Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated plasma asymmetric dimethylarginine levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction

ABSTRACT Objectives: Beta-thalassemia major is associated with the increased risk of cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) has been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. In this study, we aimed to investigate circulating ADMA concentrations in children with beta-thalassemia major. Methods: Thirty-one beta-thalassemia major children aged between 4 and 16 year old and age, gender-matched 36 healthy controls were enrolled in the study. Plasma ADMA was measured along with the soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), P-selectin, and Pentraxin-3. Results: Age, gender and body mass index were similar in two groups. Plasma ADMA, sVCAM-1, and sICAM-1 measurements were significantly higher in beta-thalassemia major patients than the control group (p < 0.004 for ICAM-1, p < 0.001 for other parameters). There were positive significant correlations between ADMA, sVCAM-1 and sICAM-1 (r = 0.437, p < 0.001; r = 0.544, p < 0.001; r = 0.405, p < 0.001, respectively) in the whole group. Discussion: The findings of the current study show us that increased plasma ADMA levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction and may play a role in the development of premature atherosclerosis in beta-thalassemia major patients.
Congenital craniofacial anomalies

Purpose of review Congenital abnormalities of the cranium and face present complex diagnostic and therapeutic challenges to the ophthalmologist. Recent findings Patients with craniofacial anomalies are best treated by a multidisciplinary team that includes specialists from plastic surgery, neurosurgery, ophthalmology, otolaryngology, oromaxillofacial surgery, orthodontics, anesthesia, and genetics as well as specialists in support disciplines such as nursing, social work, and nutrition. Other subspecialty needs may be important to address behavioral and developmental issues as well as associated systemic anomalies and medical conditions. The specialists must work together to provide for the overall well being of the patient. To assist in the evaluation and treatment of these patients, the ophthalmologist must possess an understanding of craniofacial syndromes as well as the necessary medical and surgical interventions required to improve ocular and adnexal problems. Summary This article systematically reviews the major craniofacial anomalies of ophthalmic importance and highlights salient treatment issues.
Perceptions of the nurse practitioner role

Practice nurses' perceptions of the nurse practitioner role have not been widely investigated. It is the aim of this study to identify considerations that would influence a practice nurse's decision to become a nurse practitioner. Semi-structured interviews were conducted with 16 practice nurses in three primary care trusts in England. Collected data was examined by content analysis. It was found that confusion remains about the definition of the nurse practitioner role and the academic requirements to become one.
Impact of hepatitis C virus eradication on hepatocellular carcinogenesis

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related death in the world. Infection with hepatitis C virus (HCV) represents one of the most common risk factors for HCC development, and cases of HCV‐related complications have been rising over the last 2 decades. Although the standard for HCV therapy has been interferon (IFN)‐based for many years, the therapeutic revolution spurred by the development of direct‐acting antivirals (DAAs) promises to usher in a new era in which chronic HCV becomes a rare disease. On the basis of long‐term follow‐up of patients experiencing IFN‐based sustained virological responses (SVRs), it can be expected that rates of HCV‐associated HCC will decrease significantly after the widespread adoption of DAAs, but there remains a persistent risk for HCC even among some patients with advanced fibrosis who have achieved SVR. As such, individuals treated for HCV with advanced fibrosis should continue to be screened regularly for HCC after SVR. Furthermore, as the population of SVR patients grows, it will become imperative to accurately identify those individuals at high risk for developing HCC, appropriately allocate resources for screening, and consider cost‐effective chemopreventive strategies. Risk factors include preexisting advanced fibrosis/cirrhosis, older age, diabetes mellitus, and ethanol use. In addition, laboratory biomarkers and genetic signatures are currently being identified that not only predict the likelihood of HCC development in SVR patients but also may serve as dynamic indicators of therapeutic response. Cancer 2015;121:2874–2882. © 2015 American Cancer Society.
Ranibizumab versus bevacizumab for the treatment of neovascular age-related macular degeneration

