Quantitative CT Metrics Associated with Variability in the Diffusion Capacity of the Lung of Post-COVID-19 Patients with Minimal Residual Lung Lesions.

(1) Background: A reduction in the diffusion capacity of the lung for carbon monoxide is a prevalent longer-term consequence of COVID-19 infection. In patients who have zero or minimal residual radiological abnormalities in the lungs, it has been debated whether the cause was mainly due to a reduced alveolar volume or involved diffuse interstitial or vascular abnormalities. (2) Methods: We performed a cross-sectional study of 45 patients with either zero or minimal residual lesions in the lungs (total volume < 7 cc) at two months to one year post COVID-19 infection. There was considerable variability in the diffusion capacity of the lung for carbon monoxide, with 27% of the patients at less than 80% of the predicted reference. We investigated a set of independent variables that may affect the diffusion capacity of the lung, including demographic, pulmonary physiology and CT (computed tomography)-derived variables of vascular volume, parenchymal density and residual lesion volume. (3) Results: The leading three variables that contributed to the variability in the diffusion capacity of the lung for carbon monoxide were the alveolar volume, determined via pulmonary function tests, the blood vessel volume fraction, determined via CT, and the parenchymal radiodensity, also determined via CT. These factors explained 49% of the variance of the diffusion capacity, with p values of 0.031, 0.005 and 0.018, respectively, after adjusting for confounders. A multiple-regression model combining these three variables fit the measured values of the diffusion capacity, with R = 0.70 and p < 0.001. (4) Conclusions: The results are consistent with the notion that in some post-COVID-19 patients, after their pulmonary lesions resolve, diffuse changes in the vascular and parenchymal structures, in addition to a low alveolar volume, could be contributors to a lingering low diffusion capacity.

Synthesis, characterization, and antimicrobial activities of a starch-based polymer.

Due to the rise of nosocomial infections and the increasing threat of antibiotic resistance, new techniques are required to combat bacteria and fungi. Functional antimicrobial biodegradable materials developed from low-cost renewable resources like polysaccharides would enable greater applications in this regard. Our group has developed and characterized a new antimicrobial polymer using commercially available N-ethyl piperazine and starch via simple one-pot method. The prepared antimicrobial polymer was characterized by FTIR and NMR. In addition, the thermal properties of the synthesized antimicrobial polymer were examined through TGA and DSC. The antimicrobial potential of the prepared material was investigated using the bacteria, Staphylococcus aureus, Escherichia coli, and Mycobacterium smegmatis and a fungi Candida albicans. The result indicates that, as the amount of polymer increases, the antimicrobial activity also increases. SA-E-NPz exhibited a zone of inhibition in the range of 8-13 mm, and the MIC was found to be < 0.625 mg against all four microbes. The antimicrobial activity of polymer coated on fabric was also studied. Furthermore, the cytotoxicity studied against human fibroblast cell lines showed that the prepared polymer is non-toxic to the cells. The study concluded that the synthesized polymer shows good antimicrobial activity, is non-toxic to human fibroblast cells, and thus can be used for wound dressing or textile applications.

Vaccination Ameliorates Cellular Inflammatory Responses in SARS-CoV-2 Breakthrough Infections.

BACKGROUND: Data on cellular immune responses in persons with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following vaccination are limited. The evaluation of these patients with SARS-CoV-2 breakthrough infections may provide insight into how vaccinations limit the escalation of deleterious host inflammatory responses. METHODS: We conducted a prospective study of peripheral blood cellular immune responses to SARS-CoV-2 infection in 21 vaccinated patients, all with mild disease, and 97 unvaccinated patients stratified based on disease severity. RESULTS: We enrolled 118 persons (aged 50 years [SD 14.5 years], 52 women) with SARS-CoV-2 infection. Compared to unvaccinated patients, vaccinated patients with breakthrough infections had a higher percentage of antigen-presenting monocytes (HLA-DR+), mature monocytes (CD83+), functionally competent T cells (CD127+), and mature neutrophils (CD10+); and lower percentages of activated T cells (CD38+), activated neutrophils (CD64+), and immature B cells (CD127+CD19+). These differences widened with increased disease severity in unvaccinated patients. Longitudinal analysis showed that cellular activation decreased over time but persisted in unvaccinated patients with mild disease at 8-month follow-up. CONCLUSIONS: Patients with SARS-CoV-2 breakthrough infections exhibit cellular immune responses that limit the progression of inflammatory responses and suggest mechanisms by which vaccination limits disease severity. These data may have implications for developing more effective vaccines and therapies. Clinical Trials Registration. NCT04401449.

Recent advancements and perspective of ciprofloxacin-based antimicrobial polymers.

In recent years, microbial pathogens, which are major sources of infections, have become a widespread concern across the world. The number of deaths caused by infectious diseases is continually rising, according to World Health Organization records. Antimicrobial resistance, particularly resistance to several drugs, is steadily growing in percentages of organisms. Ciprofloxacin is a second-generation fluoroquinolone with significant antimicrobial activity and pharmacokinetic characteristics. According to studies, many bacteria are resistant to the antibiotic ciprofloxacin. In this article, we look into polymers as ciprofloxacin macromolecular carriers with a wide range of antibacterial activity. We also discuss the latter form of coupling, in which ciprofloxacin and polymers are covalently bonded. This article also discusses the use of antimicrobial polymers in combination with ciprofloxacin in a various sectors. The current review article provides an overview of publications in the last five years on polymer loaded or modified with ciprofloxacin having applications in numerous sectors.

