Miracle-dz/UniFAR-FTUs huggingface dataset:
Introducing dental students to e-learning at a South African university

Background. This article reports on the introduction of an innovative ‘blended learning’ approach in the Paediatric Dentistry Department at the University of the Western Cape (UWC) in Cape Town, South Africa. This intervention was the first of its kind to be introduced at UWC’s dentistry faculty. Methods. Educational resources were placed online to supplement didactic and clinical teaching and thus compensate for the lack of chair-side teaching. An online learning platform was therefore provided for students to engage with. Results. Forty-seven per cent of students accessed the site. The evaluation of the course by these 4th- and 5th-year students was mostly positive. Students who did not access the site provided a variety of reasons for not doing so, the main reasons being ‘lack of time’ (40%) and ‘lack of IT resources’ (41%). Conclusion. This intervention highlighted the fact that ‘blended learning’ definitely has its place in the dentistry curriculum, especially if minor issues such as access to resources can be addressed. The Paediatric Dentistry Department at UWC is continually pursuing current trends in teaching to provide an education that is on par with global standards.
Early Undifferentiated Spondyloarthropathy in a Patient with Sarcoidosis

Anahtar sozcukler: Inflamatuvar bel agrisi; sarkoidoz; spondiloartropati; uveit. In this article, we present a 49-year-old male case who was admitted with inflammatory back pain and uveitis when he was in remission for sarcoidosis. The concomitance of undifferentiated spondyloarthropathy and sarcoidosis with an emphasis on their possible etiological association was also discussed in the light of current diagnostic and therapeutic challenges.
Recent advances in immunotherapy for the treatment of prostate cancer

Introduction: Prostate cancer vaccines attempt to induce cancer-specific systemic immune responses and represent a new class of targeted therapies, many of which are non-toxic. Several vaccine technologies are in development. Areas covered: An autologous antigen presenting cell vaccine loaded with prostate acid phosphatase conjugated with GM-CSF, sipuleucel-T confers a survival advantage in men with metastatic castration-resistant prostate cancer (CRPC) and is now FDA approved based on the IMPACT trial. A poxvirus-based vaccine, PROSTVAC-VF TRICOM targeting prostate-specific antigen (PSA), has demonstrated improved survival in a randomized Phase II trial of patients with metastatic CRPC. Novel T lymphocyte checkpoint inhibitors of cytotoxic T lymphocyte antigen 4 and programmed death-1 are also emerging. Recognition of improved survival without an earlier clinical signal of activity by conventional criteria has led to new guidelines to evaluate immunotherapeutic agents. The clinical benefit of combining vaccines with chemotherapy, radiotherapy and other immunotherapeutic and biologic agents is being evaluated in the context of disappointing results of combination GVAX vaccine and docetaxel chemotherapy. Expert opinion: To build on the success of early phase trials, efforts must be made to optimize vaccine approaches and patient selection.
Effect of Fentanyl in Spinal Anesthesia With Bupivacaine in Opium Abusers

Background: Spinal anesthesia is a common procedure in the anesthesia. In some studies it has been shown that chronic use of opioids is associated with shorter duration of spinal anesthesia when local anesthetics are applied. Objectives: This trial was conducted in order to determine effect of fentanyl on the duration of spinal block by bupivacaine in chronic opium abusers who undergo spinal anesthesia and have lower thresholds for pain. Patients and Methods: This study was a randomized clinical trial in which 50 opium abusers (25 patients in each group) undergoing lower extremity orthopedic surgeries with spinal anesthesia were selected. The patients were randomly divided into two groups. The study group received 15 mg hyperbaric bupivacaine 0.5% plus 25 μg fentanyl, while the control group received 15mg hyperbaric bupivacaine 0.5% plus 0.25 mL normal saline. Results: All randomly selected cases were male (44.7 ± 13.6 year). The mean duration of sensory block was much longer in the study group (87.8 ± 7.22 minutes) in comparison with the control group (70.47 ± 5.45 minutes) (P < 0.001). There was no statistically significant difference between the two groups regarding their age and duration of surgery. Conclusions: Bupivacaine administration in spinal anesthesia for spinal block has a shortened duration in comparison to the combination of bupivacaine and fentanyl in chronic opium abusers.
Solanezumab for Alzheimer's disease