Purpose of review This paper reviews the recent literature regarding the effectiveness, efficacy and safety of intravitreal bevacizumab as compared with ranibizumab for the treatment of neovascular age-related macular degeneration (nAMD). Recent findings Numerous randomized clinical trials have demonstrated the safety and efficacy of ranibizumab for the treatment of nAMD. Bevacizumab, developed, labeled and approved for the management of colorectal cancer, has been used off-label for the management of nAMD. However, given its lower cost and effectiveness, it is commonly used for many cases of nAMD. Recent clinical trials have demonstrated similar effectiveness between the two compounds in terms of visual acuity and central macular thickness. However, emerging data have suggested that these two compounds may have different ocular and systemic adverse event profiles; bevacizumab has been linked to both a higher risk of severe intraocular inflammation and a higher risk of incident arterial thromboembolic events. This incremental risk for both ocular and systemic adverse events may have an impact on the incremental cost–effectiveness ratio derived from health economic models that directly compare one anti-vascular endothelial growth factor (VEGF) compound to the other. Summary Numerous clinical trials, including the Comparison of AMD Treatment Trial, are underway examining the comparative efficacy of ranibizumab versus bevacizumab for the treatment of nAMD. While these studies may demonstrate clinical noninferiority of one anti-VEGF compound over another, they may not be adequately powered to detect important differences in ocular and systemic safety. Large-scale, appropriately powered safety studies need to be conducted to evaluate differences in safety.
Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non–small cell lung cancer

Treatment options for patients with non–small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood‐brain barrier–penetrating, microtubule‐targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases.
Effect of Aging on the Pluripotential Capacity of Human Bone Marrow Derived Mesenchymal Stem Cells

Purpose: The aim of study was to compare the differentiation capacity of mesenchymal stem cells (MSCs) obtained from human bone marrow (BM) according to the age of the donors. Materials and Methods: MSCs were isolated from the BM of young (n=16, 12.5±5.8 years) and elder (n=4, 48.5±7.2 years) patients with the consent of them. We analyzed the cell morphology and the cell surface markers of the MSCs. In addition, we assessed the cell senescence with serial cultures from both age groups. Cell pluripotentiality was analyzed by osteogenic, chondrogenic, and adipogenic induction media. We performed RT-PCR, a measurement of expression of alkaline phosphatase, and staining with von Kossa, safranin O, and oil red O stain. Results: All of the MSC samples tested, irrespective of the age of the donors, MSCs were all successfully isolated from twenty bone marrows. However, the number of cells of from the young donors was five times greater than that of the elderly donors. Senescence was observed over 10 passages in both age groups. The immunophenotypes of both age groups showed similar patterns. MSCs obtained from young and older donors showed the potential to differentiate into osteogenic, chondrogenic, and adipogenic lineages with no difference for both age groups. Conclusion: Our study supports that age does not influence the pluripotential capacity of human BM derived MSCs.
How many individuals will need to be screened to increase colorectal cancer screening prevalence to 80% by 2018?

A recent study estimates that 277,000 colorectal cancer (CRC) cases and 203,000 CRC deaths will be averted between 2013 and 2030 if the National Colorectal Cancer Roundtable goal of increasing CRC screening prevalence to 80% by 2018 is reached. However, the number of individuals who need to be screened (NNS) to achieve this goal is unknown. In this communication, the authors estimate the NNS to achieve 80% by 2018 nationwide and by state.
Cataract surgery in patients with corneal disease

Purpose of review Preexisting corneal disease can be exacerbated by cataract surgery and may prevent well tolerated cataract extraction. This article reviews the current literature and describes how corneal epithelial, stromal and endothelial disease may impact and be impacted by cataract surgery while highlighting recommendations for perioperative management and surgical technique. Recent findings Modifications to surgical techniques can allow for improved intraoperative visualization and safer cataract removal. Cataract surgery can be safely performed in conjunction with newer forms of corneal transplantation such as deep anterior lamellar keratoplasty and endothelial keratoplasty; however, guidelines for when to perform combined surgery have not been established. Summary Appropriate perioperative management and advances in surgical techniques and technologies allow for successful cataract surgery in patients with corneal disease. Signs of corneal disease should be identified preoperatively to allow for surgical planning and optimal visual outcomes.
Health literacy and glaucoma

Purpose of review This review discusses the concept and measurement of health literacy, with a focus on the care of patients with glaucoma. Recent findings Nearly one-fourth of adults in the USA lack the skills needed to fully comprehend and act on verbal or written information in the healthcare environment. This problem, referred to as poor health literacy, is associated with worse health-related outcomes in many chronic diseases, including glaucoma. Patients with glaucoma and poor literacy skills are less likely to refill their prescribed medications and miss more scheduled appointments than their more literate peers. Moreover, ophthalmic educational materials are often written at a level of readability that surpasses the skills of many patients with glaucoma. Summary Patients with chronic eye diseases such as glaucoma and limited health literacy skills are vulnerable to poor visual outcomes. Attention to health literacy may improve the care and outcomes of these patients.
Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma

Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver‐directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349–1369. © 2016 American Cancer Society.
Immunotherapy drug improves survival of patients with squamous non–small cell lung cancer

Cancer October 15, 2015 W the immunotherapy drug nivolumab was compared with standard chemotherapy in a clinical trial, investigators found that squamous non–small cell lung cancer patients lived, on average, 3.2 months longer than patients receiving chemotherapy alone. The trial results were reported in The New England Journal of Medicine and presented at the 2015 annual meeting of the American Society of Clinical Oncology.1 In addition, findings showed that after a year, patients on nivolumab had a survival rate nearly double (42%) that of patients who received chemotherapy alone (24%). Julie Brahmer, MD, director of the Thoracic Oncology Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, says that the results helped researchers win approval from the US Food and Drug Administration in March to treat patients whose lung cancer had progressed with nivolumab while they were being treated with standard chemotherapy. The relatively small increase in median survival with the new immunotherapy drugs may be rather misleading because patients who respond to immunotherapy continue to respond for long durations, Dr. Brahmer adds. These lengthier responses are cut One explanation for the latter findings is that many elderly people have comorbidities, so even those who do not have cancer may well have other medical problems that lead to higher medical expenditures and greater productivity loss, Dr. Zheng says. Dr. Zheng and his colleagues conclude that the economic burden of cancer varies by cancer site and age group and that nonelderly cancer survivors experience a greater overall economic burden than elderly cancer survivors. “It’s nice to have it quantified, but the findings are not at all surprising,” says Shelley Fuld Nasso, chief executive officer for the National Coalition for Cancer Survivorship. “It reflects the costs of reduced work that some survivors experience and the additional medical expenditures and side effects that most have to deal with. ” Fuld Nasso says she wonders if the reduction of productivity might actually be a choice on the part of some survivors, as in Laura Szalay’s case, rather than something imposed on them. “Cancer changes their lives, and it may be they decide to approach life differently and not go back to their jobs,” she says. Smita Bhatia, MD, MPH, a pediatric oncologist and epidemiologist who directs the Institute for Cancer Survivorship at the University of Alabama at Birmingham, praises the study for providing new information. “While we all have speculated and thought that the economic burden would be high for cancer survivors, no one has quantitated it, and it’s a nice study to show the amount of economic burden survivors are incurring with the 3 most common cancer diagnoses,” Dr. Bhatia says.
Optical coherence tomography – current and future applications

