Project description:Direct-to-consumer (DTC) DNA testing has grown from contentious beginnings into a global industry, by providing a wide range of personal genomic information directly to its clients. These companies, typified by the well-established 23andMe, generally carry out a gene-chip analysis of single-nucleotide polymorphisms (SNPs) using DNA extracted from a saliva sample. These genetic data are then assimilated and provided direct to the client, with varying degrees of interpretation. Although much debate has focused on the limitations and ethical aspects of providing genotypes for disease risk alleles, the provision of pharmacogenetic results by DTC companies is less studied. We set out to evaluate current DTC pharmacogenetics offerings, and then to consider how these services might best evolve and adapt in order to play a potentially useful future role in delivery of personalized medicine.
Project description:Chikungunya virus (CHIKV) is an alphavirus that has spread globally in the last twenty years. Although mortality is rather low, infection can result in debilitating arthralgia that can persist for years. Unfortunately, no treatments or preventive vaccines are currently licensed against CHIKV infections. However, a large range of promising preclinical and clinical vaccine candidates have been developed during recent years. This review will give an introduction into the biology of CHIKV and the immune responses that are induced by infection, and will summarize CHIKV vaccine development.
Project description:Breast cancer is the most common cancer diagnosed among women worldwide and more than half are diagnosed above the age of 60 years. Life expectancy is increasing and the number of breast cancer cases diagnosed among older women are expected to increase. Undertreatment, mostly due to unjustifiable fears of advanced-age and associated comorbidities, is commonly practiced in this group of patients who are under-represented in clinical trials and their management is not properly addressed in clinical practice guidelines. With modern surgery and anesthesia, breast surgeries are considered safe and is usually associated with very low complication rates, regardless of extent of surgery. However, oncoplastic surgery and management of the axilla can be tailored based on patients'- and disease-related factors. Most of chemotherapeutic agents, along with targeted therapy and anti-Human epidermal growth factor receptor-2 (HER2) drugs can be safely given for older patients, however, dose adjustment and close monitoring of potential adverse events might be needed. The recently introduced cyclin-D kinase (CDK) 4/6-inhibitors in combination with aromatase inhibitors (AI) or fulvestrant, which changed the landscape of breast cancer therapy, are both safe and effective in older patients and had substituted more aggressive and potentially toxic interventions. Despite its proven efficacy, adjusting or even omitting adjuvant radiation therapy, at least in low-risk older patients, is safe and frequently practiced. In this paper, we review existing data related to breast cancer management among older patients across the continuum; from resection of the primary tumor through adjuvant chemotherapy, radiation and endocrine therapy up to the management of recurrent and advanced-stage disease.
Project description:Small-cell lung cancer (SCLC) is characterized by aggressive disease progression and tendency to metastasize. Although chemotherapy for extensive-stage SCLC (ES-SCLC) has remained unchanged for decades, immune checkpoint inhibitors have become the primary therapy for ES-SCLC. However, the number of patients benefiting from immunotherapy is limited, and the treatment outcomes remain unsatisfactory. In addition, predictive biomarkers for immunotherapy have not yet been identified. Recent reports have shed light on the genomics of SCLC and defined four distinct molecular subtypes based on transcription factor expression. This may increase our understanding of the biology of SCLC and identify novel therapeutic targets and drugs. In this article, we review the current standard management of ES-SCLC and present the most recent reports to further our understanding of molecular classification, predictive biomarkers, and prospective therapies, including immunotherapy, chemotherapy, and targeted therapy.
Project description:Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy.
Project description:The treatment of medical conditions with cannabis and cannabinoid compounds is advancing. Although there are numerous reports related to the genetic variations of the cannabinoid receptor, a lack of studies that examine the relationship between other pharmacogenetic markers and health outcomes currently exists. Herein, we advocate for the legalization of marijuana in the United States in order to perform more randomized controlled trials to help elucidate the role of other pharmacogenetic targets and cannabis for use in clinical practice.
Project description:AbstractPneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust, usually as the result of certain occupations. The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis, which can eventually lead to death caused by respiratory and/or heart failure. Pneumoconiosis is widespread globally, seriously threatening global public health. Its high incidence and mortality lie in improper occupational protection, and in the lack of early diagnostic methods and effective treatments. This article reviews the epidemiology, safeguard procedures, diagnosis, and treatment of pneumoconiosis, and summarizes recent research advances and future research prospects.
