Upper Respiratory Tract Infection Research Articles

Nasal irrigation for the prevention and treatment of upper respiratory tract infection by SARS-CoV-2: a narrative review.

The World Health Organization declared an end to the global emergency status of COVID-19 in May of 2023. However, the impact of COVID-19 is far from over. Individuals who have recovered from COVID-19 continue to experience physiological, psychological, or cognitive symptoms, such as fatigue, shortness of breath, dizziness, and loss of smell or taste, known as long COVID. This review aims to describe the clinical characteristics of the upper respiratory tract infection (URTI) caused by SARS-CoV-2, and provide evidence for the prevention and treatment of SARS-CoV-2 infection by using nasal irrigation. COVID-19 and nasal irrigation: Nasal irrigation presents a promising adjunct to standard COVID-19 prevention and treatment protocols. This practice is theorized to diminish viral presence in the upper respiratory tract, a region identified as a primary site for SARS-CoV-2 replication and shedding. By facilitating the removal of viral particles and enhancing mucociliary clearance, nasal irrigation could potentially lessen the severity of URTI symptoms and slow transmission rates. The review consolidates current evidence of the efficacy and safety of this approach across various populations, underscoring its practicality in both preventive and therapeutic contexts. We recommend that saline nasal irrigation is an effective, safe and convenient strategy to prevent the transmission of SARS-CoV-2 and alleviate the symptoms of URTI across various age groups.

High prevalence of antibodies against feline calicivirus in Australian feral and stray cat (Felis catus) populations.

Feline calicivirus (FCV) commonly causes upper respiratory tract, oral and ocular infections in species of the family Felidae, with high prevalence amongst domestic cat (Felis catus) populations worldwide. Detection of FCV-specific antibodies in serum provides evidence of previous infection with FCV and an indication of whether a cat may be protected against clinical FCV disease. This study describes the most extensive sampling for anti-FCV antibodies in feral and stray cat populations in Australia, and examines variation in prevalence associated with cat age, sex and location. Blood samples were opportunistically collected from 669 feral, stray or Indigenous community cats from the Northern Territory, South Australia, Victoria, south-east Tasmania and south-west New South Wales. The sera were harvested and tested for antibodies capable of neutralising the FCV vaccine strain F9 by serum-virus neutralisation assay. Of the 669 cats tested, 69.7% had detectable FCV-F9-neutralising antibodies (titres ≥5). Maturity was significantly associated with higher seroprevalence and higher antibody titres, with adult cats being more than twice as likely to have detectable FCV-neutralising antibodies than subadults. Male cats had a higher seroprevalence and slightly higher antibody titres than females. Cats living in closer proximity to humans had significantly higher seroprevalences and higher FCV-neutralising antibody titres than feral cats from more remote regions of Australia. Australian feral and stray cats have a high risk of natural exposure to and infection with FCV, with the prevalence and levels of pre-existing immunity to FCV being highest amongst adult cats living in highly modified urban, peri-urban and agricultural environments.

PCR-based RFLP and ERIC-PCR patterns of Helicobacter pylori strains linked to multidrug resistance in Egypt.

