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Although there are no approved drugs for targeting the IDOL-LDLR pathway, recent studies demonstrate that IDOL could serve as a potential therapeutic target for hyperlipidemia. Herein, we have summarized these novel studies to present the pathological role of IDOL in CVD, further assessing its pharmacological effects for lipid-lowering therapy.

Health technology assessment (HTA) can increase the appropriateness and transparency of pricing and reimbursement decisions. Jordan is still in the early phase of its HTA implementation, although the country has very limited public resources for the coverage of healthcare technologies. The study objective was to explore and validate priorities in the HTA road map for Jordan and propose to facilitate the preferred HTA status.

Health policy experts from the public and private sectors were asked to participate in a survey to explore the current and future status of HTA implementation in Jordan. Semistructured interviews with senior policy makers supported by literature review were conducted to validate survey results and make recommendations for specific actions.

Survey and interview results indicated a need for increased HTA training, including both short courses and academic programs and gradually increasing public funding for technology assessment and appraisal. Multiple HTA bodies with central coordinacisions by increasing the weight of local evidence in HTA recommendations.Glycosylation affects clinical efficacy and safety; therefore, is a critical quality attribute of therapeutic monoclonal antibodies. Glycans are often labile and complex in patterns, giving rise to macro- and micro-heterogeneity. Recombinant production, diverse geographical locations, associated transportation and storage conditions further compound the problem. Two-way studies comparing glycoprofile of the originator and its given biosimilar are aplenty. However, the extent of analytical variation and similarity in glycoprofile across all approved versions of a drug is hardly explored. Using UHPLC and mass spectrometry, we compared the glycoprofiles of eight rituximab drug samples licensed for sale in India. While the types of glycans were found identical, the abundance of some glycans varied significantly within the tested population. The quality range of glycosylation parameters of the tested sample population differed significantly from the previously established values for US/EU licensed rituximab. As ththe tested rituximab versions. However, the QR limits corresponding to important glycosylation parameters differed significantly across all tested samples from the previously established QR limits of US- and EU-licensed rituximab in statistical terms. Such an approach may be useful in defining the true range of glycan variations in licensed versions of therapeutic mAbs.The superfamily Cosmocercoidea comprises three families Cosmocericidae, Kathlaniidae and Atractidae. Information on the nucleotide sequences of the Cosmocercoidea is quite limited, and the molecular classification of the whole superfamily has been slow to progress. The genus Grassenema of the family Atractidae is a parasitic nematode group that occurs in the digestive tract of hyraxes and includes three species Grassenema procaviae, G. dendrohyraci, and G. hyracis. The type species of the genus, G. procaviae, was isolated from the digestive tract of Cape hyraxes (Procavia capensis) and has the potential to cause gastric ulcers. Although G. procaviae is a common parasite of Cape hyraxes, no genetic information for the parasite is currently available. In this study, we obtained the first genomic sequences of G. procaviae and performed detailed morphological observations. Furthermore, molecular phylogenetic analysis was performed, and the taxonomic position of the parasite was evaluated using 18S and 28S rDNA sequences. Those data will be useful for molecular identification of G. procaviae and future phylogenetic analysis within the Atractidae.For patients who have lost sensory function due to a neurological injury such as spinal cord injury (SCI), stroke, or amputation, spinal cord stimulation (SCS) may provide a mechanism for restoring somatic sensations via an intuitive, non-visual pathway. Inspired by this vision, here we trained rhesus monkeys and rats to detect and discriminate patterns of epidural SCS. Thereafter, we constructed psychometric curves describing the relationship between different SCS parameters and the animal's ability to detect SCS and/or changes in its characteristics. We found that the stimulus detection threshold decreased with higher frequency, longer pulse-width, and increasing duration of SCS. Moreover, we found that monkeys were able to discriminate temporally- and spatially-varying patterns (i.e. variations in frequency and location) of SCS delivered through multiple electrodes. Additionally, sensory discrimination of SCS-induced sensations in rats obeyed Weber's law of just-noticeable differences. These findings suggest that by varying SCS intensity, temporal pattern, and location different sensory experiences can be evoked. As such, we posit that SCS can provide intuitive sensory feedback in neuroprosthetic devices.Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of full-length survival motor neuron (SMN) protein due to the loss of the survival motor neuron 1 (SMN1) gene and inefficient splicing of the survival motor neuron 2 (SMN2) gene, which mostly affects alpha motor neurons of the lower spinal cord. Despite the U.S. Food and Drug Administration (FDA) approved SMN-dependent therapies including Nusinersen, Zolgensma® and Evrysdi™, SMA is still a devastating disease as these existing expensive drugs may not be sufficient and thus, remains a need for additional therapies. The involvement of microRNAs (miRNAs) in SMA is expanding because miRNAs are important mediators of gene expression as each miRNA could target a number of genes. Hence, miRNA-based therapy could be utilized in treating this genetic disorder. However, the delivery of miRNAs into the target cells remains an obstacle in SMA, as there is no effective delivery system to date. This review highlights the potential strategies for intracellular miRNA delivery into target cells and current challenges in miRNA delivery. Furthermore, we provide the future prospects of miRNA-based therapeutic strategies in SMA.