Project description:The future GCC-connected environmental risk factors expedited the progression of nCDs. Indeed, the emergence of AFs is becoming a global food security concern. AFs are lethal carcinogenic mycotoxins, causing damage to the liver, kidney, and gastrointestinal organs. Long-term exposure to AFs leads to liver cancer. Almost a variety of food commodities, crops, spices, herbaceous materials, nuts, and processed foods can be contaminated with AFs. In this regard, the primary sections of this review aim to cover influencing factors in the occurrence of AFs, the role of AFs in progression of nCDs, links between GCC/nCDs and exposure to AFs, frequency of AFs-based academic investigations, and world distribution of AFs. Next, the current trends in the application of PPs to alleviate AFs toxicity are discussed. Nearly, more than 20,000 published records indexed in scientific databases have been screened to find recent trends on AFs and application of PPs in AFs therapy. Accordingly, shifts in world climate, improper infrastructures for production/storage of food commodities, inconsistency of global polices on AFs permissible concentration in food/feed, and lack of the public awareness are accounting for a considerable proportion of AFs damages. AFs exhibited their toxic effects by triggering the progression of inflammation and oxidative/nitrosative stress, in turn, leading to the onset of nCDs. PPs could decrease AFs-associated oxidative stress, genotoxic, mutagenic, and carcinogenic effects by improving cellular antioxidant balance, regulation of signaling pathways, alleviating inflammatory responses, and modification of gene expression profile in a dose/time-reliant fashion. The administration of PPs alone displayed lower biological properties compared to co-treatment of these metabolites with AFs. This issue might highlight the therapeutic application of PPs than their preventative content. Flavonoids such as quercetin and oxidized tea phenolics, curcumin and resveratrol were the most studied anti-AFs PPs. Our literature review clearly disclosed that considering PPs in antioxidant therapies to alleviate complications of AFs requires improvement in their bioavailability, pharmacokinetics, tissue clearance, and off-target mode of action. Due to the emergencies in the elimination of AFs in food/feedstuffs, further large-scale clinical assessment of PPs to decrease the consequences of AFs is highly required.
Project description:Neurotrophic keratopathy (NK), or neurotrophic keratitis, is a degenerative condition that results from decreased innervation to the cornea. The cornea is innervated by the ophthalmic branch of the trigeminal nerve. Neurotrophic keratopathy is most commonly caused by herpes keratitis however, any condition that disrupts the normal corneal innervation can cause NK. Neurotrophic keratopathy is a clinical diagnosis and is classified into three stages based on the disease severity. Stage 1 has mild epithelial defects, such as punctate keratopathy, stage 2 disease has persistent epithelial defects, and stage 3 is defined by the presence of ulcers. Current treatment modalities consist of medical and surgical options. Stage 1 is treated with lubrication through artificial tears, eyelid taping, and punctal plug/cautery. Stage 2 treatment can involve therapeutic contact lenses, topical autologous or allogenic serum, tarsorrhaphy, botulinum toxin injections, and possibly anti-inflammatory medications. Stage 3 disease may require human nerve growth factor, amniotic membrane transplantation, conjunctival flap, or corneal neurotization. New therapies, such as matrix regenerating therapy, plasma rich in growth factors, Thymosin β4, Substance P/Insulin like growth factor-1, and nicergoline represent exciting future options.KEY MESSAGESNeurotrophic keratopathy is a rare degenerative disease defined by decreased innervation to the cornea that is associated with significant morbidity.Treatment options range from lubrication alone to various medical and surgical treatments.Matrix regenerating therapy, plasma rich in growth factors, Thymosin β4, Substance P/Insulin like growth factor-1, and nicergoline are exciting novel therapies that will influence how neurotrophic keratopathy is treated in the future.
Project description:Five decades have passed since the first mumps vaccine was licensed. Over this period, a resurgence of mumps infections has been recorded worldwide. Although global mumps infections have been controlled through vaccination, outbreaks are still on the rise, including in populations with high vaccination coverage. Several epidemiological studies suggest that this infectious virus continues to be a worldwide public health threat. The development and deployment of an improved, prophylactic mumps vaccine that provides long-lasting protection is indeed a priority. The purpose of this review is to provide an immuno-biological perspective on mumps vaccines. Here, we review the virology of mumps, licensed mumps vaccines, and the typical immune responses elicited following mumps vaccination. Furthermore, we discuss the limitations and challenges of the currently licensed mumps vaccines and provide strategies for the development of an improved mumps vaccine.