with consumers. In the next step, we evaluate multiple approaches with AR application developers on how this storyline can be enhanced in AR considering the perspective of various stakeholders like developers, behavioral scientists, and consumers. Finally, we propose a conceptual framework for how immersive narratives can be designed and validated in a collaborative, multidimensional approach for impactful AR narrative content designs to stimulate sustainable food behavior for consumers

The systemic immune response to collagen-induced arthritis and the impact of bone injury in inflammatory conditions

Rheumatoid arthritis (RA) is a systemic disease that affects the osteoarticular system, associated with bone fragility and increased risk of fractures. Herein, we aimed to characterize the systemic impact of the rat collagen-induced arthritis (CIA) model and explore its combination with femoral bone defect (FD). The impact of CIA on endogenous mesenchymal stem/stromal cells (MSC) was also investigated. CIA induction led to enlarged, more proliferative, spleen and draining lymph nodes, with altered proportion of lymphoid populations. Upon FD, CIA animals increased the systemic myeloid cell proportions, and their expression of co-stimulatory molecules CD40 and CD86. Screening plasma cytokine/chemokine levels showed increased tumor necrosis factor-a (TNF-a), Interleukin (IL)-17, IL-4, IL-5, and IL-12 in CIA, and IL-2 and IL-6 increased in CIA and CIA+FD, while Fractalkine and Leptin were decreased in both groups. CIA-derived MSC showed lower metabolic activity and proliferation, and significantly increased osteogenic and chondrogenic differentiation markers. Exposure of control-MSC to TNF-a partially mimicked the CIA-MSC phenotype in vitro. In conclusion, inflammatory conditions of CIA led to alterations in systemic immune cell proportions, circulating mediators, and in endogenous MSC. CIA animals respond to FD, and the combined model can be used to study the mechanisms of bone repair in inflammatory conditions.This research was funded by the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and AO Foundation-Switzerland (project S-15-83S). J.H.T, A.M.S, M.B.G, M.I.A and C.C were supported by FCT-Fundação para a Ciência e a Tecnologia, through the fellowships SFRH/BD/112832/2015, SFRH/BD/85968/2012, PD/BD/135489/2018, DL 57/2016/CP1360/CT0008 and DL 57/2016/CP1360/CT0004, respectively

Clinico-demographic characterization of Cutaneous leishmaniasis in patients reporting to two hospitals in Matara and Hambantota districts, Sri Lanka

Background: Cutaneous leishmaniasis (CL) is an established disease in Sri Lanka.Objectives: This study aimed to characterize clinico-demographic pattern of CL, in patients reported to District General Hospital (DGH) Matara and Base Hospital (BH) Tangalle, which report about 100 new cases monthly.Methods: Clinico-demographic findings of 47 CL confirmed patients (>18 years; Slit skin smears (SSS) and/or PCR positive) from preliminary data of a cross sectional study carried out at DGH Matara and BH Tangalle from August/2018 to January /2019 were analysed. Interviewer administered questionnaire was used to gather the demographic data.Results: Median age was 43 years. Out of the 13 cases from DGH Matara, four reported from Urugamuwa and one each from other areas of the district. Of the 34 cases from BHTangalle, 12 were from Beliaththa. Eight SSS negatives became PCR positive and one PCR negative was SSS positive. Majority of the lesions were single (n=40, 85.1%), non-tender (n=38, 80.8%), non-itchy (n=34, 72.3%) and small (< 2cm, n=36, 76.6%) ulcerated nodules (n=14, 29.8%) in upper limbs (n=25, 53.1%) with parasitic grading of 1+ (n=20, 42.5%). Nine patients reported persistent itching without any evidence of secondary pathology. Clinical evidence of secondary bacterial infection presented in four patients and out of them, two had painful lesions. Thirty two lesions were <4 months duration. In addition to ulcerated nodules and plaques, three out of nine papules were ulcerated within 4 months’ by history. Two patients had a family member with CL.Conclusions: Ulceration of papules is a novel observation. Urugamuwa is a possible emerging focus of CL in Matara where Dickwella is the known hot spot. Beliathta could be a main disease focus in Hambantota. This preliminary study based on a smaller sample size needs to be validated with a bigger sample size

Macrophages down-regulate gene expression of intervertebral disc degenerative markers under a pro-inflammatory microenvironment

