The role of membrane trafficking and retromer complex in Parkinson's and Alzheimer's disease.

Membrane trafficking is a physiological process encompassing different pathways involved in transporting cellular products across cell membranes to specific cell locations via encapsulated vesicles. This process is required for cells to mature and function properly, allowing them to adapt to their surroundings. The retromer complex is a complex composed of nexin proteins and peptides that play a vital role in the endosomal pathway of membrane trafficking. In humans, any interference in normal membrane trafficking or retromer complex can cause profound changes such as those seen in neurodegenerative disorders such as Alzheimer's and Parkinson's. Several studies have explored the potential causative mechanisms in developing both disease processes; however, the role of retromer trafficking in their pathogenesis is becoming increasingly significant with promising therapeutic applications. This manuscript describes the processes involved in membrane transport and the roles of the retromer in the onset and progression of Alzheimer's and Parkinson's. Moreover, we will also explore how these aberrant mechanisms may serve as possible avenues for treatment development in both diseases and the prospect of its future application.

Safety and Efficacy of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors After Acute Coronary Syndrome: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors (PCSK9i) have a beneficial effect on various domains of patients' lipid profiles and cardiovascular and mortality outcomes. Here, we aim to further investigate the efficacy and safety of PCSK9i in patients with ACS or who experienced recent episodes. METHODS: We comprehensively searched PubMed, Scopus, Web of Science and Cochrane CENTRAL to identify all randomized controlled trials comparing PCSK9i versus placebo. Data were extracted and analysed using Stata/MP version 17.0. RESULTS: Eleven studies (n = 24,732) were included in this meta-analysis. In terms of efficacy outcomes, compared with the control group, PCSK9i significantly decreased levels of LDL-C, TC, TG, Lp (a) and Apo-B, with the following values, respectively: Cohen's d of - 1.25, 95% confidence interval (CI - 1.64 to - 0.87); Cohen's d of - 1.32, 95% CI (- 1.83 to - 0.81); Cohen's d of - 0.26, 95% CI (- 0.37 to - 0.14); Cohen's d of - 0.70, 95% CI (- 1.15 to - 0.26); and Cohen's d of - 1.46, 95% CI (- 1.97 to - 0.94). The levels of HDL-C and Apo-A1 increased by: Cohen's d 0.27, 95% CI (0.16-0.39) and Cohen's d of 0.30, 95% CI (0.17-0.42), respectively. Regarding safety outcomes, PCSK9i was associated with lower odds of myocardial infarction (MI) and cerebrovascular events with the following values, respectively: OR = 0.87, 95% CI (0.78-0.97) and OR = 0.71, 95% CI (0.52-0.98). CONCLUSIONS: PCSK9i was associated with better lipid profile and quality of life of patients and can be recommended as an optimal treatment strategy. Further trials should study combinations of PCSK9i with other lipid-lowering drugs.

Multisystem Inflammatory Syndrome (MIS) following SARS-CoV-2 vaccinations; a systematic review.

BACKGROUND: Although SARS-CoV-2 vaccines are generally safe, there are growing concerns about their link to a potentially life-threatening multi-system inflammatory syndrome following vaccination (MIS-V). We conducted this systematic review to elucidate the prevalence of MIS, severity, treatment, and outcomes following SARS-CoV-2 vaccination. METHODS: We searched PubMed, Scopus, ScienceDirect, Google Scholar, Virtual Health Library (VHL), Cochrane Library, and Web of Science databases for articles and case reports about MIS-V. We performed a qualitative analysis of individual cases from the included studies. RESULTS: Of the 1366 studies identified by database search, we retrieved twenty-six case reports and two cohort studies. We analyzed the data of 37 individual cases extracted from 27 articles. The average age of the cases included in this review was 18 (1-67) years, with the most being male (M: F 3.1:1). Of the 37 included cases, the cardiovascular system was the most affected system by MIS (36, 97.3%), followed by the gastrointestinal tract (32, 86.5%). CONCLUSION: MIS after SARS-CoV-2 vaccinations can be fatal, but the incidence is low. Prompt recognition of MIS and ruling out the mimickers are critical in the patient's early recovery.

Clinical characteristics, course, and outcomes of amyotrophic lateral sclerosis overlapping with pregnancy: a systematic review of 38 published cases.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease that can overlap with pregnancy, but little is known about its clinical characteristics, course, and outcomes in this context. This systematic review aimed to synthesize the current evidence on ALS overlapping with pregnancy. METHODS: We comprehensively searched four databases on February 2, 2023, to identify case studies reporting cases of ALS overlapping with pregnancy. Joanna Brigs Institute tool was followed to assess the quality of the included studies. RESULTS: Twenty-six articles reporting 38 cases were identified and included in our study. Out of the 38 cases, 18 were aged < 30 years. The onset of ALS was before pregnancy in 18 cases, during pregnancy in 16 cases, and directly after pregnancy in 4 cases. ALS progression course was rapid or severe in 55% of the cases during pregnancy, and this percentage reached 61% in cases with an onset of ALS before pregnancy. While ALS progression course after pregnancy was rapid or severe in 63% and stable in 37% of the cases. Most cases (95%) were able to complete the pregnancy and gave live birth. However, preterm delivery was common. For neonates, 86% were healthy without any complications. CONCLUSION: While pregnancy with ALS is likely to survive and result in giving birth to healthy infants, it could be associated with rapid or severe progression of ALS and result in a worse prognosis, highlighting the importance of close monitoring and counselling for patients and healthcare providers.

The Utilization of Animals as Models for Human Autopsies in Medical Education, Supported by Peer-Assisted Tutoring.

Background: Human autopsy is widely used to investigate and confirm the causes of death. Commonly reported cases involve the cardiovascular and cerebral systems. However, human autopsy practices have been restricted due to ethical and religious implications in many countries. Aim: The study aims to know if using human autopsy techniques on animal models might be an effective way for teaching post-mortem autopsy to medical students and exposing them to clinical pathology involving vital organs in medical education and find out the role of peer-assisted learning in improving the process. Methods: Two pre-lab sessions were conducted to emphasize the embryological and structural similarities and explain the differences between the human brain and heart and animal models: cow brain and sheep heart. Other two sessions of organ dissection were provided to perform human autopsy techniques on animal models practically for educational purposes. Peer-assisted tutoring was implemented. Questionnaires, interviews, and the Delphi technique were used to triangulate the assessment. A year later, participating foreign exchange students were interviewed to evaluate the long-term impacts based on Kirkpatrick models. Results: The questionnaire showed students' satisfaction with the autopsy workshops and peer-assisted tutoring. The last session was attended by foreign exchange students whose feedback proves the implementation can be done in different medical education systems around the globe. Conclusion: This study shows that animal model autopsy provides a valuable alternative in medical education and improves the students' comprehension and clinical skills, and peer-assisted learning has a secondary role in enhancing it. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01735-w.

Encephalitis following COVID-19 Vaccination: A Systematic Review.

BACKGROUND: Since the advent of global COVID-19 vaccination, several studies reported cases of encephalitis with its various subtypes following COVID-19 vaccinations. In this regard, we conducted a systematic review to investigate and characterize the clinical settings of these reported cases to aid in physician awareness and proper care provision. METHODS: We systematically searched PubMed, Web of Science, and Scopus and manually searched Google Scholar. Studies published until October 2022 were included. Demographic data, clinical features, vaccine data, treatment lines, and outcomes were extracted. RESULTS: A total of 65 patients from 52 studies were included. The mean age of patients was 46.82 ± 19.25 years, 36 cases (55.4%) were males. AstraZeneca was the most-reported vaccine associated with encephalitis (38.5%) followed by Pfizer (33.8%), Moderna (16.9%), and others. Moat encephalitis cases occurred after the first dose of vaccination in 41/65 (66.1%). The mean time between vaccination and symptom onset was 9.97 ± 7.16 days. Corticosteroids (86.2 %) and immunosuppressants (81.5 %) were the most used lines of treatment. The majority of affected individuals experienced a full recovery. CONCLUSION: Our study summarizes the current evidence of reported post-vaccination encephalitis, regarding clinical presentation, symptoms onset, management, outcomes, and comorbid conditions; however, it fails to either acknowledge the incidence of occurrence or establish a causal relationship between various COVID-19 vaccines and encephalitis.

The role of hypoxia on prostate cancer progression and metastasis.

Prostate cancer is the second most common cancer diagnosed in men and the fifth-leading cause of cancer death in men worldwide. Like any solid tumor, the hypoxic microenvironment of prostatic cancer drives hypoxia-inducible factors (HIFs) to mediate cell adaptions to hypoxic conditions. HIFs direct different signaling pathways such as PI3K/Akt/mTOR, NOX, and Wnt/ß-Catenin to tumor progression depending on the degree of hypoxia. HIFs regulate cytoskeleton protein expression, promoting epithelial-mesenchymal transition (EMT), which occurs when cancer cells lose cell-to-cell adhesions and start invasion and metastasis. Through activating pathways, the hypoxic microenvironment maintains the self-renewal, potency, and anti-apoptotic function of prostate cancer cells and induces tumor metastasis and transformation. These pathways could serve as a potential target for prostate cancer therapy. HIFs increase the expression of androgen receptors on cancer cells maintaining the growth and survival of prostate cancer and the development of its castration resistance. In this review, we elaborate on the role of hypoxia in prostatic cancer pathogenesis and different hypoxia-induced mechanisms.