Αρχειοθήκη ιστολογίου

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Σάββατο 5 Ιανουαρίου 2019

Ranking Cancer Proteins by Integrating PPI Network and Protein Expression Profiles

Proteomics, the large-scale analysis of proteins, is contributing greatly to understanding gene function in the postgenomic era. However, disease protein ranking using shotgun proteomics data has not been fully evaluated. In this study, we prioritized disease-related proteins by integrating the protein-protein interaction (PPI) network and protein differential expression profiles from colon and rectal cancer (CRC) or breast cancer (BC) proteomics. We applied Local Ranking (LR) and Global Ranking (GR) methods in network with three kinds of protein sets as a priori knowledge, which were known disease proteins (KDPs) that were collected from the Online Mendelian Inheritance in Man (OMIM) database, differentially expressed proteins (DEPs), and the collection of KDPs and their direct neighborhood with differential expression (eKDPs). The cross-validations showed that GR method outperformed LR method while using eKDPs as the initial training showed significantly higher accuracy compared to using the other two a priori sets. And then we validated the top ranked proteins using RNAi-based loss-of-function screens in the DepMap database. The results showed that 75% of top 20 proteins in CRC are necessary for tumor survival. In summary, the network-based Global Ranking with protein differential expression can efficiently prioritize cancer-related proteins and discover new candidate cancer genes or proteins.

http://bit.ly/2FaNevF

Age-Specific Cut-off Values of Amino Acids and Acylcarnitines for Diagnosis of Inborn Errors of Metabolism Using Liquid Chromatography Tandem Mass Spectrometry

Liquid Chromatography tandem mass spectrometry (LC-MS/MS) is used for the diagnosis of more than 30 inborn errors of metabolisms (IEMs). Accurate and reliable diagnosis of IEMs by quantifying amino acids (AAs) and acylcarnitines (ACs) using LC-MS/MS systems depend on the establishment of age-specific cut-offs of the analytes. This study aimed to (1) determine the age-specific cut-off values of AAs and ACs in Bangladesh and (2) validate the LC-MS/MS method for diagnosis of the patients with IEMs. A total of 570 enrolled healthy participants were divided into 3 age groups, namely, (1) newborns (1-7 days), (2) 8 days–7 years, and (3) 8–17 years, to establish the age-specific cut-offs for AAs and ACs. Also, 273 suspected patients with IEMs were enrolled to evaluate the reliability of the established cut-off values. Quantitation of AAs and ACs was performed on an automated LC-MS/MS system using dried blood spot (DBS) cards. Then the specimens of the enrolled clinically suspected patients were analyzed by the established method. Nine patients came out as screening positive for different IEMs, including two borderline positive cases of medium-chain acyl-CoA dehydrogenase deficiency (MCAD). A second-tier test for confirmation of the screening positive cases was conducted by urinary metabolic profiling using gas chromatography- mass spectrometry (GC-MS). Out of 9 cases that came out as screening positive by LC-MS/MS, seven cases were confirmed by urinary GC-MS analysis including 3 cases with phenylketonuria, 1 with citrullinemia type II, 1 with methylmalonic acidemia, 1 with isovaleric acidemia and 1 with carnitine uptake defect. Two borderline positive cases with MCAD were found negative by urinary GC-MS analysis. In conclusion, along with establishment of a validated LC-MS/MS method for quantitation of AAs and ACs from the DBS cards, the study also demonstrates the presence of predominantly available IEMs in Bangladesh.

http://bit.ly/2Fc3744

Is there evidence of gender bias in the oral examination for initial certification by the American Board of Physical Medicine & Rehabilitation?

Objective Unconscious bias (UB) may result in a prejudicial evaluation of another person and lead to unfair treatment. Potential gender bias risk exists in the scoring process on the American Board of Physical Medicine and Rehabilitation (ABPMR) oral examination (Part II) because of the face-to-face interactions between candidates and examiners. This study was undertaken to determine whether performance on the ABPMR Part II Examination differed based on candidate gender or configuration of examiner/candidate gender pairings. The impact of examiner UB training on candidate performance was also assessed. Design Retrospective observational study of first time Part II PM&R Certification Examination test takers between 2013-2018 Results There were significant differences in pass rates (men 84%, women 89%) and mean scaled scores (men 6.56, women 6.81) between men and women (p

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Functional capacity change impacts the quality of life of hospitalized patients undergoing hematopoietic stem cell transplantation

Objective To compare the quality of life of patients undergoing hematopoietic stem cell transplantation (HSCT) who improved their functional capacity during hospitalization (IFC group) with that of patients who maintained or decreased functional capacity during hospitalization (DFC group). Design This observational, longitudinal study included 27 hospitalized patients undergoing HSCT. Patients were divided into IFC (16 patients) and DFC (11 patients). Functional capacity (6-minute Step Test), peripheral muscle strength (Sit-to-Stand Test and Handgrip Strength), and quality of life (EORTC-QLQ-C30) were assessed at admission and at hospital discharge. Results IFC patients had increased functional capacity and peripheral muscle strength of the lower and upper limbs at hospital discharge (P

http://bit.ly/2VwHkKo

Hyperthermic Intraperitoneal Chemotherapy as a Treatment for Epithelial Ovarian Cancer

Abstract

Treatment by cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has been an option for selected patients with peritoneal carcinomatosis. This study aims to evaluate the impact of HIPEC in epithelial ovarian cancer (EOC). A retrospective observational cohort study including 48 EOC patients treated and followed up between 2012 and 2016. Thirty-seven cases were treated by CRS only, while 11 cases were treated by CRS and HIPEC. The study was performed at National Cancer Institute (NCI)—Cairo University. There was no statistically significant difference regarding overall survival or disease-free survival between the group of EOC patients treated by CRS only and the one treated by CRS and HIPEC. Presence of ascites and histological types (serous/non-serous) were the significant independent variables related to overall survival. Presence of ascites was the only independent variable associated with a significant relation to disease-free survival. No statistically significant impact of HIPEC in treatment of EOC was found in this study.



http://bit.ly/2Qo6rLn

18 F-DOPA PET/CT in brain tumors: impact on multidisciplinary brain tumor board decisions

Abstract

Purpose

This study aimed to assess the therapeutic impact and diagnostic accuracy of 18F-DOPA PET/CT in patients with glioblastoma or brain metastases.

Methods

Patients with histologically proven glioblastoma or brain metastases were prospectively included in this monocentric clinical trial (IMOTEP). Patients were included either due to a clinical suspicion of relapse or to assess residual tumor infiltration after treatment. Multimodality brain MRI and 18F-DOPA PET were performed. Patients' data were discussed during a Multidisciplinary Neuro-oncology Tumor Board (MNTB) meeting. The discussion was first based on clinical and MRI data, and an initial diagnosis and treatment plan were proposed. Secondly, a new discussion was conducted based on the overall imaging results, including 18F-DOPA PET. A second diagnosis and therapeutic plan were proposed. A retrospective and definitive diagnosis was obtained after a 3-month follow-up and considered as the reference standard.

Results

One hundred six cases were prospectively investigated by the MNTB. All patients with brain metastases (N = 41) had a clinical suspicion of recurrence. The addition of 18F-DOPA PET data changed the diagnosis and treatment plan in 39.0% and 17.1% of patients' cases, respectively. Concerning patients with a suspicion of recurrent glioblastoma (N = 12), the implementation of 18F-DOPA PET changed the diagnosis and treatment plan in 33.3% of cases. In patients evaluated to assess residual glioblastoma infiltration after treatment (N = 53), 18F-DOPA PET data had a lower impact with only 5.7% (3/53) of diagnostic changes and 3.8% (2/53) of therapeutic plan changes. The definitive reference diagnosis was available in 98/106 patients. For patients with tumor recurrence suspicion, the adjunction of 18F-DOPA PET increased the Younden's index from 0.44 to 0.53 in brain metastases and from 0.2 to 1.0 in glioblastoma, reflecting an increase in diagnostic accuracy.

Conclusion

18F-DOPA PET has a significant impact on the management of patients with a suspicion of brain tumor recurrence, either glioblastoma or brain metastases, but a low impact when used to evaluate the residual glioblastoma infiltration after a first-line radio-chemotherapy or second-line bevacizumab.



http://bit.ly/2CTVaiF

A novel CPT1C variant causes pure hereditary spastic paraplegia with benign clinical course

Abstract

Hereditary spastic paraplegia 73 (SPG73) was currently identified in only one family with variant in the neuronal isoform of carnitine palmitoyl‐transferase 1C (CPT1C) gene. We described a new family, in which affected individuals exhibited pure hereditary spastic paraplegia with benign clinical course. Exome sequencing revealed a novel nonsense variant in the CPT1C gene. The level of CPT1C mutant transcript significantly decreased compared to that of wild‐type transcript, and can be recovered after cycloheximide administration, which indicated that nonsense‐mediated mRNA decay was a mechanism that might be responsible for the phenotype. Our findings expanded the clinical and genetic spectrum of SPG73.



http://bit.ly/2CSwzuw

Pain affect disrupted in children with posterior cerebellar tumor resection

Abstract

Objectives

Damage to the posterior cerebellum can cause affective deficits in patients. In adults, cerebellar infarcts result in thermal hyperalgesia and affect descending modulation of pain. This study evaluated the effect of resection of low‐grade cerebellar tumors on pain processing in human children.

Methods

Twelve pediatric patients treated with surgery only for low‐grade gliomas (8 females, 4 males; mean age = 13.8 ± 5.6) and twelve matched controls (8 females, 4 males; mean age = 13.8 ± 5.7) were evaluated using quantitative sensory testing and fMRI. Five patients had tumors localized to posterior cerebellar hemispheres, henceforth identified as Crus Patients.

Results

Crus Patients had significantly lower pain tolerance to a cold pressor test than controls. No significant differences were detected between subject groups for heat and cold detection thresholds (HDT, CDT), and heat and cold pain thresholds (HPT, CPT). Crus Patients also showed significantly decreased fMRI responses to painful heat in anterior insula, which has been associated with pain affect.

