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1.  Intimate partner violence and Musculoskeletal injury: bridging the knowledge gap in Orthopaedic fracture clinics 
Intimate partner violence (IPV) is a serious health issue. There have been widespread research efforts in the area of IPV over the past several decades, primarily focusing on obstetrics, emergency medicine, and primary care settings. Until recently there has been a paucity of research focusing on IPV in surgery, and thus a resultant knowledge gap. Renewed interest in the underlying risk of IPV among women with musculoskeletal injuries has fueled several important studies to determine the nature and scope of this issue in orthopaedic surgery. Our review summarizes the evidence from surgical research in the field of IPV and provides recommendations for developing and evaluating an IPV identification and support program and opportunities for future research.
doi:10.1186/1471-2474-14-23
PMCID: PMC3585708  PMID: 23316813
Intimate partner violence; Domestic violence; Identification program; Orthopaedic surgery; Musculoskeletal injury
2.  Biomarkers of peripheral muscle fatigue during exercise 
Background
Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise.
Results
BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate-metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated.
Conclusions
Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue.
doi:10.1186/1471-2474-13-218
PMCID: PMC3534479  PMID: 23136874
Biomarker; Biological marker; Muscle fatigue; Monitoring; Muscle exercise; Exercise fatigue
3.  Malformations of the craniocervical junction (chiari type I and syringomyelia: classification, diagnosis and treatment) 
BMC Musculoskeletal Disorders  2009;10(Suppl 1):S1.
Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation.
It is important to determine the needs of the patients in terms of health-care, social, educational, occupational, and relationship issues, in addition to those derived from information aspects, particularly at onset of symptoms.
Currently, there is no consensus among the specialists regarding the etiology of the disease or how to approach, monitor, follow-up, and treat the condition.
It is necessary that the physicians involved in the care of people with this condition comprehensively approach the management and follow-up of the patients, and that they organize interdisciplinary teams including all the professionals that can help to increase the quality of life of patients.
doi:10.1186/1471-2474-10-S1-S1
PMCID: PMC2796052  PMID: 20018097
4.  Probiotics, prebiotics and synbiotics- a review 
Journal of Food Science and Technology  2015;52(12):7577-7587.
The health benefits imparted by probiotics and prebiotics as well as synbiotics have been the subject of extensive research in the past few decades. These food supplements termed as functional foods have been demonstrated to alter, modify and reinstate the pre-existing intestinal flora. They also facilitate smooth functions of the intestinal environment. Most commonly used probiotic strains are: Bifidobacterium, Lactobacilli, S. boulardii, B. coagulans. Prebiotics like FOS, GOS, XOS, Inulin; fructans are the most commonly used fibers which when used together with probiotics are termed synbiotics and are able to improve the viability of the probiotics. Present review focuses on composition and roles of Probiotics, Prebiotics and Synbiotics in human health. Furthermore, additional health benefits like immune-modulation, cancer prevention, inflammatory bowel disease etc. are also discussed.
Graphical abstractPictorial summary of health benefits imparted by probiotics, prebiotics and synbiotics
doi:10.1007/s13197-015-1921-1
PMCID: PMC4648921  PMID: 26604335
Probiotics; Prebiotics; Synbiotics; Intestinal disorders; Cancer; Cardiovascular diseases
5.  Autophagy in Tuberculosis 
Autophagy as an immune mechanism controls inflammation and acts as a cell-autonomous defense against intracellular microbes including Mycobacterium tuberculosis. An equally significant role of autophagy is its anti-inflammatory and tissue-sparing function. This combination of antimicrobial and anti-inflammatory actions prevents active disease in animal models. In human populations, genetic links between autophagy, inflammatory bowel disease, and susceptibility to tuberculosis provide further support to these combined roles of autophagy. The autophagic control of M. tuberculosis and prevention of progressive disease provide novel insights into physiological and immune control of tuberculosis. It also offers host-based therapeutic opportunities because autophagy can be pharmacologically modulated.
