Chromatin dynamics governed by a set of nuclear structural proteins

Abstract

During the past three decades, the study of nuclear and chromatin organization has become of great interest. The organization and dynamics of chromatin are directly responsible for many functions including gene regulation, genome replication, and maintenance. In order to better understand the details of these mechanisms, we need to understand the role of specific proteins that take part in these processes.

The genome in the nucleus is organized in different length scales, ranging from the bead‐like nucleosomes through topological associated domains (TADs) up to chromosome territories. The mechanisms that maintain these structures, however, remain to be fully elucidated. Previous works highlighted the significance of lamin A, an important nucleoplasmic protein; however, there are other nuclear structural proteins that are also important for chromatin organization. Studying the organizational aspects of the nucleus is a complex task, and different methods have been developed and adopted for this purpose, including molecular and imaging methods.

Here we describe the use of the live‐cell imaging method and demonstrate that the dynamics of the nucleus is strongly related to its organizational mechanisms. We labeled different genomic sites in the nucleus and measured the effect of nuclear structural proteins on their dynamics. We studied lamin A, BAF, Emerin, lamin B, CTCF, and Cohesin and discuss how each of them affect chromatin dynamics. Our findings indicate that lamin A and BAF have a significant effect on chromosomes dynamics, while other proteins mildly affect the type of the diffusion while the volume of motion is not affected.

This article is protected by copyright. All rights reserved.

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Outcomes and prognostic factors in intermediate-risk prostate cancer: multi-institutional analysis of the Spanish RECAP database

Abstract

Purpose

To retrospectively assess outcomes and to identify prognostic factors in patients diagnosed with intermediate-risk (IR) prostate cancer (PCa) treated with primary external beam radiotherapy (EBRT).

Materials and methods

Data were obtained from the multi-institutional Spanish RECAP database, a population-based prostate cancer registry in Spain. All IR patients (NCCN criteria) who underwent primary EBRT were included. The following variables were assessed: age; prostate-specific antigen (PSA); Gleason score; clinical T stage; percentage of positive biopsy cores (PPBC); androgen deprivation therapy (ADT); and radiotherapy dose. The patients were stratified into one of three risk subcategories: (1) favourable IR (FIR; GS 6, ≤ T2b or GS 3 + 4, ≤ T1c), (2) marginal IR (MIR; GS 3 + 4, T2a–b), and (3) unfavourable IR (UIR; GS 4 + 3 or T2c). Biochemical relapse-free survival (BRFS), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed.

Results

A total of 1754 patients from the RECAP database were included and stratified by risk group: FIR, n = 781 (44.5%); MIR, n = 252 (14.4%); and UIR, n = 721 (41.1%). Mean age was 71 years (range 47–86). Mean PSA was 10.4 ng/ml (range 6–20). The median radiotherapy dose was 74 Gy, with mean doses of 72.5 Gy (FIR), 73.4 Gy (MIR), and 72.8 Gy (UIR). Most patients (88%) received ADT for a median of 7.1 months. By risk group (FIR, MIR, UIR), ADT rates were, respectively, 88.9, 86.5, and 86.9%. Only patients with ≥ 24 months of follow-up post-EBRT were included in the survival analysis (n = 1294). At a median follow-up of 52 months (range 24–173), respective 5- and 10-year outcomes were: OS 93.6% and 79%; BRFS 88.9% and 71.4%; DFS 96.1% and 89%; CSS 98.9% and 94.6%. Complication rates (≥ grade 3) were: acute genitourinary (GU) 2%; late GU 1%; acute gastrointestinal (GI) 2%; late GI 1%. There was no significant association between risk group and BRFS or OS. However, patients with favourable-risk disease had significantly better 5- and 10-year DFS than patients with UIR: 98.7% vs. 92.4% and 92% vs. 85.8% (p = 0.0005). CSS was significantly higher (p = 0.0057) in the FIR group at 5 (99.7% vs. 97.3%) and 10 years (96.1% vs. 93.4%). On the multivariate analyses, the following were significant predictors of survival: ADT (BRFS and DFS); dose ≥ 74 Gy (BRFS); age (OS).

Conclusions

This is the first nationwide study in Spain to report long-term outcomes of patients with intermediate-risk PCa treated with EBRT. Survival outcomes were good, with a low incidence of both acute and late toxicity. Patients with unfavourable risk characteristics had significantly lower 5- and 10-year disease-free survival rates. ADT and radiotherapy dose ≥ 74 Gy were both significant predictors of treatment outcomes.

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Multiple factors bias chromosome micronucleation

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Surgeon Experience and Medicare Expenditures for Laparoscopic Compared to Open Colectomy

Objective: To quantify the extent to which payments for laparoscopic and open colectomy are influenced by a surgeon's experience with laparoscopy. Background: Numerous studies suggest that healthcare costs for laparoscopic colectomy are lower than open surgery. None have assessed the importance of surgeon experience on the relative financial benefits of laparoscopy. Methods: We conducted a study of 182,852 national Medicare beneficiaries undergoing laparoscopic or open colectomy between 2010 and 2012. Using instrumental variable methods to account for selection bias, we compared Medicare payments for laparoscopic and open colectomy. We stratified our analysis by surgeons' annual experience with laparoscopic colectomy to determine the influence of provider experience on payments. Results: In the fully adjusted analysis, average episode payments per patient were $2640 [95% confidence interval (CI) −$4091 to −$1189] lower with the laparoscopic approach versus open. Surgeons in the highest quartile of laparoscopic experience demonstrated an average payment savings of $5456 per patient (CI −$7918 to −$2994) in their laparoscopic versus open cases. Among surgeons in the lowest quartile of laparoscopic experience, there was, however, no difference between laparoscopic and open cases (difference: $954, 95% CI −$731 to $2639). Differences in payments were explained by differences in complications rates. Both groups had similar rates of complications for open procedures (least experience, 21%, most experience, 21%; P = 0.45), but differed significantly on rates of complications for laparoscopic cases (least experience, 28%, most experience, 15%; P

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Prognosis of autoimmune hemolytic anemia in critically ill patients

