Exploring Barriers and Facilitators to COVID-19 Vaccination in People Planning Pregnancy, Trying to Conceive, Pregnant, and Postpartum: A Mixed-Methods Study.

Pregnant people are at higher risk of morbidity from COVID-19 infection, yet vaccine hesitancy remains prevalent. Our mixed-methods study utilised surveys and interviews to understand decision-making regarding COVID-19 vaccination surrounding pregnancy. The most trusted source of information was health care providers. Five themes relating to vaccination barriers and facilitators were identified: (1) COVID-19 vaccine-related policies; (2) pregnancy-specific considerations; (3) barriers, facilitators, and influencers to vaccination; (4) vaccination decisions based on personal health considerations; (5) attitudes toward COVID-19 and other vaccines. Our study underscores the importance of receiving high-quality information from a trusted source to increase vaccination.

Social Media Misinformation about Pregnancy and COVID-19 Vaccines: A Systematic Review.

OBJECTIVE: The objectives of this study were to identify common social media misconceptions about COVID-19 vaccination in pregnancy, explain the spread of misinformation, and identify solutions to guide clinical practice and policy. METHODOLOGY: A systematic review was conducted and the databases Embase and Medline were searched from December 2019 to February 8, 2023, using terms related to social media, pregnancy, COVID-19 vaccines and misinformation. The inclusion criteria were original research studies that discussed misinformation about COVID-19 vaccination during pregnancy on social media. The exclusion criteria were review articles, no full text, and not published in English. Two independent reviewers conducted screening, extraction, and quality assessment. RESULTS: Our search identified 76 articles, of which 3 fulfilled eligibility criteria. Included studies were of moderate and high quality. The social media platforms investigated included Facebook, Google Searches, Instagram, Reddit, TikTok, and Twitter. Misinformation was related to concerns regarding vaccine safety, and its association with infertility. Misinformation was increased due to lack of content monitoring on social media, exclusion of pregnant women from early vaccine trials, lack of information from reputable health sources on social media, and others. Suggested solutions were directed at pregnancy care providers (PCPs) and public health/government. Suggestions included: (i) integrating COVID-19 vaccination information into antenatal care, (ii) PCPs and public health should increase their social media presence to disseminate information, (iii) address population-specific vaccine concerns in a culturally relevant manner, and others. CONCLUSION: Increased availability of information from reputable health sources through multiple channels could increase COVID-19 vaccine uptake in the pregnant population and help combat misinformation.

The complete mitochondrial genome of Penicillium expansum: Insights into the fungal evolution and phylogeny.

Penicillium expansum is an important phytopathogenic fungus that causes blue mold disease. In this study, the novel mitochondrial genome of P. expansum was sequenced, assembled, annotated, and compared with the previously published Penicillium mitogenomes. P. expansum mitogenome is composed of circular DNA molecules with a genome size of 25,496 bp. It encodes 16 protein-encoding genes (PCGs), two rRNA genes, and 25 tRNA genes. Comparative analysis with six other Penicillium species revealed that gene length, GC content, AT skew, and GC skew were variable among the core protein-coding genes. The Penicillium species' gene synteny analysis identified several gene rearrangements. Among the core 15 PCGs, atp8 had the lowest K2P genetic distance, which shows that this gene is highly conserved. The Ka/Ks value of most PCGs was less than 1, which shows that these genes have undergone purifying selection. Phylogenetic analysis based on 14 concatenated core mitochondrial genes revealed that P. expansum shares a close relationship with P. solitum. This study served as a first report on the complete mitochondrial genome of P. expansum and its comparative analysis that will contribute to population genetics and rapid evolutionary studies among Penicillium species.

Factors Associated With Growth in Patients Treated With the Classic Ketogenic Diet for Drug-Resistant Epilepsy.

BACKGROUND: Suboptimal growth and malnutrition are often cited as complications of ketogenic diet therapy in patients with drug-resistant epilepsy; however, there is conflicting evidence on the factors that contribute to growth. METHODS: This is an observational, case-based study to evaluate growth in patients with drug-resistant epilepsy treated with the classic ketogenic diet for at least 12 months. Age, gender, height, weight, and body mass index (BMI) were collected at baseline and epilepsy clinic standard-of-care visits (one month, six months, and 12 months after diet initiation). Dietary intake and laboratory measures including glucose, bicarbonate, and beta-hydroxybutyrate were also collected. RESULTS: 119 patients were included. After ketogenic diet initiation, there was a significant fall in height z score from baseline to 12 months (-0.15, P = 0.001) but no other significant changes in weight, weight-for-length/BMI, or height z scores were noted between any time points within the 12 months after diet initiation. When separated by age, height z score changes were limited to those aged zero to three years. This was accompanied by a significant decrease in energy intake 12 months after treatment in this age group. When separated by diet route, weight z scores at each time point were significantly lower in the group eating by mouth than tube. CONCLUSIONS: Our study provides further evidence that the classic ketogenic diet impacts growth. Our population demonstrated restriction in linear growth in those aged zero to three years, which correlated with declines in energy intake, and weight declines limited to patients fed by mouth.