Autophagy enables cells to capture pathogens (e.g., Mycobacterium tuberculosis) and kill them in lysosomes. It can also suppress excessive inflammatory responses that contribute to disease progression.
doi:10.1101/cshperspect.a018481
PMCID: PMC4208715  PMID: 25167980
6.  Anthropometric Measurements and Periodontal Diseases in Children and Adolescents: A Systematic Review and Meta-Analysis123 
Advances in Nutrition  2015;6(6):828-841.
The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and adolescents. We searched PubMed, Institute for Scientific Information Web of Knowledge, Cochrane Library, and 7 additional databases, following the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, up to December 2014. Observational studies reporting data on the association between anthropometric measurements and periodontal diseases in 2–18-y-old participants were included. An initial search identified 4191 papers; 278 potentially effective studies (k = 0.82) and 16 effective studies (k = 0.83) were included after screening. The mean quality of evidence among the studies was 20.3, according to the Strengthening the Reporting of Observational studies in Epidemiology checklist (k = 0.79). Meta-analyses showed that obesity (measured by body mass index) was significantly associated with visible plaque index (OR: 4.75; 95% CI: 2.42, 9.34), bleeding on probing (OR: 5.41; 95% CI: 2.75, 10.63), subgingival calculus (OR: 3.07; 95% CI: 1.10, 8.62), probing depth (OR: 14.15; 95% CI: 5.10, 39.25) and flow rate of salivary secretion (standardized mean difference: −0.89; 95% CI: −1.18, −0.61). However, various results were reported in the effective studies that were not included in meta-analyses. In conclusion, obesity is associated with some signs of periodontal disease in children and adolescents. Further studies with a comprehensive prospective cohort design and more potential variables are recommended.
doi:10.3945/an.115.010017
PMCID: PMC4642430  PMID: 26567204
anthropometry; oral health; obesity; adolescent; systematic review
7.  Spinal metastases: From conventional fractionated radiotherapy to single-dose SBRT 
Aim
To review the recent evolution of spine SBRT with emphasis on single dose treatments.
Background
Radiation treatment of spine metastases represents a challenging problem in clinical oncology, because of the high risk of inflicting damage to the spinal cord. While conventional fractionated radiation therapy still constitutes the most commonly used modality for palliative treatment, notwithstanding its efficacy in terms of palliation of pain, local tumor control has been approximately 60%. This limited effectiveness is due to previous lack of technology to precisely target the tumor while avoiding the radiosensitive spinal cord, which constitutes a dose-limiting barrier to tumor cure.
Materials and methods
A thorough review of the available literature on spine SBRT has been carried out and critically assessed.
Results
Stereotactic body radiotherapy (SBRT) emerges as an alternative, non-invasive high-precision approach, which allows escalation of tumor dose, while effectively sparing adjacent uninvolved organs at risk. Engaging technological advances, such as on-line Cone Beam Computed Tomography (CBCT), coupled with Dynamic Multi-Leaf Collimation (DMLC) and rapid intensity-modulated (IMRT) beam delivery, have promoted an interactive image-guided (IGRT) approach that precisely conforms treatment onto a defined target volume with a rapid dose fall-off to collateral non-target tissues, such as the spinal cord. Recent technological developments allow the use of the high-dose per fraction mode of hypofractionated SBRT for spinal oligometastatic cancer, even if only a few millimeters away from the tumor.
Conclusion
Single-dose spine SBRT, now increasingly implemented, yields unprecedented outcomes of local tumor ablation and safety, provided that advanced technology is employed.
doi:10.1016/j.rpor.2015.03.004
PMCID: PMC4661345  PMID: 26696786
SBRT; SRS; Single-fraction; Stereotactic radiotherapy; Radiosurgery; IGRT
8.  Diagnosis and Management of Multiple Sclerosis in Children 
Growing evidence indicates the safety and well toleration of treatment by Disease-modifying in children suffering multiple sclerosis (MS). The treatment is not straight forward in a great number of patients, thus patients with pediatric MS must be managed by experienced specialized centers. Common treatments of multiple sclerosis for adults are first-line therapies. These therapies (firstline) are safe for children. Failure in treatment that leads to therapy alteration is almost prevalent in pediatric MS. Toleration against current second-line therapies has been shown in multiple sclerosis children. Oral agents have not been assessed in children MS patients. Although clinical trials in children are insufficient, immunomodulating managed children, experience a side effect similar to the adult MS patients. However, further prospective clinical studies, with large sample size and long follow-up are needed to distinguish the benefits and probable side effects of pediatric MS therapies.