Abstract

Patients with autoimmune hemolytic anemia (AIHA) may require intensive care unit (ICU) admission. In order to describe the characteristics of AIHA patients in ICU and identify prognosis factors, clinical and biological data from 44 patients admitted in one ICU between 2002 and 2015 were retrospectively analyzed. The main reasons for ICU admission were profound anemia without any organ failure in 19 patients (either for safer transfusion or continuous monitoring only). Twenty-five (57%) patients had a past history of hemopathy. Twenty patients presented with a direct anti-globulin test (DAT) positive for immunoglobulin G (DAT-IgG) only (46%), 8 with a DAT positive for both IgG and complement (DAT-IgG+C) (36%), and 16 with a DAT positive for complement only (DAT-IgG+C) (18%). Corticosteroids and rituximab were administered to respectively 44 (100%) and 12 (25%) patients. Red blood cell transfusion was required in 28 (64%) patients. Ten (23%) patients received vasopressors. Renal replacement therapy was necessary in 14 (31.8%) patients. Thirteen (30%) patients died in the ICU. There was no difference between survivors and non-survivors regarding associated comorbidities like hemopathy (18/31 [58%] vs. 7/13 [54%], p = 0.80). In decedents, age was higher (72 years [57.8–76.3] vs. 50 years [34.3–64], p < 0.01) and organ dysfunctions were more severe at day 1 (SOFA 8 [7–11] vs. 5.5 [3–7], p < 0.01). Patients with a DAT-IgG displayed poorer outcome in comparison with patients with DAT-IgG+C/C (hospital mortality 69% vs. 36%, p = 0.04). Mortality rate of AIHA patients requiring ICU admission is consequential and appears to be impacted by age, organ failures, and DAT-IgG.

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A lethal case of hoarding due to the combination of traumatic and confined space asphyxia

Abstract

Hoarding is defined as the acquisition of, and failure to discard, possessions of little use or value to others, usually associated with a significant degree of clutter in the individual's home. We describe a case of a woman who died from a combined traumatic and confined space asphyxia, after being trapped under some of the objects amassed in her apartment. The event was considered to be accidental; by taking into account the information gathered during assessment of the scene, we believe that the accident took place while entering or exiting the apartment. It appears that the woman, who was trying to open or close the door, could have been using her leg to keep the objects piled behind the door from falling. Unfortunately the pile of hoarded objects collapsed and the woman was fatally trapped underneath them. The age and strength of the woman played an important role in the fatal incident, she was too old and weak to remove the items that had collapsed over her body. The scarcity of space between the collapsed objects and the woman, as well as the absence of external or internal signs of violent asphyxiation, or other causes of death, allowed us to establish that the death resulted from a combined mechanism of both the traumatic and the confined space asphyxiation.

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Utilizing ticks as forensic indicators in a livestock investigation

Abstract

Although forensic parasitology remains in its infancy compared with more developed fields like forensic entomology, parasites can be useful forensic indicators. We present the case of an individual who disobeyed animal health legislation and crossed animal quarantine boundaries and two state lines with a cattle tick (Rhipicephalus australis) infested horse. Following recognition of the infestation by animal health officers, the individual asserted that the infestation had occurred either during transport or upon arrival at the site of discovery, and that they had not contravened quarantine legislation. Utilizing ticks as forensic indicators, knowledge of the life cycle and minimum age of ticks on the infested horse indicated that the individual's assertions were false, and that they had in fact transported the tick infested horse from a cattle tick endemic region across state lines and quarantine zones.

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Sex estimation using the mandibular canine index components

Abstract

The mandibular canine index (MCI) has been described as a suitable methodology for sex estimation in forensic scenarios but there are contradictory reports about its accuracy. Moreover, the two mandibular canine teeth must be available, which is not always a viable option. The aim of this study was to strip the MCI by analyzing the MCI itself and its components, in order to optimize its use for sex estimation. The mesiodistal dimensions of the mandibular canine crown and the mandibular canine arch width were measured in a sample of 120 cast models. Five predictor variables were considered in this study: the standard MCI, a variation of the MCI using the left canine, and MCI components (MD43, MD33 and D33–43). Multivariate binary logistic regression was performed using stepwise forward approach to select the most statistical relevant variables on the probability of a cast being from a female. The estimated probability was then analyzed with respect to performance in sex classification (ROC analysis and optimal cut-offs accuracy) and compared with the performance of the univariate variables. MCI43 and MCI33 presented the lowest performance (64.2% and 63.3% respectively), and the highest overall accuracy was attained using the MD43 and MD33 (85.8% in both cases). The multivariate logistic model obtained (using MD43 and MD33) exhibited the same accuracy as the logistic model based solely on MD43 (85.8%). Our results suggest that MD43 should be used instead of MCI for sex estimation.

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Targeted Therapies in CLL: Monotherapy Versus Combination Approaches

Abstract

Purpose of Review

While chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia (CLL), it is not curative, has significant relapse rates, and is not always well tolerated. Recently, novel targeted therapies have been developed to increase response rates and reduce toxicity, especially in high-risk disease. Current goals of CLL therapies are to produce deep and durable, especially minimal residual disease (MRD)-negative, remissions so as to allow patients to ultimately discontinue treatment for a while. Whether this can be achieved with single agents or combination regimens is being investigated. Here, we comment on what the results of recent and ongoing clinical trials mean for the future of CLL therapy.

Recent Findings

Large trials have proven the efficacy of novel therapies including small-molecule inhibitors like ibrutinib, idelalisib, and venetoclax. These agents are approved as monotherapy for first-line treatment and/or in the relapsed/refractory setting. However, it appears that combining these drugs with other novel agents or with chemoimmunotherapy can give higher rates of MRD-negative remission, and delay disease resistance. Chimeric antigen receptor-T cells may change the outlook for patients with heavily refractory CLL.

Summary

Further research will determine which drug combinations are optimal for the various subgroups of CLL patients.

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Post-marketing surveillance study of the safety of dexamethasone intravitreal implant in patients with retinal vein occlusion or noninfectious posterior segment uveitis

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Circumpapillary structure-function relationships with microperimetry and spectral domain optical coherence tomography in glaucoma: a pilot study

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Evaluation of the effects of formulation, food, or a proton-pump inhibitor on the pharmacokinetics of glasdegib (PF-04449913) in healthy volunteers: a randomized phase I study

Abstract

Purpose

To demonstrate the bioequivalence of the planned maleate salt-based commercial glasdegib tablet formulation [International Council for Harmonization (ICH) glasdegib] to the clinical di-hydrochloride (di-HCl) salt-based glasdegib formulation (di-HCl glasdegib). Additionally, to estimate the effects of a high-fat, high-calorie meal and proton-pump inhibitor (PPI) on the pharmacokinetics of ICH glasdegib.

Methods

This Phase I open-label study (ClinicalTrials.gov: NCT03130556) enrolled 24 healthy subjects to receive two different tablet formulations of single-dose 100-mg glasdegib under fasted conditions. A subset of healthy volunteers (n = 12) received single-dose 100-mg ICH glasdegib following a high-fat, high-calorie meal or concurrently with a PPI (rabeprazole).

