Showing papers in "Journal of Investigative Medicine in 2018"
TL;DR: The additional ability of MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat, in combination with rapid scanning protocols and efficient image analysis tools, makes quantitative MRI a powerful tool for advanced body composition assessment.
Abstract: This paper gives a brief overview of common non-invasive techniques for body composition analysis and a more in-depth review of a body composition assessment method based on fat-referenced quantitative MRI. Earlier published studies of this method are summarized, and a previously unpublished validation study, based on 4753 subjects from the UK Biobank imaging cohort, comparing the quantitative MRI method with dual-energy X-ray absorptiometry (DXA) is presented. For whole-body measurements of adipose tissue (AT) or fat and lean tissue (LT), DXA and quantitative MRIs show excellent agreement with linear correlation of 0.99 and 0.97, and coefficient of variation (CV) of 4.5 and 4.6 per cent for fat (computed from AT) and LT, respectively, but the agreement was found significantly lower for visceral adipose tissue, with a CV of >20 per cent. The additional ability of MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat, in combination with rapid scanning protocols and efficient image analysis tools, makes quantitative MRI a powerful tool for advanced body composition assessment.
291 citations
TL;DR: The role of viruses in hospital-acquired pneumonia and ventilator-associated pneumonia as causative agents or as co-pathogens and the effect of virus detection on clinical outcome are being investigated.
Abstract: Viral pathogens are increasingly recognized as a cause of pneumonia, in immunocompetent patients and more commonly among immunocompromised. Viral pneumonia in adults could present as community-acquired pneumonia (CAP), ranging from mild disease to severe disease requiring hospital admission and mechanical ventilation. Moreover, the role of viruses in hospital-acquired pneumonia and ventilator-associated pneumonia as causative agents or as co-pathogens and the effect of virus detection on clinical outcome are being investigated. More than 20 viruses have been linked to CAP. Clinical presentation, laboratory findings, biomarkers, and radiographic patterns are not characteristic to specific viral etiology. Currently, laboratory confirmation is most commonly done by detection of viral nucleic acid by reverse transcription-PCR of respiratory secretions. Apart from the US Food and Drug Administration-approved medications for treatment of influenza pneumonia, the treatment of non-influenza respiratory viruses is limited. Moreover, the evidence supporting the use of available antivirals to treat immunocompromised patients is modest at best. With the widespread use of molecular diagnostics, an aging population, and advancement in cancer therapy, physicians will face a bigger challenge in managing viral respiratory tract infections. Emphasis on infection control measures to prevent the spread of respiratory viruses especially in healthcare settings is extremely important.
61 citations
TL;DR: Although pioglitazone is emerging as the treatment of choice for NASH in patients with insulin-resistance, or those with T2DM, many other options are being tested and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming one of the cornerstones for the management of both obesity and T2 DM, and a novel alternative for the treatmentof NAFLD.
Abstract: Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM), and is associated with a cluster of metabolic factors that lead to poor cardiovascular outcomes. In non-alcoholic fatty liver disease (NAFLD), liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. It is now recognized as the most common chronic liver disease in Westernized societies, often progressing to more severe forms of the disease such as nonalcoholic steatohepatitis (NASH), or cirrhosis and hepatocellular carcinoma. However, NAFLD remains largely overlooked by healthcare providers although it affects about two-thirds of patients with obesity and it promotes the development of T2DM. NAFLD mirrors adipose tissue and systemic insulin resistance, the liver being a ’barometer9 of metabolic health. Although pioglitazone is emerging as the treatment of choice for NASH in patients with insulin-resistance, or those with T2DM, many other options are being tested. Due to their overall safety and efficacy, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming one of the cornerstones for the management of both obesity and T2DM, and a novel alternative for the treatment of NAFLD. In this review, we will briefly summarize the status of GLP-1RA for the treatment of obesity and NAFLD.
54 citations
TL;DR: Baseline Edmondson stage, T stage, accumulated tumor diameter, microvascular cancer embolus, and AFP levels may be predictive of HCC recurrence following LTx; however, CTC levels and subtypes were not.
Abstract: Although studies have shown that detection of peripheral circulating tumor cells (CTCs) is an important tool for monitoring prognosis and therapeutic response in patients with cancer, few studies have analyzed their role in patients with hepatocellular carcinoma (HCC) following liver transplantation (LTx). The present study examined whether CTC levels were associated with HCC recurrence in patients with HCC after LTx. This prospective study included 47 patients who received LTx between October 2014 and May 2016 and who underwent analysis for peripheral CTCs at least twice using the CanPatrol system. Baseline Edmondson stage, T stage, accumulated tumor diameter, microvascular cancer embolus, and alpha-fetoprotein (AFP) levels were greater in patients with recurrence (all p 0.05). In conclusion, baseline Edmondson stage, T stage, accumulated tumor diameter, microvascular cancer embolus, and AFP levels may be predictive of HCC recurrence following LTx; however, CTC levels and subtypes were not. Further large, multicenter studies are necessary to confirm these results.