PMCID: PMC4928611  PMID: 27375751
Disease-modifying therapies; Pediatric MS; Multiple sclerosis; Treatment
9.  Surgical approach to right colon cancer: From open technique to robot. State of art 
This work is a topic highlight on the surgical treatment of the right colon pathologies, focusing on the literature state of art and comparing the open surgery to the different laparoscopic and robotic procedures. Different laparoscopic procedures have been described for the treatment of right colon tumors: Totally laparoscopic right colectomy, laparoscopic assisted right colectomy, laparoscopic facilitated right colectomy, hand-assisted right colectomy, single incision laparoscopic surgery colectomy, robotic right colectomy. Two main characteristics of these techniques are the different type of anastomosis: Intracorporeal (for totally laparoscopic right colectomy, single incision laparoscopic surgery colectomy, laparoscopic assisted right colectomy and robotic technique) or extracorporeal (for laparoscopic assisted right colectomy, laparoscopic facilitated right colectomy, hand-assisted right colectomy and open right colectomy) and the different incision (suprapubic, median or transverse on the right side of abdomen). The different laparoscopic techniques meet the same oncological criteria of radicalism as the open surgery for the right colon. The totally laparoscopic right colectomy with intracorporeal anastomosis and even more the single incision laparoscopic surgery colectomy, remain a technical challenge due to the complexity of procedures (especially for the single incision laparoscopic surgery colectomy) and the particular right colon vascular anatomy but they seem to have some theoretical advantages compared to the other laparoscopic and open procedures. Data reported in literature while confirming the advantages of laparoscopic approach, do not allow to solve controversies about which is the best laparoscopic technique (Intracorporeal vs Extracorporeal Anastomosis) to treat the right colon cancer. However, the laparoscopic techniques with intracorporeal anastomosis for the right colon seem to show some theoretical advantages (functional, technical, oncological and cosmetic advantages) even if all studies conclude that further prospective randomized trials are necessary. Robotic technique may be useful to overcome the problems related to inexperience in laparoscopy in some surgical centers.
doi:10.4240/wjgs.v8.i8.564
PMCID: PMC5003935  PMID: 27648160
Mini-invasive right colectomy; Robotic right colectomy; Intracorporeal anastomosis; Extracorporeal anastomosis; Totally laparoscopic right colectomy
10.  The sympathetic/parasympathetic imbalance in heart failure with reduced ejection fraction 
European Heart Journal  2015;36(30):1974-1982.
Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy.
doi:10.1093/eurheartj/ehv087
PMCID: PMC4528097  PMID: 25975657
Baroreceptor reflex; Chemoreceptor reflex; Exercise; Heart failure; Human; Parasympathetic nervous system; Sleep apnoea; Sympathetic nervous system
11.  The Quanta Image Sensor: Every Photon Counts 
Sensors (Basel, Switzerland)  2016;16(8):1260.
The Quanta Image Sensor (QIS) was conceived when contemplating shrinking pixel sizes and storage capacities, and the steady increase in digital processing power. In the single-bit QIS, the output of each field is a binary bit plane, where each bit represents the presence or absence of at least one photoelectron in a photodetector. A series of bit planes is generated through high-speed readout, and a kernel or “cubicle” of bits (x, y, t) is used to create a single output image pixel. The size of the cubicle can be adjusted post-acquisition to optimize image quality. The specialized sub-diffraction-limit photodetectors in the QIS are referred to as “jots” and a QIS may have a gigajot or more, read out at 1000 fps, for a data rate exceeding 1 Tb/s. Basically, we are trying to count photons as they arrive at the sensor. This paper reviews the QIS concept and its imaging characteristics. Recent progress towards realizing the QIS for commercial and scientific purposes is discussed. This includes implementation of a pump-gate jot device in a 65 nm CIS BSI process yielding read noise as low as 0.22 e− r.m.s. and conversion gain as high as 420 µV/e−, power efficient readout electronics, currently as low as 0.4 pJ/b in the same process, creating high dynamic range images from jot data, and understanding the imaging characteristics of single-bit and multi-bit QIS devices. The QIS represents a possible major paradigm shift in image capture.
