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Τρίτη 12 Ιουνίου 2018

S1P1 receptor inhibits kidney epithelial mesenchymal transition triggered by ischemia/reperfusion injury via the PI3K/Akt pathway

Abstract
Ischemia/reperfusion (I/R) is a major cause of acute kidney injury (AKI), along with delayed graft function, which can trigger chronic kidney injury by stimulating epithelial to mesenchymal transition (EMT) in the kidney canaliculus. Sphingosine 1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor that is indispensable for vessel homeostasis. This study aimed to investigate the influence of S1P1 on the mechanisms underlying I/R-induced EMT in the kidney using in vivo and in vitro models. Wild-type (WT) and S1P1-overexpressing kidney canaliculus cells were subject to hypoxic conditions followed by reoxygenation in the presence or absence of FTY720-P, a potent S1P1 agonist. In vivo, bilateral arteria renalis in wild-type mice and mice with silenced S1P1 were clamped for 30 min to obtain I/R models. We found that hypoxia/reoxygenation (H/R) significantly enhanced the expressions of EMT biomarkers and down-regulated S1P1 expression in wild-type canaliculus cells. In contrast, FTY720-P treatment or overexpression of S1P1 significantly suppressed EMT in wild-type canaliculus cells. Furthermore, after 48–72 h, a significant upregulation of EMT biomarker expression was triggered by I/R in mice with silenced S1P1, while the expressions of these markers did not change in wild-type mice. A kt activity was increased with H/R-induced EMT, suggesting that the protective influence of FTY720-P was due to its inhibition of PI3K/Akt. Therefore, the results of this study provide evidence that down-regulation of S1P1 expression is essential for the generation and progression of EMT triggered by I/R. S1P1 exhibits a prominent inhibitory effect on kidney I/R-induced EMT in the kidney by affecting the PI3K/Akt pathway.

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Cancers, Vol. 10, Pages 197: Antiviral Drugs for EBV

Cancers, Vol. 10, Pages 197: Antiviral Drugs for EBV

Cancers doi: 10.3390/cancers10060197

Authors: Joseph S. Pagano Christopher B. Whitehurst Graciela Andrei

Epstein–Barr virus (EBV) infects up to 95% of the adult human population, with primary infection typically occurring during childhood and usually asymptomatic. However, EBV can cause infectious mononucleosis in approximately 35–50% cases when infection occurs during adolescence and early adulthood. Epstein–Barr virus is also associated with several B-cell malignancies including Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease. A number of antiviral drugs have proven to be effective inhibitors of EBV replication, yet have resulted in limited success clinically, and none of them has been approved for treatment of EBV infections.



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Improved Targeting and Tumor Retention of a Newly Synthesized Antineoplaston A10 Derivative by Intratumoral Administration: Molecular Docking, Technetium 99m Radiolabeling, and In Vivo Biodistribution Studies

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Histological study of the thin membranous structure made of dense connective tissue around the esophagus in the upper mediastinum

Abstract

Background

The structure of the fascia in upper mediastinum has already been reported from gross anatomical viewpoints by Sarrazin. But it is necessary to understand meticulous anatomy for thoracoscopic or mediastinoscopic surgery. So herein, we investigate histologically the thin membranous structure made of dense connective tissues.

Methods

Semi-sequential transverse sections of the mediastinum were obtained from three cadavers. Hematoxylin and eosin staining, Elastica van Gieson staining, and Masson trichrome staining were performed to identify the presence and location of the thin membranous structure made of dense connective tissues.

Results

The "visceral sheath" and "vascular sheath," as previously described by Sarrazin, were observed histologically. These two thin membranous structures do not surround the esophagus and trachea cylindrically. In addition, the "visceral sheath" on the right side of the upper mediastinum was unclear in comparison to the left side. The "visceral sheath" (on the left side) gradually became unclear, and seemed to almost disappear; the esophagus was found to be very close to the thoracic duct on the caudal side of the bifurcation of the trachea. Although the left recurrent nerve was located inside the "visceral sheath" in all cadavers, the left recurrent nerve lymph nodes were located inside the "visceral sheath" in cadaver 1 and between the "visceral sheath" and "vascular sheath" in cadaver 3.

Conclusion

The "visceral sheath" around the esophagus in the upper mediastinum was histologically demonstrated; however, the findings were not constant.



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RSS Story 01

RSS Story 01 Lorem ipsum dolor sit amet, consectetur adipiscing elit. Phasellus dignissim dapibus erat, non hendrerit tortor tempus sed....

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Allogeneic hematopoietic cell transplantation in patients with GATA2 deficiency—a case report and comprehensive review of the literature

Abstract

Recently, an immunodeficiency syndrome caused by guanine-adenine-thymine-adenine 2 (GATA2) deficiency has been described. The syndrome is characterized by (i) typical onset in early adulthood, (ii) profound peripheral blood cytopenias of monocytes, B lymphocytes, and NK cells, (iii) distinct susceptibility to disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections (particularly human papillomavirus), and (iv) a high risk of developing hematologic malignancies (myelodysplastic syndromes (MDS); acute myeloid leukemias (AML)). Considerable clinical heterogeneity exists among patients with GATA2 deficiency, but once infectious symptoms occur or MDS/AML arises, survival declines significantly. Allogeneic hematopoietic cell transplantation (HCT) currently provides the only curative treatment option for both MDS/AML and dysfunctional immunity with life-threatening opportunistic infections. Strategies regarding timing of allogeneic HCT, antimicrobial prophylaxis and treatment, intensity of the preparative regimen, and optimal donor and graft source have not been clearly defined due to the rarity of the disease. Here, we provide a comprehensive analysis of the available literature and published case reports on the use of allogeneic HCT in patients with GATA2 deficiency. In addition, a case of a young woman with GATA2 deficiency, who developed an immune reconstitution inflammatory syndrome in her mycobacterial skin lesions post allogeneic HCT is presented and illustrates distinct problems encountered in this disease context.



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Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Purpose: The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion (del[17p]) or progressive disease following B-cell receptor pathway inhibitors. Experimental Design: We conducted a comprehensive analysis of the safety of 400mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase-I/II studies. Results: Median age was 66 years and 60% had del(17p). Patients had received a median of three prior therapies (range: 0-15); 42% previously received ibrutinib or idelalisib. Median duration of exposure to venetoclax was 16 months (0-56). In the pooled analysis, the most common adverse events (AEs) of any grade were diarrhea (41%), neutropenia (40%), nausea (39%), anemia (31%), fatigue (28%), and upper respiratory tract infection (25%). The most common grade 3/4 AEs were neutropenia (37%), anemia (17%), and thrombocytopenia (14%). With the current 5-week ramp-up dosing, the incidence of laboratory TLS was 1.4% (2/166), none had clinical sequelae, and all of these patients were able to ramp-up to a daily dose of 400mg. Grade 3/4 neutropenia was manageable with growth-factor support and dose adjustments; the incidence of serious infections in these patients was 15%. Ten percent of patients discontinued venetoclax due to AEs and 8% died while on study, with the majority of deaths in the setting of disease progression. Conclusions: Venetoclax as a long-term continuous therapy is generally well-tolerated in patients with R/R CLL when initiated with the current treatment algorithm.



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Inhibition of HER2 Enriches for Jagged1-dependent Breast Cancer Stem Cells: Role for Membrane Jagged1

Purpose: Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as Cancer Stem Cells (CSCs). CSCs are implicated in radiotherapy, chemotherapy resistance, and tumor recurrence. Notch promotes breast CSCs survival and self-renewal, and overexpression of Notch1 and the Notch ligand Jagged1 predict poor outcome. Resistance to anti-HER2 therapy in HER2+ breast cancer requires Notch1, and that combination of trastuzumab and a Gamma Secretase Inhibitor (GSI) prevents tumor relapse in xenograft models. Experimental Design: The current study investigates mechanisms by which HER2 tyrosine kinase activity regulates Notch-dependent CSC survival and tumor initiation. Results: Lapatinib-mediated HER2 inhibition shifts the population of HER2+ breast cancer cells from low membrane Jagged1 expressing to higher levels, independent of sensitivity to anti-HER2 treatment within the bulk cell population. This increase in membrane Jagged1 is associated with higher Notch receptor expression, activation, and enrichment of CSCs in vitro and in vivo. Importantly, lapatinib treatment results in growth arrest and cell death of Jagged1 low-expressing cells while the Jagged1 high-expressing cells continue to cycle. High membrane Jagged1 protein expression predicts poor overall cumulative survival in women with HER2+ breast cancer. Conclusions: These results indicate that higher membrane Jagged1 expression may be used to either predict response to anti-HER2 therapy or for detection of Notch sensitive CSCs post therapy. Sequential blockade of HER2 followed by Jagged1 or Notch could be more effective than simultaneous blockade to prevent drug resistance and tumor progression.



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The widening spectrum of immunological memory

Colleen M Lau | Joseph C Sun

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Older Age, ICU, Poor Renal Fcn Up Risk of Opioid OD in Hospital

TUESDAY, June 12, 2018 -- Risk factors for opioid overdose among hospitalized patients include being age 65 years or older, being in an intensive care unit (ICU), and having renal impairment, according to a study published online May 23 in the...

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Meds With Depression As Adverse Side Effect Commonly Used

TUESDAY, June 12, 2018 -- The estimated prevalence of using medications with depression as an adverse effect is 37.2 percent, according to a study published in the June 12 issue of the Journal of the American Medical Association. Dima Mazen Qato,...

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USPSTF: No to ECG Screening to Prevent CVD in Low-Risk Adults

TUESDAY, June 12, 2018 -- The U.S. Preventive Services Task Force (USPSTF) recommends against screening with resting or exercise electrocardiography (ECG) to prevent cardiovascular disease (CVD) events in low-risk asymptomatic adults. This final...

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How Do Business Partner Data Breaches Affect Your Practice?

TUESDAY, June 12, 2018 -- Data breaches affecting health care systems or their partners need to be addressed quickly, according to an article published in Medical Economics. Noting that every successful breach against a health care system...

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Exercise May Lower Mortality in Adult Survivors of Childhood CA

TUESDAY, June 12, 2018 -- For adult survivors of childhood cancer, vigorous exercise in early adulthood is associated with reduced risk of mortality, according to a study published online June 3 in JAMA Oncology. Jessica M. Scott, Ph.D., from the...

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Midlife weight gain is a risk factor for obesity-related cancer

Midlife weight gain is a risk factor for obesity-related cancer

Midlife weight gain is a risk factor for obesity-related cancer, Published online: 13 June 2018; doi:10.1038/s41416-018-0106-x

Midlife weight gain is a risk factor for obesity-related cancer

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A Rapidly Fatal Case of Low-Dose Methotrexate Toxicity

An 82-year-old female presented with multiple oral ulcers and malena for 1 week. Her laboratory tests revealed pancytopenia and acute renal failure. She had history of rheumatoid arthritis for which she was taking 7.5 mg methotrexate weekly and stage 4 chronic kidney disease from diabetic nephropathy. During the hospital stay, she developed pneumonia and septic shock requiring norepinephrine and vasopressin. She underwent continuous venovenous hemodiafiltration. Leucovorin, filgrastim, and multiple packed red blood cell and platelet transfusions were given. She remained hypotensive and pancytopenic despite all interventions. She died on day 6 of hospital stay from acute hypoxic respiratory failure due to septic shock.