Inflammatory cytokines associated with mild traumatic brain injury and clinical outcomes: a systematic review and meta-analysis.

Mild traumatic brain injuries (mTBIs) trigger a neuroinflammatory response, which leads to perturbations in the levels of inflammatory cytokines, resulting in a distinctive profile. A systematic review and meta-analysis were conducted to synthesize data related to levels of inflammatory cytokines in patients with mTBI. The electronic databases EMBASE, MEDLINE, and PUBMED were searched from January 2014 to December 12, 2021. A total of 5,138 articles were screened using a systematic approach based on the PRISMA and R-AMSTAR guidelines. Of these articles, 174 were selected for full-text review and 26 were included in the final analysis. The results of this study demonstrate that within 24 hours, patients with mTBI have significantly higher levels of Interleukin-6 (IL-6), Interleukin-1 Receptor Antagonist (IL-1RA), and Interferon-γ (IFN-γ) in blood, compared to healthy controls in majority of the included studies. Similarly one week following the injury, patients with mTBI have higher circulatory levels of Monocyte Chemoattractant Protein-1/C-C Motif Chemokine Ligand 2 (MCP-1/CCL2), compared to healthy controls in majority of the included studies. The results of the meta-analysis also confirmed these findings by demonstrating significantly elevated blood levels of IL-6, MCP-1/CCL2, and Interleukin-1 beta (IL-1ß) in the mTBI population compared to healthy controls (p < 0.0001), particularly in the acute stages (<7 days). Furthermore, it was found that IL-6, Tumor Necrosis Factor-alpha (TNF-α), IL-1RA, IL-10, and MCP-1/CCL2 were associated with poor clinical outcomes following the mTBI. Finally, this research highlights the lack of consensus in the methodology of mTBI studies that measure inflammatory cytokines in the blood, and also provides direction for future mTBI research.

Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis.

The ongoing antibiotic-resistance crisis is becoming a global problem affecting public health. Urgent efforts are required to design novel therapeutics against pathogenic bacterial species. Brucella melitensis is an etiological agent of brucellosis, which mostly affects sheep and goats but several cases have also been reported in cattle, water buffalo, yaks and dogs. Infected animals also represent the major source of infection for humans. Development of safer and effective vaccines for brucellosis remains a priority to support disease control and eradication in animals and to prevent infection to humans. In this research study, we designed an in-silico multi-epitopes vaccine for B. melitensis using computational approaches. The pathogen core proteome was screened for good vaccine candidates using subtractive proteomics, reverse vaccinology and immunoinformatic tools. In total, 10 proteins: catalase; siderophore ABC transporter substrate-binding protein; pyridoxamine 5'-phosphate oxidase; superoxide dismutase; peptidylprolyl isomerase; superoxide dismutase family protein; septation protein A; hypothetical protein; binding-protein-dependent transport systems inner membrane component; and 4-hydroxy-2-oxoheptanedioate aldolase were selected for epitopes prediction. To induce cellular and antibody base immune responses, the vaccine must comprise both B and T-cells epitopes. The epitopes were next screened for antigenicity, allergic nature and water solubility and the probable antigenic, non-allergic, water-soluble and non-toxic nine epitopes were shortlisted for multi-epitopes vaccine construction. The designed vaccine construct comprises 274 amino acid long sequences having a molecular weight of 28.14 kDa and instability index of 27.62. The vaccine construct was further assessed for binding efficacy with immune cell receptors. Docking results revealed that the designed vaccine had good binding potency with selected immune cell receptors. Furthermore, vaccine-MHC-I, vaccine-MHC-II and vaccine-TLR-4 complexes were opted based on a least-binding energy score of -5.48 kcal/mol, 0.64 kcal/mol and -2.69 kcal/mol. Those selected were then energy refined and subjected to simulation studies to understand dynamic movements of the docked complexes. The docking results were further validated through MMPBSA and MMGBSA analyses. The MMPBSA calculated -235.18 kcal/mol, -206.79 kcal/mol, and -215.73 kcal/mol net binding free energy, while MMGBSA estimated -259.48 kcal/mol, -206.79 kcal/mol and -215.73 kcal/mol for TLR-4, MHC-I and MHC-II complexes, respectively. These findings were validated by water-swap and entropy calculations. Overall, the designed vaccine construct can evoke proper immune responses and the construct could be helpful for experimental researchers in formulation of a protective vaccine against the targeted pathogen for both animal and human use.