Low back pain is a highly prevalent clinical problem and intervertebral disc (IVD) degeneration is now accepted as the major pathophysiological mechanism responsible for this condition. Accumulating evidence suggests that inflammation plays a crucial role in the progression of human IVD degeneration, with macrophages being pointed as the key immune cell players in this process since their infiltration in degenerated IVD samples has been extensively demonstrated. Since they are highly plastic, macrophages can play different roles depending on the microenvironmental cues. The study of inflammation associated with IVD degeneration has been somehow neglected and one of the reasons is related with lack of adequate models. To overcome this, we established and characterized a new model of IVD organ culture under proinflammatory conditions to further dissect the role of macrophages in IVD associated immune response. For that, human monocyte-derived macrophages were co-cultured either with bovine caudal IVD punches in the presence of the pro-inflammatory cytokine IL-1ß, or IVD-conditioned medium (CM), to investigate how IVD-produced factors influence macrophage phenotype. After 72 h, metabolic activity, gene expression and cytokine profile of macrophages and IVD cells were measured. Our results show that macrophages and IVDs remain metabolically active in the presence of IL-1ß, significantly upregulate CCR7 gene expression and increase production of IL-6 on macrophages. When treating macrophages with IL-1ß-IVD-CM, CCR7 upregulation follows the same trend, while for IL-6 an opposite effect was observed. On the other hand, macrophages interfere with IVD ECM remodeling, decreasing MMP3 expression and downregulating aggrecan and collagen II gene expression in the presence of IL-1ß. Overall, the co-culture model established in this study can be considered a suitable approach to address the cellular and molecular pathways that regulate macrophage-IVD crosstalk, suggesting that degenerated IVD tissue tends to polarize human macrophages toward a more proinflammatory profile, which seems to aggravate IVD degeneration. This model could be used to improve the knowledge of the mechanisms that link IVD degeneration and the immune response.This work was financed by European Union funds through Bioengineered Therapies for infectious diseases and tissue regeneration (Norte-01-0145-FEDER-000012), Projetos Estruturados de I& D& I - Norte-01-0145-FEDER-000012, Portugal 2020 - FEDER, and through EUROSPINE TRF (2017_05) by the project Disc degeneration-, immune-, and neuro-modulation. The authors also acknowledge FCT – Fundação para a Ciência e a Tecnologia, in the framework of the FCT Investigator Grant of RMG (IF/00638/2014), CC Junior Research contract (DL 57/2016/CP1360/CT0004) and the Ph.D. grant of JF (PD/BI/128357/2017). The authors would like to thank Serviço de Imunohemoterapia of Centro Hospitalar Universitário de São João (CHUSJ), for kindly donating Buffy Coats

A Sparse Stress Model

Force-directed layout methods constitute the most common approach to draw general graphs. Among them, stress minimization produces layouts of comparatively high quality but also imposes comparatively high computational demands. We propose a speed-up method based on the aggregation of terms in the objective function. It is akin to aggregate repulsion from far-away nodes during spring embedding but transfers the idea from the layout space into a preprocessing phase. An initial experimental study informs a method to select representatives, and subsequent more extensive experiments indicate that our method yields better approximations of minimum-stress layouts in less time than related methods.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Evaluating heterogeneity in cumulative meta-analyses

BACKGROUND: Recently developed measures such as I(2 )and H allow the evaluation of the impact of heterogeneity in conventional meta-analyses. There has been no examination of the development of heterogeneity in the context of a cumulative meta-analysis. METHODS: Cumulative meta-analyses of five smoking cessation interventions (clonidine, nicotine replacement therapy using gum and patch, physician advice and acupuncture) were used to calculate I(2 )and H. These values were plotted by year of publication, control event rate and sample size to trace the development of heterogeneity over these covariates. RESULTS: The cumulative evaluation of heterogeneity varied according to the measure of heterogeneity used and the basis of cumulation. Plots produced from the calculations revealed areas of heterogeneity useful in the consideration of potential sources for further study. CONCLUSION: The examination of heterogeneity in conjunction with summary effect estimates in a cumulative meta-analysis offered valuable insight into the evolution of variation. Such information is not available in the context of conventional meta-analysis and has the potential to lead to the development of a richer picture of the effectiveness of interventions