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The progression of cancer is strongly influenced by the crosstalk between cancer cells and immune cells. Immune cells can have both pro- and anti-tumor functions depending on the signals present in the environment. A significant proportion of the immune compartment of most solid tumors consists of tumor-associated macrophages. Although their abundance has been associated with poor prognosis in many solid tumor types, the molecular mechanisms by which cancer cells influence macrophage phenotype and function are largely unknown. In this chapter, we provide a detailed description of in vitro assays to study the impact of cancer cells on macrophages. We provide protocols to obtain macrophages from murine bone marrow and human peripheral blood, and to expose these macrophages to cancer cell-derived secreted molecules using conditioned medium from cancer cells. We describe several assays to assess cancer cell-induced polarization of macrophages. This experimental set-up can be utilized to gain molecular insights into how cancer cells influence macrophages. © 2020 Elsevier Inc. All rights reserved.Tumor-associated macrophages (TAMs) are becoming a promising target for cancer immunotherapy. Significant efforts have been made to study the detrimental role of TAMs both in vivo and in vitro. However, it remains challenging to isolate these macrophages to study their function in human cancers and there is the need to seek alternatives to address these limitations. In this review, we will focus on the three most relevant approaches to obtain in vitro fully differentiated macrophages i.e. peripheral blood, immortalized cell lines such as THP-1 or human induced pluripotent stem cells. We will also provide protocols for the polarization of human macrophages to a TAM-like cells in vitro. © 2020 Elsevier Inc. All rights reserved.Tumor cells treated by immunogenic cell death (ICD) inducers emit danger associated molecular patterns (DAMP), including but not limited to calreticulin (CALR), which translocates from the ER lumen to the surface of the cellular membrane where it serves as de novo uptake signal for antigen presenting cells of the immune system. CALR is exposed at an early stage of ICD and dictates tumor antigen transfer and therefore the immunogenicity of cancer cell death. Here, we provide a bi-color flow cytometry protocol for the quantification of ICD-associated CALR cell surface exposure in fixed samples. As compared to the detection of surface exposed CALR by confocal microscopy, the present flow cytometry-based analysis is cost-efficient and does not require sophisticated equipment. Moreover, the staining panel can be extended to a multicolor analysis for the parallel assessment of additional parameters. © 2020 Elsevier Inc. All rights reserved.After a short summary of Arnold Pick's biography, the history of how Pick's disease (PiD) was reported is presented, from its clinical symptoms to its molecular characterization. The macroscopic description of frontotemporal atrophy by Pick is recounted followed by a description of the histological lesions observed by Alzheimer and the progressive characterization of the disease. The subsequent diagnosis has since relied on ultrastructural findings as well as immunohistochemical and biochemical techniques. The discovery of the role of the microtubule-associated τ-protein, encoded by chromosome 17, more specifically of the 3R isoform, has led to the inclusion of PiD in the 3R tauopathies. Today, both sporadic and familial PiDs, including the more frequent behavioral form, are considered as frontotemporal dementias. Experimental models have reproduced some of the lesions but the prion-like hypothesis concerning PiD has not, as yet, been proven.
.AIM Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the progressive degeneration of motor neurons. MicroRNAs are 17 - 27 nucleotide long molecules that regulate post-transcriptional mRNA expression. The aim of this study was to investigate the role of microRNAs in the skeletal muscle of ALS patients and correlate these results with the expression of histone deacetylase 4 (HDAC4) protein. MATERIALS AND METHODS We measured the expression levels of muscle-specific microRNAs (miR-1, miR-133a, miR-133b, miR-206), inflammatory micro-RNAs (miR-27a, miR-221, miR-155), and HDAC4 protein content on western blotting in muscle biopsies obtained for diagnostic reasons in 18 ALS patients 8 genetic forms (C9-ALS and SOD1-ALS), 5 sporadic cases (SALS), and 5 ALS cases affected only by upper motor neuron disease (UMN). RESULTS In muscle of patients with genetic forms of ALS, we found a strong upregulation of miR-206, a muscle-specific miRNA involved in neuromuscular junction (NMJ), regeneration and muscle atrophy, and a decreased expression of HDAC4 protein levels, which is involved both in denervation and regulation of miR-206 in ALS pathophysiology. In these patients, we also observed an increase of inflammatory miRNAs. CONCLUSION The different expression of miRNAs and HDAC4 in genetic ALS vs. SALS and UMN cases is likely to be correlated to different pathogenic mechanisms.