Introduction: Alzheimer's disease (AD) is a debilitating neurodegenerative illness affecting over 35 million people worldwide. Solanezumab is a monoclonal antibody that binds to β-amyloid (Aβ), a protein that plays a key role in the pathogenesis of AD. The drug is currently being investigated in Phase III trials as a disease-modifying treatment for AD. Areas covered: This paper reviews literature on solanezumab that is available in PubMed from 2008 to 2010, other treatment trials in clinicaltrials.gov and published abstracts from conferences. The article also provides a discussion of the early trials of AN1792 and an overview of the immunotherapies currently in development. The authors provide the reader with a critical appraisal of the to-date clinical trial data on solanezumab and its implications for the broader field of immunotherapies for AD. Expert opinion: Solanezumab can neutralize soluble Aβ peptides, which may represent the more neurotoxic of the Aβ species. Phase II findings support the compound's safety, which has been a concern for some Aβ immunotherapies. Cerebrospinal and plasma biomarker changes with solanezumab treatment are encouraging. Results of the ongoing Phase III trials will be instrumental in determining the drug's clinical significance.
Alemtuzumab in allogeneic hematopoetic stem cell transplantation

Introduction: With the use of reduced-intensity conditioning (RIC), early toxicity of allogeneic stem cell transplantation (SCT) has been much reduced. Graft-versus-host disease (GvHD) causes morbidities and mortality. Alemtuzumab is a mAb directed against CD52. When administered prior to transplant, it leads to T-cell depletion. Incorporation of alemtuzumab in RIC results in low rates of GvHD and treatment-related mortality (TRM) in haematological diseases, even in the setting of mismatched-donor transplantation. Areas covered: The use of alemtuzumab for GvHD prophylaxis in SCT. The benefit of alemtuzumab-based conditioning is partially offset by increased disease relapse due to impaired graft-versus-tumor effect (GvT) and by slower immune reconstitution, necessitating special precautions. While GvHD is prevented with alemtuzumab, post-SCT interventions are often required. Most studies find that alemtuzumab-based conditioning results in decreased chronic GvHD and TRM, but also in decreased progression-free survival. Overall survival after 3 – 5 years is usually equivalent and quality of life may be improved because of a lower incidence of sequelae of chronic GvHD. Many aspects of alemtuzumab treatment are under investigation. Expert opinion: Alemtuzumab reduces GvHD and TRM after SCT. Use of alemtuzumab requires awareness and strict management of the risk of opportunistic infections and of an increased risk of disease recurrence.
CD4+CD25+ regulatory T lymphocytes in allergy and asthma

Allergic asthma is characterized by airway hyper‐responsiveness and chronic mucosal inflammation mediated by CD4+ Th2 lymphocytes. Regulatory CD4+CD25+ T cells are important components of the homeostasis of the immune system, as impaired CD4+CD25+ T cell activity can cause autoimmune diseases and allergy. The mechanism of suppression by CD4+CD25+ T cells remains controversial; different in vivo and in vitro studies raise possible roles for the immunosuppressive cytokines interleukin‐10 and transforming growth factor‐β, forkhead transcription factor Foxp3, glucocorticoid‐induced tumor necrosis factor receptor, cytotoxic lymphocyte associated antigen‐4, 4‐1BB costimulator receptor, a CD4‐related molecule LAG‐3, and neuropilin‐1. Current data suggest that Th2 responses to allergens are normally suppressed by CD4+CD25+ T cells. Suppression by CD4+CD25+ T cells is decreased in allergic individuals. Furthermore, CD4+CD25+ T cells play a key role in regulating airway eosinophilic inflammation. The immunomodulatory properties of CD4+CD25+ T cells do extend to Th2 responses, most notably by limiting the development of a proinflammatory CD4+ Th2 phenotype characterized by reduced cytokine production. An understanding of the roles of CD4+CD25+ T cells in vivo could provide better insight into the design of novel approaches to modulate the chronic airway inflammatory reaction evident in bronchial asthma.
The development of 13-valent pneumococcal conjugate vaccine and its possible use in adults