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A Risk Score Model for Evaluation and Management of Patients with Thyroid Nodules

Horm Metab Res
DOI: 10.1055/a-0630-5239

The study is aimed to establish a simplified and practical tool for analyzing thyroid nodules. A novel risk score model was designed, risk factors including patient history, patient characteristics, physical examination, symptoms of compression, thyroid function, ultrasonography (US) of thyroid and cervical lymph nodes were evaluated and classified into high risk factors, intermediate risk factors, and low risk factors. A total of 243 thyroid nodules in 162 patients were assessed with risk score system and Thyroid Imaging-Reporting and Data System (TI-RADS). The diagnostic performance of risk score system and TI-RADS was compared. The accuracy in the diagnosis of thyroid nodules was 89.3% for risk score system, 74.9% for TI-RADS respectively. The specificity, accuracy and positive predictive value (PPV) of risk score system were significantly higher than the TI-RADS system (χ2=26.287, 17.151, 11.983; p <0.05), statistically significant differences were not observed in the sensitivity and negative predictive value (NPV) between the risk score system and TI-RADS (χ2=1.276, 0.290; p>0.05). The area under the curve (AUC) for risk score diagnosis system was 0.963, standard error 0.014, 95% confidence interval (CI)=0.934–0.991, the AUC for TI-RADS diagnosis system was 0.912 with standard error 0.021, 95% CI=0.871–0.953, the AUC for risk score system was significantly different from that of TI-RADS (Z=2.02; p <0.05). Risk score model is a reliable, simplified and cost-effective diagnostic tool used in diagnosis of thyroid cancer. The higher the score is, the higher the risk of malignancy will be.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Psychological Symptoms and Well-Being After Treatment for Primary Aldosteronism

Horm Metab Res
DOI: 10.1055/a-0628-6847

Primary aldosteronism (PA) is an increasingly identified cause of secondary hypertension. PA can be caused by an aldosterone-producing adenoma or by bilateral adrenal hyperplasia, generally treated by adrenalectomy or mineralocorticoid receptor antagonists, respectively. Recent studies suggest that PA is associated with more psychological symptoms and lower levels of well-being. The purpose of this study was to investigate the associations between subtype of PA and psychological symptoms and well-being after specific treatment. We analyzed the outcomes of the Mental Health Continuum-Short Form and the Symptom Checklist in 160 patients (mean age 57 years; 74.3% males) with PA, comparing the scores for psychological symptoms and well-being between both subtypes of PA. Additionally, we performed subgroup analyses based on gender, age, time since initiation of treatment, and co-morbidity. Moreover, we compared the results with published norm scores. Mean follow-up after adrenalectomy or start of medication was four years and two months. Depressive symptoms, anxiety and obsessive-compulsive thoughts and well-being did not differ between subtypes of PA. Subgroup analysis did not reveal any differences, except for women with bilateral adrenal hyperplasia who scored higher on the anxiety subscale than women after adrenalectomy. Compared to the general population, patients with treated PA reported more psychological symptoms. In contrast, well-being did not differ significantly from norm scores. Subtype and treatment of PA were no important determinants of psychological symptoms and well-being on the long-term. We suggest that physicians should be alert for psychological symptoms, as these were more frequently present in patients with PA.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Relation of RANKL and OPG Levels with Bone Resorption in Patients with Acromegaly and Prolactinoma

Horm Metab Res
DOI: 10.1055/a-0630-1529

The objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured. Groups were not statistically different from each other with regard to serum levels of RANKL and OPG. The RANKL/OPG ratio was higher in the prolactinoma group than in the control group (p=0.046). A positive correlation between OPG and increasing age was detected in both the prolactinoma and control groups (r=0.524, p=0.004 and r=0.380, p=0.029, respectively). An inverse correlation was observed between IGF-I and OPG after excluding age in the prolactinoma group (r=–0.412, p=0.046). OC and bone ALP were negatively associated with RANKL in the acromegaly group (r=–0.384, p=0.036 and r=–0.528, p=0.003, respectively). There was an inverse correlation between OPG and BMD at the femoral neck in the acromegaly group (r=–0.422, p=0.02). The effect of IGF-I on bone remodeling may be partly mediated by RANKL and OPG. The RANKL/OPG ratio plays an important role in prolactinoma. A positive correlation of OPG with age and an inverse correlation with IGF-I favor the compensatory response of OPG against bone loss in the aging skeleton.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Improving PHA production in a SBR of coupling PHA-storing microorganism enrichment and PHA accumulation by feed-on-demand control

With volatile fatty acids as substrates, the typical polyhydroxyalkanoates (PHAs) production by mixed culture always includes two steps: PHA-storing culture enrichment via aerobic dynamic feeding strategy and ...

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Purification and characterization of neutral protease from Aspergillus oryzae Y1 isolated from naturally fermented broad beans

The strain Y1, with a notably high production of neutral protease, was isolated from naturally fermented broad beans and subsequently identified as Aspergillus oryzae, through the analysis of its morphology chara...

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A Changing Landscape in Pancreatic Cancer

No abstract available

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Response: “Prophylactic Negative Pressure Dressing Use in Closed Laparotomy Wounds Following Abdominal Operations What We Really Know?”

No abstract available

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The Southampton Consensus Guidelines for Laparoscopic Liver Surgery: From Indication to Implementation

imageObjective: The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery. Background: The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination. Methods: A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements. Results: Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee. Conclusion: The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards.

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Response to: “Are Guidelines for Standardized Outcome Reporting in Bariatric Surgery Responsible for Missing the Big Picture in Bariatric Surgery Related Major Complications?”

No abstract available

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Overall Splenectomy Rates Stable Despite Increasing Usage of Angiography in the Management of High-grade Blunt Splenic Injury

imageObjective: The purpose of this study was to understand the contemporary trends of splenectomy in blunt splenic injury (BSI) and to determine if angiography and embolization (ANGIO) may be impacting the splenectomy rate. Background: The approach to BSI has shifted to increasing use of nonoperative management, with a greater reliance on ANGIO. However, the impact ANGIO has on splenic salvage remains unclear with little contemporary data. Methods: The National Trauma Data Bank was used to identify patients 18 years and older with high-grade BSI (Abbreviated Injury Scale >II) treated at Level I or II trauma centers between 2008 and 2014. Primary outcomes included yearly rates of splenectomy, which was defined as early if performed within 6 hours of ED admission and delayed if greater than 6 hours, ANGIO, and mortality. Trends were studied over time with hierarchical regression models. Results: There were 53,689 patients who had high-grade BSI over the study period. There was no significant difference in the adjusted rate of overall splenectomy over time (24.3% in 2008, 24.3% in 2014, P value = 0.20). The use of ANGIO rapidly increased from 5.3% in 2008 to 13.5% in 2014 (P value

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Response to: “Consideration of KRAS Mutation Status May Enhance the Prognostic Impact of Indeterminate Extrahepatic Disease in the Lungs, as Identified by 18FDG-PET, in Patients With Colorectal Liver Metastases”

No abstract available

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Value-based Surgical Care: Evidence for the Enigma

No abstract available

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DCIS and Breast Cancer: Challenging the Paradigm

No abstract available

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A Framework for a Battlefield Trauma System for Civilians

imageNo abstract available

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Opioid Overdose—the Surgeon's Role

imageWith increased focus on the potential harms of surgical opioid prescribing, surgeons should be cognizant of the risk of opioid-related adverse events in their patients, including overdose. Risk factors for overdose may be more prevalent than surgeons think, and include high current opioid use, previous or existing substance use disorder, history of overdose, or certain medical comorbidities. The first step to protecting surgical patients from opioid overdose is adequate screening for risk factors; appropriate patient counseling and prudent prescribing practices can then help protect at-risk patients.

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Efficacy of a Dual-ring Wound Protector for Prevention of Surgical Site Infections After Pancreaticoduodenectomy in Patients With Intrabiliary Stents: A Randomized Clinical Trial

imageObjective: To evaluate the efficacy of a dual-ring wound protector for preventing incisional surgical site infection (SSI) among patients with preoperative biliary stents undergoing pancreaticoduodenectomy (PD). Methods and analysis: This study was a parallel, dual-arm, double-blind randomized controlled trial. Adult patients with a biliary stent undergoing elective PD at 2 tertiary care institutions were included (February 2013 to May 2016). Patients were randomly assigned to receive a surgical dual-ring wound protector or no wound protector, and also the current standard of care. The main outcome measure was incisional SSI, as defined by the Centers for Disease Control and Prevention criteria, within 30 days of the index operation. Results: A total of 107 patients were recruited (mean age 67.2 years; standard deviation 12.9; 65% male). No significant differences were identified between the intervention and control groups (age, sex, body mass index, preoperative comorbidities, American Society of Anesthesiologists class, prestent cholangitis). There was a significant reduction in the incidence of incisional SSI in the wound protector group (21.1% vs 44.0%; relative risk reduction 52%; P = 0.010). Patients with completed PD also displayed a decrease in incisional SSI with use of the wound protector compared with those palliated surgically (27.3% vs 48.7%; P = 0.04). Multivariate analysis did not identify any significant modifying factor relationships (estimated blood loss, duration of surgery, hospital site, etc.) (P > 0.05). Conclusion: Among adult patients with intrabiliary stents, the use of a dual-ring wound protector during PD significantly reduces the risk of incisional SSI.

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Mystery of Liver Regeneration After Portal Flow Changes: The Inductive Way of Thinking May Give the Answers

No abstract available

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Incisional Hernia After Midline Versus Transverse Specimen Extraction Incision: A Randomized Trial in Patients Undergoing Laparoscopic Colectomy

imageObjective: To compare the incidence of incisional hernia (IH) between midline and transverse specimen extraction site in patients undergoing laparoscopic colectomy. Background: Midline specimen extraction incision is most commonly used in laparoscopic colectomy, but has high IH risk. IH may be lower for transverse incision. Methods: A single-center superiority trial was conducted. Eligible patients undergoing laparoscopic colectomy were randomly assigned to midline or transverse specimen extraction. Primary outcome was IH incidence at 1 year. Power calculation required 76 patients per group to detect a reduction in IH from 20% to 5%. Secondary outcomes included perioperative outcomes, pain scores, health-related quality of life (SF-36), and cosmesis (Body Image Questionnaire). Results: A total of 165 patients were randomly assigned to transverse (n = 79) or midline (n = 86) specimen extraction site, of which 141 completed 1-year follow-up (68 transverse, 73 midline). Patient, tumor, surgical data, and perioperative morbidity were similar. Pain scores were similar on each postoperative day. On intention-to-treat analysis, there was no difference in the incidence of IH at 1 year (transverse 2% vs midline 8%, P = 0.065) or after mean 30.3 month (standard deviation 9.4) follow-up (6% vs 14%, P = 0.121). On per-protocol analysis there were more IH after midline incision with longer follow-up (15% vs 2%, P = 0.013). On intention-to-treat analysis, SF-36 domains body pain and social functioning were improved after transverse incision. Cosmesis was higher after midline incision on per-protocol analysis, but without affecting body image. Conclusions: Per-protocol analysis of this trial demonstrates that a transverse specimen extraction site has a lower incidence of IH compared to midline with longer follow-up but has worse cosmesis.

