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Topic Review
Adaptive Design
In an adaptive design of a clinical trial, the parameters and conduct of the trial for a candidate drug or vaccine may be changed based on an interim analysis. Adaptive design typically involves advanced statistics to interpret a clinical trial endpoint. This is in contrast to traditional randomized clinical trials (RCTs) that are static in their protocol and do not modify any parameters until the trial is completed. The adaptation process generally continues throughout the trial, as prescribed in the trial protocol. Adaptions may include modifications to: dosage, sample size, drug undergoing trial, patient selection criteria and/or "cocktail" mix. The PANDA (A Practical Adaptive & Novel Designs and Analysis toolkit) provides comprehensive summary of different adaptive designs. In some cases, trials have become an ongoing process that regularly adds and drops therapies and patient groups as more information is gained. Importantly, the trial protocol is set before the trial begins which pre-specifies the adaptation schedule and processes.
  • 1.2K
  • 09 Oct 2022
Topic Review
Percutaneous Vertebroplasty
Vertebroplasty and kyphoplasty are similar medical spinal procedures in which bone cement is injected through a small hole in the skin (percutaneously) into a fractured vertebra with the goal of relieving back pain caused by vertebral compression fractures. It was found not to be effective in treating osteoporosis-related compression fractures of the spine. The people in both the experimental and placebo groups of the blinded study reported improvement in their pain, suggesting that the benefit noted in unblinded trials is related to the placebo effect. The cost of vertebroplasty in Europe as of 2010 was ~2,500 Euro. As of 2010 in the United States, when done as an outpatient, vertebroplasty costs around 3300 USD while kyphoplasty costs around 8100 USD and when done as an inpatient vertebroplasty cost ~11,000 USD and kyphoplasty 16,000 USD.
  • 1.2K
  • 10 Oct 2022
Topic Review
Psycho-Oncology
Psycho-oncology is an interdisciplinary field at the intersection of physical, psychological, social, and behavioral aspects of the cancer experience for both patients and caregivers. Also known as psychiatric oncology or psychosocial oncology, researchers and practitioners in the field are concerned with aspects of individuals' experience with cancer beyond medical treatment, and across the cancer trajectory, including at diagnosis, during treatment, transitioning to and throughout survivorship, and approaching the end-of-life. Founded by Jimmie Holland in 1977 via the incorporation of a psychiatric service within the Memorial Sloan Kettering Cancer Center in New York, the field has expanded drastically since and is now universally recognized as an integral component of quality cancer care. Cancer centers in major academic medical centers across the country now uniformly incorporate a psycho-oncology service into their clinical care, and provide infrastructure to support research efforts to advance knowledge in the field. Psycho-oncology deals with psychological reactions to the experience of cancer, the behavioral component of coping with cancer as well as health behavior change including preventive medicine, and social factors that are associated with diagnosis and treatment of cancer, including communication with providers and loved ones and social support. In addition, research related to the influence of psychosocial factors on biological disease-related processes has burgeoned over the past two decades. Much research takes a biopsychosocial approach to account for the interplay between biological, psychological, and social factors in coping with cancer. The integration of psycho-oncology into routine oncologic care represents a major step forward in terms of care for the whole patient.
  • 1.2K
  • 01 Nov 2022
Topic Review
Multidrug Resistance
Multidrug resistance (MDR) transporters belonging to either the ATP-Binding Cassette (ABC) or Major Facilitator Superfamily (MFS) groups are major determinants of clinical drug resistance in fungi. The overproduction of these proteins enables the extrusion of incoming drugs at rates that prevent lethal effects. The promiscuity of these proteins is intriguing because they export a wide range of structurally unrelated molecules. Research in the last two decades has used multiple approaches to dissect the molecular basis of the polyspecificity of multidrug transporters. With large numbers of drug transporters potentially involved in clinical drug resistance in pathogenic yeasts, this review focuses on the drug transporters of the important pathogen Candida albicans. This organism harbors many such proteins, several of which have been shown to actively export antifungal drugs. Of these, the ABC protein CaCdr1 and the MFS protein CaMdr1 are the two most prominent and have thus been subjected to intense site-directed mutagenesis and suppressor genetics-based analysis. Numerous results point to a common theme underlying the strategy of promiscuity adopted by both CaCdr1 and CaMdr1. 
