The association between muscle strength and activity limitations in patients with the hypermobility type of Ehlers–Danlos syndrome : the impact of proprioception

Purpose: The patients diagnosed with Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT) are characterized by pain, proprioceptive inacuity, muscle weakness, potentially leading to activity limitations. In EDS-HT, a direct relationship between muscle strength, proprioception and activity limitations has never been studied. The objective of the study was to establish the association between muscle strength and activity limitations and the impact of proprioception on this association in EDS-HT patients. Methods: Twenty-four EDS-HT patients were compared with 24 controls. Activity limitations were quantified by Health Assessment Questionnaire (HAQ), Six-Minute Walk test (6MWT) and 30-s chair-rise test (30CRT). Muscle strength was quantified by handheld dynamometry. Proprioception was quantified by movement detection paradigm. In analyses, the association between muscle strength and activity limitations was controlled for proprioception and confounders. Results: Muscle strength was associated with 30CRT (r = 0.67, p = <0.001), 6MWT (r = 0.58, p = <0.001) and HAQ (r = 0.63, p = <0.001). Proprioception was associated with 30CRT (r = 0.55, p <0.001), 6MWT (r = 0.40, p = <0.05) and HAQ (r = 0.46, p < 0.05). Muscle strength was found to be associated with activity limitations, however, proprioceptive inacuity confounded this association. Conclusions: Muscle strength is associated with activity limitations in EDS-HT patients. Joint proprioception is of influence on this association and should be considered in the development of new treatment strategies for patients with EDS-HT. Implications for rehabilitation : Reducing activity limitations by enhancing muscle strength is frequently applied in the treatment of EDS-HT patients. Although evidence regarding treatment efficacy is scarce, the current paper confirms the rationality that muscle strength is an important factor in the occurrence of activity limitations in EDS-HT patients. Although muscle strength is the most dominant factor that is associated with activity limitations, this association is confounded by proprioception. In contrast to common belief proprioception was not directly associated with activity limitations but confounded this association. Controlling muscle strength on the bases of proprioceptive input may be more important for reducing activity limitations than just enhancing sheer muscle strength

Oral Inflammatory Myofibroblastic Tumor: Case Report and Review of Literature

Inflammatory myofibroblastic tumor (IMT) is a rarely described tumor of unknown etiology and pathogenesis. It occurs primarily in the lungs, but has occurred in other extra-pulmonary sites. Histologically these lesions appear as an inflammatory infiltrate within a variably myofibrotic background. Current evidence shows that inflammatory myofibroblastic tumors are neoplastic processes resulting from chromosomal translocations that often cause an overexpression of ALK kinase, which is often assessed using immunohistochemical studies. Currently, the biological behavior of oral inflammatory myofibroblastic tumor is still uncertain. This article describes the clinical, histological, and operative features of a case of IMT of the oral cavity

High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma

BACKGROUND: HMGA2 expression has been shown to be associated with enhanced selective chemosensitivity towards the topoisomerase (topo) II inhibitor, doxorubicin, in cancer cells. Although the roles of signaling cascades and proteins as regulatory factors in development, neoplasia and adaptation to the environment are becoming well established, evidence for the involvement of regulatory small RNA molecules, such as microRNAs (miRNAs) as important regulators of both transcriptional and posttranscriptional gene silencing is presently mounting. RESULTS: Here we report that HMGA2 expression in head and neck squamous cell carcinoma (HNSCC) cells is regulated in part by miRNA-98 (miR-98). Albeit HMGA2 is associated with enhanced selective chemosensitivity towards topoisomerase (topo) II inhibitor, doxorubicin in HNSCC, the expression of HMGA2 is thwarted by hypoxia. This is accompanied by enhanced expression of miRNA-98 and other miRNAs, which predictably target HMGA2. Moreover, we show that transfection of pre-miR-98™ during normoxia diminishes HMGA2 and potentiates resistance to doxorubicin and cisplatin. These findings implicate the role of a miRNA as a key element in modulating tumors in variable microenvironments. CONCLUSION: These studies validate the observation that HMGA2 plays a prominent role in governing genotoxic responses. However, this may only represent cells growing under normal oxygen tensions. The demonstration that miRNA profiles are altered during hypoxia and repress a genotoxic response indicates that changes in microenvironment in eukaryotes mimic those of lower species and plants, where, for example, abiotic stresses regulate the expression of thousands of genes in plants at both transcriptional and posttranscriptional levels through a number of miRNAs and other small regulatory RNAs