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Response to: “Why Morbidity is Not an Adequate Metric for Evaluation of Surgical Quality”

No abstract available

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Interventions to Reduce Intraoperative Costs: A Systematic Review

imageObjective: The aim of this study was to systematically review the risks and benefits of interventions designed to reduce intraoperative costs. Summary Background Data: Episode-based payments shift financial risk from insurers onto hospitals and providers. The operating room (OR) is a resource dense environment and there is growing interest in identifying ways to reduce intraoperative costs while maintaining patient safety. Methods: We searched PubMed, Cochrane, and CINAHL for articles published between 2001 and March 2017 that assessed interventions designed to reduce intraoperative costs. We grouped interventions into 6 categories: standardization of instruments, switching to reusable instruments or removing instruments from trays, wound closure comparisons, cost feedback to surgeons, head-to-head instrument trials, and timely arrival of surgeon to the OR. Results: Of 43 included studies, 12 were randomized trials and 31 were observational studies. Gross cost estimates ranged from −$413 (losses) to $3154 (savings) per operation, with only 2 studies reporting losses; however, studies had significant methodologic limitations related to cost data. Studies evaluating standardization and cost feedback were the most robust with estimated cost savings between $38 and $732/case, with no change in OR time, length of stay, or adverse events. Conclusions: Almost all studies assessing interventions to reduce intraoperative costs have demonstrated cost savings with no apparent increase in adverse effects. Methodologic limitations, especially related to cost data, weaken the reliability of these estimates for most intervention categories. However, hospitals seeking to reduce costs may be able to do so safely by standardizing operative instruments or providing cost feedback to surgeons.

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Management of haemostatic alterations and associated disorders in cirrhosis in Spain: a national survey

knowledge of haematological abnormalities in cirrhosis has greatly improved in recent years.

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Timing of Gastrointestinal Bleeding After Implantation of Left Ventricular Assist Devices Associates With Anatomic Location, Presentation, and Management

Continuous-flow left ventricular assist devices (LVADs) for advanced heart failure have been associated with gastrointestinal bleeding (GIB). We examined the association between time of GIB after LVAD implantation and bleeding location (determined by endoscopy), etiology, and patient outcomes.

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Rapid Fire: Central Nervous System Emergencies

Neurologic complications are unfortunately common in oncology patients, with many presenting to the emergency department for diagnosis and management. This case-based review provides a brief overview of the key points in pathophysiology, diagnosis, and management of 2 oncologic central nervous system emergencies: malignant spinal cord compression and intracranial mass.

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Rapid Fire: Superior Vena Cava Syndrome

Superior vena cava syndrome occurs from obstruction of the superior vena cava. The most common cause is malignancy. Small cell lung cancer and non-Hodgkin lymphoma are the most frequent culprits. Intravascular devices associated with thrombus are becoming more common causes. Classic symptoms include edema, plethora, and distended veins of the face, neck, and chest; shortness of breath; cough; headache; and hoarseness. Treatment in the emergency department is mostly supportive, with head elevation, oxygen, and steroids. Rarely, emergent airway issues and cerebral edema must be addressed. Definitive treatment includes radiotherapy, chemotherapy, and stenting.

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Emergency Medicine Evaluation and Management of Anemia

Anemia is a common condition and is diagnosed on laboratory assessment. It is defined by abnormally low hemoglobin concentration or decreased red blood cells. Several classification systems exist. Laboratory markers provide important information. Acute anemia presents with symptoms owing to acute blood loss; chronic anemia may present with worsening fatigue, dyspnea, lightheadedness, or chest pain. Specific treatments depend on the underlying anemia and etiology. Iron is an alternative treatment for patients with microcytic anemia owing to iron deficiency. Hyperbaric oxygen is an option for alternative rescue therapy. Most patients with chronic anemia may be discharged with follow-up if hemodynamically stable.

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The Oncologic Emergency Medicine Fellowship

The United States cancer population is growing and is projected to grow further. The current cancer population has a high rate of emergency department admission. Further training about oncologic emergencies may be needed and would ideally strive to care for the whole patient, including sequelae of the malignancy, progressive disease, symptom control, adverse effects of treatment, and palliative care. The James Cancer Hospital at The Ohio State University Wexner Medical Center and The University of Texas MD Anderson Cancer Center fellowship training programs in oncologic emergency medicine are described.

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Midlife weight gain is a risk factor for obesity-related cancer



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EUS and confocal endomicroscopic diagnosis of pancreatic acinar cell cystadenoma



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Rapid Fire: Central Nervous System Emergencies

Neurologic complications are unfortunately common in oncology patients, with many presenting to the emergency department for diagnosis and management. This case-based review provides a brief overview of the key points in pathophysiology, diagnosis, and management of 2 oncologic central nervous system emergencies: malignant spinal cord compression and intracranial mass.

https://ift.tt/2t7f0Rs

Rapid Fire: Superior Vena Cava Syndrome

Superior vena cava syndrome occurs from obstruction of the superior vena cava. The most common cause is malignancy. Small cell lung cancer and non-Hodgkin lymphoma are the most frequent culprits. Intravascular devices associated with thrombus are becoming more common causes. Classic symptoms include edema, plethora, and distended veins of the face, neck, and chest; shortness of breath; cough; headache; and hoarseness. Treatment in the emergency department is mostly supportive, with head elevation, oxygen, and steroids. Rarely, emergent airway issues and cerebral edema must be addressed. Definitive treatment includes radiotherapy, chemotherapy, and stenting.

https://ift.tt/2l5a3Vq

Emergency Medicine Evaluation and Management of Anemia

Anemia is a common condition and is diagnosed on laboratory assessment. It is defined by abnormally low hemoglobin concentration or decreased red blood cells. Several classification systems exist. Laboratory markers provide important information. Acute anemia presents with symptoms owing to acute blood loss; chronic anemia may present with worsening fatigue, dyspnea, lightheadedness, or chest pain. Specific treatments depend on the underlying anemia and etiology. Iron is an alternative treatment for patients with microcytic anemia owing to iron deficiency. Hyperbaric oxygen is an option for alternative rescue therapy. Most patients with chronic anemia may be discharged with follow-up if hemodynamically stable.

https://ift.tt/2y3BXKI

The Oncologic Emergency Medicine Fellowship

The United States cancer population is growing and is projected to grow further. The current cancer population has a high rate of emergency department admission. Further training about oncologic emergencies may be needed and would ideally strive to care for the whole patient, including sequelae of the malignancy, progressive disease, symptom control, adverse effects of treatment, and palliative care. The James Cancer Hospital at The Ohio State University Wexner Medical Center and The University of Texas MD Anderson Cancer Center fellowship training programs in oncologic emergency medicine are described.

https://ift.tt/2JI1pqy

Modified technique for imaging the wrist and elbow in obese and claustrophobic patients using a non-open standard MRI scanner

Abstract

Objective

It is challenging to image extremely obese and claustrophobic patients using a standard, non-open, magnetic resonance imaging (MRI) scanner. On the other hand, installing an additional upright or open MRI scanner may not be cost-effective for most practices. Our technique with a patient in a sitting or standing position behind the standard MRI scanner may be helpful in the MR examination of the wrist/elbow in these patients using a standard wrist/elbow coil.

Material and methods

We performed wrist and elbow MRI of extremely obese and claustrophobic patients by using our modified technique with the patient sitting or standing outside the standard non-open MRI scanner. A total number of 20 cases with the following diagnosis were examined: triquetral and scaphoid bone contusions and fractures, scapholunate ligament tears, triangular fibrocartilage complex tear, and biceps tear.

Results

Comparison of image quality for diagnostic information between the standard technique and our technique showed no significant difference, which is necessary for making the diagnosis.

Conclusions

Our technique enables wrist and elbow imaging of extremely obese and claustrophobic patients who cannot otherwise be imaged using a standard MRI scanner without compromising the image quality that is essential for making a diagnosis.



https://ift.tt/2MlfbkP

Correction to: GLP-I secretion in healthy and diabetic Wistar rats in response to aqueous extract of Momordica charantia

Following publication of the original article [1], the authors reported that there was an error in the acknowledgements.

https://ift.tt/2y67ATZ

Relationship between the geometry patterns of vertebrobasilar artery and atherosclerosis

The plaques at the dorsal or lateral wall of basilar artery (BA) are associated with pontine infarcts. We sought to explore the correlations between vertebrobasilar artery geometry and BA plaque locations.

https://ift.tt/2yciLLc

Correction to: Case series of Creutzfeldt-Jakob disease in a third-level hospital in Quito

Following publication of the original article [1], Andrés Damián Ortega Heredia requested that his name be corrected from

https://ift.tt/2l5luML

Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs

57786fig1.jpg

This report describes a fast and reliable method for validating mRNA targets of cellular miRNAs. The method uses synthetic biotinylated Locked Nucleic Acid (LNA)-based miRNA mimics to capture target mRNA. Subsequently, streptavidin-coated magnetic beads are employed to pulldown the target mRNA for quantification by qPCR polymerase chain reaction.

https://ift.tt/2l8ZErH

Deposition of Porous Sorbents on Fabric Supports

57331fig1.jpg

This report details a microwave-initiated approach for deposition of porphyrin functionalized porous organosilicate sorbents on a cotton fabric and demonstrates reduction in 2-chloroethyl ethyl sulfide (CEES) transport through the fabric resulting from this treatment.

https://ift.tt/2y50Plt

Active Failures Seen in Proper Use of Personal Protective Equipment

TUESDAY, June 12, 2018 -- Active failures frequently occur in infectious agent transmission-based precautions, including personal protective equipment (PPE) use, according to a study published online June 11 in JAMA Internal Medicine. Sarah L....

https://ift.tt/2HH9n1B

Increase in Global Cancer Incidence, Drop in Death Rates

TUESDAY, June 12, 2018 -- Worldwide, cancer cases increased by 28 percent from 2006 to 2016, according to a study published online June 2 in JAMA Oncology. Christina Fitzmaurice, M.D., M.P.H., from the University of Washington in Seattle, and...

https://ift.tt/2JMQ4cg

Female Teens, Young Adults Not Getting Enough Exercise

TUESDAY, June 12, 2018 -- Female adolescents and young adults are not meeting the recommended guidelines for physical activity, according to a study published online June 11 in JAMA Pediatrics. Sarah Armstrong, M.D., from Duke University in Durham,...

https://ift.tt/2LKp8XS

Adverse Change in Employment Post-MI Tied to Worse Outcomes

TUESDAY, June 12, 2018 -- Patients with an adverse change in employment after myocardial infarction (MI) have increased likelihood of worse outcomes, according to a study published online June 12 in Circulation: Cardiovascular Quality and...

https://ift.tt/2JMQ1x6

Most Infants and Toddlers Consume Added Sugar

TUESDAY, June 12, 2018 -- Most infants and toddlers aged 6 to 23 months consume added sugar, according to a study presented during Nutrition 2018, the annual meeting of the American Society for Nutrition, held from June 9 to 12 in Boston. Kirsten...

https://ift.tt/2JMPYBq

APAGBI: Teens 13+ Should Be Assessed for VTE Prophylaxis

TUESDAY, June 12, 2018 -- In the perioperative period, post-pubertal adolescents should be assessed for venous thromboembolism (VTE) prophylaxis because of their slightly elevated risk, according to a special article from the Association of...

https://ift.tt/2HMlmek

Long-Term Type 1 Diabetes Associated With Cognitive Decline

TUESDAY, June 12, 2018 -- Both patients with type 1 and patients with type 2 diabetes show overall worse cognition than people without diabetes, according to a study published online June 5 in Diabetes Care. Gail Musen, Ph.D., from Harvard...