Interpretation

Damage to posterior cerebellar hemispheres disrupted affective pain processing and endogenous pain modulation, resulting in decreased pain tolerance to suprathreshold noxious stimuli. This suggests that surgical resection of this region in children may increase the risk of developing pain disorders.



http://bit.ly/2TxoOzD

In vivo evidence for pre‐symptomatic neuroinflammation in a MAPT mutation carrier

Abstract

Neuroinflammation occurs in frontotemporal dementia, however its timing relative to protein aggregation and neuronal loss is unknown. Using positron emission tomography and magnetic resonance imaging to quantify these processes in a pre‐symptomatic carrier of the 10 + 16 MAPT mutation, we show microglial activation in frontotemporal regions, despite a lack of protein aggregation or atrophy in these areas. The distribution of microglial activation better discriminated the carrier from controls than did protein aggregation at this pre‐symptomatic disease stage. Our findings suggest an early role for microglial activation in frontotemporal dementia. Longitudinal studies are needed to explore the causality of this pathophysiological association.



http://bit.ly/2CQPWnR

Neonatal Streptococcus pneumoniae Pneumonia Induces an Aberrant Airway Smooth Muscle Phenotype and AHR in Mice Model

Our previous study showed that neonatal S. pneumoniae infection aggravated airway inflammation and airway hyperresponsiveness (AHR) in an OVA-induced allergic asthma model. As airway smooth muscle (ASM) plays a pivotal role in AHR development, we aim to investigate the effects of neonatal S. pneumoniae pneumonia on ASM structure and AHR development. Non-lethal neonatal pneumonia was established by intranasally infecting 1-week-old BALB/C mice with the S. pneumoniae strain D39. Five weeks after infection, the lungs were collected to assess the levels of α-SMA and the contractile proteins of ASM. Our results indicate that neonatal S. pneumoniae pneumonia significantly increased adulthood lung α-SMA and SMMHC proteins production and aggravated airway inflammatory cells infiltration and cytokines release. In addition, the neonatal S. pneumoniae pneumonia group had significantly higher Penh values compared to the uninfected controls. These data suggest that neonatal S. pneumoniae pneumonia promoted an aberrant ASM phenotype and AHR development in mice model.

http://bit.ly/2FaRzyN

Issue Information



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Issue Information



http://bit.ly/2Tt6Ii7

Genetically engineered stem cell‐derived neurons can be rendered resistant to alpha‐synuclein aggregate pathology

Abstract

We discuss the implications of a recent study by Chen and collaborators which demonstrated that dopamine neurons derived from human pluripotent stem cells which had been genetically engineered to delete the alpha‐synuclein gene are resistant to the experimental induction of Lewy pathology (Chen et al., 2018). Neural transplants in Parkinson's disease patients can develop Lewy pathology over a decade after the graft surgery, and this pathology might compromise the long‐term survival and function of the grafted neurons. Therefore, the study by Chen et al has potential clinical implications where alpha‐synuclein null neurons might eventually be considered as possible donor cells in future intracerebral transplantation trials in Parkinson's disease.

This article is protected by copyright. All rights reserved.



http://bit.ly/2LZmUFz

Sleep and synaptic down‐selection

Abstract

The synaptic homeostasis hypothesis (SHY) proposes that sleep is an essential process needed by the brain to maintain the total amount of synaptic strength under control. SHY predicts that by the end of a waking day the synaptic connections of many neural circuits undergo a net increase in synaptic strength due to ongoing learning, which is mainly mediated by synaptic potentiation. Stronger synapses require more energy and supplies and are prone to saturation, creating the need for synaptic renormalization. Such renormalization should mainly occur during sleep, when the brain is disconnected from the environment and neural circuits can be broadly reactivated off‐line to undergo a systematic but specific synaptic down‐selection. In short, according to SHY sleep is the price to pay for waking plasticity, to avoid runaway potentiation, decreased signal‐to‐noise ratio, and impaired learning due to saturation. In this review we briefly discuss the rationale of the hypothesis and recent supportive ultrastructural evidence obtained in our laboratory. We then examine recent studies by other groups showing the causal role of cortical slow waves and hippocampal sharp waves/ripples in sleep‐dependent down‐selection of neural activity and synaptic strength. Finally, we discuss some of the molecular mechanisms that could mediate synaptic weakening during sleep.

This article is protected by copyright. All rights reserved.



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Erratum



http://bit.ly/2SEo7nU

Clinical significance of multiple gene detection with a 22-gene panel in formalin-fixed paraffin-embedded specimens of 207 colorectal cancer patients

Abstract

Background

Simultaneous detection of multiple molecular biomarkers is helpful in the prediction of treatment response and prognosis for colorectal cancer (CRC) patients.

Methods

A 22-gene panel consisting of 103 hotspot regions was utilized in the formalin-fixed paraffin-embedded (FFPE) tissue samples of 207 CRC patients, using the next-generation sequencing (NGS)-based multiplex PCR technique. Those 22 genes included AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, KRAS, MAP2K1, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, STK11, and TP53.

Results

Of the 207 patients, 193 had one or more variants, with 170, 20, and 3 having one, two, and three mutated genes, respectively. Of the total 414 variants identified in this study, 384, 25, and 5 were single-nucleotide variants, deletion, and insertion. The top four frequently mutated genes were TP53, KRAS, PIK3CA, and FBXW7. There was high consistency between the results of NGS–PCR technique and routine ARMS-PCR in KRAS and BRAF mutation detection. Univariate and multivariate analyses demonstrated that advanced TNM stage, elevated serum CEA, total variants number ≥ 2, AKT1 and PTEN mutation were independent predictors of shorter DFS; poor differentiation, advanced TNM stage, total variants number ≥ 2, BRAF, CTNNB1 and NRAS mutation were independent predictors of shorter OS.

Conclusions

It is feasible to detect multiple gene mutations with a 22-gene panel in FFPE CRC specimens. TNM stage and total variants number ≥ 2 were independent predictors of DFS and OS. Detection of multiple gene mutations may provide additional prognostic information to TNM stage in CRC patients.



http://bit.ly/2Atheib

Exfoliation and Analysis of Large-area, Air-Sensitive Two-Dimensional Materials

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A method for exfoliating large thin flakes of air sensitive two-dimensional materials and safely transporting them for analysis outside of a glovebox is presented.

http://bit.ly/2RsG37V

Smoking cessation attitudes and practices among cancer survivors – United States, 2015

Abstract

Purpose

The prevalence of smoking among cancer survivors is similar to the general population. However, there is little evidence on the prevalence of specific smoking cessation behaviors among adult cancer survivors.

Methods

The 2015 National Health Interview Survey (NHIS) data were analyzed to examine the prevalence of smoking cessation behaviors and use of treatments among cancer survivors. Weighted self-reported prevalence estimates and 95% confidence intervals were calculated using a sample of 2527 cancer survivors.

Results

Among this sample of US cancer survivors, 12% were current smokers, 37% were former smokers, and 51% were never smokers. Compared with former and never smokers, current smokers were younger (< 65 years), less educated, and less likely to report being insured or Medicaid health insurance (p < 0.01). More males were former smokers than current or never smokers. Current smokers reported wanting to quit (57%), a past year quit attempt (49%), or a health professional advised them to quit (66%). Current smokers reported the use of smoking cessation counseling (8%) or medication (38%).

Conclusions

Even after a cancer diagnosis, about one in eight cancer survivors continued to smoke. All could have received advice to quit smoking by a health professional, but a third did not.

Implications for Cancer Survivors

Health professionals could consistently advise cancer survivors about the increased risks associated with continued smoking, provide them with cessation counseling and medications, refer them to other free cessation resources, and inform them of cessation treatments covered by their health insurance.



http://bit.ly/2VttJDD

Long-term health-related quality of life of critically ill patients with haematological malignancies: a prospective observational multicenter study

Although outcomes of critically ill patients with haematological malignancies (HMs) have been fully investigated in terms of organ failure and mortality, data are scarce on health-related quality of life (HRQO...

http://bit.ly/2AzgU1s

Mortality in hospitalized patients with tuberculous meningitis

To evaluate the mortality in hospitalized patients with tuberculous meningitis and describe factors associated with an increased risk of mortality.

http://bit.ly/2GZnq7p

Subclinical tuberculosis among adults with HIV: clinical features and outcomes in a South African cohort

Subclinical tuberculosis is an asymptomatic disease phase with important relevance to persons living with HIV. We describe the prevalence, clinical characteristics, and risk of mortality for HIV-infected adult...

http://bit.ly/2RzXvaC

Epidemiology survey of infectious diseases in North Korean travelers, 2015–2017

Up until now, there are limited studies available on the epidemiology of infectious diseases in Democratic People's Republic of Korea (DPRK, North Korea). However, different types of infectious diseases have b...

http://bit.ly/2GZnvbd

Clinical characteristics of HIV-1-infected patients with high levels of plasma interferon-γ: a multicenter observational study

Circulating interferon-γ (IFN-γ) concentration may be sustained at a high level regardless of the initiation of antiretroviral therapy (ART) in some patients with HIV-1 infection. In the present study, we exam...

http://bit.ly/2RzXrro

Estimating the burden of care home gastroenteritis outbreaks in England, 2014–2016

Outbreaks of infectious gastroenteritis in care homes are common, with norovirus a frequent cause. In England there is no co-ordinated national surveillance system. We aimed to estimate the burden of these out...

http://bit.ly/2RsvHVB

Use of alternative medicine, ginger and licorice among Danish pregnant women – a prospective cohort study

The use of alternative medicines and dietary supplements is constantly changing, as are dietary habits. One example of this phenomenon is the current popularity of ginger products as an everyday health boost. ...

http://bit.ly/2AwyW4t

Mutation analysis by deep sequencing of pancreatic juice from patients with pancreatic ductal adenocarcinoma

Abstract

Background

Reliable methods are needed to identify patients with early-stage cancer or high-grade precancerous lesions in the pancreas. Analysis of pancreatic juice to detect somatic mutations could represent one such approach. Here we investigated the concordance between mutations found in the primary tumor and pancreatic juice from the same patient.

Methods

Amplicon-based targeted deep sequencing was performed on samples from 21 patients with pancreatic ductal adenocarcinoma (PDAC) who had undergone Whipple's operation. Mutation profiles were determined in formalin-fixed sections of the primary tumor and in pancreatic juice sampled from the main pancreatic duct during surgery.

Results

Using a cut-off of 3% for variant allele frequency, KRAS mutations were detected in 20/21 primary tumors (95%) and in 15/21 (71%) juice samples. When also considering low-frequency variants, KRAS mutations were found in 20/21 juice samples. Most juice samples exhibited multiple KRAS variants not seen in the primary tumor, and only in 11 cases (52%) did the most abundant variant of the juice correspond to the KRAS mutation detected in the tumor. TP53 mutations were found in 16 tumors (76%) and six juice samples (29%). Among the positive juice samples, only one exhibited more than a single TP53 mutation. Detection of both KRAS and TP53 mutations was fully concordant in the primary tumor and juice sample in 7/21 cases (33%).

Conclusions

Pancreatic juice from PDAC patients is rich in KRAS mutations often not seen in the primary tumor and possibly reflecting precancerous lesions in other regions of the pancreas. The inclusion of TP53 mutation detection and additional markers must therefore be considered for fully exploiting the clinical potential of pancreatic juice samples in early cancer detection.



http://bit.ly/2RdsY2Q

Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin

Abstract

Background

Gallbladder cancer (GBC) is likely to be diagnosed at progressive stages and shows a very poor prognosis. Combination therapy with gemcitabine and cisplatin (GEMCIS) has been widely used as first-line palliative chemotherapy for advanced GBC. This study was designed to investigate the efficacy of GEMCIS and identify prognostic factors in patients with unresectable GBC.