H. pylori infects approximately 50% of the world's population that causes chronic gastritis, and may lead to peptic ulcer disease (PUD). H. pylori-induced chronic infections are associated with gastric adenocarcinoma and low-grade gastric lymphoma. In Egypt, H. pylori strains are widespread and became resistant to antimicrobial agents, thus advanced typing methods are needed to differentiate infectious strains that are resistant to antibiotics, and therefore earlier prognosis and infection control. The main objectives were (i) to determine susceptibility of infectious H. pylori strains to some antimicrobial agents that are currently used in eradication therapy in Egypt; (ii) to identify diverse strains commonly detected in the gastrointestinal (GIT) endoscopy units in Egypt through phenotypic and genotypic analyses. In this observational study we isolated 167 isolates from 232 gastric biopsies (antrum and corpus) of patients who were admitted to the upper GIT endoscopy units in five governmental Egyptian hospitals. Antimicrobial susceptibility patterns were investigated using Kirby Bauer disc diffusion and agar dilution Minimum Inhibitory Concentrations (MICs) methods. Phenotypic characterization was based on biotyping and antibiogram typing techniques. Genotypic characterization was carried out using PCR-based Restriction Fragment Length Polymorphism (RFLP) and Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR analyses. H. pylori isolates were highly resistant to diverse antimicrobial agents including Metronidazole, Fluoroquinolones, Macrolides, Amoxycillin, Tetracycline and Gentamicin. Two factors contributed to the increased resistance of H. pylori to the conventional therapy seen in Egypt: (i) Metronidazole and Amoxycillin are inexpensive and available drugs being abused by patients; (ii) the regional prescribing practice of Macrolids commonly used to treat upper respiratory and urinary tract infections. Five different biotypes were identified depending on the ability of the isolates to synthesize different enzymes. Nine antibiogram types were identified. PCR-RFLP analysis revealed fifteen different fingerprints while ERIC-PCR revealed 22 fingerprints. Biotyping alone or in combination with antibiogram typing are highly useful molecular tools in the prognosis of strain relatedness. PCR-RFLP and ERIC-PCR acquired good discriminatory power for identifying H. pylori infectious sub-types.

Environmental impacts of cement production in Ewekoro, Ogun State, southwestern Nigeria from 2005 to 2006 on surface water quality, vegetation, and workers' health

ABSTRACT The present study investigated the environmental impacts of cement production on surface water quality and vegetation in the vicinity of the industry. A 2-year study was conducted, covering both wet and dry seasons. Water samples were collected from the Akinbo River, where the cement industry discharges its liquid waste and effluents, and analysed for physical and chemical parameters using standard procedures. The vegetation around the factory was analysed for chlorophyll, plant density, basal areas, and heights of woody species. The study also assessed the health impacts of cement production on the factory employees and the residents living in the vicinity of the factory. The health assessment was based on hospital information obtained from two clinics in the villages near the factory. The water quality results revealed elevated concentrations of Ca and Fe. All the trees sampled around the study area had small basal areas and short heights. There was also a significant reduction in the chlorophyll contents of the vegetation. The health study showed a high incidence of upper-respiratory tract infections, cardiovascular diseases, arthritis, and dermatitis among factory workers. This study suggests a review of the existing dust-suppressing system put in place by the industry, to protect public health.

Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE

AbstractThe ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n = 327) or ibrutinib (n = 325). At an overall median follow-up of 42.5 months, progression-free survival benefit with zanubrutinib vs ibrutinib was sustained (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.54-0.84), including in patients with del(17p)/TP53 mutation (HR, 0.51; 95% CI, 0.33-0.78) and across multiple sensitivity analyses. Overall response rate remained higher with zanubrutinib compared with ibrutinib (85.6% vs 75.4%); responses deepened over time with complete response/complete response with incomplete bone marrow recovery rates of 11.6% (zanubrutinib) and 7.7% (ibrutinib). Although median overall survival has not been reached in either treatment group, fewer zanubrutinib patients have died than ibrutinib patients (HR, 0.77 [95% CI, 0.55-1.06]). With median exposure time of 41.2 and 37.8 months in zanubrutinib and ibrutinib arms, respectively, the most common nonhematologic adverse events included COVID-19–related infection (46.0% vs 33.3%), diarrhea (18.8% vs 25.6%), upper respiratory tract infection (29.3% vs 19.8%), and hypertension (27.2% vs 25.3%). Cardiac events were lower with zanubrutinib (25.9% vs 35.5%) despite similar rates of hypertension. Incidence of atrial fibrillation/flutter was lower with zanubrutinib vs ibrutinib (7.1% vs 17.0%); no cardiac deaths were reported with zanubrutinib vs 6 cardiac deaths with ibrutinib. This analysis, at 42.5 months median follow-up, demonstrates that zanubrutinib remains more efficacious than ibrutinib with an improved overall safety/tolerability profile. This trial was registered at www.ClinicalTrials.gov as #NCT03734016.

Primary Healthcare Physicians' Insufficient Knowledge Is Associated with Antibiotic Overprescribing for Acute Upper Respiratory Tract Infections in China: A Cross-Sectional Study.

Overuse of antibiotics in healthcare remains prevalent and requires urgent attention in China, particularly in primary healthcare (PHC) facilities. This study aimed to describe the patterns of antibiotic prescriptions for acute upper respiratory tract infections (URTIs) in PHC facilities in China and to investigate how PHC physicians' knowledge influences their antibiotic prescribing behavior. A cross-sectional survey linking physician questionnaire responses and their prescription data was conducted in Shaanxi Province, China. The proportions of URTI visits that received at least one antibiotic, combined antibiotics, and broad-spectrum antibiotics were the main outcomes reflecting antibiotic prescribing behavior. Multivariate mixed-effects logistic regressions were applied to analyze the relationship between PHC physicians' knowledge about antibiotics and their antibiotic prescribing behavior. A total of 108 physicians filled out the questionnaires between February 2021 and July 2021, and a sample of 11,217 URTI visits attended by these physicians from 1 January 2020 to 31 December 2020 were included in the analysis. The overall mean score of our respondents on the knowledge questions was 5.2 (total score of 10). Over sixty percent (61.2%; IQR 50.2-72.1) of the URTI visits received antibiotics. The percentages of URTI visits prescribed with combined and broad-spectrum antibiotics were 7.8% (IQR 2.3-10.2) and 48.3% (IQR 36.7-58.7), respectively. Third-generation cephalosporins were the most frequently used antibiotics. Physicians with lower antibiotic knowledge scores were more inclined to prescribe antibiotics (p < 0.001), combined antibiotics (p = 0.001), and broad-spectrum antibiotics (p < 0.001). Physicians' insufficient knowledge was significantly associated with antibiotic overprescribing. Professional training targeting physicians' knowledge of antibiotics is urgently needed to improve the rational use of antibiotics in grassroots healthcare facilities in China.

Assessment of the Safety of Tofacitinib Among Patients With Psoriasis: A Systematic Review and Meta-Analysis.

Psoriasis is a clinically heterogeneous, lifelong skin condition. Novel medications such as Janus kinase (JAK) inhibitors have emerged as a promising class of agents that modulate the immune response. Tofacitinib could reduce skin lesions and boost patient-reported clinical outcomes, but its immunosuppressive effects might also increase patients' risk of infections and other adverse effects. To assess the safety outcomes of using Tofacitinib in comparison to placebo in terms of the incidence of serious infections, herpes zoster infection (HZ), upper respiratory tract infections (URTI), nasopharyngitis, and serious adverse events (SAE), this systematic review and meta-analysis followed the Cochrane Handbook for Systematic Reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy involved five databases. Two authors independently screened and selected studies. Only randomized controlled trials (RCTs) were eligible for inclusion. Data on baseline patient characteristics and outcomes such as serious infections, HZ infections, nasopharyngitis, and URTIs were extracted. The risk of bias was assessed using the revised version of the Cochrane risk of bias (ROB2) tool, and meta-analysis was conducted using Cochrane's Revman web. The ORwas employed to estimate outcomes. A probability value of less than 0.05 was considered statistically significant. The search strategy initially identified 998 studies; of these, six RCTs were included with a total of 2516 participants having moderate-to-severe psoriasis and treated with either Tofacitinib or placebo. The meta-analysis results revealed increases in the risks of HZ, URTIs, serious infections, nasopharyngitis, and SAE, but no significant difference was found between the intervention and placebo groups. The risk of bias was assessed using the ROB2 tool, revealing low bias across most domains, with some concerns in certain studies related to deviations from intended interventions and missing outcome data. In conclusion, while Tofacitinib is effective against moderate-to-severe psoriasis with non-significant risks, there are some safety concerns regarding the measured outcomes. Future research is needed concerning the assessment of safety outcomes with long-term use of Tofacitinib among larger populations.

Antimicrobial Susceptibility Patterns of Bacteria Associated with Upper Respiratory Tract Infections in North and South Waziristan, Pakistan

Background: Upper respiratory tract infections (URTIs) are a significant cause of outpatient visits globally, with antimicrobial resistance (AMR) presenting a growing challenge to effective treatment. In Pakistan's tribal regions, limited healthcare access exacerbates this issue.Objective: To determine the prevalence of bacterial pathogens causing URTIs and assess their antimicrobial susceptibility patterns in North and South Waziristan, Pakistan.Methods: This cross-sectional study involved 300 throat swabs collected from outpatients between January and June 2023. Samples were inoculated on Blood, MacConkey, and Chocolate agars, followed by incubation at 37°C for 24 hours. Standard biochemical tests were used for bacterial identification, and the Kirby-Bauer disc diffusion method assessed antimicrobial susceptibility. Statistical analysis was performed using SPSS version 25.0, with p-values ≤ 0.05 considered significant.Results: Pathogens were isolated in 93% of samples, with Staphylococcus aureus (40.2%), viridans group streptococci (35.7%), and Streptococcus pyogenes (17.1%) being the most common. Resistance was highest in viridans group streptococci (33.7% to tazobactam) and lowest in Streptococcus pyogenes (26.3%).Conclusion: The high rates of resistance, particularly in viridans group streptococci, highlight the need for targeted interventions to mitigate AMR in this region.

Effect of Intranasal Insulin on Olfactory Recovery in Patients with Anosmia .

Olfactory dysfunction, defined as either a complete or partial impairment of smell, is a common condition that may substantially affect a person’s quality of life and is frequently difficult to treat. Physical activity, heredity, nutrition, smoking, head trauma, medical treatments, and virus exposure all influence one’s capacity to smell. Hyposmia or anosmia, or loss of smell, affects 3% to 20% of the population. Intranasal insulin can improve cognitive performance, reduce food intake, and boost olfactory thresholds in healthy individuals. As people age, they are more likely to experience olfactory dysfunction, which may be affected by a variety of reasons, such as acute and chronic sino-nasal illness, upper respiratory infections, toxic chemical exposure, and degenerative diseases. About ten percent of those over 65 develop olfactory impairment, which can range from mild loss to total anosmia. Insulin resistance in the central nervous system has been linked to conditions like type II diabetes, Alzheimer’s disease, obesity, and poor odor identification. Reduced odor perception may contribute to reduced olfactory function in anosmic patients.

A Rare Case of Meningitis Caused by Elizabethkingia meningoseptica in a Baby at the Buea Regional Hospital, South West Region, Cameroon

Aim: This report was aimed at determining the possible source, risk factors, antimicrobial susceptibility pattern and clinical management of the first recorded case of meningitis in Cameroon caused by Elizabethkingia meningoseptica. Presentation of case: A 10 months old baby previously diagnosed with otitis media was admitted at the Buea regional hospital on the 21st of October 2023 after a referral following unsuccessful treatment. Upon admission, the baby had persistent fever, catarrh (evidence of an upper respiratory tract infection) and abdominal discomfort. Patient developed decreased body movement, altered consciousness and neck stiffness even after being placed on ampicillin and cefotaxime for two days. Based on cerebrospinal fluid analysis, the patient was considered a probable meningitis case and put on ceftriaxone to no avail. CSF culture later revealed the presence of Elizabethkingia meningoseptica susceptible to ciprofloxacin and resistant to imipenem, amoxicillin-clavulanic acid, cotrimoxazole, ampicillin and ceftriaxone. Marked improvement was noticed and the patient was discharged following full recovery after treatment with ciprofloxacin for 21 days. Epidemiological investigations and active case search did not provide any evidence of the Elizabethkingia being acquired in the hospital. Discussion and conclusion: The Elizabethkingia in this case was most likely community acquired associated with acute otitis media probably linked to a recent upper respiratory tract infection. The isolate was resistant to ceftriaxone and susceptible to ciprofloxacin. In case of meningitis caused by this pathogen, empirical treatment with fluoroquinolones may most likely be an effective option in the absence of antimicrobial susceptibility testing.

Analysis of neuraminidase activity of human parainfluenza viruses using enzyme-linked lectin assay and BTP3-Neu5Ac assay.

Human parainfluenza viruses (hPIVs) are causative agents of upper and lower respiratory tract infections and they have four serotypes. The virion surface displays hemagglutinin-neuraminidase (HN), having hemagglutinating (HA) and neuraminidase (NA) activities in a single molecule. The HA activity binds the virion to sialic acid on the viral receptor on host cells and the NA releases the progeny viruses from the cell surface. There are several methods for assaying viral NA activity, such as the thiobarbituric acid assay, 4-methylumbelliferyl-N-acetyl-α-d-neuraminic acid assay, NA-Star assay, and enzyme-linked lectin assay (ELLA). However, these are mainly used for influenza viruses and not for hPIVs. A fluorescent-based cytochemical NA assay using BTP3-Neu5Ac as the substrate was recently developed and used for orthomyxo- and paramyxoviruses, including types 1 and 3 hPIVs. In this study, we used the ELLA, and BTP-Neu5Ac assay for 14 field isolate strains of hPIVs including all four serotypes. The reaction in ELLA at pH 6.5 using peanut agglutinin (PNA) as a lectin was very low for all tested viruses except a type 3 virus strain with the maximum reaction at pH 6.5 and the acidic conditions did not enhance the reaction. ELLA with another lectin, Erythrina cristagalli agglutinin exhibited significant and stronger reactions than with PNA in some strains of types 1 and 3 viruses. The BTP3-Neu5Ac assay showed a fluorescent signal on cells infected with all the viruses except the hPIV1/Sendai/713/2018 strain in LLC-MK2 and/or MNT-1. The signal was detected in cell-free virus, as well, in all the viruses except the hPIV4a/Sendai/3935/2003 strain. The strength of the signal varied among viral strains but it was stronger in the reaction at pH 4.0 than pH 7.0 and strongest in type 2 hPIVs.

PFAPA syndrome: a case report

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a complex autoinflammatory disease characterized by recurrent episodes of fever and systemic inflammatory features. It is usually a disease of children but adult onset has also been reported. The common clinical features are aphthous stomatitis, cervical lymphadenitis, pharyngitis etc with exclusion of upper respiratory tract infection and cyclic neutropenia. The patient remains completely asymptomatic between the episodes of these clinical features with normal growth and development. Here we report a case of 20-year-old male who presented with features suggestive of PFAPA syndrome and well responded with a single dose of high dose prednisolone. BIRDEM Med J 2024; 14(3): 161-165

Primary ciliary dyskinesia: a case report of double DNAH11 mutant alleles

Primary ciliary dyskinesia (PCD), a rare disorder, is genetically varied. Mutations in proteins involved in the structure, function, or assembly of cilia are known to determine situs inversus, male infertility, and chronic destructive airway disease. PCD is inherited by an autosomal recessive pattern of inheritance in most cases. Nonetheless, patterns of autosomal dominant and X-linked inheritance have been mentioned. A history of recurrent upper and lower respiratory tract infections raised clinical suspicion of primary ciliary dyskinesia in a 10-year-old patient. Genetic tests were performed using next-generation sequencing technology (Illumina NextGen) with the multiplex ligation-dependent probe amplification technique for primary ciliopathies and syndromes subject to differential diagnosis. Genetic testing identified two pathogenic variants, not previously associated with a case report in the literature, c.7727A&gt;G (p.Asp2576Gly) and c.8578G&gt;A (p.Gly2860Ser), within the DNAH11 gene, which is associated with autosomal recessive PCD. The result also reported mutations in other genes involved in autosomal recessive PCD (DNAH8, DNAH9 and ZMYND10), which were classified as variants with uncertain clinical significance. Transmission electron microscopy of respiratory cilia and nasal nitric oxide measurement cannot be used to diagnose PCD in patients with DNAH11 mutations because the structure of cilia is normal, and the levels of NO are not constantly low. High-speed video microscopy analysis can be helpful because DNAH11 mutations cause a distinct phenotype of PCD. Nevertheless, the mutation analysis of various PCD-causing genes remains the easiest to conduct and with good results. Genetic research on PCD has identified a number of significant ciliary genes in recent years, offering fresh perspectives on the molecular processes underlying cilia assembly and function. This facilitates the development of new methods for the diagnosis, prevention, and treatment of PCD. However, because it is a highly complex and heterogeneous disease, the field of gene diagnosis and therapy in PCD is still in its infancy.

Evaluation of utilization and consequences of CRP point-of-care-testing in primary care practices: qualitative interviews with general practitioners from Germany.

The use and advantages of point-of-care tests (POCTs) for C-reactive protein (CRP) in general practice, especially for upper respiratory tract infections (uRTIs), have been studied extensively. However, there is limited knowledge about test indications, prerequisites, and integration of these tests into everyday practice. This study aims to investigate the attitudes and experiences of general practitioners (GPs) in Germany regarding the use of semi-quantitative CRP-POCTs. The study places special emphasis on implementation in routine care, including testing procedures, feasibility, opportunities and barriers for specific consultation scenarios, as well as test indications and their impact on GP-patient communication. Qualitative interview study with 10 GPs (May/2023 to Aug/2023) METHOD: Ten German GPs who participated in an observational study on CRP-POCT use in general practices were interviewed using semi-structured interviews. Audio recordings were transcribed and content analysis was performed. Interviewed GPs stated that CRP-POCTs offer several advantages for various treatment cases. They improve diagnostic confidence and certainty of GPs' therapeutic decisions, and offer a broad spectrum of indications and application scenarios. Additionally, they have a positive impact on GP-patient communication, and their ease of use enables rapid implementation into existing workflows. On the other hand, CRP-POCT increase the time required for test performance and patient consultation. Due to the numerous benefits of semi-quantitative CRP-POCTs, interviewed GPs have a favourable attitude towards their regular integration into everyday practice. Implementation barriers include increased time and personnel expenses for testing and inadequate reimbursement by German statutory health insurance.

Identification and screening of potential anti-pneumonia active ingredients and targets of Qing-Kai-Ling oral liquid via UHPLC-Q-Exactive Orbitrap mass spectrometry based on data post-processing

Qing-Kai-Ling oral liquid is commonly used clinically for the treatment of fever and upper respiratory tract infection. Moreover, studies have shown that Qing-Kai-Ling oral liquid has an anti-pneumonia effect. However, owing to its complex pharmacodynamic material basis, its pharmacological research and clinical application are limited. To address this problem, the chemical constituents of Qing-Kai-Ling oral liquid were identified by ultra-high performance liquid chromatography quadrupole-Exactive Orbitrap mass (UHPLC-Q-Exactive Orbitrap MS) and network pharmacology methods, which were used to predict its potential anti-pneumonia target and signalling pathway. A total of 150 compounds were identified and tentatively characterized, including 35 amino acids and their derivatives, 36 organic acids, 20 terpenoids, 20 alkaloids, 12 glycosides, 7 flavonoids, and 20 others. Among them, 14 compounds were accurately identified by comparing their retention time and mass spectrum data with those of reference substances. Additionally, we performed molecular simulation calculations via Density Function Theory to determine the plausibility of the compound cleavage reactions and further confirm compound structures. Furthermore, 90 key targets were screened through network pharmacology, with the particular focus on the PI3K-AKT, MAPK and TNF signalling pathways. This method achieved the first comprehensive identification of the chemical composition of Qing-Kai-Ling oral liquid and elucidated its potential mechanism of anti-pneumonia. The results provide valuable reference and data support for pharmacodynamic substance research and quality control.

Changes in memory and cognition during the SARS-CoV-2 human challenge study

Patient-reported outcomes and cross-sectional evidence show an association between COVID-19 and persistent cognitive problems. The causal basis, longevity and domain specificity of this association is unclear due to population variability in baseline cognitive abilities, vulnerabilities, virus variants, vaccination status and treatment. Thirty-four young, healthy, seronegative volunteers were inoculated with Wildtype SARS-CoV-2 under prospectively controlled conditions. Volunteers completed daily physiological measurements and computerised cognitive tasks during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Linear modelling examined differences between 'infected' and 'inoculated but uninfected' individuals. The main cognitive endpoint was the baseline corrected global cognitive composite score across the battery of tasks administered to the volunteers. Exploratory cognitive endpoints included baseline corrected scores from individual tasks. The study was registered on ClinicalTrials.gov with the identifier NCT04865237 and took place between March 2021 and July2022. Eighteen volunteers developed infection by qPCR criteria of sustained viral load, one without symptoms and the remainder with mild illness. Infected volunteers showed statistically lower baseline-corrected global composite cognitive scores than uninfected volunteers, both acutely and during follow up (mean difference over all time points=-0.8631, 95% CI=-1.3613,-0.3766) with significant main effect of group in repeated measures ANOVA (F (1,34)=7.58, p=0.009). Sensitivity analysis replicated this cross-group difference after controlling for community upper respiratory tract infection, task-learning, remdesivir treatment, baseline reference and model structure. Memory and executive function tasks showed the largest between-group differences. No volunteers reported persistent subjective cognitive symptoms. These results support larger cross sectional findings indicating that mild Wildtype SARS-CoV-2 infection can be followed by small changes in cognition and memory that persist for at least a year. The mechanistic basis and clinical implications of these small changes remain unclear. This study was funded through the UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy (BEIS) of Her Majesty's Government. WT was funded by the EPSRC through the CDT for Neurotechnology Imperial College London.

COVID-19 mutations: An overview.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the genus Beta coronavirus and the family of Coronaviridae. It is a positive-sense, non-segmented single-strand RNA virus. Four common types of human coronaviruses circulate globally, particularly in the fall and winter seasons. They are responsible for 10%-30% of all mild upper respiratory tract infections in adults. These are 229E, NL63 of the Alfacoronaviridae family, OC43, and HKU1 of the Betacoronaviridae family. However, there are three highly pathogenic human coronaviruses: SARS-CoV-2, Middle East respiratory syndrome coronavirus, and the latest pandemic caused by the SARS-CoV-2 infection. All viruses, including SARS-CoV-2, have the inherent tendency to evolve. SARS-CoV-2 is still evolving in humans. Additionally, due to the development of herd immunity, prior infection, use of medication, vaccination, and antibodies, the viruses are facing immune pressure. During the replication process and due to immune pressure, the virus may undergo mutations. Several SARS-CoV-2 variants, including the variants of concern (VOCs), such as B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), P.1 (Gamma), and B.1.1.529 (Omicron) have been reported from various parts of the world. These VOCs contain several important mutations; some of them are on the spike proteins. These mutations may lead to enhanced infectivity, transmissibility, and decreased neutralization efficacy by monoclonal antibodies, convalescent sera, or vaccines. Mutations may also lead to a failure of detection by molecular diagnostic tests, leading to a delayed diagnosis, increased community spread, and delayed treatment. We searched PubMed, EMBASE, Covariant, the Stanford variant Database, and the CINAHL from December 2019 to February 2023 using the following search terms: VOC, SARS-CoV-2, Omicron, mutations in SARS-CoV-2, etc. This review discusses the various mutations and their impact on infectivity, transmissibility, and neutralization efficacy.

GFAP expression in the brain during human postnatal development

AbstractGlial fibrillary acidic protein (GFAP) immunohistochemistry was investigated in the developing human brain using two measures; the number of GFAP‐positive cells (density, GFAP+/mm2), and a reactivity score (R‐score), which we recently introduced to indicate astrogliosis, with scores ≥120 indicative of pathological processes. The primary aim was to report on GFAP expression and cell soma size in 26 microscopically defined regions of the amygdala, basal ganglia, cerebellum, hippocampus and medulla, and to determine whether they are affected by postconceptional age (PCA) from 40 to 83 weeks. The secondary aim was to determine if GFAP expression differs according to the classification of sudden infant death syndrome (SIDS) as opposed to infant deaths of known causes, or for the presence of major SIDS risk factors of male sex, cigarette smoke exposure, upper respiratory tract infection (URTI), bed‐sharing and prone sleeping. The cerebellar molecular layer was void of GFAP+ cells, while the internal granular layer (IGL) had the highest density, with &gt;60% of infants having an R‐Score &gt;120. GFAP expression decreased with increasing PCA in the entorhinal and temporal cortex, subiculum and regions of the cerebellum and medulla. GFAP cell soma size corresponded with astrogliosis score and no effect of PCA was evident. Various region‐dependent GFAP expressional differences were seen according to SIDS classification and the risk factors studied. The findings indicate that the density of GFAP decreases in specific regions of the brain within the first year of postnatal development, and that reactive astrocytes are common, particularly within the early postnatal months.

Tofacitinib treatment for plaque psoriasis and psoriatic arthritis: A meta-analysis of randomised controlled trials.

Objectives Tofacitinib is used as an oral Janus-associated kinase (JAK) inhibitor acting on JAK1 and JAK3, in treating psoriatic disease. However, there is still no consensus on the optimal dosage and duration of tofacitinib. In this study, we aimed to evaluate the effects of tofacitinib in treating psoriatic disease. Methods and Materials A literature search was done utilising Cochrane library, Medline, EMBASE, Wiley Online library, Web of Science and BIOSIS Previews through December 18, 2022. We performed a meta-analysis of published original studies to assess the impact of tofacitinib in plaque psoriasis or psoriatic arthritis therapy based on seven randomised controlled trials (RCTs) involving 2,672 patients (receiving tofacitinib) and 853 controls (receiving placebo). Results Compared with placebo, the treatment of 5 mg twice-daily (BID) tofacitinib for 12 weeks is sufficient to significantly alleviate the main clinical manifestations of psoriasis [≥75% decrease in Psoriasis Area and Severity Index score (PASI 75): Risk ratio (RR)=4.38 (95% Confidence interval (CI) 2.51 to 7.64); ≥90% decrease in PASI score (PASI 90): RR=21.68 (95% CI 4.20 to 111.85); Physician's Global Assessment of 'clear' or 'almost clear' (PGA 0/1): RR=3.93 (95%CI 3.03 to 5.09)]. Interestingly, there was no significant difference in improvement in PGA 0/1 with 5 mg BID tofacitinib given for 16 weeks when compared with 5 mg BID tofacitinib for 12 weeks [RR=1.11 (95%CI 0.98 to 1.25)]. Additionally, the 5 mg BID tofacitinib for 16 weeks treatment schedule significantly increased the incidence of upper respiratory tract infection (URTI) [RR=1.89 (95%CI 1.06 to 3.38)] as compared to 5 mg BID tofacitinib for 12 weeks treatment schedule [RR=1.15 (95%CI 0.60 to 2.20)]. Conclusion The 5 mg BID tofacitinib for 12 weeks treatment significantly improved psoriasis without causing too many specific adverse events. This indicated that tofacitinib is an effective treatment plan for psoriatic disease by reasonably controlling dosage and dosing time.

Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections

Abstract Scope The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals &amp; pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota. Summary Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum &amp; other bacterial spp. reduce IFNγ &amp; TNF-α and increase IL-4 &amp; IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases. Conclusion The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities.