The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape and vaccine effectivity

alexandrossfakianakis shared this article with you from Inoreader The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape and vaccine effectivity via Journal of Medical Virology ABSTRACT As of November 2021, several SARS-CoV-2 variants appeared and became dominant epidemic strains in many countries, including five VOCs (Alpha (1), Beta (2), Gamma (3), Delta (4) and Omicron (5) defined by the World Health Organization (WHO) during the COVID-19 pandemic. As of August 2022, Omicron is classified into five main lineages, BA.1, BA.2 (6), BA.3, BA.4, BA.5 (7) and some sub-lineages (BA.1.1, BA.2.12.1, BA.2.11, BA.2.75, BA.4.6) (https://www.gisaid.org/). Compared to the previous VOCs (Alpha, Beta, Gamma, and Delta), all the Omicron lineages have the most highly mutations in the spike protein, and with 50 mutations accumulated throughout the genome. Early data indicated that Omicron BA.2 sub-lineage had higher infectivity and more immune escape than the early wild-type (WT) strain, the previous VOCs, and BA.1 (8, 9, 10). Recently, global surveillance data suggest a higher transmissibility of BA.4/BA.5 than BA.1, BA.1.1 and BA.2, and BA.4/BA.5 is becoming dominant strain in many countries globally (7, 11). This article is protected by copyright. All rights reserved. View on Web

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Voriconazole‐induced severe skin allergy and neurological adverse event in a liver failure patient: A case report

alexandrossfakianakis shared this article with you from Inoreader Voriconazole‐induced severe skin allergy and neurological adverse event in a liver failure patient: A case report via Journal of Clinical Pharmacy and Therapeutics Severe allergy and neurological adverse events were appeared on the 19th day, which was the next day after voriconazole injection. The adverse events were alleviated after voriconazole withdraw for 1 week. VCZ: voriconazole, 0.4 g on the 18th day, followed by 0.2 g once daily, ALP: alprazolam, 0.2 g, per night, PT: piperacillin-tazobactam, 2.5 g every 12 h, IC: Imipenem cilastatin, 0.5 g every 8 hours, ENT: entecavir, 0.5 mg once daily, ADE: ademetionine, 0.25 g once daily, VAN: Vancomycin, 1 g every 12 h. Abstract What Is Known and Objective Triazole antifungal-associated severe skin allergy has received little attention. Here we report a case of an acute-on-chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. Case Summary A 40-year-old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. What Is New and Conclusion To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration. View on Web

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Impact of Ischemia Duration on Lower Limb Salvage in Combat Casualties

alexandrossfakianakis shared this article with you from Inoreader Impact of Ischemia Duration on Lower Limb Salvage in Combat Casualties via Annals of Surgery - Most Popular Articles Introduction: The 6-hour threshold to revascularization of an ischemic limb is ubiquitous in the trauma literature, however, contemporary evidence suggests that this threshold should be less. This study aims to characterize the relationship between the duration of limb ischemia and successful limb salvage following lower extremity arterial trauma. Methods: This is a cohort study of the United States and UK military service members injured while serving in Iraq or Afghanistan between 2003 and 2013. Consecutive patients who sustained iliac, femoral, or popliteal artery injuries, and underwent surgery to attempt revascularization, were included. The association between limb outcome and the duration of limb ischemia was assessed using the Kaplan-Meier method. Results: One hundred twenty-two patients (129 limbs) who sustained iliac (2.3%), femoral (56.6%), and popliteal (41.1%) arterial injuries were included. Overall, 87 limbs (67.4%) were successfully salvaged. The probability of limb salvage was 86.0% when ischemia was ≤1 hour; 68.3% when between 1 and 3 hours; 56.3% when between 3 and 6 hours; and 6.7% when >6 hours (P View on Web