Results

The adjusted geometric mean ratio (ICH glasdegib:di-HCl glasdegib) and 90% confidence intervals (CI) of area under the plasma concentration–time curve from time zero to infinity (AUC_inf) and maximum plasma concentration (C_max) were 104.0% (99.7‒108.5%) and 101.6% (96.1‒107.4%), respectively, within the acceptance range for bioequivalence (80‒125%). The adjusted geometric mean ratio (90% CIs) for AUC_inf and C_max under fed conditions were 84.3% (78.6‒90.6%) and 69.0% (61.8‒77.0%), respectively, relative to fasted conditions. When ICH glasdegib was administered concurrently with the PPI, the adjusted geometric mean ratio (90% CI) of AUC_inf and C_max were 100.6% (93.2‒108.6%) and 80.5% (70.7‒91.6%), respectively, relative to fasted conditions. Glasdegib was generally well tolerated under all conditions studied.

Conclusions

The ICH glasdegib tablet formulation was bioequivalent to the clinical di-HCl formulation under fasted conditions. A high-fat, high-calorie meal or concurrent PPI treatment had a minimal effect on glasdegib exposure, and was not considered clinically meaningful.

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Seroepidemiology of Hepatitis B and C Virus Infections among Pregnant Women Attending Antenatal Clinic in Selected Health Facilities in East Wollega Zone, West Oromia, Ethiopia

Background. Hepatitis B virus and hepatitis C virus infections are a public health problem worldwide. It is highly endemic in Asia and Sub-Saharan Africa. Horizontal and perinatal transmissions are thought to be the major modes of transmission in these countries. Objective. This study aimed to investigate the seroepidemiology and possible risk factors for hepatitis B virus and hepatitis C virus infection among pregnant women attending antenatal care clinics. Methods. A cross-sectional study design was conducted from July to September 2014 among 421 pregnant women attending antenatal care services in randomly selected health facilities, East Wollega Zone, West Oromia, Ethiopia. Blood sample was collected from each woman and separated serum was tested for the presence of markers. A prestructured questionnaire was used to collect sociodemographic data and risk factors. The collected data was analyzed using SPSS 20.0 statistical software. Odds ratio and 95% confidence interval were used as measures of the strength of association. Result. The overall prevalence of HBsAg was 2.4% ranging from 0.0% to 5.2%. It was the highest in Sire Health Center and the lowest/nil in others. The prevalence of HCV ranged from 6.7% to 20% with an average of 8.07% in this study area where it was highest in the Getema Health Center Antenatal Care Attendants. Only address (p=0.020) and area of the health institution (p=0.021) are significantly the associated factors for HBsAg and serostatus of HCV, respectively. Conclusion. The prevalence of HBsAg carrier rate of pregnant women in the study area falls within the medium endemic prevalence and HCV prevalence was higher than HBsAg. Study participants who were from urban areas were significantly affected with HBV while study institution affects the prevalence of HCV infection so that initiating screening tests during follow up period for antenatal care services is mandatory.

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Impact of Matrix Metalloproteinase 9 on COPD Development in Polish Patients: Genetic Polymorphism, Protein Level, and Their Relationship with Lung Function

Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction. Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD. We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients. We analyzed SNP in the promoter region of MMP-9 gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals. Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) of MMP-9 (by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA). All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups. Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms. Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group. In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals. This phenomenon is probably associated with the disease-related lung environment but not with genetic features of the MMP-9.

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FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy

Audience: Consumer, Health Professional, Pharmacy The U.S. Food and Drug Administration is alerting health care professionals and patients not to use drug products intended to be sterile that were produced in an inadequately designed processing room...

https://ift.tt/2G5M5Xm

FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy

Audience: Consumer, Health Professional, Pharmacy The U.S. Food and Drug Administration is alerting health care professionals and patients not to use drug products intended to be sterile that were produced in an inadequately designed processing room...

https://ift.tt/2G5M5Xm

Diagnostic criteria for amyotrophic lateral sclerosis: a multicentre study of inter-rater variation and sensitivity

Diagnostic criteria for amyotrophic lateral sclerosis (ALS) have been developed to standardise diagnosis and patient recruitment in trials. A research group of the World Federation of Neurology (WFN) devised the "El Escorial criteria" (EEC) (Brooks et al., 1994), which were later modified to increase their diagnostic sensitivity as the "revised El Escorial Criteria" (rEEC) (Brooks et al., 2000) with the objective of encouraging earlier inclusion in trials (Ross et al., 1998). The rEEC have been found to have high specificity, but to lack sensitivity, thus failing to promote earlier patient inclusion in clinical trials (Traynor et al., 2000; Zoccolella et al., 2006; Turner et al., 2009).

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Relations between sensory symptoms, touch sensation, and sensory neurography in the assessment of the ulnar neuropathy at the elbow

Differences in biophysical properties of sensory and motor axons make the former more predisposed to the injury by the identical mechanical stress (Lin et al., 2002). In addition, cutaneous afferents appear to depend more on Na+/K+ pump action than motor fibers to keep resting membrane potentials (Burke et al., 1997; Kiernan et al., 2004). Therefore, sensory axons show greater tendency to develop ectopic activity than motor axons. Accordingly, the entrapment nerve syndrome generally presents sensory symptoms in the cutaneous territory of the injuried nerve as the first complaint.

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Assessing Neuroprotective Effects of Glycyrrhizae Radix et Rhizoma Extract Using a Transient Middle Cerebral Artery Occlusion Mouse Model

In this study, we modify an existing experimental method to obtain more reproducible results, by establishing a middle cerebral artery occlusion (MCAO) mouse model. Oral administration of Glycyrrhizae Radix et Rhizome (GR) methanol extract (GRex), following stroke induction, significantly decreased total infarction volume relative to the untreated control group.

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KRT19 and CEACAM5 mRNA-marked circulated tumor cells indicate unfavorable prognosis of breast cancer patients

Abstract

Aim

To investigate the clinical and prognostic significance of circulated tumor cells (CTC) marked by cytokeratin 19 coding gene KRT19 mRNA and carcinoembryonic antigen coding gene CEACAM5 mRNA in preoperative peripheral blood of breast cancer patients and provide molecular markers for breast cancer metastasis risk.

Methods

The mRNA levels of KRT19 and CEACAM5 in preoperative peripheral blood of breast cancer patients without (n = 603) and with (n = 76) distant metastases at the time of initial diagnosis were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between CTC_KRT19, CTC_CEACAM5 and clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), or overall survival (OS) was statistically analyzed.

