TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied. METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients with RVCL and ischemic stroke. RESULTS: After validating the specificity of our anti-TREX1 rabbit pAb, WB analysis was utilized to detect the endogenous wild-type and frame-shift mutant of TREX1 in cell lysates. Dual staining in human brain tissues from patients with RVCL and normal controls localized TREX1 to a subset of microglia and macrophages. Quantification of immunohistochemical staining of the cerebral cortex revealed that TREX1 CONCLUSIONS: TREX1 is expressed by a subset of microglia in normal human brain, often in close proximity to the microvasculature, and increases in the setting of ischemic lesions. These findings suggest a role for TREX

Gender and Ocular Manifestations of Connective Tissue Diseases and Systemic Vasculitides

Ocular manifestations are present in many connective tissue diseases which are characterized by an immune system that is directed against self. In this paper, we review the ocular findings in various connective tissue diseases and systemic vasculitides and highlight gender differences in each disease. In rheumatoid arthritis, we find that dry eyes affect women nine times more than men. The other extra-articular manifestations of rheumatoid arthritis affect women three times more commonly than men. Systemic lupus erythematosus can involve all ocular structures and women are nine times more affected than men. Systemic sclerosis is a rare disease but, again, it is more common in women with a female to male ratio of 8 : 1. Polymyositis and dermatomyositis also affect women more commonly than men but no gender differences have been found in the incidence or disease course in the systemic vasculitides associated with antineutrophil cytoplasmic antibody such as granulomatosis with polyangiitis (GPA, formerly known as Wegener’s granulomatosis). Finally, Behcet’s disease is more common in males, and male gender is a risk factor for Behcet’s disease. There is a slight female preponderance in sarcoidosis with female gender carrying a worse prognosis in the outcome of ocular disease

Exploring the quality of life of cosmetic users: A cross-sectional analysis from eight Arab countries in the Middle East

Background The use of cosmetic products is growing in dominance in the Arab population, making it essential to measure its effects on users. The production of cosmetics has been largely driven by consumerism and a bid to keep abreast with the latest trends in the beauty industry with less attention on how the users' quality of life (QoL) is affected. Aims This study aims to investigate the effect of cosmetic products on users' quality of life in eight Arab countries. Methods A cross-sectional study was carried out using an online data collection approach. A validated and specialist instrument tool called BeautyQoL, which consists of five domains and a total of 52 questions, was distributed to a sample of 2219 cosmetic users. Descriptive and inferential statistical analysis was done using SPSS® version 26.0. Results The mean age of participants was 34 ± 11.25 years, and more women were represented in the sample (71%) than men. The majority of respondents had oily skin type (39.6%) and tan skin tone (30.4%). QoL through cosmetic use is computed with a mean score of 51 out of 100. The users' mean score satisfaction from cosmetic use is centred on attractiveness (56.1), followed by self-confidence (51.8). Cosmetics have a statistically significant effect on participants who are young adults, women, single, and employed with high income. As the respondents' skin tone deepens from very fair to dark, the mean score for each domain significantly increases, whereas when skin type changes from very oily to dry, the mean score for each domain decreases. Conclusion The effect of cosmetics on the users' QoL is limited, contrary to the narrative commonly portrayed in cosmetics' advertisements. Therefore, the use of cosmetics among the Arab population should be from an informed perspective of their specific needs instead of conforming to the viral trends pedaled by influencers and bloggers on social media, which might be irrelevant for them.Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. [Correction added on 5 July 2022, after first online publication: CAUL funding statement has been added.]Scopu

The structure of the tetrasialoganglioside from human brain

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias

A pharmacist-delivered smoking cessation program in Qatar: an exploration of pharmacists' and patients' perspectives of the program

Background Tobacco use is one of the major causes of morbidity and mortality. An intensive pharmacist-delivered smoking cessation program was implemented in eight primary care pharmacies in Qatar. Objective This study aimed to qualitatively explore the perspectives of pharmacists and patients regarding their experiences in the program and their recommendations for improving it. Setting Primary care in Doha, Qatar. Method This study used a qualitative case study approach with semi-structured interviews of a sample of patients and pharmacists who participated in the program. Interviews were conducted between October 2016 and June 2017, were audio-recorded and transcribed verbatim. A thematic approach for data analysis was used. Main outcome measures Perspectives of pharmacists and patients. Results Pharmacists who delivered the program (n = 17) and patients who completed the program's outcomes assessment (n = 68) were invited through telephone call or email. Eight pharmacists and 22 patients were interviewed. Seven themes emerged: (1) both pharmacists and patients had positive experiences and both considered pharmacists as among the most suitable healthcare providers to provide smoking cessation interventions (2) both pharmacist and patient participants indicated that the program provided successful services (3) pharmacists identified several challenges for implementing the program including difficulty in motivating and in following-up patients, workplace barriers, communication and cultural barriers, (4) both pharmacists and patients perceived several barriers for quitting including lack of motivation to quit or to commit to the plan, high nicotine dependence, stress and personal problems (5) both pharmacists and patients considered several patient-related facilitators for quitting including development of smoking related complications, religious beliefs and external support; (6) use of smoking cessation medications was considered a program-related facilitator for quitting by patients whereas behavioral therapy was perceived to be a facilitator by pharmacists (7) pharmacists and patients proposed strategies for program improvement including enhancing pharmacist training and patient recruitment. Conclusion The program was perceived to be beneficial in helping patients quit smoking, and it positively contributed to advancing pharmacist role. The study findings can guide future development of successful pharmacist' smoking cessation programs in Qatar. 2021, The Author(s).This publication is made possible by a student grant by Qatar University (QUST-CPH-SPR\2017-1).Scopu