32 citations
TL;DR: It is concluded that plasma MOTS-c concentration is unaltered in human obesity, however, Mots-c associates positively with insulin resistance mostly in lean individuals, indicating that plasma HOMA concentration depends on the metabolic status in this population.
Abstract: Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide that attenuates weight gain and hyperinsulinemia when administered to high fat-fed mice. MOTS-c is therefore a potential regulator of metabolic homeostasis under conditions of high-energy supply. However, the effect of insulin resistance and obesity on plasma MOTS-c concentration in humans is unknown. To gain insight into MOTS-c regulation, we measured plasma MOTS-c concentration and analyzed its relationship with insulin sensitivity surrogates, in lean and obese humans (n=10 per group). Obese individuals had impaired insulin sensitivity as indicated by low Matsuda and high Homeostatic Model Assessment (HOMA) indexes. Although plasma MOTS-c concentration was similar in lean and obese individuals (0.48±0.16 and 0.52±0.15 ng/mL; p=0.60), it was correlated with HOMA (r=0.53; p<0.05) and Matsuda index (r=-0.46; p<0.05). Notably, when the groups were analyzed separately, the associations remained only in lean individuals. We conclude that plasma MOTS-c concentration is unaltered in human obesity. However, MOTS-c associates positively with insulin resistance mostly in lean individuals, indicating that plasma MOTS-c concentration depends on the metabolic status in this population. Such dependence seems altered when obesity settles. The implications of plasma MOTS-c for human metabolic homeostasis deserve future examination.
32 citations
TL;DR: 18F-FDG-PET and PET/CT were found to be accurate in the evaluation of primary tumors, lymph node metastasis, and distant metastasis in patients with CCA.
Abstract: This meta-analysis was performed to determine the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in assessing primary cholangiocarcinoma (CCA) and CCA with lymph node and distant metastasis. A literature search for studies reporting the use of 18F-FDG-PET for preoperative work-up/staging in patients with CCA was performed. Diagnostic OR (DOR) was used as an index of diagnostic performance of FDG-PET/CT in predicting primary CCA, lymph node metastases, and distant metastases. The pooled DOR was 9.34 (95% CI 4.27 to 20.42) and the area under the summary receiver operating characteristic (SROC) curve was 0.8643 (SE=0.0362), indicating overall good discriminatory test performance in predicting primary CCA. Subgroup analyses based on the primary tumor site showed better diagnostic performance for intrahepatic CCA (DOR=54.44, 95% CI 13.44 to 220.49), both intrahepatic and extrahepatic CCA (DOR=32.96, 95% CI 1.41 to 768.80) and gallbladder cancer (DOR=12.93, 95% CI 1.97 to 84.80), than for extrahepatic CCA (DOR=2.55, 95% CI 0.71 to 9.20) and hilar CCA (DOR=2.75, 95% CI 0.17 to 43.72). The pooled DOR for the prediction of lymph nodes metastases in 10 studies was 11.34 (95% CI 4.79 to 26.80), with moderate heterogeneity (Cochran Q=15.14, p=0.0872, I2=40.5%). The area under the SROC curve was 0.8584 (SE=0.0729). In conclusion, 18F-FDG-PET and PET/CT were found to be accurate in the evaluation of primary tumors, lymph node metastasis, and distant metastasis in patients with CCA.
30 citations
TL;DR: A case is presented that highlights the different biological responses in human hosts to asbestos exposure, and there are currently no effective means to determine which asbestos-exposed patients will develop malignancy and which will not.
Abstract: Asbestos comprises a group of fibrous minerals that are naturally occurring in the environment. Because of its natural properties, asbestos gained popularity for commercial applications in the late 19th century and was used throughout the majority of the 20th century, with predominant use in the construction, automotive, and shipbuilding industries. Asbestos has been linked to a spectrum of pulmonary diseases, such as pleural fibrosis and plaques, asbestosis, benign asbestos pleural effusion, small cell lung carcinoma, non-small cell lung carcinoma, and malignant mesothelioma. There are several mechanisms through which asbestos can lead to both benign and malignant disease, and they include alterations at the chromosomal level, activation of oncogenes, loss of tumor suppressor genes, alterations in cellular signal transduction pathways, generation of reactive oxygen and nitrogen species, and direct mechanical damage to cells from asbestos fibers. While known risk factors exist for the development of asbestos-related malignancies, there are currently no effective means to determine which asbestos-exposed patients will develop malignancy and which will not. There are also no established screening strategies to detect asbestos-related malignancies in patients who have a history of asbestos exposure. In this article, we present a case that highlights the different biological responses in human hosts to asbestos exposure.