doi:10.3390/s16081260
PMCID: PMC5017425  PMID: 27517926
photon counting; image sensor; quanta image sensor; QIS; low read noise; low power
12.  Myoelectric control of prosthetic hands: state-of-the-art review 
Myoelectric signals (MES) have been used in various applications, in particular, for identification of user intention to potentially control assistive devices for amputees, orthotic devices, and exoskeleton in order to augment capability of the user. MES are also used to estimate force and, hence, torque to actuate the assistive device. The application of MES is not limited to assistive devices, and they also find potential applications in teleoperation of robots, haptic devices, virtual reality, and so on. The myoelectric control-based prosthetic hand aids to restore activities of daily living of amputees in order to improve the self-esteem of the user. All myoelectric control-based prosthetic hands may not have similar operations and exhibit variation in sensing input, deciphering the signals, and actuating prosthetic hand. Researchers are focusing on improving the functionality of prosthetic hand in order to suit the user requirement with the different operating features. The myoelectric control differs in operation to accommodate various external factors. This article reviews the state of the art of myoelectric prosthetic hand, giving description of each control strategy.
doi:10.2147/MDER.S91102
PMCID: PMC4968852  PMID: 27555799
EMG; assistive device; amputee; myoelectric control; electric powered; body powered; bioelectric signal control
13.  Comparing the Roles of EUS, ERCP and MRCP in Idiopathic Acute Recurrent Pancreatitis 
Acute recurrent pancreatitis (ARP) is defined as more than two attacks of acute pancreatitis with complete or almost complete resolution of symptoms and signs of pancreatitis between episodes. The initial evaluation fails to detect the cause of ARP in 10%–30% of patients, whose condition is classified as idiopathic ARP. Endoscopic ultrasound (EUS) has gained increasing attention as a useful imaging modality for the pancreas and the extrahepatic biliary tree. The close proximity of the pancreas to the digestive tract allows EUS to obtain detailed images of this organ. This review aims to record pancreaticobiliary endoscopic ultrasound (EUS) and other imaging modalities in the clinical management of patients with idiopathic ARP.
doi:10.4137/CGast.S37927
PMCID: PMC4915784  PMID: 27375362
idiopathic acute recurrent pancreatitis; endoscopic ultrasound
14.  MYC Activation Is a Hallmark of Cancer Initiation and Maintenance 
The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the “hallmark” features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be “addicted” to MYC because of both tumor cell–intrinsic, cell-autonomous and host-dependent, immune cell–dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis.
Many cancers require sustained MYC activation. MYC induces tumorigenesis by evading multiple tumor-suppressing mechanisms (e.g., apoptosis). But on MYC suppression, these mechanisms are restored.
doi:10.1101/cshperspect.a014241
PMCID: PMC4031954  PMID: 24890832
15.  Pathological conditions re-shape physiological Tregs into pathological Tregs 
Burns and trauma  2015;3(1):1.
