A combined three-dimensional in vitro-in silico approach to modelling bubble dynamics in decompression sickness

The growth of bubbles within the body is widely believed to be the cause of decompression sickness (DCS). Dive computer algorithms that aim to prevent DCS by mathematically modelling bubble dynamics and tissue gas kinetics are challenging to validate. This is due to lack of understanding regarding the mechanism(s) leading from bubble formation to DCS. In this work, a biomimetic in vitro tissue phantom and a three-dimensional computational model, comprising a hyperelastic strain-energy density function to model tissue elasticity, were combined to investigate key areas of bubble dynamics. A sensitivity analysis indicated that the diffusion coefficient was the most influential material parameter. Comparison of computational and experimental data revealed the bubble surface's diffusion coefficient to be 30 times smaller than that in the bulk tissue and dependent on the bubble's surface area. The initial size, size distribution and proximity of bubbles within the tissue phantom were also shown to influence their subsequent dynamics highlighting the importance of modelling bubble nucleation and bubble–bubble interactions in order to develop more accurate dive algorithms

Immunovirotherapy for the treatment of glioblastoma

We have recently described a new murine model of glioblastoma, generated by the implantation of syngeneic glioblastoma stem cells into immunocompetent mice, that recapitulates the salient histopathological and immunological features of the human disease. We employed this model to demonstrate the multifaceted activity of an oncolytic herpes simplex virus genetically modified to express interleukin-12, G47∆-IL12

Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

IntroductionDisruption of metabolic function is a recognized feature of late onset Alzheimer's disease (LOAD). We sought to determine whether similar metabolic pathways are implicated in adults with Down syndrome (DS) who have increased risk for Alzheimer's disease (AD).MethodsWe examined peripheral blood from 292 participants with DS who completed baseline assessments in the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) using untargeted mass spectrometry (MS). Our sample included 38 individuals who met consensus criteria for AD (DS-AD), 43 who met criteria for mild cognitive impairment (DS-MCI), and 211 who were cognitively unaffected and stable (CS).ResultsWe measured relative abundance of 8,805 features using MS and 180 putative metabolites were differentially expressed (DE) among the groups at false discovery rate-corrected q< 0.05. From the DE features, a nine-feature classifier model classified the CS and DS-AD groups with receiver operating characteristic area under the curve (ROC AUC) of 0.86 and a two-feature model classified the DS-MCI and DS-AD groups with ROC AUC of 0.88. Metabolite set enrichment analysis across the three groups suggested alterations in fatty acid and carbohydrate metabolism.DiscussionOur results reveal metabolic alterations in DS-AD that are similar to those seen in LOAD. The pattern of results in this cross-sectional DS cohort suggests a dynamic time course of metabolic dysregulation which evolves with clinical progression from non-demented, to MCI, to AD. Metabolomic markers may be useful for staging progression of DS-AD

Evaluation of preparedness of healthcare student volunteers against Middle East respiratory syndrome coronavirus (MERS-CoV) in Makkah, Saudi Arabia : a cross-sectional study

Aim: To assess the knowledge and attitude of senior medical, dental, nursing and pharmacy students toward Middle East respiratory syndrome-corona virus (MERS-CoV) in Saudi Arabia. Subjects and methods: A cross-sectional survey using a 21-item questionnaire was conducted for a 3-month period from November 2015–January 2016 in Makkah, Saudi Arabia. The questionnaire was designed to evaluate students’ understanding and perception of MERS-CoV. An ANOVA test was used to determine the association of study discipline and academic year with the student knowledge score on MERS. Results: A total of 364 students were assessed during the study. The majority (62%) of the participants were in the 20–22-year age group. More than half (53%) were pharmacy students followed by (22%) medical students. More than two thirds (71%) of the participants were aware that MERS is caused by the coronavirus. More than half (59%) of the participants believed that MERS can be transmitted through direct or indirect contact with infected camels. A statistically significant association was reported between the study discipline and mean knowledge score (p < 0.0001) with medical students achieving an overall better knowledge score compared with students from other study disciplines. Conclusion: Overall, students had good knowledge about MERS epidemiology, transmission and the recommended protective measures. However, students expressed their reluctance to work in healthcare facilities with inadequate MERS infection control isolation policies