30 citations
TL;DR: A non- dipper pattern of hypertension is an independent risk factor for LV systolic dysfunction and treatment that could reverse this non-dipper pattern may reduce cardiac damage in patients with hypertension.
Abstract: A non-dipper pattern of high blood pressure is associated with increased risk of organ damage and cardiovascular disease in patients with hypertension The aim of the study was to evaluate the left ventricular (LV) remodeling and function and arterial stiffness in a dipper/non-dipper pattern of high blood pressure in patients with hypertension A total of 183 hypertensive patients with no history of adverse cardiovascular events were divided into two groups based on 24 hours ambulatory blood pressure monitoring (ABPM): 66 patients with a dipper pattern and 117 patients with non-dipper pattern Detailed transthoracic echocardiogram was performed and analyzed with advance speckle tracking 3-orthogonal direction strain analysis to assess LV systolic function and tissue Doppler-derived E/E' for LV diastolic function assessment Cardio ankle vascular index (CAVI) was used to evaluate arterial stiffness Compared with patients with dipper hypertension, those with non-dipper hypertension had increased LV mass index, higher prevalence of eccentric and concentric LV hypertrophy, more impaired LV diastolic and systolic function and peripheral arterial stiffness Multivariable analysis revealed that a non-dipper pattern was independently associated with LV systolic dysfunction evaluated by speckle tracking-derived strain analysis In conclusion, a non-dipper pattern of hypertension is an independent risk factor for LV systolic dysfunction Treatment that could reverse this non-dipper pattern may reduce cardiac damage in these patients
30 citations
TL;DR: Patients with acromegaly who presented with multiple acromEGaly-related symptoms were evidenced to have experienced higher economic burden and poorer quality of life than patients with the same diagnosis but fewer symptoms.
Abstract: The study aimed to assess the economic burden, health-related quality of life (HRQoL), and acromegaly treatment satisfaction in the USA. A web-based, cross-sectional survey was distributed to members of Acromegaly Community. Data related to comorbidities, treatment patterns, and treatment satisfaction were collected. The costs over the past 3 months included out-of-pocket cost, sick leave, leave of absence, direct loss of job due to acromegaly, unemployment, assistance to perform household chores, and family member loss of income. The HRQoL was assessed by Acromegaly Quality of Life (AcroQoL) and EQ-5D-3L questionnaires. Among 106 patients who completed the survey (mean age: 46 years, female: 76.4%), 44.3% presented with ≥5 comorbidities, and 90.6% reporting acromegaly-related symptoms. Compared with the low-symptom group 0–3 (n=41), the 4+ symptoms group (n=65) was more likely to have depression (OR=2.3, 95% CI 1.1 to 5.2) and cardiovascular disease (OR=5.8, 95% CI 2.0 to 16.7), and experienced higher costs (loss of job: $8874 vs $1717, P=0.02; unemployment disability: $17,102 vs $429, P=0.003; household chores: $2160 vs $932, P=0.0003; family members’ income loss: $692 vs $122, P=0.03). The high-symptom group had lower HRQoL scores, compared with the low-symptom group (EQ-5D-3L: 0.53 vs 0.75, P
28 citations
TL;DR: In this article, the authors investigated whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-klootho level can predict adverse renal outcomes or CKD progression.
Abstract: To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3–5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.
25 citations
TL;DR: In conclusion, miRNA-15b deteriorates cardiomyocyte apoptosis by post-transcriptionally downregulating the expression of Bcl-2 and MAPK3.
Abstract: To investigate the role of miRNA-15b in cardiomyocyte apoptosis after ischemia reperfusion injury in acute myocardial infarction (AMI), we conducted the AMI rat model by using left anterior descending ligation and performed hypoxia/reoxygenation experiments in H9c2 cells. MiRNA-15b was measured by quantitative reverse transcription PCR (qRT-PCR). Cardiomyocyte apoptosis was determined by terminal deoxynucleotide transferase dUTP nick end labeling staining. Synthesized miRNA-15b mimic and inhibitor were transfected into H9c2 cells by Lipofectamine regent. RNA expression of B cell lymphoma/leukemia-2 (Bcl-2) and mitogen-activated protein kinase 3 (MAPK3) was examined by qRT-PCR and their protein expression was determined by western blot. Ischemia reperfusion increased miRNA-15b expression in the ischemic rat heart and resulted more severe cardiomyocytes apoptosis. In H9c2 cells, hypoxia/reoxygenation induced increased miRNA-15b expression and augmented cardiomyocyte apoptosis observed at 24 hours after 24-hour hypoxia. Compared with the vehicle group, miRNA-15b mimic further raised miRNA-15b level and increased cardiomyocyte apoptosis, whereas miRNA-15b inhibitor suppressed miRNA-15b expression and protected cardiomyocytes from apoptosis. Although the mRNA expression of the target genes Bcl-2 and MAPK3 was not changed significantly, the protein expression of these two genes were markedly reduced after miRNA-15b mimic treatment and significantly increased after transfected with miRNA-15b inhibitors. In conclusion, miRNA-15b deteriorates cardiomyocyte apoptosis by post-transcriptionally downregulating the expression of Bcl-2 and MAPK3.