  • 1.2K
  • 03 Feb 2021
Topic Review
Respiratory Distress and PCD
Primary ciliary dyskinesia (PCD) is inherited in a predominantly autosomal recessive manner with over 45 currently identified causative genes. It is a clinically heterogeneous disorder that results in a chronic wet cough and drainage from the paranasal sinuses, chronic otitis media with hearing impairment as well as male infertility. Approximately 50% of patients have situs inversus totalis. Prior to the development of chronic oto-sino-pulmonary symptoms, neonatal respiratory distress occurs in more than 80% of patients as a result of impaired mucociliary clearance and mucus impaction causing atelectasis and lobar collapse. Diagnosis is often delayed due to overlapping symptoms with other causes of neonatal respiratory distress. A work up for PCD should be initiated in the newborn with compatible clinical features, especially those with respiratory distress, consistent radiographic findings or persistent oxygen requirement and/or organ laterality defects
  • 1.2K
  • 10 Mar 2021
Topic Review
Pathophysiological Perspective of Osteoarthritis
Osteoarthritis (OA) is the most well-known disease among the geriatric and the main cause of significant disability in daily living. It has a multifactorial aetiology and characterized by pathological changes of knee joint structure including cartilage erosion, synovial inflammation and subchondral sclerosis with osteophyte formation. To date, no efficient treatment is capable of altering the pathological progression of OA. This topic described significant mediators such as cytokines, proteolytic enzymes, and nitric oxide, that trigger the loss of the normal homeostasis and structural changes in the articular cartilage during the progression of OA.
  • 1.2K
  • 02 Dec 2020
Topic Review
Cerebellar Degeneration in Epilepsy
Cerebellar degeneration has been associated in patients with epilepsy, though the exact pathogenic mechanisms are not understood. The aim of this study was to identify the prevalence of cerebellar degeneration in patients with epilepsy and identify any pathogenic mechanisms. Methodology: A systematic computer-based literature search was conducted using the PubMed database. Data extracted included prevalence, clinical, neuroradiological, and neuropathological characteristics of patients with epilepsy and cerebellar degeneration. Results: We identified three consistent predictors of cerebellar degeneration in the context of epilepsy in our review: temporal lobe epilepsy, poor seizure control, and phenytoin as the treatment modality. Whole brain and hippocampal atrophy were also identified in patients with epilepsy. Conclusions: Cerebellar degeneration is prevalent in patients with epilepsy. Further prospective studies are required to confirm if the predictors identified in this review are indeed linked to cerebellar degeneration and to establish the pathogenic mechanisms that result in cerebellar insult.
  • 1.2K
  • 15 Jan 2021
Topic Review
Treatment of Rett Syndrome
Currently there is no cure for Rett syndrome. Treatment is directed towards improving function and addressing symptoms throughout life. A multi-disciplinary team approach is typically used to treat the person throughout life. This team may include primary care physician, physical therapist, occupational therapist, speech-language pathologist, nutritionist, and support services in academic and occupational settings. Treatment of Rett syndrome includes: Because of the increased risk of sudden cardiac death, when long QT syndrome is found on an annual screening EKG it is treated with an anti-arrhythmic such as a beta-blocker. There is some evidence that phenytoin may be more effective than a beta-blocker.
  • 1.2K
  • 19 Oct 2022
Topic Review
Repetitive Elements in Humans
Repetitive DNA in humans is still widely considered to be meaningless, and variations within this part of the genome are generally considered to be harmless to the carrier. In contrast, for euchromatic variation, one becomes more careful in classifying inter-individual differences as meaningless and rather tends to see them as possible influencers of the so-called ‘genetic background’, being able to at least potentially influence disease susceptibilities. Here, the known ‘bad boys’ among repetitive DNAs are reviewed. Variable numbers of tandem repeats (VNTRs = micro- and minisatellites), small-scale repetitive elements (SSREs) and even chromosomal heteromorphisms (CHs) may therefore have direct or indirect influences on human diseases and susceptibilities. Summarizing this specific aspect here for the first time should contribute to stimulating more research on human repetitive DNA. It should also become clear that these kinds of studies must be done at all available levels of resolution, i.e., from the base pair to chromosomal level and, importantly, the epigenetic level, as well.
  • 1.2K
  • 03 Mar 2021
Topic Review
Teplice Program
The Teplice Program was initiated by the Czech Ministry of Environment. The research program was prepared in collaboration with the United States Environmental Protection Agency (US EPA) and included air pollution monitoring, human exposure, biomarker studies, and health effects studies. 
  • 1.2K
  • 23 Sep 2020
Topic Review
Organoids
Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoids or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology. Microfluidic technology is used in numerous application since its allow us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results.
  • 1.2K
  • 12 Apr 2021
Topic Review
Hemochromatosis
Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper processing by the body of dietary iron which causes iron to accumulate in a number of body tissues, eventually causing organ dysfunction. It is the most common iron overload disorder.
  • 1.2K
  • 11 Nov 2022
Topic Review
Helicobacter pylori and Osteoporotic Fractures
Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world’s population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis, and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible 5-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on HPI – OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.