A Novel Immune Evasion Strategy of Candida albicans: Proteolytic Cleavage of a Salivary Antimicrobial Peptide

Oropharyngeal candidiasis is an opportunistic infection considered to be a harbinger of AIDS. The etiologic agent Candida albicans is a fungal species commonly colonizing human mucosal surfaces. However, under conditions of immune dysfunction, colonizing C. albicans can become an opportunistic pathogen causing superficial or even life-threatening infections. The reasons behind this transition, however, are not clear. In the oral cavity, salivary antimicrobial peptides are considered to be an important part of the host innate defense system in the prevention of microbial colonization. Histatin-5 specifically has exhibited potent activity against C. albicans. Our previous studies have shown histatin-5 levels to be significantly reduced in the saliva of HIV+ individuals, indicating an important role for histatin-5 in keeping C. albicans in its commensal stage. The versatility in the pathogenic potential of C. albicans is the result of its ability to adapt through the regulation of virulence determinants, most notably of which are proteolytic enzymes (Saps), involved in tissue degradation. In this study, we show that C. albicans cells efficiently and rapidly degrade histatin-5, resulting in loss of its anti-candidal potency. In addition, we demonstrate that this cellular activity is due to proteolysis by a member of the secreted aspartic proteases (Sap) family involved in C. albicans pathogenesis. Specifically, the proteolysis was attributed to Sap9, in turn identifying histatin-5 as the first host-specific substrate for that isoenzyme. These findings demonstrate for the first time the ability of a specific C. albicans enzyme to degrade and deactivate a host antimicrobial peptide involved in the protection of the oral mucosa against C. albicans, thereby providing new insights into the factors directing the transition of C. albicans from commensal to pathogen, with important clinical implications for alternative therapy. This report characterizes the first defined mechanism behind the enhanced susceptibility of HIV+ individuals to oral candidiasis since the emergence of HIV

Aptamer-modified polymer nanoparticles for targeted drug delivery

The purpose of this study was to develop a model system for targeted drug delivery. This system should enable targeted drug release at a certain tissue in the body. In conventional drug delivery systems, drugs are often delivered unspecifically resulting in unwarranted adverse effects. To circumvent this problem, there is an increasing demand for the development of intelligent drug delivery systems allowing a tissue-specific mode of delivery. Within this study, nanoparticles consisting of two biocompatible polymers are used. Because of their small size, nanoparticles are well-suited for effective drug delivery. The small size affects their movement through cell and tissue barriers. Their cellular uptake is easier when compared to larger drug delivery systems. Paclitaxel was encapsulated into the nanoparticles as a model drug, and to achieve specific targeting an aptamer directed against lung cancer cells was coupled to the nanoparticles surface. Nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), and nanotracking analysis (NTA). Also their surface charge was characterized from ζ-potential measurements. Their preparation was optimized and subsequently specificity of drug-loaded and aptamer-functionalized nanoparticles was investigated using lung cancer cells. © 2016 by De Gruyter

What factors contribute to cancer survivors’ self-management skills? A cross-sectional observational study