TL;DR: The purpose of this proceeding paper is to discuss some of the known anticancer effects of statins, while focusing on GBM therapy that includes adjunct therapy of statin with chemotherapeutic agents.
Abstract: Patients with glioblastoma multiforme (GBM) have an average life expectancy of approximately 15 months. Recently, statins have emerged as a potential adjuvant cancer therapy due to their ability to inhibit cell proliferation and induce apoptosis in many types of cancer. The exact mechanisms that mediate the inhibitory actions of statins in cancer cells are largely unknown. The purpose of this proceeding paper is to discuss some of the known anticancer effects of statins, while focusing on GBM therapy that includes adjunct therapy of statins with chemotherapeutic agents.
TL;DR: The prevalence and predictors of federal F32, mentored-K, and R01 awards among physicians and the need for research-experiential interventions along the medical education continuum to promote greater participation and diversity of US medical graduates in the federally funded, biomedical research workforce are described.
Abstract: The size and diversity of the physician-scientist workforce are issues of national concern. In this retrospective, national cohort study of US medical school matriculants who graduated in 1997–2004, we describe the prevalence and predictors of federal F32, mentored-K, and R01 awards among physicians. In multivariable logistic regression models, we identified demographic, educational, and professional development variables independently associated with each award through August 2014, reporting adjusted odds ratios and 95% confidence intervals (AOR (95% CI)). Among 117,119 graduates with complete data (97.7% of 119,906 graduates in 1997–2004), 509 (0.4%) received F32, 1740 (1.5%) received mentored-K, and 597 (0.5%) received R01 awards. Adjusting for all variables except US Medical Licensing Examination Step 1 scores, black (vs white) graduates were less likely to receive F32 (0.48 (0.28–0.82)), mentored-K (0.56 (0.43–0.72)), and R01 (0.48 (0.28–0.82)) awards; Hispanic graduates were less likely to receive mentored-K awards (0.68 (0.52–0.88)), and women less likely to receive F32 (0.81 (0.67–0.98)) and R01 (0.59 (0.49–0.71)) awards. After adding Step 1 scores, these race/ethnicity effects were not significant, but women (0.62 (0.51–0.75)) were still less likely to receive R01 awards. Graduates reporting both (vs neither) medical school research elective and authorship were more likely to receive F32 (1.89 (1.45–2.48)), mentored-K (2.48 (2.13–2.88)), and R01 (2.00 (1.54–2.60)) awards. Prior F32 (2.17 (1.46–3.21)) and mentored-K (28.08 (22.94–34.38)) awardees more likely received R01 awards. Findings highlight the need for research-experiential interventions along the medical education continuum to promote greater participation and diversity of US medical graduates in the federally funded, biomedical research workforce.
TL;DR: The aim is to review the current knowledge on the role of the immune system and immune checkpoint inhibitors in HNSCC, and discuss a few promising contenders in clinical development and highlight the need to identify better biomarkers other than programmed death-ligand 1 to improve patient selection and help predict response.
Abstract: The emergence of immunotherapy has provided significant clinical improvements in the treatment of metastatic solid tumors. Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has dismal prognosis with median survival ranging between 6and12 months. Our aim is to review the current knowledge on the role of the immune system and immune checkpoint inhibitors in HNSCC. We will focus on the landmark trials that led to the regulatory approvals of pembrolizumab and nivolumab, and discuss a few promising contenders in clinical development and highlight the need to identify better biomarkers other than programmed death-ligand 1 to improve patient selection and help predict response.
TL;DR: A novel miR-23a/FOXP2 link contributing to PDAC development and invasion is suggested, suggesting it may be a potential diagnostic and therapeutic target for PDAC.
Abstract: MicroRNAs have been reported to play an important role in tumor development and progression by targeting oncogenes and tumor suppressors. miR-23a has been described as significantly upregulated in multiple cancers and involved in tumorigenesis. The aim of this study was to evaluate the potential roles of miR-23a in pancreatic ductal adenocarcinoma (PDAC). We found that miR-23a level was significantly increased in tissues of PDAC compared with that in the control by real-time PCR. FOXP2 expression was downregulated and inversely correlated with miR-23a. miR-23a directly targeted the 3'-untranslated region of FOXP2 mRNA and repressed its expression. Mechanistically, enhancement of miR-23a by transfection with mimics in Aspc-1 cells significantly promoted cell proliferation and invasion, while miR-23a inhibitors transfection in SW1990 cells induced an inhibitory effect. Moreover, restoration of FOXP2 impaired the pro-proliferation and proinvasion effects of miR-23a, indicating FOXP2 is a direct mediator of miR-23a functions. In conclusion, our findings suggest a novel miR-23a/FOXP2 link contributing to PDAC development and invasion. It may be a potential diagnostic and therapeutic target for PDAC.
