12014 research outputs found
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NGLY1 deficiency: Novel variants and literature review
No full textNGLY1 deficiency is a recently described autosomal recessive disorder, involved in deglycosylation of proteins, and for that reason grouped as the congenital disorders of deglycosylation together with the lysosomal storage disorders. The typical phenotype is characterized by intellectual disability, liver malfunctioning, muscular hypotonia, involuntary movements, and decreased or absent tear production. Liver biopsy demonstrates vacuolar amorphous cytoplasmic storage material. NGLY1 deficiency is caused by bi-allelic variants in NGLY1 which catalyzes protein deglycosylation. We describe five patients from two families with NGLY1 deficiency due to homozygosity for two novel NGLY1 variants, and compare their findings to those of earlier reported patients. The typical features of the disorder are present in a limited way, and there is intra-familial variability. In addition in one of the families the muscle atrophy and posture abnormalities are marked. These can be explained either as variability of the phenotype or as sign of slowly progression of features as the present affected individuals are older than earlier reported patients. © 2021 Elsevier Masson SA
Chronic nanocurcumin treatment ameliorates pain-related behavior, improves spatial memory, and reduces hippocampal levels of IL-1β and TNFα in the chronic constriction injury model of neuropathic pain
No full textBackground: Memory deficit is a common cognitive comorbid in patients with neuropathic pain that need better treatment. Recent research revealed that nanocurcumin has an antinociceptive action and a protective effect against memory disorders, suggesting its possible effectiveness for the treatment of neuropathic pain and its comorbidity. Methods: Adult male albino Wistar rats (n = 32) were randomly divided into four experimental groups: CCI+ nanocurcumin, CCI + vehicle, sham + nanocurcumin, and sham + vehicle. Neuropathic pain induced by a chronic constriction injury of the sciatic nerve. Nanocurcumin or vehicle was injected intraperitoneally for 10 days. Behavioral assessment achieved to evaluate pain threshold in the von Frey test and radiant heat test, also spatial learning and memory examined by the Morris water maze (MWM) test. To explore the possible relation, IL-1β, and TNF-α levels of the hippocampus measured by enzyme-linked immunosorbent assay (ELISA). Results: Our data showed that CCI caused neuropathic pain-related behaviors and spatial learning and memory disorders in rats. Chronic treatment with nanocurcumin significantly increased pain threshold (P < 0.001; F = 27.63, F = 20.58), improved spatial memory (P < 0.01; F = 47.37), and decreased the hippocampal levels of IL-1β (P < 0.001; F = 33.57) and TNF-α (P < 0.01; F = 7.25) in CCI rats. Conclusion: Chronic nanocurcumin can ameliorate pain-related behavior, improve spatial learning and memory deficits, and is associated with the reduction of IL-1β and TNF-α levels in the hippocampus in CCI rats. Nanocurcumin may be potentially providing a therapeutic alternative for the treatment of neuropathic pain and its memory impairment comorbidity. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature
The Seismic Shift in End-of-Life Care: Palliative Care Challenges in the Era of Medical Assistance in Dying
No full textBackground: Concerns regarding personal, professional, administrative, and institutional implications of medical assistance in dying (MAiD) are of particular interest to palliative and hospice care providers (PHCPs), who may encounter additional moral distress and professional challenges in providing end-of-life (EOL) care in the new legislative and cultural era. Objective: To explore PHCPs' encountered challenges and resource recommendations for caring for patients considering MAiD. Design: Qualitative thematic analysis of audio-recorded semistructured interviews with PHCPs. Setting/Subjects: Multidisciplinary PHCPs in acute, community, residential, and hospice care in Vancouver, Canada, with experience supporting patients who have made MAiD inquiries or requests. Measurements: Interviews were deidentified, transcribed verbatim, and coded by four researchers using a common coding scheme. Key themes were analyzed. Results: Twenty-six PHCP participants included physicians (n = 7), nurses (n = 12), social workers (n = 5), and spiritual health practitioners (n = 2). Average interview length was 52 minutes (range 35-90). Analysis revealed four broad challenges associated with providing EOL care after MAiD legalization: (1) moral ambiguity and provider distress, (2) family distress, (3) interprofessional team conflict, and (4) impact on palliative care. Participants also recommended three types of resources to support clinicians in delivering quality EOL care to patients contemplating MAiD: (1) education and training, (2) pre- and debriefing for team members, and (3) tailored bereavement support. Conclusions: PHCPs encountered multilevel MAiD-related challenges, but noted improvement in organizational policies and coordination. Resources to enhance training, pre- and debriefing, and tailored bereavement may further support PHCPs in providing high-quality EOL care as they navigate the legislative and cultural shifts. © Copyright 2021, Mary Ann Liebert, Inc
The role of nanotechnology in current COVID-19 outbreak
Full text linkCOVID-19 has recently become one of the most challenging pandemics of the last century with deadly outcomes and a high rate of reproduction number. It emphasizes the critical need for the designing of efficient vaccines to prevent virus infection, early and fast diagnosis by the high sensitivity and selectivity diagnostic kits, and effective antiviral and protective therapeutics to decline and eliminate the viral load and side effects derived from tissue damages. Therefore, non-toxic antiviral nanoparticles (NPs) have been under development for clinical application to prevent and treat COVID-19. NPs showed great promise to provide nano vaccines against viral infections. Here, we discuss the potentials of NPs that may be applied as a drug itself or as a platform for the aim of drug and vaccine repurposing and development. Meanwhile, the advanced strategies based on NPs to detect viruses will be described with the goal of encouraging scientists to design effective and cost-benefit nanoplatforms for prevention, diagnosis, and treatment. © 202
TLR4 /NF-ĸB and JAK2/STAT3 signaling pathways: Cellular signaling pathways targeted by cell-conditioned medium therapy in protection against ischemic stroke
No full textHuman amniotic membrane-derived mesenchymal stem cell-conditioned medium (hAMSC-CM) has been known to improve neuronal survival following ischemic stroke. The present study was designed to examine whether protective effects of hAMSC-CM against stroke can be linked to reducing neuroinflamation by targeting TLR4 /NF-ĸB and Jak2/Stat3 signaling pathways. Immunohistochemistry of hippocampus and western blot assay were performed to evaluate the expression of TLR4 /NF-ĸB and Jak2/Stat3, respectively. Real-time PCR assay was applied to investigate the mRNA levels of Jak2/Stat3. Hematoxylin and eosin (H&E) staining was used to investigate tissue damage and morphological changes in the CA1 region of hippocampus. Increased brain edema was seen in middle cerebral artery occlusion (MCAO) rats compared to sham. Post-treatment with hAMSC-CM markedly reduced brain edema in comparison with MCAO group (P < 0.05). Compared to sham, significantly increased levels of TLR4 /NF-ĸB and Jak2/Stat3 were seen in MCAO rats. Intravenous injection of hAMSC-CM after reperfusion markedly reduced levels of TLR4 /NF-ĸB and Jak2/Stat3 in hippocampus region (P < 0.05). Tissue damage and neuronal cell increased in the CA1 region of hippocampus that reversed by post-treatment by hAMSC-CM. Interestingly, our finding showed that hAMSC-CM can be considered as good candidate to reduce injury following ischemic stroke by decreasing activity of TLR4 /NF-ĸB and Jak2/Stat3 signaling pathways. © 202
Comparison of psychological symptoms and cognitive functions in patients under maintenance treatment with methadone or buprenorphine, current opioid users and healthy subjects