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A Novel Nonantibiotic Gut-directed Strategy to Prevent Surgical Site Infections

alexandrossfakianakis shared this article with you from Inoreader A Novel Nonantibiotic Gut-directed Strategy to Prevent Surgical Site Infections via Annals of Surgery - Most Popular Articles Objective: To determine the efficacy of an orally delivered phosphate-rich polymer, Pi-PEG, to prevent surgical site infection (SSI) in a mouse model of spontaneous wound infection involving gut-derived pathogens. Background: Evidence suggests that pathogens originating from the gut microbiota can cause postoperative infection via a process by which they silently travel inside an immune cell and contaminate a remote operative site (Trojan Horse Hypothesis). Here, we hypothesize that Pi-PEG can prevent SSIs in a novel model of postoperative SSIs in mice. Methods: Mice were fed either a standard chow diet (high fiber/low fat, SD) or a western-type diet (low fiber/high fat, WD), and exposed to antibiotics (oral clindamycin/intraperitoneal cefoxitin). Groups of mice had Pi-PEG added to their drinking water and SSI incidence was determined. Gross clinical infections wound cultures and amplicon sequence variant analysis of the intestinal contents and wound were assessed to determine the incidence and source of the developing SSI. Results: In this model, consumption of a WD and exposure to antibiotics promoted the growth of SSI pathogens in the gut and their subsequent presence in the wound. Mice subjected to this model drinking water spiked with Pi-PEG were protected against SSIs via mechanisms involving modulation of the gut-wound microbiome. Conclusions: A nonantibiotic phosphate-rich polymer, Pi-PEG, added to the drinking water of mice prevents SSIs and may represent a more sustainable approach in lieu of the current trend of greater sterility and the use of more powerful and broader antibiotic coverage. View on Web

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Assessing transmission risks and control strategy for monkeypox as an emerging zoonosis in a metropolitan area

alexandrossfakianakis shared this article with you from Inoreader Assessing transmission risks and control strategy for monkeypox as an emerging zoonosis in a metropolitan area via Journal of Medical Virology Abstract Objective To model the spread of Monkeypox (MPX) in a metropolitan area for assessing the risk of possible outbreaks, and identifying essential public health measures to contain the virus spread. Methods The animal reservoir is the key element in the modelling of a zoonotic disease. Using a One Health approach, we model the spread of the MPX virus in humans considering potential animal hosts such as rodents (e.g., rats, mice, squirrels, chipmunks, etc.) and emphasize their role and transmission of the virus in a high-risk group, including gay and bisexual men-who-have-sex-with-men (gbMSM). From model and sensitivity analysis, we identify key public health factors and present scenarios under different transmission assumptions. Findings We find that the MPX virus may spill over from gbMSM high-risk groups to broader populations if efficiency of transmission increases in the higher-risk group. However, the risk of outbreak can be greatly reduced if at least 65% of symptomatic cases can be isolated and their contacts traced and quarantined. In addition, infections in an animal reservoir will exacerbate MPX transmission risk in the human population. Conclusion Regions or communities with a higher proportion of gbMSM individuals need greater public health attention. Tracing and quarantine (or "effective quarantine" by post-exposure vaccination) of contacts with MPX cases in high-risk groups would have a significant effect on controlling the spreading. Also, monitoring for animal infections would be prudent. This article is protected by copyright. All rights reserved. View on Web

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LAMP‐2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia

alexandrossfakianakis shared this article with you from Inoreader LAMP‐2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia via Brain Pathology Hippocampal astrocytic LAMP-2A knockdown inhibits astrocyte activation, maintains the integrity of neuronal morphology, and ameliorates cognitive deficits after transient global cerebral ischemia. Abstract Reactive astrogliosis and neuronal death are major features of brain tissue damage after transient global cerebral ischemia/reperfusion (I/R). The CA1 subfield in the hippocampus is particularly susceptible to cell death after I/R. Recently, attention has focused on the relationship between the autophagy–lysosomal pathway and cerebral ischemia. Lysosomal-associated membrane protein type-2A (LAMP-2A) is a key protein in chaperone-mediated autophagy (CMA). However, LAMP-2A expression in astrocytes of the hippocampus and its influence on brain injury following I/R remain unknown. Here, we show that LAMP-2A is elevated in astrocytes of the CA1 hippocampal subfield after I/R and in primary cultured astrocytes after transient oxygen–glucose deprivation (OGD). Conditional LAMP-2A knockdown in CA1 astrocytes inhibited astrocyte activation and prevented neuronal death by inhibiting the mitochondrial pathway of apoptosis after I/R, suggesting that elevated astrocytic LAMP-2A contributes to regional ischemic vulnerability. Furthermore, astrocytic LAMP-2A ablation ameliorated the spatial learning and memory deficits caused by I/R. Conditional astrocytic LAMP-2A knockdown also prevented the loss of hippocampal synapses and dendritic spines, improved the synaptic ultrastructure, and inhibited the reduced expression of synaptic proteins after ischemia. Thus, our findings demonstrate that astrocytic LAMP-2A expression increases upon I/R and that LAMP-2A ablation specifically in hippocampal astrocytes contributes to cerebroprotection, suggesting a novel neuroprotective strategy for patients with global ischemia. View on Web

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Cost‐effectiveness analysis of silver diamine fluoride to divert dental general anaesthesia compared to standard care

alexandrossfakianakis shared this article with you from Inoreader Cost‐effectiveness analysis of silver diamine fluoride to divert dental general anaesthesia compared to standard care via Australian Dental Journal ABSTRACT Background The aim is to perform a model-based cost-effectiveness analysis of a silver diamine fluoride (SDF) protocol intervention to divert dental general anaesthesia (DGA) among Victorian children aged 2- 10 years. Methods Data inputs was based on an Australian single-cohort 2017/18 study. Intervention costs for standard care were derived from two subgroups of children: 1) children who received standard care without DGA, and 2) children who received standard care with DGA. Two scenarios were modelled due to limited post-follow-up data: 1) children receiving SDF had standard care without DGA (base-case scenario), and 2) children receiving SDF did not receive standard care without DGA (alternative scenario). A simple decision-tree model with probabilistic sensitivity analysis (PSA) estimated the incremental costs per diverted DGA. Results The probability of children requiring specialist referral and offered SDF, but the primary carer opted for DGA is 0.124 (SD 0.034), and the probability of children requiring DGA in standard care is 0.346 (SD 0.036). For both the base-case and alternative scenario, the incremental cost-effectiveness ratio outcome is dominant and their cost-effectiveness being either 74.8% or 100%, respectively. Conclusions The SDF protocol intervention is cost-effective dental caries management option for young children where referral for DGA is considered. © 2022 Australian Dental Association. View on Web

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SARS‐CoV‐2‐encoded Inhibitors of Human LINE‐1 Retrotransposition

alexandrossfakianakis shared this article with you from Inoreader SARS‐CoV‐2‐encoded Inhibitors of Human LINE‐1 Retrotransposition via Journal of Medical Virology Abstract The ongoing pandemic of severe acute respiratory coronavirus 2 (SARS-CoV-2) is causing a devastating impact on public health worldwide. However, details concerning the profound impact of SARS-CoV-2 on host cells remain elusive. Here, we investigated the effects of SARS-CoV-2-encoded viral proteins on the intracellular activity of long interspersed element 1 (L1) retrotransposons using well-established reporter systems. Several non-structural or accessory proteins (Nsps) of SARS-CoV-2 (i.e., Nsp1, Nsp3, Nsp5, and Nsp14) significantly suppress human L1 mobility, and these viral L1 inhibitors generate a complex network that modulates L1 transposition. Specifically, Nsp1 and Nsp14 inhibit the intracellular accumulation of L1 open reading frame proteins (ORF1p), whereas Nsp3, Nsp5, and Nsp14 repress the reverse transcriptase activity of L1 ORF2p. Given recent findings concerning the roles of L1 in antiviral immune activation and host genome instability, the anti- L1 activities mediated by SARS-CoV-2-encoded inhibitors suggest that SARS-CoV-2 employs different strategies to optimize the host genetic environment. This article is protected by copyright. All rights reserved. View on Web

