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1.  Exploring and explaining low participation in physical activity among children and young people with asthma: a review 
BMC Family Practice  2008;9:40.
Asthma is the most common chronic illness among children and accounts for 1 in 5 of all child GP consultations. This paper reviews and discusses recent literature outlining the growing problem of physical inactivity among young people with asthma and explores the psychosocial dimensions that may explain inactivity levels and potentially relevant interventions and strategies, and the principles that should underpin them.
A narrative review based on an extensive and documented search of search of CinAHL, Embase, Medline, PsycINFO and the Cochrane Library.
Results & Discussion
Children and young people with asthma are generally less active than their non-asthmatic peers. Reduced participation may be influenced by organisational policies, family illness beliefs and behaviours, health care advice, and inaccurate symptom perception and attribution. Schools can be reluctant to encourage children to take part in physical education or normal play activity due to misunderstanding and a lack of clear corporate guidance. Families may accept a child's low level of activity if it is perceived that breathlessness or the need to take extra inhalers is harmful. Many young people themselves appear to accept sub-optimal control of symptoms and frequently misinterpret healthy shortness of breath on exercising with the symptoms of an impending asthma attack.
A multi-faceted approach is needed to translate the rhetoric of increasing activity levels in young people to the reality of improved fitness. Physical activity leading to improved fitness should become part of a goal orientated management strategy by schools, families, health care professionals and individuals. Exercise induced asthma should be regarded as a marker of poor control and a need to increase fitness rather as an excuse for inactivity. Individuals' perceptual accuracy deserves further research attention.
PMCID: PMC2447841  PMID: 18590558
2.  Critically ill patients with cancer: chances and limitations of intensive care medicine—a narrative review 
ESMO Open  2016;1(5):e000018.
This narrative review deals with the challenge of defining adequate therapy goals and intensive care unit (ICU) admission criteria for critically ill patients with cancer. Several specific complications of critically ill patients with cancer require close collaborations of intensive care and cancer specialists. Intensivists require a basic understanding of the pathophysiology, diagnosis and therapy of common cancer-specific problems. Cancer specialists must be knowledgeable in preventing, detecting and treating imminent or manifest organ failures. In case of one or more organ dysfunctions, ICU admissions must be evaluated early. In order to properly define the therapy goals for critically ill patients with cancer, decision-makers must be aware of the short-term intensive care prognosis as well as the long-term oncological options and perspectives. Multidisciplinary teamwork is key when it comes down to decisions on ICU admission, planning of therapeutic aims, patient management in the ICU and tailored therapy limiting with smooth transition into a palliative care (PC) setting, whenever appropriate.
PMCID: PMC5070251  PMID: 27843637
cancer; admission criteria; intensive care unit; palliative care
3.  Intravenous Lipid Emulsions in Parenteral Nutrition123 
Advances in Nutrition  2015;6(5):600-610.
Fat is an important macronutrient in the human diet. For patients with intestinal failure who are unable to absorb nutrients via the enteral route, intravenous lipid emulsions play a critical role in providing an energy-dense source of calories and supplying the essential fatty acids that cannot be endogenously synthesized. Over the last 50 y, lipid emulsions have been an important component of parenteral nutrition (PN), and over the last 10–15 y many new lipid emulsions have been manufactured with the goal of improving safety and efficacy profiles and achieving physiologically optimal formulations. The purpose of this review is to provide a background on the components of lipid emulsions, their role in PN, and to discuss the lipid emulsions available for intravenous use. Finally, the role of parenteral fat emulsions in the pathogenesis and management of PN-associated liver disease in PN-dependent pediatric patients is reviewed.
PMCID: PMC4561835  PMID: 26374182
fatty acids; lipid metabolism; ω-3 fatty acids; parenteral nutrition; parenteral nutrition-associated liver disease
4.  Electronic Structures of Silicene Nanoribbons: Two-Edge-Chemistry Modification and First-Principles Study 
In this paper, we investigate the structural and electronic properties of zigzag silicene nanoribbons (ZSiNRs) with edge-chemistry modified by H, F, OH, and O, using the ab initio density functional theory method and local spin-density approximation. Three kinds of spin polarized configurations are considered: nonspin polarization (NM), ferromagnetic spin coupling for all electrons (FM), ferromagnetic ordering along each edge, and antiparallel spin orientation between the two edges (AFM). The H, F, and OH groups modified 8-ZSiNRs have the AFM ground state. The directly edge oxidized (O1) ZSiNRs yield the same energy and band structure for NM, FM, and AFM configurations, owning to the same sp2 hybridization. And replacing the Si atoms on the two edges with O atoms (O2) yields FM ground state. The edge-chemistry-modified ZSiNRs all exhibit metallic band structures. And the modifications introduce special edge state strongly localized at the Si atoms in the edge, except for the O1 form. The modification of the zigzag edges of silicene nanoribbons is a key issue to apply the silicene into the field effect transistors (FETs) and gives more necessity to better understand the experimental findings.