Reversible Cerebral Vasoconstriction Syndromes Analysis of 139 Cases

Objectives: To compare the clinical, laboratory, and imaging features of patients with reversible cerebral vasoconstriction syndromes evaluated at 2 academic centers, compare subgroups, and investigate treatment effects. Design: Retrospective analysis. Setting: Massachusetts General Hospital (n = 84) or Cleveland Clinic (n = 55). Patients: One hundred thirty-nine patients with reversible cerebral vasoconstriction syndromes. Main Outcome Measures: Clinical, laboratory, and imaging features; treatment; and outcomes. Results: The mean age was 42.5 years, and 81% were women. Onset with thunderclap headache was documented in 85% and 43% developed neurological deficits. Prior migraine was documented in 40%, vasoconstrictive drug exposure in 42%, and recent pregnancy in 9%. Admission computed tomography or magnetic resonance imaging was normal in 55%; however, 81% ultimately developed brain lesions including infarcts (39%), convexity subarachnoid hemorrhage (34%), lobar hemorrhage (20%), and brain edema (38%). Cerebral angiographic abnormalities typically normalized within 2 months. Nearly 90% had good clinical outcome; 9% developed severe deficits; and 2% died. In the combined cohort, calcium channel blocker therapy and symptomatic therapy alone showed no significant effect on outcome; however, glucocorticoid therapy showed a trend for poor outcome (P = .08). Subgroup comparisons based on prior headache status and identified triggers (vasoconstrictive drugs, pregnancy, other) showed no major differences. Conclusion: Patients with reversible cerebral vasoconstriction syndromes have a unique set of clinical imaging features, with no significant differences between subgroups. Prospective studies are warranted to determine the effects of empirical treatment with calcium channel blockers and glucocorticoids.WoSScopu

A pharmacist-delivered smoking cessation program in Qatar: an exploration of pharmacists’ and patients’ perspectives of the program

Background Tobacco use is one of the major causes of morbidity and mortality. An intensive pharmacist-delivered smoking cessation program was implemented in eight primary care pharmacies in Qatar. Objective This study aimed to qualitatively explore the perspectives of pharmacists and patients regarding their experiences in the program and their recommendations for improving it. Setting Primary care in Doha, Qatar. Method This study used a qualitative case study approach with semi-structured interviews of a sample of patients and pharmacists who participated in the program. Interviews were conducted between October 2016 and June 2017, were audio-recorded and transcribed verbatim. A thematic approach for data analysis was used. Main outcome measures Perspectives of pharmacists and patients. Results Pharmacists who delivered the program (n = 17) and patients who completed the program’s outcomes assessment (n = 68) were invited through telephone call or email. Eight pharmacists and 22 patients were interviewed. Seven themes emerged: (1) both pharmacists and patients had positive experiences and both considered pharmacists as among the most suitable healthcare providers to provide smoking cessation interventions (2) both pharmacist and patient participants indicated that the program provided successful services (3) pharmacists identified several challenges for implementing the program including difficulty in motivating and in following-up patients, workplace barriers, communication and cultural barriers, (4) both pharmacists and patients perceived several barriers for quitting including lack of motivation to quit or to commit to the plan, high nicotine dependence, stress and personal problems (5) both pharmacists and patients considered several patient-related facilitators for quitting including development of smoking related complications, religious beliefs and external support; (6) use of smoking cessation medications was considered a program-related facilitator for quitting by patients whereas behavioral therapy was perceived to be a facilitator by pharmacists (7) pharmacists and patients proposed strategies for program improvement including enhancing pharmacist training and patient recruitment. Conclusion The program was perceived to be beneficial in helping patients quit smoking, and it positively contributed to advancing pharmacist role. The study findings can guide future development of successful pharmacist’ smoking cessation programs in Qatar.Other Information Published in: International Journal of Clinical Pharmacy License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s11096-021-01286-3</p