Methods

Patients with GBC who were treated with GEMCIS from January 2008 to June 2017 in a single tertiary hospital were included. All cases of GBC were diagnosed by pathologic findings and extent of the tumour was assessed by imaging tests. Combination chemotherapy consisted of cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 intravenously on days 1 and 8 every 3 weeks. To determine factors affecting prognosis, Kaplan–Meier survival analysis, log-rank test and the Cox proportional hazard regression linear model were used. All variables with P < 0.1 in univariable analysis were included in the multivariable model.

Results

A total of 173 patients received a median of 5.3 ± 4.4 cycles of chemotherapy over 3.8 ± 3.9 months. Most of the patients (94.8%) were stage IVB at the time of diagnosis and the most common site of metastasis was the liver (42.8%). Disease control rate was 59.5%: 2 (1.2%) patients with complete response, 26 (15.0%) patients with partial response and 75 (43.4%) patients with stable disease. Overall survival (OS) and progression-free survival were 8.1 (95% confidence interval [CI], 7.1–10.2) and 5.6 (95% CI 4.5–6.8) months, respectively. Multivariable regression model indicated that metastasis to liver (hazard ratio [HR] = 1.63, 95% CI 1.11–2.40; P = 0.013), neutrophil-to-lymphocyte ratio (NLR) ≥3 (HR 1.65, 95% CI 1.09–2.49; P = 0.017), CEA ≥ 5 ng/mL (HR 1.50, 95% CI 1.02–2.19; P = 0.038), and CA19–9 ≥ 500 U/mL (HR 1.59, 95% CI 1.01–2.50; P = 0.043) were significantly associated with OS.

Conclusions

GEMCIS demonstrated a high disease control rate in patients with unresectable GBC. Factors independently related to OS were metastasis to liver, NLR ≥ 3, CEA ≥ 5 ng/mL and CA19–9 ≥ 500 U/mL.



http://bit.ly/2C1CWdh

Anti-cancer effect of dung beetle glycosaminoglycans on melanoma

Abstract

Background

Dung beetle glycosaminoglycan is known to possess anti-aging activities. However, its anti-cancer mechanisms are not fully elucidated yet. The objective of this study was to evaluate the anti-cancer effect of insect-derived polymer dung beetle glycosaminoglycan (GAG) after intraperitoneally injecting it to melanoma mice induced by B16F10 cells.

Methods

To determine molecular mechanism involved in the anti-cancer effect of dung beetle GAG, its origin N-glycan under 3KD Dalton was assayed for melanoma cell cytotoxicity. Quantitative comparisons of adhesive molecule on extracellular matrix and activities of tissue inhibitor of metalloprotease 2 (TIMP-2) were also investigated. In vivo anti-cancer effect of dung beetle GAG on solid tumor size, survival time and gene-expression profiles was also assayed using B10F10 melanoma mice model. Mice with induced melanoma were then treated with Catharsius molossus (dung beetle) GAG (CaG) at 5 mg/kg for 8 weeks to investigate its anti-cancer effects compared to bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG) and Huechys sanguinea glycosaminoglycan (HEG).

Results

These N-glycans derived from these GAG were composed of many linear heparinoid polysaccharides, polymers with hexose and N-acetylhexose. Adminstration with these GAGs increased survival time and decreased melanoma sizes in mice, in accordance with their inhibitory effects on cell growth ratio of melanoma B16F10. In addition, treatment with N-glycans derived from theses glycosaminoglycan increased activities of TIMP-2 in HMVEC cells pretreated with TNF-alpha and in melanoma cells, suggesting that they had anti-inflammatory and anticancer activities. In DNA microarray results, compared to control, CaG treated mouse group showed upregulation of 192 genes including collagen,typeI,alpha1 (Col1a1), consistent with the highly increased in vitro extracellular matrix (ECM) adhesion on collagen 1 and up-regulation of heparanase (Hpse). After treatment with CaG, a total of 152 genes were down-regulated, including nuclear RNA export factor (Nxf3) and hyaluronan proteoglycan link protein1 (Hapln1).

Conclusions

Glycosaminoglycan, CaG can strengthen ECM by increasing activity of TIMP-2 and adhesion activity on collagen known to inhibit changes of ECM, leading to tumor cell invasion and progression.



http://bit.ly/2R8fO7k

Three-port single-intercostal versus multiple-intercostal thoracoscopic lobectomy for the treatment of lung cancer: a propensity-matched analysis

Abstract

Background

In this retrospective study, we aimed to demonstrated that three-port single-intercostal (SIC) thoracoscopic lobectomy is an effective choice for lung cancer by comparing the perioperative outcomes of patients with non-small-cell lung cancer treated with three-port SIC and conventional multiple-intercostal (MIC) thoracoscopic lobectomy.

Methods

From January 2013 to January 2018, 642 non-small-cell lung cancer patients underwent thoracoscopic lobectomy via a three-port SIC or MIC technique. Propensity-matched analysis incorporating preoperative clinical variables was used to compare the perioperative outcomes between the two groups.

Results

The first 20 patients were excluded to account for the learning curve effect in the SIC group. Propensity matching yielded 186 patients in each group. A small percentage of patients had major morbidity, including 4.8% in the SIC group and 6.5% in the MIC group; there was no significant difference between the two groups. Although the total number of lymph nodes harvested (25.3 vs. 23.8, p = 0.160) and stations removed (6.5 vs. 6.7, p = 0.368) were similar between the two groups, more subcarinal lymph nodes were removed (6.9 vs. 5.2, p < 0.001) in the SIC group than in the MIC group. Furthermore, other perioperative outcomes in the SIC group were not fewer than those in the MIC group.

Conclusions

Both techniques are acceptable for the treatment of non-small-cell lung cancer. Three-port SIC VATS lobectomy can provide an alternative procedure in thoracoscopic surgery.



http://bit.ly/2C1CSu3

Comparison of GeneXpert MRSA/SA ETA assay with semi-quantitative and quantitative cultures and nuc gene-based qPCR for detection of Staphylococcus aureus in endotracheal aspirate samples

Staphylococcus aureus (S. aureus) is a common cause of ventilator-associated pneumonia. Rapid and accurate detection of lower respiratory tract colonization and/or infection with S. aureus may inform targeted pre...

http://bit.ly/2GWybHG

Antimicrobial properties of a novel copper-based composite coating with potential for use in healthcare facilities

Healthcare-associated infections (HAIs) have a major impact on public health worldwide. Particularly, hospital surfaces contaminated with bacterial pathogens are often the origin of both sporadic cases and out...

http://bit.ly/2RuUBnA

Gout and the risk of Parkinson’s disease in older adults: a study of U.S. Medicare data

In the presence of limited available data, our objective was to assess the association of gout with the risk of incident Parkinson's disease (PD) in adults 65 years or older.

http://bit.ly/2saOPcb

Star-related lipid transfer protein 10 (STARD10): a novel key player in alcohol-induced breast cancer progression

Abstract

Background

Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast cancers. In this study, we demonstrate that ethanol administration promotes STARD10 and ERBB2 expression that is significantly associated with increased cell malignancy and aggressiveness.

Material and methods

We investigated the effect of ethanol on STARD10-ERBB2 cross-talk in breast cancer cells, MMTV-neu transgenic mice and in clinical ERBB2-positive breast cancer specimens with Western Blotting and Real-time PCR. We also examined the effects of their knockdown and overexpression on transient transfected breast cancer cells using promoter activity, MTT, cell migration, calcium and membrane fluidity assays in vitro.

Results

Ethanol administration induces STARD10 and ERBB2 expression in vitro and in vivo. ERBB2 overexpression causes an increase in STARD10 expression, while overexpression of ERBB2's downstream targets, p65, c-MYC, c-FOS or c-JUN induces STARD10 promoter activity, correlative of enhanced ERBB2 function. Ethanol and STARD10-mediated cellular membrane fluidity and intracellular calcium concentration impact ERBB2 signaling pathway as evaluated by enhanced p65 nuclear translocation and binding to both ERBB2 and STARD10 promoters.

Conclusion

Our finding proved that STARD10 and ERBB2 positively regulate each other's expression and function. Taken together, our data demonstrate that ethanol can modulate ERBB2's function in breast cancer via a novel interplay with STARD10.



http://bit.ly/2AwuYJ7

Does postoperative prophylactic irradiation of para-aortic lymph nodes reduce the risk of recurrence in uterine cervical cancer with positive pelvic lymph nodes?

Abstract

Background

In cervical cancer, para-aortic lymph nodes are common sites of metastasis. The purpose of the study was to evaluate the clinical benefits of prophylactic irradiation as postoperative therapy.

Methods

A retrospective cohort study was conducted during 2001–2015 at a single institution. Patients with a high risk of para-aortic lymph nodes recurrence were eligible for this study, and we identified patients who had pelvic lymph node metastasis and underwent radical surgery and concurrent chemo-radiotherapy. As a result, 33 and 46 patients were included in the treatment (prophylactic irradiation) and non-treatment groups, respectively. Baseline differences between the two groups were adjusted with the inverse probability of treatment weighting using propensity scores composed of the independent variables including age, stage, tumor size, pathological findings, lymph node status, and pathological subtypes.

Results

In the 68-month median follow-up period (range 6–178 months), 25 patients experienced recurrence, and 17 patients were dead. After adjustment with the inverse probability of treatment weighting, the recurrence rates tended to decrease in the treatment group, but there was no significant difference between the two groups [treatment vs. non-treatment, 29.4% and 44.3%, respectively; hazard ratio, 0.593 (95% CI 0.320–1.099); P = 0.097]. However, adjusted para-aortic lymph nodes recurrence rates were not significantly different [treatment vs. non-treatment, 7.8% and 11.4%, respectively; odds ratio, 0.660 (95% CI 0.187–2.322); P = 0.558]. Moreover, Kaplan–Meier curves showing post-recurrence survival revealed no significant difference between the two groups (P = 0.141).

