Abstract An international legal agreement governing the global antimicrobial commons would represent the strongest commitment mechanism for achieving collective action on antimicrobial resistance (AMR). Since AMR has important similarities to climate change—both are common pool resource challenges that require massive, long-term political commitments—the first article in this special issue draws lessons from various climate agreements that could be applicable for developing a grand...
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The American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry have released guidance for clinicians caring for children and adolescents who...
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The CDC has released new guidance for clinicians regarding the novel coronavirus (2019-nCoV) identified in China that has sickened over 200 people and killed...
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This week, the Clinical Conversations podcast talks with Prof. Joseph Doyle about an attempt at "hotspotting" — the process of identifying super-users of healthcare and...
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Dr. Frances Ue shares what she learned from a 3-day intensive program focused on theoretical and practical skills towards a clinician-educator career. Read...
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See our top picks from NEJM Group: NEJM Primary Care/Hospitalist Page: Case record: A 64-year-old man was admitted because of acute renal...
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Evidence on the size of physicians' panels and healthcare outcomes is "surprisingly thin", finds a review in the Annals of Internal Medicine. Researchers reviewed 28...
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Abstract The antiphospholipid syndrome (APS) was fully recognized as a clinical entity in the early 1980’s. Still, more than 30 years later, the epidemiology of APS is not well described and furthermore APS remains a challenge in terms of both diagnostic issues and clinical praxis involving a wide range of specialties. To date there are no diagnostic criteria for APS. The present classification criteria rely on a combination of clinical manifestations and persistently positive tests for...
20h
Abstract A paradox of so‐called developed countries is that, as the major historical causes of human mortality are eliminated or mitigated by medical progress, life‐style related diseases have become major killers. Furthermore, as life‐span is extended by the combined effects of modern medicine, health‐span is struggling to keep apace because of the burden of non‐communicable diseases linked to diet and sedentary life‐style. The gut microbiome is now recognized as a plastic environmental...
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BackgroundRecurrent pleural effusion is a common cause of dyspnoea, cough and chest pain during the course of infectious pleurisy and non-malignant diseases like congestive heart failure (CHF) or liver cirrhosis with hepatic hydrothorax (HH). With regard to the chronic character of the underlying diseases, indwelling pleural catheters (IPC) are increasingly used, not only assuring immediate symptom relief but also potentially leading to pleurodesis without sclerosing agents. Patients and methodsIn...
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Though infrequently used, random patterned local flaps offer a simple yet effective option in breast reconstruction. ePlasty, Open Access Journal of Plastic Surgery
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Despite long-standing public health efforts to eliminate lead exposure, researchers still find risks persist, pointing to decreased brain volume and lower cognitive function in children living in lower income areas. Medscape Medical News
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AimGuanidinoacetate N-methyltransferase (GAMT) is the second essential enzyme in creatine (Cr) biosynthesis. Short-term Cr deficiency is metabolically well tolerated as GAMT–/– mice exhibit normal exercise capacity and response to ischemic heart failure. However, we hypothesized long-term consequences of Cr deficiency and/or accumulation of the Cr precursor guanidinoacetate (GA).MethodsCardiac function and metabolic profile were studied in GAMT–/– mice >1 year.ResultsIn vivo LV catheterization...
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Temperature is a critical factor of insect population abundance and distribution. Monochamus alternatus Hope (Coleoptera: Cerambycidae) is a significant concern since it is transmitted vector of the pinewood nematode posing enormous economic and environmental losses. This pest shows tolerance to heat stress, especially extremely high temperatures. Exposing for 6, 12, 24, 48, or 96 h, the 50% median lethal temperatures (Ltem50) for fourth-instar larvae were 47.5, 45.5, 43.9, 43.4, and 42.3°C, respectively....
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The liver-derived hormone hepcidin plays a key role in iron metabolism by mediating the degradation of the iron export protein ferroportin 1 (FPN1). Circulating levels of hepcidin and the iron storage protein ferritin are elevated during the recovery period after acute endurance exercise, which can be interpreted as an acute phase reaction to intense exercise with far-reaching consequences for iron metabolism and homeostasis. Since absolute and functional iron deficiency (ID) potentially lead to...
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Solute Carrier (SLC) is a cluster of families of membrane bound transporters, of which many members lack defined substrate profile, and many more are poorly characterized. Many play a vital role in regulating metabolic systems, protein synthesis, and post translational modifications. SLC38 is one of the families of SLCs, which are also known as sodium-coupled neutral amino acid transporters (SNATs). In mice, it has 11 members (SNAT1-11) but in Drosophila there are two homologs for the SLC38 family;...
