Up to 30% of the human population are asymptomatically and permanently colonized with nasal
. To successfully colonize human nares,
needs to establish solid interactions with human nasal epithelial ...cells and overcome host defense mechanisms. However, some factors like bacterial interactions in the human nose can influence
colonization and sometimes prevent colonization. On the other hand, certain host characteristics and environmental factors can predispose to colonization. Nasal colonization can cause opportunistic and sometimes life-threatening infections such as surgical site infections or other infections in non-surgical patients that increase morbidity, mortality as well as healthcare costs.
This article reports the various methods used to assess diaphragmatic function by ultrasonography. The excursions of the two hemidiaphragms can be measured using two-dimensional or M-mode ...ultrasonography, during respiratory maneuvers such as quiet breathing, voluntary sniffing and deep inspiration. On the zone of apposition to the rib cage for both hemidiaphragms, it is possible to measure the thickness on expiration and during deep breathing to assess the percentage of thickening during inspiration. These two approaches make it possible to assess the quality of the diaphragmatic function and the diagnosis of diaphragmatic paralysis or dysfunction. These methods are particularly useful in circumstances where there is a high risk of phrenic nerve injury or in diseases affecting the contractility or the motion of the diaphragm such as neuro-muscular diseases. Recent methods such as speckle tracking imaging and ultrasound shear wave elastography should provide more detailed information for better assessment of diaphragmatic function.
:
(
) infections are associated with increased morbidity, mortality and health-care costs. Persistent nasal carriage of
found in 10-30% of the general population, constitutes a risk factor for these ...infections. Nasal decolonization is one of the used strategies to prevent this risk in some situations.
: Mupirocin nasal ointment has been used for the nasal decolonization and prevention of staphylococcal infections in various settings like surgeries. However, rising rates of resistance to mupirocin require the development of new decolonization agents. In this review, we will discuss mupirocin, its origins, studies that proved its efficacy and the associated resistance, as well as other decolonization agents under investigation.
: As some limitations exist to mupirocin use, further research for alternatives is encouraged. Some old approved antiseptics (chlorhexidine, povidone-iodine) or antibiotics (rifampicin, bacitracin) have been investigated for their efficacy in this indication. Other new agents (tea tree oil, retapamulin, LTX-109, XF-73, phages, lysostaphin, squalamine analogues, etc.) are being studied. Some of them are still in preclinical phases, and others have reached clinical trials, but further research is needed. Special interest should be given to single dose decolonization strategies and to molecules that do not select resistant strains.
Chest ultrasonography has proven to be useful in the diagnosis of diaphragm dysfunction. The aim of the present study was to determine the normal values of the motion of both hemidiaphragms recorded ...by M-mode ultrasonography. Healthy volunteers were studied while in a seated position. Diaphragmatic excursions and diaphragm profiles were measured during quiet breathing, voluntary sniffing and deep breathing. Diaphragmatic excursions were assessed by M-mode ultrasonography, using an approach perpendicular to the posterior part of the diaphragm. Anatomical M-mode was used for the recording of the complete excursion during deep breathing. The study included 270 men and 140 women. The diaphragmatic motions during quiet breathing and voluntary sniffing were successfully recorded in all of the participants. The use of anatomical M-mode was particularly suitable for measurement of the entire diaphragmatic excursion during deep breathing. The statistical analysis showed that the diaphragmatic excursions were larger in men compared to women, supporting the determination of normal values based on sex. The lower and upper limits of normal excursion were determined for men and women for both hemidiaphragms during the three manoeuvres that were investigated. The lower limits of normal diaphragmatic excursions during deep breathing should be used to detect diaphragmatic hypokinesia,
3.3 and 3.2 cm in women and 4.1 and 4.2 cm in men for the right and the left sides, respectively. The normal values of the diaphragmatic motion and the lower and upper limits of normal excursion can be used by clinicians to detect diaphragmatic dysfunction.