https://ift.tt/2JNp783

Eleven tips for white spots on teeth

Having white spots on your teeth can be undesirable, but they are rarely a serious medical concern. Possible reasons for them include poor dental hygiene and eating too many acidic or sugary foods. Here, we look at the most likely causes of white spots on teeth and give you 11 tips for treating and preventing them.

https://ift.tt/2l6TYyF

Clinicopathological features and outcome of type 3 gastric neuroendocrine tumours

BJS, EarlyView.


https://ift.tt/2t0EgZx

Meta‐analysis of the effect of bariatric surgery on physical function

BJS, EarlyView.


https://ift.tt/2l72TQF

Neoadjuvant chemotherapy response influences outcomes in non‐colorectal, non‐neuroendocrine liver metastases

BJS, EarlyView.


https://ift.tt/2t3cprB

Magnetic resonance tumour regression grade and pathological correlates in patients with rectal cancer

BJS, EarlyView.


https://ift.tt/2l39w6i

Prediction of Safety Margin and Optimization of Dosing Protocol for a Novel Antibiotic using Quantitative Systems Pharmacology Modeling

Clinical and Translational Science, EarlyView.


https://ift.tt/2Jx4Nsf

Anisomycin Activates Utrophin Upregulation Through a p38 Signaling Pathway

Clinical and Translational Science, EarlyView.


https://ift.tt/2ybG1sm

Zygotic Fluorescence Recovery After Photo-bleaching Analysis for Chromatin Looseness That Allows Full-term Development

57068fig1v2.jpg

Chromatin looseness appears to be involved in the developmental potential of blastomeres. However, it is not known whether chromatin looseness can be used as a reliable index for the developmental potential for embryos. Here, an experimental system in which chromatin looseness-evaluated zygotes can develop to full term has been described.

https://ift.tt/2JEqrH6

RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression

Abstract
Breast cancer is one of the most common malignancies. It is necessary to identify new markers for predicting tumor progression and therapeutic molecular targets. It has been reported that CD147 is one of the most commonly expressed proteins in primary tumors and in metastatic cells. In this study, we investigated the role of CD147 in human breast cancer metastasis and invasion, and examined its underlying molecular mechanisms. Immunohistochemistry results revealed high expression of CD147 in human breast tumor tissues, which was positively correlated with the malignancy of breast cancer. MCF-7 cells were transfected with CD147 siRNA eukaryotic expression vector, which resulted in significant knockdown of CD147. We found that CD147 siRNA dramatically inhibited cell proliferation, metastasis, and invasion. Furthermore, our results demonstrated that CD147 siRNA inhibited the synthesis of matrix metalloproteinase 9 (MMP-9) but had no significant effect on matrix metalloproteinase 2 (MMP-2). In addition, CD147 siRNA significantly inhibited the production of vascular endothelial growth factor (VEGF). Taken together, these data indicate that CD147 promotes breast cancer cell proliferation, metastasis, and invasion by modulating MMP-9 and VEGF expression. Thus, CD147 may be used as an important indicator for the judgment of malignant behavior of breast cancer, and may be a potential novel target for breast cancer therapy.

https://ift.tt/2LM3hzn

Disturbances of spatial reference frame and postural asymmetry after a chronic stroke

Abstract

Asymmetrical postural behaviors are frequently observed after a stroke. They are due in part to the sensorimotor deficit, but they could also be related to a disorder of the representation of the body in space. The objective was to determine whether the asymmetrical postural behaviors of chronic stroke patients are related with a disruption of the perception of spatial frame. 30 chronic stroke patients (mean age 60.3 year ± 10, mean delay post-stroke 4.78 year ± 3), 15 patients with right brain damage (RBD) and 15 patients with left brain damage (LBD), and 20 healthy subjects participated in the study. Postural asymmetry was detected by the evaluation of body weight repartition on a force platform (weight body asymmetry) and was related to the longitudinal body axis (LBA) and the subjective straight ahead (SSA) (egocentric space representation) and to the subjective visual vertical (SVV) (allocentric space representation) by a multivariate analysis of variance adjusted with motor function and sensitivity as covariables. Both patients with RBD (35% ± 8) and LBD (39% ± 4) had body weight asymmetry and there was still space misperception at this stage of recovery, especially in the RBD group. WBA was related to LBA when considering both patients with RBD and LBD (p = 0.03). However, this relation was dependent on the side of the lesion (p = 0.0006) with a stronger relation in the RBD group (0.01). No relation with WBA was found neither with SSA (p = 0.58) nor with SVV (p = 0.47). This study pointed out a strong relationship between disturbance in the perception of the longitudinal body axis and postural asymmetry in chronic strokes, and especially within the RBD group. Conversely, no other spatial perturbations seemed to be involved in this particular postural behavior.



https://ift.tt/2Mjcv78

A Quantitative Dot Blot Assay for AAV Titration and Its Use for Functional Assessment of the Adeno-associated Virus Assembly-activating Proteins

56766fig1.jpg

This manuscript details a straightforward dot blot assay for quantitation of adeno-associated virus (AAV) titers and its application to study the role of assembly-activating proteins (AAPs), a novel class of non-structural viral proteins found in all AAV serotypes, in promoting the assembly of capsids derived from cognate and heterologous AAV serotypes.

https://ift.tt/2yc2Hcm

Finite element analysis of the influence of three‐joint spinal complex on the change of the intervertebral disc bulge and height

International Journal for Numerical Methods in Biomedical Engineering, EarlyView.


https://ift.tt/2t1Uxgz

Few‐view CT reconstruction with group‐sparsity regularization

International Journal for Numerical Methods in Biomedical Engineering, EarlyView.


https://ift.tt/2l3HrvN

Issue Information

International Journal for Numerical Methods in Biomedical Engineering, Volume 34, Issue 6, June 2018.


https://ift.tt/2y4Bnwr

Cover Image

International Journal for Numerical Methods in Biomedical Engineering, Volume 34, Issue 6, June 2018.


https://ift.tt/2l6pRqQ

An “Omics” Approach for Lipid Oxidation in Foods: The Case of Free Fatty Acids in Bulk Purified Olive Oil

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2JJ7G5C

Enzymatic Interesterification of Heterotrophic Microalgal Oil with Rapeseed Oil to Decrease the Levels of Tripalmitin

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2Jx4cHl

Influence of apical enlargement on the repair of apical periodontitis in rats

International Endodontic Journal, EarlyView.


https://ift.tt/2sTD8HN

Release of TGF‐β1 into root canals with various final irrigants in regenerative endodontics: an in vitro analysis

International Endodontic Journal, EarlyView.


https://ift.tt/2t1gRXK

Issue Information

International Endodontic Journal, Volume 51, Issue 7, Page i-iii, 715, July 2018.


https://ift.tt/2y2WQ99

External cervical resorption: part 2 – management

International Endodontic Journal, EarlyView.


https://ift.tt/2l6fsMc

Substance P and Calcitonin gene‐related peptide expression in human periodontal ligament after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files

International Endodontic Journal, EarlyView.


https://ift.tt/2l2ZCl8

An analysis of the timing and materials associated with pulp disease following restorative dental treatment

International Endodontic Journal, EarlyView.


https://ift.tt/2t3mdSi

Clinical implication of FMR1 intermediate alleles in a Spanish population

Clinical Genetics, Volume 94, Issue 1, Page 153-158, July 2018.


https://ift.tt/2JDa79G

Issue Information ‐ Editorial Board

logo-header-1526603583437.png

Clinical Genetics, Volume 94, Issue 1, Page 1-1, July 2018.


https://ift.tt/2Mkfigp

Discovery of 4 exonic and 1 intergenic novel susceptibility loci for leprosy

Clinical Genetics, EarlyView.


https://ift.tt/2JD9YTG

Association between glutathione S‐transferase gene M1 and T1 polymorphisms and chronic obstructive pulmonary disease risk: A meta‐analysis

Clinical Genetics, EarlyView.


https://ift.tt/2JtbZFQ

Bilateral cerebellar cysts and cerebral white matter lesions with cortical dysgenesis: Expanding the phenotype of LAMB1 gene mutations

Clinical Genetics, EarlyView.


https://ift.tt/2JEOC8q

Overlapping but distinct roles for NOTCH receptors in human cardiovascular disease

Clinical Genetics, EarlyView.


https://ift.tt/2MkfGLT

Further audiovestibular characterization of DFNB77, caused by deleterious variants in LOXHD1, and investigation into the involvement of Fuchs corneal dystrophy

Clinical Genetics, EarlyView.


https://ift.tt/2y3Yibb

Pathogenetic implication of fusion genes in acute promyelocytic leukemia and their diagnostic utility

Clinical Genetics, EarlyView.


https://ift.tt/2MkGvja

Genetic analysis of adult leukoencephalopathy patients using a custom‐designed gene panel

Clinical Genetics, EarlyView.


https://ift.tt/2y5IFjB

Metagenomic insights into diazotrophic communities across Arctic glacier forefields

Abstract
Microbial nitrogen fixation is crucial for building labile nitrogen stocks and facilitating higher plant colonization in oligotrophic glacier forefield soils. Here, the diazotrophic bacterial community structure across four Arctic glacier forefields was investigated using metagenomic analysis. In total, 70 soil metagenomes were used for taxonomic interpretation based on 185 nitrogenase (nif) sequences, extracted from assembled contigs. The low number of recovered genes highlights the need for deeper sequencing in some diverse samples, to uncover the complete microbial populations. A key group of forefield diazotrophs, found throughout the forefields, was identified using a nifH phylogeny, associated with nifH Cluster I and III. Sequences related most closely to groups including Alphaproteobacteria, Betaproteobacteria, Cyanobacteria and Firmicutes. Using multiple nif genes in a Last Common Ancestor analysis revealed a diverse range of diazotrophs across the forefields. Key organisms identified across the forefields included Nostoc, Geobacter, Polaromonas and Frankia. Nitrogen fixers which are symbiotic with plants were also identified, through the presence of root associated diazotrophs, which fix nitrogen in return for reduced carbon. Additional nitrogen fixers identified in forefield soils were metabolically diverse, including fermentative and sulphur cycling bacteria, halophiles and anaerobes.

https://ift.tt/2l7SIv8

Birds, feather-degrading bacteria and preen glands: the antimicrobial activity of preen gland secretions from turkeys (Meleagris gallopavo) is amplified by keratinase

Abstract
The function of uropygial glands (preen glands) has been subject to controversial debates. In this study, we evaluated the antimicrobial potential of preen gland secretions of turkeys (Meleagris gallopavo) against 18 microbial strains by means of diffusion tests, broth microdilutions, checkerboard assays, and time-kill curves. Furthermore, we tested the hypothesis that lipids exert direct antimicrobial effects on pathogens. Moreover, we checked for mutualistic relationships between the preen gland bacterium Corynebacterium uropygiale with its hosts. We found that preen gland secretions significantly inhibited the growth of a broad spectrum of bacteria and fungi, particularly when combined with keratinase. Combinations effectively killed multidrug resistant microorganisms in a strongly synergistic manner. Since feather-degrading microorganisms (FDM) express keratinase and thereby disrupt the integrity of the plumage, our data suggests that preen gland secretions of turkeys are specifically activated in the presence of FDM, and specifically eliminate FDM from feathers. However, antimicrobial effects did not originate from lipids, but were mediated by highly polar compounds which might be antimicrobial peptides (AMPs). Finally, C. uropygiale is apparently not involved in the antimicrobial activity of preen gland secretions of turkeys. In conclusion, our results suggest that turkeys can antagonize feather-degrading microorganisms by amplifying the antimicrobial properties of their preen gland secretions.

https://ift.tt/2y8c5xy

Patient information needs in upper gastrointestinal cancer: what patients and their families want to know

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2sRKMSW

Inflammatory calcified de‐differentiated liposarcoma of the anterior mediastinum: an unusual case

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2LIO7ux

Pattern of care for cancer of the oesophagus in a western population

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2LJD0BP

Jejunal angiosarcoma: a rare cause of obscure gastrointestinal bleeding with successful resection after enteroscopic localization

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2sQw7HG

Comparison of lipase and amylase for diagnosing post‐operative pancreatic fistulae

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2LGHkBJ

Single‐ and multiple‐dose escalation study to assess pharmacokinetics, pharmacodynamics and safety of oral esaxerenone in healthy Japanese subjects

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2y8cqjO

Gaps in predicting clinical doses for cannabinoids therapy: Overview of issues for pharmacokinetics and pharmacodynamics modelling

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2MiCueV

Comment on ‘Genotype‐guided warfarin dosing versus conventional dosing strategies: a systematic review and meta‐analysis of randomized clinical trials’ by Tse et al.