TL;DR: The significance of histopathological responses seen after neoadjuvant chemotherapy in childhood solid tumors is summarized and it is suggested that toxicities from intensifying adjuvant chemotherapy might either necessitate the change of a number of arm groups in different protocol regimens or include newer chemotherapeutic agents adjuvantly for better outcome and lesser toxicities in poor tumor histopathology responders.
Abstract: The management of oncological malignancies has significantly improved over the last decades In modern medicine, new concepts and trends have emerged paving the way for the era of personalized and evidence-based strategies adapted to the patients' prognostic variables and requirements Several challenges do exist that are encountered during the management, including the difficulty to assess chemotherapy response with certainty Having known that neoadjuvant chemotherapy might be the only solution for a proportion of patients with tumors that are unresectable at diagnosis, emergence of strategies that use risk group-directed therapy became an integral part in the management of oncological malignancies Tumor histopathological change post neoadjuvant chemotherapy is one of the most important predictors of management outcome and is being used in many chemotherapy protocols as an essential determinant of the most suitable postoperative chemotherapy regimen Bone tumors are the classic models of this approach; however, other childhood solid tumors show significant variations in outcome as a result of tumor histopathological response to neoadjuvant chemotherapy The aim of this review is therefore to summarize the significance of histopathological responses seen after neoadjuvant chemotherapy in childhood solid tumors Moreover, it suggests that the effect on tumor histopathology through modifying neoadjuvant chemotherapy and, on the other hand, toxicities from intensifying adjuvant chemotherapy might either necessitate the change of a number of arm groups in different protocol regimens or include newer chemotherapeutic agents adjuvantly for better outcome and lesser toxicities in poor tumor histopathological responders
TL;DR: Four newly approved therapies for AML have demonstrated improved response in their target populations in several pivotal clinical trials with some also demonstrating improved overall survival, and several promising therapies currently in development are provided.
Abstract: The treatment of acute myeloid leukemia (AML) has remained relatively unchanged for the past 3-4 decades with generally poor outcomes, especially in elderly populations unfit for intensive therapy. Recent advancements, however, have identified several cytogenetic and molecular markers that have not only improved prognostication but have also led to the development of several new targeted therapies for specific subpopulations. In 2017, the US Food and Drug Administration approved four new treatments with indications for fms like tyrosine kinase 3 (FLT3)-mutated AML (midostaurin), newly diagnosed or relapsed/refractory CD33+AML (gemtuzumab ozogamicin), newly diagnosed therapy-related AML or AML with myelodysplasia-related changes (CPX-351) and relapsed/refractory AML with an isocitrate dehydrogenase (IDH)2 mutation (enasidenib). These newly approved therapies have demonstrated improved response in their target populations in several pivotal clinical trials with some also demonstrating improved overall survival. Additional novel therapies in development for AML include agents that target B cell lymphoma 2, FLT3, IDH1, the ubiquitination pathway, as well as cell therapy using engineered T cells with chimeric antigen receptors. This review provides a summary of the four newly approved therapies for AML, as well as several promising therapies currently in development.
TL;DR: The adjuvant, synthetic hexa-acylated lipid A derivative, glucopyranosyl lipid A (GLA) formulated in aluminum ( GLA-Alum) with recombinant Sm-p80 provided 33.13% reduction in worm burden in the mouse model and 38% worm burden reduction in vaccinated baboons.
Abstract: Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading candidate for a schistosomiasis vaccine. The prophylactic and antifecundity efficacy of Sm-p80 has been tested in three animal models (mouse, hamster and baboon) using a multitude of vaccine formulations and approaches. In our continual effort to enhance the vaccine efficacy, in this study, we have utilized the adjuvant, synthetic hexa-acylated lipid A derivative, glucopyranosyl lipid A (GLA) formulated in aluminum (GLA-Alum) with recombinant Sm-p80. The rSm-p80+GLA-Alum immunization regimen provided 33.33%–53.13% reduction in worm burden in the mouse model and 38% worm burden reduction in vaccinated baboons. Robust Sm-p80-specific immunoglobulin (Ig)G, IgG1, IgG2a and IgM responses were observed in all immunized animals. The rSm-p80+GLA-Alum coadministration induced a mix of T-helper (Th) cells (Th1, Th2 and Th17) responses as determined via the release of interleukin (IL)-2, IL-4, IL-18, IL-21, IL-22 and interferon-γ.
TL;DR: It is shown that ubiquitin-specific protease 50 (USP50) levels are increased during erythropoiesis, and this study suggests that DUBs like USP50 may regulate protein stability during eriespheresis; however, more investigation is warranted.