Dosing Variability and Clinical Outcomes of Oxybutynin: A Pediatric Cohort of Patients With Neurogenic Bladder.

Background: Despite the therapeutic advancements of the last several decades, neurogenic bladder remains a significant source of morbidity for patients with a spinal pathology. Oxybutynin is a mainstay of treatment in pediatric populations despite significant side effects and highly variable bioavailability. Objectives: To characterize the use of oxybutynin in a cohort of pediatric patients with neurogenic bladder. Methods: Retrospective data were collected of dosing, drug interactions, and urodynamics parameters in the 100 consecutive patients in a spinal differences clinic who had an appointment between October 7, 2015, and December 30, 2015. In addition to descriptive statistics, a linear regression model of oxybutynin dose versus age and sex was developed to examine the impact of age on dosing variability. Results: One hundred patients (52% female) with a median age of 6.8 years were included. The median daily dose of oxybutynin was 0.36 mg/kg (interquartile range, 0.28-0.54 mg/kg). Of the 48 patients with a recent urodynamics study, 13 had a detrusor leak point pressure (DLPP) greater than the typical cutoff of 40 cm H2O, indicating a need for management escalation. However, of these 13 patients, 38% were already on or exceeding oxybutynin's maximum recommended dose. Conclusion: The wide dosing variability and high DLPPs despite maximal dosing indicate a need for further investigation of oxybutynin's bioavailability in this population compared to its side effects and clinical outcomes. If variability in response to the medication is due to differences in bioavailability, then a precision-dosing model based on patient genomics could be developed for oxybutynin.

Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review.

Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15-20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9-213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP.

Patient Preferences Regarding Chaperone Use for Sensitive Examinations.

INTRODUCTION: Chaperones are often employed during sensitive patient encounters and have been assumed to be mutually beneficial to the patient and provider. The aim of this study is to characterize patient preferences regarding the use of chaperones. METHODS: Following Institutional Review Board Approval, a questionnaire designed to evaluate preferences regarding chaperone use from a patient perspective was distributed electronically through the ResearchMatch platform as well as to patients in an outpatient urology clinic. Descriptive statistics were used to assess responder demographics, clinical experiences and preferences. Multiple regression analysis was used to determine factors associated with a preference for having a chaperone present during health care visits. RESULTS: A total of 913 individuals completed the survey. Over half (52.9%) reported they would not want a chaperone for any part of a health care visit. Although rectal and genital/pelvic examinations were considered sensitive by 76.3% and 85% of responders, respectively, only 25.4% and 15.7% preferred a chaperone during these encounters. Reasons for not wanting a chaperone included trust in the provider (80%) and comfort with examinations (70.4%). Male responders were less likely to report a preference for a chaperone (OR 0.28, 95% CI 0.19-0.39) or consider provider gender as a significant factor in preferring a chaperone (OR 0.28, 95% CI 0.09-0.66). CONCLUSIONS: Preference regarding the use of a chaperone is primarily influenced by gender of both the patient and the provider. For sensitive examinations commonly performed in the field of urology, most individuals would not prefer a chaperone be present.

YbtT is a low-specificity type II thioesterase that maintains production of the metallophore yersiniabactin in pathogenic enterobacteria.

Clinical isolates of Yersinia, Klebsiella, and Escherichia coli frequently secrete the small molecule metallophore yersiniabactin (Ybt), which passivates and scavenges transition metals during human infections. YbtT is encoded within the Ybt biosynthetic operon and is critical for full Ybt production in bacteria. However, its biosynthetic function has been unclear because it is not essential for Ybt production by the in vitro reconstituted nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS) pathway. Here, we report the structural and biochemical characterization of YbtT. YbtT structures at 1.4-1.9 Å resolution possess a serine hydrolase catalytic triad and an associated substrate chamber with features similar to those previously reported for low-specificity type II thioesterases (TEIIs). We found that YbtT interacts with the two major Ybt biosynthetic proteins, HMWP1 (high-molecular-weight protein 1) and HMWP2 (high-molecular-weight protein 2), and hydrolyzes a variety of aromatic and acyl groups from their phosphopantetheinylated carrier protein domains. In vivo YbtT titration in uropathogenic E. coli revealed a distinct optimum for Ybt production consistent with a tradeoff between clearing both stalled inhibitory intermediates and productive Ybt precursors from HMWP1 and HMWP2. These results are consistent with a model in which YbtT maintains cellular Ybt biosynthesis by removing nonproductive, inhibitory thioesters that form aberrantly at multiple sites on HMWP1 and HMWP2.