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2Jx2bLh

The impact of ileal pouch‐anal anastomosis on graft survival following liver transplantation for primary sclerosing cholangitis

Alimentary Pharmacology &Therapeutics, EarlyView.


https://ift.tt/2t3wDkO

Issue Information

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 1-3, July 2018.


https://ift.tt/2MiB8AO

Editorial: an argument for low‐dose thiopurine allopurinol combination use as first‐line therapy in inflammatory bowel disease

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 97-98, July 2018.


https://ift.tt/2JC9bSV

Letter: all or nothing—placebo effects in a non‐drug clinical trial in IBS

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 105-106, July 2018.


https://ift.tt/2sRJur4

Editorial: Helicobacter pylori resistance and sequential therapy—authors’ reply

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 96-97, July 2018.


https://ift.tt/2JEKOnE

Editorial: HBsAg serum levels in HBeAg‐negative chronic HBV infection—is it a matter of genotype?

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 102-103, July 2018.


https://ift.tt/2sS43DT

Editorial: HBsAg serum levels in HBeAg‐negative chronic HBV infection—is it a matter of genotype? Authors’ reply

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 103-104, July 2018.


https://ift.tt/2t2uo1r

Editorial: transplantation in the setting of acute‐on‐chronic liver failure—calculating chances. Authors’ reply

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 100-101, July 2018.


https://ift.tt/2MiARhg

Editorial: Helicobacter pylori resistance and sequential therapy

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 95-96, July 2018.


https://ift.tt/2t2ugyZ

Letter: can the overall gastrointestinal safety of celecoxib be extended to all COX‐2‐selective agents?

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 108-110, July 2018.


https://ift.tt/2Mmw7ap

Editors’ declarations of interest

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 4-4, July 2018.


https://ift.tt/2JFqqTs

Letter: it is time to adopt new objective parameters to accurately identify patients with functional heartburn

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 107-108, July 2018.


https://ift.tt/2MiAJyi

Editorial: an argument for low‐dose thiopurine allopurinol combination use as first‐line therapy in inflammatory bowel disease—authors’ reply

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 98-99, July 2018.


https://ift.tt/2t2GjMG

Letter: all or nothing—placebo effects in a non‐drug clinical trial in IBS. Authors’ reply

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 106-107, July 2018.


https://ift.tt/2MnuU2H

Editorial: transplantation in the setting of acute‐on‐chronic liver failure—calculating chances

Alimentary Pharmacology &Therapeutics, Volume 48, Issue 1, Page 99-100, July 2018.


https://ift.tt/2JDULBA

Review article: Asia‐Pacific consensus recommendations on endoscopic tissue acquisition for biliary strictures

Alimentary Pharmacology &Therapeutics, EarlyView.


https://ift.tt/2MiAzXI

Risk of post‐operative surgical site infections after vedolizumab vs anti‐tumour necrosis factor therapy: a propensity score matching analysis in inflammatory bowel disease

Alimentary Pharmacology &Therapeutics, EarlyView.


https://ift.tt/2JGdHjl

Energy from ATP‐Hydrolysis Does Not Drive Biological Reactions …

logo-header-1526603583437.png

BioEssays, EarlyView.


https://ift.tt/2JN9f5C

A Scientist's Guide to Impactful Science Communication: A Priori Goals, Collaborative Assessment, and Engagement with Youth

logo-header-1526603583437.png

BioEssays, EarlyView.


https://ift.tt/2LJrYME

Agent‐Based Modeling in Molecular Systems Biology

BioEssays, EarlyView.


https://ift.tt/2JRY8sl

Primary Cilia Reconsidered in the Context of Ciliopathies: Extraciliary and Ciliary Functions of Cilia Proteins Converge on a Polarity theme?

BioEssays, EarlyView.


https://ift.tt/2LL4xTo

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases

BioEssays, EarlyView.


https://ift.tt/2JN9eyA

Dietary Micronutrients Promote Neuronal Differentiation by Modulating the Mitochondrial‐Nuclear Dialogue

BioEssays, EarlyView.


https://ift.tt/2HHODGQ

Editorial Note Referring to: An Inversion in the Wiring of an Intercellular Signal: Evolution of Wnt Signaling in the Nematode Vulva

BioEssays, EarlyView.


https://ift.tt/2JPpGye

Pentylenetetrazole-Induced Kindling Mouse Model

This protocol describes a method of chemical kindling with pentylenetetrazole and provides a mouse model of epilepsy. This protocol can also be used to investigate vulnerability to seizure induction and pathogenesis after epileptic seizures in mice.

https://ift.tt/2sY5LTe

Retraction

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2t1NGnl

Retraction

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2MfA6pr

Retraction

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2t1NynR

Thermal oxidation and hydrofluoric acid treatment on the sandblasted implant surface: A histologic histomorphometric and biomechanical study

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2MfzQqt

Dental implants placed in severely atrophic jaws reconstructed with autogenous calvarium, bovine bone mineral, and collagen membranes: A 3‐ to 19‐year retrospective follow‐up study

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2t1Nl43

Reposition of the bone plate over the antrostomy in maxillary sinus augmentation: A histomorphometric study in rabbits

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2sRe44i

Long‐term psychological and educational outcomes for survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study

Cancer, EarlyView.


https://ift.tt/2t1H0FP

Examining urban and rural differences in perceived timeliness of care among cancer patients: A SEER‐CAHPS study

Cancer, EarlyView.


https://ift.tt/2l566jJ

Reply to The persistent uncertainty of when to recommend allogeneic stem cell transplantation in follicular lymphoma

Cancer, EarlyView.


https://ift.tt/2y5BB6n

The persistent uncertainty of when to recommend allogeneic stem cell transplantation in follicular lymphoma

Cancer, EarlyView.


https://ift.tt/2l6rl4I

Association of low‐activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: A population‐based cohort study

International Journal of Cancer, EarlyView.


https://ift.tt/2MkI8NL

A prospective evaluation of plasma polyphenol levels and colon cancer risk

International Journal of Cancer, EarlyView.


https://ift.tt/2y4qzOT

T cells and ILC2s are major effector cells in influenza‐induced exacerbation of allergic airway inflammation in mice

European Journal of Immunology, EarlyView.


https://ift.tt/2JQdqh1

The bone marrow is not only a primary lymphoid organ: The critical role for T lymphocyte migration and housing of long‐term memory plasma cells

European Journal of Immunology, EarlyView.


https://ift.tt/2HJ1Dfi

Front cover story: Eur. J. Immunol. 6'18

European Journal of Immunology, Volume 48, Issue 6, June 2018.


https://ift.tt/2JN67Xq

Journal roundup

European Journal of Immunology, Volume 48, Issue 6, Page 895-895, June 2018.


https://ift.tt/2LJ85VX

Contents: Eur. J. Immunol. 6'18

European Journal of Immunology, Volume 48, Issue 6, Page 889-892, June 2018.


https://ift.tt/2JPv3O6

In this issue

European Journal of Immunology, Volume 48, Issue 6, Page 893-894, June 2018.


https://ift.tt/2LHRNN8

Impressum

European Journal of Immunology, Volume 48, Issue 6, Page 1085-1085, June 2018.


https://ift.tt/2JPAI6A

EFIS on Tour ‐ getting to know our members

European Journal of Immunology, Volume 48, Issue 6, Page 896-897, June 2018.


https://ift.tt/2HGKumE

Editorial Board: Eur. J. Immunol. 6'18

European Journal of Immunology, Volume 48, Issue 6, June 2018.


https://ift.tt/2JMCVzW

Microglial MHC class II is dispensable for experimental autoimmune encephalomyelitis and cuprizone‐induced demyelination

European Journal of Immunology, EarlyView.


https://ift.tt/2LJog5G

Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4+ T‐cell subsets in multiple sclerosis patients

European Journal of Immunology, EarlyView.


https://ift.tt/2JMXUCE

Aberrant learning in Parkinson's disease: A neurocomputational study on bradykinesia

European Journal of Neuroscience, EarlyView.


https://ift.tt/2y4JGIu

Behavioural state‐specific neurons in the mouse medulla involved in sleep‐wake switching

European Journal of Neuroscience, EarlyView.


https://ift.tt/2Jxod0o

A journey into the retina: Müller glia commanding survival and death

European Journal of Neuroscience, EarlyView.


https://ift.tt/2y4JwRo

Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

European Journal of Neuroscience, EarlyView.


https://ift.tt/2JvsS2B

Vestibulo‐cortical hemispheric dominance: The link between anxiety and the vestibular system?

European Journal of Neuroscience, EarlyView.


https://ift.tt/2JAWUy2

Emergency Department Discharge of Pulmonary Embolus Patients

Academic Emergency Medicine, EarlyView.


https://ift.tt/2LMez6r

Financial Viability of Emergency Department Observation Unit Billing Models

Academic Emergency Medicine, EarlyView.


https://ift.tt/2JMClSM

Realization of In‐Plane p–n Junctions with Continuous Lattice of a Homogeneous Material

Advanced Materials, EarlyView.


https://ift.tt/2Mnkgcf

Wearables in Medicine

Advanced Materials, EarlyView.


https://ift.tt/2JDGHbg

Protein Toxin Chaperoned by LRP‐1‐Targeted Virus‐Mimicking Vesicles Induces High‐Efficiency Glioblastoma Therapy In Vivo

Advanced Materials, EarlyView.


https://ift.tt/2JAMt1K

Metal–Organic‐Framework‐Based Catalysts for Photoreduction of CO2

Advanced Materials, EarlyView.


https://ift.tt/2y3HaCp

Pistachio‐Shuck‐Like MoSe2/C Core/Shell Nanostructures for High‐Performance Potassium‐Ion Storage

Advanced Materials, EarlyView.


https://ift.tt/2JuTVuY

Black Arsenic: A Layered Semiconductor with Extreme In‐Plane Anisotropy

Advanced Materials, EarlyView.


https://ift.tt/2JCTQ4A

Increased Exciton Delocalization of Polymer upon Blending with Fullerene

Advanced Materials, EarlyView.


https://ift.tt/2t6pS1Y

Full Electric Control of Exchange Bias at Room Temperature by Resistive Switching

Advanced Materials, EarlyView.


