Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular Effects of Nitric Oxide: The Relation to Migraine

textabstractMigraine may manifest itself in many ways and the syndrome is afflicting approximately ten percent of the worlds population. The peak incidence of the syndrome occurs in adolescents and young adults, and the prevalence is about three times as high among females than males (Staffa et al., 1994). The diversity of symptoms and the potential confusion with other types of headaches, such as tension-type headache and cluster headache, has lead to the formulation of diagnostic criteria by the International Headache Society (Olesen et al., 1988). These criteria discern between two main types of migraine. The first, migraine without aura, was previously known as common migraine and is characterized by recurrent attacks of intense headache lasting 4 to 72 hours. The headache is commonly unilateral, pulsatile and throbbing in nature. The pain is often accompanied by anorexia, nausea and vomiting, as well as aversion to noise and light (phonophobia and photophobia). In the second type, previously known as classical migraine, headache is preceded by neurological symptoms called aura symptoms. The classic aura includes visual disturbances, like scintillating scotoma and fortification spectra, that drift across the visual field. In addition, somatosensory symptoms may occur as a feeling of numbness (pins and needles) slowly ascending fi'om the fingertips to the shoulder (Spierings, 1988; Blau, 1992). The duration of the aura phase is often limited to 60 minutes, but may outlast into the headache phase.
Role of anxiety on patient intolerance during bronchoscopy.

Aims: There are no current data about the adverse effects of anxiety on patient intolerance during bronchoscopy.The aim of our study was to assess the correlation between anxiety and patient intolerance during bronchoscopy. Study Design: Retrospective research study Place and Duration of Study: Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, between January 2010 and 2013 March. Methodology: Data from 94 patients were analyzed. The mean age of the patients was 59 years. Bronchoscopy was performed for lung cancer in 54, pulmonary nodules in 26 and pulmonary infiltration in 14 patients. Hospital Anxiety Depression scale was used to appraise the anxiety symptoms. Cytologic examination of bronchoalveolar lavage, and sputum samples were performed in each patient when available. Original Research Article British Journal of Medicine & Medical Research, 4(11): 2171-2180, 2014 2172 Results: The anxiety or fear profile of the patients before bronchoscopy were as follows: dyspnea (78%), malignant disease (74%), nasal, laryngeal or tracheal irritation (70%), bronchoscopic findings (68%), and hemorrhage (42%). Bronchoscopic examination was intolerable in 14 cases while there was great difficulty to perform the procedure in 18 patients. Cytologic analysis revealed severe in 18, moderate in 22, and mild dysplasia in 25 patients while it was normal in 29 subjects. Hospital Anxiety Depression scale was over eight in 33 patients. The scale was over eight in 13 out of 14 patients who were intolerant to bronchoscopy. Cytology revealed severe in one and moderate dysplasia in another patient intolerant to bronchoscopy. Conclusions: Anxiety appears to be the predominant factor for patient intolerance during bronchoscopy. Pulmonary function, atypical or dysplastic cytomorphological changes in sputum or bronchoalveolar lavage cytology did not show correlation with patient performance.
Cleft Lip and Palate Treatment with Delayed Closure of the Hard Palate

A new routine for the surgical treatment of cleft lip and palate patients is presented. Beside the regular lip-nose surgery it includes delayed closure of the cleft in the hard palate and soft palate closure without push-back technique. The effect on early facial growth was evaluated by comparing eight of these patients, three years of age, with a matched group where the hard and soft palate was closed primarily by vomer flap and velar push-back. The new treatment method resulted in significantly less teeth in crossbite occlusion due to a wider maxillary dental arch. As yet no serious disadvantages have been recorded.
An update on niche composition, signaling and functional regulation of the adipose-derived stem cells