Abstract: Anemia is a very common blood disorder that affects the lives of billions of people worldwide. Anemia is caused by the loss of blood, increased destruction of red blood cells (RBCs), or reduced production of RBCs. Erythropoiesis is the complex process of RBC differentiation and maturation, in which protein degradation plays a crucial role. Protein ubiquitination regulates programmed protein degradation, which can be reversed by deubiquitinating enzymes (DUBs); however, the role of DUBs in erythropoiesis has not been well studied. We examined the expression of DUBs during erythropoiesis using an ex vivo human CD34+ hematopoietic progenitor cell culture system. Here we show that ubiquitin-specific protease 50 (USP50) levels are increased during erythropoiesis. USP50 mRNA levels are significantly increased on day 3 and protein levels are elevated on day 9 of erythroid differentiation. Coimmunoprecipitation and proteomics analyses reveal that Ku70, a DNA-binding protein, is associated with USP50. Overexpression of USP50 has no effect on Ku70 mRNA levels, while it reduces Ku70 protein levels by promoting Ku70 degradation, suggesting that USP50 may indirectly regulate Ku70 protein stability. USP50 protein is also not stable. USP50 protein degradation is independent of the proteasomal and the lysosomal degradation systems. This study suggests that DUBs like USP50 may regulate protein stability during erythropoiesis; however, more investigation is warranted.
TL;DR: A retrospective analysis of hospitalized young children due to viral respiratory infections found that the majority of children diagnosed with bronchiolitis were misclassified as they had prior episodes of wheezing, and many children with bron chiolitis misclassification had significant comorbidities.
Abstract: Viral respiratory infections are often grouped as a single respiratory syndrome named ‘viral bronchiolitis’, independently of the viral etiology or individual risk factors Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections Bronchiolitis was defined as the first wheezing episode less than 12 months of age Demographic variables and comorbidities were obtained by electronic medical record review The study comprised a total of 513 hospitalizations (n=453) Viral bronchiolitis was diagnosed in 144 admissions (281%) Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (98%), and congenital heart disease (98%) Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification
TL;DR: Receiver operating characteristic curve analysis showed that the cut-off point of HATCH score related to predict AF was >1 (two or more), with a sensitivity of 42% and specificity of 70%.
Abstract: The aim of this study was to investigate the association between HATCH score and atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. 369 patients (103 patients with AF and 266 patients without AF) undergoing isolated CABG surgery were analyzed. Complete medical records were retrospectively collected to investigate HATCH score. The median age of patients with AF was significantly higher than the median age of non-AF group (60.8±10.0 years vs 67.8±9.5 years, P 1 (two or more), with a sensitivity of 42% and specificity of 70%. Patients with elevated preoperative HATCH score may have higher risk for AF after CABG surgery.
TL;DR: Hypovitaminosis D is prevalent in children with GHD and significantly improved 1 year after GH therapy, and 25(OH)D should be assessed in childrenwith GHD at diagnosis and during follow-up.
Abstract: Few studies, and with controversial results, analyzed vitamin D status in children before and after growth hormone (GH) treatment. Thus, we aimed to assess vitamin D status in prepubertal children with idiopathic growth hormone deficiency (GHD), and to evaluate the effect of GHD and GH treatment on vitamin D levels. Fifty prepubertal children with isolated GHD were compared with 50 controls. All were subjected to history, anthropometric assessment and measurement of 25 hydroxyvitamin D (25(OH)D), serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone (PTH) at diagnosis and 1 year after GH therapy. Serum 25(OH)D levels
TL;DR: It is indicated that PIH had an effect of on neonatal birth weight and when pregnant women with PIH are identified then the healthcare professional initiates a closer supervision of their pregnancy in order to ameliorate the status of BP and provide a good intrauterine environment for the fetus.
Abstract: To explore the effect of pregnancy-induced hypertension (PIH) on neonatal birth weight and provide the necessary reference value for the maternal and children health service. A cross-sectional study was carried out in Shaanxi Province of China in 2013. And a total of 28 045 singleton live infants and their mothers were recruited using a stratified, multistage, probability-proportional-to-size sampling method. Among the 28 045 women of childbearing age surveyed, multiple linear regression and quantile regression analysis all showed that the birth weight of newborns whose mothers had suffered from PIH during pregnancy was significantly lower than those whose mothers had not suffered from PIH during pregnancy from very low to higher birth weight percentiles (q=0–0.85), an average decrease of 137.45 g (β=−137.45, t=−5.77 and p
TL;DR: In patients with type 2 DM, there is an association between podocyte injury and PT dysfunction, and miRNA excretion, even in the normoalbuminuria stage, which documents a potential role of the urinary profiles of miRNA21, miRNA124, andmiRNA192 in early DN.