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The normal growth and regeneration of feathers is important for improving the welfare and economic value of poultry. Feather follicle stem cells are the basis for driving feather development and are regulated by various molecular signaling pathways in the feather follicle microenvironment. To date, the roles of the Wnt, Bone Morphogenetic Protein (BMP), Notch, and Sonic Hedgehog (SHH) signaling pathways in the regulation of feather growth and regeneration are among the best understood. While these...
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Mild normobaric hypoxia (NH) and modest exercise have multiple beneficial effects on health, but the changes in physiological function induced by NH and/or exercise remain unclear. The purpose of this investigation was to examine the specific effects of NH and/or exercise on cardiac function and myocardial structure and behavior including sleep-activity and negative geotaxis in aged Drosophila. We also assessed the survival rate of flies after hypoxia and/or exercise. One-thousand wild-type w1118...
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Despite a 30% decline in mortality since 2000, malaria still affected 219 million subjects and caused 435,000 deaths in 2017. Red blood cells (RBC) host Plasmodium parasites that cause malaria, of which Plasmodium falciparum is the most pathogenic. The deformability of RBC is markedly modified by invasion and development of P. falciparum. Surface membrane area is potentially impacted by parasite entry and development, the cytoskeleton is modified by parasite proteins and cytosol viscosity is altered...
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Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction. The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility. Here, we investigated whether O-GlcNAc affects the inflammatory response and cardiovascular...
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Vasculogenesis, angiogenesis and arteriogenesis represent three crucial mechanisms involved in the formation and maintenance of the vascular network in embryonal and post-natal life. It has long been known that endothelial Ca2+ signals are key players in vascular remodeling; indeed, multiple pro-angiogenic factors, including vascular endothelial growth factor, regulate endothelial cell fate through an increase in intracellular Ca2+ concentration. Transient Receptor Potential (TRP) channel consist...
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Adaptations to low temperature play a critical role in restricting the geographical distribution of insects. Decreasing day lengths and temperatures trigger seasonal cold adaptations in insects. These adaptions include changes in expression at the miRNA, mRNA and protein levels. The rice water weevil (RWW), Lissorhoptrus oryzophilus, introduced from the Mississippi River, is a globally invasive pest of wetland rice that can survive at the northern border of China. To investigate the changes in expression...
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ObjectiveIn the present study, we investigated the associations between D-dimer levels at admission and early adverse events in patients with acute type A aortic dissection undergoing arch replacement and the frozen elephant trunk (FET).MethodsWe retrospectively analyzed data of patients with acute type A aortic dissection undergoing aortic arch surgery and FET from July 2017 to December 2018 at Beijing Anzhen Hospital. D-dimer levels were evaluated within 24 h of admission. Multivariate Cox regression...
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ObjectivesCarotid artery geometry influences blood flow disturbances and is thus an important risk factor for carotid atherosclerosis. Extracellular matrix (ECM) and yes-associated protein (YAP) expression may play essential roles in the pathophysiology of carotid artery stenosis, but the effect of blood flow disturbances of carotid bifurcation location on the ECM is unknown. We hypothesized that carotid artery anatomy and geometry are independently associated with the ECM and YAP expression.MethodsIn...
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We have recently demonstrated the existence of a region on the cardiac mechanics stress-length plane, which we have designated “The cardiac end-systolic zone.” The zone is defined as the area on the pressure-volume (or stress-length) plane within which all stress-length contraction profiles reach their end-systolic points. It is enclosed by three boundaries: the isometric end-systolic relation, the work-loop (shortening) end-systolic relation, and the zero-active stress isotonic end-systolic relation....
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Along the Norwegian coasts and margins, extensive reefs of the stony coral Lophelia pertusa act as hotspots for local biodiversity. Climate models project that the temperature of Atlantic deep waters could rise by 1–3°C by 2100. In this context, understanding the effects of temperature on the physiology of cold-water species will help in evaluating their resilience to future oceanic changes. We investigated the response of L. pertusa to stepwise short-term increases in temperature. We sampled corals...