Introduction: The self-renewal and differentiation of stem cells are controlled by both intrinsic factors and the surrounding microenvironment, which is known as the stem cell niche. Although the niches of adipose-derived stem cells (ASCs) are composed of diverse factors within the adipose tissue, the mechanisms by which niches are maintained, regulated and harmonized to support the ASCs are just beginning to be discovered. Areas covered: This review introduces the recent advances in the anatomic nature of the dynamic in vivo niches of ASCs. Additionally, new findings concerning the signaling pathways involved in the self-renewal, proliferation, differentiation and paracrine mechanisms will be described. Finally, we suggest optimized methods for expanding ASCs in vitro by mimicking the niche factors to enhance the regenerative potential of ASCs. Expert opinion: Fibroblast growth factor 2 is a self-renewal factor that can expand the lifespan of ASCs in long-term culture and platelet-derived growth factor-B/D has most potent mitogenic effects on short-term ASC expansion. Reactive oxygen species donors and stimulators of the phosphoinositide 3-kinase/protein kinase B and MAPK pathways can be used to increase the production yield of ASCs. Additionally, hypoxia can increase the proliferation of ASCs and priming under hypoxic conditions enhances the regenerative potential of ASCs.
Probody therapeutics for targeting antibodies to diseased tissue

Probodies are proteolytically activated antibodies engineered to remain inert until activated locally in diseased tissue. In principle, any therapeutic antibody can be converted into Probody™ form. In this perspective, we highlight the emerging therapeutic potential of the Probody approach in the form of conventional IgG-based Probodies as well as in the form of ‘empowered Probody’ formats such as Probody–drug conjugates.
Skeletal tissue engineering using mesenchymal or embryonic stem cells: clinical and experimental data

Introduction: Mesenchymal stem cells (MSCs) can be obtained from a wide variety of tissues for bone tissue engineering such as bone marrow, adipose, birth-associated, peripheral blood, periosteum, dental and muscle. MSCs from human fetal bone marrow and embryonic stem cells (ESCs) are also promising cell sources. Areas covered: In vitro, in vivo and clinical evidence was collected using MEDLINE® (1950 to January 2014), EMBASE (1980 to January 2014) and Google Scholar (1980 to January 2014) databases. Expert opinion: Enhanced results have been found when combining bone marrow–derived mesenchymal stem cells (BMMSCs) with recently developed scaffolds such as glass ceramics and starch-based polymeric scaffolds. Preclinical studies investigating adipose tissue–derived stem cells and umbilical cord tissue–derived stem cells suggest that they are likely to become promising alternatives. Stem cells derived from periosteum and dental tissues such as the periodontal ligament have an osteogenic potential similar to BMMSCs. Stem cells from human fetal bone marrow have demonstrated superior proliferation and osteogenic differentiation than perinatal and postnatal tissues. Despite ethical concerns and potential for teratoma formation, developments have also been made for the use of ESCs in terms of culture and ideal scaffold.
The role of integrin antagonists in the treatment of inflammatory bowel disease

Introduction: Ulcerative colitis (UC) and Crohn’s disease are chronic inflammatory diseases of the bowel associated with complex inflammatory cascades within the mucosal lining of the gut. Areas covered: INTEGRINS and their use as therapies in UC and Crohn’s. Expert Opinion: The anti-adhesion molecules are a welcome addition to the armamentarium of medical therapies for inflammatory bowel disease.
The effect of Asian sand dust-activated respiratory epithelial cells on activation and migration of eosinophils

Abstract Contest: Asian sand dust (ASD) contains various chemical and microbiological materials. ASD aggravate the inflammatory response of respiratory epithelial cells and symptoms of asthma. Objective: To evaluate the inflammatory effects of ASD on the activation of bronchial epithelial cells and the effect on the activation and migration of eosinophils. Materials and methods: BEAS-2B cells were exposed to three forms of ASD: particles less than 10 μm in diameter (PM), dried sand dust (SD) and sand dust collected from the Gobi Desert (GB). Activation of the epithelial cells was determined using interleukin-6 (IL-6), IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), regulated on activation normal T expressed and secreted (RANTES), and eotaxin. Eosinophil migration was induced with bronchial epithelial cell conditioned medium. Eosinophils were stimulated with the ASDs and production of superoxide and eosinophil cationic protein was measured. Results: PM and SD enhanced the production of IL-6, IL-8 and RANTES. However, only IL-6 production was significantly increased with GB. Conditioned medium stimulated PM and SD enhanced the migration of eosinophils. PM and SD strongly activated eosinophils. Discussion and conclusions: ASD, which contains smaller particles and air pollutants, might exacerbate the inflammatory process of bronchial tissue and asthmatic symptoms with the production of inflammatory mediators and tissue eosinophilia.
Carbon nanotubes size classification, characterization and nasal airway deposition

Abstract Workers and researchers in the carbon nanotubes (CNT)-related industries and laboratories might be exposed to CNT aerosols while generating and handling CNT materials. From the viewpoint of occupational health, it is essential to study the deposition of CNT aerosol in the human respiratory tract to investigate the potential adverse health effects. In this study, a human nasal airway replica and two types of CNT materials were employed to conduct CNT nasal airway deposition studies. The two CNT materials were aerosolized by a nebulizer-based wet generation method, with size classified by three designated classification diameters (51, 101 and 215 nm), and then characterized individually in terms of their morphology and aerodynamic diameter. The nasal deposition experiments were carried out by delivering the size classified CNTs into the nasal airway replica in three different inspiratory flow rates. From the characterization study, it showed that the morphology of the size classified CNTs could be in a variety of complex shapes with their physical dimension much larger than their classification diameter. In addition, it was found that the aerodynamic diameters of the classified CNTs were slightly smaller than their classification diameter. The nasal deposition data acquired in this study showed that the deposition efficiency of CNTs in the nasal airway were generally less than 0.1, which implies that the majority of the CNTs inhaled into the nose could easily penetrate through the entire nasal airway and transit further down to the lower airways, possibly causing adverse health effects.
Emerging analgesic drugs for Parkinson's disease

Introduction: Pain affects between 40 and 85% of Parkinson's disease (PD) patients. It is a frequently disabling and overlooked feature, which can significantly reduce health-related quality of life. Unfortunately, there are no universally recommended treatments for this condition. Areas covered: Evidence about the efficacy and safety of available analgesic treatments is summarized in this review. Potential targets for upcoming therapies are then discussed in light of what is currently known about the physiopathology of pain in PD. Protocols for efficacy and safety assessment of novel analgesic therapies are discussed. Finally, critical aspects of study protocol design such as patient selection or outcomes to be evaluated are discussed. Expert opinion: Preliminary results indicate that duloxetine, cranial electrotherapy stimulation, rotigotine, subthalamic or pallidum nuclei stimulation or lesion or levodopa could be effective for treating pain in PD. Similarly, some case reports indicate that repetitive transcranial magnetic stimulation (rTMS) or apomorphine could be effective for relieving painful off-period dystonia. Clinical trials with rTMS or oxycodone/naloxone prolonged-release tablets for neuropathic pain or botulinum toxin for off-period dystonia are underway. Success of clinical trials about analgesic strategies in PD will depend on the selection of the right PD population to be treated, according to the type of pain, and the proper selection of study outcomes and follow-up of international recommendations.
Results of the trials and light delivery evaluation on low-level laser therapy of acute and chronic pain

Although the low-level laser therapy (LLLT) has been accepted in the clinical practice, its efficiency is still questionable because of the unclear mechanisms of LLLT action. This work presents the results of LLLT applied to volunteers who need recovery from trauma or suffer from rheumatic diseases, inflammatory disorders, etc. The control group we used for comparison consisted of patients being treated by conventional therapy that included massage and acupuncture needles. The effectiveness of the LLLT was graded under four categories. Short-term and long-term side effects as well as conditions responding only to LLLT were recorded. The successful treatments were up to 70%, which coincided with the result of the control group. The LLLT was performed with a GaAs laser system provided with additional set of six light CW emitting diodes to scan a larger area of a tissue surface. To evaluate the light delivery inside the tissue, the spatial energy distribution within the laser beam was measured with a CCD camera. On its basis, the light dose absorbed in the tissue was calculated both in the boundary layer under the surface and in depth using a reduced variance Monte-Carlo code.
Associations between insulin-like growth factor I, vascular endothelial growth factor and its soluble receptor 1 in umbilical serum and endothelial cells obtained from normotensive and preeclamptic pregnancies

Abstract The aim of this study was to investigate the associations between insulin-like growth factor I (IGF-I) with vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sFlt-1) in umbilical serum and to study the effects of IGF-I upon sFlt-1 synthesis in human umbilical vein endothelial cells (HUVEC) in normotensive (NT) and preeclamptic (PE) pregnancies. As compared with the NT group, umbilical serum IGF-I and VEGF levels were lower in the PE group, while sFlt-1 concentrations were higher. Levels of sFlt-1 correlated with IGF-I in the NT group and with VEGF in the PE group. Basal concentration of sFlt-1 in HUVEC culture media was higher in the PE group. IGF-I stimulated sFlt-1 synthesis only in the NT group. In summary, umbilical serum sFlt-1 is associated with IGF-I in normotensive pregnancy and with VEGF in preeclampsia. IGF-I stimulates sFlt-1 synthesis in endothelial cells in normotensive but not in PE pregnancies.
Emerging drugs for managing kidney disease in patients with diabetes

Introduction: The need for new approaches to manage the increasing numbers of patients with diabetes and their burden of complications is urgent. Of these, chronic kidney disease imposes some of the highest costs, both in dollars and in terms of human suffering. In individuals with diabetes, the presence and severity of kidney disease adversely affects their well-being, contributes to disease morbidity and increases their risk of a premature death. Areas covered: To collect information for the strategies previously or currently under investigation for managing kidney disease in patients with diabetes, a literature search was performed through the search engines PubMed and ClinicalTrials.gov. Expert opinion: Despite advancing knowledge on the pathogenesis of diabetic kidney disease, and promising effects in experimental models, at present there are no new drugs that come close to providing the solutions we desire for our patients. Even when used in combination with standard care, renal complications are at best only modestly reduced, at the considerable expense of additional pill burden and exposure to serious off-target effects. Some of the most exciting advances over the last decade, including thiazolidinediones, direct renin inhibitors, endothelin antagonists and most recently bardoxolone methyl have all fallen at this last hurdle. Better targeted (‘smarter') drugs appear to be the best hope for renoprotective therapy.
Preparation and characterization of medium-chain fatty acid liposomes by lyophilization

In this study, medium-chain fatty acid (MCFA) liposomes were prepared by the film ultrasonic dispersion, modified ethanol injection, and reverse-phase evaporate methods. The results indicated that the liposomes prepared by the thin-film ultrasonic dispersion method had a high entrapment efficiency of 82.7% and a good distribution in size diameters. The MCFA liposomes were freeze-dried and the optimal preparation conditions of freeze-drying were as follows: The cryoprotectants were mannitol and sucrose (1:1 w/w), the hydrated medium was distilled water, and the freeze-drying time was 48 hours. Under these conditions, the freeze-dried MCFA liposomes had a perfect appearance, a small particle size, and high encapsulation efficiency. The mean diameters were 251.1 and 265.3 nm, and the encapsulation efficiencies were 80.5 and 79.2% for freshly prepared and reconstituted liposomes, respectively.
Producing the global health doctor: discourses on international medical electives

This article attempts to interrupt dominant narratives in the literature about international service-learning (ISL) in the field of medicine by critically deconstructing discourse related to a common model used to teach global health in undergraduate medical education: the international medical elective (IME). Based on a study conducted in 2012, the results have not been previously published. Using a Foucauldian discourse analysis, the study interrogated the underlying assumptions behind the nature of “service” being rendered by conveying the imagery, language, and consequences of the dominant discourses used in journal articles indexed on MEDLINE between 2000 and 2011. The analysis revealed an IMEs literature steeped in problematic discursive (re)productions of colonial constructs and imagined geographies, primarily through two dominant discourses designated as “disease and brokenness” and “romanticizing poverty. ” These discourses both justify and reinforce privileged subject positions for students engaged in these ISL experiences, while inadequately considering structures and systems that perpetuate marginalization and health inequities. Such discourses often marginalize or essentialize people of so-called “host” countries, while silencing subaltern perspectives, resistance struggles, knowledges, and epistemologies. Challenging current ISL practices in medicine requires educators to actively work towards decolonialization, in part by recognizing the ability of discourses to produce meaning and subjects.
Development and characterization of phospholipid-stabilized submicron aqueous dispersions of coenzyme Q10 presenting continuous vibrating-mesh nebulization performance

