Bacterial community development in experimental gingivitis.

Current knowledge of the microbial composition of dental plaque in early gingivitis is based largely on microscopy and cultural methods, which do not provide a comprehensive description of oral microbial communities. This study used 454-pyrosequencing of the V1-V3 region of 16S rRNA genes (approximately 500 bp), and bacterial culture, to characterize the composition of plaque during the transition from periodontal health to gingivitis. A total of 20 healthy volunteers abstained from oral hygiene for two weeks, allowing plaque to accumulate and gingivitis to develop. Plaque samples were analyzed at baseline, and after one and two weeks. In addition, plaque samples from 20 chronic periodontitis patients were analyzed for cross-sectional comparison to the experimental gingivitis cohort. All of the healthy volunteers developed gingivitis after two weeks. Pyrosequencing yielded a final total of 344,267 sequences after filtering, with a mean length of 354 bases, that were clustered into an average of 299 species-level Operational Taxonomic Units (OTUs) per sample. Principal coordinates analysis (PCoA) plots revealed significant shifts in the bacterial community structure of plaque as gingivitis was induced, and community diversity increased significantly after two weeks. Changes in the relative abundance of OTUs during the transition from health to gingivitis were correlated to bleeding on probing (BoP) scores and resulted in the identification of new health- and gingivitis-associated taxa. Comparison of the healthy volunteers to the periodontitis patients also confirmed the association of a number of putative periodontal pathogens with chronic periodontitis. Taxa associated with gingivitis included Fusobacterium nucleatum subsp. polymorphum, Lachnospiraceae [G-2] sp. HOT100, Lautropia sp. HOTA94, and Prevotella oulorum, whilst Rothia dentocariosa was associated with periodontal health. Further study of these taxa is warranted and may lead to new therapeutic approaches to prevent periodontal disease.BBSRC Industrial Case Studentship ref no. BB/G01714X/1 in collaboration with GlaxoSmithKline

Epidemiological and Immunological Features of Obesity and SARS-CoV-2

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar

SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort

Identifying the potential for Severe Acute Respiratory Syndrome : Coronavirus 2 (SARS-CoV-2) reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders, and the choice of baseline time point and show how to account for both in reinfection analysis

IL-22 Protects against Tissue Damage during Cutaneous Leishmaniasis.

Cutaneous leishmaniasis is a disease characterized by ulcerating skin lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent tissue damage. While mechanisms that control the parasites have been well studied, the factors regulating immunopathologic responses are less well understood. IL-22, a member of the IL-10 family of cytokines, can contribute to wound healing, but in other instances promotes pathology. Here we investigated the role of IL-22 during leishmania infection, and found that IL-22 limits leishmania-induced pathology when a certain threshold of damage is induced by a high dose of parasites. Il22-/- mice developed more severe disease than wild-type mice, with significantly more pathology at the site of infection, and in some cases permanent loss of tissue. The increased inflammation was not due to an increased parasite burden, but rather was associated with the loss of a wound healing phenotype in keratinocytes. Taken together, these studies demonstrate that during cutaneous leishmaniasis, IL-22 can play a previously unappreciated role in controlling leishmania-induced immunopathology

Multi-center analysis of point-of-care ultrasound for small bowel obstruction: A systematic review and individual patient-level meta-analysis

