Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere's disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (Phex Hyp-Duk /Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex Hyp-Duk /Y mice and to test the hypotheses that (a) the Phex Hyp-Duk /Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex Hyp-Duk /Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex Hyp-Duk /Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex Hyp-Duk /Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients.
Cochlear implantation is a safe and viable option for hearing rehabilitation in patients deafened by progressive AIED. Hearing outcomes in AIED patients are excellent and support transition to implantation when hearing is lost or long-term steroid therapy becomes undesirable. Cochlear fibrosis or ossification seems to affect nearly 50% of implanted ears (41.6% of patients) in this study and implies that the cochlea is at risk for ossification changes long term. In appropriate candidates, earlier implantation may be indicated before postinflammatory obliterative changes in the cochlea.
Diabetic retinopathy (DR) is one of the long-term microvascular complications of diabetes mellitus (DM) and is considered a leading cause of vision loss worldwide. Chronic hyperglycemia can cause microvascular abnormalities to the retina and the choroid as well. The vascular tissue of the choroid supplies blood to the outer retina, photoreceptors, and retinal pigment epithelium. It plays an important role in the metabolic exchange of the retina. Many experimental studies reported that choroidal pathology in diabetic patients might play a role in developing DR. Choroidal thickness (CT) can reflect changes in the vasculature of the choroid and can be used to assess the vascularity of the choroid itself. CT differs between healthy and diseased states of the eye as well as with the aging process. This means that thinner or thicker choroid may indicate an ocular disease. Choroidal vascularity index (CVI) is also used as a marker for choroidal vascularity assessment and indirectly measures choroidal vascularity quantitatively. Many studies have been conducted to evaluate the choroid in many different ocular diseases. However, the results regarding CT in DM, especially in patients with DR, are various as thickened, thinned, or no changes. Thus, the status of the choroid in patients with DM with or without DR remains controversial between researchers. In this systematic review, we reviewed 18 articles that were done to investigate the relationship between structural choroidal changes in diabetic patients with different stages of DR, focusing on CT, CVI, and some other parameters evaluating choroidal changes.
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype of B cell ALL. It accounts for 20% of all B cell ALL cases and is similar to BCR-ABL1 in gene expression profile but lacks BCR-ABL fusion. It is highly heterogeneous and is characterized by genetic alterations that activate kinase and cytokine receptor signaling. Most of these alterations are amenable to tyrosine kinase inhibitors. Ph-like ALL is prevalent in pediatric and young adults, more common in males, and frequently seen in patients with Hispanic ancestry. It is associated with inadequate response to induction therapy, high minimal residual disease (MRD) levels, and increased risk of relapse. Overall survival and event-free survival are also inferior in these patients as compared to non-Ph-like ALL. In the clinical practice, low-density array, real-time quantitative polymerase chain reaction (RQ-PCR), flow cytometry, fluorescence in situ hybridization are used to identify genetic alteration in these patients. With the advent of next-generation sequencing (NGS), our understanding of disease pathogenesis and precision medicine has been improved. In this review, we analyzed data from several studies that used NGS as one of the diagnostic methods to identify genomic lesions in this high-risk subtype of B cell ALL. Studies have shown that NGS is a vital technique to identify various genomic lesions at diagnosis and throughout the treatment that can be missed by the widely used current methods. NGS has improved our understanding of various genomic lesions associated with Ph-like ALL and has helped define disease pathogenesis, MRD evaluation, and stratify therapy to prevent over or under treatment. We are in the era of precision medicine. Therefore unbiased, comprehensive genomic characterization of Ph-like ALL is important to implicate treatment directed against these genomic lesions and improve outcomes in these patients. We also analyzed data from studies that compared NGS with multi-flow cytometry and RQ-PCR for the evaluation of MRD. In the future, more extensive prospective studies are required to confirm the prognostic usefulness of NGS.
Aneurysmal subarachnoid hemorrhage (aSAH) is a prevalent condition affecting a large portion of the population, many of them still in productive ages. Memory impairment is a common factor amongst those patients. Memory exerts a pivotal role in productivity. That is why it is important to understand how it can be affected in post-aSAH patients. There are certain areas most affected in cases of memory disturbances, as well as its functional connections with crucial cerebral regions. Active research on functional magnetic resonance and diffusion tension imaging is used to identify compromised areas within the brain. There are suggested factors regarding poor performance, such as cerebrospinal fluid drainage and new infarction areas, which should be addressed properly to benefit these patients and simultaneously help them return to a productive and functional life.
Optimal blood glucose control helps reduce the development of the complications of type II diabetes mellitus (T2DM). T2DM patients usually are at increased risk of cardiovascular (CV) events and mortality. Therapies and strategies to treat diabetes and its related CV outcomes still need more investigation to find the best management options for this population. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have several benefits over multiple organ systems of the human body. However, the comparative effectiveness of this drug class is still not well-established. Our review aims to assess SGLT-2 inhibitors' effects on the CV complications that occur because of uncontrolled diabetes. A comprehensive literature search was conducted on PubMed and PubMed Central to find the relevant studies that were done from 2016 through 2020 to gather data for this review article. Those studies include reviews, randomized clinical trials, systematic reviews, and meta-analyses. Studies used in this article found an associated decrease in CV complications and mortality in patients with T2DM who received treatment with SGLT-2 inhibitors compared to the placebo group. These drugs have shown significant efficacy and safety outcomes in diabetic patients with heart disease, as they are glycosuric and diuretics, both of which are characteristics that could provide benefits to this population. SGLT-2 inhibitors appear to reduce the risk of cardiovascular events and mortality, suggesting that the benefits of these drugs seen in people with diabetes may apply to a broad population in the real world. We recommend further studies should confirm the immense clinical benefits with SGLT-2 inhibitors in patients with T2DM.
Background: The prevalence of depression is alarming all over the world afflicting billions of individuals. Depression is a common mental disorder and is one of the major causes of morbidity worldwide. Although, there are known effective treatment for depression, but antidepressant therapy usually causes a wide range of undesirable adverse effects and also increases the risk for suicide in individuals with ongoing treatment. So in order to reduce the risks associated, a study was conducted to evaluate the antidepressant potential of Musa paradisiacal Linn, commonly known as Banana fruit and to assess whether the natural source could be used to treat depression.
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