https://ift.tt/2l49ICl

Lead‐Chalcogenide Colloidal‐Quantum‐Dot Solids: Novel Assembly Methods, Electronic Structure Control, and Application Prospects

Advanced Materials, EarlyView.


https://ift.tt/2JHnqpD

Room‐Temperature Triple‐Ligand Surface Engineering Synergistically Boosts Ink Stability, Recombination Dynamics, and Charge Injection toward EQE‐11.6% Perovskite QLEDs

Advanced Materials, EarlyView.


https://ift.tt/2MnjVGv

Photoelectric Detectors Based on Inorganic p‐Type Semiconductor Materials

Advanced Materials, EarlyView.


https://ift.tt/2y3GWLz

Ferroelectric and Piezoelectric Effects on the Optical Process in Advanced Materials and Devices

Advanced Materials, EarlyView.


https://ift.tt/2MkmvgA

Single Tungsten Atoms Supported on MOF‐Derived N‐Doped Carbon for Robust Electrochemical Hydrogen Evolution

Advanced Materials, EarlyView.


https://ift.tt/2y7vcHY

A 3D Magnetic Hyaluronic Acid Hydrogel for Magnetomechanical Neuromodulation of Primary Dorsal Root Ganglion Neurons

Advanced Materials, EarlyView.


https://ift.tt/2JAM67m

New Frontiers in Electron Beam–Driven Chemistry in and around Graphene

Advanced Materials, EarlyView.


https://ift.tt/2JCTrPC

The Organic Crystalline Materials of Vision: Structure–Function Considerations from the Nanometer to the Millimeter Scale

Advanced Materials, EarlyView.


https://ift.tt/2MkmhGg

Ultrafine Co Nanoparticles Encapsulated in Carbon‐Nanotubes‐Grafted Graphene Sheets as Advanced Electrocatalysts for the Hydrogen Evolution Reaction

Advanced Materials, EarlyView.


https://ift.tt/2y3GGw5

Phosphorene/ZnO Nano‐Heterojunctions for Broadband Photonic Nonvolatile Memory Applications

Advanced Materials, EarlyView.


https://ift.tt/2Mmc500

Unraveling the Water Impermeability Discrepancy in CVD‐Grown Graphene

Advanced Materials, EarlyView.


https://ift.tt/2JCThru

Rewritable Optical Memory Through High‐Registry Orthogonal Upconversion

Advanced Materials, EarlyView.


https://ift.tt/2MmbYS8

Development of a novel humanoid‐robot simulator for endoscope with pharyngeal reflex and real‐life responses

Digestive Endoscopy, EarlyView.


https://ift.tt/2JyojEK

Japan NBI Expert Team classification: Narrow‐band imaging magnifying endoscopic classification of colorectal tumors

Digestive Endoscopy, EarlyView.


https://ift.tt/2y11dBo

Epstein–Barr virus positivity among surgically resected intramucosal gastric cancer

Digestive Endoscopy, EarlyView.


https://ift.tt/2JzVwQ8

Crossed‐clip strangulation for the management of small intestinal polyps in patients with Peutz‐Jeghers syndrome

Digestive Endoscopy, EarlyView.


https://ift.tt/2JDpNcR

The Evolution of Transgender Surgery

Clinical Anatomy, June 2018.


https://ift.tt/2sN8pfx

The clitoral activation paradox — Claimed outcomes from different methods of its stimulation

Clinical Anatomy, June 2018.


https://ift.tt/2t3pyRg

The fasciacytes: A new cell devoted to fascial gliding regulation

Clinical Anatomy, June 2018.


https://ift.tt/2MizVto

The role of mTOR in ovarian cancer, polycystic ovary syndrome and ovarian aging

Clinical Anatomy, June 2018.


https://ift.tt/2JFsaMg

Chronic liver injury promotes hepatocarcinoma cell seeding and growth, associated with infiltration by macrophages

Cancer Science, EarlyView.


https://ift.tt/2y5uKd9

HSPC159 promotes proliferation and metastasis by inducing epithelial‐mesenchymal transition and activating the PI3K/Akt pathway in breast cancer

Cancer Science, EarlyView.


https://ift.tt/2Jvr0Hb

Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment

Cancer Science, EarlyView.


https://ift.tt/2JFrV3O

Increase in incidental detection of thyroid cancer in Osaka, Japan

Cancer Science, EarlyView.


https://ift.tt/2JvqCZf

Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog hepatocellular adenomas

Hepatology, EarlyView.


https://ift.tt/2JGZNO2

Acute hepatitis B virus infection in humanized chimeric mice has multiphasic viral kinetics

Hepatology, EarlyView.


https://ift.tt/2JxV315

Social media: Why AASLD and its members must lead the conversation

Hepatology, EarlyView.


https://ift.tt/2JDn1Et

Beyond the ‘Reading Wars’: How the Science of Reading Can Improve Literacy

A new scientific report from an international team of psychological researchers aims to resolve the so-called "reading wars," emphasizing the importance of teaching phonics in establishing fundamental reading skills in early childhood. The report, published in in Psychological Science in the Public Interest, a journal of the Association for Psychological Science, shows how early phonics skills are advanced with a rich reading curriculum throughout the school years.

Scientists Anne Castles (Macquarie University), Kathleen Rastle (Royal Holloway University of London), and Kate Nation (University of Oxford) report their conclusions as part of a thorough, evidence-based account of how children learn to read. They synthesize findings from more than 300 research studies, book chapters, and academic journal articles published across a variety of scientific fields.

"We decided to bring this knowledge together in one place to provide an accessible overview," Nation says. "We didn't want it to be buried in the scientific literature, we wanted it to be useful to teachers charged with the vital task of teaching children to read."

For several decades, the "reading wars" have been waged between teachers, parents, and policymakers who champion a phonics-based approach (teaching children the sounds that letters make) and those who support a "whole-language" approach (focused on children discovering meaning in a literacy-rich environment).

"Writing is a code for spoken language, and phonics provides instruction for children in how to crack that code," says Castles. "Phonics is an essential basis for becoming a good reader, but it isn't enough on its own — one aim of our review was to describe the other key ingredients that must be combined with phonics to support good reading development."

To acquire sophisticated literacy skills, for example, children must progress from identifying individual sounds to recognizing whole words. They must also be able to pull forth the meaning of different words quickly within a particular context in order to comprehend a whole unit of text, whether it's a sentence, a paragraph, or an entire page.

Although teachers, parents, and policymakers recognize literacy as an essential skill that all children should learn, existing policies and practices often fail to incorporate the most effective strategies for learning and teaching reading. As a result, low literacy remains a pressing issue in developed and developing nations around the world.

"We have a really strong scientific understanding of how children learn to read, and there is no longer any need for 'reading wars,'" says Rastle. "Our review describes this evidence base, and provides concrete recommendations for drawing on it in the classroom."

In a commentary accompanying the report, psychological scientist Rebecca Treiman (Washington University in St. Louis) dismantles two common misconceptions that often stymy evidence-based approaches to reading instruction: that reading to children teaches them how to read and that children learn to read though independent discovery. The new report provides critical insight, Treiman says, because it highlights the specific processes by which early phonics instruction allows children to gain understanding and reading experience over time.

"Literacy opens up knowledge, opportunity, and enjoyment. Building it requires good instruction, solid foundations in vocabulary and language comprehension, and extensive reading practice," Castles, Rastle, and Nation note. "By taking advantage of the strong evidence base around what helps children learn to read, we can support more children to go on to become confident, skilled readers."

The report was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders, the Economic and Social Research Council, and The Leverhulme Trust.

The full report and accompanying commentary are available online:

Report: Ending the "Reading Wars": Reading acquisition from novice to expert
Anne Castles, Kathleen Rastle, Kate Nation

Commentary: What research tells us about reading instruction
Rebecca Treiman



https://ift.tt/2HFhNGt

A probiotic modulates the microbiome and immunity in multiple sclerosis

Annals of Neurology, EarlyView.


https://ift.tt/2JI2PSd

Issue Information

Histopathology, Volume 73, Issue 1, Page 180-184, July 2018.


https://ift.tt/2Mkzxut

Issue Information

Histopathology, Volume 73, Issue 1, Page 1-3, July 2018.


https://ift.tt/2t1CeYT

Gleason score assignment is the sole responsibility of the pathologist

Histopathology, Volume 73, Issue 1, Page 5-7, July 2018.


https://ift.tt/2Mkzj6B

Interobserver reliability of histopathological features for distinguishing between cutaneous polyarteritis nodosa and superficial thrombophlebitis

Histopathology, EarlyView.


https://ift.tt/2JGXY3E

PD‐L1 expression in tumour‐infiltrating lymphocytes is a poor prognostic factor for primary acral melanoma patients

Histopathology, EarlyView.


https://ift.tt/2MmiBUd

The American Cancer Society public health statement on eliminating combustible tobacco use in the United States

CA: A Cancer Journal for Clinicians, EarlyView.


https://ift.tt/2t2HxHF

Correction to: Comprehensive Registry of Esophageal Cancer in Japan, 2011

In the original publication of the article, the below name of institutions were not included in the table of Institution-registered cases in 2011.



https://ift.tt/2JPcBVN

Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells

Type 2 immunity underpins diverse processes central to tissue homeostasis, allergic inflammation, and anti-helminth immunity. Halim et al. demonstrate that the local expansion of Th2 and Treg cells in response to the alarmin IL-33 is dependent on the expression of the costimulatory molecule OX40L by type 2 innate lymphoid cells (ILC2s), revealing a central role for the IL-33-ILC2-OX40L pathway in the orchestration of type 2 immunity.

https://ift.tt/2JMPZoQ

OncoArray Links Dozens of DNA Variants to Risk for Common Cancers

Researchers with the NCI-supported GAME-ON initiative and OncoArray Network are publishing studies identifying dozens of new genetic variants associated with the risk for developing some of the most common cancers.



https://ift.tt/2sXeEh1

Mcl-1 phosphorylation without degradation mediates sensitivity to HDAC inhibitors by liberating BH3-only proteins

Mcl-1, a pro-survival Bcl-2 family protein, is frequently overexpressed in cancer cells and plays a critical role in therapeutic resistance. It is well known that anti-cancer agents induce phosphorylation of Mcl-1, which promotes its binding to E3 ubiquitin ligases and subsequent proteasomal degradation and apoptosis. However, other functions of Mcl-1 phosphorylation in cancer cell death have not been well characterized. In this study, we show in colon cancer cells that histone deacetylase inhibitors (HDACi) induce GSK3β-dependent Mcl-1 phosphorylation, but not degradation or downregulation. The in vitro and in vivo anticancer effects of HDACi were dependent on Mcl-1 phosphorylation and were blocked by genetic knock-in (KI) of a Mcl-1 phosphorylation site mutant. Phosphorylation-dead Mcl-1 maintained cell survival by binding and sequestering BH3-only Bcl-2 family proteins PUMA, Bim, and Noxa, which were upregulated and necessary for apoptosis induction by HDACi. Resistance to HDACi mediated by phosphorylation-dead Mcl-1 was reversed by small-molecule Mcl-1 inhibitors that liberated BH3-only proteins. These results demonstrate a critical role of Mcl-1 phosphorylation in mediating HDACi sensitivity through a novel and degradation-independent mechanism. These results provide new mechanistic insights on how Mcl-1 maintains cancer cell survival and suggest that Mcl-1-targeting agents are broadly useful for overcoming therapeutic resistance in cancer cells.