Conclusions

Prophylactic para-aortic lymph nodes irradiation did not reduce the risk of recurrence.



http://bit.ly/2GVP4lH

Uterine Sarcomas: Experience from a Tertiary Cancer Care Center from India

Abstract

Uterine sarcomas are uncommon and aggressive tumors comprising 3–7% of all uterine malignancies. The aim is to evaluate clinical presentation, histopathologic pattern, recurrence pattern, and outcome of patients with uterine sarcomas presenting to a tertiary care cancer center over an 8-year period. A total of 11 cases of uterine sarcoma were diagnosed. The median age of patients at presentation was 51 years (range 30–67 years). Six patients had leiomyosarcoma (54.5%), 4 had endometrial stromal sarcoma (36%), and 1 had adenosarcoma (9%). The main presenting symptoms were abnormal vaginal bleeding, low abdominal pain, and white discharge. Median follow-up was 11 months ranging from 3 to 200 months. Median survivals for leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma were 6.5, 18, and 56 months. The 3- and 5-year survival by Kaplan–Meier survival analysis of the entire cohort was 30 and 20%. The mitotic index, age, adjuvant therapy (chemotherapy, radiotherapy), and performance of pelvic nodal dissection did not impact survival significantly in the patient with leiomyosarcoma. Stage and histology had the strongest bearing on survival and leiomyosarcoma has the worst survival, whereas adenosarcoma had the best prognosis. Adequately powered prospective studies are required to define the role of radiation therapy and chemotherapy in this rare disease.



http://bit.ly/2skEiLX

A longitudinal mixed methods study on changes in body weight, body composition, and lifestyle in breast cancer patients during chemotherapy and in a comparison group of women without cancer: study protocol

Abstract

Background

More than 60% of women diagnosed with early stage breast cancer receive (neo)adjuvant chemotherapy. Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect body weight and body composition. Changes in body weight and body composition may detrimentally affect their quality of life, and could potentially increase the risk of disease recurrence, cardiovascular disease and diabetes. To date, from existing single method (quantitative or qualitative) studies is not clear whether changes in body weight and body composition in breast cancer patients are treatment related because previous studies have not included a control group of women without breast cancer.

Methods

We therefore developed the COBRA-study (Change Of Body composition in BReast cancer: All-in Assessment-study) to assess changes in body weight, body composition and related lifestyle factors such as changes in physical activity, dietary intake and other behaviours. Important and unique features of the COBRA-study is that it used I) a "Mixed Methods Design", in order to quantitatively assess changes in body weight, body composition and lifestyle factors and, to qualitatively assess how perceptions of women may have influenced these measured changes pre-, during and post-chemotherapy, and II) a control group of non-cancer women for comparison. Descriptive statistics on individual quantitative data were combined with results from a thematic analysis on the interviews- and focus group data to understand patients' experiences before, during and after chemotherapy.

Discussion

The findings of our mixed methods study, on chemotherapy treated cancer patients and a comparison group, can enable healthcare researchers and professionals to develop tailored intervention schemes to help breast cancer patients prevent or handle the physical and mental changes they experience as a result of their chemotherapy. This will ultimately improve their quality of life and could potentially reduce their risk for other co-morbidity health issues such as cardiovascular disease and diabetes.



http://bit.ly/2GYir6Z

Cancer therapeutics based on BCL-2 functional conversion



http://bit.ly/2AGpY51

Perioperative transfusion and the prognosis of colorectal cancer surgery: a systematic review and meta-analysis

Abstract

Background

Perioperative transfusion can reduce the survival rate in colorectal cancer patients. The effects of transfusion on the short- and long-term prognoses are becoming intriguing.

Objective

This systematic review and meta-analysis aimed to define the effects of perioperative transfusion on the short- and long-term prognoses of colorectal cancer surgery.

Results

Thirty-six clinical observational studies, with a total of 174,036 patients, were included. Perioperative transfusion decreased overall survival (OS) (hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.24 to 0.41; P < 0.0001) and cancer-specific survival (CSS) (HR, 0.34; 95% CI, 0.21 to 0.47; P < 0.0001), but had no effect on disease-free survival (DFS) (HR, 0.17; 95% CI, − 0.12 to 0.47; P = 0.248). Transfusion could increase postoperative infectious complications (RR, 1.89, 95% CI, 1.56 to 2.28; P < 0.0001), pulmonary complications (RR, 2.01; 95% CI, 1.54 to 2.63; P < 0.0001), cardiac complications (RR, 2.20; 95% CI, 1.75 to 2.76; P < 0.0001), anastomotic complications (RR, 1.51; 95% CI, 1.29 to 1.79; P < 0.0001), reoperation(RR, 2.88; 95% CI, 2.05 to 4.05; P < 0.0001), and general complications (RR, 1.86; 95% CI, 1.66 to 2.07; P < 0.0001).

Conclusion

Perioperative transfusion causes a dramatically negative effect on long-term prognosis and increases short-term complications after colorectal cancer surgery.



http://bit.ly/2QoFA1R

Irreversible electroporation in a case of pancreatic leiomyosarcoma: a novel weapon versus a rare malignancy?

Abstract

Background

Primary pancreatic leiomyosarcoma is an extremely rare entity that needs high clinical suspicion in order to diagnose it at an early stage. Clinical characteristics, diagnosis, and management still remain challenging and controversial, especially in advanced stages, when tumor invades adjacent vessels and organs or gives distant metastases.

Case presentation

Herein, we describe a case of a 57-year-old woman suffering from advanced pancreatic leiomyosarcoma with thrombosis of the superior mesenteric vein, as well as liver lesions which were suspicious for metastasis. Multidisciplinary team decided for upfront chemotherapy to assess tumor response. Follow-up imaging after the completion of chemotherapy led tumor board to decide for subsequent surgical exploration. The patient underwent exploratory laparotomy and irreversible electroporation ablation of the pancreatic tumor. Postoperative course was uneventful, and she was discharged 10 days later with a plan to receive adjuvant therapy. To the best of our knowledge, this is the first case of pancreatic leiomyosarcoma ever reported, treated with this novel technique of irreversible electroporation that could be an alternative and feasible way for the management of these rare malignancies.

Conclusions

In conclusion, primary pancreatic leiomyosarcoma is a rare and highly malignant tumor associated with poor prognosis. Nowadays, R0 surgical resection remains the cornerstone treatment, combined with adjuvant and/or neoadjuvant chemotherapy prior to resection. In the advanced setting, when major vessel invasion and distant metastases occur, chemotherapy along with irreversible electroporation ablation could be a helpful and possibly effective modality for the management of this highly aggressive tumor.



http://bit.ly/2VE9ymu

EGFR Protein Expression of KRAS Wild-Type Colorectal Cancer: Predictive Value of the Sidedness for Efficacy of Anti-EGFR Therapy

Abstract

Right- and left-sided colorectal cancers (RSCRC and LSCRC, respectively) are different developmentally, genetically and prognostically. Clinical data also indicate that they respond differently to anti-EGFR therapies. The role of EGFR protein expression in KRAS wild type colorectal cancer is also controversial. Here we have used a cohort of anti-EGFR antibody treated KRAS-wild type colorectal cancer patients (n = 97) to analyse the prognostic role of EGFR protein expression in relation to sidedness. In our cohort EGFR copy number, determined by FISH, was not associated with the level of EGFR protein, assessed by immunohistochemistry and measured by H-scoring. There was a significantly higher EGFR H-score detected in RSCRC as compared to LSCRC in primary tumors (p = 0.04). Furthermore, in a proportion of cases (n = 31) metastatic tissues were also available and their analysis also found a significantly higher EGFR H-score in metastases of RSCRC compared to LSCRC (p = 0.018). Kaplan Meyer survival analysis demonstrated that anti-EGFR antibody therapies were more effective in case of LSCRC compared to RSCRC. Although in case of progression-free survival data just indicated a trend (p = 0.065), in case of overall survival the difference was significant favouring LSCRC (p = 0.047). These data demonstrated for the first time that the EGFR protein expression is significantly higher in KRAS wild type RSLCL as compared to LSCRC. Meanwhile it is somewhat unexpected that the lower EGFR protein expression was found to be associated with better efficacy of anti-EGFR antibody therapies of colorectal cancer, the finding of which must be further validated.



http://bit.ly/2CQ8JPP

Clinical characteristics and the long-term outcome of patients with atypical POEMS syndrome variant with undetectable monoclonal gammopathy

Abstract

The diagnosis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome requires polyneuropathy and monoclonal plasma cell proliferation as two mandatory criteria. Our aim was to summarize clinical manifestations and treatment responses of POEMS variants with no evidence of monoclonal gammopathy. We queried all medical documentation of patients referred to Peking Union Medical College Hospital from August 2012 to July 2017, and reviewed the clinical and laboratory features of 13 patients with atypical POEMS syndrome with undetectable monoclonal gammopathy, and compared to prototypes published. The prevalence of polyneuropathy, organomegaly, skin changes, and extravascular fluid overload were 100%, 100%, 92%, and 100%, respectively. Other clinical manifestations, such as endocrinopathy, pulmonary hypertension, papilledema, thrombocytosis, and polycythemia affected similar percentages of patients as seen in prototypes. POEMS variants enrolled had a median serum vascular endothelial growth factor (VEGF) level of 4998 pg/ml (range 2155–11,029 pg/ml). Long-term follow-up found that all 12 patients received autologous stem cell transplant, melphalan-based therapy or lenalidomide/thalidomide-based therapy obtained clinical improvement, of which eight experienced decreased levels of VEGF by 50% or back to normal. The median progression-free survival was 101.5 months. Our findings raised a variant of POEMS syndrome variants with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting plasma cell.



http://bit.ly/2TsqytZ

Recontextualizing the Draw A Story Assessment: Expanding the Expressive Function in Art Therapy

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http://bit.ly/2H8YvP5

Three-dimensional tumor visualization of invasive breast carcinomas using whole-mount serial section histopathology: implications for tumor size assessment

Abstract

Purpose

Linear tumor size (T-size) estimated with conventional histology informs breast cancer management. Previously we demonstrated significant differences in margin and focality estimates using conventional histology versus digital whole-mount serial sections (WMSS). Using WMSS we can measure T-size or volume. Here, we compare WMSS T-size with volume, and with T-size measured conventionally. We also compare the ellipsoid model for calculating tumor volume to direct, WMSS measurement.

Methods

Two pathologists contoured regions of invasive carcinoma and measured T-size from both WMSS and (simulated) conventional sections in 55 consecutive lumpectomy specimens. Volume was measured directly from the contours. Measurements were compared using the paired t-test or Spearman's rank-order correlation. A five-point 'border index' was devised and assigned to each case to parametrize tumor shape considering 'compactness' or cellularity. Tumor volumes calculated assuming ellipsoid geometry were compared with direct, WMSS measurements.

Results

WMSS reported significantly larger T-size than conventional histology in the majority of cases [61.8%, 34/55; means = (2.34 cm; 1.99 cm), p < 0.001], with a 16.4% (9/55) rate of 'upstaging'. The majority of discordances were due to undersampling. T-size and volume were strongly correlated (r = 0.838, p < 0.001). Significantly lower volume was obtained with WMSS versus ellipsoid modeling [means = (1.18 cm3; 1.45 cm3), p < 0.001].