Purpose: Many cancer survivors, facing the consequences of their disease and its treatment, have medical and supportive aftercare needs. However, limited knowledge exists regarding the relationship between support needs and survivors' self-management skills. The study aim is to explore factors contributing to cancer survivors’ self-management skills. Methods: A cross-sectional study was conducted among cancer survivors (n = 277) of two outpatient oncology clinics at a university hospital in the Netherlands. Patients with head and neck cancer (n = 55) who had received radiotherapy and cisplatin or cetuximab were included, as well as patients who had undergone hematopoietic stem cell transplantation (n = 222). The primary outcome was self-management skills, assessed using the Partners in Health Scale (PIH), which comprises two subscales: knowledge and coping (PIH-KC), and recognition and management of symptoms, and adherence to treatment (PIH-MSA). Secondary outcomes were quality of life (EORTC QLQ-C30), self-efficacy (SECD6), patient-centered care (CAPHS), and social support (HEIQ). Machine learning-based Random Forest models were employed to construct associative models. Feature Importance (FI) was used to express the contribution to the model. Results: High emotional quality of life (FI = 33.1%), increased self-efficacy (FI = 22.2%), and greater social support (FI = 18.2%) were identified as key factors contributing to cancer survivors' self-management knowledge (PIH-KC). Furthermore, greater support from professionals (FI = 36.1%) and higher self-efficacy (FI = 18.2%) were found to benefit participants’ recognition and management, and therapy adherence (PIH-MSA). Conclusions: A patient-centered relationship between nurses and cancer survivors is essential for therapy adherence and the management of aftercare needs. Training to provide this holistic self-management support is required.</p

Microbial interactions and differential protein expression in Staphylococcus aureus –Candida albicans dual-species biofilms

The fungal species Candida albicans and the bacterial species Staphylococcus aureus are responsible for a majority of hospital-acquired infections and often coinfect critically ill patients as complicating polymicrobial biofilms. To investigate biofilm structure during polymicrobial growth, dual-species biofilms were imaged with confocal scanning laser microscopy. Analyses revealed a unique biofilm architecture where S. aureus commonly associated with the hyphal elements of C. albicans. This physical interaction may provide staphylococci with an invasion strategy because candidal hyphae can penetrate through epithelial layers. To further understand the molecular mechanisms possibly responsible for previously demonstrated amplified virulence during coinfection, protein expression studies were undertaken. Differential in-gel electrophoresis identified a total of 27 proteins to be significantly differentially produced by these organisms during coculture biofilm growth. Among the upregulated staphylococcal proteins was l-lactate dehydrogenase 1, which confers resistance to host-derived oxidative stressors. Among the downregulated proteins was the global transcriptional repressor of virulence factors, CodY. These findings demonstrate that the hyphae-mediated enhanced pathogenesis of S. aureus may not only be due to physical interactions but can also be attributed to the differential regulation of specific virulence factors induced during polymicrobial growth. Further characterization of the intricate interaction between these pathogens at the molecular level is warranted, as it may aid in the design of novel therapeutic strategies aimed at combating fungal–bacterial polymicrobial infection

Projecting terrestrial biodiversity intactness with GLOBIO 4

Scenario-based biodiversity modelling is a powerful approach to evaluate how possible future socio-economic developments may affect biodiversity. Here, we evaluated the changes in terrestrial biodiversity intactness, expressed by the mean species abundance (MSA) metric, resulting from three of the shared socio-economic pathways (SSPs) combined with different levels of climate change (according to representative concentration pathways [RCPs]): a future oriented towards sustainability (SSP1xRCP2.6), a future determined by a politically divided world (SSP3xRCP6.0) and a future with continued global dependency on fossil fuels (SSP5xRCP8.5). To this end, we first updated the GLOBIO model, which now runs at a spatial resolution of 10 arc-seconds (~300 m), contains new modules for downscaling land use and for quantifying impacts of hunting in the tropics, and updated modules to quantify impacts of climate change, land use, habitat fragmentation and nitrogen pollution. We then used the updated model to project terrestrial biodiversity intactness from 2015 to 2050 as a function of land use and climate changes corresponding with the selected scenarios. We estimated a global area-weighted mean MSA of 0.56 for 2015. Biodiversity intactness declined in all three scenarios, yet the decline was smaller in the sustainability scenario (-0.02) than the regional rivalry and fossil-fuelled development scenarios (-0.06 and -0.05 respectively). We further found considerable variation in projected biodiversity change among different world regions, with large future losses particularly for sub-Saharan Africa. In some scenario-region combinations, we projected future biodiversity recovery due to reduced demands for agricultural land, yet this recovery was counteracted by increased impacts of other pressures (notably climate change and road disturbance). Effective measures to halt or reverse the decline of terrestrial biodiversity should not only reduce land demand (e.g. by increasing agricultural productivity and dietary changes) but also focus on reducing or mitigating the impacts of other pressures.Peer reviewe