PMCID: PMC4993729  PMID: 27550051
Silicene; Electronic structure; Localized edge states; Density functional theory
5.  Treatment of Nonalcoholic Fatty Liver Disease: Where do we Stand? An Overview 
Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, the prevalence of which had progressively increased over the past 10 years where other liver diseases remained at the same prevalence rates or are expected to decrease as in the case of hepatitis C virus (HCV). The treatment of NAFLD is of prime concern to health care professionals and patients due to the significant mortality and morbidity it implies; the problem is further escalated by the fact that standard of care medications targeting NAFLD remain experimental and without evidence base. Treatment nowadays is focused on lifestyle modification and managing the comorbid associated diseases, with a possible role for some hepatic protective agents. This review presents all the medications that had been proposed and used for the treatment of NAFLD with or without scientific rationale and includes agents for weight loss, insulin sensitizers, drugs that reduce blood lipids, glucagon-mimetics, drugs that may reduce fibrosis, angiotensin receptor blockers, and medicines believed to reduce endoplasmic reticular stress such as vitamin E, ursodeoxycholic acid, and S-adenosyl methionine. A quick review of the newer agents that proved to be promising such as obeticholic acid and GFT505 and the medicines that are still in the pipeline is also presented.
PMCID: PMC4817303  PMID: 26997214
Insulin sensitizers; liver protectors; Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis; Ursodeoxycholic acid; vitamin E
6.  Novel molecular diagnostic tools for malaria elimination: a review of options from the point of view of high-throughput and applicability in resource limited settings 
Malaria Journal  2016;15:88.
As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination. To interrupt transmission, changes in control strategies are likely to require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings. Currently available immunochromatographic lateral flow rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/µL making them insufficiently sensitive for detecting all carriers. Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time. This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination.
PMCID: PMC4754967  PMID: 26879936
Malaria elimination; High-throughput; Molecular diagnostics; LAMP; PCR; Field application
7.  DNA methylation markers for oral pre-cancer progression: A critical review 
Oral Oncology  2016;53:1-9.
Graphical abstract
•We critically reviewed DNA methylation patterns for oral pre-cancer progression.•Suggestive signals included hyper-methylated loci in p16, p14, MGMT and DAPK.•Large epigenome-wide explorations are needed to validate these markers and to identify new risk loci and biological pathways of disease progression.
Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control (n = 15), DNA-repair (n = 7), cell-cycle-signalling (n = 4) and apoptosis (n = 3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57–63.6% versus 8–32.1%; p < 0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci (TRHDE; ZNF454; KCNAB3). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease progression.
PMCID: PMC4788701  PMID: 26690652
DNA methylation; Oral pre-cancer; Bio-marker; Epigenetics; Leukoplakia; Oral sub-mucous fibrosis; Promoter regions; CpG sites; Tumour suppressor genes; Diagnostic marker
8.  Performance of Positron Emission Tomography and Positron Emission Tomography/Computed Tomography Using Fluorine-18-Fluorodeoxyglucose for the Diagnosis, Staging, and Recurrence Assessment of Bone Sarcoma 
Medicine  2015;94(36):e1462.
To investigate the performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the diagnosis, staging, restaging, and recurrence surveillance of bone sarcoma by systematically reviewing and meta-analyzing the published literature.
To retrieve eligible studies, we searched the MEDLINE, Embase, and the Cochrane Central library databases using combinations of following Keywords: “positron emission tomography” or “PET,” and “bone tumor” or “bone sarcoma” or “sarcoma.” Bibliographies from relevant articles were also screened manually. Data were extracted and the pooled sensitivity, specificity, and diagnostic odds ratio (DOR), on an examination-based or lesion-based level, were calculated to appraise the diagnostic accuracy of 18F-FDG PET and PET/CT. All statistical analyses were performed using Meta-Disc 1.4.