Conclusions

Significantly larger T-size is measured with WMSS than conventionally, due primarily to undersampling in the latter. Volume and linear size are highly correlated. Diffuse tumors interspersed with normal or non-invasive elements may be sampled less extensively than more localized masses. The ellipsoid model overestimates tumor volume.



http://bit.ly/2SFrqve

Carotid Artery Stenting: Current State of Evidence and Future Directions

Abstract

Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomised controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke, however CEA is more strongly associated with myocardial infarction. Published long‐term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in‐stent thrombosis, however evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarise the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis.

This article is protected by copyright. All rights reserved.



http://bit.ly/2RaS56j

Perampanel for treatment of status epilepticus in Austria, Finland, Germany and Spain

Summary

Objective

Novel treatments are needed to control treatment‐resistant status epilepticus (SE). We report a summary of clinical cases where perampanel was used in established SE, refractory SE (RSE), or super‐refractory SE (SRSE).

Methods

Medical records were retrospectively reviewed for perampanel administration in SE at five European hospitals between 2011 and 2015.

Results

Of 1319 patients identified as experiencing SE, 52 (3.9%) received perampanel. Median latency from SE onset to perampanel initiation was 10 days. Patients with SE had previously failed benzodiazepines (when received) and a median of five other antiepileptic drugs (AEDs). Median initial perampanel dose was 6 mg/day, up‐titrated to a median maximum dose of 10 mg/day. Perampanel was the last drug added in 32/52 (61.5%) patients, with response attributed to perampanel in 19/52 (36.5%) patients. A greater proportion of perampanel non‐responders had SRSE (51.5%; 17/33) versus perampanel responders (31.6%; 6/19), and had failed a higher mean number of AEDs before initiating perampanel (5.9 vs 5.1, respectively). Most commonly reported adverse effects during perampanel treatment were dizziness (n=1 [1.9%]) and somnolence (n=1 [1.9%]). No serious adverse effects were documented, and none led to discontinuation of perampanel.

Conclusions

Perampanel was administered to patients with established SE, RSE, or SRSE at greater initial doses than those administered in clinical practice to patients with epilepsy. The SE cases reported here represent a refractory and heterogeneous population, and rate of seizure cessation attributed to perampanel treatment (36.5%) represents a notable response. These data should be confirmed in a larger patient population.

This article is protected by copyright. All rights reserved.



http://bit.ly/2C00HCx

Detailed Pathological Analysis of the Advancing Edge of the Tumor Can Effectively Stratify Clinical T4b Colorectal Cancer Patients

Abstract

Aims

Pathological staging of colorectal cancers (CRCs) that involve adhesion to adjacent organs (clinical stage T4b, cT4b) is sometimes difficult because the morphology of the invasive front varies. To resolve this issue, we reviewed 492 surgically resected CRC samples, comprising 96 cT4b tumors and, for comparison, 335 typical pathological stage (p) T3 and 61 pT4a tumors.

Methods and results

Cases were subdivided into four groups according to the presence or absence of microscopic tumor invasion into the muscular wall of the adjacent organs and peri‐tumoral abscess along invasive front. Those that directly invaded the wall of the adjacent organs without peri‐tumoral abscess were associated with a significantly worse overall (OS) and recurrence‐free survival (RFS) than the other three types of cT4b tumors. Tumors with peritumoral abscess showed similar prognosis as typical pT3 tumors even when the advancing edge of the tumor invaded the wall of adjacent organs (staged as pT4b). Tumors showing fibrous adhesion without tumor cell invasion into the muscular wall of the adjacent organs showed similar prognosis as typical pT3 tumors and showed better prognosis than pT4a tumors.

Conclusion

In summary, only CRCs with tumor cell invasion into the muscular wall of the adjacent organs should be classified as pT4b, and it might be better to avoid "the presence of tumor cells in fibrous adhesion" to define pathological T4b CRCs. In addition, the presence of a peri‐tumoral abscess should be recorded as a predictor of better prognosis.

This article is protected by copyright. All rights reserved.



http://bit.ly/2AsLuK3

Comment on ‘Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double‐blind, randomised controlled VaSera trial’ by Faconti et al.



http://bit.ly/2saVJOE

Ischemic colitis associated with intravitreal administration of aflibercept: a first case report

Abstract

In patients with age‐related macular degeneration (AMD), the intravitreal injection of anti‐vascular endothelial growth factor (VEGF) agents reduces disease progression and choroidal neovascularization. We report on a first case of ischaemic colitis associated with intravitreal injection of the anti‐VEGF agent aflibercept in an 80‐year‐old female patient. Conservative treatment resulted in a favourable clinical outcome. The anti‐VEGF agent was discontinued, and the symptoms did not recur. Although the intravitreal injection of anti‐VEGF agents has not previously been linked to the occurrence of ischaemic colitis, consideration of aflibercept's pharmacological properties and the chronological relationship between the administration of this anti‐VEGF agent and the occurrence of this systemic adverse event are strongly suggestive of a causal relationship in the present case. Although systemic complications have been rarely associated with intravitreal injections of anti‐VEGF agents, physicians should be aware that novel adverse events can still occur in AMD patients treated with anti‐VEGF agents.



http://bit.ly/2LTbRh5

Genome‐wide DNA methylation profiling shows molecular heterogeneity of anaplastic pleomorphic xanthoastrocytoma

Cancer Science Genome‐wide DNA methylation profiling shows molecular heterogeneity of anaplastic pleomorphic xanthoastrocytoma

This report suggests that anaplastic PXA consists of clinically and biologically distinct multiple entities, and genome‐wide molecular profiling may help to identify them. This new approach will be useful for predicting prognosis and choosing treatment for anaplastic PXA patients.


In the revised World Health Organization classification 2016, anaplastic pleomorphic xanthoastrocytoma (PXA) has been newly defined as a variant of the PXA entity. Furthermore, some anaplastic PXA were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome‐wide molecular analysis, we show an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile. A full implementation of the molecular approach is the key to predict prognosis and decide the treatment strategy for anaplastic PXA.



http://bit.ly/2BYqvPo

Circadian Rhythm of Redox State Regulates Membrane Excitability in Hippocampal CA1 Neurons

Abstract

Behaviors, such as sleeping, foraging, and learning, are controlled by different regions of the rat brain, yet they occur rhythmically over the course of day and night. They are aligned adaptively with the day‐night cycle by an endogenous circadian clock in the suprachiasmatic nucleus (SCN), but local mechanisms of rhythmic control are not established. The SCN expresses a ~24‐h oscillation in reduction‐oxidation that modulates its own neuronal excitability. Could circadian redox oscillations control neuronal excitability elsewhere in the brain? We focused on the CA1 region of the rat hippocampus, which is known for integrating information as memories and where clock‐gene expression undergoes a circadian oscillation that is in anti‐phase to the SCN. Evaluating long‐term imaging of endogenous redox couples and biochemical determination of glutathiolation levels, we observed oscillations with an ~24 h period that is 180° out‐of‐phase to the SCN. Excitability of CA1 pyramidal neurons, primary hippocampal projection neurons, also exhibits a rhythm in resting membrane potential that is circadian time‐dependent and opposite from that of the SCN. The reducing reagent glutathione rapidly and reversibly depolarized the resting membrane potential of CA1 neurons; the magnitude is time‐of‐day‐dependent and, again, opposite from the SCN. These findings extend circadian redox regulation of neuronal excitability from the SCN to the hippocampus. Insights into this system contribute to understanding hippocampal circadian processes, such as learning and memory, seizure susceptibility, and memory loss with aging.

This article is protected by copyright. All rights reserved.



http://bit.ly/2GYVn87

The Power of Sisterhood: The Moderating Role of Womanism in the Discrimination-Distress Link among Women of Color in the United States

Abstract

Sexism and racism play an important role in the psychological well-being of Women of Color (WOC). It is important to understand how protective factors, such as womanism (an outgrowth of Black feminist thought focused on the intersectional concerns of WOC), might disrupt the link between discrimination and psychological distress. With a sample of 204 U.S. heterosexual WOC, we examined (a) the links between perceived lifetime and recent sexist events and psychological distress and (b) the potential moderating role in these relations of womanism (an intersectional feminist perspective). Further, we conducted exploratory analysis on (c) the potential moderating role of womanism in the association between racism and distress. Findings indicated that all measured forms of discrimination were significantly and positively related to psychological distress. Womanism was found to moderate the relationship between each form of discrimination and psychological distress. The links between each form of discrimination and psychological distress were significant and positive for WOC with lower levels of womanism and not significant for those with higher levels. As one of the first known studies to investigate womanism as a protective factor, and the first known to explore its role in buffering experiences of racism, findings suggest that placing discrimination experiences within a larger sociocultural context of oppression may reduce distress for WOC.



http://bit.ly/2RCzEH4

Moving from Rural to Urban China: How Urbanization Affects Women’s Housework

Abstract

The present study explores within-gender differences in domestic labor by studying housework variations across five different groups of women in contemporary China. We defined five groups of women according to their urbanization status in general and hukou (i.e., household registration) in particular. (a) Rural natives are women with rural hukou who have stayed in rural areas, (b) rural migrants are women with rural hukou who have migrated to an urban area but have not obtained an urban hukou, (c) policy-based converters are women with rural origins who have converted to being urban residents due to policy privileges, (d) merit-based converters are women with rural origins who have converted to urban residents because of their merit (i.e., education), and (e) urban natives are those who are born urban hukou holders. Multivariate results on a national dataset with 2186 partnered women (aged 18–60) revealed that among women with rural origins, converters spent the least time on housework, rural natives the most, and rural migrants fell in between. Successful converters, particularly merit-based converters, expressed the strongest desire to pursue gender equality and deliberately devoted less time to domestic work. Additional Propensity Score Matching (PSM) analysis that compared women who have migrated to cities with women who have stayed in rural areas provides evidence that moving to urban areas has a negative association with women's housework time, irrespective of their official household registration status, no matter whether they are migrant women who are not officially recognized or are successfully converted urban women.



http://bit.ly/2GYVjoT

Body Surveillance on Instagram: Examining the Role of Selfie Feedback Investment in Young Adult Women’s Body Image Concerns

Abstract

Selfies are self-taken self-portrait photographs captured with mobile phones, and they are among the most common forms of self-expression on the photo-based social network Instagram. Selfies display their subject's face or body to social media followers and friends, making them particularly appearance-oriented images. As with other social networks such as Facebook and Twitter, Instagram posts garner feedback in the form of "likes" and comments from online audiences. When applied to selfies, such feedback can be interpreted as aggregated evaluations of their subject's physical appearance. We employ objectification theory to explore how value placed on selfie feedback among young women relates to markers of body image disturbance, including body dissatisfaction, drive for thinness, and bulimia action tendencies. We conducted an online survey of 177 English-speaking young adult (18–30 years-old) female Instagram users who were recruited through MTurk and who post selfies to examine the relationship between investment in selfie feedback and body image disturbance. We found that women who reported higher investment in selfie feedback were more likely to express body dissatisfaction and drive for thinness through the indirect influence of body surveillance, but this effect did not extend to bulimic tendencies. Our findings suggest that young adult female Instagram users who value audience responses to their selfies are more likely to exhibit disordered eating attitudes and intentions.