Many bacteria use quorum sensing (QS), a bacterial communication system based on the diffusion and perception of small signaling molecules, to synchronize their behavior in a cell-density dependent ...manner. QS regulates the expression of many genes associated with virulence factor production and biofilm formation. This latter is known to be involved in antibiotic and phage resistance mechanisms. Therefore, disrupting QS, a strategy known as quorum quenching (QQ), appears to be an interesting way to reduce bacterial virulence and increase antibiotic and phage treatment efficiency. In this study, the ability of the QQ enzyme SsoPox-W263I, a lactonase able to degrade acyl-homoserine lactones, was investigated for quenching both virulence and biofilm formation in clinical isolates of Pseudomonas aeruginosa from diabetic foot ulcers, as well as in the PA14 model strain. These strains were further evolved to resist to bacteriophage cocktails. Overall, 10 antibiotics or bacteriophage resistant strains were evaluated and SsoPox-W263I was shown to decrease pyocyanin, protease and elastase production in all strains. Furthermore, a reduction of more than 70% of biofilm formation was achieved in six out of ten strains. This anti-virulence potential was confirmed in vivo using an amoeba infection model, showing enhanced susceptibility toward amoeba of nine out of ten P. aeruginosa isolates upon QQ. This amoeba model was further used to demonstrate the ability of SsoPox-W263I to enhance the susceptibility of sensitive and phage resistant bacteria to bacteriophage and antibiotic.
We aimed to develop a systemic sclerosis (SSc) subtypes classifier tool to be used at the patient's bedside. We compared the heart rate variability (HRV) at rest (5-min) and in response to ...orthostatism (5-min) of patients (n = 58) having diffuse (n = 16, dcSSc) and limited (n = 38, lcSSc) cutaneous forms. The HRV was evaluated from the beat-to-beat RR intervals in time-, frequency-, and nonlinear-domains. The dcSSc group differed from the lcSSc group mainly by a higher heart rate (HR) and a lower HRV, in decubitus and orthostatism conditions. Stand-up maneuver lowered HR standard deviation (sd_HR), the major axis length of the fitted ellipse of Poincaré plot of RR intervals (SD2), and the correlation dimension (CorDim) in the dcSSc group while increased these HRV indexes in the lcSSc group (p = 0.004, p = 0.002, and p = 0.004, respectively). We identified the 5 most informative and discriminant HRV variables. We then compared 341 classifying models (1 to 5 variables combinations × 11 classifier algorithms) according to mean squared error, logloss, sensitivity, specificity, precision, accuracy, area under curve of the ROC-curves and F1-score. F1-score ranged from 0.823 for the best 1-variable model to a maximum of 0.947 for the 4-variables best model. Most specific and precise models included sd_HR, SD2, and CorDim. In conclusion, we provided high performance classifying models able to distinguish diffuse from limited cutaneous SSc subtypes easy to perform at the bedside from ECG recording. Models were based on 1 to 5 HRV indexes used as nonlinear markers of autonomic integrated influences on cardiac activity.
Human tuberculosis is a life-threatening infection following the inhalation of Mycobacterium tuberculosis, while the closely related bacteria Mycobacterium bovis and Mycobacterium canettii are ...thought to be transmitted by ingestion. To explore whether M. tuberculosis could also infect individuals by ingestion, male BALBc mice were fed 2 x 106 CFUs of M. tuberculosis Beijing or phosphate-buffered saline as a negative control, over a 28-day experiment. While eight negative control mice remained disease-free, M. tuberculosis was identified in the lymph nodes and lungs of 8/14 mice and in the spleens of 4/14 mice by microscopy, PCR-based detection and culture. Whole-genome sequencing confirmed the identity of the inoculum and the tissue isolates. In these genetically identical mice, the dissemination of M. tuberculosis correlated with the results of the culture detection of four intestinal bacteria. These observations indicate that ingested M. tuberculosis mycobacteria can translocate, notably provoking lymphatic tuberculosis.
Computed tomography (CT) is routinely employed on the evaluation of dyspnea, yet limited data exist on its assessment of diaphragmatic muscle. This study aimed to determine the capability of CT in ...identifying structural changes in the diaphragm among patients with ultrasound-confirmed diaphragmatic dysfunction.
Diaphragmatic ultrasounds conducted between 2018 and 2021 at our center in Marseille, France, were retrospectively collected. Diaphragmatic pillars were measured on CT scans at the L1 level and the celiac artery. Additionally, the difference in height between the two diaphragmatic domes in both diaphragmatic dysfunction cases and controls was measured and compared.
