•The population burden of IIH is projected to rise with increasing rates of obesity.•Recent studies highlight the pathogenic role of metabolic and hormonal factors.•Neuroimaging and lumbar puncture ...assessment are required for the diagnosis of IIH.•A majority of IIH patients respond to weight loss and/or acetazolamide therapy.•Surgical interventions are available for those refractory to medical treatment.
Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure, manifested by papilledema and radiological findings, in the absence of an identifiable casual factor. The primary symptoms include headache, vision loss, and pulsatile tinnitus, and are recognized to have profound impacts on quality of life and visual function. IIH demonstrates a strong predilection towards obese women of reproductive age, and the population incidence is rising with the growing prevalence of obesity worldwide. The pathophysiology involves dysregulation of cerebrospinal fluid (CSF) dynamics and venous sinus pressure, and recent studies highlighting the pathogenic role of metabolic and hormonal factors have led to the identification of several pharmacological targets and development of novel therapeutic agents. The overarching treatment goals include symptomatic alleviation and prevention of permanent vision loss. The Idiopathic Intracranial Hypertension Treatment Trial, the first of its kind randomized controlled trial on IIH, provides class I evidence for treatment with weight loss and acetazolamide. In medically refractive or fulminant cases, optic nerve sheath fenestration, CSF diversion, and venous sinus stenting, have been successfully implemented. However, there are few high-quality prospective studies investigating the treatment and natural history of IIH, highlighting the compelling need for further research to determine the optimal treatment regimen.
Research suggests a connection between idiopathic intracranial hypertension and the cerebral glymphatic system. We hypothesized that visible dilated perivascular spaces, possible glymphatic pathways, ...would be more prevalent in patients with idiopathic intracranial hypertension. This prevalence could provide a biomarker and add evidence to the glymphatic connection in the pathogenesis of idiopathic intracranial hypertension.
We evaluated 36 adult (older than 21 years of age) patients with idiopathic intracranial hypertension and 19 controls, 21-69 years of age, who underwent a standardized MR imaging protocol that included high-resolution precontrast T2- and T1-weighted images. All patients had complete neuro-ophthalmic examinations for papilledema. The number of visible perivascular spaces was evaluated using a comprehensive 4-point qualitative rating scale, which graded the number of visible perivascular spaces in the centrum semiovale and basal ganglia; a 2-point scale was used for the midbrain. Readers were blinded to patient diagnoses. Continuous variables were compared using a Student
test.
The mean number of visible perivascular spaces overall was greater in the idiopathic intracranial hypertension group than in controls (4.5 SD, 1.9 versus 2.9 SD, 1.9, respectively;
= .004). This finding was significant for centrum semiovale idiopathic intracranial hypertension (2.3 SD, 1.4 versus controls, 1.3 SD, 1.1,
= .003) and basal ganglia idiopathic intracranial hypertension (1.7 SD, 0.6 versus controls, 1.2 SD, 0.7,
= .009). There was no significant difference in midbrain idiopathic intracranial hypertension (0.5 SD, 0.5 versus controls, 0.4 SD, 0.5,
= .47).
Idiopathic intracranial hypertension is associated with an increased number of visible intracranial perivascular spaces. This finding provides insight into the pathophysiology of idiopathic intracranial hypertension, suggesting a possible relationship between idiopathic intracranial hypertension and glymphatic dysfunction and providing another useful biomarker for the disease.
The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally ...activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity. The United States Food and Drug Administration approval of the chimeric monoclonal antibody (mAb) rituximab in 1997 for the treatment of B cell non-Hodgkin lymphoma ushered in a new era of targeted therapy for cancer. A year later, trastuzumab, a humanized mAb, was approved for patients with breast cancer. In 2001, imatinib was the first small-molecule kinase inhibitor approved. The approval of ipilimumab-the first in class immune checkpoint inhibitor-in 2011 serves as a landmark period of time in the resurgence of immunotherapy for cancer. Despite the notion that increased tumor specificity results in decreased complications, toxicity remains a major hurdle in the development and implementation of many of the targeted anticancer drugs. This article will provide an overview of the current cellular and immunological understanding of cancer pathogenesis-the foundation upon which molecularly targeted therapies were developed-and a description of the ocular and neuro-ophthalmic toxicity profile of mAbs, immune checkpoint inhibitors, and small-molecule kinase inhibitors.
Iron molybdate was prepared via simple solution chemistry method and the photocatalytic degradation of a pesticide (endosulfan) was investigated under visible light irradiation. As-prepared ...(Fe2(MoO4)3) was characterized using scanning electron microscope (SEM), x-ray diffraction (XRD), energy dispersive x-ray spectra (EDX), diffused reflectance spectroscopy (DRS) and Zeta particle sizer techniques. The iron molybdate crystallite size was 36 nm, while grain size was in the range of 160-340 nm. The particles of polymetallic compound were spherical, highly porous and with fluffy texture indicating high surface area. DRS revealed Fe2(MoO4)3 was active under visible region since band gap value calculated was 2.7 eV. Response surface methodology (RSM) was employed for the optimization of photocatalytic activity (PCA) of Fe2(MoO4)3 as a function of catalyst dose, H2O2 dose, solution pH and concentration of endosulfan and up to 77% degradation was achieved at optimum conditions, which was monitored by UV/vis spectroscopy. In response to endosulfan degradation, the chemical oxygen demand (COD) and total organic carbon (TOC) were reduced up to 76% and 67%, respectively. Results revealed that iron molybdate is highly efficient photocatalyst for the degradation of endosulfan under solar light irradiation and could possibly be used for the treatment of endosulfan containing wastewater.