Results

In different pathological stages of breast cancer, the rates of CTC_KRT19−pos and CTC_{CEACAM5−pos} increased with the increase of the stages (P = 0.077 and P = 0.004). Preoperative CTC_KRT19−pos in breast cancer patients was closely related to the lymph node metastasis statues (P < 0.0001), and had no significant correlation with other clinicopathological features. There was no significant correlation between CTC_CEACAM5 and the clinicopathological features. Patients with high levels of CTC double-marked by KRT19 and CEACAM5 mRNA had shorter DMFS (P < 0.0001) and OS (P = 0.016) for patients with breast cancer. The 7-year DMFS rates for the low-, intermediate-, and high-risk groups were 90.7%, 67.5%, and 59.1%, respectively (P < 0.0001). The prognosis of patients with decreased KRT19 and CEACAM5 mRNA after treatment is better than that of patients who have not decreased, and the combination of the two indicators is better than the single one for predicting PFS (P = 0.002 compare with P = 0.036 or P = 0.047).

Conclusion

Double-marked CTC by KRT19 and CEACAM5 mRNA is a prognostic index of breast cancer patients before surgery and after chemotherapy. Single-marked CTC by KRT19 mRNA indicates lymph node statues of preoperative patients. Therefore, the RT-qPCR-based molecular diagnosis of CTC could be used for prognostic prediction of breast cancer patients and guiding clinical treatment.

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Amelioration of Lipopolysaccharide-Induced Acute Lung Injury in Rats by Na-H Exchanger-1 Inhibitor Amiloride Is Associated with Reversal of ERK Mitogen-Activated Protein Kinase

Background. Na-H exchanger-1 (NHE-1) is expressed in the lung of rats. Accumulating evidence shows that Na-H exchangers are involved in inflammation. Amiloride, an inhibitor of NHE-1, inhibits the activation of macrophages and endothelial cells and reduces their production of cytokines. Since these processes have been implicated in acute lung injury (ALI) induced by lipopolysaccharide (LPS), we examined the protective effect of amiloride on ALI induced by LPS in rats. Material and Methods. ALI in specific pathogen-free male Sprague-Dawley rats was induced by an intravenous injection of 6 mg/kg LPS. Amiloride pretreated rats received an intravenous injection of 10 mg/kg amiloride 30 min before the administration of LPS. Controls received normal saline in a similar manner. All animals were sacrificed 6 h after LPS or normal saline administration. The degree of ALI was assessed by wet-to-dry weight ratio (W/D) and lung histological examination. Neutrophilic infiltration was determined by myeloperoxidase (MPO) activity in lung tissue. Concentrations of total protein (TP), tumor necrosis factor-alpha (TNF-α), and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid (BALF) were also measured. Expression of NHE-1 and mitogen-activated protein kinase (MAPK) p38, p-p38, ERK, and p-ERK was evaluated by western blot analysis. Results. Pretreatment with amiloride significantly reduced the increase in W/D, ALI score, lung tissue MPO activity, concentrations of TP, TNF-α, and MIP-2 in BALF, resulting in attenuation of ALI induced by LPS. Meanwhile, levels of NHE-1 and p-ERK proteins were reversed, whereas that of p-p38 was not. Conclusions. These findings suggest that NHE-1 inhibitor amiloride could attenuate ALI induced by LPS in rats. This effect is mediated through reversal of ERK.

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Assessment of Postoperative Outcomes in Spinal Epidural Abscess Following Surgical Decompression

Publication date: Available online 8 December 2018

Source: The Spine Journal

Author(s): Leonard J. Keller, Vincent J. Alentado, Joseph E. Tanenbaum, Bryan S. Lee, Amy S. Nowacki, Edward C. Benzel, Thomas E. Mroz, Michael P. Steinmetz

Abstract

Background Context

A spinal epidural abscess (SEA) is a serious condition that may be managed with antibiotics alone or with decompressive surgery combined with antibiotics.

Purpose

The objectives of this study were to assess the clinical outcomes of SEA after surgical management and to identify the patient-level factors that are associated with outcomes following surgical decompression and removal of SEA.

Study Design/Setting

Retrospective chart review analysis.

Patient Sample

An analysis of 154 consecutive patients who initially presented to a tertiary-care, academic medical center with SEA, and were subsequently treated with surgery between 2010 and 2015 was performed.

Outcome Measures

Postoperative pre-discharge American Spinal Injury Association Impairment Scale (AIS) scores, 6-month follow-up encounter AIS scores, need for revision surgery, and mortality during SEA surgery were the primary outcomes.

Physiologic Measures: AIS scores

Method

Fisher's exact and Wilcoxon rank-sum tests were used to assess the associations between patient-level factors and surgical outcomes. Moreover, an interactive, predictive model for postoperative pre-discharge AIS score was developed using a proportional odds regression model. There was no funding secured for this study and there are no conflict of interest-associated biases.

Results

154 patients (mean age of 58 years) were treated using surgical decompression in addition to antibiotics. The majority of patients were Caucasian (81%) and male (61%). No intraoperative mortality was reported. A second SEA surgery was performed in 8% of patients. A comparison of the preoperative and postoperative pre-discharge AIS scores showed that 49% of patients maintained a score of E or improved, while 45% remained at their preoperative status and 6% worsened. Among a subset of patients (n=36; 23%) for whom a 6 month follow-up encounter occurred, 75% maintained an AIS score of E or improved, 19% remained at their preoperative status, and 6% worsened. Both the presence and longer duration of preoperative paresis was associated with an increased risk of remaining at the same AIS score or worsening at the predischarge encounter (both p < 0.001). A predictive model for predischarge AIS scores was developed based on several patient characteristics.

Conclusions

Surgical decompression can contribute to improving or maintaining AIS scores in a high percentage of SEA patients. The presence and duration of preoperative paresis are prognostic for poorer outcomes and suggest that rapid surgical intervention before paresis develops may lead to improved postoperative outcomes. Our modeling tool enables an estimation of probabilities of patients' predischarge condition.