.OBJECTIVE Low-molecular-weight heparins are frequently used to prevent venous thromboembolism. Vasopressor therapy may be associated with inadequate anti-factor Xa activity, thereby increasing the risk of venous thromboembolism. Cyclopamine We aimed to assess the association between anti-factor Xa activity and norepinephrine dose in intensive care unit (ICU) patients treated with subcutaneous dalteparin for venous thromboembolism prophylaxis. MATERIALS AND METHODS This was a prospective observational pilot study in adult ICU patients treated with dalteparin 5,000 IU subcutaneously once daily and norepinephrine > 0.25 µg/kg/min. Peak anti-factor Xa activity was monitored and dalteparin doses were adjusted following a predefined dose algorithm. RESULTS From November 2016 to April 2018, 32 patients were included. No correlation was found between norepinephrine dose and anti-factor Xa activity (r = -0.01, 95% confidence interval = -0.47 - 0.27, p = 0.57). Furthermore, following dalteparin 5,000 IU once daily, 28% of the patients showed anti-factor Xa activity less then 0.10 IU/mL. Higher body mass index (BMI) (p less then 0.001) but not patients' norepinephrine dose, age, or serum creatinine were risk factors for anti-factor Xa activity less then 0.10 IU/mL. Dose increments to 7,500 IU once daily resulted in anti-factor Xa activity ≥ 0.10 IU/mL in all 5 patients (p = 0.043). CONCLUSION In this cohort of ICU patients, no association was found between norepinephrine dose and anti-factor Xa activity following subcutaneous dalteparin 5,000-IU administration once daily. Furthermore, nearly one-third of the patients showed anti-factor Xa activity below the target concentration for venous thromboembolism prophylaxis. Higher BMI was an independent risk factor for reduced anti-Xa activity.
.OBJECTIVE Vancomycin is a commonly used glycopeptide antibiotic due to its effectiveness in treating serious Gram-positive bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA) infection. Pancytopenia is a rare, yet serious, complication of vancomycin. Previous isolated cases have been reported in adults but none in children. CASE REPORT A 16-month-old boy received vancomycin for treatment of osteomyelitis caused by MRSA. During his administration of vancomycin, reversible pancytopenia, pulmonary infection, and skin rash developed, which resolved after withdrawal. CONCLUSION This is the first known case of vancomycin causing reversible pancytopenia and skin rash in a child, suggesting that pancytopenia caused by vancomycin could complicate treatment of children, and the hypothesis that pancytopenia is an immune-mediated reaction seems to be preferable. According to drug hypersensitivity syndrome (DHS) risk assessment in 10-D assessment system, this case was at grade of no risk.
.OBJECTIVE Hurricane Harvey, which made landfall in Texas on August 24, 2017, caused catastrophic damage that resulted in the closure of many schools and school districts across 4 states. We evaluated the underlying reasons and characteristics of the unplanned school closures to gain insight on how communities may cope with recommended preemptive closures as an intervention for pandemic influenza. METHODS Information was extracted from news articles, school websites, and Twitter and Facebook posts previously collected through daily systematic searches of Google, Google News, and Lexis-Nexis. This information was sorted into predefined categories describing the characteristics that may be associated with unplanned school closures that occur during a natural disaster. RESULTS Across Texas, Louisiana, Kentucky, and Tennessee, there were 3026 unplanned closures. Sixty-three percent of the closures occurred in Texas. The main reasons for the closures were flooding, power outages, and structural damage. The closed schools in Texas were sometimes used as shelters or as locations for providing food or other resources. CONCLUSION School closures associated with Hurricane Harvey were attributed to both the effects of the hurricane and use for resource allocation. These findings can help inform preparedness planning and response for future hurricane seasons and other large-scale emergencies.Emergency medical services (EMS) provides a critical role in the rapid treatment, stabilization, and transfer of patients in the prehospital setting. The national EMS provider for Israel has developed a robust and unique organization of volunteers with advanced telecommunication strategies to activate and direct them in order to improve these processes. The volunteers include local high school students, international college students, emergency medical technicians, on-call volunteers, motorcyclists, and Life Guardian first responders. The telecommunication strategies include pagers, push-to-talk over cellular, and sophisticated smartphone-based software applications. These are monitored and directed via a central command and control station. Such processes, both on an organizational as well as technical level, can be adapted to improve prehospital emergency care.Many studies have been carried out to investigate the morphological structure of the syrinx in many bird species. However, the cellular organization of the syrinx in the fowls and pigeons is still unclear. The current study revealed that in fowl and pigeon, the syrinx is formed of three main parts including tympanum (cranial) part, intermediate syringeal part, and bronchosyringeal (caudal) part, in addition to pessulus and tympaniform membranes. A great variation in the structural characteristics of syrinx of fowl and pigeon was recorded. In fowl, the tympaniform membranes showed a characteristic distribution of elastic and collagen fibers which increase the elasticity of tympaniform membranes. Moreover, the bony pessulus helps the medial tympaniform membranes to be stiffer, vibrate more strongly so that louder sound will be generated. In pigeon, the lateral tympaniform membrane is of greater thickness so that the oscillation of this membrane is reduced and the amplitude is lower. Moreover, the pessulus is smaller in size and is formed mainly of connective tissue core (devoid of cartilaginous or bony plates), resulting in the failure of stretching and vibrating of the medial tympaniform membranes, that leads to the generation of deeper sound.