Introduction: Worldwide, Streptococcus pneumoniae causes significant morbidity and mortality. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for use in persons aged 65 years and over and in adults with certain chronic medical conditions. Pneumococcal conjugate vaccines (PCVs) have been developed for use in infants and children aged less than 5 years, and are being studied for use in adult populations. Areas covered: The different types of pneumococcal vaccines are discussed. Studies comparing PPSV23 and PCVs, as well as the results of the widespread use of 7-valent PCV are covered. The possible extension of the use of 13-valent PCV to adults, particularly to vulnerable populations, is discussed. The MEDLINE database was used to identify relevant studies from literature published in English between January 1977 and January 2011. All studies of adults aged over 18 years were considered for the review. Expert opinion: Elderly individuals and adults with chronic medical conditions who are at increased risk for pneumococcal disease would benefit from more effective prevention than is provided by the currently recommended PPSV23.
Targeting methionine auxotrophy in cancer: discovery & exploration

Introduction: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. Areas covered: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. Expert opinion: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.
VEGF Promotes Angiogenesis and Functional Recovery in Stroke Rats

ABSTRACT We evaluated the effects of intranasal vascular endothelial growth factor VEGF on neurological function and angiogenesis in ischemic boundary following cerebral ischemia. Sprague–Dawley rats were randomized into sham operation group (n = 9), VEGF group (n = 18), and control group (n = 18). The VEGF and control rats were intranasally administered (IN) with VEGF or saline, starting three days after middle cerebral artery occlusion (MCAO) and daily. Neurological scores were obtained at 1, 7, and 14 days after MCAO. Rats were sacrificed at 14 days, the von Willebrand factor (vWF) immunoreactive, BrdU+/vWF+ cells, and microvessels were evaluated respectively. Compared to the control rats, intranasal administration of VEGF improved behavioral recovery, and increased the number of vWF+, BrdU+/vWF+ cells, and FITC-dextran perfused microvessels in ischemic boundary (p < .01). Our data suggest that intranasal administration of VEGF may induce angiogenesis in ischemic boundary and improve behavioral recovery following cerebral ischemia in rats, which may provide a powerful strategy for stroke.
Aerobic Exercise Prescription for Older Population: A Short Review

Aerobic exercise can lower the susceptibility to certain preventable chronic diseases, decrease mortality and improve health in the older adults. The health benefits of aerobic exercise include prevention of cardiovascular and coronary heart diseases; lowering blood pressure and blood lipids; lowering the risk of type 2 diabetes mellitus, back pain, osteoarthritis, osteoporosis, falls and, to some extent, sarcopenia; and improving quality of life and independent living in older adults. Aerobic training should be continued in order to be beneficial. If it is professionally prescribed by a physiotherapist or clinical exercise specialist using the most current research evidence, aerobic exercise can be enjoyable and safe. Professional and medical supervision during aerobic training may be needed for the older population and those who are at a higher risk for cardiovascular disease, stroke, hypertension or who have diabetes mellitus, obesity, osteoarthritis, and osteoporosis. More research is still needed to identify the physiological and cellular mechanisms that show exercise can slow the aging process. This review article presents aerobic exercise-induced cardiovascular benefits and optimal exercise prescription for promoting cardiovascular-pulmonary-muscular health and preventing age-related diseases and mortality
Mepolizumab treatment for asthma