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Feasibility of prehospital freeze-dried plasma administration in a UK Helicopter Emergency Medical Service

Background Early transfusion of patients with major traumatic haemorrhage may improve survival. This study aims to establish the feasibility of freeze-dried plasma transfusion in a Helicopter Emergency Medical Service in the UK. Patients and methods A retrospective observational study of major trauma patients attended by Kent, Surrey and Sussex Helicopter Emergency Medical Service and transfused freeze-dried plasma since it was introduced in April 2014. Results Of the 1873 patients attended over a 12-month period before its introduction, 79 patients received packed red blood cells (4.2%) with a total of 193 units transfused. Of 1881 patients after the introduction of freeze-dried plasma, 10 patients received packed red blood cells only and 66 received both packed red blood cells and freeze-dried plasma, with a total of 158 units of packed red blood cells transfused, representing an 18% reduction between the two 12-month periods. In the 20 months since its introduction, of 216 patients transfused with at least one unit of freeze-dried plasma, 116 (54.0%) patients received both freeze-dried plasma and packed red blood cells in a 1 : 1 ratio. Earlier transfusion was feasible, transferring the patient to the hospital before transfusion would have incurred a delay of 71 min (interquartile range: 59–90 min). Conclusion Prehospital freeze-dried plasma and packed red blood cell transfusion is feasible in a 1 : 1 ratio in patients with suspected traumatic haemorrhage. The use of freeze-dried plasma as a first-line fluid bolus reduced the number of prehospital packed red blood cell units required and reduced the time to transfusion. Correspondence to Joanne E. Griggs, MSc, Redhill Aerodrome, Redhill RH1 5YP, UK Tel: +44 016 3447 1900; e-mail: jog@aakss.org.uk Received August 27, 2018 Accepted October 13, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cancers, Vol. 10, Pages 500: Mitochondrial RNA Expression and Single Nucleotide Variants in Association with Clinical Parameters in Primary Breast Cancers

Cancers, Vol. 10, Pages 500: Mitochondrial RNA Expression and Single Nucleotide Variants in Association with Clinical Parameters in Primary Breast Cancers

Cancers doi: 10.3390/cancers10120500

Authors: Marjolein J. A. Weerts Marcel Smid John A. Foekens Stefan Sleijfer John W. M. Martens

The human mitochondrial DNA (mtDNA) encodes 37 genes, including thirteen proteins essential for the respiratory chain, and RNAs functioning in the mitochondrial translation apparatus. The total number of mtDNA molecules per cell (mtDNA content) is variable between tissue types and also between tumors and their normal counterparts. For breast cancer, tumors tend to be depleted in their mtDNA content compared to adjacent normal mammary tissue. Various studies have shown that primary breast tumors harbor somatic mtDNA variants. A decrease in mtDNA content or the presence of somatic variants could indicate a reduced mitochondrial function within breast cancer. In this explorative study we aimed to further understand genomic changes and expression of the mitochondrial genome within breast cancer, by analyzing RNA sequencing data of primary breast tumor specimens of 344 cases. We demonstrate that somatic variants detected at the mtRNA level are representative for somatic variants in the mtDNA. Also, the number of somatic variants within the mitochondrial transcriptome is not associated with mutational processes impacting the nuclear genome, but is positively associated with age at diagnosis. Finally, we observe that mitochondrial expression is related to ER status. We conclude that there is a large heterogeneity in somatic mutations of the mitochondrial genome within primary breast tumors, and differences in mitochondrial expression among breast cancer subtypes. The exact impact on metabolic differences and clinical relevance deserves further study.

https://ift.tt/2PsVhEW

Lipid Extraction from Spirulina sp. and Schizochytrium sp. Using Supercritical CO with Methanol

Microalgae are one of the most promising feedstocks for biodiesel production due to their high lipid content and easy farming. However, the extraction of lipids from microalgae is energy intensive and costly and involves the use of toxic organic solvents. Compared with organic solvent extraction, supercritical CO2 (SCCO2) has demonstrated advantages through lower toxicity and no solvent-liquid separation. Due to the nonpolar nature of SCCO2, polar organic solvents such as methanol may need to be added as a modifier in order to increase the extraction ability of SCCO2. In this paper, pilot scale lipid extraction using SCCO2 was studied on two microalgae species: Spirulina sp. and Schizochytrium sp. For each species, SCCO2 extraction was conducted on 200 g of biomass for 6 h. Methanol was added as a cosolvent in the extraction process based on a volume ratio of 4%. The results showed that adding methanol in SCCO2 increased the lipid extraction yield significantly for both species. Under an operating pressure of 4000 psi, the lipid extraction yields for Spirulina sp. and Schizochytrium sp. were increased by 80% and 72%, respectively. It was also found that a stepwise addition of methanol was more effective than a one-time addition. In comparison with Soxhlet extraction using methylene chloride/methanol (2:1, v/v), the methanol-SCCO2 extraction demonstrated its high effectiveness for lipid extraction. In addition, the methanol-SCCO2 system showed a high lipid extraction yield after increasing biomass loading fivefold, indicating good potential for scaling up this method. Finally, a kinetic study of the SCCO2 extraction process was conducted, and the results showed that methanol concentration in SCCO2 has the strongest influence on the lipid extraction yield.

https://ift.tt/2SzITEQ

Coronal Imbalance after Selective Posterior Thoracic Fusion in Patients with Lenke 1 and 2 Adolescent Idiopathic Scoliosis

Coronal decompensation is a common complication in Lenke 1 or 2 AIS patients after selective thoracic fusion (STF). However, the majority who developed immediately postoperative coronal decompensation experienced improvement and the related factors are not fully understood. The aim of this retrospective study was to investigate the prevalence of coronal imbalance in patients with Lenke 1 or 2 AIS and to explore radiological factors associated with spontaneous correction of coronal balance after surgery. Lenke 1 or 2 AIS patients receiving STF in our center from January 2013 to March 2015 were analyzed. Anteroposterior and lateral films were evaluated before surgery, at 1 month's and 2 years' follow-up. Patients were divided into 2 groups according to whether coronal imbalance occurred in the early postoperative period (1 month). Various radiological parameters as well as Scoliosis Research Society-22 were statistically compared between groups. Coronal decompensation was observed in 33 patients preoperatively, in 48 patients immediately postoperatively, and in 2 patients at final follow-up. Lowermost instrumented vertebra (LIV) disc angle (0.9° vs. 6.7°, p=0.019) and LIV- C7 plumb line and central sacral vertical line (CSVL) (-3.4mm vs. -13.7mm, p=0.020) increased in the final follow-up in the imbalanced group of type A modifier. The magnitude of lumbar curve was greater in the imbalanced group of type B or C modifier in the early postoperative period (19.5° vs. 12.6°, p=0.006; 25.5° vs. 13.7°, p

https://ift.tt/2SzFF4d

Biomechanical Alterations during Sit-to-Stand Transfer Are Caused by a Synergy between Knee Osteoarthritis and Obesity

