The significance of macrophage phenotype in cancer and biomaterials

Macrophages have long been known to exhibit heterogeneous and plastic phenotypes. They show functional diversity with roles in homeostasis, tissue repair, immunity and disease. There exists a spectrum of macrophage phenotypes with varied effector functions, molecular determinants, cytokine and chemokine profiles, as well as receptor expression. In tumor microenvironments, the subset of macrophages known as tumor-associated macrophages generates byproducts that enhance tumor growth and angiogenesis, making them attractive targets for anti-cancer therapeutics. With respect to wound healing and the foreign body response, there is a necessity for balance between pro-inflammatory, wound healing, and regulatory macrophages in order to achieve successful implantation of a scaffold for tissue engineering. In this review, we discuss the multitude of ways macrophages are known to be important in cancer therapies and implanted biomaterials

Would you be surprised if this patient died?: Preliminary exploration of first and second year residents' approach to care decisions in critically ill patients

BACKGROUND: How physicians approach decision-making when caring for critically ill patients is poorly understood. This study aims to explore how residents think about prognosis and approach care decisions when caring for seriously ill, hospitalized patients. METHODS: Qualitative study where we conducted structured discussions with first and second year internal medicine residents (n = 8) caring for critically ill patients during Medical Intensive Care Unit Ethics and Discharge Planning Rounds. Residents were asked to respond to questions beginning with "Would you be surprised if this patient died?" RESULTS: An equal number of residents responded that they would (n = 4) or would not (n = 4) be surprised if their patient died. Reasons for being surprised included the rapid onset of an acute illness, reversible disease, improving clinical course and the patient's prior survival under similar circumstances. Residents reported no surprise with worsening clinical course. Based on the realization that their patient might die, residents cited potential changes in management that included clarifying treatment goals, improving communication with families, spending more time with patients and ordering fewer laboratory tests. Perceived or implied barriers to changes in management included limited time, competing clinical priorities, "not knowing" a patient, limited knowledge and experience, presence of diagnostic or prognostic uncertainty and unclear treatment goals. CONCLUSIONS: These junior-level residents appear to rely on clinical course, among other factors, when assessing prognosis and the possibility for death in severely ill patients. Further investigation is needed to understand how these factors impact decision-making and whether perceived barriers to changes in patient management influence approaches to care

Shear Wave Splitting Analysis to Estimate Fracture Orientation and Frequency Dependent Anisotropy

Shear wave splitting is a well-known method for indication of orientation, radius, and length of fractures in subsurface layers. In this paper, a three component near offset VSP data acquired from a fractured sandstone reservoir in southern part of Iran was used to analyse shear wave splitting and frequency-dependent anisotropy assessment. Polarization angle obtained by performing rotation on radial and transverse components of VSP data was used to determine the direction of polarization of fast shear wave which corresponds to direction of fractures. It was shown that correct implementation of shear wave splitting analysis can be used for determination of fracture direction. During frequency- dependent anisotropy analysis, it was found that the time delays in shear- waves decrease as the frequency increases. It was clearly demonstrated throughout this study that anisotropy may have an inverse relationship with frequency. The analysis presented in this paper complements the studied conducted by other researchers in this field of research

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Serpin Induced Antiviral Activity of Prostaglandin Synthetase-2 against HIV-1 Replication

The serine protease inhibitors (serpins) are anti-inflammatory proteins that have various functions. By screening a diverse panel of viruses, we demonstrate that the serpin antithrombin III (ATIII) has a broad-spectrum anti-viral activity for HIV-1, HCV and HSV. To investigate the mechanism of action in more detail we investigated the HIV-1 inhibition. Using gene-expression arrays we found that multiple host cell signal transduction pathways were activated by ATIII in HIV-1 infected cells but not in uninfected controls. Moreover, the signal pathways initiated by ATIII treatment, were more than 200-fold increased by the use of heparin-activated ATIII. The most up-regulated transcript in HIV-1 infected cells was prostaglandin synthetase-2 (PTGS2). Furthermore, we found that over-expression of PTGS2 reduced levels of HIV-1 replication in human PBMC. These findings suggest a central role for serpins in the host innate anti-viral response. Host factors such as PTGS2 elicited by ATIII treatment could be exploited in the development of novel anti-viral interventions

A viscoelastic deadly fluid in carnivorous pitcher plants

Background : The carnivorous plants of the genus Nepenthes, widely distributed in the Asian tropics, rely mostly on nutrients derived from arthropods trapped in their pitcher-shaped leaves and digested by their enzymatic fluid. The genus exhibits a great diversity of prey and pitcher forms and its mechanism of trapping has long intrigued scientists. The slippery inner surfaces of the pitchers, which can be waxy or highly wettable, have so far been considered as the key trapping devices. However, the occurrence of species lacking such epidermal specializations but still effective at trapping insects suggests the possible implication of other mechanisms. Methodology/Principal Findings : Using a combination of insect bioassays, high-speed video and rheological measurements, we show that the digestive fluid of Nepenthes rafflesiana is highly viscoelastic and that this physical property is crucial for the retention of insects in its traps. Trapping efficiency is shown to remain strong even when the fluid is highly diluted by water, as long as the elastic relaxation time of the fluid is higher than the typical time scale of insect movements. Conclusions/Significance : This finding challenges the common classification of Nepenthes pitchers as simple passive traps and is of great adaptive significance for these tropical plants, which are often submitted to high rainfalls and variations in fluid concentration. The viscoelastic trap constitutes a cryptic but potentially widespread adaptation of Nepenthes species and could be a homologous trait shared through common ancestry with the sundew (Drosera) flypaper plants. Such large production of a highly viscoelastic biopolymer fluid in permanent pools is nevertheless unique in the plant kingdom and suggests novel applications for pest control

Doppler broadening of in-flight positron annihilation radiation due to electron momentum

An overview is given on the first observation of Doppler broadening due to electron momentum in the τ rays emitted from in-flight two-photon annihilation when highly energetic positrons traverse thin foils. This observation can serve as basis in the development of a new probe of electron momentum distributions similar to Compton or electron scattering technique

Robotic milking technologies and renegotiating situated ethical relationships on UK dairy farms

Robotic or automatic milking systems (AMS) are novel technologies that take over the labor of dairy farming and reduce the need for human-animal interactions. Because robotic milking involves the replacement of 'conventional' twice-a-day milking managed by people with a system that supposedly allows cows the freedom to be milked automatically whenever they choose, some claim robotic milking has health and welfare benefits for cows, increases productivity, and has lifestyle advantages for dairy farmers. This paper examines how established ethical relations on dairy farms are unsettled by the intervention of a radically different technology such as AMS. The renegotiation of ethical relationships is thus an important dimension of how the actors involved are re-assembled around a new technology. The paper draws on in-depth research on UK dairy farms comparing those using conventional milking technologies with those using AMS. We explore the situated ethical relations that are negotiated in practice, focusing on the contingent and complex nature of human-animal-technology interactions. We show that ethical relations are situated and emergent, and that as the identities, roles, and subjectivities of humans and animals are unsettled through the intervention of a new technology, the ethical relations also shift. © 2013 Springer Science+Business Media Dordrecht