http://bit.ly/2RA3egs

A Qualitative Multiple Case Study of the Division of Labor across the Transition to Parenthood in South-Brazilian Families

Abstract

Family roles tend to become more traditional across the transition to parenthood, which may affect satisfaction with the division of labor and the well-being and relationships of new parents. We employed a qualitative, longitudinal, multiple case study to investigate the division of labor across the transition to parenthood in South-Brazilian families with different childcare arrangements (i.e., maternal care, nanny care, and daycare center). Data were collected through semi-structured, face-to-face interviews conducted with 12 first-time mothers and fathers (six families) at 6, 12, and 18 months postpartum. Using deductive thematic analysis, we found greater sharing of childcare tasks during the first few days postpartum, followed by a decrease in fathers' contributions across the first few months. This more unequal division of labor shifted toward greater subsequent father involvement for families with nanny care and daycare arrangements, although it remained stable for families with maternal care arrangement. Parental satisfaction regarding the division of labor remained relatively high over time only for families with nanny care arrangements. Findings are discussed in the light of the roles that instrumental and social support, as well as Brazilian gender norms, play in the division of labor for new parents. Implications for practice and policy are presented.



http://bit.ly/2GW4mqO

Paternity Leave-Taking and Father Involvement among Socioeconomically Disadvantaged U.S. Fathers

Abstract

In the present study, we examine the associations between the amount of time that U.S. employed fathers took off from work after the birth of a child (i.e., paternity leave-taking) and trajectories of how frequently fathers engage with their children and take responsibility for them. To do so, we analyze longitudinal data on 2109 fathers from the Fragile Families and Child Wellbeing Study, a data set that contains information from disproportionately socioeconomically disadvantaged families from large urban areas. The results indicate that, 1 year after birth, paternity leave-taking and lengths of leave are positively associated with fathers' engagement and responsibility. In addition, paternity leave-taking is positively associated with trajectories of fathers' responsibility over the first 5 years after birth. Lengths of paternity leave are positively associated with trajectories of fathers' engagement. Finally, there is evidence that paternity leave-taking and lengths of leave-taking are especially likely to boost fathers' engagement and responsibility among nonresident fathers. Overall, the findings from the present study suggest that an expansion of paternity leave-taking may encourage higher subsequent levels of father involvement—especially among nonresident fathers.



http://bit.ly/2RCzHCK

Perceived Men’s Feminization and Attitudes Toward Homosexuality: Heterosexual Men’s Reactions to the Decline of the Anti-Femininity Norm of Masculinity

Abstract

One of the central dimensions of traditional masculinity is men's renunciation of the feminine (i.e., the anti-femininity norm), and men's endorsement of this norm constitutes one of the strongest predictors of negative attitudes toward homosexuality. However, egalitarian societies are undergoing a significant change: Gendered roles, stereotypes, and norms are evolving. Accordingly, many believe that men are becoming more feminine than before, and this change might have consequential effects. Across two studies conducted in Western countries, we investigated heterosexual men's reaction to the perceived decline of the anti-femininity norm of masculinity on their attitudes toward homosexuality. The results consistently showed that perceived men's feminization increased negative attitudes toward homosexuality (Study 1, n = 220), specifically among those participants who most strongly endorsed the anti-femininity norm (Study 2, n = 156). Furthermore, this pattern was driven by participants' discomfort with homosexuality rather than by their motivation to reinstate the challenged gender dichotomy. We discuss the relevance of these findings for both the gender and sexual prejudice literatures.



http://bit.ly/2GYVhgL

Transnormativity and Transgender Identity Development: A Master Narrative Approach

Abstract

Despite rapidly shifting social dynamics and the recent increase in scholarship on transgender identity development, existing research on transgender identity has been theoretically isolated from the broader study of identity. This study involved a series of 4 qualitative focus groups (n = 15 participants), conducted in the United States, to identify master and alternative narratives guiding transgender identity development and explore the mechanisms by which transgender individuals navigate and negotiate with these narrative constraints. Results suggest that (a) transnormativity is best conceptualized as a hegemonic alternative narrative that resists the master narrative of cisnormativity, which asserts that cisgender identities are "normal" or "standard"; (b) the components of transnormativity go beyond those which have been previously described in the literature; (c) individuals negotiate with transnormativity through both resisting transnormativity and conceding to transnormativity; and (d) border wars within the trans community form on the basis of these opposing and contradictory processes of resisting and conceding. Results demonstrate the applicability of the Master Narrative framework for studying transgender identity development and the important role of master and alternative narratives of in shaping the lives and experiences of transpeople. Psychotherapists can use these findings to engage clients in re-authoring conversations to affirm the legitimacy of clients' unique identity experiences.



http://bit.ly/2RA3eNu

Objectification in Heterosexual Romantic Relationships: Examining Relationship Satisfaction of Female Objectification Recipients and Male Objectifying Perpetrators

Abstract

Sexual objectification is one of most the common manifestations of discrimination against women in Western societies; however, few studies have examined objectification in the context of romantic relationships. The primary aim of the present research was to bring the study of objectification phenomena into the setting of heterosexual romantic relationships. The present set of studies examined the relation between sexual objectification and relationship satisfaction for both the sexual objectification recipient (Study 1) and the sexual objectification perpetrator (Study 2). The results of the first study with 206 U.S. undergraduate female students in committed romantic relationships replicated a previously identified negative association between feeling dehumanized by one's partner and intimate relationship satisfaction. Moreover, this link was mediated by greater body dissatisfaction and decreased sexual satisfaction. The second study with 94 U.S. undergraduate male students in committed romantic relationships demonstrated a negative association between sexual objectification perpetration and relationship satisfaction. Furthermore, this negative relation was mediated by greater partner objectification and lower sexual satisfaction. Results of both studies demonstrated the effect of sexual objectification (as recipient or perpetrator) on global intimate relationship health. Additionally, the results highlight poor sexual satisfaction as a key dyadic mechanism linking objectification processes to intimate relationship outcomes.



http://bit.ly/2GYVd0v

Recruitment and Collection of Dermal Interstitial Fluid Using a Microneedle Patch

Advanced Healthcare Materials Recruitment and Collection of Dermal Interstitial Fluid Using a Microneedle Patch

Interstitial fluid is a relatively unexplored body fluid which is difficult to collect from the skin. A minimally invasive, rapid, simple‐to‐use, cost‐effective microneedle patch is presented to collect interstitial fluid. Upon insertion, interstitial fluid flows through micropores to the skin surface and is collected into a thin strip of paper on the microneedle patch backing for analysis.


Abstract

Interstitial fluid (ISF) that surrounds cells in tissues of the body is a novel source of biomarker that complements conventional sources like blood, urine, and saliva. To overcome difficulties in harvesting ISF, a minimally invasive, rapid, simple‐to‐use, cost‐effective method is developed to collect ISF from the skin involving a microneedle (MN) patch. By pressing 650 µm long MNs at an angle just below the skin surface, blood‐free ISF flows through micropores to the skin surface and is absorbed into a thin strip of paper on the MN patch backing for subsequent analysis. An optimized method in rat skin in vivo is well tolerated and able to collect >2 µL of ISF within 1 min. Brief skin pretreatment with MNs followed by a 5 min delay dramatically increases subsequent ISF collection by a mechanism believed to involve increased skin hydration. ISF collection using an MN patch has the potential to simplify access to biomarkers in ISF for research and future medical diagnostic and monitoring applications.



http://bit.ly/2BZNv0j

Responsive and Synergistic Antibacterial Coatings: Fighting against Bacteria in a Smart and Effective Way

Advanced Healthcare Materials Responsive and Synergistic Antibacterial Coatings: Fighting against Bacteria in a Smart and Effective Way

Responsive and synergistic antibacterial coatings that are responsive to the bacterial microenvironment, that possess two or more killing mechanisms that interact synergistically, or that have triggered‐cleaning capability have emerged as promising solutions for bacterial infection and contamination problems. The recent development of such coatings is summarized in this review.


Abstract

Antibacterial coatings that eliminate initial bacterial attachment and prevent subsequent biofilm formation are essential in a number of applications, especially implanted medical devices. Although various approaches, including bacteria‐repelling and bacteria‐killing mechanisms, have been developed, none of them have been entirely successful due to their inherent drawbacks. In recent years, antibacterial coatings that are responsive to the bacterial microenvironment, that possess two or more killing mechanisms, or that have triggered‐cleaning capability have emerged as promising solutions for bacterial infection and contamination problems. This review focuses on recent progress on three types of such responsive and synergistic antibacterial coatings, including i) self‐defensive antibacterial coatings, which can "turn on" biocidal activity in response to a bacteria‐containing microenvironment; ii) synergistic antibacterial coatings, which possess two or more killing mechanisms that interact synergistically to reinforce each other; and iii) smart "kill‐and‐release" antibacterial coatings, which can switch functionality between bacteria killing and bacteria releasing under a proper stimulus. The design principles and potential applications of these coatings are discussed and a brief perspective on remaining challenges and future research directions is presented.



http://bit.ly/2Rd2JJS

Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

Advanced Healthcare Materials Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

Incorporating functional polymer brushes on a biodegradable structural material via surface‐initiated atomic transfer radical polymerization improves its interfacial interactions with adhesive proteins and cells, providing a platform to mimic in vivo cellular environments for regenerative medicine. Poly(ethyl acrylate) brushes polymerized on poly‐l‐lactic acid enhance its biological activity by inducing the formation of fibronectin nanonetworks which target cell adhesion and differentiation.


Abstract

Poly‐l‐lactic acid (PLLA) has been used as a biodegradable polymer for many years; the key characteristics of this polymer make it a versatile and useful resource for regenerative medicine. However, it is not inherently bioactive. Thus, here, a novel process is presented to functionalize PLLA surfaces with poly(ethyl acrylate) (PEA) brushes to provide biological functionality through PEA's ability to induce spontaneous organization of the extracellular matrix component fibronectin (FN) into physiological‐like nanofibrils. This process allows control of surface biofunctionality while maintaining PLLA bulk properties (i.e., degradation profile, mechanical strength). The new approach is based on surface‐initiated atomic transfer radical polymerization, which achieves a molecularly thin coating of PEA on top of the underlying PLLA. Beside surface characterization via atomic force microscopy, X‐ray photoelectron spectroscopy and water contact angle to measure PEA grafting, the biological activity of this surface modification is investigated. PEA brushes trigger FN organization into nanofibrils, which retain their ability to enhance adhesion and differentiation of C2C12 cells. The results demonstrate the potential of this technology to engineer controlled microenvironments to tune cell fate via biologically active surface modification of an otherwise bioinert biodegradable polymer, gaining wide use in tissue engineering applications.



http://bit.ly/2BZTkuR

Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation

Advanced Healthcare Materials Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation

In this paper, cardiac fibrotic remodeling on a chip with dynamic mechanical stimulation, which can accurately mimic the dynamic biomechanical properties of the cardiac physiological and pathological microenvironment, is developed. Upon mechanical compression, fibrotic phenotype transitions between cardiac fibroblasts and myofibroblasts in a 3D culture state reveal a strain–response correlation of mechanical stimulation.