A cross-sectional study of quantitative CT measurements associated with the diffusion capacity of the lung in recovered COVID-19 patients with normalised chest CT.

Impairment of the diffusion capacity of the lung for carbon monoxide (DLco) is commonly reported in convalescent and recovered COVID-19 patients, although the cause is not fully understood especially in patients with no radiological sequelae. In a group of 47 patients at 7 - 51 weeks post infection with either none or minimal scarring or atelectasis on chest CT scans (total < 0.1% of lung volume), dispersions in DLco-adj % and total lung capacity (TLC) % of predicted were observed, with median(quartiles) of 87(78, 99)% and 84(78, 92)%, respectively. Thirteen(27.1%) patients had DLco-adj% < 80%. Although the DLco-adj% did not significantly correlate with the severity of the illness in the acute phase, time since the onset of symptoms, the volume of residual lesions on CT, age or sex, DLco-adj/alveolar volume (Kco-adj) % predicted was correlated with the measurements of small blood vessel volume fraction (diameter <= 5mm) and parenchyma density on CT. Multivariate analysis revealed that these two CT metrics significantly contributed to the variance in DLco-adj% independent of TLC%. Comparing to between-subject variability of DLco-adj in healthy individuals, patients in this cohort with DLco-adj% < 80% were likely abnormal with a degree of disease not visually detectable on CT. However, it is not clear whether the associated variance of parenchyma density and small vessel volume fraction were a consequence of the COVID-19 disease or a pre-existing background variance.

The Role of Semaphorins and Their Receptors in Innate Immune Responses and Clinical Diseases of Acute Inflammation.

Semaphorins are a group of proteins that have been studied extensively for their critical function in neuronal development. They have been shown to regulate airway development, tumorigenesis, autoimmune diseases, and the adaptive immune response. Notably, emerging literature describes the role of immunoregulatory semaphorins and their receptors, plexins and neuropilins, as modulators of innate immunity and diseases defined by acute injury to the kidneys, abdomen, heart and lungs. In this review we discuss the pathogenic functions of semaphorins in clinical conditions of acute inflammation, including sepsis and acute lung injury, with a focus on regulation of the innate immune response as well as potential future therapeutic targeting.

Polymeric approach to combat drug-resistant methicillin-resistant Staphylococcus aureus.

ABSTRACT: The current global death rate has threatened humans due to increase in deadly unknown infections caused by pathogenic microorganisms. On the contrary, the emergence of multidrug-resistant bacteria is also increasing which is leading to elevated lethality rate worldwide. Development of drug-resistant bacteria has become one of the daunting global challenges due to failure in approaching to combat against them. Methicillin-resistant Staphylococcus aureus (MRSA) is one of those drug-resistant bacteria which has led to increase in global mortality rate causing various lethal infections. Polymer synthesis can be one of the significant approaches to combat MRSA by fabricating polymeric coatings to prevent the spread of infections. This review provides last decade information in the development of various polymers against MRSA.

IL-4 Induces IL17Rb Gene Transcription in Monocytic Cells with Coordinate Autocrine IL-25 Signaling.

IL-25 and IL-4 signaling in the setting of infection or allergic responses can drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to mediate signaling through nuclear factor κ B (NF-κB) transcriptional activation. Despite the known coexistence of these two cytokines in the Type 2 inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb protein in human lung tissue culture, primary alveolar macrophages, and the THP-1 monocytic cell line. IL-4 treatment triggers gene transcription for both IL-25 and IL-17Rb but does not alter the receptor mRNA stability. Genetic antagonism of the IL-4 second messenger, signal transducer and activator of transcription 6 (STAT6), with small interfering RNA (siRNA) blunts IL-17Rb mRNA induction by IL-4. IL-25 induces signaling through the canonical NF-κB pathway, and STAT6 or NF-κB signaling inhibitors prevent IL-17Rb expression. Blockade of IL-25 with monoclonal antibody suppresses NF-κB activation after IL-4 treatment, and IL-4-mediated induction of IL-17Rb is suppressed by IL-25 siRNA. IL-25 and IL-17Rb promoter regions harbor putative NF-κB and STAT6 consensus sites, and chromatin immunoprecipitation identified these transcription factors in complex with the IL-17Rb 5' untranslated region. In bronchoalveolar lavage RNA preparations, IL-25 and IL-17Rb mRNA transcripts are increased in asthmatics compared with healthy control subjects, and IL-25 transcript abundance correlates strongly with IL-4 mRNA levels. Thus, these results indicate that IL-4 signaling up-regulates the IL-25 axis in human monocytic cells, and that IL-25 may provide autocrine signals in monocytes and macrophages to sustain IL-17Rb expression and predispose to alternative activation.