Introduction: Five percent of asthmatics have severe symptoms despite high doses of inhaled (ICS) or additional oral corticosteroids (OCS): these patients have high morbidity, risk for asthma death, and account for half of asthma healthcare spending. A subgroup (20 – 40%) of these has persistent airway eosinophilia and frequent exacerbations. Mepolizumab is a humanized monoclonal antibody that blocks binding of the key cytokine implicated specifically in eosinophil maturation and survival, interleukin-5, to its receptor. Areas covered: Pharmacology, Phase I/IIa and Phase II/III studies of mepolizumab for asthma. Mepolizumab depleted blood and sputum eosinophils and partially reduced airway and bone marrow eosinophils. It also reduced airway remodeling. In unselected patients with moderate/severe asthma there was no clinically significant effect on lung function, but a trend to reduced exacerbation rates. When patients were selected for persistent sputum eosinophilia despite high-dose ICS/OCS, and frequent exacerbations, mepolizumab reduced exacerbations by 50%. Expert opinion: Mepolizumab can reduce exacerbation rates in the severe asthma cohort who have eosinophilic airway inflammation despite corticosteroid treatment. This may be 30% of severe asthmatics and represents a new and important treatment option. Further studies need to confirm efficacy and indications for asthma (and other eosinophilic airway disease), and to examine clinical consequences of reducing remodeling.
Limited Fluid Resuscitation Attenuates Lung and Intestine Injury Caused by Hemorrhagic Shock in Rats

ABSTRACT Background and Objective: Different volume fluid resuscitations were closely associated with different cytokine responses, which could influence shock-induced lung and intestinal destruction. The aim of the study is to compare the effects of limited and traditional resuscitation on the levels of inflammatory response and lung and intestinal injury of hemorrhagic shock (HS) rats. Method: Sprague–Dawley male rats were subjected to a blood pressure-controlled hemorrhage group following three kinds of resuscitation using lactated Ringer's (LR) solution (45, 30, 15 ml/kg·hr, respectively) and unresuscitation group. Then six rats of each group were sacrificed at 24, 48, and 72 hr, respectively. Results: The levels of plasma TNF-α, the plasma lactic acid, the intestinal permeability, and the ratio of wet weight to dry weight of lung and intestinal were lower in the group of 15 ml/kg·hr than other groups (p < .05). The lung and intestinal injury were more severe in group 45 ml/kg·hr than other groups in 24, 48, and 72 hr (p < .05). Conclusion: Comparing with conventional fluid resuscitation, limited fluid resuscitation (LFR) could not only decrease the levels of lactic acid and pro-inflammatory factors but also attenuate the intestinal and lung injury.
Nerve Growth Factor Prevents Demyelination, Cell Death and Progression of the Disease in Experimental Allergic Encephalomyelitis

Experimental allergic encephalomyelitis (EAE), a demyelinating disease induced in the animals parallels multiple sclerosis in human in several aspects, provides a useful model to investigate multiple sclerosis. In this study, we have therefore used this model to study functions of nerve growth factor (NGF) in EAE. NGF with considerable effects on neuron survival, proliferation and differentiation of the nervous system, is also known to act on cells of the immune system. Simultaneous upregulation of proinflammatory cytokines and increased level of NGF points at possible effects of the nerve growth factor in autoimmune diseases. To investigate roles of NGF in experimental allergic encephalomyelitis in vivo, we therefore decided to apply it intracerebroventricularly at a dose of 0.20 mg/mice prior to the induction of EAE. Our clinical observations showed that in the EAE induced animals who received NGF, severity of the disease was reduced significantly compared to that in saline treated EAE mice. Also neuropathological investigation of spinal cords revealed that in contrast to saline treated EAE mice, no signs of cell death, infiltration and demyelination can be seen in NGF treated EAE mice, suggesting that NGF may have clinical implications in multiple sclerosis.
Relationship between postprandial endotoxemia in nonobese postmenopausal women and diabetic nonobese postmenopausal women

Background: We hypothesised that nonobese postmenopausal women (NoPoW) and diabetic NoPoW (DNoPoW) may be independently associated with postprandial endotoxemia. Materials and Methods: NoPoW and DNoPoW were evaluated for weight, eating habits, physical activity, body circumferences, fasting plasma glucose level, postprandial plasma glucose level, and insulin level. The lipopolysaccharide (LPS) levels and circulating LPS-binding protein (LBP) were determined in serum at fasting, 1 h, 2 h, 3 h, and 4 h after meal intake and their levels were co-related in 80 NoPoW and 80 DNoPoW. Results: Both DNoPoW group and NoPoW group showed a significant increase (P < 0.05) in LPS levels and circulating LBP in plasma after the meal intake, interestingly the increase was higher in the DNoPoW group. Conclusions: Elevated LPS and circulating LBP were associated significantly with DNoPoW group and NoPoW, especially after a meal intake. These findings suggested a role of LPS and LBP in postprandial systemic inflammation in DNoPoW group. Prospective studies are needed to confirm these results.
Omalizumab for treatment of allergic rhinitis

Introduction: Immunoglobulin E (IgE) is a key pathogenic factor of allergic rhinitis, a prevalent disease adversely affecting quality of life and productivity. Areas covered: Binding of inhaled allergens to IgE on the surface of basophils and mast cells, with subsequent cross-linkage of IgE and aggregation of high-affinity receptors for IgE (FcϵRI), triggers the release of inflammatory mediators, followed by the onset of allergic rhinitis symptoms. Current therapeutic strategies include corticosteroids, mast cell stabilizers, leukotriene receptor antagonists, anticholinergics, antihistamines and allergen immunotherapy. Removal of circulating free IgE by the recombinant humanized monoclonal anti-IgE antibody, omalizumab (Xolair), represents a novel therapeutic approach. Omalizumab selectively binds to the Cϵ3 domain of IgE at the site of FcϵR1 binding, thus blocking binding of IgE to effector cells. We review omalizumab's clinical efficacy, administration, use with immunotherapy and safety in allergic rhinitis. Expert opinion: Omalizumab may provide a new treatment strategy for allergic rhinitis. The high cost of omalizumab precludes its chronic use for allergic rhinitis and it is not FDA approved for this indication; however, its periodic use may be justified in treatment resistant patients, especially those with seasonal disease.
Current gene therapy trials for vascular diseases

Introduction: In the previous gene therapy trials for vascular diseases, safety of the therapies has been demonstrated with some evidence for clinical benefits. In the future, it will be important to also test the potential clinical benefits of the treatments in randomized and controlled trials with sufficient numbers of patients. Areas covered: This review covers 15 currently ongoing cardiovascular gene therapy trials that aim to treat coronary artery disease, heart failure and peripheral artery disease. This review summarizes current trials and their main features in the cardiovascular field. Expert opinion: In the gene therapy trials for vascular diseases, some limiting factors are still present. The trials have enrolled mainly elderly and severely affected patients who might not have the capacity to respond optimally to the therapies. Also, major cardiac adverse events, major amputations, mortality and other very demanding hard clinical end points have been used in relatively small patient populations. Therefore, there is an urgent need to enroll less severely affected patients and to use more informative surrogate end points in the forthcoming clinical trials.
Acute pulmonary response of mice to multi-wall carbon nanotubes

Widespread use of carbon nanotubes is predicted for future and concerns have been raised about their potential health effects. The present study determined the pulmonary response of mice to multi-wall carbon nanotubes (MWCNTs). The MWCNT suspension in sterile phosphate-buffered saline (PBS) was introduced into mice lungs by oropharyngeal aspiration. Female C57Bl mice were treated with either 20 or 40 μg of MWCNTs in 40 μl PBS and control groups received equal volume of PBS. From each group, half of the mice were euthanized at day 1 and the remaining half at day 7 post treatment. Bronchoalveolar lavage (BAL) fluids, serum, and lung tissue samples were analyzed for inflammatory and oxidative stress markers. The results showed significant cellular influx by a single exposure to MWCNTs. Yields of total cells and the number of polymorphonuclear leukocytes in BAL cells were significantly elevated in MWCNT-treated mice post-treatment days 1 and 7. Analysis of cell-free BAL fluids showed significantly increased levels of total proteins, lactate dehydrogenase, tumor necrosis factor-α, interleukin-1β, mucin, and surfactant protein-D (SP-D) in MWCNT-treated mice at day 1 post treatment. However, these biomarkers returned to basal levels by day 7 post exposure except mucin and SP-D. An increase in the urinary level of 8-hydroxy-2’-deoxyguanosine in mice treated with MWCNT suggested systemic oxidative stress. Western analysis of lung tissue showed decreased levels of extracellular superoxide dismutase (SOD) protein in MWCNT-treated mice but copper/zinc and manganese SOD remained unchanged. It is concluded that a single treatment of MWCNT is capable of inducing cytotoxic and inflammatory response in the lungs of mice.