Abstract: MicroRNAs (miRNAs) are short non-coding RNA species that are important post-transcriptional regulators of gene expression. The aim of the study was to establish a potential explanation of podocyte damage and proximal tubule (PT) dysfunction induced by deregulated miRNAs expression in the course of type 2 diabetes mellitus (DM). A total of 68 patients with type 2 DM and 11 healthy subjects were enrolled in a cross-sectional study and assessed concerning urinary albumin:creatinine ratio (UACR), urinary N-acetyl-β-D-glucosamininidase (NAG), urinary kidney injury molecule-1, urinary nephrin, podocalyxin, synaptopodin, estimated glomerular filtration rate (eGFR), urinary miRNA21, miRNA124, and miRNA192. In univariable regression analysis, miRNA21, miRNA124, and miRNA192 correlated with urinary nephrin, synaptopodin, podocalyxin, NAG, KIM-1, UACR, and eGFR. Multivariable regression analysis yielded models in which miRNA192 correlated with synaptopodin, uNAG, and eGFR (R2=0.902; P
TL;DR: This study determined the expression of S100A4 and EMT-related markers in Met-5A cells (pleural mesothelial cells) treated with T GF-β or TGF-β inhibitor by real-time PCR and western blot, and found that theexpression of epithelial cell marker was decreased and the mesenchymal cell marker increased with S 100A4 upregulation after treatment with TGF -β.
Abstract: Pleural fibrosis can dramatically lower the quality of life. Numerous studies have reported that epithelial-mesenchymal transition (EMT) regulated by transforming growth factor-β (TGF-β) is involved in fibrosis. However, the molecular mechanism is inadequately understood. Fibroblast-specific protein-1 (S100A4) is a target of TGF-β signaling. In our previous study, we have reported that S100A4 is highly expressed in pleural fibrosis. Thus, we suggest that S100A4 took part in the TGF-β-induced EMT in pleural fibrosis. In this study, we determined the expression of S100A4 and EMT-related markers in Met-5A cells (pleural mesothelial cells) treated with TGF-β or TGF-β inhibitor by real-time PCR and western blot. In order to explore the role of S100A4, we used siRNA to knock down the expression of S100A4 in cell model. We found that the expression of epithelial cell marker was decreased and the mesenchymal cell marker increased with S100A4 upregulation after treatment with TGF-β. Moreover, the changes of EMT-related event were restricted when the expression of S100A4 was knocked down. Conversely, S100A4 can partially rescue the EMT-related expression changes induced by TGF-β inhibitor. These findings suggest that S100A4 expression is induced by the TGF-β pathway, and silencing S100A4 expression can inhibit the process of TGF-β-induced EMT.
TL;DR: The patients with RA who received LDGs treatment had a lower BMD at the spine and a higher rate of previous fractures that was associated with a significantly higher 10-year probability of fractures than those who did not receive LDG treatment.
Abstract: This study aimed to investigate the effect of low-dose glucocorticoids (LDGs) on disease activity, bone density, and fractures in patients with rheumatoid arthritis (RA). This was an interim analysis of the RA Registry. Demographic data and clinical characteristics, including fracture risk assessment tool, were collected. 25(OH) Vitamin D, bone mineral density (BMD), and intact parathyroid hormone were measured at enrollment. The study group were those who took LDGs (2.5-7.5 mg/day prednisolone or equivalent dose), and the others were included as the control group. A total of 425 participants were enrolled, including 85 (20%) in the control group and 340 (80%) in the study group. The demographics and clinical characteristics were comparable between the two groups. Compared with the control group, the LDGs group had a significantly lower vertebral BMD (L 1-4) (g/cm2), (0.854 vs 0.896, p=0.046), significantly higher rate of previous fractures (103 (30.3%) vs 13 (15.3%), p=0.006), higher 10-year probability of major fractures (14 (15.5) vs 8 (8.6), p<0.0001), and higher 10-year probability of hip fractures (4.4 (8.4) vs 2 (3.9), p<0.0001). Disease activity appeared to be similar in the patients with RA regardless of whether or not they received LDG treatment. However, the patients with RA who received LDG treatment had a lower BMD at the spine (L1-4) and a higher rate of previous fractures that was associated with a significantly higher 10-year probability of fractures than those who did not receive LDG treatment.
TL;DR: The independent predictors of prolonged LOS for bronchiolitis in the study population included age, history of prematurity, respiratory syncytial virus isolation, and initial oxygen saturation, which should be taken into account when planning policies to reduce the duration of hospital stay in infants with bronchiola.