Forty-two trials were eligible. The pooled sensitivity and specificity of PET/CT to differentiate primary bone sarcomas from benign lesions were 96% (95% confidence interval [CI], 93–98) and 79% (95% CI, 63–90), respectively. For detecting recurrence, the pooled results on an examination-based level were sensitivity 92% (95% CI, 85–97), specificity 93% (95% CI, 88–96), positive likelihood ratio (PLR) 10.26 (95% CI, 5.99–17.60), and negative likelihood ratio (NLR) 0.11 (95% CI, 0.05–0.22). For detecting distant metastasis, the pooled results on a lesion-based level were sensitivity 90% (95% CI, 86–93), specificity 85% (95% CI, 81–87), PLR 5.16 (95% CI, 2.37–11.25), and NLR 0.15 (95% CI, 0.11–0.20). The accuracies of PET/CT for detecting local recurrence, lung metastasis, and bone metastasis were satisfactory. Pooled outcome estimates of 18F-FDG PET were less complete compared with those of PET/CT.
18F-FDG PET and PET/CT showed a high sensitivity for diagnosing primary bone sarcoma. Moreover, PET/CT demonstrated excellent accuracy for the staging, restaging, and recurrence surveillance of bone sarcoma. However, to avoid misdiagnosis, pathological examination or long-term follow-up should be carried out for 18F-FDG-avid lesions in patients with suspected bone sarcoma.
PMCID: PMC4616630  PMID: 26356700
9.  The Role of Cardiolipin in Cardiovascular Health 
BioMed Research International  2015;2015:891707.
Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the gene encoding tafazzin, the transacylase that carries out the second CL remodeling step. In addition to BTHS, CL is linked to other cardiovascular diseases (CVDs), including cardiomyopathy, atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and Tangier disease. The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways. In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health.
PMCID: PMC4537736  PMID: 26301254
10.  Noninvasive intraocular pressure monitoring: current insights 
Glaucoma is the second leading cause of blindness worldwide and intraocular pressure (IOP) is currently its only modifiable risk factor. Peak IOP has for a long time been considered as a major contributor to glaucoma progression, but its effects may depend not only on its magnitude, but also on its time course. The IOP is nowadays considered to be a dynamic parameter with a circadian rhythm and spontaneous changes. The current practice of punctual measuring the IOP during office hours is therefore a suboptimal approach, which does not take into account the natural fluctuation of IOP. Because of its static nature a single IOP measurement in sitting position fails to document the true range of an individual’s IOP, peak IOP, or variation throughout the day. Phasing means monitoring a patient’s IOP during the daytime or over a 24-hour period. This can provide additional information in the management of glaucoma patients. This review focuses on the current insight of non-invasive IOP monitoring as a method of obtaining more complete IOP profiles. Invasive techniques using an implantable sensor are beyond the scope of this review.
PMCID: PMC4525787  PMID: 26257509
glaucoma; phasing; self-tonometry; contact lens sensor
11.  The Epidemiology of Tobacco Use among Khat Users: A Systematic Review 
BioMed Research International  2015;2015:313692.
Khat, an “amphetamine-like green leaf,” may influence the consumption of tobacco. This study reviews the epidemiology of tobacco use among khat users. Electronic database searches using appropriate keywords/terms were conducted to identify observational studies of khat use. Assessment of quality and risk of bias of all included studies was conducted, and the results were synthesised descriptively. Nine eligible cross-sectional studies were identified. All assessed self-reported tobacco among khat users and were carried out in Africa and the Middle East. Eight reported cigarettes and one reported waterpipes as the mode of use. Methods of tobacco use prevalence assessment varied. Prevalence of “current” tobacco use among students and university teachers ranged from 29 to 37%; “lifetime” tobacco use in university teachers was 58% and “undefined” tobacco use in nonspecific adults and students ranged from 17 to 78%. Daily tobacco use among adults was reported as 17% whilst simultaneous tobacco and khat use was reported as between 14 and 30% in students. In conclusion, tobacco prevalence among khat users appears significant. Findings should be interpreted cautiously due to self-reported tobacco use, diversity in questions assessing tobacco use, and type of tobacco consumption. Future research should address the methodological shortcomings identified in this review before appropriate policy interventions can be developed.
PMCID: PMC4529904  PMID: 26273606
12.  Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: ‘What does not kill me strengthens me' 
British Journal of Cancer  2015;112(11):1725-1732.
Therapy resistance and tumour relapse after drug therapy are commonly explained by Darwinian selection of pre-existing drug-resistant, often stem-like cancer cells resulting from random mutations. However, the ubiquitous non-genetic heterogeneity and plasticity of tumour cell phenotype raises the question: are mutations really necessary and sufficient to promote cell phenotype changes during tumour progression? Cancer therapy inevitably spares some cancer cells, even in the absence of resistant mutants. Accumulating observations suggest that the non-killed, residual tumour cells actively acquire a new phenotype simply by exploiting their developmental potential. These surviving cells are stressed by the cytotoxic treatment, and owing to phenotype plasticity, exhibit a variety of responses. Some are pushed into nearby, latent attractor states of the gene regulatory network which resemble evolutionary ancient or early developmental gene expression programs that confer stemness and resilience. By entering such stem-like, stress-response states, the surviving cells strengthen their capacity to cope with future noxious agents. Considering non-genetic cell state dynamics and the relative ease with which surviving but stressed cells can be tipped into latent attractors provides a foundation for exploring new therapeutic approaches that seek not only to kill cancer cells but also to avoid promoting resistance and relapse that are inherently linked to the attempts to kill them.
