by Linda Darling-Hammond, New York, NY, Teacher’s College Press, 2010, 394 pp., £20.91 (paperback), ISBN 978-0-8077-4962-3 In The flat world and education: how America’s commitment to equity will d...

The flat world and education: how America’s commitment to equity will determine our future

Antimicrobial resistance (AMR) has developed as one of the major urgent threats to public health causing serious issues to successful prevention and treatment of persistent diseases. In spite of different actions taken in recent decades to tackle this issue, the trends of global AMR demonstrate no signs of slowing down. Misusing and overusing different antibacterial agents in the health care setting as well as in the agricultural industry are considered the major reasons behind the emergence of antimicrobial resistance. In addition, the spontaneous evolution, mutation of bacteria, and passing the resistant genes through horizontal gene transfer are significant contributors to antimicrobial resistance. Many studies have demonstrated the disastrous financial consequences of AMR including extremely high healthcare costs due to an increase in hospital admissions and drug usage. The literature review, which included articles published after the year 2012, was performed using Scopus, PubMed and Google Scholar with the utilization of keyword searches. Results indicated that the multifactorial threat of antimicrobial resistance has resulted in different complex issues affecting countries across the globe. These impacts found in the sources are categorized into three different levels: patient, healthcare, and economic. Although gaps in knowledge about AMR and areas for improvement are obvious, there is not any clearly understood progress to put an end to the persistent trends of antimicrobial resistance.

/pdf/antimicrobial-resistance-implications-and-costs-4okxq8ll3n.pdf

Antimicrobial Resistance: Implications and Costs.

Occurrence and toxicity of antibiotics in the aquatic environment: A review.

Across a variety of adverse life circumstances, such as social isolation and low socioeconomic status, mammalian immune cells have been found to show a conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes. The present study examines whether such effects might stem in part from the selective up-regulation of a subpopulation of immature proinflammatory monocytes (Ly-6chigh in mice, CD16− in humans) within the circulating leukocyte pool. Transcriptome representation analyses showed relative expansion of the immature proinflammatory monocyte transcriptome in peripheral blood mononuclear cells from people subject to chronic social stress (low socioeconomic status) and mice subject to repeated social defeat. Cellular dissection of the mouse peripheral blood mononuclear cell transcriptome confirmed these results, and promoter-based bioinformatic analyses indicated increased activity of transcription factors involved in early myeloid lineage differentiation and proinflammatory effector function (PU.1, NF-κB, EGR1, MZF1, NRF2). Analysis of bone marrow hematopoiesis confirmed increased myelopoietic output of Ly-6chigh monocytes and Ly-6cintermediate granulocytes in mice subject to repeated social defeat, and these effects were blocked by pharmacologic antagonists of β-adrenoreceptors and the myelopoietic growth factor GM-CSF. These results suggest that sympathetic nervous system-induced up-regulation of myelopoiesis mediates the proinflammatory component of the leukocyte CTRA dynamic and may contribute to the increased risk of inflammation-related disease associated with adverse social conditions.

https://www.pnas.org/content/pnas/110/41/16574.full.pdf

Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis

Bone marrow (BM) metastasis of breast cancer (BC) can recur even decades after initial diagnosis and treatment, implying the long-term survival of disseminated cancer cells in a dormant state. Here we investigated the role of microRNAs (miRNA) transmitted from BM stroma to BC cells via gap junctions and exosomes in tumor cell quiescence. MDA-MB-231 and T47D BC cells arrest in G(0) phase of the cell cycle when cocultured with BM stroma. Analyses of miRNA expression profiles identified numerous miRNAs implicated in cell proliferation including miR-127, -197, -222, and -223 targeting CXCL12. Subsequently, we showed that these CXCL12-specific miRNAs are transported from BM stroma to BC cells via gap junctions, leading to reduced CXCL12 levels and decreased proliferation. Stroma-derived exosomes containing miRNAs also contributed to BC cell quiescence, although to a lesser degree than miRNAs transmitted via gap junctions. This study shows that the transfer of miRNAs from BM stroma to BC cells might play a role in the dormancy of BM metastases.

https://cancerres.aacrjournals.org/content/canres/71/5/1550.full.pdf

Gap Junction–Mediated Import of MicroRNA from Bone Marrow Stromal Cells Can Elicit Cell Cycle Quiescence in Breast Cancer Cells

Introduction: Antibiotic-resistant infections have become increasingly prevalent nowadays. As a result, it is essential to examine the key socioeconomic and political factors which contribute to the rise in the prevalence of antibiotic resistance in developing and developed nations. This study aims to identify the various contributors to the development of antibiotic resistance in each type of nation. Methods: PUBMED was used to identify primary research, systematic reviews, and narrative reviews published before Jan 2017. Search terms included antibiotic resistance, antimicrobial resistance, superbugs, multidrug-resistant organisms, developing countries, developed countries. Publications from different countries were included to ensure generalizability. Publications were excluded if they didn't mention factors causing resistance, focused on the molecular basis of resistance, or if they were case reports. Publicly available reports from national and international health agencies were used. Results: In developing countries, key contributors identified included: (1) Lack of surveillance of resistance development, (2) poor quality of available antibiotics, (3) clinical misuse, and (4) ease of availability of antibiotics. In developed countries, poor hospital-level regulation and excessive antibiotic use in food-producing animals play a major role in leading to antibiotic resistance. Finally, research on novel antibiotics is slow ing down due to the lack of economic incentives for antibiotic research. Conclusion: Overall, multiple factors, which are distinct for developing and developed countries, contribute to the increase in the prevalence of antibiotic resistance globally. The results highlight the need to improve the regulatory framework for antibiotic use and research globally.