https://ift.tt/2sRpHIv

Integrative genome-wide analysis of long noncoding RNAs in diverse immune cell types of melanoma patients

Genome-wide identification and characterization of long non-coding RNAs (lncRNAs) in individual immune cell lineages helps us better understand the driving mechanisms behind melanoma and advance personalized patient treatment. To elucidate the transcriptional landscape in diverse immune cell types of peripheral blood cells (PBC) in stage IV melanoma, we used whole transcriptome RNA sequencing to profile lncRNAs in CD4+, CD8+, and CD14+ PBC from 132 patient samples. Our integrative computational approach identified 27,625 expressed lncRNAs, 2,744 of which were novel. Both T cells (i.e., CD4+ and CD8+ PBC) and monocytes (i.e., CD14+ PBC) exhibited differential transcriptional expression profiles between melanoma patients and healthy subjects. Cis- and trans-level co-expression analysis suggested that lncRNAs are potentially involved in many important immune-related pathways and the programmed cell death receptor 1 (PD-1) checkpoint pathways. We also identified 9 gene co-expression modules significantly associated with melanoma status, all of which were significantly enriched for three mRNA translation processes. Age and melanoma traits closely correlated with each other, implying that melanoma contains age-associated immune changes. Our computational prediction analysis suggests that many cis- and trans-regulatory lncRNAs could interact with multiple transcriptional and post-transcriptional regulatory elements in CD4+, CD8+, and CD14+ PBC, respectively. These results provide novel insights into the regulatory mechanisms involving lncRNAs in individual immune cell types in melanoma and can help expedite cell type-specific immunotherapy treatments for such diseases.

https://ift.tt/2LFMXA3

Type I Chiari Malformation Presenting in an Adult

Description 

Type I Chiari malformations (CMs) is an acquired or congenital disorder characterised by the presence of the cerebellar tonsils at 5 mm or below of the spinal canal, which can result in abnormal cerebrospinal fluid flow and produce headaches, syrinx or hydrocephalus. CMs are still considered an uncommon disease with a prevalence in the USA of less than 1%.1 2 We present a 44-year-old man with no medical history who presented to the emergency department complaining of nausea, vomiting, vertigo and a 2-day history of headaches exacerbated with Valsalva manoeuvres. He was initially admitted with a working diagnosis of ischaemic stroke and underwent a CT scan of the brain, which was unremarkable. Further work-up with brain MRI disclosed incidental cerebellar herniation 6.5 mm below the foramen magnum (figure 1) and no abnormalities in spinal canal MRIs. The patient was treated symptomatically with oral...



https://ift.tt/2JCSKFP

Marantic endocarditis: incidental infarcts leading to diagnosis of pancreatic cancer

Non-bacterial thrombotic endocarditis (NBTE) is a well-described phenomenon associated with malignancies due to hypercoaguable state. In the setting of pancreatic cancer, NBTE is more commonly diagnosed postmortem. We describe a case of a man who was diagnosed with pancreatic carcinoma after incidental finding of NBTE. Imaging incidentally revealed multiple strokes, bilateral renal and splenic infarcts, while subsequent workup for cardioembolic source demonstrated a 1.1x0.7 cm mitral valve vegetation. As multiple blood cultures were sterile and patient lacked clinical signs of infection, an underlying malignancy was suspected. CT abdomen demonstrated a dilated pancreatic duct, MRI showed a 2.8x2.2 cm pancreatic head mass. Endoscopic biopsy of the mass revealed pancreatic adenocarcinoma. Other than NBTE, there were no other clinical or laboratory findings to clearly suggest pancreatic cancer. Thus, incidental discovery of this mitral valve vegetation led to the diagnosis of pancreatic malignancy.



https://ift.tt/2MiCXOe

Herpes zoster with cutaneous dissemination: a rare presentation of an uncommon pathology in children

Herpes zoster, caused by varicella zoster virus (VZV) reactivation, affects mainly the adult population, although it can occur in children. This happens when primary infection (varicella) has occurred at a very young age or in immunocompromised patients. Complications are rare in healthy individuals. They include VZV cutaneous dissemination, which affects 2%–10% of immunocompromised patients.

We present a previously healthy child, with history of varicella during her first month of life, which presented at age 8 with a severe case of herpes zoster, complicated with cutaneous dissemination. Immunity study was unremarkable. Causes, management and follow-up are discussed.



https://ift.tt/2JFxv6r

Central nervous system blast crisis of chronic myeloid leukaemia misdiagnosed as tubercular meningitis

Chronic Myeloid Leukaemia (CML) presenting with isolated Central Nervous System (CNS) blast crisis is an uncommon entity. A 22-year-old man, diagnosed with chronic phase CML in 2011 and was in haematological and cytogenetic remission until July 2016, had acute onset headache and vomiting with meningeal signs and was admitted elsewhere, investigated by brain imaging and cerebrospinal fluid (CSF) analysis and suspected to have tubercular meningitis, for which steroids and antitubercular medications were started. The patient's sensorium further deteriorated, and Ventriculoperitoneal shunt surgery was done for hydrocephalus by a neurosurgeon. After 2 months of the illness, he was admitted to our hospital with a persistent headache, vomiting and altered sensorium. CSF for cytospin confirmed myeloid blasts. He was still in haematological remission. So, a diagnosis of isolated CNS blast crisis was made. The patient was started on triple intrathecal chemotherapy and cranial radiotherapy. He had improvement with treatment and is still in remission.



https://ift.tt/2Mk9vYf

Resistant Gram-Negative Bacteria and Diagnostic Point-of-Care Options for the Field Setting during Military Operations

The spread of multidrug-resistant bacteria in resource-poor settings affects the military medical service in case of deployments of soldiers to war and crisis zones. Patients with war injuries are prone to colonization or infection with multidrug-resistant bacteria. Resistant Gram-negative bacteria play a dominant role in military wound infections. Problematic hygiene conditions on deployment facilitate exposition of soldiers with subsequent colonization. Although colonizing strains are frequently cleared from their hosts after returning from deployment, transmission to close contacts of the soldiers in the home country cannot be excluded and therapeutic options are reduced if colonization progresses to invasive infection. Since sophisticated culture-based diagnostic approaches are typically not available in the field setting on deployment, molecular rapid diagnostic test systems are an option for transmission control if the locally prevalent molecular resistance mechanisms are known. Efforts for global resistance surveillance can contribute to better understanding of resistance distribution and spread at deployment sites. This review summarizes experience of the military medical services with multidrug resistance on deployment and with the influx of resistant strains to the home country and discusses potential use of available molecular rapid test systems as an option for the field setting.

https://ift.tt/2t0GwzO

Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway

We first applied moderate fluid shear stress to nucleus pulposus cells. The correlation of AP-1 with type II collagen, proteoglycan, Cytokeratin 8 protein, MAP-1, MAP-2, and MAP-4 and the correlation of AP-1 with IL-1β, TNF-α, IL-6, IL-8, MIP-1, MCP-1, and NO were detected. Our results document that moderate fluid shear stress could activate the FAK-MEK5-ERK5-cFos-AP1 signaling pathway. AP1 could downregulate the construct factors of cytoskeleton such as type II collagen, proteoglycan, Cytokeratin 8 protein, MAP-1, MAP-2, and MAP-4 in nucleus pulposus cell after the fluid shear stress was loaded. AP1 could upregulate the inflammatory factors such as IL-1β, TNF-α, IL-6, IL-8, MIP-1, MCP-1, and NO in nucleus pulposus cell after the fluid shear stress was loaded. Taken together, our data suggested that moderate fluid shear stress may play an important role in the cytoskeleton of nucleus pulposus and surrounding inflammatory mediators by activating the FAK-MEK5-ERK5-cFos-AP1 signaling pathway, thereby affecting cell degeneration.

https://ift.tt/2sPOZGD

Sclerotic Bone Metastasis in Pulmonary Adenocarcinoma

Pulmonary adenocarcinoma is one of the major types of lung cancers in which metastasis is very common and it accounts approximately to one-third of all primary pulmonary cancers. Although a minority of patients with lung cancer are asymptomatic, which gets usually detected in routine chest radiography, most of the patients present with some symptoms. Lung cancer metastasis may occur virtually in every organ system. Patients with non-small-cell lung cancer commonly have extrathoracic metastases to the adrenal glands, liver, brain, bones, and lymph nodes at presentation. Approximately one-third of patients with lung cancer will present with symptoms related to extrathoracic spread. Metastasis to the bone is not uncommon in lung cancer; however, osteoblastic bone metastasis is very rare. Here we present a 30-year-old female diagnosed to have pulmonary adenocarcinoma with multiple sclerotic bony lesions in the vertebra.

https://ift.tt/2LEL7PK

How I perform sphincterotomy

Since 1973, endoscopic sphincterotomy has been one of the cornerstones in therapeutic endoscopic retrograde cholangiopancreatography (ERCP). However, the procedure adds to the overall risk of the ERCP procedure and the risk/benefit ratio must always be assessed carefully prior to performing the cut.

https://ift.tt/2l3aYFV

Su1435 FLUOROLESS SINGLE-STEP EUS-GUIDED GALLBLADDER DRAINAGE WITH CAUTERY-ENHANCED LUMEN-APPOSING METAL STENT: A MULTICENTER STUDY

Recently, a novel device has been utilized to drain pancreatic fluid collections using an EUS-guided biflanged fully covered self-expandable lumen-apposing metal stent (LAMS) with an electrocautery enhanced delivery system (cautery-enhanced LAMS: CE-LAMS). The aim of this study was to analyze the clinical effectiveness and safety of this novel device for treatment of acute cholecystitis in patients who are not surgical candidates.

https://ift.tt/2t5SIQ2

Frontmatter

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: i-iv

https://ift.tt/2JQfR3m

Highlight Issue ‘Molecular Basis of Life 2017’

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 621-622

https://ift.tt/2LLFhMv

Regulation of LRRK2: insights from structural and biochemical analysis

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 637-642

https://ift.tt/2JPIMEv

Oncogenic BRAFV600E drives expression of MGL ligands in the colorectal cancer cell line HT29 through N-acetylgalactosamine-transferase 3

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 649-659

https://ift.tt/2HGGYIX

Hypoxia and serum deprivation induces glycan alterations in triple negative breast cancer cells

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 661-672

https://ift.tt/2JPIFJ5

DNA-encoded libraries – an efficient small molecule discovery technology for the biomedical sciences

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 691-710

https://ift.tt/2HGGRx1

Protein crystallization in living cells

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 751-772

https://ift.tt/2JGENdx

Spectroscopic characterization of the Co-substituted C-terminal domain of rubredoxin-2

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 787-798

https://ift.tt/2LFvxDF

Twitch or swim: towards the understanding of prokaryotic motion based on the type IV pilus blueprint

Journal Name: Biological Chemistry
Volume: 399
Issue: 7
Pages: 799-808

https://ift.tt/2JOW0kO

Standing variation and the capacity for change: are endocrine phenotypes more variable than other traits?