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Overexpression of NIMA related kinase 2 in multiple myeloma and its relevance with disease features and prognosis to bortezomib treatment

alexandrossfakianakis shared this article with you from Inoreader Overexpression of NIMA related kinase 2 in multiple myeloma and its relevance with disease features and prognosis to bortezomib treatment via Journal of Clinical Pharmacy and Therapeutics A total of 76 multiple myeloma (MM) patients and 30 health donors (HDs) were enrolled to collect bone marrow plasma cells for NIMA related kinase 2 (NEK2) detection using RT-qPCR. Meanwhile, NEK2 siRNA was transfected into the RPMI-8226 and KMS-11 cells (MM cell lines), subsequently their cell viability was evaluated using CCK8 reagent. NEK2 expression was higher in MM patients compared with HDs. Besides, elevated NEK2 expression associated with the occurrence of the bone lesion and t (4; 14). Additionally, elevated NEK2 expression correlated with declined objective response rate (ORR) and shorter progression-free survival (PFS). What is more, NEK2 silence decreased the cell viability under bortezomib treatment and the IC50 value of bortezomib in RPMI-8226 and KMS-11 cells (MM cell lines). Abstract What is Known and Objective NIMA related kinase 2 (NEK2) promotes the malignant transformation and enhances the chemoresistance to proteasome inhibitor in multiple myeloma (MM) cell lines. The current study aimed to further investigate its correlation with clinical features and responsiveness to bortezomib treatment in MM patients. Methods Totally, 76 MM patients and 30 health donors (HDs) were enrolled to collect bone marrow plasma cells for NEK2 detection using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Meanwhile, NEK2 siRNA was transfected into the RPMI-8226 and KMS-11 cells, subsequently their cell viability was evaluated using Cell Counting Kit-8 reagent after treatment with different doses of bortezomib. Results and Discussion NEK2 expression was higher in MM patients compared with HDs (Z = −5.123, p < 0.001). Besides, elevated NEK2 expression was associated with the occurrence of the bone lesion (χ 2 = 4.610, p = 0.032) and t (4; 14) (χ 2 = 3.971, p = 0.046). Additionally, elevated NEK2 expression was correlated with declined objective response rate (ORR) (χ 2 = 4.808, p = 0.028), but not with complete response (CR) (χ 2 = 2.341, p = 0.126). More importantly, elevated NEK2 expression was correlated with shorter progression-free survival (PFS) (χ 2 = 8.352, p = 0.039), but not with overall survival (OS) (χ 2 = 5.624, p = 0.131), What is more, NEK2 silence decreased the cell viability under bortezomib treatment and the inhibitory concentration (IC50) value of bortezomib in RPMI-8226 and KMS-11 cell lines (all p < 0.05). What is New and Conclusion NEK2 overexpression links with occurrence of bone lesion, t (4; 14), and poor prognosis to bortezomib treatment in MM patients. View on Web

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Relationships between squamous cell carcinoma antigen and cytokeratin 19 fragment values and renal function in oral cancer patients

alexandrossfakianakis shared this article with you from Inoreader Relationships between squamous cell carcinoma antigen and cytokeratin 19 fragment values and renal function in oral cancer patients via International Journal of Oral and Maxillofacial Surgery via MedWorm.com Squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment (CYFRA) are used to screen and monitor oral cancer patients. However, recent studies have reported that tumour markers become elevated as renal function decreases, regardless of tumour progression. A retrospective study was performed of 423 oral cancer patients who underwent blood testing for these tumour markers and other blood analytes during a 10-year period. The values of SCC-Ag and CYFRA increased significantly with decreasing renal function (P   (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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