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BackgroundHigh salt intake is associated with both oxidative stress and chronic kidney disease (CKD) progression. Nuclear factor E2-related factor 2 (Nrf2) is a transcriptional factor regulating the antioxidant and detoxifying genes to potently antagonize oxidative stress. This study examined the effect of high salt loading on the expression of Nrf2 in kidney.MethodsMice were treated with acute salt loading, and Nrf2 expression in the kidney was detected by Western blotting and immunostaining. Reactive...
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Hypoxic injury is one of the most important factors in progressive kidney disorders. Since we have found that δ-opioid receptor (DOR) is neuroprotective against hypoxic stress through a differential regulation of mitogen-activated protein kinases (MAPKs) and anti-inflammatory cytokines, we asked if DOR that is highly expressed in the kidney can modulate renal MAPKs and anti-inflammatory cytokines under hypoxia. We exposed cultured rat kidney epithelial cells (NRK-52E) to prolonged hypoxia (1% O2)...
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Connexin (Cx) proteins form gap junction channels (GJC) and hemichannels that a allow bidirectional flow of ions and metabolites between the cytoplasm and extracellular space, respectively. Under physiological conditions, hemichannels have a very low probability of opening, but in certain pathologies, hemichannels activity can increase and induce and/or accelerate cell death. Several mechanisms control hemichannels activity, including phosphorylation and oxidation (i.e., S-nitrosylation). Recently,...
17h
Esophageal squamous cell carcinoma (ESCC) is a common malignancy with poor prognosis and survival rate. To identify meaningful long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) modules related to the ESCC prognosis, The Cancer Genome Atlas-ESCC was downloaded and processed, and then, a weighted gene co-expression network analysis was applied to construct lncRNA co-expression networks, miRNA co-expression networks, and mRNA co-expression networks. Twenty-one hub lncRNAs, seven...
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As a common therapy for prostate cancer, androgen deprivation therapy (ADT) is effective for the majority of patients. However, prolonged ADT promotes drug resistance and progression to an aggressive variant with reduced androgen receptor signaling, so called neuroendocrine prostate cancer (NEPC). Until present, NEPC is still poorly understood, and lethal with no effective treatments. Elevated expression of neuroendocrine related markers and increased angiogenesis are two prominent phenotypes of...
2h
There is a great need to improve the outlook for people facing urinary bladder cancer, especially for patients with invasive urothelial carcinoma (InvUC) which is lethal in 50% of cases. Improved outcomes for patients with InvUC could come from advances on several fronts including emerging immunotherapies, targeted therapies, and new drug combinations; selection of patients most likely to respond to a given treatment based on molecular subtypes, immune signatures, and other characteristics; and prevention,...
2h
Pancreatic ductal adenocarcinoma (PDAC) is associated with several genetic syndromes. However, the molecular mechanism underlying PDAC progression is still unknown. In this study, we showed that Laminin Subunit Beta 3 (LAMB3) was aberrantly overexpressed in PDAC and was closely associated with the overall survival rate of patients with PDAC. Functional studies demonstrated that LAMB3 played important roles in cell proliferation, the cell cycle, and invasion capacity. Using bioinformatics analysis,...
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Introduction: In the United States and Europe, endometrial endometrioid carcinoma (EEC) is the most prevalent gynecologic malignancy. Lymph node metastasis (LNM) is the key determinant of the prognosis and treatment of EEC. A biomarker that predicts LNM in patients with EEC would be beneficial, enabling individualized treatment. Current preoperative assessment of LNM in EEC is not sufficiently accurate to predict LNM and prevent overtreatment. This pilot study established a biomarker signature for...
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Object: To identify genes of prognostic value which associated with tumor microenvironment (TME) in acute myeloid leukemia (AML).Methods and Materials: Level 3 AML patients gene transcriptome profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Clinical characteristics and survival data were extracted from the Genomic Data Commons (GDC) tool. Then, limma package was utilized for normalization processing. ESTIMATE algorithm was used for calculating immune, stromal and ESTIMATE scores....
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Achieving replicative immortality is a crucial step in tumorigenesis and requires both bypassing cell cycle checkpoints and the extension of telomeres, sequences that protect the distal ends of chromosomes during replication. In the majority of cancers this is achieved through the enzyme telomerase, however a subset of cancers instead utilize a telomerase-independent mechanism of telomere elongation—the Alternative Lengthening of Telomeres (ALT) pathway. Recent work has aimed to decipher the exact...