Abstract
Circulating steroid hormone levels exhibit high variation both within and between individuals, leading some to hypothesize that these phenotypes are more variable than other morphological, physiological, and behavioral traits. This should have profound implications for the evolution of steroid signaling systems, but few studies have examined how endocrine variation compares to that of other traits or differs among populations. Here we provide such an analysis by first exploring how variation in three measures of corticosterone (CORT)— baseline, stress-induced, and post-dexamethasone injection— compares to key traits characterizing morphology (wing length, mass), physiology (reactive oxygen metabolite concentration [d-ROMs] and antioxidant capacity), and behavior (provisioning rate) in two populations of tree swallow (Tachycineta bicolor). After controlling for measurement precision and within-individual variation, we found that only post-dex CORT was more variable than all other traits. Both baseline and stress-induced CORT exhibit higher variation than antioxidant capacity and provisioning rate, but not oxidative metabolite levels or wing length. Variation in post-dex CORT and d-ROMs was also elevated in the higher-latitude population in that inhabits a less predictable environment. We next studied how these patterns might play out on a macroevolutionary scale, assessing patterns of variation in baseline testosterone (T) and multiple non-endocrine traits (body length, mass, social display rate, and locomotion rate) across 17 species of Anolis lizards. At the macroevolutionary level, we found that circulating T levels and the rate of social display output are higher than other behavioral and morphological traits. Altogether, our results support the idea that within-population variability in steroid levels is substantial, but not exceptionally higher than many other traits that define animal phenotypes. As such, circulating steroid levels in free-living animals should be considered traits that exhibit similar levels of variability from individual to individual in a population.

https://ift.tt/2LI9Tyx

A spatially explicit model shows how titin stiffness modulates muscle mechanics and energetics

Abstract
In striated muscle, the giant protein titin spans the entire length of a half-sarcomere and extends from the backbone of the thick filament, reversibly attaches to the thin filaments, and anchors to the dense protein network of the z-disk capping the end of the half-sarcomere. However, little is known about the relationship between the basic mechanical properties of titin and muscle contractility. Here, we build upon our previous multi-filament, spatially explicit computational model of the half-sarcomere by incorporating the nonlinear mechanics of titin filaments in the I-band. We vary parameters of the nonlinearity to understand the effects of titin stiffness on contraction dynamics and efficiency. We do so by simulating isometric contraction for a range of sarcomere lengths (SL; 1.6–3.25 μm). Intermediate values of titin stiffness accurately reproduce the passive force–SL relation for skeletal muscle. The maximum force–SL relation is not affected by titin for SL ≤ 2.5 μm. However, as titin stiffness increases, maximum force for the four thick filament system at SL = 3.0 μm significantly decreases from 103.2 ± 2 pN to 58.8 ± 1 pN. Additionally, by monitoring ATP consumption, we measure contraction efficiency as a function of titin stiffness. We find that at SL = 3.0 μm, efficiency significantly decreases from 13.9 ± 0.4 pN/ATP to 7.0 ± 0.3 pN/ATP when increasing titin stiffness, with little or no effect below 2.5 μm. Taken together, our results suggest that, despite an increase in the fraction of motors bound to actin along the descending limb when titin is stiffer, the force-generating capacity of the motors is reduced. These results suggest that titin stiffness has the potential to affect contractile efficiency.

https://ift.tt/2JMpFeA

Understanding the agility of running birds: Sensorimotor and mechanical factors in avian bipedal locomotion

Abstract
Birds are a diverse and agile lineage of vertebrates that all use bipedal locomotion for at least part of their life. Thus birds provide a valuable opportunity to investigate how biomechanics and sensorimotor control are integrated for agile bipedal locomotion. This review summarizes recent work using terrain perturbations to reveal neuromechanical control strategies used by ground birds to achieve robust, stable and agile running. Early experiments in running guinea fowl aimed to reveal the immediate intrinsic mechanical response to an unexpected drop ('pothole') in terrain. When navigating the pothole, guinea fowl experience large changes in leg posture in the perturbed step, which correlates strongly with leg loading and perturbation recovery. Analysis of simple theoretical models of running has further confirmed the crucial role of swing-leg trajectory control for regulating foot contact timing and leg loading in uneven terrain. Coupling between body and leg dynamics results in an inherent trade-off in swing leg retraction rate for fall avoidance versus injury avoidance. Fast leg retraction minimizes injury risk, but slow leg retraction minimizes fall risk. Subsequent experiments have investigated how birds optimize their control strategies depending on the type of perturbation (pothole, step, obstacle), visibility of terrain, and with ample practice negotiating terrain features. Birds use several control strategies consistently across terrain contexts: 1) independent control of leg angular cycling and leg length actuation, which facilitates dynamic stability through simple control mechanisms, 2) feedforward regulation of leg cycling rate, which tunes foot-contact timing to maintain consistent leg loading in uneven terrain (minimizing fall and injury risks), 3) load-dependent muscle actuation, which rapidly adjusts stance push-off and stabilizes body mechanical energy, and 4) multi-step recovery strategies that allow body dynamics to transiently vary while tightly regulating leg loading to minimize risks of fall and injury. In future work, it will be interesting to investigate the learning and adaptation processes that allow animals to adjust neuromechanical control mechanisms over short and long timescales.

https://ift.tt/2HIJE8H

The Influence of Visual, Vestibular and Hindlimb Proprioceptive Ablations on Landing Preparation in Cane Toads

Synopsis
Coordinated landing from a jump requires preparation, which must include appropriate positioning and configuration of the landing limbs and body to be successful. While well studied in mammals, our lab has been using the cane toad (Rhinella marinus) as a model for understanding the biomechanics of controlled landing in anurans, animals that use jumping or bounding as their dominant mode of locomotion. In this paper, we report new results from experiments designed to explore how different modes of sensory feedback contribute to previously identified features of coordinated landing in toads. More specifically, animals in which vision, hindlimb proprioception or vestibular feedback were removed, underwent a series of hopping trials while high-speed video was used to record and characterize limb movements and electromyographic activity was recorded from a major elbow extensor (m. anconeus). Results demonstrate that altering any sensory system impacts landing behavior, though loss of vision had the least effect. Blind animals showed significant differences in anconeus EMG timing relative to controls, but forelimb and hindlimb movements as well as the ability to successfully decelerate the body using the forelimbs were not affected. Compromising hindlimb proprioception led to distinctly different forelimb kinematics. Though EMG patterns were disrupted, animals in this condition were also able to decelerate after impact, though with less control, regularly allowing their trunks to make ground contact during landing. Animals with compromised vestibular systems showed the greatest deficits, both in takeoff and landing behavior, which were highly variable and rarely coordinated. Nevertheless, animals in this condition demonstrated EMG patterns and forelimb kinematics similar to those in control animals. The fact that no ablation entirely eliminates all aspects of landing preparation, suggests that its underpinnings are complex and that that there is no single sensory trigger for its initiation.

https://ift.tt/2JMpBvm

CD4+CD45RA−FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI

https://ift.tt/2Jwhp37

Students’ Motivation for Sport Activity and Participation in University Sports: A Mixed-Methods Study

Background. Physical activity among students is essential for complimenting sedentary behavior and for individuals' future health. This study investigates reasons for sport engagement among students and addresses the utilization of university sports programs (USP) by employing a mixed-methods approach. Methods. The NuPhA-Study consists of a quantitative online survey (n=689) followed by qualitative interviews (n=20). In the survey, we assessed reasons for sport activity using a 24-item battery and USP utilization. Quantitative results were further explored using qualitative data to check for completeness of the predefined items (content validity) and to identify opportunities to improve participating in USP. Results. A factor analysis grouped the 24 items into five factors (life balance/fitness/body image/contact with others/fun). Our qualitative study explained these in more detail and revealed missing aspects. 47.6% of students participated in USP. Potential improvements for USP include program maintenance during the semester break and temporal harmonization with the classes. Discussion. The qualitative component identified additional reasons for sport activity that were not addressed by the item battery, which provides critical implications for developing item batteries for future research. Our results may help to generate a more target-group-oriented approach to increase physical activity among students, which will reduce sedentary behavior and future disease burden.

https://ift.tt/2l2Caod

Key role of rehabilitation in new CDC guidelines for the management of Duchenne Muscular Dystrophy

No abstract available

https://ift.tt/2sPI0NV

Functional Impairments Associated with Patient Activation among Community-Dwelling Older Adults

Objectives Activity of Daily Living (ADL) stages and Instrumental Activity of Daily Living (IADL) stages demonstrated ordered associations with mortality, risk of hospitalization, and receipt of recommended care. This paper explores the associations of stages with three dimensions of patient activation: self-care efficacy, patient-doctor communication and health-information seeking. We hypothesized that higher ADL and IADL stages (greater limitation) are associated with a lower level of patient activation. Methods Patient activation factors were derived from the 2004 and 2009 Medicare Current Beneficiary Survey. In this cross-sectional study (N=8981), the associations of activity limitation stages with patient activation factors were assessed in latent factor models. Results Greater activity limitation was in general inversely associated with self-efficacy, patient-doctor communication and health information-seeking, even after adjusting for sociodemographic and clinical characteristics. For instance, the mean of self-care efficacy across ADL stages I-IV (mild, moderate, severe and complete limitation) compared to stage 0 (no limitation) decreased significantly by 0.17, 0.29, 0.34, and 0.60, respectively. Covariates associated with suboptimal patient activation were also identified. Discussion Our study identified multiple opportunities to improve patient activation, including providing support for older adults with physical impairments, at socioeconomic disadvantages, or with psychological or cognitive impairment. Disclosures: The research for this manuscript was supported by the grant from the National Institutes of Health (R01AG040105 and R01HD074756). There are no personal conflicts of interest of any of the authors, and no authors reported disclosures beyond the funding source. The opinions and conclusions of the authors are not necessarily those of the sponsoring agency. We certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on us or on any organization with which we are associated. This material has not been previously presented at a meeting. Acknowledgement: We thank Sean Hennessy, PharmD, PhD, for his valuable input in this manuscript. Corresponding Author: Ling Na, PhD, Email: lingna2000@gmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Bone marrow fat physiology in relation to skeletal metabolism and cardiometabolic disease risk in children with cerebral palsy

Individuals with cerebral palsy (CP) exhibit neuromuscular complications and low physical activity levels. Adults with CP exhibit a high prevalence of chronic diseases, which is associated with musculoskeletal deficits. Children with CP have poor musculoskeletal accretion accompanied by excess bone marrow fat, which may lead to weaker bones. Mechanistic studies to determine the role of bone marrow fat on skeletal growth and maintenance, and how it relates to systemic energy metabolism among individuals with CP, are lacking. In this review, we highlight the skeletal status in children with CP and analyze the existing literature on the interactions among bone marrow fat, skeletal health, and cardiometabolic disease risk in the general population. Clinically vital questions are proposed, including: (1) Is the bone marrow fat in children with CP metabolically distinct from typically developing children in terms of its lipid and inflammatory composition? (2) Does the bone marrow fat suppress skeletal acquisition? (3) Or, does it accelerate chronic disease development in children with CP? (4) If so, what are the mechanisms? In conclusion, while inadequate mechanical loading may initiate poor skeletal development, subsequent expansion of bone marrow fat may further impede skeletal acquisition and increase cardiometabolic disease risk in those with CP. Address of correspondence: Daniel G. Whitney, PhD, Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, MI. Phone: 734-936-9474. Fax: 734-615-1770. e-mail: dgwhit@umich.edu All authors declare no conflict of interest. There has been no previous presentation of this work. Daniel G. Whitney is supported by the University of Michigan Advanced Rehabilitation Research Training Program in Community Living and Participation from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) (90AR5020-0200). Mark D. Peterson is funded by the National Institutes of Health (NIH) (1KO1 HD074706) and NIDILRR (90IF0102-01). Christopher M. Modlesky is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH (R01 HD090126). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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