Abstract: Among inpatients suffering from bronchiolitis, approximately a quarter may undergo a prolonged length of stay (LOS) for the treatment of their respiratory condition. However, there have been few research studies that have evaluated variables that may be associated with a prolonged LOS in these patients, especially in low-income and middle-income countries, where the clinical and economic burden of the disease is the greatest. In an analytical single-center cross-sectional study, we included a population of patients with acute bronchiolitis hospitalized between March and June 2016. We collected demographic and clinical information and the LOS of each patient. Prolonged LOS for bronchiolitis was defined as at least one hospital stay of 5 or more days. A total of 303 patients were included, with 176 (58.1%) male and a median (IQR) age of 3.0 (1.0–7.0) months. After controlling for gender, history of bronchopulmonary dysplasia, number of days with respiratory symptoms, the presence of apnea as an initial manifestation of bronchiolitis, and other underlying disease conditions, we found that the independent predictors of prolonged LOS for bronchiolitis in our study population included age (OR 0.92; 95% CI 0.84 to 0.99; p=0.049), history of prematurity (OR 6.34; 95% CI 1.10 to 36.46; p=0.038), respiratory syncytial virus isolation (OR 1.92; 95% CI 1.02 to 3.73; p=0.048), and initial oxygen saturation (OR 0.94; 95% CI 0.88 to 0.98; p=0.048). The factors identified should be taken into account when planning policies to reduce the duration of hospital stay in infants with bronchiolitis.
TL;DR: The findings highlight the importance of periostin and YKL40 as serum biomarkers for assessment of asthma severity and acute asthma exacerbations in children with asthma.
Abstract: Children with severe asthma or acute asthma exacerbation may encounter difficulties in performing pulmonary function tests. In this situation, serum biomarkers can play a great role in evaluation of such patients. The aim of this study was to estimate the serum levels of human chitinase-3-like protein 1 (YKL40) and periostin in a group of Egyptian children with asthma during acute asthma exacerbation and in stable asthmatics compared with healthy control, and to correlate these findings with the severity of asthma. This cross-sectional study enrolled 120 childrenwith asthma with different degrees of asthma severity, according to the Global Initiative for Asthma guidelines, along with 60 age-matched and sex-matched healthy control. A complete blood count and an estimation of serum periostin and YKL40 levels were performed for all cases and control. Individual and mean values of periostin and YKL40 were significantly higher during acute asthma exacerbations, p<0.001. A highly significant relation between serum levels of periostin and YKL40 and asthma severity, p value for each was <0.001. Absolute eosinophil count was significantly correlated with the serum periostin levels in stable asthmatic group (p=0.01) only. There was significantly positive correlation (P<0.001) between both markers in stable asthmatic group. Spearman's correlation coefficient shows a statistically significant positive correlation between both markers and patient's age and duration of asthma, p value for each was 0.001. These findings highlight the importance of periostin and YKL40 as serum biomarkers for assessment of asthma severity and acute asthma exacerbations in children with asthma.
TL;DR: Patients who suffered dementia had a higher risk of developing injury, and the cognitive enhancers were associated with the decreased risk of injury.
Abstract: This study aimed to investigate the associations among dementia, psychotropic medications and the risk of overall injuries. In this nationwide matched cohort study, a total of 144 008 enrolled patients ≥age of 50, with 36 002 study subjects who suffered from dementia and 108 006 controls matched for sex and age, from the Inpatient Dataset, for the period 2000–2010 in Taiwan were selected from the National Health Insurance Research Database, according to International Classification of Diseases, 9th Revision, Clinical Modification. When adjusting for the confounding factors, a Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 10 years of follow-up. Of the study subjects, 6701 (18.61%) suffered injury when compared with 20 919 (19.37%) in the control group. The Cox regression analysis revealed that the study subjects were more likely to develop an injury (HR: 2.294, 95% CI=2.229 to 2.361, P
TL;DR: The kinetic of arterial dilation seems to be relevant as the magnitude of dilation in subjects with critical coronary stenosis and different degree of coronary atherosclerosis.
Abstract: Endothelial dysfunction, wall thickening and plaque are progressive manifestations of atherosclerosis. Delayed or absent brachial artery dilation after ischemic stimulus has been associated with severity of extracoronary and coronary atherosclerosis. In the current study, we aimed to verify if delayed or absent dilation associates with critical coronary stenosis. We also evaluated the association between coronary stenosis, carotid artery wall thickness and peripheral artery disease. Endothelial function was investigated by flow-mediated dilation of the brachial artery up to 3 min after ischemia, and patients classified as early, late or no dilators. Coronary angiography was performed through transradial or femoral artery approach. Computerized quantitative angiography was used to obtain percent stenosis of all lesions, while the Gensini score was used to evaluate the severity of coronary atherosclerosis. Seventy-four patients were enrolled. Carotid wall thickness and plaque, and peripheral artery disease were detected by ultrasound. Subjects with critical coronary stenosis showed a higher prevalence of delayed or absent dilation (coronary stenosis ≥70 per cent: late dilators 50 per cent, no dilators 35 per cent; coronary stenosis ≤70 per cent : late dilators 27 per cent, no dilators 6 per cent). The Gensini score was progressively higher in late dilators and no dilators compared with early dilators (early: 4.5±13.5; late 17.5±27.1; no 39.7±55.0; P