Fingolimod (FTY-720), a sphingosine-1-phosphate receptor modulator, is the first US Food and Drug Administration (FDA)-approved oral agent for the treatment of relapsing forms of multiple sclerosis ...(MS). Two recent phase III clinical studies (TRANSFORMS Trial Assessing Injectable Interferon vs FTY720 Oral in RRMS and FREEDOMS FTY720 Research Evaluating Effects of Daily Oral Therapy in MS) demonstrated a significant reduction in the annualized relapse rate in patients with relapsing-remitting MS, compared to once weekly interferon β-1a and placebo. Macular edema was a prominent adverse event reported in these and prior studies of fingolimod. Thirteen of 2,564 (0.5%) patients treated with fingolimod in FREEDOMS and TRANSFORMS developed macular edema. Fingolimod-associated macular edema (FAME) appears to be dose-dependent (observed in only 2 patients taking the FDA-approved 0.5 mg dose) and typically resolves upon cessation of therapy. Although a relatively common condition in ophthalmology, most neurologists have not encountered macular edema in clinical practice. The purpose of this review is to educate the neurologist on the etiology, clinical manifestations, diagnostic modalities, and treatment approaches in patients with FAME. We also discuss the use of fingolimod in patients with uveitis and diabetes mellitus, highlight the guidelines for surveillance ophthalmic examination, and outline the key distinguishing features between FAME and optic neuritis.
For sustainable development construction, recycle or reuse of waste materials is utilized. Many researchers conducted tried to create an innovative green concrete, utilizing waste materials. The aim ...of this research is to contribute and promote the use of plastic waste in concrete. The concrete’s flexural and workability were investigated by using different percentages of 0%, 0.2%, 0.4%, 0.6%, 0.8% and 1% of plastic fibers in concrete. In this study, M15 grade concrete beams were casted and cured for 7 and 28 days to analyze the flexural performance and workability. The outcomes demonstrated that the workability was slightly reduced by the utilizing plastic fibers where flexural strength improved by 16.5% at 0.6% addition of plastic fibers in concrete.
•A procedure is tested to complete energy balance based daily ETa series by MODIS data.•The HVB model is calibrated on 2 water balance terms; ETa and stream flow (Q).•HBV calibration on Q shows poor ...ETa results for inter-rainfall and recession periods.•Multi-variable (MV) vs. single variable calibration showed best HBV performance.•Large volume differences in Q and ETa do not essentially effect MV calibration.
In this study, streamflow (Qs) and satellite-based actual evapotranspiration (ETa) are used in a multi-variable calibration framework to reproduce the catchment water balance. The application is for the HBV rainfall–runoff model at daily time-step for the Karkheh River Basin (51,000km2) in Iran. Monte Carlo Simulation serves to estimate parameter values and to assess uncertainty for three calibration cases. In case one streamflow is used as the calibration target. In case two satellite-based ETa is used as calibration target. For both cases model performance is evaluated for the second variable that closes the water balance. In case three a preference-based multi-variable objective function is applied which is weighted for Qs and satellite-based ETa. For cloudy days a procedure is developed to complete the daily time series of satellite-based ETa that cover 4years.
Results on multi-variable calibration indicated satisfying results for both water balance terms. Results are compared against field observations and results of single-variable calibration. For cases one and two the second variable only is poorly simulated and resulted in poor reproduction of the water balance. The most important contribution of this work is that the catchment water balance is best reproduced when both Qs and satellite-based ETa serve as calibration target.
Pyrazinamide (PZA) is a key first-line antibiotic used for the short-course treatment of drug-sensitive and multidrug-resistant (MDR) isolates of tuberculosis. PZA exhibits potent action against ...semi-dormant bacilli in acidic environments. However, mutations that occur in target genes may cause technical difficulties in the diagnosis of PZA resistance during drug susceptibility testing. The objective of the current study is to identify mutations in pncAWT rpsA and rpsAWT panD genes among PZA-resistant isolates of Mycobacterium tuberculosis (MTB) circulating in the Pashtun dominant region, Khyber Pakhtunkhwa, Pakistan. We selected 18 PZA-resistant pncAWT strains from the Provincial Tuberculosis Reference Laboratory (PTRL) Khyber Pakhtunkhwa to investigate mutations in the coding region of rpsA and panD genes. The experiments were repeated for drug susceptibility testing using MGIT 960 automated system. In addition, eighteen PZA-resistant rpsA genes along with 5 susceptible strains and one H37Rv strain were sequenced. All 18 isolates were PZA-resistant. The majority of these isolates exhibited multidrug resistance (MDR) (13/18). We identified 14 non-synonymous and one synonymous mutation in the coding region of rpsA in 11 strains. All mutations were scattered throughout the gene and not reported previously. Further, we did not identify any mutation in 7 rpsAWT panD genes. Mutations in rpsA but not in panD occur in PZA-resistant pncAWT MTB isolates circulating in Khyber Pakhtunkhwa, Pakistan.
Recent studies of human populations suggest that the genome consists of chromosome segments that are ancestrally conserved ('haplotype blocks'; refs. 1-3) and have discrete boundaries defined by ...recombination hot spots. Using publicly available genetic markers, we have constructed a first-generation haplotype map of chromosome 19. As expected for this marker density, approximately one-third of the chromosome is encompassed within haplotype blocks. Evolutionary modeling of the data indicates that recombination hot spots are not required to explain most of the observed blocks, providing that marker ascertainment and the observed marker spacing are considered. In contrast, several long blocks are inconsistent with our evolutionary models, and different mechanisms could explain their origins.
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