PMCID: PMC4647245  PMID: 25965164
cell plasticity; therapy-induced drug resistance; non-genetic heterogeneity; cancer attractor; epigenetic landscape
13.  Multidisciplinary Treatment Approach for Prosthetic Vascular Graft Infection in the Thoracic Aortic Area 
Prosthetic vascular graft infection in the thoracic aortic area is a rare but serious complication. Adequate management of the complication is essential to increase the chance of success of open surgery. While surgical site infection is suggested as the root cause of the complication, it is also related to decreased host tolerance, especially as found in elderly patients. The handling of prosthetic vascular graft infection has been widely discussed to date. This paper mainly provides a summary of literature reports published within the past 5 years to discuss issues related to multidisciplinary treatment approaches, including surgical site infection, timing of onset, diagnostic methods, causative pathogens, auxiliary diagnostic methods, antibiotic treatment, anti-infective structures of vascular prostheses, surgical treatment, treatment strategy against infectious aortic aneurysms, future surgical treatment, postoperative systemic therapy, and antimicrobial stewardship. A thorough understanding of these issues will enable us to prevent prosthetic vascular graft infection in the thoracic aortic area as far as possible. In the event of its occurrence, the early introduction of appropriate treatment is expected to cure the disease without worsening of the underlying pathological condition.
PMCID: PMC4904849  PMID: 26356686
thoracic aorta; prosthetic vascular graft infection; multidisciplinary treatment
14.  Cholesterol in pregnancy: a review of knowns and unknowns 
Obstetric Medicine  2011;4(4):147-151.
Cholesterol forms part of every cell in the human body, and also helps make and metabolize hormones, bile acids and vitamin D. Human plasma cholesterol levels are determined by production in the liver and by dietary intake. Lipoproteins carry cholesterol around the body, and facilitate it crossing the placenta. Cholesterol is carefully monitored in the non-pregnant adult population, where its association with atherosclerosis and cardiovascular disease is well understood. Although it is known that cholesterol rises in pregnancy, at present it is not routinely measured or treated. The effects of maternal high cholesterol on pregnancy and on fetal development are not yet fully understood. However, a growing body of evidence from animal and human studies suggests adverse consequences of high cholesterol levels in pregnancy.
PMCID: PMC4989641  PMID: 27579113
cholesterol; pregnancy; low-density lipoprotein (LDL); high-density lipoprotein (HDL); atherosclerosis
15.  Laparoscopic and robot-assisted surgery in the management of urinary lithiasis 
Arab Journal of Urology  2012;10(1):32-39.
To review the current role of laparoscopy and robot-assisted laparoscopy for managing urinary lithiasis.
The contemporary indications for laparoscopic stone management are: anatomical variations in location or shape of the kidney (pelvic kidney, horseshoe kidney and malrotated kidney); coexisting pathologies, e.g. pelvi-ureteric junction obstruction; and stones in a renal unit with lower ureteric obstruction. The laparoscopic approach allows the simultaneous management of both the pathologies. Symptomatic stones in diverticula not amenable to endourological intervention can be treated with laparoscopy. Large impacted pelvic and ureteric calculi with a functioning renal unit are an indication for laparoscopic ureterolithotomy or pyelolithotomy. This review of current reports suggests that in a selected group of patients with complex stone disease the laparoscopic approach offers good success rates with minimal complications. There are few reports of robotic procedures in stone disease but existing data suggest that it is feasible.
Laparoscopic surgery is effective for complex renal stones and offers excellent stone clearance rates with minimal morbidity. Laparoscopic surgery is complementary in managing these stones. Robot-assisted laparoscopic technique of urinary tract stone management is in its early stage of implementation and randomised trials that compare robot assisted outcomes with other minimally invasive techniques are needed.
PMCID: PMC4442910  PMID: 26558002
CE, contrast-enhanced; PCNL, percutaneous nephrolithotomy; LAN, laparoscopic anatrophic nephrolithotomy; LU, laparoscopic ureterolithotomy; LP(P), laparoscopic pyelolithotomy (with pyeloplasty); US, ultrasonography; Laparoscopic surgery; Robotics; Stones; Review

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