  • 1.2K
  • 09 Nov 2020
Topic Review
The Vaginal Microbiota
The human vagina is a useful and accessible route for local and systemic administration of drugs, and particularly for clinical indications that are directly associated with women’s sexual and reproductive health. Spurred in part by progressive societal changes to attitudes, behaviors and stigmas around the human vagina, the past twenty years has witnessed increased interest among users, clinicians, and the pharmaceutical industry in developing and using vaginal products for therapeutic benefit.
  • 1.2K
  • 23 Jun 2021
Topic Review
Dry Needling
Dry needling is a treatment performed by skilled, trained physical therapists, certified in the procedure. A thin monofilament needle penetrates the skin and treats underlying muscular trigger points for the management of neuromusculoskeletal pain and movement impairments.
  • 1.2K
  • 02 Nov 2020
Topic Review
Non-Alcoholic Steatohepatitis
Non-alcoholic steatohepatitis (NASH) is characterized by an abnormal hepatic lipid accumulation accompanied by a necro-inflammatory process and a fibrotic response.
  • 1.2K
  • 01 Mar 2021
Topic Review
Oxidative-Stress Modulators in Hematological Malignancies
Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and associated lipid peroxidation suppress self-renewal and induce DNA damage and genomic instability, which can trigger malignancy. A richer understanding of the clinical effects of oxidative stress might improve the prognosis of these diseases and inform therapeutic strategies. The most common protein carbonylation and lipid peroxidation compounds, including hydroxynonenal, malondialdehyde, and advanced oxidation protein products, have been investigated for their potential effect on hematopoietic cells in several studies.
  • 1.2K
  • 17 Jan 2021
Topic Review
Risk Ratio
In epidemiology, risk ratio (RR) or relative risk is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. It is computed as [math]\displaystyle{ I_e / I_u }[/math], where [math]\displaystyle{ I_e }[/math] is the incidence in the exposed group, and [math]\displaystyle{ I_u }[/math] is the incidence in the unexposed group. Together with risk difference and odds ratio, risk ratio measures the association between the exposure and the outcome.
  • 1.2K
  • 01 Dec 2022
Topic Review
Burn Injury and Skin Explants
Severe burn injuries remain a major health problem due to high rates of mortality, residual morbidity, and/or aesthetic damages. To find new therapies aimed at promoting a harmonious healing of skin burns, it is important to develop models which take into account the unique properties of the human skin. Based on previously described models of burn injury performed on human skin explants, we hypothesized that maintaining explants under constant tension forces would allow to more closely reproduce the pathophysiological processes of skin remodeling. We thus. Here, we set up and characterized an improved model of deep second-degree burn injury on ex vivo cultured human skin explants at air-liquid interface and maintained under conditions of constant tension forces. A spontaneous re-epithelialization of the lesion was observed 8 to 9 days post burn and was found to rely on the proliferation of basal keratinocytes at the wound edges. Collagen VII at the dermo-epidermal junction reformed along with the progression of re-epithelializatio and a synthesis of procollagen III was observed in the dermis at the wound site. These findings indicate that our model is suitable for the assessment of clinically-relevant therapies aimed at modulating the kinetics of re-epithelialization and/or the activation of fibroblasts following skin burn injuries. In this regard, we evaluated the use of a thermoreversible poloxamer hydrogel as a vehicle for topically-testable therapeutic molecules. Our data showed that, although useful for drug formulation, the p407/p188 poloxamer hydrogel induces a delay of skin re-epithelialization in humans skin explants submitted to experimental burn injury.
  • 1.2K
  • 09 Nov 2020
Topic Review
Fatty Liver
Fatty liver, or hepatic steatosis or simple steatosis, is a reversible condition wherein large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis (i.e., abnormal retention of lipids within a cell). Despite having multiple causes, fatty liver can be considered a single disease that occurs worldwide in those with excessive alcohol intake and the obese (with or without effects of insulin resistance). The condition is also associated with other diseases that influence fat metabolism. When this process of fat metabolism is disrupted, the fat can accumulate in the liver in excessive amounts, thus resulting in a fatty liver. It is difficult to distinguish alcoholic FLD, which is part of alcoholic liver disease, from nonalcoholic FLD (NAFLD), and both show microvesicular and macrovesicular fatty changes at different stages. The accumulation of fat in alcoholic or non-alcoholic steatosis may also be accompanied by a progressive inflammation of the liver (hepatitis), called steatohepatitis. This more severe condition may be termed either alcoholic steatohepatitis or non-alcoholic steatohepatitis (NASH).
  • 1.2K
  • 01 Nov 2022
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