Osteoarthritis is one of the major causes of immobility and its current prevalence in elderly (>60 years) is 18% in women and 9.6% in men. Patients with osteoarthritis display altered movement patterns to avoid pain and overcome movement limitations in activities of daily life, such as sit-to-stand transfers. Currently, there is a lack of evidence that distinguishes effects of knee osteoarthritis on sit-to-stand performance in patients with and without obesity. The purpose of this study was therefore to investigate differences in knee and hip kinetics during sit-to-stand movement between healthy controls and lean and obese knee osteoarthritis patients. Fifty-five subjects were included in this study, distributed over three groups: healthy controls (n=22), lean knee osteoarthritis (n=14), and obese knee OA patients (n=19). All subjects were instructed to perform sit-to-stand transfers at self-selected, comfortable speed. A three-dimensional movement analysis was performed to investigate compensatory mechanisms and knee and hip kinetics during sit-to-stand movement. No difference in sit-to-stand speed was found between lean knee OA patients and healthy controls. Obese knee osteoarthritis patients, however, have reduced hip and knee range of motion, which is associated with reduced peak hip and knee moments. Reduced vertical ground reaction force in terms of body weight and increased medial ground reaction forces indicates use of compensatory mechanisms to unload the affected knee in the obese knee osteoarthritis patients. We believe that an interplay between obesity and knee osteoarthritis leads to altered biomechanics during sit-to-stand movement, rather than knee osteoarthritis alone. From this perspective, obesity might be an important target to restore healthy sit-to-stand biomechanics in obese knee OA patients.

https://ift.tt/2QGz8HD

Spectral CT Analysis of Solitary Pulmonary Nodules for Differentiating Malignancy from Benignancy: The Value of Iodine Concentration Spatial Distribution Difference

Objective. The objective is to assess the value of spatial distribution difference in iodine concentration between malignant and benign solitary pulmonary nodules (SPNs) by analyzing multiple parameters of spectral CT. Methods. Sixty patients with 39 malignant nodules and 21 benign nodules underwent chest contrast CT scans using spectral imaging mode during pulmonary arterial phase (PP), arterial phase (AP), and venous phase (VP). Iodine concentrations of proximal and distal regions in pulmonary nodules on iodine-based material decomposition images were recorded. Normalized iodine concentration (NIC) and the differences in NIC between the proximal and the distal regions (dNIC) were calculated. The two-sample t-test and Mann–Whitney U-test were performed to compare the multiple parameters generated from spectral CT between malignant and benign nodules. Receiver operating characteristic (ROC) curves were generated to calculate sensitivity and specificity. Results. NIC in the proximal region () and NIC in the distal region () between malignant and benign nodules at AP (, P=0.012; , P=0.024), and VP (, P=0.005; , P =0.004) were significantly different. at PP (P = 0.037) was also found significantly different between malignant and benign nodules; however, no significant differences were found in at PP (P = 0.093). In addition, the dNIC of malignant nodules was significantly higher than that of benign ones at PP (median and interquartiles (0.31, 0.11, 0.57 versus -0.26, -0.5, -0.1); p≤0.001), AP (mean dNIC, 0.093 ±0.094 versus -0.075±0.060; p≤0.001), and VP (mean dNIC, 0.171±0.137 versus -0.183±0.127; p≤0.001). The sensitivity and specificity (93%, 95%, respectively) of dNIC during VP were higher than other parameters, with a threshold value of -0.07. Conclusions. Spectral CT imaging with multiple parameters such as ,, and dNIC may be a new method for differentiating malignant SPNs from benign ones.

https://ift.tt/2QLcRII

Seizure and Acute Vision Loss in a Filipino Lupus Patient: A Case of Posterior Reversible Encephalopathy Syndrome with Intraparenchymal Hemorrhage

Posterior reversible encephalopathy syndrome (PRES) is a rare and poorly understood neurologic condition that has been described in some patients with systemic lupus erythematosus (SLE). Intracerebral hemorrhage is a unique and atypical presentation of PRES and has been described only in a small number of patients with SLE. We present the case of a 33-year-old female, diagnosed with SLE and active nephritis, who was admitted for seizures. She had acute-onset headache, confusion, and bilateral vision loss associated with severe hypertension. CT scan revealed right occipital and parietal lobe hemorrhage. MRI showed vasogenic edema and hyperintense foci in bilateral cortical and subcortical regions of the occipital and posterior parietal lobes which are consistent with posterior reversible encephalopathy syndrome (PRES). Strict blood pressure control and medical ICP-lowering treatment were immediately instituted, while maintaining her on anticonvulsants, high-dose steroids, and mycophenolate mofetil. The patient was discharged with improvement in vision and resolution of headache. On follow-up, she had gained her premorbid visual acuity and reported no recurrence of headache or seizures. Despite its name, reversibility remains to be conditional in PRES. A high index of suspicion is important, especially among those who present with seizure, headache, and visual loss. Early diagnosis and timely initiation of therapy is recommended, as clinical symptoms are potentially reversible and delayed therapy may result in life-threatening complications, such as coma or death.

https://ift.tt/2zMvVMX

Seasonal Variation in Essential Oils Composition and the Biological and Pharmaceutical Protective Effects of Mentha longifolia Leaves Grown in Tunisia

This research assessed the seasonal variation of the chemical composition and antibacterial and anticholinesterase activities of essential oils extracted from M. longifolia leaves. The leaves organic fractions were also investigated for their biological activities and pharmacological functions. The essential oil highest yield was recorded in the spring season. Pulegone (26.92%), 1.8 cineole (21.3 %), and L-menthone (10.66 %) were determined as its major compounds in the winter season. In the spring oil, the main components were pulegone (38.2 %) and oleic and palmitic acids (23.79 % and 15. 26 %, respectively). Oxygenated monoterpenes were predominant in the two analyzed samples. The tested oils and organic extracts exhibited promising antibacterial effects against all of the tested bacterial strains. Thanks to its richness in phenolic and flavonoid compounds, the ethyl acetate fraction (Ml EtOAcF) displayed the most active DPPH scavenging ability (IC50 =12.64 μg/ml) and an interesting β-carotene bleaching inhibition (IC50 =34.75 μg/ml) making it a potential candidate for anti-inflammatory evaluation on rats. This evaluation evidenced that M. longifolia pretreated rats showed a marked decrease in paw oedema and inflammatory cells. Additionally, a remarkable acetylcholinesterase inhibitory activity of the Ml EtOAcF (IC50 = 12.3μg/ml) and essential oils were also observed suggesting their neuroprotective property against Alzheimer's disease. Moreover, it was found that its activity level was season dependent. Our investigation, therefore, clearly revealed the medicinal characteristics of M. longifolia leave indicating their potential uses for natural remedies.

https://ift.tt/2RFJg0C

Prognostic Significance of Serum Lactic Acid, Lactate Dehydrogenase, and Albumin Levels in Patients with Metastatic Colorectal Cancer