No full textMethadone and buprenorphine can affect the psychological symptoms and cognitive functioning of substance users. This study aimed to compare psychological symptoms and neuropsychological functioning in methadone maintenance patients (MMP), buprenorphine maintenance patients (BMP), current opioid users, and healthy subjects. One hundred and twenty participants (30 in each group) matched for age, sex, and education completed the Symptom Checklist-90-Revised (SCL-90-R) and a battery of neuropsychological tests including the Wisconsin Card Sorting Test (WCST), Wechsler Memory Scale (WMS-IV), and Stroop Color-Word Test (SCWT) assessing executive functioning, working memory, and attention, respectively. Overall, opioid users showed more severe psychological symptoms compared to healthy subjects. MMP and BMP had intermediate scores in SCL-90-R subscales; however, BMP had fewer severe symptoms compared to the MMP group. In terms of cognitive functioning, healthy subjects and current users demonstrated the best and the worst performance, respectively. Also, BMP outperforms MMP on executive functions and attention. However, the MMP had a better performance in WMS (visual memory). Patients receiving maintenance treatment had fewer psychological symptoms and better cognitive performance compared to opioid users. BMP had a better profile in all psychological symptoms and better performance in executive functions and selective attention compared to the MMP suggesting buprenorphine may be a better choice for the treatment of opioid-dependent patients. © 2021 Elsevier B.V
Exosomal microRNAs and exosomal long non-coding RNAs in gynecologic cancers
No full textGynecologic cancer is a group of any malignancies affecting reproductive tissues and organs of women, including ovaries, uterine, cervix, vagina, vulva, and endometrium. Several types of molecular mechanisms are associated with the progression of gynecologic cancers. Among it can be referred to the most widely studied non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long ncRNAs (lncRNAs). As yet, lncRNAs are known to serve key biological roles via various mechanisms, such as splicing regulation, chromatin rearrangement, translation regulation, cell-cycle control, genetic imprinting and mRNA decay. Besides, miRNAs govern gene expression by modulation of mRNAs and lncRNAs degradation, suggestive of needing more research in this field. Generally, driving gynecological cancers pathways by miRNAs and lncRNAs lead to the current improvement in cancer-related technologies. Exosomes are extracellular microvesicles which can carry cargo molecules among cells. In recent years, more studies have been focused on exosomal non-coding RNAs (exo-ncRNAs) and exosomal microRNAs (exo-miRs) because of being natural carriers of lnc RNAs and microRNAs via programmed process. In this review we summarized recent reports concerning the function of exosomal microRNAs and exosomal long non-coding RNAs in gynecological cancers. © 2021 Elsevier Inc
Formulation and evaluation of inhalable microparticles of Rizatriptan Benzoate processed by spray freeze-drying
No full textThe aim of the current study was to prepare and evaluate inhalable microparticles of Rizatriptan benzoate in order to further benefit from its pulmonary delivery, the expected enhanced bioavailability and accelerated onset of action. The spray freeze drying (SFD) technique was used to produce microparticles consisting of a fixed amount of a sugar which was either mannitol or trehalose and an amino acid component including leucine, phenylalanine or serine. The powders were then characterized for particle size distribution, morphology, thermal properties and in vitro aerosolization performance. It was demonstrated that various formulations of inhalable Rizatriptan could be efficiently aerosolized and offered acceptable fine particle fraction (FPF) ranging up to 61.1. In particular, a spray-freeze-dried powder composed of trehalose and phenylalanine showed the most superior inhalation performance (FPF = 61.1), indicating better dispersion properties of those spherical porous microparticles with less adhesion and agglomeration. These results successfully demonstrated that Rizatriptan could be engineered into respirable microparticles to be proposed as a promising delivery system for fast and effective control of migraine attacks. © 2021 Elsevier B.V
The prevalence of restless legs syndrome in chronic obstructive pulmonary disease (COPD) patients
No full textTo investigate the prevalence of restless legs syndrome (RLS) in chronic obstructive pulmonary disease (COPD) patients. The symptoms and severity of RLS was evaluated by the International Restless Legs Syndrome Group Study (IRLSSG). Mann�Whitney U test, Chi-square test and Spearman correlation coefficient were used to analyze the data. Out of the 109 COPD patients, 18.3 were diagnosed with RLS. There is no statistically significant difference between RLS and non-RLS groups except the mean age (P value > 0.05). Restless legs syndrome is relatively common in patients with COPD. © 2021, Japanese Society of Sleep Research