Purpose of review Optical coherence tomography (OCT) has revolutionized the clinical practice of ophthalmology. It is a noninvasive imaging technique that provides high-resolution, cross-sectional images of the retina, retinal nerve fiber layer and the optic nerve head. This review discusses the present applications of the commercially available spectral-domain OCT (SD-OCT) systems in the diagnosis and management of retinal diseases, with particular emphasis on choroidal imaging. Future directions of OCT technology and their potential clinical uses are discussed. Recent findings Analysis of the choroidal thickness in healthy eyes and disease states such as age-related macular degeneration, central serous chorioretinopathy, diabetic retinopathy and inherited retinal dystrophies has been successfully achieved using SD-OCT devices with software improvements. Future OCT innovations such as longer-wavelength OCT systems including the swept-source technology, along with Doppler OCT and en-face imaging, may improve the detection of subtle microstructural changes in chorioretinal diseases by improving imaging of the choroid. Summary Advances in OCT technology provide for better understanding of pathogenesis, improved monitoring of progression and assistance in quantifying response to treatment modalities in diseases of the posterior segment of the eye. Further improvements in both hardware and software technologies should further advance the clinician's ability to assess and manage chorioretinal diseases.
Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Abstract The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.
Long-term alteration of the hypothalamic-pituitary-adrenal axis in children undergoing cardiac surgery in the first 6 months of life

Abstract Children with congenital heart disease (CHD) have poorer neurodevelopmental and psychological outcomes. The mechanisms underlying this remain unclear. One mechanism could be that the stressful experience of cardiac surgery early in life influences long-term hypothalamic–pituitary–adrenal (HPA) axis regulation. Dysregulation of the HPA axis has been linked to poorer neurocognitive and psychological outcomes in other study populations. This case–control study aims to compare HPA-axis regulation (circadian rhythm and reactivity) using salivary cortisol in 3- to 5-year-olds with CHD who did and did not have cardiac surgery prior to 6 months of age. Saliva samples for cortisol analysis were collected from preschoolers with CHD (N = 28, Males = 18, Females = 10) over two weekend days, and before and after an echocardiogram. Caregiver education, child age, sex, and cardiac disease severity score were included as confounders. Multilevel analysis (hierarchical linear modeling) was used to analyze the data. The analysis for the cortisol circadian rhythm shows that the early surgery group has a flatter diurnal slope secondary to lower mean weekend morning waking cortisol levels than controls but similar mean bed time values. Multilevel analysis of the stress response to an echocardiogram indicates that the early surgery group has an increased response when compared to the control group. This is the first study to show that cardiac surgery prior to 6 months of age is associated with a different pattern of HPA-axis regulation at 3–5 years of age.
STAPHYLOCOCCIC PNEUMONIA OCCURRING DURING AN EPIDEMIC OF INFLUENZA

During the late fall and early winter of 1940-1941 an epidemic of influenza involved most sections of the United States, as well as the Hawaiian Islands, Puerto Rico and probably many other areas. 1 Virus isolations during the acute phase and immunologic studies of acute and convalescent phase serums on patients from widely scattered localities indicated that the virus of influenza A was by far the predominant, if not the only, one of the known viruses implicated in the epidemic. 2 If one judges from the available reports, the disease generally was mild and pulmonary complications were neither frequent nor severe. The epidemic reached Boston late in December and persisted throughout January; most cases of the disease occurred during the first two weeks of the latter month. The clinical features of some of the uncomplicated cases, along with the results of virus isolations and immunologic studies, have been reported
Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats: Implications for neurodegenerative disorders

Many studies have shown that early life stress may lead to impaired brain development, and may be a risk factor for developing psychiatric pathologies such as depression. However, few studies have investigated the impact that early life stress might have on the onset and development of neurodegenerative disorders, such as Parkinson's disease, which is characterized in part by the degeneration of dopaminergic neurons in the nigrostriatal pathway. The present study subjected rat pups to a maternal separation paradigm that has been shown to model adverse early life events, and investigated the effects that it has on motor deficits induced by a unilateral, intrastriatal injection of 6-hydroxydopamine (12 μg/4 μl). The female rats were assessed for behavioral changes at 28 days post-lesion with a battery of tests that are sensitive to the degree of dopamine loss. The results showed that rats that had been subjected to maternal separation display significantly impaired performance in the vibrissae and single-limb akinesia test when compared to normally reared animals. In addition, there was a significant increase in the loss of tyrosine hydroxylase staining in maternally separated rats. Our results therefore suggest that adverse experiences sustained during early life contribute to making dopamine neurons more susceptible to subsequent insults occurring during more mature stages of life and may therefore play a role in the etiopathogenesis of Parkinson's disease.