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Ovarian cancer is a leading cause of death from gynecological malignancies. Although the prognosis is quite favorable if detected at an early stage, the vast majority of cases are diagnosed at an advanced stage, when 5-year survival rates are only 30–40%. Most recurrent ovarian tumors are resistant to traditional therapies underscoring the need for new therapeutic options. Theranostic agents, that combine diagnostic and therapeutic capabilities, are being explored to better detect, diagnose and treat...
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Object: To evaluate the efficacy and tolerability of consolidative chemoradiotherapy (cCRT) after induced chemotherapy (iCT) for locally advanced pancreatic cancer (LAPC).Patients and methods: Patients with LAPC were enrolled from January 2013 to November 2018. In stage one, all patients received iCT. Those without distant metastasis proceeded to stage two, received 50.4 Gy cCRT with S-1 as radiosensitizer. Efficacy and tolerability were evaluated in all patients.Results: Sixty-five patients enrolled...
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Background: Lymph node (LN) metastasis is the most important prognostic factor in esophageal squamous cell carcinoma (ESCC). Traditional clinical factor and existing methods based on CT images are insufficiently effective in diagnosing LN metastasis. A more efficient method to predict LN status based on CT image is needed.Methods: In this multicenter retrospective study, 411 patients with pathologically confirmed ESCC were registered from two hospitals. Quantitative image features including handcrafted-,...
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Ovarian cancer (OC) accounts for more than 150,000 deaths worldwide every year. Patients are often diagnosed at an advanced stage with metastatic dissemination. Although platinum- and taxane-based chemotherapies are effective treatment options, they are rarely curative and eventually, the disease will progress due to acquired resistance. Emerging evidence suggests a crucial role of long non-coding RNAs (lncRNAs) in the response to therapy in OC. Transcriptome profiling studies using high throughput...
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Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition...
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Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune escape, tumor microenvironment-associated soluble factors, and/or cell surface-bound molecules are mostly responsible for dysfunctional activity of tumor-specific CD8+T cells. These dynamic immunosuppressive networks prevent tumor rejection at several levels, limiting also the success of immunotherapies. Nevertheless,...
2h
Nanoparticles (NPs) camouflaged in cell membranes represent novel biomimetic platforms that can mimic some of the membrane functions of the cells from which these membranes are derived, in biological systems. Studies using cell membrane coated NPs cover a large repertoire of membranes derived from cells such as red blood cells, immune cells, macrophages, and cancer cells. Cancer cell membrane coated nanoparticles (CCMCNPs) typically consist of a NP core with a cancer cell plasma membrane coat that...
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Epidermal growth factor receptor (EGFR) antibodies may have detrimental effects in patients with metastatic colorectal cancer expressing oncogenic Rat sarcoma (RAS). Since a significant number of patients acquire RAS-mediated resistance during EGFR-directed treatment, understanding the molecular mechanism underlying these antibody-mediated tumor-promoting effects is of relevance to design more resistance-preventive treatment approaches. To test this, we set up a Ba/F3 cellular model system transformed...
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Cutaneous squamous cell carcinoma (cSCC) is the second common malignant cancer around the worldwide and is etiologically linked to ultraviolet radiation. miRNAs play an important role in the initiation and progression of cancers. However, the functions of miRNAs in cSCC remain to be elucidated. Here, we screened and identified miR-27a as a consistently downregulated miRNA after UVB irradiation in HaCaT cells. It was found that miR-27a expression was significantly decreased in cSCC cells and tissues....
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Hereditary papillary renal carcinoma (HPRC) is a rare autosomal dominant disease characterized by the development of multiple papillary type I renal cell carcinomas. This hereditary kidney cancer form is caused by activating mutations in MET. Descriptions of patients with HPRC are scarce in the world literature, and no cases have been described in open sources in Russia. Here, we describe a 28-year-old female Russian patient with 7 and 10 primary papillary renal cell carcinomas in the left and right...
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Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger epigenetic changes including DNA hypomethylation, one of which is a frequent lack of O6-methyl-guanine-DNA methyltransferase (MGMT) promoter methylation, resulting in increased MGMT expression. We established the NGT16 cell line with HIST1H3B K27M and ACVR1 G328E gene mutations from a DMG patient and used this cell line and other DMG cell lines with H3F3A...
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Theoretical and empirical work over the past several decades suggests that oncogenesis and disease progression represents an evolutionary story. Despite this knowledge, current anti-resistance strategies to drugs are often managed through treating cancers as independent biological agents divorced from human activity. Yet once drug resistance to cancer treatment is understood as a product of artificial or anthropogenic rather than unconscious selection, oncologists could improve outcomes for their...
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