Abstract

Cardiac tissue is characterized by being dynamic and contractile, imparting the important role of biomechanical cues in the regulation of normal physiological activity or pathological remodeling. However, the dynamic mechanical tension ability also varies due to extracellular matrix remodeling in fibrosis, accompanied with the phenotypic transition from cardiac fibroblasts (CFs) to myofibroblasts. It is hypothesized that the dynamic mechanical tension ability regulates cardiac phenotypic transition within fibrosis in a strain‐mediated manner. In this study, a microdevice that is able to simultaneously and accurately mimic the biomechanical properties of the cardiac physiological and pathological microenvironment is developed. The microdevice can apply cyclic compressions with gradient magnitudes (5–20%) and tunable frequency onto gelatin methacryloyl (GelMA) hydrogels laden with CFs, and also enables the integration of cytokines. The strain–response correlations between mechanical compression and CFs spreading, and proliferation and fibrotic phenotype remolding, are investigated. Results reveal that mechanical compression plays a crucial role in the CFs phenotypic transition, depending on the strain of mechanical load and myofibroblast maturity of CFs encapsulated in GelMA hydrogels. The results provide evidence regarding the strain–response correlation of mechanical stimulation in CFs phenotypic remodeling, which can be used to develop new preventive or therapeutic strategies for cardiac fibrosis.



http://bit.ly/2Rd3jHJ

RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases

imageObjective: To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM). Background: The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS. Methods: Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients. Results: A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not. Conclusions: Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

http://bit.ly/2GXejEt

Barriers to Regionalized Surgical Care: Public Perspective Survey and Geospatial Analysis

imageObjective: To describe public willingness to participate in regionalized surgical care for cancer. Summary of Background Data: Improved outcomes at high-volume centers following complex surgery have driven a push to regionalize surgical care. Patient attitudes toward regionalization are not well described. Methods: As part of the Cornell National Social Survey, a cross-sectional telephone survey was performed. Participants were asked about their willingness to seek regionalized care in a hypothetical scenario requiring surgery. Their responses were compared with demographic characteristics. A geospatial analysis of hospital proximity was performed, as well as a qualitative analysis of barriers to regionalization. Results: Cooperation rate was 48.1% with 1000 total respondents. They were an average of 50 years old (range 18 to 100 years) and 48.9% female. About 49.6% were unwilling to travel 5 hours or more to seek regionalized care for improved survival. Age >70 years [odds ratio (OR) 0.34, 95% confidence interval (95% CI) 0.19–0.60] and perceived distance to a center >30 minutes (OR 0.60, 95% CI 0.41–0.86) were associated with decreased willingness to seek regionalized care, while high income (OR 2.09, 95% CI 1.39–3.16) was associated with increased willingness. Proximity to a major center was not associated with willingness to travel (OR 0.92, 95% CI 0.67–1.22). Major perceived barriers to regionalization were transportation, life disruption, social support, socioeconomic resources, poor health, and remoteness. Conclusion: Americans are divided on whether the potential for improved survival with regionalization is worth the additional travel effort. Older age and lower income are associated with reduced willingness to seek regionalized care. Multiple barriers to regionalization exist, including a lack of knowledge of the location major centers.

http://bit.ly/2RxV3Bp

The Involvement of NF-κB/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion

Abstract

Lipopolysaccharide significantly increased invasion, cell proliferation, and phospho-NF-κB p65 and phospho-IGF-1R protein, but decreased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 cells in SW480 and HT29 colorectal cancer cells. In contrast, NF-κB inhibitor exhibited a counteract effect of lipopolysaccharide. Transfection of Toll-like receptor 4 shRNA significantly decreased phospho-NF-κB p65 and phospho-IGF-1R protein levels, invasion, but significantly increased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 in SW480 and HT29 cells. In conclusion, inflammation inhibits klotho gene expression in colorectal cancer cells through activation of Toll-like receptor 4 /NF-κB signal pathway.



http://bit.ly/2GVtg9P

Family and Community Medicine

A profile of physical activity, sedentary behaviors, sleep, and dietary habits of Saudi college female students
Hana A Alzamil, Manan A Alhakbany, Nora A Alfadda, Sarah M Almusallam, Hazzaa M Al-Hazzaa

Journal of Family and Community Medicine 2019 26(1):1-8

BACKGROUND: Few studies have reported valid comprehensive data on lifestyle habits of Saudi college females. In addition, studies on sedentary behaviors (SBs) and the duration of sleep of Saudi college students are rare. Saudi females appear to be less physically active and therefore, at a higher risk of noncommunicable diseases (NCDs). Therefore, the purpose of this study was to investigate lifestyle patterns of Saudi college females, including physical activity (PA), SBs, duration of sleep, and dietary habits. MATERIALS AND METHODS: A cross-sectional study was conducted among females attending health science colleges of King Saud University, using multistage stratified cluster sample (n &#61; 456). Weight, height, PA, SB, sleep, and dietary habits were all assessed using a previously validated questionnaire. RESULTS: Nearly half of the college females were physically inactive. Females exercised mostly at home or alone at no specific time of day. Their activity was for health reasons (43.4&#37;) for weight loss (28.7&#37;); lack of time (71.2&#37;) was the primary reason for inactivity. The majority (&#62;85&#37;) of females spent more time in sedentary activity (&#62;3 h/day) while 95&#37; of females had insufficient sleep (&#60;8 h/night). Over 40&#37; of the participants consumed breakfast or vegetables 5 days or more per week, whereas the corresponding proportions for fruit and milk/dairy products intake were 19.4&#37; and 58.4&#37;, respectively. The proportions of college females who consumed less healthy foods for 3&#43; days/week were fairly variable, ranging from 21.1&#37; for French fries to 60.4&#37; for chocolates/candy. The predictors of total PA time were increased the duration of sleep and reduced intake of French fries/potato chips. CONCLUSIONS: Unhealthy lifestyle habit appears prevalent among Saudi college females. Efforts toward promoting PA, decreasing SB, and insufficient sleep and improving dietary habits in Saudi females are needed to reduce future risks of NCDs.


Consistency of child self-reports with parent proxy reports on the quality of life of children with attention-deficit/hyperactivity disorder in Riyadh, 2016
Dina M Al-Habib, Fatima A Alhaidar, Ibrahem M Alzayed, Randa M Youssef

Journal of Family and Community Medicine 2019 26(1):9-16

BACKGROUND: The quality of life (QoL) of children with attention-deficit/hyperactivity disorder (ADHD) has not been addressed in Saudi Arabia despite the considerable attention it has on account of its prevalence, duration of illness, and sociopsychological effects. The aim of this study was to report on the QoL of children with ADHD and test the concord between children&#39;s and parents&#39; reports. MATERIALS AND METHODS: Using the generic PedsQL&#8482; (version 4.0) from both children&#39;s and parents&#39; perspectives, a cross-sectional study of 112 children was conducted on children aged 5&#8211;18 years with an established diagnosis of ADHD attending child psychiatry clinics of three referral hospitals in Riyadh between December 2015 and May 2016. RESULTS: A total of 112 children with an established diagnosis of ADHD were recruited from the Child Psychiatry Clinic of Al Amal Mental Health Complex (41.1&#37;), Prince Sultan Military Medical City (PSMMC), (33&#37;), and King Khalid University Hospital (KKUH), (25.9&#37;). The majority were boys (74.1&#37;) and Saudi nationals (93.8&#37;). The mean age of children with ADHD was 10.45 &#177; 3.06 years (Range 5 - 18 years). One-fourth of the mothers of children with ADHD had completed high school and 41.1&#37; had a diploma, university, or postgraduate degree. One-third of the fathers of these children had completed high school (34&#37;) and 38.4&#37; had a diploma, university, or postgraduate degree. The intra-class correlation coefficients between the scores of children and parents were good for physical functioning, fair for social functioning, but moderate for school, emotional, and psychosocial functioning. Children rated themselves significantly better than their parents for emotional, social, school, and psychosocial functioning. The standardized response means indicated a small difference for social functioning and medium differences for the other three domains. The only significant discrepancy was observed in social functioning in relation to the child&#39;s age. CONCLUSION: Parents mirrored adequately the observable physical component of the QoL of their children. The QoL report of children with ADHD with respect to communications and intellectual abilities should be taken into account whenever possible and their parents&#39; report also should be sought to provide a more comprehensive view of the child&#39;s status.


The association between waiting time and patient satisfaction in outpatient clinics: Findings from a tertiary care hospital in Saudi Arabia
Rasmah S Al-Harajin, Sara A Al-Subaie, Ahmed G Elzubair

Journal of Family and Community Medicine 2019 26(1):17-22

BACKGROUND: Patient satisfaction is an important indicator for assessing the quality of health care because it affects the timely, efficient, and patient-centered delivery of quality health care, and patient satisfaction is associated with the clinical outcomes. This study aimed to examine the relationship between waiting time and patient satisfaction in a tertiary hospital in Saudi Arabia. MATERIALS AND METHODS: A cross-sectional study was conducted at family medicine and other specialized clinics. Data were collected through a structured, self-administered questionnaire distributed to patients seen at the outpatient clinics. Variables collected were sociodemographic information and patient satisfaction scores to evaluate the association between waiting time and satisfaction. RESULTS: A total of 406 patients participated in the study. Half of the patients reported being satisfied with the waiting time, while the remaining were dissatisfied (mean satisfaction score 38.4 &#177; 6.63). Family medicine clinic scored better in waiting time than other specialized clinics; between arrival and registration (P &#60; 0.01), between registration and consultation (P &#60; 0.01), consultation time (P &#60; 0.01), and overall waiting time (P &#60; 0.01). Patients treated at the family medicine clinic were more likely to be satisfied than those seen in other specialized clinics (61.2&#37; vs. 40&#37;, P &#60; 0.01). CONCLUSION: Overall satisfaction was lower than shown in previous literature. Gender and clinic type were significantly associated with satisfaction score; those who attended the family medicine clinics were more satisfied than those attending other specialized clinics. Findings may be used to inform researchers, clinicians, and policy-makers&#39; decisions on quality improvement programs.