OBJECTIVE: The study aimed to assess the diagnostic accuracy of point-of-care ultrasound (POCUS) in identifying small bowel obstruction (SBO) and to investigate the impact of clinician experience level and body mass index (BMI) on POCUS performance for diagnosing SBO in the Emergency Department. METHODS: We systematically searched PubMed and Cochrane databases from January 2011-2022. We performed a meta-analysis using individual patient-level data from prospective diagnostic accuracy studies from which we obtained data from the corresponding authors. Overall test characteristics and subgroup analysis across clinician experience levels and a range of BMI were calculated. The primary outcome was SBO as the final diagnosis during hospitalization. RESULTS: We included Individual patient data from 433 patients from 5 prospective studies. Overall, 33% of patients had a final diagnosis of SBO. POCUS had 83.0% (95%CI 71.7%-90.4%) sensitivity and 93.0% (95%CI 55.3%-99.3%) specificity; LR+ was 11.9 (95%CI 1.2-114.9) and LR- was 0.2 (95%CI 0.1-0.3). Residents had exhibited a sensitivity of 73.0% (95%CI 56.6%-84.9%) and specificity of 88.2% (95%CI 58.8%-97.5%), whereas attendings had demonstrated a sensitivity of 87.7% (95%CI 71.1%-95.4%) and specificity of 91.4% (95%CI 57.4%-98.8%). Among those patients with BMI\u3c30 kg/m, POCUS showed a sensitivity of 88.6% (95%CI 79.5%-94.7%) and a specificity of 84.0% (95%CI 75.3%-90.6%), while patients with BMI ≥ 30 kg/m exhibited a sensitivity of 72.0% (95%CI 50.6%-87.9%) and specificity of 89.5% (95%CI 75.2%-97.1%). CONCLUSIONS: POCUS correctly identified those patients with SBO with high sensitivity and specificity. Diagnostic accuracy was slightly reduced when performed by resident physicians and among patients with a BMI ≥ 30 kg/m. REGISTRATION: PROSPERO registration number: CRD42022303598

Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing

Chronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The “mycobiome” was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylum Ascomycota were significantly greater (P = 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes

The Use of a Rapid Enzymatic Assay in the Field for the Detection of Infections Associated with Adult Periodontitis

There are few objective assays for studies of the epidemiology of periodontal diseases. The PerioScan™ is an assay capable of detecting three periodontal pathogens, namely T. denticola, P. gingivalis, and B. forsythus, which have been associated with adult periodontitis. The PerioScan™ was tested in a sample of 301 Brazilians. Clinical indices—bleeding, probing depth, gingival index, and periodontal index—were recorded from four sites in each subject. Subgingival plaque samples were collected from those sites and placed on the PerioScan™ card. Color results were scored in the field after 15 minutes. The plaque samples were screened with polyclonal antibodies for the three species by an ELISA system. The PerioScan™, when compared with the ELISA system, yields a sensitivity of 91 percent, specificity of 89 percent, and an accuracy of 90 percent. When the PerioScan™ was compared to clinical indices, there was a high sensitivity (at least 93%) and a low specificity (no less than 47%), with an accuracy of at least 61 percent.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66375/1/j.1752-7325.1993.tb02710.x.pd

Optic Nerve Sheath Diameter Measured by Point-of-Care Ultrasound and MRI

BACKGROUND AND PURPOSE: Ultrasound (US) measurement of the optic nerve sheath diameter (ONSD) and optic nerve diameter (OND) is a method frequently used to screen for an increased intracranial pressure. The aim of this study was to assess the accuracy of US measurements of ONSD and OND, when compared to magnetic resonance imaging (MRI) measurements as the criterion standard. METHODS: In this prospective, single-institution study, orbital US was performed for those patients requiring an emergent brain MRI. ONSD and OND of both eyes were measured in the axial and coronal planes in straight gaze by US. ONSD and OND from brain and orbital MRI were measured by two neuroradiologists. Correlation and agreement between readings were assessed using Pearson\u27s correlations. RESULTS: Eighty-two patients met inclusion criteria. The mean axial and coronal ONSD in the MRI examinations was 5.6 and 5.7 mm at 3-5.9 mm behind the globe, respectively. The mean ONSD from the US measurements was 6.22 and 5.52 mm in the axial and coronal planes, respectively. The mean OND in US examinations was 4.31 mm (axial) and 3.68 mm (coronal). Axial versus coronal measurements of ONSD had a modest correlation in US assessment with an r of.385 (P \u3c.001) but there were no correlations between any of the US and MRI measurements. CONCLUSIONS: In measuring ONSD and OND, US measurements showed a modest correlation between axial and coronal measurements, but no concordance was found between US and MRI in our setting.