CD4+FOXP3+ regulatory T cells (Tregs) are a subset of CD4 T cells that play an essential role in maintaining peripheral immune tolerance, controlling acute and chronic inflammation, allergy, autoimmune diseases, and anti-cancer immune responses. Over the past 20 years, significant progress has been made since Tregs were first characterized in 1995. Many concepts and principles regarding Tregs generation, phenotypic features, subsets (tTregs, pTregs, iTregs, and iTreg35), tissue specificity (central Tregs, effector Tregs, and tissue resident Tregs), homeostasis (highly dynamic and apoptotic), regulation of Tregs by receptors for PAMPs and DAMPs, Treg plasticity (re-differentiation to other CD4 T helper cell subsets, Th1, Th2, Tfh and Th17), and epigenetic regulation of Tregs phenotypes and functions have been innovated. In this concise review, we want to briefly analyze these eight new progresses in the study of Tregs. We have also proposed for the first time a novel concept that “physiological Tregs” have been re-shaped into “pathological Tregs” in various pathological environments. Continuing of the improvement in our understanding on this important cellular component about the immune tolerance and immune suppression, would lead to the future development of novel therapeutics approaches for acute and chronic inflammatory diseases, allergy, allogeneic transplantation-related immunity, sepsis, autoimmune diseases, and cancers.
doi:10.1186/s41038-015-0001-0
PMCID: PMC4662545  PMID: 26623425
regulatory T cells; immune suppression; epigenetic mechanisms; histone modifications; metabolic cardiovascular diseases
16.  Imaging of peritoneal deposits in ovarian cancer: A pictorial review 
World Journal of Radiology  2016;8(5):513-517.
As per incidence, ovarian carcinoma is the second most common gynaecological malignancy in women. In spite of advanced technology, patient awareness and effective screening methods, epithelial ovarian cancer is usually diagnosed at an advanced stage (stage III). Surgical debulking of disease is mainstay of improving the patient survival even in advanced stages. Thus exact delineation of cancer spread in the abdominal cavity guides the surgeon prior to the surgery, help them to decide resectability of lesion and plan for further need of other surgical speciality or need of neoadjuvant chemotherapy. Imaging particularly well-planned contrast-enhanced computed tomography answers most of the queries raised by the treating surgeon. The aim of this article is to review the way ovarian carcinoma spread in the peritoneal cavity and to stress the accurate interpretation of cancer deposits on imaging which can help the treating team to reach optimal management of patients.
doi:10.4329/wjr.v8.i5.513
PMCID: PMC4882408  PMID: 27247717
Ovarian carcinoma; Computed tomography; Peritoneal deposits
17.  The Impact of Massage Therapy on Function in Pain Populations—A Systematic Review and Meta-Analysis of Randomized Controlled Trials: Part II, Cancer Pain Populations 
Purpose. Pain is multi-dimensional and may be better addressed through a holistic, biopsychosocial approach. Massage therapy is commonly practiced among patients seeking pain management; however, its efficacy is unclear. This systematic review and meta-analysis is the first to rigorously assess the quality of massage therapy research and evidence for its efficacy in treating pain, function-related and health-related quality of life in cancer populations.
Methods. Key databases were searched from inception through February 2014. Eligible randomized controlled trials were assessed for methodological quality using the SIGN 50 Checklist. Meta-analysis was applied at the outcome level. A diverse steering committee interpreted the results to develop recommendations.
Results. Twelve high quality and four low quality studies were subsequently included in the review. Results demonstrate massage therapy is effective for treating pain compared to no treatment [standardized mean difference (SMD)  = −.20] and active (SMD = −0.55) comparators. Compared to active comparators, massage therapy was also found to be beneficial for treating fatigue (SMD = −1.06) and anxiety (SMD = −1.24).
Conclusion. Based on the evidence, weak recommendations are suggested for massage therapy, compared to an active comparator, for the treatment of pain, fatigue, and anxiety. No recommendations were suggested for massage therapy compared to no treatment or sham control based on the available literature to date. This review addresses massage therapy safety, research challenges, how to address identified research gaps, and necessary next steps for implementing massage therapy as a viable pain management option for cancer pain populations.
doi:10.1093/pm/pnw100
PMCID: PMC4975018  PMID: 27165967
Systematic Review; Meta-Analysis; Massage Therapy; Pain; Function; Health-Related Quality of Life
18.  New combination bronchodilators for chronic obstructive pulmonary disease: current evidence and future perspectives Dave Singh 
Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80–90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.