The impact of using the term "Diabetic Ear" for the patients with skull base osteomyelitis
Abdulaziz S AlEnazi, Salma S Al Sharhan, Laila M Telmesani, Nasser A Aljazan, Bander M Al Qahtani, Mohamed A Lotfy

Journal of Family and Community Medicine 2019 26(1):23-29

BACKGROUND: Diabetes and ear disease are some of the most widespread health concerns. The focus here is on the impact of using the term &#8220;Diabetic Ear&#8221; for patients with skull base osteomyelitis (SBM) in the context of malignant otitis externa (MOE). The aim of this study was to discover the awareness of general practitioners (GPs), residents, specialists, and consultants at Primary Health Care Centers about necrotizing otitis externa (NOE), also known previously as malignant external otitis (MOE), assess their deficiencies and provide solutions; also assist them for the early detection and possible prevention of diabetes- related ear diseases and their complications. MATERIALS AND METHODS: A cross-sectional study was conducted among a random sample of physicians (residents, specialists, and consultants) working at the Primary Health Care Centers in Al-Khobar and Dammam cities of the Eastern Province, Saudi Arabia. Data was collected using a standardized questionnaire. SPSS was used for data entry and analysis. RESULTS: The total number of medical practitioners was 84. Their mean age was 33.97 (&#177;9.55). The proportion of females was higher than males, only 28.3&#37; of the participants responded correctly when asked about MOE. Similarly, very few were aware of the risks of MOE (2.5&#37;), complications associated with it (17.3&#37;) and the necessary procedures for managing patients (24.2&#37;). The awareness of doctors in the primary health clinics about MOE was significantly better than those in hospitals (P &#61; 0.002). CONCLUSION: There was a significant deficiency in the knowledge of GPs on MOE. Therefore, health education and awareness programs on MOE are recommended. Furthermore, we recommend that it is necessary to encourage the use of the term &#8220;Diabetic EAR &#8220;to increase the level of awareness of physicians about MOE.


Effect of Zamzam water on blood methemoglobin level in young rats
Ahmed Badar, Abdullah O Bamosa, Mohammed Salahuddin, Abdullah Al Meheithif

Journal of Family and Community Medicine 2019 26(1):30-35

BACKGROUND: Methemoglobin (MetHb) level in blood indicates exposure to nitrogenous compounds. Acquired methemoglobinemia as a result of exposure to nitrates in drinking water is primarily an issue for infants. The amount of nitrates in Zamzam water is said to be on the high side. This study was designed to determine the effect of prolonged use of Zamzam water on MetHb in rat pups. MATERIALS AND METHODS: Wistar rat pups (n &#61; 52, 3 weeks old) were divided into four equal groups. All of them were given normal laboratory chow. The groups differed only in the exclusive source of water, that is ordinary bottled water, standardized mineral water, old Zamzam water (stored since 2008) or fresh Zamzam water. MetHb level was checked (using Avoximeter 4000) at the baseline, and then every week for 4 weeks from blood obtained from retro-orbital sinus. Other parameters tested were total haemoglobin, oxyhemoglobin and carboxyhemoglobin. ANOVA was used to compare the means between the groups. RESULTS: None of the rats in any of the four groups showed any sign of methemoglobinemia or toxicity. Both groups on Zamzam water showed higher increments in their total hemoglobin by the end of the study compared to their baseline (22&#37;) than the ordinary water (9&#37;) and the mineral water (5&#37;) groups. None of the groups showed any significant difference in MetHb levels on intergroup comparison at any of the weekly readings and at the end of the study. CONCLUSION: Prolonged use of Zamzam water did not induce any significant difference in MetHb concentration in rat pups, which might indicate that it is safe for infants.


Determinants of energy drinks consumption among the students of a Saudi University
Mahmoud H Alabbad, Mohammed Z AlMussalam, Ahmed M AlMusalmi, Mohammad M Alealiwi, Ali I Alresasy, Haidar N Alyaseen, Ahmed Badar

Journal of Family and Community Medicine 2019 26(1):36-44

BACKGROUND: Energy drinks contain stimulants mainly caffeine. The use of these drinks by university students is on the rise despite concerns about their safety. This study identified the determinants of the consumption of energy drinks in a cohort of Saudi university students. MATERIALS AND METHODS: This cross-sectional study was carried out at Imam Abdulrahman Bin Faisal University in Saudi Arabia. The students who volunteered to participate (n &#61; 1255) were asked to complete a pretested questionnaire soliciting information on gender, marital status, class and college of study, pattern of energy drinks use, reasons for use, any benefits as well as any untoward effects experienced. Data was analysed using IBM-SPSS (version 21) to determine frequencies and compare various categories of the energy drink users. Logistic regression analysis were performed to identify determinants of energy drinks consumption. RESULTS: Out of 1255 participants, 245 reported using energy drinks. Out of a total 1255 students, 903 (72&#37;) were from medical and 352 (28&#37;) from nonmedical colleges of the university. There were 890 junior and 365 senior students. The female participants were significantly more among both senior and junior medical students. The age of the participants (mean &#177; SD) was 20.2 &#177; 1.9 years. The frequency of energy drinks users was higher in the male nonmedical students (both senior and junior) compared to the medical students. The most significant determinants identified were male gender (odds ratio [OR] 4.2, 95&#37; confidence interval [CI] &#61;3.34, 6.12), and being single (OR &#61; 2.8, CI &#61; 1.98, 4.24). In addition, being in non-medical field of study (OR &#61; 1.3, 95&#37; CI&#61;0.61-2.13) was also found to have a reasonable association with energy drink consumption. CONCLUSION: We report male gender, unmarried status, and studying in nonmedical colleges of the university as the main determinants of the consumption of energy drinks by university students. Scrutiny of the patterns and reasons for the consumption of energy drinks might help in developing educational interventions to ensure the appropriate use of energy drinks by young adults.


Medical students' perception of their educational environment at Imam Abdulrahman Bin Faisal University, Kingdom of Saudi Arabia
Soban Q Khan, Mohammad Al-Shahrani, Abdul Khabeer, Faraz A Farooqi, Abdullah Alshamrani, Abdulrahman M Alabduljabbar, Ahmed S Bahamdan, Mohammad A Alqathani

Journal of Family and Community Medicine 2019 26(1):45-50

OBJECTIVE: The purpose of this study was to investigate students&#39; perception of the educational climate in a medical school in Dammam, Kingdom of Saudi Arabia (KSA). The difference in the perception of preclinical year students and clinical year students was also evaluated. MATERIALS AND METHODS: This cross-sectional study was conducted among 2nd to 6th year students at the medical college of Imam Abdulrahman Bin Faisal University. &#8220;Dundee Ready Educational Environment Measure&#8221; (DREEM) was used to evaluate the educational environment. RESULTS: Out of 518, 238 students participated in the study; participation rate of 45.9&#37;. The average DREEM score was 112.38 with a SD of 22.4. Students&#39; perception of atmosphere got the highest score (27.1 &#177; 6.7) of the five DREEM subscales. The 3rd year had the highest DREEM score compared to students of other levels, while the DREEM score of preclinical students was significantly higher than that of the clinical year students. CONCLUSION: Perception of medical students about the educational climate was more positive than negative. Although the DREEM score and its subdomains showed a positive educational environment, students still mentioned some problematic areas that need to be addressed. Findings of this study could encourage other medical colleges in the KSA to focus on weak areas and address the issues raised by students, especially clinical year students.


Prevalence of patients with epilepsy unfit to drive
Esra&#39; H Al Zaid

Journal of Family and Community Medicine 2019 26(1):51-56

BACKGROUND: There is no consensus among medical experts as to whether patients with epilepsy (PWEs) should be permitted to drive. PWEs who have had uncontrolled seizures in the past year are at an increased risk of road traffic accidents, often leading to the destruction of property, injury, or death. Currently, there is no clear policy on whether PWEs can drive in Saudi Arabia. Existing policies attempt to balance the potentially harmful and beneficial aspects of the issue. The purpose of this study was to measure the prevalence of PWEs who are unfit to drive. MATERIALS AND METHODS: Data were collected by interviews, a structured validated questionnaire, and a review of the medical records of 140 PWEs, with a response rate of 84&#37;. RESULTS: Fifty four percent of PWEs were found unfit to drive. Of the 118 participants, 17.7&#37; did not drive and 97 (82.3&#37;) drove. Of the 21 patients who did not drive, 14 (11.8&#37; of the total sample) never drove and 7 (5.9&#37; of the total sample) stopped driving because of epilepsy. Of the 104 patients who drove, 45 (43.2&#37; of the total sample) had a history of seizures while they drove. These incidents had resulted in the involvement of 28 patients (26.9&#37; of the total sample) in motor vehicle accidents and 17 (16.3&#37; of the total sample) patients being admitted to the emergency room. CONCLUSION: Structured regulation and licensing procedures are necessary for PWEs to drive safely. Regulations in other countries demand that seizures be controlled for 1 year before epileptic patients are allowed unrestricted driving. Such regulations would improve road safety in Saudi Arabia.


Immune's-boosting agent: Immunomodulation potentials of propolis
Mohammed Al-Hariri

Journal of Family and Community Medicine 2019 26(1):57-60

With a concomitant increase in immune-related diseases such as allergic diseases, Type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease and other immune-related responses such as immunodeficiency, various infectious, diseases, vaccines, and malignancies, it has become very important to have a well-balanced and properly functioning immune system for the maintenance of human health. Recent scientific research has strongly suggested propolis as one of the most promising immunomodulation agents. This review describes recent findings with respect to propolis and its ingredients that show potential in this respect and evaluate their potential mechanisms. The author believes that propolis or/and its ingredients alone and in combination could be promising in manipulating the immune response and inducing immunomodulation. Further exploratory studies are needed to support large clinical trials toward further development of propolis.


Chest pain as a possible side effect of pitavastatin (Livalo)
Nada R AlZahrani, Amna F Yassin

Journal of Family and Community Medicine 2019 26(1):61-63

Coronary heart disease is a serious complication of dyslipidemia. Pitavastatin is a more commonly prescribed medication for the treatment of dyslipidemia. Here, we report the case of a 37-year-old female, a known patient with well-controlled bronchial asthma. She was recently found to be dyslipidemic and started on pitavastatin calcium 4 mg once a day (OD). On the 10th day of treatment, she began to have crushing chest pain and was admitted to the hospital. All investigations for coronary heart disease came out negative. Her symptoms improved dramatically when pitavastatin was stopped. Pitavastatin is reported to cause myalgia and muscle spasm, especially at higher doses. There is evidence in literature that this medication might cause chest pain in old obese ladies if taken at high doses. We report this case as a possibility of chest pain even in younger females.