Abstract Coenzyme Q10 (CoQ10) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. The aim of this research was to develop a suitable formulation for pulmonary delivery of this anticancer agent. An appropriate selection of excipients (phospholipids) and a suitable device (Aeroneb Pro® vibrating-mesh nebulizer) were selected initially after reviewing the literature. After characterization of the bulk drug, a feasible manufacturing process was selected to obtain small particle size dispersions of CoQ10. Following selection of an appropriate process, the parameters affecting drug particle size were studied. Using LD and gravimetrical analysis, nebulization was evaluated to assess the performance of the inhalation system triad: drug–excipients–device. CoQ10 powder studied was crystalline with a melting point approximately at 51 °C and with a particle size of 30 µm. Microfluidization was found to be a suitable method to prepare submicron drug particles in aqueous dispersions. Increasing microfluidization processing to more than 50 passes did not provide further particle downsizing for both soya phosphatidylcholine (lecithin) and dipalmitoyl phosphatidylcholine (DPPC) dispersions of CoQ10, presenting Z-average values of approximately 130 and 70 nm, respectively. Nebulization performance of lecithin-stabilized CoQ10 dispersions varied according to number of passes in the microfluidizer. Formulations processed with 10 passes presented steadier nebulization over time and different rheological behavior compared to those processed with 30 or 50 passes. In conclusion, aqueous dispersions of CoQ10 were adequately produced using a microfluidizer with characteristics that were suitable for pulmonary delivery with an Aeroneb Pro® nebulizer. Furthermore, the rheology of these dispersions appeared to play a significant role in the aerosol generation from the active vibrating-mesh nebulizer used.
TrkB as a therapeutic target for ovarian cancer

Background: In many countries, ovarian cancer is the most lethal gynecological malignancy. Its poor prognosis is mainly due to the late stage of disease with metastasis at presentation. The significant failure rate of chemotherapy in patients with advanced stage disease is also a main concern. As such, developing novel therapeutic targets is essential to improve long-term survival. Overexpression of Tropomyosin-related kinase B (TrkB), a tyrosine kinase receptor, has been documented in ovarian cancer and is found to be correlated with poor prognosis. Objective/methods: We discuss the functional roles and the related downstream signaling pathways of TrkB and its ligand brain-derived neurotrophic factor (BDNF) in ovarian cancer. The possible crosstalk between TrkB/BDNF and other putative molecular targets in ovarian cancer is also discussed. Results/conclusions: All these latest findings shed light on the application of TrkB as a therapeutic target for ovarian cancer.
Formulation and characterization of nanoliposomal 5-fluorouracil for cancer nanotherapy

Abstract A scalable and safe method was developed to prepare nanoliposome carriers for the entrapment and delivery of 5-fluorouracil (5-FU). The carrier systems were composed of endogenously occurring dipalmitoylphosphatidylcholine (DPPC), negatively charged dicetylphosphate (DCP), cholesterol (CHOL) and glycerol (3%, v/v). Nanoliposomes were prepared by the heating method in which no harmful chemical or procedure is involved. Results indicated fast and reproducible formation of non-toxic liposomes that possess high entrapment efficiency (up to 96.9%) and vesicle size range of ca. 530–620 nm. Transmission electron and optical micrographs of the 5-FU liposomes revealed that they were spherical and some were multilayered. There was an increase in the release rate of 5-FU from the liposomes prepared with a high ratio of drug:lipid. The release data showed that the highest release rates were obtained for nanoliposomes containing 5-FU with the drug concentration of 500 mM and that it followed the diffusion model. Nanoliposome preparation method introduced here has the potential of large-scale manufacture of safe and efficient carriers of 5-FU.