HUBUNGAN DUKUNGAN KELUARGA DENGAN TINGKAT DEPRESI PADA NARAPIDANA NAPZA DI RUTAN KELAS IIB KAJHU ACEH BESAR

Banda Ace

Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

3D In Vitro Models for Investigating the Role of Stiffness in Cancer Invasion

BACKGROUND: Tumorigenesis is attributed to the interactions of cancer cells with the tumor microenvironment through both biochemical cues and physical stimuli. Increased matrix deposition and realignment of the collagen fibers are detected by cancer cells, inducing epithelial-to-mesenchymal transition, which in turn stimulates cell motility and invasiveness. METHODS: This review provides an overview of current research on the role of the physical microenvironment in cancer invasion. This was achieved by using a systematic approach and providing meta-analyses. Particular focus was placed on in vitro three-dimensional models of epithelial cancers. We investigated questions such as the effect of matrix stiffening, activation of stromal cells, and identified potential advances in mechano-based therapies. RESULTS: Meta-analysis revealed that 64% of studies report cancer invasion promotion as stiffness increases, while 36% report the opposite. Experimental approaches and data interpretations were varied, each affecting the invasion of cancer differently. Examples are the experimental timeframes used (24 h to 21 days), the type of polymer used (24 types), and choice of cell line (33 cell lines). The stiffness of the 3D matrices varied from 0.5 to 300 kPa and 19% of these matrices' stiffness were outside commonly accepted physiological range. 100% of the studies outside biological stiffness range (above 20 kPa) report that stiffness does not promote cancer invasion. CONCLUSIONS: Taking this analysis into account, we inform on the type of experimental approaches that could be the most relevant and provide what would be a standardized protocol and reporting strategy

Adverse drug reactions associated with chemotherapeutic agents used in breast cancer: Analysis of patients’ online forums

Background: Breast cancer is the most common type of cancer in women worldwide. The benefits of chemotherapy vary depending on the treatment regimen used and the characteristic of the tumour. However, adverse drug reactions associated with chemotherapeutic agents can cause dose delays or reductions; thereby, affecting the treatment outcomes. Objective: To explore adverse drug reactions of chemotherapeutic agents used to treat breast cancer from the patients’ perspective. Methods: A total of 110 threads from nine online discussion forums were evaluated. They were exported into NVivo for Mac where content analysis was applied. Threads were read carefully to observe emerging patterns which were then coded into sub-themes and grouped into main themes. Results: The participants’ characteristics on online discussion forums were often missing. Four hundred and eleven participants experienced 473 adverse drug reactions that were mainly associated with the nervous and immune systems. The forums’ analysis yielded three main themes: patient–patient advice, self-medication and lifestyle changes. Conclusion: Online discussion forums proposed valued source of data on adverse drug reactions associated with chemotherapeutic agents and overall patients’ experience with cancer. The adverse drug reactions experienced by patients changed their priorities and the way they dealt with the disease. Therefore, healthcare professionals must consider the patients’ experience and attitudes towards cancer when designing a treatment plan. This can be established by increasing communication between healthcare professionals and patients

Nonunion After Hybrid Plating with Locking and Nonlocking Screws in Radius and Ulna Shaft Fractures: Report of Two Cases

Conventional compression plating has been found effective in treating forearm diaphyseal fractures, providing stability as well as resistance to axial, torsional, and bending forces. Locked plating has provided stability without frictional force between the bone-plate interface, which may help preserve periosteal blood supply, and is useful in treating metaphyseal, comminuted, and osteoporotic fractures. Hybrid plating has been used in an attempt to combine the strengths of these two techniques; however, in the context of simple forearm diaphyseal fractures with healthy bone, its effectiveness is only theoretical. We describe two patients in whom open reduction and internal fixation with hybrid plating to treat radius and ulna diaphyseal fractures resulted in nonunion. We performed a revision procedure using conventional compression plating and achieved full healing with complete union in both cases. These findings suggest that hybrid fixation for treating such fractures may not lead to better outcomes than conventional plating

Exploring the adverse effects of chemotherapeutic agents used in the treatment of cervical and ovarian cancer from the patients' perspective: a content analysis of the online discussion forums.

OBJECTIVES: This study aimed to explore the adverse effects of chemotherapeutic agents used in the treatment of ovarian and cervical cancer by analysing patients' views posted in online discussion forums. METHOD: UK-centred online discussion forums were used to identify discussion threads on ovarian and cervical cancer between 2008 and 2017. The study was approved by the University of Bournemouth ethics committee. 272 discussion threads with 644 participants from four online discussion forums (Cancer Research UK, Macmillan, Ovacome and Jo's Cervical Cancer Trust) were identified. The threads were exported into NVivo and a thematic content analysis was conducted to identify study themes. RESULTS: Of the 644 participants, 19.4% had a diagnosis of cervical cancer and 80.6% had a diagnosis of ovarian cancer. Four main themes related to: (1) treatment plan, (2) adverse effects, (3) perception of treatment and (4) hospitalisation were identified. Patients' perceptions about their treatment were reported to be positive across all chemotherapeutic agents. 312 adverse effects were reported by patients with cervical cancer taking cisplatin, with fatigue (52.1%) and nausea (30.6%) being the two most frequently reported adverse effects. With regard to the treatment of ovarian cancer, 402 adverse effects were reported by patients on carboplatin and paclitaxel, with neuropathy (29.3%) and fatigue (28.0%) being the two most commonly reported adverse effects. CONCLUSION: The online discussion forums allowed patients to express their concerns in a blame-free environment that provided novel insight into the impact of chemotherapy-associated adverse effects on patients with cervical and ovarian cancers. Real-life experiences shared by patients can help the healthcare professionals to find the right balance between prolonged survival and quality of life