Aim. To identify the population of patients with high risk of distant metastasis and the poor prognosis before treatment, so as to provide early intervention and better treatment decision. Method. 69 patients with nonmetastatic colorectal cancer (non-mCRC) and 57 with metastatic CRC (mCRC) were enrolled to evaluate the prognostic value of serum albumin (ALB), serum lactate (SLA), and lactate dehydrogenase (LDH) in patients with metastatic CRC. We then followed up the 57 patients with mCRC. The T test, Chi square test, Kaplan-Meier survival analysis model, and Multivariate Cox proportional hazards regression model were applied to assess the prognostic significance of SLA, LDH, and serum ALB on the patients with mCRC. Results. Compared with the non-mCRC group, the patients with mCRC had an elevated level of blood lactate (P=0.01) and LDH (P

https://ift.tt/2Qj0hRI

A therapeutic exercise program improves pain and physical dimension of health-related quality of life in young adults. A Randomized Controlled Trial

Objective The aim of this study was to evaluate the effects of an exercise therapy program on pain and physical dimension of health-related quality of life for young adults with musculoskeletal pain. Design Randomized controlled single-blind trial. Fifty-seven subjects (58% women) were randomly assigned to experimental (n=28; 21.4±2.9 yrs) and control (n=29; 21.0±4.2 yrs) groups. The experimental group participated in a 9-week stabilization exercise therapy program, 60 minutes/once a week, while the control group did not exercise, with a pre- and post-intervention assessment. Primary outcome was Physical Component Summary of SF-36. Secondary outcomes were Nordic Musculoskeletal Questionnaire, Visual Analogue Scale, Oswestry Disability Index, Neck Disability Index, and trunk flexor endurance test. The Shapiro-Wilk, Independent t-test or Mann-Whitney U test, Chi-square (X2), or Fisher's exact test were used for statistical analysis. Results After intervention, the experimental group improved by 3.2±4.5 points on the Physical Component Summary (p=0.01); decreased prevalence of low back pain in the last month (p=0.02) and cervical disability (p=0.02); and increased flexor trunk endurance (p=0.005). Conclusions This study confirmed that a 9-week progressive exercise therapy program can improve physical health, and reduce the prevalence of cervical disability and low back pain in the last month in young adults with musculoskeletal pain. Correspondence: Beatriz Rodríguez-Romero, Psychosocial Intervention and Functional Rehabilitation Research Group, Department of Biomedical Sciences, Medicine and Physiotherapy, Faculty of Physiotherapy, University of A Coruña, A Coruña Campus, 15071 A Coruña, Spain. Tel +34981167000, Fax +34981167155. beatriz.romero@udc.es Author disclosures: Competing Interests The authors declare that they have no competing interests. Funding or grants or equipment provided for the project from any source Funding for this research, specifically for its translation, was provided by the Official Association of Physiotherapists of Galicia (Cofiga, Spain). Financial benefits to the authors None of the authors have anything to declare. Details of any previous presentation of the research, manuscript, or abstract in any form This study has never been published before. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Dynamic ultrasound imaging of peroneus longus muscle herniation- a case report and review of the literature

No abstract available

https://ift.tt/2SDdiT0

Simultaneous Evaluation of the Influence of Panax ginseng on the Pharmacokinetics of Three Diester Alkaloids after Oral Administration of Aconiti Lateralis Radix in Rats Using UHPLC/QQQ-MS/MS

Objectives. To investigate whether Panax ginseng (P. ginseng) could affect the metabolism of Diester Alkaloids (DAs) derived from Aconiti Lateralis Radix in vivo. Methods and Results. 24 male Sprague-Dawley rats were randomized for 7-day treatment with P. ginseng (low, middle, and high), or vehicle. Aconiti Lateralis Radix was administered orally to each group on the 8th day. Plasma samples were collected, and Xevo TQ-S was used to detect the concentration of aconitine, mesaconitine, and hypaconitine in plasma. We describe a fast and reproducible method to detect the concentration of aconitine, mesaconitine, and hypaconitine in plasma. Compared to the control group, the of three DAs increased in both the middle and high dosing groups. The Vz/F of three DAs in these groups as well as the CLz/F of aconitine in all P. ginseng groups and the CLz/F of mesaconitine and hypaconitine in P. ginseng middle and high groups were decreased compared to the control group. Conclusion. Orally administrated P. ginseng potentially inhibits the metabolism of DAs from Aconiti Lateralis Radix in rats.

https://ift.tt/2PuLWfA

Erythrodermic paraneoplastic dermatomyositis [Practice]

https://ift.tt/2QG0duM

Wise guidance and its challenges: the new Canadian recommendations on breast cancer screening [Commentary]

https://ift.tt/2SzV2ty

Bone health after diagnosis of breast cancer [Practice]

https://ift.tt/2QAWsXx

Primary care providers exploring value of "social prescriptions" for patients [News]

https://ift.tt/2SzE8Lu

Dog hospital [Coda]

https://ift.tt/2SDr9s7

The other side [Humanities]

https://ift.tt/2QFDPS3

Art at the McGill University Health Centre [Letters]

https://ift.tt/2SzEaTC

Occurrence of and referral to specialists for pain-related diagnoses in First Nations and non-First Nations children and youth [Research]

BACKGROUND:

Indigenous youth have higher rates of chronic health conditions interfering with healthy development, including high rates of ear, dental, chest and musculoskeletal pain, as well as headache, arthritis and mental health issues. This study explores differences in pain-related diagnoses in First Nations and non–First Nations children.

METHODS:

Data from a study population of age- and sex-matched First Nations and non–First Nations children and youth were accessed from a specific region of Atlantic Canada. The primary objective of the study was to compare diagnosis rates of painful conditions and specialist visits between cohorts. The secondary objective was to determine whether there were correlations between early physical pain exposure and pain in adolescence (physical and mental health).

RESULTS:

Although ear- and throat-related diagnoses were more likely in the First Nations group than in the non–First Nations group (ear 67.3% v. 56.8%, p < 0.001; throat 89.3% v. 78.8%, p < 0.001, respectively), children in the First Nations group were less likely to see a relevant specialist (ear 11.8% v. 15.5%, p < 0.001; throat 12.7% v. 16.1%, p < 0.001, respectively). First Nations newborns were more likely to experience an admission to the neonatal intensive care unit (NICU) than non–First Nations newborns (24.4% v. 18.4%, p < 0.001, respectively). Non–First Nations newborns experiencing an NICU admission were more likely to receive a mental health diagnosis in adolescence, but the same was not found with the First Nations group (3.4% v. 5.7%, p < 0.03, respectively). First Nations children with a diagnosis of an ear or urinary tract infection in early childhood were almost twice as likely to have a diagnosis of headache or abdominal pain as adolescents (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1–3.0, and OR 1.7, 95% CI 1.2–2.3, respectively).

