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Copyright of Canadian Journal of Hospital Pharmacy / Journal Canadien de la Pharmacie Hospitalière is the property of Canadian Society of Hospital Pharmacists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Brain‐derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making EVs attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease‐vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labelling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40–150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g., APPswe, PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with Aβ deposition. Genotype, age, and Aβ deposition modulated proteostasis‐ and immunometabolic‐related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust‐ and diverse‐ EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of a single-dose, oral vitamin D supplementation (soft gel capsule of 200,000 IU) in subjects with painful diabetic neuropathy (PDN) in Pakistan. Design: Randomized control trial. Materials and Methods: This randomized control trial was conducted at the Baqai Institute of Diabetology and Endocrinology (BIDE), Pakistan from November 2021 to August 2022. Subjects with diabetes without any signs of vitamin D deficiency were included. Baseline details were obtained by a predesigned questionnaire. Douleur neuropathy 4 (DN4) score was used for diagnosing PDN. Biochemical tests include serum 25-hydroxyvitamin D (OH)D and HbA1c for screening at baseline and at 3 months follow-up were analyzed. Subjects were categorized into two: a control group and an intervention group. The intervention group was given a single soft gel vitamin D capsule (200,000 IU) after screening by expert paramedical staff. Based on baseline serum vitamin D levels, the intervention group was further categorized into insufficient vs. deficient groups, and the control group was categorized into insufficient vs. sufficient. Results: Of 159 participants, 19.5% vs. 44.7% subjects were with insufficient vs. deficient vitamin D levels in the intervention group, and 10.7% vs. 25.1% were with insufficient vs. sufficient vitamin D levels in the control group, respectively. Though the findings are insignificant, DN4 score at follow-up in intervention groups and control groups was reduced compared to the baseline DN4 score. Furthermore, we observed a reduction in post-HbA1c levels in both the intervention groups (insufficient vs. deficient) and the control-sufficient group. Conclusion: Treatment with vitamin D supplementation in people with PDN helps to improve vitamin D levels, DN4 score, and HbA1c levels, though doseresponse is yet to be compared. [ABSTRACT FROM AUTHOR]

Objective: Measure and quantify the extent of functional limitations in knee osteoarthritis patients under 50. This could include a range of motion, mobility, and activities of daily living (ADLs). Method: This observational study was conducted at the Baqai Institute of Diabetology and Endocrinology (BIDE) in its specialized foot clinic from 2015 to 2016. Data were collected from 80 participants of all genders who were under the age of 50. Individuals with a history of road traffic accidents (RTA), osteomyelitis, tuberculosis of joints, tumors, or those who had undergone ligament surgery were excluded from the study. The collected data were subjected to descriptive analysis using statistical package for social sciences to determine the frequency of various parameters. Result: Participants were 80 (male + female) with an average age of 45.1 years and a standard deviation of 4.2. Regarding pain, the mean score was 6.5 with a standard deviation of 1.2. In terms of pain frequency, 56.3% reported constant pain. About mobility, 70% could walk normally. Of the participants, 25% had a limping gait. For descending stairs, 35% could do so without difficulty. Moreover, nearly all 98.8% experienced discomfort when squatting. Regarding muscle range of motion, active motion was associated with pain in flexion 35%, extension 7.5%, and both flexion and extension 47.5%. These unexpected results suggest a higher level of impairment than anticipated. Conclusion: Our study revealed no statistically significant difference in the intensity of stiffness. However, there was a gender difference in the pain and physical function limitations. [ABSTRACT FROM AUTHOR]

Objective To determine the efficacy of intradermal injection of platelet rich plasma in combination with methotrexate in patients of chronic plaque psoriasis. Methods It was a descriptive case series performed in department of dermatology, FJMU/SGRH Lahore from April 4, 2018 till Oct 4, 2018. A total number of 73 patients enrolled from outpatient department, after acceptance from ethical review board and written informed consent, patients fulfilling the inclusion and exclusion criteria. The demographic information like age, gender, address was collected and recorded as per proforma. All cases were treated under supervision of consultant dermatologist having more than 5 years of clinical experience to avoid bias. The study was conducted for 16 weeks, in which patients were treated for a period of 15 weeks and results were calculated by the end of 16th week. All cases were treated with PRP and MTX both. Autologous PRP was prepared from patient's peripheral blood through 2-stage centrifugation process as per established protocol. Each patient was given intra-lesional PRP in psoriatic plaques on 1st week, 0.1 ml of PRP was given at each point with 2cm spacing followed by 15mg of intralesional MTX weekly for 4 weeks i.e. 2nd, 3rd, 4th and 5th week' after 1 week of PRP injection, 15 mg of MTX were divided among the plaques so that 1.25mg was given at each point with a space of 2cm between two points. Second administration of intralesional PRP was done in the psoriatic plaques on 6th week followed by similar administration of intra-lesional MTX on 7th, 8th, 9th and 10th week. Third intralesional PRP was given on 11th week and then intra-lesional MTX was given again on 12th, 13th, 14th and 15th week. Both PRP and MTX were given through intra-lesional route to avoid toxicity associated with systemic administration. All cases were observed for the effect of treatment by the end of 16th week and PASI was calculated. Efficacy was labeled as per operational definition. Results The mean age of cases was 39.60 ±12.15 years in range of 18 and 60 years. There were 24 (32.88%) male and 49 (67.12%) female cases, with higher female cases. According to operational definition 60 (82.19%) had efficacy while 13 (17.81%) cases did not meet the criteria of efficacy. Conclusion The efficacy of intradermal injection of platelet rich plasma in combination with methotrexate in patients of chronic plaque psoriasis is highly effective. This combination can be utilized for substantial improvement in term of improvement of PASI score. [ABSTRACT FROM AUTHOR]

Brain-derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. Circulating EVs are protected from degradation, making them attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease-vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labeling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40-150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g. APPswe,PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with A deposition. Genotype, age, and Aβ deposition modulated proteostasis- and immunometabolic-related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust- and diverse- EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD.