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Nasopharyngeal carriage of <i>Streptococcus pneumoniae</i> among children <5 years of age in Indonesia prior to pneumococcal conjugate vaccine introduction

by Dodi Safari, Wa Ode Dwi Daningrat, Jennifer L. Milucky, Miftahuddin Majid Khoeri, Wisiva Tofriska Paramaiswari, Wisnu Tafroji, Korrie Salsabila, Yayah Winarti, Amin Soebandrio, Sri Rezeki Hadinegoro, Ari Prayitno, Lana Childs, Fabiana C. Pimenta, Maria da Gloria Carvalho, Tamara Pilishvili

Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged

Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3)

Por: Hazenberg · P. · Robinson · R. E. · Farrar · M. · Solorzano · C. · Hyder-Wright · A. · Liatsikos · K. · Brunning · J. · Fleet · H. · Bettam · A. · Howard · A. · Kenny-Nyazika · T. · Urban · B. · Mitsi · E. · El Safadi · D. · Davies · K. · Lesosky · M. · Gordon · S. B. · Ferreira · D. M.
Introduction

Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size.

Methods and analysis

This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of the colonisation rate. The primary outcome of this study is to determine the optimal SPN3 dose and inoculation regime to establish the highest rates of NP colonisation in healthy adults. Secondary outcomes include determining density and duration of experimental SPN3 NP colonisation and characterising mucosal and systemic immune responses to SPN3 challenge.

Ethics and dissemination

This study is approved by the NHS Research and Ethics Committee (reference 22/NW/0051). Findings will be published in peer-reviewed journals and reports will be made available to participants.

Reported side-effects following Oxford/AstraZeneca COVID-19 vaccine in the north-west province, Iran: A cross-sectional study

by Majid Eterafi, Nasrin Fouladi, Majid Golizadeh, Hamidreza Shaker, Somaieh Matin, Elham Safarzadeh

While the vaccination was introduced as a promising tool to control the Coronavirus disease 2019 (COVID-19) pandemic, concerns about vaccine-related side effects had grown. Due to the widespread administration of the COVID-19 vaccine worldwide for the first time, it was necessary to evaluate the safety and potential side effects in recipients. This study aims to assess, the incidence of adverse effects following Oxford-AstraZeneca vaccination and identify their related factors. In this cross-sectional survey-based study, 453 volunteers participated, including 235 men and 218 women. The reported adverse reactions from recipients of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine were collected by using a questionnaire. The findings showed that the incidence of adverse reactions, such as neurological, systematic, gastrointestinal, respiratory, and local symptoms were significantly higher after the first dose compared to the second dose. Systematic symptoms were the most prevalent reported side effects after the first and second dose injection. The demographical study of participants showed that individuals aged 18–34 and females were more prone to present adverse events following vaccination. However, no significant relationship was found between the occurrence of side effects and the recipients’ body mass index. Despite the life-saving role of vaccination against SARS-CoV-2, it may have some adverse reactions in recipients. The severity and frequency of side effects were different. So, they were dependent on several factors, including gender and age. Altogether, post-vaccination adverse reactions were mild and tolerable.

Characterization of Type VI secretion system in <i>Edwardsiella ictaluri</i>

by Safak Kalindamar, Hossam Abdelhamed, Adef O. Kordon, Hasan C. Tekedar, Lesya Pinchuk, Attila Karsi

Edwardsiella ictaluri is a Gram-negative facultative intracellular fish pathogen causing enteric septicemia of catfish (ESC). While various secretion systems contribute to E. ictaluri virulence, the Type VI secretion system (T6SS) remains poorly understood. In this study, we constructed 13 E. ictaluri T6SS mutants using splicing by overlap extension PCR and characterized them, assessing their uptake and survival in channel catfish (Ictalurus punctatus) peritoneal macrophages, attachment and invasion in channel catfish ovary (CCO) cells, in vitro stress resistance, and virulence and efficacy in channel catfish. Among the mutants, EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO exhibited reduced replication inside peritoneal macrophages. EiΔevpM, EiΔevpN, and EiΔevpO showed significantly decreased attachment to CCO cells, while EiΔevpN and EiΔevpO also displayed reduced invasion of CCO cells (p EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO were susceptible to oxidative stress in both nutrient-rich and minimal medium. In fish challenges, EiΔevpD, EiΔevpE, EiΔevpG, EiΔevpJ, and EiΔevpK exhibited attenuation and provided effective protection against E. ictaluri wild-type (EiWT) infection in catfish fingerlings. However, their attenuation and protective efficacy were lower in catfish fry. These findings shed light on the role of the T6SS in E. ictaluri pathogenesis, highlighting its significance in intracellular survival, host cell attachment and invasion, stress resistance, and virulence. The attenuated T6SS mutants hold promise as potential candidates for protective immunization strategies in catfish fingerlings.

Deciphering the immune landscape of head and neck squamous cell carcinoma: A single-cell transcriptomic analysis of regulatory T cell responses to PD-1 blockade therapy

by Adib Miraki Feriz, Fatemeh Bahraini, Arezou Khosrojerdi, Setareh Azarkar, Seyed Mehdi Sajjadi, Edris HosseiniGol, Mohammad Amin Honardoost, Samira Saghafi, Nicola Silvestris, Patrizia Leone, Hossein Safarpour, Vito Racanelli

Immunotherapy is changing the Head and Neck Squamous Cell Carcinoma (HNSCC) landscape and improving outcomes for patients with recurrent or metastatic HNSCC. A deeper understanding of the tumor microenvironment (TME) is required in light of the limitations of patients’ responses to immunotherapy. Here, we aimed to examine how Nivolumab affects infiltrating Tregs in the HNSCC TME. We used single-cell RNA sequencing data from eight tissues isolated from four HNSCC donors before and after Nivolumab treatment. Interestingly, the study found that Treg counts and suppressive activity increased following Nivolumab therapy. We also discovered that changes in the CD44-SSP1 axis, NKG2C/D-HLA-E axis, and KRAS signaling may have contributed to the increase in Treg numbers. Furthermore, our study suggests that decreasing the activity of the KRAS and Notch signaling pathways, and increasing FOXP3, CTLA-4, LAG-3, and GZMA expression, may be mechanisms that enhance the killing and suppressive capacity of Tregs. Additionally, the result of pseudo-temporal analysis of the HNSCC TME indicated that after Nivolumab therapy, the expression of certain inhibitory immune checkpoints including TIGIT, ENTPD1, and CD276 and LY9, were decreased in Tregs, while LAG-3 showed an increased expression level. The study also found that Tregs had a dense communication network with cluster two, and that certain ligand-receptor pairs, including SPP1/CD44, HLA-E/KLRC2, HLA-E/KLRK1, ANXA1/FPR3, and CXCL9/FCGR2A, had notable changes after the therapy. These changes in gene expression and cell interactions may have implications for the role of Tregs in the TME and in response to Nivolumab therapy.

Effects of boron citrate supplementation on cardiometabolic factors, inflammatory biomarkers and anthropometric measures in obese patients: study protocol for a randomised, double-blind clinical trial

Por: Naemi · M. · Naghshi · S. · Rostami · S. · Safaei · E. · Tutunchi · H. · Ostadrahimi · A.
Introduction

Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. The efficacy and safety of boron citrate (BC), a novel therapeutic approach, in patients with obesity are not known. The current trial will take place to determine the effects of BC supplementation on cardiometabolic factors, inflammatory biomarkers, anthropometric measures and body composition in obese patients.

Methods and analysis

This double-blind, placebo-controlled, randomised clinical trial will involve 60 eligible obese participants aged 18–60 years. Participants will randomly be allocated to receive either BC capsules (containing 10 mg of boron) in the intervention group or placebo capsules (containing 10 mg of maltodextrin) in the placebo group for 12 weeks. Moreover, physical activity and dietary recommendations will be provided for both groups. To assess the dietary intakes of participants, a 3-day food record (2 days of the week and 1 day of the weekend) will be filled. Cardiometabolic factors, inflammatory biomarkers including tumour necrosis factor α, C reactive protein, interleukin-6 and interleukin-10 levels, anthropometric measures and body composition will be assessed at the baseline and end of the intervention. The findings of this study will provide evidence for the effectiveness of BC in the management of obesity.

Ethics and dissemination

There are so far no reported adverse effects associated with the use of boron. This trial was approved by the Ethics Committee of Tabriz University of Medical Sciences (approval number: IR.TBZMED.REC.1401.350). Positive as well as negative findings will be published in peer-reviewed journals.

Trial registration number

IRCT20220806055624N1.

Effect of caring leadership intervention program for first‐line nurse managers on their managerial actions and nurse outcomes

Abstract

Aim

The aim of the study was to examine the effect of a caring leadership intervention program for first-line nurse managers (FLNM) on their caring knowledge and managerial actions as well as nurses' perceived FLNM caring behaviours and nurse outcomes.

Design

A quasi-experimental study design was implemented on two groups; study and control, including 30 FLNM and 150 nurses for each.

Methods

Self-report questionnaires about FLNMs' knowledge of caring behaviours and their managerial actions, nurses perceived line nurse managers' caring behaviours and nurses' outcomes (job satisfaction and work engagement) were utilized to collect study data from 1 July 2022 to 30 December 2022.

Results

A statistically significant difference and changes were revealed between the study and control groups in FLNMs' caring knowledge and their managerial actions, and nurses' perceived FLNMs' caring behaviours, nurses' job satisfaction and nurses' work engagement during post-test in comparison to pre-test. Higher total mean scores of post-test in the study group were recorded compared to those of control group regarding FLNMs' caring knowledge and their managerial actions as well as nurses ‘perceived FLNMs’ caring behaviour, job satisfaction and work engagement.

Conclusion

The caring leadership intervention program for FLNMs was highly effective in enhancing their caring knowledge and managerial actions as well as nurses' perceived FLNM caring behaviours and nurse outcomes.

Implications for the Profession

Caring leadership can help FLNMs to create a healthy environment, resulting in a positive outcome for nurse staff, patients and healthcare organizations.

Patient and Public Contribution

No patient and public contribution.

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