Amyloid β induces early changes in the ribosomal machinery, cytoskeletal organization and oxidative phosphorylation in retinal photoreceptor cells

Amyloid β (Aβ) accumulation and its aggregation is characteristic molecular feature of the development of Alzheimer’s disease (AD). More recently, Aβ has been suggested to be associated with retinal pathology associated with AD, glaucoma and drusen deposits in age related macular degeneration (AMD). In this study, we investigated the proteins and biochemical networks that are affected by Aβ in the 661 W photoreceptor cells in culture. Time and dose dependent effects of Aβ on the photoreceptor cells were determined utilizing tandem mass tag (TMT) labeling-based quantitative mass-spectrometric approach. Bioinformatic analysis of the data revealed concentration and time dependent effects of the Aβ peptide stimulation on various key biochemical pathways that might be involved in mediating the toxicity effects of the peptide. We identified increased Tau phosphorylation, GSK3β dysregulation and reduced cell viability in cells treated with Aβ in a dose and time dependent manner. This study has delineated for the first-time molecular networks in photoreceptor cells that are impacted early upon Aβ treatment and contrasted the findings with a longer-term treatment effect. Proteins associated with ribosomal machinery homeostasis, mitochondrial function and cytoskeletal organization were affected in the initial stages of Aβ exposure, which may provide key insights into AD effects on the photoreceptors and specific molecular changes induced by Aβ peptide

Conceptualizing and measuring distance in international business research:Recurring questions and best practice guidelines

Distance is a central concept in international business research, yet there is debate about the construct as well as its operationalization. In this editorial, we address three of the most important recurring questions posed by authors, editors, and reviewers by examining the theory, methods, and data of distance research. We discuss (1) how to theorize on distance, and (2) what method and (3) what data to use when constructing a distance index. We develop practical recommendations grounded in theory, illustrating and supporting them by calculating cross-country distance indices for all available country pairs and two of the most used distance indices: cultural and institutional. We show that, whereas a specific method to calculate distance may matter to some extent, the choice for a specific cultural or institutional framework to measure cultural or institutional distance has a major impact on country-pair distances. Overall, this editorial highlights the importance of matching data and method to the theoretical argument.</p

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Microbiological aspects of peritonitis in patients on continuous ambulatory peritoneal dialysis

The objective of the study was to identify the microbiological spectrum and drug-sensitivity pattern of peritonitis in patients on continuous ambulatory peritoneal dialysis. This was a prospective study done over a period of a year-and-a-half at a tertiary-care hospital in a hilly state of India. The effluent dialysate bags from 36 consecutive patients with peritonitis were studied. One hunderd ml dialysate fluid was processed under aseptic conditions by lysis centrifugation method. Microscopy and culture was done from the deposits for bacteriological, fungal, and mycobacterial isolates. They were identified by colony morphology and their biochemical reactions. Drug susceptibility testing was done by Kirby-Bauer disc diffusion method. In 36 dialysates, 33 (91.6%) dialysates were culture-positive and in 3 (8.4%), the culture was negative. A total of 36 microorganisms were isolated in 33 cultures. Among the 36 microorganisms, 19 (52.8%) isolates were gram-positive, 10 (27.8%) were gram-negative, 5 (13.9%) were fungi, and 2 (5.6%) were mycobacterial isolates. All gram-positive organisms were sensitive to ampicillin, amoxi-clavulanic acid, cefazolin, clindamycin, and vancomycin. Neither a methicillin-resistant Staphylococci aureus nor a vancomycin-resistant Enterococcus was isolated in gram-positive isolates. Gram-negative organisms were sensitive to ciprofloxacin, ceftriaxone, ceftazidime, cefepime, gentamicin, piperacillin-tazobactam and imipenem. One of the gram-negative isolate was an extended spectrum beta-lactamase producer. Gram-positive peritonitis was more frequent than gram-negative peritonitis in our continuous ambulatory peritoneal dialysis patients. Mycobacterial causes were responsible for peritonitis in patients with culture-negative peritonitis which was not responding to the conventional antimicrobial therapy

A Case Report of Acute Severe Necrotizing Pancreatitis following the Johnson & Johnson Vaccine against the Novel SARS-CoV-2

Acute pancreatitis is an inflammatory condition, which is a leading gastrointestinal cause of hospitalization in the United States. Several conditions are associated with acute pancreatitis. More recently, there have been a few cases reported of acute pancreatitis following the Pfizer-BioNTech COVID-19 mRNA vaccine. To our knowledge, no cases of acute pancreatitis have been yet reported following the Johnson & Johnson’s Janssen COVID-19 vaccine (J& J vaccine). Herein we report a 34-year-old male with no significant past medical history admitted with acute necrotizing pancreatitis, the day following the receipt of the J&J vaccine. Based on the Naranjo and the modified Naranjo scale, the patient met the requirements for probable drug induced pancreatitis. This case report has the objective to raise awareness of a potentially severe side effect of the J&J vaccine. We hope to use this case to support screening all patients for previous history of acute pancreatitis before administration of the J& J vaccine