doi:10.1111/bcp.12545
PMCID: PMC4415707  PMID: 25377687
bronchodilators; COPD; fixed dose combinations; QVA149; umeclidinium; vilanterol
19.  Benign liver lesions: grey-scale and contrast-enhanced ultrasound appearances 
Ultrasound is often the first point of detection of liver lesions, with up to 75% of liver lesions detected at ultrasound having benign histology. In 2012, NICE issued recommendations that ultrasound contrast be used for the evaluation of incidentally discovered liver lesions. This has been demonstrated to provide a rapid and cost-effective evaluation for incidental liver lesions, in many cases precluding the need for further CT or MRI scans. The aim of this review is to demonstrate the ultrasound features of benign liver lesions, and to demonstrate their further characterisation with contrast ultrasound.
doi:10.1177/1742271X15575805
PMCID: PMC4760573  PMID: 27433246
Benign liver lesions; contrast-enhanced ultrasound; grey-scale ultrasound
20.  Does the use of specialist palliative care services modify the effect of socioeconomic status on place of death? A systematic review 
Palliative Medicine  2015;30(5):434-445.
Background:
Cancer patients in lower socioeconomic groups are significantly less likely to die at home and experience more barriers to access to palliative care. It is unclear whether receiving palliative care may mediate the effect of socioeconomic status on place of death.
Aim:
This review examines whether and how use of specialist palliative care may modify the effect of socioeconomic status on place of death.
Design:
A systematic review was conducted. Eligible papers were selected and the quality appraised by two independent reviewers. Data were synthesised using a narrative approach.
Data sources:
MEDLINE, Embase, CINAHL, PsycINFO and Web of Knowledge were searched (1997–2013). Bibliographies were scanned and experts contacted. Papers were included if they reported the effect of both socioeconomic status and use of specialist palliative care on place of death for adult cancer patients.
Results:
Nine studies were included. All study subjects had received specialist palliative care. With regard to place of death, socioeconomic status was found to have (1) no effect in seven studies and (2) an effect in one study. Furthermore, one study found that the effect of socioeconomic status on place of death was only significant when patients received standard specialist palliative care. When patients received more intense care adapted to their needs, the effect of socioeconomic status on place of death was no longer seen.
Conclusion:
There is some evidence to suggest that use of specialist palliative care may modify the effect of socioeconomic status on place of death.
doi:10.1177/0269216315602590
PMCID: PMC4838174  PMID: 26330454
Socioeconomic factors; palliative care; place of death; review; neoplasms
21.  Cytotoxicity of Nanoparticles Contained in Food on Intestinal Cells and the Gut Microbiota 
Toxicity of nanoparticles (NPs) upon oral exposure has been studied in animals using physiological changes, behavior, histology, and blood analysis for evaluation. The effects recorded include the combination of the action on cells of the exposed animal and the reaction of the microorganisms that populate the external and internal surfaces of the body. The importance of these microorganisms, collectively termed as microbiota, for the health of the host has been widely recognized. They may also influence toxicity of NPs but these effects are difficult to differentiate from toxicity on cells of the gastrointestinal tract. To estimate the likelihood of preferential damage of the microbiota by NPs the relative sensitivity of enterocytes and bacteria was compared. For this comparison NPs with antimicrobial action present in consumer products were chosen. The comparison of cytotoxicity with Escherichia coli as representative for intestinal bacteria and on gastrointestinal cells revealed that silver NPs damaged bacteria at lower concentrations than enterocytes, while the opposite was true for zinc oxide NPs. These results indicate that silver NPs may cause adverse effects by selectively affecting the gut microbiota. Fecal transplantation from NP-exposed animals to unexposed ones offers the possibility to verify this hypothesis.
doi:10.3390/ijms17040509
PMCID: PMC4848965  PMID: 27058534
silver; zinc oxide; nanotoxicology; cytotoxicity; antimicrobial effects
22.  Bird Integumentary Melanins: Biosynthesis, Forms, Function and Evolution 
Melanins are the ubiquitous pigments distributed in nature. They are one of the main pigments responsible for colors in living cells. Birds are among the most diverse animals regarding melanin-based coloration, especially in the plumage, although they also pigment bare parts of the integument. This review is devoted to the main characteristics of bird melanins, including updated views of the formation and nature of melanin granules, whose interest has been raised in the last years for inferring the color of extinct birds and non-avian theropod dinosaurs using resistant fossil feathers. The molecular structure of the two main types of melanin, eumelanin and pheomelanin, and the environmental and genetic factors that regulate avian melanogenesis are also presented, establishing the main relationship between them. Finally, the special functions of melanin in bird feathers are also discussed, emphasizing the aspects more closely related to these animals, such as honest signaling, and the factors that may drive the evolution of pheomelanin and pheomelanin-based color traits, an issue for which birds have been pioneer study models.
doi:10.3390/ijms17040520
PMCID: PMC4848976  PMID: 27070583
melanogenesis; pheomelanin; eumelanin; avian melanins
23.  Tenascin-X: beyond the architectural function 
Cell Adhesion & Migration  2015;9(1-2):154-165.
Tenascin-X is the largest member of the tenascin (TN) family of evolutionary conserved extracellular matrix glycoproteins, which also comprises TN-C, TN-R and TN-W. Among this family, TN-X is the only member described so far to exert a crucial architectural function as evidenced by a connective tissue disorder (a recessive form of Ehlers-Danlos syndrome) resulting from a loss-of-function of this glycoprotein in humans and mice. However, TN-X is more than an architectural protein, as it displays features of a matricellular protein by modulating cell adhesion. However, the cellular functions associated with the anti-adhesive properties of TN-X have not yet been revealed. Recent findings indicate that TN-X is also an extracellular regulator of signaling pathways. Indeed, TN-X has been shown to regulate the bioavailability of the Transforming Growth Factor (TGF)-β and to modulate epithelial cell plasticity. The next challenges will be to unravel whether the signaling functions of TN-X are functionally linked to its matricellular properties.
doi:10.4161/19336918.2014.994893
PMCID: PMC4422802  PMID: 25793578
cell signaling; Ehlers-Danlos syndrome (EDS); epithelial-to-mesenchymal transition (EMT); integrin α11β1; matricellular protein; tenascin-X; TGF-β activation
24.  Tracheal resection and reconstruction for malignant disease 
Journal of Thoracic Disease  2016;8(Suppl 2):S148-S152.
Malignant tracheal neoplasms are rare diseases, mostly represented by squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC). Symptoms presentation is often misleading and diagnosis may be delayed for months or years, so clinical suspicion plays a fundamental role. Corner stones in the diagnostic pathway are represented by rigid endoscopy and computed tomography (CT) scan, necessary to correctly stage the patients and identify the optimal surgical candidate. When appropriate, surgical resection and reconstruction is still the best opportunity to achieve a long-term survival with a good quality of life, but this kind of surgery is always a very challenging procedure and a wide experience with an in-depth knowledge of every technical detail, from selection of patient, to choice of surgical approach to reconstruction techniques, are needed and recommended.
doi:10.3978/j.issn.2072-1439.2016.02.04
PMCID: PMC4775262  PMID: 26981265
Tracheal cancer; tracheal resection; tracheal surgery; adenoid cystic carcinoma (ACC); squamous cell carcinoma (SCC)
25.  Kinematic upper limb evaluation of children and adolescents with cerebral palsy: a systematic review of the literature 
[Purpose] The aim of the present study was to perform a review of the literature on objective measures of upper limb movements in children and adolescents with cerebral palsy and describe the methods used to investigate upper limb kinematics in this population. [Materials and Methods] An extensive database search was performed using the keywords kinematics, upper limb, and cerebral palsy. A total of 146 papers were identified, but only five met the inclusion criteria. [Results] No consensus was found regarding the data collection, processing, and analysis procedures or reporting of the results. [Conclusion] Standardization of the protocol for 3D upper limb movement analysis will provide the foundation for comparable, reproducible results and eventually facilitate the planning of treatment interventions.
doi:10.1589/jpts.28.695
PMCID: PMC4793036  PMID: 27065566
Upper limbs; Kinematics; Cerebral palsy

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