Dystonia occurring in the context of parkinsonism is well-known, e.g. as foot dystonia in young-onset Parkinson's disease (PD), anterocollis in multisystem atrophy (MSA) or blepharospasm (levator inhibition) in progressive supranuclear palsy. We have, however, encountered a series of patients whose phenotype differed from the above described entities.

We describe a cohort of patients in whom typical idiopathic isolated (primary) late-onset focal or segmental (predominantly cervical) dystonia preceded the development of parkinsonism by several years, sometimes decades.

In a cohort of 450 patients followed in our botulinum toxin injections clinic, we identified 11 (2.4%; 7 women) who developed parkinsonism at a median of 14 years after the onset of dystonia. Median age at onset of parkinsonism was 70 years (range 59-87), usually manifesting with a new tremor or a change of tremor pattern, complaints of 'slowing down' or new walking difficulties. Selleck (E/Z)-BCI Parkinsonism resembled PD in 5 (one pathologically confirmednia this could be an antecedent manifestation of a syndrome with parkinsonism developing later, or be a risk factor for parkinsonism. In practice, it is important for clinicians to be alert to new symptoms/signs in patients with long-standing dystonia. From a research point of view, longitudinal case-control studies would be required to further investigate the link between long-standing dystonia and subsequent parkinsonism.

As the population ages, the incidence of ventral hernias in older adults is increasing. Ventral hernia repairs (VHR) should not be considered low risk operations, particularly in older adults who are disproportionately affected by multiple age-related factors that can complicate surgery and adversely affect outcomes. Although age-related risk factors have been well established in other surgical fields, there is currently little data describing their impact on VHR.

We performed a systematic review of the literature to identify studies that examine the effects of age-related risk factors on VHR outcomes. This was conducted using Cochrane Library, Embase, PubMed (Medline), and Google Scholar databases, all updated through June 2020. We selected relevant studies using the keywords, multimorbidity, comorbidities, polypharmacy, functional dependence, functional status, frailty, cognitive impairment, dementia, sarcopenia, and malnutrition. Primary outcomes include mortality and overall complications following VHabilitation programs aimed at improving patient-centered outcomes may be particularly useful in this population.

Postoperative radiation therapy (RT) for early-stage Merkel Cell Carcinoma (MCC) decreases the risk of locoregional recurrence and improve overall survival. However, concordance with RT guidelines is unknown.

The National Cancer Database was queried for stage I/II MCC patients receiving surgical intervention from 2006-2017. The cohort was stratified by patients who had and did not have indication(s) for adjuvant RT of the primary tumor site based on National Comprehensive Cancer Network guidelines. We captured the use of RT, patient demographics, socioeconomic characteristics, and clinical characteristics. Logistic regression, Kaplan-Meier method, and propensity score weighted Cox proportional hazards model examined associations and survival benefits of RT.

2,330 stage I/II MCC patients underwent surgical intervention. 1,858 (79.7%) met National Comprehensive Cancer Network criteria for RT of the primary tumor site, of which 1,062 (57.2%) received RT. 472 (20.3%) did not meet criteria for RT, of which 2treatment of MCC for both under- and over-treatment.This work develops a new multifunctional biocompatible anticancer nanoformulation to provide targeted image-guided cancer-selective therapeutics. It consists of three active covalently bound components (1) biocompatible nitrogen-doped graphene quantum dots (GQDs) as a multifunctional delivery and imaging platform, (2) hyaluronic acid (HA) unit targeted to the CD44 receptors on a variety of cancer cells, and (3) oxidative stress-based cancer-selective ferrocene (Fc) therapeutic. The biocompatible GQD platform synthesized from glucosamine exhibits high-yield intrinsic fluorescence. It is utilized for tracking Fc-GQD-HA formulation in vitro indicating internalization enhancement in HeLa cells targeted by the HA over non-cancer HEK-293 cells not overexpressing CD44 receptor. Fc-GQD-HA, non-toxic at 1 mg/mL to HEK-293 cells, induces cytotoxic response in HeLa enhanced over time, while therapeutic ROS generation by Fc-GQD-HA is ~3 times greater than that of Fc alone. This outlines the targeted delivery, imaging, and cancer-specific treatment capabilities of the new Fc-GQD-HA formulation enabling desired cancer-focused nanotherapeutic approach.Regenerable methods for phosphate (P) recycling have received intense attention due to their potential environmental and economic benefits. In this study, to improve the electrosorptive removal of P in membrane capacitive deionization, an activated carbon (AC) electrode was coated with a heterogeneous anion-exchange resin layer, and named the AE-AC composite electrode. It was shown that the AE-AC electrode exhibited a good capacitive behavior for electrical double-layer charging. The batch-mode experiments indicted that when the solution pH changed from 5 to 8, the predominant P species shifted from monovalent H2PO4- to divalent HPO42- that was preferentially electroadsorbed for competitive electrosorption with Cl-. Importantly, the AE-AC composite electrode significantly increased the selectivity coefficient of P over Cl- to 0.56 that was 2.24-fold greater than that of the uncoated AC electrode, at 1.2 V in single-pass mode operation. This improvement can be ascribed to the preferential transport of P through the thin coating layer containing quaternary amine functional groups.