Global Contributors to Antibiotic Resistance.

Objective Angiographic embolization (AE) is a safe and effective method for controlling hemorrhage in both blunt and penetrating liver injuries. Improved survival after hepatic injuries has been documented using a multimodality approach; however, patients still have significant long-term morbidity.

Angiographic embolization for liver injuries: low mortality, high morbidity.

Background Patients with minimal head injury (MHI) and intracranial bleed (ICB) detected on cranial computed tomography (CT) scan routinely undergo a repeat cranial CT within 24 hours after injury to assess for progression of intracranial injuries. While this is clearly beneficial in patients with a deteriorating neurologic status, it is of questionable value in patients with a normal neurologic examination. The goal of this study was to prospectively assess the value of a repeat cranial CT in patients with a MHI and an ICB who have a normal neurologic examination. Methods A prospective analysis of all adult patients admitted to a Level I trauma center after blunt trauma causing a MHI (defined as the loss of consciousness or posttraumatic amnesia with a Glasgow Coma Scale (GCS) score of greater or equal to 13) and an ICB on the initial cranial CT during a 12-month period (July 2002 through July 2003) was performed. All patients with MHI were prospectively evaluated and followed until discharge. Data collected included demographics, neurologic examination and findings on the initial and repeat cranial CT scan. Outcome data included neurologic deterioration, neurosurgical intervention, and Glasgow Outcome Scale (GOS) on discharge. Results In all, 161 consecutive patients with MHI and a positive cranial CT scan were identified. The initial cranial CT lead to a neurosurgical intervention (1 craniotomy, 4 intracranial pressure monitors) in 4% of cases. The remaining 130 patients who met inclusion criteria, underwent a repeat cranial CT scan within 24 hours postadmission. Ninety nine (76%) patients had a normal neurologic examination at the time of their repeat cranial CT. After the repeat cranial CT none required immediate neurosurgical intervention or had delayed neurologic deterioration related to their head injury. Fifteen patients underwent additional neuroradiologic studies but none showed further progression of their ICB or lead to a change in management. One patient died from non-traumatic brain injury related causes and of the remaining 26 patients, 98% had an overall favorable GOS score (> 3) on discharge. In this group of patients with MHI and ICB, the negative predictive value of a normal neurologic examination was 100%. Conclusions Repeat cranial CT, in patients with a MHI and a normal neurologic examination, resulted in no change in management or neurosurgical intervention and is therefore not indicated. A multicenter prospective study would further validate these conclusions, reduce unnecessary CT scans, and likely improve our current standard of care in these patients.

A prospective evaluation of the value of repeat cranial computed tomography in patients with minimal head injury and an intracranial bleed.

Patients experiencing major trauma develop anemia, and subsequent transfusions are independent risk factors for infection, organ failure, and death.1 Previously, we have shown that bone marrow (BM) dysfunction is common in severely injured trauma patients, and this BM dysfunction is accompanied by persistent elevation of norepinephrine (NE), plasma granulocyte colony-stimulating factor (G-CSF), and the prolonged mobilization of hematopoietic progenitor cells (HPCs) into the peripheral blood.2,3 HPCs include granulocyte-erythrocyte-monocyte-macrophage progenitor cells, blast-forming unit erythroid cells (BFU-E), and colony-forming unit erythroid cells (CFU-E), which are the precursors to red blood cells. Under normal homeostatic conditions, HPCs are found within the BM and participate in erythropoiesis, and there is a reduced number of HPCs in the peripheral blood.4 G-CSF plays a direct role in the release of HPCs from the BM to the peripheral blood, and this G-CSF release is mediated by NE.4 Therefore, the combined exaggerated loss of HPCs from the BM and the suppression of HPC growth in BM after trauma contribute to prolonged BM dysfunction, which manifests as a persistent anemia that can persist for several months.5–7

The sympathetic response to severe traumatic injury is associated with a persistent systemic elevation of epinephrine and NE.2,8–11 This trauma-induced catecholamine surge has been shown to independently predict mortality, especially when there is concomitant head injury.11 In animal models, NE causes a dose-dependent reduction of BM HPC growth both in vitro and in vivo.12,13 In addition, plasma G-CSF levels are significantly elevated after trauma and shock, and this elevation is likely linked to the persistent elevation of NE.3,14 In a rodent model of injury and hemorrhagic shock, the use of propranolol reduced G-CSF and prevented excess HPC mobilization.5,14,15 Propranolol inhibits the action of endogenous catecholamines by competitively binding to all β-adrenergic receptors. Recent studies have demonstrated an association between A-blockade use and improved outcomes after injury.16,17 To date, however, propranolol has not been tested in trauma patients to examine its potential benefit on hematologic outcomes.

Therefore, we hypothesize that β-blockade would prevent prolonged HPC mobilization, persistent elevation of G-CSF, and anemia following severe injury. This study examines the effects of propranolol given after injury on BM function.

/pdf/early-propranolol-administration-to-severely-injured-4b4a2gmnjd.pdf

Ziad C. Sifri

Papers

Global Contributors to Antibiotic Resistance.

Angiographic embolization for liver injuries: low mortality, high morbidity.

A prospective evaluation of the value of repeat cranial computed tomography in patients with minimal head injury and an intracranial bleed.

Early propranolol administration to severely injured patients can improve bone marrow dysfunction.

Dose-response relationship between norepinephrine and erythropoiesis: evidence for a critical threshold