INTERPRETATION:

First Nations children were diagnosed with more pain than non–First Nations children, but did not access specific specialists or mental health services, and were not diagnosed with mental health conditions, at the same rate as their non–First Nations counterparts. Discrepancies in pain-related diagnoses and treatment are evident in these specific comparative cohorts. Community-based health care access and treatment inquiries are required to determine ways to improve care delivery for common childhood conditions that affect health and development.

https://ift.tt/2QJ5HF1

Recommendations on screening for breast cancer in women aged 40-74 years who are not at increased risk for breast cancer [Guideline]

https://ift.tt/2QJG5I3

Culture of bullying in medicine starts at the top [News]

https://ift.tt/2SzE66k

Media reporting of suicide [Letters]

https://ift.tt/2SzUnIv

Isotope once discarded as byproduct shows promise as cancer treatment [News]

https://ift.tt/2SzE26A

The Human Exhibit [Humanities]

https://ift.tt/2QGAsdv

Awareness of Biomedical Waste Management in Dental Students in Different Dental Colleges in Nepal

Aim. The aim of this study is to assess the awareness of biomedical waste management in dental students of various dental colleges of Nepal. Methodology. A structured pretested questionnaire was used among 434 (323 males and 111 females) undergraduate dental students of five different dental colleges of Nepal. First part of the questionnaire was used to describe demographic profile of the participants. Second part of the questionnaire assessed the knowledge, attitude, and practice regarding biomedical waste management. Chi-square test was applied to find out the association between different responses obtained from different colleges. Result. Majority (91.82%) of participants had a positive attitude towards safe management of biomedical waste. Regarding the knowledge of BMW management policies, majority of the students (83.1% to 98.9%) had positive attitude towards the safe management of biomedical waste, whereas more than 50% of the students were unaware of the guidelines laid down by Government of Nepal. Regarding biomedical waste disposal technique in the hospital, only 29.9% to 79.8% are aware; this shows that there is lack of strict protocol in the BMW management. Association between different responses and colleges for "improper waste management causes various health hazards" ranged from 93.3% to 98.9%. Conclusion. There exists a lacuna in the knowledge and practice of biomedical waste management among the undergraduate dental students in Nepal. Since the students had positive attitude towards addressing this concern, workshops and trainings related to proper biomedical waste management would be a step forward towards attaining a healthy environment for the future.

https://ift.tt/2E8Etkp

Aster glehni Extract Containing Caffeoylquinic Compounds Protects Human Keratinocytes through the TRPV4-PPARδ-AMPK Pathway

Aster glehni (AG) has been used in cooking and as a medicine to treat various diseases for over hundreds of years in Korea. To speculate the protective effects of AG on skin barrier, we estimated the protein levels of biomarkers related to skin barrier protection in human keratinocytes, HaCaT cells treated with sodium dodecyl sulfate (SDS), or 2,4-dinitrochlorobenzene (DNCB). The protein levels for keratin, involucrin, defensin, tumor necrosis factor alpha (TNFα), peroxisome proliferator-activated receptor delta (PPARδ), 5′ adenosine monophosphate-activated protein kinase (AMPK), serine palmitoyltransferase long chain base subunit 2 (SPTLC2), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were evaluated using western blotting or immunocytochemistry in HaCaT cells. AG extract increased the protein levels of PPARδ, phosphorylated AMPK, SPTLC2, keratin, involucrin, and defensin compared to the SDS or DNCB control group. However, TNFα expression increased by SDS or DNCB was decreased with AG extract. The order of action of each regulatory biomarker in AG pathway was identified TRPV4→PPARδ→AMPK from antagonist and siRNA treatment studies. AG can ameliorate the injury of keratinocytes caused by SDS or DNCB through the sequential regulation of TRPV4→PPARδ→AMPK pathway.

https://ift.tt/2PsIn9Y

Antiobesity Effect of Astilbe chinensis Franch. et Savet. Extract through Regulation of Adipogenesis and AMP-Activated Protein Kinase Pathways in 3T3-L1 Adipocyte and High-Fat Diet-Induced C57BL/6N Obese Mice

Astilbe chinensis Franch. et Savat. (AC) has been used in traditional medicine for the treatment of chronic bronchitis, arthralgia, and gastralgia. In this study, we investigated the antiobesity effect of AC extract on 3T3-L1 preadipocytes and high-fat-diet-fed C57BL/6N obese mice. We found that AC extracts dramatically decreased the lipid content of 3T3-L1 cells in a concentration-dependent manner without cytotoxicity. The action mechanism of AC extract was demonstrated to be the inhibition of lipid accumulation and dose-dependent decrease in the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPAR-γ), and sterol regulatory element-binding protein 1 (SREBP1). Furthermore, AC extract increased the mitochondrial phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), mitochondrial biogenesis, and lipolysis-related factors. In amice model of high-fat-diet-induced obesity, the mice administered AC extract experienced significant decrease of 64% in weight gain, 55% in insulin resistance index, 22% in plasma triglycerides (TG), 56% in total cholesterol (TC), and 21% in nonesterified fatty acid (NEFA) levels compared with those in the high-fat diet-fed control mice. Collectively, these results indicated that AC extract exerted antiobesogenic activity through the modulation of the AMPK signaling pathway, inhibition of adipogenesis, decreased lipid content, and reduced adipocyte size.

https://ift.tt/2zP6tGE

Phytochemical and Pharmacological Properties of Chaenomeles speciosa: An Edible Medicinal Chinese Mugua

Chaenomeles plants are adapted to diverse ecological zones particularly the temperate areas of Korea, Japan, and China. In China, Chaenomeles speciosa is mainly planted in Chongqing, Anhui, and Hubei provinces. Most of the studies till date have been focused on the anti-inflammatory activities of C. speciosa fractions. The present study aimed to review the maximum literature reported for the presence of various phytochemicals in C. speciosa. In addition, the pharmacological properties of these chemical compounds of this plant shall also be discussed. The extracts of the various parts of the plant are rich in diversity of antioxidants, organic acids, phenolics, terpenoids, and many different phytochemicals that bear strong anticancer, antioxidant, antiviral, antibacterial properties, anti-inflammation, antihyperlipidemic, antihyperglycemic, and anti-Parkinson properties. C. speciosa fruits have broad scope in industry as well as in medicines. Not only the leaves and fruits of C. speciosa plant, but various other parts including roots, seeds, bark twigs, and flowers all have long history of clinical trials in curing many human ailments. However, the maximum accessible data concerning the chemical compositions and their broad pharmacological properties of C. speciosa plant parts is pretty restricted that make it more appealing for in-depth investigations.

https://ift.tt/2zQnu3h