A total of 65 patients were included, comprising 24 with diaphragmatic paralysis, 13 with diaphragmatic weakness, and 28 controls. In the case group (paralysis and weakness) with left dysfunctions (n = 24), the CT thickness of the pillars at the level of L1 and the celiac artery was significantly thinner compared with controls (2.0 mm vs. 7.4 mm and 1.8 mm vs. 3.1 mm, p < 0.001 respectively). Significantly different values were observed for paralysis (but not weakness) in the right dysfunction subgroup (n = 15) (2.6 mm vs. 7.4 mm and 2.2 mm vs. 3.8 mm, p < 0.001 respectively, for paralysis vs. controls). Regardless of the side of dysfunction, a significant difference in diaphragmatic height was observed between cases and controls (7.70 cm vs. 1.16 cm and 5.51 cm vs. 1.16 cm, p < 0.001 for right and left dysfunctions, respectively). Threshold values determined through ROC curve analyses for height differences between the two diaphragmatic domes, indicative of paralysis or weakness in the right dysfunctions, were 4.44 cm and 3.51 cm, respectively. Similarly for left dysfunctions, the thresholds were 2.70 cm and 2.48 cm, respectively, demonstrating good performance (aera under the curve of 1.00, 1.00, 0.98, and 0.79, respectively).
In cases of left diaphragmatic dysfunction, as well as in paralysis associated with right diaphragmatic dysfunction, CT revealed thinner pillars. Additionally, a notable increase in the difference in diaphragmatic height demonstrated a strong potential to identify diaphragmatic dysfunction, with specific threshold values.
Abstract
Introduction
The diaphragm function assessed by ultrasound has been well-studied in COPD, asthma, and intensive care. However, there are only a few studies on diffuse interstitial lung ...disease, while dyspnea and quality of life are major issues in the management that may depend on the diaphragm.
Methods
We retrospectively included idiopathic pulmonary fibrosis (IPF) patients followed in our center (Marseille, France) between January 2020 and February 2023 who underwent diaphragmatic ultrasound. Our objectives were to describe the diaphragmatic function of IPFs compared to healthy controls and to correlate with clinical, functional, and lung density on CT-scan.
Results
24 IPF patients and 157 controls were included. The diaphragmatic amplitude in IPF was increased at rest (median of 2.20 cm vs 1.88 cm on the right, p < 0.007, and 2.30 cm vs 1.91 cm on the left, p < 0.03, in IPF and controls respectively) and decreased in deep breathing (median of 4.85 cm vs 5.45 cm on the right, p < 0.009, and 5.10 cm vs 5.65 cm on the left, p < 0.046, in IPF and controls respectively). Diaphragmatic thickness was significantly reduced at rest on the right side (median of 1.75 mm vs 2.00 mm, p < 0.02, in IPF and controls respectively) and in deep breathing on both sides compared to controls (mean of 3.82 mm vs 4.15 mm on the right, p < 0.02, and 3.53 mm vs 3.94 mm, on the left, p < 0.009, in IPF and controls respectively). Diaphragmatic amplitude in deep breathing was moderate to strongly correlated with FVC, DLCO, and 6MWT and negatively correlated with the dyspnea and lung density on CT scan.
Conclusion
The diaphragmatic amplitude and thickness were impaired in IPF compared to controls. Diaphragmatic amplitude is the parameter best correlated with clinical, functional, and lung density criteria. Further studies are needed to determine if diaphragmatic amplitude can be a prognostic factor in IPF.
The effectiveness of antibiotic molecules in treating Pseudomonas aeruginosa pneumonia is reduced as a result of the dissemination of bacterial resistance. The existence of bacterial communication ...systems, such as quorum sensing, has provided new opportunities of treatment. Lactonases efficiently quench acyl-homoserine lactone-based bacterial quorum sensing, implicating these enzymes as potential new anti-Pseudomonas drugs that might be evaluated in pneumonia.
The aim of the present study was to evaluate the ability of a lactonase called SsoPox-I to reduce the mortality of a rat P. aeruginosa pneumonia.
To assess SsoPox-I-mediated quorum quenching, we first measured the activity of the virulence gene lasB, the synthesis of pyocianin, the proteolytic activity of a bacterial suspension and the formation of biofilm of a PAO1 strain grown in the presence of lactonase. In an acute lethal model of P. aeruginosa pneumonia in rats, we evaluated the effects of an early or deferred intra-tracheal treatment with SsoPox-I on the mortality, lung bacterial count and lung damage.
SsoPox-I decreased PAO1 lasB virulence gene activity, pyocianin synthesis, proteolytic activity and biofilm formation. The early use of SsoPox-I reduced the mortality of rats with acute pneumonia from 75% to 20%. Histological lung damage was significantly reduced but the lung bacterial count was not modified by the treatment. A delayed treatment was associated with a non-significant reduction of mortality.
These results demonstrate the protective effects of lactonase SsoPox-I in P. aeruginosa pneumonia and open the way for a future therapeutic use.
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